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[ "8081350" ]

[ "The use of cranial electrotherapy stimulation in the treatment of closed-head-injured patients." ]

[ "This double-blind study sought to discover if cranial electrotherapy stimulation (CES), which is a known treatment of depression, anxiety and insomnia in non-head-injured patients, could be an effective, drug-free treatment of stress-related symptoms in the closed-head-injured (CHI) patient. In this study 10 CHI patients treated for 45 min daily, 4 days a week for 3 weeks, responded significantly on all negative mood factors of the Profile Of Mood States, while five sham-treated and six placebo controls did not. While the majority of the patients were known seizure cases, no patient suffered a seizure during CES therapy. No placebo effects were found, nor were any negative effects from CES treatment seen." ]

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[ "Evaluation of different doses of soluble ibuprofen and ibuprofen tablets in postoperative dental pain.", "Efficacy and quality of ibuprofen and acetaminophen plus codeine analgesia.", "A placebo-controlled comparative evaluation of diclofenac dispersible versus ibuprofen in postoperative pain after third molar surgery.", "Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain.", "Ibuprofen compared with ibuprofen plus caffeine after third molar surgery.", "The comparative efficacy of aceclofenac and ibuprofen in postoperative pain after third molar surgery.", "The efficacy of a novel adenosine agonist (WAG 994) in postoperative dental pain.", "Ibuprofen, zomepirac, aspirin, and placebo in the relief of postepisiotomy pain.", "Ibuprofen and acetaminophen in the relief of acute pain: a randomized, double-blind, placebo-controlled study.", "Analgesic dose-response relationship of ibuprofen 50, 100, 200, and 400 mg after surgical removal of third molars: a single-dose, randomized, placebo-controlled, and double-blind study of 304 patients.", "Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of pain after abdominal or pelvic surgery in women: a randomized, double-blind, placebo- and active-controlled parallel-group study.", "Multicenter clinical trial of ibuprofen and acetaminophen in the treatment of postoperative dental pain.", "Ibuprofen liquigel for oral surgery pain.", "Analgesic efficacy of two ibuprofen-codeine combinations for the treatment of postepisiotomy and postoperative pain.", "Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain.", "Tramadol and acetaminophen tablets for dental pain.", "A double-blind, randomized study of naproxen sodium, ibuprofen, and placebo in postoperative dental pain.", "Analgesic efficacy of a hydrocodone with ibuprofen combination compared with ibuprofen alone for the treatment of acute postoperative pain.", "Ibuprofen and acetaminophen in the relief of postpartum episiotomy pain.", "Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial.", "Combination analgesic efficacy: individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain.", "Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain.", "The efficacy of buffered ketoprofen in postoperative pain after third molar surgery.", "Comparison of single-dose ibuprofen lysine, acetylsalicylic acid, and placebo for moderate-to-severe postoperative dental pain.", "Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief of postoperative pain.", "Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain.", "Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.", "Pregabalin in patients with postoperative dental pain.", "MK-0703 (a cyclooxygenase-2 inhibitor) in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study.", "Evaluation of trismus, bite force, and pressure algometry after third molar surgery: a placebo-controlled study of ibuprofen.", "Characterization of rofecoxib as a cyclooxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model.", "Combination oxycodone 5 mg/ibuprofen 400 mg for the treatment of postoperative pain: a double-blind, placebo- and active-controlled parallel-group study.", "The Analgesic Interaction of Misoprostol with Nonsteroidal Anti-Inflammatory Drugs.", "Comparative analgesic potency of aspirin and ibuprofen.", "A comparison of rofecoxib versus celecoxib in treating pain after dental surgery: a single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study using the dental impaction pain model.", "Onset and duration of analgesia for low-dose ketoprofen in the treatment of postoperative dental pain.", "Etoricoxib in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study.", "An evaluation of different ibuprofen preparations in the control of postoperative pain after third molar surgery.", "Analgesic efficacy of low-dose ibuprofen in dental extraction pain.", "A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain.", "A comparison of ibuprofen and dihydrocodeine in relieving pain following wisdom teeth removal.", "Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain.", "Analgesic efficacy of single oral doses of lumiracoxib and ibuprofen in patients with postoperative dental pain.", "Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain.", "Single dose and multidose analgesic study of ibuprofen and meclofenamate sodium after third molar surgery.", "Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.", "Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial.", "Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen.", "Analgesic efficacy of celecoxib in postoperative oral surgery pain: a single-dose, two-center, randomized, double-blind, active- and placebo-controlled study.", "The correlation between blood levels of ibuprofen and clinical analgesic response.", "The analgesic efficacy of diclofenac dispersible and ibuprofen in postoperative pain after dental extraction.", "Syrup formulations for post-tonsillectomy analgesia: a double-blind study comparing ibuprofen, aspirin and placebo.", "Analgesic effect of fendosal, ibuprofen and aspirin in postoperative oral surgery pain.", "Analgesic efficacy of an ibuprofen-codeine combination.", "Ibuprofen arginate provides effective relief from postoperative dental pain with a more rapid onset of action than ibuprofen." ]

[ "The object of the study was to assess the comparative efficacy of three single doses (200, 400, 600 mg) of soluble ibuprofen and ibuprofen tablets after third molar surgery in 148 patients and aged 18-40 years. Outcome was measured by overall assessment of pain (AUC360) assessed from serial visual analogue scales, the number of patients taking additional analgesic and by overall assessment of medication evaluated on a five-point categorical scale. Over the 6-hour investigation period all the ibuprofen treatments with the exception of ibuprofen tablets 200 mg resulted in significantly less pain (p < 0.05) than placebo treatment. A large number of patients required additional analgesia during the investigation period, but the time to taking it was significantly earlier in the placebo group. No significant dose response (p > 0.05) was observed for either ibuprofen preparations assessed by the outcome variable of overall pain experience (AUC360) or time to additional analgesia. There was no significant difference in pain scores or time to taking additional analgesics between the respective doses of soluble and tablet formulations of ibuprofen. Both soluble and tablet formulations of ibuprofen provide effective pain control in the early postoperative period after removal of impacted third molars. There is little analgesic advantage in increasing the dose to 600 mg and only minimal benefit from using a soluble formulation of the drug.", "Ibuprofen, 400 mg, was compared with 300 mg acetaminophen plus 30 mg of codeine and placebo in 120 post-orthopedic surgery patients with moderate to severe pain. The study was designed as a double-blind, single-dose, parallel-group analgesic efficacy assay. Estimates of analgesia were obtained up to 6 h using categorical and visual analog measures of pain intensity and pain relief. Estimates of selected elements of mood and of sensory and affective components of pain were obtained at 0 and 2 h using contrasting mood word/phrase pairs and a portion of the McGill Pain Questionnaire, respectively. Drugs were distinguishable from placebo in total analgesic effect, and ibuprofen was more effective than acetaminophen plus codeine, especially in terms of duration. While peak effects were comparable, they occurred 1 h later following ibuprofen. Differences among treatments were more discernible using visual analog measures. Side effects were minimal. Ibuprofen provided greater improvement in selected elements of mood than acetaminophen plus codeine at comparable levels of pain relief. While decreases in the sensory component of pain were most highly associated with pain relief provided by ibuprofen, decreases in the affective component were most highly associated with pain relief following acetaminophen plus codeine. These latter results indicate that mood assessment and the discrimination between sensory and affective components of pain could be particularly useful within analgesic drug assays, especially when comparing analgesics of differing pharmacologic class and when comparing the results of such assays in pain syndromes characterized by differing pain quality.", "The analgesic efficacy of single oral doses of drinkable diclofenac dispersible 50 mg was compared with that of ibuprofen 400 mg and placebo in a randomized, double-blind, parallel-group trial in 257 adult patients (245 valid for efficacy) with severe postoperative pain after extraction of an impacted lower third molar. In this study, pain intensity (on a 100-mm visual analog scale) and pain relief from baseline (using a five-point verbal rating scale) were assessed serially during an observation period of 6 hours. Intake of rescue analgesic was permitted in case of insufficient therapeutic effect; however at least 1 hour should have elapsed after test drug consumption. On the main efficacy variable, namely, reduction in the pain intensity score, both diclofenac dispersible (n = 83) and ibuprofen (n = 80) were statistically significantly (P < .01) superior to placebo (n = 82) starting at 20 and 40 minutes, respectively, after drug intake. The active medications were also significantly (P < .01) better than placebo for the secondary efficacy parameters viz. summed pain relief scores over 6 hours (TOTPAR-6); frequency of remedication with a rescue analgesic in the three treatment groups (diclofenac, 24%; ibuprofen, 28%; placebo, 65%); mean time to remedication; and global evaluation. All the treatments were well tolerated. Thus assay sensitivity of this trial (ibuprofen significantly better than placebo) has been demonstrated; in addition, diclofenac as a dispersible formulation has been shown to be an effective analgesic for the treatment of post-surgical dental pain.", "Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia, antipyresis, and various arthritic conditions. A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets. Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension, with both a higher Cmax and an earlier tmax than any solid tablet. The objective of this single-dose, double-blind, triple-dummy, parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg, ketoprofen 25 mg compared with acetaminophen 1000 mg, and placebo in 239 patients with moderate or severe pain following third molar extractions. Treatments were compared over 6 hours using standard scales for pain intensity and relief and stopwatch onset of meaningful relief. All active treatments provided meaningful relief significantly faster compared with placebo. Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen. By the end of the study (6 h), onset of meaningful relief was achieved by 36%, 99%, 96%, and 88% of the patients in the placebo, ketoprofen, ibuprofen, and acetaminophen groups, respectively. The median times to onset of relief were > 6 hours for placebo, 25.5 minutes for ketoprofen, 24.2 minutes for ibuprofen, and 29.9 minutes for acetaminophen. In addition, both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference. Consistent results were seen with respect to the 6-hour summary efficacy variables: the three active treatments were significantly better than placebo, and ibuprofen was significantly better than both acetaminophen and ketoprofen. Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg, acetaminophen 1000 mg, and placebo. No serious adverse effects were reported in this single-dose study.", "To compare the relative merits of single doses of ibuprofen and ibuprofen plus caffeine in the treatment of pain after third molar removal.\n Randomised, double-blind, placebo-controlled, single-dose parallel-group comparison of placebo, ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50, 100 or 200 mg of caffeine.\n 161 patients undergoing lower third molar removal.\n All active treatments produced significant analgesia and mood elevation compared with placebo. There was no significant difference in the effects of 200 and 400 mg of ibuprofen. Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone. Ten patients reported 11 adverse effects, none in the highest caffeine dose group.\n Caffeine increased the analgesic effect of ibuprofen 200 mg, through an earlier onset of analgesic effect. This was achieved in this single dose context without problematic adverse effects.", "The aim of the present placebo-controlled, double-blind study was to evaluate the comparative efficacy of single doses of aceclofenac 150 mg and ibuprofen 400 mg in 217 patients with postoperative pain after third molar surgery. Outcome of primary efficacy was judged by overall assessment of the area under the curve (AUC) of graphs for pain intensity (AUC pain) pain relief (AUC relief), both measured from serial visual analogue scales over a 6 h investigation period. Other measures of efficacy included the rate of pain reduction in the first hour, the number of patients who took 'escape' analgesics and the time before they did, and an overall assessment of pain relief score on a five-point categorical scale. Ibuprofen 400 mg was significantly superior to placebo for pain relief (P < 0.01), degree of pain reduction in the first hour (P = 0.005), and the number of patients who required escape analgesia (P < 0.001), and the time before they did (P < 0.001). The outcome for patients treated with aceclofenac 150 mg was not significantly different from that of patients treated with placebo (P > 0.05). A single dose of ibuprofen 400 mg provided significant pain relief in the early postoperative period after third molar surgery, whereas a single dose of aceclofenac 150 mg was not effective in the management of postoperative pain after this operation.", "To determine the comparative efficacy of a new novel adenosine agonist (WAG 994) in postoperative pain after third molar surgery.\n One hundred and twenty-two patients with postoperative pain after third molar surgery were randomised in a placebo double-blind trial with an active control group. In the early postoperative period patients received either a single dose of WAG 994 1 mg, ibuprofen 400 mg or matched placebos. Pain intensity score was recorded on serial visual analogue scales over a 6 h investigation period. Similarly, pain relief was completed on a 4 point categorical scale at each evaluation point. Patients had access to escape analgesic and if these were taken, the time and dosage were recorded. A sparse sampling technique was used to investigate the relationship between analgesic effects and plasma concentrations of WAG 994.\n All three treatment groups were matched for various demographic variables. For all efficacy measures, WAG 994 was not significantly different from placebo (P >0.05), whereas ibuprofen 400 mg was significantly superior to placebo (P<0.001). No significant relationships (P<0.05) were found between WAG 994 pharmacokinetic variables and efficacy measures. Conclusion WAG 994, an adenosine agonist, did not show efficacy in the management of postoperative pain after third molar surgery. Although this pain responds well to nonsteroidal anti-inflammatory drugs, it appears to be resistant to compounds that interact with purinergic receptors.", "Our purpose was to compare the analgesic efficacy of single oral doses of ibuprofen, zomepirac, aspirin, and placebo in severe postepisiotomy pain. One hundred twenty subjects participated in a double-blind, single-dose, parallel-group, 4-hr trial comparing 400 mg ibuprofen, 100 mg zomepirac sodium, 600 mg aspirin, and placebo. For most parameters, including the sum of the pain intensity differences (SPID) and the sum of the hourly pain relief values (TOTAL), which are summary variables, each of the drugs was more effective than placebo. Ibuprofen was more effective than aspirin and zomepirac. Zomepirac and aspirin were equally effective for most of the analgesic variables. There were no adverse effects. Ibuprofen, 400 mg, is an effective oral analgesic and is more effective than 100 mg zomepirac and 600 mg aspirin in most parameters of pain.", "To determine the relative analgesic efficacy of ibuprofen 400 mg and acetaminophen 1000 mg, we conducted a single-dose, double-blind, placebo-controlled, randomized clinical trial using a standard assay for analgesic agents, the dental pain model. At regular intervals over 6 hours, 184 patients who had undergone dental impaction surgery rated pain intensity and relief on categorical scales and pain half-gone on a dichotomous nominal scale; a categorical overall evaluation was completed at the end of 6 hours. Both active agents were effective compared to placebo. Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for Sum Pain Intensity Difference (SPID), Total Pain Relief (TOTPAR), sum pain half-gone, and overall evaluation (P less than .05 to P less than .001). The time-effect curves demonstrated a greater peak effect and longer duration of action for ibuprofen 400 mg compared to acetaminophen 1000 mg. Side effects were reported in five ibuprofen patients, 11 acetaminophen-treated patients, and seven placebo patients. Based on the results of this clinical study, we conclude that ibuprofen 400 mg is a safe and more effective analgesic than acetaminophen 1000 mg for patients with acute pain.", "The purpose of this single-dose, randomized, placebo-controlled, and double-blind study was to evaluate the analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen after third molar surgery. Patients were instructed to take a single dose of either placebo or 50 mg, 100 mg, 200 mg, or 400 mg of ibuprofen when the postoperative pain was moderate to severe. Acetaminophen 500 mg was used as a rescue medication. Pain intensity, pain relief, and any possible adverse events were recorded on self-administered questionnaires hourly for 6 hours after intake of study medication. If rescue medication was taken, the time of intake was registered. A total of 304 patients entered the study, and 258 complied with the protocol. A positive analgesic dose-response relationship of 50-mg, 100-mg, 200-mg, and 400-mg doses of ibuprofen was observed when evaluated by pain intensity difference, sum of pain intensity difference, pain relief, total pain relief, and survival distribution of patients not taking rescue medication. Although significant pain relief was seen after a dose of 50 mg ibuprofen, ibuprofen 400 mg provided maximum pain relief and the longest duration of analgesic effect. Mild transient adverse events were reported by 6.8% of the patients. However, there was no significant difference in frequency between the placebo and 50 mg, 100 mg, 200 mg, and 400 mg ibuprofen dose groups.", "The sensation of pain arises from both central and peripheral sites, and inflammation may be one of its underlying causes. Combination therapy with analgesic agents having multimodal mechanisms of action and complementary pharmacokinetic properties enhances pain relief by addressing the different pathways of pain while limiting individual drug doses and, therefore, the potential for adverse effects caused by any single agent. Oxycodone and ibuprofen each have been used effectively as monotherapy and in other combinations for the treatment of acute pain; a fixed combination of these analgesics may improve pain relief in the setting of abdominal or pelvic surgery, where trauma and any resultant inflammation may be present at the same time.\n This study evaluated and compared the analgesic efficacy and tolerability of a single-dose combination tablet containing oxycodone 5 mg/ibuprofen 400 mg with either agent alone and with placebo in women who had undergone abdominal or pelvic surgery.\n In this multicenter, randomized, double-blind,placebo- and active-controlled, parallel-group trial, women experiencing moderate to severe pain between 14 and 48 hours after surgery were randomized per protocol to receive a single dose of study medication in a 3:3:1:1 ratio (combination oxycodone/ibuprofen, ibuprofen, oxycodone, and placebo, in that order). Over a 6-hour study period, patients recorded their assessments of pain intensity (100-mm visual analog scale and 4-point scale), relief from starting pain, and overall evaluation of study drug based on prespecified definitions and rating scales. Based on these data, the following primary efficacy end points were determined: total pain relief 6 hours after dosing (TOTPAR6) and sum of pain intensity differences 6 hours after dosing (SPID6). Other end points included the time to onset of pain relief, time to use of rescue medication, and patient's global rating of analgesic effectiveness. Tolerability was evaluated on the basis of observed and patient-reported adverse events and findings on physical examination.\n Four hundred fifty-six women participated in the study. They were primarily white and had a mean age of 41.6 years and a mean body weight of 171.5 pounds. Combination treatment was associated with significantly better TOTPAR6 and SPID6 scores compared with ibuprofen alone (P < 0.02 and P < 0.015, respectively), oxycodone alone (P < 0.009 and P < 0.001), or placebo (both, P < 0.001). Fewer patients receiving combination treatment required rescue medication, and the time to use of rescue medication was significantly longer in the combination-treatment group compared with the other groups (P < 0.05). Patients' global ratings of analgesic efficacy were significantly higher in the combination-treatment group compared with all other groups (P < 0.044 vs ibuprofen alone; P < 0.001 vs oxycodone alone and placebo). The onset of pain relief occurred within 15 minutes of dosing with all 4 regimens. Nausea was the most frequently reported treatment-emergent adverse event in all 4 groups. The incidence of treatment-emergent adverse events was highest with placebo (55.0%), followed by oxycodone alone (44.2%), ibuprofen alone (42.3%), and combination treatment (40.8%).\n In this population of women who had undergone abdominal or pelvic surgery, the combination of oxycodone 5 mg/ibuprofen 400 mg was significantly more effective than either agent alone or placebo in the treatment of moderate to severe postoperative pain.", "Pharmacological management of pain for acute and chronic conditions has been guided by a scientific understanding of peripheral and central acting mechanisms for the control of inflammation as well as pain. Oral surgery pain is a reliable model to reference the effectiveness of commonly used analgesics such as ibuprofen and acetaminophen. A total of 706 patients who were experiencing moderate to severe pain received a single dose of ibuprofen, acetaminophen, or placebo. After 6 hours, the degree of pain relief and tolerance was assessed. Ibuprofen has important implications for postoperative pain in clinical practice.", "Ibuprofen liquigel is a solubilized potassium ibuprofen 200-mg gelatin capsule formulation that was approved for over-the-counter use in 1995.\n This study compared the analgesic efficacy and tolerability of ibuprofen liquigel 200 mg, ibuprofen liquigel 400 mg, acetaminophen caplets 1000 mg, and placebo in patients experiencing moderate or severe pain after surgical removal of impacted third molars.\n This randomized, double-blind, parallel-group, 6-hour study was conducted in 210 patients experiencing moderate or severe postoperative pain. Ratings of pain intensity and pain relief were recorded every 15 minutes for the first hour, at 90 and 120 minutes, and then hourly through hour 6. The onsets of first perceptible relief and meaningful relief were recorded using 2 stopwatches. An analysis of variance model was employed to test for significant differences (P < or = 0.05) between treatment groups with respect to pain relief, pain intensity difference, total pain relief (TOTPAR), and summed pain intensity difference (SPID). Stopwatch measures were analyzed using the Cox proportional hazards model. Drug tolerability was assessed by monitoring the occurrence of adverse events.\n During the first 2 hours of the study (TOTPAR 2 and SPID 2), all active treatments were significantly more efficacious than placebo (P < 0.001), with ibuprofen liquigel 200 and 400 mg significantly more efficacious than acetaminophen 1000 mg (P < 0.05 and P < 0.01, respectively). For the entire duration of the study (TOTPAR 6 and SPID 6), only the 2 doses of ibuprofen liquigel were significantly more efficacious than placebo (P < 0.001). Ibuprofen liquigel 200 and 400 mg were also significantly more efficacious than acetaminophen 1000 mg on the summary measures TOTPAR 6 and SPID 6 (P < 0.01 and P < 0.001, respectively). Analysis of the stopwatch data revealed that all active treatments displayed significantly more rapid onsets to confirmed first perceptible relief (P < 0.001 to < 0.05) and meaningful relief (P < 0.001 to < 0.01) than did placebo, with ibuprofen liquigel 400 mg displaying a significantly more rapid onset to meaningful relief than acetaminophen 1000 mg (P < 0.05) and a significantly more rapid onset to confirmed first perceptible relief than acetaminophen 1000 mg (P < 0.001) and ibuprofen liquigel 200 mg (P < 0.01). All adverse events were considered mild or moderate, with an overall incidence of 11.5% in the ibuprofen liquigel 200-mg group, 6.8% in the ibuprofen liquigel 400-mg group, 19.0% in the acetaminophen 1000-mg group, and 25.9% in the placebo group.\n Ibuprofen liquigel provided greater peak and overall analgesic effects and a more rapid onset to analgesia than did acetaminophen 1000 mg.", "Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety-five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double-blind, stratified, parallel-group study. Patients were observed during a 4-hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone 1/2, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low-dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents.", "This single-dose, double-blind, parallel-group, single-site study compared ibuprofen lysine 400 mg with acetaminophen 1000 mg and placebo in 240 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, overall analgesic efficacy, duration of effect, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, need for additional analgesic medication, and patient global evaluation. Both ibuprofen lysine 400 mg and acetaminophen 1000 mg were significantly (P < or = 0.05) more effective than placebo. Ibuprofen lysine had a significantly (P < or = 0.05) faster onset of action with greater peak and overall analgesic effect than did effect than did acetaminophen. All treatments were generally well tolerated.", "The purpose of this work was to compare the efficacy and time to analgesia of a new tramadol/acetaminophen combination tablet to those of tramadol or acetaminophen (APAP) alone. A meta-analysis was performed of 3 separate single-dose, double-blind, parallel-group trials in patients with moderate or severe pain following extraction of 2 or more third molars. Patients in each study were evenly randomized to a single dose of tramadol/APAP (75 mg/650 mg), tramadol 75 mg, APAP 650 mg, ibuprofen 400 mg, or placebo. Active control with ibuprofen was used to determine model sensitivity. Pain relief (scale, 0-4) and pain intensity (scale, 0-3) were reported at 30 minutes after the dose and then hourly for 8 hours. Total pain relief over 8 hours (TOTPAR8) and the sum of pain intensity differences (SPID8) were calculated from the hourly scores. Time to onset of pain relief was determined by the double-stopwatch technique, and patients were advised to wait at least 2 hours before taking supplemental analgesia. Patients assessed overall efficacy (scale, 1-5) upon completion. In all, 1197 patients (age range, 16-46 years) were evaluable for efficacy; treatment groups in each study were similar at baseline. Pain relief was superior to placebo (P < or = .0001) for all treatments. Pain relief provided by tramadol/ APAP was superior to that of tramadol or APAP alone, as shown by mean TOT-PAR8 (12.1 vs 6.7 and 8.6, respectively, P < or = .0001) and SPID8 (4.7 vs 0.9 and 2.7, respectively, P < or = .0001). Estimated onset of pain relief was 17 minutes (95% CI, 15-20 minutes) for tramadol/APAP compared with 51 minutes (95% CI, 40-70 minutes) for tramadol, 18 minutes (95% CI, 16-21 minutes) for APAP, and 34 minutes (95% CI, 28-44 minutes) for ibuprofen. Median time to supplemental analgesia and mean overall assessment of efficacy were greater (P < .05) for the tramadol/APAP group (302 minutes and 3.0, respectively) than for the tramadol (122 minutes and 2.0) or APAP (183 minutes and 2.7) monotherapy groups. A new combination analgesic, tramadol/APAP, is superior to tramadol or APAP alone with respect to pain relief and duration of action. It is also superior to tramadol alone with respect to time to onset.", "In a double-blind, parallel, placebo-controlled study, 203 patients with post-operative dental pain following the extraction of one or two bony impacted third molars were randomized to receive a single dose of naproxen sodium 220 mg, ibuprofen 200 mg or placebo. Pain intensity and pain relief were assessed at intervals for 12 hours postdose. Both active drugs demonstrated superior analgesic efficacy over placebo. Naproxen sodium and ibuprofen were comparable both in onset of analgesic action and in pain relief. From 1 to 12 hours postdose, naproxen sodium showed a trend for superior analgesic efficacy compared with ibuprofen; this trend reached statistical significance at the 12-hour time point. Both drugs were well-tolerated and effective analgesics for postoperative dental pain.", "Hydrocodone is a semisynthetic opioid with analgesic and antitussive properties qualitatively similar to other opioid agonists. Ibuprofen is a nonsteroidal antiinflammatory agent with analgesic and antipyretic activity and is an effective, primarily peripheral-acting antiinflammatory analgesic. The objective of this clinical trial was to determine the additive analgesic effect of the combination of 15 mg hydrocodone bitartrate with 400 mg ibuprofen, relative to 400 mg ibuprofen alone and placebo, in the treatment of postoperative pain. The single-dose analgesic efficacy of the combination of hydrocodone bitartrate with ibuprofen was compared with ibuprofen alone and placebo in 120 patients with moderate or severe postoperative pain after abdominal surgery. Analgesia was measured during the 6-hour period after dosing based on onset of relief, hourly and summary variables, and duration of effect. A significantly greater proportion of patients treated with the hydrocodone/ibuprofen combination reported onset of relief compared with ibuprofen or placebo; however, the distribution functions for time to onset of relief did not differ among treatments. Hydrocodone with ibuprofen and ibuprofen alone were significantly more effective than placebo for all measures of analgesia. The combination of hydrocodone with ibuprofen was significantly superior to ibuprofen for all hourly analgesic evaluations, weighted sum of pain intensity differences (SPID), total pain relief (TOTPAR), and global rating of study medication. No patients in the hydrocodone with ibuprofen group required analgesic remedication during the 6-hour study period, compared with 25% and 82% in the ibuprofen and placebo groups, respectively. The analgesic superiority of 15 mg hydrocodone bitartrate combined with 400 mg ibuprofen compared with 400 mg ibuprofen alone was demonstrated across many efficacy variables.", "A single-dose, double-blind, randomized clinical trial was conducted to examine the relative analgesic efficacy of ibuprofen 400 mg (n = 36), acetaminophen 1000 mg (n = 37), and placebo (n = 38) in postpartum patients who had moderate to severe pain after episiotomy. At regular intervals over 4 hours, patients evaluated pain severity and relief on categorical scales and completed a categorical overall evaluation at the end of the trial. Both active agents were effective compared with placebo (P less than .05). Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for the sum of pain intensity difference, total pain relief, and reduction of pain by more than 50% (P less than .05), suggesting a more rapid onset of action and a more prolonged effect by ibuprofen 400 mg. No adverse effects were reported. Based on the results of this conventional postpartum episiotomy pain model, both agents are considered efficacious and ibuprofen 400 mg is a more effective analgesic for the relief of acute pain than acetaminophen 1000 mg.", "Previous data have suggested that rofecoxib, a cyclooxygenase (COX)-2-specific inhibitor, had analgesic effects similar to those of the nonsteroidal anti-inflammatory drugs when tested in the post-dental surgery pain model. The objective of this parallel-group, double-masked, randomized, placebo- and active comparator-controlled clinical trial was to assess more fully the analgesic efficacy of rofecoxib in the treatment of postoperative dental pain. After dental surgery, 151 patients (50.3% women; mean age, 18.3 years; 93.4% white) experiencing moderate-to-severe pain were to receive a single dose of placebo, rofecoxib 50 mg, or ibuprofen 400 mg. Analgesic efficacy was assessed for up to 24 hours postdose using self-administered questionnaires. Tolerability was assessed using spontaneous reports of adverse experiences, physical findings, and laboratory measurements. The results of this study demonstrated that rofecoxib 50 mg was more effective than placebo on all measures of analgesic efficacy. Rofecoxib 50 mg exhibited overall analgesic effects, onset of analgesia, and peak analgesic effects that were not significantly different from those of ibuprofen 400 mg, with a significantly longer duration of action (P < 0.05). We concluded that rofecoxib was efficacious in the treatment of postoperative dental pain and that COX-2-derived prostanoids play a role in treatment of the pain associated with dental surgery.", "The primary aims of this study were to assess the analgesic efficacy and adverse effects of single-dose oral tramadol plus acetaminophen in acute postoperative pain and to use meta-analysis to demonstrate the efficacy of the combination drug compared with its components. Individual patient data from seven randomized, double blind, placebo controlled trials of tramadol plus acetaminophen were supplied for analysis by the R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey, USA. All trials used identical methods and assessed single-dose oral tramadol (75 mg or 112.5 mg) plus acetaminophen (650 mg or 975 mg) in adult patients with moderate or severe postoperative pain. Summed pain intensity and pain relief data over six and eight hours and global evaluations of treatment effect after eight hours were extracted. Number-needed-to-treat (NNT) for one patient to obtain at least 50% pain relief was calculated. NNTs derived from pain relief data were compared with those derived from pain intensity data and global evaluations. Information on adverse effects was collected. Combination analgesics (tramadol plus acetaminophen) had significantly lower (better) NNTs than the components alone, and comparable efficacy to ibuprofen 400 mg. This could be shown for dental but not postsurgical pain, because more patients were available for the former. Adverse effects were similar for the combination drugs and the opioid component alone. Common adverse effects were dizziness, drowsiness, nausea, vomiting, and headache. In sum, this meta-analysis demonstrated analgesic superiority of the combination drug over its components, without additional toxicity.", "Two randomized, double-blind, parallel-group single-dose 2 x 2 factorial analgesic studies compared a single-dose or a 2-tablet dose of a combination of 7.5 mg hydrocodone bitartrate with 200 mg ibuprofen with each constituent alone and with a placebo in women with moderate or severe postoperative pain from abdominal or gynecologic surgery. A nurse-observer recorded patient reports of pain intensity and pain relief periodically for 8 hours. In both studies, the combination was significantly superior to placebo for sum of the pain intensity differences (SPID), total pain relief (TOTPAR), peak pain intensity difference (PID) and pain relief, global evaluation, and time to remedication. The combination was likewise significantly superior to both hydrocodone and ibuprofen for most of these summary measures of analgesia. In a factorial analysis, both the hydrocodone and ibuprofen effects were significant for most summary measures of analgesia, whereas results of the interaction contrast were consistent with the concept that the analgesic effect of the combination represents the additive analgesia of its 2 constituents.", "To evaluate in a randomised, double-blind, placebo-controlled trial, the efficacy (time to onset of meaningful pain relief) of single doses of buffered ketoprofen (12.5 mg) and ibuprofen (200 mg) in 180 patients with postoperative pain after third molar surgery.\n 180 adult patients who had undergone third molar surgery under general anaesthesia participated in this study. After dosing, patients recorded their time to meaningful pain relief, pain intensity on both visual analogue scales and verbal rating scales, pain relief and the need for additional analgesia. Pain recordings were made at fixed time points over a 6-h investigation period.\n Buffered ketoprofen (12.5 mg) provided quicker meaningful pain relief than placebo (P = 0.023). For secondary efficacy measures (SPIDS4, SPIDS6, TOTPAR4, TOTPAR6), the buffered ketoprofen was significantly superior to both placebo (P < 0.001) and ibuprofen (200 mg) (P < 0.05). Similarly, the amount of time before taking an escape analgesic was significantly less in the placebo group than both the ibuprofen and buffered ketoprofen groups (P < 0.03).\n Buffered ketoprofen (12.5 mg) provides effective pain control in the early postoperative period after third molar surgery. This ketoprofen preparation was also superior to ibuprofen (200 mg) with respect to both reducing pain intensity and providing an earlier onset of pain relief.", "In a single-dose, double-blind, parallel-group, single-site study, ibuprofen lysine 200 mg (IBL 200) was compared with acetylsalicylic acid 500 mg (ASA 500) and placebo in 183 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, duration and degree of analgesia, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, global evaluation, and requirement for additional analgesic medication; both IBL 200 and ASA 500 were significantly more effective than placebo. IBL 200 also had a significantly faster onset of action, greater peak and overall analgesic effect, and longer duration of analgesia than ASA 500. All treatments were generally well tolerated.", "The objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study.", "Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications.", "We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.", "Pregabalin is an analogue of the inhibitory neurotransmitter gamma-aminobutyric acid. In preclinical models, it has shown activity as an analgesic agent. A randomized, double-blind, placebo-controlled, parallel-group trial was undertaken to compare pregabalin to placebo and 400 mg of ibuprofen using a dental pain model. Study medication was administered postoperatively to patients who had undergone elective surgery to remove one or two third molars, at least one of which was mandibular and fully or partially impacted in bone. The study was conducted in the UK at a single centre and evaluated pregabalin at doses of 50 and 300 mg. Primary efficacy parameters included pain relief (PR), pain intensity difference (PID), pain relief intensity difference (PRID), time to onset of analgesia, and duration of analgesia. The patient's global impression of the study medication was used as a secondary efficacy parameter. Efficacy data were evaluated for the intent-to-treat (ITT) population, defined as all randomized patients who took study medication. Results showed that there were statistically significant differences in PR, PID, and PRID between the 300-mg pregabalin group and placebo. In addition, the 300-mg pregabalin group had a significantly longer duration of analgesia than the ibuprofen group and had the highest score on the patient global impression of study medication. Adverse events were reported more frequently in the pregabalin 300-mg group. Pregabalin appears to have significant analgesic properties in the third molar extraction model. Further research is needed to confirm these findings.\n Copyright 2001 European Federation of Chapters of the International Association for the study of pain.", "MK-0703 is a selective cyclooxygenase-2 inhibitor investigated for the treatment of acute pain and inflammation. The purpose of this single-dose, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was to compare MK-0703 12.5, 50, and 100 mg with ibuprofen 400 mg or placebo in patients who experienced moderate to severe pain after surgical removal of at least 2 third molars. Overall analgesic effect, duration of analgesic effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. The primary endpoint of this study was total pain relief over 8 hours postdose. The study included 121 patients (mean age, 23 yr); 16, 31, 28, 31, and 15 patients enrolled in the placebo, MK-0703 12.5 mg, MK-0703 50 mg, MK-0703 100 mg, and ibuprofen 400 mg groups, respectively. Both MK-0703 50 and 100 mg were significantly more effective than placebo for all endpoints (P < 0.01) and comparable with ibuprofen 400 mg. The onset of analgesic effect in the MK-0703 50 mg and 100 mg and ibuprofen 400 mg groups did not differ significantly from each other (P > 0.20). MK-0703 was generally well tolerated in single doses up to 100 mg. In summary, MK-0703 50 and 100 mg were efficacious in the treatment of postoperative dental pain and were indistinguishable from the active comparator, ibuprofen 400 mg.", "This study evaluated trismus, bite force, and pressure algometry as measures of analgesic efficacy after third molar removal.\n Fifty-seven patients (36 females and 21 males) developed at least moderate pain after surgical removal of a mandibular third molar and were given either ibuprofen, 400 mg (n = 26), or placebo (n = 31) in a double-blind study. Pain intensity and pain relief were rated on a five-point verbal rating scale during the 4-hour study period. Recordings of trismus, bilateral pressure pain detection and tolerance thresholds, and bite force were performed before surgery, at medication, and hourly for 4 hours. Changes in the functional variables were calculated as percent change from baseline (before surgery).\n The pain intensity and pain relief ratings showed significant differences between the ibuprofen- and placebo-treated patients in the 4-hour study period. The changes in trismus, bite force, and pressure pain thresholds were in accordance with these pain ratings. Pressure pain detection threshold on the operated side was significantly lower in the placebo-treated patients compared with the ibuprofen-treated patients 2 and 3 hours after medication, whereas pressure tolerance threshold showed a significant difference after 2 hours. Bite force on the operated side was significantly less reduced 3 hours after treatment with ibuprofen when compared with placebo.\n The functional measures used support the results obtained by rating of pain intensity and pain relief, and could be of value as measures of the efficacy of an analgesic to reduce functional impairment caused by postoperative pain.", "Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin (INN, indometacin) inhibit both the constitutive (COX-1) and inducible (COX-2) isoforms of cyclooxygenase. The induction of COX-2 after inflammatory stimuli has led to the hypothesis that COX-2 inhibition primarily accounts for the therapeutic properties of NSAIDs.\n Chinese hamster ovary (CHO) cell lines that express each COX isoform were used to characterize the in vitro selectivity of rofecoxib. Single oral doses of rofecoxib and indomethacin were then assessed in subjects with use of ex vivo COX-isoform specific assays (serum thromboxane B2 [TXB2] and lipopolysaccharide [LPS]-stimulated whole blood prostaglandin E2 and assays of COX-1 and COX-2 activity, respectively). A double-blind, parallel-group study compared the analgesic efficacy of rofecoxib to placebo and ibuprofen in 102 patients with dental pain.\n Rofecoxib showed a >800-fold COX-2 selectivity with use of CHO cells that express human COX-1 and COX-2. In subjects, dose- and concentration-dependent inhibition of LPS-stimulated prostaglandin E2 was observed with both rofecoxib (IC50 [the concentration estimated to produce 50% inhibition], 0.77 micromol/L) and indomethacin (IC50, 0.33 micromol/L). Whereas indomethacin inhibited TXB2, (IC50, 0.14 micromol/L), no inhibition was observed with rofecoxib even at doses of up to 1000 mg. In the dental pain study, total pain relief (TOTPAR) over the 6 hours after dosing was similar between 50 mg and 500 mg rofecoxib and 400 mg ibuprofen (P > .20). All active treatments showed greater improvement than placebo (P < .001)\n Rofecoxib inhibited COX-2 without evidence of COX-1 inhibition, even at oral doses of up to 1000 mg. Nonetheless, rofecoxib showed analgesic activity indistinguishable from that observed with ibuprofen, a nonisoform-selective COX inhibitor. These results support the hypothesis that the analgesic effects of NSAIDs primarily derive from inhibition of COX-2.", "This study compared the efficacy and safety of a single dose of oxycodone 5 mg/ibuprofen 400 mg versus its individual components and placebo in a third-molar extraction model.\n In this multicenter, double-blind, double-dummy, parallel-group investigation, subjects with moderate to severe pain within 5 hours after extraction of > or =2 ipsilateral bony impacted third molars were randomized to single doses of oxycodone 5 mg/ibuprofen 400 mg, ibuprofen 400 mg, oxycodone 5 mg, or placebo. Primary efficacy variables were the sum of pain intensity difference over 6 hours (SP1D6) and total pain relief through 6 hours (TOTPAR6). The pharmacokinetics of oxycodone and ibuprofen, alone and in combination, were also determined in a subset of patients.\n A total of 498 subjects were randomized to treatment (187 to oxycodone 5 mg/ibuprofen 400 mg, 186 to ibuprofen 400 mg, 63 to oxycodone 5 mg, and 62 to placebo). Baseline demographics were generally similar among treatment groups, despite differences in sex (P = 0.041) and race (P = 0.023). Combination therapy was associated with greater analgesia than ibuprofen alone, oxycodone alone, or placebo (mean [SE] TOTPAR6: 13.3 [0.52], 12.2 [0.52], 4.3 [0.82], and 4.2 [0.83], respectively [P < 0.001 vs oxycodone or placebo, P = 0.012 vs ibuprofen]; mean [SE] SP1D6: 6.54 [0.42], 5.41 [0.44], 0.14 [0.60], and 0.32 [0.59], respectively [P < 0.001 vs oxycodone or placebo, P = 0.002 vs ibuprofen]). Combination therapy was well tolerated. Pharmacokinetic results implied no interaction between oxycodone and ibuprofen.\n In this study, a single dose of oxycodone 5 mg/ibuprofen 400 mg was fast-acting, effective, and well tolerated in subjects with moderate to severe pain after dental surgery. Oxycodone 5 mg alone did not provide an efficacy benefit over placebo in this study.", "The purpose of this project was to evaluate the analgesic efficacy of misoprostol when combined with ibuprofen or diclofenac Na. Animal experiments using the inflamed rat paw formalin model suggested that misoprostol potentiates the analgesic effect of some NSAIDs (nonsteroidal anti-inflammatory drugs) including diclofenac Na but not propionic acid derivatives or opiates. The dental pain model was used to evaluate the clinical relevance of this interaction. Patients received a single oral dose of study medication following surgical removal of impacted teeth. Patients were medicated for moderate to severe postsurgical pain and then filled in an analgesic diary for a 6-h observation period. Several blood samples were taken over the observation period. In addition, microdialysis samples were taken directly from the extraction socket and were analyzed for immunoreactive prostaglandin E(2) levels. The studies were single-dose, parallel group and double-blind assays. In the first study, 70 patients received an oral dose of either placebo (n = 13), misoprostol 200 &mgr;g (n = 18), ibuprofen 200 mg (n = 19), or the combination of misoprostol + ibuprofen (n = 20). Misoprostol alone demonstrated a small analgesic effect compared to placebo. Both the ibuprofen and combination groups were substantially more effective than placebo but not different from each other. The combination group had higher ibuprofen blood levels during the first 45 min but had a lower C(max) and longer time to T(max). The second study evaluated oral doses of placebo (n = 11), misoprostol 200 &mgr;g (n = 21), diclofenac Na 50 mg (n = 18), and the combination of misoprostol + diclofenac Na (n = 20). Relative to placebo, misoprostol performance was similar to the first study. When the results of the two studies were combined, there was a small, but statistically significant, analgesic effect for misoprostol. Diclofenac Na was superior to both placebo and to misoprostol alone. The combination was the most effective treatment, and for hours 4--6 it was significantly better than diclofenac Na alone. Analysis of the blood samples showed an earlier and higher peak effect for the diclofenac Na group compared to the combination, and the combination again had a lower C(max). The microdialysis probe assays demonstrated that misoprostol depressed PGE(2) levels at the peripheral site of trauma over the first 2 h after surgery. These pilot studies used small samples, and the results only suggest trend effects. Both studies demonstrated that misoprostol 200 &mgr;g, a prostaglandin analog, does have an analgesic effect. When combined with ibuprofen, there was no potentiation of analgesia. In contrast, the combination of misoprostol + diclofenac Na demonstrated an enhanced peak effect, total effect for pain intensity difference and pain relief (sum pain intensity difference [SPID] and total pain relief [TOTPAR]), and", "The object of a study was to evaluate the analgesic efficacy of ibuprofen for dental pain. The subjects were outpatients who were undergoing surgical removal of impacted teeth. We compared aspirin, 325 mg; aspirin, 650 mg; ibuprofen, 200 mg; ibuprofen, 400 mg; and placebo. Each patient received a single dose of one of the test medications; there was a minimum of 37 patients in each treatment group. Patients recorded pain intensity before receiving medication; then hourly, for four hours after medication, they recorded pain intensity, amount of relief, and side effects. Time-effect and dose-response curves were generated from the relief and change in pain-intensity scores. First-hour scores, peak scores, and total scores were analyzed. All active medications were significantly better than placebo and the mean effect for ibuprofen was significantly more than for aspirin.", "Rofecoxib and celecoxib, selective cyclooxygenase-2 inhibitors, have analgesic efficacy similar to that of nonselective nonsteroidal anti-inflammatory drugs.\n This study was designed to confirm earlier findings that the overall analgesic efficacy of rofecoxib 50 mg was superior to that of celecoxib 200 mg and to extend the comparison to include celecoxib 400 mg.\n In this single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study, patients who experienced moderate or severe pain after surgical extraction of at least 2 third molars received a single oral dose of either rofecoxib 50 mg, celecoxib 400 mg, celecoxib 200 mg, ibuprofen 400 mg, or placebo. Patients recorded scores of pain intensity, pain relief, and global assessment at prespecified time intervals throughout the 24-hour period after dosing. The end points were total pain relief (TOPAR) score over 8 hours (TOPAR8; primary end point), TOPAR score over 12 hours (TOPAR12), sum of pain intensity difference (SPID) over 8 and 12 hours (SPID8 and SPID12), patient's global assessment of study drug at 8 hours, time to confirmed perceptible pain relief (ie, time to onset of analgesic effect), peak pain intensity difference (PID), peak pain relief, time to first dose of rescue medication (ie, duration of analgesic effect), and percentage of patients using rescue medication.\n A total of 482 patients (358 females, 124 males; mean age, 22.1 years) were enrolled. Rofecoxib 50 mg (n = 151 patients) demonstrated significantly greater overall analgesic efficacy compared with celecoxib 400 mg (n = 151), as measured by TOPAR8 (least squares mean [SE] 17.2 [0.8] vs 15.0 [0.8]; P < 0.05) and TOPAR12 (25.3 [1.2] vs 21.0 [1.2]; P < 0.05), as well as a significantly longer duration of analgesic effect (P < 0.05). Time to onset of analgesic effect and peak analgesic effect were similar for rofecoxib 50 mg and celecoxib 400 mg. Rofecoxib also showed significantly greater overall analgesic efficacy than did celecoxib 200 mg (n = 90), including greater TOPAR8 scores (17.2 [0.8] vs 11.5 [1.1]; P < 0.001), faster onset of analgesic effect (P < 0.001), greater peak analgesic effect (P < 0.001 for peak pain relief and peak PID), and longer duration of analgesic effect (P < 0.001). The overall analgesic efficacy of rofecoxib 50 mg was similar to that of ibuprofen 400 mg (n = 45), except that the duration of analgesic effect of rofecoxib 50 mg was significantly longer (P < 0.001). All active treatments produced significantly greater overall analgesic efficacy compared with that of placebo (P < 0.001 for all scores [TOPAR8, TOPAR12, SPID8, SPID12, and patient's global assessment] for all study drugs). The adverse-events (AE) profile was generally similar in all treatment groups. The 3 most common AEs were nausea, postextraction alveolitis, and vomiting.\n In this study, rofecoxib 50 mg provided generally superior overall analgesic efficacy compared with that of celecoxib 400 and 200 mg, including a significantly longer duration of analgesic effect. The overall analgesic efficacy of rofecoxib 50 mg was generally similar to that of ibuprofen 400 mg, except for a significantly longer duration of analgesic effect.", "The objective of this single dose, double-blind study was to determine the relative analgesic efficacy of low-dose ketoprofen (6.25 mg, 12.5 mg, and 25 mg) compared with ibuprofen (200 mg) and placebo in 175 patients with moderate to severe postoperative pain secondary to extraction of impacted third molars. Analgesia was measured during the 6-hour period after administration based on onset of relief, hourly and summary variables, and duration of treatment effect. All active treatments were significantly more effective than placebo for many hourly measures and for the summary measures sum of pain intensity differences (SPID), sum of hourly pain relief values (TOTPAR), time to peak pain relief, and patient global assessment of study medication. The three ketoprofen doses were significantly more effective than placebo beginning at 30 minutes, whereas ibuprofen was significantly better than placebo beginning at 1 hour. A dose-response relationship was observed for ketoprofen, with the two higher doses providing significantly greater analgesia than the lower dose. However, a plateau effect was seen between the 12.5-mg and 25-mg dose levels. A significantly greater proportion of patients treated with each of the active treatments (ranging from 0.83 to 0.88) reported onset of relief compared with placebo (0.20). The distribution functions of onset of relief differed significantly among treatments, with ketoprofen 12.5 mg and 25 mg having a faster onset than ibuprofen 200 mg and ketoprofen 6.25 mg. The duration of effect was generally shorter for ketoprofen than for ibuprofen, and these difference were significant. This study provides evidence that at the dose levels of 12.5 mg and 25 mg, ketoprofen is an effective analgesic in providing relief of postoperative dental pain. Ketoprofen 12.5 mg and 25 mg provide significantly greater relief in the earlier time period, with a faster onset and shorter duration of effect than ibuprofen 200 mg. The two higher doses of ketoprofen provided similar analgesia, and no additional benefit was obtained by increasing the dose of ketoprofen to 25 mg. Therefore, we conclude that ketoprofen 12.5 mg is an appropriate dose for over-the-counter use.", "Patients experiencing acute pain after surgery, including dental surgery, often require analgesia. Ideally, the chosen analgesic should have a rapid onset and sustained effect. Etoricoxib is a new cyclooxygenase-2-selective inhibitor that has demonstrated analgesic efficacy in the treatment of acute pain with a rapid onset and long-lasting pain relief.\n The goal of this study was to determine the analgesic effect of single oral doses of etoricoxib 60, 120, 180, and 240 mg compared with placebo in the treatment of pain after dental surgery. Ibuprofen was used as an active control.\n This was a randomized, double-blind, parallel-group, single-dose, placebo- and active comparator-controlled study performed at a single center. It consisted of 3 visits (prestudy, treatment, and poststudy). Eligible patients were aged > or =16 years with moderate or severe pain after surgical extraction of > or =2 third molars, of which > or =1 was an impacted mandibular molar. Patients were assessed over 24 hours and reported pain intensity and pain relied at 14 predefined time points. Plasma samples for a pharmacokinetic/pharmacodynamic analysis were collected from a subset of patients at baseline and the 14 predefined time points. The end points included total pain relief over 8 hours (TOPAR8, the primary end point), sum of pain intensity difference over 8 hours, patient's global evaluation of treatment, median time to onset of pain relief (2-stopwatch method), peak pain relief, and duration of analgesic effect (median time to use of rescue medication). Adverse events were collected up to 14 days postdose.\n Three hundred ninety-eight (63.1% women, 36.9% men; mean age, 21.1 years; 72.1% white, 27.9% other; mean number of third molars removed, 3.5; 65.2% experiencing moderate pain) were randomly allocated to receive etoricoxib 60 mg (n = 75), etoricoxib 120 mg (n = 76), etoricoxib 180 mg (n = 74), etoricoxib 240 mg (n = 76), ibuprofen 400 mg (n = 48), and placebo (n = 49). All active treatments had significantly greater overall analgesic effect (TOPAR8) compared with placebo (P < or 0.001). Patients who received etoricoxib 120 and 180 mg had significantly higher TOPAR8 scores than those who received etoricoxib 60 mg ( P < = 0.001) and ibuprofen (P < 0.05 etoricoxib 120 mg; P < or = 0.001 etoricoxib 180 mg). Least-squares mean TOPAR8 scores for etoricoxib 60, 120, 180, and 240 mg, ibuprofen, and placebo were 16.0, 22.0, 23.5, 20.7, 18.6, and 5.2, respectively. The median time to onset of analgesia was 24 minutes for etoricoxib 120, 180, and 240 mg, and 30 minutes for etoricoxib 60 mg and ibuprofen. There were no significant differences in the onset of analgesia between etoricoxib 120, 180, and 240 mg and ibuprofen. The duration of analgesic effect was >24 hours for etoricoxib 120, 180, and 240 mg, and 12.1 hours for etoricoxib 60 mg. The duration of effect was significantly longer with all 4 etoricoxib doses compared with ibuprofen (10.1 hours; P < 0.05 etoricoxib 60 mg; < or = 0.001etoricoxib 120, 180, and 240 mg) and compared with placebo (2.1 hours; P < = 0.001). In the pharmacokinetic/pharmacodynamic analysis (n approximately 120), there was a linear relationship between plasma etoricoxib concentrations and pain relief scores up to the maximum observed concentration, followed by a decline in plasma concentrations with persistent analgesia. The most common adverse events were postextraction alveolitis and nausea. Conclusions: In this dose-ranging study, etoricoxib 120 mg was determined to be the minimum dose that had maximal efficacy in patients with moderate to severe acute pain associated with dental surgery. Both etoricoxib and ibuprofen were generally well tolerated.", "1. Two separate placebo-controlled studies of parallel design were carried out to evaluate the efficacy of single doses (400 mg) of soluble ibuprofen, ibuprofen liquid in a gelatin capsule and ibuprofen tablets (Nurofen), in patients with postoperative pain after third molar surgery. 2. All ibuprofen preparations provided significant pain relief (P less than 0.05) over a 6 h investigation period. 3. Mean pain scores after ibuprofen tablets and ibuprofen liquid in a gelatin capsule were similar. 4. Soluble ibuprofen 400 mg provided an earlier onset of pain relief (20 min) than ibuprofen tablets (30 min). 5. No unwanted effects were reported in the various ibuprofen treatment groups. 6. The ibuprofen preparations evaluated in this study are effective up to 4 h for controlling postoperative pain after third molar surgery. The soluble form is more efficacious with regard to onset of action.", "A single-dose, double-blind, randomized, parallel trial was conducted to compare the analgesic efficacy of oral ibuprofen (I) 100, 200, or 400 mg, aspirin (ASA) 650 mg, and placebo in moderate to severe pain after extraction of impacted teeth. Subjective, self-evaluated pain intensity and pain relief reports, hourly for 6 hours, were used as indexes of analgesic response. Data on 227 evaluable patients showed significant differences among the 4 active treatments and placebo (p less than 0.001) by most measurements of analgesia. Although no consistent, significant differences were observed among the active drugs, I 400 mg performed the best, followed by I 200 mg, ASA 650 mg, and I 100 mg. Remedication was required by 59% patients receiving I 400 mg, 67% taking I 200 mg, 73% taking ASA 650 mg, 74% taking I 100 mg, and 96% receiving placebo. Differences between I 400 mg and I 100 mg were significant for remedication data (p less than 0.05). Side effects were minor, infrequent, and not dose related. In this study, I 100 mg was distinctly superior to placebo and probably as effective as ASA 650 mg in relieving pain. Only a shallow dose response of ibuprofen was observed.", "Because of its enhanced pharmacokinetic characteristics, ibuprofen arginate might be expected to provide faster pain relief than standard ibuprofen formulations in patients experiencing acute pain.\n This study assessed the analgesic efficacy, speed of onset, and tolerability of ibuprofen arginate compared with a commercially available form of ibuprofen in patients with postoperative dental pain.\n Patients were randomized to receive ibuprofen arginate 200 or 400 mg, ibuprofen 200 or 400 mg, or placebo in this multicenter, double-blind, double-dummy, parallel-group trial. Patients were observed for 6 hours after administration of a single dose of study medication. A repeated-dose, open-label phase followed. Pain intensity and pain relief were measured using traditional verbal descriptor scales; onset of analgesia was assessed using 2 stopwatches to measure the time to achievement of specific pain relief criteria.\n A total of 498 patients (219 men, 279 women; mean age, 21.5 years) participated in this study. Baseline pain was moderate in 388 patients (78%) and severe in 110 patients (22%). Meaningful pain relief was reached after a median of 29 and 28 minutes with ibuprofen arginate 200 and 400 mg, respectively, and after 52 and 44 minutes with ibuprofen 200 and 400 mg, respectively (all, P < 0.05). The percentages of patients who achieved meaningful pain relief within the first hour after treatment were 77.6% and 83.7% for ibuprofen arginate 200 and 400 mg, respectively, 61.0% and 63.0% for ibuprofen 200 and 400 mg, respectively, and 39.8% for placebo. The differences between ibuprofen arginate and ibuprofen were statistically significant (both doses, P < 0.05). Significantly greater numbers of patients achieved meaningful pain relief with ibuprofen arginate 400 mg compared with placebo from 20 minutes through 6 hours and with ibuprofen arginate 200 mg from 30 minutes through 6 hours (P < 0.05). Compared with placebo, a greater number of patients achieved meaningful pain relief with ibuprofen 400 mg from 45 minutes through 6 hours; with ibuprofen 200 mg. the corresponding interval was from I through 6 hours. After the first hour, pain reduction was similar for the similar doses of the 2 ibuprofen preparations. Median remedication times with both doses of ibuprofen arginate were similar to those with both doses of ibuprofen, ranging from 4.0 to 5.2 hours. Adverse-event profiles were similar between the 2 active medications.\n Ibuprofen arginate was effective in this population of patients experiencing moderate to severe pain after surgical extraction of > or = 1 impacted third molar, with 16 to 24 minutes' faster time to meaningful pain relief than with ibuprofen. The 2 formulations had similar tolerability profiles.", "Although dihydrocodeine (DF118) is widely prescribed by general dental practitioners, there is little evidence that it is successful in controlling post-operative dental pain. Ibuprofen is known to be effective in this situation. A single dose, double-blind study was carried out in 148 patients to compare 400 mg ibuprofen with 30 mg dihydrocodeine and placebo for treating moderate to severe pain following the removal of unilateral, impacted mandibular third molar teeth under local anaesthesia. An additional dose of either ibuprofen or dihydrocodeine was available after 2 hours. The post-operative ibuprofen reduced pain and produced more pain relief than dihydrocodeine or placebo. Furthermore, fewer patients receiving ibuprofen took additional analgesic at 2 hours. Patients who received ibuprofen as supplementary medication also experienced less pain and had greater pain relief than those receiving dihydrocodeine as supplementary medication, even when their post-operative treatment had been placebo. More patients reported the medication as having been effective if they took ibuprofen either post-operatively or as supplementary analgesia. Ibuprofen is an appropriate analgesic for treating post-operative dental pain.", "Two hundred forty-one outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of bromfenac 5, 10, or 25 mg, aspirin 650 mg, ibuprofen 400 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief for 8 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments were significantly superior to placebo, and the slope of the dose-response curve for bromfenac was significant. Bromfenac 5 mg and aspirin 650 mg were equianalgesic; bromfenac 25 mg was slightly more efficacious than ibuprofen 400 mg. Bromfenac 25 mg and ibuprofen 400 mg were significantly superior to the other active treatments. Adverse effects were transient and consistent with the pharmacologic profiles of the medications evaluated.", "This randomised, double-blind study compared single dose lumiracoxib (a cyclooxygenase-2 selective inhibitor) 100 and 400 mg, ibuprofen 400 mg and placebo in patients with postoperative dental pain over 12 h. The primary efficacy variable was pain intensity difference. Lumiracoxib 400 mg and ibuprofen were superior to placebo from 1 to 12 h post dose while lumiracoxib 100 mg was superior from 1.5 to 9 h. Lumiracoxib 400 mg demonstrated the fastest median time to onset of analgesia (37.4 min) followed by ibuprofen (41.5), and lumiracoxib 100 mg (52.4; all p < or = 0.001 vs. placebo). Median time to rescue medication (h) was longer for lumiracoxib 400 mg (> or = 12), lumiracoxib 100 mg (approximately 7) and ibuprofen (approximately 8) than placebo (approximately 2; all p < or = 0.001 vs. placebo). Patients rated lumiracoxib 400 mg superior to the other active treatments (p < 0.05); lumiracoxib 100 mg was comparable with ibuprofen and superior to placebo (p < 0.001). Lumiracoxib provided rapid, effective and well-tolerated analgesia.", "Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double-blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self-rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti-inflammatory drugs other than acetaminophen or aspirin.", "The purpose of this study was to compare the analgesic efficacy and safety of meclofenamate sodium with ibuprofen after dental impaction surgery. This study was double-blind and used a unique methodology. Patients (N = 254) were first randomized into the single dose phase of the study that included placebo, meclofenamate 50 mg, meclofenamate 100 mg, ibuprofen 200 mg, and ibuprofen 400 mg, followed by a 7-day multidose phase in which patients in the placebo group were rerandomized into one of the active treatment cells. In the single dose phase, all active treatments were significantly more efficacious than placebo for every summary analgesic measure. A positive dose-response was seen for both active drugs with meclofenamate 100 mg and ibuprofen 400 mg exhibiting the greatest efficacy for pain relief, pain reduction, time to remedication, and overall evaluation. Side effects were reported by 26 patients. They were evenly distributed among treatment groups with headache and drowsiness being the most common. During the multidose phase, there were only small differences in efficacy measures among active treatment groups. However, meclofenamate produced a higher incidence of stomach cramps and diarrhea than did ibuprofen (8.8% and 7.2% versus 0.8% and 0.8%). This study indicates that higher doses of nonsteroidal anti-inflammatory drugs are most effective immediately after surgery and that lower doses of these drugs can be used after the first postoperative day. The side effect profile of nonsteroidal anti-inflammatory analgesics is best observed with the use of a multidose study design.", "The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.", "Pain is a common complaint, often occurring in conjunction with inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic agents in ambulatory patients. In recent studies, the cyclooxygenase-2 (COX-2) inhibitor rofecoxib demonstrated analgesic effects similar to those of NSAIDs in the treatment of acute pain and primary dysmenorrhea. The present randomized, single-dose, double-blind, double-dummy, placebo- and active-comparator-controlled, parallel-group study was undertaken to compare the analgesic efficacy of the COX-2 inhibitors rofecoxib 50 mg and celecoxib 200 mg with that of ibuprofen 400 mg and placebo in patients with postoperative dental pain. Two hundred and seventy-two patients experiencing pain after the removal of > or =2 third molars were randomized according to pain severity (moderate vs severe) to receive a single dose of placebo (n = 45), rofecoxib 50 mg (n = 90), celecoxib 200 mg (n = 91), or ibuprofen 400 mg (n = 46). Using a patient diary, patients recorded pain intensity, pain relief, and global evaluations throughout the 24-hour period after dosing. The overall analgesic effect, onset of action, peak effect, and duration of effect were evaluated, with the primary end point being total pain relief over 8 hours (TOPAR8). The safety profile was assessed on the basis of physical findings, laboratory results, and spontaneous reports of adverse experiences. The results showed that compared with celecoxib, rofecoxib had superior analgesic effects on all measures of analgesic efficacy, including overall analgesic effect (TOPAR8, 18.3 vs. 12.5; P<0.001), time to onset of effect (30 vs. 60 minutes; P = 0.003), peak pain relief (score, 2.8 vs 2.3; P<0.05), and duration of effect (>24 vs. 5.1 hours; P<0.001). In addition, rofecoxib's analgesic efficacy was similar to that of ibuprofen (TOPAR8, 18.3 vs. 17.0; P = 0.460), but the duration was longer (P<0.05); with ibuprofen, the time to on set was 24 minutes, peak pain relief score was 2.9, and duration of analgesic effect was 8.9 hours. The safety profile was similar across all treatment groups. Thus rofecoxib provided analgesic efficacy superior to that of celecoxib and comparable to that of ibuprofen in the treatment of patients with acute postoperative dental pain.", "Peripheral nociceptive barrage after tissue injury results in acute pain and a variety of physiologic responses, including pituitary secretion of beta-endorphin. This study evaluated whether administration of the pharmacologically active S(+)-isomer of ibuprofen suppresses acute pain and plasma beta-endorphin levels in the oral surgery model of acute pain.\n Subjects in a single-dose, double-blind, parallel-group study received either 200 mg S(+)-ibuprofen, 400 mg S(+)-ibuprofen, 400 mg racemic ibuprofen, or placebo. Both doses of S(+)-ibuprofen resulted in significantly greater analgesia over the first 60 minutes in comparison to racemic ibuprofen and placebo; the 400 mg dose of S(+)-ibuprofen also produced greater analgesia at 2 and 3 hours. Plasma levels of immunoreactive beta-endorphin decreased over time coincident with the onset of analgesia in all groups but were significantly less than placebo after both doses of S(+)-ibuprofen from 30 to 120 minutes.\n These findings show that, compared with racemic ibuprofen, administration of the S(+)-isomer of ibuprofen results in faster analgesic onset, greater peak analgesia, similar duration of action, and a low incidence of adverse effects, while suppressing nociceptive activation of the pituitary-adrenal axis.", "Celecoxib 200 mg has been reported to reduce pain following dental extraction but to offer poorer pain relief than active comparators.\n The aim of this study was to compare the efficacy and tolerability of celecoxib 400 mg, the recommended loading dose for treatment of acute pain, with that of ibuprofen 400 mg and placebo following oral surgery.\n This was a single-dose, 2-center, randomized, double-blind, active- and placebo-controlled study in which patients with moderate to severe pain following third molar extraction were randomized to receive a single dose of celecoxib 400 mg, ibuprofen 400 mg, or placebo. Pain assessments were completed using a 4-point pain intensity scale where 0=no pain and 3=severe pain and a 5-point pain relief scale where 0=no pain relief and 4= complete pain relief at baseline and 18 time points over 24 hours. Primary efficacy outcome measures were time to onset of analgesia (the median time to perceptible pain relief in those patients who achieved meaningful pain relief), time-specific pain intensity difference (PID), time-specific pain relief (PR), time-specific sum of PID and PR, and time to use of rescue medication. Times to perceptible and meaningful pain relief (secondary efficacy outcome measures) were recorded using 2 stopwatches. Tolerability was assessed through recording of adverse events, clinical laboratory tests, and physical examinations (including collection of vital signs).\n One hundred seventy-one patients were randomized to celecoxib 400 mg (30 women and 27 men; mean [SD] age, 21.4 [4.2] years); ibuprofen 400 mg (30 women and 27 men; mean [SD] age, 22.0 [4.7] years); or placebo (34 women and 23 men; mean [SD] age, 21.6 [5.0] years). Mean times to onset of analgesia with celecoxib 400 mg and ibuprofen 400 mg were rapid and comparable (median 28 minutes and 26 minutes, respectively) and were significantly shorter than with placebo (>24 hours) (both, P<0.05 vs placebo). Compared with placebo, mean time-specific PID scores were significantly greater with celecoxib from 0.5 to 24 hours and with ibuprofen from 0.5 to 16 hours (all, P<0.05 vs placebo). Time-specific PR scores with celecoxib and ibuprofen were significantly greater from 0.75 and 0.5 hour, respectively, compared with placebo (all, P<0.05 vs placebo). PID was significantly greater with celecoxib compared with ibuprofen beginning at 11 hours (all, P<0.05). PR scores were significantly higher with celecoxib versus ibuprofen beginning at 9 hours (all, P<0.05). Median (95% CI) time to use of rescue medication with celecoxib (>24 hours) was significantly longer than with ibuprofen (10 hours, 58 minutes [8 hours, 30 minutes- 14 hours, 34 minutes]) or placebo (1 hour, 51 minutes [1 hour, 40 minutes-2 hours, 22 minutes]) (both, P<0.05). The 3 most common adverse events experienced in the celecoxib group were headache (9 [15.8%] patients), nausea (9 [15.8%] patients), and dizziness (6 [10.5%] patients).\n In this postsurgical dental pain study, the onset and magnitude of pain relief with celecoxib 400 mg and ibuprofen 400 mg were found to be comparable. In addition, patients who received celecoxib 400 mg as a single dose had a significantly longer time to use of rescue medication and had higher pain relief scores later in the study than those who received ibuprofen 400 mg. Celecoxib was well tolerated compared with placebo.", "A clinical trial comparing ibuprofen, 400, 600, and 800 mg, with aluminum ibuprofen, 400 mg, and placebo was conducted in patients with moderate or severe pain subsequent to third molar extraction. Pain intensity ratings and ibuprofen serum levels were obtained at baseline, 30 minutes, 1 hour, and hourly thereafter for 3 hours. Pain intensity ratings were also obtained at hours 4, 5, and 6. Serum levels at 1, 2, and 3 hours correlated significantly with the log dose of ibuprofen (r = 0.35, 0.49, and 0.48, respectively) and with global analgesic response as measured by the percentage of the sum of the pain intensity scores (r = 0.28, 0.34, and 0.26, respectively). However, possibly because of differences in drug formulation, the percentage of the sum of the pain intensity scores did not correlate significantly with log dose. The highest correlations were found between contemporaneous serum levels and pain intensity difference values, particularly at hour 1 (r = 0.54). Our results support the proposition that increased ibuprofen serum levels lead to increased analgesia.", "We have compared single oral doses of drinkable diclofenac dispersible (50 mg) with ibuprofen (400 mg) and placebo in a randomized, double-blind, parallel-group trial in 127 adults complaining of at least moderately severe pain after removal of an impacted third molar. Within 40 min both diclofenac and ibuprofen produced significant pain relief that persisted for 6 h. There were no differences between diclofenac and ibuprofen in analgesic efficacy.", "Post-tonsillectomy analgesia from ibuprofen, aspirin and placebo is compared in a double-blind study. The results are reported showing ibuprofen to have greater therapeutic benefit than placebo whereas aspirin did not. Methods of providing pain relief after tonsillectomy and the relative clinical merits of ibuprofen and aspirin are discussed.", "The analgesic efficacy of a single 200-mg dose of fendosal, a nonnarcotic, nonsteroidal antiinflammatory analgesic, was compared, in a double-blind study, with aspirin 650 mg, ibuprofen 400 mg and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medicating. Each active medication was significantly superior to placebo. The peak analgesic effect of fendosal 200 mg was similar to that of the aspirin 650-mg standard. Although fendosal's onset of action was slow (3 hours), its effect persisted for 8 hours, substantially longer than that of aspirin. Ibuprofen 400 mg was statistically significantly superior to aspirin 650 mg and fendosal 200 mg for most measures of peak and total analgesia, and its effect persisted for 8 hours. The results of this study raise some questions concerning the comparability of data from studies that employ different criteria for remedication and/or different criteria for the inclusion of data in the analyses of efficacy.", "Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given, under double-blind, randomized conditions, a single dose of either codeine 60 mg, aspirin 650 mg, ibuprofen 400 mg, aspirin 650 mg + codeine 60 mg, ibuprofen 400 mg + codeine 60 mg, or placebo. A total of 249 subjects were included in the statistical analysis. On a report form, subjects recorded pain intensity, pain relief, and side effects hourly for four hours. They also gave an overall impression at the end of the observation period. Analysis of variance and pairwise contrasts were used to analyze the data. For the sum of pain intensity differences, the total of the hourly pain relief scores, and overall impression, there was a significant analgesic effect for codeine, aspirin, and ibuprofen and no significant interaction when they were used in combination. Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination. The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter, but it was not statistically superior to ibuprofen alone. The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model. There was no notable difference in the frequency or intensity of side effects among the treatment groups, and no subject had to withdraw due to an adverse effect. This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination. Codeine added a small amount of additional analgesia when used in combination with ibuprofen.", "Ibuprofen is a safe and effective analgesic, but some formulations have a slow onset of action. Ibuprofen arginate is a rapidly absorbed salt designed to promote more rapid onset of analgesia. A clinical trial was conducted in 226 patients with postoperative dental pain to assess the analgesic efficacy and speed of onset of the arginine salt of ibuprofen compared with one of the commercially available forms of ibuprofen. Patients were administered a single dose of either ibuprofen arginate (200 mg or 400 mg), ibuprofen (200 mg or 400 mg), or placebo in this double-blind, randomized trial. To determine the onset of action of the study medication patients were required to note time to \"any\" pain relief and then time to \"meaningful\" pain relief, using the two-stopwatch method. Pain intensity and relief were assessed using traditional categorical scales over a 6-h period. Meaningful pain relief was achieved in 42 min and 24 min for ibuprofen arginate 200 mg and 400 mg, respectively, compared with 50 min and 48 min for ibuprofen 200 mg and 400 mg, respectively ( P<0.05). The results for the measurements of analgesic effectiveness [sum of pain intensity difference, total pain relief (TOTPAR), peak pain relief and overall evaluation of treatment] all showed that both doses of ibuprofen arginate and both doses of ibuprofen were significantly better than placebo and both 200-mg and 400-mg ibuprofen arginate doses were significantly better than ibuprofen 200 mg for peak pain relief. Mean plasma ibuprofen concentrations at 30 min and 60 min, respectively, were: ibuprofen arginine 200 mg, 13.9 micro g/ml and 15.7 micro g/ml; ibuprofen arginine 400 mg, 29.5 micro g/ml and 29.3 micro g/ml; ibuprofen 200 mg 2.5 micro g/ml and 5 micro g/ml; ibuprofen 400 mg, 2.3 micro g/ml and 7.4 micro g/ml. ( P<0.05). Adverse event profiles were similar across treatment groups. These results overall suggest that ibuprofen arginate when taken at doses equivalent to commercially available ibuprofen formulations produces analgesia that is faster in onset." ]

