{ "Contributors": [ "EBMSummariserCorpus" ], "Source": [ "EBMSummariserCorpus" ], "URL": [ "https://sourceforge.net/projects/ebmsumcorpus/" ], "Categories": [ "Question Answering" ], "Definition": [ "Provide a justification or evidence to support a given statement." ], "Reasoning": [], "Input_language": [ "English" ], "Output_language": [ "English" ], "Instruction_language": [ "English" ], "Domains": [ "Medical Knowledge" ], "Positive Examples": [], "Negative Examples": [], "Instances": [ { "input": "Evidence suggests that neonatal circumcision decreases the incidence of childhood urinary tract infections, phimosis, paraphimosis, balanitis and other genital dermatoses, invasive penile cancer, and the sexually transmitted diseases human papilloma virus (HPV) and HIV.", "output": "In a series of 89 men with penile cancer, only 2 had been circumcised in infancy, while 87 were uncircumcised." }, { "input": "Evidence suggests that neonatal circumcision decreases the incidence of childhood urinary tract infections, phimosis, paraphimosis, balanitis and other genital dermatoses, invasive penile cancer, and the sexually transmitted diseases human papilloma virus (HPV) and HIV.", "output": "Evidence from case series supports the protective effect of circumcision on the rates of penile cancer. A review of 592 cases of penile cancer revealed that none of those affected had been circumcised in infancy." }, { "input": "Evidence suggests that neonatal circumcision decreases the incidence of childhood urinary tract infections, phimosis, paraphimosis, balanitis and other genital dermatoses, invasive penile cancer, and the sexually transmitted diseases human papilloma virus (HPV) and HIV.", "output": "A randomized controlled trial of circumcision for UTI prevention was not during the neonatal period (average age was 30 months) and focused on secondary prevention. It demonstrated a statistically significant decrease in the rate of bacteriuria. The long-term effect on UTI incidence, renal scarring, and subsequent complications such as hypertension and end-stage renal disease is unknown." }, { "input": "Evidence suggests that neonatal circumcision decreases the incidence of childhood urinary tract infections, phimosis, paraphimosis, balanitis and other genital dermatoses, invasive penile cancer, and the sexually transmitted diseases human papilloma virus (HPV) and HIV.", "output": "The number of male infants that need to be circumcised to prevent 1 UTI is estimated to be between 44 and 100." }, { "input": "Evidence suggests that neonatal circumcision decreases the incidence of childhood urinary tract infections, phimosis, paraphimosis, balanitis and other genital dermatoses, invasive penile cancer, and the sexually transmitted diseases human papilloma virus (HPV) and HIV.", "output": "Observational studies have shown at least a 10- to 12-fold increase in urinary tract infections (UTIs) in uncircumcised male infants compared with their circumcised counterparts." }, { "input": "The benefits of decreased incidence of HPV and HIV infections go beyond the index patient and have public health implications on the transmission of these diseases.", "output": "In a meta-analysis of 7 case-control studies, penile HPV was detected 2.7 times more often in uncircumcised men after controlling for confounders. In this same meta-analysis, monogamous female partners of high-risk circumcised men (men with more than 6 lifetime partners) had a lower risk of cervical cancer than women whose high-risk partner was uncircumcised (adjusted odds ratio=0.42; 95% confidence interval [CI], 0.23-0.79)." }, { "input": "The benefits of decreased incidence of HPV and HIV infections go beyond the index patient and have public health implications on the transmission of these diseases.", "output": "A meta-analysis of 15 observational studies in Africa, with adjustment for potential confounding factors, found that circumcision decreased the risk of acquiring HIV by more than half (relative risk [RR]=0.42; 95% CI, 0.34-0.54)." }, { "input": "The benefits of decreased incidence of HPV and HIV infections go beyond the index patient and have public health implications on the transmission of these diseases.", "output": "A recent prospective study from India showed a strong protective effect of circumcision against HIV infection (RR=0.15; 95% CI, 0.04-0.62). This study found no protective effect of circumcision against herpes, syphilis, or gonorrhea, suggesting a biological rather than a behavioral explanation for the protective effect of circumcision against HIV." }, { "input": "The benefits of decreased incidence of HPV and HIV infections go beyond the index patient and have public health implications on the transmission of these diseases.", "output": "Circumcision may also be protective against genital dermatoses; a case-control study found an age-adjusted odds ratio of 3.2 (95% CI, 2.3-4.6) for penile skin diseases in uncircumcised men compared with circumcised men." }, { "input": "A decrease in HPV incidence and transmission may lead to a lower incidence of cervical cancer.", "output": "In a meta-analysis of 7 case-control studies, penile HPV was detected 2.7 times more often in uncircumcised men after controlling for confounders. In this same meta-analysis, monogamous female partners of high-risk circumcised men (men with more than 6 lifetime partners) had a lower risk of cervical cancer than women whose high-risk partner was uncircumcised (adjusted odds ratio=0.42; 95% confidence interval [CI], 0.23-0.79)." }, { "input": "While there appears to be some evidence for reduced morbidity with routine circumcision, decisions regarding routine neonatal circumcision requires balancing risks and benefits of the procedure with the alternatives in the context of social, familial, and religious beliefs.", "output": "A conservative estimate of the post-neonatal childhood circumcision rate for purely medical reasons is 2% to 5%; estimates go as high as 7% to 10%." }, { "input": "Patients exhibiting stroke symptoms should have brain imaging immediately within 3 hours of symptom onset.", "output": "The British National Health Service Health Technology Assessment (HTA) Programme published a systematic review on optimal brain imaging strategies for the diagnosis of stroke in July 2004. The HTA searched Medline and EMBASE from 1980 to 1999 and found 1903 studies relevant to diagnostic imaging for stroke. Only 25 studies reported the type of stroke diagnosed and the imaging reference standard. Thirteen of these 25 studies describe the time interval from symptom onset to imaging. The Programme advises \"scan all immediately\" for diagnosing new neurological deficits with the understanding that CT scans were most available and cost-effective." }, { "input": "In the first 3 hours after a suspected cerebrovascular accident CVA, noncontrast head computerized tomography CT is the gold standard for diagnosis of acute hemorrhagic stroke.", "output": "In 2003, the Stroke Council, appointed by the American Heart Association, stated: \"For most cases and at most institutions, CT remains the most important brain imaging test. A physician skilled in assessing CT studies should be available to interpret the scan.\" The Stroke Council further recommends that \"in patients seen within 6 hours of onset, CT currently may be preferred as the first imaging study because MRI detection of acute intracerebral hemorrhage has not been fully validated." }, { "input": "The sensitivity for hemorrhage declines steeply 8 to 10 days after the event. Eligibility guidelines for acute thrombolytic therapy are currently based on use of CT to rule out acute hemorrhagic stroke.", "output": "The HTA performed a prospective cohort study comparing CT with MRI obtained in random order on the day of presentation. They enrolled 228 patients presenting to a general hospital with stroke symptoms: (1) lasting longer than 1 day, but causing little or no decrease in function, or (2) lasting longer than 5 days. The mean time from onset of symptoms to scanning was 21.5 days. CT detected hemorrhagic stroke in 50%, and late hemorrhagic transformation in 20%, of those patients found to have hemorrhagic stroke on MRI, which was considered the criterion standard of chronic stroke diagnosis. The earliest hemorrhagic stroke missed by CT was 11 days old, and the latest hemorrhage correctly identified by CT was 14 days old." }, { "input": "Magnetic resonance imaging MRI may be equally accurate in diagnosing an acute hemorrhagic stroke if completed within 90 minutes of presentation for patients whose symptoms began fewer than 6 hours earlier.", "output": "A prospective cohort study comparing imaging modalities in the acute time frame has been published. The study enrolled 129 patients with stroke symptoms of less than 3 hours, as well as 71 patients with between 3 and 6 hours of symptoms. Patients underwent multimodal MRI (including gradient recalled echo and diffusion-weighted imaging) and noncontrast CT within 90 minutes of presentation. Two stroke specialists and 2 neuroradiologists, masked to clinical information, read the scans independently at a later date. Interrater reliability was good (= 0.75-0.94) for identifying acute hemorrhage. There was 96% concordance between the MRI and CT interpretations. The 4 hemorrhages \"missed\" by CT were hemorrhagic transformations of acute infarct, and the 4 hemorrhages \"missed\" by MRI were misclassified as chronic when they were acute. The clinical implications of this study are uncertain. Without recognition of 1 imaging modality as the reference standard, it is difficult to say whether a hemorrhage \"missed\" on CT was a false negative on CT or a false positive on MRI." }, { "input": "MRI is more sensitive than CT for ischemic stroke in the first 24 hours of symptoms.", "output": "The HTA found a wide range of sensitivities for CT and MRI for both hemorrhagic and ischemic strokes at different time periods and noted that the quality of most of these studies was poor. Most of the studies identified were performed in academic stroke centers and had small sample sizes. Interpretation was masked in only 58% of studies. Few data were available on interobserver reliability, and neuroradiologists usually interpreted images. Two studies, totaling 165 patients, compared CT and MRI scans performed on the same day. However, the most \"acute\" time period reported was within 48 hours from symptom onset; neither study reported the order in which scans were performed, and only 1 study masked the neuroradiologist to the interpretation of the other modality. Time since symptom onset for ischemic stroke: CT- >3 hours: 64-85%; >6 hours: 47 - 80%; <48 hours: 23-81%; MRI - >6 hours: 65%; <48 hours: 84-88%." }, { "input": "MRI is more sensitive than CT in the diagnosis of hemorrhagic or ischemic stroke greater than 1 week after symptom onset.", "output": "The HTA performed a prospective cohort study comparing CT with MRI obtained in random order on the day of presentation. They enrolled 228 patients presenting to a general hospital with stroke symptoms: (1) lasting longer than 1 day, but causing little or no decrease in function, or (2) lasting longer than 5 days. The mean time from onset of symptoms to scanning was 21.5 days. CT detected hemorrhagic stroke in 50%, and late hemorrhagic transformation in 20%, of those patients found to have hemorrhagic stroke on MRI, which was considered the criterion standard of chronic stroke diagnosis. The earliest hemorrhagic stroke missed by CT was 11 days old, and the latest hemorrhage correctly identified by CT was 14 days old." }, { "input": "The best treatment strategy for impaired glucose tolerance IGT and impaired fasting glucose IFG is lifestyle intervention with a structured weight loss program of diet and exercise. Patients with IGT and IFG should be counseled to lose 5% to 7% of their body weight and instructed on moderate intensity physical activity for ~150 minutes per week.", "output": "In the Finnish Diabetes Prevention Study, the lifestyle intervention group had a 12.5% absolute risk reduction compared with the control group (NNT=8). Successful lifestyle interventions included weight loss of 5% to 7%, decreased fat intake, increased fiber intake, and 150 minutes of exercise per week." }, { "input": "The best treatment strategy for impaired glucose tolerance IGT and impaired fasting glucose IFG is lifestyle intervention with a structured weight loss program of diet and exercise. Patients with IGT and IFG should be counseled to lose 5% to 7% of their body weight and instructed on moderate intensity physical activity for ~150 minutes per week.", "output": "In the US Diabetes Prevention Program (DPP), 3234 patients with IGT and a body-mass index (BMI) of at least 24 kg/m2 were randomly assigned to one of the following groups: placebo, metformin, or intensive lifestyle modification. After an average follow-up of 2.8 years, there was a 14% absolute risk reduction in the progression to diabetes in the lifestyle intervention group compared with placebo (number needed to treat [NNT]=7). Successful lifestyle interventions included weight loss of 5% to 7%, decreased fat intake, increased fiber intake, and 150 minutes of exercise per week." }, { "input": "Metformin Glucophage, acarbose Precose, and troglitazone Rezulin are also effective, but lifestyle interventions appear superior. The American Diabetes Association defines IFG as a fasting glucose of between 100 and 125 mg/dL, and IGT as glucose between 140 and 199 mg/dL after a 2-hour oral glucose challenge.", "output": "In the placebo-controlled DPP trial, metformin use was associated with a reduction in progression to diabetes mellitus (NNT=14)." }, { "input": "Metformin Glucophage, acarbose Precose, and troglitazone Rezulin are also effective, but lifestyle interventions appear superior. The American Diabetes Association defines IFG as a fasting glucose of between 100 and 125 mg/dL, and IGT as glucose between 140 and 199 mg/dL after a 2-hour oral glucose challenge.", "output": "In the STOP-NIDDM trial of 1429 persons over 3.3 years of follow-up, acarbose 100 mg 3 times daily resulted in a 9% reduction of progression to diabetes, compared with placebo (NNT=11)" }, { "input": "Metformin Glucophage, acarbose Precose, and troglitazone Rezulin are also effective, but lifestyle interventions appear superior. The American Diabetes Association defines IFG as a fasting glucose of between 100 and 125 mg/dL, and IGT as glucose between 140 and 199 mg/dL after a 2-hour oral glucose challenge.", "output": "In the TRIPOD study, troglitazone use was associated with a 17% absolute risk reduction in the incidence of diabetes in high-risk Hispanic women (NNT=6 over an average of 30 months). The preventive effect of the drug was maintained more than 8 months after troglitazone therapy was discontinued (due to withdrawal from the US market). Current trials with other thiazolidinediones are underway." }, { "input": "Chloroquine and mefloquine have superior safety profiles in pregnancy, though all antimalarials are effective for prophylaxis. Antimalarials will decrease the severity of maternal malaria infection and malaria-associated anemia, while decreasing the incidence of low birth weight and perinatal death in women having their first or second baby.", "output": "WHO recommends chloroquine as first-line prophylaxis in pregnancy plus proguanil if the region exhibits emerging chloroquine resistance. In areas with proven chloroquine resistance, mefloquine is the drug of choice. Other antimalarials-such as quinine, pyrimethamine, sulfadoxine, and artesunate-should not be withheld if the preferred drugs are not available, or if the infection is life-threatening." }, { "input": "Chloroquine and mefloquine have superior safety profiles in pregnancy, though all antimalarials are effective for prophylaxis. Antimalarials will decrease the severity of maternal malaria infection and malaria-associated anemia, while decreasing the incidence of low birth weight and perinatal death in women having their first or second baby.", "output": "Antimalarials were found to decrease the incidence of maternal infections relative risk [RR]=0.27; 95% confidence interval [CI], 0.17-0.44 and reduce maternal anemia RR=0.62; 95% CI, 0.50-0.78 in low-parity women-ie, during a first or second pregnancy." }, { "input": "You can determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/destinationlist.aspx. Urge women to delay travel until after pregnancy if possible.", "output": "The Centers for Disease Control and Prevention CDC also recommends avoiding travel to malaria-endemic regions during pregnancy, but if travel is necessary, the CDC advises use of chloroquine or mefloquine in regions with chloroquine resistance. The CDC discourages the use of atovaquone/proguanil, doxycycline, and primaquine, due to known adverse fetal effects or inadequate experience in pregnancy." }, { "input": "It's not clear. Neither routine chest x-ray (with or without sputum cytology) nor low-dose computed tomography (CT) have been proven to reduce mortality when used for lung cancer screening, although low-dose CT screening does identify lung cancer at an early stage in high-risk patients.", "output": "A cohort study using annual CT scanning to screen 3246 patients for lung cancer came to a different conclusion. The authors compared the observed number of lung cancer cases, resections, advanced lung cancer diagnoses, and deaths in screened patients with the expected rates based on validated prediction models. Lung cancer was diagnosed in 144 patients compared with 44 expected cases (RR=3.2; 95% CI, 2.7-3.8). Subsequently, 109 patients underwent lung resection compared with 11 expected (RR=10.0; 95% CI, 8.2-11.9). However, there was no decline in advanced cancers (42 actual vs 33 expected; P=.14) and no difference in deaths due to lung cancer (38 actual vs 38.8 expected; P=.9). The 81 patients diagnosed in this study with stage I disease who underwent surgical resection had 4-year estimated survival rates of 94% (95% CI, 85%-97%), matching the prior low-dose CT study." }, { "input": "It's not clear. Neither routine chest x-ray (with or without sputum cytology) nor low-dose computed tomography (CT) have been proven to reduce mortality when used for lung cancer screening, although low-dose CT screening does identify lung cancer at an early stage in high-risk patients.", "output": "A 2006 study followed a cohort of at-risk patients using low-dose CT screening. There were 31,567 patients evaluated initially, of which 27,456 had an annual repeat screening. Most patients were current or former smokers (83%); patients with exposure to occupational and secondhand smoke were also included. A positive initial screen was defined as a solid or partly solid noncalcified nodule \u22655 mm in diameter; a nonsolid, noncalcified nodule \u22658 mm in diameter; or a solid endobronchial nodule. A positive screen during follow-up was defined as any new noncalcified nodule, regardless of size. Positive tests occurred in 13% of baseline screens and 5% of annual screens. Biopsies were performed according to a study protocol based on a nodule's size and behavior over time. Out of a total of 5646 positive screens, there were 535 biopsies, and a diagnosis of cancer in 492 patients. Of those with cancer, 412 (84%) had clinical stage I lung cancer; the authors estimated their 10-year survival rate was 88% (95% CI, 84%-91%). If patients with stage I disease underwent surgical resection within 1 month of diagnosis, their estimated 10-year survival increased to 92% (95% CI, 88%-95%)." }, { "input": "It's not clear. Neither routine chest x-ray (with or without sputum cytology) nor low-dose computed tomography (CT) have been proven to reduce mortality when used for lung cancer screening, although low-dose CT screening does identify lung cancer at an early stage in high-risk patients.", "output": "A Cochrane review identified 6 randomized controlled trials (RCTs) and 1 non-RCT (with a total of 245,610 patients) that screened patients with serial chest x-rays, with or without sputum cytology. Most patients were current or ex-smokers or had significant exposure to industrial smoke. No studies included an unscreened control group, and only 1 included women. Positive tests occurred in 13% of baseline screens and 5% of annual screens. Biopsies were performed according to a study protocol based on a nodule's size and behavior over time. Out of a total of 5646 positive screens, there were 535 biopsies, and a diagnosis of cancer in 492 patients. Of those with cancer, 412 (84%) had clinical stage I lung cancer; the authors estimated their 10-year survival rate was 88% (95% CI, 84%-91%). If patients with stage I disease underwent surgical resection within 1 month of diagnosis, their estimated 10-year survival increased to 92% (95% CI, 88%-95%)." }, { "input": "Herbal formulations, certain probiotics, elimination diets based on immunoglobulin G IgG antibodies, cognitive behavioral therapy, and self-help books have been shown to decrease global symptoms of irritable bowel syndrome IBS and improve overall quality of life.", "output": "One RCT compared the probiotic formula Bifidobacterium infantis 35624 with Lactobacillus and placebo, and found that IBS symptom scores and quality of life measures were better with the Bifidobacterium preparation (P<.05)." }, { "input": "Herbal formulations, certain probiotics, elimination diets based on immunoglobulin G IgG antibodies, cognitive behavioral therapy, and self-help books have been shown to decrease global symptoms of irritable bowel syndrome IBS and improve overall quality of life.", "output": "A multicenter RCT compared 2 herbal formulations with placebo. The first contained extracts of bitter candy-tuft, chamomile, peppermint, caraway, and licorice. The second, a commercial preparation called Iberogast, had the same ingredients as the first, as well as lemon balm, celandine, angelica, and milk thistle. The study demonstrated global IBS symptom reduction, with a relative risk [RR] of 1.68 (99% confidence interval [CI], 1.00-2.8) for Iberogast, and RR=1.90 (99% CI, 1.15-3.14) for the first formulation. Both formulations were well tolerated and more effective than placebo in the treatment of IBS, regardless of the dominant symptom." }, { "input": "Herbal formulations, certain probiotics, elimination diets based on immunoglobulin G IgG antibodies, cognitive behavioral therapy, and self-help books have been shown to decrease global symptoms of irritable bowel syndrome IBS and improve overall quality of life.", "output": "A Cochrane review of herbal therapies evaluated 75 randomized controlled trials (RCTs), including 7957 patients; it concluded that some herbal preparations may reduce symptoms of IBS. However, more rigorous studies are needed: There was never more than 1 trial comparing a given herbal medicine with a specific control, making it difficult to combine trials in a meaningful way." }, { "input": "For patients with severe refractory IBS, hypnosis has been shown to relieve symptoms.", "output": "A single-blinded study comparing cognitive behavioral therapy (CBT) with patient education alone found CBT more effective. The effect size was 0.50 (defined as moderate; 95% CI, 0.2-0.8). Analysis of response rates found that 73% responded to CBT vs 41.3% in the education group (NNT=3.2)." }, { "input": "For patients with severe refractory IBS, hypnosis has been shown to relieve symptoms.", "output": "A RCT tested the use of an educational self-help guidebook. Outcomes were symptom score, perception of improvement, and primary care consultation rates. At 1 year, the self-help guidebook group had 1.56 visits/year less than the control group (95% CI, 1.15-1.98), a 60% decrease. The self-help guidebook group reported a higher degree of perceived improvement, with a mean effect of 0.51 (95% CI, 0.23-0.79); there were no differences in severity scores." }, { "input": "For patients with severe refractory IBS, hypnosis has been shown to relieve symptoms.", "output": "A systematic review found 6 studies with a control and 8 without, for a total of 644 patients. An average of 80% of the patients reported global IBS symptom relief. Patients with typical IBS responded to hypnosis; however, males with diarrhea-predominant symptoms, and all subjects with atypical symptoms or comorbid psychopathology were less likely to respond." }, { "input": "Soluble fiber is more effective than insoluble fiber at improving global IBS symptom ratings.", "output": "A systematic review of 17 RCTs (9 of soluble fiber, 8 of insoluble) (N=1363) found soluble fiber more effective than placebo (pooled RR=1.55; 95% CI, 1.35-1.78) for reduction in global symptoms and constipation. Insoluble fiber was no better than placebo (pooled RR=0.89; 95% CI, 0.72-1.11). Abdominal pain was not reduced with either fiber." }, { "input": "Soluble fiber is more effective than insoluble fiber at improving global IBS symptom ratings.", "output": "An elimination diet, based on the presence of IgG antibodies to various foods, was compared with a sham diet in an RCT. Those who fully adhered to the diet reported symptom reduction, with a mean symptom score 98 points lower (95% CI, 52-144; NNT=2.5). (A 50-point drop was considered clinically significant.)" }, { "input": "Clinical evaluation and chest x-ray are recommended for asymptomatic patients with a positive purified protein derivative PPD test result, to exclude the slight possibility of active tuberculosis TB. Patients with radiographic evidence of old healed TB infection should also undergo sputum testing.", "output": "Clinical evaluation with medical history and physical exam, chest radiography, and selected sputum sampling to exclude active tuberculosis are part of the recommended algorithm for all patients who develop a positive PPD. These recommendations are derived from expert opinion, and their usefulness has not been evaluated in any population-based study of asymptomatic PPD-positive patients." }, { "input": "Treatment with isoniazid INH monotherapy 300 mg/d reduces progression of latent tuberculosis to active disease.", "output": "A comprehensive review of RCTs from the 1950s and 1960s demonstrated that INH treatment of patients with latent tuberculosis infection is effective in decreasing the progression to active tuberculosis. A series of double-blinded RCTs performed by the US Public Health Service included 25,923 patients with latent tuberculosis who were randomized to receive either daily INH or placebo for 1 year with 6- to 10-year follow-up. Groups studied included household contacts of patients with active tuberculosis rate of progression to active disease in placebo group [baseline rate]=27/1000, relative risk with INH [RR]=0.4, number needed to treat [NNT]=63, patients in mental institutions baseline rate=12/1000, RR=0.3, NNT=121, and patients with x-ray findings of healed tuberculosis baseline rate=69/1000, RR=0.4, NNT=23." }, { "input": "For treatment with isoniazid INH monotherapy for latent tuberculosis, 9 months is the optimal treatment length.", "output": "The optimal length of treatment for PPD-positive patients without active disease was evaluated through 1 double-blinded RCT enrolling 28,000 patients with 5-year follow-up after 12, 24, or 52 weeks of INH or placebo. Active TB developed in 0.35% 24/6919 after 52 weeks of INH compared with 0.49% 34/6965 after 24 weeks RR=1.4, NNT=708. Incidence in the placebo group was 1.4%. Subgroup analysis determined that maximum efficacy with fewest side effects was achieved at 9 months." }, { "input": "A 3-month course of combined rifampin 600 mg/d and INH 300 mg/d is equivalent in efficacy to INH monotherapy and is associated with similar rates of toxicity, but this regimen is not included in Centers for Disease Control and Prevention recommendations.", "output": "INH monotherapy was compared with combination INH and rifampin in a 2005 meta-analysis of 5 RCTs of variable quality involving 1926 patients. This meta-analysis found equivalency in risk of active TB and mortality between INH monotherapy for 6 to 12 months and the combination of rifampin and INH for 3 months pooled risk difference=0%; 95% confidence interval [CI], -1% to 2%. This study also showed similar rates of adverse events in both groups pooled risk difference=-1%; 95% CI, -7% to 5%. Short-course combination rifampin and pyrazinamide is no longer recommended after an open-label RCT with 589 patients demonstrated severe hepatoxicity in 7.7% 16/207 on a 2-month course of pyrazinamide and rifampin, compared with 1% 2/204 on 6 months of INH RR=7.9, number needed to harm=15." }, { "input": "Scant evidence exists for the best duration of steroid therapy for contact dermatitis due to plants rhus. Review articles recommend 10 to 21 days of treatment with topical or oral corticosteroids for moderate to severe contact dermatitis due to plants. The primary reason given for the duration of 2 to 3 weeks is to prevent rebound dermatitis.", "output": "A review recommends using prednisone for children with allergic contact dermatitis involving more than 10% of the total body surface area." }, { "input": "Scant evidence exists for the best duration of steroid therapy for contact dermatitis due to plants rhus. Review articles recommend 10 to 21 days of treatment with topical or oral corticosteroids for moderate to severe contact dermatitis due to plants. The primary reason given for the duration of 2 to 3 weeks is to prevent rebound dermatitis.", "output": "A review recommends using systemic steroids for severe cases, defined as involvement of greater than 20% of total body surface area, bullae formation, or extensive facial involvement. That review recommends a starting dose of 1 mg/kg/d, or 40 to 60 mg/d in adults, followed by a 2- to 3-week taper of oral prednisone." }, { "input": "Scant evidence exists for the best duration of steroid therapy for contact dermatitis due to plants rhus. Review articles recommend 10 to 21 days of treatment with topical or oral corticosteroids for moderate to severe contact dermatitis due to plants. The primary reason given for the duration of 2 to 3 weeks is to prevent rebound dermatitis.", "output": "One review recommends a tapering dose of oral prednisone to prevent rebound recurrence if the rash affects >25% of the body surface area, has severe blistering or itching, or significantly involves the face, hands, or genital area. That review suggests starting with oral prednisone 60 mg/d for 4 days, followed by a 10-day taper (50 mg/d for 2 days, 40 mg/d for 2 days, 30 mg/d for 2 days, 20 mg/d for 2 days, then 10 mg/d for 2 days)." }, { "input": "Scant evidence exists for the best duration of steroid therapy for contact dermatitis due to plants rhus. Review articles recommend 10 to 21 days of treatment with topical or oral corticosteroids for moderate to severe contact dermatitis due to plants. The primary reason given for the duration of 2 to 3 weeks is to prevent rebound dermatitis.", "output": "One case report noted failure of a tapering dose over 5 days of oral methylprednisolone for treatment of poison ivy contact dermatitis." }, { "input": "Screening patients with chronic hepatitis B infection HBsAg+ for hepatocellular carcinoma by alpha-fetoprotein AFP or by AFP plus ultrasound AFP/US detects hepatocellular carcinoma tumors at earlier stages and increases resection rates.", "output": "Many serum markers and screening methods have been proposed to detect hepatocellular carcinoma at a treatable stage, but only 2-AFP and US-are in clinical use." }, { "input": "It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality.", "output": "A trial was performed in Shanghai, China and included 18,816 HBsAg+ patients aged 35 to 55 years. Subjects were recruited from their place of employment and randomized to either AFP/US every 6 months (n=9373) or to no screening (n=9443). Fifty-one hepatocellular carcinomas were diagnosed in the control group and 86 in screened group. Screened subjects had a significantly higher percentage of tumors that were less than 5 cm at the time of diagnosis and a higher number of patients who underwent resection. While the 5-year survival for those with hepatocellular carcinoma in the screened group was higher, the disease-specific mortality rate was not statistically different between the 2 groups." }, { "input": "It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality.", "output": "Additional data became available in 2002. The original study authors of the Shanghai trial claimed the new data showed a statistically significant disease-specific mortality rate ratio of 0.63, favoring the screened group." }, { "input": "It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality.", "output": "The Cochrane group performed their own analysis on the same data and determined that no statistically significant difference in the disease-specific mortality rates existed between the 2 groups.." }, { "input": "It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality.", "output": "Another randomized control trial took place in Toronto, and included 1069 patients, 71% of whom were of Asian ancestry. Subjects had AFP testing every 6 months, and half were randomly assigned to have US performed every 6 months. Eight of the 11 incident tumors would have been diagnosed based on AFP levels alone, and 3 would have been missed with US alone. The authors conclude that for AFP, sensitivity=64.3% and specificity=91.4%; for US, sensitivity=78.8% and specificity=93.8%. However, their study was too small to determine if AFP/US is superior to AFP for hepatocellular carcinoma screening in a HBsAg+ population. They estimate that detecting such a difference would take a sample size of 10,000 or more." }, { "input": "There is no evidence of increased risk for major bleeding as a result of falls in hospitalized patients taking warfarin.", "output": "A study of 400 consecutive falls among 264 post-stroke patients in a rehab hospital found no difference in minor injury rates (19% vs 18%, NS); no major hemorrhagic complications were seen following 131 falls in the anticoagulation group (93 patients) and 269 falls in the group not on anticoagulation (175 patients). Patients on anticoagulation had an average protime of 16.1 seconds (INR was not reported). The calculated risk of major hemorrhage in an anticoagulated patient from a single fall was 2.3% or less. The study was limited because most falls were from a seated position or partially controlled by an attendant; few patients fell from a standing position." }, { "input": "There is no evidence of increased risk for major bleeding as a result of falls in hospitalized patients taking warfarin.", "output": "One retrospective study of 2633 falls in 1861 hospital inpatients compared the rate of major hemorrhage between those taking anticoagulation therapy with those not taking it. Major hemorrhage was defined as bruising or cuts requiring immediate attention from a physician. The rate of major hemorrhage was 6.2% for patients taking warfarin and 11.3% for patients receiving no therapy. Patients with INR=2-3 had a major hemorrhage rate of 6.9% compared with 10.1% for those with INR <1.3. Criteria for using warfarin were not reported; there may have been selection bias in favor of prescribing warfarin for patients judged less likely to fall." }, { "input": "In the average patient taking warfarin for atrial fibrillation, the risk of intracranial hemorrhage from a fall is much smaller than the benefit gained from reducing risk of stroke.", "output": "A study presented a Markov decision analysis (comparison of risk estimates in separate disease states) evaluating whether risk from falls should influence choice of anticoagulation therapy in elderly patients with atrial fibrillation. Risk of intracranial bleeding from falls was calculated from prospective cohort studies and retrospective case series from anticoagulation clinics, and stroke reduction benefit from anticoagulation was taken from a meta-analysis of 5 randomized controlled trials. Sensitivity analyses were performed to test the results of the decision analysis. The calculated risk of subdural hematoma from falling was such that a patient with a 5% annual stroke risk from atrial fibrillation would need to fall 295 times in a year for the fall risk to outweigh the stroke reduction benefit of warfarin." }, { "input": "Of the different strategies available for managing cervical intraepithelial neoplasia grade 1 CIN1, testing for high-risk subtypes of the human papillomavirus hr-HPV DNA at 12 months has the highest sensitivity for predicting the development of CIN2 or CIN3 and leads to the lowest rate of referral to repeat colposcopy. If the hr-HPV DNA test result is negative at 12 months, then the patient may return to routine cytology screening. If the hr-HPV DNA test result is positive, the patient should undergo repeat colposcopy.", "output": "A study attempted to determine the appropriate follow-up for women diagnosed with CIN1 on adequate colposcopic biopsy. This 2-year prospective study examined a subpopulation of 1539 women from the ASCUS/LSIL (atypical squamous cells of uncertain significance)/low-grade squamous intraepithelial lesion) Triage Study (ALTS) to determine the ideal follow-up strategy for women diagnosed with CIN1 or HPV effect on colposcopic biopsy-obtained histology. This study randomly assigned these women with CIN1 or HPV effect to either HPV testing or colposcopic examination at 6, 12, and 18 months. Every woman under-went an exit colposcopy at 24 months. The study found that hr-HPV testing 12 months after the initial colposcopic exam had the highest sensitivity for detecting advanced disease (92.2%) and lowest referral rate to repeat colposcopy (55%). Follow-up of these patients with repeat cytology alone at 6 and 12 months had a lower sensitivity for detection of advanced disease (85%) and greater referral rate to repeat colposcopy (60%) when compared with HPV testing at 12 months alone. Three cytologic evaluations at 6, 12, and 18 months without HPV testing increased sensitivity (95%), although this increase was not statistically significant. A much higher percentage of patients were referred to colposcopy with this strategy. Combining both hr-HPV testing and cytology at 12 months did not significantly increase the identification of advanced disease and resulted in a higher re-referral rate to colposcopy." }, { "input": "Compared with planned repeat low-transverse cesarean section, vaginal birth after cesarean section VBAC is not associated with increased risk of maternal or neonatal mortality.", "output": "An additional risk of uterine rupture by 2.7 per 1000 cases 95% confidence interval [CI], 0.73-4.73 rate is often quoted in VBAC reviews and was cited in the Agency for Healthcare Research and Quality evidence report; it is based on 1 prospective, nonrandomized cohort trial and 1 retrospective cohort study." }, { "input": "Compared with planned repeat low-transverse cesarean section, vaginal birth after cesarean section VBAC is not associated with increased risk of maternal or neonatal mortality.", "output": "In an attempt to quantify the risks of VBAC, a systematic review determined that attempted VBAC, compared with repeat low-transverse cesarean section, increased the risk of uterine rupture by 2.7 per 1000 cases 95% confidence interval [CI], 0.73-4.73." }, { "input": "Compared with planned repeat low-transverse cesarean section, vaginal birth after cesarean section VBAC is not associated with increased risk of maternal or neonatal mortality.", "output": "The most recent Cochrane Review found that both VBAC and repeat lowtransverse cesarean section have benefits and risks associated with them; however, after reviewing the limited data, they concluded that no trial exists to adequately help women and their caregivers make an informed decision between the two. A strong theme in the Cochrane Review, echoed in most reviews, was the absence of high-quality prospective randomized data." }, { "input": "Morbidity is slightly increased, as evidenced by higher uterine rupture rates and some neonatal outcome measures.", "output": "The effect of VBAC on neonatal morbidity and mortality is unclear. A large, multicenter, prospective, nonrandomized trial involving 33,699 patients found no significant difference between VBAC and planned cesarean for hysterectomy (0.2% vs 0.3%; odds ratio [OR]=0.77; 95% CI, 0.51-1.17), maternal death (0.02% vs 0.04%; OR=0.38; 95% CI, 0.1-1.46), and neonatal death (0.08% vs 0.05%; OR=1.82; 95% CI, 0.73-4.57). Significant associations were found for uterine rupture rates in spontaneous labor (24/6685 [0.4%] vs no cases; number needed to harm [NNH]=279) and neonatal hypoxic-ischemic encephalopathy (0.46 cases per 1000 vs no cases; NNH=2174)." }, { "input": "Morbidity is slightly increased, as evidenced by higher uterine rupture rates and some neonatal outcome measures.", "output": "The effect of VBAC on neonatal morbidity and mortality is unclear. A retrospective Canadian cohort trial of 308,755 women also demonstrated an association of VBAC with uterine rupture(0.65% of trial-of-labor cases; OR=2.38; 95% CI, 2.12-2.67), and a trend towards higher maternal mortality in the cesarean group (1.6 per 100,000 for VBAC vs 5.6 per 100,000 for planned cesarean; OR=0.32; 95% CI, 0.07-1.47)." }, { "input": "Morbidity is slightly increased, as evidenced by higher uterine rupture rates and some neonatal outcome measures.", "output": "The effect of VBAC on neonatal morbidity and mortality is unclear. A small retrospective cohort of 24,529 births found a higher association of perinatal death for trial of labor (adjusted OR=11.7; 95% CI, 1.4-101.6). The perinatal death rate was similar to rates in nulliparous women." }, { "input": "Morbidity is slightly increased, as evidenced by higher uterine rupture rates and some neonatal outcome measures.", "output": "The effect of VBAC on neonatal morbidity and mortality is unclear. One retrospective cohort trial showed VBAC was associated with an increase in neonatal sepsis (1% vs 0%; CI not given) compared with planned cesarean, but VBAC resulted in less transient tachypnea (5% vs 7%) and hyper-bilirubinemia (2% vs 6%)." }, { "input": "Interventions that include a combination of behavioral and lifestyle modifications-including decreased caloric intake, specific aids to changing diet, increased physical activity, and treatment of binge eating disorders-have modest benefit with appropriate use.", "output": "Initial weight loss-ie, weight loss in the first few months of the behavioral intervention-was a good predictor of long-term adherence to behavioral interventions." }, { "input": "Interventions that include a combination of behavioral and lifestyle modifications-including decreased caloric intake, specific aids to changing diet, increased physical activity, and treatment of binge eating disorders-have modest benefit with appropriate use.", "output": "One RCT addressed both behavioral therapy and the importance of face-to-face interaction. The study randomized 122 subjects to either Internet video sessions biweekly with a therapist which included behavioral therapy, access to an associated chat room and e-mail correspondence, or to biweekly face-to-face sessions with a therapist. The active intervention spanned 24 weeks, but the therapist met with the face-to-face group and interacted in the chat room and with e-mail for another 6 months. At 18 months, the mean weight loss in the Internet group was 5.7 kg compared with 10.4 kg in the face-to-face group." }, { "input": "Interventions that include a combination of behavioral and lifestyle modifications-including decreased caloric intake, specific aids to changing diet, increased physical activity, and treatment of binge eating disorders-have modest benefit with appropriate use.", "output": "Two RCTs, showed significant benefit from behavioral interventions combined with social support and relapse prevention training." }, { "input": "Interventions that include a combination of behavioral and lifestyle modifications-including decreased caloric intake, specific aids to changing diet, increased physical activity, and treatment of binge eating disorders-have modest benefit with appropriate use.", "output": "One RCT in the review evaluated different types of maintenance programs to promote ongoing weight loss among 125 people randomized to 1 of 5 maintenance programs after an initial 20-week behavioral weight loss program: 1 control-no further contact with the behavioral therapists; 2 behavioral-ongoing problem-solving behavioral therapy sessions; 3 social-peer support and participant presentations, with some financial incentives; 4 exercise-therapy sessions, as in group 2, plus an aerobic exercise program; and 5 combined-using therapy sessions, social support and an exercise program. Mean weight loss at 1.8 months for the 4 intervention programs was significantly greater than for the control group 2, 11.4 kg; group 3, 8.4 kg; group 4, 9.1 kg; group 5, 13.5 kg vs 3.6 kg." }, { "input": "Interventions that include a combination of behavioral and lifestyle modifications-including decreased caloric intake, specific aids to changing diet, increased physical activity, and treatment of binge eating disorders-have modest benefit with appropriate use.", "output": "One RCT involved 163 patients and compared behavioral therapy alone with behavioral therapy plus specific aids to changing diet: use of grocery lists, meal plans, and specific instructions to reduce total fat intake. The average weight loss after 1 year in the behavioral therapy with specific aids group, was statistically significantly greater than the weight loss in the behavioral therapy alone group 6.9 kg vs 3.3 kg." }, { "input": "Interventions that include a combination of behavioral and lifestyle modifications-including decreased caloric intake, specific aids to changing diet, increased physical activity, and treatment of binge eating disorders-have modest benefit with appropriate use.", "output": "A 1997 systematic review of 99 weight loss studies, including randomized and nonrandomized controlled trials of at least 1 year's duration, found 21 behavioral intervention trials that included dietary, exercise, and behavioral approaches. The reviewers concluded that long-term behavioral techniques, dietary changes with very specific instructions to assist adherence, exercise, relapse prevention training, and social/community support were optimal for promoting weight loss." }, { "input": "Interventions that include a combination of behavioral and lifestyle modifications-including decreased caloric intake, specific aids to changing diet, increased physical activity, and treatment of binge eating disorders-have modest benefit with appropriate use.", "output": "Obesity rates in the US have risen significantly in recent years: 30% of US adults 60 million people and 16% of children 6 to 19 years old more than 9 million, are obese, and trends suggest rates will continue to increase. Eating behaviors are learned and reinforced within families, peer groups, and other important social groups. Behavioral techniques to treat obesity attempt to reduce reinforcement for unhealthy eating behaviors and teach and reinforce healthy eating behaviors. Cue avoidance is a common behavioral intervention: the patient avoids situations in which he has overeaten in the past, such as \"all-you-can-eat\" buffets. Role play to practice restraint from overeating, or to resist social pressure to eat at an open buffet, uses cognitive therapy as a behavioral technique. Involving family members in an obesity treatment plan and using group therapy such as Overeaters Anonymous are other standard behavioral techniques." }, { "input": "Hypnosis can be used as an adjunct to behavioral therapy for weight loss.", "output": "Hypnosis has been used as an adjunct to behavioral therapy for weight loss in multiple small studies. Two meta-analyses, concluded that behavioral therapy alone yielded an average weight loss of 6.05 kg; with the addition of hypnosis, the average weight loss rose to 14.88 kg." }, { "input": "The electrocardiogram ECG is a fairly accurate test in the diagnosis of myocardial infarction MI. However, given more sensitive technologies, such as cardiac biomarker testing, its primary role should be as an important adjunct in the evaluation and detection of MI.", "output": "As part of the Myocardial Infarction Triage and Intervention Project, the investigators found that when compared with a single ECG, serial exams increased the diagnostic sensitivity for acute coronary syndrome from ~34% to 46% with a reduction in specificity from 96% to 93% and positive predictive value from 88% to 84%. This particular study was unusual in that it used the hospital discharge diagnosis to define the outcome. In most other studies, cardiac enzymes were used as the gold standard for defining outcome." }, { "input": "The electrocardiogram ECG is a fairly accurate test in the diagnosis of myocardial infarction MI. However, given more sensitive technologies, such as cardiac biomarker testing, its primary role should be as an important adjunct in the evaluation and detection of MI.", "output": "A systematic review performed by a NHAAP working group evaluating different technologies in the emergency department diagnosis of ACI found only 1 study on the accuracy of serial ECGs in acute MI (sensitivity 39%, specificity 88%)." }, { "input": "The electrocardiogram ECG is a fairly accurate test in the diagnosis of myocardial infarction MI. However, given more sensitive technologies, such as cardiac biomarker testing, its primary role should be as an important adjunct in the evaluation and detection of MI.", "output": "In 2001, a working group of the National Heart Attack Alert Program (NHAAP) performed a systematic review to define the accuracy of \"out of hospital\" ECG in the diagnosis of acute cardiac ischemia (ACI) and MI. Based on the 8 studies for which data were available, the random effects pooled sensitivity for acute MI was 68% (95% CI, 59%-76%), the specificity was 97% (95% CI, 89%-92%), and the diagnostic odds ratio (DOR) was 104 (95% CI, 48-224)." }, { "input": "The electrocardiogram ECG is a fairly accurate test in the diagnosis of myocardial infarction MI. However, given more sensitive technologies, such as cardiac biomarker testing, its primary role should be as an important adjunct in the evaluation and detection of MI.", "output": "A systematic review of the workup of acute chest pain found that the ECG was the most useful bedside test for MI. In this review, ST segment elevation and Q waves were found to be equally reliable predictors of MI (positive likelihood ratio [LR+]=22). A normal ECG was also found to be the most important bedside finding for ruling out the diagnosis of MI (LR-=0.2)." }, { "input": "The sensitivity of ECG for detection of MI is directly related to what is defined as positive findings on the ECG for MI. The single most specific ECG finding is the presence of new ST segment elevation of at least 1mm. Other findings such as the development of new pathologic Q waves and ST depression can also be valuable in making the diagnosis.", "output": "New ST segment elevation is the most important ECG feature in increasing the probability of diagnosing an MI, with LRs ranging from 5.7 to 53.9." }, { "input": "The sensitivity of ECG for detection of MI is directly related to what is defined as positive findings on the ECG for MI. The single most specific ECG finding is the presence of new ST segment elevation of at least 1mm. Other findings such as the development of new pathologic Q waves and ST depression can also be valuable in making the diagnosis.", "output": "A systematic review revealed similar findings where ST segment elevation (most commonly defined as at least 1 mm in 2 or more contiguous limb leads or at least 2 mm in 2 contiguous precordial leads) had a LR+=13.1 (95% confidence interval [CI], 8.28-20.6). This review also found that a \"completely normal\" ECG is reasonably useful in ruling out MI with a LR-=0.14 (95% CI, 0.11-0.20)." }, { "input": "The annual rate of decline in forced expiratory volume for 1 second (FEV1) has been researchers' gold standard as an objective measure for progression of chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS) do not consistently have a statistically significant impact on FEV1 decline, and thus on the progression of COPD. In those studies that did show improvements in FEV1 decline, the change does not appear to be clinically significant (7.7 to 9.0 mL/year). These findings do not take into account the potential impact of ICS on such patient oriented outcomes as exacerbation rates, quality of life, outpatient visits, hospitalization, and mortality.", "output": "Some systematic reviews and other randomized trials suggest that ICS have significant benefit on these patient outcomes." }, { "input": "The annual rate of decline in forced expiratory volume for 1 second (FEV1) has been researchers' gold standard as an objective measure for progression of chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS) do not consistently have a statistically significant impact on FEV1 decline, and thus on the progression of COPD. In those studies that did show improvements in FEV1 decline, the change does not appear to be clinically significant (7.7 to 9.0 mL/year). These findings do not take into account the potential impact of ICS on such patient oriented outcomes as exacerbation rates, quality of life, outpatient visits, hospitalization, and mortality.", "output": "In mild to moderate COPD, patients treated with triamcinolone had fewer respiratory symptoms (P=.005), fewer visits to a physician because of respiratory illness (P=.003), and improved airway reactivity (P=.02)." }, { "input": "The annual rate of decline in forced expiratory volume for 1 second (FEV1) has been researchers' gold standard as an objective measure for progression of chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS) do not consistently have a statistically significant impact on FEV1 decline, and thus on the progression of COPD. In those studies that did show improvements in FEV1 decline, the change does not appear to be clinically significant (7.7 to 9.0 mL/year). These findings do not take into account the potential impact of ICS on such patient oriented outcomes as exacerbation rates, quality of life, outpatient visits, hospitalization, and mortality.", "output": "Exacerbation rates significantly decreased by 25% (P=.026), and health status improved (P=.0043) among patients with moderate to severe COPD who were taking fluticasone compared with those taking placebo." }, { "input": "The annual rate of decline in forced expiratory volume for 1 second (FEV1) has been researchers' gold standard as an objective measure for progression of chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS) do not consistently have a statistically significant impact on FEV1 decline, and thus on the progression of COPD. In those studies that did show improvements in FEV1 decline, the change does not appear to be clinically significant (7.7 to 9.0 mL/year). These findings do not take into account the potential impact of ICS on such patient oriented outcomes as exacerbation rates, quality of life, outpatient visits, hospitalization, and mortality.", "output": "A trial evaluated post-bronchodilator FEV1 decline in 48 patients with early signs and symptoms of COPD for 2 years. Subjects were assigned to medium-dose fluticasone propionate or placebo. Early initiation of ICS treatment did not affect the progressive deterioration of lung function as no modifying effect on annual FEV1 decline was observed, however, the study only had power to detect a 60-mL annual drop in FEV1." }, { "input": "The annual rate of decline in forced expiratory volume for 1 second (FEV1) has been researchers' gold standard as an objective measure for progression of chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS) do not consistently have a statistically significant impact on FEV1 decline, and thus on the progression of COPD. In those studies that did show improvements in FEV1 decline, the change does not appear to be clinically significant (7.7 to 9.0 mL/year). These findings do not take into account the potential impact of ICS on such patient oriented outcomes as exacerbation rates, quality of life, outpatient visits, hospitalization, and mortality.", "output": "A meta-analysis of 6 randomized, placebo-controlled trials with a duration of at least 2 years (n=3571) found a nonsignificant trend in favor of ICS, with a difference in FEV1 decline of 5.31 mL/year (P=.08) between the ICS and placebo groups." }, { "input": "The annual rate of decline in forced expiratory volume for 1 second (FEV1) has been researchers' gold standard as an objective measure for progression of chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS) do not consistently have a statistically significant impact on FEV1 decline, and thus on the progression of COPD. In those studies that did show improvements in FEV1 decline, the change does not appear to be clinically significant (7.7 to 9.0 mL/year). These findings do not take into account the potential impact of ICS on such patient oriented outcomes as exacerbation rates, quality of life, outpatient visits, hospitalization, and mortality.", "output": "One meta-analysis evaluated 8 controlled clinical trials lasting at least 2 years (n=3715) and found that, when compared with placebo, ICS significantly reduced the rate of FEV1 decline by 7.7 mL/year (P=.02) and that high-dose ICS had a greater effect of 9.9 mL/year (P=.01)." }, { "input": "Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations.", "output": "The THOP trial was a single-blinded, randomized controlled trial of hypertensive treatment based on SMBP vs OBP. Four hundred patients were randomized to SMBP or OBP, with medication adjustments made by a blinded clinician. The trial design called for both treatment groups to be titrated to a diastolic blood pressure of 80 to 89 mm Hg. The follow-up was approximately 1 year. Graphical data indicate that both groups were equally effective in meeting the blood pressure goals outlined in the methods." }, { "input": "Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations.", "output": "The correlation between OBP and SMBP can be derived via three different mathematical models using data from multiple studies. The accepted cutoff for SMBP defined hypertension is 135/85 mm Hg." }, { "input": "Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations.", "output": "SMBP correlates better than OBP with surrogate measures of hypertensive control, such as left ventricular mass." }, { "input": "Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations.", "output": "SMBP correlates better than OBP with surrogate measures of hypertensive control, such as ambulatory blood pressure measurement." }, { "input": "Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations.", "output": "Office blood pressure measurements exhibit large variability (decreased precision) and are subject to multiple biases (decreased accuracy). Self-measured blood pressures at home became common when \"white-coat hypertension\" was recognized to be clinically significant. It allows for a larger number of measurements for individual patients, resulting in greater precision than OBP." }, { "input": "Self-measured blood pressures (SMBP) can be precise and accurate and, thus, reliably be used as an adjunct to office blood pressure measurements in selected clinical situations.", "output": "Two large prospective cohort studies of the relationship between SMBP and morbidity and mortality made comparative baseline blood pressure measurements and followed the cohorts without suggestions or attempts to change management. The first was a rural population-based study with 1789 subjects (90% of the population) from Ohasama, Japan. Mean follow-up was 6.6 years with less than 1% dropout rate. The second large cohort study (SHEAF trial) included patients 60 years old with the diagnosis of hypertension. A total of 4939 cases were analyzed. Mean follow-up was 3.2 years with less than 1% dropout rate. Both studies show that each mm Hg increase in SMBP was a better predictor of cardiovascular events than an equivalent increase in OBP." }, { "input": "Whether hypertensive treatment should be based primarily on SMBP is unclear, and currently undergoing study. Clinicians should recommend multiple daily measurements with a validated and standardized device, preferably equipped with memory or transmission capabilities, in order to avoid patient error in transcribing and reporting values. Wrist or finger devices cannot reliably be used.", "output": "In addition to diagnosing white-coat hypertension, World Health Organization/International Society of Hypertension Guidelines Committee has recommended that home blood pressure measurement is useful in the following circumstances: Unusual variability of blood pressure over the same or different visits. Office hypertension in subjects with low cardiovascular risk. Symptoms suggesting hypotensive episodes. Hypertension resistant to drug treatment." }, { "input": "Bacterial vaginosis BV is associated with preterm delivery.", "output": "In 2003, a Cochrane meta-analysis of 5 studies involving 622 women with previous preterm birth showed a decrease in the risk of low birth weight infants born to women receiving antibiotics vs placebo for the treatment of BV (odds ratio [OR]=0.31; 95% CI, 0.13-0.75). Treatment also decreased the risk of preterm-prelabor rupture of membranes (OR=0.14; 95% CI, 0.05-0.38) compared with placebo. Unfortunately, these studies did not always specify whether women were asymptomatic for BV infection. In many of the trials, symptomatic women were excluded as they were automatically treated with antibiotics." }, { "input": "Bacterial vaginosis BV is associated with preterm delivery.", "output": "A meta-analysis of 7 RCTs reviewed the evidence of screening for BV in pregnancy. In this meta-analysis, 5 of the trials specified that women were asymptomatic, and the other 2 did not comment on whether the women were symptomatic or not. In general, there was no benefit to routine screening and treatment of BV. However, a subgroup of high-risk women seems to benefit from screening and treatment. They defined high-risk women as those have had a preterm delivery, premature rupture of membranes, birth weight <2500 g, or spontaneous abortion. Treating BV in women with a high-risk pregnancy decreased preterm delivery (absolute risk reduction [ARR]=0.22; 90% confidence interval [CI], 0.13-0.31; number needed to treat [NNT]=4.5) regardless of antibiotic choice. However, 2 trials of high-risk women who were empirically treated for BV, but did not have BV, showed an increase in preterm delivery less than 34 weeks (number needed to harm [NNH]=11)." }, { "input": "Bacterial vaginosis BV is associated with preterm delivery.", "output": "Bacterial vaginosis in early pregnancy is a risk factor for preterm delivery. The role of BV in preterm labor is not well understood, but it has been consistently associated with preterm labor and delivery. The detection of BV in early pregnancy seems to be a stronger risk factor for preterm delivery than BV in later pregnancy." }, { "input": "Treating asymptomatic, low-risk women with BV does not always prevent preterm delivery.", "output": "A large study in 2000 that looked at the use of metronidazole in the treatment of asymptomatic women for BV did not demonstrate any reduction in preterm birth. In this study, 21,965 asymptomatic women between 8 and 22 weeks gestation were screened for BV with Gram stain using Nugent's criteria. Then, 1953 women with BV were randomized to receive either 1 g of metronidazole orally for 2 days or placebo. Between 24 and 29 weeks, all of the women were then rescreened for BV by Gram stain. Even if the results were negative, women received another course of the metronidazole or placebo. In this study, preterm delivery rates did not improve for either low- or high-risk women. Specifically, a subgroup analysis of 213 women with previous preterm delivery did not show any benefit to treatment with metronidazole." }, { "input": "There is some benefit to early screening by Gram stain using Nugent's criteria and treating BV-positive women with a history of preterm delivery, premature rupture of membranes, low birth weight infants, or spontaneous abortion. In this group, treatment has been associated with decreased rates of preterm labor, preterm prelabor rupture of membranes, and low birth weight infants.", "output": "A study evaluating screening for vaginal infections in pregnancy has demonstrated a reduction in preterm delivery. In this study, looking at a general obstetrical population in Austria, 4429 asymptomatic pregnant women between 15 and 19.6 weeks gestation had a vaginal screen for bacterial vaginosis, candidiasis and trichomoniasis. The 2048 women in the intervention group were given the results of the screen from their maternity care provider. The 2097 women in the control group and their providers did not receive the results of the vaginal screen. There were 447 women in the intervention group and 441 women in the control group with positive screens. Using the Nugent criteria, women who were diagnosed with BV received a 6-day course of intravaginal clindamycin 2% cream. Those with positive test results for Candida were treated with intravaginal clotrimazole 0.1 g; those with positive results for trichomonas received intravaginal metronidazole 500 mg for 7 days. After treatment, women with a positive test result in the intervention group had a second vaginal smear between 24 and 28 weeks. Persistent BV was treated with oral clindamycin 300 mg twice daily for 7 days. If Candida or trichomonas were noted, women were treated with the intravaginal clotrimazole or metronidazole. A statistically significant reduction was seen in preterm births in the intervention group(3.0% vs 5.3%, 95% CI, 1.2-3.6; P=.0001; number needed to screen=44)." }, { "input": "There is some benefit to early screening by Gram stain using Nugent's criteria and treating BV-positive women with a history of preterm delivery, premature rupture of membranes, low birth weight infants, or spontaneous abortion. In this group, treatment has been associated with decreased rates of preterm labor, preterm prelabor rupture of membranes, and low birth weight infants.", "output": "In 2003, a RCT evaluating the early treatment of asymptomatic BV in low- and high-risk patients showed a decrease in preterm labor. The RCT included 409 asymptomatic women between 13 and 20 weeks gestation with BV by Gram stain using Nugent's criteria. Investigators randomized women to intravaginal clindamycin each night for 3 days. At a second visit, 20 to 24 days after treatment, women were retested for BV and if they were positive, they received a 7-day course of intravaginal clindamycin or placebo based on the previous randomization. In this study, the incidence of preterm birth was reduced from 10% to 4% (relative risk [RR]=0.38; 95% CI, 0.16-0.90; NNT=17). This study only included 21 women with previous preterm delivery and a subgroup analysis was not performed." }, { "input": "There is some benefit to early screening by Gram stain using Nugent's criteria and treating BV-positive women with a history of preterm delivery, premature rupture of membranes, low birth weight infants, or spontaneous abortion. In this group, treatment has been associated with decreased rates of preterm labor, preterm prelabor rupture of membranes, and low birth weight infants.", "output": "In 2003, a RCT evaluating the early treatment of asymptomatic BV in low- and high-risk patients showed a decrease in preterm labor. The RCT included 494 asymptomatic pregnant women who presented for prenatal care between 12 and 22 weeks gestation. If women had BV detected by Gram stain using Nugent's criteria, they were randomized to receive either 300 mg oral clindamycin twice daily for 5 days or placebo. In the general population, treatment with clindamycin reduced the rate of late miscarriage and spontaneous preterm delivery by 10.4% (95% CI, 5.0-15.8). In women with a previous preterm delivery or a late miscarriage the proportion of preterm delivery or late miscarriage was reduced (16.6% vs 42%)." }, { "input": "Empirically treating high-risk women without documented infection has been associated with an increase in preterm deliveries and neonatal infections.", "output": "A randomized trial of the prophylactic intravaginal clindamycin 2% cream to prevent preterm birth in high-risk women showed an increase in spontaneous preterm delivery in women who actually used all of the medication and did not have BV (NNH=12.3; P<.05)." }, { "input": "Amitriptyline is the best-supported option for the treatment of chronic daily headaches for those patients who have not been treated by conservative measures.", "output": "A meta-analysis from 2001 reviewed 38 RCTs of antidepressants as prophylaxis for chronic headache. Nineteen studies investigated TCAs, 18 examined serotonin blockers, and 7 focused on SSRIs. Patients taking antidepressants were twice as likely to report headache improvement rate ratio [RR]=2.0; 95% confidence interval [CI], 1.6-2.4, with the average amount of improvement considered to be large standard mean difference=0.94; 95% CI, 0.65-1.2. Serotonin blockers, most of which are not available or commonly used in the US, and TCAs were all effective in decreasing the headache burden, while the results for SSRIs were less clear. Dosages of amitriptyline ranged from 10 to 150 mg daily; most of the studies used 60 to 100 mg daily." }, { "input": "For patients who overuse symptomatic headache medications, medication withdrawal is effective.", "output": "Medication withdrawal therapy is a treatment strategy for chronic daily headaches associated with the paradoxical induction of headaches by the frequent, long-term use of immediate relief medications such as aspirin, NSAIDs, acetaminophen, caffeine, codeine, ergotamine, and sumatriptan. A retrospective study tracked 101 men and women who underwent a controlled outpatient withdrawal of their overused medications. Headache diaries kept for 1 to 3 months reflected that 56% of the patients had at least a 50% reduction in headache days after removal of overused drugs. Twenty-two patients who had no success with withdrawal and continued to have headaches were treated with amitriptyline. Subsequently, 10 of these patients experienced a 50% reduction in headache frequency." }, { "input": "For patients who overuse symptomatic headache medications, medication withdrawal is effective.", "output": "A systematic review of the therapeutic approaches to medication-induced headache looked at 18 studies from 1966 to 1998. Although most were uncontrolled small trials, medically monitored withdrawal of all symptomatic headache medications is recommended by the authors. No long-term outcome comparisons between withdrawal strategies are available." }, { "input": "Additional therapies include other tricyclic antidepressants TCAs, selective serotonin reuptake inhibitors SSRIs, and prophylactic treatments for migraine.", "output": "Other therapies for treating chronic daily headache include the skeletal muscle relaxant tizanidine Zanaflex, which was studied in an industry-sponsored, double-blind, placebo-controlled trial of 92 patients. The medication was used as prophylaxis, titrating up to a dose of 8 mg 3 times daily. The overall headache index a measure of headache intensity, frequency, and duration significantly decreased. The headache index decreased in the tizanidine group from 2.6 to 1.2, and in the placebo group from 2.6 to 2.1 P =.0025. Decreases in headache frequency and headache intensity were less dramatic but still significant. This trial lasted only 12 weeks, so longer-term outcomes are not available." }, { "input": "Statins coenzyme-A reductase inhibitors should not be used with the single intent to delay the onset or slow the progression of dementia. Large randomized control trials RCTs found that the administration of a statin had no significant effect on preventing or slowing all-cause cognitive decline.", "output": "The largest RCT of a statin agent, the Heart Protection Study, enrolled more than 20,000 people and randomized them to simvastatin Zocor or placebo. After a median of 5 years of follow-up, there was no difference in cognitive scores or the rate of diagnosis of dementia between the 2 groups." }, { "input": "Statins coenzyme-A reductase inhibitors should not be used with the single intent to delay the onset or slow the progression of dementia. Large randomized control trials RCTs found that the administration of a statin had no significant effect on preventing or slowing all-cause cognitive decline.", "output": "The PROSPER trial, which was designed to test the effect of pravastatin Pravachol on coronary heart disease and stroke, randomized 5804 study participants into 1 group assigned to take pravastatin and another group assigned to take placebo. An additional study endpoint was pravastatin's effect on cognitive function as measured by 4 different tests, including the Mini-Mental Status Exam MMSE. Overall cognitive function declined at the same rate in treatment and placebo groups. There was no significant difference between the 2 groups over 3 years using 4 different methods of assessment. In particular, the MMSE scores differed by only 0.06 points 95% confidence interval [CI], 0.04-0.16; P=.26." }, { "input": "Specifically, there is insufficient evidence that statins delay the onset or slow the progression of Alzheimer's dementia.", "output": "A systematic review concluded that no good evidence recommended statins for reducing the risk of Alzheimer's dementia. Notably, the review did find a body of inconclusive evidence that lowering serum cholesterol may retard disease pathogenesis." }, { "input": "While 3 epidemiologic studies have found a decreased incidence of dementia among those taking statins, these studies have significant methodological shortcomings and do not show a causal relationship.", "output": "An observational study of 56,790 charts included in the computer databases of 3 hospitals found that the prevalence of probable Alzheimer's dementia in the cohort taking statins was 60% to 73% P<.001 lower than in the total patient population or in patients taking antihypertensive or cardiovascular medications." }, { "input": "While 3 epidemiologic studies have found a decreased incidence of dementia among those taking statins, these studies have significant methodological shortcomings and do not show a causal relationship.", "output": "A nested case-control study of 1364 patients found an adjusted relative risk for dementia of 0.29 95% CI, 0.013-0.063; P=.002 among those taking statins. This study did not distinguish between Alzheimer's dementia and other forms of dementia. These studies do not demonstrate a causal relationship between statins and Alzheimer's dementia." }, { "input": "In pregnant women with preexisting type 1 diabetes mellitus, maintaining near-normal blood glucose levels decreases the rate of major congenital anomalies defined as those causing death or a serious handicap necessitating surgical correction or medical treatment. Prolonged preconception control of blood sugar to near normal levels reduces the rate of major congenital anomalies close to those seen in women without diabetes.", "output": "A meta-analysis comparing 16 studies of women with pregestational diabetes-13 of which included only women with type 1 diabetes-found that women receiving preconception care had lower early first trimester HbA1c levels than those who did not (7.9% vs 9.6%) and delivered fewer infants with major congenital anomalies (relative risk [RR]=0.36; 95% confidence interval [CI], 0.22-0.59). One limitation of this study was that preconception care was not consistently defined among the included studies." }, { "input": "In pregnant women with preexisting type 1 diabetes mellitus, maintaining near-normal blood glucose levels decreases the rate of major congenital anomalies defined as those causing death or a serious handicap necessitating surgical correction or medical treatment. Prolonged preconception control of blood sugar to near normal levels reduces the rate of major congenital anomalies close to those seen in women without diabetes.", "output": "Two studies show that in type 1 diabetes mellitus, elevated blood glucose levels in early pregnancy (HbA1c=6%-8%) are associated with a threefold increase in fetal malformations. Maintaining preconception and early pregnancy blood glucose levels in the normal range can reduce this risk." }, { "input": "Intensive management reduces the risk of congenital anomalies more than conventional therapy, and lowers the risk of neonatal hypoglycemia.", "output": "A 10-year RCT evaluated the outcomes of 270 pregnancies in women who had received either intensive (SQ infusion or multiple daily injections) or conventional insulin regimens prior to pregnancy. Women were advised to use intensive therapy when they were trying to conceive, and all were changed to intensive therapy if pregnancy was confirmed. Women in the intensive therapy group had normal HbA1c levels for an average of 40 months before conception. Women receiving intensive therapy had lower mean HbA1c levels at conception (7.4 \u00b1 1.3 SD vs 8.1 \u00b1 1.7 SD) and fewer major congenital anomalies (0.7% vs 5.9%; number needed to treat=19) than did women in the conventional group. When infants with genetic malformations were excluded from the analysis, rates of congenital malformations were similar in women switched to intensive therapy either before or after conception (3.8% vs 3.6%). No differences were seen between neonatal mortality, spontaneous abortion rates, birth weights, Apgar scores, and hypocalcemia or hypoglycemia rates." }, { "input": "Very tight control does not reduce clinically significant neonatal morbidity but does increase the risk of maternal hypoglycemia.", "output": "When tight and very tight control of glucose in pregnant women with pregestational diabetes were compared in a Cochrane systematic review, rates of maternal hypoglycemia in the very tightly controlled group were higher (odds ratio [OR]=25.96; 95% CI, 4.91-137.26). An RCT of 118 women with pregestational diabetes compared 4-times-daily vs twice-daily doses of insulin. Infants born to women receiving 4-times-daily insulin had significantly lower rates of neonatal hypoglycemia (RR=0.17; 95% CI, 0.04-0.74). While the trend was toward improved neonatal metabolic effects in the trials, the clinical significance of these findings is not clear." }, { "input": "In women with impaired glucose tolerance, dietary control reduces neonatal hypoglycemia. To date, studies have not found statistically significant reductions in admission rates to the special care nursery or birth weights above the 90th percentile.", "output": "A Cochrane systematic review evaluating a small number of trials, with variable quality and inconsistent outcome measures, compared dietary management to routine care in gestational diabetics. While fewer infants with birth weights >4000 g were delivered in the diet therapy group (OR=0.78; 95% CI, 0.45-1.35), the results were not statistically significant. No other important clinical differences were found." }, { "input": "Colchicine has been shown to reduce symptomatic recurrences of gout, although the data to support its use is limited.", "output": "A cohort study of 208 men with confirmed gout who used either daily colchicine alone or colchicine with uricosurics for 2 to 10 years found marked improvements in attack frequency in both groups, yet there was no difference between the intervention groups." }, { "input": "Colchicine has been shown to reduce symptomatic recurrences of gout, although the data to support its use is limited.", "output": "A double-blinded crossover study of 38 veteran men with recurrent gout found that the addition of daily colchicine to uricosurics reduced the frequency of attacks by nearly two thirds in 6 months of follow-up." }, { "input": "Allopurinol has been shown to reduce symptomatic recurrences of gout, although the data to support its use is limited.", "output": "Allopurinol was studied in 46 patients using prophylactic colchicine with an average follow-up of 12 months." }, { "input": "Allopurinol has been shown to reduce symptomatic recurrences of gout, although the data to support its use is limited.", "output": "In one study, attack rates were unchanged for the first several weeks followed by a decline in the attack rate and a regression of tophi. When allopurinol was added to uricosurics in 48 patients, tophi were reduced." }, { "input": "Weight loss has been shown to reduce symptomatic recurrences of gout, although the data to support its use is limited.", "output": "An average weight loss of 7.7 kg had a beneficial effect on serum uric acid levels and gout attack rates in 13 nondiabetic men, who were placed on a carefully controlled 1600-calorie diet with 40% of calories from complex carbohydrates." }, { "input": "The evidence suggests that despite their serum uric acid-lowering effects, uricosurics such as probenecid fail to reduce gout attacks.", "output": "In a small study, the addition of uricosurics did not reduce the gout attack rate in 14 patients with nontophaceous gout." }, { "input": "other", "output": "A prospective study of primary gout involving 47,150 men followed over 12 years noted a relative risk (RR) of gout 1.41 (95% confidence interval [CI], 1.07-1.86) in the highest quintile of meat eaters, a RR of 1.51 (95% CI, 1.17-1.95) in the highest quintile of seafood eaters, and an inverse relationship of dairy intake with gout risk." }, { "input": "other", "output": "An additional study followed 734 patients including some of the subjects in the first cohort study and reported similar outcomes." }, { "input": "other", "output": "Patients were followed over 12 to 15 months in a crossover study of colchicine and placebo versus colchicine and sulfinpyrazone. Although this study had limited power, a larger cohort study had similar findings over a longer follow-up period." }, { "input": "other", "output": "Thiazide diuretics appear to increase the likelihood of a gout diagnosis and if used, could be discontinued, although no studies have investigated this intervention. Most of the gout studies were performed in the 1960s using simple cohort designs and limited statistical analysis; some used combinations of medications and variable dosing. Only allopurinol appears effective in resorbing tophi and may have greater utility for patients with severe tophaceous gout, in those intolerant to uricosurics, in gross overproduction of uric acid, for patients with uric acid stones, or for those with renal impairment." }, { "input": "The risk of rupture of a small cerebral aneurysm (<10 mm) is very low in asymptomatic patients who have never had a subarachnoid hemorrhage. Because the risk of morbidity and mortality from surgical intervention significantly exceeds that of nonsurgical monitoring for this group, primary care physicians do not need to refer patients with this condition to a neurosurgeon for clipping.", "output": "In the largest cohort study to date, patients without a history of subarachnoid hemorrhage had an overall risk of rupture of 0.05% per year over 7.5 years. This study also found that surgery-related morbidity and mortality at 1 year among patients aged <45 years was 6.5%, compared with 14.4% for those aged 45 to 64 years, and 32% for those aged >64 years." }, { "input": "The risk of rupture of a small cerebral aneurysm (<10 mm) is very low in asymptomatic patients who have never had a subarachnoid hemorrhage. Because the risk of morbidity and mortality from surgical intervention significantly exceeds that of nonsurgical monitoring for this group, primary care physicians do not need to refer patients with this condition to a neurosurgeon for clipping.", "output": "One study of the natural history of unruptured cerebral aneurysm included 130 patients with 161 unruptured intracranial aneurysms who were followed for a mean of 8.3 years. This prospective investigation found that 15 patients suffered an intracranial hemorrhage. There were no ruptures of the 102 aneurysms that were \u226410 mm in diameter at the time of discovery." }, { "input": "For patients managed conservatively, annual office follow-up and imaging evaluation should be considered, and is necessary if a specific symptom should arise.", "output": "For patients managed conservatively, periodic follow-up imaging should be considered; imaging is necessary if a specific symptom should arise. If changes in aneurysmal size or configuration are observed, special consideration for treatment should be made." }, { "input": "Accurate diagnosis of acute sinusitis in both children and adults depends on the history and clinical examination of the patient. While the clinical signs and symptoms of acute sinusitis are often difficult to distinguish from viral upper respiratory infection, such an assessment remains the best approach to diagnosing acute sinusitis.", "output": "In children and adults without symptoms of sinusitis, the prevalence of sinusitis signs on CT and MRI is 45% and 42%, respectively." }, { "input": "Accurate diagnosis of acute sinusitis in both children and adults depends on the history and clinical examination of the patient. While the clinical signs and symptoms of acute sinusitis are often difficult to distinguish from viral upper respiratory infection, such an assessment remains the best approach to diagnosing acute sinusitis.", "output": "Lau and colleagues reviewed 14 studies that compared various imaging studies with clinical evaluation or sinus puncture and aspiration with culture or both. A positive aspirate for bacterial pathogens was defined as the gold standard for diagnosis of sinusitis." }, { "input": "Accurate diagnosis of acute sinusitis in both children and adults depends on the history and clinical examination of the patient. While the clinical signs and symptoms of acute sinusitis are often difficult to distinguish from viral upper respiratory infection, such an assessment remains the best approach to diagnosing acute sinusitis.", "output": "In a prospective trial and subsequent review of the literature, Lindbaek suggests that several key clinical signs and symptoms can provide a level of sensitivity that approaches that of CT or magnetic resonance imaging (MRI), while enhancing specificity: Purulent secretion reported as a symptom or found in the nasal cavity by the doctor, Pain in the teeth, Pain on bending forward (inconsistent findings between studies), Two phases in the illness history, Elevated erythrocyte sedimentation rate or increased C-reactive protein, Symptoms for at least 7 days." }, { "input": "There is no role for imaging in the diagnosis of acute sinusitis. For patients who have persistent symptoms, or those for whom surgery is being considered, some guidelines suggest that coronal computed tomography (CT) scan of the paranasal sinuses be considered.", "output": "Varonen concluded that clinical evaluation has a sensitivity of roughly 0.75, whereas radiographic methodologies have sensitivities>0.80." }, { "input": "There is no role for imaging in the diagnosis of acute sinusitis. For patients who have persistent symptoms, or those for whom surgery is being considered, some guidelines suggest that coronal computed tomography (CT) scan of the paranasal sinuses be considered.", "output": "aging methodologies are better reserved for patients in whom surgery is being contemplated, or for whom chronic sinusitis is a concern." }, { "input": "Desmopressin reduces the number of nights of primary noctural enuresis by at least 1 per week, and increases the likelihood of \"cure\" (defined as 14 consecutive dry nights) while treatment is continued (number needed to treat [NNT]=5-6)", "output": "One randomized controlled trial found a linear dose response for oral desmopressin in reducing wet nights. After 2 weeks of treatment, the number of wet nights was decreased by 27%, 30%, and 40% at doses of 0.2 mg, 0.4 mg, and 0.6 mg, respectively, compared with 10% with placebo." }, { "input": "Desmopressin reduces the number of nights of primary noctural enuresis by at least 1 per week, and increases the likelihood of \"cure\" (defined as 14 consecutive dry nights) while treatment is continued (number needed to treat [NNT]=5-6)", "output": "A Cochrane review of 16 randomized controlled trials found nasal desmopressin to be better than placebo in reducing the number of wet nights per week mean 1.34 fewer wet nights/week; 95% confidence interval, 1.11-1.57. Desmopressin at doses of 20 \u00b5g, 40 \u00b5g, and 60 \u00b5g similarly increased the likelihood of a cure 14 consecutive dry nights during treatment in 3 trials reporting this outcome relative risk for failure to achieve 14 dry nights with 20 \u00b5g=0.84; NNT for cure=5.6. No difference was found in cure rates after treatment was stopped. Data were insufficient to judge the effectiveness of the oral versus nasal route of desmopressin." }, { "input": "Evidence suggests that the benefits of desmopressin are temporary, with a high relapse rate once treatment is discontinued.", "output": "Snajderova and colleagues studied desmopressin as a long-term treatment for 55 children with primary nocturnal enuresis. Intranasal desmopressin was titrated upward until bedwetting stopped 7-21 \u00b5g; 89.1% responders; children in whom no response occurred to a maximum of 28 \u00b5g were excluded. Every 3 months, a weaning attempt was made; if relapse occurred, the previous successful dose was reinstated. At the end of each of the 3 years, the number of responders remained higher 72.7%, 70.9%, 61.6% than the spontaneous cure rate of 15%." }, { "input": "Evidence suggests that the benefits of desmopressin are temporary, with a high relapse rate once treatment is discontinued.", "output": "The Swedish Enuresis Trial SWEET demonstrated a similar outcome in an open-label study of 399 children." }, { "input": "Evidence is inadequate to judge the relative efficacy of the nasal vs oral forms of desmopressin.", "output": "Data were insufficient to judge the effectiveness of the oral versus nasal route of desmopressin." }, { "input": "Evidence-based guidelines for determining prognosis in some noncancer diseases have been developed. However, despite their widespread use, limited data exist to support their accuracy. Moreover, a high degree of prognostic accuracy may be unattainable given the unpredictable course of common noncancer chronic diseases. Hospice eligibility for patients with nonmalignant disease is based on clinical judgment.", "output": "A recent Clinical Inquiry addressed the issue of hospice care for patients with late-stage Alzheimer's disease. That evidence-based answer concluded that criteria superior to the NHO guidelines or clinical judgment had been established for prognosis of Alzheimer's disease. However, using those improved criteria yielded only marginally more accurate prognostication. At best, 71% of the patients predicted to live less than 6 months did so, but only if the patients had progressed through the disease in an orderly fashion. For the larger subset of patients, those who did not progress through Alzheimer's in a predictable way, only 30% of the patients actually died within 6 months." }, { "input": "Evidence-based guidelines for determining prognosis in some noncancer diseases have been developed. However, despite their widespread use, limited data exist to support their accuracy. Moreover, a high degree of prognostic accuracy may be unattainable given the unpredictable course of common noncancer chronic diseases. Hospice eligibility for patients with nonmalignant disease is based on clinical judgment.", "output": "The National Hospice Organization (NHO) has created guidelines for determining prognosis in selected noncancer diseases including heart disease, pulmonary disease, dementia, HIV, liver disease, renal disease, stroke, coma, and amyotrophic lateral sclerosis (ALS). To validate these guidelines, one group identified 2607 patients who meet the NHO guidelines. Only 655 (25%) were dead within 6 months. The estimated median survival of these identified patients was 804 days. When every potential prognostic criterion was met (far more than NHO standards) only 19 of the 2607 patients qualified for hospice, and yet 10 of them were still alive at 6 months. Unlike many cancers, in which there is a steady terminal decline, diseases such as chronic obstructive pulmonary disease, congestive heart failure, and liver failure are characterized by a baseline of moderate functioning with intermittent-often life-threatening-exacerbations." }, { "input": "Evidence-based guidelines for determining prognosis in some noncancer diseases have been developed. However, despite their widespread use, limited data exist to support their accuracy. Moreover, a high degree of prognostic accuracy may be unattainable given the unpredictable course of common noncancer chronic diseases. Hospice eligibility for patients with nonmalignant disease is based on clinical judgment.", "output": "Brickner et al's survey demonstrated that physicians find accurate prognostication difficult. Furthermore, many of the common noncancer diseases have erratic and unpredictable courses, making prognosis even harder." }, { "input": "While home apnea monitoring may find an increased incidence of apnea and bradycardia in preterm infants compared with term infants, no association links these events with sudden infant death syndrome SIDS. Apnea of prematurity is not a proven risk factor for SIDS. Since apnea of prematurity has not been shown to be a precursor to SIDS, home apnea monitoring for the purpose of preventing SIDS cannot be recommended.", "output": "A prospective cohort study of 1079 infants monitored for cardiorespiratory events, the Collaborative Home Infant Monitor Evaluation (CHIME) study, demonstrated that prior to 43 weeks postconceptional age, preterm infants had a statistically significant greater risk of extreme events (apnea or bradycardia longer than 30 seconds) compared with healthy term infants (Table 2). After 43 weeks postconceptional age, there were no differences in incidence of apnea or bradycardia, comparing preterm and term infants. Neither preterm infants nor infants with apnea, bradycardia, or apparent life-threatening events had increased incidences of SIDS." }, { "input": "While home apnea monitoring may find an increased incidence of apnea and bradycardia in preterm infants compared with term infants, no association links these events with sudden infant death syndrome SIDS. Apnea of prematurity is not a proven risk factor for SIDS. Since apnea of prematurity has not been shown to be a precursor to SIDS, home apnea monitoring for the purpose of preventing SIDS cannot be recommended.", "output": "Multiple case-control studies have identified risk factors for SIDS.1-6 None of these case-control studies found apnea of prematurity to be a risk factor for SIDS." }, { "input": "Neonates with significant neurologic or pulmonary disease may benefit from apnea monitoring.", "output": "Significant financial costs are associated with home monitoring. The average monthly cost is $300 to $400, not including physician fees. This would lead to an estimated annual cost of $24 million dollars if every infant <1500 grams in the United States were monitored." }, { "input": "Neonates with significant neurologic or pulmonary disease may benefit from apnea monitoring.", "output": "The psychological costs of home apnea monitoring have been studied. One hundred and four parents of monitored and unmonitored infants were enrolled in a questionnaire study to determine emotional distress and family functioning. As is common among families in the postpartum period, all experienced increased stress. But parents of monitored infants, compared with parents of unmonitored infants, had an increased incidence of subjective depression (number needed to harm [NNH]=7) and hostility (NNH=12) at 2 weeks postpartum. Interestingly, at 1-year follow-up interviews, 83% of parents who had consistently used the monitor reported feeling more secure for having used it and 69% believed that monitor use had been helpful." }, { "input": "When hydroxymethyl glutaryl coenzyme A (HMG CoA) inhibitors (statins) are stopped by asymptomatic patients, there appears to be no increased risk of cardiovascular events.", "output": "A post-hoc analysis of the washout period of a prospective study of 9473 asymptomatic outpatients who were previously taking statins showed that for these lower-risk patients, similar rates of cardiovascular events could be expected during withdrawal (any statin) or initiation of atorvastatin therapy. The monthly event rate during the discontinuation phase was 0.20% and during initiation was 0.26% (P=NS)" }, { "input": "For patients who have recently experienced a cardiovascular event, discontinuation of statins increases the risk of further events and death.", "output": "One retrospective case-control study evaluated 4870 patients who had statin therapy withdrawn on admission to the hospital for non-ST segment elevation MI (NSTEMI). Patients who had their statins withheld had increased rates of heart failure, arrhythmia, shock, and death (hazard ratio=2.32; 95% confidence interval [CI], 2.02-2.67)." }, { "input": "For patients who have recently experienced a cardiovascular event, discontinuation of statins increases the risk of further events and death.", "output": "A post-hoc analysis of data from the PRISM trial found that among the 86 patients who were admitted for chest pain and had their statin withdrawn, a higher rate of death and nonfatal MI was observed, compared with the 379 patients whose statins were continued (hazard ratio=2.93; 95% CI, 1.64-6.27). This effect was seen in the first week and was independent of cholesterol levels and measures of severity of illness." }, { "input": "other", "output": "Studies of patients with stroke and those with only risk factors for cardiovascular disease show that platelet activity is increased when statins are discontinued." }, { "input": "other", "output": "Animal studies of stroke in mice showed mice whose statin was abruptly stopped had more damage from stroke than those whose statin was continued." }, { "input": "other", "output": "Tissue plasminogen activator levels are decreased after discontinuation of statins, resulting in a relatively hypercoagulable state." }, { "input": "Physical therapy is minimally effective in the treatment of fibromyalgia, with immediate post-treatment improvement in pain and tender points, and both short- and longer-term improved self-efficacy confidence in performing tasks.", "output": "We examined the results of a systematic review of exercise for treating fibromyalgia. The authors found 7 high-quality studies, 4 of aerobic training, and concluded that supervised aerobic exercise training had beneficial effects on physical capacity, tender-point threshold, and pain. Other investigators have questioned the usefulness of aerobic exercise because long-term benefit remains unclear and compliance is poor." }, { "input": "Physical therapy is minimally effective in the treatment of fibromyalgia, with immediate post-treatment improvement in pain and tender points, and both short- and longer-term improved self-efficacy confidence in performing tasks.", "output": "In a trial comparing 2 physical therapies- body awareness therapy and the Mensendieck system-Kendall and colleagues found greater improvements at 18-month follow-up in the Mensendieck group. Benefits were seen on the Fibromyalgia Impact Questionnaire, self-efficacy measures, and pain at worst site. The Mensendieck system uses individual interview, analysis of movement patterns, a discussion of possible corrections followed by practice, and relaxation exercises." }, { "input": "Physical therapy is minimally effective in the treatment of fibromyalgia, with immediate post-treatment improvement in pain and tender points, and both short- and longer-term improved self-efficacy confidence in performing tasks.", "output": "In a trial of muscle strengthening vs flexibility training, investigators found no difference between groups on measures including tender points and disease and symptom severity. They did find benefits in symptoms and self-efficacy over baseline, but it is not known whether these were sustained." }, { "input": "Physical therapy is minimally effective in the treatment of fibromyalgia, with immediate post-treatment improvement in pain and tender points, and both short- and longer-term improved self-efficacy confidence in performing tasks.", "output": "Keel and colleagues found no immediate treatment benefit following 15 weeks of education, cognitive behavioral therapy, and exercise vs relaxation training in their small randomized controlled trial." }, { "input": "Physical therapy is minimally effective in the treatment of fibromyalgia, with immediate post-treatment improvement in pain and tender points, and both short- and longer-term improved self-efficacy confidence in performing tasks.", "output": "In a study, 45 patients with fibromyalgia were randomly assigned to a 6-week program combining exercise and multidisciplinary education or to a control group. The treatment group had significant improvements in walking distance and for 2 measures on the Fibromyalgia Impact Questionnaire (feeling bad and morning fatigue)." }, { "input": "Physical therapy is minimally effective in the treatment of fibromyalgia, with immediate post-treatment improvement in pain and tender points, and both short- and longer-term improved self-efficacy confidence in performing tasks.", "output": "A trial randomized 99 patients to 3 groups: education and cognitive behavioral therapy; education, cognitive behavioral therapy and exercise; or a wait-list control group. At the 6-month follow-up, the education group scored significantly higher than the others-but only on self-reported measures of daily functioning and self-efficacy." }, { "input": "Physical therapy is minimally effective in the treatment of fibromyalgia, with immediate post-treatment improvement in pain and tender points, and both short- and longer-term improved self-efficacy confidence in performing tasks.", "output": "In the highest-quality trial, Buckelew and colleagues randomized 119 subjects to 1 of 4 groups: biofeedback and relaxation training, exercise training, combination treatment, and an education and attention control program. Individuals were evaluated on measures of pain, function, disease impact, and self-efficacy. Evaluators were blinded to treatment group. Patients were followed for 2 years, and follow-up information was available on 85% of patients. At immediate postintervention follow-up, all treatment groups were significantly improved on tender-point index score compared with the control group, but this was due to a modest deterioration for the control group rather than improvements in the treatment groups. In addition, all groups showed improvements in self-efficacy for function compared with the control group but not for other self-efficacy measures. While within-group improvements in the treatment groups were seen, no significant differences were seen from the control group." }, { "input": "Multidisciplinary rehabilitation is probably not effective for this disorder but warrants future research, as trial quality is poor.", "output": "In a systematic review of 7 studies fulfilling inclusion criteria (a total of 1050 patients), Karjalainen and colleagues concluded that although education combined with physical training seemed to have some positive results at long-term follow-up, the level of scientific evidence required for recommending these programs for fibromyalgia was lacking." }, { "input": "Physicians and their staff may experience a resolution of anxiety and guilt that can improve their well-being.", "output": "Most data suggest that physician well-being is improved by discussion of errors with patients and colleagues." }, { "input": "Physicians and their staff may experience a resolution of anxiety and guilt that can improve their well-being.", "output": "Even though physicians feel that disclosure of errors is important, they may lack the skills to make a successful disclosure or feel they do not have institutional support for disclosure." }, { "input": "Physicians and their staff may experience a resolution of anxiety and guilt that can improve their well-being.", "output": "Physicians and nurses describe negative emotional consequences when they realize they have made an error." }, { "input": "Full disclosure has little effect, however, on the likelihood that an injured patient will seek legal counsel.", "output": "Regardless of whether a full disclosure occurred, patients are more likely to seek legal advice if they perceive the error as having serious consequences." }, { "input": "Full disclosure has little effect, however, on the likelihood that an injured patient will seek legal counsel.", "output": "Very little evidence exists regarding the effect of disclosure on the likelihood of legal action in actual practice." }, { "input": "Successful disclosure of a medical error can improve a patient's confidence in the physician and lead to improved outcomes.", "output": "Survey data suggest that patients prefer detailed disclosure about what happened, why it happened, the consequences, and strategies for preventing future errors. (RED:1,2,3,4)" }, { "input": "Jaw claudication, diplopia, or a temporal artery abnormality on physical exam increase the likelihood of temporal arteritis. A finding of thrombocytosis in a patient with suspected temporal arteritis moderately increases the likelihood of this diagnosis.", "output": "Five studies have documented that thrombocytosis (platelets >375,000/mm) is more helpful for ruling in temporal arteritis than an elevated ESR. Conversely, normal platelets are more accurate for ruling out temporal arteritis than a normal ESR." }, { "input": "Jaw claudication, diplopia, or a temporal artery abnormality on physical exam increase the likelihood of temporal arteritis. A finding of thrombocytosis in a patient with suspected temporal arteritis moderately increases the likelihood of this diagnosis.", "output": "A 2002 systematic review and a 2005 decision analysis examined validating cohort studies to determine the likelihood ratios of symptoms, signs, and blood tests (TABLE). These cohort studies are subject to verification bias, as most cohorts represent a selected sample of patients who had a positive temporal artery biopsy. The authors of the 2005 decision analysis note that unilateral temporal artery biopsy has a mean sensitivity of 86.9% (95% confidence interval [CI], 83.1%-90.6%) when compared with a gold standard derived from bilateral artery biopsy, American College of Rheumatology criteria, or clinical diagnosis." }, { "input": "Use the Ottawa Knee Rules. When there is a possibility of fracture, they can guide the use of radiography in adults who present with isolated knee pain. However, information on use of these rules in the pediatric population is limited.", "output": "A prospective study of the Ottawa rules among children with acute knee injury demonstrated a positive likelihood ratio (LR+) of 1.81 (95% CI, 1.47-2.21) and an LR- of 0.16 (95% CI, 0.02-1.04). However, limited information is available in the pediatric population." }, { "input": "Use the Ottawa Knee Rules. When there is a possibility of fracture, they can guide the use of radiography in adults who present with isolated knee pain. However, information on use of these rules in the pediatric population is limited.", "output": "In a systematic review, the Ottawa rules had a pooled negative likelihood ratio (LR-) of 0.05 (95% confidence interval [CI], 0.02-0.23)." }, { "input": "Use the Ottawa Knee Rules. When there is a possibility of fracture, they can guide the use of radiography in adults who present with isolated knee pain. However, information on use of these rules in the pediatric population is limited.", "output": "The Ottawa Knee Rules recommend knee x-rays for any patient meeting one of these criteria: 1) \u226555 years of age. 2) Tenderness over the head of the fibula or isolated to the patella without other bony tenderness. 3) Unable to flex the knee to 90\u00ba, or unable to bear weight (for at least 4 steps) both immediately and in the emergency department." }, { "input": "Specific physical examination maneuvers (such as the Lachman and McMurray tests) may be helpful when assessing for meniscal or ligamentous injury.", "output": "Physical examination (including the Lachman test, Drawer sign, and McMurray test) by an orthopedist or sports medicine-trained physician was 74% to 88% sensitive and 72% to 95% specific for suspected meniscal or ligamentous injuries; MRI added marginal value in referral decisions regarding these conditions." }, { "input": "Sonographic examination of a traumatized knee can accurately detect internal knee derangement.", "output": "In a small nonrandomized study of adult knee trauma, sonographic diagnosis of an effusion (by an expert) had an LR+ for diagnosing an internal derangement of the knee of 2.0 (95% CI, 0.67-5.96) and an LR- of 0.33 (95% CI, 0.12-0.96), as compared with the gold standard of MRI." }, { "input": "Magnetic resonance imaging (MRI) of the knee is the noninvasive standard for diagnosing internal knee derangement, and it is useful for both adult and pediatric patients.", "output": "In a retrospective study of adolescents (11 to 17 years of age) having knee MRIs and undergoing knee surgery, MRI compared favorably with the operative (gold standard) diagnosis." }, { "input": "Magnetic resonance imaging (MRI) of the knee is the noninvasive standard for diagnosing internal knee derangement, and it is useful for both adult and pediatric patients.", "output": "In a nonrandomized prospective study of adults receiving MRI of the knee prior to arthroscopy, MRI identified meniscal and ligamentous lesions of the knee satisfactorily." }, { "input": "Angiotensin receptor blockers (ARBs) have been shown to reduce the progression of nephropathy in several consistent studies. While ACE inhibitors have not been as well studied for the endpoint of nephropathy, patients with nephropathy exhibit reduced mortality when treated with an ACE inhibitor.", "output": "The mortality benefit with ARBs has not been as consistent as that shown with ACE inhibitors. Both classes of drugs conferred reduced mortality as seen with ramipril in the HOPE Heart Outcomes Prevention Evaluation trial and losartan in the LIFE Losartan Intervention For Life trial. However, a survival benefit was not seen with irbesartan in the RENAAL and IDNT trials." }, { "input": "Angiotensin receptor blockers (ARBs) have been shown to reduce the progression of nephropathy in several consistent studies. While ACE inhibitors have not been as well studied for the endpoint of nephropathy, patients with nephropathy exhibit reduced mortality when treated with an ACE inhibitor.", "output": "A double-blind, placebo-controlled trial-IDNT Irbesartan Diabetic Nephropathy Trial-randomized 1715 patients to irbesartan, amlodipine Norvasc, or placebo for a median follow-up of 2.6 years. Each group could also use other conventional antihypertensive therapy but again excluding ACE inhibitors, ARBs, and calcium-channel blockers. Irbesartan reduced progression of nephropathy defined by doubling of the serum creatinine and the onset of end-stage renal disease more effectively than amlodipine NNT=12 or placebo NNT=16. Irbesartan did not decrease cardiovascular mortality, nonfatal myocardial infarction, heart failure resulting in hospitalization, neurologic deficit caused by a cerebrovascular event, or above-ankle lower-limb amputation." }, { "input": "Angiotensin receptor blockers (ARBs) have been shown to reduce the progression of nephropathy in several consistent studies. While ACE inhibitors have not been as well studied for the endpoint of nephropathy, patients with nephropathy exhibit reduced mortality when treated with an ACE inhibitor.", "output": "The 2-year IRMA Irbesartan Microalbuminuria study, a multicenter, randomized, double-blind, placebo-controlled trial, randomized 590 patients with type 2 diabetes, hypertension, and persistent microalbuminuria to receive 150 or 300 mg of irbesartan Avapro or placebo. Additional antihypertensive agents were allowed in each arm with the exception of ACE inhibitors, ARBs, and dihydropyridine calcium-channel blockers. The primary outcome was the development of overt nephropathy defined by a urinary albumin excretion rate >200 \u00b5g/min that is at least 30% higher than the baseline rate. This trial showed that irbesartan delayed progression to nephropathy independent of its effect on blood pressure compared with conventional therapy NNT=16 at the 150-mg dose and NNT=11 at the 300-mg dose." }, { "input": "Angiotensin receptor blockers (ARBs) have been shown to reduce the progression of nephropathy in several consistent studies. While ACE inhibitors have not been as well studied for the endpoint of nephropathy, patients with nephropathy exhibit reduced mortality when treated with an ACE inhibitor.", "output": "The RENAAL Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan study-a multicenter, randomized, double-blind, placebo-controlled trial-followed 1513 patients with type 2 diabetes and nephropathy over a mean of 3.4 years. Patients were randomized to receive losartan Cozaar or placebo, both taken in addition to conventional anti-hypertensive therapy but not including renin-angiotensin-aldosterone system antagonist medications. The primary outcome was a composite of a doubling of serum creatinine, end-stage renal disease, or death. The number needed to treat NNT for the composite outcome was 34. The NNT for a doubling of the serum creatinine was 25, and for end-stage renal disease was 17." }, { "input": "Those who test positive for high-risk types of HPV should be referred for colposcopy. Those with a negative test result for high-risk types of HPV may resume regular Pap testing in 12 months. If HPV testing is unavailable, an alternative strategy is to repeat the Pap smear at 4- to 6-month intervals. After 2 negative Pap smears are obtained, usual screening may resume. But if either of the repeat Pap smears results in ASCUS or worse, the woman should be referred for colposcopy.", "output": "For women aged 29 years or older, HPV testing resulted in a much lower colposcopy referral rate, 31% vs 65% for younger women, without sacrificing sensitivity." }, { "input": "Those who test positive for high-risk types of HPV should be referred for colposcopy. Those with a negative test result for high-risk types of HPV may resume regular Pap testing in 12 months. If HPV testing is unavailable, an alternative strategy is to repeat the Pap smear at 4- to 6-month intervals. After 2 negative Pap smears are obtained, usual screening may resume. But if either of the repeat Pap smears results in ASCUS or worse, the woman should be referred for colposcopy.", "output": "A cost-effectiveness analysis that modeled data from the ASCUS-LSIL Triage Study (ALTS) found that reflex HPV testing was most cost-effective." }, { "input": "Those who test positive for high-risk types of HPV should be referred for colposcopy. Those with a negative test result for high-risk types of HPV may resume regular Pap testing in 12 months. If HPV testing is unavailable, an alternative strategy is to repeat the Pap smear at 4- to 6-month intervals. After 2 negative Pap smears are obtained, usual screening may resume. But if either of the repeat Pap smears results in ASCUS or worse, the woman should be referred for colposcopy.", "output": "The recent ASCUS-LSIL Triage Study (ALTS), a multicenter randomized trial, directly addressed the appropriate evaluation of ASCUS. The trial compared 3 management strategies for ASCUS Pap smears: reflex HPV-DNA testing (the initial Pap sample is tested for HPV only if the results are ASCUS), immediate referral for colposcopy, and repeat Pap smears. Reflex HPV testing had a sensitivity of 96% for detecting HSIL and a negative predictive value of 98%. The 44% of women with ASCUS who tested negative for high-risk HPV were able to avoid colposcopy. A single repeat Pap smear within 4 to 6 months, with referral for colposcopy if abnormal, had a sensitivity of 85% (sensitivity might be expected to improve with a second repeat test) and a similar colposcopy referral rate." }, { "input": "For children, antibiotics do not appear to improve short-term (3-6 weeks) or long-term (3 months) outcomes of chronic rhinosinusitis.", "output": "Another study randomized 79 children with chronic sinusitis to treatment with cefaclor vs placebo following antral washout. Measured outcomes were similar to those in the prior study. At 6 weeks, 12.3% more patients in the antibiotic group achieved cure than the placebo group (64.8% vs 52.5%), but this difference was not statistically significant (P=.28). At 12 weeks, no differences in improvement were seen between the 2 groups (89% vs 89.5%)." }, { "input": "For children, antibiotics do not appear to improve short-term (3-6 weeks) or long-term (3 months) outcomes of chronic rhinosinusitis.", "output": "Two placebo-controlled trials have evaluated antibiotic treatment of chronic rhinosinusitis in children. In 1 study, 141 children with chronic rhinosinusitis were randomly assigned to 1 of 4 treatment arms: saline nose drops; xylometazoline (Otrivin) drops with oral amoxicillin 3 times daily; surgical drainage; or surgical drainage, amoxicillin 3 times daily and xylometazoline drops. Outcomes were resolution of purulent rhinitis, no purulent drainage on exam, and no abnormalities of maxillary sinus on x-ray. The absence of all 3 findings constituted cure. At 6 weeks there was a non-statistically significant higher resolution in the fourth group, but by 26 weeks the groups were indistinguishable. At 6 weeks, 53%, 50%, 55%, and 79% of each group, respectively, were cured. These results increased to 69%, 74%, 69%, and 64% at 26 weeks." }, { "input": "Warfarin (Coumadin) is effective in preventing deep venous thrombosis (DVT) among patients with a history of DVT. Conventional dosing and longer durations are the most effective, but the ideal length of therapy is unknown.", "output": "A multicenter randomized trial showed that risk for recurrence was the same after treatment was stopped, regardless of the length of treatment." }, { "input": "Warfarin (Coumadin) is effective in preventing deep venous thrombosis (DVT) among patients with a history of DVT. Conventional dosing and longer durations are the most effective, but the ideal length of therapy is unknown.", "output": "A multicenter randomized controlled trial found extending warfarin treatment for 12 months vs 3 months resulted in a 95% relative risk reduction RRR in risk of DVT recurrence 95% CI, 63-99; NNT=5." }, { "input": "Warfarin (Coumadin) is effective in preventing deep venous thrombosis (DVT) among patients with a history of DVT. Conventional dosing and longer durations are the most effective, but the ideal length of therapy is unknown.", "output": "A meta-analysis found treatment with warfarin for 12 to 24 weeks decreased DVT recurrence compared with 2- to 6-week regimens relative risk [RR]=0.60; 95% CI, 0.45-0.79; NNT=21." }, { "input": "Warfarin (Coumadin) is effective in preventing deep venous thrombosis (DVT) among patients with a history of DVT. Conventional dosing and longer durations are the most effective, but the ideal length of therapy is unknown.", "output": "A double-blind randomized controlled trial of 738 patients demonstrated that conventional-intensity warfarin therapy INR=2.0-3.0 was more effective than low-intensity therapy INR=1.5-1.9 in prevention of recurrent DVT. There were 1.9 vs 0.7 DVTs per 100 person-years in the low-intensity vs conventional-intensity therapy groups hazard ratio=2.8; 95% CI, 1.1-7.0; number needed to treat [NNT]=37. No significant difference was seen in the frequency of bleeding complications between the groups. This and other studies suggest that low-intensity warfarin therapy reduces the relative risk of thrombosis by about 75%, and conventional-intensity therapy reduces this risk by over 90%." }, { "input": "Warfarin (Coumadin) is effective in preventing deep venous thrombosis (DVT) among patients with a history of DVT. Conventional dosing and longer durations are the most effective, but the ideal length of therapy is unknown.", "output": "Warfarin, at both low and conventional doses, has been shown to be effective in preventing recurrence of DVT. A large, 4-year placebo-controlled randomized controlled trial showed that long-term low-dose warfarin international normalized ratio [INR], 1.5-1.9 was more effective than placebo for prevention of DVT hazard ratio=0.36; 95% confidence interval [CI], 0.19-0.67." }, { "input": "Warfarin is useful in preventing DVT in patients with cancer, specifically those treated with chemotherapy.", "output": "In patients with cancer, warfarin was shown to be more effective than placebo in prevention of DVT. In a trial of 311 breast cancer patients receiving chemotherapy, treatment with very-low-dose warfarin INR=1.3-1.9 decreased thrombotic events compared with placebo, with no increase in bleeding complications RRR=85%; P=.031; NNT=27." }, { "input": "Warfarin is useful in preventing DVT in patients with cancer, specifically those treated with chemotherapy.", "output": "A cost analysis showed that very-low-dose warfarin can be used in prevention of DVT in breast cancer patients on chemotherapy without an increase in health care costs." }, { "input": "Warfarin may be effective in pre-venting DVT in immobilized patients such as those with trauma, spinal cord injury, or stroke.", "output": "A few small studies suggest that warfarin reduces DVT rates in spinal-cord-injured patients. A small trial randomized stroke patients undergoing rehabilitation to placebo or fixed 1- or 2-mg doses of warfarin. This underpowered study showed a nonsignificant decrease in the risk of development of DVT RR=0.39; 95% CI, 0.13-1.37." }, { "input": "Prior bacille Calmette-Gu\u00e9rin (BCG) vaccination increases the likelihood of a positive tuberculosis (TB) 5TU purified protein derivative (PPD) skin test. The PPD response following BCG vaccine varies with age at vaccination, number of years since the BCG vaccination, number of times vaccinated, and number of PPDs performed. An induration of greater than 14 mm is unlikely to be due to prior BCG vaccination.", "output": "A 2002 meta-analysis showed that the person's age at the time of their BCG vaccination and the years since vaccination influence the relative risk of a positive PPD. The highest relative risk of a positive PPD occurred among patients who received BCG vaccination after infancy and within 15 years of the PPD testing. This same meta-analysis also examined the significance of the size of the PPD response; a subset of 4 studies showed that equal proportions of BCG vaccinated and unvaccinated patients had indurations of 14 mm or more." }, { "input": "The variable reaction after BCG vaccination, along with the desire to detect all cases of TB, has led to recommendations that all patients with a positive PPD test be treated as true positives. These patients should undergo chest radiography and appropriate treatment, regardless of history of BCG vaccine.", "output": "A Brazilian case-control study found that reactions by those BCG recipients later exposed to TB were significantly greater than those with no TB exposure.3 The study noted that 47.5% of exposed children (defined as those with a household contact) had PPD readings of >10 mm, compared with just 3.6% of control children." }, { "input": "The variable reaction after BCG vaccination, along with the desire to detect all cases of TB, has led to recommendations that all patients with a positive PPD test be treated as true positives. These patients should undergo chest radiography and appropriate treatment, regardless of history of BCG vaccine.", "output": "In a Quebec cohort of 1198 foreign-born children and young adults, prior BCG vaccination could account for 50% of PPDs with induration of 5 to 9 mm, but only 4% of reactions 10 mm or greater. This study also showed that patients from countries with a high or moderate incidence of TB were more likely to have reactive PPDs than those from countries of low incidence, suggesting that exposure to TB accounts for some of the positive PPDs." }, { "input": "A recently developed alternative is the interferon-gamma assay (QuantiFERON-TB Gold test), which may be used in place of, or in addition to, the PPD skin test for patients who are known to have received a BCG vaccine.", "output": "A Japanese study of 216 BCG-vaccinated individuals showed interferon-gamma assays to be 98.1% specific. The same study reported 89.0% sensitivity for the combination of 2 interferon-gamma assays among 118 TB culture-confirmed individuals." }, { "input": "A recently developed alternative is the interferon-gamma assay (QuantiFERON-TB Gold test), which may be used in place of, or in addition to, the PPD skin test for patients who are known to have received a BCG vaccine.", "output": "A published report estimated the cost to the health care system per patient tested by a single interferon-gamma release assay as $33.67, compared with approximately $11 for PPD testing." }, { "input": "Frequent coughing is a concern for approximately 35% of those with typical gastroesophageal reflux disease (GERD) symptoms of heartburn and acid regurgitation as compared with 11% in those who do not have these symptoms. Among pulmonary clinic patients with complaints of chronic cough, GERD may be the underlying cause in 40%.", "output": "Among patients with cough caused by GERD, 50% to 75% do not have classic symptoms of reflux or regurgitation. Finally, cough may initiate GERD and start a cough-reflux cycle." }, { "input": "Frequent coughing is a concern for approximately 35% of those with typical gastroesophageal reflux disease (GERD) symptoms of heartburn and acid regurgitation as compared with 11% in those who do not have these symptoms. Among pulmonary clinic patients with complaints of chronic cough, GERD may be the underlying cause in 40%.", "output": "In as many as 40% of patients with cough, GERD is the underlying cause." }, { "input": "Frequent coughing is a concern for approximately 35% of those with typical gastroesophageal reflux disease (GERD) symptoms of heartburn and acid regurgitation as compared with 11% in those who do not have these symptoms. Among pulmonary clinic patients with complaints of chronic cough, GERD may be the underlying cause in 40%.", "output": "A population-based survey showed that symptoms of reflux and acid regurgitation are experienced by almost 60% of the population each year. The prevalence of frequent heartburn and acid reflux was approximately 20%. Bronchitis, defined as cough that occurs as often as 4 to 6 times per day on 4 or more days per week, was reported by more than 20% of those with frequent typical GERD symptoms (occurring at least weekly) and by 15% of those with infrequent GERD symptoms. Interestingly, bronchitis was reported by almost 11% of those without GERD. This study showed the association of cough with GERD but did not address whether the cough was the initial presenting complaint." }, { "input": "However, no studies directly address prevalence of coughing as a presenting complaint in patients with GERD.", "output": "Chronic cough may be triggered by more than one condition (eg, GERD, postnasal drip, or asthma) in 18% to 93% of patients." }, { "input": "There is some limited evidence supporting the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the initial treatment of shoulder pain. There is no evidence in support of most other therapies, including intra-articular or subacromial corticosteroid injection, intra-articular NSAID injection, oral corticosteroid treatment, physiotherapy, ultrasound, heat or ice therapy, laser treatment, electrotherapy, and iontophoresis", "output": "A randomized single-blind study of primary care patients reported superiority of manipulative therapy over classic physiotherapy in the treatment of shoulder pain (70% vs 10% cure rate at 5 weeks). Manipulative therapy as performed by general practitioners or physiotherapists included mobilization and manipulation of the upper spine and ribs, acromioclavicular joint, and the glenohumeral joint. Classic physiotherapy as performed by physiotherapists included only exercise therapy, massage, and physical applications. For the patients with synovial pain, intra-articular corticosteroid injection was superior to both manipulative therapy and classic physiotherapy (cure rates of 75% vs 40% and 20%, respectively, at 5 weeks), yet many primary care physicians may not have enough experience to specifically diagnose synovial pain." }, { "input": "There is some limited evidence supporting the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the initial treatment of shoulder pain. There is no evidence in support of most other therapies, including intra-articular or subacromial corticosteroid injection, intra-articular NSAID injection, oral corticosteroid treatment, physiotherapy, ultrasound, heat or ice therapy, laser treatment, electrotherapy, and iontophoresis", "output": "A randomized controlled trial found 14-day treatment with oral NSAIDs superior to placebo for relieving acute shoulder pain (86% vs 56%; absolute risk reduction 30%; 95% confidence interval, 10%-50%)." }, { "input": "There is some limited evidence supporting the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the initial treatment of shoulder pain. There is no evidence in support of most other therapies, including intra-articular or subacromial corticosteroid injection, intra-articular NSAID injection, oral corticosteroid treatment, physiotherapy, ultrasound, heat or ice therapy, laser treatment, electrotherapy, and iontophoresis", "output": "The pooled analyses of 2 studies of rotator cuff tendinitis suggested that NSAIDs may be superior to placebo in improving the range of abduction, but there was no significant weighted difference between pain scores." }, { "input": "There is some limited evidence supporting the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the initial treatment of shoulder pain. There is no evidence in support of most other therapies, including intra-articular or subacromial corticosteroid injection, intra-articular NSAID injection, oral corticosteroid treatment, physiotherapy, ultrasound, heat or ice therapy, laser treatment, electrotherapy, and iontophoresis", "output": "A Cochrane Review concluded that there is little evidence to either support or refute the efficacy of most common interventions for shoulder pain." }, { "input": "Topical therapy is effective for tinea pedis. Topical terbinafine has a 70% cure rate, is available over the counter OTC, and requires only 1 to 2 weeks of therapy. Two other OTC topicals, tolnaftate and miconazole, require 2 to 4 weeks to achieve slightly lower cure rates, but are considerably less expensive.", "output": "The Cochrane Database of Systemic Reviews reported 72 placebo-controlled trials of topical agents that yielded the following cure rates: undecenoic acid, 72%; allylamines (terbinafine, naftifine, butenafine), 70%; tolnaftate, 64%; azoles (miconazole, clotrimazole, ketoconazole, econazole, oxiconazole), 47%. A meta-analysis of 11 RCTs suggests that allylamines are slightly more effective than azoles." }, { "input": "The most effective treatment for tinea pedis is oral terbinafine 250 mg twice a day for 2 weeks 94% clinical cure rate. However, oral terbinafine is expensive and not approved for this indication. Oral therapy may be required for patients with hyperkerototic soles, severe disease, topical therapy failure, chronic infection or immunosuppression.", "output": "In a large double-blind multicenter study of all forms of tinea pedis, De Keyser et al compared 2 weeks of terbinafine at 250 mg/day to 2 weeks of itraconazole at 100 mg/day. After 8 weeks they found terbinafine superior to itraconazole for clinical cure (94.1% vs 72.4%). In a single multicenter open study the cure rate for fluconazole 150 mg was 77% when used once weekly for 3 weeks." }, { "input": "other", "output": "Griseofulvin has been used for more than 30 years, is well tolerated, and efficacious in treating dermatomycoses in the range of 60%. Ketoconazole's cure rate is similar, but its use in cutaneous infections is limited by multiple drug interactions and serious side effects." }, { "input": "Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Pneumococcal vaccination is indicated for patients after splenectomy. This immunization should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day.", "output": "In a study of 561 Danes, those vaccinated within 14 days of splenectomy (before or after) had a significantly higher need for revaccination than those who were vaccinated more than 14 days before or after surgery." }, { "input": "Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Pneumococcal vaccination is indicated for patients after splenectomy. This immunization should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day.", "output": "In 2 recent RCTs, the 23-valent pneumococcal polysaccharide vaccine was tested on patients 1, 7, 14, and 28 days after splenectomy. The studies demonstrated that the immunogenicity of the vaccine was best when given at or after day 14 after the operation. In both studies, patients immunized at day 14 had immunoglobulin G (IgG) antibody levels approaching those of control subjects with intact spleens. There were no differences in antibody levels among those patients immunized at day 14 compared with those immunized on day 28. However, those subjects immunized on days 1 and 7 had significant lower antibody levels than the control subjects or those immunized on day 14." }, { "input": "Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Meningococcal and Haemophilus influenzae (Hib) vaccinations are indicated for patients after splenectomy. These immunizations should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day.", "output": "In a study, 130 asplenic individuals were compared with 48 age-matched controls after receiving a meningococcal vaccine. The majority (93%) achieved bactericidal immunoglobulin levels following immunization. This study demonstrated the need to have antibody titers drawn to ensure immunization response, as 20% of the subjects required a second dose of vaccine to achieve adequate levels. No clear evidence supports the timing of the meningococcal vaccine post-splenectomy." }, { "input": "Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Meningococcal and Haemophilus influenzae (Hib) vaccinations are indicated for patients after splenectomy. These immunizations should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day.", "output": "Two recent studies look at the immunogenicity of the Hib for asplenic patients. The first study demonstrated increased antibody titers to Hib at 2, 6, 12, 24, and 36 months after immunization. Fifty of the 57 patients in the study (88%) maintained adequate antibody titers 3 years after immunization. No symptomatic infections were observed during the 3-year study period." }, { "input": "Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Meningococcal and Haemophilus influenzae (Hib) vaccinations are indicated for patients after splenectomy. These immunizations should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day.", "output": "In a study of 561 Danes, those vaccinated within 14 days of splenectomy (before or after) had a significantly higher need for revaccination than those who were vaccinated more than 14 days before or after surgery." }, { "input": "Split tablets of lisinopril are as effective as whole tablets of the same dose for hypertension.", "output": "A randomized trial (n=29) evaluated tablet-splitting by patients taking lisinopril for hypertension. Patients were randomized to split tablets or whole tablets for 2 weeks, then crossed over to the other group for 2 weeks. There was no difference in blood pressures between groups." }, { "input": "Similarly, split tablets of atorvastatin, lovastatin, and simvastatin are no less effective for lowering cholesterol.", "output": "A retrospective study of simvastatin evaluated 1098 patients taking whole tablets and 1098 patients converted to split tablets of the same dose. There was no difference in average final low-density lipoprotein (LDL) cholesterol (111\u00b130 mg/dL vs 112\u00b132 mg/dL) or mean ala-nine aminotransferase (ALT) level." }, { "input": "Similarly, split tablets of atorvastatin, lovastatin, and simvastatin are no less effective for lowering cholesterol.", "output": "A retrospective study evaluated tablet-splitting by 512 patients taking statins atorvastatin, lovastatin, simvastatin. Cholesterol values after 12 or more weeks on a stable whole-tablet dose were compared with those 6 to 52 weeks after initiating tablet-splitting; no significant change was seen in total cholesterol or triglycerides. There was a statistically significant decrease in LDL (102\u00b128 vs 97\u00b129 mg/dL, P<.001), an increase in high-density lipoprotein (HDL) cholesterol (46\u00b112 vs 48\u00b112 mg/dL, P<.001), and an increase in aspartate aminotransferase (AST) (26\u00b18 vs 28\u00b110 units/L, P<.001), which was attributed to higher medication dosage from accidental ingestion of whole tablets and to diet and lifestyle modifications." }, { "input": "Similarly, split tablets of atorvastatin, lovastatin, and simvastatin are no less effective for lowering cholesterol.", "output": "A retrospective evaluation of 109 patients with split atorvastatin or simvastatin found no significant difference in total cholesterol or LDL values after initiating the tablet-splitting program." }, { "input": "Extended-release, enteric-coated, or tablets that cannot be split accurately are not appropriate for splitting.", "output": "A study using 5 medications found that 0% to 44% of split tablets deviated from ideal weight by 20%, depending on tablet shape." }, { "input": "The accuracy of splitting also depends on device used and user skill.", "output": "In a study, 94 healthy volunteers (mean age, 46.2 years) each split 10 hydrochlorothiazide 25 mg tablets by hand. Forty-one percent of the split products were more than 10% off ideal weight; 12% of tablets were more than 20% off.6 Manufacturing regulations require that medication doses vary by less than 10% of the nominal dose." }, { "input": "The accuracy of splitting also depends on device used and user skill.", "output": "Thirty patients aged 50 years or older, half of whom received instruction and a demonstration, evaluated 2 tablet-splitters with different blade positions and types of guide. One device (Apex Pill Splitter) produced more accurate results by 10% to 20% (P value not provided) with metoprolol, warfarin, and lisinopril tablets. Instructed patients were 1% to 10% more accurate, as were those with experience splitting warfarin tablets (P=.003)." }, { "input": "Perform a scrotal ultrasonography immediately to determine whether emergency surgery is necessary for patients with an exam or history that suggests testicular torsion or rupture.", "output": "In a study of 209 emergency scrotal explorations, clinical exam by general practitioners and surgeons correctly diagnosed only 92.5% and 94% of testicular torsion cases, respectively, compared with the surgical diagnosis. If torsion cannot be reliably excluded, emergent surgical exploration is mandatory." }, { "input": "In less urgent cases, ultrasound is also useful for verifying diagnoses made by physical exam, and to exclude conditions such as neoplasm, for which further workup is indicated.", "output": "In a study, which used surgery as the diagnostic gold standard, color Doppler ultrasound had a sensitivity of 93.5% for the diagnosis of testicular torsion." }, { "input": "In less urgent cases, ultrasound is also useful for verifying diagnoses made by physical exam, and to exclude conditions such as neoplasm, for which further workup is indicated.", "output": "For patients who have a nonacute scrotal mass, ultrasound is often indicated to distinguish intratesticular from extratesticular masses." }, { "input": "In less urgent cases, ultrasound is also useful for verifying diagnoses made by physical exam, and to exclude conditions such as neoplasm, for which further workup is indicated.", "output": "In a small study comparing clinical exam with ultrasound for diagnosis of testicular tumor, the negative predictive value of ultrasound was 100%." }, { "input": "In those cases in which ultrasound and clinical exam are inconclusive or conflicting, magnetic resonance imaging MRI can provide additional information to improve management and decrease unnecessary surgery.", "output": "MRI can help distinguish inflammation or abscess from neoplasm, thus preventing a patient from undergoing unnecessary surgical intervention." }, { "input": "In those cases in which ultrasound and clinical exam are inconclusive or conflicting, magnetic resonance imaging MRI can provide additional information to improve management and decrease unnecessary surgery.", "output": "If testicular neoplasm cannot be excluded based on clinical and radiographic findings, surgery is indicated." }, { "input": "MRI has a high sensitivity and specificity in the detection of cancer or infection, but it is not particularly specific when evaluating lumbar radiculopathy. Poor specificity can lead to finding clinically irrelevant abnormalities.", "output": "The lower specificity of MRI for radiculopathy means that MRI can detect disk herniations that do not cause the patient's signs or symptoms. In one study, MRI demonstrated herniated disks in 25% of asymptomatic persons." }, { "input": "The overall evidence for the appropriate use of MRI in low back pain is limited and weak.", "output": "Unfortunately, there are too few studies to guide clinicians in the appropriate use of MRI in the evaluation of low back pain." }, { "input": "Screening diabetic patients for microalbuminuria identifies those who may benefit from treatments that delay progression to renal failure.", "output": "Expert opinion recommends diagnosing microalbuminuria after 2 positive test results. The American Diabetes Association recommends annual screening for microalbuminuria-after 5 years of established type 1 disease, and at time of diagnosis for type 2 diabetes without macroalbuminuria. Initial screening can use 1 of 3 methods: measurement of the albumin-to-creatinine ratio in a random, spot collection; 24-hour collection with creatinine, allowing the simultaneous measurement of creatinine clearance; timed eg, 4-hour or overnight collection. At least 2 of 3 tests measured within a 6-month period should show elevated levels before a patient is said to have microalbuminuria." }, { "input": "Screening diabetic patients for microalbuminuria identifies those who may benefit from treatments that delay progression to renal failure.", "output": "No prospective randomized trials of screening have been reported. There is uncertainty about what method of screening is most effective and practical in primary care settings." }, { "input": "A combination of beta-lactam and aminoglycoside antibiotics are the recommended empiric agents for the treatment of acute chorioamnionitis, given that no head-to-head trials exist.", "output": "A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis." }, { "input": "Intrapartum antibiotic treatment is not superior to postpartum antibiotics for reducing neonatal sepsis and pneumonia.", "output": "Gibbs et al performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours. Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis." }, { "input": "Intrapartum antibiotic treatment is not superior to postpartum antibiotics for reducing neonatal sepsis and pneumonia.", "output": "Intrapartum treatment with antibiotics was associated with a \"significant\" clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00-1.44) and pneumonia (RR=0.15; 95% CI, 0.01-2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to a Cochrane review." }, { "input": "Intrapartum antibiotic treatment is not superior to postpartum antibiotics for reducing neonatal sepsis and pneumonia.", "output": "One study randomized 133 women into 2 arms-treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone-and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20-23.21) or neonatal death (RR=0.72; 95% CI, 0.12-4.16)" }, { "input": "Only high-risk close contacts of known cases should receive prophylactic antibiotics, according to the Centers for Disease Control and Prevention (CDC). The CDC defines high-risk as (1) infants who are <12 months, (2) those especially vulnerable to the complications of pertussis, or (3) those, such as health care workers, in close contact with high-risk individuals.", "output": "Macrolides (erythromycin, clarithromycin, or azithromycin) are recommended for postexposure prophylaxis. Trimethoprim-sulfamethoxazole is a second-line agent. A short course of erythromycin (7 days), azithromycin (3-5 days), or clarithromycin (7 days) is as effective as a 2-week course of erythromycin in eradicating Bordetella pertussis from the nasopharynx." }, { "input": "Only high-risk close contacts of known cases should receive prophylactic antibiotics, according to the Centers for Disease Control and Prevention (CDC). The CDC defines high-risk as (1) infants who are <12 months, (2) those especially vulnerable to the complications of pertussis, or (3) those, such as health care workers, in close contact with high-risk individuals.", "output": "Despite the paucity of RCTs, the CDC and other public health agency guidelines recommend postexposure prophylaxis for certain close contacts to protect high-risk individuals, defined as those who could develop severe disease or experience adverse outcomes if pertussis developed." }, { "input": "Evidence is insufficient to support a benefit of prophylactic antibiotic treatment for all household pertussis contacts to prevent the development or spread of illness.", "output": "A Cochrane review of antibiotic use for pertussis prophylaxis, including studies published through 2002, found only 2 randomized, well-controlled trials (RCTs) that compared attack rates between contacts receiving placebo or antibiotic therapy. Neither trial included infants under age 6 months. The reviewers concluded that evidence was insufficient to determine a treatment benefit." }, { "input": "Evidence is insufficient to support a benefit of prophylactic antibiotic treatment for all household pertussis contacts to prevent the development or spread of illness.", "output": "In one RCT, no (0/60) fully immunized child in a household with pertussis developed whooping cough, with or without antibiotic prophylaxis. Among unimmunized children, pertussis developed in 4/20 receiving erythromycin prophylaxis and 2/11 receiving placebo." }, { "input": "There isn't a single best method, but there are 5 that adequately purify water according to environmental Protection agency (EPA) standards. These include 1) boiling for 1 minute if below 2000 m (6562 feet) and 3 minutes if above, 2) chlorine dioxide tablets, 3) MIoX purifier, 4) ultraviolet light (steriPEN), and 5) portable filtration with a absolute pore size <1 micrometer combined with halogenation or charcoal filtration.", "output": "When combined with either halogenation or charcoal filters, filtration can be effective against all pathogens." }, { "input": "There isn't a single best method, but there are 5 that adequately purify water according to environmental Protection agency (EPA) standards. These include 1) boiling for 1 minute if below 2000 m (6562 feet) and 3 minutes if above, 2) chlorine dioxide tablets, 3) MIoX purifier, 4) ultraviolet light (steriPEN), and 5) portable filtration with a absolute pore size <1 micrometer combined with halogenation or charcoal filtration.", "output": "Filtration with an absolute pore size of <0.1 micrometer (10 times smaller than the EPA standard) has been generally accepted as effective against protozoa and bacteria, but it is not effective against viruses because of their small size." }, { "input": "There isn't a single best method, but there are 5 that adequately purify water according to environmental Protection agency (EPA) standards. These include 1) boiling for 1 minute if below 2000 m (6562 feet) and 3 minutes if above, 2) chlorine dioxide tablets, 3) MIoX purifier, 4) ultraviolet light (steriPEN), and 5) portable filtration with a absolute pore size <1 micrometer combined with halogenation or charcoal filtration.", "output": "Chlorine dioxide tablets, the MIOX purifier, and UV light SteriPEN have all met EPA standards for lower pathogen counts under ideal conditions." }, { "input": "There isn't a single best method, but there are 5 that adequately purify water according to environmental Protection agency (EPA) standards. These include 1) boiling for 1 minute if below 2000 m (6562 feet) and 3 minutes if above, 2) chlorine dioxide tablets, 3) MIoX purifier, 4) ultraviolet light (steriPEN), and 5) portable filtration with a absolute pore size <1 micrometer combined with halogenation or charcoal filtration.", "output": "Expert opinion recommends bringing water to a rapid boil for at least 3 minutes and letting it cool as an effective means of water purification." }, { "input": "Halogenation alone (ie, chlorine and iodine) is not effective against Cryptosporidium.", "output": "Halogenation does not reduce Cryptosporidium below the microbiological hazard of 99.9%, but it is generally accepted to effectively treat viruses, bacteria, and other protozoa after filtering through a cloth to remove large particles." }, { "input": "Tramadol (Ultram, generic and with acetaminophen in Ultracet) carries a risk of substance abuse.", "output": "Another prospective study assessed the subjective tramadol withdrawal experience in 219 patients with a diagnosis of \"Tramadol misuse\" who were attending 6 drug detoxification centers in China. Validated drug dependence symptom scales found that while the degree of physical dependence reported was uniformly mild, the majority of patients reported the psychic dependence symptom of tramadol craving." }, { "input": "Tramadol (Ultram, generic and with acetaminophen in Ultracet) carries a risk of substance abuse.", "output": "A 3-year post-marketing cohort study measured tramadol's nonmedical misuse rates using urine drug testing for tramadol among 1601 participants in 4 US state monitoring programs for impaired healthcare professionals. Tramadol exposure occurred in 140 (8.7%) participants. Thirty-nine (28%) were classified as extensive experimentation or abuse of tramadol. Overall, the rate of extensive experimentation or abuse was 18 cases per thousand personyears. The Hawthorne effect, where awareness of being monitored alters a subject's behavior, may threaten these measured frequency rates' generalizability." }, { "input": "Tramadol (Ultram, generic and with acetaminophen in Ultracet) carries a risk of substance abuse.", "output": "The Drug Abuse Warning Network (DAWN) is a federally operated, national surveillance system that monitors trends in drug-related emergency department visits. Over the period from 1995 to 2002, DAWN reported drug-related emergency department visits mentioning tramadol in more than 12,000 cases. Tramadol case numbers significantly increased 165% during this time. For perspective, during the same period, DAWN found nalbuphine (Nubain, also not CSA scheduled) in 118 cases, propoxyphene drug combinations (CSA Class IV) in more than 45,000 cases, codeine drug combinations (CSA Classes III & V) in about 50,000 cases, and hydrocodone drug combinations (CSA Class III) in around 128,000 cases." }, { "input": "Tramadol (Ultram, generic and with acetaminophen in Ultracet) carries a risk of substance abuse.", "output": "MedWatch has received 766 case reports of abuse associated with tramadol, as well as 482 cases of withdrawal associated with tramadol from the drug's initial US marketing in 1995 through September 2004." }, { "input": "It appears that tramadol's risk of substance abuse is low.", "output": "The FDA's Drug Abuse Advisory Committee performed a formal review of the tramadol abuse evidence in 1998, including the data from OrthoMcNeil's surveillance studies and federal case reporting/surveillance programs. The FDA did not recommend changing tramadol's unscheduled status. The FDA's considered decision to not schedule tramadol as a controlled substance implies its abuse risk to the general population is low. in comparison to its novel analgesic benefit." }, { "input": "Tramadol is associated with a withdrawal syndrome usually typical of opioid withdrawal.", "output": "Using data from observational postmarketing studies, investigators have extrapolated a tramadol abuse rate for the general tramadolexposed population. Ortho-McNeil, Ultram's manufacturer, funded a surveillance program that compiled tramadol abuse and withdrawal case reports from 2 sources: (1) periodic surveys for tramadol abuse case reports from a group of 255 substance abuse experts studying and caring for addiction communities, and (2) voluntary ADE case reports from health care professionals and consumers received by Ortho-McNeil. Over 3 years of surveillance, the program received 454 case reports classified as tramadol abuse. Over 5 years of surveillance, 422 cases of substance withdrawal, with primarily opioid withdrawal symptoms, were reported. There are significant threats to the validity and generalizability of the investigators' estimated abuse rate of 1 to 3 cases per 100,000 tramadol-exposed patients. The abuse cases were collected in nonrepresentative samples of the tramadol-exposed population. Tramadol exposure is likely suppressed in addiction communities with access to preferred, more potent or euphoriant opioids than tramadol. Voluntary case reports of tramadol abuse significantly underestimate the actual number of abuse cases in the tramadol-exposed population. In addition, the low survey return rate (49%) further decreases the accuracy of any estimation of tramadol abuse rates." }, { "input": "If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years.", "output": "In summary, limitations in DEXA precision mean any changes in BMD of less than 5.6% at the femoral neck may be due to measurement error, and BMD response to bisphosphonates vacillates in the first few years of use but can be expected to increase femoral neck BMD 3% to 6% over 3 years. Therefore, if serial DEXA scanning is preformed on patients prescribed bisphosphonate therapy, it should be considered no earlier than 2 to 3 years after therapy begins. When monitoring osteoporosis therapy, a BMD change within the LSC should be interpreted as \"no change\" and should not lead to changes in patient management. If the BMD has decreased beyond the LSC there is cause for concern and reevaluation of diagnosis and treatment are warranted." }, { "input": "If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years.", "output": "A second analysis showed that when women were divided into 8 groups, the group with the greatest increase in BMD in the first year (10.4%) also had the greatest decrease (1.0%) in year 2. In addition, the group with the greatest decrease in year 1 (6.6%) had the greatest increase in year 2 (4.8%). The variability in response among the 8 groups was approximately 17% (+10.4% and -6.6%) in year 1 and narrowed to a 6% difference in year 2 This regression to the mean leads to a normalization of bone density results. This patient variability in BMD response to the prescribed therapy should be considered when deciding to retest." }, { "input": "If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years.", "output": "Frequent testing, as seen in bisphosphonate clinical trials, demonstrates the phenomenon of regression to the mean. One analysis of the FIT trial, which compared alendronate with placebo in postmenopausal women with low BMD and at least 1 vertebral fracture, focused on the early evaluation of BMD. The study found a high degree of variability in BMD when tested after 1 year of treatment. This wide variety of response in the first year normalized in the second year." }, { "input": "If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years.", "output": "Alendronate continues to increase BMD: following 10 years of treatment, it increased BMD by 13.7% in the lumbar spine, 6.7% in the total hip, and 5.4 % in the femoral neck." }, { "input": "If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years.", "output": "It is not clinically useful to retest BMD before a therapy would have time to affect bone turnover. Alendronate and risedronate increase lumbar spine BMD by 5% to 7% and hip BMD by 3% to 6% when used for approximately 3 years." }, { "input": "Reducing environmental tobacco smoke exposure decreases health care utilization among poor asthmatic children. Dust mite reduction by chemical measures is potentially harmful.", "output": "In a randomized trial of predominantly poor minority subjects, fewer acute asthma medical visits were needed by children whose household members underwent behavioral education aimed at decreasing smoke exposure." }, { "input": "Evidence is insufficient for or against dust mite reduction by physical means, use of synthetic or feather bedding, removal of cats, use of air filters or reducing indoor humidity.", "output": "A group of researchers found that home visits by care providers may decrease acute medical visits, specific allergy avoidance steps did not make a difference." }, { "input": "Evidence is insufficient for or against dust mite reduction by physical means, use of synthetic or feather bedding, removal of cats, use of air filters or reducing indoor humidity.", "output": "Two authors reported that the use of chemicals for house dust mite control and the use of synthetic pillows in lieu of feather pillows may actually exacerbate asthma." }, { "input": "Evidence is insufficient for or against dust mite reduction by physical means, use of synthetic or feather bedding, removal of cats, use of air filters or reducing indoor humidity.", "output": "A Cochrane review was inconclusive on the risks or benefits of feather bedding." }, { "input": "Evidence is insufficient for or against dust mite reduction by physical means, use of synthetic or feather bedding, removal of cats, use of air filters or reducing indoor humidity.", "output": "A Cochrane Review of 15 trials noted a small, statistically significant improvement in asthma symptom scores, but the results were not clinically important enough to recommend such measures. The potential harm of chemical measures was reiterated in this review." }, { "input": "For treating seasonal allergic rhinitis, inhaled nasal corticosteroids are superior to nonsedating antihistamines.", "output": "A meta-analysis of 16 RCTs compared the efficacy of intranasal steroids and oral antihistamines for alleviating nasal, eye, and global allergy symptoms. Intranasal steroids were superior to oral antihistamines for all patient-oriented nasal symptom and global symptom ratings. Eye symptom scores and adverse events were similar in each treatment group." }, { "input": "Combining nasal steroids and nonsedating antihistamines yields no additional benefits. Unless patient preference limits their use, nasal steroids should be first-line therapy.", "output": "A large RCT has addressed whether combining the nasal steroids and nonsedating antihistamines would achieve greater symptom control. The study found combination therapy to be superior. This RCT compared beclomethasone dipropionate with loratadine or placebo daily in 154 patients. Total symptom scores were better for the combination group mainly due to improved relief from ocular symptoms." }, { "input": "Combining nasal steroids and nonsedating antihistamines yields no additional benefits. Unless patient preference limits their use, nasal steroids should be first-line therapy.", "output": "Fluticasone propionate aqueous nasal spray (FPANS) was evaluated alone and in combination with cetirizine in a multicenter double-blind study of 454 patients. The mean symptom scores for nasal and eye symptoms were not significantly different between the 2 groups." }, { "input": "Combining nasal steroids and nonsedating antihistamines yields no additional benefits. Unless patient preference limits their use, nasal steroids should be first-line therapy.", "output": "An RCT compared FPANS with loratadine and with combined therapy. This double-blinded placebo-controlled trial, which included 600 patients, measured patient- and clinician-rated total symptom scores, individual nasal symptom scores, and overall evaluations after 7 and 14 days of therapy. Although the symptom scores for the FPANS group were significantly lower than those in the loratadine and placebo groups, no significant difference in scores was found between the FPANS and combined groups. The results were the same for the quality-of-life questionnaire scores." }, { "input": "Combining nasal steroids and nonsedating antihistamines yields no additional benefits. Unless patient preference limits their use, nasal steroids should be first-line therapy.", "output": "In an RCT of 106 patients, budesonide nasal spray's efficacy was tested against terfenadine alone and in combination; the nasal steroid alone was more effective than the histamine. Combining the 2 drugs yielded no significant improvements." }, { "input": "Combining nasal steroids and nonsedating antihistamines yields no additional benefits. Unless patient preference limits their use, nasal steroids should be first-line therapy.", "output": "The newer nasal steroids such as fluticasone may be more effective because of their stronger affinities to glucocorticoid receptors, but no clinical evidence confirms this hypothesis." }, { "input": "In low-prevalence communities, evidence is insufficient to recommend for or against a targeted screening approach, employing locale-specific demographic risk factors and personal risk questionnaires to inform screening decisions.", "output": "In low-prevalence areas, questionnaires may inform screening decisions. A questionnaire inquiring about age of housing, presence of peeling paint, ongoing renovations, siblings or playmates with elevated blood lead levels, adults in the home with occupational exposures to lead, and proximity to industrial sources of lead has a sensitivity for detecting blood lead levels 10 \u00b5g/dL ranging from 32% to 87%. Sensitivity varies depending on the population and geographic location in which the questionnaire is tested. Accuracy is improved by tailoring the questionnaire based on locally important risk factors." }, { "input": "Oral and topical nasal decongestants result in a statistically significant improvement in subjective symptoms of nasal congestion and objective nasal airway resistance in adults' common colds.", "output": "A Cochrane review of 4 randomized controlled trials compared single doses of oxymetazoline, pseudoephedrine, and phenylpropanolamine. Included studies involved from 30 to 106 participants, were double-blinded and placebo-controlled, used either topical or oral decongestants for symptoms of less than 5 days' duration, and measured either subjective or objective relief or adverse events. All 4 studies used nasal airway resistance as an objective measure of nasal congestion, and a combined symptom score as a subjective measure of relief. One study also administered a side-effect questionnaire. In all studies, topical and oral decongestants were equally efficacious, producing a 13% reduction in subjective symptoms and a significant decrease in nasal airway resistance after 1 dose of decongestant. Only 1 study investigated repeated doses of decongestants and found no significant additional improvement from repeated doses over a 5-day period. More studies are needed to evaluate efficacy of multiple doses. Clinical interpretation of these results must take into consideration that quality-of-life measures were not evaluated and that none of the studies included children under 12." }, { "input": "Evidence is lacking to support the use of decongestants in acute sinusitis.", "output": "One placebo-controlled, randomized controlled trial evaluated the effect on mucociliary clearance from adding nasal saline, nasal steroids, or oxymetazoline to antibiotics in acute bacterial sinusitis. The group using oxymetazoline increased mucociliary clearance immediately (within 20 minutes). However, at 3 weeks, the improvement in mucociliary clearance in the oxymetazoline group was not significantly different than in the other groups." }, { "input": "Evidence is lacking to support the use of decongestants in acute sinusitis.", "output": "A prospective, placebo-controlled study evaluated improvement in x-ray findings as well as subjective symptoms in acute sinusitis using phenoxymethyl-penicillin (penicillin V) in combination with oxymetazoline or placebo administered via a variety of nasal delivery systems. Oxymetazoline was not significantly different from placebo. Controlled prospective studies are lacking to support the use of decongestants in acute sinusitis." }, { "input": "Beta-blockers (class II antiarrhythmics) reduce sudden death and total mortality in patients with heart failure.", "output": "Meta-analyses, weakened by heterogeneity and the inclusion of patients without heart failure, detected a significant 21% to 25% RRR for sudden death, and an ARR of 2% to 3% per year. The pooled data from the placebo-controlled heart failure trials showed nonsignificant trends: 1.6% per year ARR for sudden death, 0.6% per year for total mortality." }, { "input": "Beta-blockers (class II antiarrhythmics) reduce sudden death and total mortality in patients with heart failure.", "output": "The largest placebo-controlled trial in heart failure failed to detect a significant decrease in sudden death." }, { "input": "Beta-blockers (class II antiarrhythmics) reduce sudden death and total mortality in patients with heart failure.", "output": "A randomized controlled trial in heart failure showed a significant ARR of 2.9% for sudden death, but was unblinded." }, { "input": "Beta-blockers (class II antiarrhythmics) reduce sudden death and total mortality in patients with heart failure.", "output": "The beta-blockers bisoprolol, carvedilol, and metoprolol were studied in large randomized controlled trials. The relative risk reduction (RRR) for sudden death ranged from 10% to 52% in the larger trials and 30% to 39% in meta-analyses. The absolute risk reduction (ARR) was about 2% to 3% per year for sudden death and 3% to 5% for total mortality (number needed to treat=20-33 per year). These beta-blockers were well-tolerated, even in class IV New York Heart Association patients, and improved other endpoints. Although we cannot say whether the benefits are a class effect, they were seen with both beta-1 selective and nonselective agents." }, { "input": "Amiodarone (class III) may reduce sudden death in heart failure, but evidence is weak that it reduces total mortality, and it has significant side effects.", "output": "Possible benefits must be balanced against the risk of harm from amiodarone, including excess rates of pulmonary infiltrate (1.1% per year), thyroid dysfunction (6.8% per year), liver enzyme abnormalities (0.6% per year), neuropathy (0.3% per year), and bradycardia (1.6% per year), as well as a discontinuation rate of 41% compared with 27% for placebo." }, { "input": "Class I and other class III antiarrhythmic agents appear to cause an increase in mortality due to sudden death in heart failure.", "output": "Class I antiarrhythmics and other class III agents have not been studied in heart failure trials, but were associated with increased mortality in studies of patients at high risk for ventricular arrhythmia, including patients with left ventricular dysfunction. Because this increase in mortality is thought to be due to proarrhythmic properties of the drugs, further trials in heart failure patients are unlikely to occur." }, { "input": "Brief counseling, nicotine replacement therapy, antidepressants, and varenicline all work well. Physician intervention should begin with routine assessment of smoking status for all patients. Brief (3 minutes or less) smoking cessation counseling improves quit rates.", "output": "Another systematic review of 188 RCTs concluded that an estimated 2% (95% CI, 1%-3%; P<.001) of all smokers stopped smoking and did not relapse for as long as a year after receiving advice and encouragement to quit smoking from their physician in a single routine consultation." }, { "input": "Brief counseling, nicotine replacement therapy, antidepressants, and varenicline all work well. Physician intervention should begin with routine assessment of smoking status for all patients. Brief (3 minutes or less) smoking cessation counseling improves quit rates.", "output": "A Cochrane analysis of pooled data from 17 randomized trials that compared brief advice to no advice or usual care showed a small but significant increase in the odds of smoking cessation (odds ratio [OR]=1.74; 95% confidence interval [CI], 1.48-2.05). The absolute difference in cessation rate was about 2.5% (number needed to treat [NNT]=40)." }, { "input": "Brief counseling, nicotine replacement therapy, antidepressants, and varenicline all work well. Physician intervention should begin with routine assessment of smoking status for all patients. Brief (3 minutes or less) smoking cessation counseling improves quit rates.", "output": "Good evidence suggests that physician-administered smoking cessation counseling lasting less than 3 minutes improves quit rates." }, { "input": "Nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), and the nicotine receptor partial agonist varenicline are effective and should be offered to help smokers quit.", "output": "NRT reduces withdrawal symptoms associated with stopping smoking by partially replacing nicotine in the blood. Abstinence rates are superior to placebo based on a Cochrane review (OR=1.77; 95% CI, 1.66-1.88; NNT=20; 95% CI, 17-23)." }, { "input": "Nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), and the nicotine receptor partial agonist varenicline are effective and should be offered to help smokers quit.", "output": "The Cochrane review also concluded that all commercially available forms of NRT are effective for smoking cessation. Also, recent studies have established no association between NRT and further cardiac events." }, { "input": "Nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), and the nicotine receptor partial agonist varenicline are effective and should be offered to help smokers quit.", "output": "A large double-blind, placebo controlled trial compared the relative efficacy of sustained-release bupropion (n=244), nicotine patch (n=244), bupropion plus nicotine patch (n=245), and placebo (n=160). At 1 year, the bupropion groups had higher self-reported point-prevalence abstinence rates (abstinence during the previous 7 days) than the placebo and nicotine-patch-alone groups (bupropion 30%, placebo 16%, nicotine-patch-alone 16%; absolute risk reduction [ARR]=0.14, NNT=7, P<.001). Continuous abstinence (abstinence from quit date) was also higher for the bupropion groups compared with placebo (bupropion 18%, placebo 6%; ARR=0.12; NNT=8; P<.001). Adding nicotine replacement to bupropion therapy increased 1-year smoking cessation rates by 5% over bupropion alone but was not statistically significant." }, { "input": "Nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), and the nicotine receptor partial agonist varenicline are effective and should be offered to help smokers quit.", "output": "A Cochrane review assessing the efficacy of antidepressants for smoking cessation showed that, when used as monotherapy, bupropion (31 trials; OR=1.94; 95% CI, 1.72-2.19) and nortriptyline (4 trials; OR=2.34; 95% CI, 1.61-3.41) both doubled the odds of smoking cessation." }, { "input": "Nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), and the nicotine receptor partial agonist varenicline are effective and should be offered to help smokers quit.", "output": "Varenicline, a partial agonist at the \u03914\u03b22 nicotinic acetylcholine receptor, aids smoking cessation by relieving nicotine withdrawal symptoms. A Cochrane meta-analysis concluded that varenicline resulted in significantly greater continuous abstinence at 12 months than placebo (OR=3.22; 95% CI, 2.43-4.27; NNT=8; 95% CI, 5-11)." }, { "input": "Yes - to a point. Antepartum perineal massage reduces both the incidence of perineal trauma requiring suturing and the likelihood of episiotomy in women who have never given birth vaginally. It reduces the incidence of postpartum perineal pain in women who have given birth vaginally. Perineal massage doesn't reduce the frequency of first- or second-degree lacerations or third- and fourth-degree perineal trauma.", "output": "Massage reduced postpartum perineal pain in multigravidas, according to a questionnaire administered at 3 months in 1 study, to which 376 of 493 women 76% responded RR=0.45; 95% CI, 0.02-0.87; NNT=13. A subgroup of women who massaged more often than 3.5 times a week had a larger reduction in pain RR=0.51; 95% CI, 0.33-0.79; NNT=11. At 3 months, massage produced no difference in rates of dyspareunia, sexual satisfaction, or incontinence of urine or feces when compared with standard care." }, { "input": "Yes - to a point. Antepartum perineal massage reduces both the incidence of perineal trauma requiring suturing and the likelihood of episiotomy in women who have never given birth vaginally. It reduces the incidence of postpartum perineal pain in women who have given birth vaginally. Perineal massage doesn't reduce the frequency of first- or second-degree lacerations or third- and fourth-degree perineal trauma.", "output": "Beginning at 34 weeks, women or their partners performed perineal massage once a day for 10 minutes. Massage was performed by inserting 1 or 2 fingers 3 to 5 cm into the vagina and sweeping downward and from side to side, using almond oil for lubrication." }, { "input": "Yes - to a point. Antepartum perineal massage reduces both the incidence of perineal trauma requiring suturing and the likelihood of episiotomy in women who have never given birth vaginally. It reduces the incidence of postpartum perineal pain in women who have given birth vaginally. Perineal massage doesn't reduce the frequency of first- or second-degree lacerations or third- and fourth-degree perineal trauma.", "output": "Beginning at 34 weeks, women or their partners performed perineal massage for 4 minutes, 3 to 4 times a week. Massage was performed by inserting 1 or 2 fingers 3 to 5 cm into the vagina and sweeping downward and from side to side, using almond oil for lubrication." }, { "input": "Yes - to a point. Antepartum perineal massage reduces both the incidence of perineal trauma requiring suturing and the likelihood of episiotomy in women who have never given birth vaginally. It reduces the incidence of postpartum perineal pain in women who have given birth vaginally. Perineal massage doesn't reduce the frequency of first- or second-degree lacerations or third- and fourth-degree perineal trauma.", "output": "A systematic review evaluating whether antepartum perineal massage reduced perineal trauma included 3 RCTs with a total of 1941 primagravidas and 493 multigravidas. Women were randomized to receive either instruction in perineal massage or no instruction. Massage reduced perineal trauma requiring suturing by 10% among primigravid patients, compared with controls (relative risk [RR]=0.90; 95% confidence interval [CI], 0.84-0.96; number needed to treat [NNT]=14). Subgroup analysis revealed an inverse relationship between reduced trauma and frequency of massage: Primagravidas who massaged fewer than 1.5 times a week showed a 17% reduction (RR=0.83; 95% CI, 0.75-0.92; NNT=9), compared with an 8% reduction for women who massaged 1.5 to 3.4 times a week (RR=0.92; 95% CI, 0.85-1.00; NNT=22) and a statistically insignificant 7% reduction for the group that massaged more than 3.5 times a week (RR=0.93; 95% CI, 0.86-1.02). Perineal massage reduced the incidence of episiotomy by 15% among primigravidas compared with controls (RR=0.85; 95% CI, 0.74-0.97; NNT=20); the largest reduction occurred in primagravidas who massaged as often as 1.5 times per week (RR=0.72; 95% CI, 0.57-0.91). This effect was not seen in primagravidas who massaged more often. Multigravid patients didn't experience a statistically significant reduction in episiotomy. Perineal massage didn't affect the overall incidence of first- and second-degree perineal lacerations (first-degree laceration: RR=0.95; 95% CI, 0.78-1.16; second-degree laceration: RR=0.98; 95% CI, 0.84-1.15), nor the incidence of third- or fourth-degree lacerations (RR=0.81; 95% CI, 0.56-1.15). No difference was noted in the incidence of instrument delivery (RR=0.94; 95% CI, 0.81-1.08)." }, { "input": "Mammography is best. It is considered as effective for screening women who have undergone augmentation mammoplasty as those who have not. This question has not been well studied, however.", "output": "All available findings suggest that clinicians who perform mammography should be trained in imaging the augmented breast." }, { "input": "Mammography is best. It is considered as effective for screening women who have undergone augmentation mammoplasty as those who have not. This question has not been well studied, however.", "output": "Mammography appears to be the most effective screening method for women with breast implants. Despite the small differences in cancer characteristics at diagnosis between augmented and nonaugmented women, overall prognosis and survival rates are no different. This is true whether a screening mammogram or diagnostic mammogram is used." }, { "input": "Mammography is best. It is considered as effective for screening women who have undergone augmentation mammoplasty as those who have not. This question has not been well studied, however.", "output": "Although studies comparing screening methods have not been performed in the United States, a small Taiwanese study directly compared ultrasound to mammography in 105 women without breast implants. This retrospective cohort study found sonography to be a more useful diagnostic tool than mammography in Taiwanese women. Sonography had the highest sensitivity (87.5%) compared to physical examination (50.0%) and mammography (25.5%). Sonography was recommended as the imaging tool for Asian women with smaller, denser breasts. However, it is unclear whether this result applies to US women or women who have undergone breast augmentation surgery." }, { "input": "Mammography is best. It is considered as effective for screening women who have undergone augmentation mammoplasty as those who have not. This question has not been well studied, however.", "output": "A study of 2956 cancer patients found that mammography detected an abnormal breast mass in 66.3% of augmented women compared with 94.6% of nonaugmented women (P=.001). No significant differences were noted in cancer characteristics at diagnosis or survival rates (P=.78). The authors of this study concluded that mammography should be used for augmented women until a more effective screening tool is found." }, { "input": "Mammography is best. It is considered as effective for screening women who have undergone augmentation mammoplasty as those who have not. This question has not been well studied, however.", "output": "A 2006 study of 4082 breast cancer patients concluded that mammography yielded a false-negative rate of 41.4% in augmented patients compared with 8.8% in nonaugmented patients (P<.0001). However, both augmented (n=129) and nonaugmented (n=3953) women had a comparable prognosis at diagnosis. The authors of the studies suggested diagnostic mammography for augmented patients and correlation with physical exam findings." }, { "input": "Mammography is best. It is considered as effective for screening women who have undergone augmentation mammoplasty as those who have not. This question has not been well studied, however.", "output": "A 2004 prospective cohort study of 986,270 women found that, among asymptomatic women diagnosed with breast cancer (40 augmented, 238 nonaugmented), the sensitivity of screening mammograms was lower in women with breast implants (45%; 95% confidence interval [CI], 29.3%-61.5%) than those without (66.8%; 95% CI, 60.4%-72.8%); P=.008). Similarly, in symptomatic women diagnosed with breast cancer (41 augmented, 145 nonaugmented), screening sensitivity was lower in the augmented women (73.2%) than the nonaugmented women (81.4%)-although the results weren't significant (P=.25). Despite lower screening sensitivity, breast tumors in asymptomatic women, whether augmented or not, had similar characteristics, except for larger tumor size (3 mm) at diagnosis in augmented women. Symptomatic women with breast implants had cancers that were smaller, lower-grade, and more likely to be estrogen receptor dependent and invasive (P=.052) compared with nonaugmented women. The authors concluded that augmentation doesn't influence the prognostic characteristics of tumors, and they recommended screening mammography at appropriate intervals." }, { "input": "Nystatin oral suspension is a safe first-line therapy; fluconazole is more effective, but has not been approved by the Food and Drug Administration (FDA) for use in immunocompetent infants.", "output": "In the only prospective RCT (unblinded) to compare oral suspensions of fluconazole and nystatin, 34 infants were randomized to receive either nystatin (1 mL of 100,000 IU/mL) qid for 10 days or fluconazole (3 mg/kg) once a day for 7 days. Mothers of breastfed infants applied nystatin cream to their nipples twice a day for the duration of the infant's treatment. The clinical cure rate-defined as absence of oral plaques at the end of therapy (day 10 for the nystatin group, day 7 for the fluconazole group)-was significantly higher in the group treated with fluconazole (100% for fluconazole, 32% for nystatin; P<.0001, NNT=2). The eradication rate was also higher with fluconazole (73.3% for fluconazole, 5.6% for nystatin; P<.0001, NNT=2). The patients treated with fluconazole experienced no side effects." }, { "input": "Nystatin oral suspension is a safe first-line therapy; fluconazole is more effective, but has not been approved by the Food and Drug Administration (FDA) for use in immunocompetent infants.", "output": "Fluconazole has been shown to be effective, safe, and easy to use to treat thrush in immunocompromised children, but has not been approved by the FDA for use in healthy infants." }, { "input": "Miconazole oral gel is also more effective than nystatin suspension, but is not commercially available in the united states.", "output": "Nystatin has proved less effective than either miconazole gel or oral fluconazole." }, { "input": "Miconazole oral gel is also more effective than nystatin suspension, but is not commercially available in the united states.", "output": "An unblinded RCT assigned 83 immunocompetent infants with culture-positive oral thrush to receive either 25 mg miconazole oral gel (not commercially available in the United States) or nystatin suspension (1 mL of 100,000 IU/mL) qid after meals. The clinical cure rate, defined as absence of plaques by day 12, was significantly higher in the miconazole group (99% for miconazole, 54% for nystatin; P<.0001, number needed to treat [NNT]=2). The eradication rate, confirmed by cultures collected in a blinded manner on the day of clinical cure, was also higher in the miconazole group (55.7% for miconazole, 15.2% for nystatin; P<.0001, NNT=3). In successfully treated patients, infection recurred with similar frequency in both treatment groups within 4 weeks (miconazole, 12.4%; nystatin, 13.0%). Side effects-mostly vomiting and, infrequently, diarrhea-were rare in both groups (miconazole, 4.5%; nystatin 3.5%)." }, { "input": "Miconazole oral gel is also more effective than nystatin suspension, but is not commercially available in the united states.", "output": "An unblinded RCT of 95 infants compared miconazole gel to 2 nystatin oral gels (gel A: 250,000 IU/g with 250,000 IU administered as single dose; gel B: 100,000 IU/g with 50,000 IU administered as single dose). Each medication was given qid over the course of 8 to 14 days. The study confirmed higher clinical cure rates with miconazole gel (85.1% for miconazole vs 42.8% for nystatin gel A [P<.0007, NNT=2] and 48.5% for nystatin gel B [P<.004, NNT=3])." }, { "input": "Gentian violet may be effective, but it stains skin and clothes and is associated with mucosal ulceration.", "output": "A retrospective cohort study that reviewed 69 cases of oral thrush showed that gentian violet achieved a 75% cure rate in an average of 11 days (compared to 55% in 10 days for nystatin). Both treatments shortened the duration of illness compared with the average of 34 days for untreated children." }, { "input": "Gentian violet may be effective, but it stains skin and clothes and is associated with mucosal ulceration.", "output": "Gentian violet can stain skin and clothes, and case studies have shown an association with ulceration of the buccal mucosa." }, { "input": "No randomized controlled trials RCT have addressed pharmacologic prophylaxis of migraine for pregnant women. Two studies suggest that nonpharmacologic therapies combinations of skin warming, relaxation, biofeedback, and physical therapy not only relieved acute pain, but also decreased the frequency of headaches.", "output": "Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed alleviation of symptoms for 15 of 19 women. The second, a small unblinded RCT, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. Over 72% of the treatment arm improved compared with nearly 29% of the control group. The 30 women (19 from the original cohort and the 11 from the intervention arm of the RCT) were then followed as a cohort for the duration of pregnancy and 1 year postpartum. More than 67% of the patients continued to report a decrease in the frequency and severity of headache. Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community." }, { "input": "No randomized controlled trials RCT have addressed pharmacologic prophylaxis of migraine for pregnant women. Two studies suggest that nonpharmacologic therapies combinations of skin warming, relaxation, biofeedback, and physical therapy not only relieved acute pain, but also decreased the frequency of headaches.", "output": "Guidelines recommend considering prophylaxis for nonpregnant patients if they experience at least 3 or 4 prolonged severe attacks per month." }, { "input": "Practice guidelines and most review articles recommend avoiding prophylactic medications if possible. If a medication must be used, base the selection on both effectiveness for nonpregnant patients and established pregnancy safety from surveillance studies.", "output": "Practice guidelines published by the American Academy of Neurology recommend avoidance of prophylactic medications in pregnancy, if possible. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy. If drug treatment is necessary, they recommend selecting an agent with the lowest risk of adverse effects to the fetus." }, { "input": "Practice guidelines and most review articles recommend avoiding prophylactic medications if possible. If a medication must be used, base the selection on both effectiveness for nonpregnant patients and established pregnancy safety from surveillance studies.", "output": "Most review articles state that, if medication is necessary, it should be tailored towards other comorbidities, if possible; if there are no coexisting conditions, then calcium channel blockers or beta blockers would be the treatment of choice, based on safety data." }, { "input": "For children aged >6 months, a liberal amount of water-resistant, child-safe, broad-spectrum sunscreen (protecting from both UVA and UVB), with SPF \u226515 should be rubbed well into all exposed skin before going outside.", "output": "SPF-15 is considered by experts to be adequate to prevent sunburn, assuming use of a 2 mg/cm2 layer of sunscreen (typically, 30 cc for an average adult). However, observations suggest people apply less than half that." }, { "input": "Effectiveness may be increased if sunscreen is applied 30 minutes before exposure and reapplied every 2 hours, particularly if swimming. Tightly woven protective clothing, a wide-brimmed cap, and eye protection should also be used whenever possible.", "output": "A paired, split-body study of children receiving supervised single vs multiple applications of SPF-25 sunscreen to randomly assigned lateral halves of their bodies found protection to be equal for 6 hours of direct sunlight exposure. When the study was repeated with 8 hours of exposure, half the children developed mild erythema on the side with 1 application." }, { "input": "Sunburn early in life is a marker for increased risk of skin cancer in adulthood;however, evidence is insufficient that sunscreens lower skin cancer risk, as they also allow increased sun exposure.", "output": "A retrospective study of 6- to 7-year-old children found that sunscreen use correlated with an increasing number of nevi, though wearing clothing to cover skin while in the sun was protective." }, { "input": "Sunburn early in life is a marker for increased risk of skin cancer in adulthood;however, evidence is insufficient that sunscreens lower skin cancer risk, as they also allow increased sun exposure.", "output": "Case-control studies demonstrate that sunburn in childhood raises the risk of melanotic and nonmelanotic skin cancers, particularly among those with fair skin." }, { "input": "Sunburn early in life is a marker for increased risk of skin cancer in adulthood;however, evidence is insufficient that sunscreens lower skin cancer risk, as they also allow increased sun exposure.", "output": "A randomized controlled trial in adults supports that daily sunscreen use reduces the risk of squamous cell carcinoma but not basal cell carcinoma (number needed to treat=884 for 4.5 years)." }, { "input": "Sunburn early in life is a marker for increased risk of skin cancer in adulthood;however, evidence is insufficient that sunscreens lower skin cancer risk, as they also allow increased sun exposure.", "output": "A meta-analysis of 18 observational studies did not show an association between sunscreen use and melanoma incidence." }, { "input": "Sunburn early in life is a marker for increased risk of skin cancer in adulthood;however, evidence is insufficient that sunscreens lower skin cancer risk, as they also allow increased sun exposure.", "output": "A randomized controlled trial (RCT) demonstrated that regular use of broad-spectrum sunscreen in young school-aged children resulted in fewer melanotic nevi compared with controls." }, { "input": "Reactions to sunscreens are generally limited to skin irritation from the active ingredients or vehicles.", "output": "Sunscreens can cause skin irritation or allergic reaction to either the active ingredient or vehicle." }, { "input": "Reactions to sunscreens are generally limited to skin irritation from the active ingredients or vehicles.", "output": "A RCT of 603 adults found no allergic reactions to active sunscreen ingredients, though 19% of subjects had an irritant reaction or allergy to the base compounds." }, { "input": "Donepezil (Aricept) has potential benefit in delaying risk of progression to Alzheimer's disease in the first year of treatment, but this benefit is not seen at 3 years. Donepezil does not improve memory for patients with mild cognitive impairment.", "output": "A 24-week multicenter RCT included 270 patients with amnestic mild cognitive impairment. Patients were randomized to receive placebo or donepezil (5 mg/d for 42 days, followed by 10 mg/d). The primary end-points were changes on the New York University Paragraph Delayed Recall test and the Alzheimer's disease Cooperative Study Clinician's Global Impression of Change for Mild Cognitive Impairment (ADCS CGIC-MCI). No significant differences were found in the primary endpoints at 24 weeks-32.6% in the donepezil group vs 24.3 % in the placebo group showed minimal or moderate improvement, and 51.7% in the donepezil group vs 60.4% in the placebo group showed no change. Secondary endpoints included the modified ADAS-cog, the Patient global Assessment (PGA) and other neuropsychological tests. The ADAS-cog focuses on psychomotor speed and attention tests. Analysis of the ADAS-cog favored the donepezil group, with 22.3% showing a \u22657-point score vs 12.1% in the placebo group. There were no significant differences on the PGA in the intention-to-treat analysis. The donepezil group had a higher rate of adverse drug reactions (P<.03) including diarrhea, nausea, vomiting, leg cramps, and abnormal dreams. The discontinuation rate was 22% in the donepezil group compared with 8% in the placebo group (number needed to harm=7)." }, { "input": "Donepezil (Aricept) has potential benefit in delaying risk of progression to Alzheimer's disease in the first year of treatment, but this benefit is not seen at 3 years. Donepezil does not improve memory for patients with mild cognitive impairment.", "output": "The donepezil group had significantly higher rates diarrhea, muscle cramps, insomnia, nausea, and abnormal dreams (P<.01). There was no difference in discontinuation rates between the groups." }, { "input": "Donepezil (Aricept) has potential benefit in delaying risk of progression to Alzheimer's disease in the first year of treatment, but this benefit is not seen at 3 years. Donepezil does not improve memory for patients with mild cognitive impairment.", "output": "The National Institute of Aging conducted a double-blind RCT multicenter study, which enrolled a total of 769 subjects with mild cognitive impairment. The primary outcome was the development of possible or probable Alzheimer's disease, and secondary outcomes included cognition and function. Subjects were randomly assigned to receive 2000 IU of vitamin E, 10 mg of donepezil, or placebo daily for 3 years. Of the total, 214 (28%) of the study subjects progressed to dementia, with 212 classified as possible or probable Alzheimer's disease. Analysis of the treatment effects at 6-month intervals showed a decreased probability of progression to Alzheimer's disease in the donepezil group during the first 12 months of the study, compared with placebo (14.7% vs 6.3%; P=.04; number needed to treat [NNT]=12), but this change did not persist to 3 years. Several of the psychometric tests showed statistically significant differences (scores for Mini-Mental State Examination [MMSE], Clinical Dementia Rating [CDR] sum of boxes, Global Deterioration Scale, and modified Alzheimer's disease Assessment Scale-cognitive subscale [ADAS-cog]) early in the study, but the effect was only detected in the first 12 months of the study." }, { "input": "The evaluation of toe-walking focuses on differentiating normal children from those with mild cerebral palsy. Gait analysis may be a useful diagnostic tool, but further investigation is needed to confirm its reliability.", "output": "Kinematic analysis and observation of gait and measurement of ankle range of motion have been studied as diagnostic tools to differentiate idiopathic toe-walking from cerebral palsy." }, { "input": "The evaluation of toe-walking focuses on differentiating normal children from those with mild cerebral palsy. Gait analysis may be a useful diagnostic tool, but further investigation is needed to confirm its reliability.", "output": "In a study (23 children with mild cerebral palsy and 22 with idiopathic toe-walking), maximal knee extension occurred at ground contact in the idiopathic toe-walking group whereas in the mild cerebral palsy group, the knee was flexed at ground contact." }, { "input": "The evaluation of toe-walking focuses on differentiating normal children from those with mild cerebral palsy. Gait analysis may be a useful diagnostic tool, but further investigation is needed to confirm its reliability.", "output": "The only aspect of EMG testing that has been useful in differentiating cerebral palsy from idiopathic toe-walking is gastrocnemius coactivation during resisted knee extension-a finding indicative of neurologic pathology." }, { "input": "The evaluation of toe-walking focuses on differentiating normal children from those with mild cerebral palsy. Gait analysis may be a useful diagnostic tool, but further investigation is needed to confirm its reliability.", "output": "Case series with small numbers of subjects (range=27-41) have used gait electromyography (EMG) to distinguish cerebral palsy from idiopathic toe-walking. The overlap in gait EMG values in cerebral palsy and idiopathic toe-walking precludes its use as a differentiating diagnostic test." }, { "input": "Observation alone is generally as successful as serial casting and surgery in decreasing the frequency of toe-walking at follow-up.", "output": "In a case series (n=136), the frequency of toe-walking decreased in 51% of those in both the observation and casted groups. In this same study, the surgical group had lower rates of toe-walking, but no direct comparisons could be made to the nonsurgical groups because the patients in the surgical group were older and had longer follow-up than the other groups." }, { "input": "Observation alone is generally as successful as serial casting and surgery in decreasing the frequency of toe-walking at follow-up.", "output": "Three smaller studies (from 13 to 18 subjects) also showed decreased toe-walking at follow-up, regardless of treatment." }, { "input": "In short-term studies, furosemide reduces edema, reduces hospitalizations, and improves exercise capacity in the setting of systolic dysfunction (strength of recommendation.", "output": "A placebo-controlled trial assessed quality of life, edema, and New York Heart Association (NYHA) class, and demonstrated no change in these outcomes in the treatment and placebo groups." }, { "input": "In short-term studies, furosemide reduces edema, reduces hospitalizations, and improves exercise capacity in the setting of systolic dysfunction (strength of recommendation.", "output": "Faris et al conducted a meta-analysis of randomized controlled trials that used diuretics (pertanide, furosemide, furosemide-hydrochlorothiazide) in congestive heart failure (TABLE).4 Of the 18 trials, 8 were placebo-controlled and 10 used active controls (diuretics vs angiotensin-converting enzyme [ACE] inhibitors, digoxin, or ibopamine, a dopamine agonist). Three placebo-controlled trials (N=221) showed an absolute risk reduction in death of 8% in diuretic-treated patients (number needed to treat [NNT]=12.5). Four placebo-controlled trials (N=448) showed a significantly lower rate of admissions for worsening failure among diuretic-treated patients (NNT=8.5), and 4 of the active-controlled trials (N=150) showed a nonsignificant trend toward decreased admissions. Six active-controlled studies (N=174) showed significantly increased exercise capacity for patients on diuretics. The studies used in this meta-analysis had numerous shortcomings: the individual trials had small numbers of patients (N=14-139), short follow-up periods (typically 4-8 weeks), and inadequate statistical power to clearly demonstrate morbidity/mortality reductions. There was significant heterogeneity between studies. Crossover studies were included, some studies did not clearly report masking and assessment of outcome measures, and assessment of study validity was not clear. Studies employed a variety of diuretic types and doses, used different controls, and did not clarify whether patients' congestive heart failure was caused primarily by diastolic or systolic dysfunction." }, { "input": "There is potential morbidity with the use of high-dose loop diuretics (volume contraction, electrolyte disturbances, and neuroendocrine activation). Use of high-dose loop diuretics for systolic dysfunction is associated with increased mortality, sudden death, and pump failure death. However, diuretic resistance or disease severity may explain these latter findings.", "output": "One large retrospective study evaluated 6796 patients using potassium-sparing diuretics vs non-potassium-sparing diuretics in the Studies of Left Ventricular Dysfunction (SOLVD) trial. Rates of hospitalization or death from worsening congestive heart failure were significantly higher in the non-potassium-sparing diuretic population than in the nondiuretic population (relative risk [RR]=1.31, 95% confidence interval [CI], 1.09-1.57; number needed to harm=5.78). This increased risk was not found for patients taking potassium-sparing diuretics (RR=0.99; 95% CI, 0.76-1.30)." }, { "input": "There is potential morbidity with the use of high-dose loop diuretics (volume contraction, electrolyte disturbances, and neuroendocrine activation). Use of high-dose loop diuretics for systolic dysfunction is associated with increased mortality, sudden death, and pump failure death. However, diuretic resistance or disease severity may explain these latter findings.", "output": "A retrospective study of 1153 patients with NYHA Class III to IV heart failure, who were enrolled in the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), found high diuretic doses to be independently associated with mortality (adjusted hazard ratio [HR]=1.37; P=.004), sudden death (HR=1.39; P=.042), and pump failure death (HR=1.51; P=.034)." }, { "input": "There is potential morbidity with the use of high-dose loop diuretics (volume contraction, electrolyte disturbances, and neuroendocrine activation). Use of high-dose loop diuretics for systolic dysfunction is associated with increased mortality, sudden death, and pump failure death. However, diuretic resistance or disease severity may explain these latter findings.", "output": "A retrospective study of SOLVD patients found a significant and independent association with increased risk of arrhythmic death among patients taking non-potassium-sparing diuretics (RR=1.33; 95% CI, 1.05-1.69)." }, { "input": "Because dehydration is a risk factor for developing contrast nephropathy, periprocedural hydration is routinely recommended.", "output": "Clinical Evidence found support for the use of low-osmolality contrast media, periprocedural hydration, and acetylcysteine as interventions to reduce the risk of contrast nephropathy." }, { "input": "Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline.", "output": "An RCT showed that periprocedural hydration with isotonic saline is superior to half-normal saline in preventing contrast nephropathy (NNT=77)." }, { "input": "Single studies have suggested that isotonic saline is associated with less risk than half-normal saline, and hydration with fluids containing sodium bicarbonate is more efficacious than those containing isotonic saline.", "output": "An RCT showed decreased risk of contrast nephropathy for patients pretreated with intravenous fluids containing sodium bicarbonate compared with those pretreated with a sodium chloride solution (number needed to treat [NNT]=8.4)." }, { "input": "Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration. Acetylcysteine's low cost and favorable side effect profile make it an appealing option.", "output": "Periprocedural administration of acetylcysteine reduces the risk of contrast nephropathy in high-risk patients (odds ratio=0.56; 95% confidence interval, 0.37-0.84)." }, { "input": "Oral acetylcysteine lowers the risk of post-contrast elevations in creatinine if taken more than 24 hours before contrast administration. Acetylcysteine's low cost and favorable side effect profile make it an appealing option.", "output": "Preliminary evidence shows that intravenous administration of acetylcysteine immediately before contrast administration lowers the risk of contrast nephropathy. Oral acetylcysteine is low in cost and has no known side effects." }, { "input": "Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media", "output": "A single study suggested that iso-osmolar contrast media generate less contrast induced nephropathy than low-osmolar contrast media." }, { "input": "Hypoosmolar contrast media are less likely to induce contrast nephropathy than hyper-osmolar media", "output": "Several studies have demonstrated decreased risk of contrast nephropathy for high-risk patients when low-osmolality contrast media are used rather than high-osmolality contrast media (NNT=27)." }, { "input": "Finally, hemofiltration might be considered for patients with extremely high risk of developing contrast nephropathy.", "output": "A single RCT suggests that hemofiltration initiated 4 to 6 hours before contrast administration reduces the incidence of contrast nephropathy among high-risk patients. The study was unusual in that patients in the intervention group experienced statistically significant reductions in several clinically relevant outcomes, including in-hospital mortality and cumulative 1-year mortality (in-hospital mortality, NNT=8.3; cumulative 1-year mortality, NNT=5)." }, { "input": "No, in most cases, counseling does not prevent postpartum depression (PPD), though it can treat the disorder. Overall, psychosocial interventions don't offer a significantly greater benefit than standard care in preventing PPD-although studies do suggest a preventive benefit when the intervention is administered postnatally, in the home, and targeted toward individual at-risk women.", "output": "The National Collaborating Centre for Women's and Children's Health recommends against offering educational interventions to pregnant women because such interventions haven't been found to reduce PPD." }, { "input": "No, in most cases, counseling does not prevent postpartum depression (PPD), though it can treat the disorder. Overall, psychosocial interventions don't offer a significantly greater benefit than standard care in preventing PPD-although studies do suggest a preventive benefit when the intervention is administered postnatally, in the home, and targeted toward individual at-risk women.", "output": "An RCT of a 6-session cognitive-behavioral, midwife-administered intervention in mothers of preterm infants showed no preventive benefit (N=176; RR=1.02; 95% CI, 0.87-1.20)." }, { "input": "No, in most cases, counseling does not prevent postpartum depression (PPD), though it can treat the disorder. Overall, psychosocial interventions don't offer a significantly greater benefit than standard care in preventing PPD-although studies do suggest a preventive benefit when the intervention is administered postnatally, in the home, and targeted toward individual at-risk women.", "output": "A Cochrane meta-analysis of pooled data from 15 RCTs (7697 women) found that psychological interventions didn't prevent PPD based on comparison of initial depression scores with scores at the conclusion of the studies (relative risk [RR]=0.81; 95% confidence interval [CI], 0.65-1.02).1 Although some studies suggested short-term benefit (N=4091; RR=0.65; 95% CI, 0.43-1.00), benefits diminished over time and weren't noted when the definition of depression was limited to an Edinburgh Postpartum Depression Scale (EPDS) score below 12 (out of a maximum of 30). Some differences were found when the data were stratified. Certain interventions were found to prevent depressive symptoms (defined differently in the various studies). They were: home visits provided by healthcare professionals (2 RCTs, N=1663; RR=0.68; 95% CI, 0.55-0.84), interventions targeting at-risk women (7 RCTs, N=1162; RR=0.67; 95% CI, 0.51-0.89), and interventions begun postnatally (10 RCTs, N=6379; RR=0.76; 95% CI, 0.58-0.98). Notably, the level of training of providers of psychological interventions included in the meta-analysis was highly variable." }, { "input": "Psychotherapy and counseling-including interpersonal therapy, individual and group cognitive behavioral therapy (CBT), psychodynamic therapy, and nondirective counseling-are effective in treating PPD.", "output": "A systematic review of 5 RCTs (N=450) investigated the effectiveness of interpersonal psychotherapy, CBT (individual and group), nondirective counseling, and psychodynamic therapy in reducing PPD symptoms. Interpersonal therapy (12 weekly sessions) significantly reduced PPD symptoms as measured by the Hamilton Depression Rating Scale (HAM-D) compared with a wait-list control group (1 RCT, N=120, RR=2.11; 95% CI, 1.04-4.28). Individual CBT and ideal standard care (weekly 20- to 60-minute supportive meetings) were equally effective in reducing depression scores immediately postintervention and 6 months thereafter as measured by the EPDS (1 RCT, N=37). Although a trend toward greater benefit for CBT was noted, the study was underpowered to identify a significant difference. Nondirective counseling reduced the proportion of women with depression (N=55; RR=0.49; 95% CI, 0.26-0.95) and lowered EPDS scores (N=193; treatment effect=-2.1; 95% CI, -3.8 to -0.3; P=.02) compared with routine primary care. Individual CBT also reduced EPDS scores, when compared to routine primary care (N=55; treatment effect=-2.7; 95% CI, -4.5 to -0.9; P=.003). Psychodynamic therapy reduced the proportion of women with major depression (N=55; RR=1.89; 95% CI, 1.33-2.33). All of these interventions improved PPD immediately following treatment compared with routine primary care, but the benefits were not sustained at long-term follow-up (6 months). Study limitations included failure to control for multiple comparisons, pretreatment group differences, differential attrition among groups, and lack of sufficient power." }, { "input": "Psychotherapy and counseling-including interpersonal therapy, individual and group cognitive behavioral therapy (CBT), psychodynamic therapy, and nondirective counseling-are effective in treating PPD.", "output": "An RCT (N=121) also found psychological interventions (group CBT and group and individual counseling) to be superior to routine primary care, with individual counseling yielding the greatest improvement in PPD symptoms (P<.05)." }, { "input": "Psychotherapy and counseling-including interpersonal therapy, individual and group cognitive behavioral therapy (CBT), psychodynamic therapy, and nondirective counseling-are effective in treating PPD.", "output": "The Scottish Intercollegiate Guidelines Network recommends \"postnatal visits, interpersonal therapy, and/or antenatal preparation\" to prevent PPD. To treat PPD, they recommend psychosocial interventions, preferably those that include more than 1 family member." }, { "input": "Not enough evidence exists to compare the benefits of antidepressant medication with CBT.", "output": "In an RCT (N=87), fluoxetine and placebo were each paired with 1 or 6 CBT sessions. After 12 weeks of treatment, fluoxetine was superior to placebo as measured by mean symptom score reduction on the HAM-D, EPDS, and clinical interview schedule; 6 CBT sessions were superior to a single session as measured by mean symptom score reduction on the Hamilton Depression Scale and clinical interview schedule. No significant interaction effect was found." }, { "input": "Not enough evidence exists to compare the benefits of antidepressant medication with CBT.", "output": "A small RCT (N=35) compared 12 weeks of paroxetine with a combination of paroxetine and CBT. Significant improvements-defined as percentage of patients in each group demonstrating at least a 50% score reduction on the HAM-D (paroxetine, 87.5%; combination, 78.9%) and EPDS (paroxetine, 61.5%; combination, 58.3%)-occurred in both groups (P<.01), but no difference was found between the groups. The study didn't include a placebo control group." }, { "input": "Evaluative management (including prosthesis adjustment, treatment of referred pain, and residual limb care) should be tried initially.", "output": "Because residual limb pain can exacerbate PLP, adjusting a poorly fitting prosthesis or providing the patient with NSAIDs when there is evidence of stump inflammation may adequately control pain." }, { "input": "Evaluative management (including prosthesis adjustment, treatment of referred pain, and residual limb care) should be tried initially.", "output": "Anatomically distant pain syndromes, such as hip or lower back pain, can also aggravate PLP and should be managed to provide optimal pain relief." }, { "input": "Other first-line treatments such as transcutaneous electrical nerve stimulation (TENS) can reduce PLP", "output": "Desensitization, using TENS, has reduced PLP in multiple placebo-controlled trials and epidemiologic surveys." }, { "input": "Other first-line treatments such as transcutaneous electrical nerve stimulation (TENS) can reduce PLP", "output": "The long-term effectiveness of TENS in alleviating PLP remains unknown. Some experts suggest that pain reductions after 1 year of treatment are comparable to placebo." }, { "input": "Biofeedback can reduce PLP.", "output": "Psychotherapy can reportedly reveal the underlying mechanisms (muscle spasm, vascular insufficiency) and therefore direct therapeutic interventions by biofeedback or other focus techniques." }, { "input": "Biofeedback can reduce PLP.", "output": "Psychotherapy, including biofeedback, has been found in several case studies to effectively treat chronic PLP." }, { "input": "Pharmacotherapy, including opioids, anticonvulsants (gabapentin), and nonsteroidal anti-inflammatory drugs NSAIDs, can relieve pain.", "output": "Morphine (number needed to treat [NNT]=2.5; 95% confidence interval [CI], 1.9-3.4) and other opioids, including tramadol (NNT=3.9; 95% CI, 2.7-6.7 in neuropathic pain) help some patients." }, { "input": "Pharmacotherapy, including opioids, anticonvulsants (gabapentin), and nonsteroidal anti-inflammatory drugs NSAIDs, can relieve pain.", "output": "Although PLP is typically treated as neuropathic pain, only a few medications have been critically evaluated for treating it." }, { "input": "Pharmacotherapy, including opioids, anticonvulsants (gabapentin), and nonsteroidal anti-inflammatory drugs NSAIDs, can relieve pain.", "output": "Pharmacotherapy is best used as an adjunct to other treatments." }, { "input": "Pharmacotherapy, including opioids, anticonvulsants (gabapentin), and nonsteroidal anti-inflammatory drugs NSAIDs, can relieve pain.", "output": "A 2006 RCT of gabapentin did not identify significant pain reductions." }, { "input": "Pharmacotherapy, including opioids, anticonvulsants (gabapentin), and nonsteroidal anti-inflammatory drugs NSAIDs, can relieve pain.", "output": "One 2002 RCT showed benefit regarding an improvement of the visual analog scale by an average of 3 points (on a 10-point scale) after 6 weeks of gabapentin therapy." }, { "input": "Pharmacotherapy, including opioids, anticonvulsants (gabapentin), and nonsteroidal anti-inflammatory drugs NSAIDs, can relieve pain.", "output": "Anticonvulsants, including gabapentin, have documented benefit in neuropathic pain modalities and are often used for PLP. However, their value in reducing PLP is still under investigation." }, { "input": "Pharmacotherapy, including opioids, anticonvulsants (gabapentin), and nonsteroidal anti-inflammatory drugs NSAIDs, can relieve pain.", "output": "Despite the proven benefit of tricyclic antidepressants (TCAs) in other neuropathic pain conditions, a recent RCT demonstrated no benefit of TCAs over placebo in PLP." }, { "input": "Adjuvant therapies (mirror box therapy, acupuncture, calcitonin, and N-methyl d-aspartate receptor antagonists) haven't been rigorously investigated for alleviating PLP, but can be considered for patients who have failed other treatments.", "output": "Of the adjuvant treatments, only mirror box therapy has shown promise. This technique allows the amputee to perceive the missing limb by focusing on the reflection of the remaining limb during specific movements and activities. Theoretically, this perception allows reconfiguration of the amputee's sensory cortex. Virtual reality therapy employs similar techniques based on the idea that the brain can be deceived. Initial case studies are promising and have prompted further research." }, { "input": "No evidence clearly supports the practice of increased fetal surveillance in the pregnancies of women with well-controlled (ie, fasting blood sugar <105 mg/dL) class A1 gestational diabetes.", "output": "A Cochrane review found no evidence for or against increased surveillance in A1 gestational diabetes: \"A lack of conclusive evidence has lead clinicians to equate the risk of adverse perinatal outcome with pre-existing diabetes. Consequently women are often managed with increased obstetrical monitoring, dietary regulation, and [pharmacological] treatment. However, no sound evidence base supports such intensive treatment.\"" }, { "input": "No evidence clearly supports the practice of increased fetal surveillance in the pregnancies of women with well-controlled (ie, fasting blood sugar <105 mg/dL) class A1 gestational diabetes.", "output": "A retrospective study followed 97 pregnant patients with gestational diabetes, 69 of whom were diet-controlled (class A1, fasting glucose <105 mg/dL).5 Antepartum surveillance consisted of maternal monitoring and non-stress testing. At 28 weeks, pregnant patients assessed daily fetal activity; reassuring fetal well-being was defined as 10 fetal movements in a 12-hour period. At 40 weeks, a non-stress test was performed weekly. Contraction stress testing was performed for those with nonreactive non-stress tests. To observe for macrosomia, serial ultrasonography was performed every 4 to 6 weeks, starting at 28 weeks. Forty-four patients (64%) had spontaneous labors without intervention, while the rest required induction of labor or cesarean section (primary or failed induction). Five patients had primary cesarean section for suspected macrosomia, 3 patients had intervention for suspected intrauterine growth restriction, and only 4 (5.7%) patients were delivered due to fetal indications, defined as decreased fetal movement or a nonreactive nonstress test. No stillbirths or neonatal deaths occurred. Perinatal complications included hypoglycemia (n=13; 19%), hyperbilirubinemia (n=12; 17%), and macrosomia (n=11; 16%). The study did not compare complication rates between diet-controlled and insulin-requiring patients." }, { "input": "No evidence clearly supports the practice of increased fetal surveillance in the pregnancies of women with well-controlled (ie, fasting blood sugar <105 mg/dL) class A1 gestational diabetes.", "output": "One study evaluated antepartum predictors of fetal distress requiring a cesarean delivery among 2134 pregnant women with gestational diabetes. Antepartum surveillance consisted of biweekly nonstress testing with amniotic fluid index determination starting at 34 weeks gestation. Of the 1501 eligible participants, the study included 810 and 580 class A1 and A2 patients, respectively; the remaining 111 were classes B-T. They considered women with A1 gestational diabetes with fasting plasma glucose levels <105 mg/dL to be well-controlled. Results of antepartum surveillance did not significantly differ among the different diabetic classes." }, { "input": "Some patients who have been diagnosed with Barrett's esophagus will develop dysplasia and, in some cases, esophageal carcinoma.", "output": "Surveillance by serial endoscopy with biopsy has been recommended in an effort to find high-grade dysplasia or carcinoma in an early, asymptomatic, and potentially curable stage." }, { "input": "Endoscopic surveillance is recommended for all patients with Barrett's esophagus as it is superior to other methods for detecting esophageal cancer.", "output": "A systematic review assessing screening tools for esophageal carcinoma found standard endoscopy to be superior (90%-100% sensitivity) to other less invasive methods such as questionnaire (60%-70%), and fecal occult blood testing (20%). Additional endoscopy tools such as brush and balloon cytology increased the cost of surveillance without any improvement in diagnostic yield." }, { "input": "The degree of dysplasia noted on biopsy specimens correlates with the risk of esophageal carcinoma development and should guide the frequency of subsequent evaluations.", "output": "The degree of dysplasia on esophageal biopsy in Barrett's esophagus patients is currently the best indicator of risk of progression to esophageal carcinoma. The data reviewed by the ACG for the practice guideline was drawn from several prospective studies and one available registry. In sum, a total of 783 Barrett's esophagus patients were followed for a mean of 2.9 to 7.3 years. Esophageal carcinoma developed in 2% of patients with no dysplasia, 7% of patients with low-grade dysplasia (LGD) and 22% of patients with high-grade dysplasia (HGD). The ACG recommendations regarding frequency of esophagogastroduodenoscopy (EGD) were not based on an explicit critical appraisal of the literature. Recent cohort studies are consistent with recommendations for graded surveillance frequency. A randomized clinical trial to determine optimal endoscopic frequency and benefit has not been reported." }, { "input": "The degree of dysplasia noted on biopsy specimens correlates with the risk of esophageal carcinoma development and should guide the frequency of subsequent evaluations.", "output": "A case-series reported a series of 34 patients with LGD at initial pathologic examination. On subsequent surveillance endoscopy with repeat biopsy, 73% no longer demonstrated dysplasia. Such patients can be allowed to return to having surveillance every 3 years." }, { "input": "The degree of dysplasia noted on biopsy specimens correlates with the risk of esophageal carcinoma development and should guide the frequency of subsequent evaluations.", "output": "Recommendations for frequent endoscopic surveillance are also weakened by the overall low rate of mortality from esophageal carcinoma noted in Barrett's esophagus patients. A recent population based study demonstrated that there was no difference in overall mortality in those with a Barrett's esophagus diagnosis compared with the general population.6 An increased risk of death from esophageal carcinoma was seen in patients with Barrett's esophagus (4.7% seen in Barrett's esophagus patients compared with 0.8% predicted in the general population; P<.05). The overall increased effect on mortality, however, was relatively small. Esophageal carcinoma accounted for less then 5% of deaths in Barrett's esophagus patients reported during the study's 6-year follow-up period." }, { "input": "The optimal frequency of endoscopy has yet to be determined in any randomized trial.", "output": "Recommendations for frequent endoscopic surveillance are also weakened by the overall low rate of mortality from esophageal carcinoma noted in Barrett's esophagus patients. A recent population based study demonstrated that there was no difference in overall mortality in those with a Barrett's esophagus diagnosis compared with the general population.6 An increased risk of death from esophageal carcinoma was seen in patients with Barrett's esophagus (4.7% seen in Barrett's esophagus patients compared with 0.8% predicted in the general population; P<.05). The overall increased effect on mortality, however, was relatively small. Esophageal carcinoma accounted for less then 5% of deaths in Barrett's esophagus patients reported during the study's 6-year follow-up period." }, { "input": "The optimal frequency of endoscopy has yet to be determined in any randomized trial.", "output": "Inter-rater reliability of the interpretation of pathology specimens varies substantially. Adequate reliability has been demonstrated among pathologists assigning results to 2 categories (either no dysplasia and LGD or HGD and carcinoma) (\u03f0=0.7). Assignment to four distinct pathologic grades, however, was not reliable (\u03f0=0.46, where 1.0 is complete agreement). The length of the dysplastic Barrett's esophagus segment is emerging as a potentially predictive risk factor. While the ACG cautions that esophageal cancer has been reported in patients with so-called \"short segment\" Barrett's esophagus (SSBE) (\u22643 cm)." }, { "input": "The optimal frequency of endoscopy has yet to be determined in any randomized trial.", "output": "A case-series reported a series of 34 patients with LGD at initial pathologic examination. On subsequent surveillance endoscopy with repeat biopsy, 73% no longer demonstrated dysplasia. Such patients can be allowed to return to having surveillance every 3 years." }, { "input": "Recommendations from the 2002 American College of Gastroenterology (ACG) Practice Guideline provide guidance as to the frequency of endoscopy surveillance but were not based on an explicit systematic review of the literature.", "output": "The ACG recommendations regarding frequency of esophagogastroduodenoscopy (EGD) were not based on an explicit critical appraisal of the literature." }, { "input": "Yes, taking this step helps asthmatic children, and may even help nonasthmatic children. In families of asthmatic children, education to reduce exposure to secondhand smoke leads to fewer medical visits.", "output": "A trial that measured changes in urine cotinine randomized 91 families with a smoking parent and an asthmatic child into 3 groups: A control group received usual care (regular office visits at an asthma clinic and medication management); A monitoring group used a parental smoking diary and a children's asthma symptom diary; And a counseling group received 5 counseling sessions and also kept diaries. An environmental monitor in the home was used to assess exposure to secondhand smoke. In the counseling group, 21.4% of patients (6 of 28) maintained 0% exposure throughout the 30-month trial period compared with 3.6% and 3.8% in the monitoring and control groups, respectively (P<.05 for comparison of counseling group to monitoring and control)." }, { "input": "Yes, taking this step helps asthmatic children, and may even help nonasthmatic children. In families of asthmatic children, education to reduce exposure to secondhand smoke leads to fewer medical visits.", "output": "A 2001 trial randomized 81 families with a smoking parent and an asthmatic child between 3 and 12 years of age to 3 sessions of behavioral and educational counseling or usual care at an outpatient asthma clinic. Parental education included information on second-hand smoke, basic asthma education, and feedback about urine cotinine levels (a marker of nicotine absorption). Behavioral counseling focused on reducing second-hand smoke exposure by caregivers. The education group had a significantly reduced risk of 2 or more asthma-related clinic visits in the following 12 months compared with usual care (odds ratio=0.32; P=.03; number needed to treat=5). No significant decrease was noted in mean urine cotinine levels between groups (adjusted mean difference=-0.38 ng/mg favoring education; P=.26)." }, { "input": "The effects of educating families of nonasthmatic children about secondhand smoke are not known, but parents who smoke outside expose their children to much less nicotine than parents who smoke in the house.", "output": "A 2003 cross-sectional survey of 164 households in the United Kingdom with at least 1 smoking parent and 1 bottle-fed infant looked for a correlation between strategies to reduce second-hand smoke and urine cotinine-to-creatinine ratios in the infants. Parents were classified into 3 groups according to whether they maintained a strict ban on smoking in the home, a less strict ban (smoking at home but not near the infant), or no ban. The mean infant urinary cotinine-to-creatinine ratio was 2.43 in the no-ban group and 2.61 in the less-strict ban group (difference not significant). The combined mean for these 2 groups-2.58-was significantly higher than the mean of 1.26 in the strictest group (P<.001)." }, { "input": "The effects of educating families of nonasthmatic children about secondhand smoke are not known, but parents who smoke outside expose their children to much less nicotine than parents who smoke in the house.", "output": "A study recruited a convenience sample of 49 interested families with a smoking mother and a nonbreastfeeding infant between 2 and 12 months of age. Families were classified by smoking history into one of 3 groups: nonsmoking households, smoking households where efforts were made to limit smoke exposure, and smoking households where no efforts were made to limit exposure. Urine samples were obtained 3 times over 1 week. Urine cotinine levels in infants averaged 0.33 ng/mL in nonsmoking households, 2.47 ng/mL in smoking households with limited exposure, and 15.47 ng/mL in smoking households with unlimited exposure (P<.001 for all comparisons)." }, { "input": "The effects of educating families of nonasthmatic children about secondhand smoke are not known, but parents who smoke outside expose their children to much less nicotine than parents who smoke in the house.", "output": "A case-control study that recruited families with asthmatic and nonasthmatic children assessed the effectiveness of parental behaviors to reduce second-hand smoke in 182 households with 1 smoking parent and a child between 6 and 12 years of age. Researchers measured room air nicotine and salivary cotinine concentrations. The nicotine levels on children's belts and in their bedrooms and the family room were approximately 3 log units lower in houses with strict smoking bans compared with households with any degree of indoor smoking (P<.0001). Similarly, salivary cotinine levels were approximately 4 log units lower in children of households with indoor smoking bans (P<.0001)." }, { "input": "Topical or oral nonsteroidal anti-inflammatory medications (NSAIDs), corticosteroid injection, and acupuncture are more helpful than placebo in treating lateral epicondylitis, or tennis elbow.", "output": "A Cochrane systematic review evaluating the efficacy of topical and oral NSAIDs to treat lateral epicondylitis found that topically applied diclofenac gel was more effective than placebo, as measured by overall patient satisfaction (relative risk [RR]=0.39; 95% confidence interval [CI], 0.23-0.66; number needed to treat [NNT]=3). Topical diclofenac or benzydamine gel had a significant effect on the patient's perception of pain compared with placebo, but not beyond 4 weeks of therapy (weighted mean difference [WMD] on a 10-point scale=-1.88 points; 95% CI, -2.54 to -1.21). However, no difference was noted in functional outcomes, measured by grip or wrist extension strength. Patients who used topical NSAIDs reported more adverse events than those using placebo, including minor skin irritation (RR=2.26; 95% CI, 1.04-4.94). Oral diclofenac reduced pain scores at 4 weeks compared with placebo (WMD on 100-point scale=-13.9 points; 95% CI, -23.21 to -4.59). Adequate studies are lacking to show a benefit of oral NSAIDs past 4 weeks. Significantly more complaints of abdominal pain occurred with oral diclofenac than placebo (RR=3.17; 95% CI, 1.35-7.41; number needed to harm [NNH]=5).." }, { "input": "Topical or oral nonsteroidal anti-inflammatory medications (NSAIDs), corticosteroid injection, and acupuncture are more helpful than placebo in treating lateral epicondylitis, or tennis elbow.", "output": "An individual RCT, cited in a Cochrane review, showed acupuncture had a very short-term benefit for pain relief compared with placebo (WMD=18.8 hours; 95% CI, 10.1-27.5). Another individual RCT, which was not included in the meta-analysis because of methodologic problems in the other studies, found that a short course of 10 acupuncture treatments resulted in an excellent or good outcome as reported by participants compared with placebo (RR=0.09; 95% CI, 0.01-0.64; NNT=4). No benefit was noted after 3 or 12 months." }, { "input": "A corticosteroid injection is effective for short-term therapy-as long as 6 weeks-but produces no long-term improvement. Physiotherapy or a wait-and-see approach are superior to corticosteroid injection at 52 weeks.", "output": "A subanalysis of 4 studies in another systematic review found corticosteroid injections to be superior to other conservative treatments such as elbow supports, oral NSAIDs, and physiotherapy at 2 to 6 weeks (RR=0.50; 95% CI, 0.36-0.70). The positive effects weren't maintained at 6 weeks." }, { "input": "A corticosteroid injection is effective for short-term therapy-as long as 6 weeks-but produces no long-term improvement. Physiotherapy or a wait-and-see approach are superior to corticosteroid injection at 52 weeks.", "output": "I a randomized study with 3 treatment arms, 185 patients were treated with a corticosteroid injection, physiotherapy, or a wait-and-see approach (ergonomic advice, rest, and oral anti-inflammatory medication). Corticosteroid injections were significantly more effective for the patients' main complaint at 6 weeks compared with wait-and-see (mean difference in improvement [MDI] on a 100-point scale=24; 95% CI, 14-35; NNT=2) or physiotherapy (MDI=20; 95% CI, 10-31; NNT=2). By contrast, at 26 and 52 weeks' follow-up, physiotherapy was more effective than steroid injections (MDI=15; 95% CI, 5-25) but statistically equivalent to a wait-and-see approach (MDI=7; 95% CI, -4 to 17)." }, { "input": "There's insufficient evidence to support specific physiotherapy methods or orthoses (braces), shock wave therapy, ultrasound, or deep friction massage.", "output": "In an RCT, physiotherapy and exercise were significantly better than a wait-and-see approach at 6 weeks for pain-free grip force, rating of pain severity, and global improvement (RR=0.5; 99% CI, 0.2-0.8; NNT=3), but by 52 weeks the outcomes were statistically equal." }, { "input": "There's insufficient evidence to support specific physiotherapy methods or orthoses (braces), shock wave therapy, ultrasound, or deep friction massage.", "output": "In a meta-analysis of 3 trials, shock wave therapy provided no significant benefit at 4 to 6 weeks compared with placebo (WMD on a 100-point scale=-9.42; 95% CI, -20.70 to 1.86)." }, { "input": "There's insufficient evidence to support specific physiotherapy methods or orthoses (braces), shock wave therapy, ultrasound, or deep friction massage.", "output": "Systematic reviews of specific physiotherapy or orthotic (bracing) treatments are hampered by the large number of treatment options available and the heterogeneity of the available studies, which prevent statistically useful evaluation." }, { "input": "There's insufficient evidence to support specific physiotherapy methods or orthoses (braces), shock wave therapy, ultrasound, or deep friction massage.", "output": "Another Cochrane review found no added benefit in function from combining deep transverse friction massage with ultrasound or a placebo ointment (RR=3.3; 95% CI, 0.4-24.3)." }, { "input": "There's insufficient evidence to support specific physiotherapy methods or orthoses (braces), shock wave therapy, ultrasound, or deep friction massage.", "output": "Pooling 2 studies in a different systematic review showed weak evidence that ultrasound reduced pain at 13 weeks compared with placebo (standardized mean difference=-0.98; 95% CI, -1.64 to -0.33)." }, { "input": "Surgery may succeed in refractory cases that have failed extensive conservative measures.", "output": "Splinting, acupuncture, and corticosteroid administration by injection or iontophoresis may reduce pain for as long as 2 to 6 weeks. If these conservative measures fail, surgical treatment is recommended as a last resort." }, { "input": "It may, depending on the stage of labor and whether the woman has given birth previously. Routine amniotomy doesn't significantly reduce the duration of first-stage labor in either primiparous or multiparous women.", "output": "A Cochrane review of 14 trials (4893 women) investigated the risks and benefits of routine amniotomy vs intention to leave membranes intact. All trials included only very-low-risk women in spontaneous labor at term with a singleton fetus in vertex presentation. Five of the trials (1127 women) reported length of first-stage labor. No statistically significant difference was found between amniotomy and control groups (weighted mean difference [WMD]=-20.43 minutes; 95% confidence interval [CI], -95.93 to 55.06). Furthermore, subgroup analysis found no statistically significant reduction in length of first-stage labor for nulliparous (WMD=-57.93 min; 95% CI, -152.66 to 36.80) or multiparous women (WMD= 23.10 min; 95% CI, -50.89 to 97.09)." }, { "input": "It may, depending on the stage of labor and whether the woman has given birth previously. Routine amniotomy doesn't significantly reduce the duration of first-stage labor in either primiparous or multiparous women.", "output": "The extent to which amniotomy alone shortens labor varies widely from study to study, and no clear consensus exists concerning the potential harms or unintended effects of this practice." }, { "input": "Routine amniotomy slightly shortens second-stage labor in primiparous women only.", "output": "The extent to which amniotomy alone shortens labor varies widely from study to study, and no clear consensus exists concerning the potential harms or unintended effects of this practice.-." }, { "input": "Routine amniotomy slightly shortens second-stage labor in primiparous women only.", "output": "A Cochrane review of 14 trials (4893 women) investigated the risks and benefits of routine amniotomy vs intention to leave membranes intact. All trials included only very-low-risk women in spontaneous labor at term with a singleton fetus in vertex presentation.Seven trials (1237 women) in the Cochrane review reported length of second-stage labor. No statistically significant difference was noted between amniotomy and control groups (WMD=-2.38 minutes; 95% CI, -5.27 to 0.50). However, subgroup analysis of primiparous women showed a statistically significant reduction in length of second-stage labor in the amniotomy group (WMD=-6.59 minutes; 95% CI, -12.34 to -0.84)." }, { "input": "A trend toward increased rates of cesarean section has been noted in low-risk women who undergo routine amniotomy.", "output": "A Cochrane review of 14 trials (4893 women) investigated the risks and benefits of routine amniotomy vs intention to leave membranes intact. All trials included only very-low-risk women in spontaneous labor at term with a singleton fetus in vertex presentation. Nine trials (4370 women) included in the Cochrane review reported cesarean section rates. Women in the amniotomy group had an increased risk of cesarean delivery compared with the control group, but the difference did not reach statistical significance (relative risk=1.26; 95% CI, 0.98-1.62). Because cesarean section was surprisingly rare in this low-risk patient population compared with the national average, the studies were not powered to show statistical significance in this secondary outcome." }, { "input": "The procedure doesn't appear to affect neonatal outcomes.", "output": "No significant differences between the amniotomy and intact groups were noted in less uniformly reported maternal outcomes, including need for oxytocin to augment labor, rate of infection, serious morbidity, or death. Likewise, differences in neonatal outcomes-such as sepsis, respiratory failure, admission to the special care unit, and death-weren't statistically significant. Notably, however, these secondary outcomes occurred too rarely to measure the effect precisely." }, { "input": "other", "output": "ACOG bulletin on induction of labor reports that \"the potential risks associated with amniotomy include prolapse of the umbilical cord, chorioamnionitis, significant umbilical cord compression, and rupture of vasa previa.\"." }, { "input": "other", "output": "The American College of Obstetricians and Gynecologists ACOG hasn't issued a statement on the use of routine amniotomy in normal labor. With regard to labor dystocia, ACOG states that \"amniotomy may enhance progress in the active phase and negate the need for oxytocin augmentation, but it may increase the risk of chorioamnionitis.\"." }, { "input": "Tricyclic antidepressants and intensive multi-disciplinary programs are moderately effective for reducing chronic back pain; tricyclics are also effective for diabetic neuropathy and irritable bowel syndrome.", "output": "Tricyclics are effective for diabetic neuropathy (number needed to treat [NNT]=3.5 for 50% reduction of pain), and they are effective for reducing pain but not for global symptoms in irritable bowel syndrome. Amitriptyline reduces the pain of diabetic peripheral neuropathy in a dose related manner up to 150 mg/d, although much lower doses are often effective and cause fewer anticholinergic side-effects." }, { "input": "Tricyclic antidepressants and intensive multi-disciplinary programs are moderately effective for reducing chronic back pain; tricyclics are also effective for diabetic neuropathy and irritable bowel syndrome.", "output": "It appears that those with only SSRI activity are not effective improving chronic pain." }, { "input": "Tricyclic antidepressants and intensive multi-disciplinary programs are moderately effective for reducing chronic back pain; tricyclics are also effective for diabetic neuropathy and irritable bowel syndrome.", "output": "Amitriptyline and other tricyclic and tetracyclic antidepressants moderately improve pain control for patients with chronic back pain.1,2 The pain reduction was independent of the presence of depression, although patients who were depressed had a significant improvement in mood. The outcome on chronic pain of antidepressants with serotonin and norepinephrine reuptake inhibitory activity is still being evaluated." }, { "input": "Cognitive therapies are modestly effective for reducing pain in the following: chronic back pain, other chronic musculoskeletal disorders including rheumatoid arthritis.", "output": "For chronic back pain, a Cochrane review including 1964 patients found strong evidence for pain reduction and modest evidence for functional improvement from intensive (>100 hours) multidisciplinary biopsychosocial rehabilitation. Less intense and less comprehensive psychophysical programs did not reduce pain or improve function. It was unclear if the intensive programs were generalizable" }, { "input": "Cognitive therapies are modestly effective for reducing pain in the following: chronic back pain, other chronic musculoskeletal disorders including rheumatoid arthritis.", "output": "A review found that cognitive and progressive relaxation therapy had a moderate effect on short-term pain control vs waiting-list controls for chronic back pain. However, only a third of the studies were of \"high quality,\" and the total number of patients in the relaxation analysis was 39." }, { "input": "Cognitive therapies are modestly effective for reducing pain in the following: chronic back pain, other chronic musculoskeletal disorders including rheumatoid arthritis.", "output": "A systematic review of 25 studies (1672 patients) found significant effect sizes for cognitive therapies in reducing pain and other symptoms in chronic musculoskeletal pain, including rheumatoid arthritis, fibromyalgia, back, and other pain syndromes. However, many of the trials were small or taken from \"samples of convenience\" from rehabilitation and pain clinics, and most lacked documentation of randomization." }, { "input": "Cognitive therapies are modestly effective for reducing pain in the following: chronic back pain, other chronic musculoskeletal disorders including rheumatoid arthritis.", "output": "For rheumatoid arthritis alone, a systematic review of 19 studies found cognitive therapies had a small but statistically significant effect on pain, functional disability, depression, coping, and self-efficacy for 1298 patients at initial follow-up. However, only \"tender points\" and coping remained improved at subsequent follow-ups averaging 8.5 months." }, { "input": "Cognitive therapies are modestly effective for reducing cronic cancer pain.", "output": "In adults with cancer pain, a recent meta-analysis of 1723 patients showed modest but significant effects on pain from psycho-educational interventions in 25 studies. Although just 3 of the studies lasted 52 weeks or longer, effects were found from good-quality studies for \"relaxation-promoting,\" educational, and supportive counseling plus content therapies." }, { "input": "other", "output": "A significant confounder in many of these studies may be that some treatments seem more effective in secondary care than in primary care settings, as based on a systemic review of interventions for somatic symptoms in primary care." }, { "input": "Pentoxifylline improves short-term survival in patients admitted to the hospital with severe alcoholic hepatitis.", "output": "In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant)." }, { "input": "Pentoxifylline improves short-term survival in patients admitted to the hospital with severe alcoholic hepatitis.", "output": "In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks. Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures. Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given)." }, { "input": "Pentoxifylline improves short-term survival in patients admitted to the hospital with severe alcoholic hepatitis.", "output": "In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B12 tablets) for 4 weeks. The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 x [prothrombin time in seconds - control time] + bilirubin (mg/dL). Medical management was \"individualized according to each patient's condition\". Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed." }, { "input": "Pentoxifylline does not improve survival when it is substituted for steroids in hospitalized patients who aren't responding to steroids.", "output": "A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn't respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day. In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn't statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency)." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "Most authorities recommend empiric treatment with cryotherapy during the acute inflammatory phase-the first 24 to 48 hours after injury.Although not rigorously studied, some sources recommend applying cold to the involved muscle for the first 4 hours after injury at intervals of 10 to 20 minutes every 30 to 60 minutes." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "A study of 21 rats showed improvement in associated physiological components with cryotherapy, but no statistically significant improvement in edema." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "One study cited a significant reduction in inflammatory cells, based on histologic examination, in 43 rats between 6 and 24 hours after trauma." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "Laboratory studies on rats have also demonstrated beneficial effects of cryotherapy after simulated soft-tissue injuries." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "A 2007 review evaluated 66 publications and found only 1 randomized controlled trial conducted on humans. The intervention in this trial involved applying cold gel 4 times a day for the first 14 days after the injury. The control group received a room-temperature gel application; neither group was aware of the temperature differential. The study found significant reduction in pain at rest, pain with movement, and functional disability at intervals of 7, 14, and 28 days postinjury (P<.001) among patients receiving cold-gel applications. Patients receiving cold-gel treatment also reported increased satisfaction with treatment compared with the controls. At 28 days, cold-gel treatment patients scored 71 on a 100-point satisfaction scale compared with 44 for controls (P<.001). Inconclusive results or significant design flaws limited the validity of all other trials cited in this review." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "Cryotherapy has been the recommended initial treatment for muscle strain for more than 30 years, based generally on expert opinion and physiological models, not clinical trials. Theoretically, cryotherapy controls hemorrhage and tissue edema, whereas heat enhances the inflammatory response." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "A comprehensive review of the literature revealed no studies that compare heat and cryotherapy to treat acute soft-tissue injury. Well-designed human trials of general management of acute soft-tissue injury are rare." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "Authoritative textbooks consistently recommend applying ice for initial treatment of musculoskeletal and soft-tissue strains." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "A 2006 Cochrane review that addressed treatment of lower back muscular strain, not soft-tissue injuries in general, found moderate evidence that heat therapy reduces pain by 17% and disability in the acute setting (P=.001). The review also cited 2 head-to-head trials that compared heat and cryotherapy; however, the study designs were poor and the results were contradictory." }, { "input": "Cryotherapy is better than heat for treating acute muscle strain.", "output": "The literature focuses more on the optimal temperature for cryotherapy than on the duration and frequency of therapy. Temperatures below 15\u00bato 25\u00baC may actually result in vasodilatation rather than vasoconstriction." }, { "input": "Either is fine. Timing alone doesn't influence the drug's efficacy in preventing postpartum bleeding.", "output": "A prospective cohort study concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively). The study was neither blinded nor controlled for nonpharmacologic interventions, however." }, { "input": "Either is fine. Timing alone doesn't influence the drug's efficacy in preventing postpartum bleeding.", "output": "A RCT concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively). The study was neither blinded nor controlled for nonpharmacologic interventions, however." }, { "input": "Either is fine. Timing alone doesn't influence the drug's efficacy in preventing postpartum bleeding.", "output": "A prospective cohort study noted a significant reduction in the risk of PPH when oxytocin was given after delivery of the anterior shoulder, compared with the placenta. In this study, 82 patients received 5 units of oxytocin on delivery of the anterior shoulder, and 52 received an identical dose after delivery of the placenta. The incidence of PPH \u2265500 mL was 7.3% in the anterior shoulder group and 19.2% in the placenta group. However, the study was not blinded and was limited by its small sample size." }, { "input": "Either is fine. Timing alone doesn't influence the drug's efficacy in preventing postpartum bleeding.", "output": "A double-blinded RCT found that PPH occurred significantly less often when oxytocin was delayed until after delivery of the placenta. The study comprised 51 patients; 27 received 10 units of oxytocin on delivery of the anterior shoulder and 24 received an identical dose after delivery of the placenta. The incidence of PPH \u2265500 mL was 0% when oxytocin was given after delivery of the placenta vs 14.8% when it was given on delivery of the anterior shoulder (P=.049). However, the study was limited by its size and potential inaccuracies in estimating blood loss." }, { "input": "Either is fine. Timing alone doesn't influence the drug's efficacy in preventing postpartum bleeding.", "output": "A well-constructed double-blinded RCT found no significant difference in the incidence of PPH when oxytocin was given after delivery of the anterior shoulder or the placenta. The study included 1486 patients; 745 received 20 units of oxytocin on delivery of the anterior shoulder, and 741 received an identical dose of oxytocin on delivery of the placenta. The incidence of PPH was 5.4% for the anterior shoulder group and 5.8% for the placenta group (P=.72). Likewise, no significant difference between the groups was noted in the proportion of women with estimated blood loss (EBL) \u2265500 mL (7.5% vs 9.7%; P=.15)." }, { "input": "Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals. Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women.", "output": "The American Heart Association/American College Cardiology AHA/ACC Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures and the American Society of Nuclear Cardiology updated guidelines for cardiac radionuclide imaging in 2003. In this consensus statement a nonsystematic review of literature and expert opinion, they reported test characteristics to detect a 50% angiographic lesion as follows-exercise SPECT: sensitivity 87%, specificity 73%; vasodilator adenosine or dipyridamole SPECT: sensitivity 89%, specificity 75%. They noted that quantitative analysis performs as well as qualitative analysis of radionuclide images. Gated SPECT is slightly more specific and just as sensitive as nongated SPECT. The Taskforce recommended that radionuclide perfusion scans be performed in patients with baseline electrocardiogram ECG abnormalities such as left bundle branch block, hypertrophy, digitalis effect, etc, patients who cannot perform an exercise stress test, and to assess the functional effect of indeterminate lesions found on angiography. They also note that the repeat use of radionuclide testing 3 to 5 years after an event in asymptomatic high-risk patients and the initial use of radionuclide testing in patients at very high risk are both somewhat controversial, but the weight of limited evidence suggests some benefit to their use." }, { "input": "Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals. Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women.", "output": "Four meta-analyses report diagnostic accuracy of radionuclide cardiac imaging." }, { "input": "Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals. Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women.", "output": "A position paper from the American College of Physicians stating that the test may be appropriate for a patient with intermediate risk of coronary artery disease." }, { "input": "Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals. Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women.", "output": "A systematic review reported estimates of sensitivity ranging from 68% to 96% and specificity from 65% to 100%." }, { "input": "Stress radionuclide testing is a moderately accurate test compared with coronary angiography for the diagnosis of coronary artery disease (CAD) in intermediate-risk individuals. Variations in technique of imaging (planar or single-photon emission computed tomography [SPECT]) and stress (exercise or pharmacologic) do not significantly alter the accuracy of this test, although there is some evidence for decreased accuracy in women.", "output": "Stress radionuclide imaging-specifically its diagnostic accuracy-has been the subject of numerous studies. Detrano et al reported the first pooled data (56 studies); they concluded that estimates of sensitivity (85%) and specificity (85%) are biased by studies that were not blinded, included subjects with prior myocardial infarction (MI), or had a work-up (verification) bias (ie, use of the gold standard test is affected by the result on the test under question)." }, { "input": "Abnormal stress radionuclide screening in vascular surgical candidates also predicts an increased rate of perioperative cardiac events.", "output": "Patient-centered outcomes were reported in a meta-analysis of dipyridamole-thallium imaging in the preoperative evaluation of vascular surgery patients. The summary odds ratio for any perioperative cardiac event (in patients with abnormal tests) was 3.5 (95% confidence interval [CI], 2.5-4.8); the odds ratio for MI or cardiac death was 3.9 (95% CI, 2.5-5.6), leading the authors to conclude that there is sound evidence to use radionuclide testing in intermedi.ate-risk patients during preoperative screening." }, { "input": "Subclinical hyperthyroidism (SCH) is defined as a low thyroid-stimulating hormone (TSH) level with normal free T4 and free T3 levels in patients without specific symptoms of hyperthyroidism.", "output": "It is worth noting that individuals treated with levothyroxine have a prevalence of iatrogenic SCH from 14% to 21%." }, { "input": "Subclinical hyperthyroidism (SCH) is defined as a low thyroid-stimulating hormone (TSH) level with normal free T4 and free T3 levels in patients without specific symptoms of hyperthyroidism.", "output": "Progression to overt hyperthyroidism is uncommon, occurring in 4.3% of subjects at 4 years." }, { "input": "Subclinical hyperthyroidism (SCH) is defined as a low thyroid-stimulating hormone (TSH) level with normal free T4 and free T3 levels in patients without specific symptoms of hyperthyroidism.", "output": "When followed up at 1 year, 40% to 60% of subjects with suppressed TSH levels will have normal TSH values." }, { "input": "Subclinical hyperthyroidism (SCH) is defined as a low thyroid-stimulating hormone (TSH) level with normal free T4 and free T3 levels in patients without specific symptoms of hyperthyroidism.", "output": "The prevalence of SCH depends on the level of TSH used as a threshold. When the lower limit of TSH is set at 0.4 mIU/L, the prevalence was 3.2%." }, { "input": "Subclinical hyperthyroidism (SCH) is defined as a low thyroid-stimulating hormone (TSH) level with normal free T4 and free T3 levels in patients without specific symptoms of hyperthyroidism.", "output": "The decreased TSH level seen in SCH results from the pituitary's response to minor elevations in serum or tissue T4 and T3 levels." }, { "input": "There is no evidence that treating SCH results in improved cardiovascular outcomes and evidence is insufficient that it improves neuropsychiatric outcomes.", "output": "In patients with SCH aged >60 years, the cumulative incidence of atrial fibrillation after 10 years varied with the serum TSH level: it was 28% in those with serum TSH <0.1 mIU/L; 16% in those with values between 0.1 and 0.4 mIU/L, and 11 % in those with normal values." }, { "input": "There is no evidence that treating SCH results in improved cardiovascular outcomes and evidence is insufficient that it improves neuropsychiatric outcomes.", "output": "Patients with SCH have been reported to have increased heart rate, contractility, left ventricular mass, and increased risk of diastolic dysfunction and atrial arrhythmias." }, { "input": "There is no evidence that treating SCH results in improved cardiovascular outcomes and evidence is insufficient that it improves neuropsychiatric outcomes.", "output": "Patients aged >60 years with at least 1 suppressed TSH value have an increase in mortality over 5 years (standardized mortality ratio [SMR]=1.8; 95% confidence interval [CI], 1.2-2.7). At 10 years, the SMR was 1.2 (95% CI, 0.9-1.7). It appears that this is primarily related to cardiovascular mortality." }, { "input": "Bone mineral density may be increased with treatment of SCH.", "output": "One study of postmenopausal women with endogenous SCH (defined as TSH <0.1 mIU/L) randomly assigned women to take methimazole (Tapazole) or placebo. Both groups were followed for 2 years and none received any medication with known effects on bone metabolism in the past or during the study period. The untreated patients with SCH had significantly higher bone mineral density loss (>5%) at both 18 and 24 months." }, { "input": "Persons traveling to or working in countries that have high or intermediate rates of infection.", "output": "Prospective studies indicate that persons traveling in areas with high rates of HAV are themselves at 44 times increased risk." }, { "input": "Men who have sex with men.", "output": "Among men who have sex with men, numerous cohort studies reveal increased rates of infection due to anal-oral sexual practices and higher number of sexual partners." }, { "input": "Illegal-drug users (whether drug is injected or not).", "output": "Intravenous drug users and non-IV illicit drug users are both at increased risk of HAV infection." }, { "input": "Persons who have occupational risk for infection (eg, research settings working with nonhuman primates).", "output": "Less strong evidence exists for vaccinating those with occupational hazards (for example, working in a research setting with nonhuman primates) or persons with clotting factor disorders." }, { "input": "Persons with clotting-factor disorders.", "output": "Less strong evidence exists for vaccinating those with occupational hazards (for example, working in a research setting with nonhuman primates) or persons with clotting factor disorders." }, { "input": "Persons with chronic liver disease.", "output": "Patients with chronic liver disease may be at higher risk of developing fulminant hepatitis A." }, { "input": "Children (age 2 to 18) living in states, counties, and communities where rates of hepatitis A are at least twice the national average. These states include: Alaska, Arizona, California, Idaho, Nevada, New Mexico, Oklahoma, Oregon, South Dakota, Utah, and Washington. Consider giving hepatitis A vaccine to children (age 2 to 18) in areas with rates greater than the national average but less than twice the national average. These states include Arkansas, Colorado, Missouri, Montana, Texas, and Wyoming", "output": "In the United States, children living in states with increased HAV incidence rates are also considered to be at high risk." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "The ratio of adiponectin to leptin hormone may show diagnostic merit. Adipocytes secrete adiponectin which acts as an insulin sensitizer, antiatherogenic and anti-inflammatory agent. Obesity and type 2 phenotype correlate with lower levels of adiponectin, but are associated with higher levels of leptin hormone, another molecule secreted by adipocytes. A recent case-control study of children aged 6 to 21 years analyzed adiponectin and leptin hormone levels in patients with classical type 1 and 2 diabetes, as determined by 2 pediatric endocrinologists; interestingly, 29% of the type 1 patients were autoantibody negative. After plotting a ROC curve, they found the area under the curve was 0.97 (95% CI, 0.93-1.00). At an adiponectin-to-leptin ratio cutoff less than 0.7, they found the sensitivity to diagnose type 2 was 88% (95% CI, 64-99%), the specificity was 90% (95% CI, 77-97), and the likelihood ratio for a positive test was 8.8." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "A study in young adults with type 2 or unclassified diabetes from Sweden found 93% of patients who were GADAb+ required insulin at 3 years, compared with 51% who were GADAb-(OR=18.8; 95% CI, 1.8-191)." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "Autoantibodies do predict an earlier need for insulin. One prevalence study of 101 type 2 adult patients found 20% were positive for glutamic acid decarboxylase autoantibody (GADAb), which was positively associated with insulin dependence at 4 years postdiagnosis (OR=5.8; 95% CI, 1.8-18.9). Eighty percent of patients with autoantibodies required insulin compared with 41% of patients without autoantibodies." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "A history of diabetic ketoacidosis (DKA) also does not reliably distinguish between types 1 and 2. A retrospective chart review gathered data on adults over 18 years of age who were admitted for DKA in a urban US hospital. Many patients with DKA were subsequently diagnosed with type 2 diabetes. Rates of type 2 diabetes in patients with DKA varied by race: 47% of Hispanics, 44% of African Americans, and 17% of Caucasians had type 2 diabetes." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "Guidelines from the American Diabetes Association admit that many diabetic individuals do not easily fit into a distinct diagnostic category; however, they only provide criteria for the general diagnosis of diabetes, not specific criteria to distinguish type 1 from type 2." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "The National Academy of Clinical Biochemistry and the American Association of Clinical Endocrinologists recommend against routine testing of insulin, C-peptide, autoantibodies and genetic markers." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "A patient's age may suggest, but does not reliably distinguish, diabetes types. A study of 569 new-onset type 1 and type 2 diabetic children and adolescents showed that older age was only weakly associated with type 2 diagnosis (odds ratio [OR]= 1.4 for each 1-year increment in age; 95% confidence interval [CI], 1.3-1.6)." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "Newly diagnosed 12-year-old children have an equal incidence of type 1 as type 2 diabetes. Likewise, adults with type 2 phenotype (no initial insulin requirement) can present with positive autoantibodies typically found in younger type 1 patients. Older patients who fit this profile have been classified as type 1.5 diabetes or latent autoimmune disease in adults (LADA)." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "Although daily variation in serum insulin levels limits its use, C-peptide levels show more promise. Random C-peptide levels were superior to fasting or glucagon stimulated levels in 1093 patients, who were followed for 3 years to confirm insulin requirements. Using a receiver operating characteristic (ROC) curve, the area under the curve for random C-peptide levels to distinguish diabetes types was 0.98 (95% CI, 0.97-0.99). For patients under the optimal cutoff of 0.5 nmol/L, the positive predictive value was 96% for diagnosing type 1 and the likelihood ratio was 22.5." }, { "input": "No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1.", "output": "One study proposed treating those with autoantibody-positive diabetes (presumed type 1 or type 1.5) with insulin immediately, while initiating oral medications in those who test negative (presumed type 2 diabetes). This approach lacks significant patient-oriented outcome data, but his small RCT of 55 patients was encouraging. With a 3-year follow-up rate of 89%, early insulin use in GADAb+ patients preserved C-peptide levels and possibly prolonged pancreatic beta cell survival. Insulin dependency, defined as needing insulin for survival, occurred in 47% of controls (who received oral sulfonylureas) and only 13% of patients receiving insulin (number needed to treat [NNT]= 4; P=.043). The theoretical benefit is that if beta cell exhaustion can be delayed, endogenous insulin production could be maintained to assist prevention of damaging postprandial glucose spikes." }, { "input": "Though clinical preparticipation exams (PPE) are recommended by experts and required in most states, we found no medium- or better-quality evidence that demonstrates they reduce mortality or morbidity. PPEs detect only a very small percentage of cardiac abnormalities among athletes who subsequently die suddenly.", "output": "A case series reviewed 158 sudden deaths that occurred in trained athletes in the US from 1985 to 1995. The athletes were identified from news accounts, the National Center for Catastrophic Sports Injury Registry, and informal communications and reports. The authors interviewed families, witnesses, and coaches, and they analyzed postmortem information. Of the 115 athletes who had a standard preparticipation medical evaluation, only 4 (3%) were suspected of having cardiovascular disease. The cardiovascular abnormality responsible for sudden death was prospectively identified in only 1 athlete." }, { "input": "Though clinical preparticipation exams (PPE) are recommended by experts and required in most states, we found no medium- or better-quality evidence that demonstrates they reduce mortality or morbidity. PPEs detect only a very small percentage of cardiac abnormalities among athletes who subsequently die suddenly.", "output": "A systematic review of the literature on PPE identified 310 studies of athletes age <36 years. The authors searched multiple electronic databases and reviewed the bibliographies of retrieved articles but did not perform hand searches of journals or contact authors directly. The review did not find any prospective cohort or randomized trials addressing the effectiveness of clinical PPE. The 5 studies that assessed the format of the PPE concluded that it is not adequately standardized, does not consistently address the American Heart Association (AHA) recommendations for cardiovascular screening and exam, and is administered by a variety of health care professionals, some without proper training." }, { "input": "PPEs are unable to accurately identify athletes with exercise-induced bronchospasm.", "output": "A prospective cross-sectional study studied 352 adolescents from 3 suburban Washington state schools. The students completed a 14-item exercise-induced bronchospasm (EIB) questionnaire, had a physical exam, and underwent a 7-minute exercise challenge spirometry. Complete data were available for 256 of the students. EIB was diagnosed by spirometry in 9.4% of the athletes. No student had EIB detected solely by physical exam. Using a cutoff of 2 positive questions, the questionnaire had a sensitivity of 71% and a specificity of 47%, with a negative and positive predictive value of 6% and 12%, respectively. This study concluded that EIB occurs frequently in adolescent athletes, but screening by physical exam and medical history does not accurately detect it." }, { "input": "PPEs are poorly predictive of which athletes are at increased risk of orthopedic injuries.", "output": "A study surveyed 1204 student athletes (aged 13-20 years) from Richmond County, Georgia, who had a standardized PPE before participating in sports. The questionnaire was administered via mail or telephone and inquired about injuries sustained after the PPE. The response rate to the survey was 56%. The study found that a history of knee or ankle injury and abnormal findings on exam in male athletes slightly increased the likelihood of repeated injury of the same joint. However, the sensitivities of history or physical exam for ankle or knee injuries were all <25%." }, { "input": "Medications collectively referred to as \"triptans\" (eg, sumatriptan, naratriptan, etc) have been shown to be effective for acute migraine.", "output": "Systematic reviews of randomized controlled trials (RCTs) summarized that oral sumatriptan (Imitrex), eletriptan (Relpax), and rizatriptan (Maxalt) reduced migraine headache pain and increased the pain-free response rate for adults when compared with placebo. The number needed to treat (NNT) ranged from 3.9 to 9.9 for a given triptan's lower dose to 2.6 to 5.1 for the higher dose. RCTs reported superior efficacy of oral almotriptan (Axert), frovatriptan (Frova), and zolmitriptan (Zomig), as well as intranasal sumatriptan and zolmitriptan when compared with placebo." }, { "input": "Nonsteroidal anti-inflammatory drugs (NSAIDs)-including aspirin, ibuprofen, naproxen sodium, diclofenac potassium, ketoprofen, tolfenamic acid, and ketorolac-are also effective.", "output": "The following NSAIDs reduced headache severity more than placebo 2 hours after treatment: aspirin (1000 mg; NNT=2.4), ibuprofen (1200 mg; NNT=1.8), naproxen (750 mg; NNT=2.0), tolfenamic acid (not available in the US; NNT=1.2)." }, { "input": "The combination of acetaminophen/aspirin/caffeine is effective.", "output": "The combination product of acetaminophen/aspirin/caffeine (Excedrin Migraine, et al) (NNT=1.7)." }, { "input": "Parenteral dihydroergotamine (DHE), when administered with an antiemetic, is as effective as, or more effective than meperidine, valproate, or ketorolac.", "output": "A systematic review revealed that dihydroergotamine (DHE) alone was less effective than subcutaneous sumatriptan in migraine pain reduction (OR=0.44; 95% CI, 0.25-0.77) or headache resolution (OR=0.05; 95% CI, 0.01-0.42). No differences were seen between DHE alone and chlorpromazine or lidocaine. Three studies revealed DHE plus metoclopramide was more effective than or equal to other agents for headache pain reduction at 2 hours: one vs ketorolac IM (OR=7; 95% CI, 0.86-56.89), one vs meperidine (Demerol) plus hydroxyzine (Vistaril, Atarax) IM (OR=47.67; 95% CI, 4.32-526.17), and one vs valproate IV (OR=0.67; 95% CI, 0.19-2.33). Specifically, treatment with DHE plus metoclopramide was superior to ketorolac for pain reduction (P=.03), but patients did not differ in disability scores (P=.06). DHE plus metoclopramide achieved greater reductions in pain scale scores than meperidine plus hydroxyzine (P<.001). No significant difference in pain reduction was noted between DHE plus metoclopramide and valproate (P=.36)." }, { "input": "Prochlorperazine is more effective than metoclopramide in headache pain reduction.", "output": "When compared with other antiemetics (chlorpromazine [Thorazine] and prochlorperazine [Compazine]), metoclopramide was either less effective (OR=0.39; 95% CI, 0.18-0.87) or no different (OR=0.64; 95% CI, 0.23-1.76) than other therapies for reducing migraine pain." }, { "input": "Isometheptene mucate/dichloralphenazone/acetaminophen is as effective as low-dose oral sumatriptan.", "output": "A multicenter, double-blind, randomized parallel group study showed no difference between the combination product isometheptene mucate, dichloralphenazone with acetaminophen (Midrin, Duradrin, etc) (used as recommended in the package insert with a maximum of up to 5 tablets within 24 hours) vs oral sumatriptan (initial dose of 25 mg with a repeat 25 mg dose in 2 hours). No placebo arm was used in this study." }, { "input": "No studies evaluate the commonly used indications for bariatric surgery. Consensus guidelines suggest that the surgical treatment of obesity should be reserved for patients with a body-mass index (BMI) >40 kg/m2 or with BMI >35 kg/m2 and 1 or more significant comorbid conditions, when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity and mortality.", "output": "The American College of Preventive Medicine, in its policy statement on weight management counseling, recommends limiting surgical therapy for obesity to severely obese patients, defined as BMI >40." }, { "input": "No studies evaluate the commonly used indications for bariatric surgery. Consensus guidelines suggest that the surgical treatment of obesity should be reserved for patients with a body-mass index (BMI) >40 kg/m2 or with BMI >35 kg/m2 and 1 or more significant comorbid conditions, when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity and mortality.", "output": "The American Gastroenterological Association AGA medical position statement on obesity finds surgical therapy to be the most effective approach for achieving long-term weight loss. The AGA recommends surgery for patients with a BMI >40, or those with BMI >35 and 1 or more severe obesity-related medical complication eg, hypertension, heart failure, or sleep apnea if they have been unable to achieve or maintain weight loss with conventional therapy, have acceptable operative risks, and are able to comply with long-term treatment and follow-up." }, { "input": "No studies evaluate the commonly used indications for bariatric surgery. Consensus guidelines suggest that the surgical treatment of obesity should be reserved for patients with a body-mass index (BMI) >40 kg/m2 or with BMI >35 kg/m2 and 1 or more significant comorbid conditions, when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity and mortality.", "output": "A meta-analysis proved bariatric surgery not only efficacious for weight loss, but showed that a substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or significant improvement of their comorbid condition after surgery." }, { "input": "No studies evaluate the commonly used indications for bariatric surgery. Consensus guidelines suggest that the surgical treatment of obesity should be reserved for patients with a body-mass index (BMI) >40 kg/m2 or with BMI >35 kg/m2 and 1 or more significant comorbid conditions, when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity and mortality.", "output": "The possibility of significant adverse effects remains. The postoperative mortality rate for bariatric surgery is approximately 0.2%. Reoperation is required for up to 25% of patients within 5 years. Other complications are wound infection, staple failure, vitamin deficiency, diarrhea, and hemorrhage. The long-term health effects of bariatric surgery are not well known." }, { "input": "No studies evaluate the commonly used indications for bariatric surgery. Consensus guidelines suggest that the surgical treatment of obesity should be reserved for patients with a body-mass index (BMI) >40 kg/m2 or with BMI >35 kg/m2 and 1 or more significant comorbid conditions, when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity and mortality.", "output": "Patients with a BMI >40 have substantially more serious health consequences and a reduced life expectancy. Obesity significantly impairs quality of life, and the risk of morbidity and mortality increases with the degree of obesity. Those who are extremely obese often do not have sustained benefit from more conservative treatment. The benefits of nonsurgical treatment are significantly limited by the failure to maintain reduced body weight. The NIH statement \"Gastrointestinal Surgery for Severe Obesity\" concluded that the benefits outweigh the risks and that surgical treatment is reasonable in those who strongly desire substantial weight loss and have life-threatening comorbid conditions." }, { "input": "No studies evaluate the commonly used indications for bariatric surgery. Consensus guidelines suggest that the surgical treatment of obesity should be reserved for patients with a body-mass index (BMI) >40 kg/m2 or with BMI >35 kg/m2 and 1 or more significant comorbid conditions, when less invasive methods of weight loss have failed and the patient is at high risk for obesity-associated morbidity and mortality.", "output": "Mmultiple RCTs have compared the weight-reducing effects of different bariatric surgical techniques against each other. All studies included patients who had a BMI >40 kg/m2, or a BMI >35 kg/m2 with at least 1 comorbidity, such as cardiovascular disease, sleep apnea, uncontrolled type 2 diabetes, or weight-induced physical problems interfering with performance of daily life activities. It is these study inclusion criteria that, by default, have become widely accepted indications for bariatric surgery. Weight loss in all RCTs was substantial, ranging from 50 to 100 kg over 6 months to 1 year. Comorbid factors associated with obesity showed either resolution or improvement after surgery in 91% of patients." }, { "input": "Monitor the patient and treat her with intrapartum chemoprophylaxis based on identified risk factors, unless a rapid, highly sensitive (\u226585%) polymerase chain reaction (PCR) test is immediately available to evaluate for group B Streptococcus (GBS).", "output": "The GBS status of 5% to 10% of term patients remains unknown at onset of labor because of inadequate prenatal care or out-of-date GBS culture results (>5 weeks)." }, { "input": "Monitor the patient and treat her with intrapartum chemoprophylaxis based on identified risk factors, unless a rapid, highly sensitive (\u226585%) polymerase chain reaction (PCR) test is immediately available to evaluate for group B Streptococcus (GBS).", "output": "The Centers for Disease Control and Prevention's (CDC) 2002 revised guidelines recommend universal screening by culture at 35 to 37 weeks, with 2 exceptions: women who had GBS bacteriuria during the current pregnancy and women who have given birth to an infant with invasive GBS disease." }, { "input": "Monitor the patient and treat her with intrapartum chemoprophylaxis based on identified risk factors, unless a rapid, highly sensitive (\u226585%) polymerase chain reaction (PCR) test is immediately available to evaluate for group B Streptococcus (GBS).", "output": "A multistate retrospective cohort study (N=5144) concluded that universal screening by culture for GBS at 35 to 37 weeks' gestation is more effective than treating patients based on risk-factor criteria (relative risk [RR]=0.46; 95% confidence interval [CI], 0.36-0.60)." }, { "input": "Six to eight weeks after the start of levothyroxine therapy you should reexamine patients and measure their serum thyroid-stimulating hormone (TSH).", "output": "The full effects of thyroid hormone replacement on the TSH level may not become apparent until 8 weeks of therapy." }, { "input": "Six to eight weeks after the start of levothyroxine therapy you should reexamine patients and measure their serum thyroid-stimulating hormone (TSH).", "output": "Serial serum TSH measurements are adequate to follow adults with newly diagnosed, uncomplicated primary hypothyroidism. However, serum thyroid hormone levels normalize before serum TSH. Serum thyroid hormone concentrations increase first, then the TSH secretion falls because of the negative feedback action of levothyroxine on the pituitary and hypothalamus. Levothyroxine has a 1-week plasma half-life; a steady state is achieved about 6 weeks (6 half-lives) after the start of treatment or a change in dose. The TSH level should, therefore, be evaluated no earlier than 6 weeks after initiating therapy or adjusting levothyroxine dosage." }, { "input": "If thyroid function is normal at that time, examine the patient and measure serum TSH again in 4 to 6 months because clearance of levothyroxine increases in the euthyroid (normal) state.", "output": "If the initial dose doesn't require adjustment, reevaluate the patient and measure serum TSH again in 4 to 6 months because levothyroxine clearance can increase after the euthyroid state is established." }, { "input": "If thyroid function is normal at that time, examine the patient and measure serum TSH again in 4 to 6 months because clearance of levothyroxine increases in the euthyroid (normal) state.", "output": "If a dosage change is needed, make adjustments every 6 weeks, based on serum TSH values, until TSH values return to the reference range. Successful treatment reverses all the signs and symptoms of hypothyroidism, although some neuropsychologic and biochemical abnormalities, such as depressed mood and lipid abnormalities, may persist for several months." }, { "input": "Once the proper maintenance dose of levothyroxine is achieved, evaluate the patient and obtain a serum TSH at least annually, or as clinically indicated.", "output": "If a dosage change is needed, make adjustments every 6 weeks, based on serum TSH values, until TSH values return to the reference range. Successful treatment reverses all the signs and symptoms of hypothyroidism, although some neuropsychologic and biochemical abnormalities, such as depressed mood and lipid abnormalities, may persist for several months." }, { "input": "Once the proper maintenance dose of levothyroxine is achieved, evaluate the patient and obtain a serum TSH at least annually, or as clinically indicated.", "output": "Although monitoring less often than once a year can be justified in younger adult patients whose weight is stable, patients older than 65 years must be monitored annually to avoid overreplacement. With age, thyroid binding may decrease, and the serum albumin level may decline. This can result in a 20% reduction in the dose of levothyroxine required." }, { "input": "Once the proper maintenance dose of levothyroxine is achieved, evaluate the patient and obtain a serum TSH at least annually, or as clinically indicated.", "output": "Generally, once a stable maintenance dosage of levothyroxine is achieved, the dosage will remain adequate until the patient has a significant weight change or reaches his or her seventh or eighth decade." }, { "input": "Women on standard estrogen/progestin hormone replacement therapy (HRT) regimens frequently have irregular bleeding during the first 12 months of treatment. Therefore, those taking HRT should usually be evaluated after 1 year of treatment if bleeding continues.", "output": "Any woman taking HRT who has irregular bleeding after a year should have a Pap test, since cervical abnormalities are not uncommon." }, { "input": "Women on standard estrogen/progestin hormone replacement therapy (HRT) regimens frequently have irregular bleeding during the first 12 months of treatment. Therefore, those taking HRT should usually be evaluated after 1 year of treatment if bleeding continues.", "output": "HRT causes irregular bleeding for 8% to 60% of these women at 6 months and 4% to 30% at 12 months. Roughly half of those bleeding at 6 months are no longer bleeding at a year." }, { "input": "Women on standard estrogen/progestin hormone replacement therapy (HRT) regimens frequently have irregular bleeding during the first 12 months of treatment. Therefore, those taking HRT should usually be evaluated after 1 year of treatment if bleeding continues.", "output": "Vaginal bleeding can be a sign of endometrial hyperplasia or cancer. Fifty-year-old perimenopausal women with an intact uterus have a 5% prevalence of hyperplasia." }, { "input": "Evaluation of this bleeding should begin with a pelvic examination and Papanicolaou (Pap) test (if not done in the previous 12 months), then transvaginal ultrasound (TVUS), followed by endometrial biopsy or hysteroscopy, if indicated.", "output": "Any woman taking HRT who has irregular bleeding after a year should have a Pap test, since cervical abnormalities are not uncommon." }, { "input": "Evaluation of this bleeding should begin with a pelvic examination and Papanicolaou (Pap) test (if not done in the previous 12 months), then transvaginal ultrasound (TVUS), followed by endometrial biopsy or hysteroscopy, if indicated.", "output": "TVUS showing an endometrial stripe of 5 mm or greater is more than 90% sensitive in detecting endometrial disease (cancer, complex hyperplasia, polyps). Approximately 3% of endometrial stripes are unmeasurable by TVUS and should be treated as abnormal. TVUS also shows many structural abnormalities, including those outside of the endometrium." }, { "input": "Evaluation of this bleeding should begin with a pelvic examination and Papanicolaou (Pap) test (if not done in the previous 12 months), then transvaginal ultrasound (TVUS), followed by endometrial biopsy or hysteroscopy, if indicated.", "output": "A negative TVUS using the 5-mm criterion is associated with a 0.6% to 1% chance of endometrial cancer." }, { "input": "Evaluation of this bleeding should begin with a pelvic examination and Papanicolaou (Pap) test (if not done in the previous 12 months), then transvaginal ultrasound (TVUS), followed by endometrial biopsy or hysteroscopy, if indicated.", "output": "Abnormal sonograms or persistent unexpected bleeding after a normal sonogram requires further evaluation. Endometrial biopsy is a straightforward office procedure, and is as sensitive as dilatation and curretage." }, { "input": "Evaluation of this bleeding should begin with a pelvic examination and Papanicolaou (Pap) test (if not done in the previous 12 months), then transvaginal ultrasound (TVUS), followed by endometrial biopsy or hysteroscopy, if indicated.", "output": "Endometrial biopsy fails (eg, from cervical stenosis) or is nondiagnostic in 2% to 28% of attempts." }, { "input": "Evaluation of this bleeding should begin with a pelvic examination and Papanicolaou (Pap) test (if not done in the previous 12 months), then transvaginal ultrasound (TVUS), followed by endometrial biopsy or hysteroscopy, if indicated.", "output": "Hysteroscopy is also accurate but sometimes requires paracervical and general anesthesia. It also requires additional training and equipment. Zero percent to 12% of attempts fail (failures are less common in patients taking HRT), and the false-negative rate is roughly 3%." }, { "input": "Tight control of hypertension treatment is key in preventing the vascular complications of diabetes. ACE inhibitors appear to have a protective effect that is independent of their antihypertensive effect. Unless there is a contraindication, all patients with diabetes who have hypertension should be treated with ACE inhibitors. Patients with diabetes who have microalbuminuria should be treated with ACE inhibitors, even if normotensive, as should those with overt nephropathy.", "output": "ACE inhibitors may slow the progression of microalbuminuria in those with type 2 diabetes, even in the absence of hypertension." }, { "input": "Tight control of hypertension treatment is key in preventing the vascular complications of diabetes. ACE inhibitors appear to have a protective effect that is independent of their antihypertensive effect. Unless there is a contraindication, all patients with diabetes who have hypertension should be treated with ACE inhibitors. Patients with diabetes who have microalbuminuria should be treated with ACE inhibitors, even if normotensive, as should those with overt nephropathy.", "output": "ACE inhibitors have been demonstrated to slow the progression of diabetic nephropathy in patients with type 1 diabetes." }, { "input": "Tight control of hypertension treatment is key in preventing the vascular complications of diabetes. ACE inhibitors appear to have a protective effect that is independent of their antihypertensive effect. Unless there is a contraindication, all patients with diabetes who have hypertension should be treated with ACE inhibitors. Patients with diabetes who have microalbuminuria should be treated with ACE inhibitors, even if normotensive, as should those with overt nephropathy.", "output": "Cardiovascular disease (CVD) accounts for 60% to 75% of all deaths in patients with diabetes. Those patients with diabetes who do not have clinical evidence of CVD have a similar mortality rate from CVD as patients who do not have diabetes but do have known CVD. The Heart Outcomes Prevention Evaluation (HOPE) study and the MICRO-HOPE substudy added a low dose of ramipril to the current regimen in patients with diabetes who are older than 55 years and have additional risk factors, which lowered the risk of death, cardiovascular events, and nephropathy by 24% to 25% each. The cardiovascular effect was greater than that attributed to the decrease in blood pressure. It is not possible to generalize from this study the effects on risk reduction of treatment of nonhypertensive or lower-risk patients with diabetes." }, { "input": "Tight control of hypertension treatment is key in preventing the vascular complications of diabetes. ACE inhibitors appear to have a protective effect that is independent of their antihypertensive effect. Unless there is a contraindication, all patients with diabetes who have hypertension should be treated with ACE inhibitors. Patients with diabetes who have microalbuminuria should be treated with ACE inhibitors, even if normotensive, as should those with overt nephropathy.", "output": "There is no evidence that ACE inhibitors are superior to b-blockers or diuretics in preventing cardiovascular outcomes at similar levels of blood pressure reduction." }, { "input": "Tight control of hypertension treatment is key in preventing the vascular complications of diabetes. ACE inhibitors appear to have a protective effect that is independent of their antihypertensive effect. Unless there is a contraindication, all patients with diabetes who have hypertension should be treated with ACE inhibitors. Patients with diabetes who have microalbuminuria should be treated with ACE inhibitors, even if normotensive, as should those with overt nephropathy.", "output": "ACE inhibitors are superior to calcium channel blockers (CCBs) in preventing cardiovascular outcomes in patients with diabetes. It is not clear if this is due to beneficial effects of ACE inhibitors or adverse effects of CCBs." }, { "input": "Tight control of hypertension treatment is key in preventing the vascular complications of diabetes. ACE inhibitors appear to have a protective effect that is independent of their antihypertensive effect. Unless there is a contraindication, all patients with diabetes who have hypertension should be treated with ACE inhibitors. Patients with diabetes who have microalbuminuria should be treated with ACE inhibitors, even if normotensive, as should those with overt nephropathy.", "output": "Several large randomized controlled trials, have demonstrated that control of hypertension in patients with diabetes prevents development or progression of nephropathy, retinopathy, and cardiovascular conditions." }, { "input": "There is insufficient evidence to recommend for or against an EST for screening asymptomatic individuals of any age.", "output": "One study of middle-aged asymptomatic men and recorded the presence of a first-degree relative with heart disease, systolic blood pressure of 140 mm Hg or greater, smoking, or total cholesterol higher than 250 mg per dL. Men with any of these risk factors had significantly higher CHD event incidence if they had 2 or more EST abnormalities than those with less than 2 EST abnormalities. The authors concluded that routine screening of asymptomatic men without these risk factors was not warranted, but the uncertain efficacy of earlier intervention remains." }, { "input": "There is insufficient evidence to recommend for or against an EST for screening asymptomatic individuals of any age.", "output": "Screening individuals in occupations that can affect public safety, such as airline pilots, would identify some individuals at risk for sudden cardiac death, though the population impact of this would be miniscule. Screening individuals who will be engaging in strenuous physical activity would also be effective at detecting at least some people who are at risk of sudden death. However, only 2% of cardiac deaths occur during exercise, and it again is not clear that early intervention improves outcome." }, { "input": "There is insufficient evidence to recommend for or against an EST for screening asymptomatic individuals of any age.", "output": "Several case series have demonstrated that occult coronary heart disease (CHD) can be identified by screening asymptomatic adults with an EST, some of whom will ultimately experience CHD death. The best estimates of sensitivity and specificity of the EST for identifying occult CHD are 45% and 85%, respectively." }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "A systematic review of 4 studies on treatments to restore depleted Lactobacilli concluded that \"these trials do not constitute enough evidence to recommend using yogurt or Lactobacillus to cure vaginal infections.\"" }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "One review reports that ampicillin and erythromycin are ineffective and ampicillin sulbactam and ciprofloxacin are less effective than oral metronidazole." }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "Metronidazole (400 mg or 500 mg twice daily) achieved significantly higher cure rates compared with ofloxacin (200 mg or 300 mg twice daily) 1 to 7 days post-treatment." }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "A systematic review showed a significantly lower cure rate with a single 2-g dose compared with the 7-day regimen (54% vs 88%)." }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "A meta-analysis of 10 clinical trials compared different dosing regimens of oral metronidazole. The results showed comparable cure rates (85% to 87%) among groups treated with either a single 2-g dose or 500 mg twice daily for 7 days." }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "Metronidazole 0.75% gel used once daily for 5 days had equal efficacy compared with twice-daily dosing (cure rate = 77% vs 80%). One study found a cure rate of 94% with oral clindamycin 300 mg twice daily for 7 days and 96% with metronidazole 500 mg twice daily for 7 days." }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "One systematic review calculated cure rates from 5 randomized controlled trials comparing oral metronidazole, clindamycin 2% vaginal cream, and metronidazole 0.75% vaginal gel. Cumulative cure rates at 5 to 10 days and 4 weeks post-treatment were essentially equal for all treatments. The most common side effects were vaginal Candida infections (for both treatments) and gastrointestional symptoms (for metronidazole tablets and gels)." }, { "input": "Either oral or vaginal metronidazole or vaginal clindamycin provides equivalent treatment for bacterial vaginosis in nonpregnant women. Oral clindamycin 300 mg twice daily for 7 days is an effective alternative. There is conflicting evidence regarding the efficacy of a single 2-g dose of oral metronidazole. Ofloxacin 200 mg or 300 mg twice daily is less effective but could be considered for women with intolerance to metronidazole or clindamycin. Overall recurrence rates of up to 30% have been reported.", "output": "One systematic review of 6 randomized controlled trials found no benefit from treating male partners of women with bacterial vaginosis." }, { "input": "The Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS), a semi-structured interview, along with clinical evaluation by a childhood mental health specialist, is used most frequently in major research studies.", "output": "KSADS is not meant as a stand-alone test, but to be used in conjunction with a clinical evaluation by a trained mental health professional." }, { "input": "The Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS), a semi-structured interview, along with clinical evaluation by a childhood mental health specialist, is used most frequently in major research studies.", "output": "Concerns about the validity of KSADS still exist because of lack of sufficient testing, vagueness of the diagnostic criteria, and the subjective nature of the test. Because specialized training is required to administer the test and testing can last a full day, its use in most office settings is impractical." }, { "input": "The Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS), a semi-structured interview, along with clinical evaluation by a childhood mental health specialist, is used most frequently in major research studies.", "output": "Different versions of the KSADS have been used in most research studies on bipolar disorder." }, { "input": "High or low scores on parent-reported screening tests (Parent Young Mania Rating Scale [P-YMRS], Parent General Behavior Inventory [P-GBI], and Child Behavior Checklist [CBCL]) also significantly increase or decrease the likelihood of diagnosis.", "output": "Three screening tests (CBCL, P-GBI, and P-YMRS) available for the office setting use parent-reported scores, and perform best when compared with KSADS as the standard. These instruments were associated with likelihood ratios that significantly improved the odds of diagnosis and could allow clinicians to stratify patients as high or low risk." }, { "input": "other", "output": "Compared with adults, children and adolescents are more difficult to diagnose because they are less likely to have discrete episodes of mania, and instead present with severe irritability, rapid cycling, or mixed mania." }, { "input": "other", "output": "The criteria in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) cannot be easily applied to most children and adolescents with bipolar disorder because most do not meet the criteria for Bipolar I or II, but fall into the less well-defined category Bipolar NOS (not otherwise specified)." }, { "input": "other", "output": "Retrospective analysis of 2 large cohort studies of adults with bipolar disorder indicated that at least 50% of these patients had an onset of illness before age 19, establishing support for the presence of bipolar disorder among children and adolescents." }, { "input": "No randomized clinical trials or prospective studies have demonstrated adequate evidence to screen individuals for diabetes mellitus. A recently published meta-analysis for the United States Preventative Services Task Force (USPSTF) stated that \"until we have better evidence about its benefits, harms, and costs, the role of screening as a strategy to reduce the burden of suffering of diabetes will remain uncertain\".", "output": "No randomized trials have tested whether screening provides any benefits. In a thorough systematic review using USPSTF methodologies, several potential postscreening interventions were evaluated. While tight glycemic control reduces progression of albuminuria and retinopathy, it is unclear how large the long-term clinical benefit would be, or at what cost. Reasonable evidence supports more aggressive control of blood pressure for patients with diabetes to reduce adverse cardiovascular outcomes. It is important to note that the data for these interventions (aggressive blood sugar and blood pressure control) were derived in studies of patients with established diabetes; no studies have tested these interventions for patients who had early diagnosis by screening." }, { "input": "The group of patients most likely to benefit from diabetes screening are patients with hypertension.", "output": "The ADA recommends screening for patients who have signs of insulin resistance or conditions associated with insulin resistance, such acanthosis nigricans, hypertension, dyslipidemia, and polycystic ovary syndrome. They note that this advice is based on expert opinion and should be carried out at the discretion of the health care provider." }, { "input": "The group of patients most likely to benefit from diabetes screening those whose risk for coronary heart disease is such that a diagnosis of diabetes would mandate addition of aspirin or lipid-lowering agents.", "output": "It is well documented that diabetes significantly increases the risk of morbidity and mortality, especially due to retinopathy, nephropathy, neuropathy, and coronary artery disease." }, { "input": "Tricyclic antidepressants, anticonvulsants, and capsaicin reduce the pain of diabetic neuropathy; limited data suggests that lidocaine patches may also be efficacious. Both tricyclic antidepressants and anticonvulsants are superior to placebo in relieving painful diabetic neuropathy. Compared with placebo, patients taking tricyclic antidepressants report reduced pain (number needed to treat [NNT] for at least 50% reduction= 3.5) (strength of recommendation.", "output": "A well-done meta-analysis summarized available randomized placebo-controlled trials of antidepressants (including tricyclics and SSRIs) and anticonvulsants (including phenytoin, carbamazepine, and gabapentin). Almost all trials compare individual agents against placebo, and there have been no head-to-head trials that address functional outcomes, quality of life, patient satisfaction, or cost. Most trials do not describe diagnostic criteria, consider causes of pain other than diabetes or address diabetic control, which is known to predict frequency of neuropathy. Finally, very few trials include typical primary care patients in a primary care setting or control for important confounding variables such as over-the-counter medications or comorbid illnesses. Within the constraints of this literature, placebos have a substantial impact, with an aggregate 32% of patients receiving placebo reporting at least 50% reduction in pain. A total of 16 trials have addressed the efficacy of antidepressants for diabetic neuropathy. Compared with placebo, tricyclic antidepressants have an aggregate NNT of 3.5 (95% confidence interval [CI], 2.6-4.7) for patients reporting at least 50% reduction of pain, along with an NNH of 2.7 (95% CI, 2.1-3.9) for minor adverse effects (typically the muscarinic effects of dry mouth, constipation, and blurred vision) and 17 (95% CI, 10-43) for side effects severe enough to cause withdrawal from a trial. Dosages were in the low to middle range of those used to treat depression; there was no significant difference in efficacy between trials less than 3 weeks and those greater than 3 weeks. A total of 4 randomized placebo-controlled trials (1 each for phenytoin [Dilantin], carbamazepine [Tegretol], gabapentin [Neurontin], and valproate [Depakote]) have extractable data about the efficacy of anticonvulsants for the pain of diabetic neuropathy. As a class, the NNT for patients reporting at least a 50% reduction in pain was 2.7 (95% CI, 2.2-3.8); the NNH for minor adverse effects (typically transient central nervous system effect such as dizziness, somnolence, or disturbance in gait) was 2.7 (95% CI, 2.2-3.4)." }, { "input": "Tricyclic antidepressants, anticonvulsants, and capsaicin reduce the pain of diabetic neuropathy; limited data suggests that lidocaine patches may also be efficacious. Both tricyclic antidepressants and anticonvulsants are superior to placebo in relieving painful diabetic neuropathy. Patients taking anticonvulsants report reduced pain (NNT for at least 50% reduction in pain=2.7).", "output": "A well-done meta-analysis summarized available randomized placebo-controlled trials of antidepressants (including tricyclics and SSRIs) and anticonvulsants (including phenytoin, carbamazepine, and gabapentin). Almost all trials compare individual agents against placebo, and there have been no head-to-head trials that address functional outcomes, quality of life, patient satisfaction, or cost. Most trials do not describe diagnostic criteria, consider causes of pain other than diabetes or address diabetic control, which is known to predict frequency of neuropathy. Finally, very few trials include typical primary care patients in a primary care setting or control for important confounding variables such as over-the-counter medications or comorbid illnesses. Within the constraints of this literature, placebos have a substantial impact, with an aggregate 32% of patients receiving placebo reporting at least 50% reduction in pain. A total of 16 trials have addressed the efficacy of antidepressants for diabetic neuropathy. Compared with placebo, tricyclic antidepressants have an aggregate NNT of 3.5 (95% confidence interval [CI], 2.6-4.7) for patients reporting at least 50% reduction of pain, along with an NNH of 2.7 (95% CI, 2.1-3.9) for minor adverse effects (typically the muscarinic effects of dry mouth, constipation, and blurred vision) and 17 (95% CI, 10-43) for side effects severe enough to cause withdrawal from a trial. Dosages were in the low to middle range of those used to treat depression; there was no significant difference in efficacy between trials less than 3 weeks and those greater than 3 weeks. A total of 4 randomized placebo-controlled trials (1 each for phenytoin [Dilantin], carbamazepine [Tegretol], gabapentin [Neurontin], and valproate [Depakote]) have extractable data about the efficacy of anticonvulsants for the pain of diabetic neuropathy. As a class, the NNT for patients reporting at least a 50% reduction in pain was 2.7 (95% CI, 2.2-3.8); the NNH for minor adverse effects (typically transient central nervous system effect such as dizziness, somnolence, or disturbance in gait) was 2.7 (95% CI, 2.2-3.4)." }, { "input": "Tricyclic antidepressants, anticonvulsants, and capsaicin reduce the pain of diabetic neuropathy; limited data suggests that lidocaine patches may also be efficacious. Both tricyclic antidepressants and anticonvulsants are superior to placebo in relieving painful diabetic neuropathy. Patients taking anticonvulsants report reduced pain (NNT for at least 50% reduction in pain=2.7).", "output": "A report did not allow calculation of NNT, but the findings were consistent with these results. Phenytoin dosage was 300 mg/d; carbamazepine dosage was titrated to 200-600 mg/d, gabapentin from 300-3600 mg/d, and valproate 1200 mg/d. Patients taking anticonvulsants did not have a higher rate of withdrawal compared to those taking placebo. Limited evidence suggests no significant differences among anticonvulsants; there is insufficient evidence to determine optimal dosage of any of these agents." }, { "input": "Limited evidence suggests that selective serotonin reuptake inhibitors SSRIs are no more efficacious than placebo.", "output": "Limited evidence suggests that SSRIs are no more efficacious than placebo." }, { "input": "Compared with placebo, topical capsaicin also reduces pain (NNT=4).", "output": "Studies involving topical agents are also limited. According to an information summary,3 a total of 4 trials have addressed the efficacy of topical capsaicin for neuropathic pain. Compared with placebo, capsaicin reduces pain (NNT=4; 95% CI, 2.9-6.7)." }, { "input": "A single case series demonstrates that lidocaine patches are efficacious for neuropathic pain, though expensive.", "output": "One case series has suggested that lidocaine patches are efficacious for diabetic neuropathy." }, { "input": "Patients who receive inhaled beta-agonists for cough due to acute upper respiratory infections (URI) are just as likely to report a productive cough at 7 days compared with patients treated with placebo.", "output": "A systematic review looking at beta-agonists for acute bronchitis included the clinical diagnoses of both acute bronchitis and acute cough because a standard definition of bronchitis is lacking. Only two trials in this review examined inhaled beta-agonists. When results from these trials were combined for the outcome of productive cough at 7 days, inhaled beta-agonists showed no benefit. However, the authors note that details of the individual trials may help to clarify the effect of inhaled beta-agonists." }, { "input": "One trial showed a reduction in overall cough at 7 days (number needed to treat [NNT]=3).", "output": "One trial, a randomized controlled trial of adult patients with acute bronchitis in 2 community-based family practices, compared 23 patients receiving albuterolin a multidose inhaler (MDI) with 23 patients receiving placebo inhaler. Patients were also randomized to receive erythromycin or placebo tablets. Patients with pneumonia or a history of asthma or chronic obstructive pulmonary disease (COPD) were excluded. At 7 days, 61% of patients in the albuterol group reported cough compared with 91% in the control group (P=.02, NNT=3). No statistically significant difference was seen in productive cough or night cough. Smokers responded to inhaled albuterol similarly to nonsmokers. Erythromycin had no effect on cough and side effects were similar among all groups." }, { "input": "A trial found a reduction in overall symptom score in smokers and those with wheezing on initial exam.", "output": "A trial was a randomized controlled trial of 80 adults with cough due to acute respiratory infection; it compared fenoterol aerosol 4 times daily with placebo. Inhaled fenoterol is not available in the US but is similar to albuterol. This study showed no difference in cough at 7 days (relative risk [RR]=0.83; 95% confidence interval [CI], 0.52-1.30). In a subgroup analysis, however, smokers and those wheezing on initial exam had lower overall symptom scores when treated with fenoterol." }, { "input": "The use of yoga is consistent with recommendations for activity, as tolerated, for patients with low back pain. Literature evaluating the effectiveness of yoga for low back pain is scant, so it is unclear if yoga is equivalent to, or superior to, standard therapies", "output": "A randomized controlled trial studied a 6-week modified hatha yoga protocol with 22 patients. The yoga group spent an hour with a certified instructor twice weekly, while the control group received the same intervention delayed until the study phase was completed. This underpowered pilot study found trends in functional measurement scores for improved balance and flexibility, as well as decreased disability and depression in the yoga group, but the sample size was too small to detect significant changes." }, { "input": "The use of yoga is consistent with recommendations for activity, as tolerated, for patients with low back pain. Literature evaluating the effectiveness of yoga for low back pain is scant, so it is unclear if yoga is equivalent to, or superior to, standard therapies", "output": "In a case series, 21 women aged \u226560 years (mean age, 75) with hyperkyphosis, participated in twice-weekly 1-hour sessions of hatha yoga for 12 weeks. Measured height increased by a mean of 0.52 cm, forward curvature diminished, patients were able to get out of chairs faster, and they had longer functional reach. Eleven patients (48%) reported increased postural awareness/improvement and improved well-being; 58% perceived improvement in their physical functioning." }, { "input": "The use of yoga is consistent with recommendations for activity, as tolerated, for patients with low back pain. Literature evaluating the effectiveness of yoga for low back pain is scant, so it is unclear if yoga is equivalent to, or superior to, standard therapies", "output": "In a case series of 16 patients using various asanas for rehabilitation, 11 (69%) reported significant improvement, with near normal mobility and absence of pain. Those who reported recurring back pain also reported irregular practice of yoga." }, { "input": "The use of yoga is consistent with recommendations for activity, as tolerated, for patients with low back pain. Literature evaluating the effectiveness of yoga for low back pain is scant, so it is unclear if yoga is equivalent to, or superior to, standard therapies", "output": "In a survey of 3000 people receiving yoga for health ailments (1142 [38%] with back pain), 98% claimed that yoga benefited them." }, { "input": "Methylphenidate (Ritalin) is effective in the short-term treatment of attention deficit/hyperactivity disorder (ADHD).", "output": "The effectiveness of short-term methylphenidate in the treatment of adolescents with ADHD. Most participants in these studies are males aged <13 years. Therefore, any conclusions about the effectiveness of methylphenidate in older adolescents must be inferred." }, { "input": "Methylphenidate (Ritalin) is effective in the short-term treatment of attention deficit/hyperactivity disorder (ADHD).", "output": "Most children with ADHD will have symptoms persisting into teenage years, and methylphenidate has been increasingly prescribed for them." }, { "input": "Methylphenidate (Ritalin) is effective in the short-term treatment of attention deficit/hyperactivity disorder (ADHD).", "output": "A comprehensive systematic review found 8 well-controlled crossover trials with an average sample size of 24.8 (range, 9-48). The average duration of the studies was 6 weeks. The majority of the participants were white males with a mean age of 13 years. Each study showed statistically significant improvement from treatment with methylphenidate. Average effect sizes were calculated for 3 domains: ADHD symptoms (0.94), social behavior (1.06), and academic performance (1.25). Effect sizes were calculated using a modified Cohen's d, which is the difference between the treated and untreated means divided by the standard deviation in the untreated condition. It is difficult to translate these changes in effect size into clinically meaningful outcome measures, although one rule of thumb estimates an effect size of 0.8 is moderate to large. Of the 3 studies that reported the proportion of subjects with clinically significant improvement, the modal result was about one half showings improvement with methylphenidate. Of trials assessing dosing levels, <50% found significant differences between \"low\" and \"high\" doses. However, the researchers did not give their definition of low and high doses. Also, diminishing clinical improvement was noted with higher methylphenidate doses." }, { "input": "Though the immediate-release preparation is the best studied of methylphenidate formulations, extended-release methylphenidate (Concerta) has similar benefits, with a dosing regimen that may better suit an adolescent lifestyle.", "output": "A single study on the once-daily stimulant preparation, extended-release methylphenidate, shows statistically significant improvement in adolescent ADHD. In this multicenter, randomized, double-blind, placebo-controlled trial of 177 adolescents, subjects were given placebo (n=87) or extended-release methylphenidate (n=90) at titrated doses from 18 mg/d to 72 mg/d. Following a subsequent 2-week randomization phase, clinical investigators found extended-release methylphenidate significantly superior to placebo (P=.001) on the ADHD scale. Subjects also rated it significantly superior to placebo (P=.001) on the Conners-Wells' Self-Report Scale. Mean dose and average age were not reported. This study has been presented as an abstract and is not yet published." }, { "input": "Though the immediate-release preparation is the best studied of methylphenidate formulations, extended-release methylphenidate (Concerta) has similar benefits, with a dosing regimen that may better suit an adolescent lifestyle.", "output": "The American Academy of Child and Adolescent Psychiatry AACAP supports the prescribing of methylphenidate in adolescents with ADHD. Given the unique psychosocial, environmental, and scheduling challenges of adolescence, the AACAP mentions extended-release methylphenidate as \"well-suited for treatment of adolescents.\"." }, { "input": "Testing for thyroid-stimulating hormone TSH finds more cases of unrecognized hypothyroidism than history and physical examination.", "output": "A cohort study evaluated 1154 women (aged 50-72) in a primary care setting using both history and physical and TSH testing. TSH testing found 3 women with overt hypothyroidism not identified by history and physical. History and physical identified 286 women with indications for TSH testing, 2 of whom had mild hypothyroidism and 1 with mild hyperthyroidism." }, { "input": "Testing for thyroid-stimulating hormone TSH finds more cases of unrecognized hypothyroidism than history and physical examination.", "output": "In a cohort study, 2000 adults from a primary care population underwent history and physical and TSH testing. The TSH screen identified 19 cases of hypothyroidism not found by history and physical, while the history and physical prompted evaluation of 35 patients without abnormal TSH." }, { "input": "Women with an initial screening TSH >10 mU/L are more likely to develop complications of hypothyroidism and to benefit from treatment.", "output": "A study followed 2779 adults (1494 women) with all types of thyroid disease for 20 years and found that 55% of women with TSH >6 and a positive antibody test developed overt hypothyroidism. Ninety percent of patients with an initial TSH >10 eventually progressed to overt disease." }, { "input": "Women with an initial screening TSH >10 mU/L are more likely to develop complications of hypothyroidism and to benefit from treatment.", "output": "A prospective study of 30 patients (6 women) with subclinical hypothyroidism found 16 (3 women) who progressed to overt disease within 24 months. The remaining patients maintained normal FT4 levels for at least 15 years despite persistently elevated TSH." }, { "input": "Women with an initial screening TSH >10 mU/L are more likely to develop complications of hypothyroidism and to benefit from treatment.", "output": "Among 1210 primary care patients (700 women) aged >60 years, 73 women with subclinical hypothyroidism were identified and followed for 12 months. Of these, 13 (18%) progressed to overt disease." }, { "input": "Treating women who have asymptomatic hypothyroidism and a screening TSH >10 mU/L prevents progression to symptomatic overt disease.", "output": "A meta-analysis combined 13 studies, involving 247 patients with subclinical hypothyroidism, all of whom were given thyroid replacement. All studies reported a decrease in total cholesterol (mean -7.9 mg/dL), and 9 reported a decrease in LDL (mean -10 mg/dL)." }, { "input": "Treating women who have asymptomatic hypothyroidism and a screening TSH >10 mU/L prevents progression to symptomatic overt disease.", "output": "A meta-analysis with 278 hypothyroid patients given thyroid replacement found a reduction of total cholesterol (mean -15 mg/dL). LDL effects were not reported. The clinical significance of lipid changes in these circumstances is unknown." }, { "input": "Treating women who have asymptomatic hypothyroidism and a screening TSH >10 mU/L prevents progression to symptomatic overt disease.", "output": "A retrospective study of 709 women referred to an endocrine clinic for evaluation of abnormal lipoprotein levels identified 34 (4.8%) with undiagnosed hypothyroidism. Thyroid hormone treatment significantly reduced total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with initial TSH >10, but not in those with a TSH <10." }, { "input": "Treating women who have asymptomatic hypothyroidism and a screening TSH >10 mU/L reduces serum lipid levels.", "output": "A randomized trial involving 42 women with subclinical hypothyroidism measured lipid levels before and after 6 months of levothyroxine treatment. Levothyroxine reduced total cholesterol and LDL significantly compared with placebo. Additionally, the subclinical hypothyroidism patients had higher baseline lipid levels when compared with 27 euthyroid controls." }, { "input": "Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms, and its effect on cardiac disease remains controversial.", "output": "Whether treatment prevents myocardial infarction and atherosclerosis is unknown." }, { "input": "Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms, and its effect on cardiac disease remains controversial.", "output": "A cohort study, involving 2779 adults studied aged >20 years, did not find an association between subclinical hypothyroidism and ischemic heart disease." }, { "input": "Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms, and its effect on cardiac disease remains controversial.", "output": "Four small randomized controlled trials used symptom-rating scales to measure symptom relief with treatment of subclinical hypothyroidism. One study involved patients found by screening; the other 3 did not indicate means of diagnosis. Three studies found no significant improvement." }, { "input": "Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms, and its effect on cardiac disease remains controversial.", "output": "A small randomized controlled trial involving 33 unblinded patients found that those taking thyroid replacement had lower symptom scores (number needed to treat [NNT]=3.5)." }, { "input": "Treating women who have subclinical hypothyroidism found by screening does not reduce symptoms, and its effect on cardiac disease remains controversial.", "output": "A randomized controlled trial of 20 people with subclinical hypothyroidism found significantly improved left ventricular function assessed by echocardiography after 6 months of treatment with levothyroxine vs placebo." }, { "input": "Treatment may increase bone loss in premenopausal women.", "output": "A meta-analysis of 41 controlled, cross-sectional studies involving 1250 women treated with thyroid replacement for all causes (ie, not specifically subclinical hypothyroidism) found that replacement therapy (mean duration of treatment, 7 to 9 years) was associated with bone loss in premenopausal women, but not in postmenopausal women." }, { "input": "Treatment may increase bone loss in premenopausal women.", "output": "A randomized trial of 37 patients over 55 with subclinical hypothyroidism (28 of whom were women), found that thyroid hormone reduced bone mineral density, as assessed by dual-energy x-ray absorptiometry (DEXA) scans over a 10-month period." }, { "input": "Treatment may cause symptoms in certain individuals.", "output": "In several trials, patients withdrew due to adverse effects. Two of 37 patients receiving L-thyroxine in 1 study withdrew because of new atrial fibrillation and worsened angina, and 2 of 20 patients in another study withdrew because of nervousness and palpitations." }, { "input": "The best way to prevent recurrent bacterial vaginosis is to treat the initial episode with the most effective regimen. Metronidazole (500 mg orally twice daily for 7 days) has the lowest recurrence rate among antimicrobial regimens for bacterial vaginosis (20% vs 34%-50% for other agents).", "output": "A meta-analysis by the Centers for Disease Control and Prevention's (CDC) bacterial vaginosis working group reviewed the indications for therapy and best treatments for bacterial vaginosis. The group found 25 trials evaluating oral metronidazole therapy involving 2742 women. Although cure rates using either 500 mg twice daily for 5 to 7 days or 2 g as a single dose were similar at 2 weeks post follow-up (85%; range 67%-98%), the single-dose regimen led to higher relapse rates 1 month after treatment (35%-50% vs 20%-33%). Six trials enrolling 946 women assessed the efficacy of various topical vaginal treatments. Metronidazole gel, clindamycin cream, and clindamycin ovules had a wide range of initial cure rates (50%-95%), but all had higher relapse rates at 4 weeks than did oral metronidazole for 1 week (34%-49%)." }, { "input": "Women should be treated if they are symptomatic.", "output": "The CDC reviewers identified causal relationships between bacterial vaginosis and plasmacell endometritis, postpartum fever, and posthysterectomy vaginal-cuff cellulitis. They therefore concluded it is reasonable to try to prevent post-procedure infections by treating women who have asymptomatic bacterial vaginosis before hysterectomy or pregnancy termination. Although bacterial vaginosis has been associated with preterm labor, trials evaluating treatment of bacterial vaginosis to prevent preterm delivery are conflicting. A Cochrane review of bacterial vaginosis and preterm labor suggests treating women at high risk for preterm birth may reduce the risk of low birthweight and preterm prelabor rupture of membranes." }, { "input": "Women should be treated if they are at risk for preterm labor.", "output": "A Cochrane review of bacterial vaginosis and preterm labor suggests treating women at high risk for preterm birth may reduce the risk of low birthweight and preterm prelabor rupture of membranes." }, { "input": "When bacterial vaginosis recurs, providers should confirm the diagnosis.", "output": "For women who continue to have recurrent or unresolved vaginal symptoms not explained by candidiasis or sexually transmitted infections such as trichomoniasis, consider less common causes such as atrophic vaginitis, chemical/irritant vaginitis, allergic vaginitis, Behcets disease, desquamative interstitial vaginitis, or erosive lichen planus vaginitis." }, { "input": "When bacterial vaginosis recurs, providers should identify and control risk factors for recurrence.", "output": "Douching is the best-studied risk factor for bacterial vaginosis. A recent multicenter cross-sectional study of 1200 women assessed douching practices and found that recent douching increased the risk of bacterial vaginosis twofold (odds ratio=2.1; 95% confidence interval, 1.3-3.1)." }, { "input": "When bacterial vaginosis recurs, providers should consider other causes while retreating bacterial vaginosis.", "output": "For women who continue to have recurrent or unresolved vaginal symptoms not explained by candidiasis or sexually transmitted infections such as trichomoniasis, consider less common causes such as atrophic vaginitis, chemical/irritant vaginitis, allergic vaginitis, Behcets disease, desquamative interstitial vaginitis, or erosive lichen planus vaginitis." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "Current practice is to slowly taper and discontinue medication after 12-18 months of maintenance treatment if there are no significant residual symptoms, no increased psychosocial stressors, and no history of severe or recurrent relapse." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "Before treating, evaluate patients for comorbid mood, anxiety, personality, substance use, or medical disorders, which affect 40%-50% of patients with panic disorder, and may influence the choice of treatment." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "An adequate trial of medication requires 6-8 weeks." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "CBT and imipramine each reduce symptoms in 45%-48% of patients; combining them reduces symptoms in 60%. Imipramine is more effective initially; CBT is more durable9 but effects may be therapist-dependent." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "Two meta-analyses concluded that CBT is as effective as antidepressants or BDZs during acute treatment and during long-term follow-up (31-121 weeks)." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "Adding a BDZ to an SSRI for the first 3 weeks can rapidly stabilize symptoms." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "Clomipramine is serotoninergic and was more effective than other tricyclics in an RCT." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "In 2 randomized head-to-head trials, remission rates (eliminating symptoms) were 50%-65% for paroxetine, 37%-53% for clomipramine, and 32%-34% for placebo after 9-12 weeks of therapy; differences between the 2 active drugs were not significant." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "SSRIs were equivalent to imipramine or alprazolam in an effect-size analysis." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "SSRIs were more effective than imipramine or alprazolam in a meta-analysis." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "Behavioral therapy with exposure homework has good long-term results." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines (BDZs), and cognitive behavioral therapy (CBT) are effective for panic disorder (PD) with or without agoraphobia (NNT5 for complete remission). SSRIs may be most effective, but BDZs work faster. Clomipramine is more effective than other TCAs. CBT improves response and decreases relapse rates when used with medication. Severe symptoms may warrant short-term use of a BDZ until other therapies take effect.", "output": "When used in conjunction with medication, graded exposure to panicinducing situations reduces agoraphobia but does not improve relapse rates." }, { "input": "With adults, oral theophylline may help lower the dosage of inhaled steroids needed to control chronic asthma. It offers no benefit for acute asthma exacerbations. For children, intravenous aminophylline may improve the clinical course of severe asthma attacks. Side effects and toxicity limit use of these medications in most settings.", "output": "The largest RCT of aminophylline in children demonstrated a reduced intubation rate (NNT = 14 CI: 7.8-77). Children receiving aminophylline experienced more vomiting (RR = 3.69; 95%CI: 2.15-6.33)." }, { "input": "With adults, oral theophylline may help lower the dosage of inhaled steroids needed to control chronic asthma. It offers no benefit for acute asthma exacerbations. For children, intravenous aminophylline may improve the clinical course of severe asthma attacks. Side effects and toxicity limit use of these medications in most settings.", "output": "Treatment with aminophylline did not reduce length of hospital stay or the number of rescue nebulizers needed." }, { "input": "With adults, oral theophylline may help lower the dosage of inhaled steroids needed to control chronic asthma. It offers no benefit for acute asthma exacerbations. For children, intravenous aminophylline may improve the clinical course of severe asthma attacks. Side effects and toxicity limit use of these medications in most settings.", "output": "Intravenous aminophylline does appear to be clinically beneficial for children with severe exacerbations, defined as an FEV 1 of 35%-40% of predicted value. Critically ill children receiving aminophylline in addition to usual care exhibited an improved FEV 1 at 24 hours (mean difference = 8.4%; 95% CI: 0.82 to 15.92) and reduced symptom scores at 6 hours." }, { "input": "With adults, oral theophylline may help lower the dosage of inhaled steroids needed to control chronic asthma. It offers no benefit for acute asthma exacerbations. For children, intravenous aminophylline may improve the clinical course of severe asthma attacks. Side effects and toxicity limit use of these medications in most settings.", "output": "When added to low-dose ICS for maintenance, theophylline was as effective as high-dose ICS alone in improving FEV 1 , decreasing day and night symptoms, and reducing the need for rescue medications and the incidence of attacks. This suggests theophylline has utility as a steroid sparing agent." }, { "input": "With adults, oral theophylline may help lower the dosage of inhaled steroids needed to control chronic asthma. It offers no benefit for acute asthma exacerbations. For children, intravenous aminophylline may improve the clinical course of severe asthma attacks. Side effects and toxicity limit use of these medications in most settings.", "output": "When compared with placebo in the management of acute exacerbations, theophylline confers no added benefit to beta-agonist therapy (with or without steroids) in improving pulmonary function or reducing hospitalization rates. Side effects occurred more often in the theophylline group: palpitations/arrhythmias (OR = 2.9; 95% CI: 1.5 to 5.7) and vomiting (OR = 4.2; 95% CI: 2.4 to 7.4). For moderately severe asthma in patients already receiving inhaled corticosteroids (ICS), theophylline as maintenance therapy equaled long-acting beta-2-agonists in increasing FEV 1 and PEFR, but was less effective in controlling night time symptoms." }, { "input": "Ferrous salt preparations ferrous sulfate, ferrous gluconate, and ferrous fumarate are equally tolerable.", "output": "A randomized, double-blinded, placebo-controlled study in 1496 subjects examined side-effect rates of 3 iron salt formulations using equal dosages of elemental iron. Gastrointestinal GI side-effect rates were not significantly different. The side-effect rate in the ferrous sulfate group 23% was significantly different from that of the placebo group 14%; thus, for every 11 patients treated with ferrous sulfate, 1 patient would have GI side effects attributable to the iron salt number needed to harm [NNH] = 11." }, { "input": "Controlled-release iron preparations cause less nausea and epigastric pain than conventional ferrous sulfate, although the discontinuation rates between the 2 iron formulations were similar.", "output": "A double-blinded study found a lower rate of nausea and epigastric pain in the controlled-release iron formulation among 1376 blood donors receiving 200 mg/day elemental iron 3.3% vs 6.4%, P <.05, NNH = ~32." }, { "input": "Controlled-release iron preparations cause less nausea and epigastric pain than conventional ferrous sulfate, although the discontinuation rates between the 2 iron formulations were similar.", "output": "A nonblinded randomized trial of 543 non-anemic adult patients taking 50 mg/day elemental iron also found a lower rate of stomach-related side effects in the controlled-release group 12.2% vs 27.2%, P <.001, NNH = ~7." }, { "input": "Controlled-release iron preparations cause less nausea and epigastric pain than conventional ferrous sulfate, although the discontinuation rates between the 2 iron formulations were similar.", "output": "A study of 159 subjects found fewer subjects discontinuing the polysaccharide-iron complex taken with meals than ferrous sulfate taken on an empty stomach." }, { "input": "Controlled-release iron preparations cause less nausea and epigastric pain than conventional ferrous sulfate, although the discontinuation rates between the 2 iron formulations were similar.", "output": "A study of 60 subjects taking both preparations on an empty stomach found no difference in side-effect rates." }, { "input": "Controlled-release iron preparations cause less nausea and epigastric pain than conventional ferrous sulfate, although the discontinuation rates between the 2 iron formulations were similar.", "output": "Two small, randomized, blinded studies found no difference in rates of GI side effects between carbonyl iron and ferrous sulfate." }, { "input": "other", "output": "Wintrobe's Clinical Hematology and Williams Hematology recommend ferrous sulfate as the standard oral iron preparation, and assert that claims of improved tolerability of one oral iron preparation over another have not been substantiated." }, { "input": "Rate control with long-term anticoagulation is recommended for most patients with atrial fibrillation.", "output": "Two systematic reviews have looked at the efficacy of medications for ventricular rate control in atrial fibrillation. The first analyzed 54 trials involving 17 agents and focused on digoxin calcium-channel blockers and beta-blockers. The second systematic review evaluated 45 trials with similar agents. Both reviews were unable to perform mathematical pooling due to the heterogeneity of the studies. However, both showed strong evidence for superior ventricular rate control at both exercise and rest with verapamil and diltiazem compared with placebo. All beta-blockers tested were effective in rate-control during exercise and most excluding labetalol and celiprolol were effective at rest." }, { "input": "A rhythmcontrol strategy provides no survival or quality-of-life benefit when compared with rate control and causes more adverse drug effects and increased hospitalizations.", "output": "The AFFIRM trial, the largest (n=4060), was a nonblinded, randomized, multicenter study with an average follow-up of 3.5 years. The patients were aged 65 years or older and had at least 1 other risk factor for stroke. The rhythm-control group was given an antiarrhythmic medication chosen by the treating physician, while the rate-control group was given either a beta-blocker, a calcium-channel blocker, digoxin, or a combination of these as needed. Heart-rate goals were a resting pulse under 80 beats per minute, and a pulse after a 6-minute walk under 110 beats per minute. An intention-totreat analysis was followed. There was no difference between the 2 groups for the composite endpoints of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, or cardiac arrest. A nonsignificant trend was observed for mortality favoring the rate-control group (relative risk [RR]=1.15; 95% confidence interval [CI], 0.99-1.34). Quality-of-life measures were equivalent in the 2 groups at all points in the study." }, { "input": "A rhythmcontrol strategy provides no survival or quality-of-life benefit when compared with rate control and causes more adverse drug effects and increased hospitalizations.", "output": "An RCT found no greater benefit with a rhythm-control strategy vs rate-control for most patients with atrial fibrillation." }, { "input": "Non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) and most beta-blockers are effective for controlling heart rate both at rest and during exercise.", "output": "Two systematic reviews have looked at the efficacy of medications for ventricular rate control in atrial fibrillation. The first analyzed 54 trials involving 17 agents and focused on digoxin calcium-channel blockers and beta-blockers. The second systematic review evaluated 45 trials with similar agents. Both reviews were unable to perform mathematical pooling due to the heterogeneity of the studies. However, both showed strong evidence for superior ventricular rate control at both exercise and rest with verapamil and diltiazem compared with placebo. All beta-blockers tested were effective in rate-control during exercise and most excluding labetalol and celiprolol were effective at rest." }, { "input": "Digoxin is only effective for rate control at rest and should be reserved for patients with systolic dysfunction or as an adjunct for those inadequately rate-controlled on calcium-channel blockers or beta-blockers.", "output": "Two systematic reviews have looked at the efficacy of medications for ventricular rate control in atrial fibrillation. The first analyzed 54 trials involving 17 agents and focused on digoxin calcium-channel blockers and beta-blockers. The second systematic review evaluated 45 trials with similar agents. Both reviews were unable to perform mathematical pooling due to the heterogeneity of the studies. However, both showed strong evidence for superior ventricular rate control at both exercise and rest with verapamil and diltiazem compared with placebo. All beta-blockers tested were effective in rate-control during exercise and most excluding labetalol and celiprolol were effective at rest." }, { "input": "Digoxin is only effective for rate control at rest and should be reserved for patients with systolic dysfunction or as an adjunct for those inadequately rate-controlled on calcium-channel blockers or beta-blockers.", "output": "Digoxin was ineffective during exercise and less effective than beta-blockers or calcium-channel blockers at rest." }, { "input": "Subgroups in whom rhythm control may be superior are patients with persistent fatigue and dyspnea despite ventricular rate control and those unable to achieve adequate rate control. Both pharmacologic conversion is an appropriate option in these patients.", "output": "Pharmacologic conversion for patients who desire a rhythm-control strategy are described as appropriate options." }, { "input": "Subgroups in whom rhythm control may be superior are patients with persistent fatigue and dyspnea despite ventricular rate control and those unable to achieve adequate rate control. Both pharmacologic conversion is an appropriate option in these patients.", "output": "A meta-analysis of 60 RCTs evaluated 8 drugs for acute cardioversion. Ibutilide, flecainide, dofetilide, propafenone, and amiodarone were found to have the strongest evidence of efficacy. There was moderate evidence for quinidine and insufficient evidence for disopyramide and sotalol. Studies of pharmacologic conversion suffer from small ample size, short follow-up, and variable duration of atrial fibrillation. A review of limited research reveals an 80% to 85% immediate success rate for DC cardioversion, with rare side-effects of ventricular tachycardia, transient AV node dysfunction, and significant skin blistering." }, { "input": "Direct-current cardioversion is an appropriate option in these patients.", "output": "A meta-analysis of 60 RCTs evaluated 8 drugs for acute cardioversion. Ibutilide, flecainide, dofetilide, propafenone, and amiodarone were found to have the strongest evidence of efficacy. There was moderate evidence for quinidine and insufficient evidence for disopyramide and sotalol. Studies of pharmacologic conversion suffer from small ample size, short follow-up, and variable duration of atrial fibrillation. A review of limited research reveals an 80% to 85% immediate success rate for DC cardioversion, with rare side-effects of ventricular tachycardia, transient AV node dysfunction, and significant skin blistering." }, { "input": "Long-term anticoagulation is necessary for high-risk patients even if they are successfully managed with rhythm control.", "output": "For patients who elect a rhythm-control approach, RCTs demonstrate the need for continued long-term anticoagulation in high-risk patients even if they are maintained in sinus rhythm. (High-risk patients are defined as those aged >65 years, or those <65 years with 1 or more stroke risk factors: diabetes, hypertension, heart failure, prior transient ischemic attack or stroke or systemic embolism, or echocardiographic evidence of a left atrium >50 mm, a shortening fraction <25%, or an ejection fraction <40%.)." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "Several cohort studies (N=316, N=313, N=54) have found no statistically significant relationship between early solid feeding and obesity at 6 months, 5 years, and 6 years, respectively." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "A randomized, prospective trial (N=165) compared early and late introduction of solids with fat mass at 3, 6, and 12 months of age. No significant difference in adiposity between treatment groups was noted at any end point." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "A Dutch prospective cohort study (N=2558) not only confirmed the findings that there is no benefit in delaying solids longer than 4 months or potentially allergenic solids longer than 6 months to prevent eczema, but found a higher risk of atopy at 2 years of age after delayed introduction of solids, even after accounting for reverse causation (delaying solids in children with early atopic symptoms)." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "A German prospective cohort study (N=5991) found no benefit in delaying solids longer than 4 months or potentially allergenic solids longer than 6 months to prevent eczema." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "Subsequent studies have not showed evidence of an association between early solid introduction and eczema." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "A 10-year New Zealand cohort study (N=1265) showed some evidence of an association between early solid introduction and eczema. The study concluded that introducing solids and increasing food diversity before 4 months of age was associated with eczema at 2 to 10 years." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "A 2006 meta-analysis of 13 studies examining the risk of atopic diseases associated with early introduction of solids concluded that \"there is insufficient evidence to suggest that, on its own, the early introduction of solids to infants is associated with an increased risk of asthma, food allergy, allergic rhinitis, or animal allergies.\" The meta-analysis showed some evidence of an association between early solid introduction and eczema, the strongest being a 10-year New Zealand cohort study (N=1265)." }, { "input": "Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness. Very weak evidence suggests an increased risk of atopic dermatitis.", "output": "A cohort study (N=455) in Dundee, Scotland, reported that infants fed solids before 12 weeks were \"significantly heavier\" at 26 weeks but not at 52 or 104 weeks; this finding has limited validity, however, because the study didn't control for parental weight. The Dundee study also found no significant association between gastrointestinal illness and the timing of introduction of solids." }, { "input": "A single cohort study found an association between early gluten exposure and increased risk of celiac disease in high-risk infants, who carry the HLA-DR3 or DR4 allele.", "output": "A prospective observational study (N=1560) of infants at increased risk of celiac disease (defined as having either the HLA-DR3 or DR4 allele) determined that the optimum time for introducing gluten-containing foods is 4 to 6 months. Infants exposed in the first 3 months of life had a 5-fold increased risk of developing celiac disease, and babies exposed after the sixth month had nearly a 2-fold increased risk." }, { "input": "The evaluation of a suspected rotator cuff tear should start with a history and a clinical exam of the shoulder.", "output": "A meta-analysis of 10 cohort studies found the overall sensitivity and specificity of a clinical exam to rule out a full-thickness rotator cuff tear to be 0.9 (95% confidence interval [CI], 0.87-0.93) and 0.54 (95% CI, 0.47-0.61). However, no single physical exam finding provided comparable accuracy." }, { "input": "Three clinical test results in particular-supraspinatus weakness, weakness of external rotation, and impingement-or 2 positive tests for a patient older than 60 years were highly predictive of rotator cuff tear.", "output": "A prospective study of 400 patients comparing 23 different clinical exams found that 3 simple clinical tests-supraspinatus weakness, weakness in external rotation, and the presence of impingement-were highly predictive of rotator cuff tear. When all 3 tests were positive, or when 2 tests were positive for a patient aged >60 years, there was a 98% chance of the patient having a rotator cuff tear." }, { "input": "Either magnetic resonance imaging (MRI) or ultrasound can confirm a possible full-thickness tear.", "output": "In a systematic review of 38 cohort studies, the overall sensitivity and specificity of ultrasound for full-thickness rotator cuff tears was 0.87 (95% CI, 0.84-0.89) and 0.96 (95% CI, 0.94-0.97). For partial-thickness tears, ultrasound sensitivity was 0.67 (95% CI, 0.61-0.73). Positive and negative predictive values of a test depend on the prevalence of the condition in the study population. In the case of rotator cuff tears, such differences in prevalence of rotator cuff tears in the 38 cohort studies left it unclear whether a negative ultrasound could reliably rule out a tear." }, { "input": "Either magnetic resonance imaging (MRI) or ultrasound can confirm a possible full-thickness tear.", "output": "A meta-analysis of 29 cohort studies of MRI for the diagnosis of full-thickness tears found a pooled sensitivity of 0.89 (95% CI, 0.86-0.92) and a pooled specificity of 0.93 (95% CI, 0.91-0.95), respectively. For partial-thickness tears, the pooled MRI sensitivity was lower at 0.44 (95% CI, 0.36-0.51), but with a high specificity of 0.90 (95% CI, 0.87-0.92).1 This implies that MRI is the most valuable test to rule out a partial-thickness tear. However, we found no studies that directly compared the test characteristics of ultrasound and MRI." }, { "input": "Either magnetic resonance imaging (MRI) or ultrasound can confirm a possible full-thickness tear.", "output": "The incidence of rotator cuff tears increases with age and with athletic activity." }, { "input": "If a patient has an implantable device prohibiting MRI imaging, conventional arthrography is an alternative.", "output": "One prospective trial (in which patients were randomized to the order in which MRI or arthrography were performed) of 38 patients showed arthrography to have a sensitivity of 0.50 and a specificity of 0.96 when used to diagnose full-thickness tears." }, { "input": "Suspected partial-thickness tears are best verified with an ultrasound.", "output": "Magnetic resonance arthrography (MRA), based on 6 cohort studies, may be accurate in the diagnosis of a full-thickness tear, with a sensitivity of 0.95 (95% CI, 0.82-0.98) and specificity of 0.93 (95% CI, 0.84-0.97). In these studies, diagnosis of partial-thickness tears with MRA was inconsistent. The invasiveness of MRA limits its utility as compared with MRI and ultrasound." }, { "input": "Infants and toddlers with suspected iron-deficiency anemia (IDA) should begin treatment with oral ferrous sulfate (3 mg/kg/d of elemental iron). A rise in hemoglobin >1 g/dL after 4 weeks supports the diagnosis of iron deficiency, and supplementation should continue for 2 additional months to replenish iron stores. Recheck hemoglobin at the end of treatment and again 6 months later.", "output": "An RCT of 557 anemic children under 24 months of age in Ghana demonstrated that ferrous sulfate (5 mg/kg/d) given once daily was equivalent to 3-times-daily dosing in terms of effectiveness (61% vs 56%) and tolerance. Less frequent dosing has been studied in developing countries with mixed results." }, { "input": "Infants and toddlers with suspected iron-deficiency anemia (IDA) should begin treatment with oral ferrous sulfate (3 mg/kg/d of elemental iron). A rise in hemoglobin >1 g/dL after 4 weeks supports the diagnosis of iron deficiency, and supplementation should continue for 2 additional months to replenish iron stores. Recheck hemoglobin at the end of treatment and again 6 months later.", "output": "Consensus recommendations suggest that iron deficiency should be the presumptive diagnosis in a child with anemia, and that a trial of ferrous sulfate at a dose of 3 mg/kg/d of elemental iron be instituted because of low cost, tolerability, and relative simplicity." }, { "input": "Infants and toddlers with suspected iron-deficiency anemia (IDA) should begin treatment with oral ferrous sulfate (3 mg/kg/d of elemental iron). A rise in hemoglobin >1 g/dL after 4 weeks supports the diagnosis of iron deficiency, and supplementation should continue for 2 additional months to replenish iron stores. Recheck hemoglobin at the end of treatment and again 6 months later.", "output": "In an Indonesian randomized controlled trial (RCT), baseline Bayley scores were 10% to 15% lower (P<.01) for infants (12-18 months) with IDA compared with both nonanemic iron-deficient and iron-sufficient infants. Following treatment with ferrous sulfate (3 mg/kg/d of elemental iron) for 4 months, the IDA infants' Bayley scores improved compared with those of nonanemic children." }, { "input": "For primary prevention, counsel parents on the use of iron-fortified formula for non-breastfed infants until the age 12 months.", "output": "In a cohort study, infants given iron-fortified formula (n=98) were less likely to become iron-deficient by their 12-month visit than infants fed whole cow milk (n=69) (11.2% vs 24.6%, number needed to treat [NNT]=8)." }, { "input": "For primary prevention, counsel parents on the use of iron-fortified formula for non-breastfed infants until the age 12 months.", "output": "In a RCT of innercity children who had been switched to cow's milk by 6 months, half (n=50) were randomized to receive iron-fortified formula for another year, resulting in a decreased risk of anemia at 24 months (0% vs 26%, NNT=4), and smaller declines in developmental functioning compared with those on cow's milk." }, { "input": "Parents should introduce iron-rich foods between 4 and 6 months to breastfed babies.", "output": "The AAP recommends that parents should refrain from feeding cow's milk to infants until after age 12 months and introduce iron-enriched foods between ages 4 and 6 months." }, { "input": "Alternative antiplatelet therapy for stroke prevention is indicated for patients who experience transient ischemic attacks (TIAs) while on aspirin therapy.", "output": "A meta-analysis evaluated 158 randomized trials involving primary and secondary prevention of stroke, concluding that antiplatelet therapy results in a 30% reduction in occurrence of ischemic stroke (95% confidence interval [CI], 24-35; P<.0001). Data that evaluate the antiplatelet efficacy following a TIA while on aspirin therapy are limited." }, { "input": "The combination of aspirin and extended-release dipyridamole reduces the risk of stroke following a TIA.", "output": "Combination aspirin and dipyridamole (Aggrenox) therapy reduces the risk of secondary stroke. Several randomized controlled trials (RCTs) that evaluated this combination for prevention of stroke included patients who had TIAs. Although the combination reduced the occurrence of a subsequent stroke, the difference was not significant compared with aspirin alone, possibly due to the use of high-dose aspirin in the comparison group." }, { "input": "The combination of aspirin and extended-release dipyridamole reduces the risk of stroke following a TIA.", "output": "A large-scale RCT including patients with previous stroke or TIA concluded that the combination of aspirin and extended-release dipyridamole reduced the occurrence of stroke by 23% (P<.001) compared with aspirin (number needed to treat [NNT]=35; 95% CI, 20-130). In this trial, patients with a prior TIA comprised only one quarter of the patients studied. Subgroup analyses of patients on aspirin prior to experiencing a TIA have not been reported." }, { "input": "Thienopyridines (eg, clopidogrel and ticlopidine) are an alternative for patients at high risk for a cardioembolic event. Ticlopidine reduces the risk of stroke following TIA, specifically showing benefit for patients previously on aspirin.", "output": "An RCT studying secondary prevention of stroke, in which 50% of the study population experienced a TIA as their qualifying event, concluded that ticlopidine (Ticlid) reduced the risk of stroke by 21% (95% CI, 0.04-0.38; P=.024)." }, { "input": "Thienopyridines (eg, clopidogrel and ticlopidine) are an alternative for patients at high risk for a cardioembolic event. Ticlopidine reduces the risk of stroke following TIA, specifically showing benefit for patients previously on aspirin.", "output": "Subgroup analysis indicated that ticlopidine provided superior benefit for patients on aspirin or anticoagulant therapy at the time of their qualifying event." }, { "input": "Clopidogrel has not shown significant reduction in reoccurrence of stroke and has not been studied for patients with a previous TIA. Aspirin and a thienopyridine do not provide significant additional reduction in secondary strokes.", "output": "A large-scale RCT concluded that the combination of clopidogrel and aspirin did not provide additional benefit in reducing a combined endpoint of cardioembolic events in comparison with aspirin alone for patients with prior stroke or TIA. The combination resulted in a significantly greater number of life-threatening and major bleeding complications." }, { "input": "Clopidogrel has not shown significant reduction in reoccurrence of stroke and has not been studied for patients with a previous TIA. Aspirin and a thienopyridine do not provide significant additional reduction in secondary strokes.", "output": "An RCT comparing clopidogrel with aspirin found a nonsignificant risk reduction of 0.3% (95% CI, -0.03 to 0.9; P=.26) in occurrence of stroke when compared with aspirin for patients with previous stroke, myocardial infarction, or peripheral arterial disease. A 0.9% absolute reduction in combined risk of cardioembolic events was reported for patients randomized to clopidogrel (NNT=111; 95% CI, 57-2454; P=.043), but patients with TIA were excluded from the study population." }, { "input": "other", "output": "The American Heart Association addresses the lack of evidence in treating patients who experience a TIA while on aspirin therapy. They recommend therapy be individualized for each patient to receive either the combination of extended-release dipyridamole and aspirin or clopidogrel daily for secondary prevention. Clopidogrel 75 mg daily is recommended over ticlopidine 250 mg twice daily due to its favorable safety profile. Similarly, the American College of Chest Physicians recommends use of dipyridamole and aspirin 200/25 mg twice daily or clopidogrel 75 mg daily." }, { "input": "Several small studies report some benefit from use of a hypoallergenic (protein hydrolysate) formula, maternal diet adjustment (focusing on a low-allergen diet), and reduced stimulation of the infant. While dicyclomine has been shown to be effective for colic, there are significant concerns about its safety, and the manufacturer has contraindicated its use in this population. An herbal tea containing chamomile, vervain, licorice, fennel, and balm-mint was also effective in a small RCT, but the volume necessary for treatment limits its usefulness", "output": "A systematic review analyzed controlled clinical trials lasting at least 3 days involving infants less than 6 months of age who cried excessively. Twenty-seven studies were included; the outcome measure was colic symptoms, typically reported as duration of crying. Two reports studying hypoallergenic (protein hydrolysate) formula in nearly 130 infants found an effect size of 0.22 (95% confidence interval [CI], 0.10-0.34) for the hypoallergenic formula. Additionally, 3 behavioral trials (involving nearly 200 infants) revealed the benefits of reduced stimulation of the colicky infant (effect size of 0.48; 95% CI, 0.23-0.74)." }, { "input": "Several small studies report some benefit from use of a hypoallergenic (protein hydrolysate) formula, maternal diet adjustment (focusing on a low-allergen diet), and reduced stimulation of the infant. While dicyclomine has been shown to be effective for colic, there are significant concerns about its safety, and the manufacturer has contraindicated its use in this population. An herbal tea containing chamomile, vervain, licorice, fennel, and balm-mint was also effective in a small RCT, but the volume necessary for treatment limits its usefulness", "output": "A systematic review followed a similar high-quality search strategy and identified 22 articles, and reported a number needed to treat (NNT) of 6 for the 2 hypoallergenic formula studies identified in the previous review. Because of concern regarding the quality of the behavioral studies involving infants with colic, the authors of this second review only included 1 small (42 patients) trial of decreased stimulation, which resulted in a relative risk (RR) of 1.87 (95% CI, 1.04-3.34) and a NNT of 2. There was some inconclusive evidence to suggest benefit to dietary adjustment for breastfeeding mothers (specifically, the avoidance of cow's milk and other potential allergens like nuts, eggs, and wheat)." }, { "input": "Several small studies report some benefit from use of a hypoallergenic (protein hydrolysate) formula, maternal diet adjustment (focusing on a low-allergen diet), and reduced stimulation of the infant. While dicyclomine has been shown to be effective for colic, there are significant concerns about its safety, and the manufacturer has contraindicated its use in this population. An herbal tea containing chamomile, vervain, licorice, fennel, and balm-mint was also effective in a small RCT, but the volume necessary for treatment limits its usefulness", "output": "A randomized controlled trial showed significant improvement in distress scores of infants whose mothers followed a low-allergen diet (excluding dairy, soy, wheat, eggs, peanuts, tree nuts, and fish) for 7 days. This well-designed study included 107 patients (a relatively large sample in the published research about colic), and showed an absolute risk reduction of 37% (NNT=3) for those mothers following the challenge." }, { "input": "Several small studies report some benefit from use of a hypoallergenic (protein hydrolysate) formula, maternal diet adjustment (focusing on a low-allergen diet), and reduced stimulation of the infant. While dicyclomine has been shown to be effective for colic, there are significant concerns about its safety, and the manufacturer has contraindicated its use in this population. An herbal tea containing chamomile, vervain, licorice, fennel, and balm-mint was also effective in a small RCT, but the volume necessary for treatment limits its usefulness", "output": "A small RCT (43 patients) suggested efficacy in the substitution of a whey hydrolysate formula in place of cow's milkbased formula for infants with colic (casein hydrolysate formula has been more widely studied), but there continues to be controversy regarding the preferred protein hydrolysate formula (whey vs casein) in the treatment of colic." }, { "input": "Several small studies report some benefit from use of a hypoallergenic (protein hydrolysate) formula, maternal diet adjustment (focusing on a low-allergen diet), and reduced stimulation of the infant. While dicyclomine has been shown to be effective for colic, there are significant concerns about its safety, and the manufacturer has contraindicated its use in this population. An herbal tea containing chamomile, vervain, licorice, fennel, and balm-mint was also effective in a small RCT, but the volume necessary for treatment limits its usefulness", "output": "Several medications have been tested in RCTs; only dicyclomine has shown an effect in a few small RCTs. However, there have been reports of apnea and other serious, although infrequent, adverse effects. For that reason, the manufacturer has contraindicated the use of this medication in infants aged <6 months." }, { "input": "Several small studies report some benefit from use of a hypoallergenic (protein hydrolysate) formula, maternal diet adjustment (focusing on a low-allergen diet), and reduced stimulation of the infant. While dicyclomine has been shown to be effective for colic, there are significant concerns about its safety, and the manufacturer has contraindicated its use in this population. An herbal tea containing chamomile, vervain, licorice, fennel, and balm-mint was also effective in a small RCT, but the volume necessary for treatment limits its usefulness", "output": "A small (n=68) study of an herbal tea showed reduced symptoms (RR=0.57 favoring the active tea), although the mean volume of tea consumption (32 mL/kg/d) is a nutritional concern in this age group. No adverse events were noted, but the small sample size limits the ability to detect any but the most common events." }, { "input": "For patients whose echocardiograms show advanced calcification of the aortic valves, a jet velocity of > 4.0 m/s, or a progression in jet velocity of 0.3m/s/year; and for patients who have an abnormal exercise response or an impaired functional status, consider referral for valve replacement prior to the onset of symptoms.", "output": "A study followed 128 patients for 4 years and found that moderate to severe valvular calcification and an increase in jet velocity of 0.3 m/s/year were the best prognostic predictors. Almost 80% of those with both calcification and a rapid change in jet velocity underwent surgery or died within 2 years." }, { "input": "For patients whose echocardiograms show advanced calcification of the aortic valves, a jet velocity of > 4.0 m/s, or a progression in jet velocity of 0.3m/s/year; and for patients who have an abnormal exercise response or an impaired functional status, consider referral for valve replacement prior to the onset of symptoms.", "output": "One prospective study found the severity of stenosis at baseline to be the strongest prognostic predictor. Patients with a jet velocity of < 3.0 m/s were unlikely to develop symptoms within 5 years; those with a jet velocity of 4.0 m/s had a > 50% likelihood of developing symptoms or dying within 2 years." }, { "input": "other", "output": "One series of 1243 elderly women (mean age of 82) found mild stenosis in 10%, moderate stenosis in 6%, and severe stenosis in 2%." }, { "input": "other", "output": "Natural history studies show that once classic symptoms develop, average survival decreases to 5 years with the onset of angina, 3 years after cardiac syncope, and 2 years after heart failure." }, { "input": "other", "output": "The incidence of sudden death increases from < 1% annually among asymptomatic patients to 15% to 20% among symptomatic patients." }, { "input": "other", "output": "In one prospective study of 123 patients, those who had a greater increase in valve area, cardiac output, and blood pressure and a smaller decrease in stroke volume on stress echocardiogram were more likely to remain asymptomatic for the entire length of their time in the study, an average of 2.5 years." }, { "input": "No randomized trials directly address the question of frequency of liver enzyme monitoring with niacin use. Niacin use is associated with early and late hepatotoxicity (strength of recommendation", "output": "Because LA/SR niacin has an active metabolite (nicotinamide), hepatotoxicity is more likely to occur with the LA/SR formulation than with IR niacin." }, { "input": "No randomized trials directly address the question of frequency of liver enzyme monitoring with niacin use. Niacin use is associated with early and late hepatotoxicity (strength of recommendation", "output": "11 case reports have linked IR nicotinic acid to a wide range of hepatotoxicities. For patients taking LA/SR niacin doses \u22653 g/d or switching from the IR to the LA product, 21 case reports have linked LA/SR niacin with adverse outcomes. In several of the LA/SR cases, patients were rechal-lenged with IR formulations with no recurrent hepatocellular damage. In these case reports, onset of hepatotoxicity ranged from 2 days to 18 months. In a retrospective cohort of 969 veterans taking LA/SR niacin, those who developed hepatotoxicity had onset between 1 and 28 months of initiating treatment." }, { "input": "No randomized trials directly address the question of frequency of liver enzyme monitoring with niacin use. Niacin use is associated with early and late hepatotoxicity (strength of recommendation", "output": "Published incidence of niacin-induced hepatotoxicity varies according to the definition of hepatotoxicity, with a 0% to 46% rate of elevated hepatic enzymes. Hepatotoxicity includes mild liver enzyme elevations, steatosis, hepatitis, abnormal liver biopsies, or fulminant hepatic failure." }, { "input": "Long-acting forms of niacin (Slo-Niacin) are more frequently associated with hepatotoxicity than the immediate-release (Niacor, Nicolar) or extended-release (Niaspan) forms", "output": "In a retrospective cohort of 969 veterans taking LA/SR niacin, those who developed hepatotoxicity had onset between 1 and 28 months of initiating treatment." }, { "input": "Long-acting forms of niacin (Slo-Niacin) are more frequently associated with hepatotoxicity than the immediate-release (Niacor, Nicolar) or extended-release (Niaspan) forms", "output": "Because LA/SR niacin has an active metabolite (nicotinamide), hepatotoxicity is more likely to occur with the LA/SR formulation than with IR niacin." }, { "input": "Long-acting forms of niacin (Slo-Niacin) are more frequently associated with hepatotoxicity than the immediate-release (Niacor, Nicolar) or extended-release (Niaspan) forms", "output": "In a small prospective comparative study of IR and LA/SR niacin (n=46), 0/23 patients taking IR niacin exhibited hepatic toxicity, compared with 12/23 (52%) of patients taking the LA/SR formulation. In this study, patients receiving 1 g/d of LA/SR niacin had increases in transaminases similar to those of patients on 3 g/d of IR niacin. It is therefore recommended that if a patient cannot tolerate IR niacin and is switched to the LA/SR form, the dosage be reduced by 50% to 70%. At doses >2 g/d of LA/SR niacin, mean transaminases approached 3 times the upper limit of normal (ULN), supporting recommendations not to exceed this dose for LA/SR niacin." }, { "input": "Screening has been recommended at baseline, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually.", "output": "The American Society of Health-System Pharmacists ASHP recommends screening at baseline, every 2 to 3 months for the first year and every 6 to 12 months there-after. The ASHP also recommends that patients be started on IR niacin products, with consideration of ER products only when IR products are not tolerated or alternative products are ineffective. ASHP makes no mention of LA/SR products in their recommendations; and for patients who demonstrate signs/symptoms of toxicity nausea, vomiting, malaise, loss of appetite, right upper quadrant pain, jaundice, and dark urine." }, { "input": "Screening has been recommended at baseline, 6 to 8 weeks after reaching a daily dose of 1500 mg, 6 to 8 weeks after reaching the maximum daily dose, then annually.", "output": "ASHP recommend more frequent monitoring for high-risk patients-risks include doses >2 g/d for LA/SR and >3 g/d for IR; LA/SR formulations; switching between formulations; taking concomitant drugs that interact ie, sulfonylureas; excessive alcohol use undefined; and preexisting liver disease based on a bivariate analysis of factors associated with increased risk of hepatic toxicity from a single retrospective cohort study." }, { "input": "Currently, there is no evidence to support labor induction in women with suspected fetal macrosomia.", "output": "The purpose of induction for fetal macrosomia would be to prevent maternal and neonatal morbidities. However, studies have shown that the incidence of cesarean and instrumented deliveries was not decreased, and perinatal morbidity was not changed." }, { "input": "Currently, there is no evidence to support labor induction in women with suspected fetal macrosomia.", "output": "Gonen and colleagues followed 273 women at 38 weeks or more with ultrasound-determined fetal weights between 4000 and 4500 g. Women were excluded if they had diabetes, noncephalic presentations, a previous cesarean delivery, or other indications for induction. The induction group received either prostaglandin or pitocin for induction, depending on cervical status. Patients in the expectant management group were induced at 42 weeks. There was no change in cesarean delivery rate or in neonatal morbidity." }, { "input": "Cesarean delivery may be considered for suspected fetal macrosomia with estimated fetal weight (EFW) greater than 5000 g in women without diabetes and greater than 4500 g in women with diabetes.", "output": "Tey and coworkers randomized 40 women who did not have diabetes at 37 to 42 weeks with EFWs between 4000 and 4500 g to induction versus expectant management. Induction was performed with prostaglandin if the cervix was unfavorable (Bishop score <6), followed by pitocin. Women were excluded if there was an indication for delivery at the time of enrollment. There was no statistical difference in the cesarean delivery rate or incidence of shoulder dystocia between the 2 groups." }, { "input": "other", "output": "The definition of macrosomia is fetal weight of 4000 to 4500 g or greater, regardless of gestational age. This differs from \"large for gestational age\", which is a birth weight greater than 90th percentile for a given gestational age. Ten percent of all US live born infants weigh more than 4000 g, and 1.5% weigh more than 4500 g." }, { "input": "other", "output": "Ultrasound prediction of EFW in babies 4500 g or larger can be off by as much as 13%." }, { "input": "other", "output": "Detection of fetal macrosomia is difficult, because there are no reliable methods for determining EFW. Ultrasound estimate of fetal weight may be less accurate than estimates by multiparous patients and clinicians using Leopold maneuvers." }, { "input": "Breastfed and formula-fed infants should receive intramuscular vitamin K soon after birth to prevent classic hemorrhagic disease of the newborn.", "output": "The Cochrane Database of Systematic Reviews looked at randomized trials to determine the effectiveness of vitamin K prophylaxis in preventing classic hemorrhagic disease of the newborn. Two trials demonstrated that a single dose of intramuscular vitamin K reduced clinical bleeding at 1 to 7 days. Oral vitamin K has been studied for its effects on biochemical indices of coagulation status, but not for its clinical effects on bleeding. A single oral vitamin K dose at birth resulted in lower vitamin K levels at 2 weeks and 1 month, compared with a single dose of intramuscular vitamin K at birth." }, { "input": "Routine iron supplementation for all term, healthy, breastfed infants is not proven to be safe or necessary. Formula-fed infants should be consuming formula that contains 10 to 12 mg/L of iron.", "output": "The iron status of exclusively breastfed infants vs formula-fed infants was evaluated in a nonrandomized cohort study. Twenty-five healthy, breastfed infants and 15 healthy infants fed high-iron formula were followed for 9 months. No differences in mean hemoglobin values were seen at any age between the 2 groups." }, { "input": "Routine iron supplementation for all term, healthy, breastfed infants is not proven to be safe or necessary. Formula-fed infants should be consuming formula that contains 10 to 12 mg/L of iron.", "output": "A randomized controlled trial investigated the efficacy of daily and weekly iron supplementation on iron status in 67 exclusively breastfed infants. At age 4 months the infants were randomized into 3 groups: daily iron, weekly iron, and no iron. No significant differences were detected in the mean weight, height, and head circumference among the groups. The mean values of hemoglobin, mean corpuscular volume, serum iron, and transferrin saturation were