[ "18675959", "17454195", "3105906" ]

[ "Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study.", "Ovarian function after cancer treatment in young women affected by Hodgkin disease (HD).", "Failure to preserve fertility in patients with Hodgkin's disease." ]

[ "To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not.\n Prospective randomized controlled study.\n Department of Obstetrics and Gynecology, Mansura University Hospital, Mansura, Egypt.\n Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study. Patients were assigned randomly to receive combined GnRHa and chemotherapy or chemotherapy alone. One woman in each group dropped out.\n Return of spontaneous menstruation and ovulation. Hormonal changes (FSH, LH, E(2), P) during and after the course of treatment.\n In the study group, 89.6% resumed menses and 69.2% resumed spontaneous ovulation within 3-8 months of termination of the GnRHa/chemotherapy cotreatment; 11.4% experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment. In the control group (chemotherapy without GnRHa), 33.3% resumed menses and 25.6% resumed normal ovarian activity. The median FSH and LH concentrations, 6 months after completion of the GnRHa/chemotherapy cotreatment group, were significantly less than the control group. During the GnRHa/chemotherapy cotreatment the concentrations of FSH, LH, and P decreased to almost prepubertal levels. However, within 1-3 months after the last GnRHa injection, an increase in LH and FSH concentrations was detected, followed several weeks later in by an increase in P concentrations to within normal levels.\n GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years. Long-term studies are required.", "We have evaluated the best method to assess the ovarian reserve and the ovarian protective effect of GnRH-analog (GnRH-a), in 29 women with Hodgkin's disease (HD) treated with chemotherapy (CHT). The ovarian reserve was studied by measuring the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, antimullerian hormone (AMH) and the ultrasound antral follicular count (AFC). The patients were randomly treated with or without GnRH-a. At the time of study menstrual function was normal in 21 cases (72.4%), but absent in 8 (27.5%). Mean basal values of FSH, LH, AMH, inhibin B and AFC were normal in patients less than 30 years old and in the group treated four years or less before observation. AFC appeared to be the best marker of reduced ovarian reserve and a combination of AFC-AMH or inhibin B appeared the best predictor. In the GnRH-a group, no women had amenorrhoea, although ovarian reserve assessment was not significantly different from those who were not treated. The time-interval from CHT was the only significant predictor of ovarian function in GnRH-a treated patients. In conclusion, ovarian reserve evaluation, in young patients treated by CHT, can be performed by AFC. GnRH-a treatment does not have a protective effect, but could delay the development of ovarian failure.", "The hypothesis that the \"down-regulated\" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility." ]

[ "21345699", "12145036", "15845718", "10320157", "12154422", "10319771", "12538221", "11574339", "11574338", "7978133", "17061636", "6338893", "18635497" ]

[ "Efficacy and safety of hydroxyethyl starch 6% 130/0.4 in a balanced electrolyte solution (Volulyte) during cardiac surgery.", "Early postoperative respiratory acidosis after large intravascular volume infusion of lactated ringer's solution during major spine surgery.", "A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation.", "Hextend, a physiologically balanced plasma expander for large volume use in major surgery: a randomized phase III clinical trial. Hextend Study Group.", "A prospective, randomized comparison of thromboelastographic coagulation profile in patients receiving lactated Ringer's solution, 6% hetastarch in a balanced-saline vehicle, or 6% hetastarch in saline during major surgery.", "Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery.", "Intraoperative colloid administration reduces postoperative nausea and vomiting and improves postoperative outcomes compared with crystalloid administration.", "Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study.", "The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients.", "A comparison of Plasmalyte 148 and 0.9% saline for intra-operative fluid replacement.", "A comparison of 5% dextrose in 0.9% normal saline versus non-dextrose-containing crystalloids as the initial intravenous replacement fluid in elective surgery.", "Effect of different intraoperative fluid regimens on circulating metabolites and insulin during abdominal surgery.", "The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation." ]

[ "The infusion of large amounts of saline-based solutions may contribute to the development of hyperchloremic metabolic acidosis and the use of a balanced carrier for colloid solutions might improve postoperative acid-base status. The equivalence of 2 hydroxyethyl starch (HES) solutions and the influence on chloride levels and acid-base status by selectively changing the carrier of rapidly degradable modern 6% HES 130/0.4 were studied in cardiac surgery patients.\n A prospective, randomized, double-blinded study.\n A clinical study in 2 cardiac surgery institutions.\n Eighty-one patients.\n Patients received either 6% HES130/0.4 balanced (Volulyte; Fresenius Kabi, Bad Homburg, Germany) or 6% HES130/0.4 saline (Voluven; Fresenius Kabi, Bad Homburg, Germany) for intra- and postoperative hemodynamic stabilization.\n The therapeutic equivalence of both HES formulations regarding volume effect and superiority of the balanced electrolyte solution regarding serum chloride levels and acid-base status were measured. Similar volumes of both HES 130/0.4 balanced and HES 130/0.4 saline were administered until 6 hours after surgery, 2,391 ± 518 mL in the HES 130/0.4 balanced group versus 2,241 ± 512 mL in the HES 130/0.4 saline group. The 95% confidence interval for the difference between treatments (-77; 377 mL; mean, 150 mL) was contained entirely in the predefined interval (-500, 500 mL), thereby proving equivalence. The serum chloride level (mmol/L) was lower (p < 0.05 at the end of surgery), and arterial pH was higher in the balanced group at all time points except baseline, and base excess was less negative at all time points after baseline (p < 0.01).\n Volumes of HES needed for hemodynamic stabilization were equivalent between treatment groups. Significantly lower serum chloride levels in the HES balanced group reflected the lower chloride load of similar infusion volumes. The HES balanced group had significantly less acidosis.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "In this study, we compared the effects of large intravascular volume infusion of 0.9% saline (NS) or lactated Ringer's (LR) solution on electrolytes and acid base balance during major spine surgery and evaluated the postoperative effects. Thirty patients aged 18-70 yr were included in the study. General anesthesia was induced with 5 mg/kg thiopental and 0.1 mg/kg vecuronium IV. Anesthesia was maintained with oxygen in 70% nitrous oxide and 1.5%-2% sevoflurane. In Group I, the NS solution, and in Group II, the LR solution were infused 20 mL. kg(-1). h(-1) during the operation and 2.5 mL. kg(-1). h(-1), postoperatively. Electrolytes (Na+, K+, Cl-) and arterial blood gases were measured preoperatively, every hour intraoperatively and at the 1st, 2nd, 4th, 6th, and 12th hours postoperatively. In the NS group, pHa, HCO3 and base excess decreased, and Cl- values increased significantly at the 2nd hour and Na+ values increased at the 4th hour intraoperatively (P < 0.001). The values returned to normal ranges at the 12th hour postoperatively. In the LR group, blood gas analysis and electrolyte values did not show any significant difference intraoperatively, but the increase in PaCO2 and the decrease in pHa and serum Na+ was significant at the 1st hour postoperatively. Although intraoperative 20 mL. kg(-1). h(-1) LR infusion does not cause hyperchloremic metabolic acidosis as does NS infusion, it leads to postoperative respiratory acidosis and mild hyponatremia.\n The infusion of large-volume lactated Ringer's solution does not cause hyperchloremic metabolic acidosis as does 0.9% saline during major surgery, but leads to postoperative mild hyponatremia and respiratory acidosis.", "Normal saline (NS; 0.9% NaCl) is administered during kidney transplantation to avoid the risk of hyperkalemia associated with potassium-containing fluids. Recent evidence suggests that NS may be associated with adverse effects that are not seen with balanced-salt fluids, e.g., lactated Ringer's solution (LR). We hypothesized that NS is detrimental to renal function in kidney transplant recipients. Adults undergoing kidney transplantation were enrolled in a prospective, randomized, double-blind clinical trial of NS versus LR for intraoperative IV fluid therapy. The primary outcome measure was creatinine concentration on postoperative Day 3. The study was terminated for safety reasons after interim analysis of data from 51 patients. Forty-eight patients underwent living donor kidney transplants, and three patients underwent cadaveric donor transplants. Twenty-six patients received NS, and 25 patients received LR. There was no difference between groups in the primary outcome measure. Five (19%) patients in the NS group versus zero (0%) patients in the LR group had potassium concentrations >6 mEq/L and were treated for hyperkalemia (P = 0.05). Eight (31%) patients in the NS group versus zero (0%) patients in the LR group were treated for metabolic acidosis (P = 0.004). NS did not adversely affect renal function. LR was associated with less hyperkalemia and acidosis compared with NS. LR may be a safe choice for IV fluid therapy in patients undergoing kidney transplantation.", "Hextend (BioTime, Inc., Berkeley, CA) is a new plasma volume expander containing 6% hetastarch, balanced electrolytes, a lactate buffer, and physiological levels of glucose. In preclinical studies, its use in shock models was associated with an improvement in outcome compared with alternatives, such as albumin or 6% hetastarch in saline. In a prospective, randomized, two-center study (n = 120), we compared the efficacy and safety of Hextend versus 6% hetastarch in saline (HES) for the treatment of hypovolemia during major surgery. Patients at one center had a blood sample drawn at the beginning and the end of surgery for thromboelastographic (TEG) analysis. Hextend was as effective as HES for the treatment of hypovolemia. Patients received an average of 1596 mL of Hextend: 42% received >20 mL/kg up to a total of 5000 mL. No patient received albumin. Hextend-treated patients required less intraoperative calcium (4 vs 220 mg; P < 0.05). In a subset analysis of patients receiving red blood cell transfusions (n = 56; 47%), Hextend-treated patients had a lower mean estimated blood loss (956 mL less; P = 0.02) and were less likely to receive calcium supplementation (P = 0.04). Patients receiving HES demonstrated significant prolongation of time to onset of clot formation (based on TEG) not seen in the Hextend patients (P < 0.05). No Hextend patient experienced a related serious adverse event, and there was no difference in the total number of adverse events between the two groups. The results of this study demonstrate that Hextend, with its novel buffered, balanced electrolyte formulation, is as effective as 6% hetastarch in saline for the treatment of hypovolemia and may be a safe alternative even when used in volumes up to 5 L.\n Hextend (BioTime, Inc., Berkeley, CA) is a new plasma volume expander containing 6% hetastarch, balanced electrolytes, a lactate buffer, and a physiological level of glucose. It is as effective as 6% hetastarch in saline for the treatment of hypovolemia but has a more favorable side effects profile in volumes of up to 5 L compared with 6% hetastarch in saline.", "To compare the effects of lactated Ringer's solution (LR), 6% hetastarch in a balanced-saline vehicle (HS-BS), and 6% hetastarch in normal saline (HS-NS) on coagulation using thromboelastography.\n Prospective, randomized double-blinded evaluation of previously published clinical trial.\n Tertiary-care medical center.\n Patients undergoing elective noncardiac surgery with an anticipated blood loss >500 mL. A total of 90 patients were enrolled with 30 patients in each group.\n Patients received a standardized anesthetic. LR, HS-BS, and HS-NS were administered intraoperatively based on a fluid administration algorithm. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range.\n Thromboelastography variables for r time, k time, maximum amplitude, and alpha angle (mean +/- SD) were recorded at induction of anesthesia, at the end of surgery, and 24 hours postoperatively. Patients in the LR group showed a state of hypercoagulation at the end of surgery with reductions (p < 0.005) in r time (-3.8 +/- 6.7 mm) and k time (-1.7 +/- 2.5 mm). This state of hypercoagulation continued into the postoperative period. Patients in the HS-NS group showed a state of hypocoagulation with increases (p < 0.05) in r time (+6.2 +/- 8.5 mm) and k time (+1.7 +/- 3.9 mm) and a reduction in maximum amplitude (-8.0 +/- 9.8 mm) at the end of surgery. This state of hypocoagulation was reduced in the postoperative period. Patients in the HS-BS group showed no significant changes in coagulation status at end of surgery, with the smallest changes in r time (-0.3 +/- 4.1 mm), k time (+0.1 +/- 3.1 mm), maximum amplitude (-5.4 +/- 12.3 mm), and alpha angle (0.3 +/- 12.5 degrees ).\n LR-treated patients exhibited a hypercoagulative profile that persisted into the postoperative period. HS-BS administration was associated with a lesser change in the coagulation profile compared with HS-NS, which was associated with a hypocoagulative state.\n Copyright 2002, Elsevier Science (USA). All rights reserved.", "Changes in acid-base balance caused by infusion of a 0.9% saline solution during anesthesia and surgery are poorly characterized. Therefore, the authors evaluated these phenomena in a dose-response study.\n Two groups of 12 patients each who were undergoing major intraabdominal gynecologic surgery were assigned randomly to receive 0.9% saline or lactated Ringer's solution in a dosage of 30 ml x kg(-1) x h(-1). The pH, arterial carbon dioxide tension, and serum concentrations of sodium, potassium, chloride, lactate, and total protein were measured in 30-min intervals. The serum bicarbonate concentration was calculated using the Henderson-Hasselbalch equation and also using the Stewart approach from the strong ion difference and the amount of weak plasma acid. The strong ion difference was calculated as serum sodium + serum potassium - serum chloride - serum lactate. The amount of weak plasma acid was calculated as the serum total protein concentration in g/dl x 2.43.\n Infusion of 0.9% saline, but not lactated Ringer's solution, caused a metabolic acidosis with hyperchloremia and a concomitant decrease in the strong ion difference. Calculating the serum bicarbonate concentration using the Henderson-Hasselbalch equation or the Stewart approach produced equivalent results.\n Infusion of approximately 30 ml x kg(-1) x h(-1) saline during anesthesia and surgery inevitably leads to metabolic acidosis, which is not observed after administration of lactated Ringer's solution. The acidosis is associated with hyperchloremia.", "The debate over colloid versus crystalloid as the best solution for intraoperative fluid resuscitation is not resolved. Published studies have shown that mortality is not related to the specific fluid used for resuscitation. In addition, the quality of postoperative recovery between colloid and crystalloid has not been well investigated. In a prospective, blinded fashion, we investigated the effects of colloid and crystalloid resuscitation on nausea and vomiting and on the postoperative patient recovery profile. Patients undergoing major elective noncardiac surgery were randomized to receive 6% hetastarch in saline (HS-NS), 6% hetastarch in balanced salt (HS-BS), or lactated Ringer's solution (LR) on the basis of a fluid administration algorithm. The anesthetic was standardized. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. A postoperative morbidity survey was performed at baseline and daily after surgery. Ninety patients participated in the study, with 30 patients in each group. The amounts of study fluid (mean +/- SD) administered were 1301 +/- 1079 mL, 1448 +/- 759 mL, and 5946 +/- 1909 mL for the HS-NS, HS-BS, and LR groups, respectively (P < 0.05, HS-NS and HS-BS versus LR). Both the HS-NS and HS-BS (colloid) groups had a significantly less frequent incidence of nausea and vomiting, use of rescue antiemetics, severe pain, periorbital edema, and double vision. We concluded that intraoperative fluid resuscitation with colloid, when compared with crystalloid administration, is associated with an improvement in the quality of postoperative recovery.", "Metabolic acidosis and changes in serum osmolarity are consequences of 0.9% normal saline (NS) solution administration. We sought to determine if these physiologic changes influence patient outcome. Patients undergoing aortic reconstructive surgery were enrolled and were randomly assigned to receive lactated Ringer's (LR) solution (n = 33) or NS (n = 33) in a double-blinded fashion. Anesthetic and fluid management were standardized. Multiple measures of outcome were monitored. The NS patients developed a hyperchloremic acidosis and received more bicarbonate therapy (30 +/- 62 mL in the NS group versus 4 +/- 16 mL in the LR group; mean +/- SD), which was given if the base deficit was greater than -5 mEq/L. The NS patients also received a larger volume of platelet transfusion (478 +/- 302 mL in the NS group versus 223 +/- 24 mL in the LR group; mean +/- SD). When all blood products were summed, the NS group received significantly more blood products (P = 0.02). There were no differences in duration of mechanical ventilation, intensive care unit stay, hospital stay, and incidence of complications. When NS was used as the primary intraoperative solution, significantly more acidosis was seen on completion of surgery. This acidosis resulted in no apparent change in outcome but required larger amounts of bicarbonate to achieve predetermined measurements of base deficit and was associated with the use of larger amounts of blood products. These changes should be considered when choosing fluids for surgical procedures involving extensive blood loss and requiring extensive fluid administration.\n Predominant use of 0.9% saline solution in major surgery has little impact on outcome as assessed by duration of mechanical ventilation, intensive care unit stay, hospital stay, and postoperative complications, but it does appear to be associated with increased perioperative blood loss.", "The IV administration of sodium chloride solutions may produce a metabolic acidosis and gastrointestinal dysfunction. We designed this trial to determine whether, in elderly surgical patients, crystalloid and colloid solutions with a more physiologically balanced electrolyte formulation, such as Hartmann's solution and Hextend, can provide a superior metabolic environment and improved indices of organ perfusion when compared with saline-based fluids. Forty-seven elderly patients undergoing major surgery were randomly allocated to one of two study groups. Patients in the Balanced Fluid group received an intraoperative fluid regimen that consisted of Hartmann's solution and 6% hetastarch in balanced electrolyte and glucose injection (Hextend). Patients in the Saline group were given 0.9% sodium chloride solution and 6% hetastarch in 0.9% sodium chloride solution (Hespan). Biochemical indices and acid-base balance were determined. Gastric tonometry was used as a reflection of splanchnic perfusion. Postoperative chloride levels demonstrated a larger increase in the Saline group than the Balanced Fluid group (9.8 vs 3.3 mmol/L, P = 0.0001). Postoperative standard base excess showed a larger decline in the Saline group than the Balanced Fluid group (-5.5 vs -0.9 mmol/L, P = 0.0001). Two-thirds of patients in the Saline group, but none in the Balanced Fluid group, developed postoperative hyperchloremic metabolic acidosis (P = 0.0001). Gastric tonometry indicated a larger increase in the CO2 gap during surgery in the Saline group compared with the Balanced Fluid group (1.7 vs 0.9 kPa, P = 0.0394). In this study, the use of balanced crystalloid and colloid solutions in elderly surgical patients prevented the development of hyperchloremic metabolic acidosis and resulted in improved gastric mucosal perfusion when compared with saline-based solutions.\n This prospective, randomized, blinded trial showed that, in elderly surgical patients, the use of balanced IV solutions can prevent the development of hyperchloremic metabolic acidosis and provide better gastric mucosal perfusion compared with saline-based fluids.", "Thirty patients undergoing major hepatobiliary or pancreatic surgery were randomly allocated to receive either 0.9% saline or Plasmalyte 148 (a balanced salt solution), at 15 ml.kg-1.h-1. Arterial blood gas analysis was performed before and after surgery. Plasma biochemistry (Na+, K+, Cl-, lactate) measurements were made before and after surgery and at 24 h after surgery. The patients receiving 0.9% saline had significantly increased chloride concentrations (p < 0.01), decreased standard bicarbonate concentrations (p < 0.01) and increased base deficit (p < 0.01) compared to those receiving Plasmalyte 148. There were no significant changes in plasma sodium or potassium or blood lactate concentrations in either group. The exclusive use of 0.9% saline intra-operatively can produce a temporary hyperchloraemic acidosis which could be given false pathological significance. In addition it may exacerbate an acidosis resulting from an actual pathological state. The use of a balanced salt solution such as Plasmalyte 148 may avoid these complications.", "Intravenous fluid replacement in adult elective surgery is often initiated with dextrose-containing fluids. We sought to determine if this practice resulted in significant hyperglycaemia and if there was a risk of hypoglycaemia if non-dextrose-containing crystalloids were used instead. We conducted a randomized controlled trial in 50 non-diabetic adult patients undergoing elective surgery which did not involve entry into major body cavities, large fluid shifts, or require administration of >500 ml of intravenous fluid in the first two hours of peri-operative care. Patients received 500 ml of either 5% dextrose in 0.9% normal saline, lactated Ringer's solution, or 0.9% normal saline over 45 to 60 minutes. Plasma glucose, electrolytes and osmolarity were measured prior to infusion, and at 15 minutes and one hour after completion of infusion. None of the patients had preoperative hypoglycaemia despite average fasting times of almost 13 hours. Patients receiving lactated Ringer's and normal saline remained normoglycaemic throughout the study period. Patients receiving dextrose saline had significantly elevated plasma glucose 15 minutes after completion of infusion (11.1 (9.9-12.2, 95% CI) mmol/l). Plasma glucose exceeded 10 mmol/l in 72% of patients receiving dextrose saline. There was no significant difference in plasma glucose between the groups at one hour after infusion, but 33% of patients receiving DS had plasma glucose > or = 8 mmol/l. We conclude that initiation of intravenous fluid replacement with dextrose-containing solutions is not required to prevent hypoglycaemia in elective surgery. On the contrary, a relatively small volume of 500 ml causes significant, albeit transient, hyperglycaemia, even in non-diabetic patients.", "The effects of infusion i.v. of 0.9% sodium chloride solution, Hartmann's and 5% dextrose solution on the concentrations of circulating metabolites and insulin were compared in patients undergoing cholecystectomy. Hartmann's solution had a similar effect on the metabolic response to 0.9% sodium chloride solution, but the use of 5% dextrose was associated with an exacerbation of the hyperglycaemic response to surgery. Plasma insulin concentrations increased significantly in the group receiving 5% dextrose showing that the usual suppression of insulin during abdominal surgery can be overcome by a strong glycaemic stimulus.", "This study aimed to quantify changes in acid-base balance, potassium and lactate levels as a function of administration of different crystalloid solutions during kidney transplantation, and to determine the ideal fluid for such patients.\n In this double-blind study, patients were randomized to three groups (n = 30 each) to receive either normal saline, lactated Ringer's, or Plasmalyte, all at 20-30 mL x kg(-1) x h(-1). Arterial blood analyses were performed before induction of anesthesia, and at 30-min intervals during surgery, and total IV fluids recorded. Urine volume, serum creatinine and BUN, and creatinine clearance were recorded on postoperative days 1, 2, 3, and 7.\n There was a statistically significant decrease in pH (7.44 +/- 0.50 vs 7.36 +/- 0.05), base excess (0.4 +/- 3.1 vs -4.3 +/- 2.1), and a significant increase in serum chloride (104 +/- 2 vs 125 +/- 3 mM/L) in patients receiving saline during surgery. Lactate levels increased significantly in patients who received Ringer's lactate (0.48 +/- 0.29 vs 1.95 +/- 0.48). No significant changes in acid-base measures or lactate levels occurred in patients who received Plasmalyte. Potassium levels were not significantly changed in any group.\n All three crystalloid solutions can be safely used during uncomplicated, short-duration renal transplants; however, the best metabolic profile is maintained in patients who receive Plasmalyte." ]

[ "9766764", "108739", "3536890", "12128237", "8104964", "3907277", "3316312" ]

[ "Short-term augmentation of fluoxetine with clonazepam in the treatment of depression: a double-blind study.", "A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness.", "Comparative effects of limbitrol and amitriptyline on sleep efficiency and architecture.", "Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression?", "Hypnotics as concurrent medication in depression. A placebo-controlled, double-blind comparison of flunitrazepam and lormetazepam in patients with major depression, treated with a (tri)cyclic antidepressant.", "A double blind study in out-patients with primary non-agitated depression treated with imipramine in combination with placebo, diazepam or dixyrazine.", "Alprazolam: an antidepressant? Alprazolam, desipramine, and an alprazolam-desipramine combination in the treatment of adult depressed outpatients." ]

[ "Because selective serotonin reuptake inhibitors (SSRIs) require 2-4 weeks to reach efficacy, the authors determined whether clonazepam augmentation of fluoxetine is superior to fluoxetine alone at the beginning of treatment for major depression.\n Eighty adult outpatients with major depression who were rated as \"moderately ill\" or \"markedly ill\" on the Clinical Global Impression of Severity underwent 8 weeks of double-blind, randomized treatment with fluoxetine, 20 mg/day for all patients initially and 40 mg/day if needed after 6 weeks. One-half of these patients received clonazepam, 0.5 mg h.s. adjusted to two tablets by day 10 if needed, and the remainder received placebo, likewise adjusted. Clonazepam/placebo was gradually discontinued during days 21-33. Efficacy was evaluated by means of the Hamilton Depression Rating Scale, the Clinical Global Impression of Improvement, and a patient rating of global improvement.\n The patients taking clonazepam improved significantly more during the first 3 weeks of treatment according to ratings on the Hamilton scale (> or =50% improvement) and the clinician- and patient-rated global improvement measures (\"much\" or \"very much\" improved). Analysis of variance confirmed a significant effect of clonazepam for average Hamilton depression scores. No serious adverse events were found in either treatment group. Taper effects appeared modest and transitory.\n Clonazepam augmentation of fluoxetine was superior to fluoxetine alone in the first 3 weeks of treatment. This strategy may reduce suffering during early SSRI treatment, may partially suppress SSRI side effects, may increase compliance, and could possibly reduce the risk of suicide.", "In a multicenter, placebo-controlled, clinical trial, the efficacy of Limbitrol was compared with that of its components, amitriptyline and chlordiazepoxide. All patients had a diagnosis of primary depression. Data from 279 patients were evaluated using the Hamilton depression scale, the Beck depression inventory, and physician and patient global change measures. Statistically significant differences favoring Limbitrol occurred after 1 week of treatment, and a trend in favor of Limbitrol continued throughout the remaining 3 weeks. In most efficacy comparisons, the combination was as good as, or better than, amitriptyline alone. It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment. Each component produced an independent contribution to the total therapeutic effect: the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks. A trend favoring amitriptyline over chlordiazepoxide was evident by week 4. The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups. Limbitrol-treated patients exhibited more sedation, but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects.", "Chlordiazepoxide-amitriptyline (Limbitrol) has been shown to be more rapidly effective than amitriptyline alone for treating depression. A double-blind, randomized study was designed to compare the effects of Limbitrol and amitriptyline on insomnia, anxiety, and depression. The rate of improvement of symptoms was faster with Limbitrol. No differences were noted between groups in the degree or rate of improvement of the sleep laboratory parameters nor in sleep Stages 1 to 4. Percentages of rapid eye movement (REM) sleep and REM latency were similarly affected by the drugs, but REM density showed a significantly greater decrease with Limbitrol. Phasic REM factors may be crucial in the role of REM sleep and depression.", "Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension.\n Fifty outpatient volunteers aged 18-65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months.\n No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, df=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy.\n Small sample size (N=50) limited power and rendered conclusions tentative.\n Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated.\n Copright 2002 Elsevier Science BV.", "The addition of benzodiazepine hypnotics to a treatment with tricyclic antidepressants has received little systematic study. In a double-blind placebo-controlled design, the effects on mood and on sleep of two benzodiazepine hypnotics (lormetazepam and flunitrazepam) were studied in patients with major depression who were also treated with maprotiline or nortriptyline. After 4 weeks of combined treatment, lormetazepam resulted in a significantly greater decrease in the score on the Hamilton Depression Subscale than placebo, while there was a non-significant trend in favour of lormetazepam in comparison with flunitrazepam. With respect to sleep EEGs, lormetazepam resulted in a significantly greater suppression of REM sleep. The differences between lormetazepam and flunitrazepam may be partly explained by the shorter half-live of lormetazepam.", "Sixty-three out-patients suffering from primary non-agitated depression were included in a double-blind, between-patient randomized study. All patients were treated with imipramine (100-200 mg-day) combined with either placebo, diazepam (10 mg/day) or dixyrazine (50 mg/day) for 8 weeks. The clinical efficacy assessed with a subscale of CPRS was significantly (p1 less than or equal to 0.05) better for the imipramine-dixyrazine combination than for the imipramine-diazepam or imipramine-placebo combination. Serum concentration of imipramine was significantly higher (p1 less than or equal to 0.05) in the group treated with dixyrazine than in the other two groups. Further, serum concentration of imipramine in the diazepam group was significantly lower (p1 less than or equal to 0.05) than in the placebo group. At the end of the study, 67% in both the placebo and the diazepam group and 86% in the dixyrazine group were practically symptom-free.", "The antidepressant efficacy of alprazolam (ALP) was tested in a double-blind controlled comparison with desipramine (DMI) and an ALP-DMI combination in outpatients diagnosed with major depressive disorder by Research Diagnostic Criteria (90% met criteria for endogenous subtype). Following a placebo period of at least 1 week, subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale (HDRS) scores were administered oral doses of the active medication (N = 79), in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI. Treatment continued for 6 weeks, and all subjects who completed at least 2 weeks (N = 69) were included in endpoint analyses. Following the placebo baseline, symptoms were rated again at day 5 and at the end of weeks 1, 2, 4, and 6. Final doses averaged 4.6 +/- 1.3 mg for the ALP group, 230 +/- 61 mg for the DMI group, and 4.6 +/- 1.2 mg ALP + 229.5 +/- 1.2 mg DMI for the combination group. The final outcome was a comparable degree of improvement at the endpoint among the three treatment groups on measures of depression (HDRS and Beck Depression Inventory), anxiety (Hamilton Anxiety Rating Scale), and global improvement (Global Assessment Scale, and Physician and Patient Global Impressions). A similar outcome was found for the subgroup of patients who completed all 6 weeks (N = 56). Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression, anxiety, and global status. These results suggest that ALP alone is as effective as a standard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication. Side effect profiles were compared among treatment groups and are discussed, as are other clinical studies that have investigated ALP's potential antidepressant efficacy." ]

[ "20831528", "8741040", "10321674" ]

[ "Effects of pentoxifylline on coagulation profile and disseminated intravascular coagulation incidence in Egyptian septic neonates.", "Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis.", "Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: a placebo-controlled, double-blind trial." ]

[ "Neonatal sepsis is frequently associated with pathological activation of the coagulation system, leading to microcirculatory derangement and multiple organ dysfunction syndrome (MODS). The key role in the pathogenesis of sepsis has been attributed to proinflammatory cytokines. These trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. Pentoxifylline (PTX), a methylxanthine derivative that is used in peripheral vascular disease, has the potential to modify inflammatory response. The current work was designed to evaluate the potential protective effects of PTX against sepsis-induced microcirculatory derangement in Egyptian neonates.\n A double-blind placebo-controlled quasi-randomized design was used. Thirty-seven neonates with sepsis were randomly allocated into two groups. Seventeen patients were given PTX (5 mg/kg/h for 6 h; for 6 successive days). Twenty patients received equivalent volume of normal saline and represented the placebo group. Prothrombin time (PT), Activated partial thromboplastin time (APTT), fibrinogen, d-dimer, C-reactive protein (CRP), complete blood count (CBC), also hemodynamic parameters comprising arterial blood pressure, heart rate, capillary refill and urinary output were assessed in both groups before and after treatment.\n Coagulation parameters in the two groups showed no significant differences. However, a higher incidence of DIC was observed in the placebo group neonates. PTX significantly lowered the percentage of bleeding (P = 0.0128) and less frequent use of FFP was observed in the PTX group (35.53% in PTX group vs. 80% in placebo group, P = 0.003). Incidence of MODS was significantly lower (P = 0.037) and hospital stay duration of survivors was significantly shorter (P = 0.044) in the PTX treated-infants.\n Pentoxifylline protects against sepsis-induced microcirculatory derangement in neonates. It significantly lowered the incidence of bleeding and MODS and shortened the length of hospital stay.", "Increased plasma tumour necrosis factor alpha (TNF) concentration correlates with mortality in sepsis. We suggested that pentoxifylline (PTXF), which is known to inhibit TNF production, may improve survival and attenuate clinical symptoms of sepsis in neonates. Plasma TNF levels were evaluated in 29 newborn infants with sepsis. Patients were randomly assigned into two groups, receiving PTXF in a dose of 5 mg/kg per hour for 6 h or placebo (saline), on 3 successive days. Both groups were subjected to the same conventional therapy. TNF was evaluated before and after PTXF or placebo administration on the 1st and 3rd days of therapy. There was a statistically significant decrease in plasma TNF level in the PTXF group when the values before the first and after the last PTXF infusion were compared [mean: 671.5 pg/ml; SD: 438; med: 729.6 vs mean: 41.0 pg/ml; SD: 64.1; med: 11.5; P < 0.000004]. In the placebo group, decrease was not significant [mean: 633.0 pg/ml SD: 488.6; med: 618.9 vs 246.9 pg/ml; SD: 243.9; med: 191.0]. A significantly higher plasma TNF level, evaluated after the last PTXF infusion, was found in the placebo group [246.9 pg/ml vs 41.0 pg/ml; P < 0.001]. Only one of four infants with signs of shock in the placebo group survived, whereas all of five newborns with symptoms of shock in the PTXF group survived [P < 0.04]. An increased incidence of metabolic acidosis [P < 0.05], necrotizing enterocolitis [P < 0.04] and renal insufficiency [P < 0.05] was observed in infants in the placebo group.\n PTXF inhibits production of TNF and may have therapeutic value in the treatment of premature infants with sepsis complicated by shock.", "To evaluate the influence of the methylxanthine derivative, pentoxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 in prematurely delivered infants with generalized bacterial infections and to assess the effect of this immunomodulating drug on the clinical outcome in newborns with sepsis.\n A prospective, randomized, double-blind trial.\n The neonatal intensive therapy units in university teaching hospitals.\n One hundred patients with sepsis admitted during a 1.5-yr period.\n Patients were randomly assigned to receive pentoxifylline (pentoxifylline group) in a dose of 5 mg/kg/hr for 6 hrs on 6 successive days or an identically presented placebo (placebo group).\n Only infants with sepsis confirmed by positive blood culture were recruited into the study. There were no significant differences at randomization between the pentoxifylline and placebo groups with regard to the birth weight, gestational age, gender, Apgar score, hypotension, neutropenia, thrombocytopenia, metabolic acidosis, plasma levels of cytokines, and occurrence of shock. Plasma levels of TNF, IL-1, and IL-6 were evaluated before and after the drug or placebo administration on the first, third, and sixth days of therapy. Cytokines were determined by immunoenzymetric test EASIA (TNF) and Endogen Interleukin-Elisa (IL-1, IL-6). The frequency of gram-negative sepsis was similar in both groups (37.5% and 36.8%). Pentoxifylline significantly diminished plasma TNF levels (p = .009) but had no effect on plasma IL-1 levels. Mean plasma IL-6 levels, which were measured in the pentoxifylline group on the 6th day of the study, were significantly lower compared with respective data obtained in the placebo group. Only 1 of 40 infants with sepsis in the pentoxifylline group died, whereas 6 of 38 infants in the placebo group did not survive (p = .046). An increased incidence of disordered peripheral circulation and metabolic acidosis (p = .048), anuria or oliguria (p = .03), disseminated intravascular coagulation (p = .043), and the occurrence of clinical symptoms of necrotizing enterocolitis (p = .025) was observed in the course of sepsis in infants in the placebo group.\n Pentoxifylline significantly affects the synthesis of TNF and IL-6 as well as reduces the mortality rate in premature infants with sepsis. The dosage and schedule of drug administration in this study attenuated the severity of the clinical course of sepsis in this group of patients." ]

[ "16163369", "15192630", "8090164", "15173537" ]

[ "Surfactant administration by transient intubation in infants 29 to 35 weeks' gestation with respiratory distress syndrome decreases the likelihood of later mechanical ventilation: a randomized controlled trial.", "Early surfactant for neonates with mild to moderate respiratory distress syndrome: a multicenter, randomized trial.", "Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. Danish-Swedish Multicenter Study Group.", "Early extubation and nasal continuous positive airway pressure after surfactant treatment for respiratory distress syndrome among preterm infants <30 weeks' gestation." ]

[ "To assess, among premature infants with early respiratory distress syndrome (RDS), the effect of one dose of intratracheally administered surfactant followed by extubation to nasal continuous positive airway pressure (NCPAP) on subsequent mechanical ventilation (MV), when compared with NCPAP alone.\n Randomized, blinded trial in infants 29 to 35 weeks' gestation with mild-to-moderate RDS requiring supplemental oxygen and NCPAP. Infants were randomized to intubation, surfactant treatment, and immediate extubation (surfactant group N=52), or to no intervention (control group N=53). All infants were subsequently managed with NCPAP.\n Need for later MV was 70% in the control group and 50% in the surfactant group. Surfactant group subjects had lower inspired oxygen fraction (FiO(2)) after study intervention and were less likely to require subsequent surfactant. Overall surfactant use, duration of O(2) therapy, length of stay, and bronchopulmonary dysplasia were unaffected.\n Among premature infants with mild-to-moderate RDS, transient intubation for surfactant administration reduces later MV.\n Journal of Perinatology (2005) 25, 703-708. doi:10.1038/sj.jp.7211381; published online 15 September 2005.", "We studied the efficacy and safety of electively providing surfactant to preterm infants with mild to moderate respiratory distress syndrome (RDS) not requiring mechanical ventilation.\n A 5-center, randomized clinical trial was performed on 132 infants with RDS, birth weight >or=1250 grams, gestational age <or=36 weeks, postnatal age 4 to 24 hours, Fio(2) >or=40% for >or=1 hour, and no immediate need for intubation. Infants were randomly assigned to intubation, surfactant (Survanta, Ross Laboratories, Columbus, Ohio) administration, and expedited extubation (n=65) or expectant management (n=67) with subsequent intubation and surfactant treatment as clinically indicated. The primary outcome was duration of mechanical ventilation.\n Infants in the surfactant group had a median duration of mechanical ventilation of 2.2 hours compared with 0.0 hours for control infants, since only 29 of 67 control infants required mechanical ventilation (P=.001). Surfactant-treated infants were less likely to require subsequent mechanical ventilation for worsening respiratory disease (26% vs 43%, relative risk=0.60; 95% CI, 0.37, 0.99). There were no differences in secondary outcomes (duration of nasal continuous positive airway pressure, oxygen therapy, hospital stay, or adverse outcomes).\n Routine elective intubation for administration of surfactant to preterm infants >or=1250 grams with mild to moderate RDS is not recommended.", "In southern Scandinavia most babies with respiratory distress syndrome are initially treated with nasal continuous positive airway pressure. We performed a multicenter trial to investigate whether the addition of a single dose of porcine surfactant administered during a short intubation before the occurrence of serious deterioration could reduce the subsequent need for mechanical ventilation.\n We randomly assigned 35 infants with moderate-to-severe respiratory distress syndrome to surfactant therapy (Curosurf, 200 mg per kilogram of body weight) plus nasal continuous positive airway pressure and 33 infants to nasal continuous positive airway pressure alone. The study was not blinded. The indications for mechanical ventilation were a ratio of arterial to alveolar oxygen tension of less than 0.15, severe apneic attacks, or both.\n Six hours after randomization, when the median age of the babies was 18 hours, the mean ratio of arterial to alveolar oxygen tension was 0.37 in the surfactant-treated babies, as compared with 0.25 in the controls (P < 0.001). The need for subsequent mechanical ventilation was reduced with surfactant therapy (to 43 percent of the surfactant-treated babies as compared with 85 percent of the controls; P = 0.003). When 17 infants with ratios of arterial-to-alveolar oxygen tension of less than 0.15 at randomization were excluded, the need for mechanical ventilation was still significantly reduced in the surfactant-treated group (to 33 percent [9 of 27 babies], as compared with 83 percent [20 of 24 babies] in the control group; (P < 0.001). After 28 days, two of the surfactant-treated babies had died, as compared with five of the control babies.\n In babies with moderate-to-severe respiratory distress syndrome treated with nasal continuous positive airway pressure, a single dose of surfactant reduced the need for subsequent mechanical ventilation.", "To test the hypothesis that preterm infants with infant respiratory distress syndrome who are treated with nasal continuous positive airway pressure (NCPAP) and surfactant administration followed by immediate extubation and NCPAP application (SURF-NCPAP group) demonstrate less need for mechanical ventilation (MV), compared with infants who receive MV after surfactant administration (SURF-MV group).\n A prospective randomized study was conducted, in which infants <30 weeks' gestation were randomized to the SURF-NCPAP group or the SURF-MV group.\n At 7 days of life, no patient in the SURF-NCPAP group but 6 patients (43%) in the SURF-MV group still were undergoing MV. The duration of oxygen therapy, NCPAP, and MV, the need for a second dose of surfactant, and the length of stay in the intensive care unit were significantly greater in the SURF-MV group.\n The immediate reinstitution of NCPAP after surfactant administration for infants with infant respiratory distress syndrome is safe and beneficial, as indicated by the lesser need for MV and the briefer requirement for respiratory supports, compared with the institution of MV after surfactant treatment. Moreover, this strategy contributed to reducing the need for surfactant treatment and reducing the time and costs involved in keeping the infants in the neonatal intensive care unit." ]

[ "19702706" ]

[ "Cataract surgery in high-risk age-related macular degeneration: a randomized controlled trial." ]

[ "To investigate if cataract surgery causes progression, from high-risk early age-related macular degeneration (AMD) to choroidal neovascularization (CNV), in the postoperative period.\n Randomized controlled trial. Patients, with visually significant cataract and fundus features of early AMD at high risk of progression to CNV, were randomized into two groups and were evaluated at baseline and 6 months. The study patients (n = 27) underwent immediate cataract surgery. The control group (n = 29) comprised patients who had cataract surgery deferred until after the 6-month visit. Assessment included visual acuity, quality of life (QoL) and fundus fluorescein angiography (FFA).\n Of 68 eligible eyes, 60 participated and 56 completed the study. Three referred eyes (3.2%) were ineligible on the basis of a pre-existing, unsuspected occult CNV that was detected by baseline FFA. All three cases had end-stage exudative AMD in the fellow eye. Of the study eyes in the immediate surgery arm (n = 27), one (3.7%) developed CNV compared with none (0/29) in the deferred arm (chi(2); P = 1.0) at 6 months. In the operated group, there was a 2.8-line improvement in logMAR visual acuity and 2.1-fold average gain in QoL at 6 months.\n No increased short-term risk of progression of AMD to CNV in high-risk fundi following uncomplicated phacoemulsification surgery was found. A low threshold for performing preoperative imaging in patients with AMD, especially in those with exudative AMD in the fellow eye, to exclude undetected CNV is recommended. Provided there is no CNV, there are distinct benefits of cataract surgery in people with early AMD." ]

[ "16422733", "6759553", "10347518", "3361457", "9588369", "7795873", "8502770", "9801935", "3396372", "9204803", "15059051", "10455633", "6565735", "15867701", "2394540", "7960335", "1760125", "10745855", "8433469", "7906329", "14652518", "8850903", "12964222", "10670292", "11933449", "6123027", "18037257", "9104123", "9832744", "15764622", "3985778", "20687915", "11905977", "12889398", "9729952", "17708377", "1496149", "9274063", "16750060", "15766343" ]

[ "A 4-cm thermoactive viscoelastic foam pad on the operating room table to prevent pressure ulcer during cardiac surgery.", "A clinical trial of a bead bed system for the prevention of pressure sores in elderly orthopaedic patients.", "A comparative study of an alternating air mattress for the prevention of pressure ulcers in surgical patients.", "Clinical trial of foam cushions in the prevention of decubitis ulcers in elderly patients.", "Low airloss hydrotherapy versus standard care for incontinent hospitalized patients.", "Evaluation of the effectiveness of two support surfaces following myocutaneous flap surgery.", "The role of support surfaces and patient attributes in preventing pressure ulcers in elderly patients.", "A sequential randomised controlled trial comparing a dry visco-elastic polymer pad and standard operating table mattress in the prevention of post-operative pressure sores.", "Effect of a rotating bed on the incidence of pulmonary complications in critically ill patients.", "A comparison of two pressure-relieving devices on the prevention of heel pressure ulcers.", "Preventing pressure ulcers with the Australian Medical Sheepskin: an open-label randomised controlled trial.", "Challenging the pressure sore paradigm.", "Do mattresses make a difference?", "Research comparing three heel ulcer-prevention devices.", "The role of alternating air and Silicore overlays in preventing decubitus ulcers.", "Pressure ulcer prophylaxis in elderly patients using polyurethane foam or Jay wheelchair cushions.", "Prevention of pressure ulcers in elderly nursing home residents: are special support surfaces the answer?", "Randomized controlled trial to determine the safety and efficacy of a multi-cell pulsating dynamic mattress system in the prevention of pressure ulcers in patients undergoing cardiovascular surgery.", "Clinical utility and cost-effectiveness of an air suspension bed in the prevention of pressure ulcers.", "Pressure sores and pressure-decreasing mattresses: controlled clinical trial.", "Randomized clinical trial comparing 2 support surfaces: results of the Prevention of Pressure Ulcers Study.", "Pressure-reducing mattresses.", "Profiling beds versus standard hospital beds: effects on pressure ulcer incidence outcomes.", "Evaluating the Pegasus Trinova: a data hierarchy approach.", "Effect of visco-elastic foam mattresses on the development of pressure ulcers in patients with hip fractures.", "Use of the 'air wave system' to prevent pressure sores in hospital.", "[Prevention of heel pressure sores with a foam body-support device. A randomized controlled trial in a medical intensive care unit].", "Evaluation of the new Cairwave Therapy System in one hospital trust.", "A randomised controlled trial of two pressure-reducing surfaces.", "Effectiveness of an alternating pressure air mattress for the prevention of pressure ulcers.", "Special mattresses: effectiveness in preventing decubitus ulcers in chronic neurologic patients.", "An economic appraisal of the Australian Medical Sheepskin for the prevention of sacral pressure ulcers from a nursing home perspective.", "A randomized control trial to evaluate pressure-reducing seat cushions for elderly wheelchair users.", "Randomised controlled trial to evaluate a new double-layer air-cell overlay for elderly patients requiring head elevation.", "Study results: prediction and prevention of pressure ulcers in surgical patients.", "Clinical effectiveness of a low-tech versus high-tech pressure-redistributing mattress.", "Effects of position and mattress overlay on sacral and heel pressures in a clinical population.", "Mattress replacement or foam overlay? A prospective study on the incidence of pressure ulcers.", "Pressure relieving support surfaces: a randomised evaluation.", "Pressure ulcer prevention in intensive care - a randomised control trial of two pressure-relieving devices." ]