similar among all the groups at ages 5, 6, and 7 months." }, { "input": "Routine iron supplementation for all term, healthy, breastfed infants is not proven to be safe or necessary. Formula-fed infants should be consuming formula that contains 10 to 12 mg/L of iron.", "output": "A randomized, double-blind, placebo-controlled iron supplementation trial involved 214 exclusively breastfed infants from 4 to 9 months of age in Sweden and Honduras. Iron supplementation did not affect weight gain in the groups, but length gain from ages 4 to 9 months was less in the iron-supplemented groups than in the placebo group (P<.05 for placebo vs Fe). This effect was greater in Sweden, and only existed in Honduras for infants aged 4 to 6 months with initial mean Hgb of at least 11 mg/dL. The researchers conclude that iron supplementation may pose risks in iron-replete infants." }, { "input": "Healthy, term infants at the highest risk for vitamin D deficiency are those who are breastfeeding and have dark skin or little sun exposure.", "output": "A case review of nutritional rickets in North Carolina between 1990 and 1999 found that all 30 patients identified were breastfed African American infants." }, { "input": "Healthy, term infants at the highest risk for vitamin D deficiency are those who are breastfeeding and have dark skin or little sun exposure.", "output": "Among the 166 published cases of rickets in the US from 1986 to 2003, 83% were categorized as African American or black. Ninety-six percent of cases were breastfed." }, { "input": "Infants older than 6 months should receive an oral fluoride supplement of 0.25 mg if they consume fluids with a water fluoride level less than 0.3 ppm.", "output": "A systematic review that evaluated fluoride for preventing dental caries in primary teeth in children aged <5 years found 6 small clinical trials. Although the studies were not of high quality, they consistently showed that the incidence of caries was reduced by 32% to 72%." }, { "input": "Infants older than 6 months should receive an oral fluoride supplement of 0.25 mg if they consume fluids with a water fluoride level less than 0.3 ppm.", "output": "No infant under 6 months of age should receive fluoride supplementation to prevent dental caries because of the risk of enamel fluorosis." }, { "input": "There is no single most effective modality for the treatment of fibromyalgia syndrome, and no objective comparison of the results from the different studies is available. Low-dose tricyclic antidepressants (TCAs) improve sleep quality and global well-being and have a moderate beneficial effect on tenderness and stiffness.", "output": "A meta-analysis of 5 RCTs on cyclobenzaprine, a muscle relaxant chemically related to TCAs, demonstrated its effect in improving pain and sleep disturbance (NNT=5)." }, { "input": "There is no single most effective modality for the treatment of fibromyalgia syndrome, and no objective comparison of the results from the different studies is available. Low-dose tricyclic antidepressants (TCAs) improve sleep quality and global well-being and have a moderate beneficial effect on tenderness and stiffness.", "output": "Evidence supporting the effectiveness of TCAs is strong, especially amitriptyline, in fibromyalgia-related symptoms. A metaanalysis that included 10 trials of low-dose TCAs (eg, 25-50 mg of amitriptyline) showed moderate improvement in sleep, pain, fatigue, and overall well-being (number needed to treat [NNT] for improvement=4)." }, { "input": "The serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine (Cymbalta) and milnacipran (Ixel, not currently available in the US) improve pain and other symptoms.", "output": "Single RCTs conducted on duloxetine and milnacipran, new SNRIs, demonstrated them to be more effective than placebo in improving pain and scores on the Fibromyalgia Impact Questionnaire (FIQ)." }, { "input": "Tramadol (Ultram) improves pain and other outcomes.", "output": "Three RCTs have shown that tramadol (with or without acetaminophen) is more effective than placebo in improving pain, number of tender points and FIQ score." }, { "input": "Aerobic exercise improves overall functional capacity and sense of well-being for patients with fibromyalgia.", "output": "A systematic review assessing various exercise programs on symptoms of fibromyalgia showed that aerobic exercise produces short-term improvements in cardiovascular fitness, tender-point pressure pain threshold, and patient- and physicianrated global well-being. Three of these trials included long-term follow-up of the exercise group participants. Patients who continued exercising maintained their improved physical functioning." }, { "input": "Cognitive behavioral therapy improves patients' self-reported symptoms.", "output": "Cognitive behavioral therapy has been shown to reduce symptoms in 5 RCTs." }, { "input": "Even though the most common reason to order a chest x-ray in the evaluation of an acute-onset, productive cough is to rule out pneumonia, there is no strong evidence to help a physician decide when to order this chest x-ray. However, acute cough patients who have rhinorrhea, sore throat, respiratory rate \u226425 breaths per minute, temperature <100\u00baF, and the absence of night sweats, myalgia, and all-day sputum production, have minimal to no risk of pneumonia and thus do not need a chest x-ray.", "output": "Almost all studies that have developed prediction rules preselected higher-risk patients-those who had already been selected to get a chest x-ray (based on unknown signs and symptoms). The signs and symptoms that predict pneumonia for patients already selected for a chest x-ray may be different than for unselected patients." }, { "input": "Even though the most common reason to order a chest x-ray in the evaluation of an acute-onset, productive cough is to rule out pneumonia, there is no strong evidence to help a physician decide when to order this chest x-ray. However, acute cough patients who have rhinorrhea, sore throat, respiratory rate \u226425 breaths per minute, temperature <100\u00baF, and the absence of night sweats, myalgia, and all-day sputum production, have minimal to no risk of pneumonia and thus do not need a chest x-ray.", "output": "Individual clinical findings such as pulse above 100 beats per minute, respiratory rate above 25 breaths per minute, temperature above 99.9\u00baF, local dullness to percussion, rales, asymmetric respirations, pleural rubs, egophony, increased fremitus, and cachexia are weak predictors of pneumonia, being present in 4% to 28% of radiographically proven pneumonia. Individual symptoms such as chills, night sweats, fever, and sputum production are found in 31% to 79% of those with pneumonia, but also in 18% to 62% of those without pneumonia. Therefore prediction rules, using combinations of statistically significant factors, have been developed to help us decide when to order a chest x-ray to diagnose pneumonia." }, { "input": "Lyme titers should be ordered for patients with signs or symptoms of disseminated Lyme disease, but who do not have the pathognomonic erythema migrans rash. Symptomatic patients with erythema migrans should be treated without being tested, given the high probability of having Lyme disease.", "output": "A review article recommends serologic testing for patients with a moderate pretest probability (ie, patients with objective signs of Lyme disease from a highly or moderately endemic area). Patients from highly endemic areas who present with erythema migrans have a high enough pretest probability to make the diagnosis of Lyme disease without serologic testing." }, { "input": "Testing should be 2-tiered, including an initial highly sensitive test (enzyme-linked immunosorbent assay [ELISA]) followed by a supplemental highly specific test (Western blot).", "output": "Guidelines established by a joint CDC/Association of State and Territorial Public Health Laboratory Directors commission require a 2-tiered laboratory approach to diagnosis. A highly sensitive initial test (ELISA) is followed by a highly specific supplemental test (Western blot)." }, { "input": "other", "output": "In a prospective study of 46 treated patients with culture-proven erythema migrans, 91% had a positive ELISA or immunoglobulin M (IgM) immunoblot result at 8 to 14 days after baseline. Peak IgM antibody levels were seen at this time among patients with localized or disseminated disease. Detectable IgM levels appeared within a few days of onset of erythema migrans and were found in most individuals with disease of at least 2 weeks duration." }, { "input": "other", "output": "A small study of 55 treated patients found peak antibody response at 8 to 12 days into treatment." }, { "input": "other", "output": "In a prospective, crosssectional survey of Wisconsin physicians, only 20% of ordered tests were appropriate. Tests were classified as inappropriate if ordered (1) for asymptomatic patients, (2) for patients with physician-diagnosed erythema migrans, (3) for patients receiving empiric antibiotic treatment, or (4) as test-of-cure." }, { "input": "A short-term course of erythromycin, azithromycin, or clarithromycin is as effective as a long-term (2-week) erythromycin therapy in eradicating Bordetella pertussis from the nasopharynx.", "output": "Although tetracycline and chloramphenicol are effective treatments for pertussis, they are not recommended because of their side effects." }, { "input": "A short-term course of erythromycin, azithromycin, or clarithromycin is as effective as a long-term (2-week) erythromycin therapy in eradicating Bordetella pertussis from the nasopharynx.", "output": "A large, multicenter RCT of 477 children of 6 months to 16 years of age demonstrated that a 5-day treatment with azithromycin eradicated B pertussis from the nasopharynx as effectively as a 10-day course of erythromycin estolate. Similarly, trimethoprim/sulfamethoxazole proved as effective as erythromycin in eliminating B pertussis from the nasopharynx." }, { "input": "A short-term course of erythromycin, azithromycin, or clarithromycin is as effective as a long-term (2-week) erythromycin therapy in eradicating Bordetella pertussis from the nasopharynx.", "output": "A 2005 Cochrane review of 11 RCTs and 1 quasi-randomized trial, with a total of 1720 adults and children, investigated several antibiotics for treatment and prophylaxis of pertussis. The outcome measures used to assess the efficacy of antibiotic treatment or prophylaxis vary between the trials and most of them did not report the immunization status of the participants. The Cochrane review included 1 meta-analysis of 3 studies with 252 participants, comparing azithromycin for 3 days, erythromycin estolate for 7 days, and clarithromycin for 7 days (short-term treatment) with erythromycin estolate for fourteen days (long-term treatment). The study showed equal efficacy in eradication of B pertussis from the nasopharynx of 99.2% to 97.7% (absolute risk reduction [ARR]=1.44%; 95% confidence interval [CI], -1.58 to 4.46). There were fewer side effects with the short-term treatment (32.1% vs 48.9%; ARR=16%; 95% CI, 7.84 to 25.84)." }, { "input": "Evidence is insufficient to determine the benefit of antibiotic prophylaxis for pertussis contacts. However, due to high mortality and morbidity, prophylaxis is recommended for families who have an infant less than 6 months old.", "output": "Six randomized trials failed to show any statistically significant difference between antibiotics and placebo on frequency and severity of cough or duration of pertussis disease." }, { "input": "Evidence is insufficient to determine the benefit of antibiotic prophylaxis for pertussis contacts. However, due to high mortality and morbidity, prophylaxis is recommended for families who have an infant less than 6 months old.", "output": "A randomized, placebo-controlled trial studied 300 household contacts of children with culture-positive pertussis. There was no statistically significant difference in either the frequency of pertussis disease or rate of positive cultures in household contacts between the erythromycin group (2.1%) and the placebo group (5.1%) (ARR=2.95%; 95% CI, -1.21 to 7.11)." }, { "input": "Evidence is insufficient to determine the benefit of antibiotic prophylaxis for pertussis contacts. However, due to high mortality and morbidity, prophylaxis is recommended for families who have an infant less than 6 months old.", "output": "A Cochrane review of 8 trials examined the effectiveness of the symptomatic treatment of cough in children and adults with pertussis. There were many problems with the methodological quality of these trials, including small sample sizes and poor reporting of the methods. Diphenhydramine, pertussis immunoglobulin, corticosteroids and salbutamol were compared with placebo. There were no statistically significant differences in coughing paroxysms, mean number of whoops per 24 hours or in duration of hospital stay between these interventions and placebo." }, { "input": "other", "output": "Extracorporeal circulatory life support has been used to maintain perfusion for patients with severe disease. The mortality of these patients is very high." }, { "input": "Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.", "output": "A 2-question screen has good sensitivity but poor specificity (43% of nondepressed patients will be labeled as depressed by this instrument)." }, { "input": "Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.", "output": "A systematic review of case-finding instruments for depression in primary care found that most instruments are similar in accuracy (84% sensitive, 72% specific). If applied to a group of fatigued patients with a 25% probability of depression, 50% of patients with an abnormal result on one of these case-finding instruments would be depressed compared with only 7% who had a normal or negative result." }, { "input": "Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.", "output": "Patients with a previous diagnosis of anxiety or depression (odds ratio [OR] =3.0; 95% confidence interval [CI], 1.4 - 6.1), those with symptoms for more than 3 months (OR= 2.1, 95% CI, 1.1 - 4.1), and those with more education (OR=3.5; 95% CI, 3.2 - 3.8) were more likely to remain fatigued at follow-up." }, { "input": "Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.", "output": "Physicians performed a thorough history and physical; took a complete blood count; tested the levels of blood or urine glucose, electrolytes, sedimentation rate, TSH, and urea; and tested for mononucleosis (if younger than 40). Only 19 (8%) were given a diagnosis based on the laboratory evaluation: 8 had anemia, 3 were hypothyroid, 3 had mononucleosis, 3 had other infections, 1 had diabetes, and 1 had carcinomatosis. Regarding prognosis, 59% of patients were still fatigued after 6 months." }, { "input": "Half of all patients presenting with fatigue have a psychological cause. Patients with a history of anxiety or depression or those with a duration of symptoms for more than 3 months are more likely to remain symptomatic 6 months later. Physicians should perform a physical examination, take a thorough history, and screen patients for depression using a validated primary care instrument, such as the Beck Depression Inventory or Prime-MD. Physicians may also consider a directed laboratory evaluation with sedimentation rate, blood count, and glycohemoglobin and thyroid stimulating hormone (TSH) levels, particularly in older patients.", "output": "A guideline developed by a group of family physicians provides the best overview of the topic. They recommend performing a detailed history and physical examination with further investigation reserved for patients with signs and symptoms of treatable causes of fatigue, such as anemia or hypothyroidism. They also recommend a somewhat more aggressive approach to investigation for patients older than 65 years." }, { "input": "Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.", "output": "Lojander et al compared uvulopharyngopalatoplasty (UPPP) to conservative management (weight loss, smoking cessation, and alcohol avoidance advice) in 32 patients. Patients were excluded if they had asthma, obesity (body mass index >40), restless leg syndrome, hypothyroidism, chronic obstructive pulmonary disease, or intolerance of missed work because of somnolence. Remaining patients were selected as possible surgical candidates by a team of hospital-based experts then randomized to surgery or conservative therapy. At 1 year of follow-up, they found no change in nocturnal oxygen desaturation but some improvement in the mean score of a visual analog scale of daytime sleepiness and in the mean self-report of out-of-bed sleeping episodes. Unfortunately these subjective outcome measures have not been validated and are subject to bias. This, in addition to lack of intention-to-treat analysis, renders these results uninterpretable." }, { "input": "Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.", "output": "The nonrandomized design of some trials may overestimate treatment effects by more than 40%." }, { "input": "Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.", "output": "the most optimistic review estimates that less than 50% of patients with obstructive sleep apnea will benefit from surgery." }, { "input": "Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.", "output": "Current recommendations in favor of surgical therapy are based solely on case series, poorly designed trials, expert opinion or pathophysiologic reasoning." }, { "input": "Current evidence is insufficient to recommend surgery for symptom relief for patients with obstructive sleep apnea. More convincing evidence exists supporting the use of Continuous Positive Airway Pressure (CPAP) or dental appliances for reducing symptoms of sleep apnea.", "output": "A trial compared UPPP with dental appliances in late 1999 and found dental appliances superior to surgery for improving apnea scores." }, { "input": "Hemoglobin A1c HbA1c levels correlate closely, though not perfectly, with blood glucose levels in patients with diabetes.", "output": "Four cohort studies of patients with diabetes have compared overall mean blood glucose levels with HbA1c levels. All but one were limited to patients with type 1 diabetes. Study periods ranged from 1 to 6 months, and frequency of blood glucose measurement ranged from 2 to 4 times per day. Correlation coefficients between mean blood glucose levels and HbA1c levels ranged from 0.71 to 0.86, implying that 50% to 74% of the variance in HbA1c is explained by the mean blood glucose (in each study, correlation was significant [P<.02])." }, { "input": "Correlation is higher for blood glucose levels later in the day than earlier in the day, higher for blood glucose levels in the most recent 30 days than from the prior 31-120 days, and higher for patients with type 2 diabetes compared with patients with type 1 diabetes.", "output": "5 studies comparing blood glucose measurements at specific times of day with HbA1c levels. Data from 3 studies comparing blood glucose values after lunchtime with those earlier in the day suggest that the lunchtime levels are more closely associated with HbA1c levels." }, { "input": "Correlation is higher for blood glucose levels later in the day than earlier in the day, higher for blood glucose levels in the most recent 30 days than from the prior 31-120 days, and higher for patients with type 2 diabetes compared with patients with type 1 diabetes.", "output": "No consistent difference was shown between preprandial and postprandial blood glucose levels in their strength of association with HbA1c levels. In 1 of these studies, a blood glucose level of 150 mg/dL 2 hours after lunch predicted a HbA1c of 7% with 85% sensitivity and 85% specificity." }, { "input": "Correlation is higher for blood glucose levels later in the day than earlier in the day, higher for blood glucose levels in the most recent 30 days than from the prior 31-120 days, and higher for patients with type 2 diabetes compared with patients with type 1 diabetes.", "output": "One study provided only limited information on blood glucose-HbA1c correlations in relation to mealtimes but did report that the times of day at which the 2 were best correlated were in the periods from midnight to 5:00 AM and between noon and 3:00 PM." }, { "input": "Correlation is higher for blood glucose levels later in the day than earlier in the day, higher for blood glucose levels in the most recent 30 days than from the prior 31-120 days, and higher for patients with type 2 diabetes compared with patients with type 1 diabetes.", "output": "One study compared patients with type 1 and type 2 diabetes and found a higher correlation between blood glucose and HbA1c levels in the latter." }, { "input": "Correlation is higher for blood glucose levels later in the day than earlier in the day, higher for blood glucose levels in the most recent 30 days than from the prior 31-120 days, and higher for patients with type 2 diabetes compared with patients with type 1 diabetes.", "output": "The relationship between HbA1c and blood glucose levels is such that blood glucose levels from the preceding 30 days determine about 50% of the total HbA1c." }, { "input": "No studies clearly demonstrate the best initial treatment for Parkinson's disease. Levodopa improves motor function in Parkinson's disease; however, long-term use is associated with irreversible dyskinesias and motor fluctuations. Compared with placebo, selegiline improves the motor symptoms of Parkinson's disease and allows a physician to delay the introduction of levodopa by 9 to 12 months.", "output": "Studies found no increase in mortality in patients with a history of selegiline use." }, { "input": "No studies clearly demonstrate the best initial treatment for Parkinson's disease. Levodopa improves motor function in Parkinson's disease; however, long-term use is associated with irreversible dyskinesias and motor fluctuations. Compared with placebo, selegiline improves the motor symptoms of Parkinson's disease and allows a physician to delay the introduction of levodopa by 9 to 12 months.", "output": "One large randomized controlled trial showed no difference in disability scores and an increase in mortality at 5.6 years when comparing selegiline combined with levodopa to levodopa alone. A re-analysis of this study has not supported this conclusion and found no increase in mortality in patients with a history of selegiline use." }, { "input": "No studies clearly demonstrate the best initial treatment for Parkinson's disease. Levodopa improves motor function in Parkinson's disease; however, long-term use is associated with irreversible dyskinesias and motor fluctuations. Compared with placebo, selegiline improves the motor symptoms of Parkinson's disease and allows a physician to delay the introduction of levodopa by 9 to 12 months.", "output": "Two trials found that selegiline delayed the need for levodopa for 9 to 12 months." }, { "input": "Dopamine agonists-alone or combined with levodopa-have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson's Disease Rating Scale (UPDRS) when compared with levodopa alone.", "output": "Two Cochrane reviews found that patients who tolerated the dopamine agonist bromocriptine-when administered alone or with levodopa-had delayed dyskinesias and motor complications compared with levodopa alone. There was no change in off-time with the combination." }, { "input": "Dopamine agonists-alone or combined with levodopa-have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson's Disease Rating Scale (UPDRS) when compared with levodopa alone.", "output": "A large randomized controlled trial comparing bromocriptine with levodopa demonstrated that at 3 years, disability scores were lower in the patients initially assigned to bromocriptine, but the difference was no longer significant at 9 years. The bromocriptine group in this trial showed a lower incidence of dyskinesias when data from all patient groups were combined. However, when moderate to severe cases were analyzed separately, there was no significant difference." }, { "input": "Dopamine agonists-alone or combined with levodopa-have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson's Disease Rating Scale (UPDRS) when compared with levodopa alone.", "output": "There was no difference in mortality between patients initially treated with bromocriptine vs levodopa." }, { "input": "Dopamine agonists-alone or combined with levodopa-have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson's Disease Rating Scale (UPDRS) when compared with levodopa alone.", "output": "Studies of other dopamine agonists show results comparable with bromocriptine. Lisuride (not available in the US) with rescue levodopa vs levodopa alone had fewer motor complications at 4 years but lower UPDRS and activities of daily living scores." }, { "input": "Dopamine agonists-alone or combined with levodopa-have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson's Disease Rating Scale (UPDRS) when compared with levodopa alone.", "output": "A study comparing lisuride with or without levodopa vs levodopa alone found no difference in motor complications at 5 years." }, { "input": "Dopamine agonists-alone or combined with levodopa-have fewer associated dyskinesias and other motor complications but produce lower scores on activities of daily living and Unified Parkinson's Disease Rating Scale (UPDRS) when compared with levodopa alone.", "output": "Studies with cabergoline, pramipexole, and pergolide-alone or combined with levodopa-vs levodopa alone showed a decrease in motor complications with the dopamine agonist but lower activities of daily living and UPDRS scores." }, { "input": "Postherpetic neuralgia occurs rarely among patients aged <50 years with herpes zoster. The incidence, duration, and severity of post-herpetic neuralgia increases with age, but older patients usually have only mild pain. Most cases resolve spontaneously within 3 months. Even in the highest-risk group, people aged >70 years, 25% had some pain at 3 months, but only 10% had pain at 1 year, and none had severe pain. Only a few patients have pain that persists for years.", "output": "Among the 14 patients in a prospective study with pain persisting >12 months, 7 had complete resolution of pain, 5 had persisting pain that either improved or remained mild, 1 had ongoing moderate pain at 7 years, and 1 was lost to follow-up.No recurrence of pain was found among 183 randomly selected patients who had had resolution by 1 year." }, { "input": "Postherpetic neuralgia occurs rarely among patients aged <50 years with herpes zoster. The incidence, duration, and severity of post-herpetic neuralgia increases with age, but older patients usually have only mild pain. Most cases resolve spontaneously within 3 months. Even in the highest-risk group, people aged >70 years, 25% had some pain at 3 months, but only 10% had pain at 1 year, and none had severe pain. Only a few patients have pain that persists for years.", "output": "In a prospective study performed in a primary care setting in Iceland, all cases of herpes zoster and postherpetic neuralgia occurring over 4.5 years in a population of 100,000 were identified, and all cases of postherpetic neuralgia were followed for up to 7.6 years. Few patients (4%) received antiviral medication. In this study, postherpetic neuralgia followed herpes zoster in 2% of patients under age 40, 21% between the ages of 40 and 60, and in 40% of those over age 60. Subjects self-described pain as none, mild, moderate, or severe. Patients aged >60 years had the worst prognosis: 18% still had mild pain at 3 months and 6% had moderate or severe pain. At 1 year, 8% had mild pain and 2% had moderate pain. No patients had severe pain after 12 months." }, { "input": "Higher doses of nicotine gum or lozenge (4 mg vs 2 mg) increase quit rates in heavy smokers.", "output": "A Cochrane Review of 110 trials evaluating the efficacy of nicotine replacement therapy in 35,600 smokers found higher quit rates among heavy smokers using 4-mg compared with 2-mg nicotine gum (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.69-4.22)." }, { "input": "No studies have demonstrated that cessation of breastfeeding in jaundiced infants improves clinical outcomes, although this has only been studied in term infants. Temporarily disrupting or supplementing breastfeeding in jaundiced infants is associated with premature cessation of breastfeeding.", "output": "In a prospective cohort study of 138 breastfed term infants, more than twice as many mothers of jaundiced infants had stopped breastfeeding compared with mothers of nonjaundiced infants, at the end of 1 month (42% vs 19%; number needed to harm [NNH]=4; P<.01). In addition, 64% of the jaundiced infants whose nursing had been interrupted in the hospital had stopped breastfeeding by 1 month, compared with only 36% of those who had no interruption (relative risk [RR]=1.8; P<.05; NNH=4)." }, { "input": "No studies have demonstrated that cessation of breastfeeding in jaundiced infants improves clinical outcomes, although this has only been studied in term infants. Temporarily disrupting or supplementing breastfeeding in jaundiced infants is associated with premature cessation of breastfeeding.", "output": "Late initiation of breastfeeding and temporary cessation or supplementation of breastfeeding increase the likelihood of premature breastfeeding termination." }, { "input": "Jaundiced breastfed term infants have no significant difference in length of phototherapy, and no increased rate of exchange transfusion or kernicterus compared with jaundiced bottle-fed term infants.", "output": "In a prospective cohort study of 163 healthy, jaundiced newborn infants undergoing phototherapy (total serum bilirubin \u226517 mg/dL), exclusively breastfed infants had slower response to phototherapy in the first 24 hours than formulafed or formula-supplemented infants (bilirubin decreases of 17.1% vs 18% and 22.9%, respectively; P=.03). However, there were no significant differences in total length of phototherapy among the 3 groups (phototherapy time of 64.5 hours vs 54.1 hours and 54.9 hours, respectively; P=.06)." }, { "input": "Jaundiced breastfed term infants have no significant difference in length of phototherapy, and no increased rate of exchange transfusion or kernicterus compared with jaundiced bottle-fed term infants.", "output": "In a randomized, nonblinded clinical trial, 125 jaundiced breastfed newborns (total serum bilirubin level of \u226517mg/dL) were assigned to 4 treatment groups: (1) continue breastfeeding and observe; (2) discontinue breastfeeding, substitute with formula; (3) discontinue breastfeeding, substitute with formula, and administer phototherapy; and (4) continue breastfeeding, administer phototherapy. The study did not find a clinically significant difference in serum bilirubin reduction to normal levels at 48 hours between breastfed and bottle-fed groups undergoing phototherapy (RR=1.07; 95% confidence interval [CI], 0.6-1.92; P=.818), or between breastfed and bottle-fed groups who did not have phototherapy (RR not calculated; P=.051). No patient required exchange transfusion, and in no case did total serum bilirubin exceed 23 mg/dL." }, { "input": "Screening urinalysis in asymptomatic children has not been shown to be beneficial.", "output": "The prevalence of glomelonephropathies is <0.05%." }, { "input": "Screening urinalysis in asymptomatic children has not been shown to be beneficial.", "output": "For those children with asymptomatic bacteriuria, fewer than 10% progress to symptomatic urinary tract infections." }, { "input": "Screening urinalysis in asymptomatic children has not been shown to be beneficial.", "output": "The American Academy of Family Physicians, Bright Futures, Canadian Task Force on the Periodic Health xamination, and the United States Preventive Services Task Force do not recommend screening for asymptomatic bacteriuria in children. The Institute for Clinical Systems Improvement recommends that consideration be given to eliminating routine urinalyses in asymptomatic children." }, { "input": "Screening urinalysis in asymptomatic children has not been shown to be beneficial.", "output": "Expert opinion varies as to the necessity of screening urinalysis. No prospective randomized trials demonstrate improved outcomes, and limited evidence suggests that detection and treatment of asymptomatic bacteriuria improves long-term outcomes such as renal scarring, hypertension, or pyelone phritis." }, { "input": "other", "output": "The prevalence of urinary tract infection in childhood has been estimated to be roughly 1%." }, { "input": "other", "output": "Currently vailable screening urinalyses using chemical dipstick testing have reported sensitivities ranging from 53% to 93% and specificities of 72% to 98% for detecting significant bacteriuria." }, { "input": "There is no direct evidence of an effect of dietary fiber on colon cancer incidence. A diet high in fiber has not been shown to be effective in the short-term (2- to 4-year) prevention of recurrent colon polyps.", "output": "In a trial of ispaghula husk fiber, the intervention group actually had significantly more recurrent adenomas after 3 years 29.3% vs 20.2%; RR=1.67; 95% CI, 1.01-2.76; P=.04." }, { "input": "There is no direct evidence of an effect of dietary fiber on colon cancer incidence. A diet high in fiber has not been shown to be effective in the short-term (2- to 4-year) prevention of recurrent colon polyps.", "output": "A Cochrane meta-analysis of 5 trials including 4349 subjects of increased dietary fiber to prevent recurrence of colon adenomas found no difference between intervention and control groups for development of at least 1 adenoma relative risk [RR]=1.04; 95% confidence interval [CI], 0.95-1.13." }, { "input": "Epidemiological evidence is inconsistent in demonstrating an association between dietary fiber consumption and the occurrence of colon cancer.", "output": "A systematic review of dietary fiber and colorectal neoplasia (which included case-control and cohort studies as well as randomized controlled trials) showed that 13 of 24 case-control studies found an association with high dietary fiber as a possible protective factor, while only 3 of 13 longitudinal studies found such an association." }, { "input": "Central nervous system stimulants improve symptoms of attention deficit-hyperactivity disorder (ADHD) in adults.", "output": "A less rigorous systematic review identified 15 studies of stimulant efficacy in adults. Researchers concluded that under controlled conditions, stimulants are efficacious in the treatment of ADHD in adults. The rate of response among the studies ranged from 25% to 78%." }, { "input": "Central nervous system stimulants improve symptoms of attention deficit-hyperactivity disorder (ADHD) in adults.", "output": "A high-quality study was a 7-week randomized controlled trial using a crossover comparison of methylphenidate and placebo. There was a favorable response in 78% (18/23) of subjects while takin methylphenidate, in contrast to 4% (1/23) while taking placebo (number needed to treat [NNT]=1.4; P<.0001). A favorable response was assessed by the Clinical Global Impression Scale, a measure of illness severity and improvement, and a >30% reduction in symptoms as measured by the ADHD Rating Scale." }, { "input": "Central nervous system stimulants improve symptoms of attention deficit-hyperactivity disorder (ADHD) in adults.", "output": "A well-done systematic review of 12 trials assessing the efficacy of stimulant therapy in the treatment of adult ADHD did not find sufficient evidence that stimulants were effective. Significant heterogeneity and poor reporting of methodology was seen among the studies." }, { "input": "Although not the focus of this question, nonstimulant medications (including buproprion, modafinil, and guanfacine) have also been studied in the treatment of ADHD in adults. Recently, atomoxetine became the only nonstimulant medication to receive approval by the US Food and Drug Administration for the treatment of ADHD.", "output": "A good study was a randomized, double-blind, 3-phase crossover study of dextroamphetamine, modafinil (a drug used to treat narcolepsy), and placebo. Each phase was 2 weeks long, with a 4-day washout in between. A favorable response was defined as a reduction of ADHD symptoms by at least 30% on the DSM-IV ADHD Behavior Checklist for Adults. Dextroamphetamine and modafinil showed the same response rate in 10 of 21 patients. Both treatments had a significant improvement over placebo (P<.001). It was unclear from the study what percentage of subjects responded to placebo." }, { "input": "Although not the focus of this question, nonstimulant medications (including buproprion, modafinil, and guanfacine) have also been studied in the treatment of ADHD in adults. Recently, atomoxetine became the only nonstimulant medication to receive approval by the US Food and Drug Administration for the treatment of ADHD.", "output": "A study compared dextroamphetamine, guanfacine (an antihypertensive agent), and placebo in 17 patients. On the DSM-IV ADHD Behavior Checklist for Adults, subjects taking dextroamphetamine or guanfacine reported similar decreases in mean ADHD scores compared with placebo (24 vs 22 vs 30; P<.05). They did not report the number of subjects who had a 30% reduction in symptoms. Of note: at the end of the study but prior to unblinding, subjects were asked which medication they preferred. Twelve subjects chose dextroamphetamine, 4 chose guanfacine, and 1 chose placebo. Subjects' stated reason for choosing dextroamphetamine was the positive effect it had on their motivation." }, { "input": "Although not the focus of this question, nonstimulant medications (including buproprion, modafinil, and guanfacine) have also been studied in the treatment of ADHD in adults. Recently, atomoxetine became the only nonstimulant medication to receive approval by the US Food and Drug Administration for the treatment of ADHD.", "output": "A study was a randomized controlled trial of mixed amphetamine salts. Of the 27 adults who completed the study, 19 (70%) responded favorably to mixed amphetamine salts compared with 2 (7.4%) receiving placebo (NNT=1.6; P<.001). Favorable response was defined as more than a 30% reduction of symptoms on the ADHD Rating Scale." }, { "input": "Although not the focus of this question, nonstimulant medications (including buproprion, modafinil, and guanfacine) have also been studied in the treatment of ADHD in adults. Recently, atomoxetine became the only nonstimulant medication to receive approval by the US Food and Drug Administration for the treatment of ADHD.", "output": "A 7-week randomized controlled trial compared methylphenidate with sustained-release buproprion. Thirty out of 37 subjects completed at least 1 week of the study. The primary indicator of a favorable response was the Clinical Global Impression Scale. The rate of response was 50% for methylphenidate, 64% for sustained-release buproprion, and 27% for placebo (P<.14)." }, { "input": "Vitamin B6 (50-100 mg/d) and elemental calcium (1200 mg/d) are safe, inexpensive, and moderately effective.", "output": "One well-designed, randomized controlled trial of calcium therapy showed > 50% decrease in symptom complex scores after 3 months in more than half of subjects taking 1200 mg/d supplemental elemental calcium NNT=6." }, { "input": "Vitamin B6 (50-100 mg/d) and elemental calcium (1200 mg/d) are safe, inexpensive, and moderately effective.", "output": "Pooled results of 9, generally poor-quality studies of Vitamin B6 show some benefit. Doses higher than 100 mg/d may cause peripheral neuropathy." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs) and some other antidepressants are more effective, but are also more costly and more likely to cause side effects or treatment dropout.", "output": "Among SSRIs, fluoxetine 20 mg/d is well-studied and effective. Gonadotropin-releasing hormone agonists may be effective, but troublesome anti-estrogenic side effects limit their utility. Estrogen and progesterone \"add-back\" therapy to counter side effects further complicates this approach. The gonadotropin inhibitor danazol has a high treatment dropout rate at higher doses 200-400 mg/d continuously, but can be effective in individuals who are able to tolerate it" }, { "input": "Selective serotonin reuptake inhibitors (SSRIs) and some other antidepressants are more effective, but are also more costly and more likely to cause side effects or treatment dropout.", "output": "Benzodiazepines have shown mixed results in treating PMS, and overall their benefit appears smaller than that of SSRIs." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs) and some other antidepressants are more effective, but are also more costly and more likely to cause side effects or treatment dropout.", "output": "Danazol is expensive and causes significant androgenic side effects. Lower-dose danazol 200 mg/d luteal phase only is better tolerated but ineffective." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs) and some other antidepressants are more effective, but are also more costly and more likely to cause side effects or treatment dropout.", "output": "Gonadotropin-releasing hormone agonists may be effective, but troublesome anti-estrogenic side effects limit their utility. Estrogen and progesterone \"add-back\" therapy to counter side effects further complicates this approach. The gonadotropin inhibitor danazol has a high treatment dropout rate at higher doses 200-400 mg/d continuously, but can be effective in individuals who are able to tolerate it." }, { "input": "Selective serotonin reuptake inhibitors (SSRIs) and some other antidepressants are more effective, but are also more costly and more likely to cause side effects or treatment dropout.", "output": "For severe PMS, SSRIs are the initial drug of choice. Alprazolam may be useful when these interventions are ineffective." }, { "input": "Antidepressant dosing only during the luteal phase may be effective and more tolerable.", "output": "Benzodiazepines have shown mixed results in treating PMS, and overall their benefit appears smaller than that of SSRIs. Luteal phase-only dosing theoretically reduces the risk of benzodiazepine withdrawal or dependence." }, { "input": "Hormonal therapies (oral contraceptives, gonadotropin-releasing hormone agonists, danazol, estrogen) lack convincing evidence of efficacy and cause many side effects; progesterone is no more beneficial than placebo.", "output": "Consider oral contraceptives for primarily physical symptoms and reserve gonadotropin-releasing hormone for severe cases unresponsive to other treatments." }, { "input": "Hormonal therapies (oral contraceptives, gonadotropin-releasing hormone agonists, danazol, estrogen) lack convincing evidence of efficacy and cause many side effects; progesterone is no more beneficial than placebo.", "output": "A meta-analysis of progesterone found no evidence to support its efficacy." }, { "input": "A detailed history and exam, confirmation of euthyroid status, and imaging when appropriate is the best approach to euthyroid patients with thyroid enlargement in regions where goiters are not endemic. Ultrasound imaging is recommended in any case of diagnostic uncertainty. Evaluate dominant or suspicious nodules further, while diffuse goiters without symptoms require no further evaluation and can be followed clinically.", "output": "Patients with a reassuring initial work-up can be followed clinically and should be assessed with serial clinical evaluations. No evidence could be found regarding optimal intervals for examination and testing; yearly exams and TSH testing are considered adequate by some experts." }, { "input": "Suppressive therapy with levothyroxine can be used to decrease thyroid size for cosmetic reasons or in the case of mild local symptoms, although response is variable.", "output": "One placebo-controlled trial of thyroid suppression in nontoxic multinodular goiter showed regression of thyroid size with suppressive therapy (58% reduction in size in treatment group vs 5% reduction in control group). However, not all goiters responded to this therapy, and the thyroid size returned to pretreatment size within 9 months of discontinuation of suppressive therapy." }, { "input": "Patients with severe local symptoms should receive further evaluation and possible surgical management.", "output": "Computed tomography and magnetic resonance imaging perform better for visualization of extension of thyroid tissue substernally and are also preferred for evaluation of the neck in cases of severe local complications of goiter, such as compressive symptoms." }, { "input": "One to 2 daily drinks of alcohol lowers LDL-C, if consumed regularly for more than 4 weeks.", "output": "One 5-year-long cohort study (N=933) showed that alcohol was associated with LDL-C reduction in a dose-dependent manner. Two crossover trials (4-6 weeks in duration) conducted among heavy drinkers showed that LDL-C increased when alcohol intake decreased. Two randomized crossover trials (8-12 weeks in duration) found a statistically significant decrease in LDL-C with consumption of 1 to 2 drinks daily." }, { "input": "Counseling by physicians, dieticians, or pharmacists is effective at increasing patient compliance with medications, thereby lowering LDL-C.", "output": "An RCT (N=167) with 8 years of follow-up found that patient education and counseling effectively improved medication adherence." }, { "input": "Counseling by physicians, dieticians, or pharmacists is effective at increasing patient compliance with medications, thereby lowering LDL-C.", "output": "An RCT (N=1162) lasting 1 year found that nutrition counseling by primary care physicians resulted in no significant change in LDL-C compared with usual care." }, { "input": "Weight loss has been associated with reductions in LDL-C. However, other factors-including degree of caloric restriction, drug intervention, and diet composition-may play a more significant role than weight loss alone.", "output": "A meta-analysis found a 0.8 mg/dL LDL-C decrease for every kg of weight lost. Long-term follow-up, however, showed that LDL-C returned to baseline even when weight loss was maintained. Eight clinical trials failed to demonstrate a reduction in LDL-C postintervention with up to 10 kg of weight loss. Studies using weight-loss drugs (Sibutramine, Orlistat) found more significant weight loss during treatment, along with greater decrease in LDL-C, when compared with studies using only lifestyle modifications." }, { "input": "Exercise significantly lowers LDL-C.", "output": "Aerobic exercise effectively lowers LDL-C. This reduction is enhanced by weight loss and diet and mitigated by weight gain. An analysis of 4 RCTs showed that LDL-C also decreased with resistance training." }, { "input": "Smoking cessation may have a beneficial effect.", "output": "One meta-analysis found a dose-dependent relationship between smoking and LDL-C, with overall LDL-C 1.7% higher for smokers compared with nonsmokers. Two RCTs investigated the effect of smoking cessation on LDL-C with mixed results. One (N=935) showed a decrease in nonfasting LDL-C while a second (N=140) showed no difference in LDL-C." }, { "input": "Exercise-based alternative practices yoga and tai chi lower LDL, and meditation may have a beneficial effect.", "output": "Two RCTs investigated the effect of meditation on LDL-C with mixed results. One (N=16) showed a significant decrease in LDL-C over 8 weeks, while a second (N=60) showed no difference in LDL-C. A high-quality RCT (N=91) with a combined intervention (counseling, exercise, and meditation over 1 year) showed a significant decrease in LDL-C." }, { "input": "Depot medroxyprogesterone acetate (DMPA; Depo-Provera) and the combination contraceptive vaginal ring (NuvaRing) are most effective for obese women because they don't appear to be affected by body weight.", "output": "ACOG notes that no higher rates of pregnancy are observed among overweight women using DMPA." }, { "input": "Depot medroxyprogesterone acetate (DMPA; Depo-Provera) and the combination contraceptive vaginal ring (NuvaRing) are most effective for obese women because they don't appear to be affected by body weight.", "output": "A higher body weight appeared to be associated with increased likelihood of ovulation using the contraceptive vaginal ring, though it did not lead to any pregnancies in a multicenter study." }, { "input": "Depot medroxyprogesterone acetate (DMPA; Depo-Provera) and the combination contraceptive vaginal ring (NuvaRing) are most effective for obese women because they don't appear to be affected by body weight.", "output": "A secondary analysis of the contraceptive vaginal ring efficacy trials did not show an increased pregnancy rate among heavier women." }, { "input": "Depot medroxyprogesterone acetate (DMPA; Depo-Provera) and the combination contraceptive vaginal ring (NuvaRing) are most effective for obese women because they don't appear to be affected by body weight.", "output": "The efficacy of the contraceptive vaginal ring does not appear to be affected by body weight, but the mean BMI in intent-to-treat population studies was only 22.9\u00b12.9." }, { "input": "Depot medroxyprogesterone acetate (DMPA; Depo-Provera) and the combination contraceptive vaginal ring (NuvaRing) are most effective for obese women because they don't appear to be affected by body weight.", "output": "Data suggest that increased body weight does not decrease the efficacy of DMPA. In 2 large open-label studies, no pregnancies were observed, regardless of BMI." }, { "input": "On the other hand, women using the combination contraceptive patch (Ortho Evra) who weigh \u226590 kg may experience decreased contraceptive efficacy.", "output": "One retrospective cohort analysis found that women weighing >70.5 kg had an increased risk of pregnancy compared with women of lower weight (relative risk [RR]=1.6; 95% confidence interval [CI], 1.1-2.4), after controlling for parity. Pill compliance was not accounted for in this study." }, { "input": "On the other hand, women using the combination contraceptive patch (Ortho Evra) who weigh \u226590 kg may experience decreased contraceptive efficacy.", "output": "A follow-up case-control study demonstrated that the risk of pregnancy for consistent pill users doubled for women with a BMI >27.3 (odds ratio [OR]=2.17; 95% CI, 1.38-3.41); results were similar for those with a BMI >32.2 (OR=2.2; 95% CI, 1.18-4.20)." }, { "input": "On the other hand, women using the combination contraceptive patch (Ortho Evra) who weigh \u226590 kg may experience decreased contraceptive efficacy.", "output": "A large cohort study did not find any association between failure of the oral contraceptive pill or progestin-only pill and obesity; however, the total number of pregnancies among obese women was too small to achieve statistical significance." }, { "input": "On the other hand, women using the combination contraceptive patch (Ortho Evra) who weigh \u226590 kg may experience decreased contraceptive efficacy.", "output": "In a randomized trial studying the efficacy of an extended-cycle oral contraceptive (Seasonale), no woman weighing >90 kg became pregnant." }, { "input": "On the other hand, women using the combination contraceptive patch (Ortho Evra) who weigh \u226590 kg may experience decreased contraceptive efficacy.", "output": "When it comes to the combination contraceptive patch, the data show a significant association between baseline body weight and pregnancy. In an analysis of pooled data, 5 of 15 pregnancies occurred in a subgroup of women with a baseline body weight \u226590 kg. Less than 3% of the study population weighed more than 90 kg. Specific data for this subgroup were not presented in the study results, so measures of effect cannot be calculated. The mechanism of the decreased efficacy of the combined contraceptive patch for obese women is unclear." }, { "input": "On the other hand, women using the combination contraceptive patch (Ortho Evra) who weigh \u226590 kg may experience decreased contraceptive efficacy.", "output": "The World Health Organization generally recommends hormonal contraceptives as safe for obese women. The group acknowledges that data are limited regarding effectiveness of oral contraceptives, and efficacy may be lower for the combination contraceptive patch when used by obese women." }, { "input": "Obese women using oral contraceptives may also have an increased risk of pregnancy.", "output": "The data on the levonorgestrel intrauterine system do not examine weight and efficacy." }, { "input": "Obese women using oral contraceptives may also have an increased risk of pregnancy.", "output": "The American College of Obstetrics and Gynecology ACOG suggests that despite the possibility of higher failure rates with oral and transdermal contraception, motivated obese women should still be encouraged to use these methods preferentially over known less effective methods." }, { "input": "A/SOME DO. DEXTROMETHORPHAN (DM) for adults and honey for children provide some relief. DM may modestly decrease cough in adults compared with placebo.", "output": "A Cochrane review found DM to be modestly effective in 2 of 3 studies. In the first study-a meta-analysis of 6 industry-sponsored RCTs of 710 adults-a single 30-mg dose of DM decreased coughing bouts by 12% (P=.004) and increased the time between bouts by 17 % (P=.002) in the 3 hours after treatment. A second study of 3 successive industry-sponsored, blinded RCTs enrolling a total of 451 adults found that 30 mg of DM decreased cough counts between 19% and 36% (P<.05) over a 3-hour follow-up period. Neither of the 2 studies specified whether the outcome assessors were blinded to treatment groups. A third double-blinded RCT evaluating a single 30-mg dose of DM in 43 adults during a 3-hour follow-up period showed no statistically significant improvement in cough outcomes compared with placebo." }, { "input": "The data supporting zinc for the common cold are mixed.", "output": "Zinc lozenges containing 13.3 mg of zinc acetate taken every 2 to 3 hours decreased the duration of cough from 5.35 to 2.14 days (P<.001) in a double-blinded placebo-controlled RCT of 50 adults." }, { "input": "The data supporting zinc for the common cold are mixed.", "output": "A recent systematic review showed mixed results: Half the studies found no benefit for zinc in treating upper respiratory infection." }, { "input": "Antihistamines, antihistamine-decongestant combinations, and guaifenesin don't provide greater relief than placebo in adults.", "output": "The results of 2 guaifenesin trials were split. In a double-blinded RCT of 239 adults, more patients taking guaifenesin reported decreased cough frequency and intensity (75% vs 31%; P<.01). However, another double-blinded RCT of 65 patients found guaifenesin to be no more effective than placebo in reducing subjective cough frequency." }, { "input": "In children, antihistamines, decongestants, DM, or combinations of them don't relieve cough better than placebo.", "output": "Two double-blinded RCTs (total of 155 children) showed that antihistamine-decongestant combinations (brompheniramine-phenylpropanolamine and brompheniramine-phenylephrine-propanolamine) didn't reduce cough more than placebo. No studies have evaluated guai-fenesin in children." }, { "input": "In children, antihistamines, decongestants, DM, or combinations of them don't relieve cough better than placebo.", "output": "DM was no more effective than placebo for decreasing cough in 2 RCTs enrolling a total of 107 children. Another single-blinded RCT of 100 children showed that neither DM nor diphenhydramine relieved cough better than placebo." }, { "input": "Honey may modestly decrease frequency and severity of cough compared with DM or no treatment.", "output": "In a partially double-blinded RCT (the \"no treatment\" group was not blinded) of 105 children, a single dose of buckwheat honey decreased cough frequency, as assessed by parents, by 1.89 points on the 7-point Likert scale compared with DM (1.39) and no treatment (0.92; P<.001). Overall improvement in symptom score averaged 10.71 out of a total 30 points for honey compared with 6.41 for no treatment (P=.04). Cough frequency and overall symptom scores for DM didn't differ significantly from no treatment. Hyperactivity, nervousness, and insomnia were reported more often with honey (5 patients) than DM (2 patients) or no treatment (0 patients); (P=.04)." }, { "input": "A/CHASTEBERRY TREE AND CALCIUM have demonstrated efficacy and safety in treating symptoms of premenstrual syndrome (PMS).", "output": "A RCT (466 patients) comparing 1000 and 1200 mg of calcium with placebo found a significant decrease in PMS symptoms after 3 treatment cycles. Calcium improved negative affect, water retention, food cravings, and pain. The study found that, by the third treatment cycle, patients taking calcium had an overall 48% reduction in total symptom scores, compared with a 30% reduction in the control group. The most common adverse effects were headache, rhinitis, and nonspecific pain." }, { "input": "A/CHASTEBERRY TREE AND CALCIUM have demonstrated efficacy and safety in treating symptoms of premenstrual syndrome (PMS).", "output": "A RCT (33 patients) comparing 1000 and 1200 mg of calcium with placebo found a significant decrease in PMS symptoms after 3 treatment cycles. Calcium improved negative affect, water retention, food cravings, and pain. In the study, 73% of patients preferred taking calcium, compared with 15% who preferred placebo." }, { "input": "A/CHASTEBERRY TREE AND CALCIUM have demonstrated efficacy and safety in treating symptoms of premenstrual syndrome (PMS).", "output": "A study comparing chasteberry tree with fluoxetine in 19 patients found a decrease in premenstrual symptom scores for both fluoxetine (13 of 19 patients) and chasteberry tree (11 of 19 patients). No statistically significant differences were noted between the 2 groups. Chasteberry tree was well tolerated; most adverse effects occurred in patients receiving fluoxetine. The most frequent adverse effects with chasteberry tree were nausea in 5 patients and headache in 4." }, { "input": "A/CHASTEBERRY TREE AND CALCIUM have demonstrated efficacy and safety in treating symptoms of premenstrual syndrome (PMS).", "output": "A prospective, open-label study of chasteberry tree for PMS symptoms in 43 patients found a 42% decrease in self-assessed PMS symptom scores, with the greatest improvement in pain, behavior changes, negative feelings, and fluid retention. No serious adverse events occurred." }, { "input": "A/CHASTEBERRY TREE AND CALCIUM have demonstrated efficacy and safety in treating symptoms of premenstrual syndrome (PMS).", "output": "A double-blind RCT comparing chasteberry tree with placebo in 170 patients found a decrease in self-reported PMS symptom scores and an increase in response rate (defined as a 50% reduction in symptoms)-52% vs 24%-in the intervention group (number needed to treat [NNT]=3.5). Patients taking chasteberry tree had 1 occurrence of multiple abscesses and 1 of urticaria." }, { "input": "Pyridoxine and saffron may be effective, but high doses of pyridoxine can cause neuropathy.", "output": "A meta-analysis of pyridoxine in doses from 50 to 600 mg per day for PMS included 9 RCTs. Relative to placebo, pyridoxine improved PMS symptom scores (odds ratio=2.32, 95% confidence interval, 1.95-2.54). The overall quality of studies was poor, however, with few subjects, widely varying doses, and different outcome measurements." }, { "input": "Pyridoxine and saffron may be effective, but high doses of pyridoxine can cause neuropathy.", "output": "Two RCTs of 40 and 96 patients failed to demonstrate reduced premenstrual symptoms. Long-term use of pyridoxine in doses >200 mg/d can cause neuropathy." }, { "input": "Pyridoxine and saffron may be effective, but high doses of pyridoxine can cause neuropathy.", "output": "A double-blind RCT evaluated the effect of 2 cycles of treatment with saffron (Crocus sativus L), 30 mg twice daily, on PMS symptoms in 50 patients. Nineteen patients in the saffron group showed a response, defined as 50% reduction in symptom severity, compared with 2 patients in the placebo group (NNT=2). The study found no statistically significant difference in frequency of adverse effects." }, { "input": "Insufficient evidence exists to recommend magnesium. St. John's wort and evening primrose oil aren't effective for managing PMS.", "output": "A RCT comparing magnesium with placebo had low precision because of small numbers and short treatment duration. The study (N=28) demonstrated reduced total Moos Menstrual Distress Questionnaire scores." }, { "input": "Insufficient evidence exists to recommend magnesium. St. John's wort and evening primrose oil aren't effective for managing PMS.", "output": "A study, begun as an open trial of magnesium infusion for premenstrual dysphoric disorder (N=6), found a dramatic reduction in mood symptom scores. After converting to a randomized, blinded design (N=10), no difference was found compared with placebo." }, { "input": "Insufficient evidence exists to recommend magnesium. St. John's wort and evening primrose oil aren't effective for managing PMS.", "output": "A RCT comparing magnesium with placebo had low precision because of small numbers and short treatment duration. The study reported a decrease in fluid retention symptoms by 2 points on an 80-point scale (P<.009) at 2 months, but no difference in total score." }, { "input": "Insufficient evidence exists to recommend magnesium. St. John's wort and evening primrose oil aren't effective for managing PMS.", "output": "Two double-blind crossover studies of 27 and 38 patients found that evening primrose oil had no effect on PMS symptoms." }, { "input": "Insufficient evidence exists to recommend magnesium. St. John's wort and evening primrose oil aren't effective for managing PMS.", "output": "One randomized, double-blind controlled trial (N=125) of 600 mg St. John's wort vs placebo over 2 cycles of treatment found no significant changes in symptom score from baseline." }, { "input": "No evidence was found to support black cohosh or vitamin E.", "output": "The Premenstrual Syndrome Guidelines of the American College of Obstetricians and Gynecologists (ACOG) state that calcium and magnesium have been shown to be effective in small trials and must be validated in larger trials before a strong evidence-based recommendation can be made. ACOG's guidelines also report minimal effectiveness with vitamin B6 and vitamin E." }, { "input": "A/yes, lithium, triiodothyronine, (T3), and atypical antipsychotics are all effective adjuncts. Lithium (serum levels >0.5 mEq/L) can produce clinical improvement when added to ineffective antidepressant treatment.", "output": "A meta-analysis of 8 studies with a total of 292 patients found that patients who received T3 augmentation of tricyclic antidepressant therapy were twice as likely to respond as controls (relative response=2.09; 95% CI, 1.31-3.32). The corresponding pooled absolute difference in response rate was 23.2% with a corresponding NNT of 4.3. T3 dosage in the studies ranged from 25 to 50 mcg/day and duration varied from 7 to 35 days. Analysis of data from RCTs alone produced a lower pooled relative response of 1.53 (95% CI, 0.70-3.35) and an NNT of 12.5. A major drawback of T3 augmentation is that little information is available about its efficacy in combination with newer antidepressant agents." }, { "input": "A/yes, lithium, triiodothyronine, (T3), and atypical antipsychotics are all effective adjuncts. Lithium (serum levels >0.5 mEq/L) can produce clinical improvement when added to ineffective antidepressant treatment.", "output": "A meta-analysis concluded that a lithium dose sufficient to produce serum levels of at least 0.5 mEq/L and a minimum treatment duration of 2 weeks resulted in a pooled OR of response to lithium augmentation compared with placebo of 3.31 (95% CI, 1.46-7.53). Lithium augmentation is a reasonable alternative for depressed patients who don't respond to conventional antidepressants." }, { "input": "A/yes, lithium, triiodothyronine, (T3), and atypical antipsychotics are all effective adjuncts. Lithium (serum levels >0.5 mEq/L) can produce clinical improvement when added to ineffective antidepressant treatment.", "output": "A meta-analysis of 10 augmentation studies reported that adding lithium to various antidepressant agents increased the chances of clinical response 3-fold relative to placebo (odds ratio [OR]=3.11; 95% confidence interval [CI], 1.80-5.37), yielding a number needed to treat (NNT) of 5. The mean response rate was 41.2% in the lithium group and 14.4% in the placebo group (P<.001). The meta-analysis included only RCTs that enrolled subjects with unipolar or bipolar disorder (depressive phase) who were treated with any antidepressant plus lithium in any dose compared with placebo." }, { "input": "A/yes, lithium, triiodothyronine, (T3), and atypical antipsychotics are all effective adjuncts. Lithium (serum levels >0.5 mEq/L) can produce clinical improvement when added to ineffective antidepressant treatment.", "output": "As many as 30% of patients with major depression fail to respond to treatment with a single antidepressant drug given in adequate dosage for an appropriate period. Pharmacologic approaches such as switching antidepressant classes are often attempted first, followed by augmentation with another agent if needed." }, { "input": "Thyroid supplementation using T3 at doses no higher than 50 mcg per day also increases the effectiveness of antidepressant therapy.", "output": "The American Psychiatric Association and the Institute for Clinical Systems Improvementrecommend considering a trial of lithium or thyroid augmentation for patients who respond only partially to initial antidepressant therapy." }, { "input": "Atypical antipsychotic agents are less effective adjuncts for patients with treatment-resistant major depressive disorder.", "output": "A meta-analysis of 10 clinical trials involving 1500 outpatients studied the efficacy of augmenting standard antidepressants with atypical antipsychotic agents to treat resistant major depressive disorder. Across the trials, the pooled risk ratio (RR) for remission was 1.75 (95% CI, 1.36-2.24) and for response rates was 1.35 (95% CI, 1.13-1.63). Pooled rates for remission and response were 47.4% vs 22.3% (NNT=4) and 57.2% vs 35.4% (NNT=4.6), respectively. Although the meta-analysis found no difference in overall discontinuation rates (P=.929), the rate of discontinuation because of adverse events was lower among placebo-treated patients (RR=3.38, P<.0001). These results suggest a role for atypical antipsychotic agents in augmenting standard antidepressants for treatment-resistant major depressive disorder." }, { "input": "Diuretics that do not contain a sulfonamide group (eg, amiloride hydrochloride, eplerenone, ethacrynic acid, spironolactone, and triamterene) are safe for patients with an allergy to sulfa. The evidence is contradictory as to whether a history of allergy to sulfonamide antibiotics increases the risk of subsequent allergic reactions to commonly used sulfonamide-containing diuretics (eg, carbonic anhydrase inhibitors, loop diuretics, and thiazides).", "output": "In a literature review-in which the main focus was cross-reactivity between sulfonamide antibiotics and celecoxib-the authors concluded that little evidence supported definitive cross-reactivity between sulfonamide antibiotics and diuretics." }, { "input": "Diuretics that do not contain a sulfonamide group (eg, amiloride hydrochloride, eplerenone, ethacrynic acid, spironolactone, and triamterene) are safe for patients with an allergy to sulfa. The evidence is contradictory as to whether a history of allergy to sulfonamide antibiotics increases the risk of subsequent allergic reactions to commonly used sulfonamide-containing diuretics (eg, carbonic anhydrase inhibitors, loop diuretics, and thiazides).", "output": "A literature review of Medline from 1966 to early 2004 revealed 21 case series, case reports, and \"other articles\" that evaluated the presence of cross-reactivity. When the authors of this literature reviewed drilled down to diuretics, they found 5 case reports for cross-reactivity to acetazolamide, 2 case reports for furosemide, 1 case series, and 2 case reports for indapamide (a thiazide diuretic). After reviewing the studies, the authors concluded that little evidence suggested a problem with cross-reactivity either with acetazolamide or furosemide and that there may be an association of cross-reactivity between sulfonamide antibiotics and indapamide. This study was limited by its small numbers and lack of explicit critical appraisal." }, { "input": "Diuretics that do not contain a sulfonamide group (eg, amiloride hydrochloride, eplerenone, ethacrynic acid, spironolactone, and triamterene) are safe for patients with an allergy to sulfa. The evidence is contradictory as to whether a history of allergy to sulfonamide antibiotics increases the risk of subsequent allergic reactions to commonly used sulfonamide-containing diuretics (eg, carbonic anhydrase inhibitors, loop diuretics, and thiazides).", "output": "Researchers involved in a retrospective study of 363 hospital charts examined 34 patients with a self-reported history of sulfa allergy who were subsequently given acetazolamide (a carbonic anhydrase inhibitor), furosemide (a loop diuretic), or both. The nature of the self-reported sulfa allergic reaction was documented in 79% of the 34 patients. These reported reactions included urticarial rash, nonspecified rash, dyspnea, swelling, nausea or vomiting, throat swelling, red eyes, and bullae. Two patients who were given acetazolamide developed urticaria. No allergic reactions occurred for those patients given furosemide. The researchers concluded that there was little clinical or pharmacological evidence to suggest that a self-reported sulfa allergy was likely to produce a life-threatening cross-reaction with acetazolamide or furosemide. Small numbers and the lack of a standard definition for an allergic reaction limited the strength of their conclusion." }, { "input": "Diuretics that do not contain a sulfonamide group (eg, amiloride hydrochloride, eplerenone, ethacrynic acid, spironolactone, and triamterene) are safe for patients with an allergy to sulfa. The evidence is contradictory as to whether a history of allergy to sulfonamide antibiotics increases the risk of subsequent allergic reactions to commonly used sulfonamide-containing diuretics (eg, carbonic anhydrase inhibitors, loop diuretics, and thiazides).", "output": "A large retrospective cohort study using Britain's General Practice Research Database identified 20,226 patients seen from 1987 through March 1999 who were prescribed a systemic sulfonamide antibiotic, and then at least 60 days later received a nonantibiotic sulfonamide (eg, thiazide diuretic, furosemide, oral hypoglycemic). Researchers reviewed records to determine whether patients described as having an allergic reaction to a sulfonamide antibiotic were at increased risk of having a subsequent allergic reaction to a sulfonamide nonantibiotic. researchers identified allergies to sulfonamide antibiotics in 969 patients. Of this group, 96 patients (9.9%) had a subsequent reaction to a sulfonamide nonantibiotic, which included drugs from the loop and thiazide diuretic classes (including bumetanide, chlorothiazide, furosemide, hydrochlorothiazide, indapamide, and torsemide). It was unclear if any patients taking a carbonic anhydrase inhibitor experienced an allergic reaction. For comparison purposes, of the 19,257 patients who were not identified as having an allergy to a sulfonamide antibiotic, again using the broad definition, 315 (1.6%), had a subsequent allergic reaction to a sulfonamide nonantibiotic, for an unadjusted odds ratio of 6.6 (95% confidence interval [CI], 5.2-8.4). When the results were adjusted for age, sex, history of asthma, use of medications for asthma or corticosteroids, the adjusted odds ratio for individuals experiencing an allergy to a nonantibiotic sulfonamide in those persons with a history of allergy to a sulfonamide antibiotic was 2.8 (95 % CI, 2.1-3.7). Of note, the adjusted odds ratio for the occurrence of a penicillin allergy in a patient with a history of sulfonamide antibiotic allergy was significantly higher at 3.9 (95% CI, 3.5-4.3)" }, { "input": "A detailed history appears to be the most important initial diagnostic tool.", "output": "One reasonable algorithm recommends an initial work-up including a complete blood count, thyroid-stimulating hormone (TSH) and erythrocyte sedimentation rate (ESR) level, a purified protein derivative (PPD) and HIV test, and a chest x-ray. If the results are unrevealing, a trial of antireflux medication is recommended. If the patient does not improve, consider a diary of nocturnal temperatures to help discern the presence or absence of febrile pulses and further evaluate for suspected endocarditis or lymphoma." }, { "input": "No clinical trials have directly studied symptomatic relief of night sweats alone. Among menopausal women with hot flashes associated with night sweats, oral hormone therapy is highly effective in reducing their frequency.", "output": "A large Cochrane meta-analysis found that oral hormone therapy-estrogens alone or estrogens with progesterone-reduced the frequency of night sweats associated with hot flashes among menopausal women by 75% when compared with placebo alone." }, { "input": "No clinical trials have directly studied symptomatic relief of night sweats alone. Among menopausal women with hot flashes associated with night sweats, oral hormone therapy is highly effective in reducing their frequency.", "output": "Neither primrose oil nor foot reflexology proved effective." }, { "input": "Antireflux therapy may be effective.", "output": "A cohort study found that 80% of the patients with frequent night sweats responded to antireflux therapy." }, { "input": "Therapy aimed at decreasing perspiration has been suggested.", "output": "One author suggests using therapies aimed at relieving hyperhydrosis. These include local treatment with aluminum chloride hexahydrate (Drysol), antiperspirants, scopolamine, or phenoxybenzamine hydrochloride (Dibenzyline)." }, { "input": "There is no single best evidence-based approach to the diagnostic evaluation of night sweats, given the limited number of studies on the subject.", "output": "Several authors agree that certain medications are frequently associated with night sweats, although the exact incidence is unknown due to a lack of published epidemiologic data." }, { "input": "There is no single best evidence-based approach to the diagnostic evaluation of night sweats, given the limited number of studies on the subject.", "output": "In the only study that specifically addressed the causes of night sweats in an ambulatory population, Reynolds interviewed 200 consecutive patients, 70% from a primary care practice and 30% from a gastroenterology practice. Of the 81 patients who reported having an episode of night sweats at least once a week, esophageal reflux and menopause were the most frequent causes." }, { "input": "Routine infant diarrhea requires no lab work or cultures.", "output": "Consensus reports have suggested laboratory studies are unnecessary unless dehydration is severe or IV fluids are required; stool cultures are necessary only for bloody or prolonged diarrhea, systemically ill infants, suspected food poisoning, or recent travel abroad." }, { "input": "The degree of dehydration can be determined reliably by percent body weight change.", "output": "Effective management of infant diarrhea is based on the degree of dehydration, which can be estimated by percent body weight loss-the difference between the baseline and acute weights, divided by the baseline weight." }, { "input": "Bicarbonate may help rule out dehydration.", "output": "A systematic review suggested the only blood test reliable for ruling out dehydration is a serum bicarbonate greater than 15 to 17 mEq/L." }, { "input": "Electrolytes and blood urea nitrogen may be useful in evaluating complicated diarrhea with severe dehydration or when intravenous fluids are required; stool cultures are indicated for bloody or prolonged diarrhea, suspected food poisoning, or recent travel abroad.", "output": "Consensus reports have suggested laboratory studies are unnecessary unless dehydration is severe or IV fluids are required; stool cultures are necessary only for bloody or prolonged diarrhea, systemically ill infants, suspected food poisoning, or recent travel abroad." }, { "input": "Oral rehydrating solution is adequate fluid replacement for diarrhea associated with mild to moderate dehydration, followed by prompt refeeding with an age-appropriate diet.", "output": "For infants with mild to moderate dehydration, however, rehydration using oral rehydrating solution is the initial therapy, followed by continued hydration to replace ongoing losses." }, { "input": "Oral rehydrating solution is adequate fluid replacement for diarrhea associated with mild to moderate dehydration, followed by prompt refeeding with an age-appropriate diet.", "output": "A meta-analysis of randomized controlled trials (RCTs) in developed countries demonstrated equivalent efficacy of oral fluids compared with IV fluids, with an overall failure rate of only 3.6% for infants and children treated with oral rehydrating solution (95% confidence interval [CI], 1.4-5.8). There was no significant difference between oral rehydrating solution of varying sodium concentrations, and no increased risk of hypernatremia or hyponatremia compared with the IV treatment arm." }, { "input": "Oral rehydrating solution is adequate fluid replacement for diarrhea associated with mild to moderate dehydration, followed by prompt refeeding with an age-appropriate diet.", "output": "Infants with diarrhea who are not dehydrated should continue age-appropriate nutrition." }, { "input": "Oral rehydrating solution is adequate fluid replacement for diarrhea associated with mild to moderate dehydration, followed by prompt refeeding with an age-appropriate diet.", "output": "In a systematic review of RCTs comparing lower-concentration oral rehydrating solution with standard World Health Organization solution, lower-concentration solution showed superior efficacy. These resulted in fewer unscheduled infusions of IV fluids (OR=0.59; 95% CI, 0.45-0.79) and less stool output without increasing the incidence of hyponatremia." }, { "input": "Intravenous fluids are recommended for severe dehydration.", "output": "For obtunded or severely dehydrated infants, or those with an ileus or persistent vomiting, expert opinion suggested IV fluids." }, { "input": "Probiotics have been shown to safely reduce the duration and frequency of diarrhea.", "output": "An RCT showed that Lactobacillus supplementation shortened the duration of diarrhea for infants and young children." }, { "input": "Probiotics have been shown to safely reduce the duration and frequency of diarrhea.", "output": "An RCT showed that Lactobacillus supplementation shortened the duration of diarrhea for infants and young children. Lactobacillus supplementation reduced the risk of diarrhea persisting more than 3 days (relative risk [RR]=0.43; 95% CI, 0.34-0.53; P<.001; number needed to treat [NNT]=4)." }, { "input": "For children who have recurrent episodes of clinically diagnosed acute otitis media (AOM), antibiotic prophylaxis significantly reduces recurrence, although the effect is not large.", "output": "A review article states: \"Many children with acute otitis media do not benefit from antimicrobial therapy because the cause of their illness is not bacterial or the infection is cleared by the immune system without use of a drug. At present, we do not have clinical criteria for distinguishing which children are in need of antibiotic therapy for AOM.\"." }, { "input": "For children who have recurrent episodes of clinically diagnosed acute otitis media (AOM), antibiotic prophylaxis significantly reduces recurrence, although the effect is not large.", "output": "A randomized, double blind, placebo-controlled study of prophylaxis for ear infections enrolled 194 children aged 3 months to 6 years with at least 3 documented AOM episodes in the preceding 6 months. The children were given amoxicillin (20 mg/kg/d) either once daily (n=55) or divided twice daily (n=44) or placebo (n=59). Excluding 36 noncompliant subjects, the percentages without a recurrent episode were 63% for the placebo group, 64% for the once-daily amoxicillin group, and 61% for the twice-daily amoxicillin group. There was no significant difference in the incidence of new AOM episodes among the children in the 3 groups." }, { "input": "For children who have recurrent episodes of clinically diagnosed acute otitis media (AOM), antibiotic prophylaxis significantly reduces recurrence, although the effect is not large.", "output": "A systematic review of antibiotic prophylaxis for recurrent AOM examined 9 RCTs with a total of 958 children. Recurrent AOM was defined as 3 or more episodes per 6 to 18 months. The studies were low to moderate in quality (mean methodologic quality score of 11.8 out of 29 possible points). The most commonly used antibiotics were amoxicillin, cotrimoxazole, and sulfamethoxazole, given for 3 to 24 months (dosing not reported). Children taking antibiotics had 0.11 (95% confidence interval [CI], 0.03-0.19) fewer episodes of recurrent AOM per patient-month than those taking placebo. The rate in the control group was 0.19 (95% CI, 0.13-0.26). Nine children would have to be treated per month to prevent 1 ear infection (NNT=9; 95% CI, 5-33). Only 2 of the 9 studies had statistically significant results; both used sulfisoxazole for 10 to 12 weeks and were of similar methodologic quality (12.5 out 29 points). A trend towards a better outcome in studies that used sulfisoxazole did not reach significance compared with those using other medications (ie, ampicillin, amoxicillin, cotrimoxazole). Shorter treatment intervals (<6 months) trended toward being more effective than longer intervals, but this also did not reach significance. Children with more frequent episodes of AOM did no better than those with less frequent episodes." }, { "input": "Influenza vaccination of residents effectively prevented pneumonia in nursing home patients", "output": "A meta-analysis of 20 cohort studies showed a 53% efficacy (95% confidence interval [CI], 35-66)-defined as 1 minus the odds ratio-for influenza immunization in preventing pneumonia." }, { "input": "Influenza vaccination of caregivers effectively prevented pneumonia in nursing home patients", "output": "A cluster randomized trial in British long-term care facilities demonstrated that influenza vaccination of health care workers (61% of 1078 workers) reduced the total nursing home mortality rate (odds ratio [OR]=0.56 [95% CI, 0.4-0.8]) for a drop in mortality rate from 17% to 10% (number needed to treat [NNT]=14.3)." }, { "input": "Pneumococcal vaccination of residents effectively prevented pneumonia in nursing home patients", "output": "Pneumococcal vaccination of residents was reported in a review. The evidence comes primarily from 2 clinical trials in which the NNT to prevent 1 episode of pneumonia was about 35." }, { "input": "Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.", "output": "In a single study, 366 patients in 11 Japanese nursing homes were divided into controls (self-care) and those treated with rigorous oral care (by staff). The intervention group had a relative risk of 0.6 (95% CI, 0.36-0.99; NNT=12.5) for pneumonia over a 2-year period. The NNT for preventing a death by pneumonia was 11 (P<.01). This intriguing result merits follow up in larger groups in US nursing homes to see if this approach is feasible." }, { "input": "Two other suggested interventions have not been extensively tested: antiviral chemoprophylaxis during an influenza outbreak in the nursing home, and oral hygiene programs for nursing home residents.", "output": "Observational studies strongly suggest that amantadine, rimantadine, and oseltamivir are all effective in reducing spread of influenza during outbreaks in nursing homes. Oseltamivir acts against influenza B as well as A and has fewer side effects, but it is more expensive. Presumably, decreasing the rate of influenza also reduces the rate of subsequent pneumonia." }, { "input": "Using a threshold of <= 5 mm, transvaginal ultrasound (TVUS) can be used to identify those patients with postmenopausal bleeding who are at low risk for endometrial cancer, polyps, or atypical hyperplasia at a sensitivity comparable with that of endometrial biopsy and dilatation and curettage (D&iC).", "output": "A Consensus Conference Statement from the Society of Radiologists in Ultrasound recommended that either TVUS or endometrial biopsy could be used in the initial evaluation of patients with postmenopausal bleeding. Using a threshold of >5 mm as abnormal, they concluded that the sensitivities of TVUS and endometrial biopsy are comparable when \"sufficient tissue\" is obtained with endometrial biopsy. They felt that data was currently insufficient to clearly state which technique is more effective." }, { "input": "Using a threshold of <= 5 mm, transvaginal ultrasound (TVUS) can be used to identify those patients with postmenopausal bleeding who are at low risk for endometrial cancer, polyps, or atypical hyperplasia at a sensitivity comparable with that of endometrial biopsy and dilatation and curettage (D&iC).", "output": "A 2002 meta-analysis of 57 cohort studies, without consistently applied reference standards, published between 1966 and 2000 included a total of 9031 women with postmenopausal bleeding. Because many of the studies were felt to use inadequately stringent criteria for diagnosis, the authors limited their final analysis to only 4 studies. They concluded that a negative result using a 5-mm threshold rules out endometrial pathology with fair certainty (LR- = 0.21)." }, { "input": "Using a threshold of <= 5 mm, transvaginal ultrasound (TVUS) can be used to identify those patients with postmenopausal bleeding who are at low risk for endometrial cancer, polyps, or atypical hyperplasia at a sensitivity comparable with that of endometrial biopsy and dilatation and curettage (D&iC).", "output": "A 1998 meta-analysis of 35 exploratory cohort studies published between 1966 and 1996 included a total of 5892 women with postmenopausal bleeding. TVUS evaluations were followed by endometrial tissue sampling and results were compared. Using endometrial thickness of \u22645 mm as the threshold, ultrasound was very accurate at ruling out patients with endometrial cancer but only fair at diagnosing cancer (likelihood ratio for a positive test [LR+]=2.5; LR for a negative test [LR-]=0.06). In addition, the 5-mm threshold was accurate at ruling out any endometrial abnormality (cancer, polyp, atypical hyperplasia: LR- = 0.01). The authors suggested that TVUS can reliably rule out significant endometrial disease among postmenopausal women with vaginal bleeding." }, { "input": "Very few studies examine the evaluation of chronic cough among young children. Based on expert opinion, investigation of chronic cough should begin with a detailed history, physical examination, and chest radiograph.", "output": "Chest radiography may be most helpful for infants at increased risk for foreign-body aspiration." }, { "input": "Before pursuing additional studies, remove potential irritants from the patient's environment. Work-up for persisting cough should consider congenital anomalies and then be directed toward common causes of chronic cough like those seen in older children and adults, including postnasal drip syndrome, gastroesophageal reflux disease (GERD), and asthma.", "output": "If the initial evaluation is not revealing, further investigation should focus on congenital anomalies, asthma, postnasal drip, and GERD. Aberrant innominate artery and asthma were the most frequent diagnoses among children aged <18 months old referred for otolaryngology consultation." }, { "input": "Before pursuing additional studies, remove potential irritants from the patient's environment. Work-up for persisting cough should consider congenital anomalies and then be directed toward common causes of chronic cough like those seen in older children and adults, including postnasal drip syndrome, gastroesophageal reflux disease (GERD), and asthma.", "output": "Because pulmonary function testing is not practical for infants, a trial of aggressive therapy in combination with a \"cough diary\" kept by the parents may be used to diagnose asthma. Sinus computed tomography films are not routinely recommended to evaluate for postnasal drip, as sinusitis among children does not correlate well with postnasal drip." }, { "input": "Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women.", "output": "Some studies did not attempt to biopsy all patients screened with ultrasound." }, { "input": "Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women.", "output": "The relevance of several studies is affected by small sample size (range, 36-85)." }, { "input": "Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women.", "output": "A study evaluated 1926 asymptomatic postmenopausal women with transvaginal ultrasound. Of these, 1833 had endometrial thickness <6 mm and 1750 of this cohort underwent biopsy. Five cases of serious endometrial abnormality were identified in this group (1 adenocarcinoma and 4 atypical hyperplasia). Specificity in this group was 98%, but sensitivity for accurately detecting an abnormality was low at 17%. The negative predictive value was greater than 99%. An inadequate number of patients with endometrial thickness >6 mm were biopsied (45%) to allow for accurate calculation of positive predictive value in those with a >6 mm stripe. The study concludes that transvaginal ultrasonography may not be an effective screening procedure for this population." }, { "input": "Transvaginal ultrasound should not replace endometrial biopsy for detection of endometrial disease among asymptomatic postmenopausal patients. Endometrial biopsy has been considered a standard for the clinical diagnosis of endometrial disease among asymptomatic patients, but it is invasive, may be uncomfortable, and may not be able to be performed for some patients with cervical stenosis. Ultrasound evaluation is less invasive and more comfortable and can be performed for patients with cervical stenosis. The positive predictive value of ultrasound is not adequate to allow it to replace endometrial biopsy for screening of asymptomatic women.", "output": "In a trial of postmenopausal estrogen use, 448 asymptomatic postmenopausal women were monitored with both endometrial biopsy and transvaginal ultrasound. Biopsy detected 11 cases of serious disease. At a threshold of 5 mm for endometrial thickness, ultrasound had a positive predictive value of 9% for detecting any abnormality with 90% sensitivity and 48% specificity. At this threshold, more than half of women evaluated with ultrasound would require endometrial biopsy as well, and only 4% of these patients would have serious disease. This study concludes that transvaginal ultrasound has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease for this asymptomatic population." }, { "input": "Good evidence supports the use of surgery for carpal tunnel syndrome over nonsurgical therapies such as wrist splints, nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, occupational therapy, local steroid injections, work modification, and oral vitamin B6.", "output": "One cohort study of 429 patients found that surgery (open or closed endoscopic) was more effective with respect to symptom relief and functional status than various nonsurgical therapies (NSAIDs, splints, physical or occupational therapy, local steroid injections, work modification, or vitamin B6) at 30 months follow-up. In this study the patients' pretreatment symptom and functioning scores were worse in the surgery group than in the nonsurgical group. The authors controlled for functional status scores, but not for symptom severity." }, { "input": "Good evidence supports the use of surgery for carpal tunnel syndrome over nonsurgical therapies such as wrist splints, nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, occupational therapy, local steroid injections, work modification, and oral vitamin B6.", "output": "One cohort study of 90 patients concluded that with respect to symptom control and return to function, open release surgery was as effective as local steroid injection at 1 month follow-up.3 However, at 4 to 6 months after the operation, surgery patients were found to have significantly improved symptom and function scores, with continued improvement compared with patients who received the steroid injection. In this study the patients' pretreatment symptom and functioning scores were worse in the surgery group than in the nonsurgical group. The investigators in this study did not report controlling for these scores." }, { "input": "Good evidence supports the use of surgery for carpal tunnel syndrome over nonsurgical therapies such as wrist splints, nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, occupational therapy, local steroid injections, work modification, and oral vitamin B6.", "output": "A well-designed RCT of 176 patients published since that Cochrane review stated that with regard to overall improvement of symptoms and function status, surgical treatment of carpal tunnel syndrome was more effective than wrist splinting 18 months posttreatment. The investigators found that surgery resulted in worse short-term outcomes at 1 month follow-up (29% vs 42% success), but by 3 months the improvement in all outcomes was greater in the surgery group (80% vs 54% success). The number needed to treat (NNT) over 18 months was only 2 patients in the treatment-received (per protocol) analysis (92% vs 37% success) and 7 in the intention-to-treat analysis (90% vs 75% success). Patients in the conservative treatment group who underwent surgery after splinting had failed had a higher success rate after 18 months follow-up than patients who did not have surgery (94% vs 62% success rate; NNT = 3)." }, { "input": "Good evidence supports the use of surgery for carpal tunnel syndrome over nonsurgical therapies such as wrist splints, nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, occupational therapy, local steroid injections, work modification, and oral vitamin B6.", "output": "A Cochrane review based on only 1 RCT of 22 patients published in 1964 concluded that surgical treatment of carpal tunnel syndrome appears to be more effective than wrist splinting." }, { "input": "Surgery is likely worth the extra costs when conservative therapy (up to 3 months) fails to improve symptoms and return of function, because delayed surgery is as successful as surgery performed shortly after diagnosis. Closed endoscopic release and open release surgery are equally effective therapies for controlling symptoms.", "output": "One systematic review of 14 RCTs comparing types of surgical therapies for carpal tunnel syndrome concluded that none of the alternative surgical procedures, including closed endoscopic release, appeared to give better symptom relief than open release; and that the evidence is conflicting as to whether endoscopic release results in earlier return to work or improved level of function." }, { "input": "Ambulatory blood pressure monitoring is currently the gold standard for detecting patients with white-coat hypertension. Women and all patients with lower office systolic blood pressures, stage I hypertension, and no target organ damage are more likely to have white-coat hypertension.", "output": "A recent study did not find body-mass index distinguished white-coat hyperten-sion from sustained hypertension." }, { "input": "Ambulatory blood pressure monitoring is currently the gold standard for detecting patients with white-coat hypertension. Women and all patients with lower office systolic blood pressures, stage I hypertension, and no target organ damage are more likely to have white-coat hypertension.", "output": "A study of more than 600 men over 20 years in Finland compared those who developed white-coat hypertension and those with sustained hypertension. The hypertensive patients had more microalbuminuria, a greater left ventricular mass on echo, increased cholesterol esters, and a greater body-mass index (all P.05) than patients with white-coat hypertension. Smoking status was similar in both groups, in contrast to other studies." }, { "input": "Ambulatory blood pressure monitoring is currently the gold standard for detecting patients with white-coat hypertension. Women and all patients with lower office systolic blood pressures, stage I hypertension, and no target organ damage are more likely to have white-coat hypertension.", "output": "In another analysis of 1333 Italian subjects, the prevalence of white-coat hypertension was 33.3% in those with stage I hypertension, 11% with stage II, and 3 % with stage III." }, { "input": "Ambulatory blood pressure monitoring is currently the gold standard for detecting patients with white-coat hypertension. Women and all patients with lower office systolic blood pressures, stage I hypertension, and no target organ damage are more likely to have white-coat hypertension.", "output": "A large international database of 2492 subjects found that women, older subjects, and those with lower and fewer office systolic blood pressure measurements were more likely to have white-coat hypertension." }, { "input": "Ambulatory blood pressure monitoring is currently the gold standard for detecting patients with white-coat hypertension. Women and all patients with lower office systolic blood pressures, stage I hypertension, and no target organ damage are more likely to have white-coat hypertension.", "output": "In a joint multivariate analysis of 2 cohort studies, which enrolled 1564 subjects with uncomplicated stage I hypertension, white-coat hypertension was associated with lower office systolic blood pressure, female gender, and nonsmoking." }, { "input": "Self or home blood pressure monitoring has also been used to detect patients with white-coat hypertension. However, it has a low sensitivity (61%-68%) and low positive predictive value (PV+) (33%-48%).", "output": "In the THOP study (247 subjects), which used ambulatory blood pressure monitoring as the reference method, home blood pressure had a high specificity (89%) and high negative predictive value (PV-) (97%) but a lower sensitivity (68%) and low PPV (33%). In other words, if home blood pressure shows hypertension, there is a 97% chance the patient has sustained hypertension, but if home blood pressure returns to normal in patients with office hypertension, two thirds of patients will still have sustained hypertension." }, { "input": "Self or home blood pressure monitoring has also been used to detect patients with white-coat hypertension. However, it has a low sensitivity (61%-68%) and low positive predictive value (PV+) (33%-48%).", "output": "In a study that enrolled patients from a hypertension clinic, 133 untreated patients with dias-tolic blood pressure 90 to 115 mm Hg underwent ambulatory blood pressure monitoring for a reference standard. The sensitivity of home blood pressure monitoring in identifying white-coat hypertension was 61% and the PV+ was 48%." }, { "input": "other", "output": "A Clinical Inquiry summarized 3 cohort trials-2 showed white-coat hypertension patients had lower risk of cardiovascular events and 1 showed no difference between patients with white-coat hypertension and patients with sustained hypertension." }, { "input": "All patients with infectious mononucleosis should be considered at risk for splenic rupture since clinical severity, laboratory results, and physical exam are not reliable predictors of rupture.", "output": "In a case-control study, 29 patients were admitted to an ear, nose, and throat department with infectious mononucleosis and were evaluated serially for splenic and hepatic enlargement by ultrasound. Diagnosis was based on clinical picture, a positive heterophile test, and other blood tests. Four patients were included despite negative serology due to compelling clinical presentations and symptoms. Serial ultrasound imaging showed that all had enlarged spleens (mean enlargement 50%-60%); 50% had hepatic enlargement (5%-20% enlargement). The patients were compared with a control group of 8 patients admitted with peritonsillar abscess, as verified by tonsillectomy. No controls had hepatic or splenic enlargement. Physical examinations detected splenomegaly in only 17% of the study patients. The exams were conducted by house staff without blinding, randomization, or tests of reproducibility. Ultrasound scanning was completed on days 1, 3, 5, 10, 20, 90, and 120. The spleen was significantly larger in the infectious mononucleosis group than in the control group for the first 30 days, and no difference in size was found over the subsequent 3 months. No correlation existed between laboratory values and enlargement of the spleen or liver." }, { "input": "All patients with infectious mononucleosis should be considered at risk for splenic rupture since clinical severity, laboratory results, and physical exam are not reliable predictors of rupture.", "output": "A retrospective analysis of 8116 patients with infectious mononucleosis at the Mayo Clinic estimated the risk of spontaneous splenic rupture to be 0.1% of cases, correlating with rates found in other studies. The study's criteria for definite spontaneous rupture are: no recent trauma; recent symptoms; hematologic, serologic, and histologic (splenic) evidence of infectious mononucleosis. Five patients with rupture (average age, 22) were identified; 3 were male. Splenectomy was performed for all patients. Follow-up over 33-years found all patients healthy with minimal subsequent illness." }, { "input": "Clinical evidence indicates that most splenic ruptures occur within 4 weeks of symptom onset, which correlates with ultrasound data showing resolution of splenomegaly by 30 days from symptom onset.", "output": "A review of 55 cases found almost all splenic ruptures occurred between the fourth and twenty-first days of illness, and that all affected spleens were enlarged, although only half were palpable on exam. Ninety percent of the ruptures occurred in males, and more than half were nontraumatic. There was no correlation between severity of illness and susceptibility to splenic rupture. No specifics were given on duration of illness or how splenomegaly was diagnosed." }, { "input": "Given the morbidity and mortality associated with splenic rupture, instruct patients to refrain from vigorous physical activity for 1 month after symptom onset.", "output": "Clinical Sports Medicine recommends athletes refrain from sporting activities until all acute symptoms resolve and contact sports avoided while the spleen is enlarged. No recommendation is given on determining spleen size." }, { "input": "Given the morbidity and mortality associated with splenic rupture, instruct patients to refrain from vigorous physical activity for 1 month after symptom onset.", "output": "Team Physician Handbook recommends athletes do no cardiovascular work, lifting, strength training, or contact sports for 2 weeks because of the risk of splenic rupture. Activity is then gradually increased as the athlete improves. Athletes are to avoid contact or weight-lifting for 4 weeks unless they feel well and ultrasound reveals a normal-sized spleen." }, { "input": "other", "output": "Sports Medicine Secrets advises ultrasound or CT of the spleen to be obtained if there is any suspicion of splenomegaly or if return to play before 4 weeks is contemplated. Light athletic activity may be resumed approximately 3 weeks after symptom onset if the spleen is not tender or enlarged on examination, the patient is afebrile, liver enzymes are normal, and all other complications are resolved. Contact sports may be resumed 4 weeks after symptom onset if there is no documentation of splenomegaly, the athlete feels ready, and all other complications have resolved." }, { "input": "other", "output": "No quality studies evaluate the risks of physical activity in infectious mononucleosis. Case reports of rupture have found comparable rates between traumatic and nontraumatic causes. In addition, no clinical trials evaluate imaging in decisions regarding return to activity and its effect on splenic rupture. Ultrasound is often used in the athletic setting for these decisions but no evidence supports its use as routine practice. The routine use of ultrasound for this purpose would cost more than $1 million to prevent 1 traumatic rupture." }, { "input": "In patients with congestive heart failure due to systolic dysfunction who are in normal sinus rhythm, digoxin therapy reduces rates of hospitalization, as well as clinical deterioration, defined as worsening New York Heart Association (NYHA) classification or an increase in clinical signs and symptoms", "output": "Patients receiving digoxin experienced reduced rates of hospitalization due to worsening heart failure (odds ratio [OR]=0.68; 95% confidence interval [CI], 0.61-0.75; number needed to treat [NNT]=13-17) and less clinical deterioration (OR=0.31; 95% CI, 0.21-0.43; NNT=3-61). The wide range in NNT for the reduction in clinical deterioration reflects varying baseline rates of worsening clinical status found among the 12 studies for patients receiving placebo. The narrow CI associated with the odds ratio for reduced rates of clinical deterioration reflects the fact that the majority of patients whose clinical status was evaluated as an outcome came from a single large study, the DIG trial. This trial followed 6800 patients with NYHA classifications I to III. Ninety-four percent of patients in this trial were additionally on angiotensin-converting enzyme (ACE) inhibitors and 82% were taking diuretics. Patients were followed for a mean of 37 months. A subgroup analysis of 988 patients with diastolic dysfunction (ejection fraction >45%) in this study suggested no clear benefits or harms when digoxin was used in combination with other therapies vs placebo; however, it did show a positive trend towards the combined outcome of reduced hospitalizations and less clinical deterioration (relative risk [RR]=0.82; 95% CI, 0.63-1.07). Increased rates of supraventricular dysrhythmias (RR=2.08; 95% CI, 1.44-2.99; number needed to harm [NNH]=77) and second- and third-degree heart block were demonstrated for patients receiving digoxin (RR=2.93; 95% CI, 1.61-5.34; NNH=125)." }, { "input": "In patients with congestive heart failure due to systolic dysfunction who are in normal sinus rhythm, digoxin therapy reduces rates of hospitalization, as well as clinical deterioration, defined as worsening New York Heart Association (NYHA) classification or an increase in clinical signs and symptoms", "output": "A post-hoc subgroup analysis focusing only on sex-based differences in the DIG trial suggested women benefit less than men from reduced hospitalizations: -4.2% (95% CI, -8.9 to 0.5) vs -8.9% (95% CI, -11.4 to -6.5) (P=.053). When a multivariable analysis was performed, digoxin use for women was associated with a higher risk of mortality (adjusted hazard ratio vs placebo=1.23; 95% CI, 1.02-1.47)." }, { "input": "Patients treated with digoxin are at increased risk of developing supraventricular dysrhythmias and second- or third-degree atrioventricular block.", "output": "Increased rates of supraventricular dysrhythmias (RR=2.08; 95% CI, 1.44-2.99; number needed to harm [NNH]=77) and second- and third-degree heart block were demonstrated for patients receiving digoxin (RR=2.93; 95% CI, 1.61-5.34; NNH=125)." }, { "input": "It is unclear if patients with diastolic dysfunction experience similar benefits or harms.", "output": "A subgroup analysis of 988 patients with diastolic dysfunction (ejection fraction >45%) in this study3 suggested no clear benefits or harms when digoxin was used in combination with other therapies vs placebo; however, it did show a positive trend towards the combined outcome of reduced hospitalizations and less clinical deterioration (relative risk [RR]=0.82; 95% CI, 0.63-1.07)." }, { "input": "Digoxin use for women may be associated with an increased risk of mortality.", "output": "A post-hoc subgroup analysis focusing only on sex-based differences in the DIG trial suggested women benefit less than men from reduced hospitalizations: -4.2% (95% CI, -8.9 to 0.5) vs -8.9% (95% CI, -11.4 to -6.5) (P=.053). When a multivariable analysis was performed, digoxin use for women was associated with a higher risk of mortality (adjusted hazard ratio vs placebo=1.23; 95% CI, 1.02-1.47)." }, { "input": "Raynaud's phenomenon is diagnosed by history, which also plays a key role in distinguishing primary from secondary Raynaud's phenomenon.", "output": "Experts differ on whether laboratory evaluation with erythrocyte sedimentation rate and an antinuclear antibody test is necessary for patients with primary Raynaud's phenomenon." }, { "input": "Raynaud's phenomenon is diagnosed by history, which also plays a key role in distinguishing primary from secondary Raynaud's phenomenon.", "output": "Raynaud's phenomenon is diagnosed by a history of cold temperatures or emotional stress precipitating episodic digital artery vasospasm, according to expert opinion. This presents as well-demarcated digital pallor and cyanosis, often followed by reactive hyperemia occurring 15 to 20 minutes after rewarming. No reliable office test confirms the diagnosis. By definition, primary Raynaud's phenomenon occurs in the absence of associated diseases and is considered an exaggerated vasoconstrictive response to cold. It must be distinguished from normal mottling of the digits in response to cold temperatures, effects of vasoconstrictive medications, environmental injury (frostbite, use of vibrating tools), neuropathy, and thoracic outlet syndrome." }, { "input": "The initial treatment includes conservative measures such as the use of gloves, cold avoidance, and rapid rewarming.", "output": "Conservative management is helpful for all patients with Raynaud's phenomenon, and may be the only treatment needed. Experts advise dressing warmly, wearing gloves when appropriate, using abortive strategies such as placing the hands into warm water, and avoiding sudden cold exposure, emotional stress, and vasoconstrictive agents such as nicotine." }, { "input": "In refractory cases, the vasodilatory agents nifedipine or prazosin alleviate symptoms.", "output": "Three trials showed subjective improvement in symptom severity with nifedipine vs placebo." }, { "input": "In refractory cases, the vasodilatory agents nifedipine or prazosin alleviate symptoms.", "output": "A systematic review of 2 randomized controlled trials with a total of 40 patients found prazosin modestly effective in secondary Raynaud's phenomenon, but it was less well-tolerated than calcium channel blockers." }, { "input": "In refractory cases, the vasodilatory agents nifedipine or prazosin alleviate symptoms.", "output": "A meta-analysis of 6 randomized crossover studies compared nifedipine or nicardipine with placebo in 59 patients with secondary Raynaud's phenomenon and underlying systemic sclerosis. Nifedipine significantly decreased the frequency and severity of attacks. Nicardipine showed a trend towards reduced symptoms in 1 trial with only 15 patients." }, { "input": "Evidence is conflicting regarding the risk of cardiovascular complications from white-coat hypertension. Some but not all studies show lower cardiovascular event rates for patients with white-coat hypertension compared with those with sustained hypertension.", "output": "A recent 10-year longitudinal study of 146 normotensive people, 76 people with white-coat hypertension, and 344 with sustained hypertension showed that cardiovascular event rates were similar for patients with white-coat and sustained hypertension, and were significantly higher than in the normotensive group (P=.03 overall, P=.03 between white-coat hypertension and normotension and P=.01 between sustained hypertension and normotension)." }, { "input": "Evidence is conflicting regarding the risk of cardiovascular complications from white-coat hypertension. Some but not all studies show lower cardiovascular event rates for patients with white-coat hypertension compared with those with sustained hypertension.", "output": "A prospective cohort study compared fatal and nonfatal cardiovascular event rates among patients who had white-coat hypertension, sustained hypertension, or were normotensive. Investigators performed 24-hour ABPM on 1187 patients who had clinic blood pressures over 140/90 on three visits. They found that 228 patients had white-coat hypertension, defined as mean ambulatory blood pressures below the 90th percentile of a normotensive population, and 959 patients had sustained hypertension. They followed these patients, along with 205 normotensive controls, for a mean of 3.2 years. Cardiovascular event rates did not differ significantly between normotensive and white-coat hypertension patients (P=.83), but the difference in event-free survival between the sustained hypertension group and both the white-coat hypertension and normotensive groups was highly significant (P=.002)." }, { "input": "Evidence is conflicting regarding the risk of cardiovascular complications from white-coat hypertension. Some but not all studies show lower cardiovascular event rates for patients with white-coat hypertension compared with those with sustained hypertension.", "output": "A prospective cohort study compared cardiovascular events among patients with white-coat hypertension vs those with sustained hypertension. The study evaluated 479 patients with persistently elevated clinic systolic blood pressures of 140 to 180 mm Hg. Using 24-hour intraarterial ambulatory blood pressure monitoring (ABPM), they found that 126 patients had ambulatory blood pressures below 140/90 mm Hg (white-coat hypertension) while 353 patients maintained pressures above 140/90 mm Hg (sustained hypertension). On average, white-coat hypertension patients were younger than sustained hypertension patients (44 vs 52 years) but were otherwise similar. Over the next 9 years, patients with white-coat hypertension had significantly fewer cardiovascular events than patients with sustained hypertension." }, { "input": "Little information is available about the use of antihypertensive medication for white-coat hypertension. In 1 small randomized trial, the difference in stroke incidence and cardiovascular complications between active treatment and placebo did not reach statistical significance.", "output": "One randomized trial evaluated outcomes of antihypertensive therapy for white-coat hypertension for patients aged >60 years. Ninety-nine patients with white-coat hypertension were identified on the basis of systolic blood pressure greater than 160 mm Hg in clinic and normal 24-hour ABPM and were randomized to either place-bo or drug therapy. Active treatment did not significantly lower ambulatory blood pressure in white-coat hypertension, but it did reduce blood pressure measured in clinic. After a year, medication produced an absolute reduction in cardiovascular events of 8.6%, and in stroke of 4.2%. Neither result was statistically significant due to the small sample size." }, { "input": "Some experts recommend that patients with white-coat hypertension should be evaluated for evidence of target organ injury and monitored for the development of sustained hypertension.", "output": "Experts agree that patients with white-coat hypertension should be indefinitely monitored for the development of sustained hypertension. Treatment is not needed unless the patient has sustained hypertension, evidence of cardiovascular disease, or signs of target organ injury. Typically, expert opinion recommends confirming the diagnosis of white-coat hypertension with home blood pressure records or ambulatory blood pressure monitoring." }, { "input": "Percutaneous vertebroplasty has been used to treat aggressive vertebral hemangiomas, osteoporotic vertebral compression fractures, and vertebral lesions from metastatic disease or myeloma. Consider it for patients with severe acute or chronic pain related to one of these lesions who have failed a reasonable course of medical therapy.", "output": "The Medicare Coverage Advisory Committee, in its review of the 2005 CMS report, suggested that percutaneous vertebroplasty produces a clinically important net health benefit for patients with vertebral compression fracture compared to conservative care for both acute and chronic fractures." }, { "input": "Percutaneous vertebroplasty has been used to treat aggressive vertebral hemangiomas, osteoporotic vertebral compression fractures, and vertebral lesions from metastatic disease or myeloma. Consider it for patients with severe acute or chronic pain related to one of these lesions who have failed a reasonable course of medical therapy.", "output": "In their guideline on rehabilitation of the patient with osteoporosis, the National Osteoporosis Foundation states an experienced practitioner may perform percutaneous vertebroplasty on a patient with unremitting pain for whom conservative medical therapy has not helped." }, { "input": "Contraindications include an uncorrectable coagulation disorder, infection in the area, spinal cord compression, destruction of the posterior wall of the vertebral body, and severe degrees of vertebral body collapse.", "output": "Two structured, but not systematic, reviews of percutaneous vertebroplasty in vertebral fractures included 15 small observational studies, of which only 1 was included in the CMS report. These reviews examined outcomes of vertebroplasty performed from less than 1 month to a mean of 7 months after fracture, using similar inclusion criteria to those used in the CMS report. The studies' common patient exclusion criteria were uncorrectable coagulation disorder, infection in the area, spinal cord compression, destruction of the posterior vertebral wall, and severe degrees of vertebral body collapse (defined as >67% collapse). The 2 reviews found between 67% and 100% of patients reported pain reduction after vertebroplasty in follow-up periods ranging from 24 hours to up to 10 years." }, { "input": "Pain relief from vertebroplasty for osteoporotic vertebral fractures may be less for older fractures.", "output": "A 2005 Technology Assessment by the Centers for Medicare and Medicaid Services (CMS) provides the best evidence about indications and efficacy of percutaneous vertebroplasty for vertebral fractures. Fifteen studies were included. The common inclusion requirement was severe pain attributable to vertebral fracture. Nine of the studies further specified failure of analgesics or conservative treatments. The studies showed statistically significant decreases in comparative visual analog pain scale scores in the short term. Four studies showed pain reduction lasting up to 1 year. These results favor the conclusion that percutaneous vertebroplasty provides short- and long-term pain reduction for patients meeting the inclusion criteria." }, { "input": "Surgery within 24 hours of hip fracture is a critical step in reducing complications, and may decrease mortality compared with conservative care.", "output": "A 2006 observational study found that delay in operating was associated with an increased risk of death in the hospital, even after adjusting for comorbidities. For all deaths in the hospital, the odds ratio [OR] for delaying more than 1 day, relative to 1 day or less, was 1.27 (95% confidence interval [CI], 1.23-1.32)" }, { "input": "Surgery within 24 hours of hip fracture is a critical step in reducing complications, and may decrease mortality compared with conservative care.", "output": "Some studies did not find decreased mortality with earlier surgical intervention. Complication rates (such as decubitus ulcers) increase with a delay in surgery." }, { "input": "Surgery within 24 hours of hip fracture is a critical step in reducing complications, and may decrease mortality compared with conservative care.", "output": "Some studies found decreased mortality with earlier surgical intervention." }, { "input": "Surgery within 24 hours of hip fracture is a critical step in reducing complications, and may decrease mortality compared with conservative care.", "output": "A meta-analysis found few randomized trials comparing operative with nonoperative therapy; it concluded that surgical treatment seems to be associated with a reduced length of hospital stay and improved rehabilitation." }, { "input": "Give patients heparin at the time of admission to prevent venous thromboembolism (VTE).", "output": "After a hip fracture, patients are at very high risk for VTE. For untreated patients, the rate of deep vein thromboses (DVT) may be as high as 50%, with an associated fatal pulmonary embolism rate as high as 7.5%." }, { "input": "Give patients heparin at the time of admission to prevent venous thromboembolism (VTE).", "output": "The effectiveness of unfractionated and low-molecular-weight heparin was evaluated in a 2002 Cochrane systematic review. While evidence was insufficient to recommend 1 agent over another, both were found to significantly decrease the incidence of lower-extremity DVT over placebo (for unfractionated heparin, relative risk [RR]=0.59 [95% CI, 0.49-0.72]; for low-molecular-weight heparin, RR=0.60 [95% CI, 0.50-0.71]). Number needed to treat [NNT] with either agent was 7." }, { "input": "Anticoagulation should be continued in some form for 10 days or until the patient is fully ambulatory.", "output": "Anticoagulation should routinely continue for 10 days after surgery or until the patient is ambulatory. If anticoagulation is contraindicated, mechanical prophylaxis of VTE with foot and calf pumping devices is recommended." }, { "input": "Patients should get prophylactic antibiotics in the 2 hours before surgery.", "output": "Classen et al found that patients treated less than 2 hours before surgery had a 0.6% rate of infection (10/1208), compared with a 3.85% rate for those treated 2 to 24 hours ahead (14/369) (NNT=31)." }, { "input": "Patients should get prophylactic antibiotics in the 2 hours before surgery.", "output": "It is unclear whether multiple-dose therapy provides additional benefit when administered over the first 24 to 36 hours after surgery (OR=0.60; 95% CI, 0.18-2.02). First- or second-generation cephalosporins were used in most studies." }, { "input": "Patients should get prophylactic antibiotics in the 2 hours before surgery.", "output": "Antibiotic prophylaxis has been supported by a Cochrane review, which concluded that single-dose antibiotic prophylaxis before surgery significantly reduced the risk of deep wound infections (RR=0.40; 95% CI, 0.24-0.67; NNT=55), as well as superficial wound, urinary, and respiratory tract infections." }, { "input": "Reduce the risk of postoperative delirium by avoiding certain medications, minimizing sleep disturbances, and providing adequate analgesia.", "output": "One study showed that prophylaxis with haloperidol for hip fracture patients did not decrease the incidence of postoperative delirium but did reduce its duration and severity." }, { "input": "Reduce the risk of postoperative delirium by avoiding certain medications, minimizing sleep disturbances, and providing adequate analgesia.", "output": "Sleep deprivation, delayed mobility, and inadequate pain control are associated with the development of delirium." }, { "input": "Reduce the risk of postoperative delirium by avoiding certain medications, minimizing sleep disturbances, and providing adequate analgesia.", "output": "Studies suggest avoiding use of meperidine, benzodiazepines, and medications with anticholinergic side effects." }, { "input": "Reduce the risk of postoperative delirium by avoiding certain medications, minimizing sleep disturbances, and providing adequate analgesia.", "output": "Haloperidol prophylaxis was associated with shorter hospital stays. Treatment with haloperidol or risperidone for the agitation of postoperative delirium has been recommended when behavioral interventions fail." }, { "input": "Aggressive pain control should be top of mind-higher pain scores are associated with longer hospital stays, delayed ambulation, and long-term functional impairment.", "output": "In a 2003 prospective cohort study, patients without sufficient analgesia had an increased risk of poor functional recovery and longer hospitalization." }, { "input": "Aggressive pain control should be top of mind-higher pain scores are associated with longer hospital stays, delayed ambulation, and long-term functional impairment.", "output": "In a cohort study, those patients whose pain was inadequately controlled also had an increased risk for delirium (RR=9.0; 95% CI, 1.8-45.2). Meperidine use increased the risk for delirium compared with other opioid analgesics (RR=2.4; 95% CI, 1.3-4.5)." }, { "input": "No single test has sufficient sensitivity to rule out the diagnosis of INPH.", "output": "There is no definitive test or physical finding for INPH. For patients over 40 years of age, INPH has an insidious onset, a progressive course, and lacks an identifiable antecedent cause. A brain imaging study reveals ventricular enlargement not attributable to other causes. Some suggest that the diagnosis be assessed as \"probable\", \"possible\", and \"unlikely\" based on the degree of fulfillment of a set of historical, imaging, clinical, and physiological criteria." }, { "input": "No single test has sufficient sensitivity to rule out the diagnosis of INPH.", "output": "A systematic review of the most commonly used prognostic tests identified a response to a large-volume (40-50 mL) CSF tap test as having a positive predictive value (PPV) between 73% and 100% but a negative predictive value (NPV) of only 23% to 42%. Thus, observing an improvement of function after such a test is a good predictor of improvement after shunting, but many patients who do not respond to the test respond to shunting. A variation of the CSF tap test is the extended lumbar drainage test, which involves placing a lumbar intrathecal catheter and allowing the drainage of 10 mL of CSF/hour for 72 hours. The PPV for this test ranges from 80% to 100%, and NPV from 66% to 100%. A third possible test is the measurement of resistance to an infusion of saline into the lumbar subarachnoid space (CSF Ro test). This test has multiple variations of technique. Reported values for PPV are 75% to 92%, and for NPV of 27% to 92%. Other tests, such as radionuclide cisternography or magnetic resonance imaging CSF flow void, have predictive values too low or have too few studies to be recommended." }, { "input": "It's unclear whether disease-modifying antirheumatic agents (DMARDs) as first-line therapy in nonrheumatoid rheumatologic diseases are effective because the question has not been studied.", "output": "A Cochrane systematic review identified 13 randomized controlled trials enrolling a combined 1022 patients with psoriatic arthritis randomly assigned to receive a DMARD-methotrexate, sulfasalazine (Azulfidine), azathioprine (Imuran/ Azasan), or etretinate (Tegison; no longer available in the US)-compared with placebo. All agents were better than placebo; however, only 2 agents (parenteral high-dose methotrexate and sulfasalazine) had clinically important benefits for more than half the patients. The studies were too small to establish toxicity or to evaluate the other agents." }, { "input": "As second-line therapy, the use of some DmArDs appears to be beneficial for patients with psoriatic arthritis.", "output": "NSAIDs are still the preferred first-line therapy, concluded a recent publication on the treatment of psoriatic arthritis, which looked at 54 different studies; however, second-line therapy could include methotrexate, sulfasalazine, etanercept (Enbrel), infliximab (Remicade), cyclosporine, or combination therapy. Sulfasalazine appeared to be clinically beneficial for peripheral psoriatic arthritis." }, { "input": "As second-line therapy, the use of some DmArDs appears to be beneficial for patients with ankylosing spondylitis", "output": "Two recent Cochrane systematic reviews on ankylosing spondylitis examined the use of sulfasalazine and methotrexate as second-line agents. Eleven trials were included in the sulfasalazine analysis, with a total of 895 patients. Sulfasalazine demonstrated some benefit in reducing erythrocyte sedimentation rates (ESRs) and morning stiffness, but there was no evidence that the drug reduced pain or improved physical function, spinal mobility, or rate of enthesitis. Sulfasalazine was well tolerated and may be useful in early mild disease for patients with peripheral arthritis and high ESRs. On the other hand, evidence was insufficient to determine whether methotrexate benefited patients with ankylosing spondylitis." }, { "input": "As second-line therapy, the use of some DmArDs appears to be beneficial for patients with ankylosing spondylitis", "output": "A study (84 patients) showed that 60% of patients on etanercept vs 20% on placebo had good clinical benefit at only 12 weeks (P<.001, NNT=2.5)." }, { "input": "As second-line therapy, the use of some DmArDs appears to be beneficial for patients with ankylosing spondylitis", "output": "One study of infliximab vs placebo showed 61.2% vs 19.2% patients with good clinical benefit at 24 weeks and only mild or moderate adverse events (P<.001; NNT=2.38)." }, { "input": "Data on the safety and efficacy of DMARDs as second-line therapy for other arthritic conditions is limited.", "output": "A recent randomized controlled trial of 100 patients with antineutrophil cytoplasmic antibody-associated systemic vasculitis showed methotrexate may be able to replace cyclosporine for both induction of remission (methotrexate=89.8% vs cyclosporine=93.5%; P=.041) and maintenance of remission (69.5% vs 46.5% at 18 months; P=.023)." }, { "input": "Strict bed rest in the hospital for pregnant women with preeclampsia does not appear to lower rates of perinatal mortality, neonatal mortality, or neonatal morbidity, including preterm birth, endotracheal intubations, or neonatal intensive care unit (NICU) admissions.", "output": "A RCT of 135 nonproteinuric but hypertensive pregnant patients with diastolic blood pressures between 90 and 109 mm Hg also demonstrated no difference between patients treated with bed rest and sedation or normal activity in fetal or neonatal outcomes." }, { "input": "Strict bed rest in the hospital for pregnant women with preeclampsia does not appear to lower rates of perinatal mortality, neonatal mortality, or neonatal morbidity, including preterm birth, endotracheal intubations, or neonatal intensive care unit (NICU) admissions.", "output": "A trial was a multicenter RCT involving 218 patients between 28 to 38 weeks gestation with nonproteinuric hypertension (blood pressure >140/90 mm Hg). The patients were randomized to 2 groups: bed rest in the hospital but allowed to move around the ward, and normal activity at home without restrictions. The outcomes were measured by masked assessors. There were no statistical differences in perinatal or neonatal mortality, or in the neonatal morbidities of preterm birth, newborns small for their gestational age, or NICU admissions between the 2 groups." }, { "input": "Strict bed rest in the hospital for pregnant women with preeclampsia does not appear to lower rates of perinatal mortality, neonatal mortality, or neonatal morbidity, including preterm birth, endotracheal intubations, or neonatal intensive care unit (NICU) admissions.", "output": "A small, unblinded RCT of 40 preeclamptic patients treated in the hospital with strict bed confinement or without restrictions found no significant difference in fetal or perinatal mortality. No power calculations were reported for detecting differences in neonatal outcome rates in either of these studies." }, { "input": "Strict bed rest in the hospital for pregnant women with preeclampsia does not appear to lower rates of perinatal mortality, neonatal mortality, or neonatal morbidity, including preterm birth, endotracheal intubations, or neonatal intensive care unit (NICU) admissions.", "output": "A single-center RCT investigated bed rest treatment for 105 patients with preeclampsia and gestational ages between 26 to 38 weeks. Patients were assigned to either strict bed rest with bathroom privileges in the hospital until delivery, or to bed rest with the ability to move freely around the hospital. Outcome assessors were not blinded to patient treatment allocation. There was no statistical difference between the 2 groups in perinatal or neonatal mortality, or in the neonatal morbidities of preterm births, endotracheal intubations, or NICU admissions." }, { "input": "Methyldopa has been the drug of choice for oral treatment, as it is the only medication to have any extended follow-up study. However, a recent meta-analysis raised the possibility of increased fetal mortality.", "output": "In comparing one agent with another, methyldopa was the most commonly tested agent, with 14 randomized controlled trials of more than 1010 subjects demonstrating its efficacy at reducing blood pressure. Other antihypertensive agents appear better than methyldopa in terms of reducing the risk of infant mortality (RR=0.49; 95% CI, 0.24-0.99)." }, { "input": "Methyldopa has been the drug of choice for oral treatment, as it is the only medication to have any extended follow-up study. However, a recent meta-analysis raised the possibility of increased fetal mortality.", "output": "Methyldopa is consistently the drug of choice in all those making a specific recommendation." }, { "input": "Labetalol is an effective alternative, but concerns remain that treatment with any beta-blocker increases the risk that infants will be small for gestational age (SGA).", "output": "Meta-analyses of beta-blocker trials show a borderline increase in SGA infants, with no related increase in perinatal mortality, as well as a decrease in the incidence of respiratory distress syndrome." }, { "input": "There is limited evidence that calcium channel blockers and diuretics are safe alternatives, although evidence is insufficient to prove a clear benefit.", "output": "Calcium channel blockers, though generally regarded as safe and effective, have mostly been evaluated for use late in pregnancy, so their benefit-to-risk ratio remains uncertain." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), due to similar mechanisms of action, are contraindicated in pregnancy.", "output": "ACE inhibitors and, by extension, ARBs, due to their similar mechanisms of action, are contraindicated in pregnancy, having been linked to miscarriage, fetal death, fetal renal failure, and malformation." }, { "input": "Evidence is conflicting with regard to the comparative frequency of venous thrombolic events (VTE) among women using the transdermal patch when compared to an oral contraceptive (OC), even though the patch produces a relatively high serum ethinyl estradiol (EE) level.", "output": "In a nested case-control study, investigators verified 57 diagnoses of VTE, controlling for confounding factors. The incidence of VTE in this study was 40.8 per 100,000 women-years among patch users and 18.3 per 100,000 women-years among users of the norgestimate-35 \u00b5g EE OC. The study reported a more than 2-fold increased risk of VTE in patch users compared to OC users (OR=2.4; 95% CI, 1.1-5.5; IRR=2.2; 95% CI, 1.3-3.8)." }, { "input": "Evidence is conflicting with regard to the comparative frequency of venous thrombolic events (VTE) among women using the transdermal patch when compared to an oral contraceptive (OC), even though the patch produces a relatively high serum ethinyl estradiol (EE) level.", "output": "The overall incidence of VTE in this study was 52.8 per 100,000 women-years (95% confidence interval [CI], 35.8-74.9) among patch users and 41.8 per 100,000 women-years among OC users (95% CI, 29.4-57.6). The study concluded that the risk of nonfatal VTE for the patch isn't higher than the risk for an OC containing 35 \u00b5g EE and norgestimate (odds ratio [OR]=0.9; 95% CI, 0.5-1.6; incidence rate ratio [IRR]=1.1; 95% CI, 0.7-1.8)." }, { "input": "Evidence is conflicting with regard to the comparative frequency of venous thrombolic events (VTE) among women using the transdermal patch when compared to an oral contraceptive (OC), even though the patch produces a relatively high serum ethinyl estradiol (EE) level.", "output": "In January 2008, the FDA approved an additional update to include the results of a new study that found users of the patch to be at higher risk of developing VTE than OC users." }, { "input": "Evidence is conflicting with regard to the comparative frequency of venous thrombolic events (VTE) among women using the transdermal patch when compared to an oral contraceptive (OC), even though the patch produces a relatively high serum ethinyl estradiol (EE) level.", "output": "In November 2005, the FDA issued an update to the labeling of the OrthoEvra contraceptive patch, reporting increased systemic estrogen exposure, which may increase the risk of blood clots. The FDA warned that the transdermal patch exposes the user to 60% more estrogen than the typical birth control pill containing 35 \u00b5g EE." }, { "input": "The vaginal ring has a risk of VTE comparable to that of an OC.", "output": "One pharmacokinetic study found that exposure to EE differed among delivery systems. The area under the EE concentration-vs-time curve in the patch group was 1.6 times higher than in the OC group (P<.05) and 3.4 times higher than in the vaginal ring group (P<.05)." }, { "input": "The vaginal ring has a risk of VTE comparable to that of an OC.", "output": "A 1-year, open-label, randomized Phase III study of 1030 women compared the NuvaRing with a combination OC containing levonorgestrel and 30 \u00b5g EE. One case of deep venous thrombosis occurred in the NuvaRing group. In reviewing the data, the authors concluded that the NuvaRing demonstrated comparable safety and tolerability to the OC." }, { "input": "The vaginal ring has a risk of VTE comparable to that of an OC.", "output": "NuvaRing users experienced similar side effects compared with OC users." }, { "input": "Combining nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for short courses provides more relief of pain in osteoarthritis without an increase in side effects.", "output": "One randomized, double-blind, crossover trial compared single doses of tolmetin (Tolectin, 100, 150, 200 mg) and acetaminophen (400 mg) alone and in combination with placebo in the control of experimentally induced pain (thermal and electrical stimulation). Acetaminophen alone did not differ from placebo in pain control; however, the combinations of acetaminophen with tolmetin provided similar pain relief to higher doses of tolmetin alone. No studies have evaluated the efficacy or safety of acetaminophen combined with rofecoxib or celecoxib." }, { "input": "Combining nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for short courses provides more relief of pain in osteoarthritis without an increase in side effects.", "output": "One double-blind, double-dummy crossover trial of 18 patients with osteoarthritis of the hip compared naproxen at doses of 500 mg and 1000 mg, with and without 4 g/d of acetaminophen, and 1500 mg/d of naproxen alone over 5 one-week trial periods. Adding acetaminophen improved patient-reported pain scores compared with naproxen alone. Higher doses of naproxen alone provided less pain relief than a lower dose of naproxen combined with acetaminophen. GI side effects increased with the increase in naproxen dose, but were unaffected by the addition of acetaminophen. Functional ability was not affected during this short study. A similar study by the same researchers of patients with rheumatoid arthritis found similar results." }, { "input": "Combining nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for short courses provides more relief of pain in osteoarthritis without an increase in side effects.", "output": "A 6-week randomized double-blind crossover trial of 227 patients comparing 75 mg diclofenac and 200 mg misoprostol (Arthrotec) with acetaminophen 4 g/d found the diclofenac-misoprostol combination provided more pain control than acetaminophen alone. Adverse events were slightly more common in the diclofenac group (54% vs 46%; P=.046)." }, { "input": "Over the long term, this combination may increase the risk of upper gastrointestinal (GI) bleeding more than that conferred by the NSAID alone. If combination therapy is necessary, limiting the dose of acetaminophen to 2 g/d minimizes gastrointestinal toxicity. Acetaminophen alone at the lowest dose to provide pain relief is the safest pharmacologic choice for patients with osteoarthritis.", "output": "One nested case-control study based on the entire enrollment panel of the British National Health Service characterized the risk of upper GI side effects among persons taking NSAIDs or acetaminophen alone or in combination. The study evaluated medications in use at the time of an upper GI bleed, controlling for age, sex, and concomitant medications (corticosteroids, H2 receptor antagonists, omeprazole, anticoagulants, and others) and excluding patients with varices, alcohol-related disorders, liver disease, and cancer; no attempt was made to control other comorbidities. The relative risk of upper GI perforation or bleeding for patients taking 2g/d acetaminophen or high-dose NSAIDs was 2.4 (95% confidence interval [CI], 1.7-3.5) and 3.6 (95% CI, 2.9-4.3), respectively. Concomitant use of an NSAID with 2 g/d of acetaminophen showed a relative risk of upper GI perforation or bleed of 16.6 (95% CI, 11.0-24.9). Acetaminophen doses <2 g/d conferred no additional risk for serious upper GI side effects." }, { "input": "Over the long term, this combination may increase the risk of upper gastrointestinal (GI) bleeding more than that conferred by the NSAID alone. If combination therapy is necessary, limiting the dose of acetaminophen to 2 g/d minimizes gastrointestinal toxicity. Acetaminophen alone at the lowest dose to provide pain relief is the safest pharmacologic choice for patients with osteoarthritis.", "output": "A meta-analysis of randomized controlled trials found a higher incidence of serious thrombotic cardiovascular events among patients taking COX-2 inhibitors compared with naprosyn. The safety profile of rofecoxib and celecoxib in the long-term treatment of pain is not fully understood at this time." }, { "input": "Over the long term, this combination may increase the risk of upper gastrointestinal (GI) bleeding more than that conferred by the NSAID alone. If combination therapy is necessary, limiting the dose of acetaminophen to 2 g/d minimizes gastrointestinal toxicity. Acetaminophen alone at the lowest dose to provide pain relief is the safest pharmacologic choice for patients with osteoarthritis.", "output": "A systematic review of selective COX-2 inhibitors vs naproxen found fewer endoscopically detected ulcers in patients taking celecoxib but no difference in serious gastrointestinal bleeds." }, { "input": "other", "output": "One randomized controlled trial comparing 750 mg/d naproxen (Aleve, Naprosyn) with 2600 mg/d acetaminophen for 2 years found similar pain relief for both medications and a dropout rate of 65% in both groups. Similar numbers of persons taking acetaminophen or naproxen dropped out because of adverse effects (20%) or lack of efficacy (19%), and no difference was seen in functional improvement between the 2 groups." }, { "input": "other", "output": "The COX-2 inhibitors rofecoxib (Vioxx) and celecoxib (Celebrex) have been shown to provide equal pain relief compared with naproxen for patients with osteoarthritis." }, { "input": "other", "output": "Several small randomized controlled trials have compared the individual efficacy of NSAIDs and acetaminophen in osteoarthritis and have found that both provide more pain relief than placebo." }, { "input": "other", "output": "One industry-sponsored randomized trial found rofecoxib superior to celecoxib, and both superior to acetaminophen in treatment of osteoarthritis pain. There was no difference in the incidence of side effects among the 3 medications. Thirty percent of patients taking 4 g/d acetaminophen discontinued the study because of lack of efficacy, compared with 20% of those taking either celecoxib or rofecoxib." }, { "input": "Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux.", "output": "One study of resistance found that children who received antibiotics for more than 4 weeks in the previous 6 months were more likely to have resistant Escherichia coli isolates than children who had not received prolonged antibiotic treatment (odds ratio [OR]=13.9; 95% CI, 8.2-23.5). Children with abnormalities of the genitourinary tract were approximately 4 times more likely to have resistant isolates of E coli than children without abnormalities of the genitourinary tract (OR=3.9; 95% CI, 2.7-5.7)." }, { "input": "Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux.", "output": "One study found that in children taking low-dose trimethoprim, 97% of the parents reported giving antibiotics on daily basis, but in 31% of subjects, trimethoprim was not detectable in the urine. Risk of prophylaxis includes nausea, vomiting, and rash in 8% to 10% of patients; development of resistant organisms; and change in indigenous microflora." }, { "input": "Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux.", "output": "A meta-analysis of 15 controlled clinical trials in children with neurogenic bladder due to spinal cord dysfunction. This analysis showed that antibiotic prophylaxis was associated with a reduction in asymptomatic bacteruria among children with acute spinal cord injury (P<.05), but there was no significant reduction in symptomatic infections. Prophylaxis resulted in an approximately twofold increase in antimicrobial-resistant bacteria. The researchers concluded that although a clinically important effect has not been excluded, the regular use of antimicrobial prophylaxis for most patients who have neurogenic bladder caused by spinal cord dysfunction is not supported at this time." }, { "input": "Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux.", "output": "A recent systematic review of studies done in children with normal urinary tracts, as well in children with neurogenic bladders, found that the available evidence is of low quality. Only 6 out of 31 potential studies fulfilled the inclusion criteria. These were small (mean sample size was 28), and the quality scores of all 6 trials were low, indicating that the evidence may be unreliable. Two of 3 studies done in children with normal urinary tracts demonstrated statistically significant higher rates of UTI recurrence in control groups compared with treatment groups receiving 6 to 10 months of either nitrofurantoin or cotrimoxazole (RR=24-31). The third study showed no difference between groups. One of 2 trials in children with neurogenic bladder demonstrated higher recurrence rates of 2.9 per 10 patient years for patients receiving antibiotics compared with 1.5 in the untreated group. The other study showed lower recurrence rates of 17.1 for patients receiving antibiotics, compared with 33 in the untreated group. Neither of these findings were statistically significant." }, { "input": "Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux.", "output": "No randomized controlled trials assess whether prophylaxis prevents the development of new renal scars in children." }, { "input": "Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux.", "output": "There was a clinically, but not statistically, significant trend towards reduced risk of UTI during long-term antibiotic treatment (risk reduction [RR]=0.31; 95% confidence interval [CI]=0.10-1.00); however, no sustained benefit was seen once antibiotics were stopped (RR=0.79; 95% CI, 0.61-1.02). There were many problems with the methodological quality of these trials, including significant heterogeneity. The researchers concluded that well-designed randomized controlled trails are still needed to evaluate this commonly used intervention in the pediatric population." }, { "input": "Evidence is insufficient to recommend for or against antibiotic prophylaxis to prevent recurrent urinary tract infections (UTI) in children with anatomic abnormalities. Guidelines acknowledge this lack of evidence, but still recommend using prophylactic antibiotics in children with vesiculoureteral reflux.", "output": "A systematic review evaluated the use of antibiotics to prevent UTI in children. This review of 5 randomized controlled trials included a total of 463 children between the ages of 2 months to 16 years. Three out of 5 trials evaluated the effectiveness of antibiotic treatment for 2 to 6 months to prevent subsequent off-treatment recurrence. The 2 smaller trials (n=71) evaluated the use of low-dose long-term antibiotics to prevent UTI. Benefits for long-term prophylaxis are even less clear in children with low-grade reflux (I-II)." }, { "input": "Healthy, unimmunized children who have not had varicella infection should be vaccinated.", "output": "A trial showed efficacy of 72% over 29 months." }, { "input": "Healthy, unimmunized children who have not had varicella infection should be vaccinated.", "output": "In children aged 10 months to 14 years, 1 randomized controlled trial found protective efficacy of 100% over 9 months and 98% over 7 years." }, { "input": "Healthy, unimmunized children who have not had varicella infection should be vaccinated.", "output": "Cohort studies of children report that the vaccine is 84% to 86% effective in preventing varicella and 100% effective in preventing moderate to severe infections." }, { "input": "Healthy, unimmunized children who have not had varicella infection should be vaccinated.", "output": "Varicella is the leading cause of vaccine-preventable death in children." }, { "input": "Use of the vaccine in immunocompromised children is still being studied and has not been approved by the Food and Drug Administration (FDA).", "output": "Some evidence suggests the incidence of herpes zoster is reduced in immunocompromised vaccine recipients, but long-term observation is needed to assess the effect on healthy recipients." }, { "input": "Use of the vaccine in immunocompromised children is still being studied and has not been approved by the Food and Drug Administration (FDA).", "output": "The FDA has not approved this live-virus vaccine for use in pregnant women and immunocom-promised persons, including transplant recipients and persons receiving corticosteroid therapy. However, the vaccine has been very well-studied in children with leukemia. A review of these studies found that optimal seroconversion requires 2 sequential vaccine doses (86% efficacy). A rash of varying severity was the predominant adverse event in 20% to 50% of vacinees." }, { "input": "Use of the vaccine in immunocompromised children is still being studied and has not been approved by the Food and Drug Administration (FDA).", "output": "Study of vaccine use in other immunocompromised children has been limited. Early results from a trial in HIV-infected children who were not severely immunocompromised suggests similar tolerance and efficacy compared with children without HIV." }, { "input": "Both drug classes increase exercise capacity and alleviate symptoms of COPD, although neither alters disease progression.", "output": "A review of 33 double-blind randomized placebo-controlled studies showed a significant effect of bronchodilator therapy on exercise capacity in COPD patients in about one half of studies. Anticholinergic agents had significant beneficial effects in the majority, and these effects tended to be somewhat dose-dependent. Short-acting \u03b22-agonists improved exercise capacity in more than two thirds of the studies, but long-acting agents led to mixed outcomes. The researchers identified no superior agent between the 2 classes, citing a lack of adequate studies making a direct comparison." }, { "input": "Both drug classes increase exercise capacity and alleviate symptoms of COPD, although neither alters disease progression.", "output": "A recent Cochrane Review comparing the short-term effects of ipratropium to \u03b22-agonists in changes in FEV1and arterial oxygen pressure (PaO2) concluded there was no evidence that the degree of bronchodilation from ipratropium was greater than that from short-acting \u03b22-agonists. Subjective endpoints such as dyspnea and quality of life were not assessed, and neither of the above reviews included studies focusing on long-term outcomes." }, { "input": "Both drug classes increase exercise capacity and alleviate symptoms of COPD, although neither alters disease progression.", "output": "A 12-week double-blind, double-placebo-controlled parallel group study published in 2000 followed 144 patients (age 64 \u00b1 7 years with a FEV1of 44 \u00b111% predicted) randomized to receive salmeterol 50 \u00b5g twice daily alone, salmeterol 50 \u00b5g twice daily plus ipratropium 40 \u00b5g 4 times daily, or placebo. Patients were assessed for changes in FEV1, daytime symptom scores, specific airway conductance, and the need for rescue medication. The study demonstrated a significant benefit from the addition of ipratropium to salmeterol in terms of reduction of airway obstruction, but not in symptom control or need for rescue medication. However, no patients were randomized to receive ipratropium alone, so comparison of the relative contribution of the 2 classes is limited." }, { "input": "Both drug classes increase exercise capacity and alleviate symptoms of COPD, although neither alters disease progression.", "output": "A 6-month, randomized double-blind placebo-controlled study evaluating the efficacy of salmeterol 50 \u00b5g twice daily vs tiotropium (a new long-acting inhaled anticholinergic) 18 \u00b5g once daily was published in 2002. Endpoints in 623 patients were assessed using 12-hour spirometric performance, transition dyspnea index (TDI), and the St. George Respiratory Questionnaire (SGRQ). (SGRQ is a validated disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being. It measures activity limitations, symptoms, and psychosocial impact.) Tiotropium showed superiority over salmeterol in all endpoints assessed (0.14 L increase in morning FEV1vs 0.09 L, 1.02 U improvement in TDI score vs 0.24, and -5.14 U improvement of SGRQ total score from baseline vs -3.54). However, it should be noted that a difference of 1 on the TDI score was necessary to suggest a clinical benefit. While the overall difference in SGQR between tiotropium and salmeterol did not reach statistical significance, the proportion of patients in the tiotropium group that reached the clinically significant threshold of 4 units improvement in SGRQ score was significantly higher than in the salmeterol group (51% vs 40%; P<.05)." }, { "input": "Both drug classes increase exercise capacity and alleviate symptoms of COPD, although neither alters disease progression.", "output": "In a study in 2003, 1207 patients were randomized to receive the above doses of salmeterol, tiotropium, or placebo. Over the course of 6 months, tiotropium was associated with a significant delay in onset of the first exacerbation compared with placebo, and overall it led to the fewest exacerbations per patient-year. Fewer hospital admissions were also demonstrated in the tiotropium group per patient-year, and the number of days that patients were unable to perform usual activities was lowest for the tiotropium group. Again, improvement in TDI and SGRQ scores was significantly greater with tiotropium than placebo. In almost all outcomes, the salmeterol results were intermediate between those of tiotropium and placebo, and were not statistically different from placebo." }, { "input": "Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test.", "output": "The risk of contrast reaction during IVP is between 5% and 10%, with a mortality of approximately 1 in 40,000. Helical CT (when evaluating for stones) does not use contrast, although the radiation exposure is approximately twice that of IVP." }, { "input": "Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test.", "output": "The costs of helical CT and IVP are comparable, and helical CT becomes more cost effective when the shorter time to discharge with a definitive diagnosis is considered." }, { "input": "Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test.", "output": "The accuracy of ultrasonography appears to fall somewhere in between hematuria testing and IVP." }, { "input": "Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test.", "output": "A study found that urine dipstick testing for hematuria yielded positive likelihood ratios of 1.25 and a negative likelihood ratio of 0.55." }, { "input": "Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test.", "output": "The Belgian study enrolled 53 of 70 consecutive patients. This study compared helical CT with intravenous pyelography (IVP) and used the gold standard of recovery and direct visualization of a stone. In this study, helical CT correctly identified every instance of urinary tract stones. In contrast, IVP failed to detect stones in a third of the patients with stones, and 44% of the negative readings were false-negatives. Both tests did well in reporting negative results for those patients without stones (specificity = 97% for both tests). In terms of likelihood ratios, helical CT and IVP had positive likelihood ratios of 29 and 19, respectively, and negative likelihood ratios of 0 and 0.36 (a lower negative likelihood ratio is better). In other words, helical CT appears to be far superior to IVP in ruling out the presence of urinary tract stones." }, { "input": "Over the past 3 years, helical (or spiral) computerized tomography (CT) has proved the best method of testing for urinary tract stones. All reviewed studies published since mid-1998 found helical CT scan to be the safest and most accurate test.", "output": "The Australian study enrolled 40 consecutive patients. This study compared helical CT with intravenous pyelography (IVP) and used the gold standard of recovery and direct visualization of a stone. In this study, helical CT correctly identified every instance of urinary tract stones. In contrast, IVP failed to detect stones in a third of the patients with stones, and 44% of the negative readings were false-negatives. Both tests did well in reporting negative results for those patients without stones (specificity = 97% for both tests). In terms of likelihood ratios, helical CT and IVP had positive likelihood ratios of 29 and 19, respectively, and negative likelihood ratios of 0 and 0.36 (a lower negative likelihood ratio is better). In other words, helical CT appears to be far superior to IVP in ruling out the presence of urinary tract stones." }, { "input": "No evidence was identified that provides a basis for determining whether EGD leads to improved outcomes in patients with GERD. However, patients with GERD referred for elective EGD who were found to have Barrett's esophagus were more likely to have symptoms for more than 1 year than patients who did not have Barrett's esophagus. Patients with esophageal adenocarcinoma were more likely to have frequent, severe, or longer duration of GERD symptoms. The calculated odds ratios (OR) for esophageal adenocarcinoma increased with increasing frequency, severity, or duration of GERD symptoms, independently or in combination.", "output": "There is no current evidence that evaluation of GERD patients with EGD improves outcomes, although 2 retrospective studies have shown improved outcomes for patients with Barrett's esophagus undergoing surveillance endoscopy compared with those without surveillance." }, { "input": "No evidence was identified that provides a basis for determining whether EGD leads to improved outcomes in patients with GERD. However, patients with GERD referred for elective EGD who were found to have Barrett's esophagus were more likely to have symptoms for more than 1 year than patients who did not have Barrett's esophagus. Patients with esophageal adenocarcinoma were more likely to have frequent, severe, or longer duration of GERD symptoms. The calculated odds ratios (OR) for esophageal adenocarcinoma increased with increasing frequency, severity, or duration of GERD symptoms, independently or in combination.", "output": "Among Swedish men aged 50 to 79 years with symptoms at least 1 time per week and BMI greater than 30, 594 endoscopies (95% CI, 385-972) are needed to find 1 case of esophageal adenocarcinoma. These authors estimate incidence of adenocarcinoma using population-wide surveillance data." }, { "input": "No evidence was identified that provides a basis for determining whether EGD leads to improved outcomes in patients with GERD. However, patients with GERD referred for elective EGD who were found to have Barrett's esophagus were more likely to have symptoms for more than 1 year than patients who did not have Barrett's esophagus. Patients with esophageal adenocarcinoma were more likely to have frequent, severe, or longer duration of GERD symptoms. The calculated odds ratios (OR) for esophageal adenocarcinoma increased with increasing frequency, severity, or duration of GERD symptoms, independently or in combination.", "output": "Obesity was a risk factor for esophageal adenocarcinoma in this population. Patients with a body mass index (BMI) greater than 30 had increased risk of adenocarcinoma compared with patients with a BMI less than 25 (OR=16.2; 95% CI, 6.3-41.4). These authors calculated numbers of endoscopies needed to detect 1 case of esophageal adenocarcinoma." }, { "input": "No evidence was identified that provides a basis for determining whether EGD leads to improved outcomes in patients with GERD. However, patients with GERD referred for elective EGD who were found to have Barrett's esophagus were more likely to have symptoms for more than 1 year than patients who did not have Barrett's esophagus. Patients with esophageal adenocarcinoma were more likely to have frequent, severe, or longer duration of GERD symptoms. The calculated odds ratios (OR) for esophageal adenocarcinoma increased with increasing frequency, severity, or duration of GERD symptoms, independently or in combination.", "output": "A Swedish case-controlled study compared 189 cases of esophageal adenocarcinoma and 167 cases of squamous cell carcinoma with 820 control subjects recruited from the general population. Patients with esophageal adenocarcinoma were 7.7 times more likely to report symptoms of GERD at least once weekly 5 years before their diagnosis with adenocarcinoma. Other ORs are as follows: symptoms once per week (5.1), symptoms more than 3 times per week (16.7), nocturnal symptoms at least once per week (10.8), and duration more than 20 years (16.4)." }, { "input": "No evidence was identified that provides a basis for determining whether EGD leads to improved outcomes in patients with GERD. However, patients with GERD referred for elective EGD who were found to have Barrett's esophagus were more likely to have symptoms for more than 1 year than patients who did not have Barrett's esophagus. Patients with esophageal adenocarcinoma were more likely to have frequent, severe, or longer duration of GERD symptoms. The calculated odds ratios (OR) for esophageal adenocarcinoma increased with increasing frequency, severity, or duration of GERD symptoms, independently or in combination.", "output": "A total of 701 patients referred for EGD by gastroenterologists for GERD symptoms yielded 77 cases of Barrett's esophagus. Compared with patients without Barrett's esophagus, patients with the condition were more likely to have symptoms greater than 1 year: 1 to 5 years (OR=3.0 [95% confidence interval (CI), 1.2-8.0]), 5 to 10 years [OR=5.1 (95% CI, 1.2-14.7)], more than 10 years [OR=6.4 (95% CI, 2.4-17.10)]." }, { "input": "The primary motivation to screen asymptomatic women after a hysterectomy is to prevent morbidity and mortality from gynecologic cancer. However, primary vaginal cancer is rare, the vaginal Pap test is not particularly accurate, and the natural history of precancerous vaginal lesions is uncertain. Based on these facts there is no compelling reason to screen women after hysterectomy for benign disease with routine Pap tests.", "output": "In the largest cohort study, 9610 vaginal cuff Pap tests from 5682 women who had had a hysterectomy for benign disease were reviewed. The authors found 104 test results (from 79 women) were abnormal. Of these, 52 showed atypical squamous cells of undetermined significance, 44 were low-grade squamous intraepithelial lesions, 6 were high-grade squamous intraepithelial lesions, and 2 were read as carcinoma. Of the 79 women 27 were referred for colposcopy. Colposcopy results showed that 19 had normal mucosa, and 8 had VAIN 1 or 2. Six of these cases resolved without further treatment. Two were lost to follow-up, and no cancers were diagnosed. One of the women with a Pap-based diagnosis of cancer was lost to follow-up; the other had VAIN 1. No confirmed cases of carcinoma were found. The positive predictive value (the probability that an abnormal test result meant the patient had cancer) was 0% (95% confidence interval, 0.0%-33.0%)." }, { "input": "The primary motivation to screen asymptomatic women after a hysterectomy is to prevent morbidity and mortality from gynecologic cancer. However, primary vaginal cancer is rare, the vaginal Pap test is not particularly accurate, and the natural history of precancerous vaginal lesions is uncertain. Based on these facts there is no compelling reason to screen women after hysterectomy for benign disease with routine Pap tests.", "output": "Fetters and colleagues estimated that the positive predictive value of an abnormal vaginal Pap test result was 0.05%; only 1 in 2000 women with abnormal test results would have cancer." }, { "input": "A high-fiber diet may help; available evidence doesn't support other interventions. A high-fiber diet is often prescribed after recovery from acute diverticulitis, based on extrapolation from epidemiologic data showing an association between low-fiber diets and diverticulosis.", "output": "A 2006 Family Physicians Inquiries Network Clinical Inquiry on diverticulosis found inconsistent evidence that fiber decreases the risk of symptomatic diverticular disease." }, { "input": "No direct evidence establishes a role for fiber in preventing recurrent diverticulitis, however.", "output": "A 2007 literature review found no systematic reviews or randomized controlled trials (RCTs) of fiber for preventing complications of diverticular disease. The reviewers noted that observational studies have found less diverticulosis in populations with higher fiber consumption." }, { "input": "No evidence supports the common advice to avoid nuts and seeds to prevent diverticulitis. Eating nuts, corn, and popcorn doesn't increase the risk; in fact, nuts and popcorn may have a protective effect.", "output": "A trial conducted as part of a large prospective cohort study-the Health Professionals Follow-up Study-followed 47,228 male health professionals in the United States, ages 40 to 75 years, from 1986 to 2004. The subjects, all of whom returned a food-frequency questionnaire, were at baseline free of diverticulosis and related complications, cancer, and inflammatory bowel disease. During the follow-up period, 801 cases of diverticulitis and 383 cases of diverticular bleeding (the main outcome measures) occurred. The investigators found an inverse association between consumption of nuts and popcorn and risk of diverticulitis. Men with the highest intake of each food (at least twice per week) compared with men with the lowest intake (less than once per month) had a hazard ratio of 0.80 (95% confidence interval [CI], 0.63-1.01; P for trend=.04) for nuts and 0.72 (95% CI, 0.56-0.92; P for trend=.007) for popcorn. No association was noted between corn consumption and diverticulitis or between nut, corn, or popcorn consumption and diverticular bleeding or uncomplicated diverticulosis." }, { "input": "There isn't enough evidence to recommend the anti-inflammatory drug mesalamine or a polybacterial lysate for immunostimulation.", "output": "A 2007 systematic review found 1 RCT of the anti-inflammatory drug mesalamine (mesalazine, 5-aminosalicylic acid) for preventing diverticulitis. Mesalamine reduced the recurrence rate of diverticulitis from 46% to 15% among 166 subjects. The reviewers judged the study to be flawed by unreported diagnostic criteria and a high withdrawal rate. They concluded that the effectiveness of mesalamine remains unknown." }, { "input": "Retrospective data don't support routine prophylactic colectomy after 1 or 2 episodes of acute diverticulitis.", "output": "A decision analysis using a Markov model found that performing a colectomy after a fourth, rather than a second, episode of diverticulitis would result in somewhat fewer deaths and colostomies, equivalent quality-adjusted years of life, and cost savings per patient of $1035 to $5429. The results held for both older and younger patients." }, { "input": "Retrospective data don't support routine prophylactic colectomy after 1 or 2 episodes of acute diverticulitis.", "output": "One large retrospective study followed 3165 patients for 6 to 12 years after hospitalization for diverticulitis. Of the patients treated nonoperatively, 13% had a single recurrence and 4% had multiple recurrences; the annual recurrence rate was approximately 2%. The authors concluded that routine elective colectomy is rarely indicated after a first episode of uncomplicated acute diverticulitis." }, { "input": "Retrospective data don't support routine prophylactic colectomy after 1 or 2 episodes of acute diverticulitis.", "output": "No randomized trials have compared surgical with medical therapy to prevent recurrent diverticulitis. Extensive retrospective literature fails to support elective surgery after a second episode. Sixty-eight percent to 96% of patients requiring surgery for diverticulitis-associated perforation or abscess had no previous symptoms and couldn't be helped by prophylactic surgery, and diverticulitis symptoms persisted after bowel resection in 27% to 33% of patients." }, { "input": "Case series from tertiary-care centers report toddler's diarrhea, cow's milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis.", "output": "A case series study from India evaluated 47 children over 6 months of age who had diarrhea for more than 15 days and were unresponsive to medications (mostly antibiotics) or relapsing after treatment. The diagnoses included tropical enteropathy (46.8%), nonspecific diarrhea (21.8%), giardiasis (14.8%), irritable bowel syndrome (10.6%), and celiac disease (6.8%), although these findings probably do not apply to patients in more developed countries." }, { "input": "Case series from tertiary-care centers report toddler's diarrhea, cow's milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis.", "output": "A small tertiary-care pediatric study defining chronic diarrhea as occurring for more than 3 weeks and dependent on parenteral nutrition for more than 50% of daily caloric intake included only 20 patients. The diagnoses included autoimmune enteropathy, congenital microvillous atrophy, chronic intestinal pseudo-obstruction, and multiple food intolerance." }, { "input": "Case series from tertiary-care centers report toddler's diarrhea, cow's milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis.", "output": "A pedriatic study included 381 children from a tertiary-care center with chronic diarrhea defined as lasting longer than 14 days. In this case series, 31% of children had toddler's diarrhea, defined as chronic diarrhea with no definitive cause in an otherwise healthy baby who is growing normally. Cow's milk sensitivity enteropathy comprised an additional 30% of cases. Etiologies for diarrhea in the remaining cases were infectious (11.8%), idiopathic (8.9%), celiac (7.3%), and other (10.2%)." }, { "input": "Case series from tertiary-care centers report toddler's diarrhea, cow's milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis.", "output": "A case series of adult chronic diarrhea patients was identified. The study evaluated 103 patients referred to the same tertiary-care center. It is unclear whether these patients had a prior workup for chronic diarrhea. Secretory diarrhea was the most common etiology overall (45%). Other etiologies included malabsorption (28%), microscopic colitis (9%), inflammatory bowel disease (10%), and celiac sprue (3%)." }, { "input": "Case series from tertiary-care centers report toddler's diarrhea, cow's milk sensitivity enteropathy, infection, celiac disease, and idiopathic chronic diarrhea as the most common etiologies in the pediatric population. In adults, the most common etiologies were secretory diarrhea (idiopathic, laxative abuse, irritable bowel syndrome, diabetes mellitus, and fecal incontinence), malabsorption (pancreatic disease, noninflammatory short bowel syndrome, postgastrectomy, hyperthyroidism, and cholestasis), microscopic colitis, inflammatory bowel disease, celiac sprue, and radiation colitis.", "output": "A case series of adult chronic diarrhea patients was identified. The study evaluated 193 patients referred to a tertiary-care center for diarrhea. Secretory diarrhea was the most common etiology overall (21%). Other etiologies included malabsorption (35%), microscopic colitis (15%), inflammatory bowel disease (16%), and celiac sprue (0%)." }, { "input": "Low-carbohydrate diets raise high-density lipoprotein (HDL) cholesterol levels by approximately 10%; soy protein with isoflavones raises HDL by 3%.", "output": "A systematic review with meta-analysis of 23 RCTs evaluating effect of various amounts of soy protein with isoflavones on lipid profile found a 3% increase in HDL with an absolute difference 1.5 mg/dL (95% CI, 0.0-2.8)." }, { "input": "Low-carbohydrate diets raise high-density lipoprotein (HDL) cholesterol levels by approximately 10%; soy protein with isoflavones raises HDL by 3%.", "output": "An uncontrolled prospective trial showed a 12% increase in HDL." }, { "input": "Low-carbohydrate diets raise high-density lipoprotein (HDL) cholesterol levels by approximately 10%; soy protein with isoflavones raises HDL by 3%.", "output": "A systematic review with meta-analysis of 5 randomized controlled trials (RCTs) of low-carbohydrate versus low-fat diets showed a 10% increase in HDL attributed to the low-carbohydrate diet, which translated to an absolute increase of 4.6 mg/dL (95% confidence interval [CI], 1.5-8.1)." }, { "input": "The Dietary Approaches to Stop Hypertension (DASH) diet and multivitamin supplementation raise HDL 21% to 33%.", "output": "The DASH diet was studied as an intervention in a RCT of 116 patients with the metabolic syndrome. Men responded with an in crease of 21% and women with an increase of 33%." }, { "input": "Antibiotics (including those given orally) reduce mortality and treatment failures for hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (COPD).", "output": "A low quality meta-analysis of 9 randomized controlled trials (RCTs) with 1101 patients with presumed COPD, which also compared antibiotic therapy with placebo for acute exacerbations. Specific diagnostic criteria were not stated for the diagnosis of either COPD or an acute exacerbation. No single outcome measure was common to all studies. The authors found a summary beneficial effect size of antibiotic therapy of 0.22 (95% CI, 0.10-0.34), which is generally interpreted as small. One clinical parameter, peak expiratory flow rate (PEFR), was reported in 6 of the studies. Antibiotic therapy resulted in an average 10.75 L/min improvement in PEFR compared with placebo (95% CI, 4.96-16.54 L/min)." }, { "input": "Antibiotics (including those given orally) reduce mortality and treatment failures for hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (COPD).", "output": "A recent Cochrane review identified 11 randomized controlled trials (RCTs) (with a total of 917 patients) addressing antibiotic therapy for COPD exacerbations characterized by 1 or more of the following: an increase in sputum purulence or volume, dyspnea, wheezing, chest tightness, or fluid retention. Eight trials were conducted on hospital wards, 1 was in a medical intensive care unit, and 2 trials were in the outpatient setting. Antibiotics were given orally in 9 of the 11 studies. Overall, antibiotics reduced risk of short-term mortality by 77% (relative risk [RR]=0.23; 95% confidence interval [CI],0.10-0.52; number needed to treat [NNT]=8), treatment failure by 53% (RR=0.47; 95% CI, 0.36-0.62; NNT=3), and sputum purulence by 44% (RR=0.56; 95% CI, 0.41-0.77; NNT=8). A subgroup analysis that excluded the outpatient and intensive-care unit studies did not change the result. Another subgroup analysis of the 2 outpatient studies failed to find a significant effect, although the studies had very different designs." }, { "input": "Antibiotics may be prescribed in the outpatient setting for those with severe exacerbations.", "output": "Two RCTs addressing antibiotic use in the outpatient setting were identified in the Cochrane review. One double-blind crossover trial performed in Canada compared antibiotic with placebo therapy for 173 outpatients with 362 exacerbations classified according to severity. The protocol used oral trimethoprim-sulfamethoxazole, amoxicillin, or doxycycline (according to the attending physician's preference) or a look-alike placebo. Symptom resolution was seen by 21 days in 68% of antibiotic users vs 55% of those on placebo (P<.01, NNT=8). Ten percent of patients taking antibiotics deteriorated to the point where hospitalization or unblinding of the therapy was necessary, compared with 19% in the placebo group (P<.05, NNT=11). For patients with all 3 cardinal COPD symptoms (increased dyspnea, sputum production, and sputum purulence) at enrollment, there was resolution at 21 days in 63% with antibiotics vs 43% for placebo (P value not given). Antibiotics did not benefit patients with 1 cardinal symptom (74% success with antibiotics vs 70% on placebo; P value not given)." }, { "input": "Antibiotics may be prescribed in the outpatient setting for those with severe exacerbations.", "output": "A Cochrane review identified a Danish RCT that studied 278 patients presenting to their general practitioners with subjective acute worsening of their COPD. Patients were randomized to 7 days of oral amoxicillin or placebo. There was no difference between the groups in terms of symptom resolution at 1 week (odds ratio=1.03, favoring placebo; 95% CI, 0.75-1.41) or in changes in PEFR (weighted mean difference=-0.89, favoring placebo; 95% CI, -29 to 27 L/min)." }, { "input": "Switching to other antidepressants or augmenting with non-antidepressant drugs has the best supporting evidence.", "output": "The strongest evidence is from the recent STAR*D trial, a randomized study that assigned patients in one arm of the study who had no relief from (or did not tolerate) therapy with citalopram (Celexa) to 1 of 3 drugs-sustained-release bupropion (Wellbutrin SR), sertraline (Zoloft), or extended-release venlafaxine (Effexor XR). The study concluded that approximately 1 in 4 patients have remission after switching to an antidepressant from another drug class." }, { "input": "Switching to other antidepressants or augmenting with non-antidepressant drugs has the best supporting evidence.", "output": "Further switches in antidepressant monotherapy have a low success rate (10%-20%)." }, { "input": "Various antidepressants are used as add-on therapy.", "output": "There is cohort study evidence that combining citalopram and bupropion is more effective than switching to the alternate antidepressant, but other cohort studies did not find a significant difference between switching and augmenting." }, { "input": "Various antidepressants are used as add-on therapy.", "output": "Evidence from a meta-analysis with aggregate data from 3 studies representing a total of 110 patients showed that augmentation of various antidepressants with lithium leads to improved outcomes (number needed to treat [NNT]=3.7)." }, { "input": "Various antidepressants are used as add-on therapy.", "output": "An arm of the STAR*D trial added either sustained-release bupropion or buspirone (Buspar) to the failed citalopram therapy. Thirty percent of patients with depression unresponsive to citalopram had remission when bupropion-SR or buspirone was added. The STAR*D reports do not compare the 2 strategies of switching or combining drugs directly." }, { "input": "Various antidepressants are used as add-on therapy.", "output": "A small (23-patient) randomized trial of lamotrigine (Lamictal) suggests that it may augment the effect of fluoxetine." }, { "input": "Various antidepressants are used as add-on therapy.", "output": "A cohort study of augmentation with an atypical antipsychotic agent such as aripiprazole (Abilify) suggest improved outcomes, but similar studies found no benefit." }, { "input": "Psychotherapy is often recommended, though the evidence of benefit after a failed course of initial therapy is sparse.", "output": "A systematic review of psychological therapies in treatment-resistant depression found 2 controlled studies (of cognitive therapy and cognitive behavioral therapy) out of 12 total studies meeting their inclusion criteria that demonstrated improved scores on the Hamilton Rating Scale for Depression. Further study of these therapies was recommended." }, { "input": "The evidence supporting use of electroconvulsive therapy (ECT) in treatment-resistant depression is weak.", "output": "The evidence supporting use of ECT for treatment-resistant depression comes from studies following failure of treatment with tricyclic antidepressants and monoamine oxidase (MAO) inhibitors. Methodological problems in these older studies do not permit an estimate of response rate." }, { "input": "other", "output": "The first step in treatment-resistant depression should be optimizing dose and duration of therapy. For fluoxetine (Prozac), based on a nonrandomized open trial, patients should receive 8 weeks of treatment before the SSRI course is deemed adequate. Only 23% of patients who have not responded to 8 weeks of fluoxetine respond to a still longer course of fluoxetine." }, { "input": "Non-supine sleep position and parental tobacco use are known risk factors for sudden infant death syndrome (SIDS). Recent studies show that co-sleeping (bed sharing) slightly increases the overall risk of SIDS and is greatest for infants less than 11 weeks old", "output": "Four stratified analyses indicate that the risk of co-sleeping is greatest among infants of smokers (OR=4.6-17.7) as compared with infants of nonsmokers (OR=1.0-2.2)." }, { "input": "Non-supine sleep position and parental tobacco use are known risk factors for sudden infant death syndrome (SIDS). Recent studies show that co-sleeping (bed sharing) slightly increases the overall risk of SIDS and is greatest for infants less than 11 weeks old", "output": "Studies demonstrated co-sleeping to be an independent risk factor for SIDS, especially for infants younger than 11 weeks old." }, { "input": "Non-supine sleep position and parental tobacco use are known risk factors for sudden infant death syndrome (SIDS). Recent studies show that co-sleeping (bed sharing) slightly increases the overall risk of SIDS and is greatest for infants less than 11 weeks old", "output": "Overall, 5 of 6 studies demonstrated co-sleeping to be an independent risk factor for SIDS (odds ratio [OR]=2.0-16.5)." }, { "input": "The relationship between bed sharing and SIDS is strongest for infants whose parents use tobacco.", "output": "Four stratified analyses indicate that the risk of co-sleeping is greatest among infants of smokers (OR=4.6-17.7) as compared with infants of nonsmokers (OR=1.0-2.2)." }, { "input": "Infants who sleep in a room separate from their caregivers or on a couch or an armchair are at increased risk for SIDS.", "output": "Three of 4 studies found that infants sleeping in separate rooms from their caregivers had a 3-fold increased risk of SIDS." }, { "input": "Infants who sleep in a room separate from their caregivers or on a couch or an armchair are at increased risk for SIDS.", "output": "One study found the risk was present in infants less than 20 weeks, but was inconclusive for those greater than 20 weeks." }, { "input": "Infants who sleep in a room separate from their caregivers or on a couch or an armchair are at increased risk for SIDS.", "output": "A study found a 10-fold increased risk." }, { "input": "Using bedding accessories such as duvets or pillows may increase an infant's risk of SIDS.", "output": "A study on duvet use found it to be a risk factor for SIDS OR=1.82." }, { "input": "Using bedding accessories such as duvets or pillows may increase an infant's risk of SIDS.", "output": "Two of 3 studies found pillow use unrelated to SIDS." }, { "input": "Using bedding accessories such as duvets or pillows may increase an infant's risk of SIDS.", "output": "4 studies evaluating sleep surface found a significantly increased risk of SIDS for infants sleeping on sofas or armchairs compared with infants sleeping in beds or cribs. Fifty-five of 772 total cases (7.1%) from the 4 studies slept on a non-bed surface compared with 8 of 1854 controls (0.4%)." }, { "input": "Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays.", "output": "Patients with karyotype abnormalities and those with diabetes are also more likely to have false-negative serologic tests." }, { "input": "Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays.", "output": "IgG AGA has similar sensitivity to the IgA assay-approximately 80%-with a slightly lower specificity of 80%. The discrepancy in the sensitivity of IgG tTG and IgG EMA between studies occurs because of differing antibody levels with variations in dietary gluten." }, { "input": "Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays.", "output": "In a cross-sectional study, 100% of 20 untreated celiac disease patients with IgA deficiency had positive IgG tests for tTG, AGA, and EMA despite negative IgA tests for the same antibodies. Eleven patients with celiac disease and no IgA deficiency all had positive tTG, AGA, and EMA tests, whether testing for the IgA or IgG forms." }, { "input": "Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays.", "output": "Patients with selective IgA deficiency often have falsely negative serum IgA assays (for EMA, tTG, and AGA), so IgG is a diagnostic alternative." }, { "input": "Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays.", "output": "In a systematic review, there was no statistically significant difference between IgA EMA and IgA tTG-both had sensitivities greater than 90% and specificities greater than 95%. IgA AGA did not perform as well (sensitivity 80%-90%, specificity 85%-95%). IgG tTG and IgG EMA had specificities of 95% but sensitivities of only 40%." }, { "input": "Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays.", "output": "In 2 studies of the diagnostic accuracy of IgA tTG, 95% to 98% of biopsy-proven celiac disease patients had positive tests, while only 5% to 6% of controls were positive." }, { "input": "Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance.", "output": "A study addressed whether glucosamine taken at recommended doses for the treatment of osteoarthritis had any detrimental effect on glucose metabolism. Fourteen patients participated and had a baseline 4-hour meal tolerance test and a frequently sampled intravenous glucose tolerance test, before and after 4 weeks of glucosamine sulfate treatment (500 mg orally 3 times daily). After 4 weeks they found no change in fasting plasma glucose, insulin, glucose tolerance, or difference in insulin sensitivity in the group of subjects.7 The study was limited by a small subject number and short duration of study." }, { "input": "Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance.", "output": "One double-blinded RCT evaluated whether oral glucosamine supplementation altered glycosylated hemoglobin (HbA1c) concentrations for patients with well-controlled diabetes mellitus. Thirty-eight patients were randomized to receive either treatment with glucosamine/chondroitin at the recommended doses or placebo. After 3 months of treatment HbA1c levels did not change and were not significantly different between groups (P=.2)." }, { "input": "Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance.", "output": "An RCT published in 2004 tested whether glucose intolerance occurs when healthy adults consume normal, recommended dosages of glucosamine sulfate. Nineteen healthy adults were randomized to receive either 1500 mg of glucosamine sulfate or placebo orally each day for 12 weeks. Three-hour oral glucose tolerance tests were performed using 75 g of dextrose. These occurred before the study, at 6 weeks, and at 12 weeks. There were no significant differences between fasting levels of serum insulin or blood glucose. Glucosamine sulfate supplementation did not alter serum insulin or plasma glucose during the tests. Limitations to the study include the small number of subjects, the short duration period, and the fact that the tests were performed before the patient's daily glucosamine dosing." }, { "input": "Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance.", "output": "A Cochrane systematic review of 20 randomized controlled trials (RCTs) including 2570 patients in order to evaluate the effectiveness and toxicity of glucosamine in osteoarthritis found that glucosamine was as safe as placebo in terms of adverse reactions. However, they did not comment specifically on diabetic patients or hyperglycemia per se." }, { "input": "Some preliminary evidence suggests that glucosamine may worsen glucose intolerance for patients with untreated or undiagnosed glucose intolerance or diabetes.", "output": "A recent study examined insulin and glucose levels with and without the simultaneous ingestion of 1500 mg of glucosamine. Sixteen fasting volunteers with osteoarthritis but without known diabetes or glucose intolerance received 7 g of glucose with or without ingestion of 1500 mg glucosamine sulfate. The authors unexpectedly uncovered undiagnosed diabetes or impaired glucose tolerance in 3 subjects. These 3 subjects showed a statistically significant (P=.04) 31% increase in the area under the curve of glucose levels following the test. There was no effect of glucosamine sulfate ingestion on patients with normal baseline glucose testing or on insulin levels. Their results might be important since they are the first to suggest that glucosamine ingestion may affect glucose levels in individuals who have untreated diabetes or glucose intolerance." }, { "input": "Inhaled short-acting beta-agonists (SABAs) are most effective in preventing exercise-induced bronchoconstriction, followed by inhaled mast cell stabilizers and anticholinergic agents.", "output": "Therapies awaiting further study include a combination of budesonide (Pulmicort) and formoterol (Foradil), which is similar to the currently available preparation of fluticasone and salmeterol (Advair Diskus) but contains a long-acting beta-agonist with quicker onset. The phosphodiesterase-4 inhibitors roflumilast (Daxas) and cilomilast (Ariflo)-neither of which have been FDA-approved-and inhaled low-molecular-weight heparin have potential efficacy." }, { "input": "Inhaled short-acting beta-agonists (SABAs) are most effective in preventing exercise-induced bronchoconstriction, followed by inhaled mast cell stabilizers and anticholinergic agents.", "output": "A systematic review of 24 RCTs (of which 13 evaluated children) showed that SABAs, mast cell stabilizers, and anticholinergics provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects (the child subgroup analyses did not differ significantly from pooled results). Mast cell stabilizers were found less effective at attenuating bronchoconstriction than SABAs, with an average maximum decrease in the forced expiratory volume in 1 second (FEV1) of 11.9% compared with 4.6% for beta-agonists (child subgroup: weighted mean difference=7.3%; 95% confidence interval [CI], 3.9-10.7). Complete protection (defined in this study as maximum % decrease in FEV1 <15% post-exercise) and clinical protection (50% improvement over placebo) measures were included. Fewer children had complete protection (pooled: 66% vs 85%, odds ratio [OR]=0.3; 95% CI, 0.2-0.5) or clinical protection (pooled: 55% vs 77%, OR=0.4; 95% CI, 0.2-0.8). Mast cell stabilizers were more effective than anticholinergic agents, with average maximum FEV1 decrease of 9.4% compared with 16.0% on anticholinergics (child subgroup: weighted mean difference=6.6%; 95% CI, 1.0-12.2). They also provided more individuals with complete protection (pooled: 73% vs 56%, OR=2.2; 95% CI, 1.3-3.7) and clinical protection (pooled: 73% vs 52%, OR=2.7; 95% CI, 1.1-6.4). Combining mast cell stabilizers with SABAs did not produce significant advantages in pulmonary function over SABAs alone. No significant subgroup differences were seen based on age, severity, or study quality." }, { "input": "Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination.", "output": "A systematic review of 20 RCTs (15 studying children and 5 studying adults) with patients aged >6 years showed that 4 mg of nedocromil (Tilade) inhaled 15 to 60 minutes before exercise significantly reduced the severity and duration of exercise-induced bronchoconstriction compared with placebo. It had a greater effect on patients with severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function >30% from baseline)." }, { "input": "Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination.", "output": "Eight RCTs (5 studying children) were included in a systematic review of patients aged >6 years that found no significant difference between nedocromil and cromoglycate with regards to decrease in FEV1, complete protection, clinical protection, or side effects." }, { "input": "Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination.", "output": "Leukotriene antagonists have been recommended on a trial basis with follow-up to evaluate the treatment response." }, { "input": "Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination.", "output": "A recent study assessed the effects of montelukast (Singulair) on 64 children with exercise-induced bronchoconstriction. After 8 weeks of treatment, the montelukast group showed significant improvements (compared with placebo) in asthma symptom scores (24.3\u00b18.2 before vs 17.8\u00b16.8 after 8 weeks of montelukast treatment, P<.05; vs 17.7\u00b16.7 8 weeks after stopping treatment, P<.05), maximum percent fall in FEV1 after exercise (36.5\u00b110.2% before vs 27.6\u00b114.4% after 8 wks of treatment, P<.01; vs 26.7\u00b119.4% 8 weeks after stopping treatment, P<.01), and time to recovery (41.8\u00b18.1 min before vs 25.3\u00b123.3 min after 8 weeks of treatment, P<.01; vs 27.7\u00b126.5 min 8 weeks after stopping, P<.05)." }, { "input": "Underlying asthma, which commonly contributes to exercise-induced bronchoconstriction, should be diagnosed and controlled first.", "output": "The National Asthma Education and Prevention Program recommends prevention of exercise-induced bronchoconstriction by optimally controlling underlying asthma. If a patient remains symptomatic during exercise, you should review medication usage, understanding of dosage instructions, and administration technique before any changes in the treatment regimen." }, { "input": "Good evidence supports fecal occult blood testing (FOBT) for patients up to age 75.", "output": "One case control study of FOBT showed a significant reduction in risk of mortality from CRC for individuals younger than 75 years, but not for patients older than 75; however, confidence intervals were wide." }, { "input": "Good evidence supports fecal occult blood testing (FOBT) for patients up to age 75.", "output": "The upper age limits of patients was 74." }, { "input": "Good evidence supports fecal occult blood testing (FOBT) for patients up to age 75.", "output": "The upper age limits of patients was 64." }, { "input": "Good evidence supports fecal occult blood testing (FOBT) for patients up to age 75.", "output": "The upper age limits of patients was 75." }, { "input": "There is insufficient evidence to recommend for or against colorectal cancer (CRC) screening after age 75.", "output": "The upper age limits of patients was 80. In the study that included subjects to age 80, only 13% were older than 70 years." }, { "input": "CRC screening may be discontinued between ages 75 and 80, preferably after at least 1 negative screening examination result. Unusually healthy individuals may choose to continue screening until a later age.", "output": "Average time from onset of polyp to carcinoma is 10 to 15 years." }, { "input": "CRC screening may be discontinued between ages 75 and 80, preferably after at least 1 negative screening examination result. Unusually healthy individuals may choose to continue screening until a later age.", "output": "The average life expectancy is 11.2 years at age 75 and 8.5 years at age 80. Given the slow progression from polyp to carcinoma, such patients may not live long enough to achieve any screening benefits. Similar reasoning suggests that even high-risk patients (eg, those with a family history of CRC) with repeatedly normal endoscopic examination results may be able to discontinue screening between ages 75 and 80, unless they are unusually healthy." }, { "input": "For larger trunk varicose veins, as in the saphenous vein, therapeutic options include conservative measures (such as leg elevation and compression stockings), injection sclerotherapy, and surgical vein ligation, with or without stripping. Long-term outcomes appear superior with surgical treatment.", "output": "Beresford and colleagues also concluded that surgery lessened the likelihood of additional treatment." }, { "input": "For larger trunk varicose veins, as in the saphenous vein, therapeutic options include conservative measures (such as leg elevation and compression stockings), injection sclerotherapy, and surgical vein ligation, with or without stripping. Long-term outcomes appear superior with surgical treatment.", "output": "Belcaro reported results of a 10-year randomized trial including 121 subjects, 96 of whom completed the study. Surgery consisted of ligation of the saphenopopliteal junction without stripping. At 10 years, 16.1% of patients receiving surgery plus sclerotherapy had distal venous incompetence (assessed with color duplex scanning and ambulatory venous pressure measurement), compared with 36.4% of those who underwent surgery alone and 43.8% of those who received sclerotherapy alone. The authors concluded that long-term outcomes (defined as saphenofemoral junction competence) are superior with strategies that included surgery, but at greater cost." }, { "input": "For larger trunk varicose veins, as in the saphenous vein, therapeutic options include conservative measures (such as leg elevation and compression stockings), injection sclerotherapy, and surgical vein ligation, with or without stripping. Long-term outcomes appear superior with surgical treatment.", "output": "Graduated elastic compression stockings improve lower-extremity hemodynamics (including reflux and residual volume measured by color flow duplex scanning) in patients with varicosities, and can improve symptoms such as swelling, discomfort, and leg tightness." }, { "input": "For larger trunk varicose veins, as in the saphenous vein, therapeutic options include conservative measures (such as leg elevation and compression stockings), injection sclerotherapy, and surgical vein ligation, with or without stripping. Long-term outcomes appear superior with surgical treatment.", "output": "A randomized trial showed that saphenous vein stripping reduced by two thirds the need for reoperation due to recurrent saphenofemoral incompetence, compared with saphenofemoral junction ligation alone." }, { "input": "For mid-sized reticular veins and spider telangiectasias, several options are available, including sclerotherapy, laser ablation, and thermal ablation. However, no randomized trials have compared the relative effectiveness of these treatments.", "output": "A Cochrane review concluded that existing evidence supports the use of sclerotherapy for recurrent varicose veins after surgery and for relatively minor \"thread\" veins. Data did not show that any particular type of sclerosant or pressure dressing or duration of post-treatment compression have significant effect on outcomes, such as disappearance of varicosities and cosmetic improvement." }, { "input": "For mid-sized reticular veins and spider telangiectasias, several options are available, including sclerotherapy, laser ablation, and thermal ablation. However, no randomized trials have compared the relative effectiveness of these treatments.", "output": "A Cochrane protocol is in progress regarding comparison of the outcomes of surgery and sclerotherapy." }, { "input": "Venotonic medications (primarily plantderived and synthetic flavonoids, such as horse chestnut seed extract, that improve venous tone) provide symptom relief. Head-to-head comparisons are needed to identify the most efficacious therapies.", "output": "A meta-analysis studied the effectiveness of venotonic medications (such as rutoside, flunarizine, and dihydroergotamine) in chronic venous insufficiency. These agents significantly reduced pain, leg heaviness, cramps, and paresthesias. However, a Cochrane Collaboration reviewer questioned the validity of pooling results from this heterogeneous group of studies into a single meta-analysis." }, { "input": "Venotonic medications (primarily plantderived and synthetic flavonoids, such as horse chestnut seed extract, that improve venous tone) provide symptom relief. Head-to-head comparisons are needed to identify the most efficacious therapies.", "output": "A Cochrane Review did find that horse chestnut seed extract significantly improves leg pain, edema, pruritus, and lower leg volume and circumference, but suggests that larger randomized trials are needed to establish conclusively this agent's efficacy." }, { "input": "Osteoporosis is common, and its prevalence increases with age.", "output": "In a prospective observational study of women over 50 years of age, 39.6% had osteopenia and 7.2% had osteoporosis. Osteoporosis was associated with a fracture rate 4 times that of normal bone mineral density." }, { "input": "Osteoporosis is common, and its prevalence increases with age.", "output": "For women aged >65 years with no other risks, 12% to 28% have osteoporosis." }, { "input": "Low bone mineral density predicts fracture risk.", "output": "In a prospective observational study of women over 50 years of age, 39.6% had osteopenia and 7.2% had osteoporosis. Osteoporosis was associated with a fracture rate 4 times that of normal bone mineral density." }, { "input": "Low bone mineral density predicts fracture risk.", "output": "A meta-analysis of 11 prospective cohort trials showed that all sites of bone mineral density measurements correlated with fractures (relative risk [RR], 1.5; 95% confi-dence interval [CI], 1.4-1.6.). However, DEXA of the femoral neck predicted hip fracture better than other measures (RR, 2.6; 95% CI, 2.0-3.5)." }, { "input": "The likelihood of osteoporotic fracture is reduced with therapy, such as alendronate 10 mg/day or risedronate 5 mg/day plus adequate daily calcium and vitamin D.", "output": "A meta-analysis of 11 randomized controlled trials including 11,808 women found fewer hip fractures in women taking 10 mg/day of alendronate (RR, 0.51; 95% CI, 0.38-0.69; number needed to treat [NNT]=24), and fewer vertebral fractures in women taking 5 mg/day of alendronate (RR, 0.52; 95% CI, 0.43-0.65; NNT=72)." }, { "input": "Women under 60 years should not be screened.", "output": "In 1998, the National Osteoporosis Foundation, in collaboration with many other professional organ-izations, recommended bone mineral density test-ing for all women aged >65 years and younger postmenopausal women who have had or are at risk for fractures." }, { "input": "Women under 60 years should not be screened.", "output": "Based on their outcomes model, the US Preventive Services Task Force recommends screening for women aged >65 years, and those aged 60 to 65 years who have risk factors." }, { "input": "Most meta-analyses show a modest, short-term reduction in effusion rates. However, the most rigorous meta-analysis shows no benefit.", "output": "Conflicting evidence indicates short-term or no benefit for antibiotics, and complications such as nausea, vomiting, diarrhea, and rash have been reported in 2%-32% of children. Long-term antibiotics lead to poor adherence, more office visits, and antibiotic resistance." }, { "input": "No significant effect was noted on longer-term (>1 month) outcomes after treatment.", "output": "Longitudinal studies show spontaneous resolution in more than half of children within 3 months of the development of the effusion. After 3 months, the rate of spontaneous resolution remains constant, so that only a small percentage of children have OME a year or longer. There is a theoretical basis for the use of antibiotics for OME, since between 27%-50% of middle-ear aspirates of patients with OME contain bacteria." }, { "input": "No significant effect was noted on longer-term (>1 month) outcomes after treatment.", "output": "A meta-analysis that restricted inclusion to only randomized, blinded, placebo-controlled trials. The small difference reported (4%) was not significant. None of the studies that assessed outcomes beyond a month showed a significant difference in the persistence of OME. The meta-analyses vary significantly in methodology, inclusion/exclusion criteria, and interpretation, making a definitive conclusion on treatment results difficult. The included trials varied in antibiotics chosen, use of placebo, duration of therapy, time to measurement of OME resolution, and method of diagnosis (tympanography, otoscopy, audiometry)." }, { "input": "There is no compelling evidence that outpatient diagnostic workup of patients with transient ischemic attack (TIA) is less safe than inpatient workup, or that hospitalization prevents stroke or improves stroke outcomes after TIA.", "output": "In a retrospective case review of TIA and stroke patients, the hospital admissions of 4 of 21 TIA patients were retrospectively categorized as medically justified. Admission was categorized as medically justified if the patient had 1 or more of the following criteria: another diagnosis that warranted admission, inadequate home situation, altered mental status, an adverse event during hospitalization including worsening of the deficit, and if the patient underwent some hospital-based treatment that could not be provided on an out-patient basis. Ease and rapidity of evaluation was not considered medically justifiable and outcome improvement (stroke prevention) was not studied." }, { "input": "Because the risk of stroke is substantial in the week following a TIA.", "output": "A large prospective cohort study recently estimated the risk of stroke after a TIA or minor stroke to be 8% to 12% at 7 days and 11% to 15% at 1 month." }, { "input": "Evaluation and treatment for reversible stroke risk factors should be initiated urgently and completed within a week of initial presentation.", "output": "The AHA recommends that the diagnostic evaluation of patients seen within 7 days of a TIA should be completed within 1 week or less. The AHA leaves the decision whether to hospitalize a patient up to the physician based on a patient's circumstances. The goals of diagnostic testing are to identify or exclude causes of TIA requiring specific therapy, to assess modifiable risk factors, and to determine prognosis." }, { "input": "Risk factors for patients at highest risk for stroke or other cardiovascular events after TIA include age >60 years, diabetes, TIA lasting longer than 10 minutes, and a TIA associated with weakness or speech impairment,", "output": "In a large retrospective cohort study, 5% of TIA patients returned to the emergency department with a stroke within the first 2 days after TIA. Another 6% returned with a stroke within 90 days. Five independent risk factors were identified: age >60 years, diabetes mellitus, duration of TIA longer than 10 minutes, signs or symptoms of weakness, and speech impairment. Thirty-four percent of patients with all 5 risk factors, and none of the patients without any risk factors, had a stroke within 90 days. Of note, 13% of the TIA patients had an arrhythmia, congestive heart failure, unstable angina, myocardial infarction, stroke, or recurrent TIA within 4 days of initial presenting with a TIA. Twenty-five percent of the patients experienced 1 of these cardiovascular events during the 3 months of follow-up." }, { "input": "Hospitalization may be prudent for patients at high risk for cardiovascular events or for those with mental status changes, an inadequate home situation, or the physician's inability to obtain expedient evaluation,", "output": "In a retrospective case review of TIA and stroke patients, the hospital admissions of 4 of 21 TIA patients were retrospectively categorized as medically justified. Admission was categorized as medically justified if the patient had 1 or more of the following criteria: another diagnosis that warranted admission, inadequate home situation, altered mental status, an adverse event during hospitalization including worsening of the deficit, and if the patient underwent some hospital-based treatment that could not be provided on an out-patient basis. Ease and rapidity of evaluation was not considered medically justifiable and outcome improvement (stroke prevention) was not studied." }, { "input": "other", "output": "Transient ischemic attack is a temporary, focal brain or retinal deficit caused by vascular disease that clears completely in less than 24 hours." }, { "input": "other", "output": "In 1 study of TIA patients presenting to an emergency department, 81% had a computed tomography scan, 75% had electrocardiogram, and 74% had a complete blood count. Carotid Doppler imaging was performed in the emergency department in 16%, and 26% were referred for outpatient Doppler studies. One percent had an ECG in the emergency department, and 16% were given ECGs as outpatients. Seventy-five percent of patients were discharged home. Those hospitalized had a median length of stay of 1 day." }, { "input": "other", "output": "In a study, 31% of the TIA patients had no diagnostic studies performed during the first month after presenting to their primary care physician." }, { "input": "There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration.", "output": "The Air Force/Texas Coronary Atherosclerosis Prevention Study was the only primary prevention randomized controlled trial that titrated the dose of medication (either 20 mg or 40 mg of lovastatin daily) to reach a LDL-C of 110 mg/dL2 or lower. Titration was done after 3 months of therapy." }, { "input": "There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration.", "output": "The Munster Heart Study (PROCAM) demonstrated that \"the ranking of continuous risk factors in terms of predicting major coronary events was LDL-C, total cholesterol (TC), high-density lipoprotein (HDL-C), triglycerides (TG)....