[ "In this experimental study, a 4-cm thermoactive viscoelastic foam overlay and a heating source on the operating room table was compared with the standard operating room table with a heating source for the effect on the postoperative pressure ulcer incidence in cardiac surgery patients.\n Pressure ulcer incidence in the cardiac surgery population is reported to be up to 29.5%. The prolonged compressive forces from lying on the operating room table are one source of pressure ulcer development in this population. Pressure-reducing devices on the operating room (OR)-table should reduce the patients' interface pressure and thus the hazard of skin breakdown.\n A randomized controlled trial was performed to test the effect of a 4-cm thermoactive viscoelastic foam overlay with a water-filled warming mattress on the OR-table (test OR-table) compared with the standard OR-table (a water-filled warming mattress, no pressure-reducing device) on the postoperative pressure ulcer incidence in cardiac surgery patients.\n The pressure ulcer classification system of the European Pressure Ulcer Advisory Panel (EPUAP) was used for pressure ulcer grading.\n The results show that patients lying on the 4-cm thermoactive viscoelastic foam overlay suffer slightly more pressure ulcer (17.6%) than patients on the standard OR-table without the foam overlay (11.1%). Because of the clinical relevance of the results, the randomized controlled trial was terminated after 175 patients at the interim analysis although the power calculation stated 350 patients.\n The combination of a 4-cm viscoelastic foam overlay and a warming source cannot be recommended for pressure ulcer prevention on the operating room table.\n Foam overlays are used to prevent pressure ulcers in patients. It is necessary to use such devices according to patient safety and use of resources.", "This paper summarizes the results of the trial of the Beaufort Bead Bed system designed to reduce the incidence and severity of pressure sores. Elderly orthopaedic admissions were allocated alternately to the Beaufort system and to the usual trolley, table and bed surfaces, and followed from admission to hospital until separation. The incidence of pressure sores was 15.6% in the 32 'trial' patients, which was significantly less than the 48.8% in the 43 'control' patients, as was the mean maximum diameter of the pressure sores incurred: 6.4 mm for the 'trials' as against 29.5 mm for the 'controls'. In particular the trial group were free from pressure lesions to the heel, which affected 32.6% of the control group. The groups were well matched on a variety of criteria on admission, and we conclude that the Beaufort system successfully reduces the incidence and severity of pressure sores for elderly orthopaedic patients. The system--renamed recently the 'Neumark-Macclesfield Support System'--is now in regular and satisfactory use.", "Research indicates that 8.5% of all patients undergoing surgical procedures for more than 3 hours develop pressure ulcers. In some types of surgery, incidence rates in excess of 25% have been reported. An 11-month study was conducted on the safety and efficacy of an experimental alternating air device in comparison with a tertiary care facility's conventional practice. A series of 217 patients undergoing surgical procedures scheduled for a minimum of 3 hours were enrolled. No ulcers developed in the experimental group and 11 ulcers developed in seven patients in the control group (8.75% incidence rate). Of the 11 ulcers, one was Stage I, four were Stage II, and six were unstageable secondary to eschar. The difference between the groups is significant at the P = 0.005 level. Individuals who developed ulcers had a length of stay approximately 7 days longer than the hospital average for comparable patients who did not develop ulcers.", "Polyurethane foam cushions in a slab form or a customized contoured form are commonly used in wheelchairs to prevent the development of decubitus ulcers (DU) in elderly chronically ill persons. Sixty-two consenting subjects, 60 years or older, were randomly assigned to sit on one of the two types of cushions for 3 or more hours daily for 5 months. A total of 72 DU developed in the 52 subjects who completed the study. These were mostly in the areas of ischial tuberosities, buttocks, and thighs; were of persistent erythema level in severity; and took an average of 6 to 8 weeks to heal. No statistically significant differences were found in the incidence, location, severity, or healing time of the sores that developed in the subjects who used the slab (N = 26) and those who used the contoured (N = 26) cushions. But, more severe sores did develop among the slab cushion group in the area of ischial tuberosities. It appears that foam customization for elderly persons could be justified only if DU have been a particular problem in this region. Incontinence as a contributory factor to DU formation should receive careful attention with respect to prevention. The trials described are being continued, using a larger number of subjects.", "To determine whether low airloss hydrotherapy reduces the incidence of new skin lesions associated with incontinence in hospitalized patients and results in more rapid healing of existing pressure sores compared with standard care. To assess subjectively patient and nursing satisfaction related to using low airloss hydrotherapy beds.\n Randomized, prospective, unblinded study.\n Acute and chronic hospital wards.\n A total of 116 newly admitted, incontinent, hospitalized patients with and without existing pressure sores.\n Low airloss hydrotherapy compared with treatment on hospital beds and mattresses ordered by the patient's attending physician.\n Incidence rates of new skin lesion development, e.g., pressure sores, candidiasis, and chemical irritation; improvement in existing pressure sore size, volume, and status; subjective assessment of patient and nursing satisfaction.\n Possible hypothermia was identified in two patients during the first week of the study, and patient and nursing dissatisfaction with low airloss hydrotherapy remained high throughout the first months of the study. Therefore, two major modifications in the initial protocol were made: (1) increased patient temperature monitoring for hypothermia was initiated in Week 2 of the study and (2) increased staff resources for in-service training on bed use began in Week 18 of the study. After the latter change, 58 subjects were randomized to low airloss hydrotherapy and 58 to standard care. Subjects were old (median age > or = 80 years), and almost all were bedbound or nonambulatory. The median (range) length of follow-up for subjects in the treatment group was significantly shorter than for those in the control group (4 (1-60) days versus 6 (1-62) days, respectively, P = .017) because there were more dropouts from the treatment group (24 (36%) of 58 versus 2 (3%) of 58, P = .0001). The major reasons dropout occurred were patient or family dissatisfaction (12 (21%)), new or worsened skin lesions thought to be related to bed use (4 (7%)), and hypothermia < 97 degrees F (4 (7%)). The total cumulative incidence of new truncal skin lesions within 9 days of enrollment was greater in the treatment than in the control group (48% versus 14%, respectively, P < 0.01). Too few patients with existing pressure sores were treated for too short a period of time to assess the effect of low airloss hydrotherapy on pressure sore healing. Because only 10 patients treated on low airloss hydrotherapy beds were able to complete satisfaction surveys meaningfully, interpretation of these data is difficult. Only nine (21%) of 44 nurses subjectively reported overall satisfaction using the low airloss hydrotherapy bed.\n This study shows the value of a rigorously designed clinically based evaluation of a new product developed for older patients. The results of the study led to re-engineering of the prototype low airloss hydrotherapy bed as well as a change in marketing strategy. Studies of products targeted to the prevention and treatment of pressure sores in older patients should be undertaken before generalized marketing begins.", "Recurrence of pressure ulcers is a serious problem following myocutaneous flap surgery and can lead to prolonged and expensive hospitalization. One of the most important aspects of patient care after surgery is the monitoring of reduced pressure in the area of the flap. Usually reducing pressure requires an expensive high-tech support surface. The purpose of this study was to evaluate the effectiveness of a less expensive support surface. There were 12 patients involved in a clinical trial that lasted 14 days and compared the effectiveness of the ROHO dry-floatation mattress to that of the Clinitron bed. Findings indicated that post-operative patients were effectively treated on either support surface.", "Nurses caring for elderly patients often need to select support surfaces that reduce the likelihood of pressure ulcers, but there is little information about the effectiveness of different support surfaces. This randomized trial compared two support surfaces and investigated patient attributes related to the risk of developing a pressure ulcer. Eighty-four elderly patients were nursed on a convoluted or solid foam overlay and assessed three times a week for pressure ulcers. Stepwise Cox proportional hazards regression revealed a statistically significant relationship between the risk of developing a pressure ulcer and the variables mobility and type of support surface.", "Four hundred and forty-six general, vascular and gynaecological surgical patients were recruited to a two centre, double triangular sequential randomised controlled trial to compare the post-operative pressure sore incidence in patients positioned on the standard operating table mattress with those positioned on the dry visco-elastic polymer pad (Action Products Inc.). Two hundred and twenty two patients were randomised to the experimental group and 224 to the standard mattress. The main endpoint failure rate (a pressure sore) was found to be 11% (22/205) for patients allocated to the dry visco-elastic polymer pad and 20% (43/211) for patients allocated to the standard operating table mattress. There was a significant reduction in the odds of developing a pressure sore on the dry visco-elastic polymer pad as compared to the standard, [symbol see text] = 0.46 with 95% confidence interval of (0.26, 0.82), P = 0.010. The adjusted point estimates of the probability of developing a pressure sore on the dry visco-elastic polymer pad and the standard operating table mattress were 0.11 and 0.21 respectively.", "The risk of nosocomial pneumonia and atelectasis is high among critically ill immobilized patients. We hypothesized that continuous turning on the kinetic treatment table would reduce their incidence. Sixty-five critically ill patients, immobilized because of head injury or traction, were prospectively randomized for treatment in a conventional bed (n = 38) or the kinetic treatment table (n = 27). Patients were well matched for baseline demographic and pulmonary risk factors. Patients in the conventional bed group had a higher incidence of cigarette smoking. The combined incidence of significant atelectasis or pneumonia was higher (66%) in the conventional vs. kinetic treatment table (33%) groups (p less than .01). Atelectasis, pneumonia, adult respiratory distress syndrome, requirements for ventilator treatment, for PEEP, and for an FIO2 greater than 0.50 were not significantly different, but tended to be higher in the control group. Survival and the incidence of decubitus ulcers were similar.", "The effectiveness of hospital pillows versus a commercial heel elevation device (the Foot Waffle [EHOB incorporated]) in preventing heel pressure ulcers was examined using an experimental balanced factorial design with repeated measures on 52 patients (ages 27 to 90) in randomized groups. Heel interface pressures were taken with patients in supine and right lateral tilt positions. Logistic regression demonstrated a statistically significant difference between interface pressures on left and right heels (p = .004) and a trend toward significance between the pillow and Foot Waffle (p = .069). The Generalized Estimating Equations (GEE) method revealed the Foot Waffle was four times more likely not to suspend the heel off the bed than the pillow, and the left heel was four-and-a-half times more likely to have higher interface pressures than the right. There was no significant difference between groups in incidence of lower-extremity pressure ulcers, but patients using the Foot Waffle developed pressure ulcers significantly sooner (10 days versus 13 days for the pillow). Heels require additional protection beyond the use of specially beds and mattress overlays. In order to provide continuous heel suspension, clinicians must consider proper fit, turning schedules, patient position, patient activity, and presence of additional equipment when selecting heel protection products. This study illustrates how difficult it is to control for all these factors when doing clinical research. Note: This study was done with a Foot Waffle model that has since been redesigned. No research is available on the new model.", "To estimate the effectiveness of a new high-performance Australian medical sheepskin (meeting Australian Standard 4480.1-1998) in preventing pressure ulcers in a general hospital population at low to moderate risk of these ulcers.\n Open-label randomised controlled clinical trial.\n A large metropolitan teaching hospital in Melbourne, Victoria, in 2000.\n 441 patients aged over 18 years admitted between 12 June and 30 November 2000, with expected length of stay over 2 days and assessed as at low to moderate risk of developing pressure ulcers.\n Patients were randomly allocated to receive a sheepskin mattress overlay for the duration of their hospital stay (218 patients) or usual treatment, as determined by ward staff (referent group, 223 patients).\n Incidence rate and cumulative incidence of pressure ulcers, assessed daily throughout hospital stay.\n 58 patients developed pressure ulcers (sheepskin group, 21; referent group, 37). Cumulative incidence risk was 9.6% in the sheepskin group (95% CI, 6.1%-14.3%) versus 16.6% in the referent group (95% CI, 12.0%-22.1%). Patients in the sheepskin group developed new pressure ulcers at a rate less than half that of referent patients (rate ratio, 0.42; 95% CI, 0.26-0.67).\n The Australian Medical Sheepskin is effective in reducing the incidence of pressure ulcers in general hospital inpatients at low to moderate risk of these ulcers.", "This study determines the effectiveness of a new low-unit-cost support system in patients at very high risk of developing pressure sores. In a prospective randomised controlled trial, a low-pressure inflatable mattress and cushion system (Repose) was compared to a dynamic support mattress (Nimbus II) used in conjunction with an alternating-pressure cushion (Alpha TranCell) in 80 patients with fractured neck of femur and high scores on a pressure sore risk assessment scale. All patients received best standard care, including turning at regular intervals. Skin condition was assessed in 17 locations on admission, preoperatively, and seven and 14 days postoperatively. No difference was found between the groups in skin condition or the occurrence and severity of pressure sores at any time point.", "nan", "To compare 3 pressure-reduction devices for effectiveness in prevention of heel ulcers in moderate-risk to high-risk patients.\n A prospective quasi-experimental 3-group design was used.\n A sample of 338 \"moderate-risk to high-risk\" adult inpatients, ages 18 to 97, at 2 medical centers in South Texas were studied.\n The Braden Scale for Pressure Ulcer Risk and investigator-developed history and skin assessment tools were used.\n Subjects were randomly assigned to the High-Cushion Kodel Heel Protector (bunny boot), Egg Crate Heel Lift Positioner (egg crate), or EHOB Foot Waffle Air Cushion (foot waffle). Data are demographics, Braden scores, comorbidities, skin assessments, lengths of stay, and costs of devices. Analyses were Chi-square, analysis of variance, and regression.\n Of 240 subjects with complete data, 77 (32%) were assigned to the bunny boot group, 87 (36.3%) to the egg crate, and 76 (31.7%) to the foot waffle. Twelve ulcers developed in 240 subjects (5% incidence). Six subjects had only 1 foot. Eleven ulcers were Stage I (nonblanchable erythema), and 1 was Stage II (partial thickness). Overall incidence was 3.9% for the bunny boot, 4.6% for the egg crate, and 6.6% for the foot waffle (not significantly different among groups). The bunny boot with pillows was most cost effective (F[3], N = 240) = 1.342, p <or= .001).\n In this study, the bunny boot was as effective as higher-tech devices. The results, however, were confounded by nurses adding pillows to the bunny boot group.", "Patients with chronic neurological diseases who were at high risk of decubitus ulcers were randomly assigned to alternating air on silicore mattress overlays for a period of 3 months. Of 148 subjects who completed the trial, more than 50% in each group developed one or more ulcers. No statistically significant differences between groups were found in the incidence, severity, healing duration or the location of the ulcers; with the exception of a significant difference (p less than 0.001) in the categorical location of the trochanters.", "A significantly lower proportion of the patients in the Jay group (25%) experienced pressure ulcer formation during the three months of observation as compared to the foam group (41%). No statistically significant differences were found between groups on the location, severity, or healing duration of the pressure ulcers. Most lesions (65%) were limited to persistent erythema of intact skin, and healed in three to four weeks. Significantly higher proportions of patients in the Jay groups (7%) rejected their cushion because of discomfort as compared to foam (1%). The incidence of pressure ulcers was significantly higher among those patients who experienced peak interface pressures recorded at 60 mmHg or higher, had low Norton scores (< or = 11), or were malnourished.", "This article describes a research study that compared the effectiveness of two pressure-reducing devices in a group of elderly nursing home residents. The results obtained revealed no significant differences between the two devices--an air-filled overlay and a gel mattress--in terms of pressure ulcer incidence, severity, and healing. Several factors contributed to these results and illustrate the problems encountered when preventing pressure ulcer development in a group of elderly, debilitated nursing home residents. These factors include ease of use of the pressure-reducing device, caregiver and facility characteristics, and critical patient variables. Until these variables are addressed, it is impossible for any device to be effective in preventing pressure ulcer development in nursing homes.", "The purpose of this study was to determine the efficacy and safety of a multi-cell pulsating dynamic mattress system in comparison with conventional management for the prevention of pressure ulcers in the operative and postoperative period in patients having cardiovascular surgery. The study was a single center, prospective, randomized, controlled trial. Patients who were having cardiovascular surgery for a duration of at least 4 hours were randomly assigned, prior to surgery, to dynamic mattress system or conventional management--both of which were initiated in the operating room and continued for up to 7 days postoperatively. Patients were assessed daily using a standardized scoring system. The results of the study showed that 198 patients in the dynamic pressure system (n = 98) or conventional management group (n = 100) were similar at baseline. A strong trend of decreased pressure ulcers existed in the dynamic pressure system group (n = 2) compared to the conventional management group (n = 7). The study concluded that a multi-cell pulsating dynamic mattress system is safe and mitigates risks for and decreases incidence of pressure ulcers in patients who undergo cardiovascular surgery.", "To determine, in critically ill patients at risk, both the clinical utility and cost-effectiveness of using an air suspension bed in the prevention of pressure ulcers.\n Randomized, parallel group, controlled clinical trial with accompanying cost-effectiveness analysis.\n 30-bed multidisciplinary intensive care unit.\n 100 consecutive patients at risk for the development of pressure ulcers randomly assigned to receive treatment on either an air suspension bed or a standard intensive care unit bed. Patients considered at risk were those at least 17 years of age with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 15 who had an expected intensive care unit stay of at least 3 days.\n The development of pressure ulcers by site and severity and the costs associated with each of the two programs.\n The air suspension bed was associated with fewer patients developing single, multiple, or severe pressure ulcers. In patients at risk, the use of an air suspension bed in the prevention of pressure ulcers was a cost-effective therapy.\n Despite intense nursing care, pressure ulcers are more prevalent in the critically ill patient population than in the general hospital population. Air suspension therapy provides a clinically effective means of preventing pressure ulcers in these patients. In patients at risk, air suspension therapy was a cost-effective means of managing pressure ulcers compared with the standard hospital bed.", "Pressure sores are a problem, especially in elderly patients. Our study was designed to determine the effectiveness in pressure-sore prevention of a new interface-pressure decreasing mattress. In a prospective randomised controlled clinical trial we tested the Comfortex DeCube mattress (Comfortex, Winona, USA) against our standard hospital mattress in 44 patients with femoral-neck fracture and concomitant high pressure-sore risk score. In addition both groups were treated according to the Dutch consensus protocol for the prevention of pressure sores. On admission and 1 and 2 weeks after admission, pressure sores were graded. The two groups were similar in patient characteristics and pressure-sore risk factors. At 1 week, 25% of the patients nursed on the DeCube mattress and 64% of the patients nursed on the standard mattress had clinically relevant pressure sores (grade 2 or more). At 2 weeks the figures were 24% and 68%, respectively. The maximum score over the several body regions of the pressure-sore grading, measured on a 5-point sale, was significantly different in favour of the DeCube mattress at 1 week (p = 0.0043) and 2 weeks (p = 0.0067) postoperatively. We show that the occurrence of pressure sores and their severity can be significantly reduced when patients at risk are nursed on an interface-pressure decreasing mattress.", "To determine whether a viscoelastic polymer (energy absorbing) foam mattress was superior to a standard hospital mattress for pressure ulcer prevention and to analyze the cost-effectiveness in comparison with standard hospital mattresses.\n Unblinded, randomized, prospective trial.\n Elderly acute care, rehabilitation, and orthopedic wards at 3 hospitals in the United Kingdom.\n 1168 patients at risk of developing pressure ulcers (Waterlow score, 15 to 20), with a median age of 83 years (25th to 75th percentile range, 79-87).\n Participants were allocated to either the experimental equipment (CONFOR-Med mattress/cushion combination) or a standard mattress/cushion combination; all were given standard nursing care. Pressure areas were observed daily.\n Development of nonblanching erythema.\n A significant decrease in the incidence of blanching erythema (26.3% to 19.9%; P =.004) and a nonsignificant decrease in the incidence of nonblanching erythema occurred in participants allocated to the experimental equipment. However, when the survival curve plots were analyzed at 7 days, both categories showed statistically significant decreases (P =.0015 and P =.042, respectively). Participants on standard equipment had a relative odds ratio of 1.36 (95% confidence interval [CI], 1.10-1.69) for developing blanching erythema or worse and 1.46 (95% CI, 0.90-1.82) for developing nonblanching erythema or worse. To prevent nonblanching erythema, the number needed to treat (NNT) was 41.9 (95% CI, -82.6-15.3). To prevent any erythema (blanching or nonblanching), the NNT was 11.5 (95% CI, 41.6-9.3). Participants with blanching or nonblanching erythema were significantly less mobile than participants with normal skin and more likely to have worsening mobility (P <.001). For participants with similar pressure ulcer status, mattress type was not associated with difference in mobility.\n Regardless of prevention routine, pressure ulcers occur. In this study, the experimental equipment showed statistical significance to standard equipment for prevention of blanching erythema; significance was not achieved for nonblanching erythema. Trend and survival analysis show that a larger study is required to determine whether this nonsignificant difference is genuine.", "A clinical evaluation of eight base foam pressure-reducing mattresses was undertaken at Addenbrooke's NHS Trust, Cambridge. Data were collected on the medical and nutritional status, skin condition, medication, weight and Waterlow score for each patient, together with ratings on mattress comfort. At the beginning and end of the study, mattresses were assessed for interface pressures and the general condition of each mattress and its cover was evaluated.", "Most standard hospital beds are flat based with a pull-out backrest, resulting in a tendency for the patient to slide down the bed. This study aimed to compare the outcome for patients at high risk of developing pressure ulcers nursed on either this type of bed or an electrically operated, multi-sectioned profiling bed. A total of 100 patients were randomly assigned either to the profiling bed with a pressure-reducing foam mattress (experimental group) or a flat-based bed with an appropriate pressure-redistributing mattress (control group) for a maximum of 10 days. Risk status and pressure damage were assessed daily. Both a patient and a nurse questionnaire were completed. Data from 70 patients who participated in the study for five days or more were included in the analysis. Pressure ulcer incidence was 0% in both groups. All patients (35) in the experimental group were able to maintain a sitting position compared with only 12/35 in the control group (p = 0.0001). While the questionnaire results suggest there were significant differences in postural control and ease of transfer between patients in the two groups, it was not possible to map this to pressure ulcer formation. Poor recruitment into the study was due to the 'blocking' of electric beds by heavily dependent patients who did not meet the inclusion criteria, precluding a significant result in terms of pressure ulcer outcomes. This nurse-led use of the profiling beds was examined alongside the main study to investigate why they were allocated in this way.", "Understanding the efficacy of patient support surfaces is essential if pressure sore management is to be both efficient and effective. However, laboratory and clinical studies in this area are fraught with well recognized problems. This investigation reports a combination of laboratory, randomized controlled trial (efficacy data) and measures of effectiveness to illustrate the beneficial role of a new dynamic integrated mattress and seat cushion system: the Pegasus Trinova. Successful prevention of sores among a vulnerable patient population, along with positive comments regarding the system's comfort and 'user-friendliness' are supported by laboratory measures of interface pressure to provide a hierarchy of data. Such an approach may present one solution to the lack of timeliness of most mattress clinical trials, thus allowing decisions regarding new support surfaces to be made upon the basis of evidence, not on anecdote or solely upon marketing claims.", "This study had three aims: to investigate if visco-elastic foam mattresses are more effective than standard hospital mattresses in reducing the incidence of pressure ulcers in patients with hip fractures; to compare pressure ulcer grade and location and documented nursing prevention and treatment interventions in patients using the two types of mattresses; to identify possible predictors of pressure ulcer development. Using a prospective randomised controlled trial design 101 patients (mean age: 84 years) were randomly allocated either a visco-elastic foam mattress or a standard mattress. There was no significant difference in the incidence of pressure ulcers between the two groups, but patients on standard mattresses tended to develop more severe pressure ulcers. Furthermore, according to the documentation, patients with grade I pressure ulcers who were allocated a standard mattress received more preventive interventions, which may have reduced the differences in outcomes between the two groups. The researchers concluded that the results support the use of the test mattress. Significant predictors of pressure ulcer development were long waiting times for surgery and low haemoglobin levels at hospital admission.", "nan", "To assess in a prospective controlled study the efficacy and safety of a specific foam body-support device designed as to prevent heel pressure ulcers.\n A randomization table was used to allocate 70 patients into 2 groups. The control group was treated with our standard pressure sore prevention protocol (half-seated position, water-mattress and preventive massages 6 times a day); the experimental group was treated with the same standard protocol as well as with the foam body-support device being evaluated. Patients were included if their Waterlow score was >10, indicating a high risk of developing pressure ulcers and if they had no skin lesion on the heels. Foam devices, covered with jersey, were constructed for the legs and allowed the heels to be free of any contact with the bed; another foam block was arranged perpendicularly to the first, in contact with the soles, to prevent ankles from assuming an equinus position (to prevent a dropfoot condition). The principal criterion for efficacy was the number of irreversible skin lesions on the heel (that is, beyond the stage of blanching hyperemia, reversible after finger pressure); these lesions were assessed every day until the end of the study (up to 30 days).\n The number of irreversible heel pressure ulcers was lower in the experimental (3 patients, 8.6%) than in the control group (19 patients, 55.4%) (p<0.0001). Mean time without any pressure ulcer was higher in the experimental group (5.6 days, compared with 2.8 days, p=0.01). The groups did not differ in the number of pressure sores on the sacrum and leg.\n An anatomical foam body-support is effective in preventing heel pressure ulcers in patients on a medical intensive care unit and is well tolerated.", "The Pegasus Airwave mattress has been used for many years in the Eastbourne NHS Trust and has proven its efficiency in the prevention of pressure sores. Pegasus has now produced a new, improved, model: the Cairwave Therapy System. This article looks at criteria that may be used to determine whether the new model is suitable for patient care. The evaluation took the form of a randomized controlled study in which 12 mattresses were randomly allocated to patients--six Airwave mattresses and six Cairwave Therapy Systems--over a 4-month period. The results of the evaluation showed that patients found the mattress comfortable. An encompassing cover reduced the risk of cross-infection, rehabilitation was supported by the firm edges of the bed and patient movement was easier due to the soft cover. During the trial all patients remained free from pressure sores.", "This randomised controlled trial of two dry-flotation pressure-reducing surfaces evaluates pressure sore incidence, patient comfort and the appropriate use of equipment in 100 orthopaedic patients. The trial involved five full Roho mattresses, five Sofflex mattresses and 10 Roho Quatro cushions to be used to complement the beds. Given the low rate of pressure sore incidence in this high-risk group it is not possible to determine whether there is any difference in effectiveness between the two mattresses. Both appear to provide similar levels of comfort, with the majority of patients finding them either comfortable or very comfortable. The initial setting of the equipment was, however, unsatisfactory.", "studies of the effectiveness of alternating pressure air mattresses (APAMs) for the prevention of pressure ulcers are scarce and in conflict.\n evaluating whether an APAM is more or equally effective as the standard prevention.\n randomised controlled trial. Setting and subjects: patients admitted to 19 surgical, internal, or geriatric wards in seven Belgian hospitals were included if they were in need of prevention of pressure ulcers. To define this need, two methods were used randomly: the Braden Scale or the presence of non-blanchable erythema (NBE).\n 447 patients were randomised into either an experimental or a control group. In the experimental group, 222 patients were lying on an APAM (Alpha-X-Cell, Huntleigh Healthcare, UK). In the control group, 225 patients were lying on a visco-elastic foam mattress (Tempur, Tempur-World Inc., USA) in combination with turning every 4 hours. Both groups had identical sitting protocols.\n there was no significant difference in incidence of pressure ulcers (grade 2-4) between the experimental (15.6%) and control group (15.3%) (P = 1). There were significantly more heel pressure ulcers in the control group (P = 0.006). There was an interaction effect between the risk assessment method and preventive measures for the development of all pressure ulcers and sacral pressure ulcers.\n fewer patients developed heel pressure ulcers on an APAM. Patients identified as being in need of prevention based on the presence of NBE had a tendency to develop fewer pressure ulcers on an APAM. Patients identified as being in need of prevention, based on the Braden Scale, appeared to develop more sacral pressure ulcers on an APAM.", "Thirty-two chronic neurologic patients between 19 and 60 years of age were randomly assigned, for a period of three months, to either an alternating air mattress or a silicore mattress to test the preventive qualities of special mattresses in the occurrence of decubitus ulcers. The two groups were comparable on the variables of age, weight, diagnoses, history of disease process, history of being wheelchair bound, history of previous pressures, and mean scores on Norton's scale of risk, which is based on the subject's physical condition, mental alertness, ambulation, mobility and incontinence. No significant differences were observed in the preventive qualities of the two types of special mattresses in terms of the incidence, location, severity, or healing duration of the subjects' decubitus ulcers. Improved studies of common special mattresses are suggested.", "Many devices are in use to prevent pressure ulcers, but from most little is known about their effects and costs. One such preventive device is the Australian Medical Sheepskin that has been proven effective in three randomized trials. In this study the costs and savings from the use of the Australian Medical Sheepskin were investigated from the perspective of a nursing home.\n An economic model was developed in which monetary costs and monetary savings in respect of the sheepskin were balanced against each other. The model was applied to a fictional (Dutch) nursing home with 100 beds for rehabilitation patients and a time horizon of one year. Input variables for the model consisted of investment costs for using the sheepskin (purchase and laundry), and savings through the prevented cases of pressure ulcers. The input values for the investment costs and for the effectiveness were empirically based on a trial with newly admitted rehabilitation patients from eight nursing homes. The input values for the costs of pressure ulcer treatment were estimated by means of four different approaches.\n Investment costs for using the Australian Medical Sheepskin were larger than the monetary savings obtained by preventing pressure ulcers. Use of the Australian Medical Sheepskin involves an additional cost of approximately 2 euro per patient per day. Preventing one case of a sacral pressure ulcer by means of the Australian Medical Sheepskin involves an investment of 2,974 euro when the sheepskin is given to all patients. When the sheepskin is selectively used for more critical patients only, the investment to prevent one case of sacral pressure ulcers decreases to 2,479 euro (pressure ulcer risk patients) or 1,847 euro (ADL-severely impaired patients). The factors with the strongest influence on the balance are the frequency of changing the sheepskin and the costs of washing related to this. The economic model was hampered by considerable uncertainty in the estimations of the costs of pressure ulcer treatment.\n From a nursing home perspective, the investment costs for use of the Australian Medical Sheepskin in newly admitted rehabilitation patients are larger than the monetary savings obtained by preventing pressure ulcers.", "To determine if the use of pressure-reducing wheelchair cushions for elderly nursing home resident wheelchair users who are at high risk for developing sitting-acquired pressure ulcers would result in a lower incidence rate of pressure ulcers, a greater number of days until ulceration, and lower peak interface pressures compared with the use of convoluted foam cushions over a 12-month period. To determine the feasibility of conducting a subsequent full-scale definitive trial to evaluate the use of pressure-reducing seat cushions for elderly nursing home resident wheelchair users.\n Randomized control trial\n 2200-bed skilled nursing facilities (1 suburban and 1 urban academic medical center)\n 32 male and female at-risk nursing home residents who were wheelchair users > or = 65 years of age. Participants had Braden Scale scores < or = 18, Braden Activity and Mobilitysubscale scores < or = 5, no sitting surface pressure ulcers, and a daily wheelchair sitting tolerance of more than 6 hours. All met criteria for using the ETAC Twin wheelchair.\n Seating evaluation with pressure-mapping and subsequent seating prescription. Subjects were assigned to either a foam (n=17) or pressure-reducing cushion (n=15) group and weekly assessments of skin and pressure ulcer risk were made.\n Incidence of pressure ulcers, days to ulceration, and peak interface pressure.\n At a 95% confidence interval, a 2-tailed analysis showed no differences between the FOAM and pressure-reducing cushion groups for pressure ulcer incidence, total days to pressure ulcer, or initial peak interface pressure. Pressure-reducing cushions were more effective in preventing sitting-acquired (ischial) pressure ulcers (P<.005). Higher interface pressures were associated with a higher incidence of pressure ulcers (P<.001).\n A definitive randomized control multicenter cushion trial is feasible with a sample size of 50 to 100 per study group. In the definitive trial, the definition of sitting-acquired pressure ulcers should be limited to lesions occurring over the ischial tuberosities.", "A clinical investigation was conducted concerning the effects of a newly designed double-layer air-cell overlay in preventing the onset of pressure ulcers for patients with a Braden scale score of < or = 16, and who require a head-elevated position of 45 degrees or higher. A randomised controlled trial was undertaken involving 82 patients from a general hospital ward using one of the following three support surfaces: a double-layer air-cell overlay, a single-layer air-cell overlay or a standard hospital mattress. A significantly lower percentage of patients using the double-layer air-cell overlay developed pressure ulcers (3.4%) compared to 19.2% and 37.0% for those patients using the single-layer air-cell overlay and standard mattress respectively. Based on these findings, a double-layer air-cell overlay should be more effective in preventing the onset of pressure ulcers than either a single-layer air-cell overlay or a standard hospital mattress for subjects requiring head elevation.", "nan", "To compare the effectiveness of a high-specification foam mattress (control) with a high-tech (Duo2, Hill Rom) alternating/continuous low-pressure mattress (treatment) in the prevention of pressure ulceration. The study also evaluated if there is a difference in performance between the two working modalities (alternating and continuous low pressure) of the high-tech mattress in a comparable sample of patients. MethoD: Thirty-three patients were observed for two weeks in the control group. In the treatment group, 86 patients were randomised to receive alternating low pressure and 84 continuous low pressure. Incidence of pressure ulcers in both arms was recorded. Student's t-test was used to compare all Braden scores, and the chi-square test and Fisher's exact test to evaluate differences between groups.\n There was a high difference in the number of new pressure ulcers in the control group when compared with the treatment group. There was no difference in performance between the alternating and continuous low-pressure modes. However, the sample size is too small to prove or disprove a statistically significant difference between the two modalities.\n The high-tech mattress was markedly more effective than the high-specification foam mattress in preventing the onset of pressure ulcers. Initial data suggest that the use of alternating or continuous low pressure made little or no difference to the results.", "A comparison of pressure reducing properties of alternating air, static air, and water mattress overlays was conducted with 57 patients in a surgical intensive care unit. Sacral and heel pressures in both recumbent and semi-Fowler's positions were tested for each surface using a repeated measures design. Mean pressures for the alternating air mattress were significantly higher than pressures with other surfaces, regardless of position or site. There were significant main effects for position and site, with higher pressures in the semi-Fowler's position and at the sacral site. A significant interaction between surface, site, and position was found. Pressure sores developed in eight patients, but the incidence was not significantly different across groups. A pressure measuring device constructed from available clinical materials proved to be both sensitive and reliable. The findings suggest alternating air overlays should be avoided, and that positioning and periodic position change to reduce sacral pressures for patients requiring prolonged upper body elevation is important.", "The purpose of this study was to compare the incidence of pressure ulcers in 40 newly admitted at-risk (Braden Scale score < 18) skilled-nursing-facility residents, randomly assigned to Iris 3000 (Bio Clinic of Sunrise Medical Corp, Ontario, CA) foam mattress overlays (n = 20) or a MAXIFLOAT (BG Industries, Northridge, CA) foam mattress replacements (n = 20). Head-to-toe skin assessments were done 3 times weekly for a maximum of 21 days, using Bergstrom Skin Assessment Tool. Subjects on MAXIFLOAT had fewer pressure ulcers (chi 2[1, N = 40] = 5.013, p = .025) despite heavier body mass (t[35] = 2.60, p = .013) and more days on the surface (t[38] = 2.24, p = .03). MAXIFLOAT proved to be more effective in preventing pressure ulcers in an at-risk skilled-care population and was cost-effective. Research findings on efficacy, adequate feedback from nursing staff, residents, and ancillary staff regarding issues of patient comfort, ease of use, and cost are important factors in decision-making when considering product changes.", "To determine differences between alternating pressure overlays and alternating pressure replacement mattresses with respect to the development of new pressure ulcers, healing of existing pressure ulcers, patient acceptability and cost-effectiveness of the different pressure-relieving surfaces. Also to investigate the specific additional impact of pressure ulcers on patients' well-being.\n A multicentre, randomised, controlled, open, fixed sample, parallel-group trial with equal randomisation was undertaken. The trial used remote, concealed allocation and intention-to-treat (ITT) analysis. The main trial design was supplemented with a qualitative study involving a purposive sample of 20-30 patients who developed pressure ulcers, to assess the impact of the pressure ulcers on their well-being. In addition, a focus group interview was carried out with clinical research nurses, who participated in the PRESSURE (Pressure RElieving Support SUrfaces: a Randomised Evaluation) Trial, to explore the experiences of their role and observations of pressure area care.\n The study took place in 11 hospital-based research centres within six NHS trusts in England.\n Acute and elective patients aged 55 years or older and admitted to vascular, orthopaedic, medical or care of the elderly wards in the previous 24 hours were investigated.\n Patients were randomised to either an alternating pressure overlay or an alternating pressure mattress replacement, with mattress specifications clearly defined to enable the inclusion of centres using products from different manufacturers, and to exclude hybrid mattress systems (which either combine foam or constant low pressure with alternating pressure in one mattress, or can be used as either an overlay or a replacement mattress).\n Development of a new pressure ulcer (grade < or =2, i.e. partial-thickness wound involving epidermis/dermis only) on any skin site. Also healing of existing pressures ulcers, patient acceptability and cost-effectiveness.\n In total, 6155 patients were assessed for eligibility to the trial and 1972 were randomised: 990 to the alternating pressure overlay (989 after one postrandomisation exclusion) and 982 to the alternating pressure mattress replacement. ITT analysis found no statistically significant difference in the proportions of patients developing a new pressure ulcer of grade 2 or above [10.7% overlay patients, 10.3% mattress replacement patients, a difference of 0.4%, 95% confidence interval (CI) -2.3 to 3.1%, p = 0.75]. When logistic regression analysis was used to adjust for minimisation factors and prespecified baseline covariates, there was no difference between the mattresses with respect to the odds of ulceration (odds ratio 0.94, 95% CI 0.68 to 1.29). There was no evidence of a difference between the mattress groups with respect to time to healing (p = 0.86). The Kaplan-Meier estimate of the median time to healing was 20 days for each intervention. More patients allocated overlays requested mattress changes due to dissatisfaction (23.3%) than mattress replacement patients (18.9%, p = 0.02) and more than one-third of patients reporting difficulties associated with movement in bed and getting into or out of bed. There is a higher probability (64%) that alternating mattress replacements are cost-saving; they were associated with lower overall costs (74.50 pounds sterling per patient on average, mainly due to reduced length of stay) and greater benefits (a delay in time to ulceration of 10.64 days on average). Patients' accounts highlighted that the development of a pressure ulcer could be pivotal in the trajectory from illness to recovery, by preventing full recovery or causing varied impacts on their quality of life.\n There is no difference between alternating pressure mattress replacements and overlays in terms of the proportion of patients developing new pressure ulcers; however, alternating pressure mattress replacements are more likely to be cost-saving. The results suggest that when renewing alternating pressure surfaces or ordering equipment within a rental contract, mattress replacements should be specified; however, overlays are acceptable if no replacement mattress is available. Similarly, patient preferences can be supported, without any great increase in risk, if individual patients request an overlay rather than a replacement mattress. Further research could include a randomised controlled trial comparing alternating pressure mattress replacements and high-specification foam mattresses in patients at moderate to high risk; an accurate costing study to understand better how much pressure ulcers cost health and social services in the UK; and trials in higher risk groups of patients. Also future trials should measure time to ulceration as the primary end-point, since this is more informative economically and possibly also from a patient and clinical perspective.", "Pressure sores are a potential complication of intensive care. Modern methods of pressure sore prevention centre around the use of pressure-relieving devices. Few studies exist that confirm the effectiveness of these devices. This study evaluates the effectiveness of two devices, the Hill-Rom Duo mattress and the KCI TheraPulse. High-risk patients were randomly assigned to receive one of two devices. We excluded those patients who had pressure sores upon admission. Those patients that did develop a pressure sore had their wound digitally photographed and graded by two independent tissue viability nurses. Sixty-two patients were included (30 TheraPulse, 32 Duo. Nine developed a pressure sore (6 Duo, 3 TheraPulse). No statistical differences between the two devices could be found. The longer a patient was nursed on a device, the greater the risk of pressure sore development. Despite the use of these devices, pressure sores can still develop in the Intensive Care patient population." ]

[ "9684641", "8937280" ]

[ "Treatment of chronic Chagas' disease with itraconazole and allopurinol.", "Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection." ]

[ "Four hundred four patients with chronic Chagas' disease were treated with itraconazole (6 mg/kg of body weight/day for 120 days), allopurinol (8.5 mg/kg of body weight/day for 60 days), or with a placebo of pure starch. Patients were monitored over a period of four years by clinical examination, serology, xenodiagnosis, hemoculture, and electrocardiogram. Drug tolerance was good, with only four treatments discontinued due to side effects that subsided after suspension of treatment. Parasitologic cure was evident in 44% of the those treated with allopurinol and 53% of those treated with itraconazole, and the electrocardiographic evaluation showed normalization in 36.5% and 48.2%, respectively, of patients with chronic or recent cardiopathy.", "Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection.\n Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection.\n Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001).\n The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy." ]

[ "17413915", "7593107", "15915033", "3896019", "1872429", "12502992", "1874226", "15282985", "12548273", "16320011", "17142005", "8842667", "7446914", "11028724", "10588563" ]

[ "Fascia iliaca compartment blockade for acute pain control in hip fracture patients: a randomized, placebo-controlled trial.", "Femoral nerve block in extracapsular femoral neck fractures.", "Effect of postoperative epidural analgesia on rehabilitation and pain after hip fracture surgery: a randomized, double-blind, placebo-controlled trial.", "Analgesia following femoral neck surgery. Lateral cutaneous nerve block as an alternative to narcotics in the elderly.", "Postoperative analgesia after triple nerve block for fractured neck of femur.", "Preoperative cardiac events in elderly patients with hip fracture randomized to epidural or conventional analgesia.", "Post-operative analgesia following femoral-neck surgery--a comparison between 3 in 1 femoral nerve block and lateral cutaneous nerve block.", "[Femoral nerve block as pain relief in hip fracture. A good alternative in perioperative treatment proved by a prospective study].", "Three-in-one femoral nerve block as analgesia for fractured neck of femur in the emergency department: a randomized, controlled trial.", "[Acute pain management in proximal femoral fractures: femoral nerve block (catheter technique) vs. systemic pain therapy using a clinic internal organisation model].", "[Analgesia after hip fracture repair in elderly patients: the effect of a continuous femoral nerve block: a prospective and randomised study].", "The value of continuous blockade of the lumbar plexus as an adjunct to acetylsalicyclic acid for pain relief after surgery for femoral neck fractures.", "Anaesthesia for surgical correction of fractured femoral neck. A comparison of three techniques.", "Epidural infusion of bupivacaine and fentanyl reduces perioperative myocardial ischaemia in elderly patients with hip fracture--a randomized controlled trial.", "Continuous psoas compartment block for anesthesia and perioperative analgesia in patients with hip fractures." ]

[ "Hip fracture patients are in severe pain upon arrival at the emergency department. Pain treatment is traditionally based on systemic opioids. No study has examined the effect of fascia iliaca compartment blockade (FICB) in acute hip fracture pain management within a double-blind, randomized setup.\n Forty-eight patients with suspected hip fracture were included immediately after arrival in the emergency department, before x-ray confirmation of their fracture. Included patients were randomly assigned to two groups of 24. In the FICB group, the patients received an FICB with 1.0% mepivacaine and a placebo intramuscular injection of isotonic saline. In the morphine group, the patients received a placebo FICB with 0.9% saline and an intramuscular injection of 0.1 mg/kg morphine. Patients received intravenous rescue morphine when necessary.\n Maximum pain relief was superior in the FICB group both at rest (P < 0.01) and on movement (P = 0.02). The median total morphine consumption was 0 mg (interquartile range, 0-0 mg) in the FICB group and 6 mg (interquartile range, 5-7 mg) in the morphine group (P < 0.01). More patients (P = 0.05) were sedated in the morphine group at 180 min after block placement as compared with the FICB group.\n Pain relief was superior at all times and at all measurements in the FICB group. The study supports the use of FICB in acute management of hip fracture pain because it is an effective, easily learned procedure that also may reduce opioid side effects in this fragile, elderly group of patients.", "We randomised 50 patients with extracapsular fractures of the femoral neck to receive either a bupivacaine femoral nerve block or systemic analgesia alone. A femoral nerve block was found to be an easy and effective procedure which significantly reduced perioperative analgesic requirements and postoperative morbidity.", "Hip fracture surgery usually carries a high demand for rehabilitation and a significant risk of perioperative morbidity and mortality. Postoperative epidural analgesia may reduce morbidity and has been shown to facilitate rehabilitation in elective orthopedic procedures. No studies exist on the effect of postoperative epidural analgesia on pain and rehabilitation after hip fracture surgery.\n Sixty elderly patients were included in a randomized, double-blind study comparing 4 days of continuous postoperative epidural infusion of 4 ml/h bupivacaine, 0.125%, and 50 mug/ml morphine versus placebo. Both patient groups received balanced analgesia and intravenous nurse-controlled analgesia with morphine. All patients followed a well-defined multimodal rehabilitation program. Pain, ability to participate in four basic physical functions, and any factors restricting participation were assessed on the first 4 postoperative days during physiotherapy.\n Epidural analgesia provided superior dynamic analgesia during all basic physical functions, and patients were significantly less restricted by pain, which was the dominating restricting factor in the placebo group. Motor blockade was not a restricting factor during epidural analgesia. Despite improved pain relief, scores for recovery of physical independence were not different between groups.\n Postoperative epidural analgesia after hip fracture surgery provides superior analgesia attenuating pain as a restricting factor during rehabilitation without motor dysfunction. However, superior analgesia did not translate into enhanced rehabilitation. Future studies with multimodal rehabilitation are required to establish whether superior analgesia can be translated into enhanced rehabilitation and reduced morbidity in hip fracture patients.", "In a prospective controlled randomised trial on patients undergoing operative repair of fractured neck of femur via a lateral incision, the postoperative analgesic requirements of one group of patients who received a lateral cutaneous nerve block were compared with a second group who received no block. The former group were found to need significantly less intramuscular pethidine in the first 24 hours, and 44% required no supplementary analgesia whatsoever during this period. The time to first dose of opioid in the remainder was greatly increased. No untoward sequelae associated with the nerve block were seen.", "Fifty patients with fractured neck of femur that required surgical correction with either a compression screw or pin and plate device were randomly allocated to receive one of two anaesthetic techniques, general anaesthesia combined with either opioid supplementation or triple nerve block (three in one block) with subcostal nerve block. The nerve blocks significantly reduced the quantity of opioid administered after operation; 48% of these patients required no additional analgesia in the first 24 hours. Plasma prilocaine levels in these patients were well below the toxic threshold, and peak absorption occurred 20 minutes after the injection. No untoward sequelae were associated with the nerve blocks.", "Perioperative myocardial ischemia occurs in 35% of unselected elderly patients undergoing hip fracture surgery. Perioperative epidural analgesia may reduce the incidence of adverse cardiac events.\n The effect of early administration of epidural analgesia during the stressful period, on cardiac events was evaluated in a prospective randomized study in 68 patients with hip fractures who either had known coronary artery disease or were at high risk for coronary artery disease. On admission to the emergency room, patients were assigned to receive a usual care analgesic regimen (intramuscular meperidine, control group, n = 34) or continuous epidural infusion of local anesthetic and opioid (epidural group, n = 34). Monitoring in the preoperative period included a preoperative history and physical examination, daily assessment of cardiac adverse events, serial electrocardiograms, cardiac enzymes, and pain scores.\n Preoperative adverse cardiac events were significantly more prevalent in the control group compared with the epidural group (7 of 34 0 of 34; = 0.01). Adverse cardiac events included fatal myocardial infarction in three, fatal congestive heart failure in one, nonfatal congestive heart failure in one, and new onset atrial fibrillation in two. The incidence of intraoperative and postoperative adverse cardiac events was similar for the two groups. The significant difference between groups in the incidence of preoperative cardiac events prompted interruption of the study after the planned interim analysis.\n The authors' data indicate that compared with conventional analgesia, early administration of continuous epidural analgesia is associated with a lower incidence of preoperative adverse cardiac events in elderly patients with hip fracture who have or are at risk for coronary artery disease. Preoperative epidural analgesia may be advantageous for this surgical population.", "A prospective controlled randomized trial on patients receiving surgery for fractured neck of femur was carried out, in which post-operative analgesic requirements in three separate groups were compared. Patients in Group 1 acted as controls, whilst those in Groups 2 and 3 received lateral cutaneous nerve blocks and 3 in 1 femoral nerve blocks, respectively. Patients in Group 3 needed significantly less analgesia than the other two groups, and the time to first administration of analgesia was significantly longer. No complications of either of the nerve blocks was noted.", "Almost 25% of all patients with hip fracture experience temporary confusion pre- and directly postoperatively due to trauma, advanced age, transport between units, and the use of analgesics, 35-50% of the patients suffer temporary or chronic decubitus. Analgesics often lead to nausea. A femoral nerve block can interrupt sensory impulses from the hip joint and provide complete pain relief without affecting the CNS, thus making preoperative care easier and postoperative rehabilitation can be started earlier. 80 consecutive patients with hip fracture were randomized to femoral nerve block or pharmacological treatment only. Paracetamol and tramadol were the standard analgesics used. All patients were followed up with regard to pain, duration of the block, number of analgesics doses, temporary confusion and time for postoperative mobilization. Pain was estimated by the patients using the visual analogue scale (VAS). A nerve block was performed to block the femoral nerve, the lateral femoral cutaneous nerve and the obturator nerve with 30 ml of ropivacaine 7.5 mg/ml. Mental status was evaluated with Pfeiffer-test. All patients experienced relatively intense pain on admission with an average VAS of 6. After nerve block the VAS was 2. Pain relief was the same in the control group. Pain relief was sustained for 15 hours. The time for mobilization after surgery was significantly lower, 23 hours compared to 36 for the control group. There was a lower number of patients temporarily confused in the block group compared to the control group, however no significant differences were seen. Femoral nerve block provides adequate pain relief, equivalent to pharmacological treatment in most patients. The time for postoperative mobilization was shorter and less temporary confusion was seen. There were no complications in this group, making nerve block a good alternative to traditional pharmacological preoperative treatment for patients with hip fractures.", "We determine whether 3-in-1 femoral nerve block is effective as analgesia for fractured neck of femur when administered by emergency physicians.\n This was a prospective, randomized controlled trial with blinded assessors conducted in a district general hospital emergency department in the United Kingdom. Over a 6-month period, all patients with fractured neck of femur were considered for study. Patients were randomly assigned to receive 3-in-1 nerve block with bupivacaine plus intravenous morphine or intravenous morphine. An accreditation package for all ED medical staff was devised to ensure competence in the technique of 3-in-1 nerve block. Pain scores were recorded on arrival and at intervals up to 24 hours after admission. Morphine consumption in the first 24 hours was recorded.\n Ninety-four patients sustained fractured neck of femur during the study period; 50 were studied. Of 44 not studied, 42 were confused, 1 did not consent, and 1 was overlooked. Patients receiving 3-in-1 nerve blocks recorded a faster time to reach the lowest pain score: 2.88 hours for patients with nerve block and 5.81 hours for control patients (mean difference -2.93 h; 95% confidence interval [CI] -5.48 to -0.38 h). Nerve block recipients required significantly less morphine per hour than control patients (mean of 0.49 mg/h versus 1.17 mg/h; mean difference -0.68 mg/h; 95% CI -1.23 to -0.12 mg/h).\n Three-in-one femoral nerve block is an effective method of providing analgesia to patients with fractured neck of femur in the ED. All grades of medical staff were able to apply and consolidate this skill.", "The aim of this study was to compare safety and efficacy of catheter-mediated femoral nerve block analgesia with systemic pain therapy in patients with proximal femoral fractures in the pre-operative and post-operative setting using a protocol for coordinating pain management.\n In a prospective randomised trial of patients attending the emergency department, 100 individuals were selected with a clinically diagnosed proximal femoral fracture. Patients were divided into two equal groups A and B. Group A (n=50) received a catheter-mediated femoral nerve block with 1% prilocaine (40 ml) and post-operatively 0.2% ropivacaine (30 ml) 6 hourly. Group B (n=50) initially received intravenous metamizol (1 g) and a fixed combination of oral tilidine (100 mg) + naloxone (8 mg). Patients aged 90 years or more received a reduced dose (tilidine 75 mg + naloxone 6 mg). In the post-operative period regular oral ibuprofen (400 mg, 8 hourly) in addition to oral tilidine (50 mg) + naloxone (4 mg) was given as required for break through pain. Pain intensity was measured using a verbal rating scale (VRS) from 1 to 5: pain free (=1), mild pain (=2), moderate pain (=3), severe pain (=4), excruciating pain (=5). Pain scores were recorded at rest (R), during passive anteflection (30 degrees) of the hip (PA) on arrival and at 15 and 30 min after initial administration of analgesia. Thereafter, recordings were made 4 times a day up to the third post-operative day.\n Pain scores were comparable for both groups on admission (VRS in R 2.50 vs. 2.46; VRS during PA 4.30 vs. 4.34). Significant pain relief was achieved in both groups following initial administration of analgesia, but the total pain scores in group A were significantly lower than in group B (VRS in R 1.22 vs. 1.58, p<0.01 and VRS during PA 2.66 vs. 3.26; p<0.001). No difference was noted between the two groups during the first 3 post-operative days. No severe complications occurred as a result of analgesia, however, the catheter was dislodged in 20% of patients in group A resulting in the need for systemically administered analgesia.\n All patients presenting with proximal femoral fractures should receive adequate analgesia within the emergency department even prior to radiographic imaging. Femoral nerve block should be considered as the method of choice. The insertion of a femoral nerve block catheter has the dual advantage of early analgesia permitting repeated clinical examination in addition to continued post-operative pain management. The cumbersome logistics inherent in this technique within the clinical setting limits its practical application. An initial single-shot regional nerve block followed by a systemic post-operative analgesia protocol was considered an appropriate alternative. The execution of safe, consistent and appropriate regional nerve block anaesthesia is reliant on formal guidelines and protocols as agreed by the multidisciplinary teams involved with patient-directed pain management and good clinical practice.", "The usefulness of peripheral femoral nerve block for pain management after hip fracture has been established. This prospective and randomised study compared the analgesia effect of a continuous femoral nerve block (CF) versus two conventional analgesia procedures after hip fracture.\n Patients. (n=62) scheduled for surgery under spinal anaesthesia were prospectively included. After surgery, analgesia (48 hours) was randomised: group FC (femoral catheter, anterior paravascular approach, initial bolus followed by continuous infusion of ropivacaine 0.2%), group P (iv 2 g propacetamol/6 hours), group M (sc morphine, 0.05 mg/kg per 4 hour). Intravenous morphine titration was performed, followed by subcutaneous (sc) morphine every 4 hours according to the VAS score. The primary end-point was the morphine requirements. Secondary end-points were VAS score, side effects, and mortality.\n Demographic data and surgical procedures were similar between groups. After morphine titration, the VAS pain score did not differ between groups. All patients in-group M received additional morphine. Morphine mean consumption was increased in CF group: 26 mg (5-42) versus P: 8 mg (3-12) (p=0.0001) or M: 19 mg (8-33) (p<0.006) while constipation was decreased in P group vs CF. Percentage of patients requiring no morphine was similar between P (n=6; 28%) and CF (n=6; 28%) and greater than M (n=0; 0%). Hospital discharge, cardiovascular or pulmonary complications and mortality after 6 months showed no statistical difference.\n Continuous femoral nerve block provided limited pain relief after hip fracture did not reduced side effects and induced an expensive cost.", "In a randomized, double-blind investigation the analgesic effect of continuous blockade of the lumbar plexus as an adjunct to acetylsalicyclic acid by suppository after surgery for femoral neck fractures under spinal anaesthesia was examined in 20 patients. Before surgery, a catheter was inserted into the femoral nerve sheath. The patients were allocated randomly to receive bupivacaine or saline by bolus and then continuous infusion, started immediately after the operation. No statistically significant differences in additional morphine requirements, visual analogue pain scores or adverse effects were observed between the two treatment groups. It is concluded that continuous blockade of the lumbar plexus as an adjunct to rectal acetylsalicyclic acid offers no major additional pain relief after surgery for femoral neck fractures under spinal anaesthesia.", "Sixty patients with fractured neck of femur and scheduled for surgical correction were randomly allocated to receive one of three anaesthetic techniques: general anaesthesia; spinal analgesia; psoas compartment block. The patients in the local anaesthetic groups also received a light general anaesthetic. There was little difference in the pre-, intra- and postoperative events, and no difference in postoperative mortality.", "Perioperative myocardial ischaemia is an important risk factor for cardiac morbidity and mortality after noncardiac surgery. The impact of analgesic management on the incidence and severity of cardiac ischemia was studied in 77 elderly patients undergoing surgical treatment of traumatic hip fracture.\n After hospital admission and written consent, patients were randomised to conventional analgesic regimen (intramuscular oxycodone, OPI group) or continuous epidural infusion of bupivacaine/fentanyl (EPI group). The analgesic regimens were started preoperatively. Patients were operated under spinal anaesthesia and the treatments were continued three days postoperatively. ECG was continuously recorded. ST segment depression of > or = 0.1 mV or elevation of > or = 0.2 mV lasting > or = 1 min were considered as ischaemic episodes. Nocturnal arterial oxygen saturation (SaO2) was recorded perioperatively, and subjective pain was assessed every morning using a visual analogue scale (VAS).\n Fifty-nine (OPI 30, EPI 29) patients were evaluable for efficacy. Thirteen patients (43%) in the OPI and 12 patients (41%) in the EPI group had ischaemic episodes (NS). However, significantly more patients in the OPI group had ischaemic episodes during the surgery (8 vs. 0 in the EPI group, P=0.005). The median (quartal deviation) total ischaemic burden (i.e. integral of ST-change vs. time) in patients with ischaemic episodes was ten times larger in the OPI group (340 [342] mm x min) compared with the EPI group (30 [36] mm x min) (P=0.002). There were no significant differences between the groups in average heart rates or in heart rates at the start of ischaemic episodes or in maximal heart rates during the attacks. Average nocturnal SaO2 was similar in the two groups and there were no differences in the number of hypoxaemic (SaO2<90%) episodes. Preoperatively there were no differences in subjective pain, but postoperative and average perioperative VAS scores for pain were almost 40% lower in the EPI group (P=0.006). Perioperative myocardial infarctions were not detected.\n Continuous epidural bupivacaine/fentanyl analgesic regimen, started preoperatively, reduces the amount of myocardial ischaemia in elderly patients with hip fracture.", "The perioperative use of continuous psoas compartment block (CPCB) was compared with traditional pain management for patients with fracture of the femur. The anatomy of CPCB was also tested in cadavers.\n Forty consecutive patients (range, 67-96 years old) were prospectively randomized either to group A (given local anesthetics using a CPCB) or group B (given perioperative analgesia with meperidine). In another part of the study, CPCB was performed in 15 fresh cadavers, and dissection of the lumbar region was performed after dye injection.\n Continuous psoas compartment block was performed successfully in all patients in group A and was used in the pre- (16-48 hours) and postoperative (72 hours) periods. Visual analog scale score in group A was lower than in group B in 5/7 preoperative and 9/9 postoperative 8 hourly assessments. Differences reached statistical significance (P < .05) in 3 and 5 of the assessments, respectively. Patient satisfaction was higher in group A in the pre- (P < .05) and postoperative periods (P<.03). The block failed to achieve surgical anesthesia in 85% (17/20) of the patients, and additional anesthesia was needed. The anatomic study failed to support the existence of a defined \"psoas compartment\" previously described, and supported the clinical findings. Injected dye was found in the region of the origin of the sciatic nerve (essential for the production of anesthesia for hip surgery) in only 26% (4/15) of cadavers.\n The CPCB seems to be an appropriate technique for efficient and safe perioperative pain control. However, in our dissections, the psoas compartment was not well defined in all patients, thus, using this route for anesthesia may result in only partial success." ]

[ "9313662", "7540705", "2423337" ]

[ "A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group.", "Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group.", "A double-blind trial of the effect of beta-sitosteryl glucoside (WA184) in the treatment of benign prostatic hyperplasia." ]

[ "To report the results of a double-blind, placebo-controlled trial to evaluate Azuprostat, a beta-sitosterol, in patients with symptoms of outlet obstruction caused by benign prostatic hyperplasia (BPH).\n A randomized, double-blind and placebo-controlled clinical trial was conducted to assess the efficacy and safety of 130 mg free beta-sitosterol (phytosterol) daily, using the international prostate symptom score (IPSS) as the primary outcome variable. In total, 177 patients with BPH were recruited for 6 months of treatment in 13 study centres. In addition to the relative difference in the IPSS, changes in quality of life, peak urinary flow rate (Qmax) and post-void residual urinary volume (PVR) were recorded. The drug used in the trial consisted of a chemically defined extract of phytosterols, derived for example from species of Pinus, Picea or Hypoxis, with beta-sitosterol as the main component.\n There were significant (P < 0.01) improvements over placebo in those treated with beta-sitosterol; the mean difference in the IPSS between placebo and beta-sitosterol, adjusted for the initial values, was 5.4 and in the quality-of-life index was 0.9. There were also significant improvements in the secondary outcome variables, with an increase in Qmax (4.5 mL/s) and decrease in PVR (33.5 mL) in favour of beta-sitosterol when adjusted for the changes after placebo.\n These results show that beta-sitosterol is an effective option in the treatment of BPH.", "Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multicentre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg beta-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6.7 (SD 4.0) points in the beta-sitosterol-treated group versus -2.1 (3.2) points in the placebo group p < 0.01. There was a decrease in IPSS (-7.4 [3.8] points in the beta-sitosterol-treated group vs -2.1 [3.8] points in the placebo group) and changes in urine flow parameters: beta-sitosterol treatment resulted in increasing peak flow (15.2 [5.7] mL/s from 9.9 [2.5] mL/s), and decrease of mean residual urinary volume (30.4 [39.9] mL from 65.8 [20.8] mL). These parameters did not change in the placebo group (p < 0.01). No relevant reduction of prostatic volume was observed in either group. Significant improvement in symptoms and urinary flow parameters show the effectiveness of beta-sitosterol in the treatment of benign prostatic hyperplasia.", "Cholesterol-lowering agents are still used in some countries for the treatment of benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled urodynamic study, carried out on 53 patients with proven outflow obstruction, has failed to prove that the drug, beta-sitosteryl beta-D-glucoside (WA184), is superior to placebo in the treatment of outflow obstruction due to BPH when administered at a dose of 0.3 mg/day. Possible reasons for this include an insufficient dose and duration of treatment (this drug is known to have a potent effect on cholesterol metabolism in the prostate) and the predominantly stromal pathological changes which characterize BPH and which may be unaffected by such agents." ]

[ "17995495", "11095258" ]

[ "A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women.", "Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial." ]

[ "To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen.\n Randomised controlled trial.\n A tertiary teaching hospital.\n One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy.\n Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen.\n De novo endometrial pathology at 1 year of tamoxifen.\n Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year.\n LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.", "Tamoxifen is currently the most commonly used adjuvant treatment for breast cancer, however, it frequently causes episodes of unscheduled uterine bleeding, which could be associated with proliferative changes of the endometrium, or even endometrial cancer. We aimed to assess whether a levonorgestrel intrauterine system could modulate the uterine responses to tamoxifen. We also aimed to assess women's tolerance of the screening procedures, the insertion, removal, and potential side-effects of the device.\n We did a randomised controlled trial, in which postmenopausal women who had had at least 1 year of adjuvant tamoxifen treatment and who were undergoing regular follow-up for breast cancer were randomly assigned to either endometrial surveillance alone, or endometrial surveillance before and after insertion of the levonorgestrel intrauterine system for 12 months. We assessed tolerance of the surveillance procedures and the device with visual analogue scales.\n Baseline assessment showed only benign uterine changes in all women (n=122). Hysteroscopic assessment indicated a uniform decidual response (confirmed histologically in 40 of 41 cases) in all women fitted with the intrauterine system; there were no new polyps in these women and 13% had fewer fibroids than in controls. Both screening procedures and device were well tolerated. There was an excess of bleeding in the women fitted with intrauterine systems but this resolved to a baseline similar to those receiving surveillance only.\n The levonorgestrel-releasing intrauterine system had a protective action against the uterine effects of tamoxifen. The effectiveness of this device in preventing uterine changes in the endometrium needs to be assessed in the context of decreasing the need for repeated investigations of postmenopausal bleeding in women taking tamoxifen." ]

[ "11704175", "15194252", "15366405", "8677064", "16714913", "16336366", "9611015", "15668838", "10162961", "18547413", "18436331", "12039085", "2013952", "17540908", "9065192", "9116534" ]

[ "A randomized controlled trial of intervention in fear of childbirth.", "Mandatory second opinion to reduce rates of unnecessary caesarean sections in Latin America: a cluster randomised controlled trial.", "Effect of peer review and trial of labor on lowering cesarean section rates.", "Effect of external peer review on cesarean delivery rates: a statewide program.", "Does relaxation education in anxious primigravid Iranian women influence adverse pregnancy outcomes?: a randomized controlled trial.", "Making choices for childbirth: a randomized controlled trial of a decision-aid for informed birth after cesarean.", "Effect of departmental policies on cesarean delivery rates: a community hospital experience.", "Evaluation of the impact of birth preparation courses on the health of the mother and the newborn.", "Equalizing physician fees had little effect on cesarean rates.", "Special features of health services and register based trials - experiences from a randomized trial of childbirth classes.", "Financial incentives do not always work: an example of cesarean sections in Taiwan.", "Randomised clinical trial on the effect of the Dutch obstetric peer review system.", "Opinion leaders vs audit and feedback to implement practice guidelines. Delivery after previous cesarean section.", "Two decision aids for mode of delivery among women with previous caesarean section: randomised controlled trial.", "Randomized controlled trial of a prenatal vaginal birth after cesarean section education and support program. Childbirth Alternatives Post-Cesarean Study Group.", "The impact of legislatively imposed practice guidelines on cesarean section rates: the Florida experience." ]

[ "To compare intensive and conventional therapy for severe fear of childbirth.\n In Finland, 176 women who had fear of childbirth were randomly assigned at the 26th gestational week to have either intensive therapy (mean 3.8 +/- 1.0 sessions with obstetrician and one with midwife) or conventional therapy (mean 2.0 +/- 0.6 sessions), with follow-up 3 months postpartum. Pregnancy-related anxiety and concerns, satisfaction with childbirth, and puerperal depression were assessed with specific questionnaires. Power analysis, based on previous studies, showed that 74 women per group were necessary to show a 50% reduction in cesarean rates.\n Birth-related concerns decreased in the intensive therapy group but increased in the conventional therapy group (linear interaction between the group and birth-concerns P =.022). Labor was shorter in the intensive therapy group (mean +/- standard deviation 6.8 +/- 3.8 hours) compared with the conventional group (8.5 +/- 4.8 hours, P =.039). After intervention, 62% of those originally requesting a cesarean (n = 117) chose to deliver vaginally, equally in both groups. Cesarean was more frequent for those who refused to fill in the questionnaires than for those who completed them (57% compared with 27%, P =.001). In the log-linear model, parous women who had conventional therapy and refused to fill in the questionnaires chose a cesarean more often than expected (standardized residual 2.54, P =.011). There were no differences between groups in satisfaction with childbirth or in puerperal depression.\n Both kinds of therapy reduced unnecessary cesareans, more so in nulliparous and well-motivated women. With intensive therapy, pregnancy- and birth-related anxiety and concerns were reduced, and labors were shorter.", "Latin America has a high rate of caesarean sections. We tested the hypothesis that a hospital policy of mandatory second opinion, based on the best existing scientific evidence, reduces the hospital caesarean section rate by 25%, without increasing maternal and perinatal morbidity and mortality.\n 36 hospitals in Argentina (18), Brazil (eight), Cuba (four), Guatemala (two), and Mexico (four), were randomly assigned to intervention or control in a matched pair design. All physicians in the intervention hospitals deciding a non-emergency caesarean section had to follow a policy of mandatory second opinion. The primary outcome was the overall caesarean section rate in the hospitals after a 6-month implementation period. We also assessed women's satisfaction with labour and delivery care and physicians'acceptance of the second opinion policy.\n A total of 34 hospitals attending 149?276 deliveries were randomised and completed the protocol. The mandatory second opinion policy was associated with a small but significant reduction in rates of caesarean section (relative rate reduction 7.3%; 95% CI 0.2-14.5), mostly in intrapartum sections (12.6%; 0.6-24.7). Other maternal and neonatal outcomes and women's perceptions and satisfaction with the process of care were similarly distributed between the groups.\n In hospitals applying this policy of second opinion, 22 intrapartum caesarean sections could be prevented per 1000 deliveries, without affecting maternal or perinatal morbidity, and without affecting mothers' satisfaction with the care process.", "In an attempt to lower cesarean section rates, a cesarean surveillance system and a selective trial of labor were introduced in a tertiary hospital in Taiwan.\n From 1997 to 2000, 2 physicians were appointed as consultants for the pre-cesarean surveillance, and a trial of labor after a cesarean section was employed concurrently. We organized a weekly departmental Cesarean Indication Conference on Mondays. Comparisons of the cesarean rates between 1993-96 and 1997-2000 were made using the chi-square test. Comparisons of the proportion of overall cesarean sections contributed by each indication for both 1993 and 2000 were also made by chi-square test.\n A comparison of the 4-year periods before and after 1997 showed that the total cesarean rate had decreased from 37.0 to 30.7% (p < 0.001), primary cesarean rate from 21.3 to 17.8% (p < 0.001), and repeat cesarean rate from 15.7 to 12.9% (p < 0.001). No uterine rupture occurred. Among the 54 indications for primary cesareans, compared between 1993 and 2000, the proportion rates for dystocia, fetal distress, preeclampsia, induction failure, gestational diabetes, and elderly primigravidahad decreased substantially.\n The efficient way to lower the repeat cesarean rate is trial of labor, and the way to reduce the number of primary cesareans is in practicing of the guidelines for various indications. The cesarean surveillance system can solidify these guidelines, leading to a lower cesarean rate and an avoidance of inappropriate indications.", "To assess the effectiveness of a joint-specialty society and health department statewide peer-review program to reduce cesarean rates.\n Forty-five of the 165 hospitals with active delivery services were reviewed between 1989 and 1993. Differences in total and repeat cesarean rates and vaginal birth after cesarean (VBAC) rates were compared by hospital review status using Student t tests and linear regression for the years before and after completion of the program.\n Reviewed hospitals reduced their total cesarean rate by 3% and repeat cesarean rate by 0.7%, and increased their VBAC rate by 14.6% compared with nonreviewed hospitals, for which the respective reduction in rates was 1%, 0.6%, and 12.7%. Statistically, there was no difference between reviewed and nonreviewed hospitals in terms of rate changes.\n This joint-specialty society and health department peer review had no apparent impact on cesarean rates.", "Maternal anxiety and stress are found to be predictors of adverse pregnancy outcomes, including low birth weight and prematurity.\n The aim of the study was to determine whether relaxation education in anxious pregnant Iranian women in their first pregnancy affects selected pregnancy outcomes, including birth weight, preterm birth, and surgical delivery rate.\n A total of 110 obstetrically and medically low-risk primigravid women in Iran with a high anxiety level demonstrated by Spielberger's State-Trait Anxiety Inventory were randomly assigned into experimental and control groups.\n In this randomized controlled trial, the experimental group received routine prenatal care along with 7-week applied relaxation training sessions, while the control group received only routine prenatal care. Anxiety and perceived stress were measured by pre-educational and post-educational intervention. Data related to pregnancy outcomes include birth weight, gestational age at birth, and type of delivery.\n Significant reductions in low birth weight, cesarean section, and/or instrumental extraction were found in the experimental group compared with the control group. No significant differences were found in the rate of preterm birth.\n The findings suggest beneficial effects of nurse-led relaxation education sessions during the prenatal period. This intervention could serve as a resource for improving pregnancy outcomes in women with high anxiety.", "Decision-making about mode of birth after a cesarean delivery presents challenges to women and their caregivers and requires a balance of risks and benefits according to individual circumstances. The study objective was to determine whether a decision-aid for women who have experienced previous cesarean birth facilitates informed decision-making about birth options during a subsequent pregnancy.\n A prospective multicenter randomized controlled trial of 227 pregnant women was conducted within 3 prenatal clinics and 3 private obstetric practices in New South Wales, Australia. Women with 1 previous cesarean section and medically eligible for trial of vaginal birth were recruited at 12 to 18 weeks' gestation; 115 were randomized to the intervention group and 112 to the control group. A decision-aid booklet describing risks and benefits of elective repeat cesarean section and trial of labor was given to intervention group women at 28 weeks' gestation. Main outcome measures included level of knowledge, decisional conflict score, women's preference for mode of birth, and recorded mode of birth.\n Women who received the decision-aid demonstrated a significantly greater increase in mean knowledge scores than the control group (increasing by 2.17 vs 0.42 points on a 15-point scale) (p < 0.001, 95% CI for difference = 1.15-2.35). The intervention group demonstrated a reduction in decisional conflict score (p < 0.05). The decision-aid did not significantly affect the rate of uptake of trial of labor or elective repeat cesarean section. Preferences expressed at 36 weeks were not consistent with actual birth outcomes for many women.\n A decision-aid for women facing choices about birth after cesarean section is effective in improving knowledge and reducing decisional conflict. However, little evidence suggested that this process led to an informed choice. Strategies are required to better equip organizations and practitioners to empower women so that they can translate informed preferences into practice. Further work needs to examine ways to enhance women's power in decision-making within the doctor-patient relationship.", "During 1994, our department adopted several strategies in an attempt to decrease our cesarean delivery rates. This study evaluates the effect of these changes on our cesarean delivery rates.\n We studied data of women who delivered at our community hospital obstetric unit over a period of 6 years, from January 1, 1991, to December 31, 1996. During 1994, our department adopted labor management and cesarean delivery guidelines, with review of every cesarean delivery that did not meet guidelines and confidential individual feedback; established 24-hour in-house coverage; and attempted to achieve the goal of an annual cesarean delivery rate of less than 15%. These data were evaluated by chi2 analysis. Women who delivered in the first 3 years (group A) were compared with those who delivered in the second 3 years (group B) (ie, when the changes occurred). P < .05 was considered significant.\n Groups A and B shared similar demographic characteristics. The total cesarean delivery rate decreased from 22.5% (group A) to 18.6% (group B) (P = .001), whereas the primary cesarean delivery rate decreased from 13.5% to 10.6% (P = .001) and the repeat cesarean delivery rate decreased from 9.0% to 7.9% (P = .03). The proportion of women who received oxytocin and regional anesthesia and underwent vacuum-assisted deliveries increased (P < .001), whereas perinatal mortality and morbidity did not change.\n The cesarean delivery rate safely decreased. These data suggest the importance of the commitment of attending physicians to a lower cesarean delivery rate, of service improvements, and of detailed feedback.", "This study was carried out to evaluate the impact of birth preparation courses on the health of the mother and the newborn. A randomized clinical trial study was carried out on 200 primigravid women younger than age 35 years with gestational age of 20 weeks. Subjects were randomly divided into two groups: control and trial. Birth preparation classes were introduced to the trial group in eight sessions during pregnancy, whereas the control group received only routine care. Measurable clinical, obstetrical, and neonatal advantages were monitored and compared in two groups. Patients in the trial group suffered from back and pelvic pain and headache significantly less often than patients in control group (two-tailed p(2) < 0.05). Preparation is significantly related to reduction in dystocic deliveries and cesarean section ( p(2) = 0.044). Antenatal preparation could play a major role in the health of mother and newborn during labor and postpartum. In addition, antenatal preparation should be introduced to all women during pregnancy as a national health policy in Iran.", "nan", "Evaluating complex interventions in health services faces various difficulties, such as making practice changes and costs. Ways to increase research capacity and decrease costs include making research an integral part of health services and using routine data to judge outcomes. The purpose of this article is to report the feasibility of a pilot trial relying solely on routinely collected register data and being based on ordinary health services.\n The example intervention was education to public health nurses (PHN) (childbirth classes) to reduce caesarean section rates via pre-delivery considerations of pregnant women. 20 maternity health centers (MHC) were paired and of each 10 pairs, one MHC was randomly allocated to an intervention group and the other to a control; 8 pairs with successful intervention were used in the analyses (1601 mothers). The women visiting to the study maternity centers were identified from the Customer Register of Helsinki City. A list of the study women was made using the mother's personal identification number, visit date, the maternity center code, birth date and gestation length. The mode of delivery and health outcomes were retrieved from the Finnish Medical Birth Register (MBR). Process data of the intervention are based on observations, written feedback and questionnaires from PHNs, and project correspondence.\n It took almost two years to establish how to obtain permissions and to actually obtain it for the trial. Obtaining permissions for the customer and outcome data and register linkages was unproblematic and the cluster randomization provided comparable groups. The intervention did not succeed well. Had the main aim of the trial been to cause a change in PHNs behavior, we would have very likely intensified the intervention during the trial.\n Our experiences encourage the use of trials that obtain their outcomes from registers. Changing the behavior of ordinary health service providers is a challenging intervention.\n not registered (see Results).", "To test the hypothesis that cesarean sections are less likely to be performed after equalizing the fees for vaginal births and cesarean sections.\n Population-based National Health Insurance inpatient claims in Taiwan are used. Pre-periods and post-periods are identified to investigate the impact of the policy changes. Logistic regressions are employed.\n The cesarean section rates for the first, second and higher-order births are 29, 37.4 and 39.3%, while the primary cesarean section rates are 29, 11.8 and 12.1%, respectively. After taking into consideration the case-mix and birth order, the second and higher-order births were approximately 60% less likely to be cesarean deliveries compared to the first births and the increase in the VBAC fee had an additional negative effect on them. A fee equalization policy was not found to influence the cesarean delivery. The total cesarean section rate was primarily determined by the cesarean section rate for the first birth.\n Cesarean section rates are greater for the higher-order births because of the practice \"once a cesarean section, always a cesarean section\". Against the background of a rapidly declining fertility rate, females play a more important role in the mode of delivery than ever before. As such, financial incentives designed specifically for obstetricians do not have the desired impact. Policies that are aimed at altering behavior should be designed within the social context.", "The project \"Obstetric Peer Review Interventions\" (Verloskundige Onderlinge Kwaliteitsspiegeling Interventies, VOKSINT) was set-up in The Netherlands in 1994. It provided annual comparison data (quality ranking, league tables) for secondary care obstetric departments adjusted for population differences, based on the data registered in the Perinatal Database of The Netherlands (Landelijke Verloskunde Registratie, LVR). The aim of the so-called VOKS reports was to influence obstetricians' interventions in such a way that they led to a more homogeneous policy. To assess this influence, a trial was set-up, with departments randomly assigned to be or not to be informed about the VOKS results. Obstetric intervention rates and the morbidity of newborns including neonatal neurological examinations (NNEs) were assessed. Obstetric intervention rates were similar in the report group and the control group. Practice in the report group became more homogeneous (adjusted for population differences) than in the control departments, but this was only statistically significant for term caesarean section.", "A randomized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section. The guideline recommended clinical actions to increase trial of labor and vaginal birth rates. Charts for all 3552 cases in the study groups were audited. After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group, but rates were 46% and 85% higher, respectively, among physicians educated by an opinion leader. Duration of hospital stay was lower in the opinion leader education group than in the other two groups. The overall cesarean section rate was reduced only in the opinion leader education group. There were no adverse clinical outcomes attributable to the interventions. The use of opinion leaders improved the quality of care.", "To determine the effects of two computer based decision aids on decisional conflict and mode of delivery among pregnant women with a previous caesarean section.\n Randomised trial, conducted from May 2004 to August 2006.\n Four maternity units in south west England, and Scotland.\n 742 pregnant women with one previous lower segment caesarean section and delivery expected at >or=37 weeks. Non-English speakers were excluded.\n Usual care: standard care given by obstetric and midwifery staff. Information programme: women navigated through descriptions and probabilities of clinical outcomes for mother and baby associated with planned vaginal birth, elective caesarean section, and emergency caesarean section. Decision analysis: mode of delivery was recommended based on utility assessments performed by the woman combined with probabilities of clinical outcomes within a concealed decision tree. Both interventions were delivered via a laptop computer after brief instructions from a researcher.\n Total score on decisional conflict scale, and mode of delivery.\n Women in the information programme (adjusted difference -6.2, 95% confidence interval -8.7 to -3.7) and the decision analysis (-4.0, -6.5 to -1.5) groups had reduced decisional conflict compared with women in the usual care group. The rate of vaginal birth was higher for women in the decision analysis group compared with the usual care group (37% v 30%, adjusted odds ratio 1.42, 0.94 to 2.14), but the rates were similar in the information programme and usual care groups.\n Decision aids can help women who have had a previous caesarean section to decide on mode of delivery in a subsequent pregnancy. The decision analysis approach might substantially affect national rates of caesarean section. Trial Registration Current Controlled Trials ISRCTN84367722.", "Our objective was to assess whether, for women with previous cesarean section, a prenatal education and support program promoting vaginal birth after cesarean delivery increases the probability of vaginal delivery.\n Women with a single previous cesarean were recruited before 28 weeks' gestation. Women's self-assessed motivation to attempt vaginal birth after a previous cesarean delivery was measured on a 10 cm visual analog scale: stratum I, low motivation; stratum II, high motivation. Women were randomized by stratum to one of two groups. Those in the \"Verbal\" group participated in an individualized education program. Those in the \"Document\" group were provided with a pamphlet detailing the benefits of planned vaginal birth after cesarean delivery.\n Rates of vaginal birth after cesarean section were similar in the verbal and document groups: verbal, 339 of 641 (53%); document, 310 of 634 (49%); relative risk 1.1, 95% confidence interval 1.0 to 1.2. There was no evidence of heterogeneity across motivational strata. Regardless of treatment group, women with low motivation for vaginal birth after cesarean section were more than three times as likely to undergo elective repeat cesarean than were women with high motivation (47% vs 13%).\n There was no evidence that an individualized prenatal education and support program, when offered to all women with previous cesarean delivery, results in a clinically significant increase in the rate of vaginal birth after cesarean section.", "Florida legislation implemented in the fall of 1992, unique in the nation, mandated that practice guidelines regarding cesarean section deliveries be disseminated to obstetric physicians. The law also required that peer review boards at hospitals be established to review cesarean deliveries and that the exact dates of implementation of the guidelines be reported to a state agency. To determine the impact of the legislation, we conducted a retrospective analysis of 366,246 total live births occurring in Florida hospitals during 1992 and 1993, before and after formal hospital certification of the implementation of the guidelines. Changes in primary and repeat cesarean rates were analyzed for 108 independent groups of births, controlling for the mother's age, race, payment source, and the timing of the implementation of the guidelines at hospitals. The guideline certification program did not accelerate the consistent but gradual downward trend in cesarean births which had already been evident in the three prior years. The data do suggest that the guideline program may have affected repeat cesareans more than primary cesareans, especially in the first quarter of 1993, immediately after the hospital certification period. Reductions in repeat cesareans involved both Medicaid and commercially insured births, whereas reductions in primary cesareans were found almost exclusively within commercially insured mothers, where the existing rates are highest. Although births with a prior cesarean represent only 12.5% of all births, significant decreases in repeat cesareans were found in groups representing 72.6% of this population. By comparison, significant decreases in primary cesareans were found in groups representing only 36.5% of the births without a prior cesarean. The date of guideline implementation reported by hospitals was not related to any systematic change in observed cesarean section rates. We concluded that the mere dissemination of practice guidelines by a state agency may not achieve either the magnitude or the specificity of the results desired without an explicit and thorough guideline implementation program. Blunt legislative mandates may be ineffective when multiple initiatives are already achieving desired outcomes." ]

[ "3115770", "3089202" ]

[ "Clobazam in therapy-resistant patients with partial epilepsy: a double-blind placebo-controlled crossover study.", "Clobazam for refractory focal epilepsy. A controlled trial." ]

[ "Clobazam was compared with placebo as antiepileptic adjunct medication in 129 therapy-resistant epileptic patients who were mainly suffering from complex partial seizures. The study was performed in five European countries according to a double-blind crossover design lasting 7 months. Two treatment periods of 3 months (1 month adjustment and 2 months maintenance medication) were separated by one medication switch-over month. The difference in seizure reduction between clobazam and placebo was significant (p less than 0.05). Nineteen percent of patients receiving clobazam became seizure-free during the maintenance dose period. In contrast, freedom from seizures was not observed in any placebo patient. Electroencephalogram (EEG) signs, mood ratings, and global impressions also indicated therapeutic effects of clobazam in epilepsy. The most frequent adverse reactions to clobazam were drowsiness and dizziness. However, the sedative effects of clobazam seemed to be less pronounced in comparison with other benzodiazepines. The study gives evidence of the therapeutic value of clobazam as adjunct medication in therapy-resistant partial seizures. The use of clobazam as monotherapy and long-term treatment, as well as the particular seizure response pattern to clobazam, has to be further investigated.", "The effect of 1,5-benzodiazepine clobazam was assessed in a double-blind add-on trial in 20 patients with chronic complex partial seizures uncontrolled by maximally tolerable daily dosage of standard antiepileptic drug therapy. The number of seizures was lower during the three months of active treatment. At the end of the third month, eight (40%) of the patients had a seizure reduction by more than 75%, including four patients (20%) who had complete control. Tolerance to the antiepileptic effect of clobazam was noted in 56% of the patients, and mild transient sedation occurred in 40% of the patients. Despite these drawbacks, clobazam is an effective add-on drug for individual patients with refractory focal epilepsy." ]

[ "21761149", "21712704", "20115970", "17060762" ]

[ "Negative pressure wound therapy to prevent seromas and treat surgical incisions after total hip arthroplasty.", "A prospective randomized trial comparing subatmospheric wound therapy with a sealed gauze dressing and the standard vacuum-assisted closure device.", "A randomized, prospective, controlled study of forearm donor site healing when using a vacuum dressing.", "Effectiveness of negative pressure closure in the integration of split thickness skin grafts: a randomized, double-masked, controlled trial." ]

[ "The purpose of this study was to evaluate the use of negative pressure wound therapy (NPWT) to improve wound healing after total hip arthroplasty (THA) and its influence on the development of postoperative seromas in the wound area.\n The study is a prospective randomised evaluation of NPWT in patients with large surgical wounds after THA, randomising patients to either a standard dressing (group A) or a NPWT (group B) over the wound area. The wound area was examined with ultrasound to measure the postoperative seromas in both groups on the fifth and tenth postoperative days.\n There were 19 patients randomised in this study. Ten days after surgery, group A (ten patients, 70.5 ± 11.01 years of age) developed seromas with an average size of 5.08 ml and group B (nine patients, 66.22 ± 17.83 years of age) 1.97 ml. The difference was significant (p = 0.021).\n NPWT has been used on many different types of traumatic and non traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas in the wound and improved wound healing.", "Two methods of subatmospheric pressure wound therapy--wall suction applied to a sealed gauze dressing (GSUC) and the vacuum-assisted closure device (VAC)--were compared in hospitalized patients at University of Chicago Medical Center.\n VAC therapy is widely used, but can be expensive and difficult to apply; it also fails in some patients.\n A randomized prospective study of 87 patients (N = 45 in the GSUC arm and N = 42 in the VAC arm) was undertaken between October 2006 and May 2008. The study comprised patients with acute wounds resulting from trauma, dehiscence, or surgery.\n Demographics and wound characteristics were similar in both groups. There were significant reductions in wound surface area and volume in each group. In the GSUC group, the reductions in wound surface area and volume were 4.5%/day and 8.4%/day, respectively (P < 0.001 for both), and in the VAC group, this was 4.9%/day and 9.8%/day, respectively (P < 0.001 for both). The reductions in wound surface area and volume were similar in both groups (P = 0.60 and 0.19, respectively, for the group-by-time interaction). The estimated difference (VAC - GSUC) was 0.4% (95% confidence interval: -1.0, 1.7) for wound surface area and 1.4% (95% confidence interval: -0.7, 3.5) for volume. The mean cost per day for GSUC therapy was $4.22 versus $96.51 for VAC therapy (P < 0.01) and the average time required for a GSUC dressing change was 19 minutes versus 31 minutes for a VAC dressing change (P < 0.01). The sum of pain intensity differences was 0.50 in the GSUC group compared with 1.73 for the VAC group (P = 0.02).\n GSUC is noninferior to VAC with respect to changes in wound volume and surface area in an acute care setting. In addition, GSUC dressings were easier to apply, less expensive, and less painful.", "1) Compare skin graft healing of the radial forearm free flap (RFFF) donor site when using a negative pressure dressing (NPD) versus a static pressure dressing (SPD). 2) Examine the association of graft size and medical comorbidities with healing of RFFF donor site.\n Randomized, controlled trial.\n Tertiary care hospital.\n After the study was approved, consenting adults undergoing RFFF for head and neck reconstructions were randomized into two arms: SPD and NPD groups. Fifty-four patients were enrolled from March 2007 to August 2009. Pre- and postoperative data were collected, including medical comorbidities, graft size, and area of graft failure/tendon exposure. Data were collected at two postoperative time points.\n The overall wound complication rate was 38 percent (19/50). Wound complications at the first postoperative visit (44.4% [12/27] SPD and 30.4% [7/23] NPD) were not significantly different between groups (P = 0.816). Similarly, wound complications at the second visit (68.8% [11/16] SPD and 80% [12/15] NPD) were not significantly different (P = 0.55). Percentage of area of graft failure between the groups also showed no difference (4.5% SPD vs 7.2% NPD, P = 0.361). The association of graft size with wound complications was analyzed by dividing the data set into three groups (<50 cm(2), 51-100 cm(2), and >100 cm(2)). This difference was not found to be significant (P = 0.428). Finally, when evaluating comorbidities, 50 percent (8/16) of subjects with comorbidities experienced complications compared with 32.4 percent (11/34) without comorbidities, also not reaching significance (P = 0.203).\n Although an attractive option for wound care, the NPD does not appear to offer a significant improvement over an SPD in healing of the RFFF donor site.\n Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.", "To determine the effectiveness of the negative pressure closure (NPC) technique in the integration of split-thickness skin grafts (STSG) to the recipient site.\n Randomized, double-masked, controlled trial. Setting: A tertiary burn unit. Patient characteristics: Between May 2003 and October 2004, 60 patients having wounds with skin loss which hindered primary closure, were incorporated to this study. We excluded patients with > or =20% of total body surface burns, polytraumatized, surgical contraindications, those who were enlisted in other clinical trials, and those who rejected the informed consent. Interventions: In all the patients, surgical cleaning of the recipient site and STSG were performed after which they were randomly assigned between 2 groups: a group that received a NPC dressing and were connected to the central aspiration system at -80 mm Hg versus a control group with similar dressing but without connection to negative pressure. Loss of STSG area at the fourth postoperative day, days of hospital stay.\n Sixty patients were included. The median loss of the STSG in the NPC group was 0.0 cm versus 4.5 cm in the control group (P = 0.001). The median hospital stay was of 13.5 days in the NPC group versus 17 days in the control group (P < 0.001).\n The use of NPC significantly diminishes the loss of STSG area, as well as shortens the days of hospital stay. Therefore, it should be routinely used for these kinds of procedures." ]

[ "8197566", "7793222", "12954840", "1519364", "8792730", "8083709", "12177257", "11465435", "9421852", "2058822", "2042462", "17430467", "8292113", "19057729" ]

[ "Autologous blood transfusion for hepatectomy in patients with cirrhosis and hepatocellular carcinoma: use of recombinant human erythropoietin.", "Perioperative autotransfusion and functional coagulation analysis in total hip replacement.", "Preoperative use of recombinant human erythropoietin before total joint arthroplasty.", "Feasibility of a predeposit autologous blood donation program in colorectal cancer patients: results from a randomized clinical study.", "Autologous blood transfusion in hip replacement. No effect on blood loss but less increase of plasminogen activator inhibitor in a randomized series of 80 patients.", "Blood transfusion-modulated tumor recurrence: first results of a randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery.", "A prospective, randomized study of preoperative autologous donation for hip replacement surgery.", "Autologous blood transfusion in oral and maxillofacial surgery patients with the use of erythropoietin.", "Modulation of immune response by blood transfusion: evidence for a differential effect of allogeneic and autologous blood in colorectal cancer surgery.", "[A comparison of autologous transfusion procedures in hip surgery].", "Predonation autologous blood in hip arthroplasty.", "Effect of packed red blood cells transfusion on plasma fibronectin during liver resection.", "Blood transfusions and prognosis in colorectal cancer.", "Preoperative autologous blood donation reduces the need for allogeneic blood products: a prospective randomized study." ]