\"" }, { "input": "There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration.", "output": "Grover and colleagues found that the TC/HDL-C and the LDL-C/HDL-C ratios both performed better than the TC in predicting heart disease mortality." }, { "input": "There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration.", "output": "The Framingham Study confirmed the usefulness of TC and HDL-C in assessing risk." }, { "input": "There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration.", "output": "The National Cholesterol Education Program (NCEP) recommends that LDL-C be monitored every 6 weeks after the initiation of treatment. After the goal LDL-C is attained, measurement every 4 to 6 months is adequate." }, { "input": "Therapy with interferon and ribavirin (dual therapy) has been shown in randomized placebo-controlled trials to lead to sustained viral response in 30% to 50% of patients compared with 6% to 21% with PEG-interferon alpha-2b (Viraferson PEG) therapy only. Evidence is lacking on the optimum monitoring approach for patients taking dual therapy.", "output": "Long-term sustained viral response was at least 50% at 2 years after dual therapy. Long-term response rates have been 30% with dual therapy in genotype 1 and 60% to 70% with genotypes 2 through 6." }, { "input": "Therapy with interferon and ribavirin (dual therapy) has been shown in randomized placebo-controlled trials to lead to sustained viral response in 30% to 50% of patients compared with 6% to 21% with PEG-interferon alpha-2b (Viraferson PEG) therapy only. Evidence is lacking on the optimum monitoring approach for patients taking dual therapy.", "output": "The safety profiles for dual therapy and monotherapy are similar." }, { "input": "Therapy with interferon and ribavirin (dual therapy) has been shown in randomized placebo-controlled trials to lead to sustained viral response in 30% to 50% of patients compared with 6% to 21% with PEG-interferon alpha-2b (Viraferson PEG) therapy only. Evidence is lacking on the optimum monitoring approach for patients taking dual therapy.", "output": "Discontinuation is greater for those taking dual therapy than taking monotherapy, more so with 48 weeks of therapy (20%) than with 24 weeks of therapy (9%)." }, { "input": "Therapy with interferon and ribavirin (dual therapy) has been shown in randomized placebo-controlled trials to lead to sustained viral response in 30% to 50% of patients compared with 6% to 21% with PEG-interferon alpha-2b (Viraferson PEG) therapy only. Evidence is lacking on the optimum monitoring approach for patients taking dual therapy.", "output": "Several randomized trials have shown that dual therapy with PEG-interferon alpha-2b (3 million units subcutaneously 3 times weekly) and ribavirin (1000 mg to 1200 mg orally each day) is at least twice as effective as interferon alone. The best results were seen in women who had a genotype other than 1, low viral loads, and absence of cirrhosis at the outset." }, { "input": "Findings consistent with CTS include a history of repetitive hand work, asymmetric paresthesias in the distribution of the median nerve, hypoalgesia, weak thumb abduction, or latency of nerve conduction studies. Tingling in the median nerve distribution or on the entire palmar surface also supports the diagnosis. Common conditions associated with CTS are pregnancy, obesity, and hypothyroidism.", "output": "A meta-analysis of studies reviewing the precision and accuracy of the history and physical examination in the diagnosis of CTS in adults found that hypoalgesia (LR+, 3.1), classic or probable hand diagram results (LR+ 2.4, LR- 0.2), and weak thumb abduction strength (weakness of resisted movement of the thumb at right angles to the palm; LR+ 1.8, LR- 0.5) best distinguish those with and those without CTS. A classical distribution is in that of the median nerve, while a probable distribution involves the entire palmar surface. The reference standard for these studies was a nerve conduction study. Nocturnal paresthesias, Phalen and Tinel signs, and thenar atrophy had little or no diagnostic utility." }, { "input": "Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability.", "output": "A retrospective chart review reported improved pain and decreased disability in patients with chronic low back pain after 6 weeks of exercise." }, { "input": "Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability.", "output": "A RCT showed that a progressive intervention program that included cognitive behavioral management was more effective than exercise alone to decrease pain and self-reported disability." }, { "input": "Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability.", "output": "A review reported that exercise, back manipulation, and intense back schools were equally efficacious." }, { "input": "Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability.", "output": "A 1996 review of 13 RCTs examining specific types of exercises found that both intensive dynamic extension exercises and mild isometric flexion and extension exercises were more effective than placebo. Although the intensive exercises were more efficacious than normal exercises at the 3-month follow-up, they were equally efficacious at 12 months. Evidence was conflicting in a comparison of flexion and extension exercises." }, { "input": "Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability.", "output": "A meta-analysis was conducted in 2000, since the quality of original studies had improved a great deal during the intervening decade. This analysis showed strong evidence favoring exercise over \"usual care\" by primary care physicians (medications and resumption of usual activities). Exercise was found equally efficacious as conventional physiotherapy. Evidence was conflicting in a comparison of exercise with inactive treatment (ice or heat packs, rest). None of the studies showed a particular exercise format as superior. The included studies included a wide variety of structured exercise programs. Exercise demonstrated no benefit in situations of acute back pain." }, { "input": "Exercise is more effective for chronic low back pain than treatment with medication plus return to usual activity and as effective as conventional physiotherapy. The evidence is less consistent in showing that any particular exercise format provides greater benefit or that exercise provides a long-term increase in function or a decrease in pain or disability.", "output": "The first meta-analysis of 16 chronic low back pain RCTs in 1991 had inconsistent results on the efficacy of exercise and showed little evidence in favor of any specific exercise format." }, { "input": "For acute Jones' fractures in recreationally active patients, early intramedullary screw fixation results in lower failure rates and shorter times to both clinical union and return to sports than non-weightbearing short leg casting.", "output": "37 active-duty military personnel with acute Jones' fractures were randomized to either 8 weeks of no weight-bearing in a short leg casting, followed by a walking cast or hard-soled shoe until clinical union; or to early outpatient intramedullary screw fixation followed by no weight-bearing for 2 weeks, then weight-bearing as tolerated in a hard-soled shoe until clinical union. Screw fixation significantly reduced both time to clinical union and time to return to sports-by nearly 50% when compared with non-weightbearing short leg casting. Furthermore, at 26 weeks the casting group saw a significant 44% failure rate compared with only 5% in the surgical group (number needed to treat [NNT]=2.6). Six patients in the surgical group had mild discomfort from the screw head, and 3 needed the screw to be removed. Generalization of the results was limited by the mostly male military population." }, { "input": "Non-weightbearing short leg casting achieves union in 56% to 100% of patients but can require prolonged casting.", "output": "The rates and times of union with short leg casting vary over a wide range in the research literature. The casting group in the RCT above had union rates of 56% and median time to union of 14.5 weeks (lower and upper quartile range, 10.5-18.5)." }, { "input": "Non-weightbearing short leg casting achieves union in 56% to 100% of patients but can require prolonged casting.", "output": "A prospective registry of 68 consecutive acute Jones' fractures in primarily young military service members showed a 72% union rate with non-weightbearing short leg casting with average time to union of 21.2 weeks." }, { "input": "Non-weightbearing short leg casting achieves union in 56% to 100% of patients but can require prolonged casting.", "output": "A heterogeneous group of 5 retrospective follow-up studies of short leg casting reported wide ranges in union rates of 72% to 100%, and in time to healing of 7 weeks to 21 months. These studies varied in average age, sex, and athletic ability of their samples as well as type of immobilization and weight-bearing status during treatment." }, { "input": "For avulsion fractures of the fifth metatarsal tuberosity, a soft Jones-dressing allows earlier return to pre-injury levels of activity than rigid short leg casting.", "output": "A 12-week RCT in 89 consecutive patients presenting to an emergency department with fifth metatarsal tuberosity avulsion fractures compared a nonrigid, soft Jones' dressing consisting of alternating layers of cast padding and elastic bandages with a rigid short leg casting. The Jones' dressing had a significant 28% reduction in time to return to pre-injury levels of activity. Other outcomes-time in treatment modality, time to radiographic healing, and functional foot score-were not different between intervention groups. Validity was limited by the 32% lost to follow-up rate." }, { "input": "other", "output": "DeLee and Drez's Orthopaedic Sports Medicine recommends immobilization in a cast or below-the-knee boot with strict non-weightbearing for at least 6 weeks for acute Jones' fractures. It recommends surgical treatment, followed by 6 weeks of cast immobilization, then progression to weight bearing based on radiographic findings, for nonoperative treatment failures or with desire to return high-performance athletes to activity." }, { "input": "other", "output": "Tuberosity avulsion fractures are proximal fifth metatarsal styloid fractures resulting from a forceful pull of the lateral band of the long plantar ligament or the peroneus brevis tendon during ankle inversion. A 12-week RCT in 89 consecutive patients presenting to an emergency department with fifth metatarsal tuberosity avulsion fractures compared a nonrigid, soft Jones' dressing consisting of alternating layers of cast padding and elastic bandages with a rigid short leg casting. The Jones' dressing had a significant 28% reduction in time to return to pre-injury levels of activity. Other outcomes-time in treatment modality, time to radiographic healing, and functional foot score-were not different between intervention groups. Validity was limited by the 32% lost to follow-up rate." }, { "input": "other", "output": "In Fracture Management for Primary Care, the authors recommend posterior splinting and non-weightbearing with crutches for acute Jones' fractures, followed by non-weightbearing short leg casting application at 3 to 5 days from injury. After a minimum of 6 to 8 weeks of casting, they recommend options of 4 additional weeks of casting or internal fixation for clinical or radiographic nonunion." }, { "input": "Calcium, in combination with vitamin D, prevents bone loss and is recommended in all patients.", "output": "A systematic review of 5 RCTs (N=274) confirmed clinically and statistically significant prevention of bone loss at the lumbar spine for patients receiving glucocorticoids who also received calcium (500-1000 mg daily) and vitamin D (400-800 IU) daily." }, { "input": "Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months).", "output": "A two-year RCT of 208 patients receiving steroids who also received alendronate or placebo demonstrated an incidence of vertebral fracture of 0.7% and 6.8% (NNT=16; RRR=90%; ARR = 5.9%; P=.026), respectively." }, { "input": "Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months).", "output": "A 48-week RCT involving 477 patients receiving steroids who also received alendronate or placebo demonstrated a 2.3% and 3.7% in incidence of vertebral fracture, respectively (RRR = 38%; ARR = 1.4%; P= NS)." }, { "input": "Replacement of sex hormones for hypogonadal women prevents bone loss and increases bone mineral density (BMD).", "output": "In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3-4%; men 5%; all P<.05). Fracture reduction and risk of long-term use were not studied." }, { "input": "Replacement of sex hormones hypogonadal men prevents bone loss and increases bone mineral density (BMD).", "output": "In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3-4%; men 5%; all P<.05). Fracture reduction and risk of long-term use were not studied." }, { "input": "Calcitonin prevents bone loss for up to 1 year.", "output": "In a systematic review of 9 RCTs, including 441 patients, calcitonin preserved bone mass in the lumbar spine but not the femoral neck during the first year of steroid therapy. Lumbar spine BMD values with calcitonin were significantly higher than with placebo at 6 and 12 months, but were similar at 24 months." }, { "input": "Urodynamic testing is indicated for older adults with incontinence when the underlying cause remains unclear.", "output": "Two RCTs suggest that, despite the wide use of urodynamic testing, reproducibility is limited and may lack sufficient sensitivity and specificity to identify underlying pathology. Specific concerns raised in these studies included test-retest variation, as well as concerns about possible interpretation error of urodynamic testing." }, { "input": "Urodynamic testing is indicated for older adults with incontinence when the underlying cause remains unclear.", "output": "A recent small RCT (n=87) found that, of patients with previous genitourinary surgery or more severe stress incontinence, about one quarter were more likely to have their management revised after urodynamic studies. Patients who demonstrated little or no improvement during the first few months of conservative treatment also ran a higher risk of misdiagnosis. Despite these findings, no difference in treatment outcomes was detected for women randomized to urodynamic testing." }, { "input": "Urodynamic testing is indicated for older adults with incontinence when the underlying cause remains unclear.", "output": "One well designed retrospective cohort study of 950 women found that the positive predictive value of clinical symptoms in urinary incontinence alone (74% in the context of a 53% prevalence of incontinence) was not accurate enough to rely on for decisions about surgery. This study supports the need for urodynamic evaluation in most women prior to surgical incontinence treatment." }, { "input": "Simple cystometry-specifically, measuring post void residual and bladder capacity-is helpful in the evaluation of urinary incontinence when the cause has remained unclear. It may also offer benefit when surgery is under consideration, when there is a history of genitourinary surgery, or when a conservative therapeutic trial has not had an adequate response.", "output": "Simple cystometry, (measuring post-void residuals and determining bladder capacity), has proved particularly useful in detecting abnormalities of detrusor compliance and contractility, especially when the cause of incontinence is unclear." }, { "input": "Oral metronidazole and oral vancomycin are equally effective treatments for Clostridium difficile-associated diarrhea (CDAD).", "output": "No published data exist indicating that vancomycin is more effective than metronidazole in any clinical setting. A dose-range study showed that 125 mg of oral vancomycin 4 times a day is as effective as higher doses." }, { "input": "Oral metronidazole and oral vancomycin are equally effective treatments for Clostridium difficile-associated diarrhea (CDAD).", "output": "Two randomized controlled trials have compared the efficacy of oral metronidazole and oral vancomycin for treatment of CDAD. Both studies demonstrated statistically equivalent cure rates exceeding 90%, with relapse rates of 10% to 20% for each drug. These small trials lacked the power to detect small but potentially significant differences in treatment response." }, { "input": "Oral vancomycin is considerably more expensive and may select for colonization with vancomycin-resistant enterococci, leading the American College of Gastroenterology to recommend oral metronidazole as preferred therapy. They recommend therapy with vancomycin for those who are pregnant, breast feeding, less than 10 years old, nonresponders to metronidazole, critically ill, or allergic or intolerant to metronidazole.", "output": "Patients who cannot take medication by mouth should receive intravenous metronidazole, 500 mg 4 times per day. Unlike vancomycin, metronidazole achieves potentially effective concentrations in the intestinal lumen following intravenous administration." }, { "input": "Oral vancomycin is considerably more expensive and may select for colonization with vancomycin-resistant enterococci, leading the American College of Gastroenterology to recommend oral metronidazole as preferred therapy. They recommend therapy with vancomycin for those who are pregnant, breast feeding, less than 10 years old, nonresponders to metronidazole, critically ill, or allergic or intolerant to metronidazole.", "output": "The American College of Gastroenterology and the American College of Physicians treatment guidelines for CDAD both call for treatment with oral metronidazole 250 mg 4 times daily or 500 mg 3 times daily. The American College of Gastroenterology recommends vancomycin 125 mg orally 4 times daily when there is an intolerance or confirmed resistance to metronidazole, failure of response, when the patient is pregnant, breast feeding, or under 10 years of age, critically ill from colitis, or when the diarrhea could be related to Staphylococcus aureus. In milder cases, treatment may involve only discontinuation of antibiotics and supportive therapy with observation. Opiates and antispasmodics should be avoided. These guidelines do not recommend any treatment over another for therapy of multiple recurrences." }, { "input": "Treat first recurrences the same as primary infection. In persons with recurrent infection, addition of the probiotic agent Saccharomyces boulardii. reduces the risk of further recurrences.", "output": "Treatment of first recurrences of infection with metronidazole or vancomycin produces response rates similar to treatment of initial infections. A minority of patients suffers multiple relapses of infection, and there are few data to guide therapy in this setting." }, { "input": "Treat first recurrences the same as primary infection. In persons with recurrent infection, addition of the probiotic agent Saccharomyces boulardii. reduces the risk of further recurrences.", "output": "A randomized, double-blinded, placebocontrolled study evaluated the impact of adding the probiotic agent Saccharomyces boulardii. to either metronidazole or vancomycin. For persons with recurrent infection, addition of S boulardii. led to a 30% decrease in the absolute risk of relapse (64% relapse vs 34%; number needed to treat=3; P.<.05). There was also a nonsignificant trend toward reduced recurrences in the treatment of primary infections. The 2 minor side effects noted with this treatment were dry mouth (number needed to harm [NNH]=11) and constipation (NNH=9). S boulardii. capsules are available from health food stores and via the Internet. Several published case series describe various additional approaches to therapy of recurrent CDAD." }, { "input": "Medical conditions putting persons at high risk for hypomagnesemia are alcoholism, congestive heart failure, diabetes, chronic diarrhea, hypokalemia, hypocalcemia, and malnutrition.", "output": "In a group of 5100 consecutive patients (predominantly outpatient, middle-aged, and female) presenting to a diagnostic lab, the most common diagnoses associated with hypomagnesemia were diabetes (20% of cases) and diuretic use (14% of cases); however, other potential causes, including alcoholism, were not identified." }, { "input": "Medical conditions putting persons at high risk for hypomagnesemia are alcoholism, congestive heart failure, diabetes, chronic diarrhea, hypokalemia, hypocalcemia, and malnutrition.", "output": "Diseases associated with a high prevalence of hypomagnesemia include cardiovascular disease (hypertension, congestive heart failure, coronary artery disease), diabetes, diarrhea, diuretics use, hypokalemia, hypocalcemia, and malabsorption" }, { "input": "Evidence suggests that magnesium deficiency is both more common and more clinically significant than generally appreciated.", "output": "Estimates of the prevalence of hypomagnesemia in the general population range from 2.5% to 15%. A study of 11,000 white urban Americans aged 45 to 64 years (probability sampling) found 2.5% with magnesium <0.7 mmol/L and 5% with magnesium <0.75 mmol/L; rates for 4000 African Americans were twice as high" }, { "input": "Well-child visits are the appropriate time to screen all children for a history of snoring and apnea.", "output": "Experts advise screening all children for obstructive sleep apnea by asking about snoring and sleep apnea at routine health supervision visits." }, { "input": "Children should be further evaluated for obstructive sleep apnea if parents note habitual nightly snoring, especially if accompanied by pauses, snorts, or gasps. Single overnight polysomnography is the test of choice to evaluate a child for obstructive sleep apnea, since it can't be excluded by history or physical exam.", "output": "A prospective case-series of 62 consecutive children referred to a sleep clinic for suspected obstructive sleep apnea correlated nightly snoring (relative risk [RR]=10.67; 95% confidence interval [CI], 2.72-41.8) and observed apnea (RR=3.43; 95% CI, 1.42-6.76) with obstructive sleep apnea diagnosed by polysomnography." }, { "input": "Children should be further evaluated for obstructive sleep apnea if parents note habitual nightly snoring, especially if accompanied by pauses, snorts, or gasps. Single overnight polysomnography is the test of choice to evaluate a child for obstructive sleep apnea, since it can't be excluded by history or physical exam.", "output": "A retrospective, nonconsecutive cohort study of 50 children previously diagnosed with obstructive sleep apnea found that all presented with \"continuous heavy snoring, interrupted by pauses and associated with snorts\"." }, { "input": "Children should be further evaluated for obstructive sleep apnea if parents note habitual nightly snoring, especially if accompanied by pauses, snorts, or gasps. Single overnight polysomnography is the test of choice to evaluate a child for obstructive sleep apnea, since it can't be excluded by history or physical exam.", "output": "A systematic review of 12 studies including 1058 children under age 18 compared evaluation by polysomnography with clinical evaluation by history and physical examination alone. Clinical evaluation had a positive predictive value (PPV) of 55.8% (95% CI, 42.1%-69.6%); no single component demonstrated sensitivity and specificity more than 65%." }, { "input": "Children should be further evaluated for obstructive sleep apnea if parents note habitual nightly snoring, especially if accompanied by pauses, snorts, or gasps. Single overnight polysomnography is the test of choice to evaluate a child for obstructive sleep apnea, since it can't be excluded by history or physical exam.", "output": "Experts consider overnight polysomnography to be the gold standard test for obstructive sleep apnea. Physical examination alone usually has normal results." }, { "input": "Children should be further evaluated for obstructive sleep apnea if parents note habitual nightly snoring, especially if accompanied by pauses, snorts, or gasps. Single overnight polysomnography is the test of choice to evaluate a child for obstructive sleep apnea, since it can't be excluded by history or physical exam.", "output": "A study recruited 70 consecutive children (ages 2 to 17 years) from a sleep lab and performed polysomnography on 2 consecutive nights. The first test correctly identified obstructive sleep apnea in 64 children; the second identified 6 additional cases, all of which were \"mild\"." }, { "input": "Other evaluation methods for sleep apnea lack either adequate sensitivity or specificity.", "output": "An investigator-blinded RCT, scored 20-minute recordings of \"worst breathing\" in 59 consecutive children referred for snoring or nocturnal breathing problems, 47% of whom had sleep apnea. Results: PPV=62%, NPV=83%, sensitivity=88%, specificity=52%." }, { "input": "Other evaluation methods for sleep apnea lack either adequate sensitivity or specificity.", "output": "A retrospective, cross-sectional study of 349 children between the ages of 6 months and 18 years determined that abnormal home pulse oximetry studies were highly predictive of obstructive sleep apnea on polysomnography (positive likelihood ratio [LR+]=19.4; CIs not given; posttest probability=97%), but that inconclusive or normal pulse oximetry studies were not predictive of negative polysomnographies (LR+=0.58; CIs not given; posttest probability 47%). Children had been referred for suspected obstructive sleep apnea, and the pretest probability was 60%. Oximetry records were evaluated by a sleep laboratory physician blinded to clinical and polysomnography data." }, { "input": "Other evaluation methods for sleep apnea lack either adequate sensitivity or specificity.", "output": "A prospective cohort study of home sleep video recordings included 58 consecutive children who were 2 to 6 years of age with snoring or labored breathing during sleep. Parents filmed 30 minutes of sleep during \"worst breathing\" episodes. An expert investigator evaluated the recordings using both a standardized scoring system and subjective impression, and compared these with overnight polysomnography results, finding 94% sensitivity and 68% specificity." }, { "input": "Other evaluation methods for sleep apnea lack either adequate sensitivity or specificity.", "output": "A retrospective chart review included 143 children between 1 and 18 years of age with adenotonsillar hypertrophy referred for overnight polysomnography after normal or mildly abnormal \"nap polysomnography.\" Mildly abnormal nap polysomnography predicted abnormal overnight polysomnography (PPV=77%; P<.0001), but normal nap polysomnography were not predictive of normal overnight polysomnography (NPV=49%; P=.8)." }, { "input": "Other evaluation methods for sleep apnea lack either adequate sensitivity or specificity.", "output": "A prospective cohort study of 35 children compared the tonsillar-pharyngeal ratio measured from lateral neck x-rays to overnight polysomnography. X-ray measurements predicted moderate or severe obstructive sleep apnea on polysomnography (sensitivity=96%, specificity=82%, PPV=92%, NPV=90%), but did not accurately differentiate normal children from those with mild obstructive sleep apnea." }, { "input": "Moderate exercise reduces mortality for patients with known coronary heart disease but does not significantly decrease the risk of recurrent nonfatal myocardial infarction (MI).", "output": "Six studies showed particularly significant improvement in total cardiac mortality. Exercise was variably defined. Training sessions lasted 30 minutes and occurred on 2 to 5 days per week. Intensity was typically 75% to 85% of a maximum work capacity determined on an exercise test before initiating the training sessions. The type of exercise ranged from cycling alone to circuit training with 6 stationary devices. Patients were trained with supervision 1 to 36 months and followed for a mean of 24 months (range, 6-60 months). A trend was observed toward decreased recurrence of nonfatal MI with exercise-based cardiac rehabilitation, which did not reach significance (RR=0.78; 95% CI, 0.59-1.03). An inadequate number of subjects is the most likely reason; however, other possibilities include an increase in the frequency of nonfatal MI after rehabilitation, or an increased rate of survival after MI for patients undergoing exercise-based rehabilitation. The studies included in these reviews had several limitations. The population appears skewed in age (mean=54 years, with patients aged >65 years excluded from most studies) and gender (4.9% female); ethnicity was rarely reported. The adequacy of randomization was poor or unclear in 71% of studies, and only 4 trials reported blind assessment of outcomes. Finally, in 34% of studies the loss of participants to follow-up was more than 20%." }, { "input": "Exercise-based cardiac rehabilitation reduces all-cause mortality", "output": "A systematic review of cardiac rehabilitation programs evaluated 14 randomized controlled trials with exercise-based interventions. An updated review added 5 more for a total of 2984 patients with coronary heart disease. Patients with coronary heart disease comprised those with prior MI, prior coronary artery bypass graft surgery, or PTCA, and those with angina pectoris and angiographically confirmed coronary heart disease. Exercise-based cardiac rehabilitation significantly reduced all-cause mortality (relative risk [RR]=0.76; 95% confidence interval [CI], 0.59-0.98) compared with usual care (NNT=66; 95% CI, 35-273). Cardiac mortality also decreased significantly with exercise (RR=0.73; 95% CI, 0.56-0.96) compared with usual care (NNT=49; 95% CI, 26-120)." }, { "input": "For patients with stable angina, a daily exercise program is more effective than percutaneous transluminal coronary angioplasty (PTCA) with stenting in preventing major cardiovascular events (number needed to treat [NNT]=5.5).", "output": "A well-done study randomized 101 male patients (age <70 years) with stable angina to either a daily exercise program or standard PTCA with stenting. After 12 months, event-free survival was significantly greater among patients randomized to exercise than in those randomized to PTCA with stenting (88% vs 70%; P=.023; NNT=5.5). Cardiovascular events were defined as percutaneous interventions, hospitalizations, acute MI, cerebrovascular accidents, coronary artery bypass graft operation, and death." }, { "input": "Among antibiotics, only rifampin has been demonstrated to interfere with the effectiveness of oral contraceptives (OCs).", "output": "The MMWR Recommendations and Reports (2003) recommend that women of reproductive potential on OCs who are also taking rifampin should add a barrier method of contraception." }, { "input": "Among antibiotics, only rifampin has been demonstrated to interfere with the effectiveness of oral contraceptives (OCs).", "output": "Multiple studies have looked at OC serum levels with and without antibiotic treatment. These studies show that the coadministration of antibiotics (ampicillin, tetracycline, doxycycline, metronidazole, erythromycin, clarithromycin, temafloxacin, fluconazole, ciprofloxacin, or ofloxacin) did not reduce serum levels of either the estrogen or progestin components of the oral contraceptives." }, { "input": "Among antibiotics, only rifampin has been demonstrated to interfere with the effectiveness of oral contraceptives (OCs).", "output": "Multiple studies have looked at OC serum levels with and without antibiotic treatment. These studies show that the coadministration of antibiotics (ampicillin, tetracycline, doxycycline, metronidazole, erythromycin, clarithromycin, temafloxacin, fluconazole, ciprofloxacin, or ofloxacin) did not reduce serum levels of either the estrogen or progestin components of the oral contraceptives. Rifampin is a potent inducer of the cytochrome P450 system, capable of reducing serum estrogen and progestin levels, and a small-scale study has suggested breakthrough ovulation among 2 of 9 women taking oral contraceptives and rifampin." }, { "input": "There is little convincing evidence to show a systematic interaction between other antibiotics and oral contraceptive steroids.", "output": "More than 200 occurrences have been reported anecdotally, in adverse-event monitoring systems, and in retrospective surveys of OC failure for women treated with various antibiotics. But no prospective RCTs have been done, and most of the retrospective case series have not used control groups. All the pharmacokinetic and retrospective studies have a small sample size, which may conceal an interaction within the normal OC failure rate. 4 retrospective surveys on women taking OCs who were treated with antibiotics (erythromycin, tetracycline, minocycline, penicillin, ampicillin, sulfa, cephalosporins) found OC failure rates of 1.2% to 1.6%, within the range for typical populations. Studies show that the coadministration of antibiotics (ampicillin, tetracycline, doxycycline, metronidazole, erythromycin, clarithromycin, temafloxacin, fluconazole, ciprofloxacin, or ofloxacin) did not reduce serum levels of either the estrogen or progestin components of the oral contraceptives." }, { "input": "There is little convincing evidence to show a systematic interaction between other antibiotics and oral contraceptive steroids.", "output": "Studies show that the coadministration of antibiotics (ampicillin, tetracycline, doxycycline, metronidazole, erythromycin, clarithromycin, temafloxacin, fluconazole, ciprofloxacin, or ofloxacin) did not reduce serum levels of either the estrogen or progestin components of the oral contraceptives." }, { "input": "There is little convincing evidence to show a systematic interaction between other antibiotics and oral contraceptive steroids.", "output": "Some antibiotics still have in their labeling that they may reduce the effectiveness of OCs, but that this is likely not true." }, { "input": "There is little convincing evidence to show a systematic interaction between other antibiotics and oral contraceptive steroids.", "output": "The World Health Organization (WHO) states that there have been suspicions that broad-spectrum antibiotics may lower OC effectiveness based on case reports, but that pregnancy rates are similar among women on OCs and women on both OCs and antibiotics." }, { "input": "However, current studies may not have separately evaluated the minority of women whose metabolism of contraceptive steroids makes them more vulnerable to OC failure. Given the significant consequences of unintended pregnancy, some experts recommend a conservative approach, including patient education and backup forms of birth control.", "output": "The women most likely to have pill failure are those with low rates of ethinyl estradiol hydroxylation, high rates of hepatic conjugation, low plasma concentrations of ethinyl estradiol, extensive intestinal hydrolysis of estrogen conjugates, or gut flora particularly susceptible to the antibiotic. Unfortunately, they cannot be identified by any routine diagnostic tests. The most conservative approach emphasizes patient education and additional forms of nonhormonal contraception for any woman on OCs during any antibiotic therapy and for at least 1 week after treatment." }, { "input": "However, current studies may not have separately evaluated the minority of women whose metabolism of contraceptive steroids makes them more vulnerable to OC failure. Given the significant consequences of unintended pregnancy, some experts recommend a conservative approach, including patient education and backup forms of birth control.", "output": "It is possible, however, that a true interaction between antibiotics and OCs may only manifest itself in the very small subset of women who have unusually low steroid hormone levels. These women may be identified by symptoms of breakthrough bleeding, cramping, nausea, vomiting or diarrhea, or by unwanted pregnancy." }, { "input": "However, current studies may not have separately evaluated the minority of women whose metabolism of contraceptive steroids makes them more vulnerable to OC failure. Given the significant consequences of unintended pregnancy, some experts recommend a conservative approach, including patient education and backup forms of birth control.", "output": "The women most likely to have pill failure are those with low rates of ethinyl estradiol hydroxylation, high rates of hepatic conjugation, low plasma concentrations of ethinyl estradiol, extensive intestinal hydrolysis of estrogen conjugates, or gut flora particularly susceptible to the antibiotic. Unfortunately, they cannot be identified by any routine diagnostic tests. The most conservative approach emphasizes patient education and additional forms of nonhormonal contraception for any woman on OCs during any antibiotic therapy and for at least 1 week after treatment." }, { "input": "Although no studies specifically evaluate this question, treatment for Group A beta-hemolytic streptococcal (GABHS) pharyngitis without laboratory confirmation in the general population is not advisable due to poor diagnostic accuracy.", "output": "According to 1 meta-analysis, a history of exposure to strep in the previous 2 weeks had a sensitivity of 19%, with a specificity ranging from 87% to 94%. This results in a likelihood ratio (LR) of 1.9 if the patient has an exposure (eg, the patient's odds of having strep are 1.9 times higher than baseline), and a patient without an exposure has an LR of 0.94. (Typically, LRs of 0.5 to 2.0 are not helpful for diagnostic testing). In a population at a 10% risk of GABHS as the cause of pharyngitis, the positive predictive value of streptococcal exposure was 17%, and the negative predictive value of no known exposure was 91%." }, { "input": "Although no studies specifically evaluate this question, treatment for Group A beta-hemolytic streptococcal (GABHS) pharyngitis without laboratory confirmation in the general population is not advisable due to poor diagnostic accuracy.", "output": "Only 5% to 10% of adults and 20% to 25% of children presenting in an office setting with acute pharyngitis actually have GABHS pharyngitis. The prevalence of GABHS pharyngitis is higher for patients presenting to urgent care centers or emergency rooms than office practices. Of the primary clinical prediction rules for pharyngitis, only the Walsh Diagnostic Algorithm explicitly includes a history of streptococcal exposure. In that algorithm, only patients with tender or enlarged cervical lymph nodes who either had exudative pharyngitis or a recent exposure were in the highest risk category (23% prevalence of GABHS)." }, { "input": "When you suspect GABHS pharyngitis either clinically or epidemiologically, confirm the diagnosis of pharyngitis by a laboratory test. Patients with a positive throat culture or a rapid antigen detection test should receive appropriate treatment with antimicrobial therapy.", "output": "The number needed to treat (NNT) for antibiotics given to GABHS-positive patients is 3.5 for resolution of symptoms by day 3; for GABHS-negative patients it is 5.5, and for patients who did not have a culture, it is 14.5. When properly prescribed, antibiotics decrease communicability of GABHS to 24 hours, and symptoms by 1 day (NNT=5 patients to decrease symptoms). Antibiotics also decrease the incidence of rheumatic heart disease (NNT=100) and peritonsillar abscesses. Due to the decreased incidence of glomerulonephritis, the evidence is inadequate to determine the role of antibiotics in preventing this complication." }, { "input": "Simplification of the dosing regimen (eg, once-daily instead of multiple dosing) improves patients' adherence to antihypertensive medications.", "output": "A Cochrane review included 38 randomized controlled trials (RCTs) of 58 various types of interventions (some tested in factorial trials) designed to improve patient adherence to antihypertensive medications in ambulatory settings. The quality of the studies was generally low due to inadequate allocation concealment, lack of blinding of outcome assessors, loss to follow-up, and the small number of participants in trials. The authors grouped interventions into 4 broad categories: simplification of dosing regimens; patient education; patient motivation, support, and reminders; and complex interventions. Comparison groups received either no intervention, usual care, or-in the case of simplification of dosing regimens-a daily regimen consisting of more than 1 pill per day vs a once-daily regimen. Because of various types of interventions and different methods of assessing outcomes, pooling of results was, appropriately, not done. Of all the interventions, simplification of dosing regimens had the most evidence of effectiveness, with 7 out of 9 studies demonstrating a statistically significant improvement in adherence in the intervention group. In the other 2 studies, improved adherence was observed in the intervention group; however, the effect was either not statistically significant or not reported." }, { "input": "Dietary advice promotes modest short-term improvements in self-reported fat intake and fruit and vegetable consumption.", "output": "A Cochrane review of dietary advice for reducing cardiovascular disease risk among healthy adults included 29 trials. Individuals or groups of patients received verbal or printed dietary advice over 1 or more personal contacts. They also received advice by telephone. Ten RCTs of dietary advice in 4328 participants or groups of participants assessed self-reported dietary fat intake. Overall, intake of dietary fat (expressed as a percentage of total caloric intake) fell by 6.2% (95% confidence interval [CI], reduced 8.4% to increased 4.0%) with dietary intervention over 6 to 48 months. Due to significant heterogeneity between the studies, this overall estimate must be viewed with caution. Eight RCT studies in 3952 participants or groups of participants assessed self-reported fruit and vegetable intake as an outcome. Overall, intake of fruits and vegetables increased by 1.2 servings per day (95% CI, 0.43-2.1) with interventions over 6 to 48 months. Again, there was significant heterogeneity between the studies. Therefore, this overall estimate must be viewed with caution. In general, the quality of the studies included in this systematic review was low due to poor descriptions of randomization, lack of allocation concealment, and lack of blinding of outcome assessment. The use of food frequency questionnaires to measure fat and fruit/vegetable intake likely led to reporting bias in these dietary intervention studies. Also, the trials were in healthy adults and not specific to hypertensive patients." }, { "input": "Educational interventions alone, in general, do not improve patient adherence to antihypertensive medication regimens.", "output": "In a Cochrane review, only 1 of 6 studies of patient education intervention demonstrated improved adherence, but the trial was small (n=110), and the effect was not seen in the other studies (total of 1103 patients)." }, { "input": "Educational interventions alone, in general, do not improve patient adherence to antihypertensive medication regimens.", "output": "Out of 18 studies of interventions classified as complex health and organizational interventions, including many with an educational or motivational component, interventions in 8 studies led to a statistically significant improvement in adherence. Complex interventions included structured hypertension management programs such as worksite care provided by trained nurses. An example of an intervention given in combination is a program of home visits, education, and specialized dosing devices. Because these interventions varied considerably, an overall statement of effectiveness is not appropriate." }, { "input": "Educational interventions alone, in general, do not improve patient adherence to antihypertensive medication regimens.", "output": "Overall, out of 24 RCTs studying motivational, support, and reminder interventions, 10 demonstrated statistically significant but small improvements in adherence. These studies relied on measures such as pill counts and self-report to assess adherence rather than electronic monitoring. The marked inconsistency among the body of evidence makes it difficult to determine whether motivational, support, and reminder interventions alone are effective in improving adherence." }, { "input": "Physicians' advice to increase physical activity is not effective, even as part of a self-care plan for hypertension", "output": "We found 1 randomized trial that evaluated the effectiveness of a physician's advice to increase physical activity among patients with hypertension in a general practice setting. Physical activity was measured using a validated questionnaire. Patients given the advice as part of self-care for hypertension (n=192) were no more likely to have increased their physical activity than those not given the advice (n=108) at 2- and 6-month follow-ups." }, { "input": "Ketoconazole (Nizoral) shampoo appears to be a safe and efficacious treatment for infants with cradle cap.", "output": "A small (n=13) phase I safety trial of infants demonstrated that ketoconazole shampoo applied twice weekly for 1 month resulted in no detectable serum ketoconazole levels or elevation in liver function tests." }, { "input": "Ketoconazole (Nizoral) shampoo appears to be a safe and efficacious treatment for infants with cradle cap.", "output": "The guidance from PRODIGY the UK's National Health Service primary care database recommends regular washing with baby shampoo followed by gentle brushing. Alternatively, softening the scale with mineral oil, followed by gentle brushing and shampooing is an alternative approach. Ketoconazole 2% shampoo or cream once a day has been shown to be effective; PRODIGY recommends avoiding topical corticosteroids." }, { "input": "Ketoconazole (Nizoral) shampoo appears to be a safe and efficacious treatment for infants with cradle cap.", "output": "A small (n=19) uncontrolled study of once-daily ketoconazole 2% cream, 79% of infants affected with seborrheic dermatitis of the scalp and diaper area showed good response by day 10 (no statistical methods reported). Peak plasma ketoconazole levels in this study were only 1% to 2% of those documented after systemic administration." }, { "input": "Ketoconazole (Nizoral) shampoo appears to be a safe and efficacious treatment for infants with cradle cap.", "output": "An uncontrolled multicenter trial with 575 adults found ketoconazole shampoo was superior to placebo for treatment of scalp seborrheic dermatitis with an 88% \"excellent response\" rate (P<.0001, no relative risk or confidence intervals given)." }, { "input": "Limit topical corticosteroids to severe cases because of possible systemic absorption.", "output": "Several studies have demonstrated systemic absorption and, in some cases, adrenocortical suppression when using mild topical steroids such as 1% hydrocortisone cream in pediatric populations." }, { "input": "Limit topical corticosteroids to severe cases because of possible systemic absorption.", "output": "The guidance from PRODIGY the UK's National Health Service primary care database recommends regular washing with baby shampoo followed by gentle brushing. Alternatively, softening the scale with mineral oil, followed by gentle brushing and shampooing is an alternative approach. Ketoconazole 2% shampoo or cream once a day has been shown to be effective; PRODIGY recommends avoiding topical corticosteroids." }, { "input": "Overnight application of emollients followed by gentle brushing and washing with baby shampoo helps to remove the scale associated with cradle cap.", "output": "Overnight use of emollients such as mineral oil to soften scales followed by gentle brushing and washing with baby shampoo is an accepted treatment, although no trials could be found to show its efficacy for infants." }, { "input": "Enzyme-linked immunosorbent assay (ELISA) tests based on herpes simplex virus 2's (HSV-2) glycoprotein G have demonstrated high sensitivity and specificity in determining seropositivity for HSV-2 antibodies.", "output": "Using the Western blot technique as the gold standard, a total of 158 serum samples from patients with either HSV-1 or HSV-2 infection-without mention of symptomatology-were used to compare the performance of several commercially available ELISA assays. The glycoprotein G and non-glycoprotein G ELISA tests were both found to have sensitivities >90%, but the non-glycoprotein G ELISA tests had specificities under 90%. In 47% to 82% of the samples tested with non-glycoprotein G ELISA, there was cross-reactivity between HSV-1 and HSV-2 antibodies." }, { "input": "ELISA tests not based on glycoprotein G are also highly sensitive, but they are less specific for HSV-2 and are prone to false-positive results because of cross-reactivity with HSV-1 antibodies.", "output": "Using the Western blot technique as the gold standard, a total of 158 serum samples from patients with either HSV-1 or HSV-2 infection-without mention of symptomatology-were used to compare the performance of several commercially available ELISA assays. The glycoprotein G and non-glycoprotein G ELISA tests were both found to have sensitivities >90%, but the non-glycoprotein G ELISA tests had specificities under 90%. In 47% to 82% of the samples tested with non-glycoprotein G ELISA, there was cross-reactivity between HSV-1 and HSV-2 antibodies." }, { "input": "ELISA tests not based on glycoprotein G are also highly sensitive, but they are less specific for HSV-2 and are prone to false-positive results because of cross-reactivity with HSV-1 antibodies.", "output": "The College of American Pathologists found that 46% to 84% of laboratories using non-glycoprotein G ELISA tests incorrectly identified an HSV-1 sample as being HSV-2. All laboratories reporting use of glycoprotein G ELISA tests correctly identified the sample as containing only HSV-1 antibodies." }, { "input": "Random anogenital cultures are not sensitive for diagnosing HSV-2 infection.", "output": "A prospective cohort study compared the viral shedding by Western blot among 52 asymptomatic seropositive patients with 90 seropositive and symptomatic patients. Daily genital swabs were done for 3 months for each patient. The asymptomatic individuals had HSV-2 positive cultures on 3% of culture days. Genital culture appears to have a very poor sensitivity (5%) for diagnosis of HSV-2 infection among asymptomatic individuals." }, { "input": "Trimethoprim/sulfamethoxazole (TMP/SMX) has a high success rate in eradicating bacteriuria for women with urinary tract infection and is compatible with breastfeeding.", "output": "One South African series measured breast milk levels of both trimethoprim and sulfamethoxazole among 50 Bantu women treated with TMP/SMX for various infections (including UTI). The women received 160 mg TMP and 800 mg SMX 2 or 3 times daily for up to 5 days. The average level of TMP in breast milk was 2 mcg/mL, and the level of SMX was 4.7 mcg/mL. Researchers calculated that the average breastfeeding infant would ingest only 1 mg of TMP and 2.5 mg of SMX per day. TMP/SMX is generally considered safe for infants in the absence of G6PD deficiency." }, { "input": "Trimethoprim/sulfamethoxazole (TMP/SMX) has a high success rate in eradicating bacteriuria for women with urinary tract infection and is compatible with breastfeeding.", "output": "TMP/SMX is not recommended if the local resistance rate is more than 10% to 20%. Beta-lactams are associated with high levels of resistance and therefore not recommended in empiric treatment of UTI." }, { "input": "Trimethoprim/sulfamethoxazole (TMP/SMX) has a high success rate in eradicating bacteriuria for women with urinary tract infection and is compatible with breastfeeding.", "output": "The best evidence for efficacy of UTI treatments comes from a 1999 meta-analysis of uncomplicated UTI in nonpregnant, nonlactating women. They found TMP/SMX to be the most widely studied antibiotic and to have a 93% bacterial eradication rate; it was therefore used as a standard for comparison of other treatments. Nitrofurantoin and quinolones (ofloxacin, ciprofloxacin, and others) had comparable eradication rates to TMP/SMX in the same study; 7-day courses of nitrofurantoin were more efficacious than shorter ones. Three-day therapy for uncomplicated UTI is more effective than single-dose therapy and equal to longer courses for most antibiotics. A longer course (7 days) may be required for nitrofurantoin." }, { "input": "Quinolones (ciprofloxacin, ofloxacin) are effective and probably compatible with breastfeeding; however, their use has not been recommended by many investigators based on arthropathy in animal studies.", "output": "A case series administered ciprofloxacin 750 mg, pefloxacin 400 mg, or ofloxacin 400 mg twice daily to 3 groups of 10 women each. Milk samples were obtained 6 times over 24 hours following the third dose of antibiotic. Maximum levels in breast milk occurred 2 hours after the dose, and were 3.79, 3.54, and 2.41 mcg/mL for ciprofloxacin, pefloxacin, and ofloxacin respectively. All 3 quinolones achieved higher concentrations in breast milk than in serum." }, { "input": "Quinolones (ciprofloxacin, ofloxacin) are effective and probably compatible with breastfeeding; however, their use has not been recommended by many investigators based on arthropathy in animal studies.", "output": "While TMP/SMX and nitrofurantoin are generally considered safe when given to infants and children (barring G6PD deficiency), data are mixed regarding the safety of quinolones. Ciprofloxacin's FDA indication for pediatric patients is limited to postexposure anthrax prophylaxis due to evidence of fluoroquinolone-induced joint toxicity in animal studies." }, { "input": "Quinolones (ciprofloxacin, ofloxacin) are effective and probably compatible with breastfeeding; however, their use has not been recommended by many investigators based on arthropathy in animal studies.", "output": "A report was published summarizing safety data from the Bayer database of compassionate use of ciprofloxacin. The report indicates that 2030 treatment courses of ciprofloxacin were given to 1795 children up to age 17 for a variety of infections; only 3% were under age 5. Most patients received 21 to 40 mg/kg of ciprofloxacin per day; treatment duration was from 1 to 303 days. Arthralgia occurred in 1.5% of patients, most of whom had cystic fibrosis. Of the 31 patients affected, arthralgias resolved in 25, improved in 1, and remained unchanged in 1. (Data regarding resolution were unavailable for 4 patients.)" }, { "input": "A 7-day course of nitrofurantoin has similar efficacy to TMP/SMX and is compatible with breastfeeding, but it should be avoided in populations at risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency (also known as favism, most often found in patients of mediterranean or african descent).", "output": "In a case series, 9 lactating mothers were given nitrofurantoin 100 mg orally every 6 hours for 1 day. On day 2, after a single 100 to 200 mg dose, drug levels in the breast milk 2 hours post-dose ranged from none (in 6 of the 9 women) to a maximum of 0.5 mcg/mL in one. Since even a very small amount of the drug may trigger a hemolytic reaction among G6PD-deficient individuals, the researchers called for caution when prescribing to mothers from high-risk populations." }, { "input": "No single test has adequate sensitivity and specificity to reliably identify pelvic inflammatory disease (PID) and thus help to spare women serious sequelae, including infertility.", "output": "A study developed a model using vaginal WBC (the single most sensitive factor at 78%), serum WBC (the single most specific factor at 88%), CRP, and ESR. The model was 100% sensitive if the diagnosis only required 1 positive test, although the specificity was only 18%. The positive predictive value was 65%. If all 4 were positive, specificity was 95%, with 29% sensitivity, a positive predictive value of 90%, and a negative predictive value of 47%. Prevalence was 60% in the group studied." }, { "input": "No single test has adequate sensitivity and specificity to reliably identify pelvic inflammatory disease (PID) and thus help to spare women serious sequelae, including infertility.", "output": "A study of serum CA-125 levels showed a predictive value of 97% for values >16 U/mL in diagnosing salpingitis. This test might therefore be useful in confirming peritoneal involvement when PID is suspected clinically." }, { "input": "No single test has adequate sensitivity and specificity to reliably identify pelvic inflammatory disease (PID) and thus help to spare women serious sequelae, including infertility.", "output": "One study found CRP >10 to be 93% sensitive and 83% specific in a cohort of women admitted to the emergency department with an acute gynecological disorder. This population had a high baseline incidence of PID, pregnancy, and intrauterine device use." }, { "input": "No single test has adequate sensitivity and specificity to reliably identify pelvic inflammatory disease (PID) and thus help to spare women serious sequelae, including infertility.", "output": "A study proposed the use of a clinical criteria model including low abdominal pain and 2 or more of the following other criteria: vaginal discharge, temperature greater than 38\u00baC, vomiting, irregular menses, urologic or proctitis symptoms, pelvic tenderness, adnexal mass or swelling, and ESR \u226515. This model had a reported sensitivity of 87%, specificity of 52.5%, and false-positive and false-negative rates of 21.2% and 33.3%, respectively." }, { "input": "No single test has adequate sensitivity and specificity to reliably identify pelvic inflammatory disease (PID) and thus help to spare women serious sequelae, including infertility.", "output": "The Lund analysis includes data collected between 1960 and 1969 at Lund University Hospital in Sweden on women with suspected PID, with about 625 cases included for these analyses. Simms et al found insufficient evidence from these data for any existing diagnostic criteria." }, { "input": "No single test has adequate sensitivity and specificity to reliably identify pelvic inflammatory disease (PID) and thus help to spare women serious sequelae, including infertility.", "output": "A systematic review of 19 fair-to good-quality cohort studies found a sensitivity of only 64% for laparoscopy, 50% to 87% for endometrial biopsy, and up to 80% for microbiological tests. Results were not consistent for the reported sensitivity of WBC, ESR, or CRP." }, { "input": "No single test has adequate sensitivity and specificity to reliably identify pelvic inflammatory disease (PID) and thus help to spare women serious sequelae, including infertility.", "output": "One systematic review of 12 fair- to good-quality studies, based in Europe and the US, included urban populations treated in Ob/Gyn departments, emergency rooms, and sexually transmitted disease clinics. This review supports a thorough evaluation when more severe disease is suspected and the use of sensitive diagnostic tests for suspected mild disease-eg, CRP (74%-93% sensitivity) and ESR (64%-81% sensitivity for value >20 or 15 mm/h)." }, { "input": "However, even the modified 2002 CDC criteria fail to identify women with subclinical PID who are at roughly equivalent risk for PID sequelae as those with acute symptomatic disease.", "output": "Cross-sectional analysis of a multisite US randomized treatment trial supported using adnexal tenderness as a minimum clinical criterion to increase sensitivity." }, { "input": "However, even the modified 2002 CDC criteria fail to identify women with subclinical PID who are at roughly equivalent risk for PID sequelae as those with acute symptomatic disease.", "output": "A cohort study study compared clinical criteria to several reference standards (laparoscopy, histology, microbiological markers, and transvaginal ultrasound) and found clinical criteria, specifically adnexal tenderness, most sensitive (87%), and laparoscopy most specific (100%)." }, { "input": "However, even the modified 2002 CDC criteria fail to identify women with subclinical PID who are at roughly equivalent risk for PID sequelae as those with acute symptomatic disease.", "output": "Analysis of a trial suggests that some asymptomatic women are at equivalent risk of developing sequelae compared with symptomatic women diagnosed with PID. Those asymptomatic women who met diagnostic criteria with a positive endometrial biopsy were more likely to have pelvic tenderness than asymptomatic women who were not diagnosed." }, { "input": "However, even the modified 2002 CDC criteria fail to identify women with subclinical PID who are at roughly equivalent risk for PID sequelae as those with acute symptomatic disease.", "output": "A cohort study evaluated 176 consecutive admissions for clinically diagnosed PID, 76% of which were laparoscopically confirmed. Reviewing clinical indicators, they found that a combination of adnexal tenderness, symptoms for <1 week, and elevated WBC was the most sensitive set of predictors (sensitivity 86.6%, specificity 45.7%) with positive predictive value of 0.84 and negative predictive value of 0.52." }, { "input": "other", "output": "Clinical Evidence found no RCTs that compared empiric treatment of suspected PID with waiting for microbiological test results for guidance." }, { "input": "other", "output": "The Agency for Healthcare Research and Quality recommends requiring the presence of lower abdominal, adnexal and cervical tenderness, without alternative diagnosis, for the diagnosis of PID. Temperature >101\u00baF, cervical or vaginal discharge, elevated ESR, and positive gonococcal or chlamydia cultures all increase specificity of diagnosis." }, { "input": "other", "output": "The CDC recommends empiric treatment of women with lower abdominal or pelvic pain who are at risk for sexually transmitted diseases with uterine, adnexal, or cervical motion tenderness and no other identifiable cause." }, { "input": "other", "output": "The United Kingdom's national guideline recommends maintaining a low threshold for empirical treatment, citing a lack of definitive diagnostic criteria and potential for sequelae, but does recommend testing for gonorrhea and chlamydia." }, { "input": "Yes, moderately. Exercise helps reduce the pain, but it's unclear whether it helps with stiffness. Exercise moderately reduces pain in elderly patients with osteoarthritis.", "output": "Two other reviews examined strengthening and aerobic exercises for osteoarthritis, including studies using isokinetic, concentric, and eccentric strengthening; water therapy; walking; yoga; and tai chi. The exercises appeared to have beneficial effects on pain. However, results from the studies of each type of exercise weren't combined and ES wasn't calculated." }, { "input": "Yes, moderately. Exercise helps reduce the pain, but it's unclear whether it helps with stiffness. Exercise moderately reduces pain in elderly patients with osteoarthritis.", "output": "In a Cochrane systematic review that evaluated the intensity of exercise, only 1 study with 39 participants met the inclusion criteria. This limited-power study found no difference between the effect of low-intensity and high-intensity exercise on pain reduction or function." }, { "input": "Yes, moderately. Exercise helps reduce the pain, but it's unclear whether it helps with stiffness. Exercise moderately reduces pain in elderly patients with osteoarthritis.", "output": "A systematic review examined the effect of therapeutic exercise on hip and knee osteoarthritis. The standardized mean difference in ES for pain reduction was moderate, 0.46 (95% CI, 0.35-0.57). For self-reported physical functioning, the standardized mean difference was small, 0.33 (95% CI, 0.23-0.43). Study limitations included enrollment of patients with only early or mild osteoarthritis, low numbers of intent-to-treat studies, short-term nature of the studies, and inadequate sample sizes." }, { "input": "Exercise has a small effect on reducing self-reported disability.", "output": "A 2005 systematic review examined aerobic walking and quadriceps strengthening for knee osteoarthritis using pain as the primary outcome and self-reported disability as the secondary outcome. In the exercise group, the weighted, pooled ES for pain reduction and self-reported disability was moderate at 0.52 (95% CI, 0.34-0.70) and 0.46 (95% CI, 0.25-0.67) respectively. The quadriceps strengthening group showed a small weighted, pooled ES for pain reduction of 0.32 (95% CI, 0.23-0.42) and disability of 0.32 (95% CI, 0.23-0.41); pain and disability measures were variable. None of the included clinical trials were blinded." }, { "input": "Psychological interventions for the family-such as parenting skills training and behavioral therapy for the child, the parents, or the whole family-reduce conflict behaviors in adolescents with oppositional defiant disorder (ODD).", "output": "A meta-analysis of 8 RCTs (with a total of 749 children) of various behavioral treatments for conduct disorder and juvenile delinquency among children aged 10 to 17 years found significant reductions in rearrest rates (relative risk [RR]=0.66; 95% confidence interval [CI], 0.44-0.98; number needed to treat [NNT] to prevent 1 rearrest=3.7) and time spent in institutions (mean difference, 51 days) with family and parenting interventions (comprising 1 to 6 months of individual and group parenting training, short and long-term family therapy, and individual and group adolescent interventions)." }, { "input": "Psychological interventions for the family-such as parenting skills training and behavioral therapy for the child, the parents, or the whole family-reduce conflict behaviors in adolescents with oppositional defiant disorder (ODD).", "output": "A 2-year case-control study of 158 self-referred families with young adolescents (11 to 14 years old) without a formal ODD diagnosis but with reported problem behaviors (defined as smoking, negative engagement in family problem solving, and parental ratings of unpleasant events) found significant improvements (P<.01) with parent-only, teen-only, and parent-teen behavioral interventions for negative engagement behaviors (average of 30% reduction in scores), and with parent and teen interventions for unpleasant events (average of 9% reduction in scores). Interventions comprised 12 weekly 90-minute sessions, with the parent-only group targeting family management practices and communication skills, the teen-only group targeting adolescent self-regulation and pro-social behavior, and the parent-teen group following a structured curriculum." }, { "input": "Psychological interventions for the family-such as parenting skills training and behavioral therapy for the child, the parents, or the whole family-reduce conflict behaviors in adolescents with oppositional defiant disorder (ODD).", "output": "A Clinical Inquiry summarized 8 well-done systematic reviews of ODD treatments of preadolescent children and found improved behavior with parenting interventions and behavioral therapy. Each of the systematic reviews assessed multiple randomized controlled trials (RCTs) using a variety of parenting and behavioral therapy interventions. The most rigorous systematic review (which included 16 RCTs), compared group-based parenting skills training with untreated wait-list controls and found decreased aggression, noncompliance, and temper tantrums by children aged 3 to 10 years (total number of subjects not given) by an average effect size of 0.6 to 2.9. (Effect size is the difference between the means of the experimental and control groups expressed in standard deviations. An effect size of 0.2 is considered small, 0.5 is medium, and 0.8 is moderate to large.) Behavioral therapy (cognitive-behavioral therapy, social problem-solving skills training, parent management training), comprising 12 to 25 sessions with either the child alone or with teachers or parents, decreased disruptive or aggressive behaviors by 20% to 30%." }, { "input": "ODD most commonly does not occur as a solitary diagnosis. When ODD is associated with attention deficit/hyperactivity disorder (ADHD) or other medication-responsive comorbid conditions, medical treatment reduces overall symptoms.", "output": "Approximately half to two-thirds of adolescents with ODD also have ADHD." }, { "input": "ODD most commonly does not occur as a solitary diagnosis. When ODD is associated with attention deficit/hyperactivity disorder (ADHD) or other medication-responsive comorbid conditions, medical treatment reduces overall symptoms.", "output": "A meta-analysis evaluated 28 studies of stimulant medication (methylphenidate, amphetamine, or pemoline) for children with comorbid ADHD and ODD. A total of 683 patients aged 8 to 18 years were included. Stimulants reduced aggression-related behaviors in these children by an effect size of 0.84 for overt aggression and 0.69 for covert aggression. Stimulants typically reduce aggressive behaviors by similar effect sizes when prescribed for children with ADD alone. The study groups did not separate children with ADHD and ODD from those with ADHD and conduct disorder; they also grouped adolescents together with younger children." }, { "input": "ODD most commonly does not occur as a solitary diagnosis. When ODD is associated with attention deficit/hyperactivity disorder (ADHD) or other medication-responsive comorbid conditions, medical treatment reduces overall symptoms.", "output": "An RCT of different doses of atomoxetine (Strattera) treatment vs placebo for children ages 8 to 18 (mean age=11) with ADHD alone (N=178) and children with both ADHD and ODD (N=115) found significant effect sizes for atomoxetine in both groups. Two dosages of atomoxetine (1.2 and 1.8 mg/kg/d) produced equivalent effect sizes in the ADHD-only group (0.55 and 0.56); however, the higher dosage had a greater effect size (0.49 vs 0.69) in the group with ODD comorbid with ADHD." }, { "input": "ODD most commonly does not occur as a solitary diagnosis. When ODD is associated with attention deficit/hyperactivity disorder (ADHD) or other medication-responsive comorbid conditions, medical treatment reduces overall symptoms.", "output": "A double-blind crossover RCT evaluated divalproex (Depakote) vs placebo for 20 children (aged 10 to 18 years) with explosive temper and mood lability who also met DSM-IV criteria for either ODD or conduct disorder. Patients with significant medical problems, such as bipolar disorder, major depression, or mental retardation, were excluded. Divalproex significantly (P=.003) reduced aggressive behaviors and anger-hostility items by approximately 33% as reported by child, parent, school, and clinician on 2 standardized scales." }, { "input": "ODD most commonly does not occur as a solitary diagnosis. When ODD is associated with attention deficit/hyperactivity disorder (ADHD) or other medication-responsive comorbid conditions, medical treatment reduces overall symptoms.", "output": "Experts say antidepressant medications may be helpful in treating children with conduct disorder and comorbid major depression." }, { "input": "Low-molecular-weight heparin (LMWH) prophylaxis significantly reduces the total incidence of deep venous thrombosis (DVT) for patients with lower-limb fractures managed with surgical fixation and cast immobilization.", "output": "An RCT evaluated tinzaparin (yet another European LMWH) in 300 adult outpatients immobilized in plaster for at least 3 weeks. Most patients (205 out of 300) underwent venography, and the overall DVT rate was 10% (tinzaparin) vs 17% (controls). Among the 150 fracture patients who underwent venography, the DVT rate was 11% (tinzaparin) vs 13% (controls). This difference was not significant, probably due to insufficient numbers. None of the DVTs was clinically detectable." }, { "input": "Low-molecular-weight heparin (LMWH) prophylaxis significantly reduces the total incidence of deep venous thrombosis (DVT) for patients with lower-limb fractures managed with surgical fixation and cast immobilization.", "output": "An RCT evaluated reviparin (another European LMWH) vs placebo in 440 outpatients with lower limb injuries, of whom 293 had fractures. About half had surgical management and all were treated with a plaster cast or brace for an average of 44 days. Most were ambulatory with crutches. All underwent venography within a week of cast removal. The DVT rate for fracture patients using reviparin was 10.4%, vs 18.2% among those without LMWH prophylaxis (absolute risk reduction=7.8%; NNT=12.8). Three fourths of the DVTs were in distal veins, and 21% of the DVTs in the LMWH patients occurred in deep veins compared with 34% in patients without. Two pulmonary emboli occurred, both in patients without LMWH prophylaxis." }, { "input": "Low-molecular-weight heparin (LMWH) prophylaxis significantly reduces the total incidence of deep venous thrombosis (DVT) for patients with lower-limb fractures managed with surgical fixation and cast immobilization.", "output": "An RCT evaluated LMWH (Mono-Embolex, a European LMWH) prophylaxis in 328 outpatients with lower limb injuries, which included fractures, severe contusions, and ligamentous injuries. All were treated nonsurgically with cast immobilization (mean=18.8 days, range=2-72 days) and 176 patients used daily LMWH injections. All underwent Doppler evaluation for leg thromboses after cast removal, and positive results were confirmed with venograms. Overall, there were no DVTs among the LMWH prophylaxis group and 7 DVTs (4.3%) in the group without LMWH prophylaxis (P<.006). Among those with fractures, the untreated DVT rate was 5.9% (vs 0% with LMWH prophylaxis). Those over age 40 who did not use LMWH had a DVT rate of 11.4% (vs 1.7% in younger patients). Without LMWH prophylaxis, casting for more than 10 days approximately doubled the risk of DVT compared with less than 10 days (6.1% vs 3.1%). This study did not report on the anatomic location of DVTs or if they were clinically evident." }, { "input": "Low-molecular-weight heparin (LMWH) prophylaxis significantly reduces the total incidence of deep venous thrombosis (DVT) for patients with lower-limb fractures managed with surgical fixation and cast immobilization.", "output": "An RCT evaluated 253 patients with lower-limb fractures immobilized in plaster casts after surgical fixation. Half the patients received subcutaneous LMWH (nadroparin [Fraxiparin], a European LMWH similar to enoxaparin), and half received no thrombosis prophylaxis. Based on compression ultrasound at the time of cast removal (17 days postinjury, on average), the overall DVT incidence was 11%. Six patients (5%) receiving LMWH had DVTs vs 21 (17%) in the control group (number needed to treat [NNT]=8 to prevent 1 DVT detectible by compression ultrasound). Two thirds of patients with DVT were asymptomatic. One third had clinical signs of DVT, including 1 patient diagnosed with PE on clinical grounds. There was no difference in bleeding complications between the treatment groups." }, { "input": "Low-molecular-weight heparin (LMWH) prophylaxis significantly reduces the total incidence of deep venous thrombosis (DVT) for patients with lower-limb fractures managed with surgical fixation and cast immobilization.", "output": "Incidence of DVT and PE was also evaluated in a cohort of 102 unselected patients who underwent operative fixation for lower-limb fractures, excluding patella, ankle, and foot fractures. All underwent venography approximately 9 days after fixation and were followed clinically for 6 weeks. The overall incidence of DVT was 28% (40% with femoral shaft, 43% with tibial plateau, 22% with tibial shaft, and 12% with tibial plafond [distal articular tibia]). Four developed clinical evidence of PE during hospitalization but only 1 had objective confirmation. None of the patients showed clinical evidence of PE as outpatients." }, { "input": "Low-molecular-weight heparin (LMWH) prophylaxis significantly reduces the total incidence of deep venous thrombosis (DVT) for patients with lower-limb fractures managed with surgical fixation and cast immobilization.", "output": "In 1968, a prospective observational study evaluated the natural history of DVT and pulmonary embolism (PE) in tibial fractures treated with open reduction and internal fixation with early mobilization. Seventy-six consecutive patients with 79 tibial fractures were evaluated with venograms, most within 1 month of injury. The overall incidence of thrombosis was 45%. Half were minor, involving 1 to 3 of the paired deep venous trunks of the lower leg without clinical signs of embolism. Twelve patients (16%) had extensive thrombosis, involving 4 to 6 of the deep venous trunks. Three of these had nonfatal PE diagnosed clinically, and 1 had a fatal PE confirmed at autopsy. The mean age of those with extensive thrombosis or PE was 54 years, and these events were uncommon below age 25 years." }, { "input": "Sodium alginate reduces vomiting and improves parents' assessment of symptoms.", "output": "A large manufacturer-sponsored RCT found that sodium alginate significantly reduced emesis episodes in treated infants. Sodium alginate is marketed in the UK as Gaviscon Infant. While this trial included breastfed infants, it did not report the numbers of breastfed infants in the 2 treatment groups or present data separately for breastfed infants." }, { "input": "Formula thickened with rice cereal decreases the number of postprandial emesis episodes in infants with gastroesophageal reflux disease (GERD).", "output": "In 1 RCT, formula thickened with rice cereal decreased emesis episodes." }, { "input": "There are conflicting data on the effect of carob bean gum as a formula thickener and its effect on regurgitation frequency.", "output": "An uncontrolled, comparative trial of carob bean gum vs rice cereal suggested superiority of carob bean gum as a thickener, although both treatments yielded improvement." }, { "input": "There are conflicting data on the effect of carob bean gum as a formula thickener and its effect on regurgitation frequency.", "output": "Two studies of carob bean gum-thickened formula vs plain formula yielded conflicting results. In the study showing improvement with carob bean gum, the parents were not blinded to the treatment, which may have led to bias favoring the treatment." }, { "input": "Omeprazole and metoclopramide each improve the reflux index as measured by esophageal pH probe.", "output": "A small RCT of metoclopramide shows significant improvement in reflux index measured by pH probe. However, metoclopramide yielded no improvement in symptom counts." }, { "input": "Omeprazole and metoclopramide each improve the reflux index as measured by esophageal pH probe.", "output": "A small RCT of omeprazole shows significant improvement in reflux index measured by pH probe. However, the study resulted in no differences in \"cry-fuss time\" between treatment groups." }, { "input": "Evidence is conflicting for other commonly used conservative measures (such as positional changes) or other medications for symptomatic relief of infant GERD. There is very limited evidence or expert opinion regarding breastfed infants, particularly with regard to preservation of breastfeeding during therapy.", "output": "Prone positioning is no longer recommended due to the risk of Sudden Infant Death Syndrome (SIDS)." }, { "input": "Evidence is conflicting for other commonly used conservative measures (such as positional changes) or other medications for symptomatic relief of infant GERD. There is very limited evidence or expert opinion regarding breastfed infants, particularly with regard to preservation of breastfeeding during therapy.", "output": "Three trials studied the effects of other conservative therapies such as positional changes and pacifiers on reflux measured by pH probe; unfortunately, none assessed clinical outcomes such as emesis or regurgitation. Reflux by pH probe was worsened in a trial studying the infant seat for positioning. In the trial studying elevating the head of the bed to 30\u00ba in the prone position, reflux measured by pH probe was also unchanged. The trial of pacifier use showed improvement of reflux by pH probe when used in the seated position, but worsening in the prone position. Since pH probe does not necessarily reflect clinical symptoms, the utility of the information from these studies is limited." }, { "input": "other", "output": "In a cross-sectional survey of 948 parents of healthy infants aged 0 to 13 months, regurgitation occurred daily in half of infants from birth to 3 months old, peaked to 67% at age 4 months, and was absent in 95% by age 12 months." }, { "input": "Tissue adhesives are effective and yield results comparable to those with conventional suturing of superficial, linear, and low-tension lacerations. The cosmetic outcome is similar; wound complications, such as infection and dehiscence, may be lower with tissue adhesives. Wound closure of superficial lacerations by tissue adhesives is quicker and less painful compared with conventional suturing", "output": "Pain outcomes in the studies showed that closure with tissue adhesive was less painful due to the lack of a need for anesthesia." }, { "input": "Tissue adhesives are effective and yield results comparable to those with conventional suturing of superficial, linear, and low-tension lacerations. The cosmetic outcome is similar; wound complications, such as infection and dehiscence, may be lower with tissue adhesives. Wound closure of superficial lacerations by tissue adhesives is quicker and less painful compared with conventional suturing", "output": "In a clinical trial reported after the Cochrane review, Holger and colleagues studied tissue adhesives against standard wound closure using either nylon or absorbable gut sutures. The study included 145 patients, 84 of whom had at least a 9-month follow-up. No significant difference was noted in a visual analog grading scale, with a 10- to 15-mm difference (out of 100 mm) considered significant." }, { "input": "Tissue adhesives are effective and yield results comparable to those with conventional suturing of superficial, linear, and low-tension lacerations. The cosmetic outcome is similar; wound complications, such as infection and dehiscence, may be lower with tissue adhesives. Wound closure of superficial lacerations by tissue adhesives is quicker and less painful compared with conventional suturing", "output": "A multicenter, randomized trial studied 924 wounds (383 traumatic, 541 surgical) and reported no difference in cosmetic appearance upon grading by both a clinician and the patients themselves." }, { "input": "Tissue adhesives are effective and yield results comparable to those with conventional suturing of superficial, linear, and low-tension lacerations. The cosmetic outcome is similar; wound complications, such as infection and dehiscence, may be lower with tissue adhesives. Wound closure of superficial lacerations by tissue adhesives is quicker and less painful compared with conventional suturing", "output": "A Cochrane review found 10 studies, which included 970 patients in the emergency-room setting. Review of these articles found no significant difference in cosmetic appearance between tissue adhesive closure and standard suture closure with a 3-month follow-up period in acute, linear wounds under low tension. Wound erythema (number needed to treat [NNT]=10) and dehiscence rates (NNT=25) were lower for tissue adhesives. In the 6 studies that reported time data, treatment with tissue adhesive took 4.7 fewer minutes. In all 6 studies that reported patients' perception of pain, pain was significantly less with tissue adhesive (weighted mean difference=13.7 mm [on 100-mm scale]; 95% confidence interval [CI], -20.0 to -6.9)." }, { "input": "While a common first-line treatments is dietary fiber, the evidence is insufficient to support this approach in the geriatric population.", "output": "A good-quality systematic review of dietary fiber in the treatment of constipation for older patients located 8 moderate- to high-quality studies (6 RCTs and 2 blinded before-after studies), with 269 study participants in institutional settings. Results among studies were inconsistent, casting doubt on the efficacy of fiber treatment for constipation in the institutionalized elder." }, { "input": "While a common first-line treatment is exercise, the evidence is insufficient to support this approach in the geriatric population.", "output": "Two RCTs investigating the effect of exercise on 246 institutionalized older patients showed no improvement in constipation. One study was of good quality, reporting adequate power and used an intention-to-treat analysis. The other was of fair quality." }, { "input": "Herbal supplements (such as aloe), alternative treatments (biofeedback), lubricants (mineral oil), and combination laxatives sold in the US have not been sufficiently studied in controlled trials to make a recommendation.", "output": "Two good-quality systematic reviews looked at 10 RCTs comparing laxatives with placebo, and 10 RCTs comparing 1 laxative with another. The studies generally had few participants, were of short duration, and were conducted in institutional settings. Most lacked power to make valid conclusions. These studies varied in the reported outcome measures, including stool frequency, stool consistency, straining, decrease in laxative use, and symptom scores. The reviews concluded that the best pharmacologic treatment for chronic constipation in the elderly has not been established." }, { "input": "Herbal supplements (such as aloe), alternative treatments (biofeedback), lubricants (mineral oil), and combination laxatives sold in the US have not been sufficiently studied in controlled trials to make a recommendation.", "output": "Biofeedback has been studied in adult populations, but no RCTs with placebo or sham-controls have been published." }, { "input": "Herbal supplements (such as aloe), alternative treatments (biofeedback), lubricants (mineral oil), and combination laxatives sold in the US have not been sufficiently studied in controlled trials to make a recommendation.", "output": "A high-quality systematic review of constipation management among adults of all ages in North America found a lack of quality RCTs examining herbal supplement treatment." }, { "input": "Herbal supplements (such as aloe), alternative treatments (biofeedback), lubricants (mineral oil), and combination laxatives sold in the US have not been sufficiently studied in controlled trials to make a recommendation.", "output": "The American College of Gastroenterology Chronic Constipation Task Force evidence-based guidelines make no reference to age, but state that evidence is best for treatment with psyllium, tegaserod, polyethylene glycol, and lactulose. They found insufficient evidence to support use of stimulants, stool softeners, lubricants, herbal supplements, biofeedback, and alternative treatments." }, { "input": "An abdominal kneading device can be used to treat chronic constipation, but the evidence is limited.", "output": "One before-after cohort study investigated an external kneading mechanical device (Free-Lax) that was applied to the abdomen for 20 minutes once daily in 30 randomly selected chronically constipated nursing home residents. Researchers found significant improvements in bowel movement frequency, stool consistency and volume, and colonic transit time without side effects." }, { "input": "Polyethylene glycol has not been studied in the elderly. A newer agent, lubiprostone (Amitiza), appears to be effective for the treatment of chronic constipation for elderly patients.", "output": "Lubiprostone, a chloride channel activator approved by the FDA for the treatment of chronic idiopathic constipation, has been studied in 6 placebo-controlled, double-blind, randomized Phase II and III clinical trials. In 2 unpublished pooled analyses of 3 of the trials, lubiprostone was found to be effective in a total of 220 elderly patients 65 years of age and older." }, { "input": "Polyethylene glycol has not been studied in the elderly. A newer agent, lubiprostone (Amitiza), appears to be effective for the treatment of chronic constipation for elderly patients.", "output": "Two high-quality systematic reviews, including medium- to high-quality RCTs of pharmacologic management of chronic constipation, found good evidence to support treatment with polyethylene glycol and tegaserod in adults of all ages. Of the 8 RCTs looking at polyethylene glycol, only 1 of the studies-a high-quality crossover comparison of polyethylene glycol vs placebo with 37 out-patient subjects-included a population with a mean age >60 years (mean age 62, range 42-89 years)." }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "There are samples of refusal of consent forms." }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "In addition to the discussion with the patient, the medical record should describe any involvement of family or other third parties. If imminently or potentially serious consequences are likely to result from patient refusal, health care providers might consider having the refusal signed and witnessed." }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "Medical records that clearly reflect the decision-making process can be pivotal in the success or failure of legal claims. (REF:6" }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "The reasons for the refusal should be documented." }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "The reasons for the refusal should be explored." }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "The general standard of disclosure has evolved to what an ordinary, reasonable patient would wish to know." }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "The law of informed consent defines the right to informed refusal. Thus, each case must establish: 1) that the patient or decision maker is competent, 2) that the decision is voluntary, and 3) that the physician disclosed the risks of the choice to the patient, including a discussion of risks and alternatives to treatment, and potential consequences of treatment refusal, including jeopardy to health or life." }, { "input": "Your documentation of a patient's refusal to undergo a test or intervention should include: an assessment of the patient's competence to make decisions, a statement indicating a lack of coercion; a description of your discussion with him (or her) regarding the need for the treatment, alternatives to treatment, possible risks of treatment, and potential consequences of refusal; and a summary of the patient's reasons for refusal.", "output": "A study of annotated case law revealed that the \"discharge against medical advice\" forms used by some hospitals might provide little legal protection." }, { "input": "Yes. Steroid injections are an effective first-line therapy for flexor tenosynovitis of the hand, with a number needed to treat [NNT] of 2.3 for injection of steroids and lidocaine.", "output": "A prospective, double-blinded RCT published by an orthopedic group in 1995 compared 24 patients with primary flexor tenosynovitis. Patients were injected with either 1 cc of betamethasone (Celestone 6 mg) and 3 cc of 1% lidocaine, or 4 cc of 1% lidocaine alone. A successful outcome was defined as absence of triggering and pain, both subjectively and on examination. Follow-up examination was completed for all patients at 3 weeks and 4 months after injection. The treatment group had success outcomes for 10 of 14 patients (71%) at 3 weeks and 9 of 14 patients (64%) at 4 months, compared with 2 of 10 (20%) at both 3 weeks and 4 months in the control group (NNT=2.3; P<.05 at 4 months). No significant side effects were noted. It is unclear how the study blinded the white, thick consistency of betamethasone compared with the clear nature of lidocaine alone." }, { "input": "Injection into the tendon sheath may not be critical to a successful outcome.", "output": "In a prospective, uncontrolled trial, 107 patients with flexor tenosynovitis were injected with 1 cc of betamethasone, 0.5 cc of 1% lidocaine, and 0.5 cc of radio opaque dye. Some patients got their injections in the tendon sheath at the A1 pulley site, others got their injections in the subcutaneous tissue surrounding the pulley, and a third group got injections in both sites. Patients graded their relief subjectively as either good (total alleviation of symptoms), fair (lasting improvement), or poor (only transient improvement or none at all). Those who received an intrasheath injection reported good results 47% of the time at 2 weeks follow-up, compared with 70% and 50% for patients in the subcutaneous and mixed groups, respectively. There was no statistically significant difference between the groups, suggesting that the exact location of injection may not be important." }, { "input": "For de quervain's tenosynovitis, steroid injections without splinting are more effective than injection plus splinting or splinting alone. The cure rates are 83% (steroid alone), 61% (steroid plus splinting), and 14% (splinting alone).", "output": "A pooled quantitative literature search concerning the treatment of de Quervain's tenosynovitis compared 7 studies (a total of 459 wrists) with identical diagnostic and success criteria. Average follow-up was 9.6 months (range, 1 week to 7 years). There were no control groups in the studies, and none of the studies were randomized. Of the 226 cases treated with steroid injection alone, 83% were cured, though 30 of these needed a second injection. Sixty-one percent of those treated with injection and splint were cured, while 14% treated with splint alone reported cure." }, { "input": "For de quervain's tenosynovitis, steroid injections without splinting are more effective than injection plus splinting or splinting alone. The cure rates are 83% (steroid alone), 61% (steroid plus splinting), and 14% (splinting alone).", "output": "A retrospective study compared steroid injection with splinting and nonsteroidal anti-inflammatory drugs (NSAIDs). Researchers stratified subjects into minimal, mild, or moderate-to-severe, based on their severity of disease and limitation on their activities of daily living. Mean follow-up was 2.3 years. Of those cases treated with splinting and NSAIDs, 15 of 17 in the minimal group had resolution of symptoms, but only 4 of 20 in the mild group and 2 of 8 in the moderate-to-severe group had symptoms resolve. The injection group obtained better results, with 100% of cases in the minimal and mild groups resolving and 76% of those in the more severe group resolving completely, with an additional 7% reporting improvement." }, { "input": "Injecting into the tendon compartments was more effective than injecting into the surrounding soft tissues.", "output": "In 1 small, controlled, prospective, double-blinded study, the authors attempted to correlate clinical relief of de Quervain's tenosynovitis with accuracy of injection into the first dorsal compartment. The researchers enrolled 19 patients. The same hand surgeon injected 3 cc of 1% lidocaine, 1 cc betamethasone, and 1 cc Omnipaque 300 dye into the abductor pollicis longus sheath and then attempted, with ulnar deviation of the needle, to fill the extensor pollicis brevis sheath. Patients were followed-up at 1 month and 3 months postinjection. Success-defined as a negative Finkelstein's test, absence of pain, and normal activities of daily living-was noted in 11 of 19 patients at 3 months. In a radiographic check, 4 of 5 of the patients with dye in both compartments were asymptomatic, while the 3 who had no dye in either compartment remained symptomatic. This suggests that the location of injection may be important in de Quervain's tenosynovitis." }, { "input": "The risk of bowel strangulation is estimated to be small-less than 1% per year.", "output": "A retrospective study of 70 patients with incarcerated inguinal hernias presenting for emergency surgery in Northern Spain reported a cumulative 2.8% probability of strangulation at 3 months, rising to 4.5% after 2 years. This study did not include patients presenting for elective repair of hernias, and therefore it likely overestimated the rate of strangulation among patients in a primary care setting." }, { "input": "The risk of bowel strangulation is estimated to be small-less than 1% per year.", "output": "The mean follow-up time in a trial which had 80 control group participants, was 1.6 years; 29% of patients eventually crossed over for repair." }, { "input": "The risk of bowel strangulation is estimated to be small-less than 1% per year.", "output": "In a trial with 364 control group patients, median follow-up was only 3.2 years (maximum 4.5 years), and by 4 years 31% of patients had crossed over to the treatment group for elective repair." }, { "input": "The risk of bowel strangulation is estimated to be small-less than 1% per year.", "output": "In 2 randomized controlled trials (RCTs) comparing elective repair of inguinal hernias with watchful waiting, the cohorts who made up the control groups experienced strangulation rates of 1.8 per thousand (0.18%) and 7.9 per thousand (0.79%) occurrences per patient-year." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "A chart review found that the risk of strangulation was higher for hernias of shorter duration." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "Older age increases the risk of a poor outcome, peaking in the seventh decade." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "Patient comorbidity and late hospitalization make emergent repair more risky." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "A Turkish study of patients needing emergent surgical repair found morbidity to be significantly related to American society of Anesthesiologists (ASA) class, with mortality rates of 3% and 14% for ASA class III and IV patients, respectively. This was a retrospective chart review that analyzed factors responsible for unfavorable outcomes; it found increased complications in hernia patients who had coexisting disease, hernias of longer duration, as well as higher ASA class. This study found the need for emergent repair peaked for patients 70 to 80 years of age." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "Another retrospective study found the need for emergent repair peaked for patients 70 to 80 years of age." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "The Spanish retrospective review of emergent surgical repair of incarcerated hernias (noted earlier) reported a 3.4% postoperative mortality rate. All deaths were among patients over 65 years of age and ASA class III or IV. This review also found more postoperative complications and a higher mortality for hernias present for more than 10 years." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "A retrospective study from Israel also showed that patients who underwent emergency repair were older, had a longer history of herniation than those undergoing elective repair, and had higher ASA scores." }, { "input": "Experts recommend repair for patients with risk factors for poor outcomes after potential strangulation. These risk factors include advanced age, limited access to emergency care, significant concomitant illness, inability to recognize symptoms of bowel incarceration, and poor operative risk (American society of Anesthesiologists class III and IV).", "output": "A case-control study found that the risk of strangulation was higher for hernias of shorter duration." }, { "input": "It is reasonable to offer elective surgery or watchful waiting to low-risk patients who understand the risks of strangulation.", "output": "The avoidable risks of strangulation and emergent operation lead most experts to favor operative treatment." }, { "input": "No studies directly compare low-density lipoprotein (LDL) levels <70 mg/dL to levels of 71 to 100 mg/dL in very-high-risk patients. However, no evidence suggests a \"floor\" for LDL cholesterol levels beyond which further reductions of heart disease risk can't be achieved.", "output": "A 19-trial meta-regression analysis (81,859 patients with stable CHD) demonstrated that each 1% reduction in LDL cholesterol corresponded to a 1% decrease in risk for CHD. This result held true regardless of different approaches to treatment, which included diet, bile-acid sequestrant, statins, or ileal bypass surgery." }, { "input": "No studies directly compare low-density lipoprotein (LDL) levels <70 mg/dL to levels of 71 to 100 mg/dL in very-high-risk patients. However, no evidence suggests a \"floor\" for LDL cholesterol levels beyond which further reductions of heart disease risk can't be achieved.", "output": "The ENHANCE study, a double-blind, randomized trial conducted over a period of 24 months, compared the effects of 80 mg per day of simvastatin with either placebo or 10 mg per day of ezetimibe in 720 patients with familial hypercholesterolemia. The primary outcome measure was a change in intima-media thickness of the walls of the carotid and femoral arteries. The results of the study have raised the question of whether it is appropriate to target LDL cholesterol primarily to reduce CHD risk, because ezetimibe did not affect carotid artery intima-media thickness, despite its effectiveness in reducing LDL cholesterol." }, { "input": "No studies directly compare low-density lipoprotein (LDL) levels <70 mg/dL to levels of 71 to 100 mg/dL in very-high-risk patients. However, no evidence suggests a \"floor\" for LDL cholesterol levels beyond which further reductions of heart disease risk can't be achieved.", "output": "Two meta-analyses supported the use of intensive statin regimens to reduce cardiovascular risk, but didn't find evidence for lowering LDL to a particular target level." }, { "input": "No studies directly compare low-density lipoprotein (LDL) levels <70 mg/dL to levels of 71 to 100 mg/dL in very-high-risk patients. However, no evidence suggests a \"floor\" for LDL cholesterol levels beyond which further reductions of heart disease risk can't be achieved.", "output": "The safety and tolerability of higher and standard statin doses are similar." }, { "input": "No studies directly compare low-density lipoprotein (LDL) levels <70 mg/dL to levels of 71 to 100 mg/dL in very-high-risk patients. However, no evidence suggests a \"floor\" for LDL cholesterol levels beyond which further reductions of heart disease risk can't be achieved.", "output": "A meta-analysis concluded that intensive lipid lowering with high-dose statin therapy confers a significant benefit over standard-dose therapy for preventing predominantly nonfatal cardiovascular events." }, { "input": "No studies directly compare low-density lipoprotein (LDL) levels <70 mg/dL to levels of 71 to 100 mg/dL in very-high-risk patients. However, no evidence suggests a \"floor\" for LDL cholesterol levels beyond which further reductions of heart disease risk can't be achieved.", "output": "In the Heart Protection Study, patients with CHD, other occlusive arterial disease, or diabetes were randomized to 40 mg simvastatin or placebo. Simvastatin reduced relative risk of CHD-regardless of baseline LDL-even in patients with a baseline LDL <116 mg/dL. Further analysis showed that among the many types of high-risk patients, 5 years of simvastatin at 40 mg daily would prevent about 70 to 100 people in 1000 from suffering at least 1 major vascular event (myocardial infarction, stroke, or the need for revascularization). Interestingly, patients with relatively smaller reductions in LDL (those in the lowest third) showed the same decrease in CHD events as patients in the highest third-although the overall difference in LDL wasn't large." }, { "input": "Comparing larger (80 mg) with smaller doses of atorvastatin shows that larger doses reduce LDL and major cardiac events more than smaller doses. No studies report patient-oriented outcomes of treatments for patients who fail to reach target LDL levels <100 mg/dL.", "output": "The Treating to New Targets (TNT) study showed that in patients with stable CHD, intensive lipid lowering with atorvastatin 80 mg daily delivered significant clinical benefit beyond that provided by atorvastatin 10 mg daily. The mean LDL achieved in TNT was 77 mg/dL on 80 mg atorvastatin, compared with 101 mg/dL on 10 mg. Patients with diabetes who took 80 mg had a 2.26% absolute risk reduction for major cardiovascular events (number needed to treat=43). Secondary outcomes-including all cardiovascular events, cerebrovascular events, and congestive heart failure with hospitalization-also improved on 80 mg atorvastatin. Although this study enrolled a total of 10,001 patients with clinically evident CHD, it was not sufficiently powered to demonstrate differences in overall mortality between the 2 groups. While it is clear that patients in the 80-mg group had better outcomes than patients in the lower-dose group, the exact role of LDL lowering cannot be easily separated from other potentially beneficial effects of the higher dose of atorvastatin." }, { "input": "Regular physical activity decreases long-term weight gain.", "output": "A systematic review of the effects of physical activity on weight reduction and maintenance analyzed 46 studies, including 8 RCTs that investigated interventions to reduce weight and 3 that examined measures to maintain it. More than 80% of the studies showed a benefit from physical exercise. Prevention of weight gain appears to be dose-dependent. More exercise leads to less weight gain; a minimum of 1.5 hours per week of moderate exercise is needed to prevent weight gain." }, { "input": "Regular physical activity decreases long-term weight gain.", "output": "A systematic review of obesity prevention studies found 9 RCTs demonstrating that dietary and physical activity interventions can prevent weight gain, but lacking sufficient evidence to recommend a specific type of program." }, { "input": "Decreasing fat intake may decrease weight gain.", "output": "The Women's Health Initiative studied 46,808 postmenopausal women between 50 and 79 years of age who were randomly assigned to an intervention or control group. The intervention group received intensive group and individual counseling from dieticians aimed at reducing fat intake to 20%, increasing consumption of vegetables and fruits to 5 or more servings per day, and increasing consumption of grains to 6 or more servings per day. The control group received dietary education materials. Neither group had weight loss or calorie restriction goals or differences in physical activity. The intervention group had a mean decrease in weight 1.9 kg greater than the controls at 1 year (P<.001) and 0.4 kg at 7.5 years (P<.01). Weight loss was greater in women who consumed more fruits and vegetables and greatest among women who decreased energy intake from fat." }, { "input": "Increasing fruit and vegetable consumption may decrease weight gain.", "output": "The Women's Health Initiative studied 46,808 postmenopausal women between 50 and 79 years of age who were randomly assigned to an intervention or control group. The intervention group received intensive group and individual counseling from dieticians aimed at reducing fat intake to 20%, increasing consumption of vegetables and fruits to 5 or more servings per day, and increasing consumption of grains to 6 or more servings per day. The control group received dietary education materials. Neither group had weight loss or calorie restriction goals or differences in physical activity. The intervention group had a mean decrease in weight 1.9 kg greater than the controls at 1 year (P<.001) and 0.4 kg at 7.5 years (P<.01). Weight loss was greater in women who consumed more fruits and vegetables and greatest among women who decreased energy intake from fat." }, { "input": "Combined dietary and physical activity interventions prevent weight gain.", "output": "A systematic review of obesity prevention studies found 9 RCTs demonstrating that dietary and physical activity interventions can prevent weight gain, but lacking sufficient evidence to recommend a specific type of program." }, { "input": "Family involvement helps maintain weight.", "output": "A systematic review of family-spouse involvement in weight control and weight loss found that involving spouses tended to improve the effectiveness of weight control." }, { "input": "Family involvement helps maintain weight.", "output": "A family-based trial of weight gain prevention randomized 82 families to a group that was encouraged to eat 2 servings of cereal a day and increase activity by 2000 steps a day, or to a control group. In the intervention group, body mass index (BMI) decreased by 0.4% in mothers (P=.027), and BMI percentage for age decreased by 2.6% in daughters (P<.01). Male family members showed no significant differences, however." }, { "input": "Daily or weekly weight monitoring reduces long-term weight gain.", "output": "An RCT, found an association between self-weighing and preventing weight gain. Patients who weighed themselves daily or weekly were less likely to gain weight than patients who weighed themselves monthly, yearly, or never." }, { "input": "Daily or weekly weight monitoring reduces long-term weight gain.", "output": "A study found an association between self-weighing and preventing weight gain. Patients who weighed themselves daily or weekly were less likely to gain weight than patients who weighed themselves monthly, yearly, or never." }, { "input": "Clinic-based, direct-contact, and Web-based programs that include behavior modification may reduce weight gain in adults.", "output": "In one study, 67 patients were assigned to 4 months of clinic-based or home-based counseling to increase exercise and reduce fat intake, or to a control group. Weight change was-1.9 kg in the clinic-based group,-1.3 kg in the home-based group, and +0.22 kg in the control group (P=.007)." }, { "input": "Clinic-based, direct-contact, and Web-based programs that include behavior modification may reduce weight gain in adults.", "output": "An RCT randomized 284 healthy 25- to 44-year-old women with BMI <30 kg/m2 to group meetings, lessons by mail, or a control group that received an information booklet. The study found no significant difference among the 3 groups in weight maintenance at a 3-year follow-up; 40% maintained weight, and 60% gained more than 2 pounds." }, { "input": "Clinic-based, direct-contact, and Web-based programs that include behavior modification may reduce weight gain in adults.", "output": "In one study, 1032 overweight or obese adults with hypertension and/or dyslipidemia who completed a weight-loss program were randomly assigned to receive monthly personal contact, unlimited access to a Web-based intervention, or a self-directed control group. At 30 months, participants in the personal contact group had regained less weight than the Web-based or control groups (4.0, 5.1, and 5.5 kg, respectively; P<.01)." }, { "input": "Behavior modification delivered by personal contact is more effective than mail, Internet, or self-directed modification programs", "output": "In a study, 1032 overweight or obese adults with hypertension and/or dyslipidemia who completed a weight-loss program were randomly assigned to receive monthly personal contact, unlimited access to a Web-based intervention, or a self-directed control group. At 30 months, participants in the personal contact group had regained less weight than the Web-based or control groups (4.0, 5.1, and 5.5 kg, respectively; P<.01)." }, { "input": "Though fatigue is a commonly reported symptom, high-quality studies evaluating it as a marker for diseases among menopausal women are lacking. Middle-aged women who report fatigue are more apt to screen positive for clinical depression or anxiety.", "output": "A prospective cohort study, using a 1-page questionnaire that included 2 fatigue scales, identified 276 (24%) of 1159 primary care patients who indicated fatigue as a major problem. The mean age of patients was 57 years and 66% were women. Extensive laboratory testing was not helpful in determining the cause of fatigue. The Beck Depression Inventory, the Modified Somatic Perception Questionnaire, and the Social Readjustment Rating Scale identified depression or anxiety in 80% of patients with fatigue and 12% of controls. There are no similar studies for strictly menopausal women." }, { "input": "Fatigue may signal obstructive sleep apnea.", "output": "In a retrospective chart review of patients referred for evaluation of snoring, 22 (91%) of the women with studies) were more likely to report daytime fatigue as a presenting symptom than were the 44 (55%) of men with obstructive sleep apnea (P<.01). Most striking was a sub-group (40%) of women with documented obstructive sleep apnea who reported only fatigue and morning headache but did not note apnea or restless sleep. (ERF:6)" }, { "input": "For menopausal women with cardiac risk factors, extreme fatigue may be a sign of coronary artery disease.", "output": "A retrospective study of 515 women 4 to 6 months after a myocardial infarction explored self-reported symptoms. The mean age was 66\u00b112 years and 93% were white. Unusual fatigue was the most frequent prodromal symptom experienced by 70.7% of women 1 month before a myocardial infarction, with 42.9% reporting fatigue in the acute setting. Though this retrospective study is limited both by its methodological quality and by the narrow population studied, the results suggest a gender difference between men and women in their report of symptoms of coronary artery disease." }, { "input": "Yes. Overweight at any age in childhood increases the risk for overweight in adulthood. The relative risk (RR) ranges from 1.9 to 10.1 and increases as children get older. Not all overweight children become overweight adults, however.", "output": "A 2008 systematic review found 25 prospective or retrospective longitudinal studies that examined the risk of overweight in adulthood based on overweight in childhood or adolescence. Studies had to include at least 1 anthropomorphic measurement before age 18 and at least 1 after age 18. The informativeness and validity of the studies were assessed using a standard evaluation tool. Because the review sought to provide results that could be generalized to large populations, it didn't include studies of specific populations, such as former premature infants. All of the 13 studies judged to be high quality found an elevated RR or odds ratio (OR) for adult obesity among participants who had been overweight as children. The authors didn't calculate a composite measure of effect, but RRs in the individual studies ranged from 1.9 to 10.1. The systematic review considered children (\u226412 years) and adolescents (>12 years) separately. Four high-quality studies assessed how many overweight children became overweight adults; 2 high-quality studies examined how many overweight children became obese adults. Overweight children had RRs between 1.9 and 3.6 for being overweight in adulthood compared with average-weight children; 1 study reported an OR of 7.0. One study showed older overweight children to be at greater risk than younger children for overweight in adulthood: children who were overweight at 2 years of age had an RR of 2.7, whereas children who were overweight at 11 years had an RR of 3.6. Obese children had similar results. A study of 4 age cohorts showed that children who were obese at 1 or 2 years of age had an OR of 1.3 for obesity in adulthood compared with average-weight peers. Obese children in the 3- to 5-year-old cohort had an OR of 4.7; obese children in the 6- to 9-year-old cohort had an OR of 8.8; and obese 10- to 14-year-olds had an OR of 22.3. As with children, overweight adolescents had a higher risk of being overweight in adulthood. And the association between older age and higher ORs persisted into adolescence. One study found an OR of 17.5 for adult overweight among youngsters who were overweight at 10 to 14 years of age and an OR of 22.3 for adolescents who were overweight at 15 to 17 years. The systematic review also revealed sex differences. Two studies showed that overweight or obese boys were not only more likely to be overweight in adulthood than their average-weight peers (OR=15.0 in 1 study; RR=9.8 in the other), but also more likely to be overweight later in life than overweight or obese girls. The girls had an OR of 12.0 for adult overweight in 1 study and an RR of 6.8 in the other." }, { "input": "The cremasteric reflex or a nontender testicle usually excludes testicular torsion, but case reports have noted the opposite to be true.", "output": "A consecutive case series evaluated 245 boys, newborn to 18 years of age, with acute scrotal swelling. None of the 125 subjects who had an intact cremasteric reflex had ipsilateral testicular torsion. The cremasteric reflex was absent in all 56 subjects with testicular torsion. An absent cremasteric reflex in boys with acute scrotal swelling had a sensitivity of 100% (95% confidence interval [CI], 91%-100%), a specificity of 66% (95% CI, 59%-72%), and a likelihood ratio of a negative test (presence of a cremasteric reflex) of 0.01 (95% CI, 0.001-0.21)." }, { "input": "The cremasteric reflex or a nontender testicle usually excludes testicular torsion, but case reports have noted the opposite to be true.", "output": "A retrospective study reviewed the records of 90 hospitalized patients, 18 years or younger, who were discharged with a diagnosis of testicular torsion, epididymitis, or torsion appendix testis. The cremasteric reflex was absent, and testicular tenderness present, in all 13 patients with testicular torsion." }, { "input": "An abnormal testicular lie can help establish the diagnosis, but occurs in fewer than 50% of cases.", "output": "The presence or absence of physical exam findings-such as abnormal testicular lie has 46% sensitivity, 99% specificity." }, { "input": "Other findings are less reliable.", "output": "Tender epididymitis: 23% sensitivity, 20% specificity. Isolated tenderness: 4% sensitivity, 83% specificity." }, { "input": "The standard of care for diagnosing testicular torsion relies on studies beyond the physical examination.", "output": "The American College of Radiology recommends color Doppler ultrasound (CDU) or radionuclide scrotal imaging (RNSI) to evaluate testicular perfusion. The group notes that 'although some authors still suggest immediate surgical exploration in patients with a strong clinical impression of testicular ischemia, if either CDU or RNSI is readily available and can be performed within 30 to 60 minutes of the request to simultaneously prepare an operating room, there is ample evidence that fewer patients with infection will be operated on.'" }, { "input": "The standard of care for diagnosing testicular torsion relies on studies beyond the physical examination.", "output": "UpToDate notes that 'the diagnosis of testicular torsion can be made clinically,' but states that 'radiologic evaluation (a color Doppler ultrasound or nuclear scan of the scrotum) should be undertaken if the certainty of the diagnosis is in question and the performance of imaging studies will not significantly delay treatment.'" }, { "input": "The standard of care for diagnosing testicular torsion relies on studies beyond the physical examination.", "output": "When evaluating patients suspected to have testicular torsion, the European Society for Pediatric Urology (ESPU) recommends looking for absence of a cremasteric reflex and abnormal testicular position. The ESPU notes that 'in many cases it is not easy to determine the cause of acute scrotum based on history and physical examination alone.' The society recommends using Doppler ultrasound as an adjunct to the history and physical." }, { "input": "Progesterone produces a small but significant decrease in miscarriage among pregnant women with 3 or more unexplained pregnancy losses.", "output": "A Cochrane meta-analysis on the use of progesterone to prevent pregnancy loss looked at a subset of 3 small RCTs that evaluated women with 3 or more pregnancy losses. Patients with primary recurrent spontaneous abortion (RSA) (no prior live births), were not differentiated from those with secondary RSA (previous live birth with subsequent miscarriages). Progesterone administration resulted in a significant reduction in miscarriage compared with placebo (odds ratio [OR]=0.37; 95% confidence interval [CI], 0.17-0.91), independent of administration routes (oral, vaginal, or intramuscular). This benefit was lost in the larger meta-analysis when studies containing women with fewer than 3 pregnancy losses were included." }, { "input": "Human chorionic gonadotropin (HCG) reduces the rate of recurrent pregnancy loss among women with 2 or more unexplained pregnancy losses.", "output": "A meta-analysis reviewed 4 trials (n=180 total) of varying methodological quality, which were constructed to determine if women, with at least 2 consecutive miscarriages of unknown cause, derive any protective effect when they receive HCG during the first trimester. Although the overall outcome favored the use of HCG (OR=0.26 compared with placebo; 95% CI, 0.14-0.52), the trials contained major methodological weaknesses (poor description of methods, no power calculations, selection and unclear randomization techniques)." }, { "input": "Four types of immunotherapy are ineffective for preventing miscarriage.", "output": "A systematic review of 22 RCTs evaluating 4 different types of immunotherapy for recurrent miscarriage found no significant improvement in live birth rates. All studies were of high quality with a low level of bias. Only onelacked double-blinding. Immunotherapy types included: paternal leukocyte immunization (PLI) (11 trials, 596 women) (OR=1.05; 95% CI, 0.75-1.47); intravenous immune globulin (IVIG) (OR=0.98; 95% CI, 0.61-1.58); third-party donor cell immunization (3 trials, 156 women) (OR=1.39; 95% CI, 0.68-2.82); and trophoblast membrane infusion (1 trial, 37 women) (OR=0.40; 95% CI, 0.11-1.45)." }, { "input": "Four types of immunotherapy are ineffective for preventing miscarriage.", "output": "An RCT evaluating PLI (32 patients) vs placebo (19 patients) among women with unexplained primary RSA did find significantly higher birth rates with PLI (84% vs 25%; P=.001). This small study used different techniques than previous PLI studies." }, { "input": "Four types of immunotherapy are ineffective for preventing miscarriage.", "output": "An RCT comparing PLI with placebo among 79 women with primary RSA of unknown cause again found no significant difference in live birth rates (89% vs 71%, respectively)." }, { "input": "Four types of immunotherapy are ineffective for preventing miscarriage.", "output": "A later meta-analysis of 5 RCTs including a total of 246 patients also found that IVIG did not improve the subsequent live birth rate for women with a history of primary or secondary RSA (OR=0.98; 95% CI, 0.45-2.13)." }, { "input": "Aspirin therapy is ineffective for preventing recurrent miscarriage for women who do not have an autoimmune explanation for previous pregnancy losses.", "output": "A second (unblinded) trial randomized 805 women from a large referral center (mean age 34 years) with a history of first-trimester RSA (not differentiated between primary and secondary RSA) of unknown cause to either 75 mg of aspirin daily or no treatment. There was no significant difference in the live birth rate between those who took aspirin (251/367; 68.4%) and those who did not (278/438; 63.5%; OR=1.24; 95% CI, 0.93-1.67)." }, { "input": "Aspirin therapy is ineffective for preventing recurrent miscarriage for women who do not have an autoimmune explanation for previous pregnancy losses.", "output": "An RCT involving 54 pregnant women (mean age 32.7 years) with a history of primary RSA of unknown cause (negative standard workup) evaluated 50 mg of aspirin daily (n=27) vs placebo (n=27). The method of blinding was not reported. The live birth rate was identical for the 2 groups (88%)." }, { "input": "Breastfeeding protects against all-cause diarrhea in infants.", "output": "Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developing countries." }, { "input": "Breastfeeding protects against all-cause diarrhea in infants.", "output": "Breastfeeding has been associated with decreased overall rates of diarrhea in infants in developed countries." }, { "input": "Several studies demonstrate that breastfeeding does not prevent acquisition of rotavirus but does decrease the severity of its course.", "output": "Prospective cohort studies conducted in Canada and the United States showed no difference in the incidence of rotavirus gastroenteritis between infants up to 2 years of age who were breastfed and those who were not. Although differences were not found between either the incidence or the duration of rotavirus infections, these studies showed a significant decrease in the frequency of vomiting among breastfed infants." }, { "input": "Several studies demonstrate that breastfeeding does not prevent acquisition of rotavirus but does decrease the severity of its course.", "output": "A case-control study in Bangladesh suggests that breastfed infants have a higher incidence of rotavirus diarrhea, but selection of diarrhea patients as controls may have underestimated the protective effect. Although breastfeeding was not found to provide overall protection from developing rotavirus gastroenteritis, exclusive breastfeeding appeared to protect against severe rotavirus diarrhea for infants aged <2 years." }, { "input": "Several studies demonstrate that breastfeeding does not prevent acquisition of rotavirus but does decrease the severity of its course.", "output": "A US study showed that risk for rotavirus infection did not differ for infants who were exclusively breastfed, partially breastfed, or exclusively formula-fed. However, the breastfed infants were more likely to have milder symptoms." }, { "input": "Athletes sustaining a concussion should be held from contact activities a minimum of 7 days; they must be asymptomatic and their coordination and neuropsychological tests should have returned to their pre-injury baseline.", "output": "Sport concussion assessments should include testing for cognition, postural stability, and self-reported symptoms. Results can then be compared with each individual's preseason baseline. Examples of screening instruments include SCAT (the Sideline Concussion Assessment Tool), SAC (the Standardized Assessment of Concussion), BESS (the Balance Error Scoring System), as well as ImPACT or other neurocognitive tests, to evaluate and document memory, brain processing speed, reaction time, and postconcussive symptoms. Results from these tests should be interpreted in light of all other aspects of the injury (physical exam, age, sex, history of previous concussion, etc) to guide the decision on returning to play. After neurological and balance symptoms have resolved, noncontact exercise may be allowed. When neuropsychological testing has returned to preseason baseline, full contact may be permitted." }, { "input": "Athletes sustaining a concussion should be held from contact activities a minimum of 7 days; they must be asymptomatic and their coordination and neuropsychological tests should have returned to their pre-injury baseline.", "output": "Sport concussion assessments should include testing for cognition, postural stability, and self-reported symptoms. Results can then be compared with each individual's preseason baseline. Examples of screening instruments include SCAT (the Sideline Concussion Assessment Tool), SAC (the Standardized Assessment of Concussion), BESS (the Balance Error Scoring System), as well as ImPACT or other neurocognitive tests, to evaluate and document memory, brain processing speed, reaction time, and postconcussive symptoms. Results from these tests should be interpreted in light of all other aspects of the injury (physical exam, age, sex, history of previous concussion, etc) to guide the decision on returning to play. After neurological and balance symptoms have resolved, noncontact exercise may be allowed. When neuropsychological testing has returned to preseason baseline, full contact may be permitted." }, { "input": "Athletes sustaining a concussion should be held from contact activities a minimum of 7 days; they must be asymptomatic and their coordination and neuropsychological tests should have returned to their pre-injury baseline.", "output": "Sport concussion assessments should include testing for cognition, postural stability, and self-reported symptoms. Results can then be compared with each individual's preseason baseline. Examples of screening instruments include SCAT (the Sideline Concussion Assessment Tool), SAC (the Standardized Assessment of Concussion), BESS (the Balance Error Scoring System), as well as ImPACT or other neurocognitive tests, to evaluate and document memory, brain processing speed, reaction time, and postconcussive symptoms." }, { "input": "Athletes sustaining a concussion should be held from contact activities a minimum of 7 days; they must be asymptomatic and their coordination and neuropsychological tests should have returned to their pre-injury baseline.", "output": "A cohort study of US college football players found that while postural stability commonly returns in just a day or 2, cognitive recovery often takes 3 to 5 days, and symptoms last over 7 days post-injury for 1 of 8 concussed athletes." }, { "input": "Athletes sustaining a concussion should be held from contact activities a minimum of 7 days; they must be asymptomatic and their coordination and neuropsychological tests should have returned to their pre-injury baseline.", "output": "A prospective cohort study of boxers at the US Military Academy found that it takes 3 to 7 days for recovery of neurocognitive function" }, { "input": "Athletes sustaining a concussion should be held from contact activities a minimum of 7 days; they must be asymptomatic and their coordination and neuropsychological tests should have returned to their pre-injury baseline.", "output": "A prospective study of high-school athletes demonstrated that neuropsychological dysfunction takes a week or longer to resolve in \"ding\" concussions (defined as no loss of consciousness and overt symptoms resolved within 15 minutes)." }, { "input": "High-risk athletes (eg, those with a history of previous concussion, high-school age or younger, or female) may need to avoid contact even after all these criteria are met.", "output": "A large prospective cohort study of 2900 US college football players found that players with 1 previous concussion had a 40% increased risk of future concussion, and those with 3 previous concussions had a three-fold increase in risk." }, { "input": "High-risk athletes (eg, those with a history of previous concussion, high-school age or younger, or female) may need to avoid contact even after all these criteria are met.", "output": "High school students with concussions are 3 to 4 days slower in recovering memory function than college students" }, { "input": "High-risk athletes (eg, those with a history of previous concussion, high-school age or younger, or female) may need to avoid contact even after all these criteria are met.", "output": "Women with concussions are 1.7 times more likely to have cognitive impairment than men." }, { "input": "For children with primary nocturnal enuresis, treatment with enuresis alarms reduced the number of wet nights by almost 4 per week, with almost half of patients remaining dry for 3 months after treatment.", "output": "The Cochrane Incontinence Group Trials demonstrated that enuresis alarms led to nearly 4 fewer wet nights per week compared with no treatment or placebo (weighted mean difference [WMD]=-3.65; 95% confidence interval [CI], -4.52 to -2.78). The relative risk of failure was 0.36 compared with placebo (95% CI, 0.26 to 0.40). The number needed to treat (NNT) to achieve 14 consecutive dry nights is 2. About half the children relapse after stopping treatment, compared with nearly all children after control interventions (55% vs 99%). Evidence is insufficient to say whether the addition of dry bed training (scheduled awakenings, cleanliness training, social reinforcement, positive practice) improves the outcomes. Alarms that wake the child immediately (vs a time delay) and alarms that wake the child (instead of the parents) were slightly more effective." }, { "input": "Desmopressin (DDAVP) and tricyclic drugs reduce the number of wet nights by 1 to 2 per week during treatment, although the effect is not sustained after treatment is finished.", "output": "A meta-analysis also showed that desmopressin (10-60 \u00b5g) at bedtime reduced bedwetting by 1 to 2 nights per week compared with placebo (WMD=1.34; 95% CI, -1.57 to -1.11 with a dose of 20 \u00b5g). The NNT to achieve 14 consecutive dry nights is 7. However, the data suggest once treatment stops, there is little difference between desmopressin and placebo. This combination treatment did not show a benefit with failure rates (not attaining 14 consecutive dry nights) or a statistically significant difference in failure and relapse rates once treatment stopped." }, { "input": "Desmopressin (DDAVP) and tricyclic drugs reduce the number of wet nights by 1 to 2 per week during treatment, although the effect is not sustained after treatment is finished.", "output": "Some evidence suggested that a desmopressin dose higher than 10-60 \u00b5g was more likely to decrease the number of wet nights; however, there was no difference in cure rates. Evidence comparing intranasal with oral administration is insufficient." }, { "input": "Desmopressin (DDAVP) and tricyclic drugs reduce the number of wet nights by 1 to 2 per week during treatment, although the effect is not sustained after treatment is finished.", "output": "In a Cochrane review, children treated with desmopressin had 1.7 fewer wet nights (WMD=1.7; 95% CI, -2.95 to -0.45) in the first week compared with children treated with alarms. However, at the end of 3 months, alarms were associated with 1.4 fewer wet nights per week than children treated with desmopressin (WMD=1.4; 95% CI, 0.14 to 2.66)." }, { "input": "Desmopressin (DDAVP) and tricyclic drugs reduce the number of wet nights by 1 to 2 per week during treatment, although the effect is not sustained after treatment is finished.", "output": "One RCT in which desmopressin nonresponders were supplemented with alarms showed no added benefit in remission rates compared with conditioning alarms plus placebo (51% vs 48% in achieving 28 dry nights). Neither was there added benefit in relapse rates once treatment stopped." }, { "input": "Desmopressin (DDAVP) and tricyclic drugs reduce the number of wet nights by 1 to 2 per week during treatment, although the effect is not sustained after treatment is finished.", "output": "Children treated with tricyclic drugs compared with those treated with placebo had approximately 1 less night of enuresis per week (WMD=1.19; 95% CI, -1.56 to-0.82).8 More children achieved 14 dry nights while on imipramine compared with placebo (21% vs 5%; NNT=6); however, this advantage was not sustained once treatment finished (96% vs 97% relapsed). Little evidence exists to compare desmopressin with tricyclic drugs." }, { "input": "Dry bed training with an alarm results in an additional reduction of wet nights over alarms alone.", "output": "Dry bed training refers to comprehensive regimes, including enuresis alarms, waking routines, positive practice, cleanliness training, and bladder training in various combinations. A meta-analysis examining dry bed training including an enuresis alarm showed children had fewer wet nights compared with children receiving no treatment (relative risk [RR] of failure=0.17; 95% CI, 0.11-0.28). Additionally, more children remained dry after treatment stopped (RR of relapse=0.25; 95% CI, 0.16-0.39). However, evidence was not sufficient to show a remission benefit for dry bed training without an alarm (RR of failure=0.82; 95% CI, 0.6-1.02), highlighting the key role for alarm therapy. On the other hand, dry bed training including bed alarms may reduce the relapse rate compared with alarm monotherapy (RR for failure or relapse=0.5; 95% CI, 0.31-0.8)." }, { "input": "Treating elderly patients with pantoprazole (Protonix) after resolution of acute esophagitis results in fewer relapses than with placebo.", "output": "A multicenter, randomized, double-blind trial of GERD maintenance therapy started with an initial open phase in which elderly patients with GERD and documented esophagitis were treated and then had documented resolution of esophagitis by endoscopy after 6 months. The researchers then randomized 105 of these elderly patients to receive treatment with either low-dose (20 mg/d) pantoprazole or placebo for 6 months. Endoscopy was performed after 12 months for all patients, unless indicated sooner. Intention-to-treat analysis showed a disease-free rate of 79.6% (95% CI, 68.3-90.9) in the treatment group, compared with 30.4% (95% CI, 18.3-42.4) in the placebo group (number needed to treat [NNT]=2). Symptom reports concerning the same patients also suggest a marked drop in symptoms that correlated with healing." }, { "input": "Laparoscopic antireflux surgery for treating symptomatic GERD among elderly patients without paraesophageal hernia reduces esophageal acidity, with no apparent increase in postoperative morbidity or mortality compared with younger patients", "output": "A prospective, nonequivalence, before-after study compared efficacy of, and complications from, laparoscopic surgery for symptomatic GERD between younger and older (\u226565 years) patients. The investigators examined postoperative morbidity and mortality for 359 patients referred for laparoscopic surgery, either a partial or Nissen (full) fundoplication. They excluded those requiring more extensive surgery or repair of paraesophageal hernia. The 42 elderly patients had a higher mean American Society of Anesthesiologists score compared with the younger patients, reflecting higher preoperative comorbidity, but were similar with regard to weight and gender. Before surgery, investigators performed 24-hour ambulatory pH monitoring. Preoperative exposure times to a pH below 4 (TpH <4) were similar for the younger and older patients (median 14.2% and 13.9%, respectively). Postoperative complication rates were similar for both groups. No deaths occurred. Minor postoperative complications involved 7% of the elderly patients and 6% of the younger group. The 24-hour pH monitoring scores showed improvement at 6 weeks after surgery for both groups, with the median TpH <4 at 1.1% (95% CL, 0.5) in the elderly vs a median of 1.8% (95% CL, 1.9) in the younger patients. At 1 year postoperatively, the values were also similar between the two groups; the median TpH <4 (95% CL) were 1.4% (1.5) in the elderly group and 1.2% (0.6) in the younger patient group. The results of this study should be interpreted with caution, however. The study design is prone to bias, the patients had relatively low symptom scores at baseline, and sicker patients may have been excluded during the referral process." }, { "input": "Upper endoscopy is recommended for elderly patients with alarm symptoms, new-onset GERD, or longstanding disease.", "output": "The Institute for Clinical Systems Improvement guidelines on dyspepsia and GERD recommend that all patients aged \u226550 years with symptoms of uncomplicated dyspepsia undergo upper endoscopy non-urgently because of the increased incidence of peptic ulcer disease, pre-neoplastic lesions, malignancy, and increased morbidity out of proportion to symptoms that are more common in an older patient population. The guidelines also recommend endoscopy for patients aged \u226550 years with uncomplicated GERD and the presence of symptoms for greater than 10 years because of the increased risk of pre-neoplastic and neoplastic lesions, including Barrett's esophagus." }, { "input": "Upper endoscopy is recommended for elderly patients with alarm symptoms, new-onset GERD, or longstanding disease.", "output": "The Veterans Health Affairs/Department of Defense clinical practice guidelines recommend differentiating GERD (feelings of substernal burning associated with acid regurgitation) from dyspepsia (chronic or recurrent discomfort centered in the upper abdomen), of which GERD is a subset. The guidelines recommend gastroenterology consultation or upper endoscopy to rule out neoplastic or pre-neoplastic lesions if alarm symptoms (TABLE) suggesting complicated GERD are present." }, { "input": "other", "output": "Aggregated data from 2 randomized reflux esophagitis trials conducted in the United Kingdom were analyzed with respect to patient age. Comparison of symptom relief and esophageal lesion healing showed that elderly patients treated with omeprazole (Prilosec) fared better than those treated with either cimetidine (Tagamet) or ranitidine (Zantac). The pooled data involved 555 patients with endoscopically proven reflux esophagitis, 154 of whom were over the age of 65. After 8 weeks, rates of esophageal healing among the elderly were 70% for those receiving omeprazole and 29% for those receiving H2RAs (41% difference; 95% confidence interval [CI], 26-55), while the rate of asymptomatic elderly patients was 79% for the omeprazole group and 51% for the H2RA group (28% difference; 95% CI, 12-44). Patients treated with omeprazole healed faster than those taking H2RAs, as shown by endoscopy, and more of them experienced symptom relief." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "The Sanford Guide to Antimicrobial Therapy (2005) recommends topical butenafine and terbinafine as primary agents of choice for tinea cruris due to their fungicidal activity." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "An open-pilot study of 14 patients with tinea cruris demonstrated 71% mycological cure with a honey, olive oil, and beeswax (1:1:1) mixture, applied 3 times daily up to 3 weeks, likely due to honey's inhibitory effect on fungus and beeswax's anti-inflammatory properties." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "Ajoene 0.6% gel (isolated from garlic), was as effective as terbinafine 1% cream (both applied twice daily for 2 weeks) in a RCT of 60 Venezuelan Army soldiers. Sixty days after treatment, 73% of the Ajoene-treated patients and 71% in the terbinafine group were asymptomatic." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "Miconazole 2% cream (Micatin, Monistat) (used twice daily for 2 weeks by inmates in a Florida prison) demonstrated 75.5% clinical clearing (against tinea cruris, pedis, or corporis, or Candida cutaneous infections) when compared with placebo (NNT=1.57). Of the 99 patients evaluated, 48 were diagnosed with tinea cruris; however, results were not broken down into diagnostic category. The length of follow-up for these patients was not disclosed." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "A systematic review on tinea pedis topical therapy acknowledges the higher cure rates by allylamines, compared with azoles, but concludes that azoles remain the most costeffective in the treatment of tinea pedis." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "The American Academy of Family Physicians recommends any of the topical antifungal treatments as first-line treatment for tinea cruris." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "Butenafine (Mentax), a benzylamine antifungal, was 88% to 93% mycologically effective in a noncomparative study, when used twice daily for 2 weeks." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "79% mycological cure were seen in a placebo-controlled trial with 70 patients using once daily naftifine 1% cream after 2 weeks of treatment (NNT=2)." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "In a 4-week study involving 104 patients, naftifine 1% cream (Naftin) was compared with econazole 1% cream (Spectazole) (both applied twice daily). At the end of the study, naftifine 1% cream had a higher (but not statistically significant) mycological and clinical cure rate of 78% compared with 68% with econazole 1% cream." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "In a multicenter, double-blind RCT funded by the manufacturers of terbinafine, bifonazole 1% cream for 3 weeks was compared with terbinafine 1% cream used daily for 1 week (followed by 2 weeks of its vehicle cream). Mycological and clinical cure rates were greater than 95% in both groups at 3 weeks. At the 8-week follow-up, no statistically significant differences were seen in KOH positivity rates (20.24% of patients in the bifonazole-treated group were KOH-positive vs 11.76% in the terbinafine group). Symptom relapse rates at 8 weeks were not available." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "A placebo-controlled study of 66 patients demonstrated 100% microscopic cure of terbinafine 1% solution by week 2 and maintaining 90% cure at 4 weeks." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "Data combined from 2 RCTs yielded 83% efficacy 3 weeks post-treatment when 66 patients were treated with terbinafine 1% cream, compared with 12% efficacy for 73 patients using the vehicle cream (NNT=1.4)." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "One placebo controlled trial showed the 1% emulsion-gel version (Lamisil) was effective in 89% of the study population vs 23% of the placebo group (NNT=1.5); it was particularly suitable on hairy skin. Seven weeks post-treatment, 84% of the intent-to-treat population of the Lamisil group remained mycologically negative." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "One RCT compared cure rates for 139 patients for clotrimazole 1% cream compared with ciclopirox olamine 1% cream when both were applied twice daily for 28 days. By the end of the 4-week period, 69% of the clotrimazole group was clinically and mycologically cured compared with 64% of the ciclopirox group." }, { "input": "After clinical diagnosis and microscopic confirmation, tinea cruris is best treated with a topical allylamine or an azole antifungal. Differences in current comparison data are insufficient to stratify the 2 groups of topical antifungals. Determining which group to use depends on patient compliance, medication accessibility, and cost. The fungicidal allylamines (naftifine and terbinafine) and butenafine (allylamine derivative) are a more costly group of topical tinea treatments, yet they are more convenient as they allow for a shorter duration of treatment compared with fungistatic azoles (clotrimazole, econazole, ketoconazole, oxiconazole, miconazole, and sulconazole).", "output": "in a study of 76 patients with tinea cruris; after 2 weeks of daily application, 78% (modified intent-to-treat group) were mycologically cured. Mycological cure plus \"cleared\" or \"excellent\" clinical evaluation remained for 73% at day 42 vs 5% of the placebo group (NNT=1.47)." }, { "input": "Cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as acetaminophen and nonselective NSAIDs in treating of osteoarthritis, and are equally effective in reducing pain and inflammation and improving of joint function for patients with rheumatoid arthritis, when compared with nonselective NSAIDs. The COX-2 selective NSAIDs also have a better gastrointestinal safety profile in short-term (6-12 month) treatment.", "output": "A recent double-blind, randomized placebo-controlled trial found that 12 weeks of treatment with a combination of low-dose aspirin and a COX-2 selective NSAID (rofecoxib) had more than twice the incidence of endoscopically confirmed gastric and duodenal ulcers, compared with aspirin alone, and no difference with a nonselective NSAID. This has raised the safety concern of concomitant use of a COX-2 selective NSAID with low-dose aspirin." }, { "input": "Cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as acetaminophen and nonselective NSAIDs in treating of osteoarthritis, and are equally effective in reducing pain and inflammation and improving of joint function for patients with rheumatoid arthritis, when compared with nonselective NSAIDs. The COX-2 selective NSAIDs also have a better gastrointestinal safety profile in short-term (6-12 month) treatment.", "output": "A Cochrane review (26 randomized controlled trials) found that rofecoxib (Vioxx) was more effective than placebo (NNT=5), and equally effective with other NSAIDs in the management of osteoarthritis. They reported fewer GI adverse events (endoscopically observed gastric erosion and ulcers) with rofecoxib than with other NSAIDs-naproxen (Naprosyn), ibuprofen (Motrin), diclofenac (Cataflam), nabumetone (Relafen), diclofenac/misoprostol (Arthrotec), and nimesulide. However, the withdrawal rate due to adverse events and the increase in blood pressure and edema were significantly greater with rofecoxib than placebo at 6 weeks." }, { "input": "Cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as acetaminophen and nonselective NSAIDs in treating of osteoarthritis, and are equally effective in reducing pain and inflammation and improving of joint function for patients with rheumatoid arthritis, when compared with nonselective NSAIDs. The COX-2 selective NSAIDs also have a better gastrointestinal safety profile in short-term (6-12 month) treatment.", "output": "A Cochrane review (6 randomized controlled trials, N=1689, mean duration 5.8 weeks) assessed the efficacy and safety of acetaminophen in the management of osteoarthritis, comparing it with placebo and NSAIDs. Acetaminophen was superior to placebo in pain reduction and global assessment (number needed to treat [NNT]=2) with a similar safety profile. NSAIDs were better than acetaminophen in pain reduction, patient (NNT=6) and physician global assessment (NNT=17), but no better for functional improvement. Compared with nonselective NSAIDs, acetaminophen led to fewer withdrawals (number needed to harm [NNH]=20) and fewer GI adverse events (NNH=9), but there was no statistical difference when compared with COX-2 selective NSAIDs." }, { "input": "Of the available oral therapies for common warts, none has sufficient evidence to recommend it as an effective therapy.", "output": "1 nonrandomized controlled trial found levamisole at 5 mg/kg for 3 days every 2 weeks to be superior to placebo in achieving complete cure of warts in a group of 40 patients." }, { "input": "Of the available oral therapies for common warts, none has sufficient evidence to recommend it as an effective therapy.", "output": "Levamisole (Ergamisol), used in combination with cimetidine, has been compared with cimetidine alone in 2 trials, and was found to be effective at speeding regression of warts, with patients in the combination arm showing a mean regression time of 7.8 weeks compared with 11 weeks in the cimetidine alone group. These small studies involved 48 and 44 patients, respectively." }, { "input": "Of the available oral therapies for common warts, none has sufficient evidence to recommend it as an effective therapy.", "output": "Cimetidine (Tagamet) has been compared with placebo in 3 trials and was not found superior to placebo." }, { "input": "To date, no oral agent has been shown to be effective in a randomized, placebo-controlled, double-blinded trial. Very limited evidence is emerging that zinc may be effective.", "output": "Zinc is the only agent to demonstrate efficacy in a completely randomized and placebo-controlled study. However, this trial was unblinded, had only 40 subjects assigned to each agent, had a dropout rate of 46%, and did not follow intention-to-treat analysis." }, { "input": "Polycystic ovarian syndrome (PCOS) is diagnosed for women of childbearing age presenting with 2 of the following: 1) oligo- or anovulatory menstrual irregularities, 2) evidence of hyperandrogenism in the absence of secondary cause; 3) enlarged ovaries with multiple small follicular cysts on transvaginal ultrasound.", "output": "A 2002 American College of Obstetricians and Gynecologists guideline adopted the 1990 National Institutes of Health consensus panel criteria for diagnosing PCOS (ie, chronic anovulation and clinical or biochemical signs of hyperandrogenism, excluding other causes), and recommends that all patients have documentation of elevated testosterone levels; thyroid-stimulating hormone (TSH), prolactin, and 17-hydroxyprogesterone levels to exclude secondary causes of hyperandrogenism; and evaluation for metabolic abnormalities with a 2-hour glucose tolerance test and fasting lipid panel." }, { "input": "Polycystic ovarian syndrome (PCOS) is diagnosed for women of childbearing age presenting with 2 of the following: 1) oligo- or anovulatory menstrual irregularities, 2) evidence of hyperandrogenism in the absence of secondary cause; 3) enlarged ovaries with multiple small follicular cysts on transvaginal ultrasound.", "output": "Evidence for hyperandrogenism includes hirsutism, acne, or elevated total testosterone levels." }, { "input": "Polycystic ovarian syndrome (PCOS) is diagnosed for women of childbearing age presenting with 2 of the following: 1) oligo- or anovulatory menstrual irregularities, 2) evidence of hyperandrogenism in the absence of secondary cause; 3) enlarged ovaries with multiple small follicular cysts on transvaginal ultrasound.", "output": "Because PCOS is a clinical syndrome, no single diagnostic criterion is sufficient for diagnosis. Clinical features include menstrual irregularities or infertility, hirsutism, male-pattern balding, acne, ovarian enlargement, and signs of insulin resistance (eg, central obesity, acanthosis nigricans). A 2003 international consensus panel concluded that the presence of 2 of 3 criteria (oligo/anovulation, hyperandrogenism, polycystic ovaries), in the absence of other secondary causes, is sufficient to make the diagnosis. A high luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio supports the diagnosis. However, because this measure varies considerably in relation to ovulation, body-mass index (BMI), and the particular measurement assay used, the consensus panel recommended against its use as a diagnostic criterion." }, { "input": "Polycystic ovarian syndrome (PCOS) is diagnosed for women of childbearing age presenting with 2 of the following: 1) oligo- or anovulatory menstrual irregularities, 2) evidence of hyperandrogenism in the absence of secondary cause; 3) enlarged ovaries with multiple small follicular cysts on transvaginal ultrasound.", "output": "Polycystic ovarian syndrome is a condition of unexplained hyperandrogenic chronic anovulation that affects at least 4% of women of reproductive age." }, { "input": "Polycystic ovarian syndrome (PCOS) is diagnosed for women of childbearing age presenting with 2 of the following: 1) oligo- or anovulatory menstrual irregularities, 2) evidence of hyperandrogenism in the absence of secondary cause; 3) enlarged ovaries with multiple small follicular cysts on transvaginal ultrasound.", "output": "Based on optimum receiver operator characteristic curve analyses, ultrasound criteria include the presence of 12 or more follicles in each ovary measuring 2 to 9 mm in diameter (sensitivity=75%, specificity=99%, positive predictive value [PPV]=75%, negative predictive value [NPV]=99%, assuming 4% prevalence) or ovarian volume over 7 mL (sensitivity=67.5%, specificity=91.2%, PPV=24%, NPV 99%)." }, { "input": "Depending on the clinical presentation, secondary causes should be excluded.", "output": "Secondary causes of hyperandrogenism may be suggested by clinical findings, including 1) abrupt onset, short duration, or sudden progressive worsening of hirsutism; 2) onset of symptoms in the third decade of life or later; or 3) signs of virilization (deepening voice, clitoromegaly)." }, { "input": "Depending on the clinical presentation, secondary causes should be excluded.", "output": "A 2002 American College of Obstetricians and Gynecologists guideline adopted the 1990 National Institutes of Health consensus panel criteria for diagnosing PCOS (ie, chronic anovulation and clinical or biochemical signs of hyperandrogenism, excluding other causes), and recommends that all patients have documentation of elevated testosterone levels; thyroid-stimulating hormone (TSH), prolactin, and 17-hydroxyprogesterone levels to exclude secondary causes of hyperandrogenism; and evaluation for metabolic abnormalities with a 2-hour glucose tolerance test and fasting lipid panel." }, { "input": "While not among the diagnostic criteria, insulin resistance is common, and patients with PCOS should be evaluated for metabolic abnormalities, particularly hyperlipidemia and glucose intolerance or diabetes.", "output": "Women with PCOS often experience insulin resistance, and are at increased risk for developing type 2 diabetes, dyslipidemia, and cardiovascular disease. One cross-sectional study of 122 women with PCOS between 13.5 and 40 years of age found that 35% had impaired glucose tolerance, and another 10% had non-insulindependent diabetes." }, { "input": "While not among the diagnostic criteria, insulin resistance is common, and patients with PCOS should be evaluated for metabolic abnormalities, particularly hyperlipidemia and glucose intolerance or diabetes.", "output": "A prospective case-control study of young women (aged <35 years) found that compared with age- and BMI-matched controls, those with PCOS had higher levels of fasting glucose, insulin, total and low-density lipoprotein cholesterol, and altered left ventricular mass and cardiac function on echocardiogram. Once PCOS is suspected, the diagnostic work-up should include a 2-hour glucose tolerance test and lipid panel to assess cardiovascular risk, particularly among obese women." }, { "input": "The use of inhaled corticosteroids at conventional doses for asthma and chronic obstructive pulmonary disease (COPD) does not appear to be associated with significant bone loss at 2 to 3 years of follow-up.", "output": "A fair-quality 2004 RCT did not demonstrate any clinically relevant effect on BMD at 2 years follow-up. This study used 800 mcg/day of fluticasone for patients with mild asthma." }, { "input": "The use of inhaled corticosteroids at conventional doses for asthma and chronic obstructive pulmonary disease (COPD) does not appear to be associated with significant bone loss at 2 to 3 years of follow-up.", "output": "A fair-quality 2004 meta-analysis of 14 randomized trials (2300 participants) included 2 studies (448 subjects) that overlapped with the Cochrane review. There were no significant changes in BMD with moderately high doses of inhaled corticosteroids at 1 to 3 years follow-up. Annual changes in lumbar and femoral neck BMD (-0.23% and -0.17%, respectively) were not statistically significant. Mean changes in lumbar BMD were not significantly different from controls (-0.02)." }, { "input": "The use of inhaled corticosteroids at conventional doses for asthma and chronic obstructive pulmonary disease (COPD) does not appear to be associated with significant bone loss at 2 to 3 years of follow-up.", "output": "Three RCTs (792 subjects total) examined the effect of conventional doses of inhaled corticosteroids on BMD and 2 of the RCTs (892 participants total) collected fracture data. No demonstrable effect was seen on vertebral fracture (odds ratio [OR]=1.87; 95% confidence interval [CI], 0.5-7.03) or BMD at 2 years follow-up. The subjects were otherwise healthy people with asthma or COPD with an average age of 40 years; men outnumbered women 2 to 1." }, { "input": "Higher doses of inhaled corticosteroids may be associated with negative bone density changes at up to 4 years of follow-up.", "output": "There is some evidence that higher doses of inhaled corticosteroids can result in adverse BMD changes. In a high-quality RCT of 412 participants, aged 40 to 69 years, with mild to moderate COPD, use of higher-dose triamcinolone (1200 mcg/day) was associated with decreased lumbar and femoral neck BMD over 3 to 4 years. The differences in BMD between the inhaled corticosteroids and placebo groups at the femoral neck and lumbar spine were 1.78% (P<.001) and 1.33% (P=.007), respectively. However, the risk of fracture or height loss did not increase at follow-up." }, { "input": "Higher doses of inhaled corticosteroids may be associated with negative bone density changes at up to 4 years of follow-up.", "output": "A large fair-quality RCT from 2001 included in both meta-analyses demonstrated a dose-related fall in BMD within the subjects over 2 years at the lumbar spine (standard deviation, 3.4%; P<.010). This finding remained statistically significant after adjusting for asthma severity, but BMD changes were not different between the inhaled corticosteroids and placebo groups. However, this finding may be the result of higher oral corticosteroids use in the reference group." }, { "input": "The use of topical triple-antibiotic ointments significantly decreases infection rates in minor contaminated wounds compared with a petrolatum control. Plain petrolatum ointment is equivalent to triple-antibiotic ointments for sterile wounds as a post-procedure wound dressing.", "output": "A randomized controlled trial of 933 outpatients-with a total of 1249 wounds from sterile dermatologic surgeries-compared white petrolatum with bacitracin zinc ointment prophylaxis. The study found no statistically significant differences in post-procedure infection rates, though only 13 patients developed an infection (2% in petrolatum group vs. 0.9% in bacitracin zinc group; 95% CI for the difference, -0.4 to 2.7)." }, { "input": "The use of topical triple-antibiotic ointments significantly decreases infection rates in minor contaminated wounds compared with a petrolatum control. Plain petrolatum ointment is equivalent to triple-antibiotic ointments for sterile wounds as a post-procedure wound dressing.", "output": "Topical bacitracin zinc (Bacitracin), a triple ointment of neomycin sulfate, bacitracin zinc, and polymyxin B sulfate (Neosporin), and silver sulfadiazine (Silvadene) were compared with petrolatum as a control in a well-conducted RCT of 426 patients with uncomplicated wounds seen at a military community hospital. Wound infection rates were 17.6% (19/108) for petrolatum, 5.5% (6/109) for Bacitracin (number needed to treat [NNT]=8), 4.5% (5/110) for Neosporin (NNT=8), and 12.1% (12/99) for Silvadene (NNT=18). Most (60%) of the infections were \"stitch abscesses\" and were treated with local care only. There was no difference in rates of more serious infections between groups. One patient (0.9%) developed a hypersensitivity reaction to Neosporin." }, { "input": "The use of topical triple-antibiotic ointments significantly decreases infection rates in minor contaminated wounds compared with a petrolatum control. Plain petrolatum ointment is equivalent to triple-antibiotic ointments for sterile wounds as a post-procedure wound dressing.", "output": "A clinical trial compared the efficacy of a cetrimide, bacitracin zinc, and polymyxin B sulfate gel (a combination not available in the US) with placebo and povidone-iodine cream in preventing infections in 177 minor wounds (cuts, grazes, scrapes, and scratches) among children. The antibiotic gel was found to be superior to placebo and equivalent to povidone-iodine, in that it reduced clinical infections from 12.5% to 1.6% (absolute risk reduction [ARR]=0.109; 95% confidence interval [CI], 0.011-0.207; NNT=11)." }, { "input": "Mupirocin cream is as effective as oral cephalexin in the treatment of secondarily infected minor wounds and, because of better tolerability, is the treatment of choice for the prevention and treatment of Staphylococcus aureus and Staphylococcus pyogenes infections. Emerging resistance, including methicillin-resistant S aureus (MRSA), makes it prudent to check for clinical response in 24 to 48 hours. Major contaminated wounds requiring parenteral antibiotics do not appear to additionally benefit from topical antibiotics.", "output": "A double-blind study of 59 patients found Neosporin superior to placebo ointment in the prevention of streptococcal pyoderma for children with minor wounds. Infection occurred in 47% of placebo-treated children compared with 15% treated with the triple-antibiotic ointment (NNT=32; P=.01)." }, { "input": "Mupirocin cream is as effective as oral cephalexin in the treatment of secondarily infected minor wounds and, because of better tolerability, is the treatment of choice for the prevention and treatment of Staphylococcus aureus and Staphylococcus pyogenes infections. Emerging resistance, including methicillin-resistant S aureus (MRSA), makes it prudent to check for clinical response in 24 to 48 hours. Major contaminated wounds requiring parenteral antibiotics do not appear to additionally benefit from topical antibiotics.", "output": "A small randomized prospective trial of 99 patients, who self-reported compliance with wound care and dressing changes, compared Neosporin with mupirocin (Bactroban) in preventing infections in uncomplicated soft tissue wounds. The study found no statistical difference in infection rates, and the authors recommend the more cost-effective Neosporin, as well as a larger trial to confirm the results." }, { "input": "Topical antibiotics may aid in the healing of chronic wounds.", "output": "An open randomized trial with 48 volunteers compared the effects of Neosporin with several antiseptics (3% hydrogen peroxide, 1% povidone-iodine, 0.25% acetic acid, 0.5% sodium hydrochloride) and a wound protectant (Johnson & Johnson First Aid Cream without antimicrobial agent) on blister wounds (6 blisters per volunteer) intentionally contaminated with S aureus. Only Neosporin eliminated the infection after 2 applications (at 16 and 24 hours). Both the antibiotic ointment and the wound protectant led to faster wound healing by about 4 days compared with the antiseptics or no treatment." }, { "input": "Topical antibiotics may aid in the healing of chronic wounds.", "output": "A small but well-designed study of 62 patients with major contaminated wounds failed to show any additional benefit when topical piperacillin/tazobactam (not available in US as a topical agent) was added to parenteral piperacillin/tazobactam (Zosyn) alone. Two of 31 patients on just parenteral antibiotics and 3 of 31 patients on both topical and parenteral antibiotics developed wound infections (P>.05)." }, { "input": "Topical antibiotics may aid in the healing of chronic wounds.", "output": "A study with 2 parallel, identical RCTs of a total of 706 patients found mupirocin cream (Bactroban) to be equivalent to oral cephalexin in the treatment of secondarily infected minor wounds, such as small lacerations, abrasions, or sutured wounds. Clinical success (95.1% for mupirocin and 95.3% for cephalexin), bacteriologic success (96.9% for mupirocin and 98.9% for cephalexin), as well as the intention-to-treat success rate of 83% at follow-up were equivalent in the 2 groups." }, { "input": "Topical antibiotics may aid in the healing of chronic wounds.", "output": "A systematic review of the treatment of chronic wounds, such as diabetic foot ulcers, found 30 trials, including 25 RCTs, mostly of low quality. Little evidence supports the routine use of systemic antibiotics for patients with chronic wounds; however, some topical antiseptic and antimicrobial agents may hasten the healing of these wounds. Topical preparations that may be helpful include dimethyl sulfoxide (Rimso-50), silver sulfadiazine (Silvadene), benzoyl peroxide (Benzac, Brevoxyl, Desquam, Triaz, ZoDerm), oxyquinoline (Trimo-san Vaginal Jelly), and gentamicin (Garamycin)." }, { "input": "The application of honey may aid in the healing of chronic wounds.", "output": "Honey may make an acceptable wound dressing for chronic wounds, as it has been repeatedly shown to suppress bacterial growth. Infection with Clostridium spores does not appear to be a concern when treating chronic wounds with honey." }, { "input": "Low-dose inhaled corticosteroids are the preferred treatment for children with mild persistent asthma because they demonstrate superior reduction in severity and frequency of asthma exacerbations compared with alternatives.", "output": "In the inhaled Steroid Treatment As Regular Therapy (START) in early asthma study, budesonide demonstrated a 44% relative reduction in time to first severe asthma related event, compared with placebo (95% confidence interval [CI], 0.45-0.71; NNT=44; P=.0001)." }, { "input": "Low-dose inhaled corticosteroids are the preferred treatment for children with mild persistent asthma because they demonstrate superior reduction in severity and frequency of asthma exacerbations compared with alternatives.", "output": "The Childhood Asthma Management Program (CAMP) study, which included 1041 children, evaluated treatment with either budesonide or nedocromil vs placebo. Patients taking budesonide had a lower rate of urgent care visits (absolute risk reduction [ARR]=10%; number needed to treat [NNT]=10; P=.02) compared with children taking nedocromil (ARR=6%; NNT=17; P=.02). The urgent care visits were reported as number of visits per 100 person-years. Children taking budesonide experienced 21.5% more episode-free days than those taking placebo (P=.01). No change was observed in the nedocromil group." }, { "input": "As add-on therapy, nedocromil, theophylline, and cromolyn have all demonstrated a modest benefit in symptom control; leukotriene receptor antagonists are also recommended based on data from older children.", "output": "Theophylline is considered an alternative to inhaled corticosteroids. One study compared beclomethasone with theophylline in 195 children. This study found near-equivalent efficacy in doctor visits, hospitalizations, monthly peak expiratory flow rates, and FEV1; however, beclomethasone was superior to theophylline in maintaining symptom control and decreasing the use of inhaled bronchodilators and systemic steroids. When compared with beclomethasone, theophylline was linked to 14% more central nervous system adverse effects (P<.001) and 17% more gastrointestinal disturbances (P<.001). Although beclomethasone induced more oral candidiasis compared with theophylline (8.9% vs 2.4%; P<.001), the incidence of this infection can be reduced by using a spacer." }, { "input": "As add-on therapy, nedocromil, theophylline, and cromolyn have all demonstrated a modest benefit in symptom control; leukotriene receptor antagonists are also recommended based on data from older children.", "output": "A systematic review of 15 trials reported that the protective effect of leukotriene receptor antagonists is inferior to inhaled corticosteroids for adults (relative risk [RR]=1.71; 95% CI, 1.40-2.09); however, evidence is insufficient to extrapolate this to children." }, { "input": "Unlike treatment of moderate or severe asthma, long-acting beta-agonists are not recommended.", "output": "Evidence does not support use of long-acting beta-agonists as monotherapy or in combination with other medications for children with mild persistent asthma. Although 1 study showed an improvement in lung function for children taking budesonide plus formoterol compared with budesonide alone, the rate of severe exacerbations was lower for those taking budesonide alone (62% decrease vs 55.8% decrease; P=.001). Both groups had a 32% decrease in the number of rescue inhalations per day when compared with placebo (P=.0008)." }, { "input": "For patients without initial inflammatory symptoms, biopsy is recommended if the lymph node enlargement persists beyond 4 to 6 weeks, continues to enlarge, or is >3 cm.", "output": "Lymph nodes with concomitant malignancy risk factors warrant immediate evaluation. For lymph nodes without signs or symptoms of inflammation or malignancy, observation for 4 to 6 weeks has been recommended. Further evaluation with imaging or biopsy is indicated if the node persists beyond 4 to 6 weeks, continues to enlarge, is located within the supraclavicular fossa, or is >3 cm." }, { "input": "Biopsy is also indicated if there is a supraclavicular lymph node or concomitant constitutional symptoms (weight loss or night sweats).", "output": "A study of 550 patients identified 5 significant predictors of malignancy: male gender (risk ratio [RR]=2.72; 95% confidence interval [CI], 1.63-4.56), increasing age (RR=1.05; 95% CI, 1.04-1.07), white ethnicity (RR=3.01; 95% CI, 1.19-7.6), supraclavicular lymph nodes (RR=3.72; 95% CI, 1.52-9.12), and 2 or more regions of lymph nodes (RR=6.41; 95% CI, 2.82-14.58)." }, { "input": "Ultrasound or computerized tomography (CT) can also be helpful in determining which method of biopsy to choose.", "output": "Another study demonstrated an ultrasound sensitivity of 100% and specificity of 97% for 154 patients with lymphadenopathy." }, { "input": "Ultrasound or computerized tomography (CT) can also be helpful in determining which method of biopsy to choose.", "output": "A study of 50 patients with lymphadenopathy on CT demonstrated the sensitivity of ultrasound was 92% in identifying the same nodes." }, { "input": "Fine-needle aspiration is a minimally invasive method for obtaining a tissue sample, but excisional biopsy can provide a definitive diagnosis.", "output": "Histologic evaluation after excisional biopsy is the gold standard for diagnosis. Fine-needle aspiration is an alternate, minimally invasive option for further work-up. Fine-needle aspiration had a sensitivity of 49% and specificity of 97% in a study of 550 patients." }, { "input": "Fine-needle aspiration is a minimally invasive method for obtaining a tissue sample, but excisional biopsy can provide a definitive diagnosis.", "output": "A study of 1103 patients found a 97% sensitivity (3.4% false-negative rate) and a 99% specificity (0.9% false-positive rate) for fine-needle aspiration.4 In cases where pathology is equivocal, or where concern for malignancy is exceptionally high, excisional biopsy provides a more definitive diagnosis." }, { "input": "Fine-needle aspiration is a minimally invasive method for obtaining a tissue sample, but excisional biopsy can provide a definitive diagnosis.", "output": "In a study of 309 patients with supraclavicular lymphadenopathy, fine-needle aspiration had a sensitivity of 97%, a specificity of 98%, and a positive predictive value of 98%. A study of 94 patients found that clinical exam alone was 78% sensitive in diagnosing the cause of lymphadenopathy; this improved to 93% sensitivity with fine-needle aspiration." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "In very small randomized trial of 20 patients with type 2 diabetes, adding 16 mg of candesartan to the maximal dose of an ACE inhibitor decreased albuminuria an additional 28%." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "During a 2-year trial-in which 590 patients with diabetes and microalbuminuria were randomized to receive placebo, 150 mg irbesartan, or 300 mg irbesartan-14.9% of the placebo group, 9.7% of the 150-mg group, and only 5.2% of the 300-mg group progressed to overt nephropathy." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "There is good evidence that screening for microalbuminuria can identify those who might benefit from treatments that delay the onset of nephropathy." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "The American Diabetes Association (ADA) recommends that patients with diabetes and hypertension and those aged >55 years with other cardiovascular risk factors (history of cardiovascular disease, dyslipidemia, or tobacco use) be started on ACE inhibitors or ARBs." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "For patients with diabetes who develop microalbuminuria, the evidence is good for starting ACE inhibitors or ARBs for renal protection." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "One study that followed 5097 patients with type 2 diabetes over a median of 10.4 years found that 2% of patients progressed from normal levels of urinary protein to microalbuminuria; 2.8% changed from microalbuminuria to macroalbuminuria (urine albumin >300 mg in a 24-hour period); and 2.3% progressed to chronic renal disease (creatinine \u22652 mg/dL) from macroalbuminuria per year. Chronic renal disease is more likely to occur in those patients whose hypertension or hyperglycemia is poorly controlled." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "Diabetes mellitus is the leading cause of end-stage renal disease in the Western world. The prevalence of diabetic nephropathy continues to rise along with the rapidly rising prevalence of obesity and diabetes, with 40% of patients with diabetes at risk of developing nephropathy." }, { "input": "No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression.", "output": "Experts argue that it may benefit patients to continue regular surveillance for the presence or progression of microalbuminuria even if they are already taking an ACE inhibitor or ARB so that therapy can be maximized." }, { "input": "In African Americans with hypertension, therapy is best initiated with the low-sodium Dietary Approaches to Stop Hypertension (DASH) diet and a thiazide-type diuretic.", "output": "An RCT studied the effect of different levels of dietary sodium in conjunction with the DASH diet. A total of 412 participants were randomly assigned to eat either a control diet or the DASH diet. Within the assigned diet, participants ate foods with high (150 mmol/d), intermediate (100 mmol/d), and low (50 mmol/d) levels of sodium in random order. In this study, low-sodium DASH diet was associated with additional lowering of blood pressure, an effect that was also found to be stronger for African Americans patients than others. When compared with the combination of the control diet and a high level of sodium, the DASH diet and a low level of sodium lowered systolic blood pressure by 11.5 mm Hg for participants with hypertension (12.6 mm Hg for blacks; 9.5 mm Hg for others), and by 7.1 mm Hg for participants without hypertension (7.2 mm Hg for blacks; 6.9 mm Hg for others)." }, { "input": "In African Americans with hypertension, therapy is best initiated with the low-sodium Dietary Approaches to Stop Hypertension (DASH) diet and a thiazide-type diuretic.", "output": "Among African Americans with hypertension, the DASH diet was even more beneficial, reducing their systolic and diastolic blood pressure by 13.2 mm Hg and 6.1 mm Hg respectively." }, { "input": "In African Americans with hypertension, therapy is best initiated with the low-sodium Dietary Approaches to Stop Hypertension (DASH) diet and a thiazide-type diuretic.", "output": "An RCT compared the effects of consuming the DASH diet (consisting of 4-5 servings of fruit, 4-5 servings of vegetables, 2-3 servings of low-fat dairy per day, and <25% fat) with a typical high-fat control diet among 459 adults with normal or elevated blood pressure. Among 133 patients with hypertension, the DASH diet reduced systolic and diastolic blood pressure by 11.4 mm Hg (97.5% confidence interval [CI], -15.9 to -6.9) and 5.5 mm Hg (97.5% CI, -8.2 to -2.7) respectively when compared with the control diet." }, { "input": "If the blood pressure goal is not achieved with thiazide monotherapy, a calcium channel blocker, angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or a beta-blocker can be added. An initial combination treatment is recommended for patients with systolic blood pressure >15 mm Hg or diastolic blood pressure >10 mm Hg above target.", "output": "The ALLHAT trial, a double-blind RCT of 42,448 high-risk hypertensive patients aged >55 years, compared chlorthalidone (a thiazide-type diuretic) with amlodipine (Norvasc), lisinopril (Prinivil, Zestril), or doxazosin (Cardura). In this study, which included 36% African Americans, chlorthalidone, lisinopril, and amlodipine did not differ in preventing major cardiovascular events. However, lisinopril was associated with an increased risk for heart failure (relative risk [RR] for African Americans=1.32; 95% CI, 1.11-1.58) and stroke (RR for African Americans=1.4; 95% CI, 1.17-1.68), and amlodipine was associated with a higher risk of heart failure (RR in African Americans=1.47; 95% CI, 1.24-1.74). Additionally, ACE inhibitor-induced angioedema or cough occurred more frequently among African American patients than white patients." }, { "input": "If the blood pressure goal is not achieved with thiazide monotherapy, a calcium channel blocker, angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or a beta-blocker can be added. An initial combination treatment is recommended for patients with systolic blood pressure >15 mm Hg or diastolic blood pressure >10 mm Hg above target.", "output": "A double-blind RCT of 1094 African American patients with renal insufficiency, compared the effects of an ACE inhibitor (ramipril [Altace]), a dihydropyridine calcium channel blocker (amlodipine), or a beta blocker (metoprolol [Lopressor]) on the progression of hypertensive renal disease. The AASK trial confirmed that ACE inhibitors can provide significant clinical benefits for African Americans with hypertensive renal disease. The study showed a 44% relative risk reduction (95% CI, 13%-65%; number needed to treat [NNT]=25) in progression to end-stage renal disease, and a significant decrease in the combined endpoints of glomerular filtration rate events (decrease >50%), end-stage renal disease, and death (decreased by 38%) in the ramipril group compared with the amlodipine group (95% CI, 13%-56%; NNT=56 per patient-year)." }, { "input": "If the blood pressure goal is not achieved with thiazide monotherapy, a calcium channel blocker, angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or a beta-blocker can be added. An initial combination treatment is recommended for patients with systolic blood pressure >15 mm Hg or diastolic blood pressure >10 mm Hg above target.", "output": "Metoprolol appeared to have intermediate outcomes." }, { "input": "African Americans have reduced blood pressure responses to monotherapy with beta-blocker, ACE inhibitor, or ARBs when compared to diuretics or calcium channel blockers.", "output": "A randomized controlled trial demonstrated that African Americans may be less responsive to monotherapy with ACE inhibitors." }, { "input": "African Americans have reduced blood pressure responses to monotherapy with beta-blocker, ACE inhibitor, or ARBs when compared to diuretics or calcium channel blockers.", "output": "A review of multiple studies demonstrated that African Americans may be less responsive to monotherapy with ACE inhibitors." }, { "input": "However, cardiac and renal indications for prescribing these medications should be equally applied to African American patients.", "output": "The ISHIB report emphasizes the need for not overlooking renal protection with an ACE inhibitor for African Americans with renal disease. The American Diabetes Association recommends that all patients with diabetes and hypertension be treated with a regimen that includes either an ACE inhibitor or an ARB." }, { "input": "Screening patients for asymptomatic microhematuria does not appear to improve outcomes, since screening does not identify a population with increased prevalence of urologic malignancy.", "output": "A prospective cohort study similarly evaluated 1034 patients with asymptomatic micro-hematuria found through annual health screening of Japanese adults; 471 (45%) had some urologic diagnosis, including 30 (2.9%) with serious disease (urologic malignancies or progressive glomerulopathy), 195 (18.9%) with moderate disease (such as stones, infection, stable glomerulopathy), and the remainder with less serious disease." }, { "input": "Screening patients for asymptomatic microhematuria does not appear to improve outcomes, since screening does not identify a population with increased prevalence of urologic malignancy.", "output": "A retrospective cohort study of 2005 British men aged >40 years found 85 (4%) with asymptomatic microhematuria. Subsequent evaluation including intravenous pyelogram and cystoscopy found 2 men with infections-1 with bladder cancer and 1 with polycystic kidneys. Benign prostatic hypertrophy, prostatitis, anatomic abnormalities, and stones accounted for the rest." }, { "input": "Screening does not identify the presence of urologic disease of any type.", "output": "A retrospective cohort study assessed the prevalence of urologic disease in patients with asymptomatic microhematuria compared with those without. Of 501 male steel-workers-an occupation believed to have a higher risk for urologic malignancy-57 men had urologic disease of any type. Six men with urolog-ic disease had asymptomatic microhematuria, while 51 men with urologic disease did not. The correlation between asymptomatic microhema-turia and the presence of urologic disease was not significant (P>.05). There were 3 cases of urolog-ic cancer in the study, all diagnosed in men without asymptomatic microhematuria." }, { "input": "Asymptomatic microhematuria is sometimes associated with urologic disease that requires intervention to prevent death or disability.", "output": "Among 20,751 California HMO patients who had a periodic health appraisal, screening identified 598 patients with asymptomatic microhematuria (prevalence=2.9%). The medical records for all patients were reviewed for the year prior to screening to find pre-existing urologic disease and then reviewed for new diagnoses over the next 6 years. Three cases of urologic cancer occurred in the group of patients with asymptomatic microhematuria (incidence=0.5%) and 102 cancer cases among the 20,153 patients without asymptomatic microhematuria (incidence=0.5%). Its presence was not significantly associated with either uro-logic cancers or other serious urologic disease." }, { "input": "Asymptomatic microhematuria is sometimes associated with urologic disease that requires intervention to prevent death or disability.", "output": "A retrospective cohort study assessed the prevalence of urologic disease in patients with asymptomatic microhematuria compared with those without. Of 501 male steel-workers-an occupation believed to have a higher risk for urologic malignancy-57 men had urologic disease of any type. Six men with urolog-ic disease had asymptomatic microhematuria, while 51 men with urologic disease did not. The correlation between asymptomatic microhema-turia and the presence of urologic disease was not significant (P>.05). There were 3 cases of urolog-ic cancer in the study, all diagnosed in men without asymptomatic microhematuria." }, { "input": "Antipyretics appear to have minor and variable effects on the course of febrile illness. Aspirin and acetaminophen do not prolong the course of rhinovirus illness, although they may prolong the period of viral shedding and worsen nasal congestion.", "output": "In 2 double-blind trials, 45 adults infected with rhinovirus were given aspirin or placebo for 5 days, beginning on the day after viral exposure (as opposed to the typical use in response to symptoms). Aspirin treatment improved symptoms of conjunctivitis significantly, but did not change the duration of illness. Other symptoms (headache, sneezing, chills, malaise, nasal discharge) were not significantly different. Aspirin increased the amount of viral shedding by 36% in 1 trial and 17% in the other (P<.01), potentially increasing risk of spread." }, { "input": "Antipyretics appear to have minor and variable effects on the course of febrile illness. Aspirin and acetaminophen do not prolong the course of rhinovirus illness, although they may prolong the period of viral shedding and worsen nasal congestion.", "output": "A randomized controlled trial involving 60 volunteers given intranasal rhinovirus type 2 monitored the effect of aspirin, acetaminophen, ibuprofen, or placebo on virus shedding, immune response, and clinical status. There was no difference in duration of illness. There was a trend toward longer duration of virus shedding in the aspirin and acetaminophen groups, but serum neutralizing antibody response was suppressed (P<.05 vs placebo). Aspirin and acetaminophen worsened symptoms of turbinate edema and nasal obstruction (P<.05 vs placebo)." }, { "input": "Acetaminophen did not affect symptoms, overall condition, or time to complete healing in children with varicella, although it increased the time to total scabbing of lesions.", "output": "In a randomized controlled trial evaluating antipyretic effects on the duration or severity of childhood varicella, 31 children received placebo and 37 received acetaminophen for 4 days. There was no difference in itching, appetite, activity, or overall condition between the 2 groups. Children treated with acetaminophen took 1.1 days longer to total scabbing (P<.05), although the number of days until the appearance of the last new vesicle and the time to total healing were unchanged. The duration of viral shedding was not measured, but it is possible that the delay in healing of lesions would prolong viral shedding as well." }, { "input": "Aspirin and acetaminophen may prolong influenza A illness.", "output": "A retrospective observational study of 54 volunteers demonstrated prolonged illness in subjects infected with influenza A that received antipyretic therapy. Patients who got antipyretics were sick 3.5 days longer than those who did not (8.8 \u00b1 2.3 days vs 5.3 \u00b1 3.0 days; P<.001). Only patients with temperatures >38.9\u00baC on 2 readings 6 hours apart received antipyretics, indicating that the longer course correlated with greater severity of illness as well as with antipyretic use." }, { "input": "Acetaminophen may prolong the course of Shigella sonnei infection.", "output": "In a retrospective observational study of 54 volunteers, antipyretics were associated with a trend towards prolonged duration of illness in a group of 21 patients infected with S sonnei (4.6 \u00b1 2.1 days with antipyretics vs 1.9 \u00b1 1.6 days without; P=not significant)." }, { "input": "It does not affect malaria cure rate, and there are insufficient data to assess clearance of Plasmodium falciparum.", "output": "A Cochrane review examined 3 trials of acetaminophen vs placebo for fever in 128 adults and children with P falciparum malaria. Although fever clearance varied between the trials, the malaria cure rate was similar in all, and the review concluded that data were insufficient to evaluate an effect on parasitemia." }, { "input": "High levels of serum homocysteine have been associated in several studies with an increased risk for CAD.", "output": "In 22 of 27 retrospective case-control studies, patients with CAD had significantly higher plasma homocysteine levels than control subjects (odds ratio [OR]=1.2-10.9, after adjustment for other CAD risk factors). However, only 4 of 7 prospective nested case-control trials showed a correlation between elevated homocysteine and myocardial infarction (MI) and coronary death." }, { "input": "Folate supplementation decreases the level of serum homocysteine. This indirect evidence suggests that folate supplementation may be of benefit in slowing the progress of arteriosclerosis.", "output": "A meta-analysis of 12 randomized controlled trials found that folate supplementation, with vitamin B6 and B12, reduces plasma homocysteine levels. However, the long-term clinical consequences of these interventions are unknown." }, { "input": "Folate supplementation decreases the level of serum homocysteine. This indirect evidence suggests that folate supplementation may be of benefit in slowing the progress of arteriosclerosis.", "output": "At doses of 1 gm/d folate has no known side-effects." }, { "input": "Two randomized controlled trials measuring the clinical benefits of folate supplementation for patients with CAD have been completed, with differing results. One study showed no benefit of 0.5 mg/d of folate for patients with stable CAD already on statin therapy. The other study found that patients given 1 mg/d of folate with vitamins B6 and B12 had a decreased restenosis rate after percutaneous coronary intervention (PCI)", "output": "A randomized, placebo-controlled trial of folate reporting clinical endpoints has been completed. The study analyzed folate supplementation in 553 post-PCI patients. Patients were treated with 1 mg of folate plus 10 mg of vitamin B6 and 400 \u00b5g of vitamin B12 for 6 months after the PCI. After a mean follow-up of 11 months, the rate of restenosis requiring revascularization was lower in the vitamin-treated study arm (9.9% vs 16% restenosis rate; relative risk [RR]=0.62; 95% confidence interval [CI], 0.40-0.97; number needed to treat=16). There was also a nonsignificant trend toward fewer deaths and MIs in the treated arm at both 6 and 12 months after intervention (death: 1.5% vs 2.8%; RR=0.54; 95% CI, 0.016-1.7; MI: 2.6% vs 4.3%; RR=0.60; 95% CI, 0.24-1.51). Statin use was similar in both control (71%) and treatment groups (69%)." }, { "input": "Two randomized controlled trials measuring the clinical benefits of folate supplementation for patients with CAD have been completed, with differing results. One study showed no benefit of 0.5 mg/d of folate for patients with stable CAD already on statin therapy. The other study found that patients given 1 mg/d of folate with vitamins B6 and B12 had a decreased restenosis rate after percutaneous coronary intervention (PCI)", "output": "A randomized, placebo-controlled trial of folate reporting clinical endpoints has been completed. The study analyzed folate supplementation in a patient population with known, stable CAD and found no difference in clinical endpoints at 24 months. In this study, 593 patients were randomized to receive either 0.5 mg/d of folic acid or placebo. The primary study endpoint was a composite of events including: overall mortality, sudden death, MI, stroke, and major vascular surgery. The study was powered to detect a 50% reduction in clinical events based on existing observational data in populations with CAD. An event rate of 15% for the 2-year interval was assumed. All patients in this study were on statin therapy prior to initiation of folate supplementation." }, { "input": "Metered-dose inhalers with a spacer (MDI/S) are as good as, or better than, nebulizers for children with asthma. This is based on numerous randomized controlled trials that compared outcomes such as hospital admission rates, asthma severity scores, and pulmonary function scores.", "output": "A review article examined 14 randomized controlled trials for beta-agonist delivery for patients aged 5 to 15 with stable asthma. They found no obvious benefit of 1 type of device over another, including nebulizer, MDI/S, and dry powder inhalers. These last 2 articles claimed to be systematic reviews, although they do not clearly state their search methodology." }, { "input": "Metered-dose inhalers with a spacer (MDI/S) are as good as, or better than, nebulizers for children with asthma. This is based on numerous randomized controlled trials that compared outcomes such as hospital admission rates, asthma severity scores, and pulmonary function scores.", "output": "A review article from the British literature examined 3 randomized controlled trials involving 51 patients and found no superiority of nebulizer vs MDI/S." }, { "input": "Metered-dose inhalers with a spacer (MDI/S) are as good as, or better than, nebulizers for children with asthma. This is based on numerous randomized controlled trials that compared outcomes such as hospital admission rates, asthma severity scores, and pulmonary function scores.", "output": "One article reviewed the literature from 1980 to 1996 and examined 17 prospective clinical trials. Outcomes measured included pulmonary function measures and clinical scores. The researchers recommended that MDI/S be used due to clinical benefit, safety, lower cost, personnel time, and speed and ease of administration." }, { "input": "Metered-dose inhalers with a spacer (MDI/S) are as good as, or better than, nebulizers for children with asthma. This is based on numerous randomized controlled trials that compared outcomes such as hospital admission rates, asthma severity scores, and pulmonary function scores.", "output": "A double-blinded randomized controlled trial of 33 children aged 6 to 14 years showed no difference in MDI/S vs nebulizer, as measured by clinical score, respiratory rate, oxygen saturation, and forced expiratory volume at 1 second (FEV1). The researchers calculated the study had 90% power to detect a clinically meaningful difference in FEV1 of 12% of the predicted value between the groups." }, { "input": "Metered-dose inhalers with a spacer (MDI/S) are as good as, or better than, nebulizers for children with asthma. This is based on numerous randomized controlled trials that compared outcomes such as hospital admission rates, asthma severity scores, and pulmonary function scores.", "output": "A randomized controlled trial of 152 patients found no difference in primary outcomes of asthma severity score, oxygen saturation, and percent predicted peak expiratory flow rate (PEFR). Several secondary outcomes slightly favored MDI/S: number of treatments given, whether steroids were used, change in heart rate, side effects, rate of hospital admission, and treatment time in the emergency department." }, { "input": "Metered-dose inhalers with a spacer (MDI/S) are as good as, or better than, nebulizers for children with asthma. This is based on numerous randomized controlled trials that compared outcomes such as hospital admission rates, asthma severity scores, and pulmonary function scores.", "output": "One study showed a lower admission rate in 85 patients who were 2 to 24 months in the MDI/S group. Controlling for the initial Pulmonary Index score, children using an MDI and Aerochamber spacer were admitted less often (5% vs 20%, number needed to treat=7; P=.05) than children using nebulizers. Since the results of this single small trial are the only data available for this younger age group, using MDI/S instead of nebulizers should be done with caution for children aged <2 years." }, { "input": "Metered-dose inhalers with a spacer (MDI/S) are as good as, or better than, nebulizers for children with asthma. This is based on numerous randomized controlled trials that compared outcomes such as hospital admission rates, asthma severity scores, and pulmonary function scores.", "output": "A Cochrane review of 10 randomized controlled trials comparing nebulizers with MDI/S, both in adults and in children aged >2 years, showed a substantial trend towards improvement in hospital admission rates with MDI/S use. Sample size for each study was small, ranging from 18 to 152 patients, with a total sample size of 880 children and 444 adults. The relative risk of admission for MDI/S vs nebulizer for children was 0.65 (95% confidence interval, 0.4-1.06). Secondary outcomes were equivalent or slightly improved, including duration in the emergency department, changes in respiratory rate, blood gases, pulse, tremor, symptoms score, lung function, and use of steroids. Patients with life-threatening asthma (for example, those considered for ventilation) or other chronic illnesses were excluded." }, { "input": "Your initial risk assessment should include the patient's smoking history, advancing age, cancer history, and chest radiography features.", "output": "The authors found that 3 clinical variables (age, smoking history, and cancer history) plus 3 radiographic variables (diameter, spiculation, and nodule location in the upper lobes) were independent predictors of malignancy." }, { "input": "Your initial risk assessment should include reviewing old chest radiographs.", "output": "A recent study calculated the predictive value of benign nature based on no growth to be only 65% (95% confidence interval [CI], 47%-83%)." }, { "input": "A solitary pulmonary nodule unchanged for >2 years on chest radiograph or containing benign central calcifications requires no further work-up..", "output": "The presumed benign nature of lesions that are either unchanged over 2 years or have central calcifications is based on 3 retrospective studies from the 1950s." }, { "input": "While radiologists' interpretations of a nodule's calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases.", "output": "Three comparative studies observed 8 to 12 radiologists' readings of high-resolution CT images of 28 to 56 patients with solitary pulmonary nodules (established diagnoses by either histology or stability over time). Approximately half the nodules represented malignant lesions. Radiologists assigned a level of confidence to their assessment of each case as benign or malignant. At a minimum, they were informed of each patient's age and gender, and in 2 studies they also knew other information, such as the patient's smoking and cancer histories. The study showed that the radiologists would have correctly diagnosed a pair of solitary pulmonary nodule cases, one malignant and one benign, between 75% and 83% of the time. Conversely, 17% to 25% of the time they would have diagnosed the case pair incorrectly." }, { "input": "While radiologists' interpretations of a nodule's calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases.", "output": "Also, a study assessing the accuracy of radiologists' assessment of calcification in solitary pulmonary nodules compared with thin-section CT found that 7% of \"definitely calcified\" nodules on chest radiograph lacked calcification on thin-section CT." }, { "input": "Spiral CT with contrast is still diagnostically useful in making decisions regarding watchful waiting, needle biopsy, or surgery.", "output": "A recent systematic review of studies evaluating patients with suspected lung cancer looked into the diagnostic sensitivity of various methods of histologic and cytologic tests. Researchers compared the evaluated test results to a reference standard of pathology/histology, definitive cytology, or at least 1-year radiographic follow-up. Transbronchial needle aspiration showed a sensitivity of 67% (95% CI, 64%-70%) for peripheral lung malignancy of any size; however, only 5 studies met study criteria and their sample sizes varied greatly (n=20 to n=480). Eight studies looking at bronchoscopy (including brush or biopsy) for peripheral lung lesions <2 cm in diameter yielded a sensitivity of only 33% (95% CI, 28%-38%). In the same systematic review, 61 studies of transthoracic needle aspiration for localized pulmonary lesions of any size had a pooled sensitivity of 90% (95% CI, 88%-92%). The prevalence of malignancy in the studies ranged from 0.58 to 0.93.15 Factors affecting heterogeneity between studies included the wide range in study dates, imaging technology used, and study sizes." }, { "input": "18-fluorodeoxyglucose positron emission tomography (FDG PET) is useful for assessing malignancy risk.", "output": "CT appears cost-effective when the pretest probability of malignancy is <90%; therefore, consider it on virtually all new cases of solitary pulmonary nodules. Also, when CT and pretest risk-assessments are discordant (eg, a patient has a low pretest probability of malignancy but his CT is suggestive of malignancy), the FDG PET scan is the most economically feasible at less than $20,000 per quality-adjusted life year." }, { "input": "18-fluorodeoxyglucose positron emission tomography (FDG PET) is not useful for solitary pulmonary nodules <1 cm.", "output": "A meta-analysis of 40 studies of FDG PET scanning for solitary pulmonary nodules yielded a maximum joint sensitivity and specificity of 90% (95% CI, 86.4%- 92.7%). The methodological quality of studies included in the meta-analysis was fair, with small sample sizes (inclusion criteria were for a minimum of 10 patients with pulmonary nodules and malignant prevalence of at least 0.5); masking was frequently incomplete." }, { "input": "other", "output": "Although early detection of malignancy portends a major improvement in survival (up to 75% at 5 years following surgical resection of stage IA disease), most lung cancers progress asymptomatically until quite advanced." }, { "input": "other", "output": "The best available clinical decision rule was derived and validated from a single split population of patients with solitary pulmonary nodules. The outcome variable was defined as malignancy based on histologic tissue analysis or benignity by radiographic stability or resolution over 2 years. The authors did not report whether those determining outcomes and predictors were appropriately blinded." }, { "input": "other", "output": "A solitary pulmonary nodule, or \"coin lesion\", is an intraparenchymal finding on chest radiograph or CT that is less than 3 to 4 cm in diameter and not associated with atelectasis or adenopathy. Malignancy rates range from 15% to 75%, depending on the population studied." }, { "input": "Exercise treadmill testing has a sensitivity of 70% and specificity of 61% for the detection of coronary artery disease (CAD) in women.", "output": "A large meta-analysis of 19 studies looked specifically at women (n=3721) and found that noninvasive exercise tests only \"moderately useful\" for the detection of CAD. Exercise treadmill testing in women had a specificity of 0.70 (95% confidence interval [CI], 0.64-0.75), a sensitivity of 0.61 (95% CI, 0.54-0.68), a positive likelihood ratio of 2.25 (95% CI, 1.84-2.66) and a negative likelihood ratio of 0.55 (95% CI, 0.47-0.62). In comparison, exercise treadmill testing in men had a sensitivity of 0.70 and a specificity of 0.77. Among the theoretical reasons for the diminished accuracy of the exercise treadmill testing in women are the varying catecholamine response to exercise, a higher incidence of mitral valve prolapse, and chest wall anatomy different than that in men." }, { "input": "It is useful for detecting CAD in symptomatic women who have an intermediate risk as determined by age and symptoms.", "output": "The Institute for Clinical Systems Improvement states that exercise treadmill testing has application for the detection of coronary artery disease in those women with an intermediate 10%-90% pretest probability of coronary artery disease as determined by age, gender, and symptoms. The intermediate category includes women aged 30 to 49 years with typical symptoms of angina, women aged 50 to 59 years with typical or atypical symptoms of angina, and women aged 60 to 69 years with atypical or nonanginal chest pain. All other women fall into groups with pretest probability either high enough or low enough that the exercise treadmill testing is less useful." }, { "input": "It is useful for detecting CAD in symptomatic women who have an intermediate risk as determined by age and symptoms.", "output": "The American College of Cardiology ACC and the American Heart Association concluded that the diagnosis of CAD in women presents difficulties not experienced with men, due primarily to the lower sensitivity and specificity of exercise treadmill testing. The ACC recommends exercise treadmill testing for the diagnosis of CAD in patients with an intermediate pretest probability of coronary disease based on age, gender, and symptoms." }, { "input": "Exercise treadmill testing may also have an application in determining exercise capacity and potential as a tool to predict cardiovascular death in women.", "output": "A large cohort study of 2994 asymptomatic women found that those women with a below-average peak exercise capacity and heart-rate recovery rate were 3.5 times more likely to die of cardiovascular causes than women who were above average (95% CI, 1.57-7.86)." }, { "input": "Exercise treadmill testing may also have an application in determining exercise capacity and potential as a tool to predict cardiovascular death in women.", "output": "A cohort study of 5721 women found that an exercise capacity of <5 metabolic equivalents (METS) tripled the risk of death as compared with those with an exercise capacity of >8 METS. These studies support the role of exercise treadmill testing for risk stratification for CAD disease in women." }, { "input": "Adverse reactions to long-term tetracycline therapy are rare, and most will occur within 2 months of initiating therapy.", "output": "A study of the safety of tetracycline, which used reports in a drug safety database and a literature review of reported adverse events, concluded that rare but serious events do occur with tetracycline. Severe cutaneous adverse reaction was the most common reported single-organ dysfunction. Other rare events included hypersensitivity syndrome reactions and serum sickness-like reactions. Since baseline rates of tetracycline use are unknown, it is impossible to ascertain the event rates for these rare reactions. Most of these serious adverse events occur less than 2 months after initiating therapy; they typically include general symptoms such as fever, malaise, and arthralgias, but may also include major organ involvement. The study suggested no clear treatment for these complications, but recommended discontinuing tetracycline and avoiding the entire tetracycline class of drugs. No evidence supports previous concerns that tetracycline causes drug-induced lupus." }, { "input": "Rare but serious drug reactions include a severe cutaneous reaction, hypersensitivity syndrome reaction, serum sickness-like reaction, and isolated single-organ dysfunction.", "output": "A study of the safety of tetracycline, which used reports in a drug safety database and a literature review of reported adverse events, concluded that rare but serious events do occur with tetracycline. Severe cutaneous adverse reaction was the most common reported single-organ dysfunction. Other rare events included hypersensitivity syndrome reactions and serum sickness-like reactions." }, { "input": "Rare but serious drug reactions include a severe cutaneous reaction, hypersensitivity syndrome reaction, serum sickness-like reaction, and isolated single-organ dysfunction.", "output": "Minor adverse side effects of tetracycline therapy are reported in about 8% of patients." }, { "input": "Duration of antibiotic treatment is strongly associated with increased bacterial resistance.", "output": "A systematic review confirms that treating acne with long-term systemic antibiotics leads to increased antimicrobial resistance." }, { "input": "Duration of antibiotic treatment is strongly associated with increased bacterial resistance.", "output": "A well-designed cohort trial showed that Propioni-bacteri-um acnes resistance was directly related to duration of antibiotic therapy." }, { "input": "Duration of antibiotic treatment is strongly associated with increased bacterial resistance.", "output": "Rotating antibiotics on a long-term basis actually increases bacterial resistance patterns and can exacerbate the problems of increasing resistance and poor treatment outcomes." }, { "input": "Antibiotics for acne do not appear to interfere with oral contraceptive efficacy.", "output": "A relatively large retrospective cohort study of oral contraceptive users in a dermatological practice showed no difference in contraceptive failure rates between those prescribed common antibiotics (including tetracycline) and controls (1.6% vs 0.96%; 95% confidence interval [CI] for the difference, 0.81-2.1)." }, { "input": "Laboratory monitoring is not indicated in otherwise healthy patients.", "output": "A systematic review of 8 studies reported on 777 patients taking antibiotics for acne, and examined the need for laboratory monitoring of long-term tetracycline users, including renal, liver, and blood components. The authors found only 1 adverse drug reaction (mild hyperbilirubinemia). They concluded that routine lab monitoring for all patients on long-term antibiotics for acne rarely detects clinically concerning adverse drug reactions and would be cost-prohibitive." }, { "input": "No reports have been published regarding long-term topical tretinoin (Retin A) therapy. Short-term follow-up reports note no systemic effects.", "output": "Topical tretinoin has been in clinical use for more than 25 years. Topical delivery results in a very low systemic exposure; plasma retinoid levels measured after topical use remain at or below endogenous levels, likely due to very limited absorption." }, { "input": "Short-term follow-up reports note no teratogenicity.", "output": "Topical tretinoin is not associated with an increased risk for major congenital disorders. A retrospective study of 215 women on tretinoin during the first trimester compared with 430 controls found that the relative risk for a major congenital anomaly was 0.7 (95% CI, 0.2-2.3). The authors concluded that topical tretinoin did not increase congenital anomaly risk." }, { "input": "Short-term follow-up reports note negligible systemic absorption.", "output": "A multicenter, double-blind parallel study compared the safety and efficacy of 2 formulations of tretinoin gel formulations. These cutaneous irritant side effects, while noted in up to 50% of treated patients, peaked in 7 days and decreased significantly over time." }, { "input": "Long-term topical tretinoin is presumed to be safe.", "output": "Topical tretinoin has been in clinical use for more than 25 years. Topical delivery results in a very low systemic exposure; plasma retinoid levels measured after topical use remain at or below endogenous levels, likely due to very limited absorption." }, { "input": "No individual or combination of blood tests can reliably diagnose pelvic inflammatory disease (PID).", "output": "A meta-analysis from 1991 assessed the laboratory criteria for the diagnosis of PID. No single or combination diagnostic indicator was found to reliably predict PID." }, { "input": "The combination of white blood cell count, Creactive protein (CRP), erythrocyte sedimentation rate (ESR), and vaginal white blood cells can reliably exclude PID if results for all 4 tests are normal (sensitivity=100%).", "output": "A prospective cohort study of 120 women presenting to an ambulatory center with symptoms of PID evaluated the tests commonly used to support the clinical diagnosis of PID. The objective criteria used for diagnosis included histologic evidence of acute endometritis via endometrial biopsy, purulent exudates in the pelvis on laparoscopy, or microbiologic evidence of Neisseris gonorrhea or Chlamydia trachomatis from the upper genital tract. The Table shows the sensitivities, specificities, and predictive values for an elevated white blood cells (>10,000/mm), ESR (>15 mm/hr), CRP (>5 mg/dL), and increased vaginal white blood cells (>3 white blood cells/high-power field) for detection of PID. If all 4 test results are negative, PID is reliably ruled out with a sensitivity of 100%. These results may be an overestimate, as the gold standard was not uniformly applied." }, { "input": "The combination of CRP and ESR is helpful in excluding PID (sensitivity=91%) and may be especially useful in distinguishing mild from complicated cases.", "output": "The role of CRP and ESR in the diagnosis of acute PID was studied in 41 women with clinically suspected acute PID who presented to a university department of obstetrics and gynecology. Women underwent laparoscopy, endometrial sampling, and cultures of the upper genital tract to confirm the diagnosis. When considered together, a positive value in either the ESR (cutoff level of 15 mm/hr) or CRP (cutoff >20 mg/dL) had a sensitivity of 91% and a specificity of 50%." }, { "input": "The combination of CRP and ESR is helpful in excluding PID (sensitivity=91%) and may be especially useful in distinguishing mild from complicated cases.", "output": "A report looked at the ability of ESR and CRP to differentiate between mild, moderate, and severe PID in 72 women undergoing laparoscopy at a university department of gynecology.4 The cutoff levels were ESR >40 mm/hr and CRP >60 mg/dL. If either test was abnormal, the sensitivity and the negative predictive value for severe disease were 97% and 96%, respectively. All patients with tuboovarian abscess or perihepatitis and 6 of 7 patients who had anaerobic bacteria isolated from the fallopian tubes tested positive with these cutoff levels." }, { "input": "Individual tests do not appear to significantly improve diagnostic accuracy, although the CRP and ESR are somewhat useful to rule out PID.", "output": "A meta-analysis from 1991 found 12 studies, not including any of the above studies, and assessed the laboratory criteria for the diagnosis of PID. No single or combination diagnostic indicator was found to reliably predict PID. However, the CRP and the ESR were useful in ruling out PID, with good sensitivities for CRP in 4 of 4 studies analyzed (74%-93%) and for the ESR in 4 of 6 studies (64%-81%). Ten of 12 studies used laparoscopy as the gold standard." }, { "input": "Evidence on the use of leukotriene inhibitors in children is insufficient to permit conclusions regarding efficacy. Given the proven efficacy of inhaled corticosteroids in asthma management, leukotriene inhibitors should not replace inhaled corticosteroids for maintenance of asthma in children.", "output": "A randomized, double-blind, placebo-controlled study of 338 patients aged 12 years to adult compared zafirlukast (Accolate) with fluticasone propionate (Flovent) for control of persistent asthma. This study concluded that fluticasone was superior for all clinical outcomes measured including symptom scores, albuterol use, nighttime awakenings pulmonary function, and number of exacerbations requiring oral corticosteroids. Pooling of adult and adolescent cases in this study limits generalized application of these results to pediatric practice." }, { "input": "Evidence on the use of leukotriene inhibitors in children is insufficient to permit conclusions regarding efficacy. Given the proven efficacy of inhaled corticosteroids in asthma management, leukotriene inhibitors should not replace inhaled corticosteroids for maintenance of asthma in children.", "output": "One randomized, double-blind crossover study of 279 children with corticosteroid-dependent (persistent) asthma compared montelukast 5 mg (Singulair) once a day plus inhaled budesonide 200 \u00b5g (Pulmicort) twice a day with placebo plus budesonide (Rhinocort). Each study period lasted only 4 weeks, starting after a 4-week run-in period. Montelukast modestly improved asthma control over placebo. Compared with the placebo period, montelukast decreased the average use of beta-agonists by 1 puff per day. Asthma exacerbation days decreased by about 1 per month during montelukast treatment. The effects of montelukast and placebo on forced expiratory volume in 1 second (FEV1), quality of life, and adverse events did not differ significantly." }, { "input": "Evidence on the use of leukotriene inhibitors in children is insufficient to permit conclusions regarding efficacy. Given the proven efficacy of inhaled corticosteroids in asthma management, leukotriene inhibitors should not replace inhaled corticosteroids for maintenance of asthma in children.", "output": "Asthma is characterized by inflammation of the bronchial airways. Leukotrienes are potent mediators of inflammation and are believed to contribute significantly to the inflammatory pathophysiology of asthma. Leukotriene inhibitors interfere with leukotriene production or leukotriene receptors and thus inhibit inflammation. There is insufficient evidence to support the use of leukotriene inhibitors in children as monotherapy or as an addition to corticosteroids." }, { "input": "The best treatment for minor, self-limited constipation (infant dyschezia) may be observation and parental education about its benign nature.", "output": "Infant dyschezia, a self-limited condition related to immature muscle coordination, requires only parental reassurance." }, { "input": "For cases requiring treatment, limited evidence suggests that 2 weeks of 2% or 4% lactulose normalizes stool passage and consistency.", "output": "One uncontrolled trial of 220 functionally constipated, bottle-fed infants younger than 6 months showed normalization of stools in 90% of infants within 2 weeks of treatment with 2% or 4% lactulose. No other evidence has been published about the benefits or harms of sorbitol-containing juices, fiber, osmotic laxatives, formula switching, rectal stimulation with rectal thermometers, or glycerin suppositories." }, { "input": "No data are available about the benefits or harms of rectal thermometer stimulation, glycerin suppositories, sorbitol or sorbitol-containing juices, barley malt extract, or corn syrup. The significant risks of sodium phosphate enemas and mineral oil consumption make their use contraindicated.", "output": "Mineral oil has been associated with lipoid aspiration pneumonia in infants less than 1 year of age." }, { "input": "No data are available about the benefits or harms of rectal thermometer stimulation, glycerin suppositories, sorbitol or sorbitol-containing juices, barley malt extract, or corn syrup. The significant risks of sodium phosphate enemas and mineral oil consumption make their use contraindicated.", "output": "Sodium phosphate enemas in children under 2 years of age have been associated with electrolyte disturbances, dehydration, and cardiac arrest." }, { "input": "other", "output": "Infants experience normal physiologic variation in stool frequency and consistency, moderated in part by diet." }, { "input": "Leg cramps are very common.", "output": "More than two thirds of people aged >50 years have experienced leg cramps." }, { "input": "Most cases of leg cramps have no detectable cause.", "output": "Though leg cramps are common, little is known about their actual causation." }, { "input": "Arterial vascular disease and neurological diseases are more prevalent among male patients with leg cramps.", "output": "A small, retrospective chart review, limited to male patients, identified an association of vascular and neurologic diseases among patients taking quinine, presumably for leg cramps." }, { "input": "History and physical should focus on detecting precipitating factors for iron deficiency anemia (gastrointestinal bleeding, frequent blood donations, menorrhagia), electrolyte imbalance (renal disease, fluid losses), endocrine disorders (thyroid, Addison's disease), neuromuscular disorders (neuropathies and myopathies), and medication use (antidepressants and diuretics). Laboratory testing is guided by the history and physical and may include ferritin, electrolytes, blood sugar, magnesium, zinc, creatinine, blood urea nitrogen, liver function test, and thyroid-stimulating hormone.", "output": "The physical examination should include a search for obvious physical signs of symptoms noted in the history." }, { "input": "History and physical should focus on detecting precipitating factors for iron deficiency anemia (gastrointestinal bleeding, frequent blood donations, menorrhagia), electrolyte imbalance (renal disease, fluid losses), endocrine disorders (thyroid, Addison's disease), neuromuscular disorders (neuropathies and myopathies), and medication use (antidepressants and diuretics). Laboratory testing is guided by the history and physical and may include ferritin, electrolytes, blood sugar, magnesium, zinc, creatinine, blood urea nitrogen, liver function test, and thyroid-stimulating hormone.", "output": "All reviews suggest that the best diagnostic approach to leg cramps is a thorough history, and careful physical and neurological examination. The health care provider should clarify the onset and duration of leg cramps, any precipitating activity, and factors that provide relief. A detailed history should focus on precipitating factors for iron deficiency anemia (gastro-intestinal bleeding, frequent blood donations, menorrhagia), a history of renal disease (especially end-stage renal failure) and medication use (antidepressants and diuretics)." }, { "input": "History and physical should focus on detecting precipitating factors for iron deficiency anemia (gastrointestinal bleeding, frequent blood donations, menorrhagia), electrolyte imbalance (renal disease, fluid losses), endocrine disorders (thyroid, Addison's disease), neuromuscular disorders (neuropathies and myopathies), and medication use (antidepressants and diuretics). Laboratory testing is guided by the history and physical and may include ferritin, electrolytes, blood sugar, magnesium, zinc, creatinine, blood urea nitrogen, liver function test, and thyroid-stimulating hormone.", "output": "Although commonly idiopathic, leg cramps are sometimes associated with various disorders including endocrine, metabolic, occupational, structural, neuromuscular, vascular, and congenital disorders, as well as toxin- and drug-related causes." }, { "input": "History and physical should focus on detecting precipitating factors for iron deficiency anemia (gastrointestinal bleeding, frequent blood donations, menorrhagia), electrolyte imbalance (renal disease, fluid losses), endocrine disorders (thyroid, Addison's disease), neuromuscular disorders (neuropathies and myopathies), and medication use (antidepressants and diuretics). Laboratory testing is guided by the history and physical and may include ferritin, electrolytes, blood sugar, magnesium, zinc, creatinine, blood urea nitrogen, liver function test, and thyroid-stimulating hormone.", "output": "Though neurophysiological research shows that true muscle cramps are caused by explosive hyperactivity of motor nerves, using diagnostic tools such as electromyography, muscle biopsy, and muscle enzymes are seldom needed." }, { "input": "History and physical should focus on detecting precipitating factors for iron deficiency anemia (gastrointestinal bleeding, frequent blood donations, menorrhagia), electrolyte imbalance (renal disease, fluid losses), endocrine disorders (thyroid, Addison's disease), neuromuscular disorders (neuropathies and myopathies), and medication use (antidepressants and diuretics). Laboratory testing is guided by the history and physical and may include ferritin, electrolytes, blood sugar, magnesium, zinc, creatinine, blood urea nitrogen, liver function test, and thyroid-stimulating hormone.", "output": "Neurological examination can exclude most disorders that simulate leg cramps such as contractures, dystonia, myalgia and peripheral neuropathy." }, { "input": "History and physical should focus on detecting precipitating factors for iron deficiency anemia (gastrointestinal bleeding, frequent blood donations, menorrhagia), electrolyte imbalance (renal disease, fluid losses), endocrine disorders (thyroid, Addison's disease), neuromuscular disorders (neuropathies and myopathies), and medication use (antidepressants and diuretics). Laboratory testing is guided by the history and physical and may include ferritin, electrolytes, blood sugar, magnesium, zinc, creatinine, blood urea nitrogen, liver function test, and thyroid-stimulating hormone.", "output": "The choice of laboratory investigations such as ferritin, electrolytes, blood sugar, magnesium, zinc, creatinine, blood urea nitrogen, liver function test, and thyroid function test are largely governed by the findings from the history and physical examination." }, { "input": "For current and former smokers, the evidence does not support yearly chest x-rays to decrease lung cancer mortality.", "output": "The National Cancer Institute (NCI) sponsored 3 randomized controlled trials on lung cancer screening for male smokers involving 3 major medical centers. The studies were designed to determine the incremental benefit of adding sputum cytology to chest x-ray screening. In 2 of the NCI studies, participants were randomly assigned to receive annual chest x-ray only or a dual screen with annual chest x-ray and sputum cytologies every 4 months. In both studies, there was no statistical difference in lung cancer mortality between the 2 groups." }, { "input": "For current and former smokers, the evidence does not support yearly chest x-rays to decrease lung cancer mortality.", "output": "A trial involved male smokers who were randomized to undergo chest x-ray and sputum cytology either every 6 months or after 3 years. After 3 years, both groups were screened annually with chest x-ray alone for an additional 3 years. There was no significant difference in lung cancer mortality at any point, including at a 15-year post-trial follow-up." }, { "input": "For current and former smokers, the evidence does not support yearly chest x-rays to decrease lung cancer mortality.", "output": "In two randomized controlled trials that included former as well as current smokers and nonsmokers-subjects were randomized to undergo chest x-ray studies every 6 months, or at baseline and again at the end of the 3-year study. After 3 years, there was no statistically significant mortality difference with more frequent chest x-rays." }, { "input": "Even with the addition of sputum cytology and more frequent chest x-rays, lung cancer mortality was unchanged.", "output": "The National Cancer Institute (NCI) sponsored 3 randomized controlled trials on lung cancer screening for male smokers involving 3 major medical centers. The studies were designed to determine the incremental benefit of adding sputum cytology to chest x-ray screening. In 2 of the NCI studies, participants were randomly assigned to receive annual chest x-ray only or a dual screen with annual chest x-ray and sputum cytologies every 4 months. In both studies, there was no statistical difference in lung cancer mortality between the 2 groups." }, { "input": "Even with the addition of sputum cytology and more frequent chest x-rays, lung cancer mortality was unchanged.", "output": "No significant difference in lung cancer mortality, even after an extended follow-up of 20.5 years. Adding sputum cytology to chest x-ray only improved lung cancer detection rates over chest x-ray alone." }, { "input": "Progestin-only contraceptives are an effective form of birth control. For the treatment of premenstrual syndrome or dysfunctional uterine bleeding, inadequate evidence exists to support using progestin-only options.", "output": "Evidence is lacking to support use of progestin-only contraceptives for premenstrual syndrome or dysfunctional uterine bleeding." }, { "input": "other", "output": "The risk of pregnancy with progestinonly contraceptives ranges from 0.0% to 13.2% based on the method that is selected." }, { "input": "Breast self-examination has little or no impact on breast cancer mortality and cannot be recommended for cancer screening.", "output": "Two large RCTs, conducted in St Petersburg, Russia (122,471 women) and Shanghai, China (266,064 women), were found. Both studies used cluster randomization (by worksite) and involved large numbers of women who were meticulously trained in proper breast self-examination technique and had numerousreinforcement sessions. Study compliance and follow-up were excellent. Outcomes assessment was explicitly blinded in the Shanghai study. Neither trial demonstrated a reduction in breast cancer mortality or improvement in the number or stage of cancers detected during 9 to 11 years of follow-up, but there is evidence for harm: a nearly 2-fold increase in false-positive results, physician visits, and biopsies for benign disease." }, { "input": "Clinical breast examination is an important means of averting some deaths from breast cancer, but demands careful attention to technique and thoroughness.", "output": "No trials comparing screening clinical breast examinations alone to no screening have been reported, but good indirect evidence of efficacy comes from the results of the Canadian National Breast Screening Study-2 (CNBSS-2). A total of 39,405 women aged 50 to 59 years were randomized to screening with clinical exams plus mammography or clinical exams alone." }, { "input": "Clinical breast examination is an important means of averting some deaths from breast cancer, but demands careful attention to technique and thoroughness.", "output": "Large RCTs have shown a consistent benefit to mammography screening for women aged 50 to 59 years (in-depth independent reviews of recent criticism of the trials have concluded that their flaws do not negate mammography's efficacy in reducing breast cancer mortality)." }, { "input": "Clinical breast examination is an important means of averting some deaths from breast cancer, but demands careful attention to technique and thoroughness.", "output": "The CNBSS-2 trial showed no mortality advantage when mammography was added to an annual, standardized 10- to 15-minute breast examination, implying that careful, detailed, annual clinical breast examinations may be as effective as a mammography screening program." }, { "input": "We found no evidence for changed outcomes from early detection of renal artery stenosis (RAS). Treatment of RAS in refractory hypertension modestly improves blood pressure control. There was a trend toward improved clinical outcomes but studies were underpowered to demonstrate this.", "output": "A meta-analysis (3 RCTs, total n=210 patients) examining balloon angioplasty for RAS and poorly controlled hypertension showed modest but significant effect on blood pressure control.1 Comparing the angioplasty group with medical management, the mean reduction in blood pressure was -7 mm Hg systolic (95% confidence interval [CI], -12 to -1) and -3 mm Hg diastolic (95% CI, -6 to -1). Patients treated with balloon angioplasty were more likely to use fewer antihypertensive medications (unable to synthesize data for quantity) and to have fewer major cardiovascular and renovascular complications (not defined specifically) (odds ratio [OR]=0.27; 95% CI, 0.06-1.23; P=.09)." }, { "input": "We found no evidence for changed outcomes from early detection of renal artery stenosis (RAS). Treatment of RAS in refractory hypertension modestly improves blood pressure control. There was a trend toward improved clinical outcomes but studies were underpowered to demonstrate this.", "output": "One cohort study of 150 patients found that stenting bilateral (vs unilateral) RAS predicted a more beneficial blood pressure response (OR=4.6; P=.009)." }, { "input": "Treatment of RAS in chronic renal impairment does not appear to improve renal function nor change clinical outcomes, but data are conflicting.", "output": "One RCT of 106 patients with atherosclerotic RAS and serum creatinine (Cr) of <2.3 mg/dL compared PTRA with medical therapy of hypertension. By an intentionto-treat analysis, there was no significant difference in renal function at 12 months between the groups." }, { "input": "Treatment of RAS in chronic renal impairment does not appear to improve renal function nor change clinical outcomes, but data are conflicting.", "output": "A nonblinded RCT of 85 patients found no change in mortality or renal function with intervention. Three groups were compared: observation of 52 patients with unilateral RAS (>50%), intervention on 12 patients with bilateral RAS, and observation of 21 patients with bilateral RAS. All groups reported 32% mortality at 2 years. Only 3 of the 27 deaths were directly related to renal disease (2 from the observation group with unilateral RAS and one from the intervention group)." }, { "input": "Subgroups of patients who have recurrent episodes of congestive heart failure or flash pulmonary edema exhibit functional improvement following percutaneous transluminal renal angioplasty (PTRA) with stent placement.", "output": "Patients who have recurrent episodes of congestive heart failure or flash pulmonary edema with severe RAS have marked functional improvement following PTRA with stenting. One retrospective cohort study (n=39) reported a decrease in hospitalizations (from 2.4 \u00b11.4 per year to 0.3 \u00b10.7 per year; P<.001) and improvement in New York Heart Association heart failure functional classification (2.9 \u00b10.9 to 1.6 \u00b10.9)." }, { "input": "Computed tomography (CT) angiography and magnetic resonance angiography (MRA) are the most accurate and cost-effective noninterventional diagnostic modalities for RAS.", "output": "MRA (sensitivity 99%, specificity 93%) and CT angiography (sensitivity 97%, specificity 95%) are the most accurate and cost-effective, based on a large meta-analysis." }, { "input": "While revascularization effectively improves patency, the complication rate is high and deaths have occurred.", "output": "Combining 3 studies (n=632), there were 5 procedurerelated deaths." }, { "input": "While revascularization effectively improves patency, the complication rate is high and deaths have occurred.", "output": "Serious or potentially serious complications (ie, bleeding, renal artery injury, need for hemodialysis) were seen in 13% to 25% of patients who underwent angioplasty." }, { "input": "Patients with worse renal function tend to do more poorly.", "output": "Worsened patient survival correlated with Cr >1.7 mg/dL or age >70 (OR=9.96, P<.0001 and OR=3.4, P=.001, respectively). Worsened renal survival was present in the same subgroups (OR=7.8, P<.001 and OR=2.7, P<.01, respectively)." }, { "input": "Patients with a new diagnosis of hypertension should be evaluated with a history and physical exam and the following initial studies: serum potassium and creatinine, fasting serum glucose and lipid panel, hematocrit, urinalysis, and electrocardiogram.", "output": "A cohort study followed 2363 patients for 14 years who had untreated hypertension and were without pre-existing cardiovascular disease. After controlling for age, sex, diabetes, and mean blood pressure, LVH by ECG conferred a significant increased risk for cerebrovascular events (relative risk=1.79; 95% confidence interval [CI], 1.17-2.76). However, in a cohort of 4684 subjects from the Framingham Heart Study, ECG had a sensitivity of only 6.9% for the detection of LVH (specificity 98.8%; positive likelihood ratio=5.3; negative likelihood ratio=0.94)." }, { "input": "Patients with a new diagnosis of hypertension should be evaluated with a history and physical exam and the following initial studies: serum potassium and creatinine, fasting serum glucose and lipid panel, hematocrit, urinalysis, and electrocardiogram.", "output": "A cohort study evaluating 356,222 men aged 35 to 57 years found a continuous, positive, graded correlation between plasma cholesterol levels and coronary risk." }, { "input": "Patients with a new diagnosis of hypertension should be evaluated with a history and physical exam and the following initial studies: serum potassium and creatinine, fasting serum glucose and lipid panel, hematocrit, urinalysis, and electrocardiogram.", "output": "An abnormal glucose level may also reveal glucose intolerance, one of the diagnostic criteria of metabolic syndrome. Up to 60% of patients with diabetes also have hypertension." }, { "input": "Patients with a new diagnosis of hypertension should be evaluated with a history and physical exam and the following initial studies: serum potassium and creatinine, fasting serum glucose and lipid panel, hematocrit, urinalysis, and electrocardiogram.", "output": "Four international expert panels recommend: A) measuring serum potassium and creatinine in order to: 1 monitor the effects of diuretics and angiotensin-converting enzyme (ACE) inhibitors used in hypertension therapy, 2 screen for unexplained hypokalemia that may indicate a low-renin form of hypertension, 3 calculate baseline creatinine clearance, and 4 screen for chronic kidney disease. B) measuring a fasting glucose level to screen for diabetes. C) screening for dyslipidemia with a fasting lipid panel to assess cardiovascular risk. D) hematocrit to screen for anemia, which may be due to chronic kidney disease. E) urinalysis to screen for renal disease. And F) an ECG to screen for findings associated with hypertension, including left ventricular hypertrophy (LVH), myocardial infarction, and rhythm abnormalities." }, { "input": "Consensus is lacking for measuring serum sodium, calcium, and uric acid.", "output": "Serum sodium was recommended by 2 panels and an online text." }, { "input": "Consensus is lacking for measuring serum sodium, calcium, and uric acid.", "output": "Serum calcium was recommended by 1 panel and the text." }, { "input": "Consensus is lacking for measuring serum sodium, calcium, and uric acid.", "output": "Uric acid was recommended by 1 panel." }, { "input": "Consensus is lacking for measuring serum sodium, calcium, and uric acid.", "output": "The text lists uric acid as optional." }, { "input": "Testing for microalbuminuria is optional in the work-up for a patient without diabetes.", "output": "All panels listed microalbuminuria testing as an optional study for patients without diabetes because of its association with an increased incidence of cerebrovascular disease." }, { "input": "Testing for microalbuminuria is optional in the work-up for a patient without diabetes.", "output": "It is unclear whether microalbuminuria results from the increased intraglomerular pressure in hypertension or if it represents glomerular damage." }, { "input": "Some expert panels list limited echocardiography as another option.", "output": "An online text recommends echocardiography, preferably limited echo, as an optional study." }, { "input": "Some expert panels list limited echocardiography as another option.", "output": "A systematic review of studies comparing the sensitivities and specificities of ECG and echo found that each was highly specific for the detection of LVH 77%-97%, but the sensitivity of echocardiography 88%-93% exceeded that of ECG 21%-54%. However, LVH detected by ECG is a better predictor of cardiovascular complications." }, { "input": "Some expert panels list limited echocardiography as another option.", "output": "Two panels recommend echocardiography, preferably limited echo, as an optional study. Because echocardiography may help assess disease duration and guide management, both panels recommend it for patients with severe or refractory hypertension but without other target organ damage." }, { "input": "In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel.", "output": "In contrast to the pretreatment times for all other malarial prophylaxes, the generally accepted pretreatment time for mefloquine is 1 to 2 weeks before entering a risk area. However, this may still be inadequate due to the drug's long half-life, which results in a long delay in reaching therapeutic blood levels. The evidence indicates that mefloquine should be started at least 2, and as many as 7, weeks before travel." }, { "input": "In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel.", "output": "The standard recommended dose of 250 mg/week of mefloquine \"produces maximum steady-state plasma concentrations of 1000 to 2000 mcg/L, which are reached only after 7 to 10 weeks.\"" }, { "input": "In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel.", "output": "One study of 293 children under the age of 5 years in Malawi found that plasma concentrations of mefloquine were below prophylactic level (500 mcg/mL) against P falciparum until the fourth to seventh week of once-weekly dosing (P<.0003)." }, { "input": "In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel.", "output": "One way of reaching prophylactic levels earlier would be to give mefloquine 250 mg daily for 3 days followed by 250 mg weekly. A safety study of 157 healthy US Marine volunteers showed that preloading achieves prophylactic blood levels of mefloquine by the third day while weekly mefloquine is subprophylactic until the fifth week." }, { "input": "In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel.", "output": "A study of the long-term use of mefloquine in 421 healthy Peace Corps volunteers has shown it to be safe." }, { "input": "In areas with chloroquine-resistant Plasmodium falciparum, travelers will need to take atovaquone/proguanil, doxycycline, or primaquine 1 day before entering the area, or mefloquine 2 to 7 weeks before travel.", "output": "Clinical trials and case reports indicate that a loading dose of mefloquine is associated with adverse drug events, which include neuropsychiatric and gastrointestinal symptoms." }, { "input": "No, COX-2 inhibitors, as a class, do not worsen renal function for those without renal disease. Celecoxib is the only COX-2 inhibitor available, and it is associated with a lower risk of renal dysfunction and hypertension when compared with controls. Available data do not allow for adjusted risk assessment for patients with preexisting renal disease on COX-2 inhibitors.", "output": "A randomized controlled trial compared standard dosing of diclofenac (75 mg twice daily) and ibuprofen (800 mg 3 times daily) with high-dose celecoxib (400 mg twice daily) for patients with normal kidney function being treated for osteoarthritis and rheumatoid arthritis. The mean increase in serum creatinine in the celecoxib arm was less than that noted in the diclofenac controls (0.009 mg/dL vs 0.027 mg/dL; P<.05; number needed to harm [NNH]=56). No difference in mean serum creatinine was seen among those patients using ibuprofen (800 mg 3 times daily) compared with those using high-dose celecoxib." }, { "input": "No, COX-2 inhibitors, as a class, do not worsen renal function for those without renal disease. Celecoxib is the only COX-2 inhibitor available, and it is associated with a lower risk of renal dysfunction and hypertension when compared with controls. Available data do not allow for adjusted risk assessment for patients with preexisting renal disease on COX-2 inhibitors.", "output": "A 2006 meta-analysis, including 114 trials and 116,094 patients randomized to either cyclooxygenase-2 (COX-2) inhibitor or control (placebo, nonsteroidal anti-inflammatory drug [NSAID], or mixed), indicated that the COX-2 inhibitors, as a class, had no effect on renal endpoints. Trials were reviewed for data on renal endpoints, including peripheral edema, hypertension, and renal dysfunction (defined as significant worsening of serum urea or creatinine, or clinical evidence of kidney disease and renal failure). When viewed separately, rofecoxib (Vioxx) was associated with a composite relative risk (RR) of 1.53 (95% confidence interval [CI], 1.33-1.76) for all renal endpoints compared with controls. In contrast, the composite RR for the same endpoints among patients taking celecoxib (Celebrex) was 0.97 (95% CI, 0.84-1.12), indicating no effect on renal function. In fact, for the specific outcomes of hypertension and renal dysfunction, celecoxib was associated with a decreased risk compared with controls. Stratified analysis by type of control (placebo, alternate NSAID, or mixed) yielded consistent results; rofecoxib was uniquely associated with adverse renal outcomes. No effect on renal function was noted for celecoxib compared with the same controls: the RR for adverse renal effects was 0.87 (95% CI, 0.55-1.38), 0.93 (95% CI, 0.70-1.23), and 1.26 (95% CI, 0.94-1.69) for celecoxib vs placebo, NSAID, and mixed controls, respectively. Statistical analysis for heterogeneity showed that the variation in effects on renal function among the COX-2 inhibitors was more likely due to actual differences than due to chance (heterogeneity [I2]=57%; P<.001)." }, { "input": "Infants with an undescended testis should be referred between ages 6 and 15 months, since almost all who experience spontaneous descent do so by 6 months.", "output": "A study found cryptorchidism at birth in 90 of 6414 (2.7%) infant boys. At follow-up, 45 of 90 had testicular descent at 1 month, 60 of 90 at 3 months, 67 of 90 at 9 months and at 1 year." }, { "input": "Infants with an undescended testis should be referred between ages 6 and 15 months, since almost all who experience spontaneous descent do so by 6 months.", "output": "One study of 10,730 consecutive male term infants found cryptorchidism at birth in 2.7%, dropping to 1.22% by 6 months of age, but without further change at 1 year." }, { "input": "Infants with an undescended testis should be referred between ages 6 and 15 months, since almost all who experience spontaneous descent do so by 6 months.", "output": "A study followed 6935 infant boys, finding cryptorchidism at birth in 3.7%, which decreased to 1% at 3 months and remained unchanged at 1 year." }, { "input": "The incidence of germ cell aplasia in undescended testes begins to rise at 15 months.", "output": "A literature review of fertility after orchiopexy for undescended testis found inconclusive results. While epidemiological and pathological data (testicular biopsy, hormonal analysis, and sperm counts performed after orchiopexy) predict diminished fertility potential for men with unilaterally undescended testes, studies evaluating paternity find no difference from normal men. Biopsy studies of undescended testes at the time of orchiopexy show increased incidence of germ cell aplasia with older age at surgery (0.5%, 2%, 20%, and 45% at 6, 12, 24, and 48 months, respectively)." }, { "input": "Evidence is inconclusive that orchiopexy at this age results in higher rates of paternity success.", "output": "A retrospective cohort study found 87% successful paternity after orchiopexy for 24 patients with unilateral undescended testis and 33% success for 9 with bilateral undescended testes but there was no normal control group. The boys were aged 1 to 14 years (mean, 7 years) at surgery, and there was no relationship between timing of orchiopexy and paternity success." }, { "input": "Orchiopexy may allow earlier detection of testicular tumors.", "output": "The benefits of orchiopexy for testicular cancer are also unclear; expert opinion suggests that orchiopexy may allow earlier detection of testicular tumors." }, { "input": "Orchiopexy has not been shown to reduce the risk of testicular cancer.", "output": "A cohort study of boys with cryptorchidism showed an increased risk of testicular cancer (relative risk=5.2). However, risk did not decrease after orchiopexy in early childhood." }, { "input": "Orchiopexy has not been shown to improve 5-year survival rates for those patients diagnosed with testicular cancer.", "output": "A retrospective cohort study of 137 men with cryptorchidism who developed testicular cancer found no difference in 5-year survival between those who had orchiopexy (at ages 2 to 42) and those who had not (61% vs 63%, respectively." }, { "input": "It's best to start with nonsteroidal anti-inflammatory drugs (NSAIDs), which effectively reduce heavy menstrual bleeding.", "output": "A Cochrane review of 16 small RCTs that examined the use of NSAIDs for menorrhagia found NSAIDs to be superior to placebo and comparable to other medical treatments such as luteal progestin, oral contraceptive pills, and progestin-releasing intrauterine systems." }, { "input": "Perimenopausal women with heavy bleeding not controlled by NSAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone.", "output": "An RCT of 132 perimenopausal women compared 24 weeks of combination hormonal therapy (20 mcg ethinyl estradiol/1 mg norethindrone acetate) with placebo for treating climacteric symptoms, including abnormal uterine bleeding. The combination therapy shortened the menstrual cycle (27.7 vs 30.4 days), decreased its variability (17.5-46.7 days vs 22.4-66 days), and lowered bleeding severity scores (6.9 vs 10.2). Hormonal therapy didn't shorten bleeding episodes, however, and was associated with a higher incidence of intermenstrual bleeding during the first 3 months of treatment." }, { "input": "Perimenopausal women with heavy bleeding not controlled by NSAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone.", "output": "An RCT of 120 perimenopausal women with irregular menstrual cycles compared low-dose (1 mg) continuous estradiol and cyclical progestogens (10 mg dydrogesterone) with cyclical progestogens alone. In the combined treatment group, the incidence of cyclical menstrual bleeding was 86%, and 76% of all cycles were rated normal in amount and duration of bleeding. In the cyclical progestogen group, the incidence of cyclical menstrual bleeding during treatment was 76%, and 70% of all cycles were rated normal." }, { "input": "Perimenopausal women with heavy bleeding not controlled by NSAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone.", "output": "A systematic review, comprised primarily of RCTs, examined uterine bleeding patterns in 3000 postmenopausal women taking combined continuous hormones (various regimens of estrogen and progestin). In 22 of 23 studies that included data past 6 months, 75% or more of participants became amenorrheic while on therapy. Irregular uterine bleeding before 6 months of therapy was common, however, and was presumed to lower patient compliance." }, { "input": "Perimenopausal women with heavy bleeding not controlled by NSAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone.", "output": "A more recent Cochrane review of 30 RCTs examined hormone replacement therapy for irregular bleeding and endometrial hyperplasia in postmenopausal women who had been amenorrheic for at least 6 months (a more liberal criterion for inclusion). The review concluded that many of the women treated with continuous estrogen and progestin became amenorrheic after 1 year of therapy. It also reiterated that unopposed estrogen increased the risk of endometrial hyperplasia, whereas continuous combined estrogen and progestogen treatment didn't." }, { "input": "Perimenopausal women with heavy bleeding not controlled by NSAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone.", "output": "A Cochrane review examined the use of cyclical progestogens (given from 10 to 20 days per cycle) for heavy menstrual bleeding. Cyclical progestogens appeared comparable in efficacy to NSAIDs for their effect on duration of menstruation; no statistically significant difference in menstrual blood loss was noted. Progestogens given in more continuous regimens offered greater benefit in terms of blood loss." }, { "input": "Intrauterine devices (IUDs) containing levonorgestrel also effectively reduce bleeding and may avoid surgical intervention.", "output": "A Cochrane review found that progestogen-releasing IUDs significantly reduce heavy menstrual bleeding and are more effective than cyclical norethisterone (21 days). Patients did, however, report greater progestogenic side effects (breast tenderness and intermenstrual bleeding) than cyclical therapy. One unblinded RCT that randomized women scheduled for hysterectomy for heavy bleeding to the levonorgestrel intrauterine device (LNG-IUD) or their existing medical therapy (not further described) found that women in the LNG-IUD group were more likely to cancel surgery. Another RCT comparing hysterectomy with the LNG-IUD found that women with the LNG-IUD reported greater pain. The LNG-IUD was more cost effective at 1 and 5 years, primarily because of reduced surgical expenses. Some patients or physicians may have ethical issues with the device's mechanism of action." }, { "input": "If medical management fails, endometrial ablation offers an effective, minimally invasive alternative to hysterectomy.", "output": "An RCT of 187 women, average age 42 years, compared immediate transcervical resection of the endometrium to medical management for heavy menstrual bleeding. A 5-year follow-up was completed on 144 patients. The study showed transcervical resection of the endometrium to be superior with regard to menstrual status (less bleeding or no bleeding), patient satisfaction with outcomes, and health-related quality of life as indicated on patient questionnaires." }, { "input": "If medical management fails, endometrial ablation offers an effective, minimally invasive alternative to hysterectomy.", "output": "A review article of currently available evidence on endometrial ablation for heavy menstrual bleeding concluded that both resectoscopic endometrial ablation (via hysteroscopy) and nonresectoscopic endometrial ablative technologies (radio-frequency electrosurgical ablation, balloon thermal ablation, free fluid ablation, cryotherapy, microwaves) significantly reduce menstrual blood flow. These minimally invasive techniques were an option for women who weren't concerned about preserving fertility. However, 20% to 40% of patients who were followed for more than 5 years required repeat treatment or hysterectomy." }, { "input": "Hysterectomy should be considered when medical management or endometrial ablation fails.", "output": "A Cochrane review of 5 RCTs that compared endometrial resection and ablation with hysterectomy for heavy menstrual bleeding reported a significant advantage for hysterectomy in symptom resolution and patient satisfaction. Although the initial cost was higher for the hysterectomy group, the difference narrowed over time because of the need for retreatment in the endometrial destruction group." }, { "input": "Hysterectomy should be considered when medical management or endometrial ablation fails.", "output": "An RCT of 63 premenopausal women (30-50 years of age) with abnormal uterine bleeding compared hysterectomy with medical treatment. Hysterectomy was superior with regard to symptom resolution and health-related quality of life after 6 months." }, { "input": "other", "output": "A review of 500 perimenopausal women seen sequentially by a gynecology service found that 18% had menorrhagia (heavy bleeding), metrorrhagia (intermenstrual bleeding), or hypermenorrhea (frequent periods)." }, { "input": "Yes, but the extent of the benefit is unclear. Treating patients with early-stage Alzheimer's disease yields statistically significant, though perhaps not clinically significant, improvement in cognition and global function. In a few cases, it may delay loss of function and need for long-term care.", "output": "In established Alzheimer's disease, cholinesterase inhibitors statistically benefit patients with early and moderate disease and probably benefit patients with severe disease. The treatment effect is small, however-3 points on a 70-point cognitive scale. Comparison studies show mixed results; no single agent appears to be most effective." }, { "input": "Yes, but the extent of the benefit is unclear. Treating patients with early-stage Alzheimer's disease yields statistically significant, though perhaps not clinically significant, improvement in cognition and global function. In a few cases, it may delay loss of function and need for long-term care.", "output": "An RCT of galantamine showed initial cognitive improvement in MCI patients." }, { "input": "Yes, but the extent of the benefit is unclear. Treating patients with early-stage Alzheimer's disease yields statistically significant, though perhaps not clinically significant, improvement in cognition and global function. In a few cases, it may delay loss of function and need for long-term care.", "output": "An RCT of donepezil showed initial cognitive improvement in MCI patients. However, the only trial carried out for 3 years showed no persistent benefit at that time." }, { "input": "Treating patients with mild cognitive impairment (MCI)-the most likely precursor to Alzheimer's disease-with cholinesterase inhibitors seems to have an initial, but perhaps unsustained, benefit over no treatment.", "output": "An RCT of donepezil showed initial cognitive improvement in MCI patients. However, the only trial carried out for 3 years showed no persistent benefit at that time." }, { "input": "Treating patients with mild cognitive impairment (MCI)-the most likely precursor to Alzheimer's disease-with cholinesterase inhibitors seems to have an initial, but perhaps unsustained, benefit over no treatment.", "output": "An RCT of galantamine showed initial cognitive improvement in MCI patients." }, { "input": "Treating patients with mild cognitive impairment (MCI)-the most likely precursor to Alzheimer's disease-with cholinesterase inhibitors seems to have an initial, but perhaps unsustained, benefit over no treatment.", "output": "In established Alzheimer's disease, cholinesterase inhibitors statistically benefit patients with early and moderate disease and probably benefit patients with severe disease. The treatment effect is small, however-3 points on a 70-point cognitive scale." }, { "input": "Withdrawing anticholinergic drugs from patients taking them promises to reduce symptoms of MCI, but is unlikely to reduce rates of Alzheimer's.", "output": "A longitudinal cohort study found that patients taking anticholinergic drugs had an 80% prevalence of MCI, compared with a 35% prevalence in a matched population of patients not using these drugs; yet Alzheimer's disease hadn't increased among the anticholinergic drug users at 8-year follow-up. Attributable risk for MCI from anticholinergic drug use was 19%. Stopping anticholinergic medications may reduce the prevalence of MCI." }, { "input": "Moderately accurate, depending on which tool you use. Questionnaires, physical examination, and clinical prediction rules estimate the pretest probability of obstructive sleep apnea hypopnea syndrome (OSAHS), but are not specific enough to make the diagnosis.", "output": "A 2004 prospective evaluation examined a clinical decision rule on 837 patients referred for polysomnogram that used age, sex, BMI, snoring, and cessation of breathing during sleep to stratify patients into low-, moderate-, or high-risk groups. The study found OSAHS prevalences of 8%, 51%, and 82%, respectively." }, { "input": "Moderately accurate, depending on which tool you use. Questionnaires, physical examination, and clinical prediction rules estimate the pretest probability of obstructive sleep apnea hypopnea syndrome (OSAHS), but are not specific enough to make the diagnosis.", "output": "A 2000 prospective study of 4 previously developed clinical prediction models for OSAHS in sleep center populations found sensitivities of 75% to 96% and specificities of 13% to 54% for identifying patients, using a criterion of AHI >9." }, { "input": "Moderately accurate, depending on which tool you use. Questionnaires, physical examination, and clinical prediction rules estimate the pretest probability of obstructive sleep apnea hypopnea syndrome (OSAHS), but are not specific enough to make the diagnosis.", "output": "A systematic review and meta-analysis of 249 studies of sleep apnea diagnosis from 1980 through November 1997 concluded that studies of focused questionnaires were too heterogeneous to be combined in a meta-analysis. Sensitivity and specificity were good for clinical prediction rules in general, but evidence was insufficient to justify adoption of any single model." }, { "input": "The Epworth Sleepiness Scale is a reliable measure of daytime sleepiness.", "output": "The Epworth Sleepiness Scale rates the likelihood of dozing in 8 situations. Factor analysis of test-retest on 104 medical students and 150 patients with various sleep disorders showed that the scale was internally consistent but measured only daytime sleepiness." }, { "input": "The Berlin Questionnaire, Mallampati score, and truncal obesity can be used to assess pretest probability of OSAHS.", "output": "The Berlin Questionnaire assesses snoring, daytime sleepiness, history of hypertension, age, and body mass index (BMI). The questionnaire was evaluated in 744 adults presenting for unrelated problems at 5 primary care sites. Of 100 patients who underwent sleep studies, a finding of high risk on the Berlin Questionnaire predicted an AHI >5 with 86% sensitivity and 77% specificity, a positive likelihood ratio of 3.79." }, { "input": "The Berlin Questionnaire, Mallampati score, and truncal obesity can be used to assess pretest probability of OSAHS.", "output": "A cross-sectional study correlating OSAHS with truncal obesity in 192 patients referred to a sleep clinic found that the likelihood of OSAHS was 2.6 times greater if the waist-to-hip ratio was >1 in men and >0.85 in women." }, { "input": "The Berlin Questionnaire, Mallampati score, and truncal obesity can be used to assess pretest probability of OSAHS.", "output": "Mallampati scoring grades visibility of the posterior pharynx when the patient opens his mouth and sticks out his tongue. Visibility is ranked on a scale of 1 to 4, with 1 representing the greatest visibility and 4 the least. Prospective multivariate assessment of Mallampati scores in adults referred to a sleep clinic yielded likelihood ratios of OSAHS for Mallampati grades 1 to 4 of 0.4, 0.7, 1.6, and 1.7, respectively." }, { "input": "other", "output": "The syndrome is defined as an apnea-hypopnea index (AHI) of 5 or more events per hour during a sleep polysomnogram, accompanied by either excessive daytime sleepiness or 2 of the following: choking or gasping during sleep, recurrent awakenings from sleep, daytime fatigue, and impaired concentration." }, { "input": "other", "output": "OSAHS is marked by daytime somnolence, snoring, difficult-to-control hypertension, refractory arrhythmias, angina, or heart failure." }, { "input": "For pharmacologic management, the best evidence supports osmotic laxatives.", "output": "A Cochrane systematic review found no RCTs of stimulant laxatives for CFC and concluded that evidence concerning the efficacy of these agents is insufficient." }, { "input": "For pharmacologic management, the best evidence supports osmotic laxatives.", "output": "A small RCT found that mineral oil treated constipation more successfully than senna at 3 and 10 months of follow-up." }, { "input": "For pharmacologic management, the best evidence supports osmotic laxatives.", "output": "One fair-quality RCT of 48 children with fecal impaction compared PEG with mineral oil. PEG was more effective, but high-volume PEG caused more vomiting and less compliance." }, { "input": "For pharmacologic management, the best evidence supports osmotic laxatives.", "output": "A good-quality RCT showed that PEG + E effectively relieved fecal impaction (92% of 63 children) and was superior to lactulose for maintenance treatment. The rate of adverse effects (abdominal pain) was 64% with PEG + E and 83% with lactulose." }, { "input": "For pharmacologic management, the best evidence supports osmotic laxatives.", "output": "One good-quality RCT (100 children, 6 months to 15 years old with CFC) compared PEG + E with lactulose. Both significantly increased stool frequency and decreased encopresis. However, PEG + E had a markedly higher success rate (56% vs 29%; NNT=3.7; P=.02). The 8-week trial found significantly more complaints about bad taste in the PEG + E group; the lactulose group reported higher rates of abdominal pain, straining, and pain at defecation. The only dropout because of adverse events (bad taste) occurred in the PEG + E group." }, { "input": "For pharmacologic management, the best evidence supports osmotic laxatives.", "output": "A recent high-quality RCT compared the osmotic laxative polyethylene glycol 3350 plus electrolytes (PEG + E) with placebo in 51 children with CFC, 2 to 11 years of age. The mean number of defecations per week was higher for children on PEG + E (3.12 vs 1.45; P<.001); straining or pain and stool consistency improved." }, { "input": "For pharmacologic management, the best evidence supports osmotic laxatives.", "output": "One poor-quality RCT found that senna was less effective than lactulose and had more side effects (colicky pain, diarrhea)." }, { "input": "Fiber and behavior modification may have a role. Increased fiber and behavior modification are the most often recommended first steps in managing chronic functional constipation (CFC) in children, but only limited evidence supports this approach.", "output": "A fair-quality crossover RCT (31 children, mean age 7 years, with CFC) compared fiber (glucomannan) with placebo for 4 weeks. More children were successfully treated with fiber than placebo (45% vs 13%; number needed to treat [NNT]=3.125; P<.05). Parents rated children as doing better on fiber (68% vs 13%), and abdominal pain occurred less often (10% vs 42%; P<.05). No adverse effects were associated with fiber." }, { "input": "Increased fiber and behavior modification are the most often recommended first steps in managing chronic functional constipation (CFC) in children, but only limited evidence supports this approach.", "output": "A Cochrane systematic review of 9 small, poor-quality RCTs in children with functional fecal incontinence found no significant improvement when biofeedback was added to conventional treatment for as long as 12 months (odds ratio=1.11; 95% confidence interval, 0.78-1.58).9 In 1 small trial, however, adding behavior modification to laxative therapy significantly reduced soiling episodes." }, { "input": "There are several steps you can take. Monitor the growth of exclusively breastfed babies by plotting routine weights and lengths on the World Health Organization (WHO) growth curve.", "output": "A meta-analysis showed a dose-dependent relationship between longer duration of breastfeeding and decreased risk of overweight in later life (<1 month of breastfeeding: odds ratio [OR]=1.0; 95% confidence interval [CI], 0.65-1.55; 1-3 months: OR=0.81; 95% CI, 0.74-0.88; 4-6 months: OR=0.76; 95% CI, 0.67-0.86; 7-9 months: OR=0.67; 95% CI, 0.55-0.82; >9 months: OR=0.68; 95% CI, 0.50-0.91)." }, { "input": "There are several steps you can take. Monitor the growth of exclusively breastfed babies by plotting routine weights and lengths on the World Health Organization (WHO) growth curve.", "output": "The WHO growth curves (http://www.who.int/childgrowth/standards/en/), rather than the CDC charts, should be used to monitor the growth of exclusively breastfed babies. The CDC charts reflect a heavier and shorter sample of infants. Moreover, the WHO charts are based on shorter measurement intervals and may therefore be a better tool for measuring rapidly changing rates of growth." }, { "input": "There are several steps you can take. Monitor the growth of exclusively breastfed babies by plotting routine weights and lengths on the World Health Organization (WHO) growth curve.", "output": "Healthy breastfed infants have a different growth curve than formula or mix-fed babies. The WHO Working Group on Infant Growth studied infants whose sole nourishment was breast milk until 4 months of age." }, { "input": "Reassure parents that higher-than-normal weight gain in infants who are breastfeeding easily without supplementation has no known adverse effects. Advise parents to change behaviors that result in overfeeding or insufficient physical activity.", "output": "Because overweight has no known adverse health outcomes for exclusively breastfed infants, lactation experts don't advise mothers to reduce feeding for these babies." }, { "input": "Reassure parents that higher-than-normal weight gain in infants who are breastfeeding easily without supplementation has no known adverse effects. Advise parents to change behaviors that result in overfeeding or insufficient physical activity.", "output": "Overfeeding may contribute to higher-than-normal weight gain in both breastfed and formula-fed infants." }, { "input": "Reassure parents that higher-than-normal weight gain in infants who are breastfeeding easily without supplementation has no known adverse effects. Advise parents to change behaviors that result in overfeeding or insufficient physical activity.", "output": "Maternal behavior changes that may taper unusual weight gains include cuddling rather than breastfeeding in response to all distress signals and encouraging movement and crawling." }, { "input": "Refer parents to a lactation consultant to manage large volumes of milk that exceed the infant's need. In the rare case of an infant who exhibits lack of satiety or dysmorphia, consider an overgrowth syndrome and seek an endocrinology and genetics consult.", "output": "Expressing breast milk to increase infant intake increases weight gain (r=0.59); this effect gets stronger as the infant gets older (r=0.58)." }, { "input": "Refer parents to a lactation consultant to manage large volumes of milk that exceed the infant's need. In the rare case of an infant who exhibits lack of satiety or dysmorphia, consider an overgrowth syndrome and seek an endocrinology and genetics consult.", "output": "For the rare infant who exhibits hypoglycemia, lack of satiety, or dysmorphia, consider early macrosomia or an overgrowth syndrome, such as Beckwith-Wiedemann syndrome, and seek an endocrinology or genetics consult." }, { "input": "Refer parents to a lactation consultant to manage large volumes of milk that exceed the infant's need. In the rare case of an infant who exhibits lack of satiety or dysmorphia, consider an overgrowth syndrome and seek an endocrinology and genetics consult.", "output": "Referral to a lactation consultant is recommended to manage large volumes of milk that exceed infant need." }, { "input": "Empirically treat patients when they have pruritus and lesions typical of scabies in at least 2 places-even if there is no known household contact diagnosed with scabies, and even if the diagnosis cannot be confirmed by light microscopy.", "output": "The only study we found that investigated the sensitivity of clinical features in diagnosing scabies was done in sub-Saharan Africa. In this study, the presence of diffuse itching, plus lesions in at least 2 locations typical with scabies or a household member with itch, had 100% sensitivity and 96.9% specificity for scabies infection. This study used the evaluation of a dermatologist as a gold standard. The authors propose that treatment based on clinical findings with or without microscopic confirmation is appropriate; however, it is not clear how these data translate to a primary care population with a lower prevalence of scabies." }, { "input": "In hospital settings, give empiric treatment to health care workers with skin exposure to patients with scabies.", "output": "One case-control study, performed at a large tertiary-care teaching hospital, demonstrated that health care workers on a service having a patient with undiagnosed scabies were 5.3 times more likely to develop a pruritic rash than those in other units. Health care workers with more skin-to-skin contact with the patients (nurses, nursing students, and physical therapists) were 4.5 times more likely to develop scabies compared with those in less physical contact (physicians, medical students, and occupational therapists). Among the symptomatic health care workers, 17% of their household contacts developed scabies, too." }, { "input": "other", "output": "A 2000 Cochrane review, updated in 2002, concluded that permethrin was superior to lindane for topical treatment of scabies. Combining 4 trials with 718 patients, permethrin 5% appeared better than lindane 1% (odds ratio=0.66; 95% confidence interval, 0.46-0.95). However, there was significant heterogeneity between the studies, and the largest trial (n=467) found no difference." }, { "input": "other", "output": "It is known that an initial infestation with scabies will not lead to pruritus for up to 4 to 6 weeks." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "Pregabalin is effective, with an NNT of 4.93 (95% CI, 3.34-6.07) for up to 50% pain reduction." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "A systematic review found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS)." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "A Systematic Review concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN. Amitriptyline, the best studied TCA, provides at least moderate pain relief in two-thirds of patients with a pooled number needed to treat (NNT) for TCAs of 2.64 (95% confidence interval [CI], 2.1-3.54). It found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS)." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "A Systematic Review concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN. It found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS)." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "A Systematic Review concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN. It found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS)." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "A Systematic Review concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN. It found gabapentin to be effective, with a range of NNT from 2.8 to 5.3 for as much as 50% pain reduction based on the visual analog score (VAS)." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "A Systematic Review concluded that tricyclic antidepressants (TCAs) are effective treatments for PHN." }, { "input": "Tricyclic antidepressants, gabapentin, and pregabalin effectively reduce pain.", "output": "Pregabalin is effective, with an NNT of 4.93 (95% CI, 3.34-6.07) for up to 50% pain reduction." }, { "input": "Opioids have demonstrated pain relief in 3 RCTs.", "output": "A systematic review found that controlled-release oxycodone reduced pain by 50%, based on the VAS." }, { "input": "Opioids have demonstrated pain relief in 3 RCTs.", "output": "A systematic review found that controlled-release oxycodone reduced pain by 50%, based on the VAS. Tramadol, a selective opioid agonist, showed moderate effectiveness in a small RCT (N=125), with an NNT of 4.76 (95% CI, 2.61-26.97)." }, { "input": "Opioids have demonstrated pain relief in 3 RCTs.", "output": "A systematic review found that controlled-release oxycodone reduced pain by 50%, based on the VAS." }, { "input": "Opioids have demonstrated pain relief in 3 RCTs.", "output": "A systematic review found that controlled-release oxycodone reduced pain by 50%, based on the VAS. Tramadol, a selective opioid agonist, showed moderate effectiveness in a small RCT (N=125), with an NNT of 4.76 (95% CI, 2.61-26.97)." }, { "input": "Opioids have demonstrated pain relief in 3 RCTs.", "output": "A systematic review reported only limited evidence of effectiveness.6 In pooled results from systematic reviews, opioids decreased pain by 50% on the VAS (NNT=2.67; 95% CI, 2.10-3.77). Tramadol, a selective opioid agonist, showed moderate effectiveness in a small RCT (N=125), with an NNT of 4.76 (95% CI, 2.61-26.97)." }, { "input": "Opioids have demonstrated pain relief in 3 RCTs.", "output": "An RCT of 76 patients demonstrated that morphine, with methadone as backup, both reduced the intensity of pain and relieved pain more than placebo." }, { "input": "Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia.", "output": "The anesthetic lidocaine patch 5% has shown efficacy in PHN with allodynia based on 3 RCTs of lower quality (short duration, recruitment of patients who had improved on lidocaine previously, no report of baseline levels of pain); the NNT was 2 (95% CI, 1.4-3.3). A systematic review of these 3 RCTs concluded that evidence is insufficient to recommend the lidocaine patch as treatment for PHN." }, { "input": "Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia.", "output": "Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85). Blinding was limited in these studies because of the stinging associated with treatment." }, { "input": "Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia.", "output": "Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85). Blinding was limited in these studies because of the stinging associated with treatment." }, { "input": "Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia.", "output": "Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85). Blinding was limited in these studies because of the stinging associated with treatment." }, { "input": "Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia.", "output": "Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85). Blinding was limited in these studies because of the stinging associated with treatment." }, { "input": "Capsaicin and the lidocaine 5% patch relieve pain and decrease allodynia.", "output": "Capsaicin, a topical counterirritant, reduced pain in fewer than 20% of patients in 2 RCTs reported in systematic reviews, with an NNT of 3.26 (95% CI, 2.26-5.85). Blinding was limited in these studies because of the stinging associated with treatment." }, { "input": "Yes, it may decrease preterm births, especially among higher-risk women-minority women, women of low socioeconomic status, and adolescents.", "output": "The evidence from 1 RCT and 1 cohort study supports the protective effect of group prenatal care against preterm delivery for women at higher risk of adverse pregnancy outcomes." }, { "input": "Yes, it may decrease preterm births, especially among higher-risk women-minority women, women of low socioeconomic status, and adolescents.", "output": "A single cohort study compared pregnant teenagers enrolled in the CenteringPregnancy program with 2 clinic convenience samples. The group care recipients had significantly lower preterm delivery rates (NNT=7; P<.02). The study design, and therefore the detected relationship of group care to pregnancy-associated outcomes, may be particularly subject to selection bias." }, { "input": "Yes, it may decrease preterm births, especially among higher-risk women-minority women, women of low socioeconomic status, and adolescents.", "output": "One large, unblinded RCT investigated the effect of group prenatal care on a cohort of young, mostly minority women of low economic status. Women who received group prenatal care had fewer preterm births than those who received traditional care (number needed to treat [NNT]=25; P=.045)." }, { "input": "other", "output": "The matched cohort study recorded higher birth weights among infants born to mothers in group prenatal care. Subset analysis of preterm infants born to mothers in group care showed average birth weights approximately 400 g higher than those in individual care (P<.05)." }, { "input": "other", "output": "An RCT found no clinically or statistically significant differences in birth weights between intervention and control groups." }, { "input": "other", "output": "An RCT and the cohort study showed increased rates of breastfeeding initiation (NNT=8 and 6, respectively)." }, { "input": "other", "output": "An RCT demonstrated that patients in group care more often had adequate prenatal care (NNT=16)." }, { "input": "other", "output": "One cohort trial found that women enrolled in group prenatal care used the emergency department less during the third trimester (NNT=2, P=.001)." }, { "input": "other", "output": "The RCT showed increased knowledge and readiness for labor, and higher satisfaction compared with individual care (P<.001 for all outcomes)." }, { "input": "other", "output": "Lower-quality studies of group care support these findings." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "A Brazilian study found that children born in the lowest socioeconomic group had BMI measurements at 18 years of age that were an average of 1.21 kg/m2 higher than children in the highest socioeconomic group (P<.05). The study controlled for birth weight, maternal smoking, gestational age, and level of schooling eventually achieved by the child." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "Low socioeconomic status in infancy or early childhood increases the risk of childhood overweight, perhaps because of less breastfeeding and more smoking, among other factors. Socioeconomic status was determined using the International Standard Classification of Occupations; children whose parents worked at unskilled manual labor jobs or were unemployed were considered in the lowest socioeconomic group." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "A large cohort study found that each 100 g per month increase in weight gain above the mean (820 g per month) during the first 4 months of life increased the odds of overweight at 7 years of age by 38% (OR=1.38; 95% CI, 1.32-1.44)." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "One descriptive meta-analysis reported that 13 of 15 studies found a positive association between weight gain in the first year of life and overweight later in childhood, although overall OR and relative risk weren't reported." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "A meta-analysis found a positive association in 25 of 28 studies that examined birth weight and BMI in childhood. This descriptive meta-analysis didn't calculate pooled odds ratios (ORs) because of heterogeneity of the ages included and methods used to measure obesity." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "A meta-analysis found a positive association between birth weight and over-weight in childhood in 9 of 11 studies. This descriptive meta-analysis didn't calculate pooled odds ratios (ORs) because of heterogeneity of the ages included and methods used to measure obesity." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "A meta-analysis of 9 studies found that 7 showed a significantly lower risk of overweight among children who were breastfed (odds ratio [OR]=0.78; 95% confidence interval [CI], 0.71-0.85). Four of the studies demonstrated that longer duration of breastfeeding offered greater protection than shorter duration. Two of the 4 studies defined longer duration as more than 6 months, 1 defined it as more than 3 months, and 1 examined breastfeeding for periods of less than 1 week, 1 week to 1 month, 2 to 3 months, 4 to 6 months, 7 to 9 months, and longer than 9 months, showing a duration-dependent decrease in risk. The other studies in the meta-analysis evaluated never-breastfed vs ever-breastfed infants." }, { "input": "Variables that increase the risk of overweight in childhood include formula feeding, high birth weight, high rate of weight gain in the first 4 months of life, low socioeconomic status, and maternal obesity.", "output": "Infants of obese parents were more likely to be overweight at 7 years, compared with children whose mothers were normal weight (OR=10.44; 95% CI, 5.11-21.23)." }, { "input": "There is insufficient evidence to recommend for or against routine screening mammography beyond the age of 69 years. The best candidates to stop screening are elderly women who have significant comorbidities, poor functional status, low bone mineral density (BMD), little interest in preventive care, or an unwillingness to accept the potential harm of screening.", "output": "A incorporated comorbidities in another model and found a small benefit for women older than 69 years that gradually diminished as they approached the age of 85. This benefit was halved in the presence of a major comorbidity. Both of these models assumed that the efficacy of screening in younger women applies to older women." }, { "input": "There is insufficient evidence to recommend for or against routine screening mammography beyond the age of 69 years. The best candidates to stop screening are elderly women who have significant comorbidities, poor functional status, low bone mineral density (BMD), little interest in preventive care, or an unwillingness to accept the potential harm of screening.", "output": "In a cost-effectiveness analysis, Kerlikowske and coworkers included BMD in the model, which is positively associated with breast cancer risk. They found a small benefit to screening for women with the highest quartile BMD (highest cancer risk) and virtually no benefit in screening the lowest quartile BMD." }, { "input": "There is insufficient evidence to recommend for or against routine screening mammography beyond the age of 69 years. The best candidates to stop screening are elderly women who have significant comorbidities, poor functional status, low bone mineral density (BMD), little interest in preventive care, or an unwillingness to accept the potential harm of screening.", "output": "A retrospective cohort study studied studied 690,000 Medicare beneficiaries in California and found a 43% reduction in the risk of metastatic breast cancer in the screened group. A 13-year Dutch study found a 20% breast cancer mortality reduction that first appeared 7 years after initiating screening. The cohorts were not randomly assigned in either study, leading to possible differences in baseline risk." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "Usually a punch biopsy is sufficient, but it should be no smaller than 4 mm. The preferred location is the central scalp in an area representative of the hair loss." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "If a patient has scarring alopecia, a scalp biopsy is almost always necessary to make a diagnosis." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "Consider a Venereal Disease Research Laboratory test to rule out syphilis." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "According to 1 small study of 50 women with diffuse alopecia, thyroid tests are not routinely warranted without supportive clinical signs." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "Ancillary laboratory evaluation is sometimes necessary if the diagnosis remains unclear.1,2 Serum ferritin or a complete blood count can be useful to look for iron-deficiency anemia; a thyroid-stimulating hormone test can rule out hypothyroidism." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "The \"pull test\" is often used to assess ongoing hair loss. If more than 10% of hairs are pulled away from the scalp, the test is positive, suggesting active hair shedding." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "All hair-bearing sites should be examined. Clinical examination should be performed in 3 stages: Inspect the scalp for inflammation, scale, and erythema to determine whether scarring is present, Examine the hair density and distribution pattern, Study the hair shaft quality, looking at caliber, fragility, length, and shape." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "A family history of alopecia areata or androgenic alopecia can point to a genetic cause. Acne or abnormal menses can indicate androgen excess, suggesting androgenic alopecia. Positive answers to thyroid screening questions can point to hypothyroidism, and abnormal diet patterns can suggest iron-deficiency anemia. Unusual hair care practices can cause traction alopecia." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "Significant considerations include the onset, duration, and pattern of hair loss; whether hair is broken or shed at the root; and whether shedding or thinning has increased." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "A detailed history-including medication use, systemic illness, endocrine dysfunction, hair care practices, severe diet restriction, and family history-is key to establishing an accurate diagnosis of alopecia." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "Serum prolactin can be useful if the patient has galactorrhea." }, { "input": "It's unclear what the best approach is given the lack of studies on this issue. Indirect evidence and expert opinion indicate that a careful history and thorough physical examination usually suggest the underlying cause of alopecia. Ancillary laboratory evaluation and scalp biopsy are sometimes necessary to make or confirm the diagnosis.", "output": "Check free testosterone, androstenedione, and dehydroepiandrosterone if virilizing signs are present, to assess hyperandrogenism." }, { "input": "Recent studies have demonstrated a small but significant risk of adverse effects from combined hormone replacement therapy (HRT), including cardiovascular disease, thromboembolic disease, and breast cancer. Time-limited HRT will control intolerable menopausal symptoms and prevent risk of fractures in newly menopausal women. However, HRT achieves its maximum efficacy in 35 years, and the risk of adverse outcomes increases as time progresses. Women considering HRT, particularly those at higher risk for vascular disease and breast cancer, should be informed of the potential risks.", "output": "Continuing HRT beyond 5 years dramatically increases the risk of coronary heart disease, stroke, thromboembolic events, breast cancer, and cholecystitis." }, { "input": "Recent studies have demonstrated a small but significant risk of adverse effects from combined hormone replacement therapy (HRT), including cardiovascular disease, thromboembolic disease, and breast cancer. Time-limited HRT will control intolerable menopausal symptoms and prevent risk of fractures in newly menopausal women. However, HRT achieves its maximum efficacy in 35 years, and the risk of adverse outcomes increases as time progresses. Women considering HRT, particularly those at higher risk for vascular disease and breast cancer, should be informed of the potential risks.", "output": "Evidence indicates that women who take HRT for 3 years and then stop achieve as much protection from osteoporotic fractures as women who continue their HRT beyond 3 years." }, { "input": "Recent studies have demonstrated a small but significant risk of adverse effects from combined hormone replacement therapy (HRT), including cardiovascular disease, thromboembolic disease, and breast cancer. Time-limited HRT will control intolerable menopausal symptoms and prevent risk of fractures in newly menopausal women. However, HRT achieves its maximum efficacy in 35 years, and the risk of adverse outcomes increases as time progresses. Women considering HRT, particularly those at higher risk for vascular disease and breast cancer, should be informed of the potential risks.", "output": "The findings of the WHI and HERS trials have been summarized in a recent meta-analysis done for the United States Preventive Services Task Force." }, { "input": "Recent studies have demonstrated a small but significant risk of adverse effects from combined hormone replacement therapy (HRT), including cardiovascular disease, thromboembolic disease, and breast cancer. Time-limited HRT will control intolerable menopausal symptoms and prevent risk of fractures in newly menopausal women. However, HRT achieves its maximum efficacy in 35 years, and the risk of adverse outcomes increases as time progresses. Women considering HRT, particularly those at higher risk for vascular disease and breast cancer, should be informed of the potential risks.", "output": "The Heart and Estrogen/progestin Replacement Study (HERS) examined the effects of HRT in postmenopausal women with coronary artery disease. HERS was a large randomized controlled trial of 2763 women with an average follow-up time of 4.1 years. It showed no statistically significant difference between the HRT (estrogen plus medroxyprog-esterone) group compared with the placebo group in either the primary outcomes (nonfatal myocardial infarction or coronary heart disease death) or in the secondary outcomes (coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease)." }, { "input": "Recent studies have demonstrated a small but significant risk of adverse effects from combined hormone replacement therapy (HRT), including cardiovascular disease, thromboembolic disease, and breast cancer. Time-limited HRT will control intolerable menopausal symptoms and prevent risk of fractures in newly menopausal women. However, HRT achieves its maximum efficacy in 35 years, and the risk of adverse outcomes increases as time progresses. Women considering HRT, particularly those at higher risk for vascular disease and breast cancer, should be informed of the potential risks.", "output": "The Women's Health Initiative (WHI), the largest randomized trial of HRT, showed that long-term use of HRT poses more risks than benefits for healthy postmenopausal women. WHI studied the use of estrogen plus progestin for prevention of coronary heart disease in 16,608 postmenopausal women age 50-79 years. After 5 years of follow-up, this arm of the study was stopped because of the adverse effects of the intervention. The researchers found that HRT increases the risk of several events: 1) coronary heart disease events (number needed to harm [NNH]=1428); 2) invasive breast cancer (NNH=1250); 3) stroke (NNH=1250); 4) venous thromboembolic events (NNH=555); 5) pulmonary embolism (NNH=1250)." }, { "input": "There is inadequate evidence to determine the extent of these risks in women who have had a hysterectomy and are taking unopposed estrogen.", "output": "An ongoing arm of WHI is studying estrogen alone in postmenopausal women who have had a hysterectomy." }, { "input": "Although transvaginal sonography (TVS) has inconsistent sensitivity (0.21-1.00) and specificity (0.53-1.00), its cost-efficiency and noninvasiveness make it the best initial test for ruling in fibroid disease.", "output": "The cost of TVS is less than half of sonohysterography or diagnostic hysteroscopy, based on Medicare allowable pricing data." }, { "input": "Although transvaginal sonography (TVS) has inconsistent sensitivity (0.21-1.00) and specificity (0.53-1.00), its cost-efficiency and noninvasiveness make it the best initial test for ruling in fibroid disease.", "output": "A systematic review of 9 heterogeneous studies evaluating TVS found wide ranges for sensitivity and specificity." }, { "input": "Although transvaginal sonography (TVS) has inconsistent sensitivity (0.21-1.00) and specificity (0.53-1.00), its cost-efficiency and noninvasiveness make it the best initial test for ruling in fibroid disease.", "output": "TVS has high sensitivity for detecting myomas in a uterus of <10-week size. The use of high-frequency probes improves the sensitivity for diagnosing small myomas, although their precise location with respect to the uterine cavity often remains uncertain. Localization of fibroids in a larger uterus or when there are many tumors is limited." }, { "input": "Sonohysterography (SHG) and hysteroscopy have superior sensitivity, specificity, and more discriminating positive and negative likelihood ratios for diagnosing fibroids than does TVS.", "output": "SHG is more sensitive and specific than TVS in detecting submucous myomas and focal endometrial lesions." }, { "input": "Sonohysterography (SHG) and hysteroscopy have superior sensitivity, specificity, and more discriminating positive and negative likelihood ratios for diagnosing fibroids than does TVS.", "output": "In a prospective study of 81 symptomatic patients, using a gold standard of surgical pathology, SHG demonstrated more discriminating positive and negative likelihood ratios (LR+, LR-) for detecting myomata than did TVS or hysteroscopy." }, { "input": "Sonohysterography (SHG) and hysteroscopy have superior sensitivity, specificity, and more discriminating positive and negative likelihood ratios for diagnosing fibroids than does TVS.", "output": "A prospective study of 56 symptomatic patients with a gold standard of hysteroscopic or surgical pathology similarly found SHG to be superior to TVS." }, { "input": "Sonohysterography (SHG) and hysteroscopy have superior sensitivity, specificity, and more discriminating positive and negative likelihood ratios for diagnosing fibroids than does TVS.", "output": "In a systematic review of 7 studies, SHG demonstrated a clinically significant LR+ of 29.7. There was too much heterogeneity in the data to calculate an LR-." }, { "input": "SHG is less painful, less invasive, and more cost-effective than hysteroscopy.", "output": "In a systematic review of 4 studies, hysteroscopy had a pooled LR+ of 29.4 for diagnosing fibroids. Due to study heterogeneity, a pooled LR- could not be calculated." }, { "input": "SHG is less painful, less invasive, and more cost-effective than hysteroscopy.", "output": "A prospective, blinded comparative study of SHG and hysteroscopy for diagnosing fibroids in 117 women found SHG to have a higher failure rate (22% vs 6%) but a statistically significant lower median pain score: 1.6 (interquartile range 0.48-3.03) vs 3.2 (1.58-5.18) (P<.001)-than hysteroscopy. Failure of SHG was most commonly due to cervical stenosis." }, { "input": "Magnetic resonance imaging (MRI) had comparable precision to TVS in a single study, but it is too expensive to be a good initial test for fibroids.", "output": "MRI costs up to twice as much as sonohysterography or diagnostic hysteroscopy, when comparing Medicare allowable pricing data." }, { "input": "Magnetic resonance imaging (MRI) had comparable precision to TVS in a single study, but it is too expensive to be a good initial test for fibroids.", "output": "In a double-blinded comparative study of 106 consecutive premenopausal women undergoing hysterectomy for benign reasons, MRI and TVS detected myomas with equal precision (TABLE). MRI is preferred in cases for which exact myoma mapping is necessary and those with multiple myomas or large uteri who are scheduled for advanced surgical procedures." }, { "input": "One study reported a strong correlation between ultrasound and bimanual examination", "output": "In a retrospective chart review of obese and nonobese patients with known uterine fibroids, clinical estimate of uterine size by bimanual examination correlated with both ultrasound fibroid sizing and posthysterectomy pathology analysis." }, { "input": "other", "output": "Additional diagnostic testing is indicated for patients with suspected fibroids and abnormal uterine bleeding, increased pelvic girth, pelvic pressure contributing to urinary frequency or constipation, or pelvic pain with intercourse or other physical activity." }, { "input": "Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy.", "output": "One study showed a trend towards improved yield; in another study, the brush with spatula significantly improved the ability to detect cytologic abnormalities in pregnant patients." }, { "input": "Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy.", "output": "Some studies did look for differences in the detection of cytologic abnormalities between the brush with spatula and the swab with spatula methods. Most small studies and a meta-analysis showed no difference." }, { "input": "Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy.", "output": "In studies including about 1900 pregnant patients, the brush with spatula caused no significantly increased risk of serious adverse outcomes, nor any trend in that direction. The device did cause a slight increase in self-limited vaginal spotting." }, { "input": "Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy.", "output": "In multiple studies involving more than 25,000 pregnant and nonpregnant patients, the brush was consistently shown to be the method obtaining the highest rate of adequate smears-ie, those containing endocervical cells." }, { "input": "Use of a nylon brush (Cytobrush and others) with spatula to obtain Papanicolaou (Pap) smears from pregnant women is more likely to obtain sufficient endocervical cells, without adverse consequence for the mother or for the fetus. This method is also most likely to be cost-effective. However, current evidence does not support any superiority of the nylon brush with spatula for any patient-oriented outcomes (eg, fewer procedures, less cancer, etc) during or after pregnancy.", "output": "A Cochrane review of Pap smear sampling devices for nonpregnant women concludes that the cervical brush with spatula is more effective at collecting endocervical cells and producing adequate Pap smears. Based on more limited evidence, the higher rate of adequate smears is associated with the detection of more cytologic abnormalities. However, the manufacturer of Cytobrush (Medscand) recommends that the device not be used after the first 10 weeks of pregnancy, raising issues of both effectiveness and safety in this population." }, { "input": "other", "output": "Studies addressed cost-effectiveness of the brush in pregnancy. Especially when including the cost of repeat Pap smears for inadequate specimens, the brush with spatula was rated most cost-effective in all 3 studies." }, { "input": "No, none of the 3-history, exam, or labs- is sufficiently accurate to diagnose acute appendicitis.", "output": "A meta-analysis of patients hospitalized for suspected acute appendicitis analyzed 28 different diagnostic variables in 24 studies. Variables included WBC, granulocyte count, PMN proportion, CRP level, and body temperature; histopathology was the gold standard. In no circumstance did an isolated elevation of any 1 factor result in a significant LR+. In addition, the absence of any 1 variable failed to yield a LR- <0.01 (low enough to exclude appendicitis)." }, { "input": "When combined, the following tests are helpful: an elevated C-reactive protein (CRP), elevated total white blood cell (WBC) count, elevated percentage of polymorphonuclear leukocyte (PMN) cells (left shift), and the presence of guarding or rebound on physical examination. The combination of any 2 of these tests yields a very high positive likelihood ratio (LR+), but the absence of these does not exclude appendicitis.", "output": "Clinicians inherently combine multiple variables when evaluating patients, and when evaluating patients with abdominal pain, this technique can result in identification of adequate likelihood ratios. In general, when 2 or more of the aforementioned inflammatory variables are present, the diagnosis of acute appendicitis is likely. When all markers of inflammation are normal, though acute appendicitis is less likely, the power is insufficient to exclude it as a possible diagnosis." }, { "input": "When combined, the following tests are helpful: an elevated C-reactive protein (CRP), elevated total white blood cell (WBC) count, elevated percentage of polymorphonuclear leukocyte (PMN) cells (left shift), and the presence of guarding or rebound on physical examination. The combination of any 2 of these tests yields a very high positive likelihood ratio (LR+), but the absence of these does not exclude appendicitis.", "output": "The value of CRP in the evaluation of suspected appendicitis was confirmed in a retrospective evaluation of 566 patients who underwent appendectomies. The sensitivity and specificity of the test improved depending on the duration of symptoms for both appendicitis and ruptured appendicitis. For appendicitis, CRP levels >1.4, 4.0, and 10.5 on Days 1, 2, and 3 had sensitivities/specificities of 0.38/0.81, 0.63/0.78, and 0.72/0.83, respectively. For ruptured appendicitis, levels of 3.3, 8.5, and 12.0 on Days 1, 2, and 3 had sensitivities/specificities of 0.77/0.89, 0.70/0.95, and 0.90/0.96, respectively." }, { "input": "When combined, the following tests are helpful: an elevated C-reactive protein (CRP), elevated total white blood cell (WBC) count, elevated percentage of polymorphonuclear leukocyte (PMN) cells (left shift), and the presence of guarding or rebound on physical examination. The combination of any 2 of these tests yields a very high positive likelihood ratio (LR+), but the absence of these does not exclude appendicitis.", "output": "In a series of 439 patients with symptoms suggestive of acute appendicitis, those with confirmed appendicitis (n=101) had a mean WBC count of 14.8 K/\u00b5L (95% CI, 13.9-15.8) and a mean neutrophil percentage of 82 (95% CI, 80-84). In contrast, those without appendicitis (n=338) had a mean WBC count of 9.2 K/\u00b5L (95% CI, 9.0-9.4) and a mean neutrophil percentage of 68 (95% CI, 66-70)." }, { "input": "History and physical examination can distinguish among most physiologic, pharmacologic, or pathologic causes of an elevated serum prolactin level (SPL).", "output": "An expert guideline recommends a history and physical examination to determine whether an elevated SPL is due to physiologic, pharmacologic, or pathologic causes. The fasting morning SPL is least variable and correlates best with a disease state. A detailed drug history is important since drug-induced elevated SPL is common.1 Laboratory evaluation includes thyroid-stimulating hormone, blood urea nitrogen, and creatinine, as well as pregnancy testing when applicable. If no cause of elevated SPL is identified by initial clinical evaluation or if the SPL is greater than 200 ng/mL, experts recommend imaging of the sella turcica with computed tomography or magnetic resonance imaging." }, { "input": "Patients with unexplained elevations of serum prolactin or with a level above 200 ng/mL should undergo imaging of the sella turcica.", "output": "If no cause of elevated SPL is identified by initial clinical evaluation or if the SPL is greater than 200 ng/mL, experts recommend imaging of the sella turcica with computed tomography or magnetic resonance imaging." }, { "input": "Mildly elevated SPL due to physiologic causes may be managed expectantly.", "output": "For patients with a mildly elevated SPL due to a physiologic cause, experts recommend expectant management. Patients should be monitored for symptoms of hypogonadism (amenorrhea, infertility, or sexual dysfunction) and have SPL measured at 6- to 12-month intervals." }, { "input": "Mildly elevated SPL due to physiologic causes may be managed expectantly.", "output": "In cohort studies, treatment of the underlying cause of elevated SPL reverses secondary physiologic changes of low estrogen or testosterone, and hypogonadism." }, { "input": "pharmacologic elevations may be treated by discontinuing the causative medication.", "output": "Eliminating a pharmacologic cause may lead to normalization of SPL, although experts recommend psychiatric consultation before discontinuing neuroleptic medications." }, { "input": "Elevated SPL due to pathologic causes requires both monitoring for complications and treatment of the underlying condition.", "output": "Experts advise treating the underlying cause of a pathologic elevation of SPL. Patients with microadenoma should have SPLs monitored to prevent complications of decreased bone mineral density and sexual dysfunction due to persistently elevated SPL. Patients with a macroadenoma (>1 cm) are at risk for tumor growth and require serial imaging studies in addition to treatment of SPL, according to expert opinion." }, { "input": "Dopamine agonists are effective for patients requiring drug treatment.", "output": "Medical therapy with a dopamine agonist is indicated for patients with either symptoms of hypogonadism due to elevated SPL, or neurologic symptoms due to the size of a macroadenoma." }, { "input": "Dopamine agonists are effective for patients requiring drug treatment.", "output": "In a review of 13 cohort studies, bromocriptine improved symptoms and reduced SPLs to normal for 229 of 280 women (82%)." }, { "input": "Dopamine agonists are effective for patients requiring drug treatment.", "output": "A cohort study of 27 patients with macroadenomas treated with bromocriptine found 10% to 50% reductions of tumor size." }, { "input": "cabergoline is more effective and better tolerated than bromocriptine.", "output": "A randomized controlled trial treating 459 women having hyperprolactinemic amenorrhea with either cabergoline or bromocriptine achieved a stable normal SPL in 83% and 59%, respectively (P<.001). Adverse effects were common but were less common with cabergoline (68% vs 78%) and resulted in fewer discontinuations (3% vs 12%)." }, { "input": "Surgery is reserved for symptomatic patients not controlled medically.", "output": "A retrospective review of patients who underwent surgical resection found a 40% recurrence rate." }, { "input": "Surgery is reserved for symptomatic patients not controlled medically.", "output": "Surgery is indicated for patients unresponsive to or intolerant of medical therapy, or who have visual field loss, cranial nerve palsy, or headache due to macroadenoma." }, { "input": "In adults with no history of cardiovascular disease, aspirin reduces the risk of nonfatal myocardial infarction (MI). Aspirin prophylaxis does not decrease all-cause mortality, risk of fatal coronary heart disease, or risk of first stroke.", "output": "Results from 1 study did achieve statistical significance (OR=0.64; 95% CI, 0.42-0.99). No differences were found between aspirin-treated and control groups for all-cause mortality or ischemic stroke reduction." }, { "input": "The benefits of aspirin use must be weighed against its potential risks, primarily gastrointestinal bleeding and cerebral hemorrhage. The benefit of aspirin increases with higher levels of cardiovascular risk, while the potential for harm remains relatively constant. Adults with a calculated 5-year coronary heart disease (CHD) event risk of 3% or greater should receive prophylaxis.", "output": "A meta-analysis of 5 placebo-controlled randomized controlled trials involving more than 50,000 patients free of CHD and stroke evaluated aspirin for primary prevention of cardiovascular disease. Since 3 of the trials excluded women, only 20% of the participants were female. The mean age of participants was 57 years. The treatment groups took aspirin 75 to 500 mg/d for 3 to 7 years. The meta-analysis found that compared with placebo, aspirin significantly reduced total CHD events (odds ratio [OR]=0.72; 95% confidence interval [CI], 0.60-0.87). Aspirin did not reduce coronary disease mortality (OR=0.87; 95% CI, 0.70-1.09);." }, { "input": "The benefits of aspirin use must be weighed against its potential risks, primarily gastrointestinal bleeding and cerebral hemorrhage. The benefit of aspirin increases with higher levels of cardiovascular risk, while the potential for harm remains relatively constant. Adults with a calculated 5-year coronary heart disease (CHD) event risk of 3% or greater should receive prophylaxis.", "output": "Aspirin increased the risk of major gastrointestinal bleeding events by almost twofold (OR=1.70; 95% CI, 1.4-2.1). Three of the 5 trials showed no significant increase of intracranial hemorrhage event rates (OR=1.4; 95% CI, 0.9-2.0). Based on combined primary and secondary prevention trials, the risk of intracranial bleeding with aspirin is estimated at 0 to 2 events per 1000 patients per year." }, { "input": "The ideal dose of aspirin for prophylaxis is unknown, but it appears that low doses 75-81 mg/d are as effective as higher doses.", "output": "Although the ideal aspirin dosage is uncertain, lower dosages (75-81 mg/d) have been shown to be as beneficial as higher dosages, and may have fewer bleeding complications. Buffered and entericcoated formulations are no more protective than plain aspirin." }, { "input": "other", "output": "The leading cause of morbidity and mortality in the United States is cardiovascular disease (ischemic CHD, stroke, peripheral vascular disease)." }, { "input": "other", "output": "Because only 2 trials included women, it is less clear whether both sexes benefit equally from aspirin prophylaxis" }, { "input": "No randomized controlled trials (RCTs) have addressed the independent role of sodium restriction in the morbidity or mortality of congestive heart failure. However, current guidelines recommend sodium restriction for secondary prevention of congestive heart failure exacerbation.", "output": "Sodium restriction is a mainstay of nonpharmacologic therapy for congestive heart failure, although no evidence proves that sodium restriction alone reduces morbidity and mortality." }, { "input": "Clinical trials of multifactorial, nondrug interventions have shown an association of sodium restriction with reduced morbidity and improved quality of life in some populations with congestive heart failure.", "output": "A small RCT compared a program of exercise, cognitive therapy/stress management, salt restriction, and weight reduction to treating congestive heart failure with digoxin or placebo. The nondrug interventions improved functional capacity, body weight, and mood but not ejection fraction in patients with congestive heart failure." }, { "input": "Clinical trials of multifactorial, nondrug interventions have shown an association of sodium restriction with reduced morbidity and improved quality of life in some populations with congestive heart failure.", "output": "A systematic review of 6 RCTs showed that multidisciplinary heart failure disease management programs, which emphasized dietary counseling and/or sodium intake reduction, improved functional capacity, patient satisfaction, and quality of life." }, { "input": "Clinical trials of multifactorial, nondrug interventions have shown an association of sodium restriction with reduced morbidity and improved quality of life in some populations with congestive heart failure.", "output": "A large RCT that investigated how sodium reduction affects hypertension and frequency of cardiovascular events (including congestive heart failure) in the elderly did not show a significant difference in primary prevention of cardiovascular events between the sodium-restricted group and controls." }, { "input": "Clinical trials of multifactorial, nondrug interventions have shown an association of sodium restriction with reduced morbidity and improved quality of life in some populations with congestive heart failure.", "output": "Two prospective cohort studies linked high sodium intake to cardiovascular mortality and all-cause mortality in overweight persons independent of other cardiovascular risk factors." }, { "input": "Significantly. Patients with coronary heart disease (CHD) who refrain from smoking over a 2-year follow-up period decrease their relative risk (RR) for morbidity and mortality by about one third.", "output": "Smoking cessation has also been found to significantly affect morbidity among cardiac patients. Short-term benefits have been demonstrated in CHD patients after a myocardial infarction or coronary artery revascularization. Smoking status at 1-year follow-up was associated with a significant reduction in subsequent cardiac events (myocardial infarction, ischemic cerebrovascular event, revascularization, or death from CHD) when smokers who quit after an initial CHD event were compared with continuing smokers (odds ratio=0.71; 95% CI, 0.38-1.33)." }, { "input": "Significantly. Patients with coronary heart disease (CHD) who refrain from smoking over a 2-year follow-up period decrease their relative risk (RR) for morbidity and mortality by about one third.", "output": "The landmark prospective, community-based cohort Framingham Heart Study (N=1422), which indicates that smoking status predicts overall and morbidity-free survival at age 85." }, { "input": "Significantly. Patients with coronary heart disease (CHD) who refrain from smoking over a 2-year follow-up period decrease their relative risk (RR) for morbidity and mortality by about one third.", "output": "A Cochrane Heart Group meta-analysis examining all-cause CHD mortality in 20 cohort studies (n=12,603 patients), found a 36% reduction in mortality risk for CHD patients who quit smoking compared with those who didn't (RR=0.64; 95% confidence interval [CI], 0.58-0.71). The review also noted a reduction in risk for nonfatal myocardial infarctions (RR=0.68; 95% CI, 0.57-0.82)." }, { "input": "People who maintain abstinence after coronary artery bypass surgery are more likely to avoid angina, repeat revascularization, significant physical impairment, and CHD-related hospital admissions than patients who continue to smoke.", "output": "Long-term quit status in post-coronary artery bypass graft (CABG) surgery patients has been found to predict decreased morbidity and lower rates of repeat revascularization surgery. Findings from the Coronary Artery Surgery Study show that, at 10-year follow-up, nonsmokers were more likely to be free of angina (54% of nonsmokers vs 42% of smokers; P=.02, NNT=8.3) and less likely to experience moderate to severe physical limitations (13% of non-smokers vs 24% of smokers; P=.0004; NNT=9.1). Nonsmokers also had fewer CHD-related admissions than smokers (2.6 vs 3.8; P<.0001)." }, { "input": "People who maintain abstinence after coronary artery bypass surgery are more likely to avoid angina, repeat revascularization, significant physical impairment, and CHD-related hospital admissions than patients who continue to smoke.", "output": "A study found similar results at 20-year follow-up: Patients who had quit smoking underwent fewer repeat CABGs than smokers (RR=1.41; 95% CI, 1.02-1.94).8 The difference between post-CABG survival curves for quitters versus smokers increased from 3% at 5 years (98% vs 95%) to 15% at 15 years (70% vs 55%; P<.0001; NNT=6.7)." }, { "input": "Unexplained hypocalcemia can usually be diagnosed by a limited number of serum tests when the cause isn't obvious from the history recent neck surgery or renal failure: calcium (corrected for serum albumin), creatinine, phosphorus, magnesium and parathyroid hormone (PTH).", "output": "The usual cause of critically low serum calcium (<7 mg/dL \"corrected\" or <3.2 mg/dL ionized) is parathyroidectomy or acute renal failure. Hypocalcemia resulting from partial parathyroidectomy or thyroidectomy (with inadvertent parathyroidectomy) occurs in approximately 5% of these surgeries; 99.5% of cases resolve completely within a year." }, { "input": "Unexplained hypocalcemia can usually be diagnosed by a limited number of serum tests when the cause isn't obvious from the history recent neck surgery or renal failure: calcium (corrected for serum albumin), creatinine, phosphorus, magnesium and parathyroid hormone (PTH).", "output": "Only severe or end-stage chronic kidney disease (glomerular filtration rate <30 cc/min, 5.8% of population) is often associated with actual hypocalcemia." }, { "input": "Unexplained hypocalcemia can usually be diagnosed by a limited number of serum tests when the cause isn't obvious from the history recent neck surgery or renal failure: calcium (corrected for serum albumin), creatinine, phosphorus, magnesium and parathyroid hormone (PTH).", "output": "Normal values for total or corrected serum calcium are 8.5-10.2 mg/dL and for ionized calcium, 4.4-5.4 mg/dL. Because total serum calcium is approximately 50% free (ionized) and 50% bound, primarily to albumin, the serum level must be \"corrected\" if hypoalbuminemia exists. Because serum calcium comprises less than 1% of body stores, severe total body deficiency of calcium can exist without hypocalcemia." }, { "input": "The most common causes, categorized according to the results of these tests, are High PTH, high phosphorus, and high creatinine: renal failure. High PTH, low or normal phosphorus, and normal creatinine: vitamin D deficiency or pancreatitis. And low PTH, high phosphorus, and normal creatinine: inadequate parathyroid gland function or hypomagnesemia.", "output": "Despite elevated PTH, serum calcium may be slightly reduced (and osteomalacia present) even in mild chronic kidney disease." }, { "input": "The most common causes, categorized according to the results of these tests, are High PTH, high phosphorus, and high creatinine: renal failure. High PTH, low or normal phosphorus, and normal creatinine: vitamin D deficiency or pancreatitis. And low PTH, high phosphorus, and normal creatinine: inadequate parathyroid gland function or hypomagnesemia.", "output": "We found no studies that established the frequency of various causes of hypocalcemia in the general population, but reviewers concurred that the most common specific causes, in order of frequency, are renal failure, vitamin D deficiency, hypomagnesemia, pancreatitis and hypoparathyroidism." }, { "input": "The most common causes, categorized according to the results of these tests, are High PTH, high phosphorus, and high creatinine: renal failure. High PTH, low or normal phosphorus, and normal creatinine: vitamin D deficiency or pancreatitis. And low PTH, high phosphorus, and normal creatinine: inadequate parathyroid gland function or hypomagnesemia.", "output": "It is not surprising that renal failure is a common cause of hypocalcemia, given the high prevalence of chronic kidney disease in adults-11.2% of the total United States population older than 20 years has at least a mildly reduced glomerular filtration rate (stage 2, chronic kidney disease, with glomerular filtration rate <90 cc/min)." }, { "input": "The most common causes, categorized according to the results of these tests, are High PTH, high phosphorus, and high creatinine: renal failure. High PTH, low or normal phosphorus, and normal creatinine: vitamin D deficiency or pancreatitis. And low PTH, high phosphorus, and normal creatinine: inadequate parathyroid gland function or hypomagnesemia.", "output": "Chronic kidney disease (66%) and vitamin D deficiency (24%) were the most common causes of hypocalcemia in a study of 594 elderly general medicine inpatients." }, { "input": "The most common causes, categorized according to the results of these tests, are High PTH, high phosphorus, and high creatinine: renal failure. High PTH, low or normal phosphorus, and normal creatinine: vitamin D deficiency or pancreatitis. And low PTH, high phosphorus, and normal creatinine: inadequate parathyroid gland function or hypomagnesemia.", "output": "An adequate supply of 25-OH vitamin D to the kidneys requires adequate gastrointestinal absorption or sun-induced skin production of vitamin D and sufficient liver function to carry out the first of the 2 hydroxylation steps." }, { "input": "The most common causes, categorized according to the results of these tests, are High PTH, high phosphorus, and high creatinine: renal failure. High PTH, low or normal phosphorus, and normal creatinine: vitamin D deficiency or pancreatitis. And low PTH, high phosphorus, and normal creatinine: inadequate parathyroid gland function or hypomagnesemia.", "output": "In a study of 62 hypocalcemic patients in a medical intensive care unit, the cause of the hypocalcemia could be determined in only 28 (45%); most of the cases were caused by hypomagnesemia (28%), renal insufficiency (8%), and pancreatitis (3%)." }, { "input": "other", "output": "The prevalence of vitamin D deficiency (<15 ng/mL of 25-OH vitamin D) is 35% to 55% in the general population." }, { "input": "other", "output": "The prevalence of vitamin D deficiency (<15 ng/mL of 25-OH vitamin D) is and 95% in institutionalized elderly patients." }, { "input": "Osgood-Schlatter disease is best managed with conservative measures activity (modification, ice, anti-inflammatory agents) and time.", "output": "A retrospective review analyzed 50 patients with Osgood-Schlatter (69 knees) for an average of 9 years. No treatments or activity restrictions were recommended. At time of follow-up, 36 (76%) had no limitations, but kneeling continued to be uncomfortable in 60%." }, { "input": "Osgood-Schlatter disease is best managed with conservative measures activity (modification, ice, anti-inflammatory agents) and time.", "output": "In a survey, 20 of 22 (91%) adolescent athletes with Osgood-Schlatter were able to manage their symptoms with ice, aspirin, and mild activity modification. Only 2 needed to stop playing all sports for any period of time, and none required surgery." }, { "input": "Osgood-Schlatter disease is best managed with conservative measures activity (modification, ice, anti-inflammatory agents) and time.", "output": "One retrospective survey of 68 young athletes with Osgood-Schlatter found they required an average of 3.2 months off all training and 7.3 months of some activity restrictions." }, { "input": "Osgood-Schlatter disease is best managed with conservative measures activity (modification, ice, anti-inflammatory agents) and time.", "output": "One case series followed the natural course of the disease in 261 patients (365 symptomatic knees) for 12 to 24 months; 237 (90.8%) patients responded well to restriction of sports activity and nonsteroidal anti-inflammatory agents." }, { "input": "In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks.", "output": "The 24 patients who did not improve with conservative measures in a case series underwent surgical excision of ossicles, and all returned to normal activities (mean time, 4.5 weeks)." }, { "input": "In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks.", "output": "In a case series of 118 patients (151 knees), 88% responded to intermittent limitation of activity (weeks to months) or cylinder casting if limiting activity was ineffective. The remaining 14 patients showed no improvement from these measures; all had surgical excision of an ossicle, sometimes combined with a tubercle-thinning procedure. Only 1 of these patients (7%) did not have complete relief and return to full activities at 6 weeks." }, { "input": "In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks.", "output": "One small case series demonstrated improvement in Osgood-Schlatter disease pain in 19 of 24 (79%) knees after using an infrapatellar strap for 6 to 8 weeks." }, { "input": "In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks.", "output": "In 1 case series, 67 patients (70 knees) (mean age 19.6, 77% male) with at least 18 months of symptoms despite conservative treatment underwent resection of an ossicle (62 cases) or excision of prominent tibial tubercle (8 cases). These patients were followed for 2.2 years, with 56 (90%) patients with ossicle-resection able to return to maximal sports activity without pain, tenderness, loss of motion, or atrophy." }, { "input": "In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks.", "output": "A case series compared 22 patients who1 underwent drilling of the tibial tubercle (with or without the removal of the tibial tubercle) with 22 patients who had excision of loose ossicles or cartilage. Seventeen of the 22 (77%) patients with ossicle excision had complete resolution of symptoms compared with 8 of the 22 (36%) in the patients who underwent tibial tubercle drilling." }, { "input": "In chronic cases that are refractory to conservative treatment, surgical intervention yields good results, particularly for patients with bony or cartilaginous ossicles. Excision of these ossicles produces resolution of symptoms and return to activity in several weeks.", "output": "One surgical series evaluated excision of tibial tuberosity in 35 patients (42 knees) who did not improve with conservative treatment for an average of 13.25 months. For 37 of 42 knees (88%), patients reported complete relief of pain, and all returned to activity without limitation. The average time to return to sports was 15.2 weeks." }, { "input": "Corticosteroid injections are not recommended.", "output": "Corticosteroid injections are generally not recommended, due to case reports of complications, primarily related to subcutaneous atrophy." }, { "input": "The jury is out as to whether you should treat asymptomatic carriers of group A streptococci (GAS), because no studies specifically address the issue. In addition, many patients are unlikely to care about their carrier status, although they probably care about symptoms and treatment side effects. Nonetheless, you may want to consider treating GAS carriers under the following circumstances: 1) Recurrent pharyngitis without cough or congestion. 2) Acute rheumatic fever or poststreptococcal glomerulonephritis outbreaks. 3) GAS pharyngitis outbreaks in a closed community. 4) Family history of acute rheumatic fever. 5) Multiple documented GAS pharyngitis episodes within a family over several weeks despite therapy. 6) Excessive patient/family anxiety about GAS. 7) All treatment options, except tonsillectomy, have been exhausted.", "output": "In 1995, the Centers for Disease Control and Prevention convened a consensus group to address the issue of prophylaxis for people exposed to GAS-positive carriers, but the consensus group failed to reach a definitive conclusion." }, { "input": "The jury is out as to whether you should treat asymptomatic carriers of group A streptococci (GAS), because no studies specifically address the issue. In addition, many patients are unlikely to care about their carrier status, although they probably care about symptoms and treatment side effects. Nonetheless, you may want to consider treating GAS carriers under the following circumstances: 1) Recurrent pharyngitis without cough or congestion. 2) Acute rheumatic fever or poststreptococcal glomerulonephritis outbreaks. 3) GAS pharyngitis outbreaks in a closed community. 4) Family history of acute rheumatic fever. 5) Multiple documented GAS pharyngitis episodes within a family over several weeks despite therapy. 6) Excessive patient/family anxiety about GAS. 7) All treatment options, except tonsillectomy, have been exhausted.", "output": "Some experts practicing in areas with a high prevalence of acute rheumatic fever take a different position: They favor routine treatment of patients with active pharyngitis and a positive throat culture, even if the patient is a known GAS carrier." }, { "input": "The jury is out as to whether you should treat asymptomatic carriers of group A streptococci (GAS), because no studies specifically address the issue. In addition, many patients are unlikely to care about their carrier status, although they probably care about symptoms and treatment side effects. Nonetheless, you may want to consider treating GAS carriers under the following circumstances: 1) Recurrent pharyngitis without cough or congestion. 2) Acute rheumatic fever or poststreptococcal glomerulonephritis outbreaks. 3) GAS pharyngitis outbreaks in a closed community. 4) Family history of acute rheumatic fever. 5) Multiple documented GAS pharyngitis episodes within a family over several weeks despite therapy. 6) Excessive patient/family anxiety about GAS. 7) All treatment options, except tonsillectomy, have been exhausted.", "output": "The Infectious Diseases Society of America (IDSA) considers GAS carriers at low risk for developing complications and spreading infection to close contacts. The 2002 IDSA practice guidelines recommend against routine screening for and treatment of GAS carriage except under the circumstances (2 through 7) outlined in the evidence-based answer. It may be reasonable to treat patients whose carrier status is unknown when they have a second case of pharyngitis. For known GAS-positive patients, however, repeated episodes of pharyngitis over months or years should raise suspicion of intercurrent viral pharyngitis rather than true GAS pharyngitis." }, { "input": "The jury is out as to whether you should treat asymptomatic carriers of group A streptococci (GAS), because no studies specifically address the issue. In addition, many patients are unlikely to care about their carrier status, although they probably care about symptoms and treatment side effects. Nonetheless, you may want to consider treating GAS carriers under the following circumstances: 1) Recurrent pharyngitis without cough or congestion. 2) Acute rheumatic fever or poststreptococcal glomerulonephritis outbreaks. 3) GAS pharyngitis outbreaks in a closed community. 4) Family history of acute rheumatic fever. 5) Multiple documented GAS pharyngitis episodes within a family over several weeks despite therapy. 6) Excessive patient/family anxiety about GAS. 7) All treatment options, except tonsillectomy, have been exhausted.", "output": "As many as 25% of patients with GAS pharyngitis remain culture-positive after an adequate regimen of antibiotic therapy and are deemed GAS carriers. Appropriate screening and management of asymptomatic carriers continues to cause confusion." }, { "input": "Oral clindamycin for 10 days is probably the most effective treatment for carriers. A single dose of intramuscular penicillin plus 4 days of oral rifampin is also effective.", "output": "A study demonstrated a significantly greater eradication rate with oral clindamycin than penicillin plus rifampin (P<.025). Compared with penicillin plus rifampin after 3 weeks of therapy, the number needed to treat (NNT) for clindamycin was 4." }, { "input": "Oral clindamycin for 10 days is probably the most effective treatment for carriers. A single dose of intramuscular penicillin plus 4 days of oral rifampin is also effective.", "output": "A study found intramuscular penicillin plus 4 days of oral rifampin superior to intramuscular penicillin alone (P<.005) or no treatment at all (P<.0005) for eradicating GAS in carriers. Compared with placebo after 3 weeks of therapy, the NNT for penicillin plus rifampin was 2." }, { "input": "Oral clindamycin for 10 days is probably the most effective treatment for carriers. A single dose of intramuscular penicillin plus 4 days of oral rifampin is also effective.", "output": "The IDSA recommends a 10-day course of amoxicillin/clavulanate as an alternative treatment option." }, { "input": "Yes-acetaminophen is a safe and effective analgesic that can be appropriately used for adult patients with stable chronic alcoholic liver disease for at least a short period of time (studies have been limited to a maximum of 48-72 hours), up to the maximum recommended dosage of 4 g daily.", "output": "In Liver and Biliary Disease, the author concludes that chronic alcoholics are at increased risk for hepatotoxicity secondary to acetaminophen even at therapeutic doses; therefore, advise them to take no more than 2 g daily." }, { "input": "Yes-acetaminophen is a safe and effective analgesic that can be appropriately used for adult patients with stable chronic alcoholic liver disease for at least a short period of time (studies have been limited to a maximum of 48-72 hours), up to the maximum recommended dosage of 4 g daily.", "output": "A systematic review (published in 2000) identified reports of acetaminophen toxicity, poisoning, or adverse events for alcohol patients. Researchers found 7 articles classified as Class I (studies utilizing randomized controlled trials) or Class 2 data (studies utilizing prospective, nonrandomized trials), and 20 articles that provided Class 3 data (retrospective case reviews and case reports). The studies of Class I and 2 data indicated therapeutic dosing of acetaminophen is safe for patients with liver disease, whereas the Class 3 (lower-quality) data suggest acetaminophen is toxic for patients with liver disease. This review concluded that, based on all the methodologically sound studies available (specifically those using the stronger evidence), therapeutic dosing of acetaminophen for the alcoholic patient is not associated with hepatic injury." }, { "input": "Yes-acetaminophen is a safe and effective analgesic that can be appropriately used for adult patients with stable chronic alcoholic liver disease for at least a short period of time (studies have been limited to a maximum of 48-72 hours), up to the maximum recommended dosage of 4 g daily.", "output": "In the 1970s and 1980s, there were a number of case reports and small literature reviews indicating that hepatic injury among regular users of alcohol (particularly chronic alcoholics) who take acetaminophen with therapeutic intent could be a \"therapeutic misadventure\"." }, { "input": "Yes-acetaminophen is a safe and effective analgesic that can be appropriately used for adult patients with stable chronic alcoholic liver disease for at least a short period of time (studies have been limited to a maximum of 48-72 hours), up to the maximum recommended dosage of 4 g daily.", "output": "Acetaminophen, while widely used, is hepatotoxic in supra-therapeutic doses." }, { "input": "There are little data to guide longer-term use of acetaminophen in this situation.", "output": "In a randomized, double-blinded, placebo-controlled study, 102 alcoholic patients were given 4 g of acetaminophen daily for 2 days. Liver enzymes were monitored for an additional 2 days. There was no elevation in aminotransferases when compared with the control group of 99 patients who received the placebo. The mean AST level on day 4 was 38.0\u00b126.7 U/L in the treatment group and 37.5\u00b127.6 in the placebo group. In this brief study, there was no increase in liver toxicity among alcoholic patients given the maximal therapeutic dose of acetaminophen." }, { "input": "Oral and intravaginal antifungals for the treatment of uncomplicated vulvovaginal candidiasis (VVC) have similar effectiveness.", "output": "For the treatment of uncomplicated VVC, both topical and oral antifungals are clinically and mycologically effective, with comparable clinical cure rates >80%. No difference in persistent symptoms between single and multiple doses, or different durations of multiple dose regimens have been found, but samples may have been too small to detect clinically significant effects. An RCT found less nausea, headache, and abdominal pain with intravaginal imidazoles, but more vulvar irritation and vaginal discharge than oral fluconazole." }, { "input": "Oral and intravaginal antifungals for the treatment of uncomplicated vulvovaginal candidiasis (VVC) have similar effectiveness.", "output": "Treating male sexual partners did not significantly improve resolution of the woman's symptoms or reduce the rate of symptomatic relapse." }, { "input": "Oral and intravaginal antifungals for the treatment of uncomplicated vulvovaginal candidiasis (VVC) have similar effectiveness.", "output": "For treatment of recurrent VVC, RCTs have shown the effectiveness of oral fluconazole and itraconazole maintenance therapy taken for 6 months after an initial regimen." }, { "input": "No randomized controlled trials (RCTs) have addressed treatment options for patients taking antibiotics. Oral antifungals are contraindicated in pregnancy. While shorter courses of intravaginal therapy can be used by nonpregnant women, 7-day treatment may be necessary during pregnancy.", "output": "A 2003 systematic review found the evidence supporting the association between antibiotics and VVC limited and contradictory. Most were case-control or cohort studies with small sample sizes. No RCTs compare the incidence of culture-confirmed VVC among women receiving antibiotics or placebo. Nineteen reports of 18 original studies had sufficient data to calculate a relative risk or odds ratio for antibiotic-associated VVC. Thirteen of the 19 reports showed an increase (around twofold; range, 0.43-5) in vaginal Candida prevalence; however, 3 of the 13 reports had no mycological culture data. Six studies did not show significant association between antibiotics and vaginal yeast." }, { "input": "Products containing Lactobacillus species do not prevent postantibiotic vulvovaginitis.", "output": "Antibiotics are thought to increase risk of VVC by killing endogenous vaginal flora (particularly Lactobacillus), allowing microorganisms resistant to the antibiotics, like Candida, to flourish." }, { "input": "Products containing Lactobacillus species do not prevent postantibiotic vulvovaginitis.", "output": "Decreasing Lactobacillus does not increase the risk of VVC." }, { "input": "Products containing Lactobacillus species do not prevent postantibiotic vulvovaginitis.", "output": "There is evidence that numbers of genital Lactobacillus are similar for women with and without symptomatic VVC." }, { "input": "Products containing Lactobacillus species do not prevent postantibiotic vulvovaginitis.", "output": "A recent RCT of 278 women on short courses of antibiotics were randomized to oral lactobacilli or placebo and vaginal lactobacilli or placebo. The study was stopped early because there was no effect seen. Overall, 23% developed symptomatic vulvovaginitis." }, { "input": "Products containing Lactobacillus species do not prevent postantibiotic vulvovaginitis.", "output": "Two poor-quality crossover RCTs provided insufficient evidence regarding effectiveness of a diet containing oral Lactobacillus yogurt to prevent recurrent VVC." }, { "input": "When the patient has 2 or more of the following CURB-65 criteria: respiratory rate \u226530, acute confusion, low blood pressure (systolic blood pressure <90 or diastolic BP \u226460 mm Hg), blood urea nitrogen [BUN] >19.6 mg/dL, and age \u226565 years.", "output": "In a split-sample (derivation and validation) analysis of 3 prospective studies involving 1068 patients presenting to the hospital with the diagnosis of pneumonia, various clinical features were analyzed for their association with 30-day mortality. The 5 parameters that were most strongly associated with mortality were: acute confusion (odds ratio [OR]=8.1; 95% confidence interval [CI], 4.8-13.7), BUN >19.6 mg/dL (OR= 5.6; 95% CI, 3.1-10), respiratory rate \u226530 (OR=1.7; 95% CI, 1.07-2.8), low blood pressure (SBP <90 or DBP \u226460) (OR=2.4; 95% CI, 1.4-3.8) and age \u226565 years (OR=5.5; 95% CI, 2.8-10.9). The 30-day mortality estimation using these 5 criteria is called CURB-65 (Confusion, Urea, Respiratory rate, low Blood pressure, and age \u226565). In patients with 2 or more of these factors, the associated rate of mortality increased significantly compared with patients who had none or only 1 of the factors. Although albumin <3.0 g/dL was also significantly associated with an increased mortality rate (OR=4.7; 95% CI, 2.5-8.7), it was not included in CURB-65 because it is not a routine lab ordered for patients with pneumonia. A variation of the CURB-65 score, CRB-65, uses only the clinical parameters without laboratory data (confusion, respiratory rate, blood pressure, and age). Patients with a score of 0 had a 0.9% 30-day mortality rate. However, the rate increased to 8.15% when patients had 1 or 2 of the 4 clinical criteria.." }, { "input": "Alternatively, consider hospitalization for patients presenting with a Pneumonia Severity Index (PSI) class of 4 or 5.", "output": "When compared with CURB-65 and CRB-65, the PSI has similar sensitivity and specificity in predicting 30-day mortality. All 3 predictive rules had high negative predictive values for mortality but a low positive predictive value at all cutoff points." }, { "input": "Antidepressants-specifically clomipramine, fluoxetine, paroxetine, and sertraline-are best and have been shown to improve symptoms of premature ejaculation.", "output": "In 1994, the first study of SSRIs in men with premature ejaculation demonstrated a delaying effect with paroxetine (Paxil)." }, { "input": "Antidepressants-specifically clomipramine, fluoxetine, paroxetine, and sertraline-are best and have been shown to improve symptoms of premature ejaculation.", "output": "A meta-analysis of 35 treatment studies with serotonergic antidepressants from 1943 to 2003 shows that, despite major differences in design and drug dosing, clomipramine, fluoxetine (Prozac), paroxetine, and sertraline (Zoloft) significantly delay ejaculation compared with placebo. The percentage increase in IELT was the primary outcome measured. The rank order of efficacy was: 1) paroxetine (1492% IELT increase; 95% confidence interval [CI], 918-2425), 2) sertraline (790% IELT increase; 95% CI, 532-1173), 3) clomipramine (512% IELT increase; 95% CI, 234-1122) and 4) fluoxetine (295% IELT increase; 95% CI, 172-506). Of the 35 studies used, 8 studies (N=263) were prospective, double-blind, real-time stopwatch studies that were separately analyzed in a subsequent meta-analysis. These 8 studies evaluated clomipramine, fluoxetine, paroxetine, sertraline, citalopram (Celexa), fluvoxamine (Luvox), mirtazapine (Remeron), and nefazodone (Serzone) against placebo. Paroxetine (783% IELT increase, 95% CI, 499-1228), clomipramine (360% IELT increase, 95% CI, 200-435), sertraline (313%, 95% CI, 161-608), and fluoxetine (295%, 95% CI, 200-435) exerted a significant delay in the IELT compared with placebo." }, { "input": "Antidepressants-specifically clomipramine, fluoxetine, paroxetine, and sertraline-are best and have been shown to improve symptoms of premature ejaculation.", "output": "Certain SSRIs and the tricyclic antidepressant clomipramine (Anafranil) have become the agents of choice for the treatment of premature ejaculation." }, { "input": "The topical application of prilocaine-lidocaine cream (trade name EMLA) improves intravaginal ejaculatory latency time (IELT), but penile numbness and loss of erection may occur.", "output": "One double-blinded RCT (N=29) showed significant improvement in the IELT (measured by stopwatch by the subject's partner) from baseline compared with placebo (8.45 min vs 1.95 min; P<.001) at 2 months." }, { "input": "The topical application of prilocaine-lidocaine cream (trade name EMLA) improves intravaginal ejaculatory latency time (IELT), but penile numbness and loss of erection may occur.", "output": "An RCT (N=84) compared EMLA cream applied 15 minutes prior to intercourse, sildenafil 50 mg orally 45 minutes prior to intercourse, EMLA cream plus sildenafil, and placebo. In the sildenafil-plus-EMLA group, 32% of the patients reported \"improvement\" and 54% reported \"cure\", which was defined as ejaculation delayed until the patient wished it. In the EMLA-only group, 27% of the patients reported \"improvement\" and 50% reported \"cure.