[ "We evaluated the benefit of autologous blood transfusion and the effect of recombinant human erythropoietin (rh-EPO) on preoperative autologous blood donation for hepatectomy in patients with cirrhosis.\n Forty-two patients with cirrhosis and hepatocellular carcinoma underwent hepatectomy, 21 of whom (group A) donated autologous blood before operation. Eleven of these patients (group A1) were administered rh-EPO before operation, and ten patients (group A2) were untreated. Twenty-one patients (group B) did not donate autologous blood.\n The frequency of homologous blood transfusion was 24% in group A and 62% in group B (p < 0.05). Preoperative erythropoiesis increased markedly in group A1, and postoperative erythropoietin production was not suppressed in this group. Postoperative hematocrits recovered significantly more rapidly in patients transfused with only autologous blood. Postoperative serum total bilirubin concentrations were significantly higher in patients with transfused homologous blood.\n Autologous blood transfusion yields clinically superior results for hepatectomy in patients with cirrhosis when compared with homologous transfusion. Preoperative rh-EPO administration minimizes presurgical decreases in hematocrit caused by autologous blood donation.", "Functional coagulation analyses like Sonoclot and thromboelastography have not been evaluated during perioperative autotransfusion. We have prospectively studied three different transfusion regimes in 45 patients undergoing total hip arthroplasty. Blood losses were replaced either with heterologous erythrocyte concentrate (group I), intra- and postoperative autotransfusion of blood salvaged with cellsaver technique (group II) or predonated autologous erythrocyte concentrates together with salvaged blood (group III). Routine and functional coagulation analyses with a Sonoclot were performed preoperatively, 6 hours postoperatively (6 h), day 1-5 and 10. An early postoperative hypo- and late postoperative hypercoagulative phase could be detected with Sonoclot signs of platelet function and fibrin deposition in all groups. Sonoclot coagulation analyses better correlated to both blood loss and dextran dosage than APTT and platelet count in the routine coagulation analyses. Functional coagulation analysis has a potential use in individualizing plasmasubstitution and thromboprophylaxis regimes during autotransfusion in THR.", "Previous reports have suggested that the use of recombinant human erythropoietin is effective for decreasing the need for perioperative allogeneic blood transfusion. The purpose of this study was to evaluate the efficacy of erythropoietin in combination with, and compared with, preoperative autologous donation for reducing allogeneic blood requirements for total joint arthroplasty.\n Two hundred and forty patients undergoing primary and revision total hip or knee arthroplasty were enrolled into three groups with different treatment regimens: (1) erythropoietin and preoperative autologous donation (Group 1), (2) erythropoietin alone (Group 2), and (3) preoperative autologous donation alone (Group 3). Patients were evaluated with regard to requirements for allogeneic transfusion, change from the baseline to the lowest postoperative hemoglobin value, postoperative complications, and adverse reactions.\n The rate of allogeneic transfusion was 11% in Group 1 (erythropoietin and preoperative autologous donation) compared with 28% in Group 2 (erythropoietin alone) and 33% in Group 3 (preoperative autologous donation alone). Within Group 1, patients who had a unilateral primary arthroplasty had an allogeneic transfusion rate of 4% and those who had a bilateral or revision arthroplasty had an allogeneic transfusion rate of 17%. In Groups 2 and 3, the allogeneic transfusion rates were 14% and 15%, respectively, for the patients who had a unilateral primary arthroplasty and 35% and 47%, respectively, for those who had a bilateral or revision arthroplasty.\n Preoperative use of erythropoietin in conjunction with preoperative autologous donation reduces the need for allogeneic blood transfusion associated with total joint arthroplasty more effectively than does either erythropoietin or preoperative autologous donation alone.", "The hematologic and transfusion data of a multicenter randomized trial investigating the effect of blood transfusions on the 5-year survival were used to study the feasibility of an autologous blood donation program in colorectal cancer patients. Three hundred and ten patients were randomized for autologous blood transfusions (predeposition of 2 units) or homologous blood transfusions, and transfusion rules were standardized. The Hb level in the patients who donated blood decreased by 20.1 +/- 1.3 g/l (mean +/- SEM) preoperatively and 4.5 +/- 1.8 g/l postoperatively, and in controls 3.7 +/- 1.1 g/l and 16.5 +/- 1.9 g/l (significantly different between the two groups, both pre- and postoperatively: p less than 0.01). Because blood loss and number of transfusions were similar in both groups, this indicated that either preoperative or postoperative erythropoiesis is stronger in patients who had donated blood. Twenty-three percent of the autologous patients and 61% of the homologous patients were exposed to homologous blood. The effectiveness of the procedure differed per tumor localization. In patients with a right-sided colon carcinoma, 22% of the control patients needed homologous blood, compared to 10% of the autologous patients. In patients with other colon carcinomas, this was 52 and 16%, respectively, and in patients with a rectal carcinoma 85 and 41%. We conclude that predeposition of 2 units of blood for colorectal cancer surgery is feasible and useful to prevent homologous blood usage in a significant number of patients with left colon carcinoma or rectal carcinoma.", "80 patients underwent total hip replacement (THR) for primary coxarthrosis. In a randomized study, half of them donated 2 units of blood before operation. One unit was collected 4 weeks and one 2 weeks before the scheduled THR. All except 1 patient tolerated the predonations well. Total blood losses were similar in both groups. Additional bank blood was given in 7/38 in the predonation group, compared to 29/40 in the control group. Hemostatic parameters were studied in 10 consecutive patients in each group. Plasminogen activator inhibitor 1 (PAI-1), a possible risk parameter for thromboembolism, was significantly more increased postoperatively in the control group, which received only homologous blood. Platelet count, prothrombin complex, antithrombin III and von Willebrand factor antigen were significantly reduced and C reactive protein increased after surgery in both groups. We recommend predonation of 2 autologous units before a primary THR. In most cases, such predonation makes homologous blood transfusion unnecessary. The use of predonated blood causes no reduction of blood loss in THRs, but the increase in PAI-1 seen after homologous transfusions is avoided.", "Allogeneic blood transfusions have reportedly been associated with a poor prognosis in patients with curatively resected cancer. To control for immunosuppression induced by a speculatively causal allogeneic blood transfusion, we designed a randomized study in which the control group received autologous blood transfusions not related to any condition of immunosuppression.\n One hundred twenty patients with potentially curative resectable colorectal cancer and the capability to predeposit autologous blood were randomly selected to receive either standard allogeneic blood transfusion or predeposited autologous blood.\n In curatively resected cancer patients, the number who needed allogeneic blood transfusions was reduced from 60% in the allogeneic blood group to 33% in the autologous blood group (P = .009). After a median follow-up duration of 22 months (range, 8 to 48) tumor recurrence was observed in 28.9% of the allogeneic blood group and 16.7% of the autologous blood group. Life-table analysis established a tendency toward a shorter tumor-free survival for the allogeneic blood group (log-rank P = .11). The problem with this analysis was the strong association of allogeneic blood transfusions with tumor recurrence, which interfered in 33% of patients in the autologous blood group who required additional allogeneic blood transfusions. Multivariate analysis of established risk factors for tumor recurrence and surgery-related variables reflecting potential immunosuppressive conditions showed that only pT stage (relative risk, 6.61; 95% confidence interval [CI], 1.82 to 23.99; P = .004), pN stage (relative risk, 8.39; 95% CI, 3.15 to 22.33; P < .001), and the need for allogeneic blood (relative risk, 6.18; 95% CI, 2.20 to 17.37; P < .001) were independent predictors of tumor recurrence. Subgroup analysis of patients who received a transfusion of < or = 2 U blood found a significantly higher risk of tumor recurrence in the allogeneic blood group (relative risk, 5.16; 95% CI, 1.13 to 23.62; P = .034), which was reduced to borderline significance (relative risk, 3.54; 95% CI, 0.76 to 16.51; P = .107) by adjustment for tumor (T) and node (N) stage.\n As indicated by these first results, the blood transfusion modality has a significant effect on tumor recurrence after surgical treatment of colorectal cancer. A change in the practice of blood transfusion might thus potentially surpass the impact of any recent adjuvant treatment strategies.", "Preoperative autologous blood donation is commonly performed to meet potential perioperative transfusion needs and is a common practice prior to total hip arthroplasty. Using standardized transfusion guidelines, we prospectively analyzed the effectiveness of preoperative autologous donation as a method for decreasing allogeneic transfusion among patients undergoing unilateral primary total hip replacement who were eligible to donate autologous blood.\n Patients who were scheduled for primary total hip replacement surgery and who had a preoperative baseline hemoglobin level >or=120 g/L were randomized either to donate two units of blood (autologous donors) or not to donate any blood (nondonors). The donors and nondonors were compared with regard to demographic data, blood-loss volumes, hemoglobin measurements, and transfusion rates. Randomization continued until data were obtained from at least forty patients per treatment group.\n Of the ninety-six patients who completed the study, forty-two were autologous donors and fifty-four were nondonors. There were no significant differences between the donors and nondonors with regard to age, male:female ratio, estimated blood volume, baseline physical condition, or operative blood loss. The hemoglobin values at the time of enrollment (baseline), at the time of hospital discharge, and six weeks postoperatively were not significantly different between the two groups, although values at the time of admission (129 +/- 13 g/L versus 138 +/- 12 g/L) and in the recovery room (104 +/- 12 g/L versus 115 +/- 13 g/L) were significantly lower in the autologous donor group (p < 0.05). No patient in either group required an allogeneic transfusion. Twenty-nine (69%) of the forty-two donors received an autologous transfusion. Thirty-four (41%) of eighty-two autologous units were wasted. At a charge of $379 per autologous unit, there was an additional cost of $758 for each patient in the donor group.\n Preoperative autologous donation provided no benefit for nonanemic patients undergoing primary total hip replacement surgery. Preoperative autologous donation increased the likelihood of autologous transfusion, wastage of predonated units, and costs.", "Autologous blood transfusion presents few infectious or immunologic side effects. The aim of the present study was to determine the impact of autologous blood transfusion with or without recombinant human erythropoietin (rHuEPO) in patients who underwent elective maxillofacial operations.\n Seventy eight consecutive patients (29 men and 49 women) underwent elective maxillofacial operations during the years 1990-95.\n The patients were randomly assigned to three groups: In group 1, 30 patients preoperatively underwent autologous blood predonation with intravenous injection of erythropoietin 600 lU/kg after each blood predonation and autologous blood transfusion intraoperatively; in group 2, 28 patients underwent the same procedure without erythropoietin and in group 3, 20 patients underwent homologous transfusion serving as control group. All patients received ferrous sulphate daily by mouth, preoperatively until one week postoperatively.\n Group 1 patients showed higher levels of haematocrit, haemoglobin and red blood cell count pre- and postoperatively than the group 2 patients. It was also shown that the use of rHuEPO contributed to an improvement of the blood parameters of the patients in the group 1 compared with those of the patients in groups 2 and 3.", "Even though blood transfusion-associated immunomodulatory effects have been reported, the basic immune mechanism is still not understood. Data from studies on the clinical effects of allogeneic blood-induced immunosuppression are contradictory. However, there are indications that autologous blood transfusion is not immunologically neutral but has intrinsic immunomodulatory potential. Therefore we investigated in vivo different immunological mediators in 56 randomized patients of a study comparing autologous and allogeneic blood transfusion in colorectal cancer surgery. Soluble IL-2 receptor, which is an indicator of general immune activation and the following immunologic refractory phase, indicated immunosuppression was more elevated at the seventh postoperative day in patients with allogeneic transfusions (p = .013) and autologous transfusions (p = .0003). The immunologic determination of TNF-alpha showed a significant postoperative increase in patients with autologous transfusions only (p = .0031). However, postoperative increase of soluble TNF-receptors p55 and p75 was also significant in patients transfused with allogenic blood (p = .022; p = .0014). The response to tetanus toxoid vaccination, an indicator of humoral immunity, was higher in patients transfused with allogeneic rather than autologous blood (p = .082), whereas responses of patients with autologous transfusions were even lower than in nontransfused patients. The reciprocal was already found for cell-mediated immunity determined by epicutaneously tested delayed-type hypersensitivity-reactions. IL-10 levels, an indicator of cellular immunosuppression, were determined in 27 additional patients before operation, immediately postoperative, and at the seventh postoperative day. IL-10 was found elevated immediately postoperative in allogeneic (p = .011) and nontransfused patients only (p = .042). The data from this study substantiate recent findings of a different immunomodulatory potential of allogeneic and autologous blood transfusion. They furthermore support the hypothesis that autologous blood transfusion does not contain immunologically neutral effects of allogeneic blood, but itself exerts an immunomodulatory effect.", "The risks associated with transfusion can be minimized with autologous blood. The efficiency of preoperative deposit, preoperative hemodilution and intra- and postoperative autotransfusion in reducing homologous transfusions has been demonstrated. There seem to be few studies, however, that compared the different methods of autologous transfusion. This study was designed to evaluate the comparative efficiency of these methods. PATIENTS AND METHODS. Sixty-four patients scheduled for total hip arthroplasty were randomly divided into four groups: group I--preoperative autologous deposit: group II--preoperative hemodilution; group III--intra- and postoperative autotransfusion; group IV--control. Preoperative autologous donations were stored in CPDA-1 buffer. Three units of 450 ml were requested. A predonation hemoglobin (Hb) concentration of 11 g dl was required. Surgery was carried out in the 5th week after the first donation. Preoperative hemodilution to Hb 9 g/dl was carried out after induction of anesthesia and initial circulatory stabilization. A cell separator was used for intra- and postoperative autotransfusion. Postoperative autotransfusion of drainage blood was continued until 6 h after the beginning of the operation. Polygeline was used for volume resuscitation. If the Hb concentration fell below 9 g/dl in the operating room and intensive care unit or below 10 g/dl in the general ward, autologous blood or homologous packed red cells were transfused. Autologous blood collected with the cell separator was retransfused at the end of the operation and after the autotransfusion period irrespective of the actual Hb concentration. RESULTS. The general data of the patients, blood loss, and Hb concentration at the beginning of the study and postoperatively were comparable in the four groups. Homologous transfusion requirements amounted to 0 (0-1250) ml (median, range) packed red cells in group I (preoperative deposit). 500 (0-2000) ml in group II (hemodilution), 125 (0-1000) ml in group III (autotransfusion) and to 500 (0-1500) ml in group IV (control). In group I 14 of 16 patients, in group II 1 of 16, in group III 8 of 16 patients, in group IV 5 of 15 patients did not require homologous transfusion. The difference between group I and IV was significant (p = 0.004 and p = 0.003). Global coagulation tests, antithrombin III, and total serum protein were comparable in the four groups. DISCUSSION. The efficiency of preoperative hemodilution to reduce homologous transfusion requirements is limited]. In the present study, as in two other recent studies, hemodilution did not reduce homologous transfusion requirements. Autotransfusion with a cell separator can save approximately 50% of the erythrocytes lost during hip arthroplasty and 70% of the drainage loss. The homologous transfusion requirements for the autotransfused group reported here were less than in the control group; the difference, however, was not statistically significant. Patients participating in preoperative autologous deposit did not require homologous blood for hip arthroplasty in 62%-70% of cases in other investigations; in the present study 88% of the patients did not require homologous blood. CONCLUSION. Under the conditions studied, preoperative autologous deposit was the most efficient method of autologous transfusion for hip arthroplasty. It should be employed primarily.", "In a prospective randomized study of elderly patients, a total of 130 units of blood were donated by 45 patients prior to a total hip arthroplasty. Fifteen patients served as controls (no phlebotomy). The average age was 71 (60-82) years. No major complication occurred with phlebotomy. All the patients were able to maintain their hematologic and chemical parameters within the normal range throughout the donation period. The autologous blood covered all the peroperative transfusion needs and 97 percent of the total transfusion requirements. There was less postoperative blood loss, as well as total blood loss, in the autologous groups compared with the control group. There was no difference in the rate of postoperative complications between the groups. The use of predeposited autologous blood in elective orthopedics, regardless of patient age, is feasible, cost effective, and avoids the risks associated with homologous blood transfusion.", "Our study aimed at evaluating the effect of blood transfusion - allogeneic or autologous - on plasma levels of fibronectin during liver resections. Thirty-five patients scheduled for liver resection were randomly allocated to receive autologous (group autologous blood transfusion (ABT), n= 19) or allogeneic (homologous) (homologous blood transfusion (HBT), n= 16) packed red blood cell to maintain serum haemoglobin concentration above 9 g. Serum levels of fibronectin were measured before induction of anaesthesia, at the end of operation and at first, third and sixth postoperative day. Perioperative morbidity and survival rate were also recorded. Serum fibronectin levels were significantly higher (P < 0.05) in the autologous group than in the allogeneic, at the first (134 +/- 49 microg mL(-1) vs. 89 +/- 31 microg mL(-1)) and third (178 +/- 51 microg mL(-1) vs. 96 +/- 41 microg mL(-1)) postoperative day. No differences in survival and complication rate between the two groups were observed. Concentrations of serum fibronectin seem to be adversely affected by allogeneic blood transfusion during liver resection surgery, although this does not seem to affect patients' morbidity and mortality.", "Blood transfusions may adversely affect the prognosis of patients treated surgically for cancer, although definite proof of this adverse effect has not been reported.\n We carried out a randomized trial to investigate whether the prognosis in patients with colorectal cancer would be improved by a program of autologous blood transfusion as compared with the current practice of allogeneic transfusion. Patients in the autologous-transfusion group were required to donate two units of blood before surgery.\n A total of 475 patients were evaluated. We found no significant difference in prognosis between the allogeneic-transfusion group (236 patients) and the autologous-transfusion group (239 patients); colorectal cancer-specific survival rates at four years were 67 percent and 62 percent, respectively (P = 0.39). Among the 423 patients who underwent curative surgery, 66 percent of those in the allogeneic-transfusion group and 63 percent of those in the autologous-transfusion group had no recurrence of colorectal cancer at four years (P = 0.93). We also found that the risk of recurrence was significantly increased in patients who received blood transfusions, either allogeneic or autologous, as compared with patients who did not require transfusions; the relative rates of recurrence were 2.1 (P = 0.01) and 1.8 (P = 0.04), respectively; these rates did not differ significantly from each other.\n The use of autologous blood as compared with allogeneic blood for transfusion does not improve the prognosis in patients with colorectal cancer. Regardless of their type, transfusions are associated with poor prognosis, probably because of the circumstances that necessitate them.", "We sought to assess the efficacy of preoperative autologous blood donation in reducing patient exposure to allogeneic blood products following elective cardiac surgery.\n We included 48 patients in a prospective study and randomly assigned them into the control or treatment group. We excluded patients with aortic stenosis, main trunk stenosis and unstable angina. Group A (n=23; coronary disease n=21 and valvular disease n=2) was the control group, and group B (n=25; coronary disease n=21, valvular disease n=4) received preoperative autologous blood donation. All patients had cardiopulmonary bypass surgery, and we processed mediastinal blood with a cell-saver device before reinfusion. All patients received aprotinin, and we reinfused blood shed from the mediastinum postoperatively.\n No major peri- or postoperative complications occurred. We interrupted preoperative blood donation in 2 patients (8%) because of worsened angina pectoris. The mean time between the first blood donation and surgery was 22.5 (standard deviation [SD] 9.4, range 12-50) days. In group A, 9 patients (39.1%) were exposed to allogeneic blood products. In group B, 11 patients (47.8%) were exposed to blood products (p=0.73), and 4 (16%) were exposed to allogeneic blood products (p=0.036).\n Preoperative blood donation was completed in 92% of the targeted low-risk population. The procedure significantly reduced exposure to perioperative allogeneic blood products." ]

[ "7657902", "2188217", "8185149", "2572748", "1307893", "6565469", "7420656", "2079896", "128907", "3249732", "971011", "1151293", "7963201", "3503315", "8214829", "8718053" ]

[ "Effectiveness of medical nutrition therapy provided by dietitians in the management of non-insulin-dependent diabetes mellitus: a randomized, controlled clinical trial.", "Comprehensive discharge planning for hospitalized elderly: a pilot study.", "Comprehensive discharge planning for the hospitalized elderly. A randomized clinical trial.", "Repeated prevalence surveys for monitoring effectiveness of hospital infection control.", "Effectiveness of nursing involvement in bedside monitoring and control of coagulation status after cardiac surgery.", "A decentralized approach to maintenance of intravenous therapy.", "Physician response to computer reminders.", "The employment of ward opinion leaders for continuing education in the hospital.", "Nurse-protocol management of low back pain. Outcomes, patient satisfaction and efficiency of primary care.", "Evaluation of a nurse-run hypertension clinic in general practice.", "A headache protocol for nurses: effectiveness and efficiency.", "Protocol management of dysuria, urinary frequency, and vaginal discharge.", "Improving compliance with immunization in the older adult: results of a randomized cohort study.", "Increasing the rate of identification of battered women in an emergency department: use of a nursing protocol.", "A randomized, controlled trial of radiograph ordering for extremity trauma in a pediatric emergency department.", "Striving to prevent falls in an acute care setting--action to enhance quality." ]

[ "To assess the effect of medical nutrition therapy (MNT) provided by dietitians on medical and clinical outcomes for adults with non-insulin-dependent diabetes mellitus (NIDDM), and to compare MNT administered according to practice guidelines nutrition care (PGC) to MNT administered with basic nutrition care (BC).\n A prospective, randomized, controlled clinical trial of two levels of MNT on metabolic control in persons newly diagnosed with or currently under treatment for NIDDM was conducted at diabetes centers in three states (Minnesota, Florida, and Colorado). BC consisted of a single visit with a dietitian; PGC involved an initial visit with a dietitian followed by two visits during the first 6 weeks of the study period. Data were collected at entry to the study and at 3 and 6 months.\n Results are reported for 179 men and women aged 38 to 76 years: 85 assigned randomly to BC and 94 to PGC. This represents 72% of the 247 subjects enrolled. An additional 62 adults with NIDDM at one site who had no contact with a dietitian were identified as a nonrandom comparison group.\n Medical outcome measures included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and serum lipid levels. Clinical outcomes included weight, body mass index, waist-to-hip ratio, and changes in medical therapy.\n Initial analysis of the discrete variables was done using the chi 2 statistic with Yates' correction. Initial analysis of continuous variables was done by analysis of variance. The changes in variables between time periods were analyzed by paired t test, and comparisons between groups were analyzed using a t test for independent groups.\n At 6 months, PGC resulted in significant improvements in blood glucose control as indicated by FPG and HbA1c levels and BC resulted in significant improvements in HbA1c level. Participants assigned to the PGC group had a mean FPG level at 6 months that was 10.5% lower than the level at entry, and those in the BC group had a 5.3% lower value. Among subjects who had diabetes for longer than 6 months, those who received PGC had a significantly better HbA1c level at 3 months compared with those receiving BC. The comparison group showed no improvement in glycemic control over a comparable 6 months. PGC subjects had significant improvements in cholesterol values at 6 months, and subjects in both the PGC and the BC groups had significant weight loss.\n MNT provided by dietitians resulted in significant improvements in medical and clinical outcomes in both the BC and PGC groups and is beneficial to persons with NIDDM. Persons with a duration of diabetes longer than 6 months tended to do better with PGC than with BC. Because of the upward trend in glucose levels after 3 months, ongoing MNT by dietitians is important for long-term metabolic control.", "The purpose of this randomized clinical trial was to examine the effects of a comprehensive discharge planning protocol implemented by a gerontological nurse specialist as compared to the hospital's general discharge planning procedure. There were no statistically significant differences between groups in length of initial patient hospitalization or in rates of posthospital infections. A statistically significant difference was found when groups were compared on the number of subjects rehospitalized during the study period. The findings of this pilot study reinforce the need for continued study of the impact of comprehensive discharge planning for hospitalized elderly.", "To study the effects of a comprehensive discharge planning protocol, designed specifically for the elderly and implemented by nurse specialists, on patient and caregiver outcomes and cost of care.\n Randomized clinical trial.\n Hospital of the University of Pennsylvania.\n 276 patients and 125 caregivers. Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups.\n Group differences in patient outcomes (length of initial hospital stay, length of time between initial hospital discharge and readmission, and rehospitalization rates) and charges for care (charges for initial hospitalization, rehospitalizations, health services after discharge, and nurse specialist services) were measured 2, 6, and 12 weeks after discharge.\n From the initial hospital discharge to 6 weeks after discharge, patients in the medical intervention group had fewer readmissions, fewer total days rehospitalized, lower readmission charges, and lower charges for health care services after discharge. No differences in these outcomes were found between the surgical intervention and control groups during this period.\n Study findings support the need for comprehensive discharge planning designed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings. The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge.", "In a 1400-bedded teaching hospital single-day prevalence surveys of hospital infection were done every six months for 3 years. The prevalence of community-acquired infection remained constant; but, after the introduction of a general infection-control policy, the prevalence of hospital-acquired infection (HAI) fell linearly from 10.5% in the second survey to 5.6% in the last. After the introduction of a specific urinary catheter care policy, the prevalence of hospital-acquired urinary tract infection (HAUTI) fell from 3.2% in the first four surveys to 2.0% in the last three. These differences persisted when the results were adjusted by logistic regression for patient risk factors, which varied between surveys: the declines for HAI and HAUTI were then 9.9% to 6.0% and 2.9% to 2.2% respectively. Infection control policies, therefore, can have substantial impact on the prevalence of HAI, and their effectiveness can readily be measured by repeated prevalence surveys.", "This study explores: (1) the feasibility of involvement of nursing staff in routine bedside testing of activated clotting time and (2) joint implementation with resident medical staff of a preformulated plan for management of mediastinal bleeding after cardiac surgery.\n Patients were divided randomly into two groups, an experimental group (n = 108) subjected to ACT testing and management by protocol, and a control group (n = 146) treated by independent medical decisions.\n Bleeding, volume of blood replaced, abnormal coagulation profiles and reoperations to control bleeding and its consequences were all reduced in the study group.\n We concluded that bedside measurement of activated clotting time by nursing staff, associated with therapy based on a flow diagram, enhanced the overall management of early mediastinal bleeding after cardiac surgery as compared with independent management decisions by resident medical staff. In addition, the method provided a sensitive and reliable means of detecting and correcting rebound heparinization in the early postoperative period.", "A prospective experiment was conducted in a university-affiliated hospital to evaluate the effectiveness of a core of specially trained staff nurses in the maintenance of IV therapy. Five staff nurses for each of two experimental units were trained for 1 month by an IV nurse educator and were expected to perform venipuncture and monitor peripheral IV care on their units. On three control units, IV therapy continued to be a shared function of all medical house staff and nurses. During this study, 876 IV infusions on 707 patients were studied. There was a decrease in the phlebitis rate on experimental units from baseline to study periods of from 33.5% to 20.9% (relative risk, controlled for duration of the use of an IV device, 0.53, p = 0.05), whereas the rate on control units increased slightly (23.8% to 26.7%, p = greater than 0.5). Regardless of duration of use, steel needles were associated with lower phlebitis rates than were plastic catheters. The mean duration that each infusion device was in place was significantly shorter on experimental units than on control units (2.4 vs. 3.3 days, p = less than 0.001). However, bacterial colonization of IV devices occurred more often on experimental units than on control units both at baseline (12.7% vs. 7.1%; p = 0.25) and during the study phase (19.4% vs. 5.9%; p = less than 0.01). This increased colonization occurred with IV infusions started by both physicians and nurses. There were no septic complications of IV therapy in the patients studied. Patient comfort, measured by number of sticks for each venipuncture and patient interview, was significantly improved (p = less than 0.001) on experimental units during the study phase. Costs to start such a decentralized IV program on 10 clinical units was calculated to be about +10,000. This study provides information useful to those making administrative decisions regarding the value of IV teams or other methods for IV therapy maintenance. We concluded that a decentralized program can be successful with commitment of time and money resources and with a system of monitoring to ensure compliance with written IV guidelines.", "A computerized medical record system was designed to detect and remind the responsible clinician about clinical events that might need corrective action. These reminders significantly increased the clinician response rate (in terms of test orders and treatment changes) to the events in question. The addition of relevant medical literature citations to the reminders did not significantly change the clinician response rate as compared with that with reminders alone, nor did it stimulate the physicians to read any of the cited articles kept in an immediately available \"library\" of reprints.", "Opinion leaders (OLs) are members within a social group with significant social influence over others. A guideline on urinary catheter care was introduced in three groups (A, B and C) of two randomly allocated wards. Two OLs per ward were identified by nurses in groups A and B, using a sociometric method. For education, inservice lectures for 30% of nurses and OLs tutorials for all nurses were used in group A; OLs tutorials in B, lectures in C and ward nurses were in turn responsible for educating new arrivals of student nurses. Before and after the education programme, the guideline's frequency of practice was assessed by surveying 30% of randomly selected nurses and by direct observation for incorrect practices. A student's quiz on the guideline was also conducted. For all three methods of measurement, the best results were in group A followed by B and C; and the differences for the three groups were significant (p less than 0.05). This indicates that continuing education in the hospital can be effectively conducted by the enlistment of ward OLs.", "To test the validity of a nurse-administered protocol for low back pain, a prospective trial of 419 patients was undertaken in a walk-in clinic. In all, 222 patients were randomly allocated to a \"nurse-protocol group\" in which they were evaluated by one of five nurses using the protocol; the nurses independently managed 53 percent of the patients and referred to a physician patients with potentially complex conditions. In addition, 197 patients in a randomly allocated control group were managed by one of 32 physicians. Care in the experimental and control groups was compared by follow-up telephone contact and by a four-month chart review. There was no significant difference in symptomatic relief or the development of serious disease in the two groups. Nurse-protocol patients expressed greater satisfaction with the care they had received; patient satisfaction correlated positively with symptom relief. In over 95 percent of the patients, there were noncomplex, nonserious, nonchronic conditions as the cause of back pain. We conclude that nurse-protocol management of this generally benign condition in a primary care setting is both effective and efficient.", "nan", "To test the effectiveness and efficiency of a nurse-administered protocol for headache in the primary care setting, we conducted a prospective controlled trial. Two hundred three randomly allocated patients were evaluated by nurses using the protocol who managed independently 55.2% of the patients and received physician consultation on the others. A total of 193 patients were randomly allocated to the physician-control group. Nurse-protocol group patients experienced equivalent symptomatic relief and expressed significantly greater satisfaction with the care they had received than did patients in the physician-control group. A retrospective study of the presenting findings in patients with serious diseases of the CNS provided evidence supporting the safety of the protocol logic. We conclude that nurse-protocol management of headache in this primary care practice was effective and efficient.", "A proctocol to be administered by nurses for the management of dysuria, frequent urination, and vaginal discharge was validated. In a randomized, controlled trial, 146 women were seen by both nurse and physician and then assigned to either the nurse-proctocol treatment plan or the physician treatment plan. The clinical data collected by the nurse showed no important differences from the physicians' data. The protocol recommended that 89 percent of the patients be sent home without seeing the physician. The physicians agreed with the protocol-recommended disposition in all but two cases. All patients with complications were appropriately referred to the physician. In follow-up, more than 95 percent of both groups reported symptomatic improvement, and repeat urine cultures were negative. We conclude that the protocol can be accurately administered, makes sound recommendations, is safe, and efficiently saves physician time.", "To compare three approaches for improving compliance with influenza and pneumococcal vaccination of elderly patients.\n Randomized controlled trial using three parallel group practices at a public urban teaching hospital.\n Public teaching hospital.\n All patients 65 years of age and older (n = 1202) seen by resident physicians (n = 66) attending three ambulatory medical practices from October 1, 1989 to March 31, 1990.\n All three provider groups received intensive education in immunization standards. The control group received no further intervention. Staff in the second group offered education to patients at their visits. In the third group, the prevention team, a flowsheet was used, patient education offered, and staff had their tasks redefined to facilitate compliance; for vaccinations, eg, nurses could vaccinate independent of MD initiative.\n Medical records were reviewed for the 1202 patients seen, including 756 patients seen during both the 1988-89 and 1989-90 influenza seasons, to determine documented offering and receipt of vaccinations. During the intervention period (1989-90), influenza vaccinations were offered significantly more frequently to prevention team patients (68.3%) than to patients in either the patient education (50.4%) or control (47.6%) groups (P = 0.006), even after adjusting for the patients' prior vaccination status, age, gender, race, and high-risk co-morbidity and for physicians' level of training. Likewise, pneumococcal vaccinations were offered more frequently to previously unvaccinated prevention team patients (28.3%) than to patient education (6.5%) or control (5.4%) group patients (P = 0.001), even after adjusting for the factors using multivariate analysis. Compliance rates did not differ between patient education and control subjects for either vaccine. Pre-intervention physician surveys documented higher perceived than actual compliance for both vaccines, with 89.0% and 52.8% of physicians believing that they complied with influenza and pneumococcal vaccination guidelines, respectively.\n The results of this trial provide strong support for organizational changes that involve non-physician personnel to enhance vaccination rates among older adults.", "In recognition of the increasing problem of family violence, the authors developed and tested an interview protocol focused on female victims of family violence. The purpose of the protocol was to increase nurses' identification of battered women receiving care in the emergency department. Using a time-series design, data were collected from patient records during four months prior to introduction of the protocol. These data were compared to comparable post-protocol data. There was a significant increase in nursing staff identification of female domestic violence victims following introduction of the protocol.", "The objectives of this study were to determine whether triage nurses using the Brand protocol would order fewer radiographs than would physicians carrying out standard practice procedures, without missing an increased number of joint or bone injuries; the test characteristics and the interobserver reliability of the Brand protocol; and whether having triage nurses order radiographs could reduce total patient waiting time in the emergency department.\n Randomized, controlled trial.\n The ED of a free-standing children's hospital with approximately 55,000 visits annually.\n Children less than 18 years of age who had a history of extremity trauma in the preceding seven days.\n Triage nurses applied the Brand protocol to determine the need for a radiograph.\n Of the Brand protocol group, 81.9% had radiographs ordered compared with 87.1% of the control group (P = .03). The percent of positive radiographs was 40.8% in the Brand protocol group compared with 42.6% in the control group (P = .21). There were 3.2% (16) missed radiographic findings in the Brand protocol group compared with none in the control group (P < .001). Patients randomized to the Brand protocol group spent 3.3 hours in the ED compared with 3.6 hours for the control group (P < .001).\n Having triage nurses use the Brand protocol reduced the number of radiographs ordered but at the same time increased the number of missed radiographic findings. However, having triage nurses order radiographs also significantly shortened waiting time in the ED.", "Although most falls do not result in serious physical injury, they can contribute to a loss of confidence and mobility which can culminate in a significant reduction in quality of life. Furthermore, the potential to fall is often increased when an individual is institutionalized because of frailty or confusion. The purpose of the study was, therefore, to establish whether a structured intervention would assist in preventing falls in an acute setting. This pre-test/post-test study was carried out over a 12-month period. Interventions included risk assessment, an alert system, reinforcing preventive actions, staff education and ongoing audits and feedback. Initial analysis of the data and comparison of fall rates indicated a significant reduction in the rate of falls between the pre- and post-intervention phases, although subsequent statistical analysis did not identify any significant relationships. It must be noted that no controls existed for extraneous variables, although patient profiles varied minimally during the period of the study. Outcomes include: a reduction in fall numbers and rates, enhanced staff morale with ownership of the programme, provision of a learning experience for staff (on which to build), and the fostering of a professional approach to improving the quality of patient care." ]

[ "17940861", "16938063", "19522781", "17855465", "15878048", "22443839", "18072842", "11861229", "12940468" ]

[ "The impact of an integrated treatment on HIV risk behavior among homeless youth: a randomized controlled trial.", "Short-term effects of a brief motivational intervention to reduce alcohol and drug risk among homeless adolescents.", "Comparison of family therapy outcome with alcohol-abusing, runaway adolescents.", "Outcomes of a brief sexual health intervention for homeless youth.", "Ecologically based family therapy outcome with substance abusing runaway adolescents.", "A family intervention to reduce sexual risk behavior, substance use, and delinquency among newly homeless youth.", "Brief motivational intervention with homeless adolescents: evaluating effects on substance use and service utilization.", "Evaluation of a mental health outreach service for homeless families.", "Reductions in HIV risk among runaway youth." ]

[ "While many studies provide useful information on the risk behaviors in which homeless youth engage, few prior studies evaluate Human Immunodeficiency Virus (HIV) risk related reduction strategies. In this study, homeless youth (n = 180) were recruited from a drop-in center and randomly assigned to one of two conditions, either an integrated individual cognitive-behavioral treatment and HIV prevention intervention that focused on skills building and education or to treatment as usual. All youth were assessed at entry into the program and at 3 and 6 month follow-up points. Findings showed an interaction between treatment condition, age and time. In the interaction, youth assigned to the integrated treatment reported greater condom usage than youth assigned to treatment as usual, with younger youth assigned to treatment as usual showing no change in condom use. The number of sexual partners reported by youth in both treatment conditions was also reduced over time. However, youth in both conditions continued to engage in other high-risk behaviors. The integrated treatment findings are promising and suggest that interventions which target both HIV risk behavior in addition to other life areas (substance use, mental health and housing) among homeless youth may be necessary in order to significantly impact high-risk behaviors among this unique group.", "The short-term results of a randomized trial testing a brief feedback and motivational intervention for substance use among homeless adolescents are presented. Homeless adolescents ages 14-19 (N = 285) recruited from drop-in centers at agencies and from street intercept were randomly assigned to either a brief motivational enhancement (ME) group or 1 of 2 control groups. The 1-session motivational intervention presented personal feedback about patterns of risks related to alcohol or substance use in a style consistent with motivational interviewing. Follow-up interviews were conducted at 1 and 3 months postintervention. Youths who received the motivational intervention reported reduced illicit drug use other than marijuana at 1-month follow-up compared with youths in the control groups. Treatment effects were not found with respect to alcohol or marijuana. Post hoc analyses within the ME group suggested that those who were rated as more engaged and more likely to benefit showed greater drug use reduction than did those rated as less engaged. Limitations of the study are discussed as are implications for development of future substance use interventions for this high-risk group.\n ((c) 2006 APA, all rights reserved).", "Treatment evaluation for alcohol problem, runaway adolescents and their families is rare. This study recruited primary alcohol problem adolescents (N = 119) and their primary caretakers from two runaway shelters and assigned them to (a) home-based ecologically based family therapy (EBFT), (b) office-based functional family therapy (FFT), or (c) service as usual (SAU) through the shelter. Findings showed that both home-based EBFT and office-based FFT significantly reduced alcohol and drug use compared with SAU at 15-month postbaseline. Measures of family and adolescent functioning improved over time in all groups. However, significant differences among the home- and office-based interventions were found for treatment engagement and moderators of outcome.", "Homeless youth face various health challenges. The effectiveness of a short intervention to promote sexual health in 572 homeless 16-23-year-olds (M = 19.467+1.89) was conducted using a quasi-experimental repeated measures design. Data collected at three time points (pre-intervention, immediately post-intervention and follow-up) via laptop computers were analyzed using multivariate general linear mixed models. A significant condition by time interaction was found for self-reported AIDS/STD knowledge; intervention participants had higher scores at first post-test. Females scored significantly higher on cognitive and behavioral outcomes while males reported significantly more sexual risk-taking behaviors. Findings support gender-specific interventions.", "Runaway youth report a broader range and higher severity of substance-related, mental health and family problems relative to non-runaway youth. Most studies to date have collected self-report data on the family and social history; virtually no research has examined treatment effectiveness with this population. This study is a treatment development project in which 124 runaway youth were randomly assigned to (1) ecologically based family therapy (EBFT) or (2) service as usual (SAU) through a shelter. Youth completed an intake, posttreatment, 6 and 12 months follow-up assessment. Youth assigned to EBFT reported greater reductions in overall substance abuse compared to youth assigned to SAU while other problem areas improved in both conditions. Findings suggest that EBFT is an efficacious intervention for this relatively severe population of youth.", "We evaluate the efficacy of a short family intervention in reducing sexual risk behavior, drug use, and delinquent behaviors among homeless youth.\n A randomized controlled trial of 151 families with a homeless adolescent aged 12 to 17 years. Between March 2006 and June 2009, adolescents were recruited from diverse sites in Southern California and were assessed at recruitment (baseline), and at 3, 6, and 12 months later. Families were randomly assigned to an intervention condition with five weekly home-based intervention sessions or a control condition (standard care). Main outcome measures reflect self-reported sexual risk behavior, substance use, and delinquent behaviors over the past 90 days.\n Sexual risk behavior (e.g., mean number of partners; p < .001), alcohol use (p = .003), hard drug use (p < .001), and delinquent behaviors (p = .001) decreased significantly more during 12 months in the intervention condition compared with the control condition. Marijuana use, however, significantly increased in the intervention condition compared with the control condition (p < .001).\n An intervention to reengage families of homeless youth has significant benefits in reducing risk over 12 months.\n Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.", "A brief motivational intervention with 117 homeless adolescents was evaluated using a randomized design and 3-month follow-up. The intervention was designed to raise youths' concerns about their substance use, support harm reduction, and encourage greater service utilization at a collaborating agency. The study was designed to strengthen initial promising results of an earlier study (P. L. Peterson, J. S. Baer, E. A. Wells, J. A. Ginzler, & S. B. Garrett, 2006). Several modifications in the clinical protocol were included to enhance engagement with the intervention. Analyses revealed no significant benefits for intervention participants when homeless youths' substance use rates were compared with those of control participants. Service utilization during the intervention period increased for those receiving the intervention but returned to baseline levels at follow-up. Participants reported overall reductions in substance use over time. Differences between sampling methods for the current and previous study are discussed, as are the limitations of brief interventions with this population. Future research needs to elucidate mechanisms of change and service engagement for highly vulnerable youth.", "To describe the characteristics of homeless children and families seen by the mental health outreach service (MHOS), to evaluate the impact of this service on the short term psychosocial functioning of children and parents, and to establish perceptions of, and satisfaction with, the service.\n Twenty seven children from 23 families who were in receipt of the MHOS and 27 children from 23 families residing in other hostels where no such service was available were studied. The MHOS was delivered by a clinical nurse specialist with expertise in child mental health, who offered the following interventions: assessment and brief treatment of mental health disorders in children; liaison with agencies; and training of homeless centre staff.\n Children in the experimental group had a significantly higher decrease in Strengths and Difficulties Questionnaire (SDQ) total scores. Having received the intervention was the strongest predictor of improvement in SDQ total scores. There was no significant impact on parental mental health (General Health Questionnaire) scores. Homeless families and staff expressed high satisfaction with the MHOS.\n This MHOS for homeless families is an innovative intervention which meets the complex and multiple needs of a vulnerable population unable to access mainstream mental health services. The primary objective of the service was to improve child mental health problems; however, the service developed in a responsive way by meeting social and practical needs of families in addition to its clinical role.", "Runaway youth are 6-12 times more likely to become infected with HIV than other youth. Using a quasi-experimental design, the efficacy of an HIV prevention program was evaluated over 2 years among 2 groups of runaways: (1) those at 2 shelters who received Street Smart, an intensive HIV intervention program, and (2) youth at 2 control shelters. Street Smart provided youth with access to health care and condoms and delivered a 10-session skill-focused prevention program based on social learning theory to youth. Prior to analysis of the intervention's outcomes, propensity scores were used to identify comparable subgroups of youth in the intervention (n = 101) and control conditions (n = 86). Compared to females in the control condition, females in the intervention condition significantly reduced their unprotected sexual acts at 2 years and alcohol use, marijuana use, and the number of drugs used over 12 months. Male adolescents in the intervention condition showed significant reductions in marijuana use over 6 months compared to control youth. Adolescent HIV prevention programs must proactively identify mechanisms for maintaining behavior change over the long-term, and innovative research designs are needed to allow examination of agency-level interventions." ]

[ "9102064", "9205633", "2113611", "9284696", "11484098", "2109197", "15465502", "9259248", "3126214", "9552083", "9274891" ]

[ "The use of etidronate and calcium versus calcium alone in the treatment of postmenopausal osteopenia: results of three years of treatment.", "Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy.", "Intermittent cyclical etidronate treatment of postmenopausal osteoporosis.", "Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a double-blind, placebo-controlled study and 1-year follow-up)", "Effect of intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis.", "Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis.", "Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study.", "The effect of a modified etidronate cyclical regimen on postmenopausal osteoporosis: a four-year study.", "Coherence therapy does not prevent axial bone loss in osteoporotic women: a preliminary comparative study.", "A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis.", "The prevention of early postmenopausal bone loss by cyclical etidronate therapy: a 2-year, double-blind, placebo-controlled study." ]