\" This was a statistically significant difference when compared with the placebo and sildenafil-only groups (number needed to treat [NNT]=3). There was no significant difference in reports of \"improvement\" or \"cure\" between the placebo and sildenafil-only groups." }, { "input": "The topical application of prilocaine-lidocaine cream (trade name EMLA) improves intravaginal ejaculatory latency time (IELT), but penile numbness and loss of erection may occur.", "output": "One small RCT (N=24) compared placebo with the application of EMLA cream 20, 30, and 45 minutes prior to sexual intercourse. Improvement was seen in IELT in the 20- and 30-minute group, but penile numbness and erection loss increased in the 30- and 45-minute group." }, { "input": "There is no evidence that phosphodiesterase type 5 (PDE5) inhibitors-such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)-decrease instances of premature ejaculation in otherwise healthy men. There is limited evidence, however, that PDE5 inhibitors reduce symptoms of premature ejaculation for men with concomitant erectile dysfunction.", "output": "A review of 14 clinical trials concluded that there is no convincing evidence for PDE5 inhibitors in the treatment of men with lifelong premature ejaculation and normal erectile function." }, { "input": "There is no evidence that phosphodiesterase type 5 (PDE5) inhibitors-such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)-decrease instances of premature ejaculation in otherwise healthy men. There is limited evidence, however, that PDE5 inhibitors reduce symptoms of premature ejaculation for men with concomitant erectile dysfunction.", "output": "A study by Li et al treated 45 men with premature ejaculation and comorbid erectile dysfunction with sildenafil. Eighty-nine percent reported improved erectile function, and 60% reported decreased severity of premature ejaculation." }, { "input": "There is no evidence that phosphodiesterase type 5 (PDE5) inhibitors-such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)-decrease instances of premature ejaculation in otherwise healthy men. There is limited evidence, however, that PDE5 inhibitors reduce symptoms of premature ejaculation for men with concomitant erectile dysfunction.", "output": "One RCT found no increase in IELT from baseline in men taking sildenafil when compared with placebo, although patients reported overall sexual satisfaction and confidence based on a questionnaire." }, { "input": "other", "output": "Studies in male rats have demonstrated that serotonin with various 5-HT receptor subtypes are involved in the ejaculatory process." }, { "input": "other", "output": "It's been suggested that lifelong premature ejaculation is a neurobiological phenomenon related to decreased central serotonergic neurotransmission, 5-HT2c receptor hyposensitivity, or 5-HT1a receptor hypersensitivity." }, { "input": "other", "output": "Premature ejaculation is the most common male sexual dysfunction, but there is no universally accepted definition or validated screening instrument. The pathophysiology and etiology remain incompletely understood. Based on surveys, prevalence rates for premature ejaculation are approximately 20% to 30%." }, { "input": "other", "output": "The introduction of selective serotonin reuptake inhibitors (SSRIs) revolutionized the treatment of premature ejaculation." }, { "input": "It can be. Spinal manipulative therapy (SMT), a component of osteopathy, has been shown to be variably effective for the treatment of headaches. For the prophylactic treatment of cervicogenic headaches and for acute tension headaches, SMT is superior to placebo.", "output": "A trial randomized 30 patients to either SMT, mobilization (small oscillatory movements to a joint within its normal range), or wait-list placement. At the end of treatment, there was a nonsignificant trend toward greater pain reduction in patients receiving SMT than either those receiving mobilization (ES=0.4; 95% CI, -0.5 to 1.4) or those on the wait list (ES=0.6; 95% CI, -0.4 to 1.5)." }, { "input": "It can be. Spinal manipulative therapy (SMT), a component of osteopathy, has been shown to be variably effective for the treatment of headaches. For the prophylactic treatment of cervicogenic headaches and for acute tension headaches, SMT is superior to placebo.", "output": "A RCT with 105 patients compared SMT (3 times a week for 3 weeks) with placebo. The SMT group reported significantly less pain after 3 weeks (ES=2.2; 95% CI, 1.7-2.7)" }, { "input": "It can be. Spinal manipulative therapy (SMT), a component of osteopathy, has been shown to be variably effective for the treatment of headaches. For the prophylactic treatment of cervicogenic headaches and for acute tension headaches, SMT is superior to placebo.", "output": "A multicenter trial randomized 200 patients with cervicogenic headaches to either SMT (8-12 sessions over 6 weeks) or placebo. The SMT group had significantly reduced pain (at 1 week, effect size [ES]=0.7; 95% confidence interval [CI], 0.3-1.2; and at 12 months, ES=0.4; 95% CI, 0.0-0.8) and fewer headaches (ES=0.7; 95% CI, 0.3-1.1 at both time points) than placebo." }, { "input": "For tension headache prophylaxis, research shows a trend toward better outcomes with amitriptyline than with SMT. For migraine prophylaxis, SMT has an effect similar to amitriptyline.", "output": "Two trials investigated the efficacy of SMT on tension-type headaches. The first, an RCT with 150 patients with recurrent headaches, compared SMT (2 sessions per week) with amitriptyline (10 mg daily week 1, 20 mg daily week 2, then 30 mg daily) for 6 weeks. At the end of 6 weeks, the SMT group reported a nonsignificant trend toward more headache pain (ES for SMT vs amitriptyline= -0.4; 95% CI, -0.8 to 0.0), but fewer side effects. They had similar headache frequency and medication use." }, { "input": "For tension headache prophylaxis, research shows a trend toward better outcomes with amitriptyline than with SMT. For migraine prophylaxis, SMT has an effect similar to amitriptyline.", "output": "A study of 22 patients compared SMT with 2 different controls (palpation and rest) for acute tension-type headache. The SMT group was significantly more likely to experience immediate improvement (ES=1.8; 95% CI, 0.4-3.2)." }, { "input": "For tension headache prophylaxis, research shows a trend toward better outcomes with amitriptyline than with SMT. For migraine prophylaxis, SMT has an effect similar to amitriptyline.", "output": "In 1 trial of migraine prophylaxis, 218 patients were randomized to either 14 sessions of SMT for 2 months or oral amitriptyline (titrated up weekly during the first month and continued at 100 mg daily over the second month). The headache index (a measure of daily pain intensity) was equivalent in both groups in the last 4 weeks of treatment (ES for SMT vs amitriptyline= -0.1; 95% CI, -0.5 to 0.3). A month after both therapies were stopped, there was a nonsignificant trend toward a lower headache index in the group that had received SMT than the group that had received amitriptyline (ES=0.4; 95% CI, 0.0-0.8). Ten percent of the medication group withdrew from this study due to side effects; no side effects were reported from SMT." }, { "input": "For tension headache prophylaxis, research shows a trend toward better outcomes with amitriptyline than with SMT. For migraine prophylaxis, SMT has an effect similar to amitriptyline.", "output": "A RCT of migraine prophylaxis with 88 patients compared SMT twice weekly for 8 weeks with mobilization techniques. At 8 weeks post-treatment, there was a nonsignificant trend favoring SMT over mobilization in decreasing pain (ES=0.4; 95% CI, -0.2 to 1.0)." }, { "input": "The differential diagnosis, in descending order, includes: elevated pulmonary artery pressure (often due to obstructive sleep apnea), congestive heart failure, idiopathic causes, venous insufficiency, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and proteinuria (>1 g daily).", "output": "A nonconsecutive cohort study evaluated the causes of bilateral leg edema among 58 ambulatory adults (between 29 and 83 years of age) enrolled from an inner-city family medicine clinic in Cleveland. Edema was present for >3 months in 78% of patients, and 84% were obese. Patients were excluded if the edema was known to be due to nifedipine, intra-abdominal malignancy, hypothyroidism, or idiopathic cyclic edema. Family physicians obtained a history and performed a physical exam on all patients and recorded a clinical diagnosis for the edema. Initial clinical impressions included: venous insufficiency (71%), congestive heart failure (18%), nephrotic syndrome (13%), uncertain (7%), and other causes (2% each). Other causes included lymphedema, pulmonary hypertension, cor pulmonale, hypoalbuminemia, NSAID or corticosteroid use, sleep apnea, and obesity. (Total percentages exceed 100% because some patients had multiple conditions.) All patients were then evaluated with a serum albumin, a 24-hour urine protein collection, echocardiogram, and lower extremity duplex venous ultrasound (13 of 58 patients did not complete the echocardiogram and venous duplex ultrasound). Investigators developed a final diagnosis using the results of this evaluation in conjunction with the clinical information obtained by the physician. Final diagnoses included pulmonary hypertension/borderline pulmonary hyper-tension (>30 mm Hg) (42%), congestive heart failure (29%), idiopathic edema (27%), venous insufficiency (22%), medication use (15%, primarily corticosteroids and NSAIDs), proteinuria >1 g/day (15%), and other causes (2% each). These other causes included transient renal disease, hypoalbuminemia, lymphedema, and stenosis of the inferior vena cava. (Total percentages again exceed 100% because some patients had multiple diagnoses.) All 15 patients with cardiac conditions and 17 of 19 patients with pulmonary hypertension were over 45 years of age. Of the 19 patients with pulmonary hypertension, 6 had CHF, 4 had chronic obstructive pulmonary disease, 4 had sleep apnea diagnosed in subsequent testing, 1 had an atrial septal defect, and 4 appeared to have primary pulmonary hypertension. The investigators recommended 3 steps to evaluate chronic leg edema. 1) Stop any potentially causative medicines, such as NSAIDs or calcium-channel blockers. 2) Obtain an echocardiogram if the patient is 45 years of age or older. 3) Obtain a sleep study if the echo-cardiogram reveals pulmonary hypertension without an apparent cause." }, { "input": "Congenital hypothyroidism is a critical cause of elevated thyroid-stimulating hormone (TSH) in newborns; evaluate all neonates with an elevated TSH for congenital hypothyroidism.", "output": "In term, healthy newborns, TSH levels normally increase to levels of 60 mU/L within 30 minutes of delivery. This is followed by a rapid decline in TSH levels over the first 5 days of life to <10 mU/L. An Australian study found more elevated TSH levels for samples drawn on day 2 of life compared with day 3 of life, likely reflecting normal postnatal physiology. Age-specific reference ranges are necessary for interpretation of TSH levels during the first 5 days of life. The second or third day of life remains the optimal time for screening when appropriate reference ranges are used." }, { "input": "Congenital hypothyroidism is a critical cause of elevated thyroid-stimulating hormone (TSH) in newborns; evaluate all neonates with an elevated TSH for congenital hypothyroidism.", "output": "Another study confirmed that TSH levels were higher in infants born preterm; babies with the earliest gestational ages had the highest TSH levels. The same study also found that TSH levels increased with increasing degrees of illness. Very preterm babies, those with cerebral pathology, low Apgar scores, respiratory distress syndrome, persistent ductus arteriosus requiring treatment, and necrotizing enterocolitis were at highest risk for having abnormally elevated TSH levels in this study. If a sample is drawn from a newborn exhibiting symptoms (such as poor feeding or hypotonia), the TSH level may be elevated in spite of normal thyroid function." }, { "input": "Congenital hypothyroidism is a critical cause of elevated thyroid-stimulating hormone (TSH) in newborns; evaluate all neonates with an elevated TSH for congenital hypothyroidism.", "output": "A study from the Netherlands examined diagnoses of infants with an increased TSH on newborn screening heelstick. Of 112 newborns with a TSH >50 mU/L, 110 (98%) had congenital hypothyroidism on further examination. However, only 34 of 594 (5.7%) newborns with a TSH between 9 and 20 mU/L were diagnosed with congenital hypothyroidism. Nineteen of 46 newborns (41%) with levels between 20 and 50 mU/L had congenital hypothyroidism." }, { "input": "Other causes of an elevated TSH include transient hypothyroidism due to neonatal illness, prematurity, iodine excess or deficiency, and maternal medication or maternal thyroid disease.", "output": "A study explored the presumed causes of elevated TSH among children who were diagnosed with transient hypothyroidism (initially elevated TSH level found to be normal on follow-up testing). The most common causes were thyroid-binding globulin deficiency (200/548 or 36% of newborns with transient hypothyroidism), severe illness (36%), prematurity (8%), and errors in screening procedures (4%). The study found that of 34 children with transient hypothyroidism, 10 had mothers with undertreated or unrecognized Graves disease." }, { "input": "Other causes of an elevated TSH include transient hypothyroidism due to neonatal illness, prematurity, iodine excess or deficiency, and maternal medication or maternal thyroid disease.", "output": "Iodine excess or iodine deficiency can cause transient hypothyroidism. Case reports have directly demonstrated the effects of topical iodine exposure on newborn TSH levels." }, { "input": "other", "output": "Deficiency of dietary iodine is a common cause of both congenital and transient hypothyroidism in newborns worldwide, although it is rare in the United States. The World Health Organization lists 54 countries with inadequate iodine intake; consider children from these countries at high risk for hypothyroidism due to iodine deficiency." }, { "input": "Multiple screening trials have demonstrated that a primary strategy of 3-card home FOBT with follow-up colonoscopy for positive results is associated with significant reduction in mortality from colorectal cancer.", "output": "A Cochrane review conducted a meta-analysis looking only at FOBT for colorectal cancer screening. This review, based on published and unpublished data from 5 controlled trials, demonstrated that 3-card home FOBT conferred a reduction in colorectal cancer mortality of 16% (relative risk [RR]=0.84; 95% confidence interval [CI], 0.77-0.92) and a number needed to screen of 1173 (95% CI, 741-2807) to prevent 1 death from colon cancer over a 10-year period. If adjusted for adherence to screening, the reduction in mortality increased to 23% (RR=0.77; 95% CI, 0.57-0.89)." }, { "input": "Multiple screening trials have demonstrated that a primary strategy of 3-card home FOBT with follow-up colonoscopy for positive results is associated with significant reduction in mortality from colorectal cancer.", "output": "Long-term follow up of one of the RCTs in a Cochrane review showed a continued reduction in colorectal cancer mortality of 34% (RR=0.66; 95% CI, 0.54-0.81) in subjects adhering to the FOBT screening protocol over a 13-year interval. Overall mortality did not differ between the screened and unscreened groups." }, { "input": "Multiple screening trials have demonstrated that a primary strategy of 3-card home FOBT with follow-up colonoscopy for positive results is associated with significant reduction in mortality from colorectal cancer.", "output": "A systematic review performed for the US Preventive Services Task Force (USPSTF) incorporated more recent data on colorectal cancer screening including colonoscopy. This review reached similar conclusions as above. This review also looked at office FOBT performed after digital rectal exam. It is important to note that a single office FOBT has a lower sensitivity than 3-card home FOBT and its effectiveness for reducing colorectal cancer mortality was unknown at the time of the systematic review. The USPSTF review also looked at the sensitivity and adverse effects of FOBT compared to colonoscopy. One-time 3-card home FOBT had a sensitivity of 30% to 40% for detecting cancer. The sensitivity of one-time colonoscopy was difficult to determine since it was the criterion standard examination, but it was estimated to be greater than 90%, with a risk of perforation of 1/2000." }, { "input": "A single negative office-based digital FOBT does not decrease the likelihood of advanced neoplasia.", "output": "A subsequent 2005 Veterans Affairs prospective cohort study found that the sensitivity for detecting advanced neoplasia was only 4.9% for digital FOBT, and negative results did not decrease the likelihood of advanced neoplasia." }, { "input": "There are no publications of screening trials with colonoscopy, but the odds of dying from colorectal cancer are lower for patients undergoing colonoscopy compared with patients not having a colonoscopy.", "output": "The USPSTF review did not find any screening trials of colonoscopy but analyzed data from the National Polyp Study and a case-control study to draw its conclusions. The review reported an odds ratio for colorectal cancer mortality for patients who had colonoscopy to be 0.43 (95% CI, 0.30-63)." }, { "input": "Both strategies (colonoscopy and FOBT) are cost-effective.", "output": "The USPSTF review found both screening strategies cost-effective (<$30,000 per additional life-year gained) compared to no screening. FOBT had a cost per life-year saved of $5691 to $17,805 compared with $9038 to $22,012 for colonoscopy performed every 10 years." }, { "input": "Unfractionated heparin and low-molecular-weight heparin are equally effective for the treatment of acute venous thromboembolism (VTE) in pregnancy.", "output": "In a prospective cohort study of 31 patients, for the initial week of treatment, the unfractionated heparin group received an IV bolus followed by infusion titrated to aPTT levels (goal 70-100s), while lowmolecular-weight heparin group received subcutaneous dalteparin 115 IU/kg twice daily adjusted to target antifactor Xa levels of 1 to 1.5 IU/mL 3 hours after injection. After 7 days, both groups received prophylactic doses of dalteparin throughout the remainder of pregnancy. There were no significant differences in outcome including bleeding or fetal effects. No cases of thrombocytopenia or pulmonary embolus were seen. There was 1 case of progressive thrombosis for a patient on low-molecular-weight heparin." }, { "input": "Low-molecular-weight heparin may be associated with fewer bleeding events than unfractionated heparin.", "output": "One randomized controlled trial compared unfractionated with low-molecular-weight heparin for VTE prophylaxis among 107 high-risk pregnant patients. The unfractionated heparin group received 7500 IU subcutaneously twice daily adjusted to aPTT levels, while the dalteparin group received weight-adjusted doses to target antifactor Xa levels >0.2 IU/mL at 3 hours. No thromboembolic complications occurred in either group (95% confidence interval, 0 to 2 in both groups). Minor bleeding complications were significantly more common with unfractionated heparin than with low-molecular-weight heparin. Two bleeds requiring transfusion and 2 lumbosacral compression fractures were also observed in the unfractionated heparin group, compared with none in the dalteparin group (difference not statistically significant)." }, { "input": "Unfractionated heparin for treatment of VTE should be given by IV bolus followed by continuous infusion, maintaining the activated partial thromboplastin time (aPTT) in therapeutic range for at least 5 days, followed by subcutaneous heparin 2 or 3 times daily to maintain aPTT levels 1.5 to 2.5 times normal for at least 3 months.", "output": "For the initial week of treatment, the unfractionated heparin group received an IV bolus followed by infusion titrated to aPTT levels (goal 70-100s), while lowmolecular-weight heparin group received subcutaneous dalteparin 115 IU/kg twice daily adjusted to target antifactor Xa levels of 1 to 1.5 IU/mL 3 hours after injection. After 7 days, both groups received prophylactic doses of dalteparin throughout the remainder of pregnancy. There were no significant differences in outcome including bleeding or fetal effects. No cases of thrombocytopenia or pulmonary embolus were seen. There was 1 case of progressive thrombosis for a patient on low-molecular-weight heparin." }, { "input": "Unfractionated heparin for treatment of VTE should be given by IV bolus followed by continuous infusion, maintaining the activated partial thromboplastin time (aPTT) in therapeutic range for at least 5 days, followed by subcutaneous heparin 2 or 3 times daily to maintain aPTT levels 1.5 to 2.5 times normal for at least 3 months.", "output": "Both the American College of Obstetrics and Gynecologists and the American College of Chest Physicians recommends treating acute VTE in pregnancy with either weight-adjusted-dose low-molecular-weight heparin goal antifactor Xa levels, 0.5-1.2 throughout pregnancy or full-dose intravenous unfractionated heparin, followed by adjusted-dose unfractionated or low-molecular-weight heparin, for the remainder of the pregnancy and at least 6 weeks postpartum." }, { "input": "Low-molecular-weight heparin should be initially dosed based on weight as for nonpregnant patients, then adjusted to goal peak antifactor Xa levels of 0.5-1.2 IU/mL.", "output": "The only study of unfractionated heparin for the treatment of VTE in pregnancy used aPTT levels extrapolated from nonpregnant patients, with a mean heparin dose of 25,430 IU/d, similar to mean doses for nonpregnant patients." }, { "input": "Low-molecular-weight heparin should be initially dosed based on weight as for nonpregnant patients, then adjusted to goal peak antifactor Xa levels of 0.5-1.2 IU/mL.", "output": "Several studies of low-molecular-weight heparin for the treatment of VTE in pregnancy used target antifactor Xa levels of 0.5 to 1.5 at 3 hours and found patients often need doses greater than those used for nonpregnantpatients." }, { "input": "Neuroimaging is warranted to evaluate headaches when patients present to an emergency department with signs or symptoms of an intracranial lesion. These signs or symptoms include abrupt onset of headache, focal neurological abnormalities.", "output": "A validating cohort study looked at 5 clinical warning criteria for patients seen in an emergency department for headache; 70 adults with acute headache as the chief complaint were included. Allpatients received computed tomography (CT) scanning as part of their evaluation. Abrupt onset and focal neurologic findings most strongly predicted intracranial lesions. Overall, 36% of the patients (25/70) had significant pathology." }, { "input": "Neuroimaging is warranted to evaluate headaches when patients present to an emergency department with signs or symptoms of an intracranial lesion, such as decreased level of consciousness.", "output": "A retrospective study reviewed records of 111 patients seen in an emergency department with headache and who had undergone neuroimaging (CT or magnetic resonance imaging [MRI]). Three symptoms predicted a lesion: decreased level of consciousness (sensitivity=23%; positive likelihood ratio [LR+]=3.8), paralysis (sensitivity=25%; LR+=3.5), and papilledema (numbers not reported). In this study, 35% (39/111) of those receiving neuroimaging had intracranial pathology." }, { "input": "Neuroimaging is also recommended in the ambulatory setting for patients with headaches of migraine type and abnormal findings on neurological exam; that are accompanied by signs or symptoms of increased intracranial pressure; or that are new for a patient who is HIV-positive.", "output": "Expert guidelines regarding headaches among ambulatory patients recommend neuroimaging for migraine patients only in the presence of persistent focal abnormal neurological findings. They note insufficient evidence for recommendations concerning neuroimaging for patients with tension-type headaches. They also note insufficient evidence for or against neuroimaging when headache occurs in the presence or absence of nonfocal symptoms: dizziness, syncope, nausea, lack of coordination, the \"worst headache ever\", headache that awakens the patient from sleep, and increasing frequency of headaches." }, { "input": "Neuroimaging is also recommended in the ambulatory setting for patients with headaches of migraine type and abnormal findings on neurological exam; that are accompanied by signs or symptoms of increased intracranial pressure; or that are new for a patient who is HIV-positive.", "output": "A case-control study reviewed hospital records of 468 patients evaluated in the emergency department for nontraumatic headache. Neuroimaging (CT scan or cerebral angiogram) was performed for 160 of these patients. Final diagnosis and outcome was obtained at 6 months. The symptoms and their ability to predict intracranial pathology are as follows: abnormal neurologic examination (sensitivity=39%; LR+=19.5), location of headache (sensitivity=78%; LR+=4.87), age of patient (sensitivity=61%; LR+=2.26), multiple associated symptoms (sensitivity=61%; LR+=2.26), mode of onset of headache (sensitivity=78%; LR+=2.23), and presence of associated symptoms (sensitivity=89%; LR+=1.41). Again, abnormal neurologic examination was the most significant indicator for imaging. This study did not define associated symptoms nor did it specify what determined which patients were imaged." }, { "input": "Neuroimaging is also recommended in the ambulatory setting for patients with headaches of migraine type and abnormal findings on neurological exam; that are accompanied by signs or symptoms of increased intracranial pressure; or that are new for a patient who is HIV-positive.", "output": "Essentials of Radiology add the following indications for imaging in headache: signs and symptoms of elevated intracranialpressure eg, papilledema; meningismus; partial seizure; nocturnal headaches that awaken the patient from sleep; increase in pain with coughing, sneezing or change in body position; sudden onset headaches that reach maximum intensity in 2 to 3 minutes; headache associated with mentalstatus changes or decreased alertness; any new headache in an HIV-positive patient." }, { "input": "other", "output": "When neuroimaging is performed, about 4% of CT scans find a significant and treatable lesion (in one sample of 293 CT scans, there were 12 true-positive scans and 2 false-positive scans)." }, { "input": "other", "output": "Information concerning the workup of headache in the ambulatory setting is limited. In actual practice, only about 3% of patients who present with a new headache in the office setting have neuroimaging ordered." }, { "input": "Three treatment studies suggest that nonpharmacological therapies (combinations of skin warming, relaxation, biofeedback, and physical therapy) were effective for pain relief.", "output": "Two studies were published together evaluating thermal biofeedback, relaxation training, and physical therapy exercises. The first, a cohort study, showed decrease in symptoms for 15 of 19 women. The second, a small randomized controlled trial, compared 11 women using the combination treatment with 14 control women who received attention from the therapist but no other intervention. More than 72% of the treatment arm improved, compared with nearly 29% of the attention control group. Interpretation of these studies is limited by small sample size and testing in settings with specialized resources that are not found in every community." }, { "input": "Three treatment studies suggest that nonpharmacological therapies (combinations of skin warming, relaxation, biofeedback, and physical therapy) were effective for pain relief.", "output": "A small case series of electromyograph (EMG) biofeedback and relaxation techniques on 5 pregnant women showed that 4 became headache-free. It is impossible to say whether it was the intervention, natural disease progression, or the attention received from the therapist that produced this result." }, { "input": "Practice guidelines and most review articles recommend acetaminophen as the first-line therapy.", "output": "Practice guidelines published by the American Academy of Neurology recommend acetaminophen as first-line therapy based on its established safety in surveillance studies, although it is of questionable efficacy for nonpregnant patients. They also recommend nonpharmacologic treatment as an acceptable option in pregnancy." }, { "input": "Practice guidelines and most review articles recommend acetaminophen as the first-line therapy.", "output": "Most review articles recommend acetaminophen alone or in combination with codeine as the treatment of first choice." }, { "input": "Treatment modalities, including medications, should be chosen based on both effectiveness for nonpregnant patients and established pregnancy safety from surveillance studies.", "output": "The US Food and Drug Administration (FDA) assigns fetal risk categories to all drugs based on controlled studies in humans, animal reproduction studies, and surveillance studies. Though no data exist on the effectiveness of other medications for migraine in pregnancy, it is reasonable to select drugs for both effectiveness for nonpregnant patients and established safety as determined by the FDA's fetal risk summary." }, { "input": "No randomized controlled trials of pharmacologic therapy for acute migraine in pregnant women are available.", "output": "One prospective controlled cohort study showed an increase in miscarriage rates that did not reach statistical significance." }, { "input": "No randomized controlled trials of pharmacologic therapy for acute migraine in pregnant women are available.", "output": "Six studies have evaluated sumatriptan use in pregnancy. All were designed to evaluate teratogenicity and harm. None evaluated treatment efficacy in pregnancy." }, { "input": "other", "output": "A single case report on the use of intravenous magnesium sulfate and prochlorperazine reported that the combination was effective for aborting a prolonged (6-day) migraine with aura for a pregnant woman." }, { "input": "Medicare guidelines are used to determine eligibility for hospice care.", "output": "Medicare adapted the National Hospice Organization guidelines to determine patients' eligibility for hospice care." }, { "input": "Medicare guidelines correlate with 6-month mortality no better than an experienced clinician's judgment.", "output": "A retrospective chart audit of 165 patients, and a subsequent prospective cohort study of 80 patients at comparable stages of progressive dementia who were consecutively admitted to a community-based hospice program. These patients had estimated life expectancy of less than 6 months, as certified by the attending and the hospice medical director, without use of explicit guidelines. The survival curves for patients who, in retrospect, did and did not meet Medicare guidelines were similarie, the Medicare guidelines were not statistically better at predicting 6-month survival than the clinical impressions of the attending and hospice medical director. In the 139 patients from the retrospective cohort included in the Cox regression analysis, 108 patients died within 6 months. Of those, 83 (77%) met Medicare criteria and 25 (23%) did not. Of the 31 who lived longer than 6 months, 22 (71%) met Medicare criteria and 9 (29%) did not. In the prospective cohort, of the 61 patients who died within 6 months, 39 (64%) met Medicare criteria and 22 (36%) did not; of the 18 who lived longer than 6 months, 9 met Medicare criteria (50%) and 9 did not." }, { "input": "Recent studies, however, have identified additional criteria that may better predict survival in select populations. These prognostic criteria include stepwise progression to Functional Assessment Staging Scale (FAST) stage 7c (inability to walk without assistance).", "output": "Two prospective cohort studies followed 47 and 45 patients enrolled in hospice over 2 years; these studies demonstrated that patients who reach FAST stage 7c (inability to walk without assistance) in an stepwise fashion are likely to live less than 6 months. In 1 of the 2 studies, patients who reached stage 7c ordinally had a mean survival time of 4.1 months; 71% died within 6 months of enrollment. For the large subset of patients who met 7c but not in an ordinal fashion (ie, they met criteria for 7c, but perhaps not 7a or 7b), only 30% died within 6 months, with median survival time 10.7 months." }, { "input": "Recent studies, however, have identified additional criteria that may better predict survival in select populations. These prognostic criteria include stepwise progression to Functional Assessment Staging Scale (FAST) stage 7c (inability to walk without assistance).", "output": "Use of antibiotics did not make a statistically significant difference in survival, and use of Foley catheters was associated with shorter survival times (3.6 months vs 9 months; P<.03.)." }, { "input": "Prognostic criteria include criteria derived from the Minimum Data Set (MDS) which include: dependency for activities of daily living, bedbound status, bowel incontinence, comorbid conditions specifically cancer, congestive heart failure, oxygen dependence, or dyspnea, medical instability, eating<25% of meals, sleeping most of the day, male gender, and age>83 years.", "output": "In a retrospective cohort study of 11,430 nursing home residents with advanced dementia (defined as a score of 5 or 6 on the Cognitive Performance Score, which is itself based on MDS data, a prognostic summary score was developed using 12 variables from the MDS, a federally mandated assessment completed by nursing home staff at the time of admission. A high score predicted 6-month mortality more accurately than using an MDS correlate of FAST stage 7c. In the derivation cohort (n=6799), 28.3% (n=1922) died within 6 months; in the validation cohort (n=4631), 35.1% (n=1626) died within 6 months. The FAST 7c correlate was found to have a positive predictive value of only 38.5% and a sensitivity of 22% in predicting death within 6 months in this population. In contrast, using the MDS variables, a higher threshold for the prognostic summary score resulted in a positive predictive value of 80%, negative predictive value of 73%, specificity of 99%, but sensitivity of only 6%. A lower cutoff yielded better sensitivity (23%), and still had good specificity (96%) and negative predictive value (76%), though the positive predictive value was slightly lower (67%). Morrison and Siu conducted a prospective cohort study of consecutive patients admitted with hip fract" }, { "input": "Two randomized clinical trials have shown that simplified dosing schedules have improved patient adherence to medication as prescribed. Some, but not all, randomized controlled trials show multidimensional interventions can also improve adherence. These interventions include combinations of patient and family education, home monitoring of disease status, and increased convenience of care, such as workplace access.", "output": "The Cochrane Database of Systematic Reviews evaluated the published, unbiased, randomized controlled trials of interventions to improve medication adherence that measured both adherence and treatment outcome. Eighty percent follow-up was required, as well as a 6-month follow-up period for long-term treatments with initial positive outcomes. A total of 4762 citations were evaluated; only 19 met their criteria for full consideration. The interventions studied included combinations of patient and family counseling (verbal, written, telephone, and automated); patient involvement in self-monitoring of outcomes (eg, blood pressure); simplified medication regimens; reminders of appointments, refills, and pill schedules; and care provided at the workplace. All interventions were for single clinical conditions including hypertension (7 studies), schizophrenia and psychosis (6), asthma (2), acute infection (2), hyperlipidemia (1), and epilepsy (1). Both of the studies concerning simplifying medication regimens showed a positive effect on medication adherence. Nine of 16 studies on varying strategies of interventions reported statistically significant increases in medication adherence." }, { "input": "Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy.", "output": "In nonpregnant adults, proton pump inhibitors are more effective than antacids and H2-blockers for gastroesophageal reflux disease (GERD). No cohort or control studies have been performed on their efficacy in pregnancy. On the basis of animal studies, omeprazole is a category C drug (potential benefit of use should outweigh potential risks). A cohort study of 113 women found no associated anomalies (relative risk=1.94; 95% confidence interval, 0.36-10.36). Pantoprazole, lansoprazole and rabeprazole are category B medications." }, { "input": "Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy.", "output": "A 2-week study that compared antacids plus ranitidine to antacids alone found a 52% decrease in symptoms in the ranitidine group and a 44% reduction in the antacid-alone group." }, { "input": "Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy.", "output": "A 4-week double-blind randomized control trial found that ranitidine 150 mg twice daily reduced patient symptoms by 44% over placebo (P <.05). This study was limited by its short duration (<1 month) and small sample size (N=30)." }, { "input": "Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy.", "output": "A single case-control study found a higher rate of congenital anomalies in children of women who took antacids in the first trimester (unadjusted odds ratio calculated from data=2.36; P <.05). This association was not detected when studied over the entire pregnancy. The rate of malformations was not different for magnesium, aluminum, and bicarbonate. The association could well be due to recall bias or other systematic biases inherent in case-control methodology." }, { "input": "Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy.", "output": "Atlay and colleagues found that sodium bicarbonate significantly reduced reflux symptoms compared with placebo (P=.021; NNT=6.0)." }, { "input": "Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy.", "output": "Patients who received a combination of magnesium and aluminum hydroxide for 7 days had no more relief of symptoms than the placebo group." }, { "input": "Ranitidine is the best-studied agent effective for treatment of heartburn in pregnancy. Some antacids are effective, but it may be prudent to avoid them in the first trimester until better safety studies are published. Although sucralfate, metoclopromide, and the proton pump inhibitors are probably safe in pregnancy, there are no data about their efficacy.", "output": "Aluminum phosphate more frequently produced complete relief of moderate to severe heartburn at 60 minutes compared with placebo (P <.001; number needed to treat [NNT] = 2.1 for mild heartburn and 20 for severe)." }, { "input": "Adults between the ages of 19 and 64 years who have chronic lung disease, including asthma, should get the vaccine, as should all patients 65 years and older.", "output": "A 5-year retrospective cohort study of 9170 patients evaluated the effect of pneumococcal vaccination on incidence and length of all-cause hospitalizations and hospitalizations related to respiratory and otorhinolaryngologic syndromes, including asthma and pneumonia. The vaccine was given to all patients older than 64 years (7834 patients [85%]) and any patient at risk for pneumococcal infection or complications, including patients with asthma, chronic obstructive pulmonary disease (COPD), bronchitis, chronic respiratory disease, cardiovascular disease, chronic renal failure, diabetes mellitus, immunodeficiency, and functional or anatomic asplenia (1336 patients [15%]). The number of all-cause hospitalizations was reduced by 58% in patients who received the pneumococcal vaccine (relative risk [RR]=0.96; 95% confidence interval [CI], 0.94-0.98). In vaccinated patients with asthma (793 patients [8.7%]), asthma-related hospitalizations decreased by 78% (RR=1.82; 95% CI, 1.35-2.45; NNT=49) and average asthma-related length of hospital stay was shortened by about 2 days (P=.039). The study found no difference in pneumonia-related hospitalizations among all vaccinated patients." }, { "input": "Evidence doesn't support routine vaccination of children with asthma or adults younger than 65 years who don't have chronic lung disease to decrease asthma-related or pneumonia-related hospitalizations.", "output": "Because the investigators didn't analyze asthma-related or pneumonia-related hospitalizations among asthmatic patients 64 years and younger, the effect of pneumococcal vaccination on this younger subgroup can't be differentiated from the entire group of patients with asthma." }, { "input": "Antibiotics are not necessary to treat uncomplicated acute otitis media (AOM) in an otherwise healthy child.", "output": "A Cochrane review of 8 randomized controlled trials (RCTs)-6 double-blinded, 2287 children total-compared antibiotics with placebo for uncomplicated AOM in otherwise healthy children. The review showed that children treated with antibiotics were no less likely to have pain at 24 hours after starting therapy than untreated children. However, 7% fewer children who received antibiotics had pain at 2 to 7 days than unmedicated children (number needed to treat [NNT]=15; 95% confidence interval [CI], 11-24). Children treated with antibiotics had no significant decrease in recurrence of AOM (mean 0.70 vs 0.63; 95% CI, -0.22 to 0.34; odds ratio [OR]=0.99) or hearing loss (reported by a combination of tympanometry and audiometry). They did have an increase in nausea, diarrhea, and rash, however. Only 1 case of mastoiditis was reported in the included studies. Of note, 2 of the studies showed a modest increase in failure rates of placebo treatment for children younger than 2 years and children with bilateral disease. Antibiotics may benefit these groups. Overall, both the potential benefits and harms of antibiotics for AOM are small." }, { "input": "Children younger than 2 years and children with bilateral infection, high fever, or vomiting may experience modest symptom relief from antibiotics.", "output": "A secondary analysis of cohorts from 6 RCTs (a total of 824 children untreated for AOM) identified age younger than 2 years (OR=2.07; 95% CI, 1.47-2.91; P<.0001) and bilateral disease (OR=1.70; 95% CI, 1.19-2.41; P=.003) as independent risk factors for pain and fever at 3 to 7 days of illness. However, the study did not address whether antibiotics would actually mitigate the risk factors." }, { "input": "Children younger than 2 years and children with bilateral infection, high fever, or vomiting may experience modest symptom relief from antibiotics.", "output": "In a secondary analysis of cohorts from a single RCT (315 patients), children with high temperature or vomiting who were treated immediately with antibiotics were less likely to be in distress by day 3 of illness (32% immediate vs 53% delayed; P=.045; NNT=5) or have night disturbance (26% immediate vs 59% delayed; P=.002; NNT=3). The greatest benefit occurred among children younger than 2 years and children with bilateral infection (NNT=4). The outcomes were reported by parents, who were not blinded." }, { "input": "No evidence supports any of the commonly used antibiotic regimens over another.", "output": "In meta-analyses of subsets of a systematic review that included 74 RCTs and 6 cohort studies, the 1- to 7-day clinical failure rate among children not given antibiotics for AOM was 19% (95% CI, 0.10-0.28). Patients treated with ampicillin or amoxicillin had a 2- to 7-dayclinical failure rate of 7% (NNT=8; 95% CI, 0.04-0.20). Pooled analyses did not show any difference in efficacy between comparisons of penicillin, ampicillin, amoxicillin (2 or 3 times daily; standard or high dose), amoxicillin-clavulanate, cefaclor, cefixime, ceftriaxone, azithromycin, and trimethoprim-sulfamethoxazole. An 8% higher incidence of diarrhea was noted for cefixime compared with amoxicillin (number needed to harm=12; 95% CI, 0.04-0.13). Azithromycin had a 19% lower adverse event rate than amoxicillin-clavulanate (NNT=5; 95% CI, 0.09-0.29)." }, { "input": "In otherwise healthy children, 5 days of therapy should be sufficient.", "output": "A 2000 Cochrane review found that 5 days of antibiotic therapy was as effective as a 10-day course of treatment in otherwise healthy children with uncomplicated AOM. A slight increase in signs, symptoms, relapse, or reinfection among children receiving 5 days of antibiotics was noted at 8 to 18 days after treatment (OR=1.52; 95% CI, 1.17-1.98), but the finding was no longer statistically significant at 30 days (OR=1.22; 95% CI, 0.98-1.54)." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "A study of patients with migraine without aura found a 57% reduction in total pain index-a value based on pain intensity and hours of headache per month-with fluoxetine compared with an insignificant 31% reduction with placebo." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "No evidence from controlled trials supports the use of fluvoxamine, paroxetine, sertraline, phenelzine, venlafaxine, mirtazapine, trazodone, or bupropion. Initial studies of delayed-release divalproex at doses ranging from 500 to 1500 mg daily found that 44% of divalproex-treated patients reported a 50% reduction in migraine frequency, compared with 21% in the placebo group (number needed to treat [NNT]=4)." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "A trial found amitriptyline to be more effective than propranolol in mixed migraine-tension-type headache, whereas propranolol was more effective for migraine alone." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "Beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) appear to be ineffective for migraine prevention. Divalproex sodium and sodium valproate show strong, consistent evidence of efficacy; they may be particularly useful for patients with prolonged or atypical migraine aura." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "A trial comparing metoprolol and nebivolol demonstrated a positive response-defined as a 50% reduction in headache frequency-to each drug at 14 weeks (57% of metoprolol-treated and 50% of nebivolol-treated patients), but noted that nebivolol was better tolerated." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "Atenolol, metoprolol, and nadolol have demonstrated a moderate effect, but less evidence exists to support their use." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "In a meta-analysis, propranolol resulted in a 44% reduction in the headache index-a composite score that takes into account both intensity and duration-compared with a 14% reduction for placebo." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "Topiramate has significantly reduced the mean frequency of episodic migraine at doses of 100 to 200 mg daily and also improved secondary end points, including number of migraine days per month, use of acute medication, and daily activity." }, { "input": "BETA-BLOCKERS without intrinsic sympathomimetic activity, amitriptyline, divalproex sodium/sodium valproate, and topiramate are the most effective drugs for preventing episodic migraine.", "output": "A study of the extended-release form of divalproex sodium demonstrated a 4-week reduction in headache rate to 1.2 from a baseline of 4.4, compared with a decrease of 0.6 for placebo (95% confidence interval [CI] of treatment difference, 0.2-1.2)." }, { "input": "Consider it for patients with failed back surgery syndrome. These patients can gain more pain relief from spinal cord stimulation (SCS) than from reoperation.", "output": "A 2004 systematic review of SCS for all indications included 51 studies and 2973 patients. Sixteen of the studies, with a total of 616 patients, focused on low back pain, specifically chronic back pain and failed back surgery syndrome. Two of the 16 studies were prospective controlled trials, 8 were prospective trials without controls, and 6 were retrospective studies. Both prospective, controlled trials (total of 62 patients) demonstrated statistically significant (P<.05) results with SCS. One measured subjective pain and the other used crossover to the other treatment arm (SCS vs surgery) as a marker for treatment failure." }, { "input": "Consider it for patients with failed back surgery syndrome. These patients can gain more pain relief from spinal cord stimulation (SCS) than from reoperation.", "output": "A 2005 prospective RCT enrolled 50 patients with failed back surgery syndrome who were considering reoperation. Twenty-four were randomized to SCS and 26 to reoperation. Success was defined as >50% pain relief measured by a validated visual analog pain scale. The average length of follow-up was 3 years. An intention-to-treat analysis demonstrated that 9 of 24 (38%) SCS insertions were successful, compared with 3 of 26 (12%) reoperations (P=.04; number needed to treat=3.8)." }, { "input": "Consider it for patients with failed back surgery syndrome. These patients can gain more pain relief from spinal cord stimulation (SCS) than from reoperation.", "output": "SCS can be used to treat patients with chronic and intractable pain, such as the pain caused by failed back surgery syndrome. The syndrome, defined as persistent or recurrent pain after lumbosacral spine surgery, occurs in 10% to 40% of patients who have undergone lumbosacral spine surgery." }, { "input": "SCS can also treat chronic low back pain effectively.", "output": "A 2004 systematic review of SCS for all indications included 51 studies and 2973 patients. Sixteen of the studies, with a total of 616 patients, focused on low back pain, specifically chronic back pain and failed back surgery syndrome. Two of the 16 studies were prospective controlled trials, 8 were prospective trials without controls, and 6 were retrospective studies. Both prospective, controlled trials (total of 62 patients) demonstrated statistically significant (P<.05) results with SCS. One measured subjective pain and the other used crossover to the other treatment arm (SCS vs surgery) as a marker for treatment failure." }, { "input": "The side effects and failure rates of SCS are well documented and should be considered before recommending the therapy to patients.", "output": "Cameron's systematic review of 51 SCS studies reported rates for a number of complications. The most common complication was lead migration-displacement of the spinal electrodes that can cause pain to recur." }, { "input": "There are several interventions for adults that are effective. They include: 1) Writing a patient-specific behavioral health \"green\" prescription. 2) Encouraging patients to join forces with accountability partners or support groups. 3)Recommending the use of pedometers.", "output": "In adults, walking normally and walking briskly for an average of 2500 steps burns 100 and 150 kcal, respectively." }, { "input": "There are several interventions for adults that are effective. They include: 1) Writing a patient-specific behavioral health \"green\" prescription. 2) Encouraging patients to join forces with accountability partners or support groups. 3)Recommending the use of pedometers.", "output": "A systematic review using meta-regression to calculate summary effects evaluated the use of pedometers by study participants for an average of 18 weeks. Pedometer users increased their physical activity significantly, by 2491 steps per day compared with controls (95% confidence interval [CI], 1098-3885 steps per day)." }, { "input": "There are several interventions for adults that are effective. They include: 1) Writing a patient-specific behavioral health \"green\" prescription. 2) Encouraging patients to join forces with accountability partners or support groups. 3)Recommending the use of pedometers.", "output": "A trial in 42 rural and urban New Zealand general practices that added 3 telephone follow-up sessions to the green prescription showed a 10% increase in achieving 150 minutes of vigorous exercise weekly among green prescription participants compared with controls (number needed to treat=10)." }, { "input": "There are several interventions for adults that are effective. They include: 1) Writing a patient-specific behavioral health \"green\" prescription. 2) Encouraging patients to join forces with accountability partners or support groups. 3)Recommending the use of pedometers.", "output": "\"Green\" prescriptions are primary care behavioral interventions that include measurable goals, self-reward, structured problem-solving, social network reinforcement, and relapse prevention counseling. In the DHHS review, 10 trials studied green prescriptions; the median net increase in physical activity time was 35.4% (interquartile range 16.7%-83.3%)." }, { "input": "There are several interventions for adults that are effective. They include: 1) Writing a patient-specific behavioral health \"green\" prescription. 2) Encouraging patients to join forces with accountability partners or support groups. 3)Recommending the use of pedometers.", "output": "The US Department of Health and Human Services (DHHS) and the Centers for Disease Control and Prevention (CDC) conducted a systematic review of 94 qualifying trials and assigned interventions to 1 of 3 approaches: \"information based,\" \"behavioral and social,\" and \"facilities and activities.\" Behavioral and social interventions have the best data support. Within this category, strong evidence backed school-based physical education and accountability partners or exercise support groups. School-based physical education resulted in a median net increase in physical activity time of 50.3% (range 6.0%-125.3%); accountability partners or support groups produced a mean net increase of 44.2% (interquartile range 19.9%-45.6%)." }, { "input": "In children and adolescents, multicomponent strategies that include school-based interventions combined with either family or community involvement increase physical activity.", "output": "A British systematic review of 24 high-quality controlled trials involving adolescents and children reported significant improvements with interventions that were school-based and either community- or family-based. Multidimensional outcomes included a 42% increase in participation in regular physical activity and an increase of 83 minutes weekly in moderate-to-vigorous physical activity." }, { "input": "In children and adolescents, multicomponent strategies that include school-based interventions combined with either family or community involvement increase physical activity.", "output": "A US meta-analysis of 11 after-school programs with an average contact time of 275 minutes per week showed a positive standardized mean difference effect size for physical activity (0.44; 95% CI, 0.28-0.60)." }, { "input": "other", "output": "Insufficient evidence exists to support other interventions, such as classroom-based informational health education, mass media campaigns, college-based health and physical education, and classroom-based education focused on reducing television viewing and video-game playing." }, { "input": "Generally speaking, treating partners empirically is as effective or more effective than traditional referral and testing. Empiric treatment of partners of female or heterosexual male patients diagnosed with gonorrhea or chlamydia using expedited partner therapy (having the index patient deliver therapy to the partner) decreases the risk of persistent or recurrent infection in the index patient. The effect is greater for gonorrhea than chlamydia.", "output": "A meta-analysis of the above studies evaluated the effect of expedited partner therapy compared with patient referral on the rate of recurrent or persistent gonorrhea, chlamydia, and trichomoniasis and the number of partners treated per index patient. Empiric therapy was associated with a lower rate of recurrent or persistent infections (risk ratio [RR]=0.73; 95% confidence interval [CI], 0.57-0.93) and a higher number of partners treated per patient (RR=1.44; 95% CI, 1.12-1.86)." }, { "input": "Generally speaking, treating partners empirically is as effective or more effective than traditional referral and testing. Empiric treatment of partners of female or heterosexual male patients diagnosed with gonorrhea or chlamydia using expedited partner therapy (having the index patient deliver therapy to the partner) decreases the risk of persistent or recurrent infection in the index patient. The effect is greater for gonorrhea than chlamydia.", "output": "An RCT showed a decrease in recurrent or persistent chlamydial infection in the index patient, but the difference didn't reach statistical significance. The RCT demonstrated a statistically significant decrease in persistent or recurrent gonococcal infection for expedited partner treatment for gonorrhea." }, { "input": "Generally speaking, treating partners empirically is as effective or more effective than traditional referral and testing. Empiric treatment of partners of female or heterosexual male patients diagnosed with gonorrhea or chlamydia using expedited partner therapy (having the index patient deliver therapy to the partner) decreases the risk of persistent or recurrent infection in the index patient. The effect is greater for gonorrhea than chlamydia.", "output": "An RCT showed a decrease in recurrent or persistent chlamydial infection in the index patient, but the difference didn't reach statistical significance." }, { "input": "Generally speaking, treating partners empirically is as effective or more effective than traditional referral and testing. Empiric treatment of partners of female or heterosexual male patients diagnosed with gonorrhea or chlamydia using expedited partner therapy (having the index patient deliver therapy to the partner) decreases the risk of persistent or recurrent infection in the index patient. The effect is greater for gonorrhea than chlamydia.", "output": "One RCT showed a statistically significant reduction in recurrent or persistent urethritis, but didn't report persistent and recurrent gonorrheal and chlamydial infections separately. The RCT showed a statistically significant decrease in recurrent or persistent urethritis, but without identifying recurrent gonorrheal and chlamydial infections separately." }, { "input": "Generally speaking, treating partners empirically is as effective or more effective than traditional referral and testing. Empiric treatment of partners of female or heterosexual male patients diagnosed with gonorrhea or chlamydia using expedited partner therapy (having the index patient deliver therapy to the partner) decreases the risk of persistent or recurrent infection in the index patient. The effect is greater for gonorrhea than chlamydia.", "output": "1 cohort study showed a statistically significant decrease in recurrent or persistent chlamydial infection in index patients." }, { "input": "Generally speaking, treating partners empirically is as effective or more effective than traditional referral and testing. Empiric treatment of partners of female or heterosexual male patients diagnosed with gonorrhea or chlamydia using expedited partner therapy (having the index patient deliver therapy to the partner) decreases the risk of persistent or recurrent infection in the index patient. The effect is greater for gonorrhea than chlamydia.", "output": "Treating partners of patients with sexually transmitted infection has been a core component of therapy since the 1940s. Traditionally, partners have been referred to a health care provider (by the index patient, the provider, or a public health officer) for evaluation before being treated. Current methods of partner referral reach only 40% to 60% of named sexual partners." }, { "input": "By contrast, expedited partner therapy for trichomoniasis appears equivalent to a test-first approach.", "output": "One RCT compared expedited partner therapy with patient referral for patients with trichomoniasis. The study did not show a statistically significant difference in recurrent or persistent infection." }, { "input": "Short-term use of metformin (Glucophage) improves ovulation rates for women with polycystic ovary syndrome (PCOS).", "output": "A meta-analysis of eight RCTs addressing the use of metformin or clomiphene for treatment of PCOS were reviewed for ovulation and pregnancy rates. Metformin is 50% better than placebo for ovulation induction among infertile PCOS patients (relative risk [RR]=1.50; 95% CI, 1.31-1.99), but this benefit is not necessarily improved with longer duration (>3 months) of therapy (RR=1.37; 95% CI, 1.05-1.79). Also, metformin is beneficial in regulating cycles for fertile PCOS patients with irregular menses (RR=1.45; 95% CI, 1.11-1.90)." }, { "input": "Metformin also decreases menstrual irregularities.", "output": "A review of 7 RCTs describes the evidence accumulated by well-designed trials and its clinical relevance. Metformin improves ovulation and menstrual cyclicity but these improvements were variable and modest. On average, 1 additional ovulation is attained in every 5-month interval with metformin treatment; specifically, the baseline of 1 ovulation per 5-month interval increased to 2 ovulations per 5-month interval. Spontaneous ovulation and normal menstruation are achieved rapidly (within 3 months of the start of therapy). These data corroborate the benefits of metformin but place its clinical significance in perspective. For PCOS patients seeking cycle regulation but not pregnancy, oral contraceptives may remain better therapy because metformin does not normalize menses." }, { "input": "When added to clomiphene, metformin increases ovulation and pregnancy rates when compared with clomiphene alone.", "output": "The most influential systematic review was a meta-analysis that reviewed 13 RCTs including 543 women to determine the effects of metformin on ovarian function in PCOS. By selecting RCTs, performing precise statistical analysis according to the Cochrane protocols, and clearly stating limitations, this review gives good evidence that metformin modestly increases the odds of ovulation for women with PCOS (odds ratio [OR]=3.88; 95% confidence interval [CI], 2.25-6.69 for metformin vs placebo) and that metformin with clomiphene (Clomid) effectively increases ovulation (OR=4.41; 95% CI, 2.37-8.22) and pregnancy rates (OR=4.40; 95% CI, 1.96-9.85) when compared with clomiphene use alone. When metformin is used as a sole agent, ovulation is achieved in 46% of recipients compared with 24% in the placebo arm (number needed to treat [NNT]=4.4). When metformin and clomiphene are used in combination, 76% of recipients ovulate compared with 42% receiving clomiphene alone (NNT=3.0)." }, { "input": "Thiazolidinediones (TZDs) improve ovulation rates as well.", "output": "Troglitazone has been taken off of the market due to hepatotoxicity, but results from a RCT of 40 patients with PCOS reported that the use of pioglitazone (Actos) for 3 months increased normal regular cycles and ovulations over placebo (41.2% vs 5.6%; P<.02). No liver effects were noted, but caution must be taken since these drugs are pregnancy class C." }, { "input": "Thiazolidinediones (TZDs) improve ovulation rates as well.", "output": "A small RCT which studied the use of rosiglitazone (Avandia) in combination with clomiphene and reported improvements in menstrual regularity (92% with combination therapy achieved improved menstrual cycles vs 68% with rosiglitazone alone; OR=0.185)." }, { "input": "Thiazolidinediones (TZDs) improve ovulation rates as well.", "output": "Studies of the most researched drug in the class, troglitazone (Rezulin), report improvements in ovulation rates and metabolic markers of PCOS." }, { "input": "Thiazolidinediones (TZDs) improve ovulation rates as well.", "output": "A small RCT which studied the use of rosiglitazone (Avandia) in combination with clomiphene reported both spontaneous and clomiphene-induced ovulation rates (52% of clomiphene-resistant women ovulated after rosiglitazone therapy and 77% vs 33% ovulated with combination therapy vs rosiglitazone alone, P=.04)." }, { "input": "Stimulant medication therapy is the most effective treatment for attention deficit/hyperactivity disorder (ADHD) in children, producing significant improvements in symptoms and modest improvements in academic achievement.", "output": "Several short-term reviews and meta-analyses show that side effects from stimulant medications are mild and have short duration. More long-term studies are required to evaluate effects on growth." }, { "input": "Stimulant medication therapy is the most effective treatment for attention deficit/hyperactivity disorder (ADHD) in children, producing significant improvements in symptoms and modest improvements in academic achievement.", "output": "In numerous systematic reviews, RCTs, and metaanalyses, 70% of children responded to stimulant medications with short-term improvements in ADHD symptoms (inattention and hyperactivity/ impulsivity) and academic achievement." }, { "input": "Stimulant medication therapy is the most effective treatment for attention deficit/hyperactivity disorder (ADHD) in children, producing significant improvements in symptoms and modest improvements in academic achievement.", "output": "A fortyyear review looked at 135 trials and 413 RCTs of methylphenidate in over 19,000 children with an average age of 8.8 years (range, 8.3-9.4 years) for an average duration of 6 weeks (range, 3.3-8.0 weeks). Study groups included mostly elementary school-aged male children, with few minorities represented. Comorbid conditions, present in 65% of children with ADHD, were often poorly controlled. Outcome measures varied among studies. The effect size from stimulant medication in these studies averaged 0.8 for symptom relief and between 0.4 and 0.5 for academic achievement. (Effect size is the difference between the means of the experimental and control groups expressed in standard deviations. An effect size of 0.2 is considered small, 0.5 is medium, and 0.8 is considered moderate to large.)" }, { "input": "Nonpharmacologic therapies, such as behavior therapy, school-based interventions, and family therapy, are not as effective as stimulants but may add modest benefit to the effects of medication.", "output": "A large randomized trial of 579 children with ADHD (20% girls) aged 7 to 9.9 years compared outcomes of 4 treatment strategies: stimulant medication, intensive behavioral treatment, combined stimulant medication and behavioral interventions, and standard community care. All children met the DSM-IV. criteria for ADHD Combined Type (the most common type of ADHD in this age group). The stimulant medication strategy included an initial dose titration period followed by monthly 30-minute visits. Intensive behavioral treatment involved child, parent, and school personnel components of therapy. Combination therapy added the regimens for medication and behavioral treatment together. Standard community care consisted of usual (nonsystematic) care, evaluated at 6 different sites. After 14 months of treatment, children in the medication group and the combined treatment groups showed more improvement in ADHD symptoms than children given intensive behavioral treatment or those who received standard community care. When combined with medication, those treated with behavioral therapy showed slight improvement in social skills, anxiety, aggression, oppositional behavior, and academic achievement over medication alone. At the conclusion of the study, 74% of the 212 children on medication were successfully maintained on methylphenidate alone, 10% required dextroamphetamine, and no children required more than one medication. This study found that higher doses of medication with more frequent office follow-up and regular school contact were important features of successful treatment. Only 40% of families were able to complete the intensive behavioral therapy." }, { "input": "Atomoxetine (Strattera) improves the symptoms of ADHD.", "output": "Based on 3 RCTs of 588 children between the ages of 7 and 18 years, atomoxetine showed dose-related improvement in ADHD rating scales. Side effects of atomoxetine are similar to stimulants and include mild but significant increases in blood pressure and pulse." }, { "input": "The combination of methylphenidate and clonidine (Catapres) improves symptoms in children with both ADHD and tics.", "output": "One RCT of 136 children with ADHD and tics showed improvement of both problems with the use of methylphenidate and clonidine, particularly in combination." }, { "input": "Clonidine is less effective alone and has significant side effects.", "output": "Second-line medications such as clonidine, pemoline (Cylert), and tricyclic antidepressants have more potential serious side effects and are not well studied." }, { "input": "Clonidine is less effective alone and has significant side effects.", "output": "A meta-analysis of 11 non-randomized trials using clonidine for ADHD showed a smaller effect size compared with stimulants." }, { "input": "Parent training is effective for treating oppositional and defiant behaviors.", "output": "A rigorous well-done systematic review looked at 16 randomized controlled trials that examined the effectiveness of training programs for children between the ages of 3 and 10 years who had externalizing problems, including temper tantrums, aggression, and noncompliance. All studies included in the review compared a group-based parent training program with a no-treatment wait-list control group and assessed outcomes using a standardized measure of behavior. In studies where sufficient data were provided, effect sizes ranged from 0.6 to 2.9. This indicates that, on a standardized child behavioral measure, parental report of children's externalizing problems decreased by 0.6 to 2.9 standard deviations from pre- to posttreatment (an effect size of >0.8 is considered large). In the 2 studies that included independent observations of child behavior, the benefits reported by parents were confirmed by these observations." }, { "input": "Parent training programs are standardized, short-term interventions that teach parents specialized strategies-including positive attending, ignoring, the effective use of rewards and punishments, token economies, and time out-to address clinically significant behavior problems. In addition to parent training, other psychosocial interventions are efficacious in treating oppositional and defiant behavior.", "output": "Parent training is typically conducted by clinical child psychologists but may also be available through certified parenting educators see the National Parenting Education Network web page for links to state organizations, at www.ces.ncsu.edu/depts/fcs/npen/. Parent training strategies are also described for parents in books such as Your Defiant Child." }, { "input": "To date, no studies have assessed the efficacy of medication in treating children with pure oppositional defiant disorder ODD. However, studies have shown amphetamines to be effective for children with ODD and comorbid attention deficit/hyperactivity disorder ADHD.", "output": "In treating oppositional behaviors among children with ADHD and comorbid oppositional defiant disorder or conduct disorder, a meta-analysis identified 28 studies of children age 7 to 15 years that addressed oppositional/aggression-related behaviors within the context of ADHD. The analysis found that stimulants are efficacious. The overall weighted effect size a measure of improvement representing the average effects across all reporters was 0.89. This indicates that raters saw a change in oppositional behaviors-noncompliance, irritability, and temper tantrums-that corresponded to a drop in scores of approximately 1 standard deviation." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "A case series of 100 patients (mean age 27 years; range 6 months to 84 years) treated with CO2 laser reported that the pyogenic granuloma was removed completely in 1 session in 98 patients. Twelve percent of patients had visible scarring and another 10% had slight textural skin changes. All patients reported satisfaction with the results." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "A case series reported on 135 patients (mean age 26 years; range 4 months to 70 years) whose pyogenic granulomas were treated with cryotherapy. Seventy-eight (58%) had complete resolution with 1 session, 30% needed 2 sessions, 8% needed 3 sessions, and 5% needed 4 sessions (mean 1.58 sessions). Ninety-four percent had an excellent cosmetic result (including 12% with a small flat scar); 5% had residual hypopigmentation." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "A prospective trial randomized 89 patients (mean age 34 years; range 11-88 years) with pyogenic granulomas that were 1.5 cm or smaller to receive either curettage or cryotherapy, then evaluated the number of treatments required and whether scarring occurred. Follow-up was 85%. A single curettage resolved pyogenic granuloma in 35 of 36 patients (97%); 9 of the 36 patients (31%) had residual scarring. Twenty-five of 40 pyogenic granulomas (63%) responded to 1 cryotherapy treatment, 13 lesions (32%) resolved after 2 treatments, and 2 (5%) resolved after 3 treatments; 17 of the 40 patients (42.5%) had a residual scar. Curettage required fewer treatments overall than cryotherapy (P<.001), but no significant difference in residual scarring was noted between the 2 treatments." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "A retrospective cohort study described treatment, recurrence rate, residual scarring, and patient satisfaction in 76 patients with pyogenic granuloma (mean age 6 years; range 4 months to 17 years). Outcomes were assessed by telephone follow-up. Fifty-eight lesions were removed by surgical excision and cautery with no recurrences (55% of patients had subtle scarring). Nine lesions were treated with pulsed dye laser (33% recurrence, 44% subtle scarring); 3 lesions were removed by CO2 laser (100% recurrence, 33% subtle scarring). Four patients were followed but not treated (no explanation given); all untreated pyogenic granulomas disappeared spontaneously within 6 to 18 months with no recurrences; 1 patient had subtle scarring." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "A case series reported results in 9 patients (median age 18 years; range 1-57 years) with pyogenic granuloma treated with a single injection of the sclerosing agent monoethanolamine oleate. All lesions disappeared without recurrence; the authors described remaining scars as inconspicuous. One patient reported residual pain lasting 4 weeks after injection of the sclerosing agent into a 1.5 cm x 1.0 cm pyogenic granuloma that hadn't responded to previous cryotherapy." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "Expert opinion states that surgical excision often results in a conspicuous linear scar." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "A retrospective cohort study audited recurrence rates in 408 patients (mean age 41 years, range 5 months to 90 years) whose pyogenic granulomas were treated with either surgical excision or combinations of curettage, shave, and cautery. Investigators identified cases of histopathologically confirmed pyogenic granuloma over a 10-year period from a hospital database. Thirty-six percent of granulomas were located on the head and neck, 33% on the arm, 15% on the trunk, and 8% on the leg. Of 326 lesions treated with surgical excision, 4 (3.7%) recurred. The overall recurrence rate was 10.3% for 82 lesions removed by combinations of curettage, shave, and cautery (the lesions weren't differentiated by removal method or location). Investigators didn't report on residual scarring with any method." }, { "input": "It's difficult to say which treatment is best, since most studies don't compare treatments directly. Pros and cons vary. Simple surgical excision is associated with a low risk of recurrence, but often leaves a visible scar. Curettage or shave excision, with cautery, is more likely to succeed in 1 session than cryotherapy; both may leave a smaller scar than surgery. Laser therapy, which may require multiple sessions, and sclerotherapy may be least likely to cause visible scarring.", "output": "A case series of 22 patients (mean age 3.4 years; range 6 months to 16 years) treated with pulsed dye laser for mostly small lesions (average diameter 4 mm) on the face reported successful removal in 20 children in 1 to 6 treatment sessions (average 2.25) with no residual scarring. Two children with larger lesions required shave excision with cautery (scarring was not assessed)." }, { "input": "Untreated pyogenic granulomas regress spontaneously within 6 to 18 months with some risk of scarring.", "output": "A retrospective cohort study described treatment, recurrence rate, residual scarring, and patient satisfaction in 76 patients with pyogenic granuloma (mean age 6 years; range 4 months to 17 years). Outcomes were assessed by telephone follow-up. Fifty-eight lesions were removed by surgical excision and cautery with no recurrences (55% of patients had subtle scarring). Nine lesions were treated with pulsed dye laser (33% recurrence, 44% subtle scarring); 3 lesions were removed by CO2 laser (100% recurrence, 33% subtle scarring). Four patients were followed but not treated (no explanation given); all untreated pyogenic granulomas disappeared spontaneously within 6 to 18 months with no recurrences; 1 patient had subtle scarring." }, { "input": "Untreated pyogenic granulomas regress spontaneously within 6 to 18 months with some risk of scarring.", "output": "A standard dermatology textbook recommends curettage with cautery, and reports that spontaneous regression is common after 6 months." }, { "input": "Excision is the most effective treatment for thrombosed external hemorrhoids.", "output": "A prospective, randomized controlled trial (RCT) of 98 patients treated nonsurgically found improved pain relief with a combination of topical nifedipine 0.3% and lidocaine 1.5% compared with lidocaine alone. The NNT for complete pain relief at 7 days was 3." }, { "input": "Excision is the most effective treatment for thrombosed external hemorrhoids.", "output": "A retrospective analysis of 340 patients who underwent outpatient excision of thrombosed external hemorrhoids under local anesthesia reported a low recurrence rate of 6.5% at a mean follow-up of 17.3 months." }, { "input": "Excision is the most effective treatment for thrombosed external hemorrhoids.", "output": "A retrospective study of 231 patients treated conservatively or surgically found that the 48.5% of patients treated surgically had a lower recurrence rate than the conservative group (number needed to treat [NNT]=2 for recurrence at mean follow-up of 7.6 months) and earlier resolution of symptoms (average 3.9 days compared with 24 days for conservative treatment)." }, { "input": "For prolapsed internal hemorrhoids, the best definitive treatment is traditional hemorrhoidectomy.", "output": "A Cochrane systematic review of 12 RCTs that compared conventional hemorrhoidectomy with stapled hemorrhoidectomy in patients with grades I to III hemorrhoids found a lower rate of recurrence (follow-up ranged from 6 to 39 months) in patients who had conventional hemorrhoidectomy (NNT=14). Conventional hemorrhoidectomy showed a nonsignificant trend in decreased bleeding and decreased incontinence." }, { "input": "For prolapsed internal hemorrhoids, the best definitive treatment is traditional hemorrhoidectomy.", "output": "A systematic review of 25 studies, including some that were of lower quality, showed a higher recurrence rate at 1 year with stapled hemorrhoidectomy than with conventional surgery." }, { "input": "Of nonoperative techniques, rubber band ligation produces the lowest rate of recurrence.", "output": "A systematic review of 3 poor-quality trials comparing rubber band ligation with excisional hemorrhoidectomy in patients with grade III hemorrhoids found that excisional hemorrhoidectomy produced better long-term symptom control but more immediate postoperative complications of anal stenosis and hemorrhage." }, { "input": "Of nonoperative techniques, rubber band ligation produces the lowest rate of recurrence.", "output": "A Cochrane systematic review of 7 RCTs enrolling a total of 378 patients with grade I to III hemorrhoids evaluated the effect of fiber supplements on pain, itching, and bleeding. Persistent hemorrhoid symptoms decreased by 53% in the group receiving fiber." }, { "input": "Of nonoperative techniques, rubber band ligation produces the lowest rate of recurrence.", "output": "Rubber band ligation had the lowest recurrence rate at 12 months compared with the other nonoperative techniques of sclerotherapy and infrared coagulation." }, { "input": "Diets lower in fat, higher in soy protein, or higher in fiber reduce serum total cholesterol, low-density lipoprotein (LDL), and triglycerides. More restrictive low-fat diets also lower high-density lipoprotein (HDL), while soy protein increases HDL. Average decreases in LDL range from 6.96 to 25.14 mg/dL, depending on the particular intervention and participants' baseline characteristics.", "output": "A meta-analysis of 67 good-quality RCTs evaluated the effects of soluble dietary fiber in 2990 subjects (mean baseline lipid values [mg/dL]: total cholesterol, 240.9; LDL, 164.4). Diets high in soluble fiber (average dose of 9.5 g/d) were associated with a statistically significant decrease in total cholesterol and LDL and no significant change in HDL or triglycerides. Type of fiber (oat, psyllium, or pectin) was not influential after controlling for initial lipid level." }, { "input": "Diets lower in fat, higher in soy protein, or higher in fiber reduce serum total cholesterol, low-density lipoprotein (LDL), and triglycerides. More restrictive low-fat diets also lower high-density lipoprotein (HDL), while soy protein increases HDL. Average decreases in LDL range from 6.96 to 25.14 mg/dL, depending on the particular intervention and participants' baseline characteristics.", "output": "A meta-analysis of 23 good-quality controlled trials with 1381 participants reported that soy protein with naturally occurring isoflavones significantly reduced total cholesterol, LDL, and triglycerides while significantly increasing HDL. The amount of soy isoflavone consumed varied across studies. One subgroup analysis showed that consumption of >80 mg/d was associated with a better effect on lipids. In subjects with baseline hypercholesterolemia (total cholesterol >240 mg/dL), greater reductions in total cholesterol, and greater increases in HDL were reported, with comparable changes in LDL and triglycerides." }, { "input": "Diets lower in fat, higher in soy protein, or higher in fiber reduce serum total cholesterol, low-density lipoprotein (LDL), and triglycerides. More restrictive low-fat diets also lower high-density lipoprotein (HDL), while soy protein increases HDL. Average decreases in LDL range from 6.96 to 25.14 mg/dL, depending on the particular intervention and participants' baseline characteristics.", "output": "A meta-analysis of 37 mostly good-quality controlled trials evaluated the former National Cholesterol Education Program (NCEP) Step I and Step II diets in 11,586 participants. The Step I diet restricted in-take of total fat (\u226430% of total calories), saturated fat (\u226410% of total calories), and cholesterol (\u2264300 mg/d). Step II goals were lower for saturated fat (<7%) and cholesterol (<200 mg/d). Mean baseline lipid values (mg/dL) were total cholesterol, 233.57; LDL, 155.10; HDL, 47.95; and triglycerides, 147.91. Both of these low-fat diets significantly reduced total cholesterol, LDL, and triglycerides. The Step II diet also reduced HDL." }, { "input": "A \"portfolio diet\" that includes cholesterol-lowering \"functional foods\" can reduce total cholesterol and LDL; a Mediterranean-type diet can lower LDL.", "output": "A randomized crossover study with 34 participants found that a \"portfolio diet\", which combines the fat intake of the NCEP Step II diet with cholesterol-lowering \"functional foods\" (including plant sterols, nuts, soluble fibers, and soy protein), markedly reduced total cholesterol and LDL. Mean baseline lipid values (mg/dL) were: total cholesterol, 261.41; LDL, 174.40; HDL, 47.56; triglycerides, 199.28." }, { "input": "A \"portfolio diet\" that includes cholesterol-lowering \"functional foods\" can reduce total cholesterol and LDL; a Mediterranean-type diet can lower LDL.", "output": "An RCT with 88 participants reported reduced LDL among subjects assigned to a Mediterranean-type diet. Mean baseline lipid values (mg/dL) were total cholesterol, 255.22; LDL, 170.15; HDL, 58.01; triglycerides, 141.71." }, { "input": "Patients in intensive care unit (ICE) settings who are receiving prolonged mechanical ventilation (for >48 hours) or who have a coagulopathy or multiple organ dysfunction (especially renal failure) should receive stress ulcer prophylaxis. Current evidence does not support prophylaxis for non-ICU patients.", "output": "Recent studies suggest that only ICU patients with certain risk factors benefit from ulcer prophylaxis." }, { "input": "Prophylaxis with H2 receptor antagonists (H2RAs) and sucralfate are equally efficacious in lowering mortality and length of hospital stay. No randomized controlled trials demonstrate that proton pump inhibitors (PPIs) are superior to H2RAs or sucralfate.", "output": "Some studies suggest that pharmacologic prophylaxis may increase the incidence of aspiration pneumonia in ventilator-dependent patients. The largest randomized trial addressing this issue (N=1200) found no significant difference between H2RAs and sucralfate in ventilator-associated pneumonia. Improved ICU management, such as frequent suctioning, upright positioning, and use of enteral nutrition may help prevent nosocomial pneumonia due to aspiration." }, { "input": "other", "output": "Critically ill patients are at increased risk of bleeding from stress-induced gastroduodenal ulceration. Decades ago, ICUs began using pharmacologic prophylaxis on most patients to prevent gastrointestinal bleeding, which had a mortality rate as high as 80%. Before the advent of prophylaxis, the incidence of upper gastro-intestinal bleeding was 6% to 25%." }, { "input": "other", "output": "Medications used to prevent gastrointestinal bleeding have included antacids, sucralfate, H2RAs, and PPIs. Sucralfate and H2RAs have been studied most frequently, and both agents significantly reduce the incidence of clinically important bleeding in high-risk patients. Compared with placebo, the odds ratio for clinically important bleeding was 0.44 with ranitidine (95% confidence interval [CI], 0.22-0.88) and 0.58 with sucralfate (95% CI, 0.34-0.99). In a population with a clinically important bleeding incidence of 3% to 6%, a range consistent with the most recent studies we reviewed, the number needed to treat to prevent 1 bleeding episode is 30 to 60 for ranitidine and 40 to 79 for sucralfate." }, { "input": "other", "output": "Since then, improvements in ICU management have decreased this incidence to 0% to 2.8%." }, { "input": "Nonsteroidal anti inflammatory drugs (NSAIDs) are more effective than placebo for pain relief in patients with acute low back pain.", "output": "A recent systematic review found NSAIDs more effective than placebo for pain relief in patients with acute low back pain." }, { "input": "Nonsteroidal anti inflammatory drugs (NSAIDs) are more effective than placebo for pain relief in patients with acute low back pain.", "output": "According to a systematic review, there is no difference in pain intensity at 3 weeks' follow-up between active patients and patients for whom variable lengths of short-term bed rest for treatment of acute low back pain have been prescribed." }, { "input": "There is no added benefit when muscle relaxants are used in combination with NSAIDs.", "output": "There is no statistically significant difference in pain relief between patients using NSAIDs alone versus those using both NSAIDs and muscle relaxants.1 The use of muscle relaxants was associated with more adverse reactions than placebo (53% vs 28%; number needed to harm [NNH] = 4)." }, { "input": "There is no consistent evidence that epidural steroid injections are effective for acute low back pain.", "output": "No consistent conclusions could be drawn regarding the effectiveness of epidural steroid injections for acute low back pain. This analysis was limited by the inclusion of all studies of patients with acute low back pain regardless of the underlying etiology and presence or absence of radicular symptoms." }, { "input": "There is no consistent evidence that epidural steroid injections are effective for acute low back pain.", "output": "A systematic review of 12 trials reported inconsistent results of facet joint, epidural, and local corticosteroid injections; however, only 1 studied epidural injections." }, { "input": "Spinal manipulation or back exercises are no more effective than medications alone.", "output": "In a randomized, controlled trial (n = 321) to assess the effectiveness of formal physical therapy for acute low back pain, patients referred to physical therapy were more satisfied with their care than were patients given handouts on back exercises, even though disability and pain scores were unchanged.7" }, { "input": "Spinal manipulation or back exercises are no more effective than medications alone.", "output": "Performance of specific flexion or extension exercises was no more effective than analgesics." }, { "input": "Spinal manipulation or back exercises are no more effective than medications alone.", "output": "Evidence is insufficient to support the use of spinal manipulation in patients with acute low back pain because of serious design flaws in the trials." }, { "input": "other", "output": "Cyclobenzaprine is more effective than placebo, according to a recent systematic review summary (odds ratio for improvement by day 10: 4.7 [2.7-8.1 95% CI]; number needed to treat [NNT] = 2.7 [2.0-4.2 95% CI])." }, { "input": "Although African American men, men with a first-degree relative with prostate cancer (CaP), and older men constitute higher-risk subgroups, no well-designed randomized controlled trials are available that show PSA testing to improve mortality or quality of life for these or any other groups of men. A trend toward detecting more localized cancers and a possible decreasing mortality rate from CaP in all men may be related to PSA testing, lead-time bias, or both.", "output": "A decision analysis, using quality-of-life measures, concluded that men would favor screening only if the prevalence of CaP were greater than any current estimate." }, { "input": "Although African American men, men with a first-degree relative with prostate cancer (CaP), and older men constitute higher-risk subgroups, no well-designed randomized controlled trials are available that show PSA testing to improve mortality or quality of life for these or any other groups of men. A trend toward detecting more localized cancers and a possible decreasing mortality rate from CaP in all men may be related to PSA testing, lead-time bias, or both.", "output": "If current therapies for localized therapy do not decrease morbidity or mortality, screening higher-risk groups merely puts them at increased risk for potentially harmful interventions. Biopsies cannot reliably predict which cancers will progress and which will lie indolent. The 30% incidence of CaP on autopsy means that more people die with CaP than from it. Using estimates of the prevalence and natural history of the disease, decision analyses report varying years saved by screening compared with watchful waiting (ranging from a gain of 2.5 quality-adjusted life years (QALYs) to an actual decrease in QALYs, depending primarily on the rate of progression to metastatic disease and efficacy of treatment." }, { "input": "Although African American men, men with a first-degree relative with prostate cancer (CaP), and older men constitute higher-risk subgroups, no well-designed randomized controlled trials are available that show PSA testing to improve mortality or quality of life for these or any other groups of men. A trend toward detecting more localized cancers and a possible decreasing mortality rate from CaP in all men may be related to PSA testing, lead-time bias, or both.", "output": "Higher-risk subgroups merit special attention. Screening the 3 groups mentioned above would improve the positive predictive value of PSA, but crucial data to determine whether this will improve outcomes are lacking. Using average estimates, if 3300 African American men (aged 50 to 65 years) were screened, 100 would have cancer. After subsequent radical prostatectomy, 1 screened man would die from the procedure, 60 would become impotent, and 20 would be incontinent." }, { "input": "Docusate sodium given 15 minutes before irrigation is most effective for facilitating cerumen removal during a single office visit.", "output": "In studies that evaluated onetime softening in the office to ease or eliminate the need for irrigation, a presoak with docusate sodium (Colace) was most effective, although its effects were not compared with those of water." }, { "input": "Treatment with 5% urea hydrogen peroxide in glycerol is most effective for facilitating cerumen removal between office visits, reducing the amount of irrigation needed.", "output": "In studies that evaluated 3 to 14 days of home ceruminolysis to obviate or ease irritation, 5% urea hydrogen peroxide in glycerol was most effective." }, { "input": "Treatment with 5% urea hydrogen peroxide in glycerol is most effective for facilitating cerumen removal between office visits, reducing the amount of irrigation needed.", "output": "Carbamide peroxide (Debrox, Murine Ear) was least effective." }, { "input": "In some children, methylphenidate may not achieve response even at high doses or may cause intolerable side effects. For these children, start a different stimulant medication.", "output": "The National Institute of Mental Health Collaborative Multisite Multimodal Treatment Study of Children with Attention Deficit/Hyperactivity Disorder (known as the MTA study) is the longest treatment study of children to date. This study-a 28-day, double-blind placebo-controlled trial-enrolled children aged 7 to 9 years with ADHD and compared 4 treatment strategies (including medication and behavioral interventions) over 14 months. Of particular interest was the dose-titration evaluation at the beginning of the study. Daily dose-switching titration of methylphenidate was used to identify the optimal starting dose for each child assigned to receive medication. In all, 289 children were randomized to receive methylphenidate, and 256 completed the titration (17 children refused to take medication, 1 moved, 4 had side effects, 4 had missing data, and 7 stopped mid-titration because of inability to follow the titration protocol). Of the 256 children who completed titration, 198 (77%) responded favorably to 1 of the following doses: low (15 mg/day), intermediate (25 mg/day), or high (35 mg/day for children weighing less than 25 kg; or 50 mg/day for children weighing 25 kg or more). Of the remaining 23%, 32 children responded best to placebo and 26 were methylphenidate nonresponders and were subsequently placed on dextroamphetamine. Children who responded to methylphenidate entered the 13-month maintenance phase on the optimal dose identified in the titration trial. They were monitored by monthly re-examination and review of information from parents and teachers regarding ADHD symptoms and potential drug side effects. The dose was changed if symptoms were not well controlled or if side effects were present. Subsequently, if no effective and well-tolerated dose of methylphenidate could be identified, the drug was deemed ineffective for that child and was replaced by another medication." }, { "input": "For children with recurrent acute otitis media (here defined as 3 or more episodes in 6 months, or 4 or more in a year), tympanostomy tubes are indicated if middle-ear effusion is present. Tubes reduce the frequency of recurrent acute otitis media by 2 to 3 episodes per year in these patients.", "output": "The Institute for Clinical Systems Improvement 2001 guidelines for recurrent acute otitis media treatment in children recommends initial antibiotic prophylaxis with amoxicillin 20 mg/kg/day for 2 to 6 months based on randomized controlled trial data. If there are 2 recurrences of acute otitis media during that time, then referral to an otorhinolaryngologist for possible tympanostomy tube placement is recommended." }, { "input": "For children with recurrent acute otitis media (here defined as 3 or more episodes in 6 months, or 4 or more in a year), tympanostomy tubes are indicated if middle-ear effusion is present. Tubes reduce the frequency of recurrent acute otitis media by 2 to 3 episodes per year in these patients.", "output": "One randomized controlled trial of 264 children, aged 7 to 35 months, with a history of recurrent acute otitis media but free of middle-ear effusion, compared tubes with medical therapy and found no difference in recurrence over 2 years. The medical therapy arm received prophylaxis with either amoxicillin or placebo. The amoxicillin arm had 0.6 fewer episodes of acute otitis media per year compared with the other 2, a statistically significant 40% decrease (relative risk reduction=0.4). The average time with otitis media of any type (acute otitis media, otitis media with effusion, or ottorhea) also decreased-15.0% in the placebo group, 10.0% in the amoxicillin group, and 6.6% in the tympanostomy tube group (amoxicillin vs. placebo, P=.03; tubes vs. placebo, P<.001). Higher dropout rates occurred in the amoxicillin and medical treatment groups." }, { "input": "For children with recurrent acute otitis media (here defined as 3 or more episodes in 6 months, or 4 or more in a year), tympanostomy tubes are indicated if middle-ear effusion is present. Tubes reduce the frequency of recurrent acute otitis media by 2 to 3 episodes per year in these patients.", "output": "The benefit of tubes for recurrent acute otitis media was demonstrated by one study which found 2.27 (95% CI, 1.03-3.51) fewer." }, { "input": "For children with recurrent acute otitis media (here defined as 3 or more episodes in 6 months, or 4 or more in a year), tympanostomy tubes are indicated if middle-ear effusion is present. Tubes reduce the frequency of recurrent acute otitis media by 2 to 3 episodes per year in these patients.", "output": "The benefit of tubes for recurrent acute otitis media was demonstrated by one study which found 3.01 (95% CI, 2.18-3.84) fewer acute episodes per year." }, { "input": "For children with recurrent acute otitis media (here defined as 3 or more episodes in 6 months, or 4 or more in a year), tympanostomy tubes are indicated if middle-ear effusion is present. Tubes reduce the frequency of recurrent acute otitis media by 2 to 3 episodes per year in these patients.", "output": "The benefit of tubes for recurrent acute otitis media was demonstrated only in studies in which middle-ear effusion was present." }, { "input": "For children with recurrent acute otitis media (here defined as 3 or more episodes in 6 months, or 4 or more in a year), tympanostomy tubes are indicated if middle-ear effusion is present. Tubes reduce the frequency of recurrent acute otitis media by 2 to 3 episodes per year in these patients.", "output": "A meta-analysis of 5 randomized trials comparing no surgery with placement of tubes for recurrent acute otitis media with or without middle-ear effusion showed that the placement of tubes resulted in a mean absolute decrease in acute otitis media incidence of 1.0 per year (95% confidence interval [CI], 0.4-1.6), and a decrease in the prevalence of middle-ear effusion by 115 days per year (95% CI, 11-220)." }, { "input": "Further benefits include improved quality of life for both child and caregiver and greater parental satisfaction.", "output": "In prospective studies of patients receiving tubes for recurrent acute otitis media and otitis media with effusion, measures of quality of life-physical suffering, emotional distress, activity limitation, hearing loss, speech development, caregiver concern/worry, parental post-tube satisfaction improved after tube placement." }, { "input": "Further benefits include improved quality of life for both child and caregiver and greater parental satisfaction.", "output": "In prospective studies of patients receiving tubes for recurrent acute otitis media and otitis media with effusion, an ear symptom score improved after tube placement." }, { "input": "Further benefits include improved quality of life for both child and caregiver and greater parental satisfaction.", "output": "A meta-analysis reporting sequelae of tympanostomy tubes found an absolute complication rate of 26% for transient otorrhea and 4% for chronic otorrhea. Within several weeks of tube placement, 79% of children had improved quality of life, 17% had trivial change, and 4% were worse." }, { "input": "Tympanostomy tubes do not decrease the number of recurrent acute otitis media episodes in children without middle-ear effusion.", "output": "One randomized controlled trial of 264 children, aged 7 to 35 months, with a history of recurrent acute otitis media but free of middle-ear effusion, compared tubes with medical therapy and found no difference in recurrence over 2 years. The medical therapy arm received prophylaxis with either amoxicillin or placebo. The amoxicillin arm had 0.6 fewer episodes of acute otitis media per year compared with the other 2, a statistically significant 40% decrease (relative risk reduction=0.4). The average time with otitis media of any type (acute otitis media, otitis media with effusion, or ottorhea) also decreased-15.0% in the placebo group, 10.0% in the amoxicillin group, and 6.6% in the tympanostomy tube group (amoxicillin vs. placebo, P=.03; tubes vs. placebo, P<.001). Higher dropout rates occurred in the amoxicillin and medical treatment groups." }, { "input": "These children run the risk of adverse outcomes of tube placement, including transient or recurrent otorrhea, tympanosclerosis, focal atrophy, perforation, and cholesteatoma.", "output": "Compared with nonsurgical treatment, complication rates for tube placement were reported in 0.7% of surgically treated ears. Complications included: tympanosclerosis (relative risk [RR]=3.5 [95% CI, 2.6-4.9]), focal atrophy (RR=1.7 [95% CI, 1.1-2.7]), perforation (RR=3.5 [95% CI, 1.5-7.1]) (2% with short-term tubes and 16% with long-term tubes), and cholesteatoma (RR=2.6 [95% CI, 1.5-4.4])." }, { "input": "These children run the risk of adverse outcomes of tube placement, including transient or recurrent otorrhea, tympanosclerosis, focal atrophy, perforation, and cholesteatoma.", "output": "A meta-analysis reporting sequelae of tympanostomy tubes found an absolute complication rate of 26% for transient otorrhea and 4% for chronic otorrhea." }, { "input": "Asymptomatic term infants whose mothers received adequate intrapartum antibiotic prophylaxis (defined as intravenous penicillin or ampicillin at least 4 hours before delivery) for group B streptococcal disease do not need work-up or treatment.", "output": "The vertical transmission rate of group B streptococcal disease, as measured by neonatal colonization (as opposed to clinical illness), is 46% when antibiotic prophylaxis is started <1 hour before delivery, 2.9% when prophylaxis is given at 2 to 4 hours, and 1.2% when given at least 4 hours before delivery." }, { "input": "Asymptomatic term infants whose mothers received adequate intrapartum antibiotic prophylaxis (defined as intravenous penicillin or ampicillin at least 4 hours before delivery) for group B streptococcal disease do not need work-up or treatment.", "output": "The duration of adequate intrapartum antibiotic prophylaxis was initially set at 4 hours, based on a study measuring antibiotic penetration into amniotic fluid." }, { "input": "Asymptomatic term infants whose mothers received adequate intrapartum antibiotic prophylaxis (defined as intravenous penicillin or ampicillin at least 4 hours before delivery) for group B streptococcal disease do not need work-up or treatment.", "output": "Intrapartum prophylaxis of women who had positive group B streptococcal disease screening cultures at 35 weeks will prevent 70% of earlyonset disease and 89% of fatalities." }, { "input": "These infants should be observed for 48 hours, but may be discharged after 24 hours in circumstances where close follow-up is available.", "output": "A large retrospective study demonstrated that infants who developed early-onset disease despite intrapartum prophylaxis developed the same clinical syndrome in the same time frame (78% of early-onset disease evident in first 24 hours and 96% by 48 hours) as infants whose mothers did not receive prophylaxis." }, { "input": "Symptomatic infants, premature infants (gestational age <35 weeks) of mothers who did not receive prophylaxis, and infants whose mothers had chorioamnionitis should receive a full evaluation (complete blood count, blood culture, and chest x-ray with or without a lumbar puncture) and an initial empiric antibiotic treatment with ampicillin or penicillin and gentamycin. If a term infant is not symptomatic and maternal antibiotic prophylaxis was not adequate, opinions differ as to whether to perform limited evaluation with empiric treatment or close observation.", "output": "As demonstrated by multicenter retrospective studies, infants aged <35 weeks are at significantly higher risk of group B streptococcal disease than term infants (relative risk=1.5-2.07), and mortality for premature infants with early-onset disease (25%-30%) is substantially higher than for term infants with early-onset disease (2%-8%)." }, { "input": "other", "output": "Implementation of these guidelines is aided by the adoption of an institution-wide policy to support point of care decision-making." }, { "input": "other", "output": "A multicenter population-based study demonstrated that basing prophylaxis on screening cultures is twice as effective as risk stratification, a previously recommended strategy." }, { "input": "other", "output": "Intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal disease by 65% in the last decade." }, { "input": "other", "output": "A retrospective study after the release of the 1996 Centers for Disease Control (CDC) guidelines concluded that hospitals with established group B streptococcal disease policies had significantly fewer cases of early-onset disease (P=.038)." }, { "input": "Yes, some are. Acupuncture relieves subjective symptoms of asthma and reduces medication use in mild to moderate asthma.", "output": "In 1 RCT, improvement in general well-being was reported by 79% of 38 patients receiving acupuncture compared with 47% of 18 patients in the control group." }, { "input": "Yes, some are. Acupuncture relieves subjective symptoms of asthma and reduces medication use in mild to moderate asthma.", "output": "While a Cochrane review of 11 RCTs with variable trial quality and a total of 324 participants found that acupuncture had no significant effect on pulmonary function or global assessment of well-being, the review noted that some studies reported significant positive changes in daily symptoms, reductions in medication use, and improved quality of life. This suggests that some patients with mild to moderate asthma may benefit from acupuncture." }, { "input": "Herbal medications, such as Ginkgo biloba, appear to improve lung function, while herbs such as Tylophora indica and Tsumura saiboku-to may decrease asthma symptoms.", "output": "A systematic review of 17 trials, with overall poor methodological quality and a total of 1445 participants, reported significant improvements in clinically relevant measures with 6 different herbal medicines. Ginkgo biloba liquor increased forced expiratory volume in 1 second (FEV1) by 10% at 4 weeks and by a more clinically relevant 15% at 8 weeks (significantly greater than placebo, P<.05). Invigorating Kidney for Preventing Asthma (IKPA) tablets increased FEV1 by 30% at 3 months compared with 17% in controls (P<.05). Wenyang Tonglulo Mixture (WTM) improved FEV1 by 30% at 8 weeks compared with a 16% increase in the control group using oral salbutamol and inhaled beclomethasone (P<.05). Dried ivy extract, thought to work as both a secretolytic and bronchospasmolytic, reduced airway resistance in children by 23.6% compared with placebo (P=.036). Tylophora indica (a rare herb also known as Indian ipecac) provided significant improvement in nocturnal dyspnea when compared with controls (P<.01) in a study that relied on patients' symptom diaries. Tsumura saiboku-to (TJ-96) provided patients in one RCT with significant, but unspecified, asthma symptom relief when compared with those in a control group (P<.01)." }, { "input": "No evidence, however, supports the use of room air ionizers, manual therapy, homeopathy, or mind-body therapy for treatment of asthma.", "output": "A Cochrane review of 6 RCTs of mixed quality, with a total of 556 patients, concluded the evidence is insufficient to evaluate the possible role of homeopathy for the treatment of asthma, due to heterogeneity of interventions, patient populations, and outcome assessments. Each study evaluated a different homeopathic remedy, making any overall assessment difficult. The review notes there have been only limited attempts to study a complete \"package of care\", which includes the in-depth, one-on-one consultation, treatment, and follow-up that characterizes most homeopathic treatment in practice." }, { "input": "No evidence, however, supports the use of room air ionizers, manual therapy, homeopathy, or mind-body therapy for treatment of asthma.", "output": "A Cochrane review of 3 moderate- to poor-quality RCTs with 156 participants reported no significant effect of chiropractic spinal manipulation (2 trials) or massage therapy (1 trial) on lung function, asthma symptoms, or medication use." }, { "input": "No evidence, however, supports the use of room air ionizers, manual therapy, homeopathy, or mind-body therapy for treatment of asthma.", "output": "Cochrane review of 6 good-quality trials with a total of 106 participants reported no significant effect of room air ionizers on pulmonary function measures, symptoms, or medication use." }, { "input": "No evidence, however, supports the use of room air ionizers, manual therapy, homeopathy, or mind-body therapy for treatment of asthma.", "output": "A pilot RCT with 33 adults found a nonsignificant reduction in medication use among the subjects practicing mental imagery, but no overall effect on lung function or quality-of-life measures." }, { "input": "Evidence from clinical trials supports the use of pneumococcal polysaccharide vaccine for prevention of pneumonia in nursing home patients.", "output": "The Centers for Disease Control and Prevention (CDC) has reported outbreaks of invasive pneumococcal disease in nursing homes where vaccination rates are low. Pneumococcal bacteremia is seen in only 10%-20% of patients with pneumococcal pneumonia but confers a significant risk of death. Therefore, pneumococcal vaccination is indicated for patients \u2265 65 years or those with chronic medical conditions." }, { "input": "Evidence from clinical trials supports the use of pneumococcal polysaccharide vaccine for prevention of pneumonia in nursing home patients.", "output": "A 6-year randomized clinical trial that studied the trivalent pneumococcal vaccine in preventing pneumonia in New York City Home (a nursing home) subjects showed an ARR=2.7% and NNT=37. While this report also did not specify whether there was blinding, any bias introduced by absence of blinding is unlikely to account for the large effect size (relative risk reduction=0.56)." }, { "input": "Evidence from clinical trials supports the use of pneumococcal polysaccharide vaccine for prevention of pneumonia in nursing home patients.", "output": "A prospective, risk-stratified, randomized study of the 14-valent pneumococcal vaccine in 1686 patients living in hospices and nursing homes in France showed an absolute risk reduction (ARR) of 2.9% in the incidence of all-cause pneumonia, corresponding to a number needed to treat (NNT) of 35. This study has 2 major limitations: the authors did not comment on whether the study was blinded, and 31% of patients were lost to follow-up." }, { "input": "Case-control studies have consistently shown the efficacy of pneumococcal vaccine in preventing invasive pneumococcal disease and bacteremia for patients with chronic medical illnesses and the elderly, patients typically found in nursing home populations.", "output": "Farr and colleagues found efficacy of 70% (95% confidence interval [CI], 37%-86%) among 2 groups of patients: those \u2265 2 years of age with chronic disease or those \u2265 65 years." }, { "input": "Case-control studies have consistently shown the efficacy of pneumococcal vaccine in preventing invasive pneumococcal disease and bacteremia for patients with chronic medical illnesses and the elderly, patients typically found in nursing home populations.", "output": "A case-control study by Sims and colleagues also found the vaccine to have efficacy of 70% (95% CI, 37%- 86%) in preventing invasive pneumococcal disease in immunocompetent patients aged \u2265 55 years." }, { "input": "When herpes simplex virus (HSV) type 1 lesions are in the papule or vesicle stage, there is no benefit to starting oral acyclovir.", "output": "Overall, acyclovir did not effect lesion progression, size, or healing time to loss of hard crust or normal skin. However, the mean duration of pain for all patients significantly decreased (2.5 days vs 3.8 days for placebo, P=.01). For the subgroup of patients who started acyclovir treatment in the prodrome or erythema stage, the mean duration of pain significantly decreased (2.5 days vs 3.9 days for placebo, P=.02), as did healing time to loss of crust (5.8 days vs 7.9 days for placebo, P=.03). Among those who started acyclovir in the papular stage, the trend was toward drug benefit, but this was not statistically significant (mean pain duration: 2.5 vs. 3.6, P=.36; mean healing time to loss of crust: 8.0 vs. 7.2, P=.52). This evidence supports early (prodrome or erythema stage) but not late (macule, papule, vesicle, or crusted stage) treatment of HSV 1 with oral acyclovir." }, { "input": "Topical acyclovir 5% cream applied 5 times a day decreases pain and the duration of hard crust.", "output": "Topical application of 5% acyclovir cream significantly decreases clinician-assessed duration of the episode and duration of patient-reported pain, based on 2 double-blind, multicenter RCTs that used a vehicle control. In these trials, 686 and 699 patients self-initiated treatment 5 times a day for 4 days beginning within 1 hour of the onset of a recurrent lesion. In the first study, the mean clinician-assessed duration of the episode with topical acyclovir was 4.3 vs 4.8 days for placebo (hazard ratio [HR]=1.23; 95% confidence interval [CI], 1.06-1.44), and the mean duration of patient-assessed pain was 2.9 vs 3.2 days (HR=1.20; 95% CI, 1.03-1.40). The second study showed a mean clinician-assessed duration with topical acyclovir of 4.6 vs 5.2 days for control (HR=1.24; 95% CI, 1.06-1.44), and the mean duration of patient-assessed pain was 3.1 vs 3.5 days (HR=1.21; 95% CI, 1.04-1.40). Benefits were seen regardless of whether treatment was initiated early (prodrome or erythema stage) or late (macule, papule, vesicle or crusted stage)." }, { "input": "If started at the onset of symptoms (during the prodrome stage), acyclovir (400 mg 5 times daily for 5 days) decreases pain and healing time to loss of crust and valacyclovir (2 g twice daily for 1 day) reduces the lesion duration and time to healing and may prevent lesion development.", "output": "Studies of valacyclovir (the L-valine ester of acyclovir, which has 3 to 5 times greater bioavailability) offer the most promise for effective self-initiated treatment of recurrent herpes labialis. In a report of 2 well-designed, multicenter RCTs, valacyclovir at the FDA-approved dosage of 2 g twice daily for 1 day at the onset of symptoms (before visible signs of a cold sore) significantly decreased the mean duration of the lesion and time to lesion healing. In the first study (n=603), episode duration was decreased by 1.1 days (5.0 days vs 6.1 days for placebo; 95% CI, -1.6 to -0.6) and in the second study (n=605) by 1.0 day (5.3 vs 6.3 days for placebo; 95% CI, -1.0 to -0.5). In the first study, the time to lesion healing was decreased by 1.3 days (4.8 vs 6.1 days for placebo; 95% CI, -1.9 to -0.7) and in the second study by 1.2 days (5.1 vs. 6.4 days; 95% CI, -1.8 to -0.7). There also was a trend towards preventing the development of lesions, but this was not statistically significant." }, { "input": "Levothyroxine (LT4) should be used alone as initial replacement for patients with hypothyroidism.", "output": "A study assessed changes in body weight, lipid profile, hypothyroid-specific health-related quality-of-life scores, and 13 neuropsychological measures pre- and posttreatment. This study detected no difference in body weight and serum lipids at baseline and after treatment. The hypothyroid-specific health-related quality-of-life scores similarly improved for both treatment groups. Twelve of 13 neuropsychological tests demonstrated no differences between treatment groups; the Grooved Peg Board Test of manual dexterity and fine visual-motor coordination demonstrated a slight improvement for the LT4 alone treatment group." }, { "input": "Levothyroxine (LT4) should be used alone as initial replacement for patients with hypothyroidism.", "output": "Initial thyroid replacement with synthetic LT4 is recommended because LT4 is safe, effective, reliably relieves symptoms, and normalizes lab tests for hypothyroid patients." }, { "input": "Levothyroxine (LT4) should be used alone as initial replacement for patients with hypothyroidism.", "output": "One study, which enrolled patients with hypothy-roidism and mild depressive symptoms, assessed scores on the Symptom Check-List-90, the Comprehensive Epidemiological Screens for Depression, and the Medical Outcomes Study health status questionnaire at baseline and multiple times over the duration of the study. For these outcomes, no differences were found between the LT4 alone and combination LT4-LT3 treatment groups within 90% confidence intervals." }, { "input": "The optimal initial dose is 1.6 \u00b5g/kg/d for healthy people aged 60 years or younger.", "output": "The initial dose of LT4 can be based on the age and health status of the patient. The mean replacement dose of LT4 is 1.6 \u00b5g/kg/d for healthy patients aged \u226460 years." }, { "input": "Patients aged more than 60 years may require less levothyroxine to achieve therapeutic serum thyroid hormone replacement, so initial replacement should be decreased to 25 to 50 \u00b5g daily.", "output": "An uncontrolled cohort study of 84 patients found that for patients aged >60 years, 25- to 50-\u00b5g doses of LT4 resulted in similar serum thyrotropin (TSH) levels as the higher (1.6 \u00b5g/kg/d) doses required for younger patients." }, { "input": "Since patients with known heart disease may develop dysrhythmias, angina, and myocardial infarctions when started on full replacement doses, experts recommend starting 12.5 to 25 \u00b5g daily for this population.", "output": "Based on expert opinion, patients of any age with heart disease should be given lower doses of 12.5 to 25 \u00b5g daily as initial treatment." }, { "input": "Brand-name (Synthroid, Levoxyl, etc) and generic LT4 are bioequivalent.", "output": "In a 1997 study, they did not examine therapeutic equivalence and from a clinical perspective, some researchers and pharmaceutical companies felt that the authors could not comment on whether the products were interchangeable." }, { "input": "Brand-name (Synthroid, Levoxyl, etc) and generic LT4 are bioequivalent.", "output": "In 1997, a bioequivalence study compared 2 generic brands to 2 name brands by having 22 women with hypothyroidism, who were euthyroid on replacement medication, take each preparation for 6 weeks. The area under the curve, peak serum concentration, and time to peak concentration for 3 indexes of thyroid function (thyroxine, triiodothyronine, and free T4 index) were not significantly different and met the FDA criterion for relative bioequivalence." }, { "input": "The US Food and Drug Administration (FDA) does not consider these products to be interchangeable until proven therapeutically equivalent.", "output": "The FDA now requires thyroxine bioavailability and bioequivalence studies to evaluate product substitution." }, { "input": "The US Food and Drug Administration (FDA) does not consider these products to be interchangeable until proven therapeutically equivalent.", "output": "The FDA lists Levothyroxine Sodium (Mylan) to be therapeutically equivalent and therefore interchangeable with Unithroid." }, { "input": "The most effective dose for preventing exacerbations appears to be 4 mg (2 puffs) 4 times a day.", "output": "An RCT compared 4 mg of inhaled nedocromil 4 times daily with inhaled placebo among 209 asthmatic children for 12 weeks.3 After 8 weeks, they found a statistically significant reduction in total daily asthma symptom scores (50% nedocromil vs 9% placebo; P<.01). The proportion of parents and children rating treatment as moderately or very effective was 78% in the treatment group and 59% in the placebo group (number needed to treat [NNT]=5.2; P<.01); clinicians' ratings were 73% for nedocromil and 50% for placebo (NNT=4.3; P<.01). The frequency of side effects-including nausea, headache, and sleepiness-did not reach statistical significance; however, the nedocromil group reported up to a 20% incidence of sore throat." }, { "input": "The most effective dose for preventing exacerbations appears to be 4 mg (2 puffs) 4 times a day.", "output": "In a Cochrane Review, 20 RCTs involving 280 participants showed that 4 mg (2 puffs) of nedocromil inhaled 15 to 60 minutes prior to exercise significantly reduced the severity and duration of exercise-induced asthma for both adults and children. The maximum percentage fall in FEV1 improved significantly compared with placebo, with a weighted mean difference of 15.5% (95% confidence interval, 13.2-18.1). In addition, the time to complete recovery was shortened from 30 minutes with placebo to 10 minutes with nedocromil." }, { "input": "More severe forms of asthma respond better to inhaled steroids than to nedocromil.", "output": "A systematic review encompassing 127 trial centers and 4723 patients concluded that inhaled nedocromil was effective for a variety of patients with asthma. Significant improvements were noted in FEV1, PEFR, use of bronchodilators, symptom scores, and quality of life scores. The reviewers found nedocromil to be most effective for patients with moderate disease already taking bronchodilators orresponding to the \"mild persistent asthma\" category." }, { "input": "More severe forms of asthma respond better to inhaled steroids than to nedocromil.", "output": "A small study of patients already on inhaled steroid found nonsignificant trends towards reductions in bronchodilator use, increased PEFR, increased FEV1, and improved quality of life." }, { "input": "Nedocromil may allow some patients with severe asthma to use lower doses of inhaled steroids.", "output": "A small study of patient considered to be steroid-resistant found nonsignificant trends towards reductions in bronchodilator use, increased PEFR, increased FEV1, and improved quality of life." }, { "input": "Nedocromil may allow some patients with severe asthma to use lower doses of inhaled steroids.", "output": "A small study of patients already on inhaled steroid found nonsignificant trends towards reductions in bronchodilator use, increased PEFR, increased FEV1, and improved quality of life." }, { "input": "Nedocromil is also effective for the treatment of exercise-induced asthma.", "output": "In a Cochrane Review, 20 RCTs involving 280 participants showed that 4 mg (2 puffs) of nedocromil inhaled 15 to 60 minutes prior to exercise significantly reduced the severity and duration of exercise-induced asthma for both adults and children. The maximum percentage fall in FEV1 improved significantly compared with placebo, with a weighted mean difference of 15.5% (95% confidence interval, 13.2-18.1). In addition, the time to complete recovery was shortened from 30 minutes with placebo to 10 minutes with nedocromil." }, { "input": "In general, about 50% to 70% of patients respond to nedocromil.", "output": "An RCT compared 4 mg of inhaled nedocromil 4 times daily with inhaled placebo among 209 asthmatic children for 12 weeks.3 After 8 weeks, they found a statistically significant reduction in total daily asthma symptom scores (50% nedocromil vs 9% placebo; P<.01). The proportion of parents and children rating treatment as moderately or very effective was 78% in the treatment group and 59% in the placebo group (number needed to treat [NNT]=5.2; P<.01); clinicians' ratings were 73% for nedocromil and 50% for placebo (NNT=4.3; P<.01). The frequency of side effects-including nausea, headache, and sleepiness-did not reach statistical significance; however, the nedocromil group reported up to a 20% incidence of sore throat." }, { "input": "Gastric bypass results in weight loss of approximately 33% at 2 years and 25% at 8 years.", "output": "A study demonstrated 25% \u00b1 6% weight loss vs 0.9% gain at 8 years." }, { "input": "Gastric bypass results in weight loss of approximately 33% at 2 years and 25% at 8 years.", "output": "The Swedish Obesity Study, a large cohort study with matched controls. Surgery produced 23 to 28 kg more weight loss at 2 years. The study demonstrated 33% \u00b1 10% weight loss for gastric bypass and 0% for medical therapy (not described) at 2 years." }, { "input": "Gastric bypass is more effective than gastroplasty for weight loss and is associated with fewer revisions, but it has more side effects.", "output": "A systematic review assessed multiple randomized controlled trials comparing gastric bypass with gastroplasty and found greater weight loss, fewer revisions, and more side effects from gastric bypass. Five trials comparing gastric bypass with horizontal gastroplasty demonstrated significantly greater weight loss from gastric bypass. Five other trials comparing weight loss from gastric bypass with vertical gastroplasty produced mixed results, with 3 trials favoring gastric bypass and 2 showing no difference. Fewer patients required revision after gastric bypass (0%-4%) compared with vertical gastroplasty (9%) or horizontal gastroplasty (19%-40%). One included trial found that postoperative dumping syndrome (28% vs 0%, P<0.05) and heartburn (59% vs 32%, P<.05) were more common with gastric bypass than with gastroplasty." }, { "input": "Limited evidence suggests that gastric bypass produces more weight loss than gastric banding.", "output": "Among bariatric surgical techniques, patients undergoing gastric bypass lost more weight than those with gastroplasty (using staples to partition the stomach, either horizontally or vertically) (P=.057, not significant or gastric banding placing a constricting ring around the stomach) (P<.05) at 8 years." }, { "input": "Bariatric surgery, including gastric bypass, improves conditions comorbid with obesity, including diabetes, abnormal lipid profiles, and low quality-of-life scores. It decreases the incidence of hypertension at 2 years after surgery, but whether this effect is sustained is unclear.", "output": "Bariatric surgery significantly lowered the incidence of hypertension at 2 years (3.2%) compared with conventional treatment (9.9%), but after 8 years this difference disappeared." }, { "input": "Bariatric surgery, including gastric bypass, improves conditions comorbid with obesity, including diabetes, abnormal lipid profiles, and low quality-of-life scores. It decreases the incidence of hypertension at 2 years after surgery, but whether this effect is sustained is unclear.", "output": "In a case series, bariatric surgery reduced triglycerides (50%) as well as total cholesterol (15%) (P<.05 for both) at 6 months and significantly increased high-density lipoprotein cholesterol levels at 1 and 5 years." }, { "input": "Bariatric surgery, including gastric bypass, improves conditions comorbid with obesity, including diabetes, abnormal lipid profiles, and low quality-of-life scores. It decreases the incidence of hypertension at 2 years after surgery, but whether this effect is sustained is unclear.", "output": "Bariatric surgery, including gastric bypass, improves a variety of obesity-related comorbid conditions. Diabetes prevalence decreased among gastric bypass patients at 2 years (0.0% vs 4.7%, P<0.005) and 8 years (3.6% vs 18.5%, P<.0005) compared with those receiving medical therapy." }, { "input": "Bariatric surgery, including gastric bypass, improves conditions comorbid with obesity, including diabetes, abnormal lipid profiles, and low quality-of-life scores. It decreases the incidence of hypertension at 2 years after surgery, but whether this effect is sustained is unclear.", "output": "In the Swedish Obesity Study, hypertriglyceridemia decreased postoperatively but hypercholesterolemia did not." }, { "input": "Bariatric surgery also improves obstructive sleep apnea, obesity hypoventilation syndrome, menstrual irregularity, and female urinary stress incontinence.", "output": "The Swedish Obesity Study found significant improvements in Health-Related Quality of Life scores at 2 years with surgery vs conventional treatment." }, { "input": "Bariatric surgery also improves obstructive sleep apnea, obesity hypoventilation syndrome, menstrual irregularity, and female urinary stress incontinence.", "output": "Bariatric surgery improved obstructive sleep apnea and obesity hypoventilation syndrome in 2 case series. In one, Epworth Sleepiness Scale scores, minimum O2 saturation, and other measures improved significantly (P<.001) by 3 to 21 months after surgery." }, { "input": "Bariatric surgery also improves obstructive sleep apnea, obesity hypoventilation syndrome, menstrual irregularity, and female urinary stress incontinence.", "output": "In a case series, menstrual irregularities decreased from 40.4% to 4.6% following surgery (P<.001) among women who lost 50% of their excess weight. The incidence of urinary stress incontinence also decreased significantly (61.2% to 11.6%, P<.001 in this study)." }, { "input": "Bariatric surgery has a complication rate of 13% and a mortality rate of 0.2%.", "output": "Bariatric surgery, including gastric bypass, has significant postoperative morbidity and mortality. Thirteen percent of patients in the Swedish Obesity Study experienced peri-operative complications, including pulmonary symptoms (6.2%), abdominal infection (2.1%), wound complications (1.8%), bleeding (0.9%), thromboembolic events (0.8%), and other miscellaneous complications (4.8%). Postoperative complications required reoperation for 2.2% of surgical patients, and there were 4 postoperative deaths (0.2% of the operative patients; 3 due to leakage, and 1 due to a technical laparoscopic error)." }, { "input": "No single clinical examination element, or combination of such elements, reliably detects meniscal injury. The McMurray test is best for ruling in meniscal pathology. Assuming a 9% prevalence of meniscal tears among all knee injuries (a rate reflecting national primary care data), the posttest probability that a patient with McMurray's sign has a meniscal injury ranges from <30% to 63%.", "output": "Authors of all meta-analyses noted the lack of standardization in physical examination maneuvers (especially the McMurray test) and, in some cases, no specification of how physical examination tests were performed. Authors analyzed the utility of the aggregate and composite knee examinations without specifying what constituted such an exam." }, { "input": "No single clinical examination element, or combination of such elements, reliably detects meniscal injury. The McMurray test is best for ruling in meniscal pathology. Assuming a 9% prevalence of meniscal tears among all knee injuries (a rate reflecting national primary care data), the posttest probability that a patient with McMurray's sign has a meniscal injury ranges from <30% to 63%.", "output": "A meta-analysis of 4 studies by Jackson compared the utility of the McMurray test and joint line tenderness. For detecting meniscal tears, the McMurray test had a clinically and statistically significant positive likelihood ratio of 17.33, corresponding to a posttest probability of nearly 61%. Negative likelihood ratios for the McMurray test and joint line tenderness (0.5 and 0.8) were not clinically significant, indicating that absence of the McMurray sign or joint line tenderness alone is of little benefit in ruling out meniscal injury." }, { "input": "No single clinical examination element, or combination of such elements, reliably detects meniscal injury. The McMurray test is best for ruling in meniscal pathology. Assuming a 9% prevalence of meniscal tears among all knee injuries (a rate reflecting national primary care data), the posttest probability that a patient with McMurray's sign has a meniscal injury ranges from <30% to 63%.", "output": "In a meta-analysis of 13 studies, no physical examination test-including assessment for joint effusion, McMurray test, joint line tenderness, or the Apley compression test-yielded clinically significant positive or negative likelihood ratios for a meniscal tear. The McMurray test performed best, but at 9% to 11% pretest probability of JFP_1104_CI.final 10/18/04 11:06 AM Page 918 meniscal lesions, based on prevalence estimates among primary care/specialist populations,2 the posttest probability of a positive exam is still <30%." }, { "input": "In contrast, the absence of any positive physical examination findings effectively rules out meniscal pathology, yielding a posttest probability of 0.8% for lateral meniscus injury, 1.0% for medial meniscus injury, and 3.8% for any meniscal injury among primary care populations.", "output": "In another meta-analysis including 9 studies of meniscal injury diagnosis, individual tests for joint line tenderness, joint effusion, the medial-lateral grind test, and the McMurray test failed to yield statistically significant likelihood ratios for the presence or absence of meniscal tears. Positive and negative likelihood ratios for aggregate physical examination were 2.7 (95% confidence interval [CI], 1.4-5.1) and 0.4 (95% CI, 0.2-0.7), which are statistically, but not clinically, significant values for ruling meniscal lesions in or out." }, { "input": "Intra-articular steroid injections appear to provide 2 to 6 weeks of pain relief for patients with knee osteoarthritis.", "output": "A randomized, double-blind, placebo-controlled trial studied the long-term safety and efficacy of treatment of knee osteoarthritis with repeated steroid injections. These investigators studied 66 patients aged 40 to 80 years recruited from rheumatology clinics. One half (n=33) received injections of triamcinolone acetonide 40 mg, and the other half received saline injections every 3 months for 2 years. At 1- and 2-year interval follow-ups, no statistically significant difference was seen between the 2 groups in loss of joint space and no progression of degenerative disease, as demonstrated by measurements of joint space widths by standardized fluoroscopically guided radiographs. Although the primary outcome measure of this study was to assess radiologic joint space narrowing with repeated injections, knee pain and stiffness appeared to improve after 2 years, although these results were not well quantified." }, { "input": "Intra-articular steroid injections appear to provide 2 to 6 weeks of pain relief for patients with knee osteoarthritis.", "output": "A randomized, single-blinded study involving 84 patients demonstrated significant self-report-ed \"overall improvement\" for patients given intra-articular triamcinolone hexacetonide (78%) compared with placebo (49%) after 1 week (P<.05). It also confirmed reports that visual analogue score for pain and distance walked in 1 minute improves significantly for both steroid- and placebo-treated groups up to 6 weeks. Only the steroid-treated patients exhibited improved walking distance at 1 week compared with baseline (P<.001)." }, { "input": "Intra-articular steroid injections appear to provide 2 to 6 weeks of pain relief for patients with knee osteoarthritis.", "output": "In a randomized, double-blind, placebo-controlled crossover study, investigators randomized 59 patients aged 51 to 89 years to receive either an intra-articular injection of 1 mL of 40 mg methylprednisolone or 1 mL of 0.9% saline. After 3 weeks, patients receiving steroid injection had a minimal change in baseline visual analogue score for pain compared with those receiving saline (median change: -2.0 mm vs 0 mm on a 100-mm scale)." }, { "input": "Higher-dose steroids with or without joint lavage can provide pain relief up to 24 weeks.", "output": "Two studies using higher-dose steroids (prednisone equivalent dose of 37.5 to 80 mg), with or without joint lavage, assessed improvement at 16 to 24 weeks. Although neither individual study showed statistically significant differences, the pooled data from the 2 studies favored symptom improvement at 16 to 24 weeks (RR=2.09; 95% CI, 1.2-3.7; NNT=4.4)." }, { "input": "In the initial management of dyspepsia for patients without \"alarm\" symptoms (weight loss, recurrent vomiting, dysphagia, anemia, evidence of bleeding, onset of dyspepsia after age 45 years), therapy based on the results of early endoscopy was not better than empiric acid suppression (antisecretory therapy) or a Helicobacter pylori \"test and treat\" strategy in reducing symptoms or improving quality of life.", "output": "Though individual studies have suggested that therapy based on endoscopy performed before any other study (early endoscopy) may be superior to empiric antisecretory therapy and as efficacious as a \"test and treat\" strategy in symptom relief, a Cochrane systematic review of 20 RCTs (11 in primary care settings) provides the best evidence on the role of early endoscopy. A subgroup analysis of 5 RCTs, which compared early endoscopy with empiric antisecretory therapy (typically for 4 weeks), revealed that early endoscopy demonstrated a trend towards improvement in self-reported symptoms and in dyspepsia symptom relief scores, but the difference was not statistically significant (relative risk [RR]=0.89; 95% confidence interval [CI], 0.77-1.1). Because each study used different symptom scores, the relative risk as calculated may under-represent the true benefit of early endoscopy when compared with empiric antisecretory therapy." }, { "input": "Results from studies of patient satisfaction comparing early endoscopy with empiric medication therapy are conflicting.", "output": "In a primary care setting, patients undergoing early endoscopy were as satisfied as those receiving empiric antisecretory therapy." }, { "input": "Results from studies of patient satisfaction comparing early endoscopy with empiric medication therapy are conflicting.", "output": "In a trial of 414 patients randomized after referral to specialty care, patients in the early endoscopy group were more satisfied with their medical care than those receiving empiric antisecretory therapy (RR=0.13; 95% CI, 0.06-0.29)." }, { "input": "Though formal cost analyses are not available, a strategy using \"test and treat\", as opposed to early endoscopy, results in significantly fewer endoscopies, which when formally evaluated, may translate into a more cost-effective strategy of care.", "output": "A subgroup analysis reported on 3 RCTs from both primary and secondary settings with 931 patients comparing H pylori \"test and treat\" to initial endoscopy. It found no significant difference in symptom reduction (RR=1.06; 95% CI, 0.98-1.26)." }, { "input": "Though formal cost analyses are not available, a strategy using \"test and treat\", as opposed to early endoscopy, results in significantly fewer endoscopies, which when formally evaluated, may translate into a more cost-effective strategy of care.", "output": "A subgroup analysis of 4 trials from the Cochrane review (1 from primary care) demonstrated a significant reduction of the number of endoscopies among patients receiving \"test and treat\" care vs those receiving early endoscopy (RR=0.23; 95% CI, 0.12-0.44). In the long-term follow-up study, fewer antisecretory medication prescriptions were needed by those patients in the \"test and treat\" group (P=.047)." }, { "input": "Long-term follow-up suggests that patients receiving \"test and treat\" therapy may require fewer antisecretory medication prescriptions compared with patients receiving early endoscopy.", "output": "A follow-up study of 1 trials included in a Cochrane systematic review reported on outcomes of a \"test and treat\" vs early endoscopy strategy at 6 years. There was no difference in days without symptoms demonstrated between the 2 groups (mean difference=0.05; 95% CI, -0.03 to 0.14 days). Self-reported symptom tracking and a poor response rate (62%) to patient questionnaires reduces the strength of this study's conclusions. Formal cost-effective analyses comparing the \"test and treat\" with early endoscopy strategy have not been done. A subgroup analysis of 4 trials from the Cochrane review (1 from primary care) demonstrated a significant reduction of the number of endoscopies among patients receiving \"test and treat\" care vs those receiving early endoscopy (RR=0.23; 95% CI, 0.12-0.44). In the long-term follow-up study, fewer antisecretory medication prescriptions were needed by those patients in the \"test and treat\" group (P=.047)." }, { "input": "Patients with diabetes who take thiazolidinediones (TZDs) have a higher incidence of congestive heart failure (CHF) than those who do not; the incidence of CHF is similar with the use of pioglitazone (Actos), troglitazone (Rezulin), or rosiglitazone (Avandia).", "output": "A retrospective cohort study of health insurance claims compared the incidence of CHF among 5441 patients with diabetes who had taken TZDs (rosiglitazone, troglitazone, or pioglitazone) vs 28,103 who had not. Patients were allowed other oral agents and insulin, and they were followed for up to 6 years. The TZD group had more patients on insulin and with pre-existing comorbidities. Based on Kaplan-Meier estimates, which control for censored information, the incidence of new heart failure at 40 months was 8.2% in the TZD group and 5.3% in the non-TZD group (number needed to harm [NNH]=34.5). Using a multivariate analysis that controlled for the coadministration of insulin, the hazard ratio for TZD use was 1.76 (95% confidence interval [CI], 1.43-2.17). The incidence of CHF was 3.24% in the troglitazone group (n=1665), 2.39% in the rosiglitazone group (n=1882), and 1.63% in the pioglitazone group (n=1347). The difference in these rates is not statistically significant. Of the 28,103 patients not on a TZD, 1.41% developed heart failure. Individual agents were not compared with placebo." }, { "input": "However, patients on regimens that include pioglitazone but not insulin have lower rates of CHF than those taking insulin but not pioglitazone.", "output": "Another manufacturer-sponsored retrospective cohort study of pioglitazone analyzed insurance claims data to compare the incidence of CHF among 1668 adult patients taking pioglitazone (and possibly other medications, but not insulin) vs 1668 adult patients taking insulin (and possibly other medications, but not a TZD). The 2 groups were matched in terms of comorbid conditions, but statistical analysis did not take disease severity into account. The incidence of CHF was 2% of pioglitazone users compared with 4% of patients using insulin (NNH for insulin=50). In addition, CHF-related hospitalizations were 0.7% for CHF in the pioglitazone group vs 2.5% in the insulin group (NNH for insulin=55). Both of these findings are statistically significant." }, { "input": "Still, patients starting any TZD should be warned of the possibility of CHF and should be monitored for its development. TZDs are contraindicated for patients with class III and IV CHF.", "output": "The American Diabetes Association/American Heart Association recommends that patients be evaluated for heart disease or heart failure before starting TZD therapy and monitored for symptoms thereafter. Patients who are at risk for developing CHF, who already have New York Heart Association class I or II CHF, or who take insulin should begin TZD therapy with low doses that are titrated up gradually. The US Food and Drug Administration has not approved TZDs for patients with class III or IV CHF, as there are no studies in these populations." }, { "input": "other", "output": "A manufacturer-sponsored study that combined data from 4 separate unpublished randomized controlled trials compared the incidence of CHF at 1 year for patients treated with pioglitazone (as monotherapy and in combination with other oral agents) with those treated only with other oral agents. Cardiac failure was noted in 12 of 1857 in the pioglitazone group vs 10 of 1856 subjects in the non-pioglitazone groups (not statistically significant). The paper did not comment on how the patients were recruited, how outcomes were measured, or why the 4 original studies were not published." }, { "input": "No examination technique objectively proves malingering.", "output": "The American Medical Association published the Guides to the Evaluation of Permanent Impairment, which states, \"Confirmation of malingering is extremely difficult and generally depends on intentional or inadvertent surveillance.\"." }, { "input": "No examination technique objectively proves malingering.", "output": "The 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines malingering as \"the intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives such as avoiding military duty, avoiding work, obtaining financial compensation, evading criminal prosecution, or obtaining drugs.\" Malingering is not considered a mental disorder because symptoms are intentionally produced for external incentives. No physical exam maneuver can determine a patien' external incentives. Traditionally, a physician uses certain exam techniques to determine if symptoms are of functional, or nonorganic, origin. Both terms denote the absence of a structural or physiological source for the phenomena, and include malingering and mental disorders such as factitious disorder, conversion disorder, and somatoform disorders. Our literature search only found studies concerning the detection of nonorganic causes of back pain, paralysis, and sensory loss." }, { "input": "Waddell's signs are associated with poor treatment outcomes but cannot discriminate organic from nonorganic causes.", "output": "Several exam tests are commonly thought to detect nonorganic causes of low back pain. Gordon Waddell described 8 signs in 5 categories used to \"identify [back pain] patients who require more detailed psychological assessment.\"." }, { "input": "Waddell's signs are associated with poor treatment outcomes but cannot discriminate organic from nonorganic causes.", "output": "A systematic review critiqued 60 studies of Waddell's signs published between 1980 and 2000. The authors performed a thorough database search, including hand searches of key pain journals, meeting abstracts, and textbooks. The majority of the reviewed studies were small and of lower quality. The review found little evidence on test-retest or interrater reliability. There was consistent evidence that Waddell's signs are associated with poorer treatment outcomes and generally consistent evidence that they are not associated with secondary gain and cannot discriminate organic from nonorganic problems." }, { "input": "Hoover's and the Abductor sign indicate nonorganic paralysis.", "output": "A small, diagnostic case-control study of Mankopf's test, which is based on the theory that pain increases heart rate, investigated 20 chronic low back pain patients considered nonorganic vs 20 pain-free controls using mechanical pain stimulus applied to subjects' fingers. There was no significant difference in heart rate response between groups, and no significant effect of pain on heart rate in either group. The authors did not define their criteria for determining patients' back pain as non-organic, nor did they include patients with low back pain caused by an identifiable pathology. There was no mention of blinding. This literature search found no published studies of McBride's test, where the patient's refusal to stand on the unaffected leg and flex the affected leg to the chest determines a feigned radiculopathy." }, { "input": "Hoover's and the Abductor sign indicate nonorganic paralysis.", "output": "A small, diagnostic case-control study of Mankopf's test, which is based on the theory that pain increases heart rate, investigated 20 chronic low back pain patients considered nonorganic vs 20 pain-free controls using mechanical pain stimulus applied to subjects' fingers. There was no significant difference in heart rate response between groups, and no significant effect of pain on heart rate in either group. The authors did not define their criteria for determining patients' back pain as non-organic, nor did they include patients with low back pain caused by an identifiable pathology. There was no mention of blinding. This literature search found no published studies of McBride's test, where the patient's refusal to stand on the unaffected leg and flex the affected leg to the chest determines a feigned radiculopathy." }, { "input": "Hoover's and the Abductor sign indicate nonorganic paralysis.", "output": "A few tests attempt to detect nonorganic causes of paralysis. In Hoover's test, a patient is asked to alternately press down with the paralyzed leg and raise the unaffected leg to resistance, while the hand of the examiner cups the heel of the affected leg." }, { "input": "Hoover's and the Abductor sign indicate nonorganic paralysis.", "output": "In a diagnostic case-control study, the single author tested 33 patients from his practice, 17 with organic paresis, and 16 with nonorganic paresis. The author differentiated organic from nonorganic paresis by history, physical exam, and various imaging studies with no independent assessment. He reported his test as 100% accurate. We did not find any published studies of the Arm Drop test, where feigned paralysis of an upper extremity is tested by holding the arm over the face of the supine patient and letting go." }, { "input": "Tacrolimus 0.1% (Protopic) appears to be both safe and effective in treating eczema in adults and children.", "output": "A total of 3 trials (732 patients) compared tacrolimus 0.1% with potent topical corticosteroids (hydrocortisone butyrate 0.1%, beta-methasone valerate 0.1%) and found it to be as effective as the topical steroids after 3 weeks of application (number needed to treat [NNT]=6)." }, { "input": "Tacrolimus 0.1% (Protopic) appears to be both safe and effective in treating eczema in adults and children.", "output": "At both the 0.03% and 0.1% strengths, tacrolimus was found to be more effective than mild topical corticosteroids (hydrocortisone acetate 1%) in 2 studies enrolling a total of 1183 children with moderate to severe atopic dermatitis." }, { "input": "Tacrolimus 0.1% (Protopic) appears to be both safe and effective in treating eczema in adults and children.", "output": "NNT=5 for the tacrolimus 0.03%, and NNT= 3 for tacrolimus 0.1%." }, { "input": "Tacrolimus 0.1% (Protopic) appears to be both safe and effective in treating eczema in adults and children.", "output": "In a meta-analysis of 3 randomized studies of head-to-head comparison of pimecrolimus 1% and tacrolimus 0.03% or 0.1% among children and adults, tacrolimus ointment was more effective than pimecrolimus cream at the end of the study for adults (P<.0001), for children with moderate-to-severe disease (P=.04), in the combined analysis (P<.0001), and at week 1 for children with mild disease (P=.04). No significant difference was seen in the incidence of adverse effects, although more pimecrolimus-treated patients withdrew from the studies because of a lack of efficacy (P\u2264.03) or adverse events (P=.002; pediatric mild)." }, { "input": "In multiple studies, it has been as effective as potent topical corticosteroids and more effective than mild topical corticosteroids.", "output": "A total of 3 trials (732 patients) compared tacrolimus 0.1% with potent topical corticosteroids (hydrocortisone butyrate 0.1%, beta-methasone valerate 0.1%) and found it to be as effective as the topical steroids after 3 weeks of application (number needed to treat [NNT]=6)." }, { "input": "In multiple studies, it has been as effective as potent topical corticosteroids and more effective than mild topical corticosteroids.", "output": "NNT=5 for the tacrolimus 0.03%, and NNT= 3 for tacrolimus 0.1%." }, { "input": "In multiple studies, it has been as effective as potent topical corticosteroids and more effective than mild topical corticosteroids.", "output": "At both the 0.03% and 0.1% strengths, tacrolimus was found to be more effective than mild topical corticosteroids (hydrocortisone acetate 1%) in 2 studies enrolling a total of 1183 children with moderate to severe atopic dermatitis." }, { "input": "In multiple studies, it has been as effective as potent topical corticosteroids and more effective than mild topical corticosteroids.", "output": "In a meta-analysis of 3 randomized studies of head-to-head comparison of pimecrolimus 1% and tacrolimus 0.03% or 0.1% among children and adults, tacrolimus ointment was more effective than pimecrolimus cream at the end of the study for adults (P<.0001), for children with moderate-to-severe disease (P=.04), in the combined analysis (P<.0001), and at week 1 for children with mild disease (P=.04). No significant difference was seen in the incidence of adverse effects, although more pimecrolimus-treated patients withdrew from the studies because of a lack of efficacy (P\u2264.03) or adverse events (P=.002; pediatric mild)." }, { "input": "Pimecrolimus (Elidel) is more effective than placebo but less effective than potent topical corticosteroids.", "output": "A study compared pimecrolimus 1% with betamethasone valerate 0.1% (a potent corticosteroid) in a study of 87 patients. At the end of 3 weeks, the pimecrolimus 1% cream was significantly less effective than betamethasone valerate 0.1% (NNT=4)." }, { "input": "Pimecrolimus (Elidel) is more effective than placebo but less effective than potent topical corticosteroids.", "output": "In a meta-analysis of 3 randomized studies of head-to-head comparison of pimecrolimus 1% and tacrolimus 0.03% or 0.1% among children and adults, tacrolimus ointment was more effective than pimecrolimus cream at the end of the study for adults (P<.0001), for children with moderate-to-severe disease (P=.04), in the combined analysis (P<.0001), and at week 1 for children with mild disease (P=.04). No significant difference was seen in the incidence of adverse effects, although more pimecrolimus-treated patients withdrew from the studies because of a lack of efficacy (P\u2264.03) or adverse events (P=.002; pediatric mild). The meta-analysis concluded that pimecrolimus 1% was more effective compared with placebo, less effective than potent topical corticosteroids, and had yet to be studied in comparison with low-potency topical corticosteroids. Tacrolimus 0.1% was more effective than placebo, more effective than mild corticosteroids, and as effective as potent topical corticosteroids. It was noted that both these agents caused more burning of the skin than topical corticosteroids-pimecrolimus 1% compared with betamethasone valerate 0.1% (number needed to harm [NNH]=50); tacrolimus 0.1% compared with betamethasone valerate 0.1% and hydrocortisone butyrate 0.1% (NNH=3); and tacrolimus 0.03% compared with the mild corticosteroid hydrocortisone acetate 1% (NNH=10)." }, { "input": "Pimecrolimus (Elidel) is more effective than placebo but less effective than potent topical corticosteroids.", "output": "A randomized, double-blinded, multicenter trial compared the use of pimecrolimus 1% cream with 0.1% triamcinolone acetonide cream and 1% hydrocortisone acetate cream for 658 adults with moderate-to-severe atopic dermatitis. The majority of patients used either form of treatment for 1 year. Although long-term safety and tolerability were similar, topical corticosteroids were more efficacious (NNT=13)." }, { "input": "It is important to note that while the studies with the topical immunosuppressive agents included patients with mild to severe atopic dermatitis, none assessed the use of these agents on patients with steroid-refractory atopic dermatitis. The US Food and Drug Administration (FDA) has recommended limited use of these agents in atopic dermatitis because of potential cancer risk.", "output": "The FDA posted a Public Health Advisory and Alerts for Healthcare Professionals regarding the potential cancer risk from the use tacrolimus and pimecrolimus products when applied to the skin to treat atopic dermatitis. These creams will carry a \"black box\" warning regarding this potential risk. They recommended use only as a second-line therapy, at minimal amounts necessary, and for short periods of time, not continuously. They also recommended against their use for children aged <2 years and for people with diminished immune systems." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are the first-line agents for reducing the risk of diabetic nephropathy. For patients intolerant to these agents, non-dihydropyridine calcium antagonists (NDCAs), such as verapamil and diltiazem, are preferred agents to treat hypertension in those with diabetes who have proteinuria.", "output": "In small studies, weight loss, use of lipid-lowering agents, and smoking cessation all revealed reduction in proteinuria." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are the first-line agents for reducing the risk of diabetic nephropathy. For patients intolerant to these agents, non-dihydropyridine calcium antagonists (NDCAs), such as verapamil and diltiazem, are preferred agents to treat hypertension in those with diabetes who have proteinuria.", "output": "A meta-analysis of RCTs in patients with non-diabetic renal disease and RCTs or time-controlled studies with nonrandomized crossover design in patients with diabetic nephropathy revealed that dietary protein restriction effectively slows the progression of both diabetic and non-diabetic renal disease." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are the first-line agents for reducing the risk of diabetic nephropathy. For patients intolerant to these agents, non-dihydropyridine calcium antagonists (NDCAs), such as verapamil and diltiazem, are preferred agents to treat hypertension in those with diabetes who have proteinuria.", "output": "Selective beta-blockers like carvedilol appear to have fewer adverse metabolic effects, although the clinical significance of this difference is unclear. In insulin-dependent patients and patients with hypoglycemic episodes, peripheral vascular disease, and bronchospastic disease, beta-blockers should be used with caution." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are the first-line agents for reducing the risk of diabetic nephropathy. For patients intolerant to these agents, non-dihydropyridine calcium antagonists (NDCAs), such as verapamil and diltiazem, are preferred agents to treat hypertension in those with diabetes who have proteinuria.", "output": "In an RCT, amlodipine was no more effective than placebo in reducing proteinuria, while irbesartan effectively reduced end-stage renal disease (number needed to treat [NNT]=25 over 2.6 years)." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are the first-line agents for reducing the risk of diabetic nephropathy. For patients intolerant to these agents, non-dihydropyridine calcium antagonists (NDCAs), such as verapamil and diltiazem, are preferred agents to treat hypertension in those with diabetes who have proteinuria.", "output": "According to a systematic review, NDCAs cause a greater reduction in proteinuria compared with DCAs (dihydropyridine calcium antagonists, such as nifedipine and amlodipine), although there was no significant differences in lowering blood pressure. Mean change in proteinuria was +2% for DCAs and -30% for NDCAs (95% confidence interval [CI], 10%-54%; P=.01)." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are the first-line agents for reducing the risk of diabetic nephropathy. For patients intolerant to these agents, non-dihydropyridine calcium antagonists (NDCAs), such as verapamil and diltiazem, are preferred agents to treat hypertension in those with diabetes who have proteinuria.", "output": "In patients with type 2 diabetes and hypertension, macroalbuminuria, and serum creatinine >1.5 mg/dL, ARBs are effective in slowing the progression of diabetic nephropathy." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are the first-line agents for reducing the risk of diabetic nephropathy. For patients intolerant to these agents, non-dihydropyridine calcium antagonists (NDCAs), such as verapamil and diltiazem, are preferred agents to treat hypertension in those with diabetes who have proteinuria.", "output": "In hypertensive and normotensive patients with type 2 diabetes and microalbuminuria, ACE inhibitors have been well studied and found to reduce the risk of mortality, major cardiovascular events, and slow the progression to overt nephropathy, in patients with diabetes and at least 1 other risk factor." }, { "input": "Diuretics are effective in treating hypertension in patients with diabetes who are at high risk for cardiovascular disease. One study suggests sustained-release indapamide (a diuretic) is effective as first-line treatment in hypertensive patients with diabetes and proteinuria.", "output": "The NESTOR study-a multinational, multicenter, double-blind, randomized controlled, 2-parallel-groups study over 1 year-found that indapamide SR (a thiazide-type diuretic) treatment is as efficacious as enalapril in reducing proteinuria and lowering blood pressure." }, { "input": "Atenolol was as effective as the ACE inhibitor captopril in lowering the risk of diabetic microvascular and macrovascular complications, according to a substudy of the United Kingdom Prospective Diabetic Study (UKPDS).", "output": "In the UKPDS-Hypertension in Diabetes study (a multicenter randomized study in patients with type 2 diabetes that evaluated the effects of different levels of blood pressure control on diabetic complications), researchers found that patients assigned to the tight-control group (blood pressure goal <150/85 mm Hg) had 37% risk reduction in microvascular endpoints (nephropathy and advanced retinopathy). There was no difference in study endpoints between the ACE inhibitor captopril and the beta-blocker atenolol." }, { "input": "other", "output": "An average of 3 antihypertensive medications are needed to achieve currently recommended blood pressure goals in those with diabetes." }, { "input": "other", "output": "Diabetic nephropathy is the leading cause of end-stage renal disease, and it occurs in 20% to 40% of patients with diabetes. Optimal glycemic (glycosylated hemoglobin [HbA1c] level <7%) and hypertension control (<130/80 mm Hg) can prevent or slow the progression of diabetic nephropathy." }, { "input": "Universal neonatal hearing screening leads to both earlier detection and earlier treatment of infants with hearing loss.", "output": "Individually, OAE and ABR accurately diagnose neonatal hearing loss. One multicenter cohort of 2995 infants measured test performance of OAE and ABR against the gold standard (visual reinforcement audiometry performed at 8-12 months). The authors used a receiver operating characteristics (ROC) curve to plot speech awareness thresholds for both tests. When middle-ear pathology and progressive hearing loss were excluded, the area under the ROC curves for ABR and OAE were 0.91 and 0.94, respectively, indication that both tests had excellent test accuracy (a perfect test would have an area under the curve of 1.0)." }, { "input": "Universal neonatal hearing screening leads to both earlier detection and earlier treatment of infants with hearing loss.", "output": "The Cochrane Collaboration published a systematic review in which no studies were found that fulfilled the inclusion criteria to evaluate the effectiveness of universal hearing screening." }, { "input": "Universal neonatal hearing screening leads to both earlier detection and earlier treatment of infants with hearing loss.", "output": "A systematic review gathered studies comparing universal hearing screening with selective screening. Most included studies used a 2-stage universal screening protocol. Infants who failed initial testing were retested within 12 weeks. Testing methods included otoacoustic emissions (OAE) and auditory brainstem response (ABR). Infants who failed the second test were referred for audiological evaluation. Using these data, a hypothetical model was created, which found that 1441 newborns would need to be screened to diagnose 1 additional case of moderate-to-profound permanent hearing loss before 10 months of age (at cost of 200 extra referrals for false-positives). Sensitivity and specificity of the hypothetical model's 2-stage screening was 85% and 97%, respectively. The estimated positive predictive value was 6.7%." }, { "input": "Available evidence suggests early identification and intervention may improve language outcomes.", "output": "In a retrospective cohort study of 150 infants examining language outcomes, participants were grouped according to age at identification of hearing loss. All participants received comprehensive in-home language intervention services plus amplification devices. Of the 85 children with normal cognitive ability, the mean receptive and expressive language quotients at 13 to 36 months were higher in the early-identified group vs the late-identified group (receptive language quotients, 79.6 vs 64.6, P<.001; expressive language quotients, 78.3 vs 63.1, P<.001). Total language quotient was also higher in the early group (language quotients, 79 vs 64; P<.001)." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "Investigators found increased mortality from coronary artery disease to be associated with smoking (relative risk [RR]=5.0 [95% CI, 2.1-11.9]), hypercholesterolemia (RR=7.6 [95% CI, 3.0-19.5]) and hypertension (RR=6.7 [95% CI, 2.9-16.0])." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "Among 25,927 healthy men followed for an average of 8.4 years, the age-adjusted risk of death from all causes of those with asymptomatic ischemia increased from 2-fold (95% confidence interval [CI], 1.1-3.8, P=.03) with no risk factors to 4 (95% CI, 2.7-5.4) with 1 risk factor, 5 (95% CI, 3.3-6.9) with 2 risk factors, and 8 (95% CI, 5.4-12.8) with 3 or more risk factors (P<.0001)." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "Post-EST heart rate recovery and the Chronotropic Index are enhancements to the DTS." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "Patients with an intermediate-risk DTS, and normal or near-normal perfusion imaging without cardiomegaly, also comprised a low-risk group with 5-year cardiac survival of 99.5%." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "A prospective cohort study confirmed that a low-risk DTS was associated with high 5-year survival. Those with an intermediate- or high-risk DTS had corresponding survival rates of 90% and 65%, respectively. The DTS was further analyzed in a 5-year follow-up of 9454 patients, 88% of whom were low-risk (75% undergoing screening EST). Most patients (1406 of 1477) with ST-segment depression \u22651 mm had asymptomatic ischemia, only 71 having EST-induced angina. A low-risk DTS was associated with 98% survival, compared with 92% for patients with an intermediate- or high-risk DTS." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "A prospective cohort study confirmed that a low-risk DTS was associated with high 5-year survival-eg, 97% among 2758 patients (median age 49, 70% male, 30% prior myocardial infarction, 49% with angina)." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "A prospective cohort study of 613 patients with suspected coronary artery disease investigated EST duration, presence of angina, and ST-segment depression as predictors of mortality. Patients with asymptomatic ischemia (2 mm of ischemic depression) whose EST lasted 15 minutes (DTS=+5, low risk) had a 5-year cardiac mortality of less than 1%, compared with 2% for those whose EST was tolerated for only 7 minutes (DTS=-3, intermediate risk)." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "While risk factor reduction seems logical for all patients who have asymptomatic ischemia, actual evidence of benefit is limited. In the MRFIT study, high-risk men with asymptomatic ischemia were randomized to either usual care or a special intervention to reduce smoking, blood cholesterol, and diastolic blood pressure. The intervention group had lower cardiac mortality than men who received usual care (22 vs 53 per 1000, P<.002)." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "Smoking cessation is also important, associated with 41% lower mortality (95% CI, 20-57)." }, { "input": "Patients with intermediate- or high-risk Duke Treadmill score (DTS) on exercise stress testing (EST) should undergo myocardial perfusion imaging or exercise echocardiography, especially if they have abnormal values of Chronotropic Index or post-EST Heart Rate Recovery. For patients who have a low-risk DTS, the 4-year mortality is less than 1% to 2%; therefore, risk-factor reduction without further investigation is appropriate.", "output": "In 2 large prospective cohort studies, one of which documented abnormal EST in 17%, males who improved their fitness had 23% (95% CI, 4-42) and 44% (95% CI, 5-59) lower mortality over 18 years of mean follow-up, respectively." }, { "input": "Yes, testosterone therapy is effective in improving libido for elderly hypogonadal males.", "output": "Regardless of the route of administration gel, transdermal patch, or intramuscular injection, testosterone replacement results in improved libido and sexual function for men with low testosterone levels. The caveat, though, is that testosterone trials of older men are characterized by very small sample sizes n=10-50, disparate outcome measures, and the inclusion of men who were not uniformly testosterone-deficient and were asymptomatic." }, { "input": "Yes, testosterone therapy is effective in improving libido for elderly hypogonadal males.", "output": "The long-term benefit/risk ratio of testosterone replacement therapy for aging hypogonadal men is unknown." }, { "input": "Testosterone combined with estrogen can also improve libido for postmenopausal women, but it's not approved by the US Food and Drug Administration (FDA) for this purpose.", "output": "Up to 50% of postmenopausal women experience sexual dysfunction." }, { "input": "Testosterone combined with estrogen can also improve libido for postmenopausal women, but it's not approved by the US Food and Drug Administration (FDA) for this purpose.", "output": "Low testosterone level is correlated with a decreased coital frequency." }, { "input": "Testosterone combined with estrogen can also improve libido for postmenopausal women, but it's not approved by the US Food and Drug Administration (FDA) for this purpose.", "output": "Some studies suggest that testosterone at supraphysiological doses-by injections, implants, or pill in combination with estrogen-improves libido and sexual function." }, { "input": "Testosterone combined with estrogen can also improve libido for postmenopausal women, but it's not approved by the US Food and Drug Administration (FDA) for this purpose.", "output": "Testosterone's major adverse effects include virilization (oily skin, acne, hirsutism, alopecia, deep voice), liver toxicity, polycythemia, breast carcinoma, and unfavorable changes in cardiovascular risk markers such as reduction in high-density lipoprotein cholesterol or insulin sensitivity." }, { "input": "other", "output": "Sexual dysfunction includes desire, arousal, orgasmic, and sex pain disorders. In the US, 43% of women and 31% of men experience sexual dysfunction. Since sexual dysfunction increases with age, the prevalence will likely increase with the aging American population." }, { "input": "other", "output": "Although the decline is gradual, by the eighth decade 30% of men have total testosterone values in the hypogonadal range and 50% have low free testosterone values." }, { "input": "other", "output": "Several cross-sectional and longitudinal studies, demonstrate that serum total and free testosterone concentrations in men decline with age." }, { "input": "other", "output": "In randomized, placebo-controlled trials, of older men with low testosterone concentrations, testosterone administration was associated with a sustained increase in testosterone levels over 1 to 3 years." }, { "input": "They're useful in diagnosing Graves' disease and, to a lesser extent, autoimmune thyroid disease; they can also help predict hypothyroidism. thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves' disease by a moderate to large degree.", "output": "In a study comparing AMA to TPOAb, the thyroid antibody test results of 32 healthy patients were compared with those of 262 clinic patients. In those with known thyroid dysfunction, TPOAb was found to be a more sensitive assay than AMA for autoimmune thyroid disorders. The sensitivity of TPOAb levels >3.1 U/mL was 88.1%; AMA sensitivity was 70.2% (P<.001)." }, { "input": "They're useful in diagnosing Graves' disease and, to a lesser extent, autoimmune thyroid disease; they can also help predict hypothyroidism. thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves' disease by a moderate to large degree.", "output": "One study of 235 people in a university endocrinology department found that a TPOAb level >190 U/mL yielded an LR+ of 10.75 and an LR- of 0.15 for chronic autoimmune (Hashimoto's) thyroiditis [CAHT]; the AMA-positive sera yielded an LR+ of 13.67 and an LR- of 0.19. Both TPOAb and AMA test characteristics were highly associated with CAHT (P<.001)." }, { "input": "They're useful in diagnosing Graves' disease and, to a lesser extent, autoimmune thyroid disease; they can also help predict hypothyroidism. thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves' disease by a moderate to large degree.", "output": "A cross-sectional study of 267 Singaporean patients with previously diagnosed thyroid disorders measured TRAb, AMA, and thyroglobulin. TRAb levels >10 U/L were found to have a positive likelihood ratio (LR+) of 13 and a negative likelihood ratio (LR-) of 0.2 for Graves' disease." }, { "input": "A positive or negative thyroid peroxidase antibody (TPOAb) test increases or decreases the probability of autoimmune thyroid disease by only a small to moderate degree.", "output": "A cross-sectional study (National Health and Nutrition Examination Survey [NHANES III]) evaluated the presence of thyroid antibodies in 17,353 people representing the geographic and ethnic distribution of the United States, 95% of whom were categorized as free of thyroid disease. The study found that TPOAb was more sensitive than thyroglobulin for diagnosing nonspecific thyroid disease. The diagnosis of thyroid disease was based on abnormal TSH and free T4 levels. Abnormally high levels of TPOAb had an LR+ of 4.3 and LR- of 0.6 (P<.0001) for thyroid disease, compared with an LR+ of 3.4 and LR- of 0.7 (P<.01) for abnormally elevated thyroglobulin." }, { "input": "Thyroid-stimulating hormone (TSH) levels >2 mU/L, although still in the normal range, can be followed up with TPOAb testing to determine whether the patient has an increased probability of developing hypothyroidism.", "output": "In the early 1970s, a cohort study of 2779 adults from Great Britain attempted to establish the incidence of thyroid disease in the general population by measuring TSH and TPOAb. Twenty years later, investigators restudied 1708 people from the original sample to determine the incidence of hypothyroidism and the prognostic value of these 2 biochemical markers for its development. At follow-up, the definition of a new case of hypothyroidism was based on an \"intention to treat by the general practitioner by meeting clear biochemical criteria and/or symptoms.\" The initial presence of abnormally high serum TPOAb levels and TSH >2.0 mU/L predicted a 4.3% annual risk of developing hypothyroidism compared with a 2.6% annual risk with serum TSH >6.0 mU/L alone in women. This risk was not estimated for men because of the small number of cases." }, { "input": "Thyroid-stimulating hormone (TSH) level is the preferred test for initial evaluation of suspected primary hypothyroidism.", "output": "In one study, no correlation was found between serum TSH and clinical and metabolic markers-such as clinical score, ankle reflex time, total cholesterol, and creatine kinase-when estimating the severity of primary thyroid failure." }, { "input": "Thyroid-stimulating hormone (TSH) level is the preferred test for initial evaluation of suspected primary hypothyroidism.", "output": "TSH had a high sensitivity (98%) and specificity (92%) when used to confirm thyroid disease in patients referred to a specialty endocrine clinic, but its positive predictive value is low when used as a screening test in primary care." }, { "input": "Thyroid-stimulating hormone (TSH) level is the preferred test for initial evaluation of suspected primary hypothyroidism.", "output": "Experts recommend TSH level as the most cost-effective initial laboratory test for suspected primary hypothyroidism." }, { "input": "If TSH is abnormal, a free thyroxine (T4) level will further narrow the diagnosis. Obtain a triiodothyronine (T3) level if TSH is undetectable and free T4 is normal. When assessing the adequacy of replacement therapy in primary hypothyroidism, the TSH is the most important parameter to monitor.", "output": "If TSH is elevated, a free T4 level can help differentiate between central hyperthyroidism and much more common peripheral hypothyroidism (99% of patients). A T3 level is necessary only if the TSH is undetectable and the free T4 is normal. Imaging the thyroid gland is reserved for evaluating structural abnormalities." }, { "input": "If TSH is abnormal, a free thyroxine (T4) level will further narrow the diagnosis. Obtain a triiodothyronine (T3) level if TSH is undetectable and free T4 is normal. When assessing the adequacy of replacement therapy in primary hypothyroidism, the TSH is the most important parameter to monitor.", "output": "In primary hypothyroidism, reassess TSH 6 weeks after the start of treatment or a change in replacement dose. This recommendation is based on the fact that levothyroxine has a half-life of about a week; a steady state would be achieved over the course of 5 half-lives. No direct patient-oriented evidence exists for this testing interval. Test free T4 if you suspect excessive replacement or noncompliance." }, { "input": "If TSH is abnormal, a free thyroxine (T4) level will further narrow the diagnosis. Obtain a triiodothyronine (T3) level if TSH is undetectable and free T4 is normal. When assessing the adequacy of replacement therapy in primary hypothyroidism, the TSH is the most important parameter to monitor.", "output": "A 2005 study suggested lowering the target TSH level for assessing adequate replacement in patients treated with standard levothyroxine because subtherapeutic T3 levels were found despite normal TSH levels in these patients." }, { "input": "If TSH is abnormal, a free thyroxine (T4) level will further narrow the diagnosis. Obtain a triiodothyronine (T3) level if TSH is undetectable and free T4 is normal. When assessing the adequacy of replacement therapy in primary hypothyroidism, the TSH is the most important parameter to monitor.", "output": "Once TSH is in the normal range, experts recommend assessing the level after 6 months and then annually." }, { "input": "Because TSH levels can't be used to monitor central hypothyroidism, use free T4 and T3 concentrations.", "output": "TSH can't be used to monitor therapy for central hypothyroidism. Follow both free T4 and T3 concentrations because elevated T3 levels, indicative of overtreatment, can occur even when free T4 measurements are normal in these patients." }, { "input": "Antidepressants and lamotrigine are effective. Atypical antipsychotics, lithium, and anticonvulsants also may help. Antidepressants, including tricyclics and selective serotonin reuptake inhibitors (SSRIs), are useful adjuncts in short-term treatment of bipolar depression and have low rates of inducing mania.", "output": "The American Psychiatric Association APA recommends lithium or lamotrigine as first-line treatment for acute bipolar depression. Antidepressant monotherapy is not recommended. Interpersonal therapy, cognitive behavior therapy, and psychosocial interventions may be useful additions." }, { "input": "Antidepressants and lamotrigine are effective. Atypical antipsychotics, lithium, and anticonvulsants also may help. Antidepressants, including tricyclics and selective serotonin reuptake inhibitors (SSRIs), are useful adjuncts in short-term treatment of bipolar depression and have low rates of inducing mania.", "output": "A systematic review of 4 RCTs (662 patients) found that antidepressants-fluoxetine, paroxetine, imipramine, tranylcypromine, and selegiline (ldeprenyl)-significantly increased treatment response for bipolar type I or II disease at 4 to 10 weeks. About 75% of patients received a concurrent mood stabilizer or an atypical antipsychotic (relative risk [RR]=1.86; 95% confidence interval [CI], 1.49-2.30; number needed to treat=4.2; 95% CI, 3.2-6.4).1 Although a few head-to-head comparisons suggested that some SSRIs and monoamine oxidase inhibitors are more effective first-line agents than tricyclics, the differences were not significant." }, { "input": "Lamotrigine is beneficial for both acute treatment of bipolar depression and prevention of recurrent episodes.", "output": "One systematic review identified a single RCT of 195 adults with type I bipolar disorder who were experiencing a major depressive episode. Lamotrigine (200 mg/day) significantly improved patient scores on the Montgomery-Asberg Depression Rating Scale (MADRS; P<.05) and increased the response to treatment (measured by mean change in scores on the Clinical Global Impression Scale; P<.05). Response rates were 51% (200 mg/day), 41% (50 mg/day), and 26% (placebo; P<.05)." }, { "input": "Some atypical antipsychotics alone effectively treat acute bipolar depression.", "output": "Two 8-week, double-blind RCTs assessed the efficacy of quetiapine in treating bipolar I or II depression. The first studied 542 outpatients with acute bipolar depression, randomly assigned to quetiapine, 300 mg/day; quetiapine, 600 mg/day; or placebo. Mean changes in MADRS total scores were the primary outcome measures. Quetiapine showed dose-dependent improvement in MADRS total scores after the first week (P<.001), with a moderate clinical effect size of 0.67 at 300 mg/day and a large effect size of 0.81 at 600 mg/day." }, { "input": "Some atypical antipsychotics alone effectively treat acute bipolar depression.", "output": "In an RCT, 509 patients were randomized to double-blind treatment with quetiapine (300 or 600 mg/day) or placebo and assessed weekly with the MADRS and Hamilton Depression Rating Scale (HDRS).6 Improvements in mean HDRS scores were greater with both quetiapine doses than with placebo (P<.001). Clinical effect sizes were moderate at week 8 (0.61 at 300 mg/day and 0.54 at 600 mg/day), although dose titration effects were not established." }, { "input": "Some atypical antipsychotics in combination with antidepressants effectively treat acute bipolar depression.", "output": "A secondary analysis assessed health-related quality of life based on the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and Quality of Life in Depression Scale (QLDS). OFC treated patients showed greater improvements in general health perception, social functioning, vitality, and a number of other depression markers compared with both the olanzapine monotherapy and placebo groups. However, the SF-36 and QLDS were administered in only 7 of 13 participating countries, possibly skewing results because of variations between countries in sociocultural factors and quality-of-life issues that may also affect mental health." }, { "input": "Some atypical antipsychotics in combination with antidepressants effectively treat acute bipolar depression.", "output": "In a double-blind, 8-week RCT involving 84 international sites, 833 adults with bipolar I depression (MADRS score of \u226520) received olanzapine, an olanzapinefluoxetine combination (OFC), or placebo. Although the trial had a low completion rate (38.5%) and no fluoxetine monotherapy arm, the olanzapine and OFC groups showed improvement in depressive symptoms (defined as \u226550% improvement in the MADRS total score). The olanzapine response rate was 39% (P<.02; odds ratio [OR]=1.46; 95% CI, 1.07-2.00); the OFC response rate was 56.1% (P<.001; OR=2.92; 95% CI, 1.23-3.26). The OFC group showed statistically greater improvement than the olanzapine group." }, { "input": "Lithium and anticonvulsants such as valproate also may be useful.", "output": "The American Psychiatric Association APA recommends lithium or lamotrigine as first-line treatment for acute bipolar depression. Antidepressant monotherapy is not recommended. Interpersonal therapy, cognitive behavior therapy, and psychosocial interventions may be useful additions." }, { "input": "Lithium and anticonvulsants such as valproate also may be useful.", "output": "A recent RCT demonstrated no improvement in bipolar depression using paroxetine or bupropion in conjunction with mood stabilizers (primarily lithium or valproate) compared with mood stabilizers alone. However, the trial also showed no difference in treatment-emergent mania between groups." }, { "input": "Yes, treatment can increase a child's final height. Injections of recombinant human growth hormone (rGH) at least 3 times a week for 4 to 6 years add 3.7 to 7.5 cm to final height in children between 8 and 16 years of age with idiopathic short stature.", "output": "Intent-to-treat analysis of patients who received at least 6 months of treatment with final height assessment revealed a positive treatment effect on height (SDS) of 0.51. This is the equivalent of a 3.7-cm difference in final height for the treatment group compared with the placebo group (P<.02; 95% CI, 0.10-0.92 SDS)." }, { "input": "Yes, treatment can increase a child's final height. Injections of recombinant human growth hormone (rGH) at least 3 times a week for 4 to 6 years add 3.7 to 7.5 cm to final height in children between 8 and 16 years of age with idiopathic short stature.", "output": "A double-blind, placebo-controlled RCT published after the Cochrane review assessed final height in a peripubertal, predominantly male population with non-growth-hormone-deficient short stature. Inclusion criteria comprised a height SDS <-2.50, but 6 participants with a height SDS between -2.25 and -2.5 were included because of a change in the criteria. Sixty-eight children were initially randomized. Of the 37 randomized to treatment, 22 were available for final height measurement. The placebo group had a higher dropout rate-only 11 of 31 patients were available for final height measurement. In an attempt to reduce the dropout rate, the final height criterion for discontinuation of injections was changed from <0.5 to <1.5 cm per year. The mean age of the treatment group was 12.5 years at initiation of treatment; average duration of treatment was 4.6 years." }, { "input": "Yes, treatment can increase a child's final height. Injections of recombinant human growth hormone (rGH) at least 3 times a week for 4 to 6 years add 3.7 to 7.5 cm to final height in children between 8 and 16 years of age with idiopathic short stature.", "output": "A 2003 Cochrane systematic review identified 9 RCTs that evaluated treatment with rGH in children with idiopathic short stature. Only 1 used near final height as its main outcome. Inclusion criteria for this RCT comprised prepubertal girls in the bottom third percentile for height without a known cause. Of the 40 subjects, only 18 provided consent for randomization. Seven of the 10 girls randomized to the treatment group and 6 of the 8 randomized to the control group completed the study to final height measurement. The average age of the treated girls at the start of therapy was 8.07 years; the average duration of treatment was 6.2 years. All participants reached stage 4 breast development, menarche, and a growth velocity of <2 cm per year in the year preceding final height measurement. Mean final height in the treatment group was 155.3 cm compared to 147.8 cm in the control group-a 7.5-cm difference (95% confidence interval [CI], 3.14-11.86 cm)." }, { "input": "other", "output": "rGH has been available since 1985. The Food and Drug Administration has approved it for such conditions as growth hormone deficiency, chronic renal insufficiency, Turner syndrome, small size for gestational age, and Prader-Willi syndrome. The use of rGH to treat idiopathic short stature introduces many clinical, economic, and ethical questions. We have attempted to discern the clinical effectiveness of treatment by focusing on RCTs of rGH therapy while leaving the other substantive issues unexplored." }, { "input": "other", "output": "Final height is arguably the most important outcome measure for the effects of rGH and may be represented as actual height or as a standard deviation score (SDS)-actual height minus mean height for age divided by standard deviation of height for age. This measure standardizes height comparisons for different age groups and is comparable to the percentile values on growth charts." }, { "input": "No, there is no well-tested, easily administered screening tool to detect drug-seeking behaviors in primary care patients taking long-term opioids or being considered for such therapy.", "output": "The ABC was tested in a population that was predominantly male." }, { "input": "No, there is no well-tested, easily administered screening tool to detect drug-seeking behaviors in primary care patients taking long-term opioids or being considered for such therapy.", "output": "The ORT study lacked standard measures of addiction." }, { "input": "No, there is no well-tested, easily administered screening tool to detect drug-seeking behaviors in primary care patients taking long-term opioids or being considered for such therapy.", "output": "The investigators who validated or evaluated the SOAPP-R and ORT included only patients at chronic pain clinics, so the instruments may not be applicable to patients in primary care settings." }, { "input": "For primary care providers, a useful screening tool for predicting drug-seeking behaviors is the Screener and Opioid Assessment for Patients with Pain (SOAPP-R).", "output": "The Screener and Opioid Assessment for Patients with Pain (SOAPP-R) is a 24-item, self-administered questionnaire that stratifies patients being considered for opioid therapy into lower or higher risk for future opioid-related aberrant behaviors. Each item queries frequency of behaviors and emotions consistent with opioid misuse and can be scored as 0 (never) to 4 (very often). The items on the SOAPP-R were developed by a consensus panel of pain and addiction experts. In a multidisciplinary pain center study, the SOAPP-R was administered to 283 chronic pain patients who were followed for 5 months. At a cutoff score of \u226518, the test had a positive likelihood ratio (LR+) of 3.80 and a negative likelihood ratio (LR-) of 0.29 for detecting opioid misuse. At this cutoff, the SOAPP-R was 81% sensitive and 68% specific for predicting patients at high risk for aberrant behavior." }, { "input": "Drug-seeking behavior in patients on long-term opioid therapy can be monitored with the Current Opioid Misuse Measure (COMM).", "output": "The Current Opioid Misuse Measure (COMM) is used to monitor aberrant behaviors in patients on opioid therapy. Scoring for the 17-item, self-administered test is similar to the SOAPP-R. In a study of 86 patients at a multidisciplinary pain center, a score of \u22659 detected opioid misuse with an LR- of 0.08 and an LR+ of 3.48, at a sensitivity of 77% and specificity of 66%." }, { "input": "No randomized controlled trials exist that identify and treat hyperlipidemia for advanced elderly patients (age >80 years). Expert and consensus guidelines state that hyperlipidemia found in any patient with coronary artery disease (CAD), or at risk of CAD, should be treated irrespective of age; however, evidence is limited to support lowering lipids for advanced elderly patients with and without known CAD.", "output": "National Cholesterol Education Program Adult Treatment Panel III guidelines outline risk identification and management of hyperlipidemia in all age groups with no exceptions noted for the very elderly." }, { "input": "No randomized controlled trials exist that identify and treat hyperlipidemia for advanced elderly patients (age >80 years). Expert and consensus guidelines state that hyperlipidemia found in any patient with coronary artery disease (CAD), or at risk of CAD, should be treated irrespective of age; however, evidence is limited to support lowering lipids for advanced elderly patients with and without known CAD.", "output": "Two cohort studies found that low cholesterol was related to all-cause mortality, even when adjusted for health status and indicators of frailty." }, { "input": "No randomized controlled trials exist that identify and treat hyperlipidemia for advanced elderly patients (age >80 years). Expert and consensus guidelines state that hyperlipidemia found in any patient with coronary artery disease (CAD), or at risk of CAD, should be treated irrespective of age; however, evidence is limited to support lowering lipids for advanced elderly patients with and without known CAD.", "output": "A meta-analysis showed an inverse relationship between total serum cholesterol and all-cause mortality for people aged 80 and above, raising the possibility that lowering cholesterol may be detrimental in this age group." }, { "input": "The 4-item Primary Care Post-Traumatic Stress Disorder screen (PC-PTSD) is a simple and effective tool to identify symptoms of post-traumatic stress disorder (PTSD) in primary care patients.", "output": "Detailed diagnostic interviews and assessments are generally impractical in primary care. Brief, easy-to-complete screening tools can help clinicians identify patients with primary symptoms of PTSD." }, { "input": "The 4-item Primary Care Post-Traumatic Stress Disorder screen (PC-PTSD) is a simple and effective tool to identify symptoms of post-traumatic stress disorder (PTSD) in primary care patients.", "output": "The PC-PTSD is a 4-item screen that assesses the underlying characteristics specific to PTSD: re-experiencing, numbing, avoidance, and hyperarousal.It's designed to be understandable to patients with an eighth-grade reading level and has been validated in a Department of Veterans Affairs (VA) primary care population (N=188). With a cutoff score of 3, the PCPTSD has a sensitivity of 78% and specificity of 87%, compared with the gold-standard Clinician-Administered PTSD Scale (CAPS)." }, { "input": "The 7-item Breslau screen also predictably identifies patients with PTSD symptoms.", "output": "Breslau's 7-item screening scale is another empirically tested, brief, simple means of identifying PTSD symptoms in primary care patients. The screen has been validated in a VA primary care clinic (N=134). With a cutoff score of 4, it has a sensitivity of 85% and specificity of 84%, yielding a positive predictive value of 71% and negative predictive value of 98%. The likelihood of a score <3 is 0.04 and a score >5 is 13.5. Scores of 3 to 5 have an indeterminate likelihood value (1.8). Patients with a positive screen should undergo further evaluation by a mental health provider." }, { "input": "other", "output": "About 8% of the US population will develop symptoms of PTSD at some point in their lives-usually as the result of a traumatic event, such as combat, a natural disaster, accident, or physical or sexual assault." }, { "input": "other", "output": "Positive responses to the PC-PTSD warrant further evaluation of trauma symptoms and completion of the CAPS by a mental health provider to determine whether the patient may have PTSD or other trauma-related problems." }, { "input": "other", "output": "Primary care settings tend to be the principal point of contact for patients with PTSD, although such patients rarely identify themselves as suffering from the disorder." }, { "input": "other", "output": "The CAPS and the civilian version of the PTSD Symptom Checklist (PCL-C), both with 17 items, are widely used as \"screens\" for PTSD. However, their length and the recommendation that they be administered by a mental health professional make them cumbersome and impractical for use in primary care." }, { "input": "Initial treatment options comprise rest, cervical immobilization, anti-inflammatory drugs (nonsteroidal and steroidal), pain relievers including muscle relaxants and antiepileptics, and physical therapy.", "output": "Initial treatments for cervical radiculopathy encompass: rest, cervical immobilization, NSAIDs, analgesics, including muscle relaxants and antiepileptics), physical therapy." }, { "input": "Initial treatment options comprise rest, cervical immobilization, anti-inflammatory drugs (nonsteroidal and steroidal), pain relievers including muscle relaxants and antiepileptics, and physical therapy.", "output": "A series of 32 patients who had failed conventional treatment showed a 62% response-defined as \"good or excellent\" pain relief-to epidural steroid injection at 14 days. At 6 months, 53% continued to report good or excellent pain relief. No significant side effects occurred. The 44% of patients who didn't report success also didn't report any further deterioration." }, { "input": "Initial treatment options comprise rest, cervical immobilization, anti-inflammatory drugs (nonsteroidal and steroidal), pain relievers including muscle relaxants and antiepileptics, and physical therapy.", "output": "One case series of cortisone epidural injections reported 60% of patients (12 of 20) had good or excellent response at long-term follow-up (mean follow-up=21.2 months; range=2-45 months). Six of the 20 patients proceeded to surgery." }, { "input": "Initial treatment options comprise rest, cervical immobilization, anti-inflammatory drugs (nonsteroidal and steroidal), pain relievers including muscle relaxants and antiepileptics, and physical therapy.", "output": "3 RCTs showed no advantages (2 studies) or modest advantages (1 study) for cervical traction over placebo or standard physical therapy without traction. Each study defined improvement differently, but most patients in all groups showed improvement." }, { "input": "Initial treatment options comprise rest, cervical immobilization, anti-inflammatory drugs (nonsteroidal and steroidal), pain relievers including muscle relaxants and antiepileptics, and physical therapy.", "output": "A case series of patients treated specifically for cervical radiculopathy found that 10 of 11 patients who underwent physical therapy (including manual therapy, cervical traction, and strengthening exercises) were improved-defined as a self-report of being \"quite a bit better\"-at 6-month follow-up." }, { "input": "As many as 60% of patients who fail initial treatments report long-term pain relief with epidural corticosteroid injections.", "output": "One case series of cortisone epidural injections reported 60% of patients (12 of 20) had good or excellent response at long-term follow-up (mean follow-up=21.2 months; range=2-45 months). Six of the 20 patients proceeded to surgery." }, { "input": "As many as 60% of patients who fail initial treatments report long-term pain relief with epidural corticosteroid injections.", "output": "A series of 32 patients who had failed conventional treatment showed a 62% response-defined as \"good or excellent\" pain relief-to epidural steroid injection at 14 days. At 6 months, 53% continued to report good or excellent pain relief. No significant side effects occurred. The 44% of patients who didn't report success also didn't report any further deterioration." }, { "input": "Surgery to reduce nerve compression can improve pain and function, but has risks.", "output": "A Cochrane review found only one RCT (N=81) that compared surgery with conservative treatment (physiotherapy and the cervical collar). Twenty patients crossed over to another treatment, including 3 surgical patients who improved before surgery and 11 who did postop physiotherapy. Patients were still analyzed by intention to treat, however. The surgery group showed greater pain improvement at 3 months, as assessed by visual analogue scale (0 to 100), than the physiotherapy group (mean difference [MD]=-14; 95% confidence interval [CI], -27.84 to -0.16) and the cervical collar (MD=-21; 95% CI, -33.32 to -8.68). At 1 year, however, no difference was seen between surgery and physiotherapy (MD=-9; 95% CI, -23.39 to 5.39) or between surgery and the cervical collar (MD=-5; 95% CI, -18.84 to 8.84). Laminectomy to reduce nerve compression may alleviate pain and improve function, but it has risks. Surgical procedures for cervical radiculomyelopathy have reported death rates of 0% to 1.8%; nonfatal complications occurred in 1% to 8% of patients." }, { "input": "The natural course of cervical radiculopathy may be spontaneous resolution of symptoms within 5 years in 75% of cases.", "output": "A 1994 community-based epidemiological survey of 561 patients showed that 75% of patients had a spontaneous symptomatic improvement within 5 years. Earlier studies (6 studies from 1957 to 1972) concluded that untreated patients wouldn't necessarily develop progressive disability and that patients with severe disability sometimes improve without treatment." }, { "input": "Ovarian cancer screening using pelvic examination, CA-125 serum tumor marker, transvaginal ultrasound (TVU), or any combination of tests is not recommended in average-risk women, or in women with only 1 first-degree relative with ovarian cancer.", "output": "Screening brings forward the diagnosis of ovarian cancer by about 8 months, but raises the possibility that earlier diagnosis may simply reflect a lead-time bias without any actual improvement in outcome." }, { "input": "Ovarian cancer screening using pelvic examination, CA-125 serum tumor marker, transvaginal ultrasound (TVU), or any combination of tests is not recommended in average-risk women, or in women with only 1 first-degree relative with ovarian cancer.", "output": "A large pilot study showed improved median survival in a screened group compared with a control group (72.9 months vs 41.8 months), but there was no significant difference in either mortality from ovarian cancer or all-cause mortality." }, { "input": "Ovarian cancer screening using pelvic examination, CA-125 serum tumor marker, transvaginal ultrasound (TVU), or any combination of tests is not recommended in average-risk women, or in women with only 1 first-degree relative with ovarian cancer.", "output": "Before screening is implemented, there should be evidence that early detection and treatment of the disease results in improved outcomes. Several ongoing randomized controlled trials address screening of average-risk women, including one sponsored by the National Institutes of Health (NIH)." }, { "input": "Ovarian cancer screening using pelvic examination, CA-125 serum tumor marker, transvaginal ultrasound (TVU), or any combination of tests is not recommended in average-risk women, or in women with only 1 first-degree relative with ovarian cancer.", "output": "There is indirect evidence that early detection prolongs survival, as well as evidence that screening results in an increase in diagnosing a tumor at stage 1." }, { "input": "There is insufficient evidence to recommend for or against screening women with 2 or more first-degree relatives with ovarian cancer. A careful discussion of risks and benefits to screening is suggested, with referral to specialists as needed to assist in the decision-making.", "output": "An NIH Consensus Conference recommends comprehensive family history and annual pelvic exam for all women, referral to a specialist for risk counseling for women with 2 or more first-degree relatives, and annual screening with pelvic examination, CA-125, and TVS in women with known hereditary ovarian cancer syndrome." }, { "input": "There is insufficient evidence to recommend for or against screening women with 2 or more first-degree relatives with ovarian cancer. A careful discussion of risks and benefits to screening is suggested, with referral to specialists as needed to assist in the decision-making.", "output": "ACOG recommends an annual pelvic examination for all women as part of routine preventive care." }, { "input": "Treatment of otitis media with effusion (OME) with nasal steroids is not recommended.", "output": "The Canadian Task Force on Preventative Health Care found insufficient evidence to recommend screening for OME to prevent delayed language development." }, { "input": "Limited evidence exists that shows nasal steroids may increase the rate of resolution of OME in the short term, alone or in combination with antibiotics. However, within 3 to 12 weeks, resolution of OME with nasal steroids is no better than placebo.", "output": "The natural course of OME was observed in a longitudinal cohort study of 1439 children aged 2 years in the Netherlands. Single or recurrent flat screening tympanograms were noted in 20% and remitted spontaneously at a rate of 50% every 3 months. This prevalence and spontaneous resolution rate is consistent with other studies." }, { "input": "Limited evidence exists that shows nasal steroids may increase the rate of resolution of OME in the short term, alone or in combination with antibiotics. However, within 3 to 12 weeks, resolution of OME with nasal steroids is no better than placebo.", "output": "The Shapiro study enrolled children who had documented allergic rhinitis and OME with failure to respond to 4 weeks of oral antihistamine and decongestant therapy at time of entry. This was the only study with short-term follow-up comparing intranasal steroids with control. The odds ratio for OME persisting after 3 weeks was 2.12 (95% confidence interval [CI], 0.65-6.90)." }, { "input": "Limited evidence exists that shows nasal steroids may increase the rate of resolution of OME in the short term, alone or in combination with antibiotics. However, within 3 to 12 weeks, resolution of OME with nasal steroids is no better than placebo.", "output": "The Tracy study enrolled children with chronic OME referred to a chronic ear clinic from October to June. Inclusion criteria included 3 episodes of acute otitis media in the prior 6 months or 4 episodes in the prior 12 months. This was a randomized comparison study with 3 treatment arms: an active nasal spray group and 2 control groups. The odds ratio for OME persisting after short-term follow-up was 0.79 (95% CI, 0.20-3.19); after intermediate follow-up the odds ratio was 0.72 (95% CI, 0.21-2.44). This study, which included a symptom score after 3 months, favored treatment, with a weighted mean difference of -4.5, but with wide 95% CI of -10.28 to 1.28. An effect was demonstrated on clearing effusions in the short term, but the advantage appeared to vanish for the most part by 3 months. The study did not evaluate improvements in hearing." }, { "input": "Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine.", "output": "Typical trends suggest that glucosamine is superior to placebo for pain relief, and less effective but safer than nonsteroidal anti-inflammatory agents." }, { "input": "Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine.", "output": "Statistically significant differences exist in some subgroup analyses and secondary endpoints." }, { "input": "Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine.", "output": "When more higher-quality studies are analyzed, trends toward benefit and the effect sizes for glucosamine diminish but remain at aggregate values ranging from 0.26 to 0.44." }, { "input": "Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine.", "output": "Those problems account for the relatively low quality scores of the studies used in meta-analyses, particularly in earlier ones. Quality scores range from 12% to 52% of optimal and make any definitive conclusions suspect. The magnitude of the treatment effect is variable. Meta-analyses demonstrate aggregate treatment effects ranging from 0.36 to 1.02- where a small effect is 0.2, a moderate effect is 0.5, and a large effect is 0.8." }, { "input": "Glucosamine may provide some pain relief. Studies have shown varied results, ranging from glucosamine being superior or equivalent to other agents, to no difference between glucosamine and placebo. However, most of these studies have small sample sizes, short duration, and often other significant flaws. Meta-analyses of available studies suggest a trend toward benefit from glucosamine.", "output": "Identified flaws in the studies include small sample size, inconsistent diagnostic criteria, variable disease sites, differing routes of administration, inconsistent doses, compositions and forms of glucosamine, the brief durations of studies, and poorly defined endpoints." }, { "input": "Patients with mild to moderate mitral regurgitation should be assessed periodically for a worsening condition; those with severe mitral regurgitation should be monitored for development of congestive heart failure, atrial fibrillation, and decline in left ventricular ejection fraction or increase in left ventricular end-diastolic diameter.", "output": "Another cohort study of patients undergoing surgery for severe mitral regurgitation compared the outcomes of 199 patients with NYHA class I/II symptoms with those of 279 patients with NYHA class III/IV symptoms. Patients with NYHA class I/II had better operative outcomes (0.5% vs 5.4%) and better 5-year (90% vs 73%) and 10-year (76% vs 48%) survival than patients with more severe symptoms. In multivariate analysis, NYHA functional class remained inversely associated with survival." }, { "input": "Patients with mild to moderate mitral regurgitation should be assessed periodically for a worsening condition; those with severe mitral regurgitation should be monitored for development of congestive heart failure, atrial fibrillation, and decline in left ventricular ejection fraction or increase in left ventricular end-diastolic diameter.", "output": "A cohort compared the outcomes of patients undergoing early surgery (within 1 month of diagnosis) with those initially treated medically. Eight patients were excluded from this study because they were unsuitable candidates for surgery. The remaining 221 patients were followed based on their original group assignment of early surgery (63 patients) or medical management (158 patients). Patients undergoing early surgery were more likely to have symptoms at enrollment than those managed medically. Patients in the early surgery group had better 5-year (89% vs 78%) and 10-year (78% vs 65%; P<.05 for both comparisons) survival and were less likely to develop congestive heart failure or atrial fibrillation. These differences remained significant after multivariate adjustment for potential confounders." }, { "input": "Patients with mild to moderate mitral regurgitation should be assessed periodically for a worsening condition; those with severe mitral regurgitation should be monitored for development of congestive heart failure, atrial fibrillation, and decline in left ventricular ejection fraction or increase in left ventricular end-diastolic diameter.", "output": "A well-done, prospective cohort study enrolled 229 patients (mean age, 66; 70% male) diagnosed with severe mitral regurgitation. Overall 10-year mortality was 43%. Older patients, those with New York Heart Association (NYHA) class III or IV heart failure, or those with left ventricular ejection fraction <60% had higher mortality. Eighty-two percent of patients had surgery within 10 years. Mortality among patients undergoing surgery was equivalent to that of the age-matched US population and significantly less than patients managed without surgery." }, { "input": "Cardiologists and general internists perform equally well in identifying severe mitral regurgitation among patients with known mitral regurgitation. Grade I or II murmurs indicate mild or moderate mitral regurgitation; grade IV or greater murmurs indicate severe mitral regurgitation, and grade III murmurs are indeterminate.", "output": "In a prospective study testing the ability of physical examination to identify severe mitral regurgitation, 170 consecutive patients with mitral regurgitation assessed by echocardiography underwent a clinical examination by internists or cardiologists blinded to the echocardiogram findings. The negative predictive value for absence of severe mitral regurgitation with a murmur less than grade III ranged from 88% to 100%. Murmurs greater than grade III had a predictive value of 91% for severe mitral regurgitation. Grade III murmurs were not predictive of severity." }, { "input": "The optimal frequency of evaluation is uncertain. Patients with severe regurgitation should be followed more frequently, with a combination of physical examination and echocardiography.", "output": "Patients with mild mitral regurgitation should undergo annual physical examination. Patients with moderate mitral regurgitation should undergo annual clinical evaluation and echocardiographic examination. Asymptomatic patients with severe mitral regurgitation should have a clinical and echocardiographic evaluation every 6 to 12 months. Patients with symptoms of heart failure or with mild left ventricular dysfunction (ejection fraction 50%-60% or end-diastolic dimension 45-50 mm) should be referred for surgery." }, { "input": "Polymerase chain reaction (PCR) techniques appear to be more sensitive and specific in detecting herpes simplex virus (HSV) in genital lesions.", "output": "In another study, daily sampling of lesions in patients with known HSV infections detected HSV DNA on 15 of 17 days with PCR and only 3 of 17 days with culture. This suggests that PCR is more effective in detecting early, as well as late, stages of infection. Currently PCR is more expensive, but it may become cheaper because of decreased labor expense when compared with culture." }, { "input": "Polymerase chain reaction (PCR) techniques appear to be more sensitive and specific in detecting herpes simplex virus (HSV) in genital lesions.", "output": "In London, 233 samples from patients at a genitourinary medicine clinic were tested with both viral culture and PCR. HSV was detected in 79 samples by culture and 132 samples by PCR. The detection by PCR was higher in early as well as late stages of infection and in both first and recurrent episodes. The reference standard for these studies was not an independent standard, but a positive result on both tests or modified versions of the PCR test. The use of a version of the test of interest (PCR) as part of the reference standard, while probably unavoidable in this situation, will tend inflate the sensitivity and specificity." }, { "input": "Polymerase chain reaction (PCR) techniques appear to be more sensitive and specific in detecting herpes simplex virus (HSV) in genital lesions.", "output": "In 110 clinical samples from dermal or genital lesions of patients with suspected HSV infection, the sensitivity of PCR was 98% (positive likelihood ratio [LR+]=\u221e negative likelihood ratio [LR-]=0.02) compared with 73% (LR+ = \u221e LR- = 0.27) for culture. The specificities of both were 100%." }, { "input": "Viral culture remains the gold standard.", "output": "A British study found the rate of virus recovery for early vesicles to be 52% to 93%. This dropped to 41% to 72% if midstage ulcers were present. Finally, the detection for late-stage crusted lesions was only 19% to 27%. Another disadvantage is that culture is labor-intensive. A positive culture takes an average of 3 days to grow, whereas a negative culture must incubate for 10 days. PCR techniques are more sensitive and results can be available in less than 4 hours." }, { "input": "Viral culture remains the gold standard.", "output": "In London, 233 samples from patients at a genitourinary medicine clinic were tested with both viral culture and PCR. HSV was detected in 79 samples by culture and 132 samples by PCR. The detection by PCR was higher in early as well as late stages of infection and in both first and recurrent episodes. The reference standard for these studies was not an independent standard, but a positive result on both tests or modified versions of the PCR test. The use of a version of the test of interest (PCR) as part of the reference standard, while probably unavoidable in this situation, will tend inflate the sensitivity and specificity." }, { "input": "Studies of serologic and antibody detection tests report higher sensitivities than viral culture.", "output": "In a study using 275 samples from genital lesions, HSV was detected in 65% of the antigen tests and 53% of the viral cultures. The sensitivity of this method is equal to culture for early lesions, but much higher in late-stage lesions (58% vs 26%)." }, { "input": "Studies of serologic and antibody detection tests report higher sensitivities than viral culture.", "output": "Serologic tests are often used to detect HSV because they can differentiate between HSV-1 and HSV-2. There is an FDA-approved point-of-care test called POCkit that gives results from capillary blood or serum during an office visit. These tests are 80% to 98% sensitive and more than 96% specific. Unfortunately, they are not readily available in all countries." }, { "input": "Cytologic tests such as the Tzanck smear and Papanicolaou (Pap) smear have poor sensitivities and specificities and should not be relied upon for a diagnosis of genital herpes.", "output": "Detection methods include the Tzanck smear, which is only 40% to 50% sensitive compared with culture, and the Pap smear, which is 60% to 70% sensitive. These tests should not be the sole method for the diagnosis of HSV. They cannot differentiate between HSV 1 and HSV 2; furthermore, the Tzanck prep will give a positive result if varicella zoster virus is present. If these tests are positive, confirmatory testing specific for HSV should be performed." }, { "input": "other", "output": "Clinical suspicion needs to be confirmed by laboratory testing because it has a direct impact on counseling and prognosis." }, { "input": "other", "output": "The diagnosis of genital herpes based on clinical history and physical examination is often inaccurate." }, { "input": "Healthy, nonpregnant women presenting with the triad of frequency, dysuria, and no vaginal symptoms have about a 96% chance of having an urinary tract infection (UTI) (positive likelihood ratio [LR+]=24.6). Since no urinalysis result would substantially change the high likelihood of disease for these patients, empiric therapy is appropriate.", "output": "An evidence-based review found 5 high-quality studies on the diagnosis of acute uncomplicated UTI among women. The triad of dysuria with frequency but without vaginal symptoms increased the probability of significant bacteriuria on culture from 50% to 96% (LR+=24.6)." }, { "input": "A triage system based only on having 1 or more urinary symptoms is more sensitive but less specific: the chance of having a UTI drops to 50% (LR+=19). While empiric therapy is still likely to be appropriate, rates of false positives and inappropriate antibiotic use may rise.", "output": "A patient presenting to a clinician with 1 or more UTI symptoms had approximately a 50% chance of having significant bacteriuria on culture. The authors estimated the pretest probability of UTI as 5% from the incidence of asymptomatic bacteriuria among healthy women. This produced a LR+ of 19 simply for presenting to a clinician with 1 or more UTI symptoms." }, { "input": "A triage system based only on having 1 or more urinary symptoms is more sensitive but less specific: the chance of having a UTI drops to 50% (LR+=19). While empiric therapy is still likely to be appropriate, rates of false positives and inappropriate antibiotic use may rise.", "output": "McIssac et al reviewed a cohort of 231 women presenting to family physicians' offices with uncomplicated cystitis symptoms. Empiric therapy resulted in approximately 40% of women unnecessarily receiving antibiotics. Treating only women with classic cystitis symptoms and pyuria would have decreased the unnecessary use of antibiotics to 26.2%, but fewer women with confirmed cystitis would have received immediate antibiotics (66.4% vs 91.8%). They derived a clinical decision rule designed to balance false positives and false negatives. It recommends immediate antibiotic treatment if women have \u22652 of 4 signs or symptoms: dysuria, leukocyte esterase (greater than trace), positive nitrites, or blood (greater than trace) on dipstick (LR+=2.29). Otherwise the rule recommends a culture to guide antibiotic therapy. This decision rule would have reduced unnecessary antibiotic use by 27.5% while ensuring that more women with confirmed UTIs received immediate antibiotics (81.3%)." }, { "input": "Empiric treatment by telephone may also be considered.", "output": "A retrospective case series evaluated a telephone guideline for the empiric treatment of UTI for 4177 women in a California HMO. UTI criteria were \u226410 days of dysuria; frequency, urgency, pressure, or increased nocturia; or gross hematuria. Women were excluded if they had any one of a variety of contraindications. Upper tract infection occurred in 21 patients (1.1%) within 60 days of telephone treatment, two thirds of which likely represented treatment failures. This is similar to rates in control groups of other studies. Fourteen women (1.5%) received care for sexually transmitted diseases or other gynecologic conditions, primarily bacterial vaginitis, within 60 days of telephone treatment. Of note, 6% of the cohort were elderly, diabetic, taking glucocorticoids or early in pregnancy and are typically excluded from other studies. This higher-risk group did not have an increased incidence of either sepsis or pyelonephritis." }, { "input": "Empiric treatment by telephone may also be considered.", "output": "Several studies have noted that telephone treatment protocols increase the use of protocol-recommended antibiotics (eg, generally less expensive agents such as trimethoprim-sulfamethoxazole), which may help limit resistance to fluoroquinolones. However, specific data are not available." }, { "input": "Empiric treatment by telephone may also be considered.", "output": "No increase in adverse outcomes was seen in another study of a telephone treatment protocol." }, { "input": "More than 80% of women with a first-trimester spontaneous abortion have complete natural passage of tissue within 2 to 6 weeks with no higher complication rate than that from surgical intervention.", "output": "A systematic review of 18 studies, including 3 RCTs, compared outcomes for expectant management (545 women) vs surgical evacuation (1408 women) for first-trimester spontaneous abortion. A successful first-trimester spontaneous abortion was defined as vaginal bleeding for 3 weeks or less, fully expelled products of conception by 14 days, and no complications (infection, transfusion, uterine perforation, hospitalization, or death). Expectant management was successful in 93% overall, and 80% using only the data from RCTs." }, { "input": "Expectant management is successful within 2 to 6 weeks without increased complications in 80% to 90% of women with first-trimester incomplete spontaneous abortion and 65% to 75% of women with first-trimester missed abortion or anembryonic gestation (presenting with spotting or bleeding and ultrasound evidence of fetal demise).", "output": "An observational study evaluated 1096 consecutive patients with suspected first-trimester abortion, classified by ultrasound as complete, incomplete, missed, or anembryonic. In the latter 3 categories, patients chose expectant management (478) or immediate surgical evacuation (208). Those choosing expectant management were monitored weekly and offered surgical evacuation if their abortion was incomplete after 1 month. Complications arose in 6 of 451 patients (1%) managed expectantly for up to 46 days, and in 5 of 208 patients (2%) managed surgically (not statistically significant). One patient in the expectant group had emergency surgery and blood transfusion." }, { "input": "Expectant management is successful within 2 to 6 weeks without increased complications in 80% to 90% of women with first-trimester incomplete spontaneous abortion and 65% to 75% of women with first-trimester missed abortion or anembryonic gestation (presenting with spotting or bleeding and ultrasound evidence of fetal demise).", "output": "An observational study evaluated 108 women with first-trimester missed abortions or anembryonic pregnancies who chose either expectant (85 women) or surgical management. They were followed with weekly ultrasound (including color Doppler imaging) and serum \u03b2-hCG for up to 1 month. Fifty-three (62%) completed a spontaneous abortion at 14 days and 71 (84%) at 28 days. There were no significant differences in the rate of complications." }, { "input": "There is no difference in short-term psychological outcomes between expectant and surgical management.", "output": "A prospective trial compared psychological morbidity for 86 women with ultrasound-confirmed first-trimester missed abortions, randomized to expectant or surgical management. At 2 weeks, a self-administered questionnaire about the experience of pregnancy loss found no significant difference in psychological reactions. No increase was seen in anxiety or depression symptoms between women who had miscarried and healthy nonpregnant working women aged 19 to 39 years." }, { "input": "Women experiencing spontaneous abortion with unstable vital signs, uncontrolled bleeding, or evidence of infection should be considered for surgical evacuation.", "output": "Expert opinion recommends that women with spontaneous abortion beyond 13 weeks, a temperature >100.4\u00ba F, unstable blood pressure, uncontrolled vaginal bleeding, or evidence of endometritis or pelvic inflammatory disease should have surgical evacuation." }, { "input": "HMG-CoA reductase inhibitors, or statins, have been shown to decrease all-cause mortality in individuals aged 65 and older with known coronary heart disease (CHD) and elevated cholesterol levels.", "output": "The overall decrease in absolute risk of death was similar (range, 4.1%-6.2%; numbers needed to treat [NNT] = 17-25). The LIPID trial demonstrated a reduction in CHD-related death (relative risk [RR] = 0.76; 95% CI, 0.62-0.93; NNT = 37) and myocardial infarctions (RR = 0.74; 95% CI, 0.60-0.91; NNT = 36) in elderly patients taking pravastatin 40 mg once daily for 6 years compared with placebo." }, { "input": "HMG-CoA reductase inhibitors, or statins, have been shown to decrease all-cause mortality in individuals aged 65 and older with known coronary heart disease (CHD) and elevated cholesterol levels.", "output": "Two randomized controlledtrials and 1 cohort study demonstrated a decrease in all-cause mortality in individuals aged 65 and older with known CHD by treating elevated cholesterol levels with either pravastatin or simvastatin." }, { "input": "The clinical benefit of statin use in older persons without known CHD, however, is uncertain. Decisions about testing for lipid levels and treatment should include discussions with the patient about the potential benefits and risks of treatment, taking into account the individual's overall risk of CHD.", "output": "Available evidence addressing the benefit of lowering lipid levels in persons with elevated cholesterol but without CHD is from the West of Scotland Coronary Prevention study, which included patients aged 45 to 64 years. This study showed a 0.5% reduction in CHD mortality (NNT = 200) and a 0.9% reduction in all-cause mortality (NNT = 111). Neither reduction reached statistical significance." }, { "input": "The clinical benefit of statin use in older persons without known CHD, however, is uncertain. Decisions about testing for lipid levels and treatment should include discussions with the patient about the potential benefits and risks of treatment, taking into account the individual's overall risk of CHD.", "output": "Statins do not decrease health-related quality of life. Approximately 1% to 4% of those who take statins experience side effects, including abnormal liver function, arthralgias, myalgias, rash, sinusitis, and diarrhea." }, { "input": "The clinical benefit of statin use in older persons without known CHD, however, is uncertain. Decisions about testing for lipid levels and treatment should include discussions with the patient about the potential benefits and risks of treatment, taking into account the individual's overall risk of CHD.", "output": "Several reports have demonstrated that statins safely and effectively lower cholesterol levels in patients aged 65 and older." }, { "input": "Standardized clinical decision rules, such as the Centor criteria, can identify patients with low likelihood of group A beta-hemolytic streptococ-cal (GABHS) pharyngitis who require no further evaluation or antibiotics.", "output": "A systematic review of the diagnosis of GABHS evaluated the accuracy of history and physical exam elements. Clinical prediction rules based on selected symptoms and signs can identify patients at low risk for GABHS. The 4 Centor criteria (history of fever, anterior cervical adenopathy, tonsillar exudates, absence of cough) are well validated in adult populations, while other clinical prediction rules (such as McIssac) are validated in populations with children and adults. The number of criteria present determines the likelihood ratio (LR), with which to calculate the posttest probability of GABHS." }, { "input": "For patients at intermediate and higher risk by clinical prediction rules, a positive rapid anti-gen detection (RAD) test is highly specific for GABHS.", "output": "A systematic review6 of RAD testing demonstrates that the newer techniques (optical immunoassay, chemiluminescent DNA probes) have a sensitivity of 80% to 90%, which compares closely with that of throat culture (90%-95%). Both have a specificity greater than 95%, so false-positive test results are uncommon (LR+ =16-19)." }, { "input": "A negative RAD test result, using the best technique, approaches the sensitivity of throat culture.", "output": "A prospective study of 465 suburban outpatients with pharyngitis assessed the accuracy of RAD diagnosis using throat culture as a reference. The RAD accuracy was 93% for pediatric patients and 97% for adults." }, { "input": "A negative RAD test result, using the best technique, approaches the sensitivity of throat culture.", "output": "In a retrospective review of RAD testing, investigators performed 11,427 RAD tests over 3 years in a private pediatric group. There were 8385 negative tests, among which follow-up cultures detected 200 (2.4%) that were positive for GABHS. In the second half of the study, a newer RAD test produced a false-negative rate of 1.4%." }, { "input": "In children and populations with an increased prevalence of GABHS and GABHS complications, adding a backup throat culture reduces the risk of missing GABHS due to false-negative RAD results.", "output": "Because of the possibility of higher false-negative RAD test rates in some settings, unless the physician has ascertained that RAD testing is comparable to throat culture in their own setting, expert opinion recommends confirming a negative RAD test in children or adolescents with a throat culture. Patients at higher risk of GABHS or GABHS complications may also warrant throat culture back up of RAD testing." }, { "input": "A combination of laxatives, behavioral therapy, and balanced diet is the treatment of choice for pediatric constipation.", "output": "A randomized controlled trial of 87 children with fecal soiling compared the effect of enhanced toilet training (including behavioral therapy) with aggressive medical management that included disimpaction, enemas, and regular laxative therapy. After 12 months, the enhanced toilet training with behavioral therapy was more effective in reducing daily frequency of soiling (78% of the children had significantly decreased average daily frequency of soiling compared with 41% in the aggressive medical management group; P<.0001; absolute risk reduction=0.37; number needed to treat for 1 year=2.7)." }, { "input": "Laxatives are used for disimpaction and maintenance therapy.", "output": "A randomized controlled trial of 87 children with fecal soiling compared the effect of enhanced toilet training (including behavioral therapy) with aggressive medical management that included disimpaction, enemas, and regular laxative therapy. After 12 months, the enhanced toilet training with behavioral therapy was more effective in reducing daily frequency of soiling (78% of the children had significantly decreased average daily frequency of soiling compared with 41% in the aggressive medical management group; P<.0001; absolute risk reduction=0.37; number needed to treat for 1 year=2.7)." }, { "input": "Trials that compare different laxatives have shown similar effectiveness, although polyethylene glycol (PEG) 3350 (MiraLax) may be better tolerated.", "output": "Laxative therapies were compared in 2 studies. An unblinded, randomized, crossover trial enrolled 37 children referred for subspecialty evaluation of functional constipation. It found that PEG 3350 and lactulose were equivalent in improving stool frequency, stool form, and ease of passage. However, there was a significant difference in total stool transit time in subjects taking PEG compared with those taking lactulose (47.6 hours vs 55.3 hours, respectively; P=.038). In addition, twice as many parents and guardians rated PEG effective as those rating lactulose effective (84% vs 46%); and 73% of parents preferred PEG to lactulose." }, { "input": "Trials that compare different laxatives have shown similar effectiveness, although polyethylene glycol (PEG) 3350 (MiraLax) may be better tolerated.", "output": "A randomized trial compared PEG with milk of magnesia in 49 children with functional constipation and encopresis. Follow-up at 1, 3, 6, and 12 months revealed similar effectiveness in increasing bowel movement frequency, decreasing soiling episodes, and decreasing abdominal pain. It also revealed that PEG was more palatable and better-tolerated than milk of magnesia (33% of children refused to take milk of magnesia, whereas none refused PEG). No side effects from PEG were reported." }, { "input": "The roles of dietary changes and acupuncture have been minimally studied.", "output": "A nonrandomized, controlled trial of acupuncture treatment enrolled 17 children with history of constipation for a minimum of 6 months. Bowel movement frequency improved in both males (1.5 \u00b1 0.1/week to 4.4 \u00b1 0.6/week; P<.01) and females (1.4 \u00b1 0.3/week to 5.6 \u00b1 1.1/week; P<.01) after 10 acupuncture sessions. No other bowel movement parameter was reported." }, { "input": "The roles of dietary changes and acupuncture have been minimally studied.", "output": "A case-control study evaluated 291 subjects with constipation and compared their diet with 1602 controls. Mean daily fiber intake was lower in the constipation group. Compared with fiber intake of more than 29 g/d, the relative risk was 8.0 for fiber intake of less than 12.4 g/d." }, { "input": "For urticarial itch, first- and second-generation antihistamines have similar clinical benefit and are superior to placebo.", "output": "One recent nonsystematic, narrative review of pruritic dermatoses concluded second-generation antihistamines appear to be more effective." }, { "input": "For urticarial itch, first- and second-generation antihistamines have similar clinical benefit and are superior to placebo.", "output": "In a single double-blind placebo-controlled study of 188 patients at least 12 years of age, they received cetirizine 10 mg daily, hydroxyzine 25 mg 3 times daily, or placebo. This study found both agents produced significant, and equivalent, pruritus reduction relative to placebo." }, { "input": "For urticarial itch, first- and second-generation antihistamines have similar clinical benefit and are superior to placebo.", "output": "A recent review of therapies for urticarial itch concluded that second-generation antihista mines were preferred." }, { "input": "For urticarial itch, first- and second-generation antihistamines have similar clinical benefit and are superior to placebo.", "output": "A Medline-based review found 7 double-blind, placebo-controlled trials that compared the benefit of first- and second-generation antihistamines in 720 patients with chronic idiopathic urticaria. Hydroxyzine was used in 682 patients, while the remainder took clemastine. Second-generation agents included cetirizine, loratadine, or acrivastine. The researchers qualitatively summarized outcomes and concluded that the treatment benefits were equivalent and superior to placebo. The clinical practice of doubling the dose of second-generation agents for initial treatment failures was not recommended, due to absence of supporting data for this approach." }, { "input": "For itch related to atopic dermatitis, antihistamines are no better than placebo.", "output": "An NHS Centre narrative review on relieving pruritus in atopic dermatitis concluded that there was little objective evidence to support the efficacy of first- or second-generation antihistamines; 803 participants from 16 case series and reports were included. There were no large RCTs. Results were not pooled or tested for heterogeneity, so they should be interpreted cautiously." }, { "input": "For itch related to atopic dermatitis, antihistamines are no better than placebo.", "output": "A systematic review focusing on pediatric patients concluded oral antihistamines are not beneficial for pruritus from atopic dermatitis. A search of Cochrane and PubMed revealed only 2 relevant RCTs involving 177 children. Cetirizine and chlorpheniramine were each compared with placebo, and no statistically significant reduction in symptoms was found." }, { "input": "Other categories of pruritus are best treated with non-antihistamine agents.", "output": "No evidence-based guidelines or consensus statements were found that address antihistamine preference in the treatment of pruritus. Although use of non-antihistamine agents is beyond the scope of this inquiry, an excellent topical review of pruritus was recently published that comprehensively outlined the Twycross classification system and detailed the evidence for usual and nontraditional treatments. Since antihistamines do not benefit atopic-related pruritus, other options include emollients, counterirritants such as menthol/camphor or capsaicin, EMLA cream, topical pramoxine, topical corticosteroids, topical doxepin, topical immunomodulators such as pimecrolimus or tacrolimus, topical aspirin, and phototherapy with psoralen ultraviolet A-range PUVA." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "One study used a protocol that delayed the chest x-ray for 2 weeks, until after empiric treatment for PNDS and evaluation for asthma. These authors eliminated half of the x-rays and achieved results equivalent to previous studies." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "One prospective study using empiric PNDS treatment as a first step decreased the number of tests required and the mean time to diagnosis compared with previously published studies.6 No studies were found evaluating empiric treatment for asthma before diagnosis. Multiple studies report a 100% negative predictive value for the methacholine challenge test, but this carries some risk and is not universally available." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "Symptoms and signs and diagnostic tests for PNDS are unreliable." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "The protocol evaluates for these 3 conditions. The key weakness of the protocol is that a positive diagnostic test result does not mean that treatment for that condition will relieve the cough.5 Recently, empiric treatment before diagnostic testing has been recommended for primary care." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "Initial empiric treatment for PNDS appears reasonable, since it is the most common single cause of chronic cough." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "The protocol evaluates for these 3 conditions. The key weakness of the protocol is that a positive diagnostic test result does not mean that treatment for that condition will relieve the cough.5 Recently, empiric treatment before diagnostic testing has been recommended for primary care." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "Irwin proposed an algorithm to evaluate chronic cough that has successfully diagnosed and treated chronic cough 82% to 100% of the time in referral centers." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "The negative predictive value of a 24-hour pH probe is between 90% and 100%, but this may also be reserved for those who fail initial empiric therapy." }, { "input": "Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients.", "output": "The best timing of the chest x-ray is also unclear. The diagnostic protocol has been historically evaluated in patients with a normal or stable chest x-ray." }, { "input": "Twenty-four hour ambulatory blood pressure monitoring (ABPM) has a higher correlation with target end-organ damage than standard office measurements and is superior for risk stratification. Because it is more complicated to implement than office-based measurements, it should be reserved for: establishing the diagnosis of white-coat hypertension or borderline hypertension in previously untreated patients; evaluating previously treated patients with resistant hypertension; diagnosing and treating hypertension disorders of pregnancy; and identifying nocturnal hypertension.", "output": "When compared with standard office measurement, management with ABPM led to less intensive antihypertensive drug therapy without loss of blood pressure control. Evidence from these and other studies indicates that ABPM can be useful for risk stratification of patients in whom the diagnosis of hypertension is not clear." }, { "input": "Twenty-four hour ambulatory blood pressure monitoring (ABPM) has a higher correlation with target end-organ damage than standard office measurements and is superior for risk stratification. Because it is more complicated to implement than office-based measurements, it should be reserved for: establishing the diagnosis of white-coat hypertension or borderline hypertension in previously untreated patients; evaluating previously treated patients with resistant hypertension; diagnosing and treating hypertension disorders of pregnancy; and identifying nocturnal hypertension.", "output": "In a randomized parallel-group trial, 419 untreated patients were followed up using either ABPM or conventional office measurements to initiate and adjust antihypertensive therapy." }, { "input": "Twenty-four hour ambulatory blood pressure monitoring (ABPM) has a higher correlation with target end-organ damage than standard office measurements and is superior for risk stratification. Because it is more complicated to implement than office-based measurements, it should be reserved for: establishing the diagnosis of white-coat hypertension or borderline hypertension in previously untreated patients; evaluating previously treated patients with resistant hypertension; diagnosing and treating hypertension disorders of pregnancy; and identifying nocturnal hypertension.", "output": "Another cohort study of 1464 patients found ABPM was linearly related to stroke risk and more predictive of a cerebrovascular event than was screening blood pressure over an average of 6.4 years." }, { "input": "Twenty-four hour ambulatory blood pressure monitoring (ABPM) has a higher correlation with target end-organ damage than standard office measurements and is superior for risk stratification. Because it is more complicated to implement than office-based measurements, it should be reserved for: establishing the diagnosis of white-coat hypertension or borderline hypertension in previously untreated patients; evaluating previously treated patients with resistant hypertension; diagnosing and treating hypertension disorders of pregnancy; and identifying nocturnal hypertension.", "output": "ABPM correlates better with disease-oriented outcomes, such as left ventricular mass, retinopathy, and microalbuminuria than does office measurement." }, { "input": "Twenty-four hour ambulatory blood pressure monitoring (ABPM) has a higher correlation with target end-organ damage than standard office measurements and is superior for risk stratification. Because it is more complicated to implement than office-based measurements, it should be reserved for: establishing the diagnosis of white-coat hypertension or borderline hypertension in previously untreated patients; evaluating previously treated patients with resistant hypertension; diagnosing and treating hypertension disorders of pregnancy; and identifying nocturnal hypertension.", "output": "Community-based cohort studies have consistently shown ABPM to be more reproducible than office blood pressure measurements." }, { "input": "Twenty-four hour ambulatory blood pressure monitoring (ABPM) has a higher correlation with target end-organ damage than standard office measurements and is superior for risk stratification. Because it is more complicated to implement than office-based measurements, it should be reserved for: establishing the diagnosis of white-coat hypertension or borderline hypertension in previously untreated patients; evaluating previously treated patients with resistant hypertension; diagnosing and treating hypertension disorders of pregnancy; and identifying nocturnal hypertension.", "output": "The accuracy of ABPM has been validated for use in the adult, pediatric, and pregnant populations." }, { "input": "Large published randomized controlled trials (RCTs) show that pravastatin and simvastatin are well-tolerated and reduce major coronary events such as death, myocardial infarction, and revascularization by about 25%. The Heart Protection Study suggested this benefit is noted even among individuals with pretreatment low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL. Fluvastatin reduces major coronary events, but current studies are too small to prove reduced overall mortality. The best evidence to date suggests that most patients at significant risk for major coronary events should be given pravastatin or simvastatin 40 mg daily, without concern for the initial or follow-up LDL levels.", "output": "The National Cholesterol Education Project NCEP recommends that patients with CAD and an LDL of more than 130 mg/dL adopt therapeutic lifestyle changes and start LDL-lowering medication, usually a statin. For patients with LDL between 100 and 130 mg/dL, the NCEP recommends therapeutic lifestyle changes, with the option of adding a statin. For patients with LDL less than 100 mg/dL, maintenance of LDL control is recommended with therapeutic lifestyle changes. For patients with high initial LDL levels that stay above 100 mg/dL on statin therapy, the NCEP recommends that additional medications, such as nicotinic acid or fibrates, as well as intensive therapeutic lifestyle changes, be considered." }, { "input": "Large published randomized controlled trials (RCTs) show that pravastatin and simvastatin are well-tolerated and reduce major coronary events such as death, myocardial infarction, and revascularization by about 25%. The Heart Protection Study suggested this benefit is noted even among individuals with pretreatment low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL. Fluvastatin reduces major coronary events, but current studies are too small to prove reduced overall mortality. The best evidence to date suggests that most patients at significant risk for major coronary events should be given pravastatin or simvastatin 40 mg daily, without concern for the initial or follow-up LDL levels.", "output": "The Heart Protection Study used simvastatin 40 mg daily, without titration. The Heart Protection Study enrolled 20,000 people with CAD or equivalent (diabetes, peripheral vascular disease, stroke, etc). The study demonstrated a reduction of major coronary events with simvastatin, with numbers needed to treat (NNT) of 19 (P <.0001); the NNT for reduction in all-cause mortality was 55 (P =.0003). The benefit of simvastatin was noted in virtually every predefined subgroup, including individuals older than 70 years, women, and patients without known CAD (but with CAD equivalents). Notably, no difference in benefit was found between patients with different pretreatment LDL levels. A significant reduction in major vascular events was noted even for the 3400 subjects with pretreatment LDL levels of less than 100 mg/dL (NNT = 22, P =.0006). A greater percentage reduction in LDL with medication did not predict better clinical outcomes." }, { "input": "Large published randomized controlled trials (RCTs) show that pravastatin and simvastatin are well-tolerated and reduce major coronary events such as death, myocardial infarction, and revascularization by about 25%. The Heart Protection Study suggested this benefit is noted even among individuals with pretreatment low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL. Fluvastatin reduces major coronary events, but current studies are too small to prove reduced overall mortality. The best evidence to date suggests that most patients at significant risk for major coronary events should be given pravastatin or simvastatin 40 mg daily, without concern for the initial or follow-up LDL levels.", "output": "The Lescol Intervention Prevention study randomized patients after angioplasty to fluvastatin 40 mg twice daily or placebo." }, { "input": "Large published randomized controlled trials (RCTs) show that pravastatin and simvastatin are well-tolerated and reduce major coronary events such as death, myocardial infarction, and revascularization by about 25%. The Heart Protection Study suggested this benefit is noted even among individuals with pretreatment low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL. Fluvastatin reduces major coronary events, but current studies are too small to prove reduced overall mortality. The best evidence to date suggests that most patients at significant risk for major coronary events should be given pravastatin or simvastatin 40 mg daily, without concern for the initial or follow-up LDL levels.", "output": "The intervention arm in the Cholesterol and Recurrent Events trial was also pravastatin 40 mg daily, with cholestyramine added if the LDL level remained higher than 175 mg/dL. Subgroup analyses suggested that patients with CAD and low initial LDL levels (< 125 mg/dL) have little to gain from pravastatin." }, { "input": "Large published randomized controlled trials (RCTs) show that pravastatin and simvastatin are well-tolerated and reduce major coronary events such as death, myocardial infarction, and revascularization by about 25%. The Heart Protection Study suggested this benefit is noted even among individuals with pretreatment low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL. Fluvastatin reduces major coronary events, but current studies are too small to prove reduced overall mortality. The best evidence to date suggests that most patients at significant risk for major coronary events should be given pravastatin or simvastatin 40 mg daily, without concern for the initial or follow-up LDL levels.", "output": "The Long-Term Intervention with Pravastatin in Ischaemic Disease study randomized patients to pravastatin 40 mg daily or placebo, without titration. Subgroup analyses suggested that patients with CAD and low initial LDL levels (< 125 mg/dL) have little to gain from pravastatin." }, { "input": "Large published randomized controlled trials (RCTs) show that pravastatin and simvastatin are well-tolerated and reduce major coronary events such as death, myocardial infarction, and revascularization by about 25%. The Heart Protection Study suggested this benefit is noted even among individuals with pretreatment low-density lipoprotein (LDL) cholesterol of less than 100 mg/dL. Fluvastatin reduces major coronary events, but current studies are too small to prove reduced overall mortality. The best evidence to date suggests that most patients at significant risk for major coronary events should be given pravastatin or simvastatin 40 mg daily, without concern for the initial or follow-up LDL levels.", "output": "The Scandinavian Simvastatin Survival study used simvastatin 20 mg daily unless total cholesterol levels did not decrease to less than 200 mg/dL." }, { "input": "Conclusions regarding the ThinPrep are difficult to make due to the complexity of cervical cancer screening and the lack of adequate outcome-based data. However, current evidence supports the following: the ThinPrep is more sensitive than the conventional Papanicolaou (Pap) smear at detecting cervical cancer.", "output": "A recent quantitative review implies that the ThinPrep increases cytologic diagnoses of cervical cancer and its precursors. A strength of this review is the inclusion of 10 articles with histology as the reference standard. The data from 21,752 patients compared the sensitivity and specificity rates of Thin Prep with conventional Pap for detecting abnormal histology. Sensitivity rates were reported as 76% (ThinPrep) and 68% (conventional), but the differences met statistical significance in only 2 of the included studies. Similarly, the overall specificity rates of the ThinPrep vs conventional Pap was 86% vs 79%, and again the differences did not usually reach statistical significance. The authors hypothesize that widespread use of ThinPrep could potentially detect an additional 162,000 patients with HSIL and 3000 patients with invasive cervical carcinoma." }, { "input": "Conclusions regarding the ThinPrep are difficult to make due to the complexity of cervical cancer screening and the lack of adequate outcome-based data. However, current evidence supports the following: the ThinPrep is more sensitive than the conventional Papanicolaou (Pap) smear at detecting cervical cancer.", "output": "This prospective, population-based study of 8636 women reported that the ThinPrep was significantly more sensitive than the conventional smears at detecting high-grade squamous intraepithelial lesions (HSIL) and cancer, with sensitivity rates of 92.9% and 100% vs 77.8% and 90.9%, respectively (P<.001). This evidence demonstrates that the ThinPrep is better at detecting cervical cancer." }, { "input": "Conclusions regarding the ThinPrep are difficult to make due to the complexity of cervical cancer screening and the lack of adequate outcome-based data. However, current evidence supports the following: the ThinPrep is more sensitive than the conventional Papanicolaou (Pap) smear at detecting cervical cancer.", "output": "The conventional Pap smear is the standard screening test for cervical neoplasia. Despite success, the Pap smear has high false-negative rates due to poor sensitivity (51%; 95% confidence interval [CI], 37%-66%). The ThinPrep was developed to improve sensitivity by providing a monolayer of cells to the cytologist for review. A population-based comparative analysis of good quality shows that the new technology is better at detecting cancer precursors, but other systematic reviews that include less rigorous studies can only suggest it." }, { "input": "Conclusions regarding the ThinPrep are difficult to make due to the complexity of cervical cancer screening and the lack of adequate outcome-based data. However, current evidence supports the following: the ThinPrep is more sensitive than the conventional Papanicolaou (Pap) smear at detecting cervical cancer.", "output": "A large meta-analysis of 25 prospective studies including over 500,000 women reported that ThinPrep increased detection of low-grade squamous intraepithelial lesions (LSIL) (odds ratio [OR]=2.15; 95% CI, 2.05-2.26) and HSIL (OR=2.26; 95% CI, 1.53-1.76), but the conclusions were severely limited by lack of a reference standard and high heterogeneity between study populations." }, { "input": "There is insufficient evidence to recommend 1 preparation over the other.", "output": "A review found insufficient evidence to even judge the new test." }, { "input": "There is insufficient evidence to recommend 1 preparation over the other.", "output": "A large evidence review done for the Agency for Healthcare Research and Quality (AHRQ) concluded that the quality of the available literature is poor. Two of the 3 trials reviewed had major methodological flaws that prevented an appropriate comparison of the data to show a modestly higher sensitivity of the ThinPrep. From these reviews, we cannot recommend one technique over the other." }, { "input": "The ThinPrep is a cost-effective screening tool if used at 3-year intervals,", "output": "The AHRQ review concluded that liquid-based cytology falls within the accepted ranges of cost-effectiveness if used at 3-year screening intervals." }, { "input": "The ThinPrep is a cost-effective screening tool if used at 3-year intervals,", "output": "A modeled cost and outcomes analysis concluded that liquid-based cytology falls within the accepted ranges of cost-effectiveness if used at 3-year screening intervals." }, { "input": "Additional advantages of the ThinPrep include being able to perform human papillomavirus (HPV) testing on the liquid. This is the preferred triage strategy for atypical squamous cells of undetermined significance (ASCUS) Pap smears.", "output": "The large ALTS trial supports the use of liquid-based cytology because it has shown HPV testing in patients with ASCUS decreases the need for colposcopy." }, { "input": "Additional advantages of the ThinPrep include being able to perform human papillomavirus (HPV) testing on the liquid. This is the preferred triage strategy for atypical squamous cells of undetermined significance (ASCUS) Pap smears.", "output": "Another computer-based model evaluated different triage strategies for ASCUS Pap smears and found that reflex HPV testing provides the same or greater life expectancy benefits and is more cost-effective. This strategy requires the use of liquid-based cytology." }, { "input": "Terbinafine is effective, safe for use in children, and relatively inexpensive, and it offers a shorter course of therapy than griseofulvin. Unfortunately, it is not available in liquid form. Fluconazole is available in liquid form and appears to be effective and safe, but fewer clinical trials have been published about it. Griseofulvin taken for 6 to 8 weeks remains an effective therapy for tinea capitis. There are insufficient randomized controlled trials directly comparing these agents to clearly establish a superior medication.", "output": "Although terbinafine is efficacious against Trichophyton tonsurans and Trichophyton violaceum, it does not work as well against Microsporum canis, which accounts for approximately 3% of the infections. Terbinafine is the most attractively priced treatment for tinea capitis, particularly if a short course is used." }, { "input": "Terbinafine is effective, safe for use in children, and relatively inexpensive, and it offers a shorter course of therapy than griseofulvin. Unfortunately, it is not available in liquid form. Fluconazole is available in liquid form and appears to be effective and safe, but fewer clinical trials have been published about it. Griseofulvin taken for 6 to 8 weeks remains an effective therapy for tinea capitis. There are insufficient randomized controlled trials directly comparing these agents to clearly establish a superior medication.", "output": "Terbinafine is an allyamine antifungal drug that has a very good safety profile. Unfortunately, there is no liquid formulation of terbinafine, but tablets may be hidden in food." }, { "input": "Terbinafine is effective, safe for use in children, and relatively inexpensive, and it offers a shorter course of therapy than griseofulvin. Unfortunately, it is not available in liquid form. Fluconazole is available in liquid form and appears to be effective and safe, but fewer clinical trials have been published about it. Griseofulvin taken for 6 to 8 weeks remains an effective therapy for tinea capitis. There are insufficient randomized controlled trials directly comparing these agents to clearly establish a superior medication.", "output": "Fluconazole is another broad-spectrum antifungal in the triazole class. It has been approved by the Food and Drug Administration (FDA) for use in children with systemic fungal infections. The safety profile is very good; it has no known significant carcinogenic potential. Fluconazole is available in both tablet and liquid formulations that make dosing in young children convenient. There are very few clinical studies comparing fluconazole with other antifungal drugs, and no head-to-head prospective randomized controlled trials with griseofulvin have been published to date." }, { "input": "Terbinafine is effective, safe for use in children, and relatively inexpensive, and it offers a shorter course of therapy than griseofulvin. Unfortunately, it is not available in liquid form. Fluconazole is available in liquid form and appears to be effective and safe, but fewer clinical trials have been published about it. Griseofulvin taken for 6 to 8 weeks remains an effective therapy for tinea capitis. There are insufficient randomized controlled trials directly comparing these agents to clearly establish a superior medication.", "output": "Itraconazole has been associated with several abnormalities of bone and soft tissue at doses exceeding normal human exposure. Additionally, at more normal doses a component of the liquid formulation causes pancreatic adenocarcinoma in rats." }, { "input": "Terbinafine is effective, safe for use in children, and relatively inexpensive, and it offers a shorter course of therapy than griseofulvin. Unfortunately, it is not available in liquid form. Fluconazole is available in liquid form and appears to be effective and safe, but fewer clinical trials have been published about it. Griseofulvin taken for 6 to 8 weeks remains an effective therapy for tinea capitis. There are insufficient randomized controlled trials directly comparing these agents to clearly establish a superior medication.", "output": "Ketoconazole was one of the first \"-azoles\" studied for the treatment of tinea in children. It is not as efficacious or as safe as other available treatments, making it unsuitable for the treatment of tinea capitis in children." }, { "input": "Terbinafine is effective, safe for use in children, and relatively inexpensive, and it offers a shorter course of therapy than griseofulvin. Unfortunately, it is not available in liquid form. Fluconazole is available in liquid form and appears to be effective and safe, but fewer clinical trials have been published about it. Griseofulvin taken for 6 to 8 weeks remains an effective therapy for tinea capitis. There are insufficient randomized controlled trials directly comparing these agents to clearly establish a superior medication.", "output": "Griseofulvin's safety and long history of use in children are its best assets. Recommended dosages and treatment duration have been increased because of fears of developing resistance. Tablets are approximately one third the cost of the liquid preparations." }, { "input": "Terbinafine is effective, safe for use in children, and relatively inexpensive, and it offers a shorter course of therapy than griseofulvin. Unfortunately, it is not available in liquid form. Fluconazole is available in liquid form and appears to be effective and safe, but fewer clinical trials have been published about it. Griseofulvin taken for 6 to 8 weeks remains an effective therapy for tinea capitis. There are insufficient randomized controlled trials directly comparing these agents to clearly establish a superior medication.", "output": "The exact efficacy of any agent is difficult to determine, because most studies were small, used different doses and definitions of cure, and were conducted in different populations. With the exception of ketoconazole, all agents seem to have roughly similar efficacy and cure rates of approximately 70% to 80%. None of these agents require laboratory monitoring at the recommended lengths of treatment for tinea capitis." }, { "input": "Patients whose family history includes 1 first-degree relative with subarachnoid hemorrhage caused by intracranial aneurysm (ICA) need not be screened for ICAs.", "output": "In a study of MRA with digital subtraction angiography backup, conducted using theoretical models, screening individuals having 2 or more first-degree relatives with aneurysm would result in severe morbidity or death in 26 individuals per 1000 patients screened, vs 15 per 1000 unscreened individuals over a 30-year period. These results were achieved assuming an ICA prevalence estimate of 9.8%, as determined from an earlier population study of individuals with at least 2 first-degree relatives with ICA. The lower ICA prevalence rate of 4% for patients with only 1 primary affected relative would yield an even more favorable result for not screening." }, { "input": "Hypertension, hyperlipidemia, ethanol use, and tobacco use do not increase the risk of ICA for patients whose primary family member had an ICA.", "output": "In a study using data from the same population, being a sibling of an ICA sufferer increased risk of ICA (relative risk=3.8, though with a wide 95% CI of 1.1-29.3). Neither hypertension nor hypercholesterolemia conferred increased risk of ICA, and the risk conferred by smoking and use of alcohol was statistically insignificant." }, { "input": "Screening for intracranial aneurysms is not cost-effective.", "output": "A mathematical model for evaluating cost effectiveness of screening for asymptomatic intracranial aneurysms in the general population determined there is a quality-adjusted life-year reduction for presumed ICA prevalence rates as high as 10%, given an annual rate of rupture of 0.05%. The average cost was $1121 for those who underwent screening vs $147 for those who did not. The presumed variables of prevalence, annual rates of ICA rupture, and surgical mortality and morbidity greatly influenced cost-effectiveness. Screening could be reasonable in populations with higher rupture rates, and if surgical morbidity and mortality decline." }, { "input": "In studies using mathematic modeling, harms associated with screening (functional impairment, severe morbidity, or death) would outweigh benefits of screening, even for individuals having 2 or more relatives with ICA.", "output": "In a study of MRA with digital subtraction angiography backup, conducted using theoretical models, screening individuals having 2 or more first-degree relatives with aneurysm would result in severe morbidity or death in 26 individuals per 1000 patients screened, vs 15 per 1000 unscreened individuals over a 30-year period. These results were achieved assuming an ICA prevalence estimate of 9.8%, as determined from an earlier population study of individuals with at least 2 first-degree relatives with ICA. The lower ICA prevalence rate of 4% for patients with only 1 primary affected relative would yield an even more favorable result for not screening." }, { "input": "Patients experience varying levels of psychological distress when offered screening for ICA.", "output": "An observational study of 980 first-degree relatives of patients with subarachnoid hemorrhage determined that offering screening for ICA did not provoke anxiety or depression." }, { "input": "Patients experience varying levels of psychological distress when offered screening for ICA.", "output": "In 1 case series of 105 patients, 35 screen-positive patients scored lower for quality of life than 70 screen-negative patients. However, only 3 patients regretted participating in screening." }, { "input": "Many combination drug therapies are effective in treating dyslipidemia. Compared with statin monotherapy, combinations that include ezetimibe (Zetia), a bile acid sequestrant, or niacin further lower low-density lipoprotein (LDL) cholesterol.", "output": "A randomized placebo-controlled trial demonstrated that combination therapy with colesevelam has similar effects. The absolute LDL cholesterol reduction of with atorvastatin (Lipitor) alone (10 mg daily) increased from 38% to 48% after adding colesevelam 3.8 g daily (10% absolute LDL cholesterol reduction)." }, { "input": "Many combination drug therapies are effective in treating dyslipidemia. Compared with statin monotherapy, combinations that include ezetimibe (Zetia), a bile acid sequestrant, or niacin further lower low-density lipoprotein (LDL) cholesterol.", "output": "A systematic review found that adding colestipol or cholestyramine to a statin provides an additional 7% to 20% absolute LDL cholesterol reduction." }, { "input": "Many combination drug therapies are effective in treating dyslipidemia. Compared with statin monotherapy, combinations that include ezetimibe (Zetia), a bile acid sequestrant, or niacin further lower low-density lipoprotein (LDL) cholesterol.", "output": "Adding a bile acid sequestrant to statin monotherapy does not appear to increase the risk of systemic toxicity." }, { "input": "Combinations that include ezetimibe (Zetia), a bile acid sequestrant, or niacin further lower low-density lipoprotein (LDL) cholesterol increase the likelihood of attaining National Cholesterol Education Program (NCEP) LDL cholesterol goals.", "output": "Statin/ezetimibe combination therapy is FDA-approved, and provides an additional 12% to 21% absolute LDL cholesterol reduction." }, { "input": "Combinations that include ezetimibe (Zetia), a bile acid sequestrant, or niacin further lower low-density lipoprotein (LDL) cholesterol increase the likelihood of attaining National Cholesterol Education Program (NCEP) LDL cholesterol goals.", "output": "A double-blind trial randomized 769 patients on statin monotherapy who were above their NCEP LDL goal to either placebo or ezetimibe 10 mg daily. Absolute LDL cholesterol reductions were 25.1% with ezetimibe vs 3.7% with placebo, and LDL goal attainment was 71.5% with ezetimibe vs 18.9% with placebo (secondary endpoint)." }, { "input": "Adding ezetimibe to a bile acid sequestrant reduces LDL cholesterol.", "output": "In one retrospective analysis, ezetimibe provided a 19% absolute LDL cholesterol reduction when added to a bile acid sequestrant." }, { "input": "Fibrate or niacin added to statin monotherapy provide mixed lipid-modifying effects for combined dyslipidemia.", "output": "Prospective controlled trials have shown regression of atherosclerotic lesions with this combination, but have also shown increased risks of myopathy." }, { "input": "Fibrate or niacin added to statin monotherapy provide mixed lipid-modifying effects for combined dyslipidemia.", "output": "Prospective controlled trials have shown regression of atherosclerotic lesions with this combination, but have also shown increased risks of myopathy." }, { "input": "Fibrate or niacin added to statin monotherapy provide mixed lipid-modifying effects for combined dyslipidemia.", "output": "Combinations of statins with fibrates (fenofibrate [Tricor], gemfibrozil [Lopid]) can treat combined dyslipidemia by decreasing LDL cholesterol more than 40%, decreasing triglycerides over 50%, and raising high-density lipoprotein (HDL) cholesterol more than 20%." }, { "input": "Fibrate or niacin added to statin monotherapy provide mixed lipid-modifying effects for combined dyslipidemia.", "output": "The combination of statin/niacin may be more desirable than statin/fibrate for patients with more severe mixed dyslipidemia, especially those with very low HDL cholesterol values, when monotherapy regimens are not completely effective. A fixed combination of lovastatin with extended-release niacin (Advicor) is commercially available." }, { "input": "Fibrate or niacin added to statin monotherapy provide mixed lipid-modifying effects for combined dyslipidemia.", "output": "The combination of statin/niacin may be more desirable than statin/fibrate for patients with more severe mixed dyslipidemia, especially those with very low HDL cholesterol values, when monotherapy regimens are not completely effective. A fixed combination of lovastatin with extended-release niacin (Advicor) is commercially available." }, { "input": "Fibrate or niacin added to statin monotherapy provide mixed lipid-modifying effects for combined dyslipidemia.", "output": "In an analysis of 36 controlled clinical trials (1674 patients) that evaluated statin-fibrate combinations, 0.12% of patients developed myopathy, but none developed rhabdomyolysis or kidney failure." }, { "input": "Fibrate or niacin added to statin monotherapy provide mixed lipid-modifying effects for combined dyslipidemia.", "output": "Adding niacin to statin monotherapy can modify combined dyslipidemia as does a statin/fibrate combination, by lowering LDL cholesterol and triglycerides, and raising HDL cholesterol to an even greater extent. Patients are more intolerant to a statin/niacin combination (eg, flushing) than to a statin/fibrate combination, but have a lower risk of myopathy with the former." }, { "input": "Most combination therapies increase the risk of intolerance or side effects, including myopathy. The statin/gemfibrozil combination has the highest risk of myopathy, whereas statin/ezetimibe or statin/bile acid sequestrant have the least increased risk.", "output": "Although considered safe, adding ezetimibe increases the incidence of elevated hepatic transaminases from 0.4% to 1.3%." }, { "input": "Most combination therapies increase the risk of intolerance or side effects, including myopathy. The statin/gemfibrozil combination has the highest risk of myopathy, whereas statin/ezetimibe or statin/bile acid sequestrant have the least increased risk.", "output": "Experts believe myopathy risk is greater with gemfibrozil than fenofibrate, based on gemfibrozil's inhibition of statin glucuronidation, and case reports in the literature. Accordingly, the maximum approved daily doses of lovastatin (Mevacor), simvastatin (Zocor), and rosuvastatin (Crestor) are lowered (20, 10, and 10 mg, respectively) when used with gemfibrozil." }, { "input": "Most combination therapies increase the risk of intolerance or side effects, including myopathy. The statin/gemfibrozil combination has the highest risk of myopathy, whereas statin/ezetimibe or statin/bile acid sequestrant have the least increased risk.", "output": "In an analysis of 36 controlled clinical trials (1674 patients) that evaluated statin-fibrate combinations, 0.12% of patients developed myopathy, but none developed rhabdomyolysis or kidney failure." }, { "input": "Most combination therapies increase the risk of intolerance or side effects, including myopathy. The statin/gemfibrozil combination has the highest risk of myopathy, whereas statin/ezetimibe or statin/bile acid sequestrant have the least increased risk.", "output": "Prospective controlled trials have shown regression of atherosclerotic lesions with this combination, but have also shown increased risks of myopathy." }, { "input": "Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention.", "output": "A well-done meta-analysis of alcohol reduction and blood pressure included 7 studies with 415 hypertensive patients. Mean baseline alcohol consumption was 3 to 6 alcoholic drinks per day, and the mean reduction in consumption was 67%. For this patient population, the average improvement was almost 4 mm Hg for SBP and nearly 2.5 mm Hg for DBP." }, { "input": "Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention.", "output": "A Cochrane review of 17 trials with 734 participants concluded that for individuals with hypertension, a reduced-salt diet results in a mean SBP and DBP reductions of 5 mm Hg and 3 mm Hg, respectively." }, { "input": "Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention.", "output": "A Cochrane review of 18 trials with 2611 participants concluded that for overweight hypertensive patients, weight loss of 3% to 9% of body weight is associated with 3 mm Hg decreases in both SBP and DBP." }, { "input": "Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention.", "output": "In a high-quality RCT, the DASH diet lowered SBP for hypertensive patients by an average of 11 mm Hg and DBP by an average of 5.5 mm Hg compared with the control group. Participants were provided with all food during the entire 8-week length of the trial." }, { "input": "Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention.", "output": "A well-done systematic review and meta-analysis from 2002 (including 15 studies with 770 participants) concluded that for hypertensive patients, aerobic exercise with at least one 40-minute session of moderate intensity per week is associated with a drop in SBP of about 5 mm Hg and a drop in DBP of about 4 mm Hg." }, { "input": "Studies of community-based interventions advocating combinations of the above have had mixed results with less reduction in blood pressure noted than for the individual interventions described above.", "output": "Thirteen randomized controlled trials of community-based interventions involving various combinations of lifestyle change advice show mixed results. In general, studies of interventions that were more intensive (ie, longer in duration, larger number of sessions, small group or one-on-one as opposed to large group lectures) and studies with shorter follow-up periods showed more positive results. The magnitude of the blood pressure improvements tended to be lower than exercise, diet, sal reduction or alcohol moderation." }, { "input": "Statins are contraindicated for women who are pregnant or breastfeeding. Data evaluating statin use for women of childbearing age is limited; however, they may be used cautiously with adequate contraception. Pravastatin may be preferred based on its low tissue-penetration properties. Cholesterol-lowering with simvastatin 40 mg/d did not disrupt menstrual cycles or effect luteal phase duration.", "output": "Highly lipophilic statins-such as simvastatin, atorvastatin (Lipitor), and lovastatin-achieve embryoplacental concentrations similar to those of maternal plasma. For this reason, if statin therapy is needed, these agents should be avoided. Pravastatin (Pravachol) is the most hydrophilic statin and has no reports of abnormal pregnancy outcomes, even in animal research." }, { "input": "Statins are contraindicated for women who are pregnant or breastfeeding. Data evaluating statin use for women of childbearing age is limited; however, they may be used cautiously with adequate contraception. Pravastatin may be preferred based on its low tissue-penetration properties. Cholesterol-lowering with simvastatin 40 mg/d did not disrupt menstrual cycles or effect luteal phase duration.", "output": "Consider initial pregnancy tests and inform all women of childbearing age of the possibility of fetal injury before starting statin therapy." }, { "input": "Statins are contraindicated for women who are pregnant or breastfeeding. Data evaluating statin use for women of childbearing age is limited; however, they may be used cautiously with adequate contraception. Pravastatin may be preferred based on its low tissue-penetration properties. Cholesterol-lowering with simvastatin 40 mg/d did not disrupt menstrual cycles or effect luteal phase duration.", "output": "A meta-analysis evaluated the benefits of lipid-lowering medication in trials of at least 1 year duration that included women. Total and coronary heart disease (CHD) mortality, nonfatal myocardial infarction, revascularization, and total CHD events were assessed among women with and without cardiovascular disease (CVD). Ten trials included statins. Of the 5 studies that reported age, the average was 61 years. For women without CVD, lipid-lowering treatment was not shown to affect total or CHD mortality. For women with known CVD, hyperlipidemia treatment did not affect total mortality, but was shown effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization; the relative risk of CHD events for statin users was 0.80 (95% confidence interval [CI], 0.71-0.91). The number of women needed to treat (NNT) to prevent an initial CHD event was 140. For secondary prevention, the NNT to prevent 1 CHD event was 26. Since women of child-bearing potential have lower probability of CHD events compared to the older women studied in this meta-analysis, the expected benefit for younger women is likely to be substantially lower." }, { "input": "Statins are contraindicated for women who are pregnant or breastfeeding. Data evaluating statin use for women of childbearing age is limited; however, they may be used cautiously with adequate contraception. Pravastatin may be preferred based on its low tissue-penetration properties. Cholesterol-lowering with simvastatin 40 mg/d did not disrupt menstrual cycles or effect luteal phase duration.", "output": "One study suggests that short-term use of simvastatin does not affect menstruation or ovulation of premenopausal women. This double-blind, randomized, placebo-controlled trial enrolled 86 normally cycling women. Mean age of women completing the study was 35. Simvastatin 40 mg/d was studied for cholesterol effects and female reproductive effects. Urinary luteinizing hormone (LH) and pregnanediol glucuronide (PDG), a progesterone metabolite, were assessed to determine if treatment with simvastatin adversely affects luteal function. Simvastatin lowered low-density lipoprotein (LDL) cholesterol by 34.3% (P<.001). Normal luteal phase duration and peak were confirmed by urinary PDG and LH levels. This study demonstrated that treatment with simvastatin for 4 months had no significant clinical changes on reproductive gonadal function compared with placebo." }, { "input": "Statins are contraindicated for women who are pregnant or breastfeeding. Data evaluating statin use for women of childbearing age is limited; however, they may be used cautiously with adequate contraception. Pravastatin may be preferred based on its low tissue-penetration properties. Cholesterol-lowering with simvastatin 40 mg/d did not disrupt menstrual cycles or effect luteal phase duration.", "output": "Use of statins is contraindicated during pregnancy based on pre-marketing animal studies showing developmental toxicities in animal fetuses; consequently they are pregnancy category X." }, { "input": "Children should be screened for hyperlipidemia when there is a history of familial hypercholesterolemia.", "output": "A control cohort from a case-control study that applied the National Cholesterol Education Program NCEP guidelines for screening in children to 501 US males less than 20 years old, and examined the effectiveness of using the recommended 2 major screening indicators family history of premature cardiovascular disease and parent cholesterol >240 mg/dL plus 5 discretionary indicators high-fat/high-cholesterol diet, hypertension, obesity, smoker, steroid/medication. If all major and discretionary indicators were applied to the cohort, 96% of the children with LDL greater than 130 mg/dL were identified. However, the individual positive predictive values PPV; probability of having LDL >130 when a child had a screening indicator ranged from 6.8% to 20.6%." }, { "input": "Children should be screened for hyperlipidemia when there is a history of familial hypercholesterolemia.", "output": "One systematic review and cost-effectiveness analysis investigated the appropriateness and cost-effectiveness of screening methods for familial hypercholesterolemia beginning at the age of 16 years. The authors identified potential screening strategies from 6 cross-sectional studies and applied these to a decision analysis. Screening of first-degree relatives of those with familial hypercholesterolemia was most effective in detecting cases of familial hypercholesterolemia (number needed to screen [NNS]=3; cost per case detected=$232; cost per life-year gained=$5397). Universal screening of all 16-year-olds was also cost-effective (cost per life-year gained=$4839), but resulted in a much larger NNS and cost of detection (NNS=1365, cost per case detected=$16,999). The authors concluded that case finding through screening of first-degree relatives was the most cost-effective strategy overall." }, { "input": "Children should be screened for hyperlipidemia when there is a history of familial hypercholesterolemia.", "output": "Children with heterozygous familial hypercholesterolemia, an autosomal dominant disorder with a prevalence of 1 in 500, are at increased risk of cardiovascular morbidity and mortality in adulthood. One quarter of males with familial hyper-cholesterolemia suffer fatal coronary heart disease (CHD) by age 50 years." }, { "input": "No clear evidence supports screening all children or just those with family history of cardiovascular disease (CVD) or hyperlipidemia.", "output": "In contrast to children affected with familial hypercholesterolemia, the relationship of blood cholesterol levels in children without familial hypercholesterolemia to CHD later in life has not been established. A paucity of data exists that links lowering of cholesterol in childhood with reduced CHD morbidity and mortality in adulthood. Therefore, the benefits of detecting and treating childhood hyperlipidemia without familial hypercholesterolemia are not known. Despite the lack of patient-oriented outcomes research in this area, 2 guidelines recommend screening all children for hyperlipidemia." }, { "input": "No clear evidence supports screening all children or just those with family history of cardiovascular disease (CVD) or hyperlipidemia.", "output": "A study used a cross-sectional design to evaluate family history of premature cardiovascular disease and hyperlipidemia screening indicators in 4183 grade-school children in Taiwan. Family history performed poorly as a mechanism for identifying children with hypercholesterolemia (total cholesterol >200 mg/dL; LDL >130 mg/dL) (PPV <12.5%7). More than 75% of the children in the Taiwan study would have been missed using family history as a screen. Study concluded that family history as a screening indicator is insensitive and inaccurate, and no more useful than general population screening." }, { "input": "No clear evidence supports screening all children or just those with family history of cardiovascular disease (CVD) or hyperlipidemia.", "output": "A study used a cross-sectional design to evaluate family history of premature cardiovascular disease and hyperlipidemia screening indicators 2217 youths in Quebec. Family history performed poorly as a mechanism for identifying children with hypercholesterolemia (total cholesterol >200 mg/dL; LDL >130 mg/dL) (PPV=7.7%). Study concluded that family history as a screening indicator is insensitive and inaccurate, and no more useful than general population screening." }, { "input": "other", "output": "Screening for hyperlipidemia using total cholesterol and low-density lipoprotein (LDL) cholesterol is recommended for adults after the age of 35 years for men and 45 years for women. Younger adults (men aged 20-35 and women aged 20-45) should be screened for lipid disorders if they have other risk factors for CVD." }, { "input": "other", "output": "The use of statins by children with familial hypercholesterolemia for up to 2 years is safe and lowers LDL cholesterol. Longer use by children has not been studied, so no comment can be made about long-term safety and decreased CHD morbidity and mortality." }, { "input": "Based on limited evidence, use of intrauterine devices (IUDs) is not contraindicated for women with HIV/AIDS.", "output": "IUDs do not increase the risk of complications among immunosuppressed HIV-positive women." }, { "input": "Use of intrauterine devices (IUDs) is not contraindicated for women with multiple sexual partners", "output": "Having multiple sexual partners was not associated with an increased risk of PID unless those partners carry specific infections, such as gonorrhea or chlamydia." }, { "input": "Use of intrauterine devices (IUDs) is not contraindicated for women with previous actinomyces colonization.", "output": "In an observational study, all of 7 women with actinomyces who had IUDs removed remained negative for actinomyces after insertion of a new IUD." }, { "input": "The risk to IUD users of pelvic inflammatory disease (PID) is similar to women using no contraception.", "output": "IUD insertion does not increase the risk of PID for women with gonorrhea or chlamydia infection compared with infected nonusers." }, { "input": "The risk to IUD users of pelvic inflammatory disease (PID) is similar to women using no contraception.", "output": "In the US, approximately 1 in 1000 women develop PID after IUD insertion." }, { "input": "Nulliparous women may experience increased insertion discomfort and higher rates of expulsion.", "output": "Nulliparous women have increased rates of discomfort with IUD placement (17.8% vs 8.8%) and may have an increased risk of expulsion (up to 18.5% in one study, compared with less than 5.7% for all IUD users)." }, { "input": "Nulliparous women may experience increased insertion discomfort and higher rates of expulsion.", "output": "Short-term (\u22643.5 years) IUD use by nulliparous women was not associated with decreased fertility in a case-control study." }, { "input": "IUD use of <3.5 years is not associated with decreased fertility.", "output": "One cohort study demonstrated lower fertility with use of a copper IUD for longer periods: hazard ratio (HR): 0.69 (95% confidence interval [CI], 0.497-0.97) for 42-78 months; HR=0.50 (95% CI, 0.34-0.73) for >78 months." }, { "input": "other", "output": "There are case reports of IUD failure and uterine perforation among women with anomalies that distort the uterine cavity." }, { "input": "other", "output": "Significant uterine enlargement can increase the risk of IUD expulsion (0 vs 4 women [13%]; P=.04 in 1 retrospective cohort study)." }, { "input": "other", "output": "Bacterial vaginosis may increase dysmenorrhea for women with IUDs (34.8 vs 13.9%, P=.03)." }, { "input": "Cognitive behavioral therapy (CBT) interventions-particularly stimulus control and sleep hygiene-are well-validated, effective treatments for chronic insomnia that are equivalent or superior to pharmacological interventions.", "output": "Researchers conducting a single-blind randomized group study in a Veterans Affairs primary care clinic concluded that an abbreviated CBT approach with two 25-minute sessions effectively improved participant sleep onset latency, and time awake after sleep onset. Researchers reviewed participants' sleep logs and a behavioral health provider offered patients a condensed education on sleep hygiene, stimulus control, and sleep restrictions strategies. The study was limited because of small sample size (<25). Generalizability to practice is restricted because sessions were conducted by a behavioral health provider, not a family physician." }, { "input": "Cognitive behavioral therapy (CBT) interventions-particularly stimulus control and sleep hygiene-are well-validated, effective treatments for chronic insomnia that are equivalent or superior to pharmacological interventions.", "output": "A systematic review with meta-analysis of 37 clinical investigations determined that stimulus control was the most effective CBT intervention." }, { "input": "Cognitive behavioral therapy (CBT) interventions-particularly stimulus control and sleep hygiene-are well-validated, effective treatments for chronic insomnia that are equivalent or superior to pharmacological interventions.", "output": "A meta-analysis of 21 studies validated behavior therapy, and revealed CBT reduced sleep onset latency by an additional 8.8 minutes over medication (95% confidence interval, 0.17-1.04 minutes)." }, { "input": "Cognitive behavioral therapy (CBT) interventions-particularly stimulus control and sleep hygiene-are well-validated, effective treatments for chronic insomnia that are equivalent or superior to pharmacological interventions.", "output": "Five high-quality randomized control trials (RCTs) confirmed findings from earlier RCTs that CBT methods improve sleep. Compared with those given a placebo or placed on a waiting list, CBT-treated patients in these RCTs reported clinically significant improvements in sleep onset latency, sleep efficiency, time awake after sleep onset, and total sleep time. In one RCT, 64% of CBT patients had improvements in sleep efficiency and time awake after sleep onset, compared with 8% who improved with a placebo intervention (number needed to treat [NNT]=1.8). Further, sleep onset latency for primary care patients with chronic insomnia was decreased from 61 to 28 minutes, compared with 74 to 70 minutes for a waiting-list group." }, { "input": "Cognitive behavioral therapy (CBT) interventions-particularly stimulus control and sleep hygiene-are well-validated, effective treatments for chronic insomnia that are equivalent or superior to pharmacological interventions.", "output": "CBT interventions combine empirically tested behavioral, cognitive, and educational procedures to alter faulty beliefs and attitudes, modify sleep habits, and regulate sleep-wake schedules." }, { "input": "Cognitive behavioral therapy (CBT) interventions-particularly stimulus control and sleep hygiene-are well-validated, effective treatments for chronic insomnia that are equivalent or superior to pharmacological interventions.", "output": "CBT interventions are based on the notion that distorted thoughts about sleep and learned behavior patterns hyperarouse the central nervous system and deregulate sleep cycles, resulting in chronic insomnia." }, { "input": "Fourteen-day triple therapy with a proton pump inhibitor (PPI) plus clarithromycin and either amoxicillin or metronidazole is superior to 7-day therapy in eradicating Heliobacter pylori.", "output": "Fourteen-day triple therapy of PPI + clarithromycin + metronidazoleoramoxicillin. A meta-analysis of 13 studies found the eradication rate for 14-day therapy was 81% (95% confidence interval [CI], 77%-85%), compared with 72% (95% CI, 68%-76%) for 7-day therapy. The eradication rate for 10-day therapy (83%; 95% CI, 75%-89%), however, was not significantly better than that for 7-day therapy (80%; 95% CI, 71%-86%). Side effects were more frequent in the longer therapies, but did not lead to discontinuation of therapy." }, { "input": "Seven-day triple therapy with a PPI or ranitidine bismuth citrate plus clarithromycin and either amoxicillin or metronidazole is also effective.", "output": "A high-quality systematic review of 82 studies using 7-day triple therapy found clarithromycin 500 twice daily yielded a higher eradication rate than clarithromycin 250 mg twice daily when combined with a PPI and amoxicillin (87% vs 81%; P<.0001). When clarithromycin was combined with a PPI and metronidazole, the higher dose of clarithromycin did not yield significantly higher eradication rates (88% vs 89%, P=.259)." }, { "input": "Seven-day triple therapy with a PPI or ranitidine bismuth citrate plus clarithromycin and either amoxicillin or metronidazole is also effective.", "output": "Seven-day triple therapy of ranitidine bismuth citrate + clarithromycin + metronidazole or amoxicillin. For these therapies, a high-quality systematic review of 8 studies reported eradication rates of 81% (95% CI, 77%-84%) with amoxicillin and 88% (95% CI, 85%-90%) with metronidazole. Side effects were not reported in a uniform manner for the 7-day therapies, but were noted to be mild and did not lead to significant discontinuation of therapy. Pooled dropout rates were similar among all regimens." }, { "input": "Three-day quadruple therapy with a combination of PPI, clarithromycin, bismuth subcitrate, and metronidazole or a combination of PPI, clarithromycin, amoxicillin, and metronidazole also appears to be effective.", "output": "A high-quality unblinded randomized clinical trial of 234 patients demonstrated that 2 days of pretreatment with lansoprazole followed by 3 days of lansoprazole with clarithromycin, amoxicillin, and metronidazole yielded eradication rates comparable with 5-day treatment (81% vs. 89%; P<.05)." }, { "input": "Three-day quadruple therapy with a combination of PPI, clarithromycin, bismuth subcitrate, and metronidazole or a combination of PPI, clarithromycin, amoxicillin, and metronidazole also appears to be effective.", "output": "A randomized clinical trial of 118 patients, blinded to investigators but not patients, showed that quadruple 3-day therapy with lansoprazole + bismuth + clarithromycin + metronidazole was as effective as 7 days of lansoprazole + clarithromycin + metronidazole (87% vs 86%; P=.94), and had significantly shorter duration of side effects (2.6 vs 6.2 days; P<.001). Eradication rates were similar in isolates that were resistant or sensitive to either metronidazole or clarithromycin." }, { "input": "Evidence from prospective and retrospective clinical trials suggests that for infants <2 months old, only those at high risk for serious bacterial infection by standardized criteria (eg, Rochester classification) require lumbar puncture.", "output": "A retrospective chart review of 492 infants aged <3 months who were hospitalized due to fever included 108 infants aged <1 month. Thirty percent (114) of the infants aged 1 to 3 months and 67% (72) of the younger infants underwent lumbar puncture at the discretion of the treating physician. All infants were retrospectively assigned to low- or high-risk groups for serious bacterial infection using the Rochester criteria. Of the 296 infants rated \"low-risk\", none developed bacterial meningitis. Ten of these infants subsequently developed evidence of another bacterial focus (predominantly urinary tract infection)." }, { "input": "Evidence from prospective and retrospective clinical trials suggests that for infants <2 months old, only those at high risk for serious bacterial infection by standardized criteria (eg, Rochester classification) require lumbar puncture.", "output": "One prospective cohort study of infants aged <1 month hospitalized for fever used a similar method for assessing risk, but added a C-reactive protein value <20 mg/L to criteria for low-risk. Of 250 infants studied, 131 (52%) were low-risk; none of these developed bacterial meningitis." }, { "input": "Evidence from prospective and retrospective clinical trials suggests that for infants <2 months old, only those at high risk for serious bacterial infection by standardized criteria (eg, Rochester classification) require lumbar puncture.", "output": "Five studies applied the standardized criteria to febrile infants and monitored them for the development of serious bacterial infection, including meningitis. Two prospective cohort studies of outpatients aged 0 to 2 months used the Rochester criteria to assign infants to risk groups. They studied a total of 1294 infants; 659 (51%) were low-risk. None of the low-risk infants developed bacterial meningitis." }, { "input": "Evidence from prospective and retrospective clinical trials suggests that for infants <2 months old, only those at high risk for serious bacterial infection by standardized criteria (eg, Rochester classification) require lumbar puncture.", "output": "Infants aged <3 months who fall into the \"high-risk\" category or appear toxic have 21% probability of a serious bacterial infection, 10% probability of bacteremia, and 2% probability of bacterial meningitis." }, { "input": "However, expert opinion suggests lumbar puncture on all infants aged 0 to 28 days with suspected sepsis, and all infants aged >2 months who are to receive empiric antibiotics.", "output": "The expert panel that devised this guideline emphasized a full sepsis evaluation including cerebrospinal fluid cultures for infants <28 days of age \"despite the low probability of serious bacterial infections in this age group and the favorable outcome of the children managed to date with careful observation\". For low-risk infants aged 1 to 2 months, lumbar puncture is not necessary unless empiric antibiotics are given; having a cerebrospinal fluid culture prior to empiric antibiotics reduces the concern of partially treated meningitis in the case of clinical deterioration after hospital discharge." }, { "input": "other", "output": "The \"low-risk\" infants have a correspondingly lower incidence of serious bacterial infection: the negative predictive value of the Rochester classification is 98.9% 95% confidence interval [CI], 97.2-99.6%." }, { "input": "In addition, the use of a knee brace following ACL reconstruction does not improve stability or hasten rehabilitation, either immediately or for up to 2 years.", "output": "In a prospective study of 62 patients, researchers found no benefit from using a postoperative knee brace at any stage (2 and 6 weeks; 3, 6, and 24 months) after surgery. Moreover, the brace did not contribute to a more stable knee during rehabilitation or 2-year follow-up." }, { "input": "In addition, the use of a knee brace following ACL reconstruction does not improve stability or hasten rehabilitation, either immediately or for up to 2 years.", "output": "A similar study of 50 patients demonstrated no significant difference in function or laxity at 2 years." }, { "input": "In addition, the use of a knee brace following ACL reconstruction does not improve stability or hasten rehabilitation, either immediately or for up to 2 years.", "output": "One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace." }, { "input": "Patients wearing a knee brace after ACL reconstruction may report subjective enhanced performance, but measured performance is better without the brace.", "output": "One study evaluated running, jumping, and turning performance with and without a functional brace in 31 patients who had had an ACL reconstruction 5 to 26 months previously. They measured significantly better performance without bracing; however, more than half the group perceived enhanced performance with the brace." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "A single uncontrolled interventional trial of valproic acid in 10 children showed a significant trend of improvement in frequency (mean of 6 attacks/month to 0.8 attacks/month) and duration (mean 5.5 hours per attack to 1.1 hour)." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "A comparative randomized controlled trial with multiple crossovers involving 33 children found that a self-hypnosis placebo decreased mean headache frequency from 13.3 per 3-month interval to 5.8 (P=.045), but found propranolol no different than placebo. Propranolol was also studied in a 3-armed randomized controlled trial in comparison with flunarizine-a drug likely to be efficacious-and placebo." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "Propranolol, although widely used in children, has conflicting evidence regarding effectiveness. One small randomized controlled trial showed reduced headache frequency in children when compared with placebo." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "A prospective cohort trial studied 192 children. Of the 146 patients available for the first follow-up visit, 84% noted subjective improvement of symptoms. Headache frequency decreased from 17.1 \u00b1 10.1 to 9.2 \u00b1 10.0 days/month (P<.001)." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "UpToDate recommends propranolol, cyproheptadine, valproate, and amitriptyline as prophylactic options based on patient parameters such as age, sex, and comorbid conditions." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "Nelson Textbook of Pediatrics recommends propranolol as a first-line agent for prevention." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "Amitryptyline was moderately efficacious in 3 small nonblinded trials." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "In a small retrospective case study, valproic acid demonstrated >50% improvement in symptoms in 78% of subjects." }, { "input": "Propranolol, valproic acid, and amitriptyline are effective prophylaxis for migraine in children to varying degrees, are widely available, and have a reasonable safety profile.", "output": "In a small retrospective case study, valproic acid demonstrated >50% improvement in symptoms in 65% of subjects." }, { "input": "Flunarizine and nimodipine have the best evidence of benefit in children; however, availability, cost, and side effects limit their usefulness.", "output": "Flunarizine was found to be effective in multiple well-designed randomized controlled trials and case series, as well as in multiple comparative trials with other agents." }, { "input": "Flunarizine and nimodipine have the best evidence of benefit in children; however, availability, cost, and side effects limit their usefulness.", "output": "In a double-blinded, placebo-controlled randomized controlled trial of 48 children, flunarizine decreased mean headache frequency (3.0 attacks/3 months vs 6.5 [P<.001])." }, { "input": "Flunarizine and nimodipine have the best evidence of benefit in children; however, availability, cost, and side effects limit their usefulness.", "output": "A randomized controlled trial in 70 children flunarizine decreased mean headache frequency." }, { "input": "Flunarizine and nimodipine have the best evidence of benefit in children; however, availability, cost, and side effects limit their usefulness.", "output": "Nimodipine, in a single randomized controlled trial with crossover design in 37 children decreased headache frequency from a mean of ~2.7 attacks/month to ~1.9 vs. no change for placebo (P<.05)." }, { "input": "Flunarizine and nimodipine have the best evidence of benefit in children; however, availability, cost, and side effects limit their usefulness.", "output": "A small, prospective, nonblinded comparative trial found that nimodipine and flunarizine have similar efficacy and are superior to placebo." }, { "input": "Flunarizine and nimodipine have the best evidence of benefit in children; however, availability, cost, and side effects limit their usefulness.", "output": "Cyproheptadine is widely used in children but is not as effective as amitriptyline and propranolol." }, { "input": "Randomized controlled trials (RCTs) have demonstrated decreased vertebral and nonvertebral fracture rates in postmenopausal osteoporotic women taking a bisphosphonate (alendronate or risedronate). Hormone replacement therapy (HRT) also has some evidence for osteoporotic fracture prevention. Concurrent calcium and vitamin D may also prevent fractures. Physical exercise and smoking cessation have been associated with increased bone density, but fracture prevention has not been reported", "output": "Smoking cessation may also increase bone density." }, { "input": "Randomized controlled trials (RCTs) have demonstrated decreased vertebral and nonvertebral fracture rates in postmenopausal osteoporotic women taking a bisphosphonate (alendronate or risedronate). Hormone replacement therapy (HRT) also has some evidence for osteoporotic fracture prevention. Concurrent calcium and vitamin D may also prevent fractures. Physical exercise and smoking cessation have been associated with increased bone density, but fracture prevention has not been reported", "output": "Raloxifene and calcitonin have some supporting evidence as well. In a large 4-year placebo-controlled trial, raloxifene decreased vertebral fracture risk (RR = 0.7; 95% CI, 0.5-0.8) but had no effect on hip fracture and a threefold increase in thromboembolic risk (RR = 3.1; 95% CI, 1.5-6.2).7 Regarding calcitonin, one RCT compared 3 doses of intranasal calcitonin and placebo in osteoporotic women and showed an increase in lumbar spine BMD in treated groups.8 Over the 5-year study (59% of participants were lost to follow-up), there was a 39% reduction in risk of radiologic deformities (P=.03) only for women taking 200 IU. Many subjects also used vitamin D and calcium, but effective doses of both agents are still in question. Combined calcium and vitamin D supplements have decreased fracture risk using 700 to 800 IU of vitamin D and 500 to 1200 mg of calcium daily,9 but a systematic review of vitamin D without calcium found no clear benefit.10 A meta-analysis showed that exercise training programs may play a preventive role, potentially preventing or reversing 1% of bone loss annually among women." }, { "input": "Randomized controlled trials (RCTs) have demonstrated decreased vertebral and nonvertebral fracture rates in postmenopausal osteoporotic women taking a bisphosphonate (alendronate or risedronate). Hormone replacement therapy (HRT) also has some evidence for osteoporotic fracture prevention. Concurrent calcium and vitamin D may also prevent fractures. Physical exercise and smoking cessation have been associated with increased bone density, but fracture prevention has not been reported", "output": "Testosterone replacement in men is less studied; some small studies demonstrate increased BMD, but long-term benefits are unknown." }, { "input": "Randomized controlled trials (RCTs) have demonstrated decreased vertebral and nonvertebral fracture rates in postmenopausal osteoporotic women taking a bisphosphonate (alendronate or risedronate). Hormone replacement therapy (HRT) also has some evidence for osteoporotic fracture prevention. Concurrent calcium and vitamin D may also prevent fractures. Physical exercise and smoking cessation have been associated with increased bone density, but fracture prevention has not been reported", "output": "HRT has been associated with increased BMD in RCTs, fewer fractures in observational studies, and fewer fractures in a recent meta-analysis of RCTs. HRT had the greatest benefit among women younger than 60 years (RR = 0.67; 95% CI, 0.56-0.94).4 For women older than 60 years, a nonsignificant trend toward benefit was found (RR = 0.88, 95% CI, 0.71-1.08). However, in a large RCT of postmenopausal women, 85% without osteoporotic BMD, 4 years of HRT did not reduce fracture incidence." }, { "input": "Randomized controlled trials (RCTs) have demonstrated decreased vertebral and nonvertebral fracture rates in postmenopausal osteoporotic women taking a bisphosphonate (alendronate or risedronate). Hormone replacement therapy (HRT) also has some evidence for osteoporotic fracture prevention. Concurrent calcium and vitamin D may also prevent fractures. Physical exercise and smoking cessation have been associated with increased bone density, but fracture prevention has not been reported", "output": "One alendronate trial in 241 osteoporotic men demonstrated increased spine and hip BMD and a decreased incidence of vertebral fractures." }, { "input": "Randomized controlled trials (RCTs) have demonstrated decreased vertebral and nonvertebral fracture rates in postmenopausal osteoporotic women taking a bisphosphonate (alendronate or risedronate). Hormone replacement therapy (HRT) also has some evidence for osteoporotic fracture prevention. Concurrent calcium and vitamin D may also prevent fractures. Physical exercise and smoking cessation have been associated with increased bone density, but fracture prevention has not been reported", "output": "Alendronate and risedronate have both reduced vertebral and nonvertebral fractures and increased BMD in clinical trials. The pooled risk estimates for alendronate's antifracture effect are 48% to 53% vertebral and hip fracture reduction and 30% reduction of all clinical fractures (relative risk [RR] = 0.70; 95% confidence interval [CI], 0.59-0.82).1 Risedronate reduced hip fractures in osteoporotic women aged 70 to 79 years (RR = 0.6; 95% CI, 0.4-0.9), but women 80 years and older with nonskeletal risk factors did not benefit." }, { "input": "Tamoxifen prevents breast cancer in women older than 60 years and in younger women with equally high risk because of breast disease and reproductive and family history, but there is no current evidence for or against long-term survival or overall health benefits. A 49% reduction in 5-year incidence of invasive and noninvasive breast cancer but increased risk for endometrial cancer, pulmonary emboli, deep vein thrombosis, and cataracts. The long-term benefits and overall health effects of tamoxifen for primary prevention of breast cancer remain unclear; the ongoing International Breast Cancer Intervention Study trial is designed to address this question.", "output": "An RCT reported that women given tamoxifen for only 5 years for ER-positive breast cancer with negative nodes had improved disease-free survival compared with women randomized to continue tamoxifen more than 5 years (92% vs 86% respectively, P=.003)." }, { "input": "Tamoxifen prevents breast cancer in women older than 60 years and in younger women with equally high risk because of breast disease and reproductive and family history, but there is no current evidence for or against long-term survival or overall health benefits. A 49% reduction in 5-year incidence of invasive and noninvasive breast cancer but increased risk for endometrial cancer, pulmonary emboli, deep vein thrombosis, and cataracts. The long-term benefits and overall health effects of tamoxifen for primary prevention of breast cancer remain unclear; the ongoing International Breast Cancer Intervention Study trial is designed to address this question.", "output": "An RCT reported no benefit from tamoxifen in young women with at least one first-degree relative with breast cancer. HRT was allowed, and the study had 90% power to detect a reduction of 50% in breast cancer incidence. Authors estimated that 36% of participants and 60% of women who developed breast cancer had a greater than 80% chance of having a breast cancer predisposition gene. Breast cancers in women with the Breast Cancer 1 gene (BRCA1) are more likely to be ER negative." }, { "input": "Tamoxifen prevents breast cancer in women older than 60 years and in younger women with equally high risk because of breast disease and reproductive and family history, but there is no current evidence for or against long-term survival or overall health benefits. A 49% reduction in 5-year incidence of invasive and noninvasive breast cancer but increased risk for endometrial cancer, pulmonary emboli, deep vein thrombosis, and cataracts. The long-term benefits and overall health effects of tamoxifen for primary prevention of breast cancer remain unclear; the ongoing International Breast Cancer Intervention Study trial is designed to address this question.", "output": "An RCT reported no overall benefit from treatment with tamoxifen in low-risk hysterectomized women, but the trial was underpowered, had a high dropout rate in the first year, and allowed hormone replacement therapy (HRT)." }, { "input": "Tamoxifen prevents breast cancer in women older than 60 years and in younger women with equally high risk because of breast disease and reproductive and family history, but there is no current evidence for or against long-term survival or overall health benefits. A 49% reduction in 5-year incidence of invasive and noninvasive breast cancer but increased risk for endometrial cancer, pulmonary emboli, deep vein thrombosis, and cataracts. The long-term benefits and overall health effects of tamoxifen for primary prevention of breast cancer remain unclear; the ongoing International Breast Cancer Intervention Study trial is designed to address this question.", "output": "An RCT reported a 49% (P <.001) reduction in incidence of invasive breast cancer and 50% in noninvasive breast cancer (P <.002) among women with a 5-year risk of breast cancer \u017e 1.66% based on the Gail Risk Index. Estrogen receptor (ER)-negative breast cancers were unaffected." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "The Study of Osteoporotic Fractures showed no beneficial effect of calcium supplements on fracture risk. This cohort study found that calcium supplements were actually associated with an increased risk of hip fracture (RR=1.5; 95% CI, 1.1-2.0) and vertebral fracture (RR=1.4; 95% CI, 1.1-1.9)." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "A randomized controlled trial in post-menopausal women with low calcium intake and previous vertebral fractures showed that 1200 mg of calcium supplementation reduced the incidence of additional fractures (RR=0.23)." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "A randomized controlled trial of elderly ambulatory women showed that supplementation with 1200 mg calcium and 800 IU vitamin D per day for 18 months decreased hip fractures (RR=0.26; 95% CI, 0.03-0.44; NNT=48) and other nonvertebral fractures (RR=0.25; 95% CI, 0.09-0.38; NNT=26)." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "A randomized controlled trial of healthy, community-dwelling people 65 years of age and older (55% women) showed daily supplementation with 500 mg calcium and 700 IU vitamin D for 3 years decreased nonvertebral fractures vs. placebo (response rate [RR]=0.54; 95% confidence interval [CI], 0.12-0.77; number needed to treat [NNT]=15)." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "The effect may be greatest in the first year of supplementation and less in subsequent years." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "A randomized controlled trial of healthy women, postmenopausal for at least 3 years, showed that calcium supplementation at 1000 mg per day for 2 years decreased bone density loss in the hip and eliminated loss in the spine." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "One double-blind, randomized controlled trial included healthy women who were 6 or more years postmenopausal and had a dietary intake of less than 400 mg of calcium per day. Women who received daily calcium citrate (500 mg) for 2 years had significantly less bone loss at the spine, hip, and radius than women taking placebo. In addition, calcium carbonate supplementation maintained bone density at the hip and radius but not the spine when compared with placebo. This dose of calcium was not associated with better outcomes in women within the first 5 years after menopause, but the dose was less than most generally recommended ranges." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "Daily supplementation of calcium (500-1200 mg) along with vitamin D (700-800 IU) is the regimen best supported by the evidence. Since the absorption of calcium decreases with single doses above 500 mg, the studies that used 1000-1200 mg of calcium split the daily doses." }, { "input": "Calcium supplementation (1000-1200 mg daily) decreases menopause-related bone loss and reduces the rate of vertebral and non-vertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700-800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency.", "output": "Reviews of rigorous randomized trials support calcium supplementation in order to decrease the risk of vertebral fracture by approximately 35% and nonvertebral fractures by approximately 25%." }, { "input": "Most recent randomized controlled clinical trials have not found a benefit in antioxidants (vitamin C, vitamin E, and/or beta-carotene) for preventing cardiovascular disease, including stroke. These recent clinical studies have not confirmed earlier observational studies that suggested a benefit. No studies have assessed only stroke patients and stroke outcomes.", "output": "Although prior observational studies have hinted at a link between antioxidants and improved cardiovascular outcomes, the recently published Health Professionals Follow-up Study found no benefit to vitamin C or E in preventing strokes, based on the dietary assessment of 43,738 men, aged 40 to 75 years, who were not known to have cardiovascular disease or diabetes." }, { "input": "Most recent randomized controlled clinical trials have not found a benefit in antioxidants (vitamin C, vitamin E, and/or beta-carotene) for preventing cardiovascular disease, including stroke. These recent clinical studies have not confirmed earlier observational studies that suggested a benefit. No studies have assessed only stroke patients and stroke outcomes.", "output": "In the Heart Protection Study, 20,536 adults between the ages of 40 and 80 years with cardiovascular disease, stroke, or diabetes were given vitamin E, vitamin C, beta-carotene, or placebo for 5 years. No significant differences were noted between vitamins and placebo in fatal or nonfatal stroke (RR = 0.99; 95% CI, 0.87-1.12)." }, { "input": "Most recent randomized controlled clinical trials have not found a benefit in antioxidants (vitamin C, vitamin E, and/or beta-carotene) for preventing cardiovascular disease, including stroke. These recent clinical studies have not confirmed earlier observational studies that suggested a benefit. No studies have assessed only stroke patients and stroke outcomes.", "output": "The Italian GISSI study of 11,324 patients with a recent myocardial infarction showed no effect of vitamin E on the combined outcomes of death, myocardial infarction, and stroke." }, { "input": "Most recent randomized controlled clinical trials have not found a benefit in antioxidants (vitamin C, vitamin E, and/or beta-carotene) for preventing cardiovascular disease, including stroke. These recent clinical studies have not confirmed earlier observational studies that suggested a benefit. No studies have assessed only stroke patients and stroke outcomes.", "output": "Subgroup analysis showed a significant decrease in cerebral infarction (RR = 0.33; 95% CI, 0.14-0.78) without increasing subarachnoid hemorrhage in hypertensive, diabetic men taking vitamin E." }, { "input": "Most recent randomized controlled clinical trials have not found a benefit in antioxidants (vitamin C, vitamin E, and/or beta-carotene) for preventing cardiovascular disease, including stroke. These recent clinical studies have not confirmed earlier observational studies that suggested a benefit. No studies have assessed only stroke patients and stroke outcomes.", "output": "In a randomized controlled clinical trial of 29,133 Finnish male smokers, the overall net stroke morbidity and mortality with antioxidants was not significantly different from placebo. However, a trend toward higher rates of subarachnoid hemorrhages was found (relative risk [RR] = 1.5; 95% confidence interval [CI], 0.97-2.32; numbers needed to harm [NNH] = 833), while the cerebral infarction rate was decreased (RR = 0.86; 95% CI, 0.75-0.99; numbers needed to treat = 239) by vitamin E. Beta-carotene increased intracerebral hemorrhage (RR = 1.61; 95% CI, 1.10-2.36; NNH = 546)." }, { "input": "Most recent randomized controlled clinical trials have not found a benefit in antioxidants (vitamin C, vitamin E, and/or beta-carotene) for preventing cardiovascular disease, including stroke. These recent clinical studies have not confirmed earlier observational studies that suggested a benefit. No studies have assessed only stroke patients and stroke outcomes.", "output": "The Heart Outcomes Prevention Evaluation HOPE trial was a 4.5-year randomized controlled clinical trial of vitamin E or placebo in 9541 patients aged 55 years or older with a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes and other cardiovascular disease risk factors. No difference was noted between vitamin E and placebo for the outcomes of stroke, death, or other cardiac outcomes for these high-risk patients." }, { "input": "Nicotine replacement therapy (NRT), including gum and patches, decreases cravings and short-term abstinence rates, but does not improve long-term abstinence.", "output": "A meta-analysis of 6 studies that examined NRT or bupropion in smokeless tobacco users. The primary outcome for the meta-analysis was tobacco abstinence 6 months or more after the intervention. Neither nicotine patches (odds ratio [OR]=1.16; 95% confidence interval [CI], 0.88-1.54) nor nicotine gum (OR=0.98; 95% CI, 0.59-1.63) were shown to improve abstinence over placebo at 6 months." }, { "input": "Nicotine replacement therapy (NRT), including gum and patches, decreases cravings and short-term abstinence rates, but does not improve long-term abstinence.", "output": "A randomized double-blind study examined nicotine transdermal patches in smokeless tobacco users. Researchers recruited 422 participants from a Minnesota college campus and surrounding metropolitan area through advertisements; they were randomly assigned to nicotine patch plus mint snuff (a nicotine-free product), nicotine patch and no mint snuff, placebo patch plus mint snuff, or placebo patch and no mint snuff. The patch was dosed as 21-mg patch for 6 weeks, 14-mg patch for 2 weeks, and 7-mg patch for 2 weeks. All patients participated in 8 weekly individual 10-minute sessions with a therapist. Continuous 10-week abstinence rates were 69% for nicotine patch and mint snuff, 58% for nicotine patch and no mint snuff, 46% for placebo patch and mint snuff, and 51% for placebo patch and no mint snuff (P=.002). After 15 weeks the abstinence rates were no longer different between the treatment groups. Patch users experienced lower total withdrawal scores (P=.002) as well as decreased craving (P<.001), irritability (P<.001), and restlessness (P=.019). Total withdrawal scores were not improved for mint snuff users; however, subsets of total withdrawal scores were lower for cravings (P=.005), irritability (P=.046), and anxiety (P=.012)." }, { "input": "Nicotine replacement therapy (NRT), including gum and patches, decreases cravings and short-term abstinence rates, but does not improve long-term abstinence.", "output": "A study randomized 234 male smokeless tobacco users to receive group behavioral treatment plus nicotine gum 2 mg (B/NRT); group behavioral treatment plus placebo (B/Pl); minimal contact plus nicotine gum 2 mg (MC/NRT); or minimal contact plus placebo (MC/Pl). Group behavioral treatment consisted of 8 group counseling sessions 45 to 60 minutes in length; minimal contact involved 4 brief one-on-one sessions with a nurse. Patients chewed a minimum of 6 pieces of nicotine or placebo gum per day. At 4 weeks, point prevalence abstinence rates were as follows: B/NRT, 63.6%; B/Pl, 66%; MC/NRT, 35.3%; and MC/Pl, 48.1% (P<.01). Abstinence rates remained significantly different at 1 and 6 month follow-ups, but not at 12 months. Post-hoc logistic regression favored group behavioral therapy plus NRT at 6 months. Moreover, survival analysis of continuous prevalence rates demonstrated that the least effective treatment was minimal contact plus NRT." }, { "input": "Nicotine replacement therapy (NRT), including gum and patches, decreases cravings and short-term abstinence rates, but does not improve long-term abstinence.", "output": "A small double-blind study randomized 79 male smokeless tobacco users to chew nicotine gum (0 mg, 2 mg, or 4 mg) for 5 days. Sixty patients completed the study. No significant differences in withdrawal symptoms, including cravings, concentration, or restlessness, were noted among the 3 groups (P>.05). However, further analysis demonstrated that patients with high blood levels of cotinine who received nicotine gum 2 mg experienced decreased cravings compared with placebo (P<.001), and a trend towards decreased cravings with 4 mg gum was noted (P<.06). Limitations of this study: quit rates were not reported, participants did not have to be motivated to quit smokeless tobacco in order to enroll, and it is not known if patients were counseled about the appropriate \"chew and park\" technique for nicotine gum." }, { "input": "It is unclear if bupropion has an effect on cessation rates.", "output": "In a meta-analysis, one small randomized trial of bupropionfound no effect on tobacco abstention (OR=1.00; 95% CI, 0.23-4.37)." }, { "input": "Behavioral interventions increase abstinence rates for smokeless tobacco users.", "output": "A study randomized 234 male smokeless tobacco users to receive group behavioral treatment plus nicotine gum 2 mg (B/NRT); group behavioral treatment plus placebo (B/Pl); minimal contact plus nicotine gum 2 mg (MC/NRT); or minimal contact plus placebo (MC/Pl). Group behavioral treatment consisted of 8 group counseling sessions 45 to 60 minutes in length; minimal contact involved 4 brief one-on-one sessions with a nurse. Patients chewed a minimum of 6 pieces of nicotine or placebo gum per day. At 4 weeks, point prevalence abstinence rates were as follows: B/NRT, 63.6%; B/Pl, 66%; MC/NRT, 35.3%; and MC/Pl, 48.1% (P<.01). Abstinence rates remained significantly different at 1 and 6 month follow-ups, but not at 12 months. Post-hoc logistic regression favored group behavioral therapy plus NRT at 6 months. Moreover, survival analysis of continuous prevalence rates demonstrated that the least effective treatment was minimal contact plus NRT." }, { "input": "Behavioral interventions increase abstinence rates for smokeless tobacco users.", "output": "A meta-analysis concluded that behavioral interventions appear to be effective for increasing tobacco abstinence rates." }, { "input": "Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality.", "output": "A Meta-analysis of RCTs showed a non-significant increase in the relative risk of death (RR, 1.08)." }, { "input": "Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality.", "output": "One RCT with an open-label design with central randomization and 4 treatment arms demonstrated no change in all-cause mortality or incidence of total cardiovascular events." }, { "input": "Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality.", "output": "One double-blind, placebo-controlled RCT demonstrated no change in all-cause mortality or incidence of total cardiovascular events. In a subgroup analysis of this study, 1862 men with history of MI also had reduced risk of non-fatal MI (RR, 0.23)." }, { "input": "Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality.", "output": "One double-blind, placebo-controlled RCT demonstrated no change in all-cause mortality or incidence of total cardiovascular events. This study of 2002 persons receiving 400-800 IU/d showed a statistically significant reduction of non-fatal coronary events (relative risk [RR], 0.62)." }, { "input": "Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality.", "output": "Four large, well-designed RCTs with a combined enrollment of nearly 25,000 individuals with known coronary artery disease (CAD) or high risk for CAD receiving vitamin E (50-800 IU/d) collectively demonstrated no change in all-cause mortality or incidence of total cardiovascular events. Three of these studies were double-blind, placebo-controlled and the fourth was an open-label design with central randomization and 4 treatment arms." }, { "input": "Antioxidant supplements of vitamins E and C do not reduce cardiovascular death in people with coronary artery disease. Vitamin E supplementation, in a variety of doses, does not decrease the incidence of cardiovascular or all-cause mortality.", "output": "One double-blind, placebo-controlled RCT demonstrated no change in all-cause mortality or incidence of total cardiovascular events." }, { "input": "There is no evidence that vitamin C decreases mortality in patients at risk for coronary disease.", "output": "Three small RCTs enrolling a total of 1034 geriatric patients, with follow-up of less than 2 years, evaluated vitamin C (50-200 mg/d) versus placebo and showed no mortality benefit." }, { "input": "Combination antioxidant regimens (Vitamins E, C, and betacarotene) seem safe, but do not decrease mortality or incidence of major coronary and vascular events.", "output": "A randomized, placebo-controlled study of simvastatin 40 mg and antioxidants (vitamin E 600 mg, vitamin C 250 mg, beta-carotene 20 mg) enrolled 20,536 adults aged 40 to 80 years with known CAD or high risk for CAD. No significant difference was found in all-cause mortality (RR, 1.04), major coronary events (RR, 1.02), any stroke (RR, 0.99), or any major vascular event (RR, 1.00). The investigators found no evidence of an adverse affect of the antioxidants on the substantial outcome benefits demonstrated with 40 mg daily of simvastatin." }, { "input": "Combination antioxidant regimens (Vitamins E, C, and betacarotene) seem safe, but do not decrease mortality or incidence of major coronary and vascular events.", "output": "A study suggests a negative interaction between simvastatin plus niacin and antioxidant supplementation (composed of vitamins E and C, beta-carotene, and selenium)." }, { "input": "There are 3: valacyclovir, acyclovir, and topical penciclovir. Valacyclovir, 2 g twice in 1 day taken during the prodromal stage of herpes labialis, reduces the episode duration and time to healing. Acyclovir, 400 mg, taken 5 times a day for 5 days, decreases the pain duration and healing time to loss of crust.", "output": "When it comes to prophylaxis, several studies have shown that oral valacyclovir and sunscreen may be effective for prophylaxis of herpes labialis." }, { "input": "There are 3: valacyclovir, acyclovir, and topical penciclovir. Valacyclovir, 2 g twice in 1 day taken during the prodromal stage of herpes labialis, reduces the episode duration and time to healing. Acyclovir, 400 mg, taken 5 times a day for 5 days, decreases the pain duration and healing time to loss of crust.", "output": "Oral acyclovir has also been shown to be effective in a well-done RCT. For a subgroup of patients who started acyclovir in the prodrome or erythema stage, the duration decreased (2.5 vs 3.9 days, P=.02), but in the papular stage, it did not decrease significantly (2.5 vs. 3.6 days, P=.36)." }, { "input": "There are 3: valacyclovir, acyclovir, and topical penciclovir. Valacyclovir, 2 g twice in 1 day taken during the prodromal stage of herpes labialis, reduces the episode duration and time to healing. Acyclovir, 400 mg, taken 5 times a day for 5 days, decreases the pain duration and healing time to loss of crust.", "output": "Two RCTs have shown that valacyclovir (the prodrug of acyclovir, which has 3 to 5 times greater bioavailability) at a dosage of 2 g twice in 1 day significantly decreased the episode duration and time to lesion healing compared with placebo. In the first study (n=603), the mean episode duration was decreased by 1.1 days (5.0 vs 6.1 days; 95% confidence interval [CI], -1.6 to -0.6); in the second study (n=615) by 1.0 day (5.3 vs 6.3 days; 95% CI, -1.0 to -0.5)." }, { "input": "Topical penciclovir 1%, acyclovir 5%, or docosanol 10% also decrease the duration of pain and healing time.", "output": "Topical penciclovir 1% cream decreases the duration of lesion healing and pain compared with a vehicle control, as shown by 2 RCTs (n=3057, 1573). Patients initiated self-treatment every 2 hours during waking hours for 4 days. In one RCT, the treatment patients lost classic lesions 31% faster than the placebo group. In another trial, healing of classical lesions was faster by 0.7 days (4.8 vs 5.5). Benefits were achieved in both the early (P=.001) and later stages (P=.0055) of recurrence." }, { "input": "Topical penciclovir 1%, acyclovir 5%, or docosanol 10% also decrease the duration of pain and healing time.", "output": "Two RCTs of topical acyclovir 5% cream, 5 times a day for 4 days (n=689, 699) showed that topical acyclovir, compared with placebo, shortened the duration of an outbreak by 0.5 day (4.3 vs 4.8) and 0.6 day (4.6 vs 5.2), respectively." }, { "input": "The best prophylaxis for herpes labialis is oral valacyclovir 500 mg daily; it reduces the frequency and severity of attacks.", "output": "UpToDate reports that recurrent herpes labialis is usually not treated with antivirals unless a prodromal stage can be identified. In these cases, oral acyclovir or penciclovir cream can be prescribed for 4 days' duration. Chronic suppressive therapy can be useful in immunocompetent patients with more than 2 episodes in 4 months, and for recurrences associated with systemic complications or those that affect job performance. As prophylaxis, oral acyclovir 200 mg 3-5 times a day is generally used, but valacyclovir 500 mg once daily is also effective." }, { "input": "Sunscreen may be effective in sunlight-induced recurrence.", "output": "When it comes to prophylaxis, several studies have shown that oral valacyclovir and sunscreen may be effective for prophylaxis of herpes labialis." }, { "input": "other", "output": "Patient-initiated treatment can be effective." }, { "input": "The work-up for secondary infertility-the inability to conceive after 1 year of regular unprotected intercourse for a couple who have previously had a child should include a history and physical exam for both patients, plus evaluation of ovulation, semen analysis, and imaging of the uterus and fallopian tubes.", "output": "To evaluate ovulation, look at menstrual history, serum progesterone, and urine luteinizing hormone (LH)." }, { "input": "The work-up for secondary infertility-the inability to conceive after 1 year of regular unprotected intercourse for a couple who have previously had a child should include a history and physical exam for both patients, plus evaluation of ovulation, semen analysis, and imaging of the uterus and fallopian tubes.", "output": "The semen sample can be taken after the patient abstains from ejaculation for 2 to 6 days. Analyze the sample for volume, pH, sperm concentration, motility, and total number. If the sample is abnormal, repeat the analysis within 3 months." }, { "input": "The work-up for secondary infertility-the inability to conceive after 1 year of regular unprotected intercourse for a couple who have previously had a child should include a history and physical exam for both patients, plus evaluation of ovulation, semen analysis, and imaging of the uterus and fallopian tubes.", "output": "Begin the evaluation of secondary infertility with a thorough history and physical, followed by semen analysis and evaluation of ovulation." }, { "input": "The work-up for secondary infertility-the inability to conceive after 1 year of regular unprotected intercourse for a couple who have previously had a child should include a history and physical exam for both patients, plus evaluation of ovulation, semen analysis, and imaging of the uterus and fallopian tubes.", "output": "If the woman has signs of androgenic dysfunction, draw tests for LH, thyroid-stimulating hormone, follicle-stimulating hormone (FSH), testosterone, prolactin, and 17-hydroxyprogesterone. A woman with irregular menses should have her LH and FSH checked." }, { "input": "Check the male partner for varicoceles: they are the leading cause of male secondary infertility. For the female partner, a hysterosalpingogram is an effective first test in the initial evaluation of the uterine cavity and tubal patency.", "output": "A retrospective chart review compared 285 men with secondary infertility with 285 men with primary infertility. Varicoceles were the cause of secondary infertility in 177 (69%) of men with secondary infertility compared with 128 (50%) of men with primary infertility (P<.0001)." }, { "input": "Laparoscopy is indicated where there is evidence or strong suspicion of endometriosis, adhesions, or significant tubal disease.", "output": "One study demonstrated increased diagnostic yield with a combined approach of hysteroscopy and laparoscopy, in communities where the risk of pelvic infection was great." }, { "input": "Laparoscopy is indicated where there is evidence or strong suspicion of endometriosis, adhesions, or significant tubal disease.", "output": "If the woman has comorbidities-such as a history of pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis-then laparoscopy should be the initial test." }, { "input": "Routine postcoital testing is unnecessary.", "output": "A randomized controlled trial compared 227 couples who received the postcoital test with 217 couples who did not. Routine use of the postcoital test led to more tests and more treatments but had no significant effect on the pregnancy rate." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "A multicenter trial of diabetic patients with onychomycosis (mean\u00b1SD age, 55.7\u00b111.7 years) revealed that terbinafine had comparable efficacy and caused no hypoglycemic reactions in this group, who were being treated with insulin or oral hypoglycemics." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "Terbinafine is well-tolerated by most patients. A telephone survey after treatment with daily terbinafine or pulse-dose itraconazole reported greater ease and convenience, and higher overall satisfaction with continuous terbinafine vs pulse-dose itraconazole." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "A randomized, double-blind, controlled trial compared daily terbinafine with pulse-dose terbinafine. Daily terbinafine (250 mg for 3 months) had a 70.9% mycologic cure, while pulse-dose terbinafine (500 mg daily for 1 week per month for 3 months) had only a 58.7% mycologic cure (relative risk [RR]=1.21 [95% CI, 1.02-1.43]; NNT=8.2). There was no significant difference in tolerability of the regimens." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "A cost-efficacy analysis of terbinafine, itraconazole, and griseofulvin found terbinafine to be the most cost-effective." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "A 5-year blinded prospective study found long-term mycologic cures of 46% for terbinafine vs 13% for itraconazole (number needed to treat [NNT]=4.3). This study also showed a lower clinical relapse for terbinafine (21% vs 48%; NNT=3.7)." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "A meta-analysis of 6 studies comparing terbinafine with itraconazole reported odds ratios ranging from 1.8 (95% confidence interval [CI], 1.1-2.8) to 2.9 (95% CI, 1.9-4.1), indicating an 80% to 190% increased likelihood of clinical cure with terbinafine compared with itraconazole." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "A meta-analysis comparing the efficacy of terbinafine (Lamisil), pulse-dosed and continuous-dosed itraconazole (Sporanox), fluconazole (Diflucan), and griseofulvin showed mycological cure rates of varying degrees for each treatment." }, { "input": "Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness.", "output": "Guidelines from the British Association of Dermatologists point out that terbinafine is superior to itraconazole, and consider it a first-line treatment because it has a better cure rate and lower relapse rate. UpToDate suggests oral terbinafine as initial treatment for onychomycosis at a dose of 250 mg daily for 12 weeks." }, { "input": "Angiotensin-converting enzyme (ACE) inhibitors make a significant difference for patients with diabetes as a whole. If patients both with and without microalbuminuria are included together, ACE inhibitors significantly reduce the progression of the albumin excretion rate.", "output": "There are 3 prospective randomized controlled trials studying the effect of ACE inhibitors on albumin excretion for patients with diabetes who do not have microalbuminuria. A 2-year randomized controlled trial compared lisinopril (Prinivil; Zestril) 10 mg/d with placebo in 530 normotensive adults (aged 20-59 years) with insulin-dependent diabetes, defined as those diagnosed with diabetes before age 36 and using continuous insulin therapy within 1 year of diagnosis. At the beginning of the study, 90 patients had microalbuminuria-defined as an albumin excretion rate (AER) >29 mg/24 hr-and 440 patients did not. When the results for all patients who had and did not have microalbuminuria were combined, there was a significantly smaller rise in the AER for the lisinopril group vs the placebo group (3.2 mg/24 hr lower; P=.03). However, for the patients without initial microalbuminuria, the reduction in the rise of AER with lisinopril was not significant (1.4 mg/24 hr lower; P=.10). The decreased rate of developing new microalbuminuria was also not significant (relative risk reduction [RRR]=12.7%; P=.10)." }, { "input": "ACE inhibitors significantly reduce the development of overt nephropathy.", "output": "MICRO-HOPE, a subset of the HOPE trial, studied ramipril (Altace) 10 mg/d vs placebo in 2437 patients with diabetes who did not have clinical proteinuria. Patients were aged 55 years or older and had either a previous cardiovascular event or at least 1 other cardiovascular risk factor. There were 1140 patients with microalbuminuria, defined as an albumin/creatinine ratio 2 mg/mmol, and 2437 patients without. After 4.5 years, 10% of patients had developed overt nephropathy, defined as albumin/creatinine >36 mg/mmol. When all patients in the study were examined together, ramipril provided significant renal protection over placebo (RRR=24%; ARR=1%; P=.027). It also lowered the risk of MI by 22%, stroke by 33%, and cardiovascular death by 37%. But in a separate analysis of the patients without microalbuminuria, ramipril did not significantly reduce overt nephropathy (P=.50). Ramipril also did not significantly reduce the risk of developing new microalbuminuria in this group (RRR=9%; P=.17). Further, for patients without microalbuminuria, ramipril did not reduce the combined outcomes of myocardial infarction, stroke, or cardiovascular death (odds ratio=0.85; 95% CI, 0.70-1.02)." }, { "input": "However, studying diabetes without microalbuminuria separately, the effect of ACE inhibitors on progression to nephropathy does not reach statistical significance. This applies to both type 1 and 2 diabetes.", "output": "A trial compared enalapril (Vasotec) 10 mg/d with placebo in 194 normotensive patients (aged 40-60) with type 2 diabetes and without microalbuminuria, defined as AER >30 mg/24 hr. Over the 6-year course of the study, the AER in the placebo group rose from 10.8 mg/24 hr to 26.5 mg/24 hr. The AER of the treatment group dropped from 11.6 mg/24 hr initially to 9.7 mg/24 hr at 2 years, then rose to 15.8 mg/24 hr at 6 years. Enalapril significantly slowed the rise in AER (RRR=0.4; P=.001). Nineteen percent of the placebo group developed microalbuminuria, compared with 6.5% of those taking enalapril (absolute risk reduction[ARR]=12.5%; number needed to treat=8; P=.042). While this study described a modest and statistically significant renal protective effect of enalapril, it did not use an intention-to-treat analysis." }, { "input": "Results are contradictory regarding whether ACE inhibition delays new onset of diabetic microalbuminuria.", "output": "There are 3 prospective randomized controlled trials studying the effect of ACE inhibitors on albumin excretion for patients with diabetes who do not have microalbuminuria. A 2-year randomized controlled trial compared lisinopril (Prinivil; Zestril) 10 mg/d with placebo in 530 normotensive adults (aged 20-59 years) with insulin-dependent diabetes, defined as those diagnosed with diabetes before age 36 and using continuous insulin therapy within 1 year of diagnosis. At the beginning of the study, 90 patients had microalbuminuria-defined as an albumin excretion rate (AER) >29 mg/24 hr-and 440 patients did not. When the results for all patients who had and did not have microalbuminuria were combined, there was a significantly smaller rise in the AER for the lisinopril group vs the placebo group (3.2 mg/24 hr lower; P=.03). However, for the patients without initial microalbuminuria, the reduction in the rise of AER with lisinopril was not significant (1.4 mg/24 hr lower; P=.10). The decreased rate of developing new microalbuminuria was also not significant (relative risk reduction [RRR]=12.7%; P=.10)." }, { "input": "Children should be at least 6 months of age and parents should provide only 100% fruit juice in a cup (not a bottle).", "output": "Excess intake of both sugar-sweetened beverages and fruit juice has been associated with increased risk of dental caries. Excess intake is defined as more than 6 oz per day in children 1 to 6 years of age and more than 12 oz per day in children 7 to 18 years. To help reduce the risk for dental caries, children should drink juice from a cup." }, { "input": "Children should be at least 6 months of age and parents should provide only 100% fruit juice in a cup (not a bottle).", "output": "Infants shouldn't be given fruit juice before 6 months of age. If juice is offered, it should be 100% fruit juice in a cup, not a bottle. Children 1 to 6 years of age should drink no more than 4 to 6 oz of 100% fruit juice per day. Children 7 to 18 years of age should limit intake to 12 oz of 100% fruit juice per day. Infants, children, and adolescents shouldn't drink unpasteurized juice." }, { "input": "Intake should be limited to 4 to 6 oz a day until 12 months of age.", "output": "Infants shouldn't be given fruit juice before 6 months of age. If juice is offered, it should be 100% fruit juice in a cup, not a bottle. Children 1 to 6 years of age should drink no more than 4 to 6 oz of 100% fruit juice per day. Children 7 to 18 years of age should limit intake to 12 oz of 100% fruit juice per day. Infants, children, and adolescents shouldn't drink unpasteurized juice." }, { "input": "It's important to reiterate to parents that breastfeeding is the preferred source of infant nutrition for the first 6 (preferably 12) months of life.", "output": "One in 5 infants routinely drinks juice before 6 months of age." }, { "input": "It's important to reiterate to parents that breastfeeding is the preferred source of infant nutrition for the first 6 (preferably 12) months of life.", "output": "Regardless of the relationship between fruit juice and obesity, it is important to emphasize that breast milk provides essential nutrients and immune protection for the growing infant. Breast milk should remain the recommended source of nutrition through the first year of life." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "Cohort data show that children who regularly consume sugar-sweetened beverages are twice as likely to be overweight by 5 years of age as children who don't." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "Consumption of fruit drinks and other sugar-sweetened beverages by American children has increased 135% since 1977; such drinks account for roughly 9% of daily energy intake." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "Data from the Feeding Infants and Toddlers Survey (FITS) indicate that 100% fruit juice and sugar-sweetened beverages are now the second and third leading sources, respectively, of energy (and carbohydrates) for American children between 1 and 2 years of age." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "Data from the National Health and Nutrition Examination Survey (NHANES) suggest that overweight children and adolescents consume more sugar-sweetened beverages than those who are not overweight." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "The role of fruit juice consumption in childhood obesity is controversial. In 1 group of 168 children 2 to 5 years of age, 9% of children who drank >12 oz of fruit juice per day were overweight, compared with 3% of those who drank <12 oz daily." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "Overweight children are more likely than normal-weight children to be overweight as adults; they're at significant risk for morbidity and mortality from hypertension, cardiovascular disease, and diabetes in adulthood. Establishing sound nutritional habits-including appropriate consumption of fruit juices, fruit drinks, and other sugar-sweetened beverages-early in life plays an important role in preventing overweight in later childhood and adulthood." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "During the transition to table foods between 4 and 11 months of age, the top 3 nonmilk sources of carbohydrate in an infant's diet are infant cereal, 100% juice, and bananas." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "One of every 6 American children is overweight or at risk of becoming overweight." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "Sugar-sweetened beverages (labeled as fruit drinks) often replace whole fruits in childhood diets. As a result, children may fail to meet recommendations for intake of whole fruits and vegetables, which contain fiber and nutrients essential to growth." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "1 cohort of 521 children followed longitudinally from 5 to 9 years showed no association between sugar-sweetened beverage intake and body fat." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "A recent systematic review of 30 studies (15 cross-sectional, 10 prospective cohort, and 5 experimental trials) supports a link between consumption of sugar-sweetened beverages and childhood obesity." }, { "input": "Sugar-sweetened fruit drinks have been linked to excess weight gain and obesity.", "output": "A recent review of 21 studies found 6 (3 longitudinal and 3 cross-sectional) that supported a relationship between juice intake and weight and 15 (9 longitudinal and 6 cross-sectional) that suggested no link between 100% fruit juice consumption and overweight in children or adolescents." }, { "input": "Sugar-sweetened beverages provide little nutritional benefit to children and should be restricted.", "output": "Overweight children are more likely than normal-weight children to be overweight as adults; they're at significant risk for morbidity and mortality from hypertension, cardiovascular disease, and diabetes in adulthood. Establishing sound nutritional habits-including appropriate consumption of fruit juices, fruit drinks, and other sugar-sweetened beverages-early in life plays an important role in preventing overweight in later childhood and adulthood." }, { "input": "Screening for herpes simplex virus type 2 (HSV-2) infection with antibody testing is not indicated for asymptomatic adults.", "output": "The Centers for Disease Control and Prevention, the United States Preventive Services Task Force, and the American Academy of Family Physicians do not recommend screening asymptomatic adults for HSV infection." }, { "input": "Screening with serology testing is not indicated for asymptomatic pregnant women.", "output": "The primary goal for screening pregnant women is prevention of neonatal transmission of HSV. A prospective observational study of 7046 women found that acquisition of HSV-2 during pregnancy was asymptomatic in 74% of 94 cases. No increase in neonatal or pregnancy-related morbidity was seen for those patients who had seroconverted by the time of labor. The main benefit of serology testing during pregnancy has been to identify patients with asymptomatic infection and counsel them on reporting new symptoms for evaluation and treatment." }, { "input": "Screening with serology testing is not indicated for asymptomatic pregnant women.", "output": "Testing of asymptomatic patients with HSV-2 serology and counseling has been recommended by some exprets for motivated patients with current or recent sexually transmitted infection or HIV infection and for partners of HSV-positive patients." }, { "input": "Screening with serology testing is not indicated for asymptomatic pregnant women.", "output": "A prospective cohort study identified seropositive pregnant women with no history of genital herpes. Forty-three of 264 (16%) of these women were able to identify and report clinical HSV to their physician during the pregnancy." }, { "input": "You may consider offering testing to asymptomatic patients with an HSV-positive partner, patients with HIV infection, and those with current or recent sexually transmitted infection or high-risk behavior.", "output": "Testing of asymptomatic patients with HSV-2 serology and counseling has been recommended by some exprets for motivated patients with current or recent sexually transmitted infection or HIV infection and for partners of HSV-positive patients." }, { "input": "The best intervention is education on proper positioning and attachment of the infant.", "output": "The International Lactation Consultant Association states that nipple pain is often the result of ineffective positioning and latch. The group recommends anticipatory guidance to prevent nipple pain. Additionally, a thorough clinical assessment of the nipple is indicated to rule out other causes, such as bacterial or fungal infection." }, { "input": "Topical agents that show some evidence of benefit include expressed breast milk, lanolin, warm water compresses, tea bag compresses, hydrogel dressings, a chlorhexidinealcohol spray, and a polyethylene film dressing.", "output": "Breast shields were ineffective in 1 RCT." }, { "input": "One type of glycerin-based hydrogel dressing was associated with an increased incidence of breast infections.", "output": "The only topical agent found to have any detrimental effect was a glycerin-based hydrogel dressing that was associated with an increased incidence of breast infections." }, { "input": "other", "output": "In another RCT performed in Sweden, women who received peripartum care in a birthing center had more nipple pain than women who delivered in a traditional hospital setting (NNT=16)." }, { "input": "other", "output": "Nipple pain during the first week of breastfeeding is common. Some studies report a prevalence as high as 96%." }, { "input": "other", "output": "We identified 2 systematic reviews and 3 additional RCTs of interventions to treat or prevent nipple pain. Most studies included women serving as their own control, randomizing 1 breast to intervention and the other to control treatment. The remainder of the studies randomized women to either the intervention or control group. Major limitations of the studies included their generally small size and lack of blinding of participants to their treatment group. In only 1 study were the participants blinded." }, { "input": "other", "output": "Two studies of educational sessions, 1 antenatal (N=75) and 1 immediately postnatal (N=160), reported less nipple pain in the intervention groups (number needed to treat [NNT]=1.6 and 5.6, respectively). The antenatal education study demonstrated higher continuation of breastfeeding at 6 weeks postpartum in the intervention group (NNT=4.5), whereas the postnatal study showed no significant difference in continuation of breastfeeding in the intervention group at 6 weeks, 3 months, and 6 months." }, { "input": "Yes. A birth weight greater than 4,000 g is associated with an increased risk of obesity in both childhood and adolescence.", "output": "The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routine screening for overweight in children and adolescents as a means of preventing adverse health outcomes." }, { "input": "Yes. A birth weight greater than 4,000 g is associated with an increased risk of obesity in both childhood and adolescence.", "output": "The American Academy of Pediatrics states that genetic, environmental, or combinations of risk factors predisposing children to obesity can and should be identified." }, { "input": "Yes. A birth weight greater than 4,000 g is associated with an increased risk of obesity in both childhood and adolescence.", "output": "A prospective cohort study of 1993 white LGA infants found a greater propensity to become obese in adolescence, but only if their mothers or fathers were also obese (RR=5.7). Children with lean parents did not have an increased risk of being over-weight in adolescence." }, { "input": "Yes. A birth weight greater than 4,000 g is associated with an increased risk of obesity in both childhood and adolescence.", "output": "A large Chinese population-based, case-control study (N=1322), found birth weight above 4.0 kg to be a risk factor for obesity in preschool-age children (OR=3.77; 95% CI, 2.06-6.29). The absolute rate of overweight increased from 8% to 26% among LGA infants." }, { "input": "Yes. A birth weight greater than 4,000 g is associated with an increased risk of obesity in both childhood and adolescence.", "output": "A US national cohort study of 3192 children adjusted for gestational age, found that large-for-gestational-age (LGA) infants with birth weights above the 90th percentile remained longer and heavier through 83 months of life. The triceps and subscapular skinfold measurements at 3 years of age for children born LGA were virtually identical to those of children born appropriate for gestational age, but by 6 years of age, skinfold measurements had diverged considerably, to more than 0.60 standard deviations. The researchers concluded that intrauterine growth is associated with obesity in early childhood." }, { "input": "Yes. A birth weight greater than 4,000 g is associated with an increased risk of obesity in both childhood and adolescence.", "output": "A retrospective cohort survey of 14,881 children born to mothers with gestational diabetes-and controlled for age, sex, and Tanner stage-found that the odds ratio (OR) for adolescent overweight was 1.4 (95% CI, 1.2-1.6) for each 1-kg increment in birth weight. The correlation persisted (OR=1.3; 95% CI, 1.1-1.5) when other covariates were controlled (television viewing, physical activity, energy intake, breastfeeding duration, birth order, household income, mother's smoking, dietary restraint, and mother's current BMI)." }, { "input": "Yes. A birth weight greater than 4,000 g is associated with an increased risk of obesity in both childhood and adolescence.", "output": "A systematic review of 19 longitudinal, observational studies comparing birth weight with later BMI indicates that the association between the 2 is positive and consistent in multiple cohorts. Eleven studies focused on outcomes in childhood; another 8 measured outcomes into adulthood. Fifteen of the 19 studies (79%), ranging in size from 1028 to 92,940 subjects, found a positive association between birth weight and later BMI. However, the data were too heterogeneous to combine into a single summary measure. One representative study quantified the relative risk (RR) for severe obesity (>95th percentile BMI) at 5 years of age as 1.7 (95% confidence interval [CI], 1.2-2.9) for birth weights between the 85th and 94th percentiles and 1.8 (95% CI, 1.1-2.9) for birth weights greater than the 95th percentile. Studies that didn't find such an association had smaller sample sizes (137 to 432 subjects) and, therefore, may have lacked the power to detect an association." }, { "input": "An ankle-brachial index is best for evaluating patients with symptoms of claudication.", "output": "A questionnaire-based history of claudication (the Edinburgh Claudication Questionnaire) has been shown to have a high positive predictive value and likelihood ratio for PVD; physical examination techniques appear to be less predictive. However, the gold standard in the questionnaire study was \"clinician determination\", which carries a risk of subjectivity and lack of testing independence that may make the test appear more accurate than it is in typical application." }, { "input": "Duplex ultrasonography or magnetic resonance angiography may be a preferable first step if immediate revascularization appears necessary.", "output": "After balancing the accuracy, cost, and risk of available tests, an appropriate stepwise approach to evaluation for PVD is: First, do a complete history and targeted physical examination (palpation of pulses). Next, obtain an ankle-brachial index to confirm the diagnosis. Then, proceed directly to either duplex ultrasonography or magnetic resonance angiography when revascularization is clearly needed." }, { "input": "A toe-brachial index may be superior to an ankle-brachial index for evaluating elderly and diabetic patients.", "output": "Methods for evaluating patients for PVD include medical history, physical examination (inspection of the extremities and palpation of peripheral pulses), and ancillary testing (ankle-brachial index, duplex ultrasound, and magnetic resonance imaging with contrast, and angiography). The toe-brachial index may be useful in the elderly and patients with advanced diabetes because noncompressible vasculature in these patients may render the ankle-brachial index unreliable." }, { "input": "After considering the accuracy, cost, and risk of available tests, an appropriate stepwise approach begins with a complete history and targeted physical examination (palpation of pulses); then obtain an ankle-brachial index to confirm the diagnosis.", "output": "After balancing the accuracy, cost, and risk of available tests, an appropriate stepwise approach to evaluation for PVD is: First, do a complete history and targeted physical examination (palpation of pulses). Next, obtain an ankle-brachial index to confirm the diagnosis. Then, proceed directly to either duplex ultrasonography or magnetic resonance angiography when revascularization is clearly needed." }, { "input": "other", "output": "The calculations assume peripheral vascular disease to have a prevalence of 14% among people older than 60 years, based on pooled results from several epidemiologic studies." }, { "input": "other", "output": "Risk factors are the same as for coronary artery disease." }, { "input": "other", "output": "PVD is a progressive atherosclerotic narrowing of arteries in the extremities. The prevalence increases with age-it is less than 1% in people between 40 and 49 years of age and 15% in people 70 years and older." }, { "input": "Pertussis should be considered in infants with apnea or severe coughing illnesses of any duration, and in older children or adults with prolonged cough (eg, longer than 2 weeks), especially if accompanied by inspiratory whoop or household exposure to a prolonged cough illness.", "output": "A case series of 9 infants aged <7 weeks requiring admission to an intensive care unit for pertussis found that 8 had been sick for less than 4 days at the time of admission. All 9 presented with poor feeding and cough, and 5 had experienced apnea." }, { "input": "Pertussis should be considered in infants with apnea or severe coughing illnesses of any duration, and in older children or adults with prolonged cough (eg, longer than 2 weeks), especially if accompanied by inspiratory whoop or household exposure to a prolonged cough illness.", "output": "Pertussis should be considered early in the evaluation of young infants with cough. In a case-control study comparing 15 fatal cases of pertussis with 32 who survived (infants aged <6 months), the mean number of days from symptom onset to hospital admission were 5.3 (fatal) and 8.6 (survivors). Rates of apnea on admission were 40% and 52%." }, { "input": "Pertussis should be considered in infants with apnea or severe coughing illnesses of any duration, and in older children or adults with prolonged cough (eg, longer than 2 weeks), especially if accompanied by inspiratory whoop or household exposure to a prolonged cough illness.", "output": "A British study of 126 infants aged <5 months admitted to the pediatric intensive care unit with apnea, bradycardia, or respiratory failure found that 20% had pertussis. Apnea as a predictor of pertussis had a sensitivity of 68% and a specificity of 60%." }, { "input": "Pertussis should be considered in infants with apnea or severe coughing illnesses of any duration, and in older children or adults with prolonged cough (eg, longer than 2 weeks), especially if accompanied by inspiratory whoop or household exposure to a prolonged cough illness.", "output": "Infants aged <6 months with pertussis are at particular risk for atypical presentations and serious complications. In a US series of 18,500 infants with pertussis, apnea was seen in 64% of infants under 1 month and in 44% between 6 and 11 months. Forty percent of the 6- to 11-month-olds had received at least 3 doses of pertussis vaccine." }, { "input": "Pertussis should be considered in infants with apnea or severe coughing illnesses of any duration, and in older children or adults with prolonged cough (eg, longer than 2 weeks), especially if accompanied by inspiratory whoop or household exposure to a prolonged cough illness.", "output": "A cohort series of children aged <5 years with suspected pertussis compared 33 with positive cultures to 55 with negative cultures. The constellation of spasmodic cough and lymphocytosis (>10,000) had a sensitivity of 83%, a LR+ of 2.5, and a LR- of 0.25. Cough >14 days with whoop and vomiting had a sensitivity of 67%, a LR+ of 3.2, and LR- of 0.42." }, { "input": "Pertussis should be considered in infants with apnea or severe coughing illnesses of any duration, and in older children or adults with prolonged cough (eg, longer than 2 weeks), especially if accompanied by inspiratory whoop or household exposure to a prolonged cough illness.", "output": "Pertussis is an important cause of cough in all age groups. Ten prevalence studies of adolescents and adults seeking medical attention for a prolonged cough (defined variously as >1-4 weeks) found acute pertussis in 12% to 32%." }, { "input": "Coughing paroxysms, posttussive vomiting, and absence of fever, while typical of pertussis, are of little help in distinguishing it from other causes of prolonged coughing illnesses.", "output": "While cough longer than 2 weeks, inspiratory whoop, posttussive vomiting, coughing paroxysms, and absence of fever are commonly associated with pertussis, relatively few studies have assessed the sensitivities and specificities of these symptoms. Comparison groups were variously defined by negative pertussis cultures, negative pertussis serology, or serologic confirmation of other respiratory infections. Likelihood ratios (LR) were calculated from the data presented in each paper. The magnitude and variability of these likelihood ratios suggest that individual symptoms may be of limited help in distinguishing pertussis from other causes of prolonged cough. Combinations of symptoms may be slightly more helpful. In a study comparing 10 patients with culture-confirmed pertussis with 10 patients with serologically confirmed mycoplasma pneumonia, the combination of cough >14 days and whoop had a sensitivity of 80%, a positive LR (LR+) of 8 and a negative LR (LR-) of 0.22." }, { "input": "Diets that result in long-term weight loss of 5% to 7%, along with moderate-intensity exercise for more than 150 minutes per week, reduce the incidence of type 2 diabetes for patients with impaired glucose tolerance (IGT).", "output": "The Finnish Diabetes Prevention Study similarly randomized 522 patients, aged 40 to 65 years, with IGT and obesity (mean BMI=31) to either intensive lifestyle intervention or control and followed them for 3.2 years. The lifestyle intervention included moderate exercise for at least 150 minutes per week and weight loss of at least 5%. Patients were offered an individualized exercise plan with supervised aerobic exercise plus circuit-type resistance sessions 3 times a week. Nutritionists met with patients 7 times in the first year and every 3 months after that. Patients were counseled to increase fiber intake, reduce total fat below 30% of total calories, and reduce saturated fat below 10%. The control group was given general information on diet and exercise without individualized programs. Most patients (86%) in the intervention group met their exercise goal, and 25% met the fiber requirement. Compared with the control group, the intervention group had greater success rate for each category. Intensive lifestyle intervention reduced the incidence of diabetes by 58% (number needed to treat=5 for 5 years." }, { "input": "Diets that result in long-term weight loss of 5% to 7%, along with moderate-intensity exercise for more than 150 minutes per week, reduce the incidence of type 2 diabetes for patients with impaired glucose tolerance (IGT).", "output": "The Diabetes Prevention Program Research Group1 randomized 3234 patients age >24 years without diabetes but with IGT and a BMI >24 to 1 of 3 groups: intensive lifestyle modification, metformin, or control; they then compared the incidence of diabetes over 3 years. Patients were men and women from primary care populations and represented diverse ethnic backgrounds. Investigators defined IGT as plasma glucose of 140 to 200 mg/dL 2 hours after a 75-g glucose bolus when the fasting glucose was <140 mg/dL. Intensive lifestyle intervention comprised individual training sessions on a low-calorie, low-fat diet, aerobic exercise (such as brisk walking), and behavior modification. Case managers met with each participant for at least 16 sessions during the first 24 weeks and at least monthly thereafter. The control group received lifestyle change recommendations without individualized attention. After 24 weeks, 50% of the lifestyle group met the 7% weight loss goal and 74% were exercising at least 150 minutes per week. At the final visit, 38% maintained their target weight and 58% met their exercise goal. Lifestyle intervention produced greater weight reduction and increased activity compared with the metformin and control groups, with a corresponding decreased incidence of diabetes. Subgroup analysis found that lifestyle intervention produced the greatest reduction in diabetes (71%) for patients aged >60 years." }, { "input": "Each of the trials demonstrating this finding included fairly intensive counseling as part of the successful intervention. Diet and exercise reduce the incidence of diabetes in both lean (body mass index [BMI] <25) and overweight patients with IGT.", "output": "The Da Qing IGT and Diabetes Study divided 577 patients with IGT into 1 control and 3 intervention groups: diet, aerobic exercise, and combined diet plus aerobic exercise. Patients in this study had the lowest average BMI (25.8) of the 3 studies. The intervention group received individual and group counseling sessions at weekly intervals for 1 month, then monthly for 3 months, and then every 3 months. The control group received generalized information on IGT and diabetes but individual or group instruction was not included. At the 6-year follow-up, the quantity of exercise was significantly higher in the exercise intervention groups, but no significant difference in caloric intake was seen among all 4 groups. The incidence of diabetes in the exercise intervention group was approximately half that in the control group overall. Exercise was more effective in reducing diabetes in lean patients (BMI <25), but both lean and overweight patients benefited. The combination of diet plus exercise and diet changes also significantly reduced diabetes, although to a lesser degree." }, { "input": "No clinical trials have studied the potential risks and benefits of routinely monitoring liver function tests for all patients taking isoniazid for latent TB infection. Data from 2 case series suggest that routine liver function test monitoring leads to withdrawal of isoniazid prophylaxis from about 6% of patients because of abnormal lab results.", "output": "Two studies, that defined hepatitis as asymptomatic liver function test elevation (>5 times normal) on monthly screening found a 6% to 6.4% incidence of hepatitis." }, { "input": "This is 10 to 60 times the hepatitis rate found in case series using a symptom-based monitoring strategy.", "output": "In 1 series, rates were 3/1000 in those aged 20 to 34 years, 12/1000 in those aged 35 to 49 years, 23/1000 in those aged 50 to 64 years, and 8/1000 after age 65." }, { "input": "This is 10 to 60 times the hepatitis rate found in case series using a symptom-based monitoring strategy.", "output": "Four case series that relied on symptom-based monitoring reported rates 0 to 60 times lower than 6% to 6.4% incidence of hepatitis." }, { "input": "other", "output": "Symptom-based monitoring strategies require stopping isoniazid promptly if symptoms of hepatotoxicity develop. In a series of 62 fatal cases of probable or possible isoniazid hepatitis, 42% had been monitored at least monthly for symptoms, and 38% stopped isoniazid within 1 week of symptom onset." }, { "input": "other", "output": "Seven of the 8 patients receiving a liver transplant following the development of fulminant, isoniazid-related hepatitis continued to take the drug for a least 10 days after onset of symptoms of hepatotoxicity." }, { "input": "other", "output": "A pooled analysis of more than 200,000 patients receiving isoniazid prophylaxis and monitored according to 1983 American Thoracic Society guidelines reported an intermediate hepatitis rate (1.2%) and only 2 deaths. Mortality from isoniazid hepatitis is rare, whichever monitoring strategy is selected. Some deaths attributed to isoniazid prophylaxis may also have had other contributing causes, such as unrecognized hepatitis C; most cases and deaths reported in these large series occurred before testing for hepatitis C became available in 1991." }, { "input": "other", "output": "Several series report increasing hepatitis risk with advancing age." }, { "input": "The clinical evaluation of failure to thrive (FTT) includes a thorough history and physical examination; observation of parent-child interactions; observation and documentation of the child's feeding patterns; and a home visit by an appropriately trained health care professional.", "output": "A detailed prenatal history (including birth weight and pregnancy complications) and medical history for both the child and parents can identify underlying metabolic, endocrine, or familial disorders. It is always important to look for signs of child abuse, because children with FTT are more likely to be victims of abuse than normal-weight peers." }, { "input": "The clinical evaluation of failure to thrive (FTT) includes a thorough history and physical examination; observation of parent-child interactions; observation and documentation of the child's feeding patterns; and a home visit by an appropriately trained health care professional.", "output": "Children with FTT are most often identified when parents raise concerns about the child's feeding or growth patterns or when a physician notes a decrease in the child's growth on physical examination. The terms \"organic\" and \"inorganic\" or \"nonorganic\" FTT, often used to guide diagnostic thinking, are outdated because most cases of FTT are influenced by many variables. FTT represents the final common pathway of disruptions in the complex system of biological, psychosocial, and environmental factors contributing to a child's growth and development." }, { "input": "other", "output": "Excessive caloric expenditure. Such expenditure is associated with underlying medical conditions such as congenital heart disease, chronic hypoxia (pulmonary disease), hyperthyroidism, metabolic disease (diabetes, renal tubular acidosis), chronic immunodeficiency, recurrent infection, or malignancy. FTT accounts for between 1% and 5% of all pediatric hospitalizations." }, { "input": "other", "output": "FTT is a generic term used to describe a child whose current weight (or trajectory of weight gain) does not equal that of other children of similar age, gender, and ethnicity. No single accepted anthropometric measure can be used to diagnose the condition." }, { "input": "other", "output": "FTT has been variously defined in children who drop more than 2 standard percentile lines on standardized growth charts." }, { "input": "other", "output": "As many as 10% of children seen in primary-care settings show signs of FTT." }, { "input": "other", "output": "FTT has been variously defined in children who have height-for-weight less than the third percentile." }, { "input": "other", "output": "FTT has been variously defined in children who have weight-for-length <80% of ideal weight." }, { "input": "other", "output": "FTT occurs when nutritive intake is insufficient to meet demands for growth. It is usually manifested by failure to gain weight. In more severe cases, height and head circumference are affected. FTT is also associated with lower developmental testing scores." }, { "input": "other", "output": "FTT is also associated with persistent poor growth, increased susceptibility to infections, and an increased prevalence of behavioral disorders and neurologic disability." }, { "input": "other", "output": "That said, other factors are responsible for poor nutritional intake in as many as 80% of cases." }, { "input": "other", "output": "Inadequate caloric intake. More than 80% of children with poor growth do not have an underlying medical disorder." }, { "input": "A single 2-g dose of tinidazole is the best treatment.", "output": "A 2006 Cochrane Review compared 34 trials of many drug therapies for giardiasis. The review, which is being updated to include additional publications, evaluated both head-to-head and placebo-controlled studies, looking at dosage as well as length of drug therapy. The review found that a single dose of tinidazole had a higher clinical cure rate than other therapies such as metronidazole (odds ratio [OR]=5.33; 95% confidence interval [CI], 2.66-10.67) along with a comparable side-effect profile. These findings favor tinidazole as the treatment of choice for symptomatic giardiasis." }, { "input": "Other drugs, such as nitazoxanide, metronidazole, mebendazole, and albendazole, can also be used but tinidazole has a higher clinical cure rate than these drugs. It also has a comparable side-effect profile and requires only 1 dose.", "output": "A 2006 Cochrane Review found no difference in clinical cure rate between short-term treatment (3 days) with metronidazole and longer therapy with metronidazole or other drugs. Subsequently, a single dose of metronidazole was found to be as effective as treatment for 5 days or longer (OR=0.33, 95% CI 0.08-1.34)." }, { "input": "Other drugs, such as nitazoxanide, metronidazole, mebendazole, and albendazole, can also be used but tinidazole has a higher clinical cure rate than these drugs. It also has a comparable side-effect profile and requires only 1 dose.", "output": "An RCT in Cuban children 5 to 15 years of age found no difference in clinical cure rate between a 5-day course of mebendazole and more traditional therapy with quinacrine." }, { "input": "Other drugs, such as nitazoxanide, metronidazole, mebendazole, and albendazole, can also be used but tinidazole has a higher clinical cure rate than these drugs. It also has a comparable side-effect profile and requires only 1 dose.", "output": "An RCT comparing 5 days of mebendazole with 7 days of metronidazole in 7- to 12-year-old Iranian children showed no statistical difference in microbiologic cure between the 2 regimens." }, { "input": "Other drugs, such as nitazoxanide, metronidazole, mebendazole, and albendazole, can also be used but tinidazole has a higher clinical cure rate than these drugs. It also has a comparable side-effect profile and requires only 1 dose.", "output": "Single-dose tinidazole was superior to 3 doses of mebendazole in a single day in an RCT of 122 Cuban children that measured microbiologic cure (NNT=5.5 patients with tinidazole vs mebendazole)." }, { "input": "Other drugs, such as nitazoxanide, metronidazole, mebendazole, and albendazole, can also be used but tinidazole has a higher clinical cure rate than these drugs. It also has a comparable side-effect profile and requires only 1 dose.", "output": "Two RCTs found nitazoxanide to be effective (number needed to treat [NNT]=1.82) compared to placebo in adolescents and adults." }, { "input": "Other drugs, such as nitazoxanide, metronidazole, mebendazole, and albendazole, can also be used but tinidazole has a higher clinical cure rate than these drugs. It also has a comparable side-effect profile and requires only 1 dose.", "output": "A 3-day course of nitazoxanide was as effective as 5 days of metronidazole (80% vs 85%, P=0.61) in resolving clinical giardiasis." }, { "input": "Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients' underlying clinical conditions and dietary potassium and sodium intake.", "output": "Morgan and Davidson performed an analysis of the published data available in 1980. They found that the average fall in potassium is less for patients taking furosemide (0.3mmol/L) than on thiazide diuretics (0.6mmol/L) and that this fall was only slightly influenced by dose or duration of treatment." }, { "input": "Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients' underlying clinical conditions and dietary potassium and sodium intake.", "output": "Recent studies have found that hydrochlorothiazide in doses above 12.5 to 25 mg do not result in significantly lower blood pressure and only lead to more electrolyte abnormalities." }, { "input": "Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients' underlying clinical conditions and dietary potassium and sodium intake.", "output": "Penhall and coworkers found hypokalemia in 24 of 54 patients receiving a fixed-combination diuretic (hydrochlorothiazide 50 mg and potassium-sparing amiloride 5 mg). Note that the dose of hydrochlorothiazide was higher in this study than is generally used today." }, { "input": "Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients' underlying clinical conditions and dietary potassium and sodium intake.", "output": "Lemieux and colleagues followed 50 patients receiving a variety of diuretic regimens (hydrochlorothiazide 50 to 100 mg daily or every other day with or without reserpine 0.25 mg daily). Only 3 patients in this group had potassium levels below 3.5 mmol/L, and all decreases were only transient. Peters and coworkers6 documented potassium levels below 3.5 mEq/L in 6 of 19 patients taking hydrochlorothiazide 25 or 50 mg for 20 weeks. Three of these patients normalized without therapy. One of these transiently hypokalemic patients was also taking triamterene, a potassium-sparing diuretic. Potassium-sparing diuretics may not free the clinician from checking a potassium level, however." }, { "input": "Case series show that hypokalemia following initiation of diuretic therapy occurs in most patients within 2 to 8 weeks. However, no studies are available that adequately predict the risk of this complex and multifactorial condition. Patients taking diuretics should have a potassium level checked in the first 2 to 8 weeks after initiating therapy. Mild hypokalemia (3.1 to 3.4 mmol/L) may be transient, so a repeat measurement may be considered before initiating potassium replacement. Dietary sodium restriction may also help to conserve potassium, because this will decrease urinary flow rate and potassium loss. The frequency with which to check potassium levels should be guided by the patients' underlying clinical conditions and dietary potassium and sodium intake.", "output": "Hypokalemia is defined as a serum potassium level less than 3.5 mmol/L (3.5 mEq/L); hypokalemia at levels between 3.1 and 3.4 mmol/L is considered mild. The incidence of hypokalemia reported for patients on diuretic therapy is broad (7.2% to 56%)." }, { "input": "other", "output": "The time period required to develop hypokalemia can be (1 week)." }, { "input": "other", "output": "The time period required to develop hypokalemia can be (>1 year)." }, { "input": "Mechanical therapies-such as taping, tension night splinting, and rigid arch support-are the most effective treatment for plantar fasciitis", "output": "One randomized controlled study of 166 patients found no evidence to support a beneficial effect on pain, function, and quality of life of extracorporeal shock wave therapy over a sham treatment. Of note, this study enrolled patients who had a minimum of 6 weeks of symptoms. All recommendations in the US are to reserve extracorporeal shock wave therapy for patients with more than 6 months of symptoms." }, { "input": "Mechanical therapies-such as taping, tension night splinting, and rigid arch support-are the most effective treatment for plantar fasciitis", "output": "From 1993-1995 an observer-blinded randomized controlled trial of 112 patients compared standard with sham extracorporeal shock wave therapy. The main outcome measure was patient satisfaction on a 4-step score at 6 months and 5 years. At 6 months, the treatment group had a significantly better 4-step score than the placebo group (P<.0001). In fact, 51% of treatment-group patients were pain-free, while none of the 48 placebo-group patients were painfree. After 5 years, the 4-step score only demonstrated a trend in favor of the treatment group (P<.071) because of a high rate of good results from subsequent surgery in the placebo group. Thirteen percent of the treatment-group patients had undergone a heel operation, compared with 58% of placebo-group patients." }, { "input": "Mechanical therapies-such as taping, tension night splinting, and rigid arch support-are the most effective treatment for plantar fasciitis", "output": "A prospective, observer-blinded study randomized 116 patients to 1 of 2 groups for 3 months. The first group of patients were treated with a nonsteroidal anti-inflammatory drug (piroxicam) and Achilles tendon stretching 3 times a day. The second group received the same treatment but also wore plastic tension night splints in 5\u00ba of dorsiflexion. After 3 months, in an intention-to-treat analysis, no statistically significant difference was detected in subjective pain between the 2 groups. In this study, patient compliance with the tension night splinting was poor, and this likely affected the outcome." }, { "input": "Mechanical therapies-such as taping, tension night splinting, and rigid arch support-are the most effective treatment for plantar fasciitis", "output": "A retrospective study of 237 subjects also concluded that mechanical treatment is better than anti-inflammatory or accommodative treatments." }, { "input": "Mechanical therapies-such as taping, tension night splinting, and rigid arch support-are the most effective treatment for plantar fasciitis", "output": "Several researchers found no statistically significant difference among treatment with tension night splinting, custom rigid orthosis, and over-the-counter arch supports." }, { "input": "Mechanical therapies-such as taping, tension night splinting, and rigid arch support-are the most effective treatment for plantar fasciitis", "output": "In a prospective, observer-blinded study, 103 subjects were randomized to 1 of 3 treatment categories: anti-inflammatory etodolac plus corticosteroid injections; accommodative viscoelastic heel cup; or mechanical low-dye tapping for 1 month followed by rigid custom orthosis for 2 months. After 3 months of treatment, 70% of patients in the mechanical treatment group rated their functional outcome as excellent, compared with only 33% of the anti-inflammatory group and 30% of the accommodative group P=.005. Additionally, the mechanically treated group was less likely to terminate treatment early because of treatment failure P<.001." }, { "input": "Mechanical therapies-such as taping, tension night splinting, and rigid arch support-are the most effective treatment for plantar fasciitis", "output": "A controlled and observer-blinded study of 302 patients with plantar fasciitis compared standard extracorporeal shock wave therapy with sham treatment. The treated patients had significantly lower pain scores (as measured on a visual analog scale) than the placebo group (1.9 vs 4.7). Three months post-treatment, half as many treated patients were taking pain medication when compared with placebo patients. After 1 year of follow-up, 94% of the treatment group patients were still pain-free, with a pain score of <2." }, { "input": "If limited or no improvement is observed after 6 months of mechanical therapy, extracorporeal shock wave therapy (Orthotripsy) is the next treatment of choice", "output": "A meta-analysis of 8 published studies involving 840 patients whose condition was not improved after conservative therapy for at least 6 months showed that up to 88% of patients experienced good to excellent outcomes with extracorporeal shock wave therapy and were satisfied with the result." }, { "input": "When mechanical therapies and extracorporeal shock wave therapy have failed for more than 1 year, surgical treatment may be considered", "output": "In a prospective study of 43 patients with 47 painful heels followed for an average of 31 months, only 49% of the patients were satisfied with their outcome. Patient expectations should be considered in preoperative counseling. In contrast to surgery, either open or endoscopic, extracorporeal shock wave therapy does not require the patient avoid weightbearing or a prolonged time for return to work." }, { "input": "Cranberry juice (200 mL daily to 250 mL 3 times daily) or cranberry concentrate tablets (at least 1:30 parts concentrated juice twice daily) reduce recurrent, symptomatic urinary tract infection (UTI) in women by 12% to 20% (absolute risk reduction [ARR]) compared with placebo (number needed to treat [NNT]=58)", "output": "In a placebo-controlled randomized trial, women with prior UTI who took 1 tablet of concentrated cranberry juice (at least 1:30 parts concentrated juice) twice daily (n=50) or drank 250 mL of pure unsweetened cranberry juice 3 times a day for 12 months (n=50) reduced their incidence of symptomatic UTI. Women who drank the juice had an ARR of 12% (32% symptomatic UTI on placebo group, 20% in cranberry juice group, NNT=8.3) over 1 year. Use of cranberry juice tablets produced an ARR of 14% (32% symptomatic UTI in placebo group; 18% in cranberry tablet group, NNT=7.1). Self-reported compliance was 75% to 90% in the juice group and 90% in the tablet group." }, { "input": "Cranberry juice (200 mL daily to 250 mL 3 times daily) or cranberry concentrate tablets (at least 1:30 parts concentrated juice twice daily) reduce recurrent, symptomatic urinary tract infection (UTI) in women by 12% to 20% (absolute risk reduction [ARR]) compared with placebo (number needed to treat [NNT]=58)", "output": "In women with prior Escherichia coli UTI, 50 mL of cranberry-lingonberry juice concentrate daily for 6 months reduced the recurrence of symptomatic UTI from 36% in the control group to 16% in the treated group (NNT=5)." }, { "input": "Substituting bupropion, nefazodone, or mirtazapine is beneficial.", "output": "Open-label nonrandomized studies of all 3 agents suggest improved sexual functioning in 60% to 85% of patients with little to no loss of antidepressant efficacy." }, { "input": "Substituting bupropion, nefazodone, or mirtazapine is beneficial.", "output": "In a randomized double-blind study, patients experiencing sexual dysfunction on sertraline improved when switched to nefazodone 400 mg daily." }, { "input": "Substituting bupropion, nefazodone, or mirtazapine is beneficial.", "output": "Data suggest that bupropion, nefazodone, and mirtazapine have little to no effect on sexual functioning. Changing from SSRIs to one of these agents may alleviate SSRI-induced sexual dysfunction." }, { "input": "Augmentation therapy with amantadine, bupropion, and buspirone is no better than placebo.", "output": "In on augmentation therapy, buspirone augmentation resulted in a statistical improvement in sexual functioning at weeks 2 and 3 of therapy, but not at weeks 1 and 4 (mean dose 48.5 mg per day)." }, { "input": "Augmentation therapy with amantadine, bupropion, and buspirone is no better than placebo.", "output": "In a trial, adding buspirone 20 to 30 mg per day, amantadine 50 to 100 mg per day, or placebo resulted in equal improvement in women's sexual function." }, { "input": "Augmentation therapy with amantadine, bupropion, and buspirone is no better than placebo.", "output": "In a trial, adding bupropion or placebo showed equal improvement in sexual function." }, { "input": "SSRI \"drug holidays\" may also be effective.", "output": "One open-label nonrandomized study of weekend \"drug holidays\" showed no benefit for fluoxetine and inconsistent results for paroxetine and sertraline." }, { "input": "Patients with chronic obstructive pulmonary disease (COPD) who use cardioselective beta-blockers (beta1-blockers) do not experience a significant worsening of their short-term pulmonary status as measured by changes in forced expiratory volume in 1 second (FEV1), or by changes in patients' self-reported symptoms. If such harmful effects do exist, they are likely to be less clinically important than the substantial proven benefits of beta-blockade for patients with concomitant cardiovascular disease.", "output": "A 2004 meta-analysis synthesized the data of 19 clinical controlled trials that compared active therapy with either placebo or prior-to-treatment controls, assessing differences in FEV1, response to a beta2-agonist, and patient-reported respiratory symptoms. Trials included in the meta-analysis used cardioselective beta-blockers and evaluated either single-dose treatments or therapy of longer duration (2 days to 3.3 months). The authors concluded that patients with COPD who received cardioselective beta-blockers (such as metoprolol, atenolol, or bisoprolol) did not experience a statistically significant short-term deterioration in FEV1, worsening of COPD symptoms, or decreased responsiveness to beta2-agonists. The authors reported similar results for an analysis restricted to only those patients with severe COPD. This meta-analysis was limited by the relatively small number of participants (N=141 in single-dose treatment studies; N=126 in studies of longer duration treatment) in the handful of eligible studies. Consequently, rare or minimally harmful effects could have gone undetected." }, { "input": "Limited evidence suggests that most patients with congestive heart failure and COPD without reversible airflow obstruction tolerate carvedilol, which causes both nonselective beta- and alpha-adrenergic blockade.", "output": "A retrospective analysis of a cohort study analyzed the tolerability of carvedilol, a nonselective beta- and alpha-adrenergic blocker, in patients with COPD who had been taking the medication for at least 3 months. Eighty-five percent of the 89 patients with COPD tolerated carvedilol. The authors of the study (which was funded by the manufacturer of carvedilol) did not state why the other 15% of patients did not tolerate carvedilol, nor did they mention whether the patients with COPD had reversible airflow obstruction." }, { "input": "Limited evidence suggests that most patients with congestive heart failure and COPD without reversible airflow obstruction tolerate carvedilol, which causes both nonselective beta- and alpha-adrenergic blockade.", "output": "A small retrospective analysis of a cohort study that examined the outcomes of 31 patients with heart failure and COPD without reversible airflow obstruction who were started on carvedilol therapy. Over the 2.4 years that the patients were followed, 1 patient stopped taking carvedilol (mean dose 29 \u00b1 19 mg daily) due to wheezing. Whether these 31 patients were also included in the larger study is unclear." }, { "input": "Limited evidence suggests that most patients with congestive heart failure and COPD without reversible airflow obstruction tolerate carvedilol, which causes both nonselective beta- and alpha-adrenergic blockade.", "output": "A 2004 narrative review article concluded that carvedilol was well-tolerated in patients with COPD without reversible airflow obstruction, but no evidence exists regarding its tolerability in patients with reversible airflow obstruction." }, { "input": "Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perl\u00e8che, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis.", "output": "Geriatric Medicine also recommends topical antifungals to treat angular cheilitis." }, { "input": "Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perl\u00e8che, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis.", "output": "Taylor's Family Medicine recommends antifungals, including nystatin pastilles, clotrimazole troches, or a single 200-mg dose of fluconazole" }, { "input": "Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perl\u00e8che, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis.", "output": "The American Dental Association does mention topical antifungal creams for the treatment of angular cheilitis when discussing oral health and diabetes." }, { "input": "Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perl\u00e8che, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis.", "output": "A study compared antifungal treatments with placebo. This randomized-controlled trial from 1975 studied lozenge use of nystatin or amphotericin B in 52 patients with red palate, angular cheilitis, or both. These patients were identified through screening of 600 consecutive patients attending the prosthetic clinic for examination or treatment. Patients were randomly given a 1-month supply of nystatin, amphotericin B, or placebo and instructed to dissolve 4 lozenges a day in their mouth. The study did not describe any blinding procedure. Both nystatin and amphotericin B had statistically significant cures rates at 1 month compared with placebo (P=.05 and P=0.01, respectively). The NNT was 2.7 for the nystatin group and 2.0 for the amphotericin B group at 1 month. A comparison of the 2 anti-fungals found no difference in cure rate. Recurrence rates at 2 months after discontinuing therapy were the same. The only adverse effect reported was the unpleasant taste of the lozenges, especially nystatin." }, { "input": "Cheilitis is a broad term that describes inflammation of the lip surface characterized by dry scaling and fissuring. Specific types are atopic, angular, granulomatous, and actinic. Angular cheilitis is commonly seen in primary care settings, and it specifically refers to cheilitis that radiates from the commissures or corners of the mouth. Other terms synonymous with angular cheilitis are perl\u00e8che, commissural cheilitis, and angular stomatitis. Evidence reveals that topical ointment preparations of nystatin or amphotericin B treat angular cheilitis.", "output": "A prospective, double-blind, placebo-controlled study of 8 patients compared the efficacy of nystatin with placebo ointment. These patients were referred to a Department of Oral Diagnosis for sore lips with detected Candida albicans lesions located bilaterally. All of the patients were instructed to use one ointment on the right side and the other on the left side. Contamination was prevented by the use of gloves changed between applications. All 8 patients demonstrated complete healing after 1 to 4 weeks of treatment by nystatin, whereas only 1 patient had complete healing after the placebo, giving a number needed to treat (NNT) of 1.14 (P<.001)." }, { "input": "Improving oral health through regular use of xylitol or xylitol/chlorhexidine acetate containing chewing gums decreases angular cheilitis in nursing home patients.", "output": "A randomized controlled, double-blind study, performed in 21 English nursing facilities, enrolled 164 patients aged 60 years and older with some natural teeth and evaluated the effects of medicated chewing gum on oral health. At the end of 1 year, the 111 patients (67%) completed the study. Fifty-seven percent of the participants wore dentures. Several aspects were measured including the presence of angular cheilitis. There were 3 arms: no gum, xylitol gum, and chlorhexidine acetate/xylitol gum. The gums were used after breakfast and the evening meal and consisted of 2 pellets to be chewed for 15 minutes. Adherence was described as chewing gum at least 12 times per week for 12 months. A blinded investigator examined patients at baseline, 3, 6, 9, and 12 months. The results demonstrated a decrease in angular cheilitis in both the xylitol and chlorhexidine acetate/xylitol group at 12 months when compared to the no gum group (P<.01). Cheilitis was found in 14% of the xylitol group (compared with 27% at baseline), 7% of the chlorhexidine acetate/xylitol group (a reduction from 28%), and 32% of the no gum group (no change). The NNT was 7.7 for the xylitol group and 4.8 for the chlorhexidine acetate/xylitol group. This effect size may be exaggerated as the study randomized by nursing home not individual patients, and there was no statistical adjustment for the cluster randomization.." }, { "input": "Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects.", "output": "The American Academy of Pediatrics recommends avoiding DEET in children under 2 months of age. For all other children, it advises using DEET with a concentration between 10% and 30%." }, { "input": "Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects.", "output": "A review was sponsored by SC Johnson and Company, the makers of OFF! brand insect repellent. It assessed animal studies, epidemiologic data, and case reports, and supported the safety of DEET in children." }, { "input": "Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects.", "output": "A review found that DEET posed essentially no risk in children." }, { "input": "Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects.", "output": "A case series collected from poison control centers, included roughly 21,000 reports of DEET exposures during the 1990s. The authors concluded that the risk of toxicity was low and that there was no clear dose-dependent relationship between exposure and extent of severity of neurologic manifestations. This report found a rate of major adverse reactions (0.1%) from DEET that was similar to the first case series. The major reactions reported included hypotension, seizures, respiratory distress, and 2 deaths (0.01%). When limiting the data to infants and children only, there were 10 major events among 17,252 reported exposures (0.06%), and no deaths. Although infants and children accounted for 83.1% of all reported exposures, the majority of the serious outcomes (including the deaths) occurred in adults. About half of all those exposed reportedly had no ill effects, the other half had minor effects (transient effects that resolved without treatment). Only 4% experienced moderate effects (non-life threatening problem, but one that would likely require treatment). There were no data presented on the overall size of the exposed population, eg, users of DEET in the US." }, { "input": "Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects.", "output": "A case series collected poison control center reports during the 1980s. The report concluded that DEET exposure rarely led to adverse effects and that the route of administration (ie, ingestion) was more closely linked to toxicity than age or gender. There were 5 major adverse reactions reported from 9086 exposures to DEET (0.05%); these included hypotension, hypotonic reaction, and syncope, and 1 death (a suicide ingestion)." }, { "input": "Typically, a topical concentration between 10% and 30% should be used.", "output": "The American Academy of Pediatrics recommends avoiding DEET in children under 2 months of age. For all other children, it advises using DEET with a concentration between 10% and 30%." }, { "input": "Increasing DEET concentration does not improve protection, but does increase the duration of action.", "output": "Increasing the concentration of DEET does not improve protection but does provide longer duration. Concentrations of 6.65% protect for about 2 hours while 23.8% DEET can last about 5 hours." }, { "input": "other", "output": "The poison control center studies indicated that toxicity did not occur in a dose-dependent manner; the clinical significance of increased penetration is not clear." }, { "input": "other", "output": "Some studies have uncovered dangerous interactions with military and industrial chemicals, but such exposures are unlikely in most children. The most practical concern regards sun-screen. One study reported that use of sun-screen increased the penetration of DEET." }, { "input": "It is highly accurate in diagnosing injury to the anterior cruciate ligament (ACL).", "output": "The ACL is the most often injured knee ligament. The incidence of ACL injury is approximately 200,000 annually in the United States; 100,000 ACL reconstructions are performed each year.2,3 A complete tear of the ACL can lead to significant knee instability and, unless repaired, may limit physical activity and quality of life." }, { "input": "It is highly accurate in diagnosing injury to the Posterior cruciate ligament (PCL).", "output": "PCL injuries don't often cause significant instability and generally respond to nonsurgical treatment; they have less impact on a patient's quality of life. Surgery for PCL injury is usually reserved for elite athletes and unstable injuries. MCL and LCL injuries also are generally treated nonsurgically with rehabilitation and bracing; they normally don't require arthroscopic evaluation and repair." }, { "input": "Insufficient data are available to evaluate the effectiveness of magnetic resonance imaging (MRI) for diagnosing injuries to the medial collateral ligament (MCL) and lateral collateral ligament (LCL).", "output": "Several prospective studies have compared MRI with arthroscopy for diagnosing ACL and PCL tears. All enrolled patients had sustained knee trauma and had had a clinical exam that suggested ligamentous injury. MRI and arthroscopy were performed regardless of MRI findings. The surgeons performing arthroscopy were blinded to the MRI results." }, { "input": "Insufficient data are available to evaluate the effectiveness of magnetic resonance imaging (MRI) for diagnosing injuries to the medial collateral ligament (MCL) and lateral collateral ligament (LCL).", "output": "Although MRI equipment and techniques varied in all the studies, the sensitivity and specificity remained consistently high for detecting ACL injuries. Thin-slice views, special oblique views, and a fast spin-echo technique didn't improve either the sensitivity or specificity compared with conventional techniques or views, nor did decreasing the time interval from injury to imaging." }, { "input": "other", "output": "Arthroscopy with direct visualization of the ligamentous structures is considered the gold standard for diagnosing intra-articular ligamentous knee injuries, but it's invasive and costly. Although clinical examination is helpful in identifying injured ligaments, it may lead to unnecessary arthroscopies when used alone because of the high false-positive rate. MRI has been shown to be an effective tool for accurately diagnosing ligamentous knee injury." }, { "input": "other", "output": "Ligamentous knee injuries from trauma are common. In 2003, patients made about 19.4 million visits to the doctor because of knee problems." }, { "input": "IT'S UNCLEAR, given that no studies directly compare the efficacy of endovascular filters with other types of prophylaxis to prevent pulmonary embolism (PE) in adults with deep venous thrombosis (DVT). Although inferior vena cava filters (IVCFs) reduced the incidence of PE in a randomized controlled trial (RCT), patients treated with IVCFs and anticoagulation with unfractionated heparin or low-molecular-weight heparin had a greater risk of developing recurrent DVT than patients treated with anticoagulation alone.", "output": "A single-center retrospective cohort study of 1731 patients with IVCFs placed for various indications showed PE in 5.6% of patients. Some embolisms were clinically suspected and not confirmed." }, { "input": "IT'S UNCLEAR, given that no studies directly compare the efficacy of endovascular filters with other types of prophylaxis to prevent pulmonary embolism (PE) in adults with deep venous thrombosis (DVT). Although inferior vena cava filters (IVCFs) reduced the incidence of PE in a randomized controlled trial (RCT), patients treated with IVCFs and anticoagulation with unfractionated heparin or low-molecular-weight heparin had a greater risk of developing recurrent DVT than patients treated with anticoagulation alone.", "output": "A retrospective cohort study (N=318) concluded that 3.1% of the patients with IVCFs had a recurrent PE, diagnosed radiographically" }, { "input": "IT'S UNCLEAR, given that no studies directly compare the efficacy of endovascular filters with other types of prophylaxis to prevent pulmonary embolism (PE) in adults with deep venous thrombosis (DVT). Although inferior vena cava filters (IVCFs) reduced the incidence of PE in a randomized controlled trial (RCT), patients treated with IVCFs and anticoagulation with unfractionated heparin or low-molecular-weight heparin had a greater risk of developing recurrent DVT than patients treated with anticoagulation alone.", "output": "A prospective cohort study followed 481 patients who received an IVCF because of either a contraindication to anticoagulation or sustained recurrent embolization despite adequate anticoagulation. Of the patients who had a filter for 6 months or longer, 2% had clinically suspected PE, but PE was confirmed in only 0.5%." }, { "input": "IT'S UNCLEAR, given that no studies directly compare the efficacy of endovascular filters with other types of prophylaxis to prevent pulmonary embolism (PE) in adults with deep venous thrombosis (DVT). Although inferior vena cava filters (IVCFs) reduced the incidence of PE in a randomized controlled trial (RCT), patients treated with IVCFs and anticoagulation with unfractionated heparin or low-molecular-weight heparin had a greater risk of developing recurrent DVT than patients treated with anticoagulation alone.", "output": "Patients with DVT generally have associated PE 10% of the time. Several cohort studies have examined the prevalence of recurrent PE in patients with IVCFs, but none compared prevalence in patients with and without filters." }, { "input": "IT'S UNCLEAR, given that no studies directly compare the efficacy of endovascular filters with other types of prophylaxis to prevent pulmonary embolism (PE) in adults with deep venous thrombosis (DVT). Although inferior vena cava filters (IVCFs) reduced the incidence of PE in a randomized controlled trial (RCT), patients treated with IVCFs and anticoagulation with unfractionated heparin or low-molecular-weight heparin had a greater risk of developing recurrent DVT than patients treated with anticoagulation alone.", "output": "The study lacked statistical power to draw any conclusion about the efficacy of IVCFs in preventing PE over shorter time periods or in reducing PE-related or overall mortality." }, { "input": "IT'S UNCLEAR, given that no studies directly compare the efficacy of endovascular filters with other types of prophylaxis to prevent pulmonary embolism (PE) in adults with deep venous thrombosis (DVT). Although inferior vena cava filters (IVCFs) reduced the incidence of PE in a randomized controlled trial (RCT), patients treated with IVCFs and anticoagulation with unfractionated heparin or low-molecular-weight heparin had a greater risk of developing recurrent DVT than patients treated with anticoagulation alone.", "output": "One RCT examined PE rates in 400 patients with acute proximal DVT who were randomized to receive or not receive a permanent IVCF and also randomized to receive either unfractionated heparin or low-molecular-weight heparin for at least the first 3 months. Patients with a contraindication to anticoagulation or history of anticoagulation failure were excluded. After 8 years of follow-up, symptomatic PE occurred less often in the filter group than the nonfilter group (6.2% vs 15.1%; P=.008; hazard ratio [HR]=0.36, 95% confidence interval [CI], 0.17-0.77; number needed to treat [NNT]=11.2). The filter group had a higher incidence of recurrent DVT than the nonfilter group (35.7% vs 27.5%; HR=1.52, 95% CI, 1.02-2.27; number needed to harm=12.2)." }, { "input": "IT'S UNCLEAR, given that no studies directly compare the efficacy of endovascular filters with other types of prophylaxis to prevent pulmonary embolism (PE) in adults with deep venous thrombosis (DVT). Although inferior vena cava filters (IVCFs) reduced the incidence of PE in a randomized controlled trial (RCT), patients treated with IVCFs and anticoagulation with unfractionated heparin or low-molecular-weight heparin had a greater risk of developing recurrent DVT than patients treated with anticoagulation alone.", "output": "One RCT examined PE rates in 400 patients with acute proximal DVT who were randomized to receive or not receive a permanent IVCF and also randomized to receive either unfractionated heparin or low-molecular-weight heparin for at least the first 3 months. Patients with a contraindication to anticoagulation or history of anticoagulation failure were excluded. After 8 years of follow-up, symptomatic PE occurred less often in the filter group than the nonfilter group (6.2% vs 15.1%; P=.008; hazard ratio [HR]=0.36, 95% confidence interval [CI], 0.17-0.77; number needed to treat [NNT]=11.2). The filter group had a higher incidence of recurrent DVT than the nonfilter group (35.7% vs 27.5%; HR=1.52, 95% CI, 1.02-2.27; number needed to harm=12.2)." }, { "input": "Patients should be considered for IVCF placement in the following circumstances: anticoagulation is contraindicated, a serious complication has resulted from anticoagulation treatment, thromboembolism recurs despite adequate anticoagulation.", "output": "The American College of Chest Physicians recommends considering an IVCF for patients with DVT who have a contraindication to anticoagulation, complication of anticoagulation, or recurrent thromboembolism despite adequate anticoagulation." }, { "input": "A morning serum cortisol level >13 mcg/dL reliably rules out adrenal insufficiency, and the test is easy and safe to perform. Because of low specificity, patients with a level of \u226413 mcg/dL need further evaluation with the cosyntropin stimulation test (CST).", "output": "A meta-analysis, based on a PubMed search of English-language studies from 1966 to 2006, compared the performance of morning serum cortisol, the 1 mcg CST, and the 250 mcg CST for diagnosing secondary adrenal insufficiency. This analysis used patient-level data obtained from the original investigators instead of reported study-level results. Data from patients described as normal, healthy control subjects were excluded. Studies included in the meta-analysis used an accepted gold-standard test, such as the insulin tolerance test or metyrapone test. Studies that were performed in a critical care setting or used older, less reliable cortisol assays were excluded, as were studies for which patient-level data couldn't be obtained. Three new studies were included, and 12 of the previously used studies were excluded. Instead of using the reported cortisol cutoff levels, the authors defined a negative test as the mean cortisol level (the \"rule-out threshold\") above which the negative likelihood ratio of adrenal insufficiency is <0.15. The rule-out thresholds for morning serum cortisol, 1 mcg CST, and 250 mcg CST were 13, 22, and 30 mcg/dL, respectively. The authors proposed an optimal testing strategy for secondary adrenal insufficiency (assuming a low or moderate pretest probability) that starts with a morning serum cortisol measurement: A serum cortisol level >13 mcg/dL can effectively rule out adrenal insufficiency, if the morning serum cortisol is <13 mcg/dL, a 1 mcg CST >22 mcg/dL can rule out adrenal insufficiency, patients would need an insulin tolerance test or metyrapone test only if the low-dose CST is <22 mcg/dL." }, { "input": "The 250 mcg CST requires intravenous (IV) or intramuscular (IM) administration of cosyntropin and multiple blood draws; a normal response reliably rules out primary adrenal insufficiency.", "output": "A meta-analysis, based on a PubMed search of English-language studies from 1966 to 2006, compared the performance of morning serum cortisol, the 1 mcg CST, and the 250 mcg CST for diagnosing secondary adrenal insufficiency. This analysis used patient-level data obtained from the original investigators instead of reported study-level results. Data from patients described as normal, healthy control subjects were excluded. Studies included in the meta-analysis used an accepted gold-standard test, such as the insulin tolerance test or metyrapone test. Studies that were performed in a critical care setting or used older, less reliable cortisol assays were excluded, as were studies for which patient-level data couldn't be obtained. Three new studies were included, and 12 of the previously used studies were excluded. Instead of using the reported cortisol cutoff levels, the authors defined a negative test as the mean cortisol level (the \"rule-out threshold\") above which the negative likelihood ratio of adrenal insufficiency is <0.15. The rule-out thresholds for morning serum cortisol, 1 mcg CST, and 250 mcg CST were 13, 22, and 30 mcg/dL, respectively. The authors proposed an optimal testing strategy for secondary adrenal insufficiency (assuming a low or moderate pretest probability) that starts with a morning serum cortisol measurement: A serum cortisol level >13 mcg/dL can effectively rule out adrenal insufficiency, if the morning serum cortisol is <13 mcg/dL, a 1 mcg CST >22 mcg/dL can rule out adrenal insufficiency, patients would need an insulin tolerance test or metyrapone test only if the low-dose CST is <22 mcg/dL." }, { "input": "A normal response moderately decreases the likelihood of secondary adrenal insufficiency.", "output": "Researchers conducting a meta-analysis of the CST in diagnosing both primary and secondary adrenal insufficiency searched MEDLINE for English-language studies from 1966 to 2002 and used summary receiver-operating characteristic (ROC) curves to combine the sensitivities and specificities from individual studies. Four studies of primary adrenal insufficiency showed a negative likelihood ratio of 0.026 for the 250 mcg CST. A negative CST would, therefore, significantly decrease the post-test probability of primary adrenal insufficiency and effectively rule out the condition." }, { "input": "The 1 mcg CST has better diagnostic discrimination, but requires an extra step to dilute the cosyntropin.", "output": "Using a ROC curve generated from 22 studies, the authors found the test characteristics of the 250 mcg CST and the 1 mcg CST to be similar. Only 7 of these studies included paired data for the standard- and low-dose CST in the same patients, however. In the 7 studies with paired data, the 1 mcg CST had better diagnostic discrimination, based on a larger area under the ROC, than the 250 mcg CST" }, { "input": "Yes, hyaluronic acid (HA) injections relieve pain more than placebo. The effect is small but similar to results from oral nonsteroidal anti-inflammatory drugs (NSAIDs) or steroid injection.", "output": "A Cochrane meta-analysis conducted the following year, HA was found to have positive results." }, { "input": "Yes, hyaluronic acid (HA) injections relieve pain more than placebo. The effect is small but similar to results from oral nonsteroidal anti-inflammatory drugs (NSAIDs) or steroid injection.", "output": "A 2005 meta-analysis evaluated the effectiveness of HA injections for osteoarthritis of the knee compared with saline placebo. Researchers identified 22 studies of 8 HA products that used the common end point of pain with movement. A decrease in pain of 15% was deemed clinically meaningful. Compared with placebo, the mean difference in pain scores with HA products was -4% (95% confidence interval [CI], -9% to 1%) after 2 to 6 weeks; -4% (95% CI, -8% to -1%) after 10 to 14 weeks; and -7% (95% CI, -12% to -2%) after 22 to 30 weeks. The authors note that the small measured effect of HA was magnified by trials that didn't report intention-to-treat results. The effect of HA was also larger in studies that didn't conceal allocation. A weakness of the analysis was its inability to assess potential differences between HA products. In this 2005 meta-analysis, HA injection didn't improve knee function in any time interval." }, { "input": "The various HA products all appear to be equally effective in reducing pain.", "output": "The comprehensive 2006 Cochrane meta-analysis reviewed single- and double-blinded RCTs that evaluated the effect of 12 HA products on osteoarthritis of the knee.3 Studies compared HA products with placebo (40), intra-articular steroids (10), NSAIDs (6), physical therapy (3), exercise (2), and each other (15). Efficacy data for different products couldn't be combined because the studies measured different sets of outcomes at different time points. Overall, the authors concluded that HA injections effectively reduced pain scores, with the largest benefit occurring within 5 to 13 weeks. The authors also noted that the reductions in pain with HA injections, although generally small, were comparable to oral NSAID therapy and intra-articular corticosteroids. The trials reported few adverse events." }, { "input": "Data concerning the effect of HA on functional ability are conflicting.", "output": "A Cochrane review determined that not enough evidence existed to evaluate HA products against each other. An RCTs compared HA products and found no differences in efficacy. The study compared Synvisc, Orthovisc, and Ostenil therapy in 660 patients over 6 months." }, { "input": "Data concerning the effect of HA on functional ability are conflicting.", "output": "A Cochrane review determined that not enough evidence existed to evaluate HA products against each other. An RCTs compared HA products and found no differences in efficacy. The study compared Synvisc with Euflexxa in 321 patients over 3 months. Notably, 8% of patients in this study who used Synvisc developed an effusion, compared with 0.6% of patients who used Euflexxa (P=.0015)." }, { "input": "There are no clinical or epidemiologic features that will help you to clearly distinguish community-acquired methicillin-resistant Staphylococcus aureus infections (CA-MRSA) from methicillin-sensitive (CA-MSSA) infections.", "output": "Abscess formation was the most common presentation of CA-MRSA, followed by purulent cellulitis. The prevalence and incidence of nonpurulent CA-MRSA is not well defined." }, { "input": "There are no clinical or epidemiologic features that will help you to clearly distinguish community-acquired methicillin-resistant Staphylococcus aureus infections (CA-MRSA) from methicillin-sensitive (CA-MSSA) infections.", "output": "Two prospective cohort studies have looked at the usefulness of clinical characteristics to help differentiate MRSA from MSSA infections. The studies-a 2002 observational study of 144 children and a 2007 study of 180 consecutively enrolled adults-found no clear distinguishing features for MRSA." }, { "input": "Incision and drainage is the primary therapy for purulent skin and soft tissue infections.", "output": "A 2007 RCT of 166 indigent, inner-city patients with confirmed MRSA investigated combining incision and drainage with 7 days of therapy using either cephalexin or placebo. The primary outcome was clinical cure or failure 7 days after incision and drainage. The trial found no advantage to adding antibiotics; MRSA would likely be resistant to cephalexin in any case." }, { "input": "Incision and drainage is the primary therapy for purulent skin and soft tissue infections.", "output": "Incision and drainage remains the mainstay of abscess treatment." }, { "input": "Incision and drainage is the primary therapy for purulent skin and soft tissue infections.", "output": "Incision and drainage remains the mainstay of abscess treatment." }, { "input": "There are inadequate data evaluating the role of oral antibiotics for MRSA.", "output": "A 2006 summary from Clinical Evidence found no RCT support for any outpatient antibiotic. No evidence exists that intranasal mupirocin or antiseptic body washes reduce the recurrence rate. We found no studies evaluating the optimal treatment of purulent skin and soft tissue infections without abscesses." }, { "input": "Yes. Emollients are effective first-line treatment to decrease symptoms of eczema and reduce the need to use steroids in children.", "output": "Emollients have demonstrated efficacy in several RCTs compared with placebo and corticosteroids alone. No 1 preparation has proved superior to another; all reduce steroid use and improve skin hydration." }, { "input": "Tar preparations work, but compliance may be limited.", "output": "Only 1 study has evaluated the use of tar: a comparison of 30 patients (mean age 11.8 years) who were treated with tar on one side of the body and 1% hydrocortisone on the other. Both treatments produced comparable results and were well tolerated. But compliance can be a problem with tar products because they smell unpleasant and stain clothing." }, { "input": "Gamma-linoleic acid preparations, borage oil, and evening primrose oil show efficacy in small studies.", "output": "Small studies have evaluated the efficacy of gamma-linoleic acid (GLA)-including borage oil (24% GLA) and evening primrose oil (7%-10% GLA). An RCT of 12 patients (ages 4-46 years, mean 18 years) that compared evening primrose oil with placebo found that patients treated with primrose oil showed a subjective improvement in skin scaling, dryness, redness, and itching." }, { "input": "Gamma-linoleic acid preparations, borage oil, and evening primrose oil show efficacy in small studies.", "output": "A double-blind, placebo-controlled trial of 32 children that assessed the effects of undershirts coated with borage oil compared with noncoated undershirts found statistically significant improvements in both itching and erythema." }, { "input": "MAS063DP cream (Atopiclair) is effective.", "output": "MAS063DP is a nonsteroidal, hydrolipidic cream containing glycyrrhetinic acid (GrA), vitis vinifera (grapevine extract), and telmestine. A recent multicenter RCT of 142 children compared MAS063DP to vehicle cream alone. The primary outcome was treatment success defined as an Investigator's Global Assessment score of \u22641 (range 0-5), measured on day 22. Therapy was successful in 77% of the treatment group vs 0% of the vehicle-only group (number needed to treat=1)." }, { "input": "Chamomile may be effective, but this treatment has not been adequately evaluated.", "output": "One RCT demonstrated topical chamomile to be equivalent to 0.25% hydrocortisone cream for treating mild eczema." }, { "input": "Bathing in acidic hot spring water may be effective, but this treatment has not been adequately evaluated.", "output": "In a case control study of 70 patients (ages 12-80 years, mean 23 years,) bathing in acidic hot spring water (42\u00ba C) helped control edema, erythema, exudation, and excoriation in refractory cases of eczema." }, { "input": "Wet wrap dressings may be effective but increase the risk of skin infections.", "output": "A critical review suggests that short-term use of wet wraps in combination with topical steroids and emollients is effective for severe eczema. However, a small RCT of 50 children found no additional benefit over standard care and an increased risk of skin infection (95% CI, 5%-42%; P=.05) with a number needed to harm of 5." }, { "input": "Hamamelis distillate creams.", "output": "Hamamelis (witch hazel) distillate cream was inferior to steroid creams." }, { "input": "Massage with essential oils/aromatherapy are ineffective.", "output": "In 1 case control study, massage with essential oils didn't improve eczema compared with massage without essential oils." }, { "input": "For grade 3 and 4 ankle sprains, ice works better than heat to speed recovery (return to play).", "output": "A retrospective cohort study of 32 patients in a sports medicine clinic demonstrated that early cryotherapy (within 36 hours of injury) for grades 3 and 4 ankle sprains, when compared with early heat therapy, resulted in earlier return to activity, as defined by ability to walk, climb stairs, run, and jump without pain. Grade 3 sprains treated with ice recovered in 11.0 days vs 14.8 days with heat. Grade 4 sprains treated with ice recovered in 13.2 days vs 30.4 days with heat. This study also showed that early application of ice (within 36 hours) decreased time to recovery compared with late application of ice." }, { "input": "No studies support faster return to play with the application of heat at any time after injury. Ice therapy also reduces edema, but the clinical significance of this finding is unclear.", "output": "One randomized controlled trial compared ice therapy (in the form of a cooling anklet applied upon presentation) with placebo in 143 patients presenting within 24 hours of injury to a university emergency department in England. All patients received high-dose nonsteroidal anti-inflammatory agents. Though a trend was found in favor of ice therapy, no statistically significant difference was found in recovery time, as defined by pain relief and ability to bear weight. The grade of sprain was not specifically accounted for in this study." }, { "input": "No studies support faster return to play with the application of heat at any time after injury. Ice therapy also reduces edema, but the clinical significance of this finding is unclear.", "output": "A randomized controlled trial compared ice with placebo in 30 patients with grade 3 and 4 sprains referred to a physiotherapy department within 2 days of ankle injury. No statistical difference was found in recovery time, defined as ability to bear weight with only mild to moderate pain." }, { "input": "No studies support faster return to play with the application of heat at any time after injury. Ice therapy also reduces edema, but the clinical significance of this finding is unclear.", "output": "A randomized controlled trial of 60 patients with acute ankle sprains of all grades presenting to an emergency department compared cryogel plus bandaging with bandaging alone (cooling vs no cooling). This study found the mean time to recovery-defined as decreased pain-was reduced from 14.8 days to 9.7 days with constant cooling for the first 48 hours." }, { "input": "No studies support faster return to play with the application of heat at any time after injury. Ice therapy also reduces edema, but the clinical significance of this finding is unclear.", "output": "The application of ice-but not heat-within 24 to 48 hours of acute ankle sprain also reduced edema. Several studies looked at reduction of edema with cooling. One study measured edema in 30 patients with grade 1 and 2 sprains treated with cold, heat, or contrast baths during the third, fourth, and fifth days. Only ice therapy alone significantly reduced edema." }, { "input": "Lithium is the first-line treatment for pregnant patients requiring medication.", "output": "Because concerns about Ebstein's anomaly are less of a problem than once thought, lithium is the first-line treatment for bipolar disorder in pregnancy." }, { "input": "Monotherapy is preferred for women of childbearing age who have bipolar disorder.", "output": "Monotherapy for bipolar illness is preferred; it generally minimizes the risk of congenital anomalies. The use of lithium for long-term management of bipolar disorder is associated with decreased rates of suicide and all-cause mortality." }, { "input": "When prescribing lithium or anticonvulsant drugs (eg, valproic acid and carbamazepine), draw blood levels monthly during the first and second trimesters, and then weekly in the third trimester.", "output": "Antiseizure medications, including carbamazepine and valproic acid, are considered human teratogens in the first trimester. If a woman has an unplanned pregnancy and presents late in the first trimester or in the second trimester, discontinuation of these medication in stable patients is not recommended. Valproate and carbamazepine are both compatible with breastfeeding." }, { "input": "When prescribing lithium or anticonvulsant drugs (eg, valproic acid and carbamazepine), draw blood levels monthly during the first and second trimesters, and then weekly in the third trimester.", "output": "Medication doses may also need to be increased up to 50% during the second and third trimesters, when creatinine clearance doubles and the plasma volume increases." }, { "input": "When prescribing lithium or anticonvulsant drugs (eg, valproic acid and carbamazepine), draw blood levels monthly during the first and second trimesters, and then weekly in the third trimester.", "output": "Monitor the levels of lithium and anticonvulsants monthly through the second trimester, then weekly during the third trimester because of blood volume changes." }, { "input": "Behavior therapy has a role as an adjunct to pharmacologic therapy, but no studies show its benefit alone in preventing mania.", "output": "Cognitive behavior therapy-which focuses on adherence to treatment, minimizing stressors, improving social and occupational function, and minimizing sleep deprivation-may help prevent mania, although there have been no studies specifically on prevention of mania using cognitive behavior therapy." }, { "input": "Electroconvulsive therapy may be beneficial for patients with refractory depressive symptoms, and may be used in pregnancy.", "output": "There have been no conclusive reports of teratogenicity with electroconvulsive therapy." }, { "input": "Electroconvulsive therapy may be beneficial for patients with refractory depressive symptoms, and may be used in pregnancy.", "output": "The most common complication, occurring in 1.5% of cases, were fetal arrhythmias. Avoiding atropine, maintaining oxygenation, avoiding excessive hyperventilation, and elevating the right hip can decrease the risk of fetal arrhythmias during electroconvulsive therapy." }, { "input": "other", "output": "Wisner et al found verapamil to be effective for mania in a nonrandomized prospective study of bipolar hypomanic/manic and depressed patients." }, { "input": "other", "output": "Following delivery, you'll need to decrease the dose of lithium to prepregnancy doses, unless there is an acute destabilization of mood." }, { "input": "other", "output": "Women with bipolar disorder have a 100-fold higher risk of developing postpartum psychosis. For this reason, treatment beyond delivery is recommended, along with close monitoring of the infant." }, { "input": "other", "output": "Women taking lithium may already be pregnant when you see them, and even a slow lithium taper may not minimize exposure to the developing fetus." }, { "input": "other", "output": "Taper lithium over 2 to 4 weeks when discontinuing the medication." }, { "input": "other", "output": "Atypical antipsychotics have not been well studied, but there is no conclusive evidence that they cause fetal malformations." }, { "input": "other", "output": "Although lamotrigine was thought to have fewer risks than other drugs, the FDA issued an alert in September 2006 suggesting a possible increased risk of cleft palate for infants exposed to lamotrigine in the first trimester." }, { "input": "other", "output": "Data on the treatment of bipolar disease among fertile women are limited to case-control studies and drug registries because of a lack of RCTs in this population." }, { "input": "other", "output": "The risk of recurrence of mania is 3 times higher with rapid discontinuation of lithium over less than 2 weeks." }, { "input": "other", "output": "Lithium is associated with 10- to 20-fold higher risk of Ebstein's anomaly, a congenital anomaly affecting the tricuspid valve and right ventricle, with varying clinical effects. However, the absolute risk is small: Ebstein's anomaly occurs in 1:20,000 unexposed pregnancies." }, { "input": "It's not clear; little evidence supports or refutes the safety of guaifenesin, a common expectorant, in pregnancy. A small number of observational and case-control studies suggest a weak association between guaifenesin use and inguinal hernias and neural tube defects in newborns. However, substantial methodological flaws, the absence of statistical significance, and low rates of prevalence cast a shadow of a doubt over the data.", "output": "Because of the significant potential for recall bias, interpret the findings of these case-control studies with caution. The mother of a child with a birth defect may search her memory more aggressively for potential causes than a mother of a healthy infant, leading to different rates of recalled, rather than actual, exposures. In the absence of confirmatory prospective data, such as medication diaries or pharmacy databases, recall bias accounts for many spurious positive findings in case control studies." }, { "input": "It's not clear; little evidence supports or refutes the safety of guaifenesin, a common expectorant, in pregnancy. A small number of observational and case-control studies suggest a weak association between guaifenesin use and inguinal hernias and neural tube defects in newborns. However, substantial methodological flaws, the absence of statistical significance, and low rates of prevalence cast a shadow of a doubt over the data.", "output": "In a study evaluating 6509 women whose pregnancies resulted in live births, 241 women reported first-trimester exposure to guaifenesin. Five of the guaifenesin-exposed infants (2.1%) had 1 of the birth defects studied (types of disorders not reported). The calculated RR of birth defect after in utero guaifenesin exposure was 1.3 (no CIs or P values reported); the authors concluded that there was no strong association between guaifenesin and the malformations studied." }, { "input": "It's not clear; little evidence supports or refutes the safety of guaifenesin, a common expectorant, in pregnancy. A small number of observational and case-control studies suggest a weak association between guaifenesin use and inguinal hernias and neural tube defects in newborns. However, substantial methodological flaws, the absence of statistical significance, and low rates of prevalence cast a shadow of a doubt over the data.", "output": "Guaifenesin use in pregnancy may also be associated with neural tube defects. In a case-control study, researchers identified 538 fetuses and live-born infants with neural tube defects between 1989 and 1991. Twelve patients with neural tube defects were exposed to guaifenesin during gestation; 6 in the control group reported exposure. The authors reported a trend towards increased risk of neural tube defects in offspring of guaifenesin-exposed mothers (odds ratio=2.04; 95% CI, 0.79-5.28). However, since the results were not statistically significant, the authors concluded that guaifenesin had not contributed to the occurrence of neural tube defects." }, { "input": "It's not clear; little evidence supports or refutes the safety of guaifenesin, a common expectorant, in pregnancy. A small number of observational and case-control studies suggest a weak association between guaifenesin use and inguinal hernias and neural tube defects in newborns. However, substantial methodological flaws, the absence of statistical significance, and low rates of prevalence cast a shadow of a doubt over the data.", "output": "Guaifenesin use in pregnancy has been associated with inguinal hernias in newborns. From 1958 to 1965, the Collaborative Perinatal Project recruited 132,500 women to participate in a multicenter study; however, selection and exclusion criteria were not consistent. From this initial group, only 50,282 mother-child pairs were studied. Trained examiners interviewed the women at the child's 4, 8, 12, and 24-month visits, and then annually thereafter to 8 years of age. The examiners identified 7 children with inguinal hernias among 197 mothers who had used guaifenesin during their first trimester (standardized relative risk [RR] of 2.6; no CI or P value reported). Twenty children had inguinal hernias among the 1337 mothers who had used guaifenesin during any trimester of their pregnancy (RR=1.1; no confidence interval [CI] or P value reported). The authors acknowledged that reporting bias among the participating centers prevented them from drawing any conclusions from the data." }, { "input": "The combination of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has been studied for treatment of heart failure, hypertension, and proteinuric renal disease. Combination therapy with an ACE inhibitor and an ARB decreases symptoms in heart failure patients, but does not appear to have an impact on overall mortality.", "output": "The VALIANT demonstrated the safety but the lack of incremental efficacy in adding valsartan to ACE inhibitors for patients with left ventricular dysfunction after a myocardial infarction." }, { "input": "The combination of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has been studied for treatment of heart failure, hypertension, and proteinuric renal disease. Combination therapy with an ACE inhibitor and an ARB decreases symptoms in heart failure patients, but does not appear to have an impact on overall mortality.", "output": "In CHARM, candesartan was added to baseline therapy among patients with heart failure. Baseline therapy included diuretics (90%), beta blockers (55%), spironolactone (17%), and other cardiovascular medications as necessary. In this study, those in the treatment arm had a decrease in the combined endpoint of cardiovascular death plus congestive heart failure admission (RR=0.85; 95% CI, 0.75-0.96), but no difference was seen in overall mortality. Of note, no adverse interaction was demonstrated for those on the triple combination of ACE inhibitors, ARBs, and beta-blockers." }, { "input": "The combination of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has been studied for treatment of heart failure, hypertension, and proteinuric renal disease. Combination therapy with an ACE inhibitor and an ARB decreases symptoms in heart failure patients, but does not appear to have an impact on overall mortality.", "output": "In ValHeFT, 5010 patients with systolic dysfunction were randomized to the ARB valsartan or placebo in addition to background therapy, which included an ACE inhibitor in 93% of subjects. The primary endpoints were mortality and combined mortality and morbidity. An increase in mortality was found among patients on the triple therapy combination of valsartan, an ACE inhibitor, and a beta-blocker (relative risk [RR]=1.4; 95% confidence interval [CI], 1.1-1.9). Among those not on beta-blockers, adding valsartan to baseline therapy of an ACE inhibitor resulted in a modest improvement in the combined endpoint (RR=0.8; 95% CI, 0.7-0.9), but no change in mortality alone was found." }, { "input": "Preliminary data from small trials indicate that combination therapy may be more effective than monotherapy with an ACE inhibitor or an ARB for lowering blood pressure", "output": "One trial of 177 patients found no significant difference in 24-hour ambulatory mean diastolic blood pressure with combination therapy vs ACE inhibitor or ARB monotherapy, but did show a decrease in clinic diastolic blood pressure." }, { "input": "Preliminary data from small trials indicate that combination therapy may be more effective than monotherapy with an ACE inhibitor or an ARB for lowering blood pressure", "output": "A small trial of 20 patients demonstrated improved ambulatory blood pressure control with combination therapy vs ACE inhibitor monotherapy." }, { "input": "Although morbidity and mortality data for the combination are not currently available. Additionally, in trials involving diabetic and nondiabetic proteinuric renal disease, the combination of ACE inhibitors and ARBs delays progression of renal disease to a greater extent than monotherapy; however, mortality data are also unavailable.", "output": "The COOPERATE trial was conducted in Japan and included 336 patients with nondiabetic renal disease. The investigators found that significantly fewer patients receiving combination therapy reached the combined primary endpoint of time to doubling of serum creatinine or end-stage renal disease compared with patients receiving monotherapy." }, { "input": "Although morbidity and mortality data for the combination are not currently available. Additionally, in trials involving diabetic and nondiabetic proteinuric renal disease, the combination of ACE inhibitors and ARBs delays progression of renal disease to a greater extent than monotherapy; however, mortality data are also unavailable.", "output": "The CALM study included 199 patients with hypertension, micro-albuminuria, and type 2 diabetes mellitus, and demonstrated significantly greater attenuation of urinary albumin/creatinine ratio and significantly improved blood pressure control with combination therapy compared with either therapy alone." }, { "input": "No evidence exists that treating isolated high triglyceride levels in the absence of other risk factors prevents coronary events. Although elevated triglycerides in some studies correlates with coronary events, the association weakens when controlled for factors such as diabetes, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, body mass index, and other cardiac risk factors.", "output": "Another meta-analysis of 3 prospective intervention trials with 15,880 enrolled subjects found that triglyceride levels did not provide any clinically meaningful information about risk beyond that provided by other cholesterol subfractions." }, { "input": "No evidence exists that treating isolated high triglyceride levels in the absence of other risk factors prevents coronary events. Although elevated triglycerides in some studies correlates with coronary events, the association weakens when controlled for factors such as diabetes, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, body mass index, and other cardiac risk factors.", "output": "One meta-analysis of 17 population-based prospective studies of triglycerides and cardiovascular disease (including 57,000 patients) showed high triglyceride levels to be predictive of cardiac events, even when adjusted for HDL and other risk factors (age, total and LDL cholesterol, smoking, body mass index, and blood pressure). After adjusting for these other risk factors, the authors found an increased risk for all cardiac endpoints (myocardial infarction, death, etc) of 14% for men and 32% for women (Men: relative risk [RR]=1.14; 95% confidence interval [CI], 1.05-1.28; Women: RR=1.37; 95% CI, 1.13-1.66)." }, { "input": "Coincident lowering of triglycerides, while treating other dyslipidemias (such as high LDL and low HDL), can contribute to decreasing coronary events.", "output": "In treatment trials, the most impressive risk reductions come from the groups who fit the lipid triad of low HDL, high LDL, and high triglycerides. Low levels of HDL appear to interact with hypertriglyceridemia to increase coronary risk, and all studies showing improved outcomes have simultaneously increased HDL while lowering triglycerides." }, { "input": "Coincident lowering of triglycerides, while treating other dyslipidemias (such as high LDL and low HDL), can contribute to decreasing coronary events.", "output": "In 3 large-scale prospective, placebo-controlled trials (the Helsinki Heart Study, a primary prevention study, and the VA-HIT and Bezafibrate Infarction Prevention trials, both secondary prevention studies), lowering triglycerides and raising HDL concurrently improved outcomes. Successful dietary and medical interventions, especially with statins and fibrates, improved overall lipid profiles-not just triglyceride levels." }, { "input": "Treating triglyceride levels over 500 to 1000 mg/dL may reduce the risk of pancreatitis.", "output": "Expert opinion suggests that patients with triglyceride levels of 500 to 1000 mg/dL may have an increased risk of pancreatitis." }, { "input": "Treating triglyceride levels over 500 to 1000 mg/dL may reduce the risk of pancreatitis.", "output": "Epidemiologic evidence suggests that patients with triglyceride levels of 500 to 1000 mg/dL may have an increased risk of pancreatitis." }, { "input": "other", "output": "Truly isolated hypertriglyceridemia is rare. To date, no good trials directly address the effect of reducing truly isolated hypertriglyceridemia on cardiovascular morbidity or mortality. High triglycerides are usually accompanied by other features of the \"metabolic syndrome\" (low HDL, high LDL, insulin resistance, diabetes, hypertension, and obesity), making it almost impossible to look at these in isolation or attribute risk to a specific component." }, { "input": "Although lowering diastolic blood pressure (DBP) is associated with reduced cardiovascular events, systolic blood pressure (SBP) is a more robust predictor of cardiovascular risk than DBP and should now be used to diagnose, stage, and treat hypertension. Lowering diastolic blood pressure (DBP) to <90 mm Hg in hypertensive individuals of all ages decreases the risk of cardiovascular events including myocardial infarction (MI), heart failure, and sudden death. However, there is no consensus regarding how far to lower DBP. A \"J-shaped\" increase in cardiovascular risks with DBP <85 mm Hg may apply under certain conditions.", "output": "A French cohort study followed over 4700 hyper-tensive men for an average of 14 years. These men had their hypertension treated in usual fashion by their own physicians. In this group, SBP was much more accurate than DBP in classifying severity of hypertension and in predicting cardiovascular risk." }, { "input": "Although lowering diastolic blood pressure (DBP) is associated with reduced cardiovascular events, systolic blood pressure (SBP) is a more robust predictor of cardiovascular risk than DBP and should now be used to diagnose, stage, and treat hypertension. Lowering diastolic blood pressure (DBP) to <90 mm Hg in hypertensive individuals of all ages decreases the risk of cardiovascular events including myocardial infarction (MI), heart failure, and sudden death. However, there is no consensus regarding how far to lower DBP. A \"J-shaped\" increase in cardiovascular risks with DBP <85 mm Hg may apply under certain conditions.", "output": "The Hypertension Optimal Treatment (HOT) trial was specifically designed to determine the optimal target blood pressure for hypertensive patients: 18,790 men and women with DBP 100 to 115 mm Hg were randomly assigned to target DBP groups of <90, <85, or <80 mm Hg. All were treated with felodipine and other agents in a stepped-care protocol; average follow-up was 3.8 years. The lowest incidence of cardiovascular events occurred at a mean DBP of 82.6 mm Hg and fewest cardiovascular deaths at 86.5 mm Hg. Further reductions in DBP neither lowered nor increased cardiovascular risk." }, { "input": "Although lowering diastolic blood pressure (DBP) is associated with reduced cardiovascular events, systolic blood pressure (SBP) is a more robust predictor of cardiovascular risk than DBP and should now be used to diagnose, stage, and treat hypertension. Lowering diastolic blood pressure (DBP) to <90 mm Hg in hypertensive individuals of all ages decreases the risk of cardiovascular events including myocardial infarction (MI), heart failure, and sudden death. However, there is no consensus regarding how far to lower DBP. A \"J-shaped\" increase in cardiovascular risks with DBP <85 mm Hg may apply under certain conditions.", "output": "A meta-analysis of 7 randomized controlled trials involving 40,233 hypertensive patients used statistical modeling to determine the shape of the \"mortality curve\" over a range of DBP categories, defined in 10-mm Hg increments from 65 to 106. The subjects received mainly beta-blockers or thiazide diuretics; controls received placebo or no treatment. Both groups demonstrated increased risk for cardiovascular and all-cause death at the lowest DBP levels. Among treated patients, overall death rate was lowest with a DBP in the range of 76 to 85 mm Hg; among controls the nadir was 86 to 95 mm Hg." }, { "input": "Although lowering diastolic blood pressure (DBP) is associated with reduced cardiovascular events, systolic blood pressure (SBP) is a more robust predictor of cardiovascular risk than DBP and should now be used to diagnose, stage, and treat hypertension. Lowering diastolic blood pressure (DBP) to <90 mm Hg in hypertensive individuals of all ages decreases the risk of cardiovascular events including myocardial infarction (MI), heart failure, and sudden death. However, there is no consensus regarding how far to lower DBP. A \"J-shaped\" increase in cardiovascular risks with DBP <85 mm Hg may apply under certain conditions.", "output": "Farnett et al derived a summary curve from 13 studies that stratified cardiovascular outcomes by level of achieved blood pressure; the nadir of the curve for ischemic heart disease events occurred at 86 to 89 mm Hg DBP. The risk was independent of type of drug therapy, and more pronounced in study subjects with known cardiovascular disease." }, { "input": "Although lowering diastolic blood pressure (DBP) is associated with reduced cardiovascular events, systolic blood pressure (SBP) is a more robust predictor of cardiovascular risk than DBP and should now be used to diagnose, stage, and treat hypertension. Lowering diastolic blood pressure (DBP) to <90 mm Hg in hypertensive individuals of all ages decreases the risk of cardiovascular events including myocardial infarction (MI), heart failure, and sudden death. However, there is no consensus regarding how far to lower DBP. A \"J-shaped\" increase in cardiovascular risks with DBP <85 mm Hg may apply under certain conditions.", "output": "There is concern that lowering DBP too much may actually increase cardiovascular risk. A 10-year observational study showed that in patients with a history of ischemic heart disease, the incidence of fatal MI was lowest when DBP was between 85 to 90 mm Hg and increased with DBP <85 mm Hg, thus demonstrating a J-shaped curve." }, { "input": "Although lowering diastolic blood pressure (DBP) is associated with reduced cardiovascular events, systolic blood pressure (SBP) is a more robust predictor of cardiovascular risk than DBP and should now be used to diagnose, stage, and treat hypertension. Lowering diastolic blood pressure (DBP) to <90 mm Hg in hypertensive individuals of all ages decreases the risk of cardiovascular events including myocardial infarction (MI), heart failure, and sudden death. However, there is no consensus regarding how far to lower DBP. A \"J-shaped\" increase in cardiovascular risks with DBP <85 mm Hg may apply under certain conditions.", "output": "The concept of a continuous graded relationship between DBP and cardiovascular risk is supported by a meta-analysis of 14 randomized clinical trials showing that lowering DBP by 6 mm Hg reduced the risk of coronary heart disease by 14% (95% confidence interval [CI], 4%-22%; P<.01; NNT=200). Throughout the range of DBP in study subjects, 70-115 mm Hg, a lower DBP was associated with a lower risk of coronary heart disease." }, { "input": "HMG Co-A reductase inhibitors (statins) are effective for primary prevention of ischemic stroke in people who have a history of occlusive artery disease, coronary artery disease, or diabetes without history of cerebrovascular disease.", "output": "The Heart Protection Study showed no difference in the number of hemorrhagic strokes between treatment and placebo groups. There were 3500 subjects with pretreatment low-density lipoprotein (LDL) cholesterol <100 mg/dL; lowering LDL to 65 mg/dL reduced major vascular event risk by about 25%." }, { "input": "HMG Co-A reductase inhibitors (statins) are effective for primary prevention of ischemic stroke in people who have a history of occlusive artery disease, coronary artery disease, or diabetes without history of cerebrovascular disease.", "output": "The Heart Protection Study followed 20,536 patients in the United Kingdom (aged 40-80 years), 3280 with a history of cerebrovascular disease (defined as nondisabling stroke, transient cerebral ischemic attack, or carotid endarterectomy or angioplasty) and 17,256 with other occlusive arterial disease, coronary artery disease, or diabetes. Patients were randomized to receive either simvastatin 40 mg or placebo for an average of 5 years. The endpoint was major vascular events: myocardial infarction, stroke of any type, and revascularization procedure. Simvastatin reduced the combined risk of non-fatal or fatal ischemic stroke for patients with no history of cerebrovascular disease (3.2% for simvastatin vs 4.8% with placebo; relative risk reduction=33%, number needed to treat [NNT]=63; P=.0001)." }, { "input": "Statins reduce the risk of ischemic stroke in hypertensive patients with multiple cardiovascular risk factors and nonfasting total cholesterol <250 mg/dL.", "output": "The ASCOT-LLA study compared atorvastatin with placebo in 10,305 hypertensive Caucasian patients with multiple cardiovascular risk factors and a total nonfasting cholesterol of 250 mg/dL (6.5 mmol/L) or less. Patients were aged 40 to 79 years and had at least 3 other cardiovascular risk factors (left ventricular hypertrophy, abnormal electrocardiogram, type 2 diabetes, peripheral artery disease, stroke or transient ischemic attack, male sex, age >55 years, proteinuria or microalbuminuria, smoking, family history of premature coronary heart disease). The study was stopped early at a median of 3.3 years because atorvastatin significantly reduced cardiac events. Atorvastatin also significantly reduced ischemic strokes when compared with placebo (relative risk [RR]=0.73, 95% confidence interval [CI], 0.56-0.96; P=.024). This study did not differentiate between first or second stroke. The NNT was 155." }, { "input": "Statins also reduce the risk of ischemic stroke for patients with coronary disease or equivalents (such as diabetes or peripheral artery disease), including patients who have a normal fasting lipid profile.", "output": "The LIPID trial randomized 9014 patients with a history of acute coronary syndromes and total cholesterol of 150 to 270 mg/dL (4 to 7 mmol/L) to either pravastatin or placebo and followed them for 6 years. Among the 350 patients with prior ischemic stroke, there were 388 new ischemic stokes over the course of the study. When adjusted for risk factors (atrial fibrillation, history of cerebrovascular accident, diabetes, hypertension, cigarette smoking, body mass index, and male sex), pravastatin reduced recurrent ischemic stroke by 21% relative to placebo (P=.024). The reduction was not modified by baseline lipid level." }, { "input": "For patients with ischemic stroke who have coronary disease, statins prevent recurrent ischemic stroke; evidence is conflicting about whether this benefit is proportional to initial cholesterol levels.", "output": "A meta-analysis of 15 randomized placebo-controlled trials using various statins (32,684 participants) assessed the risk of strokes for patients with a history of coronary disease. Among patients who had cerebrovascular disease, statins significantly reduced recurrent ischemic stroke (RR=0.74; 95% CI, 0.64-0.86). One recurrence of ischemic stroke would be prevented for every 110 coronary disease patients treated with a statin. Achieving final total cholesterol <232 mg/dL correlated with reduced risk of recurrent stroke. Three of the studies evaluated primary prevention of stroke and did not show a significant risk reduction (RR=0.85; P=.4). Statins did not reduce the rate of hemorrhagic stroke or fatal strokes." }, { "input": "Statins do not prevent hemorrhagic stroke.", "output": "The Heart Protection Study showed no difference in the number of hemorrhagic strokes between treatment and placebo groups. There were 3500 subjects with pretreatment low-density lipoprotein (LDL) cholesterol <100 mg/dL; lowering LDL to 65 mg/dL reduced major vascular event risk by about 25%." }, { "input": "Statins do not prevent hemorrhagic stroke.", "output": "Statins did not reduce the rate of hemorrhagic stroke or fatal strokes." }, { "input": "Adjusted-dose warfarin (international normalized ratio [INR]=2.0-3.0) remains the most efficacious antithrombotic regimen for the primary and secondary prevention of cardioembolic stroke in high-risk patients with nonvalvular atrial fibrillation (NVAF).", "output": "Pengo et al randomized patients with NVAF aged >60 years to fixed-dose (1.25 mg/d) or adjusted-dose warfarin (INR=2.0-3.0) to evaluate ischemic stroke rates and major bleeding. This trial enrolled 303 patients who were followed up for 14.5 months before discontinuation of the trial. The rate of ischemic stroke was significantly higher in the fixed-dose warfarin group compared with the adjusted warfarin group (3.7% vs 0% per year; NNT=27). Major bleeds were more frequent in the adjusted warfarin group (2.6% vs 1% per year, number needed to harm=63). While the combined primary endpoint did not show a significant benefit for adjusted-dose warfarin, this study suggests that fixed-dose warfarin does not protect against ischemic stroke in NVAF patients." }, { "input": "Adjusted-dose warfarin (international normalized ratio [INR]=2.0-3.0) remains the most efficacious antithrombotic regimen for the primary and secondary prevention of cardioembolic stroke in high-risk patients with nonvalvular atrial fibrillation (NVAF).", "output": "The intensity of warfarin therapy and stroke severity has recently been studied for patients with NVAF. A subtherapeutic INR (<2.0) on the day of admission was independently associated with severe stroke (odds ratio=1.9; 95% confidence interval [CI], 1.1-3.4), and risk of death at 30 days (hazard ratio, 3.4; 95% CI, 1.1-10.1) compared with an INR of 2.0 or greater. Furthermore, an admission INR of 1.5-1.9 had a similar mortality rate (18%) as an INR of <1.5 (15%), and for those patients on aspirin (15%)." }, { "input": "Adjusted-dose warfarin (international normalized ratio [INR]=2.0-3.0) remains the most efficacious antithrombotic regimen for the primary and secondary prevention of cardioembolic stroke in high-risk patients with nonvalvular atrial fibrillation (NVAF).", "output": "The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study (AFASAK-2) completed 3 of the scheduled 6 years; it compared warfarin 1.25 mg/d, warfarin 1.25 mg/d plus aspirin 300 mg, aspirin 300 mg alone, and adjusted-dose warfarin (INR=2.0-3.0) to treat NVAF for patients with a median age of 74 years (range, 44-89). The cumulative stroke event rate after 1 year was 5.8% on fixed-dose warfarin, 7.2% on combination, 3.6% on aspirin, and 2.8% on adjusted-dose warfarin. The researchers concluded that while the difference was not statistically significant, adjusted-dose warfarin seemed superior to other treatments after 1 year." }, { "input": "Aspirin therapy at a dose of 75 to 325 mg reduces the risk of stroke to a lesser degree and may be useful for low-risk patients with NVAF or patients at high risk for bleeding.", "output": "The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study (AFASAK-2) completed 3 of the scheduled 6 years; it compared warfarin 1.25 mg/d, warfarin 1.25 mg/d plus aspirin 300 mg, aspirin 300 mg alone, and adjusted-dose warfarin (INR=2.0-3.0) to treat NVAF for patients with a median age of 74 years (range, 44-89). The cumulative stroke event rate after 1 year was 5.8% on fixed-dose warfarin, 7.2% on combination, 3.6% on aspirin, and 2.8% on adjusted-dose warfarin. The researchers concluded that while the difference was not statistically significant, adjusted-dose warfarin seemed superior to other treatments after 1 year." }, { "input": "Aspirin therapy at a dose of 75 to 325 mg reduces the risk of stroke to a lesser degree and may be useful for low-risk patients with NVAF or patients at high risk for bleeding.", "output": "The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study (AFASAK-2) completed 3 of the scheduled 6 years; it compared warfarin 1.25 mg/d, warfarin 1.25 mg/d plus aspirin 300 mg, aspirin 300 mg alone, and adjusted-dose warfarin (INR=2.0-3.0) to treat NVAF for patients with a median age of 74 years (range, 44-89). The cumulative stroke event rate after 1 year was 5.8% on fixed-dose warfarin, 7.2% on combination, 3.6% on aspirin, and 2.8% on adjusted-dose warfarin. The researchers concluded that while the difference was not statistically significant, adjusted-dose warfarin seemed superior to other treatments after 1 year." }, { "input": "Combination therapy with low, fixed-dose warfarin (1-2 mg) and aspirin has not been shown to be superior to aspirin therapy alone. Moreover, this combination appears to be inferior to adjusted-dose warfarin.", "output": "Pengo et al randomized patients with NVAF aged >60 years to fixed-dose (1.25 mg/d) or adjusted-dose warfarin (INR=2.0-3.0) to evaluate ischemic stroke rates and major bleeding. This trial enrolled 303 patients who were followed up for 14.5 months before discontinuation of the trial. The rate of ischemic stroke was significantly higher in the fixed-dose warfarin group compared with the adjusted warfarin group (3.7% vs 0% per year; NNT=27). Major bleeds were more frequent in the adjusted warfarin group (2.6% vs 1% per year, number needed to harm=63). While the combined primary endpoint did not show a significant benefit for adjusted-dose warfarin, this study suggests that fixed-dose warfarin does not protect against ischemic stroke in NVAF patients." }, { "input": "To date, no clinical trials have investigated the efficacy and safety of combining adjusted-dose warfarin and aspirin for the prevention of stroke from NVAF.", "output": "The SPAF III investigators further compared adjusted-dose warfarin with low-intensity, fixed-dose warfarin plus aspirin in high-risk patients with NVAF. An interim analysis at 1.1 years revealed superiority in the reduction of ischemic strokes and systemic embolisms with adjusted-dose warfarin 7.9% vs 1.9% per year, respectively; NNT=16, which led to the trial's termination. Rates of major hemorrhage did not differ between treatment groups 2.4% per year with combination vs 2.1% per year with warfarin." }, { "input": "other", "output": "Pooled analysis with more than 2900 patients revealed an annual stroke risk of 4.5% for control patients and 1.4% for patients receiving adjusted-dose warfarin (number needed to treat [NNT] for 1 year=32)." }, { "input": "other", "output": "Thromboprophylaxis with warfarin for patients with NVAF has been studied in 5 major clinical trials." }, { "input": "other", "output": "Combined data from the Atrial Fibrillation Aspirin Anticoagulation Study (AFASAK-1), the European Atrial Fibrillation Trial, and the Stroke Prevention in Atrial Fibrillation (SPAF) I studies revealed a small but statistically significant reduction in stroke rates (relative risk reduction [RRR]=21%; 8.1% vs 6.3% annual stroke rate; NNT=55), with no increase in major bleeding risk." }, { "input": "For proximal saphenous vein thrombosis, anticoagulation is more effective than venous ligation (with or without stripping) in preventing deep venous thrombosis (DVT) and pulmonary embolus (PE).", "output": "Since saphenous vein thrombosis above the knee is associated with DVT and PE, 1 systematic review looked at papers comparing anticoagulation (IV heparin followed by 6 weeks to 6 months of warfarin) with surgical ligation of the saphenous vein (either alone or combined with vein stripping or with vein stripping and perforator ligation). The review included primarily case series with widely varying protocols. According to the authors, the data \"suggests that medical management with anticoagulants is somewhat superior\" to surgery for preventing DVT and PE. However, the fewest extensions of SVTP occurred when vein ligation was combined with stripping of the thrombosed vein and interruption of perforators." }, { "input": "For patients with superficial venous thrombophlebitis (SVTP) distal to the saphenous vein of the thigh, tenoxicam (a nonsteroidal anti-inflammatory agent [NSAID]) and low-molecular-weight heparin are similarly effective for reducing extension and subsequent DVT when administered along with compression therapy.", "output": "In a recent trial, patients randomized to subcutaneous heparin at 12,500 units twice daily for a week followed by 10,000 units twice daily had fewer vascular complications of proximal saphenous vein thrombosis than those receiving heparin at 5000 units twice daily (6/30 in the low-dose group and 1/30 in the high-dose group; P<.05; number needed to treat [NNT]=6). There were no bleeding complications in either group." }, { "input": "For patients with superficial venous thrombophlebitis (SVTP) distal to the saphenous vein of the thigh, tenoxicam (a nonsteroidal anti-inflammatory agent [NSAID]) and low-molecular-weight heparin are similarly effective for reducing extension and subsequent DVT when administered along with compression therapy.", "output": "One large double-blind randomized controlled trial compared tenoxicam (an NSAID available in Canada, similar to piroxicam), enoxaparin (Lovenox), and placebo for 8 to 12 days in 427 patients with SVTP of the leg measuring 5 cm or more. Patients were also treated with compression hose. Patients who required immediate anticoagulation or venous ligation were excluded. Within 3 months, 35% of patients taking placebo developed an extension or recurrence of their SVTP or a DVT, compared with 16% to 17% of treated patients (NNT=6). There was no significant difference in outcome between subcutaneous enoxaparin at fixed (40 mg/d) or adjusted doses (1.5 mg/kg), or 20 mg/d oral tenoxicam." }, { "input": "For patients with superficial venous thrombophlebitis (SVTP) distal to the saphenous vein of the thigh, tenoxicam (a nonsteroidal anti-inflammatory agent [NSAID]) and low-molecular-weight heparin are similarly effective for reducing extension and subsequent DVT when administered along with compression therapy.", "output": "An underpowered double-blind trial of topical heparin, piroxicam gel, and placebo (22 to 24 patients in each treatment arm) failed to find efficacy with either therapy." }, { "input": "For patients with superficial venous thrombophlebitis (SVTP) distal to the saphenous vein of the thigh, tenoxicam (a nonsteroidal anti-inflammatory agent [NSAID]) and low-molecular-weight heparin are similarly effective for reducing extension and subsequent DVT when administered along with compression therapy.", "output": "In a small randomized trial (n=40), intramuscular defibrotide provided better symptom resolution than low-dose heparin for patients with uncomplicated SVTP of the leg." }, { "input": "For patients with superficial venous thrombophlebitis (SVTP) distal to the saphenous vein of the thigh, tenoxicam (a nonsteroidal anti-inflammatory agent [NSAID]) and low-molecular-weight heparin are similarly effective for reducing extension and subsequent DVT when administered along with compression therapy.", "output": "A double-blind trial of topical heparin showed it to be superior to placebo in reducing symptoms and speeding healing." }, { "input": "For patients with superficial venous thrombophlebitis (SVTP) distal to the saphenous vein of the thigh, tenoxicam (a nonsteroidal anti-inflammatory agent [NSAID]) and low-molecular-weight heparin are similarly effective for reducing extension and subsequent DVT when administered along with compression therapy.", "output": "A double-blind trial of topical heparin showed it to be superior to placebo in reducing symptoms and speeding healing. The study showed that (n=126), 44% of patients treated with 1000 IU/g heparin gel 3 times a day were symptom-free at 1 week, compared with 26% on placebo (NNT=6)." }, { "input": "Oral or topical NSAIDs, topical heparin, and topical nitroglycerin all alleviate symptoms and speed resolution of SVTP caused by infusion catheters.", "output": "For infusion-related SVTP, a randomized controlled trial of 120 patients found both oral and topical diclofenac effective in reducing symptoms (NNT=3), although oral diclofenac had significantly more gastrointestinal side effects (number needed to harm=3 for dyspepsia)." }, { "input": "Oral or topical NSAIDs, topical heparin, and topical nitroglycerin all alleviate symptoms and speed resolution of SVTP caused by infusion catheters.", "output": "A randomized trial of infusion-related SVTP (n=100) found that 2% nitroglycerin gel eliminated pain in 50 hours vs 72 hours with topical heparin (P<.05)." }, { "input": "Excision or ablation of the transformation zone are equally effective for treating an initial diagnosis of cervical intraepithelial neoplasia (CIN) grades 2 or 3 in women with a satisfactory colposcopy and no suggestion of microinvasive or invasive disease.", "output": "Consensus guidelines from the American Society for Colposcopy and Cervical Pathology ASCCP and a practice bulletin from the American College of Obstetricians and Gynecologists ACOG both recommend immediate removal of the entire transformation zone, with either ablative or excisional treatment as initial treatment of CIN 2 and 3 for patients who are not pregnant." }, { "input": "Excision or ablation of the transformation zone are equally effective for treating an initial diagnosis of cervical intraepithelial neoplasia (CIN) grades 2 or 3 in women with a satisfactory colposcopy and no suggestion of microinvasive or invasive disease.", "output": "All 7 available surgical techniques were found to have similar efficacy, in a 2005 Cochrane review of 28 randomized trials. Resolution of CIN 2 or 3 lesions was 77% to 98%, using knife cone biopsy, laser conization, loop excision, laser ablation, cryotherapy, or 2 techniques not used commonly in the US, cold coagulation and radical diathermy. Surgical techniques were tested in various combinations, but no trial compared all of the techniques with one another. Most studies were underpowered, limiting the results." }, { "input": "Excision or ablation of the transformation zone are equally effective for treating an initial diagnosis of cervical intraepithelial neoplasia (CIN) grades 2 or 3 in women with a satisfactory colposcopy and no suggestion of microinvasive or invasive disease.", "output": "The ASCCP guidelines note that there is a benefit to excisional treatment, as it allows pathologic assessment of the excised tissue. Some of the ASCCP guideline authors recommend excisional procedures for the management of large CIN 2 and 3 lesions, which are at increased risk of having microinvasive disease." }, { "input": "Laser or loop electrosurgical excision procedure (LEEP) are the preferred treatment methods for recurrent CIN 2 and CIN 3.", "output": "All 7 available surgical techniques were found to have similar efficacy, in a 2005 Cochrane review of 28 randomized trials. Resolution of CIN 2 or 3 lesions was 77% to 98%, using knife cone biopsy, laser conization, loop excision, laser ablation, cryotherapy, or 2 techniques not used commonly in the US, cold coagulation and radical diathermy. Surgical techniques were tested in various combinations, but no trial compared all of the techniques with one another. Most studies were underpowered, limiting the results.Morbidity was compared with one-on-one trials of different techniques. The review noted that LEEP has the least morbidity (such as hemorrhage, infection, cervical stenosis, and midtrimester pregnancy loss) while providing the most reliable histology by excising tissue without causing thermal artifact." }, { "input": "Laser or loop electrosurgical excision procedure (LEEP) are the preferred treatment methods for recurrent CIN 2 and CIN 3.", "output": "A systematic review of 21 controlled trials comparing treatments for CIN 2 or 3 found a similar efficacy of all the modalities, including cone biopsy, cryotherapy, laser ablation, and LEEP. However, it also found a trend toward a higher rate of significant hemorrhage among women who received cone biopsies compared with women who received either laser ablation or LEEP." }, { "input": "For women with an unsatisfactory colposcopy or suspicion of invasive disease, a diagnostic excisional procedure is recommended.", "output": "For women with unsatisfactory colposcopy and biopsy-proven CIN 2 or 3, there is up to a 7% risk for an occult invasive cervical carcinoma. Performing a diagnostic excisional procedure is recommended on these patients." }, { "input": "Observation or deferred treatment may be acceptable for CIN 2 in adolescents with satisfactory colposcopy and negative endocervical sampling.", "output": "For adolescent patients with biopsy-proven CIN 2, a recent ACOG Committee Opinion recommends close follow-up-with Pap smears or colposcopies every 4 to 6 months-due to the high rates of resolution of CIN 2 in adolescents." }, { "input": "Limit diagnostic excisional procedures in pregnancy to cases where suspicion of invasive cancer is high.", "output": "In pregnancy, follow CIN 2 and 3 with colposcopy each trimester, and reevaluate at 6 to 12 weeks postpartum. Limit any diagnostic excisional procedures to cases where you cannot rule out invasive cancer." }, { "input": "Limit diagnostic excisional procedures in pregnancy to cases where suspicion of invasive cancer is high.", "output": "For pregnant patients, diagnostic excisional procedures are associated with complications such as bleeding and preterm delivery, while there is minimal risk of CIN 2 or 3 progressing to invasive cervical cancer." }, { "input": "other", "output": "A meta-analysis of 27 controlled cohort studies found that cold knife conization and LEEP were associated with increased obstetrical risks, such as delivery at less than 37 weeks' gestation and a birth weight <2500 g. Any resection that was more than 10 mm deep increased the risk of prematurity with future pregnancies (pooled relative risk=2.6; 95%] CI, 1.3-5.3)." }, { "input": "Obtain a urine culture in all men with suspected urinary tract infection (UTI), to reliably diagnose an infection.", "output": "The usual organisms are colonic bacteria: Escherichia coli (75%), enterococci (20%), and, less commonly, Klebsiella and Proteus." }, { "input": "Obtain a urine culture in all men with suspected urinary tract infection (UTI), to reliably diagnose an infection.", "output": "A cohort of 66 men (mean age, 66\u00b113 years) presenting to a VA urology clinic for procedures, dysuria, or bacteriuria had urine samples taken while voiding, as well as directly from the bladder, either via suprapubic aspiration or urethral catheterization. Using bladder cultures as a gold standard, midstream urine culture had a specificity and sensitivity of >97% at a threshold of 1000 CFU/mL." }, { "input": "Obtain a urine culture in all men with suspected urinary tract infection (UTI), to reliably diagnose an infection.", "output": "A urine culture is recommended to reliably diagnose an infection and guide treatment." }, { "input": "For further evaluation, ultrasonography with abdominal radiography appears at least as accurate as an intravenous pyelogram (IVP) for detecting urinary tract abnormalities such as hydronephrosis, stones, or outlet obstruction.", "output": "Another study enrolled 114 men, 18 to 85 years of age, with proven UTIs, who underwent ultrasonography and plain radiography, as well as an IVP. (Only 100 had complete data at enrollment.) All men had urinary flow rates measured. The combination of a plain abdominal film and ultrasonography detected more abnormalities than an IVP. (The primary role of the plain film was in detecting urinary calculi.) Final \"clinical\" diagnoses were reported, but the study did not report a comparison of clinical and radiological findings. Almost half of the abnormalities were lower tract obstructions (bladder outlet obstruction, underactive detrusor, and chronic retention). There was no comment on the importance or treatment of any abnormalities found." }, { "input": "Imaging of the urinary tract is not supported by the literature, for low-risk males <45 years of age after their first UTI.", "output": "A small prospective study of 85 men, 18 to 86 years of age, with febrile UTI, concluded that routine imaging of the upper urinary tract was unnecessary, and that, if indicated, further workup should focus on the lower urinary tract. Abnormalities in this group were suggested by a history of voiding problems, hematuria, or recurrent infection. One limitation of this study was the incomplete urodynamic and endoscopic evaluation of the lower urinary tract." }, { "input": "other", "output": "The incidence in elderly men is high, often attributable to a bladder outflow obstruction. (For this review, the definition of UTI is limited to bacterial infections of the kidney, ureter, or bladder, and does not include urethritis, epididymitis, prostatitis, or orchitis.)" }, { "input": "other", "output": "The lifetime of UTI prevalence is about 14%." }, { "input": "other", "output": "Approximately 20% of all UTIs occur in men." }, { "input": "other", "output": "A very small prospective study of 29 heterosexual, circumcised men 16 to 45 years old (those who were sexually active had a steady partner) who were hospitalized with a first febrile UTI failed to find any significant structural or functional urinary tract abnormalities." }, { "input": "Although antibiotics are the best initial treatment, surgical intervention is warranted when a child has: visual impairment, complete ophthalmoplegia, or well-defined abscess on presentation, or no clearly apparent clinical improvement by 24 hours.", "output": "No statistically significant long-term difference in subperiosteal abscesses (as a complication of orbital cellulitis) was found in a retrospective study comparing medical to surgical management." }, { "input": "Although antibiotics are the best initial treatment, surgical intervention is warranted when a child has: visual impairment, complete ophthalmoplegia, or well-defined abscess on presentation, or no clearly apparent clinical improvement by 24 hours.", "output": "In a prospective study to evaluate medical management (n=23), 87% of patients responded to intravenous antibiotics." }, { "input": "Although antibiotics are the best initial treatment, surgical intervention is warranted when a child has: visual impairment, complete ophthalmoplegia, or well-defined abscess on presentation, or no clearly apparent clinical improvement by 24 hours.", "output": "A small case series (n=9) found 21 children admitted to hospital for preseptal cellulitis, of whom 4 later were diagnosed with orbital cellulitis. There was a total of 9 cases of orbital cellulitis; however, only 1 required operative management of orbital cellulitis." }, { "input": "Target antimicrobial therapy toward the common pathogens associated with predisposing factors for orbital cellulitis, such as sinusitis-and pay attention to local resistance patterns.", "output": "A retrospective case series of 94 patients of all ages in China implicated Staphylococcus aureus and streptococcal species based on cultures taken from eye purulence and abscesses." }, { "input": "Target antimicrobial therapy toward the common pathogens associated with predisposing factors for orbital cellulitis, such as sinusitis-and pay attention to local resistance patterns.", "output": "A retrospective case series from Vanderbilt (n=80) found streptococci as the most common cause, based on blood and wound cultures in the Hib vaccination era; however, only 12 wounds returned positive cultures." }, { "input": "The GAD-7 has the best evidence and utility in the primary care setting for generalized anxiety disorder.", "output": "The QPD has similar likelihood ratios to the GAD-7, but it requires purchase of proprietary software, and the supporting evidence is based on a small, selected, and compensated study group." }, { "input": "The GAD-7 has the best evidence and utility in the primary care setting for generalized anxiety disorder.", "output": "The Anxiety Screening Questionnaire (ASQ-15) also has good likelihood ratios, but the sample population was small, selected, and over half of the subjects were from a psychiatric practice." }, { "input": "The GAD-7 has the best evidence and utility in the primary care setting for generalized anxiety disorder.", "output": "For diagnosing generalized anxiety disorder, the GAD-7 has the best evidence for its utility. It was studied in a large, primary care-based sample size, is brief, and is in the public domain. It has a positive likelihood ratio of 4.9 (ie, the odds that a person has generalized anxiety disorder are 4.9 times higher if the GAD-7 is positive)." }, { "input": "While the proprietary Quick PsychoDiagnostics Panel (QPD) has the best operating characteristics for panic disorder.", "output": "The QPD reports an excellent positive likelihood ratio and good negative likelihood ratio for panic disorder. As mentioned above, these results are limited by the quality of its sample size and the expense." }, { "input": "While the proprietary Quick PsychoDiagnostics Panel (QPD) has the best operating characteristics for panic disorder.", "output": "The MHI-5 screens for panic disorder with a single item taken from a larger questionnaire for panic disorder and depression. It has 100% sensitivity but a poor positive likelihood ratio. The sample size was very small-only 9 persons with panic disorder were tested." }, { "input": "While the proprietary Quick PsychoDiagnostics Panel (QPD) has the best operating characteristics for panic disorder.", "output": "The PDSR shows 100% specificity at the recommended cut-off point and a good negative likelihood ratio. Its weaknesses are a small study size, the homogeneity of the study population, who were self-selected, as well as the lengthiness of the questionnaire." }, { "input": "No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months.", "output": "Self-perceived menopausal status is moderately to highly sensitive, but the range of specificity estimates are wide. The LR+and LR-for FSH, which are of midhigh magnitude, would suggest it to be the best single diagnostic test." }, { "input": "No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months.", "output": "Typical symptoms of hot flashes, night sweats, and vaginal dryness are about as specific as laboratory tests, but are generally less sensitive." }, { "input": "No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months.", "output": "A woman's global perception of being perimenopausal can also be useful for \"rulingin\" transition to menopause within the next several years (sensitivity=0.18; specificity=1; LR+=\u221e LR-=0.82)." }, { "input": "No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months.", "output": "Change in the amount of flow is more sensitive but less specific (sensitivity=0.81; specificity=0.30; LR+=1.15; LR-=0.65)." }, { "input": "No single test for menopause is highly sensitive and specific. The best predictors that a woman will enter menopause within 4 years include age at least 50 years, amenorrhea for 3 to 11 months, and menstrual cycle irregularity within 12 months.", "output": "Several studies followed women longitudinally and found the characteristics that best predicted actual transition to menopause within 4 years were amenorrhea of between 3 and 12 months duration (sensitivity=0.16-0.32; specificity=0.98-1.0; positive likelihood ratio [LR+]=14.4-\u221e negative likelihood ratio [LR-]=0.69-0.84), cycle irregularity within 12 months (sensitivity=0.65-0.66; specificity=0.77-0.85; LR+=2.84-4.17; LR-=0.42-0.84), and age\u226550 years (sensitivity=0.35; specificity=0.98; LR+=15.4; LR-=0.66)." }, { "input": "For diagnosing perimenopause, the level of follicle-stimulating hormone (FSH) is most useful for clinical situations in which the pretest probability, as based on history, is midrange.", "output": "FSH levels are highly varied within individuals during perimenopause; and further variation due to body-mass index and ethnicity make defining diagnostic thresholds difficult." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "The best-designed studies also evaluated dietary composition with regard to key types of fat (saturated, mono- and poly-unsaturated; animal vs vegetable vs marine) and found no significant differences based on type of fat consumed." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "The meta-analysis performed by Boyd et al did find a statistically significant difference, with relative risks ranging from 1.11 for overall to 1.19 for high-saturated-fat diets. The upper limit of all confidence intervals was no higher than 1.35, however, suggesting a lack of clinical significance." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "Since the late 1990s, several meta-analyses, a systematic review of these cohort studies, and the Women's Health Initiative Randomized Controlled Diet Initiative have largely concluded that there is no difference in breast cancer incidence between women with a low-fat diet (<20% of total calories from fat) and women with average or high-fat diets (>40% total calories from fat)." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "The findings have been somewhat contradictory, with some studies showing statistically significant associations toward increased risk with higher fat intake." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "Since the late 1970s, 7 large, well-designed prospective cohort studies have examined the possible relationship between dietary fat and breast cancer." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "Case-control studies have shown some minimally increased risk related to dietary fat consumption, but there is concern about recall bias in these studies." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "Early studies evaluating national average dietary fat intake and breast cancer incidence rates showed an almost linear relationship between increased dietary fat and increased breast cancer incidence. However, increased fat intake occurs primarily in industrialized nations, providing multiple possible confounders for increased rates of breast cancer, such as pollutants and increased consumption of preservatives, pesticides, and other chemicals." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "Recently, a nested study within the Women's Intervention Nutrition Study did show that women with breast cancer who decreased their fat intake to a median of 33 g/day had a hazard ratio of 0.76 for relapse over 60 months (compared with controls who ate a median of 51 g/day)." }, { "input": "No. Studies show no evidence that reducing dietary fat decreases a woman's risk of developing postmenopausal breast cancer within the subsequent 14 years. Overall, evidence is insufficient to recommend for or against reduction in dietary fat to reduce risk of breast cancer for women, although recommendations for prudent fat intake may be justified on other grounds.", "output": "Preliminary evidence indicates that lowering dietary fat consumption may help with secondary prevention of breast cancer, but no large studies have been performed to date." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "No published study has demonstrated clinically significant advantages for oral contraceptive therapy in women with secondary amenorrhea. These women should take adequate calcium and vitamin D. Bisphosphonates are not appropriate for women of reproductive age, because of their potential teratogenicity." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "An open-label study that did examine bone mineral density (BMD) in women with hypothalamic amenorrhea before and after 13 cycles of oral contraceptives found a significant increase in BMD in the spine, but not at the hip." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "Bone loss in amenorrheic athletes may have long-term consequences, even if amenorrhea is only temporary. Some theoretical and disease-based research suggests a possible role for oral contraceptives to prevent bone loss in pre- and postmenopausal women, but little research has investigated younger women with hypothalamic amenorrhea." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "A 2002 review similarly recommends 1 rest day per week, increasing caloric intake by 200 to 300 Kcal/d, and increasing intake of calcium, B vitamins, iron, and zinc." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "A 1999 study in the International Journal of Sport Nutrition found that chronic energy deficit in amenorrheic athletes (N=4) could be reversed in a 20-week program using a sport nutrition supplement, 1 rest day per week, and a dietician to help with food selection." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "After ruling it out, the clinician may choose to exclude other causes of secondary amenorrhea before presuming a diagnosis of hypothalamic amenorrhea. Useful tests include: serum prolactin to rule out prolactinoma, follicle-stimulating hormone to rule out premature ovarian failure and thyroid-stimulating hormone to evaluate for thyroid problems. If all these tests are negative, consider a progesterone challenge test." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "Little evidence and no specific guidelines exist to guide the clinician in evaluating and managing exercise-induced amenorrhea. All athletes with amenorrhea should have a pregnancy test, because pregnancy is the most common cause of secondary amenorrhea." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "The potential negative sequelae of amenorrhea are best prevented with measures that restore physiologic menses. For exercise-induced hypothalamic bone loss, the AAP recommends decreased exercise, increased caloric intake, or both." }, { "input": "Ruling out secondary causes of amenorrhea is, of course, the first step. Once that's done, you can make a presumptive diagnosis of hypothalamic amenorrhea and advise the patient to increase caloric intake or decrease energy expenditure to promote the return of normal menses.", "output": "The Committee on Sports Medicine and Fitness of the American Academy of Pediatrics AAP encourages exercise to help maintain lean body mass and protect against obesity, diabetes, hypertension, and cardiovascular disease. Athletes with amenorrhea, however, may be at risk for sequelae such as osteopenia, fractures, and dyslipidemia. Amenorrhea during adolescence may inhibit the accretion of BMD, and the lost density may not be re-gained. Amenorrheic athletes are also at risk for the \"female athlete triad\"-disordered eating, amenorrhea, and osteoporosis." }, { "input": "A simple repositioning maneuver, such as the Epley maneuver, performed by an experienced clinician, can provide symptom relief from benign paroxysmal positional vertigo (BPPV) lasting at least 1 month.", "output": "Pooled data yielded odds ratios in favor of treatment for both objective testing (OR=5.67; 95% confidence interval [CI], 2.21-14.56) and symptom resolution (OR=4.92; 95% CI, 1.84-13.16), with no adverse outcomes reported." }, { "input": "A simple repositioning maneuver, such as the Epley maneuver, performed by an experienced clinician, can provide symptom relief from benign paroxysmal positional vertigo (BPPV) lasting at least 1 month.", "output": "Two trials compared the Epley maneuver with a sham procedure among 86 patients referred to specialty care. Outcomes included conversion of the Dix-Hallpike test from positive to negative, as well as resolution of symptoms by patient report. Assessment occurred 1-4 weeks following the intervention in the 2 trials." }, { "input": "A simple repositioning maneuver, such as the Epley maneuver, performed by an experienced clinician, can provide symptom relief from benign paroxysmal positional vertigo (BPPV) lasting at least 1 month.", "output": "The most widely studied treatments for BPPV are the single-treatment repositioning techniques, such as the Epley maneuver." }, { "input": "Medical therapy with benzodiazepines for vestibular suppression provides no proven benefit for BPPV.", "output": "Lorazepam and diazepam had no effect in 1 small randomized controlled trial. In this study, 25 BPPV patients from specialty clinics were randomized to placebo, diazepam 5 mg, or lorazepam 1 mg 3 times daily for 4 weeks. Patients reported dizziness on a 10-point scale at baseline and after 4 weeks of therapy. Nystagmus severity was also assessed using a 10-point scale at baseline and within 2 days following completion of treatment. The authors found no significant difference between the treatment and placebo arms; however, the study may have been underpowered to detect a clinically significant difference." }, { "input": "For undifferentiated dizziness, vestibular rehabilitation may provide symptomatic relief.", "output": "In a trial of vestibular rehabilitation for prolonged, undifferentiated dizziness, patients were randomized to usual care (n=76) or treatment with two 30-minute home education sessions at baseline and 6 weeks (n=67). A nurse, who had received 2 weeks of training, led the sessions, which included basic education on the vestibular system, causes of dizziness, and the rationale for exercise therapy. The nurse then taught the patients 8 sets of standard head and body movements to be performed twice daily. At 6 months, 69% of the treatment group vs 37% of the control group reported subjective improvement (OR=3.8 at 6 months; 95% CI, 1.6-8.7)." }, { "input": "other", "output": "A Cochrane review of treatments for BPPV yielded 11 trials, of which 9 were excluded due to a high risk of bias." }, { "input": "other", "output": "BPPV is characterized by brief, self-limited episodes of vertigo, provoked by typical position changes. This condition may result from free-floating debris in the endolymph of the posterior semicircular canal. This debris moves with position change, causing an abnormal perception of movement and classic symptoms of vertigo. Dix-Hallpike testing aids in the diagnosis, but treatment is often prescribed empirically." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Tricyclic antidepressants may cause anticholinergic side effects, worsen chronic heart failure, and cause ortho-static hypotension and falls. Although tra-zodone is not a tricyclic antidepressant, it can cause dry mouth, orthostatic hypotension, and (rarely) priapism." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Tolerance to the effects of chloral hydrate develops after only 2 weeks of use, and drug interactions with warfarin can occur." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Chloral hydrate has a narrow therapeutic index and is not recommended for the treatment of insomnia." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Although benzodiazepines increase sleep time and efficiency, patients quickly develop tolerance to the hypnotic effects. Additional problems associated with benzodiazepines include dependence, rebound insomnia, residual sedation, falls, hip fractures, and detrimental effects on sleep architecture." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Benzodiazepines have been used since the 1960s for their hypnotic, anxiolytic, anticonvulsant, muscle-relaxing, and amnesic properties. A recent meta-analysis showed that benzodiazepines improve sleep latency by only 4.2 minutes compared with placebo." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Antidepressants with sedative effects, such as tricyclic antidepressants and trazodone, have been used for insomnia, but minimal data support the efficacy or safety of this approach. Tricyclic antidepressants may exacerbate restless legs syndrome and periodic limb movement disorder." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "The safety and efficacy of melatonin and valerian is not regulated by the FDA." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Melatonin and valerian are \"natural\" hypnotics that are available without a prescription." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Most over-the-counter sleep aids contain diphen-hydramine, a long-acting antihistamine that is considered less effective than benzodiazepines. The anticholinergic properties of antihistamines can result in cognitive changes and urinary retention in the elderly" }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "But zolpidem increased risk of hip fracture in a case control study (adjusted odds ratio=1.95, 95% confidence interval, 1.09-3.51)." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Tolerance, withdrawal symptoms, or rebound insomnia occur less frequently than with benzodi-azepines." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Comparative studies in the elderly have demonstrated that zaleplon is more effective than placebo at decreasing sleep latency and improving sleep quality." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Comparative studies in the elderly have demonstrated that zolpidem is as effective as triazolam." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "They have been shown to decrease sleep latency, increase total sleep time, and increase sleep efficiency without disturbing sleep architecture or adversely affecting memory." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Due to their rapid absorption and short half-lives, they are particularly helpful for patients who have trouble falling asleep." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Zolpidem and zaleplon differ structurally from benzodiazepines but act at the benzodiazepine receptor." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Efficacy of intermittent use of zolpidem has been demonstrated in clinical studies, a practice that could potentially decrease risk of side effects." }, { "input": "Short-acting hypnotics such as zolpidem (Ambien) or zaleplon (Sonata) are the preferred hypnotics in the elderly because of an improved side-effect profile compared with traditional hypnotics such as benzodiazepines. Zolpidem and zaleplon have a quick onset and short duration of action, making them less likely to cause residual sedation, cognitive changes, and falls than benzodiazepines. More comparative clinical trials in the elderly are needed to determine if zolpidem and zaleplon are truly safer than benzodiazepines in this population. Hypnotics should be prescribed on a short-term, intermittent basis as part of a comprehensive treatment plan that addresses any underlying causes of poor sleep.", "output": "Side effects of zolpidem and zaleplon are considered dose-related, and a lower dose of 5 mg is recommended for older patients." }, { "input": "If statins (HMG-CoA reductase inhibitors) cause myopathy, the risk is very low.", "output": "Postmarket voluntary clinician reports point to statin myopathy in this and other countries." }, { "input": "If statins (HMG-CoA reductase inhibitors) cause myopathy, the risk is very low.", "output": "A small study of 21 patients on statins with muscle symptoms but normal creatine kinases described 4 patients who were able to distinguish statins from placebo, with objective reversible weakness and abnormal muscle biopsies." }, { "input": "If statins (HMG-CoA reductase inhibitors) cause myopathy, the risk is very low.", "output": "A large cohort study revealed a very small but statistically significant increased risk of myopathy in patients taking statins (number needed to harm=10,000/year). A large well-done British epidemiologic cohort study (n=96,193) found an increased rate of myopathy (broadly defined, not requiring creatine kinase elevation) among patients taking statins, with an absolute rate difference of 1 per 10,000 person-years." }, { "input": "If statins (HMG-CoA reductase inhibitors) cause myopathy, the risk is very low.", "output": "A pooled analysis of randomized controlled trials found similar myopathy rates in patients taking statins and placebo. Summarized myopathy data from 30 statin trials analyzed in a recent systematic review, shows similar myopathy rates in statin and placebo patients. There may be a lower myopathy rate in these trials than in routine clinical practice because of stricter exclusion criteria and more intense monitoring." }, { "input": "If statins (HMG-CoA reductase inhibitors) cause myopathy, the risk is very low.", "output": "Though some assert differential myopathy rates among statins based on cell research, case reports, or differences in metabolic clearance, no studies directly compare clinical myopathy rates among statins. There is no good evidence of a differential myopathy risk among statins currently available in the US." }, { "input": "If statins (HMG-CoA reductase inhibitors) cause myopathy, the risk is very low.", "output": "There is little evidence that statins cause myopathy. Synthesis is difficult because definitions of myopathy types differ among investigators. Proposed clinical syndrome definitions are myalgia (muscle weakness or ache with normal creatine kinase), myositis (symptoms with increased creatine kinase), and rhabdomyolysis (symptoms, markedly elevated creatine kinase, and renal insufficiency) as subsets of the more general term myopathy." }, { "input": "Case reports suggest a myopathy risk for all statins, including fatal rhabdomyolysis. Risk of myopathy may increase with higher statin doses, certain comorbid states (eg, hypothyroidism, renal insufficiency [especially with diabetes], recent trauma, perioperative periods, advanced age, small body frame) and concurrent medications, including fibrates, cyclosporine, azole antifungals, and macrolide antibiotics.", "output": "Certain comorbid states such as hypothyroidism, renal insufficiency (especially in patients with diabetes), recent trauma, and perioperative periods, as well as advanced age, small body frame, and multiple medications may increase statin myopathy risk." }, { "input": "Case reports suggest a myopathy risk for all statins, including fatal rhabdomyolysis. Risk of myopathy may increase with higher statin doses, certain comorbid states (eg, hypothyroidism, renal insufficiency [especially with diabetes], recent trauma, perioperative periods, advanced age, small body frame) and concurrent medications, including fibrates, cyclosporine, azole antifungals, and macrolide antibiotics.", "output": "Postmarket voluntary clinician reports include 3339 rhabdomyolysis FDA reports (1990 to March 2002)." }, { "input": "Case reports suggest a myopathy risk for all statins, including fatal rhabdomyolysis. Risk of myopathy may increase with higher statin doses, certain comorbid states (eg, hypothyroidism, renal insufficiency [especially with diabetes], recent trauma, perioperative periods, advanced age, small body frame) and concurrent medications, including fibrates, cyclosporine, azole antifungals, and macrolide antibiotics.", "output": "Case studies suggest an increased myopathy risk when statins are given with various medications, including fibrates, cyclosporine, azole antifungals, warfarin, nefazodone, and macrolide antibiotics." }, { "input": "Case reports suggest a myopathy risk for all statins, including fatal rhabdomyolysis. Risk of myopathy may increase with higher statin doses, certain comorbid states (eg, hypothyroidism, renal insufficiency [especially with diabetes], recent trauma, perioperative periods, advanced age, small body frame) and concurrent medications, including fibrates, cyclosporine, azole antifungals, and macrolide antibiotics.", "output": "Cerivastatin was withdrawn from the US market because of a fatal rhabdomyolysis rate 16 to 80 times higher than other statins based on FDA reports using a denominator of prescription volume (3.16 fatal cases/million prescriptions vs 0.15 for the statin class as a whole)." }, { "input": "Case reports suggest a myopathy risk for all statins, including fatal rhabdomyolysis. Risk of myopathy may increase with higher statin doses, certain comorbid states (eg, hypothyroidism, renal insufficiency [especially with diabetes], recent trauma, perioperative periods, advanced age, small body frame) and concurrent medications, including fibrates, cyclosporine, azole antifungals, and macrolide antibiotics.", "output": "Pravastatin and fluvastatin, which are not metabolized by the P450 CYP3A4 pathway, may be safer to use because of fewer drug interactions." }, { "input": "Case reports suggest a myopathy risk for all statins, including fatal rhabdomyolysis. Risk of myopathy may increase with higher statin doses, certain comorbid states (eg, hypothyroidism, renal insufficiency [especially with diabetes], recent trauma, perioperative periods, advanced age, small body frame) and concurrent medications, including fibrates, cyclosporine, azole antifungals, and macrolide antibiotics.", "output": "A tabular analysis of 74 published case reports of statin-associated rhabdomyolysis from a MEDLINE search covering 1985 to 2000 reported that in most cases the statin was safely restarted after stopping presumed interactive drugs (exact numbers not reported)." }, { "input": "No studies have directly compared myopathy rates among statins, and there is no good evidence to suggest any differences. No controlled study has directly examined statin rechallenge in patients with previous myopathy; however, case reports and expert opinion support this practice.", "output": "It is unknown whether previous myopathy, however defined, increases the risk of future myopathy with statin rechallenge. A tabular analysis of 74 published case reports of statin-associated rhabdomyolysis from a MEDLINE search covering 1985 to 2000 reported that in most cases the statin was safely restarted after stopping presumed interactive drugs (exact numbers not reported)." }, { "input": "other", "output": "The EXCEL trial (n=8245) of various lovastatin dosages included routine creatine kinase tests every 6 weeks for 48 weeks. Five lovastatin patients had muscle symptoms with creatine kinases >10 times the upper limits of normal, and in the 2 who continued treatment, symptoms and creatine kinase became normal. Of note, creatine kinase elevation of any kind at least once during 48 weeks occurred in 28.9% of placebo patients, arguing against routine creatine kinase screening in statin patients." }, { "input": "other", "output": "In the AFCAPS/TexCAPS trial, 20 of 21 statin patients (out of a study population of 3304) who had elevated creatine kinase (>10 times the upper limits of normal) recovered with continued lovastatin treatment, while the other patient resumed treatment after a brief interruption without further elevations." }, { "input": "Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months.", "output": "Other potential adverse reactions include transient hyperglycemia, sodium retention, nausea, vomiting, and insomnia." }, { "input": "Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months.", "output": "A study reported that 3 patients experienced adverse acute onset of diabetes mellitus, and peritonsillar cellulitis." }, { "input": "Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months.", "output": "A study reported that 3 patients experienced adverse events, including dehydration and severe pharyngitis." }, { "input": "Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months.", "output": "A study of a 6-day prednisone taper found no difference in resolution of symptoms in the prednisone group (N=47)." }, { "input": "Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months.", "output": "A trial of combined therapy with acyclovir and prednisolone in 94 patients found no differences in resolution of sore throat, weight loss, and absence from school or work in the treatment group." }, { "input": "Generally, no. Studies of steroids to treat infectious mononucleosis have found no significant effect on the clinical course of the illness at 1 to 3 months.", "output": "In an RCT of 40 patients, 1 dose of dexamethasone reduced throat pain at 12 hours in 60% of the treatment group, compared with placebo. However, no significant differences were noted at 1 and 7 days." }, { "input": "Although steroids have been shown to improve resolution of hematologic abnormalities, fever, and white blood cell count, and may shorten length of infirmary stay.", "output": "One small, double-blind study of prednisone (N=26 hospitalized college students) showed a significant difference in duration of fever and antibody titers compared with aspirin." }, { "input": "Although steroids have been shown to improve resolution of hematologic abnormalities, fever, and white blood cell count, and may shorten length of infirmary stay.", "output": "Two studies of the duration of fever didn't find convincing evidence of benefit, however." }, { "input": "Although steroids have been shown to improve resolution of hematologic abnormalities, fever, and white blood cell count, and may shorten length of infirmary stay.", "output": "One of these studies did find that patients' infirmary stays were shortened an average of 3 days, although the data to support this finding were not reported." }, { "input": "No significant difference was found in resolution of symptoms with or without steroids.", "output": "A Cochrane review of 6 relatively small (N=24-94) RCTs found insufficient evidence to support using steroids to manage infectious mononucleosis." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Notably, 50% of men in their 80s have testosterone levels in the hypogonadal range (<300 ng/dL), compared with 12% of men <50 years." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "A chart review study of nursing home residents found that 66% of men with hip fractures and 20% of men with vertebral fractures had low testosterone." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Because chronic hypogonadism leads to low bone density and increased risk of fracture, baseline bone densitometry may be prudent." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "In a series of 3 studies, 30% (26 of 89) of men with hemochromatosis had hypogonadism. The prevalence of hemochromatosis in males with hypogonadism hasn't been reported." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Men with very low testosterone levels (<150 ng/dL) or signs and symptoms suggesting pituitary pathology warrant pituitary imaging and measurement of thyroxine, cortisol, and prolactin levels." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Assessment of low testosterone should distinguish between pre- and postpubertal males. In prepubertal males, chromosomal analysis is indicated because hypothalamic-pituitary-gonadal axis defects are common-especially Klinefelter syndrome (1 in 500 males)." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "In some cases-including patients with obesity, type 2 diabetes, or hypothyroidism-the total testosterone level can be misleading; tests for free testosterone and sex hormone-binding globulin levels should be ordered. These tests can also help evaluate men with low-normal total testosterone levels (200-400 ng/dL)." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Serum testosterone measurements are considered the initial test of choice be-cause they're reliable, inexpensive, and widely available. Testosterone levels vary from hour to hour and diurnally, so a repeat morning measurement is recommended to confirm subnormal levels." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "A focused, cost-effective work-up will become ever more critical because an estimated 19% of men will be 65 years or older by 2050." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Many cases result from partial androgen deficiency in the aging male, because testosterone levels decline an estimated 1% to 2% per year in adult men." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Hypogonadism is a common endocrinologic disorder in men. Advancing age, increased life expectancy, and a rising prevalence of obesity and type 2 diabetes may increase the occurrence of hypogonadism." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Order biopsy or ultrasound examination of testicular masses and iron studies if hemochromatosis is suspected. Hemochromatosis is the most common single gene disorder of Caucasian Americans (1 in 250-300 are homozygous; 1 in 10 are heterozygous) and is associated with hypogonadotrophic hypogonadism." }, { "input": "Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture.", "output": "Both pre- and postpubertal males with low testosterone should have FSH, LH, and prolactin levels tested to differentiate primary from secondary hypogonadism." }, { "input": "The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin.", "output": "The American Diabetes Association and the American Association of Clinical Endocrinologists do not recommend one class of antidiabetic medication over another." }, { "input": "The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin.", "output": "Thiazolidinediones are not generally considered for first-line therapy." }, { "input": "The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin.", "output": "Patients with New York Heart Association class III or IV heart failure should not use thiazolidinediones. In addition, thiazolidinediones cost considerably more than sulfonylureas and metformin." }, { "input": "The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin.", "output": "Both of the thiazolidinediones are indicated for monotherapy and in combination with a sulfonylurea and metformin. However, only pioglitazone is indicated in combination with insulin. They are highly metabolized by the liver and should not be used in patients with liver enzymes greater than 2.5 times the upper limit of normal. Routine liver monitoring is recommended at baseline, every 2 months for the first year, and then periodically thereafter." }, { "input": "The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin.", "output": "To date, there have been reports of pulmonary edema and hepatotoxicity associated with the use of rosiglitazone. In all cases, rosiglitazone was found to be a possible, not a definite, cause." }, { "input": "The thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are effective at lowering fasting plasma glucose (FPG) and glycosylated hemoglobin (Hb A1c) in patients with type 2 diabetes when used either as monotherapy or in combination with sulfonylureas, metformin, or insulin. The glucose-lowering effects appear comparable with those of sulfonylureas and metformin alone. Currently, there are no randomized trials directly comparing patient-oriented outcomes of the thiazolidinediones with those of sulfonylureas and metformin.", "output": "Pioglitazone has consistently been shown to decrease triglycerides and increase high-density lipoprotein and rosiglitazone increases total cholesterol, HDL, and low-density lipoprotein. The clinical significance of these effects has not been established. Both medications are generally well tolerated but have the potential to cause edema and mildly decrease hemoglobin and hematocrit." }, { "input": "The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design.", "output": "Another prospective study of 208 patients found that 35% to 44% of patients had recurrence of pain within 6 months of their first episode, and 50% to 59% had a recurrence in 22 months of follow-up." }, { "input": "The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design.", "output": "In one prospective cohort study of 443 patients with low back pain, 75% had a recurrence with a mean of 2 relapses in 1 year of follow-up, but only 228 patients completed the study." }, { "input": "The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design.", "output": "A larger study involved 1555 patients during a 6-month follow up after an episode of acute low back pain. The article reports a mean of 16 days to functional recovery, although only 69% of the patients considered themselves \"completely recovered\" at 6 months." }, { "input": "The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design.", "output": "A prospective study found that 94% of patients evaluated for a new episode of low back pain were no longer visiting their physician for treatment after 3 months. However, this was not an adequate measure of resolution of pain. Only 21% (39/188) were pain free at 3 months and only 25% (42/170) were pain free at 12 months." }, { "input": "The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design.", "output": "One prospective series in a primary care setting found that 90% of patients were without pain 2 weeks after initial evaluation by their physician. This study had a 3-month follow-up period for 103 patients presenting with pain of less than 72 hours' duration." }, { "input": "The proportion of patients who are pain free or completely recovered after an acute episode of low back pain within 2 weeks to 6 months ranges from 21% to 90%, depending on the population studied and the method of measuring outcomes. The reported recurrence rates are also variable, from a low of 35% to a high of 75%, again depending on the length of follow-up and the study design.", "output": "It has been widely stated that 80% to 90% of attacks of acute low back pain resolve within approximately 6 weeks, though there is little evidence to support this claim." }, { "input": "The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient's risk is high, moderate, or low. Medication indications.", "output": "Clofibrate is no longer used because of an unexplained increase in deaths in the WHO Cooperative Trial." }, { "input": "The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient's risk is high, moderate, or low. Medication indications.", "output": "Subsequent analysis suggests that patients with a high LDL-C/HDL-C ratio (> 5) plus hypertriglyceridemia ( 205 mg/dL) benefited the most." }, { "input": "The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient's risk is high, moderate, or low. Medication indications.", "output": "Results of studies of the fibric acid derivatives are mixed. Subjects taking gemfibrozil 1200 mg per day in the 5-year Helsinki Heart Study had fewer coronary events compared with those taking a placebo (NNT = 71)." }, { "input": "The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient's risk is high, moderate, or low. Medication indications.", "output": "The 7-year Lipid Research Clinics Coronary Prevention Trial (LRC-CPPT) documented a reduction in CHD death and/or nonfatal MI (NNT = 59) with a 12.6% reduction in LDL-C with the use of cholestyramine, a bile acid resin, 24 g per day." }, { "input": "The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient's risk is high, moderate, or low. Medication indications.", "output": "Lovastatin reduced the risk of a first major acute coronary event (NNT = 24) in the 5-year AFCAPS/TexCAPS trial that enrolled 5608 men and 997 women with below-average high-density lipoprotein cholesterol (HDL-C) (men, 36 mg/dL; women, 40 mg/dL) without signs or symptoms of CHD. LDL-C was lowered 25% (from a mean of 156 to 115 mg/dL). Unpublished results suggest that simvastatin may have a similar effect. Primary prevention data are still lacking for atorvastatin and fluvastatin." }, { "input": "The levels of cholesterol that should be treated for primary prevention are based on low-density lipoprotein cholesterol (LDL-C) levels of > 100 mg/dL to > 190 mg/dL and vary according to whether the patient's risk is high, moderate, or low. Medication indications.", "output": "Statins are the most effective at reducing LDL-C and the associated cardiovascular risk. The 5-year West of Scotland study (WOSCOPS) showed that a 26% reduction in LDL-C (from a mean of 192 to 142 mg/dL) using pravastatin 40 mg per day reduced the risk of either nonfatal myocardial infarction (MI) or coronary heart disease (CHD) death (number needed to treat [NNT] = 42; relative risk [RR] = 31; 95% confidence interval [CI],17 - 43). This trial enrolled middle-aged men with an LDL-C level > 155 mg/dL without a history of prior MI, although subjects with stable angina (5% of the participants) were still eligible. Similar reductions were seen in cardiovascular death and in all-cause death (RR = 22; 95% CI = 0 - 40)." }, { "input": "Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered first-line therapy for acute Achilles tendonopathy.", "output": "A Cochrane review of treatments for acute Achilles tendonopathy included 9 randomized trials with a total of 697 patients. Two RCTs showed evidence that NSAIDs alleviate acute symptoms. In 1 trial of 212 patients who received an oral NSAID or placebo for 14 days, significantly fewer patients in the placebo group achieved a good or excellent symptom relief (relative risk [RR]=0.42; 95% confidence interval [CI], 0.21-0.86). A second RCT of 243 patients compared treatment with a topical NSAID to placebo for 21 days; significantly fewer participants who took placebo returned to their pre-injury level of activity (RR=0.78; 95% CI, 0.63-0.95). Low-dose heparin injection, heel pads, topical laser therapy, and peritendinous steroid injection produced no significant decrease in pain compared with placebo." }, { "input": "Chronic noninsertional Achilles tendonopathy should be treated with eccentric calf-muscle training (ECMT).", "output": "ECMT is an effective intervention for chronic noninsertional Achilles tendonopathy. An observational study of ECMT in 78 patients (101 tendons total) with chronic noninsertional Achilles tendonopathy found that 89% were back to their preinjury activity level after a 12-week regimen of ECMT, as indicated by significantly lower scores on a 100-point visual analog scale (67 at baseline vs 10.2 at 12 weeks; P<0.001)." }, { "input": "Chronic noninsertional Achilles tendonopathy should be treated with eccentric calf-muscle training (ECMT).", "output": "During an ECMT program, patients may be able to continue activity without exacerbating Achilles tendonopathy. An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group." }, { "input": "Chronic noninsertional Achilles tendonopathy should be treated with eccentric calf-muscle training (ECMT).", "output": "An RCT compared ECMT or repetitive shock wave therapy to a \"wait-and-see\" control group (25 patients in each group). After 4 months, both the ECMT and shock wave therapy groups reported a significant decrease in pain compared with controls (P< 0.001; mean difference in 10-point pain score, 2.4; 95% CI, 1.3-3.5). Sixty percent of participants in the ECMT group reported complete recovery or significant improvement (P<0.001; number needed to treat [NNT]=3; mean difference in 6-point Likert scale=-1.6; 95% CI, -2.4 to 0.8). 9REF:3)" }, { "input": "Continuing an activity such as running, while monitoring pain, is as effective as resting while enrolled in an eccentric strengthening program.", "output": "An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group." }, { "input": "If conservative management fails, surgery may help.", "output": "Athletes responded significantly better to surgery than nonathletic patients, returning to full activity in 4.5 months compared with 7.1 months for nonathletes (P<0.03). Fewer athletes had surgical complications (9% compared with 19% of nonathletes)." }, { "input": "If conservative management fails, surgery may help.", "output": "Surgery is an option for patients with chronic noninsertional Achilles tendonopathy who have failed conservative measures and a 3- to 6-month rehabilitation program. In a systematic review of 26 studies of patients managed surgically, the mean success rate (full return to preinjury activity level) was 77%. However, a negative correlation was observed between the reported success rate and the overall methods score, a rating of the quality of studies (r=0.53; P<0.01). Only 5 of the studies reviewed were prospective cohort studies; the remaining 21 were retrospective cohort studies and case studies." }, { "input": "First, establish that true hypercalcemia exists by repeating the serum calcium and measuring or calculating the physiologically active serum calcium when abnormalities in blood pH or albumin are found.", "output": "To determine the level, use the equation [4.0 - (plasma albumin)] x 0.8 + (serum calcium) or measure serum ionized calcium. Normal levels of serum ionized calcium for adults older than 19 years are 1.13 to 1.32 mmol/L, although the exact range can vary from laboratory to laboratory. Elevated physiologically active calcium indicates true hypercalcemia." }, { "input": "First, establish that true hypercalcemia exists by repeating the serum calcium and measuring or calculating the physiologically active serum calcium when abnormalities in blood pH or albumin are found.", "output": "Measuring calcium levels in asymptomatic patients often leads to false-positive elevations caused by random error or changes in the level of physiologically active calcium because of alterations in blood pH or serum albumin. Serum calcium levels between 10.0 and 12.0 mg/dL indicate mild hypercalcemia; levels >14.0 mg/dL are severe. Because changes in pH and serum albumin levels alter levels of physiologically active calcium, authoritative sources recommend measuring or calculating physiologically active calcium if blood pH or albumin is abnormal." }, { "input": "Patients with unexplained asymptomatic true hypercalcemia should be screened for primary hyperparathyroidism (PHPT) and malignancy using an intact parathyroid hormone (PTH) level by immunoradioassay.", "output": "Malignancy is the most common cause of low intact PTH and true hypercalcemia, especially when the calcium level is >14 mg/dL. A PTHrP >1.0 pmol/L is highly specific for malignancy because this level does not occur in healthy people." }, { "input": "Patients with unexplained asymptomatic true hypercalcemia should be screened for primary hyperparathyroidism (PHPT) and malignancy using an intact parathyroid hormone (PTH) level by immunoradioassay.", "output": "PHPT and malignancy are the two most common causes of asymptomatic true hypercalcemia." }, { "input": "Patients with unexplained asymptomatic true hypercalcemia should be screened for primary hyperparathyroidism (PHPT) and malignancy using an intact parathyroid hormone (PTH) level by immunoradioassay.", "output": "In a prospective case series of patients with hypercalcemia and malignancy, 54% had elevated PTHrP levels. The authors found that an elevated PTHrP in patients younger than 65 years of age doubles the risk of death from malignancy compared to patients the same age with normal PTHrP (hazard ratio=1.9; 95% CI, 1.1-3.4)." }, { "input": "Other recommended tests that can distinguish PHPT from malignancy and familial hypocalciuric hypercalcemia, as well as help manage patients with PHPT include urinary 24-hour calcium and creatinine levels, parathyroid hormone related peptide (PTHrP), alkaline phosphatase, calcitriol, and bone densitometry.", "output": "Serum calcitriol in association with a low intact PTH level and elevated calcium lower than 14 mg/dL helps differentiate the less common causes of hypercalcemia. Calcitriol is high in granulomatous diseases such as sarcoidosis, tuberculosis, and histoplasmosis, and normal in hyperthyroidism and Addison's disease. Immobilization as a cause of hypercalcemia can be distinguished from PHPT by history and normal PTH levels and from malignancy by a normal alkaline phosphatase level." }, { "input": "Other recommended tests that can distinguish PHPT from malignancy and familial hypocalciuric hypercalcemia, as well as help manage patients with PHPT include urinary 24-hour calcium and creatinine levels, parathyroid hormone related peptide (PTHrP), alkaline phosphatase, calcitriol, and bone densitometry.", "output": "A guideline and a review on PHPT recommend measuring creatinine clearance and obtaining a bone densitometry study of the distal third of the radius, hip, and lumbar spine to assess for end-organ changes related to the condition; declining renal function and osteoporosis may be indications for surgery." }, { "input": "Other recommended tests that can distinguish PHPT from malignancy and familial hypocalciuric hypercalcemia, as well as help manage patients with PHPT include urinary 24-hour calcium and creatinine levels, parathyroid hormone related peptide (PTHrP), alkaline phosphatase, calcitriol, and bone densitometry.", "output": "When serum calcium rises, PTH is normally suppressed. Normal intact PTH and low 24-hour urinary calcium excretion distinguishes patients with PHPT from those with less common familial hypocalciuric hypercalcemia." }, { "input": "other", "output": "Laboratory evaluation targeting these causes, beginning with an intact PTH level, is a logical first step." }, { "input": "other", "output": "Persistent hypercalcemia in the presence of elevated or inappropriately normal PTH concentrations confirms the diagnosis of PHPT." }, { "input": "other", "output": "Evaluation of the patient with true hypercalcemia should include a detailed history, physical examination, and assessment of risk factors for all causes of hypercalcemia." }, { "input": "other", "output": "Most patients with PHPT are asymptomatic, although some eventually develop bone loss, nephrolithiasis, and renal colic." }, { "input": "other", "output": "A 10-year prospective cohort study of patients with PHPT found that 21% of asymptomatic patients developed decreased bone density at one or more sites. None acquired kidney stones, but hypercalcemia and hypercalciuria did worsen in 10 of 52 patients." }, { "input": "No, the risks seem to be minimal. Arthralgias and myalgias have been observed clinically in children and adolescents exposed to fluoroquinolones, but they're transient, disappear when the drug is discontinued, and appear to be no more prevalent than with other antibiotics.", "output": "A large multicenter, prospective, non-blinded cohort study evaluated adverse effects in children receiving fluoroquinolones versus other antibiotics. Duration of fluoroquinolone use was 1 to 23 days. Arthralgias or myalgias, which were only evaluated clinically, occurred more often in children receiving fluoroquinolones-10 of 276 children (3.6%) vs 1 of 249 (0.3%), respectively (odds ratio [OR]=9.3; 95% CI, 1.2-195; P=.02). All events occurred within the first 2 weeks of fluoroquinolone treatment and resolved within 20 days. No tendonopathies were reported." }, { "input": "No, the risks seem to be minimal. Arthralgias and myalgias have been observed clinically in children and adolescents exposed to fluoroquinolones, but they're transient, disappear when the drug is discontinued, and appear to be no more prevalent than with other antibiotics.", "output": "A prospective study published in 2006 monitored joint toxicities (swelling, tenderness, or restricted movement) during acute treatment with ciprofloxacin as well as skeletal growth at follow-up based on physical examination. Preterm neonates with septicemia were treated with either ciprofloxacin (n=48) or other antibiotics (n=66). Forty infants in the ciprofloxacin group completed an average of 28 months of follow-up. No complaints or physical findings of osteoarticular joint abnormalities or skeletal growth delay were noted in either group during acute treatment or at follow-up. The incidence of tendonopathy was not reported." }, { "input": "No, the risks seem to be minimal. Arthralgias and myalgias have been observed clinically in children and adolescents exposed to fluoroquinolones, but they're transient, disappear when the drug is discontinued, and appear to be no more prevalent than with other antibiotics.", "output": "A 1997 database review compiled reports of skeletally immature patients ranging in age from 4 days to 26 years who were exposed to quinolones. Thirty-one reports met search term criteria, for a total of 7045 patients. No incidences of quinolone-associated arthralgia were documented in 30 reports (>5000 patients). The review didn't report the incidence of tendonopathy. One report of 1795 pediatric patients documented a small incidence of arthralgias (~1.5%), which was considered to be reversible and no more than expected for a comparable quinolone-na\u00efve population. Follow-up data on safety and adverse findings, from as long as 12 years after treatment, were reported for 530 (28%) of the 7045 patients. Changes in skeletal growth were evaluated using various diagnostic techniques. Clinical observation was the most common method of assessment (N=357), however. The follow-up data revealed no arthropathy or abnormal skeletal growth (rate=0%; estimated 95% confidence interval [CI]=0%-0.04%)." }, { "input": "No apparent long-term risk of developmental skeletal growth delay is associated with fluoroquinolone exposure.", "output": "A 1997 database review compiled reports of skeletally immature patients ranging in age from 4 days to 26 years who were exposed to quinolones. Thirty-one reports met search term criteria, for a total of 7045 patients. No incidences of quinolone-associated arthralgia were documented in 30 reports (>5000 patients). The review didn't report the incidence of tendonopathy. One report of 1795 pediatric patients documented a small incidence of arthralgias (~1.5%), which was considered to be reversible and no more than expected for a comparable quinolone-na\u00efve population. Follow-up data on safety and adverse findings, from as long as 12 years after treatment, were reported for 530 (28%) of the 7045 patients. Changes in skeletal growth were evaluated using various diagnostic techniques. Clinical observation was the most common method of assessment (N=357), however. The follow-up data revealed no arthropathy or abnormal skeletal growth (rate=0%; estimated 95% confidence interval [CI]=0%-0.04%)." }, { "input": "No apparent long-term risk of developmental skeletal growth delay is associated with fluoroquinolone exposure.", "output": "A prospective study published in 2006 monitored joint toxicities (swelling, tenderness, or restricted movement) during acute treatment with ciprofloxacin as well as skeletal growth at follow-up based on physical examination. Preterm neonates with septicemia were treated with either ciprofloxacin (n=48) or other antibiotics (n=66). Forty infants in the ciprofloxacin group completed an average of 28 months of follow-up. No complaints or physical findings of osteoarticular joint abnormalities or skeletal growth delay were noted in either group during acute treatment or at follow-up. The incidence of tendonopathy was not reported." }, { "input": "Fluoroquinolone use in children isn't associated with tendonopathy.", "output": "A 1997 database review compiled reports of skeletally immature patients ranging in age from 4 days to 26 years who were exposed to quinolones. Thirty-one reports met search term criteria, for a total of 7045 patients. No incidences of quinolone-associated arthralgia were documented in 30 reports (>5000 patients). The review didn't report the incidence of tendonopathy. One report of 1795 pediatric patients documented a small incidence of arthralgias (~1.5%), which was considered to be reversible and no more than expected for a comparable quinolone-na\u00efve population. Follow-up data on safety and adverse findings, from as long as 12 years after treatment, were reported for 530 (28%) of the 7045 patients. Changes in skeletal growth were evaluated using various diagnostic techniques. Clinical observation was the most common method of assessment (N=357), however. The follow-up data revealed no arthropathy or abnormal skeletal growth (rate=0%; estimated 95% confidence interval [CI]=0%-0.04%)." }, { "input": "Fluoroquinolone use in children probably carries a very low risk of tendon rupture.", "output": "A 1996 study reported the incidence of tendon disorders related to fluoroquinolones using drug surveillance data from the general population. The average age of the patients was 55 years. The author estimated the risk of tendon rupture associated with norfloxacin or ofloxacin to be 1 case per 23,130 days of treatment and only 1 case per 779,600 days of ciprofloxacin treatment. The estimated risk would likely be even lower in children, the author noted, because the risk of tendon rupture increases with age." }, { "input": "Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running. The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven't been observed.", "output": "Another study found significant increases in CK (approximate mean of 15,000 IU/L) after repetitive eccentric elbow flexor contractions in college-age males." }, { "input": "Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running. The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven't been observed.", "output": "One study followed 203 participants to evaluate the magnitude of CK elevation and the effect on renal function produced by exercise. After performing 50 maximal eccentric elbow flexor contractions, 55% of participants had CK elevations >2000 IU/L at 4 days after exercise; 25% had CK elevations >10,000 IU/L; 13% had levels >20,000 IU/L. None showed any evidence of renal compromise on clinical follow-up." }, { "input": "Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running. The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven't been observed.", "output": "A study showed that triathletes had a 12-fold mean increase in CK levels as long as 24 hours after the race." }, { "input": "Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running. The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven't been observed.", "output": "One study found that mean total CK elevations 24 hours after a marathon were 3322 IU/L (22.3 times baseline) for men and 946 IU/L (8.6 times baseline) for women." }, { "input": "Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running. The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven't been observed.", "output": "Increases in CK are more pronounced in males, blacks, and untrained people; age doesn't seem to be a factor." }, { "input": "Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running. The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven't been observed.", "output": "Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables. Increases in CK are more pronounced in males, blacks, and untrained people; age doesn't seem to be a factor. Higher-intensity, longer-duration, and weight-bearing exercise (eccentric muscular contractions and downhill running) cause the greatest rises in CK. Eccentric weight lifting and similar activities, like downhill running, may result in an increase in serum CK levels of 10 to 20 times normal, whereas other nonweight-bearing exercises and exercise involving no or minimal eccentric contractions, such as swimming and cycling, cause only nominal increases in serum CK." }, { "input": "Moderate-intensity exercise (maintaining heart rate between 55% and 90% of maximum) may elevate creatine kinase (CK) to levels that meet the diagnostic criteria for rhabdomyolysis if the exercises involve eccentric muscle contractions, such as weight lifting or downhill running. The clinical significance of exercise-induced elevations in CK is unclear because the renal complications associated with classic rhabdomyolysis haven't been observed.", "output": "Although exercise is known to elevate CK, it produces a wide range of levels, based on a host of variables." }, { "input": "Yes, some do. Breast stimulation and electroacupuncture help, while other common remedies that have been studied are ineffective, possibly unsafe, or both. Unilateral breast stimulation shortens the time until the onset of labor in women at term.", "output": "A systematic review of 6 trials with a total of 719 participants compared unilateral breast stimulation with no intervention to induce labor in women at term. In 2 trials, the 300 participants stimulated 1 breast for 1 hour a day for 3 days; in the other 4 trials, 419 women stimulated either breast alternately for 3 hours a day. Breast stimulation significantly reduced the number of women who hadn't gone into labor at 72 hours compared with nonintervention (62.7% vs 93.6%; relative risk [RR]=0.67; 95% confidence interval [CI], 0.60-0.74; number needed to treat [NNT]=3.2). This result remained significant when primiparous and multiparous women were analyzed separately, but not in the 1 trial (37 participants) that reported on women with an unfavorable cervix. Breast stimulation also reduced postpartum hemorrhage (0.7% vs 6%; RR=0.16; 95% CI, 0.03-0.87; NNT=18.8). None of the trials documented uterine hyperstimulation or meconium-stained fluid, and they didn't find significant differences in the rates of cesarean section (9% vs 10%; RR=0.90; 95% CI, 0.38-2.12). One trial reported 4 perinatal deaths in a high-risk population-3 in the breast stimulation group and 1 in the control group-but this finding was not replicated in any other trials." }, { "input": "Electroacupuncture also may stimulate the onset of labor.", "output": "A Cochrane systematic review evaluating acupuncture for inducing labor identified 1 randomized trial with methodologic flaws (allowing no conclusion), 3 case series, and 2 nonrandomized trials. The first case series used electroacupuncture at 38 to 42 weeks to successfully induce labor in 21 of 31 women. The second series, using acupuncture with and without electrical stimulation, induced labor in 10 of 12 women at 19 to 43 weeks. The third study induced labor with electroacupuncture in 78% of 41 women-34 term and postterm patients and 7 with a fetal demise. In the first nonrandomized trial, 20 of 27 women at term who received electroacupuncture gave birth between 39 weeks 3 days and 40 weeks, compared with 47 of 102 women in the control group. In the second study, 31 of 35 women who received electroacupuncture reported increased intensity of contractions compared with none of the 35 women in the control group." }, { "input": "Sexual intercourse doesn't appear to ripen the cervix or stimulate labor.", "output": "A Cochrane systematic review found 1 observational study of the effect of sexual intercourse on cervical ripening and induction of labor among 28 women at term. The study evaluated cervical Bishop scores after sexual intercourse with intravaginal semen deposition for 3 consecutive nights compared with no intercourse. The difference in Bishop score was not significant (1.0 with coitus vs 0.5 controls; P>.05) and no difference in the number of women who delivered within 3 days was noted in the 2 groups (RR=0.99; 95% CI, 0.45-2.20)." }, { "input": "Castor oil universally produces nausea and doesn't promote labor,", "output": "A Cochrane systematic review included 1 study of women at term with intact membranes who received 1 dose of castor oil to induce labor (n=52) compared with no treatment (n=48). All women who received castor oil felt nauseous, but no other differences were noted between the castor oil group and controls in rates of cesarean section, meconium-stained fluid, or Apgar scores less than 7 at 5 minutes." }, { "input": "Red raspberry leaf is likely safe but ineffective.", "output": "A prospective controlled trial that randomized 192 women to receive either red raspberry leaf tablets (1.2 g twice daily beginning at 32 weeks) or placebo found no significant differences in duration of the first stage of labor or birth outcomes. Symptom surveys of 108 women revealed no adverse effects." }, { "input": "Evening primrose oil is ineffective and possibly unsafe.", "output": "A retrospective cohort study compared pregnancy outcomes in 54 women who took evening primrose oil (500 mg 3 times a day beginning at 37 weeks) with a matched group of 54 women who did not take it. The study found no significant differences between the groups in maternal age, Apgar scores, or days of gestation. However, the women taking evening primrose oil tended to have protracted active phase of labor, prolonged rupture of membranes, arrest of descent, and oxytocin augmentation (none of which were statistically significant)." }, { "input": "Black cohosh and blue cohosh lack evidence of efficacy and may be unsafe.", "output": "A systematic review of the literature on black cohosh in pregnancy found no trials that evaluated its efficacy for inducing labor. The article described black cohosh as potentially unsafe because of the lack of trials demonstrating safety and possible deleterious estrogenic effects." }, { "input": "Black cohosh and blue cohosh lack evidence of efficacy and may be unsafe.", "output": "A systematic review of the literature on blue cohosh found only in vitro studies of efficacy (increased estradiol-induced transcription in estrogen-responsive cells and increased tone in excised guinea pig uteri) and 3 case reports of maternal adverse events after ingestion (perinatal stroke, congestive heart failure with shock, and multiorgan hypoxic injury). In vitro evidence presented in the review suggests that blue cohosh may have teratogenic, embryotoxic, and oxytocic effects." }, { "input": "Black cohosh and blue cohosh lack evidence of efficacy and may be unsafe.", "output": "A review of herbal preparations used by midwives reported a case of an infant with low Apgar scores after black cohosh use. The article described black cohosh as potentially unsafe because of the lack of trials demonstrating safety and possible deleterious estrogenic effects." }, { "input": "Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a \"wait-and-see\" approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated.", "output": "Overall, this evidence suggests that for adults, watchful waiting rather than initially treating with antibiotics is reasonable, given the self-limited nature and lack of serious outcomes in untreated patients as well as growing concern about antibiotic resistance. Note that this recommendation applies only to acute nonvenereal conjunctivitis. It is generally accepted that conjunctivitis caused by gonococcus or chlamydia should be suspected in all newborns and in severe cases in sexually active young adults. These cases warrant culturing and antibiotic treatment to prevent serious complications." }, { "input": "Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a \"wait-and-see\" approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated.", "output": "Antibiotic resistance is a growing problem. Studies of fluoroquinolone resistance rates report a range of 4% to 50% for ocular bacteria. The 50% resistance rate occurred after 4 weeks of topical treatment in postcataract surgery patients." }, { "input": "Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a \"wait-and-see\" approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated.", "output": "The rate of spontaneous remission is much higher for adults than for children (71.6% vs 28%, respectively). The Cochrane meta-analysis reported a similar clinical cure rate in children for 6 to 10 days of treatment with topical antibiotics versus placebo. A systematic review of 5 placebo-controlled RCTs reported no serious adverse outcomes in conjunctivitis patients regardless of treatment group." }, { "input": "Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a \"wait-and-see\" approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated.", "output": "Although there is a small risk of complications and longer time course when bacterial conjunctivitis is left untreated, the disease is often self-limited, with a 64% clinical remission rate in patients treated for 2 to 5 days with placebo." }, { "input": "Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a \"wait-and-see\" approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated.", "output": "One review reports that 25% of children with Haemophilus influenzae conjunctivitis develop otitis media." }, { "input": "Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a \"wait-and-see\" approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated.", "output": "A meta-analysis of 3 trials based in specialty clinics or hospitals reported significant clinical cure or improvement of bacterial conjunctivitis with 2 to 5 days of topical antibiotics compared with placebo (RR = 1.31, 95% CI, 1.11-1.55, number needed to treat = 5)." }, { "input": "Children with suspected or culture-proven acute nonvenereal bacterial conjunctivitis should be treated with topical antibiotics, which hastens clinical and microbiological remission and may prevent potentially serious morbidity. In light of recent evidence regarding the self-limiting nature of conjunctivitis in adults and the development of antibiotic resistance, a \"wait-and-see\" approach with careful follow-up may be reasonable for adults, but this approach has not been evaluated.", "output": "Treating suspected or culture-proven acute bacterial conjunctivitis with topical antibiotics significantly shortens the clinical course of the disease and results in higher microbiological cure rates than placebo." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "Studies of topical interferon show conflicting results. Systemic interferon is not beneficial. Topical 5-FU has not been studied with RCTs. Treatment duration for nonsurgical options is 4 to 8 weeks. Treatment of genital warts has not been shown to reduce transmission to sex partners. Pain occurs in less than 20% of people with imiquimod, cryotherapy, podophyllin, and electrosurgery; 39% with topical interferon; 44% with electrosurgery; 75% with podofilox; and 100% with surgical excision or laser surgery. However, pain has been measured using methods that are unlikely to be comparable across studies. Flulike symptoms, leukopenia, thrombocytopenia, and elevated aspartate transaminase levels are associated with intralesional interferon. Topical have not been studied in pregnant patients. Cryotherapy is safe in pregnancy based on case series, if only 3 or 4 treatments are given." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "Laser surgery is as effective as surgical excision." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "Although surgical treatments have not been compared with placebo or no treatment, both electrosurgery and surgical excision are superior to podophyllin in clinical trials. This RCT showed more frequent recurrence with podophyllin (60% to 65%) than with surgical excision (19% to 20%)." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "Although surgical treatments have not been compared with placebo or no treatment, both electrosurgery and surgical excision are superior to podophyllin in clinical trials. This RCT showed more frequent recurrence with podophyllin (60% to 65%) than with surgical excision (19% to 20%)." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "Cryotherapy is equivalent to electrosurgery." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "Cryotherapy is equivalent to trichloroacetic acid." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "Cryotherapy is equivalent to trichloroacetic acid. This trial showed recurrence in 22% of participants receiving electrosurgery, in 21% of those receiving cryotherapy, and in 44% of those receiving podophyllin treatment. Data are lacking on recurrence rates with imiquimod, podofilox, and intralesional interferon." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "A United Kingdom guideline on anogenital warts recommends physical ablative methods such as cryotherapy and surgical options for keratinized lesions and topical medications for soft lesions. The guideline also recommends ablative therapy for persons with a small number of warts regardless of type. Interferon and 5-FU are not recommended." }, { "input": "Podofilox (Condylox), imiquimod (Aldara), cryotherapy, and surgical options all seem reasonable alternatives that are superior to podophyllin. No studies of surgical options versus home use preparations have been reported. Trichloroacetic acid and 5-fluorouracil (5-FU) have not been sufficiently studied.", "output": "The CDC endorses podophyllin, bi- and trichloroacetic acid, podofilox, imiquimod, cryotherapy, intralesional interferon, electrosurgery, laser surgery, and surgical excision." }, { "input": "Tonsillectomy with or without adenoidectomy is minimally effective when combined with tympanostomy tube placement in preventing recurrent otitis media in the 3 years following surgery. The risks of surgery must be weighed against potential benefit.", "output": "Two RCTs showed minimal effect at 1 year and no effect at 3 years of follow-up in preventing recurrent sore throat. However, 1 of these could not be critically appraised because it was published in abstract format only." }, { "input": "Tonsillectomy with or without adenoidectomy is minimally effective when combined with tympanostomy tube placement in preventing recurrent otitis media in the 3 years following surgery. The risks of surgery must be weighed against potential benefit.", "output": "In the largest study, controls had a mean of 2.1 episodes of recurrent otitis media in the first postoperative year while those undergoing adenotonsillectomy had had 1.8 episodes (P=.25) and those undergoing adenoidectomy had 1.4 episodes (P<.001). However, these benefits did not persist beyond the first year. Several case series report no evidence of effectiveness of tonsillectomy for immunoglobulin A (IgA) nephropathy, psoriasis, or nocturnal enuresis." }, { "input": "Tonsillectomy with or without adenoidectomy is minimally effective when combined with tympanostomy tube placement in preventing recurrent otitis media in the 3 years following surgery. The risks of surgery must be weighed against potential benefit.", "output": "Two other trials of tonsillectomy and adenotonsillectomy in children, both with and without tympanostomy tube placement, have shown a small, brief reduction in episodes of recurrent otitis." }, { "input": "The evidence supporting tonsillectomy for recurrence of sore throat is controversial.", "output": "Two other trials of tonsillectomy and adenotonsillectomy in children, both with and without tympanostomy tube placement, have shown a small, brief reduction in episodes of recurrent otitis." }, { "input": "There is insufficient evidence to recommend other potential indications", "output": "Cochrane: \"There is no evidence from randomized controlled trials to guide the clinician in formulating the indications for surgery in adults or children.\"" }, { "input": "Start with a detailed history, paying particular attention to medications and alcohol use.", "output": "Liver disease-which may be confounded by alcohol abuse, medications, or cancer-is a common cause of macrocytosis." }, { "input": "Start with a detailed history, paying particular attention to medications and alcohol use.", "output": "The causes of macrocytosis vary depending on the population studied. In primary care, alcohol use and vitamin deficiency are common causes. Even after evaluation, approximately 10% of cases remain unexplained." }, { "input": "Start with a detailed history, paying particular attention to medications and alcohol use.", "output": "A history focusing specifically on alcohol use and medications-especially chemotherapeutics, antiretroviral drugs, and antiseizure medications-can provide important clues to the cause of macrocytosis. During the physical examination, look for signs consistent with chronic liver disease." }, { "input": "Blood testing can include a peripheral smear, evaluation for vitamin deficiencies (especially B12 deficiency), and liver function tests.", "output": "A normal serum B12 level may not rule out a true B12 deficiency, but normal levels of the metabolites methylmalonic acid and homocysteine do essentially rule it out." }, { "input": "Blood testing can include a peripheral smear, evaluation for vitamin deficiencies (especially B12 deficiency), and liver function tests.", "output": "Several studies suggest empiric treatment with folic acid instead of testing for a deficiency when B12 deficiency has been ruled out." }, { "input": "Blood testing can include a peripheral smear, evaluation for vitamin deficiencies (especially B12 deficiency), and liver function tests.", "output": "A prospective study of primary care patients reported little diagnostic value for the peripheral smear." }, { "input": "Blood testing can include a peripheral smear, evaluation for vitamin deficiencies (especially B12 deficiency), and liver function tests.", "output": "A retrospective chart review of 113 cases of macrocytosis in outpatients found that general practitioners often didn't order a peripheral smear and reticulocyte count to complete their diagnostic workups." }, { "input": "Thyroid testing may be useful for older patients.", "output": "Hypothyroidism is rarely a cause, but may be more prevalent in the elderly." }, { "input": "Reticulocyte count and bone marrow evaluation, although important to rule out hemolysis and myelodysplastic changes, may not be necessary for patients with isolated macrocytosis without anemia.", "output": "A prospective study of 300 hospitalized patients with macrocytosis found that 100% of marrow disorders and hemolysis that caused macrocytosis also caused an associated anemia." }, { "input": "Reticulocyte count and bone marrow evaluation, although important to rule out hemolysis and myelodysplastic changes, may not be necessary for patients with isolated macrocytosis without anemia.", "output": "Significant macrocytosis is usually defined as a mean corpuscular volume greater than 99 femtoliters (fL). The prevalence of macrocytosis (with or without anemia) ranges from 1.7% to 5.0%." }, { "input": "Reticulocyte count and bone marrow evaluation, although important to rule out hemolysis and myelodysplastic changes, may not be necessary for patients with isolated macrocytosis without anemia.", "output": "A prospective study of primary care patients found that reticulocytosis rarely caused macrocytosis." }, { "input": "Reticulocyte count and bone marrow evaluation, although important to rule out hemolysis and myelodysplastic changes, may not be necessary for patients with isolated macrocytosis without anemia.", "output": "Because no study has looked specifically at evaluating macrocytosis without anemia, extrapolation from studies of all presentations of macrocytosis (with and without anemia) must help guide evaluation." }, { "input": "In unexplained macrocytosis, bone marrow evaluation may show early marrow changes, particularly in the elderly.", "output": "A prospective study of the utility of bone marrow biopsy in 124 elderly patients with macrocytosis found that as many as 60% were diagnosed by blood tests alone. All the remaining patients with unexplained macrocytosis underwent bone marrow biopsy, which showed early dysplastic changes in 39%, but did not provide a diagnosis in nearly 50%. Twelve percent were found to have myelodysplastic syndrome, but they had a mean hemoglobin of 8.5 g/dL." } ] }