[ "The purpose of this open, prospective, controlled, randomized trial was to study the effect of intermittent, cyclic etidronate on the bone mass of osteoporotic postmenopausal women with or without fractures. Eligible subjects were asymptomatic women less than 75 years old who had been amenorrhoeic for at least 1 year. Those with secondary osteoporosis were excluded. Subjects also had to be ambulant with a bone mineral density (BMD) of the lumbar spine > 1 SD below that of age matched controls (Z-score < -1 SD). Eighty patients were enrolled, of whom 65 were recruited through a screening programme conducted in the practices of two general practitioners. The remaining patients were from other referrals. The subjects were randomized to two groups of 40 women. Treatment regimens were as follows. The etidronate group was treated with etidronate 400 mg once daily for 14 days followed by 76 days of 500 mg of elementary calcium once daily; this cycle was repeated every 3 months. The calcium group took 500 mg of elementary calcium once daily. The groups were not different in age, height, weight, time since menopause. BMD at baseline and prevalent vertebral fractures. In 50 patients (28 in the etidronate group and 22 in the calcium group) no vertebral fractures were present (67%). Sixty-four patients (35 in the etidronate group and 29 in the calcium group) completed the 3 years of the study. In the etidronate group the mean BMD of the lumbar spine, femoral neck, trochanter and Ward's triangle increased by 5.7%, 1.4%, 7.1% and 10.9% from baseline values respectively (p < 0.05 at all sites except for the femoral neck). In the calcium group no significant changes from baseline were found at any time point at any site after 3 years, except for the femoral neck, where BMD at 156 weeks decreased significantly by 3% (p < 0.003). In 3 patients, all in the calcium group, six new fractures were found. There were no serious adverse effects. We conclude that intermittent, cyclic treatment with etidronate causes a significant increase in the BMD of the lumbar spine and the proximal femur in osteopenic postmenopausal women, and that treatment is safe and has no serious adverse effects.", "This study was carried out to investigate the effectiveness and tolerability of cyclical etidronate therapy in the prevention of bone loss occurring in early postmenopausal women who are not undergoing hormone replacement therapy (HRT). A total of 109 Caucasian women aged 45-60 years were treated with etidronate 400 mg/day or placebo for 14 days followed by calcium supplementation 500 mg/day for 77 days. Ninety-one women completed the 2 years of the study. After 2 years, the estimated difference between the two groups as regards lumbar spine bone mineral density (BMD) was 2.53% (SEM 1.07%; p = 0.01); BMD of the hip and wrist were not significantly different between treatment groups. A clear reduction in bone turnover was obtained as evidenced by a significant decrease in serum alkaline phosphatase level and in urinary N-telopeptide/ creatinine ratio in the etidronate group; the difference between the two groups was -12% +/- 3.2% for serum alkaline phosphatase level (p = 0.019) and -22.9% +/- 13.7% for the urinary N-telopeptide/creatinine ratio (p = 0.047). There was no statistically significant difference between the two groups in terms of the serum osteocalcin levels and urinary hydroxyproline/ creatinine and calcium/creatinine ratios. Etidronate was generally well tolerated and its adverse event profile was similar to that of placebo. The results of this study indicate that cyclic etidronate therapy can prevent trabecular bone loss, with no deleterious effect on cortical bone, in the first 5 years of menopause and that it has a very high safety margin.", "To determine the effects of etidronate (a bisphosphonate that inhibits osteoclast-mediated bone resorption) in the treatment of postmenopausal osteoporosis, we conducted a prospective, two-year, double-blind, placebo-controlled, multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia.\n The patients were randomly assigned to treatment with phosphate (1.0 g) or placebo twice daily on days 1 through 3, etidronate (400 mg) or placebo daily on days 4 through 17, and supplemental calcium (500 mg) daily on days 18 through 91 (group 1, placebo and placebo; group 2, phosphate and placebo; group 3, placebo and etidronate; and group 4, phosphate and etidronate). The treatment cycles were repeated eight times. The bone density of the spine was measured by dual-photon absorptiometry, and the rates of new vertebral fractures were determined from sequential radiographs.\n After two years, the patients receiving etidronate (groups 3 and 4) had significant increases in their mean (+/- SE) spinal bone density (4.2 +/- 0.8 percent and 5.2 +/- 0.7 percent, respectively; P less than 0.017). The rate of new vertebral fractures was reduced by half in the etidronate-treated patients (groups 3 and 4 combined) as compared with the patients who did not receive etidronate (groups 1 and 2 combined) (29.5 vs. 62.9 fractures per 1000 patient-years; P = 0.043); the effect of treatment was most striking in the subgroup of patients with the lowest spinal bone mineral density at base line, in whom fracture rates were reduced by two thirds (42.3 vs. 132.7 fractures per 1000 patient-years; P = 0.004). The addition of phosphate provided no apparent benefit. There were no significant adverse effects of treatment.\n Intermittent cyclical therapy with etidronate for two years significantly increases spinal bone mass and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis.", "The objective of the study was to evaluate the effects of cyclical therapy with etidronate and calcium on spinal and femoral bone loss in the early post menopausal period. Fifty-four women, 53 +/- 2.8 yr old (mean +/- SD) and 2.3 +/- 1.3 yr post menopause received oral doses of either 400 mg/day etidronate for 2 weeks followed by 500 mg/day elemental calcium for 11 weeks, or placebo for 14 days followed by calcium for 11 weeks, repeated over a total of 24 months. A statistically significant increase in spinal bone mineral density (BMD) was observed after 6 months in the etidronate group. At 2 yr, the mean treatment differences in spinal and femoral neck BMD were +2.93% (P < 0.02) and 2.02% (P < 0.03), respectively. Serum osteocalcin and urinary crossLaps/creatinine excretion were decreased significantly by etidronate. Etidronate was well tolerated with a safety profile similar to that of placebo. Thirty-seven women participated in a 1-yr open-label follow-up study. Twelve months after treatment withdrawal, spinal BMD in the former etidronate group decreased by 1.43% and serum osteocalcin and urinary crossLaps returned to pretreatment values. In conclusion, cyclical etidronate is an effective therapy for the prevention of both trabecular and cortical bone loss in the early menopause and has a good safety profile.", "We evaluated intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis, with special reference to bone mineral density (BMD) and prevention of spinal fracture. The patients were 40 women, over 50 years of age, with lumbo-dorsal pain and low BMD (less than 0.70 g/cm(2)), measured by dual-energy X-ray absorptiometry (DXA). The patients were randomly assigned to two groups. The first group (HEBP) received 200 mg of HEBP per day for 2 weeks, followed by 2 g calcium lactate and 0.5 microg alphacalcidol per day for the next 10 weeks. This 12-week cycle was repeated eight times for 2 years. The second group (Ca. D) received 2 g calcium lactate and 0.5 microg alphacalcidol per day for 2 years. Lumbar BMD was measured before the treatment and every 6 months during the treatment until 24 months, and changes were evaluated. The number of fractured vertebrae was counted on X-ray films before treatment and at the final assessment. After 6 months of treatment, a significant and continuous increase in BMD was observed in the HEBP group. Moreover, the percentage of patients with new vertebral compression fractures in the HEBP group was one-tenth of that in the Ca. D group. These results suggest that intermittent cyclical treatment with HEBP and calcium plus alphacalcidol may be effective for increasing BMD and preventing fractures in postmenopausal osteoporosis.", "Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation. We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate, a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned in equal numbers to receive oral etidronate (400 mg per day) or placebo for 2 weeks, followed by a 13-week period in which no drugs were given. This sequence was repeated 10 times, for a total of 150 weeks. Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups. Vertebral bone mineral content was measured by dual-photon absorptiometry; spinal radiographs were assessed to identify new vertebral fractures. Vertebral bone mineral content increased significantly (P less than 0.01) after 150 weeks of etidronate therapy (5.3 percent; 95 percent confidence interval, 2.0 to 8.6; n = 20) but decreased with placebo (-2.7 percent; 95 percent confidence interval, -7.3 to 1.9; n = 20). The difference between groups was 8.0 percentage points (P less than 0.01; 95 percent confidence interval, 2.4 to 13.6). The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups (6 vs. 54 fractures per 100 patient-years; P = 0.023). No adverse clinical, biochemical, or bone histomorphometric effects of treatment were observed. We conclude that at the end of nearly three years, etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and, after approximately one year of treatment, a significant decrease in the rate of new vertebral fractures.", "To assess the comparative effectiveness of several medications on bone mineral density, biochemical bone markers, and the incidence of vertebral fractures in postmenopausal women with osteoporosis.\n A total of 396 postmenopausal women, aged 50 to 75 years, were allocated randomly to six equal-sized groups: hormone replacement therapy, etidronate, eel calcitonin, alfacalcidol, vitamin K (menatetrenone), or control (no treatment). Thoracic and lumbar spine radiographs, bone mineral density at the distal radius, and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study.\n Compared with baseline, the 2-year mean changes in bone mineral density were 2.0% for hormone replacement therapy, -0.5% for etidronate, 1.6% for calcitonin, -3.6% for alfacalcidol, -1.9% for vitamin K, and -3.3% for control. Seventeen (26%) of the 66 control patients developed new vertebral fractures. Compared with controls, the relative risks of vertebral fracture were 0.35 (95% confidence interval [CI]: 0.14 to 0.83) for hormone replacement therapy, 0.40 (95% CI: 0.17 to 0.92) for etidronate, 0.41 (95% CI: 0.17 to 0.93) for calcitonin, 0.56 (95% CI: 0.26 to 1.12) for alfacalcidol, and 0.44 (95% CI: 0.20 to 0.99) for vitamin K.\n We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy, etidronate, and calcitonin, and significant improvements in bone mineral density with hormone replacement therapy and calcitonin.", "To develop an improved treatment schedule for osteoporosis, a study was undertaken in 100 postmenopausal women using a modified ADFR 90-day cyclical regimen with etidronate. After one year of treatment, the etidronate-treated group showed a significant increase in bone density of the spine, which continued over the following 2 years of treatment and remained stable during the fourth year. In contrast, in the non-etidronate group, bone density decreased significantly after four years. In addition, the fracture rate was significantly lower in the etidronate group than in the non-etidronate group. Side effects were minimal in both groups and no serious adverse reactions were reported. In conclusion, it appears that a cyclical regimen using 1,25-dihydroxyvitamin D3, etidronate and calcium increases bone mass and reduces fractures with no significant side effects, thus making a useful contribution in the treatment of postmenopausal osteoporosis.", "Coherence therapy, also known as ADFR (activate, depress, free, repeat) therapy, has been proposed as a new form of treatment for osteoporosis. We compared the effects of this therapy with those of gonadal steroid and calcium and of calcium alone in 93 osteoporotic women. Thirty women were treated for 1 yr with ADFR, in the form of K-phosphate (1.5 g/day), for 3 days followed by etidronate, (400 mg/day) for 14 days, followed by 8 weeks of neither drug, plus continuous calcium carbonate therapy (1 g/day). Thirty-six women received conjugated estrogens (0.625 mg/day) for 25 days/month plus medroxyprogesterone acetate (10 mg/day) for 10 days/month and calcium, while 27 women received calcium carbonate (500 mg, twice daily). Sixteen women in the ADFR group, 15 in the calcium group, and 19 in the hormone-calcium group completed 2 yrs of treatment. Spinal bone mineral density was measured by single energy quantitative computerized tomography (QCT) and in the proximal and distal radius by single energy photon absorptiometry. The 3 groups were similar in age, initial bone mass, years since menopause, and dietary calcium intake. After 2 yrs, the mean women in the ADFR therapy group had a mean reduction of 8.0% in spinal QCT (P less than 0.05), and no change in proximal radius mineral content/bone width (BMC), and distal radius BMC. The group treated with calcium only had a decrease of 3.8% in QCT (P less than 0.05), of 5.6% in proximal BMC (P less than 0.05), and of 4.9% in distal BMC (P less than 0.05). The group treated with hormonal replacement and calcium had no change in any of their measurements. The relative bone loss in the spine at the end of the study was greater in the ADFR group than in the hormone-calcium group (P less than 0.05). Bone loss in the calcium group was slightly but not significantly greater than that in the hormone group and lower than that in the ADFR group. In conclusion, these preliminary results indicate that the ADFR regimen using phosphate and etidronate in doses of 1.5 g/day for 3 days and 400 mg/day for 14 days, respectively, is not as effective as hormonal replacement in preventing trabecular bone loss in osteoporosis, nor it is any more effective than calcium supplementation alone.", "Hormone replacement therapy (HRT) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density (BMD) in postmenopausal women. This 4-year prospective randomized study was carried out to assess the effectiveness of the combined HRT plus etidronate on BMD in postmenopausal women with established osteoporosis.\n Seventy-two postmenopausal women (mean age 64.9+/-0.5 years) attending metabolic bone disease outpatient clinics with established osteoporosis were randomly allocated into one of four treatment groups and monitored for 4 years. All patients enrolled in this study including the control group (n=18) received 1.0 g elemental calcium and 400 units vitamin D per day. The HRT group (n=18) received cyclical estrogen and progesterone; the etidronate group (n=17) received intermittent cyclical etidronate; and the combined therapy group (n=19) received both HRT and etidronate. BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years after treatment. Changes in height were recorded, and the occurrence of new vertebral fractures were documented in comparison with the baseline radiographic evaluation. In 40 patients (10 patients per group), analysis of bone histomorphometry was carried out after 4 years of treatment.\n In patients who received the combined therapy, BMD increased in the lumbar spine by 10.4% (P <0.001) and in the hip by 7.0% (P <0.001) at 4 years. For patients treated with ICE, these increases were 7.3% (P <0.001) and 0.9% (P <0.05), and with HRT, the increases were 7.0% (P <0.001) and 4.8% (P <0.01) in the vertebrae and femora, respectively. The group treated with calcium and vitamin D lost 2.5% (P <0.05) and 4.4% (P <0.01) of BMD in the vertebrae and femora, respectively, after 4 years. Patients who received combined therapy had significantly higher BMD in both the vertebrae and in the femora (P <0.05) in comparison with patients who were treated with HRT or etidronate alone after 4 years. In comparison with patients in the control group, there was a trend toward a lower rate of new vertebral fractures in the treatment groups. Height loss was significantly less in all three active treatment groups (HRT [P <0.001], etidronate [P <0.02], and combined therapy group [P <0.0001]), in comparison with the control group. The combined therapy group did not have a significant height loss, in comparison with the HRT (P <0.02) and the etidronate (P <0.001) groups. None of the patients had histomorphometric evidence of osteomalacia.\n This 4-year randomized study showed an additive effect of etidronate and HRT on hip and spine BMD in postmenopausal women with established osteoporosis.", "To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss.\n This was a 2-year outpatient, randomized, double-blind, placebo-controlled clinical trial. The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density (BMD) between 0 and -2 SD of normal values for a 50 year old woman. The women were stratified according to years since the menopause (1 to 3 years: n = 43; 4 to 6 years: n = 53; 7 to 10 years: n = 56). Measurements of lumbar spine, proximal femur and total body BMD were performed at baseline, 12 and 24 months by dual x-ray absorptiometry. Biochemical markers of bone resorption and bone formation were measured on the same visits.\n One hundred thirty-five subjects completed the study. Mean percentage change in lumbar spine BMD (and SEM) at 2 years was +2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group. Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were: 1 to 3 years: +1.73 (0.84)% and -3.30 (0.70)%; 4 to 6 years: +1.37 (0.88)% and -1.80 (0.61)%; 7 to 10 years: +3.42 (0.61)% and -0.38 (0.70)%. The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD. Treatment group, but not stratum, was significant for BMD in the proximal femur. Markers of bone resorption and bone formation were significantly decreased by etidronate therapy.\n Cyclical etidronate prevents bone loss in the total skeleton and at the clinically relevant sites (spine and proximal femur) even in the early postmenopausal years. Hence, it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD." ]

[ "9429041", "4817625", "15502060", "17176461", "44182", "11864673", "18326251", "10925565", "7566849", "2924990", "11873026", "10630057", "18500605", "7923512", "11213000", "11926643", "9855591", "18005381", "9316951", "10895743", "14642152", "9856707", "11641687", "8238138", "1443741", "20394251", "9423752" ]

[ "Intravenous fentanyl PCA during labour.", "Lumbar epidural analgesia in labour. I. Acid-base balance and clinical condition of mother, fetus and newborn child.", "A multicenter randomized controlled trial comparing patient-controlled epidural with intravenous analgesia for pain relief in labor.", "Effects of epidural lidocaine analgesia on labor and delivery: a randomized, prospective, controlled trial.", "[Peridural analgesia and by phenoperidine in normal labor. Therapeutic trial with a control series].", "A randomized trial of intrapartum analgesia in women with severe preeclampsia.", "[Transient neurological symptoms in puerperas after epidural analgesia during labor].", "Effects of epidural fentanyl on labor pain during the early period of the first stage of induced labor in nulliparous women.", "Randomized trial of epidural versus intravenous analgesia during labor.", "Epidural block or parenteral pethidine as analgesic in labour; a randomized study concerning progress in labour and instrumental deliveries.", "Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women.", "[Evolution and quality of care during labor and delivery in primiparous patients who underwent early obstetrical analgesia].", "The effects of remifentanil or acetaminophen with epidural ropivacaine on body temperature during labor.", "Can parturients distinguish between intravenous and epidural fentanyl?", "A randomised controlled trial of epidural compared with non-epidural analgesia in labour.", "The impact of intrapartum analgesia on labour and delivery outcomes in nulliparous women.", "The influence of epidural analgesia on cesarean delivery rates: a randomized, prospective clinical trial.", "Intravenous remifentanil vs. epidural levobupivacaine with fentanyl for pain relief in early labour: a randomised, controlled, double-blinded study.", "Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor.", "Randomized controlled comparison of epidural bupivacaine versus pethidine for analgesia in labour.", "Patient controlled intravenous analgesia with tramadol for labor pain relief.", "A randomized study of combined spinal-epidural analgesia versus intravenous meperidine during labor: impact on cesarean delivery rate.", "A randomized trial of labor analgesia in women with pregnancy-induced hypertension.", "The effect of intrapartum epidural analgesia on nulliparous labor: a randomized, controlled, prospective trial.", "A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia.", "Labor analgesia in preeclampsia: remifentanil patient controlled intravenous analgesia versus epidural analgesia.", "Nulliparous active labor, epidural analgesia, and cesarean delivery for dystocia." ]

[ "To evaluate the usefulness of intravenous patient-controlled analgesia (PCA) fentanyl for labour analgesia, its effectiveness for maternal pain and safety for the fetus and newborn.\n Twenty primigravidas were randomised to receive intravenous PCA fentanyl or epidural analgesia for labour pain. Maternal pain, heart rate and arterial oxyhaemoglobin saturation (SpO2) were monitored. Fetal and neonatal monitoring included cardiotocogram (CTG), APGAR, neurological scoring and static-charge-sensitive bed (SCSB) recording for 12 hr postnatally with ECG and SpO2. Fentanyl concentrations and pH of umbilical artery and vein were analysed.\n Initially, epidural analgesia was more effective (P = 0.01), and three patients in the fentanyl group were given epidural due to unsatisfactory pain relief. Overall satisfaction for analgesia did not differ between the groups. Maternal side-effects were more frequent in the fentanyl group (dizziness and tiredness most often, P = 0.0001). Severe side-effects were not reported. In CTG there were no differences between groups. All the newborns were healthy, APGAR and pH were normal. Naloxone was not used. Neurological scoring was similar in both groups. In 12 hr monitoring heart rate, breathing frequency and movement time were similar in both groups, but SpO2 was lower in the fentanyl group (P < 0.001). Umbilical cord fentanyl concentrations were low or beyond the detection limit.\n Intravenous fentanyl can be used for labour analgesia with the doses reported here as an alternative to epidural analgesia. However, the fetus and neonate must be appropriately monitored. Naloxone and oxygen should be available if neonatal distress occurs.", "nan", "In this multicenter, randomized, controlled trial, we sought to determine whether patient-controlled epidural analgesia (PCEA) for labor affected the incidence of cesarean delivery when compared with patient-controlled IV opioid analgesia (PCIA). Healthy, term nulliparous patients in 4 Canadian institutions were randomly assigned to receive PCIA with fentanyl (n = 118) or PCEA with 0.08% bupivacaine and fentanyl 1.6 microg/mL (n = 124). There was no difference in the incidence of cesarean delivery-10.2% (12 of 118) versus 9.7% (12 of 124)-or instrumental vaginal delivery-21.2% (25 of 118) versus 29% (36 of 124)-between groups. The duration of the second stage of labor was increased in the PCEA group by a median of 23 min (P = 0.02). Fifty-one patients (43%) in the PCIA group received epidural analgesia: 39 (33%) because of inadequate pain relief and 12 (10%) to facilitate operative delivery. Patients in the PCIA group required more antiemetic therapy (17% versus 6.4%; P = 0.01) and had more sedation (39% versus 5%; P < 0.001). Maternal mean pain and satisfaction with analgesia scores were better in the PCEA group (P < 0.001 and P = 0.02, respectively). More neonates in the PCIA group required active resuscitation (52% versus 31%; P = 0.001) and naloxone (17% versus 3%; P < 0.001). These observations support the hypothesis that PCEA does not result in an increased incidence of obstetrical intervention compared with PCIA. PCEA provides superior analgesia and less maternal and neonatal sedation compared with PCIA.", "Whether epidural analgesia for labor prolongs the active-first and second labor stages and increases the risk of vacuum-assisted delivery is a controversial topic. Our study was conducted to answer the question: does lumbar epidural analgesia with lidocaine affect the progress of labor in our obstetric population?\n 395 healthy, nulliparous women, at term, presented in spontaneous labor with a singleton vertex presentation. These patients were randomized to receive analgesia either, epidural with bolus doses of 1% lidocaine or intravenous, with meperidine 25 to 50 mg when their cervix was dilated to 4 centimeters. The duration of the active-first and second stages of labor and the neonatal apgar scores were recorded, in each patient. The total number of vacuum-assisted and cesarean deliveries were also measured.\n 197 women were randomized to the epidural group. 198 women were randomized to the single-dose intravenous meperidine group. There was no statistical difference in rates of vacuum-assisted delivery rate. Cesarean deliveries, as a consequence of fetal bradycardia or dystocia, did not differ significantly between the groups. Differences in the duration of the active-first and the second stages of labor were not statistically significant. The number of newborns with 1-min and 5-min Apgar scores less than 7, did not differ significantly between both analgesia groups.\n Epidural analgesia with 1% lidocaine does not prolong the active-first and second stages of labor and does not increase vacuum-assisted or cesarean delivery rate.", "The perinatal effects of phenoperidine and of epidural anaesthesia were studied in a randomised trial in which only normal patients were studied. Foetal heart rate curves, pH, pCO2 and neonatal clinical behaviour demonstrated that both kinds of analgesia had no harmful effects.", "To estimate whether the cesarean delivery rate differs between women with severe preeclampsia who receive intrapartum epidural analgesia versus patient-controlled intravenous opioid analgesia.\n Women with severe preeclampsia at at least 24 weeks' gestation were randomly assigned to receive either intrapartum epidural (n = 56) versus patient-controlled intravenous opioid analgesia (n = 60), and each was administered by a standardized protocol. The sample size was selected to have 80% power to detect at least a 50% difference in the predicted intergroup cesarean delivery rates. Data were analyzed by intent to treat.\n Selected maternal characteristics and neonatal outcomes were similar in the two groups. The cesarean delivery rates in the epidural group (18%) and the patient-controlled analgesia group (12%) were similar (P =.35). Women who received epidural analgesia were more likely to require ephedrine for the treatment of hypotension (9% versus 0%, P =.02), but their infants were less likely to require naloxone at delivery (9% versus 54%, P <.001). Epidural analgesia provided significantly better pain relief as determined by a visual analogue intrapartum pain score (P <.001) and a postpartum pain management survey (P =.002).\n Compared with patient-controlled intravenous opioid analgesia, intrapartum epidural analgesia did not significantly increase the cesarean delivery rate in women with severe preeclampsia at our level III center, and it provided superior pain relief.", "The investigation was undertaken to elucidate the impact of epidural analgesia (EA) during labor on the incidence of transient neurological symptoms (TNS). By the agreement of a local ethics committee, an informed consent was obtained from 90 healthy puerperas enrolled in the investigation. The patients were randomized into 3 groups, with 30 patients in each. At the beginning of labor, an epidural catheter was inserted in all the puerperas. For EA, 1% lidocaine solution and 0.2% ropivacaine solution were used in Groups 1 and 2, respectively; Group 3 was control in which EA was not performed. Two days after labor, an independent observer asked the females about possible neurological symptoms, by using the standard questionnaire. TNS included symmetric pain and/or dysesthesia in the buttocks, lower lumbar region, and/or legs. The patients who presented problems were proposed to indicate the degree of discomfort by a 10-score verbal scale. The findings were statistically processed using the U-test and X-test (p < 0. 05). A total of TNS occurred in 22 (25%) patients, including 7 (27%), 8 (27%), and 7 (23%) in Groups 1, 2, and 3, respectively. This difference was not statistically significant. The duration of TNS was generally short; in all the patients, the symptoms were completely resolved after 24-72 hours. Labor EA is not a cause of TNS. The type of a local anesthetic (lidocaine, ropivacaine) does not affect the incidence of TNS in puerperas after labor EA.", "It is generally accepted that epidural injection with local anesthetics and narcotics administered when the cervix has dilated to a diameter exceeding 4 cm can adequately control labor pain. However, many nulliparous women still suffer from labor pain for a few hours prior to the administration of epidural analgesia. This study examined the effectiveness of relief of labor pain obtained by injection of narcotics epidurally once the labor pain begins and the subject requests analgesia.\n Subjects scheduled for induced labour were divided into three groups: Group A (n = 60) received 5 x 10(-4)% fentanyl (10-20 mL) administered epidurally to relieve early first-stage labor pain. Group B (n = 60) received no analgesic in the early first stage of labor. For groups A and B, when cervical dilatation exceeded 4 cm, 10 to 15 mL of 5 x 10(-2)% bupivacaine and 2 x 10(-4)% fentanyl were injected epidurally and a continuous low dosage was maintained until full dilatation of the cervix resulted. Group C (n = 198) received no analgesic during the entire labor course.\n There were no significant differences in the duration of the early period of the first stage of labor, the duration of the late period of the first stage, the duration of the second stage, the Apgar score, or the arterial blood gas of neonates among the three groups. However, group C had a significantly higher cesarean section rate (28.8%) than group A (16.7%) or group B (15%). Pain scores assessed with the Visual Analog Scale (VAS) throughout the entire labor course, were lower in group A than in group B; particularly during the early period of the first stage. The VAS scores in both groups A and B were significantly lower than those in group C during the late period of the first stage of labor.\n The results indicate that once labor pain begins and the subject requests analgesia, epidural injection with fentanyl alone can relieve labor pain during the early period of the first stage. The analgesia does not cause adverse effects to the mothers or neonates. In addition, the labor course and the method of delivery are not affected.", "To compare the effects of epidural analgesia with intravenous (IV) analgesia on the outcome of labor.\n Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were randomized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor.\n Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia. However, only 65% of each randomization group accepted the allocated treatment. Four hundred thirty-seven women accepted and received meperidine as allocated, and they were compared with 432 women accepting epidural allocation. Significant associations resulted between epidural administration and prolongation of labor, increased rate of oxytocin administration, chorioamnionitis, low forceps, and cesarean delivery. Because of the high rate of noncompliance with treatment allocation, a multifactorial regression analysis was performed on the entire cohort, and a twofold relative risk of cesarean delivery persisted in association with epidural treatment. The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women (risk ratios 2.55 and 3.81, respectively). Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine.\n Although labor epidural analgesia is superior to meperidine for pain relief, labor is prolonged, uterine infection is increased, and the number of operative deliveries are increased. A two- to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women.", "A prospective randomized study was performed to evaluate the influence of epidural analgesia compared to parenteral pethidine in parturients with pain in the first stage of labour on the progress of labour and the frequency of instrumental deliveries. There was no significant difference in the two groups in the duration of either the first or second stage of labour. The overall instrumental delivery rate was 25%, with no difference between the groups. The analgesic efficacy of the epidural blockade was significantly better than that of parenteral pethidine. We conclude that epidural bupivacaine with our technique and obstetric practice did neither prolong labour nor increase the frequency of instrumental delivery.", "Controversy concerning increased cesarean births as a result of epidural analgesia for relief of labor pain has been attributed, in large part, to difficulties interpreting published studies because of design flaws. In this study, the authors compared epidural analgesia to intravenous meperidine analgesia using patient-controlled devices during labor to evaluate the effects of labor epidural analgesia, primarily on the rate of cesarean deliveries while minimizing limitations attributable to study design.\n Four hundred fifty-nine nulliparous women in spontaneous labor at term were randomly assigned to receive either epidural analgesia or intravenous meperidine analgesia. Epidural analgesia was initiated with 0.25% bupivacaine and was maintained with 0.0625% bupivacaine and fentanyl 2 microg/ml at 6 ml/h with 5-ml bolus doses every 15 min as needed using a patient-controlled pump. Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus, followed by 15 mg meperidine every 10 min as needed, using a patient-controlled pump. A written procedural manual that prescribed the intrapartum obstetric management was followed for each woman randomized in the study.\n A total of 226 women were randomized to receive epidural analgesia, and 233 women were randomized to receive intravenous meperidine analgesia. Protocol violations occurred in 8% (38 of 459) of women. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 7% [16 of 226; 95% confidence interval, 4-11%] vs. intravenous meperidine analgesia, 9% [20 of 233; 95% confidence interval, 5-13%]; P = 0.61). Significantly more women randomized to epidural analgesia had forceps deliveries compared with those randomized to meperidine analgesia (12% [26 of 226] vs. 3% [7 of 233]; P < 0.001). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received intravenous meperidine analgesia.\n Epidural analgesia compared with intravenous meperidine analgesia during labor does not increase cesarean deliveries in nulliparous women.", "Evaluations of labor and delivery progress and care quality in primiparous patients that receive obstetric analgesia by peridural way at the beginning of the active phase, was done. One-hundred-twenty-nine patients at the beginning of the active phase of the labor were randomized into two groups: Group I: Sixty-six patients that received obstetric analgesia by peridural way and Group II: Sixty-three patients did not receive analgesia by any way. Length of the cervical dilation and effacement, and expulsive period, cervical dilation rate per hour, delivery type, labor experience and perinatal outcomes were measured. The length means of the cervical dilation and effacement was 177.7 (SD +/- 89.0) and 296.0 (SD +/- 114.5) minutes to Group I and II respectively (p < 0.005). Cervical dilation rate was 2.74 and 1.6 centimeters per hour to Group I and II respectively (p < 0.05). The length of the expulsive period was 36.54 minutes (SD +/- 21.7) to Group I and 42.57 minutes (SD +/- 16.15) to Group II (p > 0.05). Labor experience was referred like very painful in the 9% and 100% to Group I and II respectively (p < 0.05). The perinatal outcomes and method of delivery were similar between two groups. Obstetric analgesia administered by peridural way at the beginning of the active phase of the labor significantly reduce the dilation and effacement period and whole labor, without modify the expulsive period length. It does not inhibit the uterine activity and improvement the care quality of the labor.", "Epidural analgesia is associated with hyperthermia during labor and presumably causes it, although no convincing mechanism has been postulated. It seems likely that fever associated with pyrogenic factors related to labor is suppressed by opioids, whereas it is expressed normally in patients given epidural analgesia. We examined this hypothesis and the possible etiology of temperature elevation in labor.\n In this prospective, randomized, controlled study, we assessed 201 parturients during spontaneous labor. Analgesia was randomly provided with one of four treatment groups: (1) epidural ropivacaine alone, (2) IV remifentanil alone, (3) epidural ropivacaine plus IV remifentanil, and (4) epidural ropivacaine plus IV acetaminophen. At randomization, patients were normothermic. Intrapartum hyperthermia (>or=38 degrees C) was correlated to the analgesic technique.\n The maximum increase in oral temperature was greatest in the ropivacaine group (0.7 +/- 0.6 degrees C) and least in the remifentanil group (0.3 +/- 0.4 degrees C; P = 0.013). The percentage of patients who became hyperthermic (>or=38 degrees C) during the first 6 h of labor was greatest in the ropivacaine group (14%) and least in the remifentanil-alone group (2%), but the difference was not statistically significant. The maximum forearm-finger gradients were lower (less vasoconstriction) in the remifentanil group when compared to the gradients in patients with epidural analgesia (1.4 +/- 1.8 vs 3.0 +/- 1.7, respectively; P < 0.001).\n Our results are consistent with the theory that low-dose opioids inhibit fever in patients not given epidural analgesia. However, in view of the negative results, the hypothesis of epidural-induced hyperthermia may be questionable.", "We tested the hypothesis that the sedative, euphoric, and analgesic effects of intravenous fentanyl would distinguish intravenous from epidural administration. One hundred ASA I and II labouring parturients received 100 micrograms fentanyl either iv or via an epidural catheter in a double-blind, randomized, cross-over fashion. Nineteen anaesthetists (8 staff and 11 residents) participated and correctly guessed the route of administration of the fentanyl in 61/66 intravenous doses and in 69/75 epidural doses yielding a sensitivity of 92.4%, a specificity of 92.0%, a positive predictive value of 91.0%, and a negative predictive value of 93.2%. Of the 41 patients that were crossed over, 38 (92.7%) were able to detect a difference between the routes of administration. Most patients experienced prompt, short-lived symptoms with iv fentanyl but no important differences in fetal heart rate pattern or in maternal desaturation were seen between the groups. This study suggests that subjective symptoms will accurately distinguish intravenous from epidural fentanyl administration in labouring parturients (P < 0.001), and should serve as a safe and reliable intravenous test dose for epidural anaesthesia in the obstetric population.", "To investigate possible short and long term side effects of epidural analgesia, compared with non-epidural analgesia for pain relief in labour.\n Randomised controlled study, with long term follow up by questionnaire. Analysis by intention-to-treat.\n Busy maternity unit within a district general hospital in England.\n Three hundred and sixty nine primigravid women in labour were included (randomised allocation: epidural n = 184, non-epidural n = 185).\n Backache at three and twelve months after delivery, instrumental delivery rates and maternal opinion of pain relief in labour.\n No significant differences were found in the reported incidence of backache between the groups at three months: middle backache [22% vs 20%, chi2 = 0.057, P = 0.81; odds ratio (95% CI) 1.4(0.9-2.3)]; low backache [35% vs 34%, chi2 = 0.009, P = 0.92; odds ratio (95% CI) 1.0(0.6-1.6)]. Nor were there significant differences at 12 months: [middle backache 16% vs 16%, chi2 = 0.013, P = 0.91; odds ratio (95% CI) 1.0(0.5-1.8)]; or low backache [35% vs 27%, chi2 = 1.91, P = 0.17; odds ratio (95% CI) 1.4(0.9-2.3)]. The incidence of instrumental delivery was somewhat higher in the epidural group [30% vs 19%, odds ratio (95% CI) 1.77(1.09-2.86)]. Maternal satisfaction was not significantly different between the groups.\n This study provided no evidence to support the suggestion of a direct association between the use of epidural anaesthesia in labour and the incidence of long term backache. Despite a significant proportion of women in each group not receiving their allocated analgesia, a significant difference in terms of instrumental delivery rates remained. Satisfaction in both groups of women was high.", "To determine if nulliparous women intending to have epidural analgesia have a similar labour profile and delivery outcome to women who intend to have their labour managed using alternative forms of pain relief.\n A prospective randomised controlled clinical trial conducted at a tertiary obstetric institution. Nulliparous women intending to deliver vaginally with a term singleton fetus were eligible for recruitment.\n 1159 women were recruited, of whom 992 were subsequently randomised to receive continuous midwifery support (CMS) or epidural analgesia (EPI) on presentation for delivery. The duration of labour was shorter in the CMS group compared with EPI (10.7 hours (inter quartile (IQ) 7.0,15.2) versus 11.4 hours (IQ 8.2,15.2), p = 0.039). The median duration of the first stage was 8.9 hours (IQ 6,12.5) versus 9.5 hours (IQ 7,12.7) (p = 0.069), and the median duration of the second stage was 1.33 hours (IQ 0.6,2.5) versus 1.48 hours (IQ 0.77,2.6) (p = 0.034). The requirement for oxytocin augmentation in spontaneous labour was 39.8% CMS versus 46.2% EPI (p = 0.129). There was no significant difference in the caesarean section rates. The need for any operative delivery was significantly lower in CMS (43.9% CMS versus 51.5% EPI, p = 0.019).\n Nulliparous women have a high usage of epidural analgesia, regardless of their prelabour intentions. In women who do not intend to use epidural analgesia, the temporal delay in insertion compared with those who use epidural analgesia as their primary analgesic modality is associated with a small but statistically significant reduction in overall labour duration and operative delivery rates.", "The effects of epidural analgesia on the progress of labor are controversial. The objective of this study was to determine the effect of epidural analgesia on cesarean delivery rates in a population of patients randomly assigned to receive either epidural analgesia or intravenous opioids for intrapartum pain relief.\n From January 1995 to May 1996, 318 spontaneously laboring, term, nulliparous patients were randomly assigned to receive either intravenous opioids or epidural analgesia for pain relief. Labor was managed according to the principles of active management of labor. Cesarean delivery was performed for obstetric indications. Data analysis was conducted on an intent-to-treat basis. A subanalysis was subsequently performed on patients who were compliant with the allocated form of treatment.\n One hundred sixty-two patients were randomly assigned to receive intravenous meperidine and 156 were randomly assigned to receive epidural analgesia. Maternal age, gravidity, race, gestational age, and cervical dilatation at admission and at first analgesic dose did not differ between the groups. Intent-to-treat data analysis revealed no significant difference in the cesarean delivery rate between the 2 groups, being 13.6% in the opioid group and 9.6% in the epidural group (relative risk 0.70, 95% confidence interval 0.38-1.31, P >.05). Cesarean delivery rates for the indication of dystocia also did not differ, being 10.5% in the opioid group and 5.8% in the epidural group (relative risk 0.56, 95% confidence interval 0.26-1.21, P >.05). Subanalysis of the data from patients who were compliant with the allocated form of treatment revealed that patients in the epidural group (n = 147) were 3 times more likely to have an active phase duration >/=8 hours and were 10 times more likely to require >/=2 hours in the second stage of labor than were those in the opioid group (n = 78). There were no significant differences in cesarean delivery rates in this subanalysis, being 7.7% in the opioid group and 8.8% in the epidural group (relative risk 1.15, 95% confidence interval 0.45-2.91, P >. 05). The cesarean delivery rates for dystocia were also similar in the subanalysis, being 3.8% in the opioid group and 5.5% in the epidural group (relative risk 1.42, 95% confidence interval 0.39-5. 22, P >.05).\n Epidural analgesia provides safe and effective intrapartum pain control and may be administered without undesirable effects on labor outcome.", "We hypothesised that intravenous patient-controlled analgesia (IV PCA) with remifentanil could provide as satisfactory pain relief for labour as epidural analgesia.\n Fifty-two parturients with singleton uncomplicated pregnancies were randomised to receive either IV PCA with remifentanil or epidural analgesia with 20 ml levobupivacaine 0.625 mg/ml and fentanyl 2 microg/ml in saline. The PCA dose of remifentanil was given over 1 min with a lockout time of 1 min. The dose was increased starting from the bolus of 0.1 microg/kg and following a dose escalation scheme up until the individual-effective dose was reached. The parturients assessed contraction pain (0-10), pain relief (0-4), sedation and nausea during 60 min.\n Forty-five parturients were included in the analysis. The median cervical opening was 4 cm before the study and 7 cm after the study. The median pain scores were 7.3 and 5.2 during remifentanil and epidural analgesia, respectively (P=0.009). The median pain relief scores were 2.5 and 2.8 (P=0.17). There was no difference between the groups in the proportion of parturients who discontinued due to ineffective analgesia, nor in the proportion of parturients who would have liked to continue the given medication at the end of the study. Sedation and low haemoglobin oxygen saturation were observed more often during remifentanil analgesia. Foetal heart rate tracing abnormalities were as common in both groups.\n In terms of pain scores, epidural analgesia is superior to that provided by IV remifentanil. However, there was no difference in the pain relief scores between the treatments.", "Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries. However, only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery. The authors' primary purpose in this randomized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative: patient-controlled intravenous analgesia.\n Seven hundred fifteen women of mixed parity in spontaneous labor at full term were randomly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia. Epidural analgesia was maintained with a continuous epidural infusion of 0.125% bupivacaine with 2 microg/ml fentanyl. Patient-controlled analgesia was maintained with 10-15 mg meperidine given every 10 min as needed using a patient-controlled pump. Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman randomized in the study.\n A total of 358 women were randomized to receive epidural analgesia, and 243 (68%) of these women complied with the epidural analgesia protocol. Similarly, 357 women were randomized to receive patient-controlled intravenous meperidine analgesia, and 259 (73%) of these women complied with the patient-controlled intravenous analgesia protocol. Only five women who were randomized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief. There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original randomization (epidural analgesia, 4% [95% CI: 1.9-6.2%] compared with patient-controlled intravenous analgesia, 5% [95% CI: 2.6-7.2%]). Similar results were observed for the analysis of the protocol-compliant groups (epidural analgesia, 5% [95% CI: 2.6-8.5%] compared with patient-controlled intravenous analgesia, 6% [95% CI: 3-8.9%]). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia.\n Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia.", "We compared the incidence of Caesarean delivery in nulliparous women randomized to receive epidural analgesia with those randomized to intramuscular (i.m.) pethidine. On admission to the delivery suite in established labour, 802 nulliparae had already agreed to be randomized with respect to their first analgesia. One hundred and eighty-eight women required either no analgesia or 50% nitrous oxide in oxygen (Entonox) only. Of the remaining 614 women, 310 were randomly allocated to receive i.m. pethidine up to 300 mg and 304 to receive epidural bupivacaine. Labour management was standardized according to the criteria for active management of labour. The intention-to-treat analysis showed similar Caesarean section rates in those randomized to epidural (12%) or pethidine analgesia (13%). The difference in Caesarean rate was -1.1% with 95% confidence intervals from -6.3% to +4.1%. The normal vaginal delivery rates were similar (epidural, 59%; pethidine, 61%).", "To evaluate the safety and analgesic efficacy of patient controlled intravenous analgesia (PCIA) with tramadol, and to compare its benefits and risks with combined spinal-epidural analgesia (CSEA)+ patient controlled epidural analgesia (PCEA).\n Eighty American Society of Anesthesiologist (ASA) I-II at term parturients in active labor were randomly divided into 3 groups: the control group (n = 30) received no analgesia; group A (n = 30) received spinal administration with ropivacaine 2.5 mg and fentanyl 5 microg, then with PCEA; group B (n = 20) received 1 mg/kg tramadol loading dose i.v. PCIA with 0.75% tramadol and it included: PCA dose 2 ml, lockout time 10 minutes, background infusion 2 ml/h, total dose no more than 400 mg. The intensity of pain was evaluated using Visual Analogue Scale (VAS).\n Both group A and B showed good pain relief. VAS pain scores were significantly decreased in group A and B compared with those in the control group (P < 0.01). In comparison with group B, the VAS pain scores decreased in group A (P < 0.05). The onset times of analgesia in group A were shorter than those in group B (P < 0.05). Apgar scores in group B were lower than those in group A (P < 0.05). The periods of second stage of labor in group A were longer than those in the control group and group B (P < 0.05). The cesarean delivery rate was significantly higher in the control group (16.7%) than in group A (3.3%) and group B (5.0%), but it did not differ between group A and B. There were no significant differences in vital signs, fetal heart rate, degree of motor block, and uterine contractions among the 3 groups.\n PCIA with tramadol is now a useful alternative when patients are not candidates for CSEA for labor, or do not want to have a neuraxial block anesthesia. However, sometimes it may not provide satisfactory analgesic effect.", "Combined spinal-epidural (CSE) analgesia produces rapid-onset pain relief and allows ambulation in early labor. Epidural local anesthetics may contribute to an increase in operative deliveries by decreasing perineal sensation and causing motor weakness. Operative delivery rates might be reduced with CSE, by avoiding or delaying administration of local anesthetics. This study compares the operative delivery rates associated with a CSE technique and those associated with intravenous meperidine for labor analgesia.\n Healthy parturients at full term were assigned randomly to receive CSE or intravenous meperidine analgesia. The CSE group received 10 microg intrathecal sufentanil, followed by epidural bupivacaine and fentanyl at their next request for analgesia. Parturients receiving intravenous meperidine had 50 mg on demand (maximum, 200 mg in 4 h). Labor and delivery outcomes in both groups were recorded and compared.\n An intent-to-treat analysis of 1,223 women indicated that CSE does not increase the rate of cesarean delivery for dystocia in nulliparous and parous women (CSE, 3.5% vs. intravenous meperidine, 4; P=not significant) or in nulliparous women alone (CSE, 7% vs. intravenous meperidine, 8%; P=not significant). Profound fetal bradycardia that necessitated emergency cesarean delivery within 1 h of the time the mother received sufentanil occurred in 8 of 400 parturients (compared with 0 of 352 who received meperidine; P < 0.01). However, the method of fetal monitoring differed between the two groups. Despite this, neonatal outcomes were similar overall.\n Combined spinal-epidural analgesia during labor does not increase the cesarean delivery rate for dystocia in healthy parturient patients at full term, regardless of parity. However, an unexpected increase in the number of cesarean deliveries for profound fetal bradycardia after intrathecal sufentanil was observed. Further investigation is warranted.", "The purpose of this study was to compare the peripartum and perinatal effects of epidural with intravenous labor analgesia in women with pregnancy-induced hypertension.\n Women with pregnancy-induced hypertension who had consented to participate were randomized to receive either epidural or intravenous analgesia for labor pain. Both methods were given according to standardized protocols. All women received magnesium sulfate seizure prophylaxis. Obstetric and neonatal outcomes were compared according to intent-to-treat allocation.\n Seven hundred thirty-eight women were randomized: 372 women were given epidural analgesia, and 366 women were given intravenous analgesia. Maternal characteristics were similar, including the severity of hypertension. Epidural analgesia was associated with a significantly prolonged second-stage labor, an increase in forceps deliveries, and an increase in chorioamnionitis. Cesarean delivery rates and neonatal outcomes were similar. Pain relief was superior with the epidural method. Hypotension required treatment in 11% of women in the epidural group.\n Epidural labor analgesia provides superior pain relief but no additional therapeutic benefit to women with pregnancy-induced hypertension.", "Our purpose was to determine the effect of epidural analgesia on nulliparous labor and delivery.\n Normal term nulliparous women in early spontaneous labor were randomized to receive either narcotic or epidural analgesia.\n When compared with the group receiving narcotic analgesia (n = 45), the group receiving epidural analgesia (n = 48) had a significant prolongation in the first and second stages of labor, an increased requirement for oxytocin augmentation, and a significant slowing in the rate of cervical dilatation. Epidural analgesia was associated with a significant increase in malposition (4.4% vs 18.8%, p < 0.05). Cesarean delivery occurred more frequently in the epidural group (2.2% vs 25%, p < 0.05), primarily related to an increase in cesarean section for dystocia (2.2% vs 16.7%, p < 0.05).\n In a randomized, controlled, prospective trial epidural analgesia resulted in a significant prolongation in the first and second stages of labor and a significant increase in the frequency of cesarean delivery, primarily related to dystocia.", "A number of recent studies have suggested that the analgesic effects of highly lipid-soluble opioids are similar when these agents are administered either epidurally or intravenously. We sought to test whether the lipid-soluble opioid sufentanil was more effective when administered intrathecally than when administered epidurally or intravenously. Twenty-four women during active labor received sufentanil 10 micrograms either intrathecally (n = 9), epidurally (n = 8), or intravenously (n = 7), using a combined spinal-epidural technique. The sufentanil was administered alone, without concomitant local anesthetics. Analgesia was assessed using the visual analogue score as well as the time elapsed from the administration of study drug to the patient's request for additional analgesia via the epidural catheter (bupivacaine 0.25%). The median duration of analgesia (median, interquartile range) was 84 (70-92) min in the intrathecal group, 30 (23-32) min in the epidural group, and 34 (17-30) min in the intravenous group (P < 0.001). The intrathecal group showed rapid and significant decrease in visual analogue scale scores, whereas visual analogue scale scores in the other two groups did not decrease and remained significantly elevated compared to those of the intrathecal group at all observation points. Side effects were limited to pruritus in 3 patients (2 moderate and 1 severe) in the intrathecal group. No patient developed post-dural puncture headache. We conclude that sufentanil 10 micrograms intrathecally provides rapid and effective analgesia of 1-2-h duration during labor. Epidural and intravenous use of this dose of sufentanil did not provide evidence of satisfactory analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)", "Epidural analgesia is considered to be the preferred method of labor analgesia in preeclamptic patients. Systemic opioids are another good effective, easy to administer alternative but may cause maternal and fetal respiratory depression. Remifentanil's rapid onset and offset of effects, should make it an ideal drug for the intermittent painful contraction during labor. Method. 30 preeclamptic patients were randomly assigned to one of two equal groups; Epidural Group: received epidural analgesia according to a standardized protocol using bupivacaine plus fentanyl. REMIFENTANIL GROUP: PCA was set up to deliver remlfentanil 0.5 microg/kg as a loading bolus infused over 20 seconds, lockout time of 5 minutes, PCA bolus of 0.25 microg/kg, continuous background infusion of 0.05 microg/kg/min, and maximum dose is 3 mg in 4 hours. Women were advised to start the PCA bolus when they feel the signs of a coming uterine contraction.\n All women demonstrated a significant decrease in VAS score in the first hour after administration of analgesia (P < 0.05). Analgesic quality as regard Visual Analog Pain Scores, sedation score, and post-delivery patient satisfaction in both groups, are comparable (P > 0.05). PCA remifentanil infusion until time of delivery produce no observable maternal, fetal or neonatal side effects (P < 0.05).\n PCA intravenous remifentanil is an effective option for pain relief with minimal maternal and neonatal side effects in labor for preeclamptic patients with contraindications to epidural analgesia or requesting opioid analgesia.", "Our purpose was to examine the effect of epidural analgesia on dystocia-related cesarean delivery in actively laboring nulliparous women.\n Active labor was confirmed in nulliparous women by uterine contractions, cervical dilatation of 4 cm, effacement of 80%, and fetopelvic engagement. Patients were randomized to one of two groups: epidural analgesia or narcotics. A strict protocol for labor management was in place. Patients recorded the level of pain at randomization and at hourly intervals on a visual analog scale. Elective outlet operative vaginal delivery was permitted.\n One hundred women were randomized. No difference in the rate of cesarean delivery for dystocia was noted between the groups (epidural 8%, narcotic 6%; p = 0.71). No significant differences were noted in the lengths of the first (p = 0.54) or second (p = 0.55) stages of labor or in any other time variable. Women with epidural analgesia underwent operative vaginal delivery more frequently (p = 0.004). Pain scores were equivalent at randomization, but large differences existed at each hour thereafter. The number of patients randomized did not achieve prestudy estimates. A planned interim analysis of the results demonstrated that we were unlikely to find a statistically significant difference in cesarean delivery rates in a trial of reasonable duration.\n With strict criteria for the diagnosis of labor and with use of a rigid protocol for labor management, there was no increase in dystocia-related cesarean delivery with epidural analgesia." ]

[ "2677386", "1792363", "16238883" ]

[ "Relaxation reduces disruption in mentally handicapped adults.", "Assertiveness and problem-solving training for mildly mentally retarded persons with dual diagnoses.", "Individual cognitive-behavioural anger treatment for people with mild-borderline intellectual disabilities and histories of aggression: a controlled trial." ]

[ "To assess the effects of modified relaxation training on subsequent disruptive behaviour, two groups of six non-institutionalized mentally handicapped adults were compared. At the end of 3 weeks training, those given relaxation training showed 71% more relaxation after relaxation sessions and 74% less disruptive behaviour later in the day, whereas controls who were only told stories showed no decrease; aggression and verbal disruption showed the most consistent effects. This suggests that modified relaxation is rapidly effective in inducing relaxation and in reducing disruption.", "This study investigated the differential effectiveness of assertiveness and problem-solving training on dually diagnosed patients' adaptive social behavior, distress and psychiatric symptoms, anger control, and problem-solving coping skills using a counterbalanced design. Assessments were conducted at pretreatment, midphase, posttreatment, and a 3-month follow-up examination. A combined assertiveness and problem-solving training package was effective for treatment of individuals with mild mental retardation with dual psychiatric diagnoses. Specifically, improvements occurred regarding both self-report measures of distress and caregiver ratings of adaptive functioning; however, no essential differences were found between these two treatment protocols. The importance of using self-regulatory models of therapy with this population is highlighted, and recommendations were made for future research.", "Anger is a significant predictor and activator of violent behaviour in patients living in institutional settings. There is some evidence for the value of cognitive-behavioural treatments for anger problems with people with intellectual disabilities. In this study, a newly designed treatment targeted at anger disposition, reactivity, and control was provided to intellectually disabled offenders with aggression histories living in secure settings.\n About forty detained patients with mild-borderline intellectual disabilities and histories of serious aggression were allocated to specially modified cognitive-behavioural anger treatment (AT group) or to routine care waiting-list control (RC group) conditions.\n AT group participants received 18 sessions of individual treatment. The AT and RC groups were assessed simultaneously at 4 time points: screen, pre- and post-treatment, and at 4-month follow-up using a range of self- and staff-rated anger measures. The effectiveness of the treatment was evaluated using ANCOVA linear trend analyses of group differences on the main outcome measures.\n The AT group's self-reported anger scores on a number of measures were significantly lower following treatment, compared with the RC wait-list condition, and these improvements were maintained at follow-up. Limited evidence for the effectiveness of treatment was provided by staffs' ratings of patient behaviour post-treatment.\n Detained men with mild-moderate intellectual disabilities and histories of severe aggression can successfully engage in, and benefit from, an intensive individual cognitive-behavioural anger treatment that also appears to have beneficial systemic effects." ]

[ "3822279", "3176957", "2321776", "8938467" ]

[ "Continuous infusion epidural analgesia with lidocaine: efficacy and influence during the second stage of labor.", "Benefits of continuous infusion epidural analgesia throughout vaginal delivery.", "Continuous epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor.", "Effect of second-stage 0.25% epidural bupivacaine on the outcome of labor." ]

[ "A randomized double-blind study evaluated the analgesic efficacy and influence of maintaining a continuous epidural infusion of 0.75% lidocaine during the second stage of labor in nulliparous women. When the cervix was 8 cm or more dilated, unidentified study solution was substituted for the known 0.75% lidocaine solution and continued until delivery. The study solution for 26 patients was 0.75% lidocaine; 27 subjects received saline. During the first stage of labor, 88% of women in the lidocaine group and 81% of women in the saline group had analgesia of excellent or good quality, a nonsignificant difference. During the second stage, there was a tendency (not statistically significant) toward improved analgesia quality in the lidocaine patients, but there was no significant difference in the frequency of perineal anesthesia (23% lidocaine, 7% saline). There was no difference between the groups in the duration of the second stage of labor (73 +/- 63 versus 76 +/- 48 minutes). Operative delivery frequency was similar (31 and 37%), as were umbilical cord blood acid-base values. It is concluded that maintenance of the continuous epidural infusion of 0.75% lidocaine did not prolong the second stage of labor, but it also did not significantly differ from saline in quality of second stage analgesia or frequency of perineal anesthesia.", "Two groups of nulliparous women with fetuses in singleton vertex presentation received continuous infusion epidural analgesia (EDA) with bupivacaine: group A (90 parturients) without infusion analgesia in the second stage of labor and group B (90 parturients) with infusion analgesia throughout delivery. The groups were compared regarding pain relief, duration of the second stage, persistent malrotation of the fetal head, and rate of instrumental vaginal delivery. The continuous infusion EDA gave satisfactory pain relief in 93.3% of the parturients in group A and 97.8% in group B. The duration of second stage was the same in both groups. There were more persistent malrotations of the fetal head in group A, but the malrotation did not affect the mode of delivery. The rate of instrumental vaginal delivery was 25.5% in both groups. The main cause of operative intervention was delay in the second stage. When the continuous infusion technique is used, it seems unreasonable to discontinue the EDA and thereby deprive the parturient of analgesia during the second stage.", "A randomized, double-blind, placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor in nulliparous women. When the cervix was fully dilated, coded study solution was substituted for the known bupivacaine-fentanyl solution. The study solution for 29 patients was 0.0625% bupivacaine-0.0002% fentanyl; 34 patients received saline placebo. The two groups had similar pain scores during the first stage of labor. During the second stage, pain scores were significantly higher in the saline-placebo group at each 30-min interval between 60 and 150 min after the diagnosis of full cervical dilation. Similarly, there was a significant difference between the two groups in global assessment of analgesia quality during the second stage, but the difference occurred in those patients with a second-stage duration of greater than or equal to 60 min. Among the women who delivered vaginally, eleven of 28 (39%) women in the bupivacaine-fentanyl group, versus five of 34 (15%) in the saline-placebo group, had surgical perineal anesthesia for vaginal delivery (P less than .05). Six of 28 (21%) women in the bupivacaine-fentanyl group, and five of 34 (15%) in the saline-placebo group, underwent instrumental vaginal delivery (P = NS). The median duration of the second stage of labor was 53 min (range = 5-283) in the bupivacaine-fentanyl group, and 63 min (range = 16-181) in the saline-placebo group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)", "To evaluate the effect of second-stage epidural bupivacaine on the outcome of labor.\n Two groups of 35 patients each were randomly allocated to receive continuous epidural bupivacaine throughout labor (group 1) or until an 8-cm dilatation of the cervix (group 2).\n There was no significant difference between the 2 groups in the rates of instrument deliveries and in their Apgar scores.\n The administration of continuous epidural bupivacaine (0.25%) throughout labor and delivery does not seem to affect the outcome of labor." ]

[ "12748973", "16462503", "19242918", "17785709", "17964881", "18797706", "17761637", "15774341", "19637345", "18581595", "18280104", "19383889", "20919481", "17785708", "19609570", "19831159", "21689848", "19242916", "12100834", "21116175", "20531162", "21190995", "18779540", "19687337", "15139072", "19834744", "7937251", "20842268", "15484202", "17944760", "18543381", "20512260", "11157015", "10326708", "12721238", "19949016", "17307761", "11879296", "15274068", "19064985", "19826172", "19234513", "21335510", "15378098", "9243585", "20973811", "20388445", "19880433" ]

[ "The group psychotherapy and home-based physical exercise (group-hope) trial in cancer survivors: physical fitness and quality of life outcomes.", "Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer?", "Exercise and quality of life during and after treatment for breast cancer: results of two randomized controlled trials.", "Randomized controlled trial of yoga among a multiethnic sample of breast cancer patients: effects on quality of life.", "Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy.", "Effect of exercise on the caloric intake of breast cancer patients undergoing treatment.", "Effects of an integrated yoga program in modulating psychological stress and radiation-induced genotoxic stress in breast cancer patients undergoing radiotherapy.", "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Impact of a walking intervention on cardiorespiratory fitness, self-reported physical function, and pain in patients undergoing treatment for solid tumors.", "Effects of supervised exercise therapy in patients receiving radiotherapy for breast cancer.", "Effects of a walking intervention on fatigue-related experiences of hospitalized acute myelogenous leukemia patients undergoing chemotherapy: a randomized controlled trial.", "Physical activity and health outcomes three months after completing a physical activity behavior change intervention: persistent and delayed effects.", "[Effects of an exercise training program on the quality of life of women with breast cancer on chemotherapy].", "Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.", "Physical activity for men receiving androgen deprivation therapy for prostate cancer: benefits from a 16-week intervention.", "A 4-week home-based aerobic and resistance exercise program during radiation therapy: a pilot randomized clinical trial.", "A randomised controlled trial testing the feasibility and efficacy of a physical activity behavioural change intervention in managing fatigue with gynaecological cancer survivors.", "Restorative yoga for women with breast cancer: findings from a randomized pilot study.", "The efficacy of a mind-body-spirit group for women with breast cancer: a randomized controlled trial.", "Strength training following hematopoietic stem cell transplantation.", "Therapeutic exercise during outpatient radiation therapy for advanced cancer: Feasibility and impact on physical well-being.", "Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation.", "Effects of aerobic exercise training in anemic cancer patients receiving darbepoetin alfa: a randomized controlled trial.", "Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients.", "Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma.", "Improving sleep quality for cancer patients: benefits of a home-based exercise intervention.", "A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy.", "Effects of yoga on symptom management in breast cancer patients: A randomized controlled trial.", "Exercise manages fatigue during breast cancer treatment: a randomized controlled trial.", "Effects of an integrated yoga programme on chemotherapy-induced nausea and emesis in breast cancer patients.", "Medical Qigong for cancer patients: pilot study of impact on quality of life, side effects of treatment and inflammation.", "[Upper limbs exercises during radiotherapy for breast cancer and quality of life].", "Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial.", "Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy.", "Resistance exercise in men receiving androgen deprivation therapy for prostate cancer.", "Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial.", "Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial.", "Fatigue and quality of life outcomes of exercise during cancer treatment.", "A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma.", "Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer.", "Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial.", "A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT.", "Lifestyle intervention in men with advanced prostate cancer receiving androgen suppression therapy: a feasibility study.", "The effect of seated exercise on fatigue and quality of life in women with advanced breast cancer.", "Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer.", "Effects of a home-based walking program on perceived symptom and mood status in postoperative breast cancer women receiving adjuvant chemotherapy.", "Yoga improves quality of life and benefit finding in women undergoing radiotherapy for breast cancer.", "Impact of medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial." ]

[ "Physical exercise has been shown to enhance quality of life (QOL) in cancer survivors using pretest-posttest designs and compared to usual care (i.e. no intervention). In the present study, we conducted a randomized controlled trial to determine if exercise could improve QOL in cancer survivors beyond the known benefits of group psychotherapy (GP). We matched 22 GP classes (N=108) on content and then randomly assigned 11 (n=48) to GP alone and 11 (n=60) to GP plus home-based, moderate-intensity exercise (GP+EX). Participants completed a physical fitness test and QOL measures (e.g. Functional Assessment of Cancer Therapy scales) at the beginning and end of GP classes (about 10 weeks). We had excellent recruitment (81%), retention (89%), and adherence (84%) rates and a modest contamination (22%) rate. Using intention-to-treat repeated measures analyses of variance, we found significant Time by Condition interactions for functional well-being, fatigue, and sum of skinfolds. We also found borderline significant interactions for physical well-being, satisfaction with life, and flexibility. All interactions favored the GP+EX condition. We conclude that a home-based, moderate intensity exercise program may im-prove QOL in cancer survivors beyond the benefits of GP, particularly in relation to physical and functional well-being.\n Copyright 2003 John Wiley & Sons, Ltd.", "Fatigue has a significant impact on the quality of life (QOL) of cancer patients. Recent research has suggested that physical activity can reduce fatigue in patients receiving active cancer treatment. In this project, we examined the impact that participation in a randomized controlled trial of a multidisciplinary intervention designed to impact overall QOL had on fatigue for advanced cancer patients actively receiving treatment.\n Patients with newly diagnosed cancer were randomly assigned to an 8-session structured multidisciplinary intervention or a standard-care arm at the beginning of their course of radiotherapy (RT) designed to impact QOL. Ninety-minute sessions were led by either a psychiatrist or psychologist, collaborating with a nurse, physical therapist, chaplain, or social worker, depending on the session's theme. The fatigue assessments used in this trial included the Linear Analogue Self Assessment (LASA), the Profile of Mood States (POMS), Spielberger's State-Trait Anxiety Inventory (STAI), and the Symptom Distress Scale (SDS).\n There were 115 participants enrolled and the 2 randomization arms were well balanced in terms of baseline characteristics and treatment received except for increased commuting distance for the patients in the intervention arm (P = 0.042). Most of scores indicated less fatigue (higher score) in the standard treatment group, but there were no statistically significant differences found at baseline and weeks 4, 8, and 27 except for SDS at week 8 (P = 0.018) with less patients reporting significant fatigue in the standard treatment arm. For the entire participant population, fatigue levels initially worsened with radiotherapy, stabilized at week 8, and returned to baseline by week 27. Disease site, chemotherapy use, and radiotherapy dose did not have a significant impact on fatigue levels.\n Radiotherapy initially caused a worsening of fatigue but with time fatigue levels returned to baseline. Clinically, this structured multidisciplinary intervention had no impact on fatigue, and there was the suggestion the multiple sessions may have contributed to worse fatigue during active cancer treatment.", "To determine the effect of exercise on quality of life in (a) a randomized controlled trial of exercise among recently diagnosed breast cancer survivors undergoing adjuvant therapy and (b) a similar trial among post-treatment survivors.\n Fifty newly diagnosed breast cancer survivors were recruited through a hospital-based tumor registry and randomized to a 6-month, home-based exercise program (n=25) or a usual care group (n=25). In a separate trial, 75 post-treatment survivors were randomized to a 6-month, supervised exercise intervention (n=37) or to usual care (n=38). Participants in both studies completed measures of happiness, depressive symptoms, anxiety, stress, self-esteem, and quality of life at baseline and 6 months.\n Forty-five participants completed the trial for newly diagnosed survivors and 67 completed the trial for post-treatment survivors. Good adherence was observed in both studies. Baseline quality of life was similar for both studies on most measures. Exercise was not associated with quality of life benefits in the full sample of either study; however exercise was associated with improved social functioning among post-treatment survivors who reported low social functioning at baseline (p<0.05).\n Exercise did not affect quality of life in either recently diagnosed or post-treatment breast cancer survivors; however this may be due in part to relatively high baseline functioning among participants in both studies. Strategies for future research include limiting enrollment to survivors who report reduced quality of life on screening questionnaires and targeting survivor subgroups known to be at particular risk for quality of life impairment.\n (c) 2009 John Wiley & Sons, Ltd.", "This study examines the impact of yoga, including physical poses, breathing, and meditation exercises, on quality of life (QOL), fatigue, distressed mood, and spiritual well-being among a multiethnic sample of breast cancer patients.\n One hundred twenty-eight patients (42% African American, 31% Hispanic) recruited from an urban cancer center were randomly assigned (2:1 ratio) to a 12-week yoga intervention (n = 84) or a 12-week waitlist control group (n = 44). Changes in QOL (eg, Functional Assessment of Cancer Therapy) from before random assignment (T1) to the 3-month follow-up (T3) were examined; predictors of adherence were also assessed. Nearly half of all patients were receiving medical treatment.\n Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (P < .0001). Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL (P < .008), emotional well-being (P < .015), social well-being (P < .004), spiritual well-being (P < .009), and distressed mood (P < .031). Sixty-nine percent of intervention participants attended classes (mean number of classes attended by active class participants = 7.00 +/- 3.80), with lower adherence associated with increased fatigue (P < .001), radiotherapy (P < .0001), younger age (P < .008), and no antiestrogen therapy (P < .02).\n Despite limited adherence, this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors. Among patients not receiving chemotherapy, yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL.", "To show fatigue prevention and quality of life (QOL) improvement from cardiovascular exercise during radiotherapy.\n Prospective enrollment (n=21), randomized to exercise (n=11) and control groups (n=10), with pre- and post-radiotherapy between- and within-group comparisons.\n Academic medical center.\n Localized prostate cancer patients undergoing radiotherapy.\n The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise.\n Pre- and post-radiotherapy differences in cardiac fitness, fatigue, depression, functional status, physical, social, and functional well-being, leg strength, and flexibility were examined within and between 2 groups.\n No significant differences existed between 2 groups at pre-radiotherapy assessment. At post-radiotherapy assessment, the exercise group showed significant within group improvements in: cardiac fitness (P<.001), fatigue (P=.02), Functional Assessment of Cancer Therapy-Prostate (FACT-P) (P=.04), physical well-being (P=.002), social well-being (P=.02), flexibility (P=.006), and leg strength (P=.000). Within the control group, there was a significant increase in fatigue score (P=.004) and a decline in social well-being (P<.05) at post-radiotherapy assessment. Between-group differences at post-radiotherapy assessment were significant in cardiac fitness (P=.006), strength (P=.000), flexibility (P<.01), fatigue (P<.001), FACT-P (P=.006), physical well-being (P<.001), social well-being (P=.002), and functional well-being (P=.04).\n An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness, flexibility, muscle strength, and overall QOL and prevented fatigue.", "The purpose of this study was to examine the effects of an exercise intervention on the total caloric intake (TCI) of breast cancer patients undergoing treatment. A secondary purpose was to determine whether or not a relationship existed between changes in TCI, body fat composition (%BF), and fatigue during the study, which lasted 6 months. Twenty females recently diagnosed with breast cancer, scheduled to undergo chemotherapy or radiation, were assigned randomly to an experimental (N = 10) or control group (N = 10). Outcome measures included TCI (3-day food diary), %BF (skinfolds), and fatigue (revised Piper Fatigue Scale). Each exercise session was conducted as follows: initial cardiovascular activity (6-12 min), followed by stretching (5-10 min), resistance training (15-30 min), and a cool-down (approximately 8 min). Significant changes in TCI were observed among groups (F1,18 = 8.582; P = 0.009), at treatments 2 and 3, and at the end of the study [experimental (1973 +/- 419), control (1488 +/- 418); experimental (1946 +/- 437), control (1436 +/- 429); experimental (2315 +/- 455), control (1474 +/- 294), respectively]. A significant negative correlation was found (Spearman rho(18) = -0.759; P < 0.001) between TCI and %BF and between TCI and fatigue levels (Spearman rho(18) = -0.541; P = 0.014) at the end of the study. In conclusion, the results of this study suggest that an exercise intervention administered to breast cancer patients undergoing medical treatment may assist in the mitigation of some treatment side effects, including decreased TCI, increased fatigue, and negative changes in body composition.", "Effects of an integrated yoga program in modulating perceived stress levels, anxiety, as well as depression levels and radiation-induced DNA damage were studied in 68 breast cancer patients undergoing radiotherapy. Two psychological questionnaires--Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS)--and DNA damage assay were used in the study. There was a significant decrease in the HADS scores in the yoga intervention group, whereas the control group displayed an increase in these scores. Mean PSS was decreased in the yoga group, whereas the control group did not show any change pre- and postradiotherapy. Radiation-induced DNA damage was significantly elevated in both the yoga and control groups after radiotherapy, but the postradiotherapy DNA damage in the yoga group was slightly less when compared to the control group. An integrated approach of yoga intervention modulates the stress and DNA damage levels in breast cancer patients during radiotherapy.", "This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained.", "Cancer treatment is associated with decline in measured and self-reported physical function and increased pain. In the current study, the authors evaluated the impact of a walking intervention on these outcomes during chemotherapy/radiation.\n Patients with breast, prostate, and other cancers (N=126) were randomized to a home-based walking intervention (exercise) or usual care (control). Exercise dose during the intervention was assessed using a 5-item Physical Activity Questionnaire. Outcome measures were cardiorespiratory fitness, expressed as peak oxygen uptake (VO2) measured during treadmill testing (n=85) or estimated by 12-minute walk (n=27), and self-reported physical function, role limitations, and pain derived from Medical Outcomes Study Short Form 36. Linear regression was used to evaluate pre-to-post intervention change outcomes between groups.\n The mean (standard deviation) age of the patients was 60.2 (10.6) years. Diagnoses included prostate (55.6%) and breast (32.5%) cancer. Treatment included external beam radiotherapy (52.3%) and chemotherapy (34.9%). Exercise patients reported worsening Medical Outcomes Study physical function role limitations by the end of cancer treatment (P=.037). Younger age was associated with improved Medical Outcomes Study physical function (P=.048). In all patients, increased exercise dose was associated with decreased Medical Outcomes Study pain (P=.046), regardless of diagnosis. The percent change of VO2 between prostate and nonprostate cancer patients when adjusted for baseline VO2 and Physical Activity Questionnaire values was 17.45% (P=.008), with better VO2 maintenance in the prostate group.\n Exercise during cancer treatment improves cardiorespiratory fitness and self-reported physical function in prostate cancer patients and in younger patients, regardless of diagnosis, and may attenuate loss of those capacities in patients undergoing chemotherapy. Exercise also reduces the pain experience.\n Copyright (c) 2009 American Cancer Society.", "Postoperative radiotherapy for breast cancer has a number of associated complications. This study examined whether supervised moderate-intensity exercise could mitigate the complications that occur during radiotherapy.\n Forty women were randomized before radiotherapy after various operations for breast cancer. Seventeen patients who were assigned to the exercise group performed supervised moderate-intensity exercise therapy for 50 min 3 times per week for 5 weeks. Twenty-three patients in the control group were asked to perform self-shoulder stretching exercise. The World Health Organization Quality of Life-BREF (WHOQOL-BREF), brief fatigue inventory (BFI), range of motion (ROM) of the shoulder, and pain score were assessed before and after radiotherapy.\n There were no significant differences noted at baseline between groups. In the exercise group, there was an increase in the WHOQOL-BREF and shoulder ROM and decrease in BFI and pain score after radiotherapy. On the other hand, patients in the control group showed decrease in the WHOQOL-BREF and shoulder ROM and increase in BFI and pain score after radiotherapy. There were statistically significant differences in the changes in the WHOQOL, BFI, shoulder ROM, and pain score between the groups.\n Patients receiving radiotherapy for breast cancer may benefit in physical and psychological aspects from supervised moderate-intensity exercise therapy.", "The purpose of this randomized, controlled clinical trial was to preliminarily examine the effects of a three-week walking exercise program (WEP) on fatigue-related experiences of acute myelogenous leukemia (AML) patients receiving chemotherapy. Eligible AML patients were randomly assigned to either an experimental group (n=11), which received 12 minutes of WEP per day, five days per week for three consecutive weeks, or to a control group (n=11), which received standard ward care. Effects of the WEP were assessed by seven indicators: worst and average fatigue intensities, fatigue interference with patients' daily life, 12-minute walking distance, overall symptom distress, anxiety, and depressive status. All patients were evaluated four times: before chemotherapy (baseline or Day 1), Day 7, Day 14, and Day 21 of chemotherapy. Data were analyzed by Generalized Estimating Equation and revealed that AML patients in the three-week WEP group had a significantly greater increase in 12-minute walking distance than the control group. Patients in the WEP also had lower levels of fatigue intensity and interference, symptom distress, anxiety, and depressive status than the control group. Although preliminary, our results strongly suggest that three weeks of systematic walking exercise is clinically feasible for AML patients undergoing chemotherapy and can effectively improve their fatigue-related experiences.", "We previously reported the effectiveness of a 12-week physical activity behavior change intervention for breast cancer survivors postintervention with this report, aiming to determine delayed and/or persistent effects 3 months after intervention completion.\n Forty-one sedentary women with stage I, II, or IIIA breast cancer currently receiving hormonal therapy were randomly assigned to receive the 12-week Better Exercise Adherence after Treatment for Cancer intervention or usual care. Assessments occurred at baseline, postintervention, and 3 months postintervention.\n Weekly minutes of greater than or equal to moderate intensity physical activity measured by accelerometer showed a significant group by time interaction (F = 3.51; P = 0.035; between group difference in the mean change from baseline to 3 months postintervention, 100.1 minute, P = 0.012). Significant group by time interactions also showed sustained improvements from baseline to 3 months postintervention in strength (F = 3.82; P = 0.027; between group difference, 11.2 kg; P = 0.026), waist-to-hip ratio (F = 3.36; P = 0.041; between group difference, -0.04; P = 0.094), and social well-being (F = 4.22; P = 0.023; between group difference, 3.9; P = 0.039). A delayed reduction in lower extremity dysfunction 3 months postintervention was noted (F = 3.24; P = 0.045; between group difference in the mean change from postintervention to 3 months follow-up; P = -7.6; P = 0.015). No group by time effect was noted for fitness, body mass index, percent fat, bone density, total quality of life (Functional Assessment of Cancer Therapy-General), fatigue, endocrine symptoms, cognitive function, or sleep.\n The intervention resulted in sustained improvements in physical activity, strength, central adiposity, and social well-being with lower extremity function benefits appearing 3 months after intervention completion. Testing translation in a multisite study is warranted.", "Exercise may reduce anxiety and depression associated to the diagnosis and treatment of cancer.\n To assess the effects of a physical training program during chemotherapy among women with breast cancer.\n Twenty two women aged 49 +/- 7 years with breast cancer voluntarily agreed to take part in the study, after surgical treatment. Functional capacity (Karnofsky Performance Status), psychological status (General Health Questionnaire, GHQ) and quality of life (EORTC QLQ-C30) were evaluated at baseline and at the end of the study. Before beginning with adjuvant chemotherapy, ten women were randomly assigned to a program of physical exercise and seven to a control group. The program lasted 18 to 22 weeks, depending on the duration of chemotherapy.\n Five women were lost from follow up. Before starting chemotherapy, 41% of women were working and all had to kit. At baseline all had a normal Karnofski score and quality of life was compromised. At the end of the study, the intervention group had an improvement of their quality of life, compared to the control group that did not experience significant changes.\n An exercise training program improves quality of life of women with breast cancer on chemotherapy.", "Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects.\n We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema.\n The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem (P = .015), aerobic fitness (P = .006), and percent body fat (adjusted P = .076). Resistance exercise was superior to usual care for improving self-esteem (P = .018), muscular strength (P < .001), lean body mass (P = .015), and chemotherapy completion rate (P = .033). Changes in cancer-specific QOL, fatigue, depression, and anxiety favored the exercise groups but did not reach statistical significance. Exercise did not cause lymphedema or adverse events.\n Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.", "Prostate cancer patients receiving androgen deprivation therapy (ADT) are vulnerable to a number of potentially debilitating side effects, which can significantly impact quality of life. The role of alternate therapies, such as physical activity (PA), in attenuating these side effects is largely understudied for such a large population. Thus, the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior, quality of life, and fitness measures.\n One hundred participants were randomized into an intervention (n = 53) or a wait-list control group (n = 47), with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing. The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions. PA, quality of life, fitness, and physiological outcomes were assessed pre and post the 16-week intervention.\n Significant increases in PA, supported by changes in girth measures and blood pressure, support the beneficial impact of the intervention. Positive trends were also evident for depression and fatigue. However, due to the high dropout rate, these results must be interpreted with caution.\n PA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy. Determining the maintenance of this behavior change will be important for understanding how the long-term benefits of increased activity levels may alleviate the late effects of ADT.", "During radiation therapy, cancer patients may report cancer-related fatigue (CRF), which impairs aerobic capacity, strength, muscle mass, and, ultimately, quality of life (QOL). The purpose of this pilot clinical trial was to examine the feasibility and initial efficacy of a home-based aerobic and progressive resistance exercise intervention for aerobic capacity, strength, muscle mass, CRF, and QOL. Daily steps walked (DSW), daily minutes of resistance exercise (MRE), and number of resistance exercise days (RED) were assessed to evaluate intervention adherence. Breast and prostate cancer patients (n = 38) beginning radiation therapy were randomized to undergo 4 weeks of exercise or no exercise. Participants in the exercise group demonstrated good adherence to the exercise intervention, with significantly more DSW, MRE, and RED at post intervention and 3 month follow-up than controls. Participants in the exercise intervention exhibited significantly higher QOL and significantly lower CRF post intervention and at 3-month follow-up than controls. Results of this pilot study provide positive preliminary evidence that exercise during radiation may be beneficial for cancer patients.", "To determine the feasibility and efficacy of a physical activity behavioural change intervention in managing cancer-related fatigue among gynaecological cancer survivors during and post anti-cancer treatments.\n A two arm, single blind, randomised controlled trial was conducted within the Northern Ireland regional Cancer Centre. Thirty three sedentary gynaecological cancer survivors (stage I-III; ≤3 years post diagnosis), experiencing cancer-related fatigue (mild-severe) took part. Participants were randomly assigned to a behavioural change, moderate intensity physical activity intervention (n=16) or a Contact Control group (n=17). The primary outcome was fatigue (Multidimensional Fatigue Symptom Inventory-Short Form and Functional Assessment in Chronic Illness Therapy-Fatigue subscale). Secondary outcomes included quality of life, physical functioning, positive and negative affect, depression, body composition, sleep dysfunction and self-reported physical activity. Feasibility was assessed based on the recruitment rate, programme and physical activity adherence and participants' programme evaluation, including optional focus groups (n=16).\n Twenty five percent of eligible women took part (33/134). Participants were 8.7 (SD=9.1) months post diagnosis, with a mean age of 53 (SD=10.3) years. The majority of the sample had a diagnosis of ovarian (n=12) or endometrial cancer (n=11). Significant differences favouring the intervention group were observed for fatigue at 12 weeks and 6 months follow-up (12 week: mean difference=-11.06; 95% confidence interval (CI)=-21.89 to -0.23; effect size (d)=0.13; p=0.046; 6 month: mean difference=-19.48; 95% CI=-19.67 to -19.15; effect size (d)=0.20; p=0.01). A mean of 10 calls (SD=1.2 calls) were delivered to the Physical Activity Group, and 10 (SD=1.6 calls) to the CC group. The intervention was positively perceived based on exit questionnaire and focus group findings.\n A physical activity behavioural change intervention for gynaecological cancer survivors is feasible in terms of participants' programme adherence and evaluation, and the intervention demonstrates improvements in fatigue. However, confirmation in the form of a larger fully powered RCT is warranted.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "Restorative yoga (RY) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors. Study goals were: to determine the feasibility of implementing a RY intervention for women with breast cancer; and to examine group differences in self-reported emotional, health-related quality of life, and symptom outcomes.\n Women with breast cancer (n=44; mean age 55.8 years) enrolled in this study; 34% were actively undergoing cancer treatment. Study participants were randomized to the intervention (10 weekly 75-minute RY classes) or a waitlist control group. Participants completed questionnaires at Week 0 (baseline) and Week 10 (immediately post-intervention for the yoga group).\n Group differences favoring the yoga group were seen for mental health, depression, positive affect, and spirituality (peace/meaning). Significant baseline*group interactions were observed for negative affect and emotional well-being. Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group. The yoga group demonstrated a significant within-group improvement in fatigue; no significant difference was noted for the control group.\n Although limited by sample size, these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients. This study demonstrates that a RY intervention is feasible for women with breast cancer; implications for study design and implementation are noted with an emphasis on program adoption and participant adherence.\n (c) 2009 John Wiley & Sons, Ltd.", "Increasing numbers of women with breast cancer are seeking alternatives to standard group support in coping with their illness. This study examines outcomes for 181 women with breast cancer randomized to either a 12-week standard group support or a 12-week complementary and alternative medicine (CAM) support intervention. Participants in the CAM group were taught the use of meditation, affirmation, imagery and ritual. The standard group combined cognitive-behavioral approaches with group sharing and support. Both interventions were found to be associated with improved quality of life (CAM, P=0.008; Standard, P=0.006), decreased depression (CAM, P=0.004; Standard, P=0.02), decreased anxiety (CAM, P=0.0003; Standard, P=0.02) and increased \"spiritual well-being\" (CAM, P=002; Standard, P=0.003). Only the CAM group showed increases in measures of Spiritual Integration (P=0.001) which were also significant between groups (P=0.003). The Standard group was associated with decreased confusion (P=0.01) and decreased helplessness/hopelessness (P=0.01), while the CAM group was associated with decreased avoidance (P=0.01). None of these latter changes were significant between groups. At baseline, very high correlations were noted between measures of quality of life, mood, and spiritual integration. At the end of the intervention, the CAM group showed higher satisfaction (P=0.006) and fewer dropouts (P=0.006) compared to the standard group. Better outcomes in quality of life in the CAM group were associated with lower initial fighting spirit (r=-.39, P=0.001). No baseline factors predicted better outcomes in the Standard group. In summary, the study found equivalence on most psychosocial outcomes between the two interventions.", "Patients receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) experience considerable reductions in physical activity and deterioration of their health status.\n The purpose of this pilot study was to test the effects of strength training compared with usual activity on physical activity, muscle strength, fatigue, health status perceptions, and quality of life following HSCT.\n Nineteen subjects were randomized to the exercise or control group. Moderate-intensity strength training began following discharge from the hospital. Dependent variables included physical activity, muscle strength, fatigue, health status perceptions, and quality of life. Variables were measured prior to admission to the hospital for HSCT, day 8 following HSCT, and 6 weeks following discharge from the hospital.\n Significant time effects were noted for many variables with anticipated declines in physical activity, muscle strength, fatigue, and health status perceptions immediately after HSCT with subsequent improvements 6 weeks following hospital discharge. One group effect was noted with subjects in the exercise group reporting less fatigue than subjects in the control group. Although no significant interactions were detected, the trends suggest that the exercise group may be more physically active following the intervention compared with the usual-activity group.\n This study demonstrates the potential positive effects of strength training on physical activity, fatigue, and quality of life in people receiving high-dose chemotherapy and HSCT.\n Preliminary evidence is provided for using strength training to enhance early recovery following HSCT. Elastic resistance bands are easy to use and relatively inexpensive.\n © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins", "To characterize the feasibility of delivering a structured physical therapy (PT) program as part of a multidisciplinary intervention to patients undergoing outpatient radiation therapy for advanced cancer.\n A single-blinded, randomized, controlled trial at a quaternary medical center outpatient clinic. One hundred three adults undergoing radiation therapy for advanced cancer with prognoses > or =6 mos and 5-yr survival estimates < or =50% were randomized to usual care or participation in eight 90-min, multidisciplinary interventional sessions with 30 mins of each session devoted to PT. PT consisted of truncal and limb isodynamic strengthening targeting major upper- and lower-limb muscle groups as well as education and provision with instructional materials. Physical well-being and fatigue were assessed with Linear Analog Scale of Assessment. The Profile of Mood States-Short form, including Fatigue-Inertia and Vigor-Activity subscales, was also administered.\n PT session attendance was 89.3%. Relative to baseline, mean physical well-being Linear Analog Self Assessment scores at week 4 improved in the intervention group, 0.4 (SD, 23.6), and declined significantly in the control group, -10.0 (SD, 21.5) (P = 0.02). Fatigue and vigor were not significantly different between the groups. All intergroup differences had resolved at 8 and 27 wks. Baseline characteristics were not associated with the magnitude or direction of change in outcomes related to physical functioning.\n Delivery of a standardized resistive exercise PT intervention is feasible during outpatient radiation therapy and is associated with preserved physical well-being. However, benefits were not sustained, and fatigue was not affected.", "Before, during, and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients experience considerable physical and psychologic distress. Besides graft-versus-host disease and infections, reduced physical performance and high levels of fatigue affect patients' quality of life. This multicenter randomized controlled trial examined the effects of a partly self-administered exercise intervention before, during, and after allo-HSCT on these side effects. After randomization to an exercise and a social contact control group 105 patients trained in a home-based setting before hospital admission, during inpatient treatment and a 6- to 8-week period after discharge. Fatigue, physical performance, quality of life, and physical/psychologic distress were measured by standardized instruments at baseline, admission to, and discharge from hospital and 6 to 8 weeks after discharge. The exercise group showed significantly improvement in fatigue scores (up to 15% improvement in exercise group vs up to 28% deterioration in control; P<.01-.03), physical fitness/functioning (P=.02-.03) and global distress (P=.03). All effects were at least detectable at one assessment time point after hospitalization or repeatedly. Physical fitness correlated significantly with all reported symptoms/variables. In conclusion, this partly supervised exercise intervention is beneficial for patients undergoing allo-HSCT. Because of low personnel requirements, it might be valuable to integrate such a program into standard medical care.\n © 2011 by The American Society of Hematology", "Anemia in patients with solid tumors is a common problem that is associated with impaired exercise capacity, increased fatigue, and lower quality of life (QoL). Erythropoiesis-stimulating agents (ESAs) have been shown to improve these outcomes; however, it is unknown if additional benefits can be achieved with aerobic exercise training.\n We conducted a single-center, prospective, randomized, controlled trial in 55 mild-to-moderately anemic patients with solid tumors. Patients were randomized to either darbepoetin alfa alone (DAL, n = 29) or darbepoetin alfa plus aerobic exercise training (DEX; n = 26). The DEX group performed aerobic exercise training three times per week at 60%-100% of baseline exercise capacity for 12 weeks. The primary endpoint was QoL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary endpoints were fatigue, cardiorespiratory fitness (VO(2peak)), hemoglobin (Hb) response, and darbepoetin alfa dosing.\n Intention-to-treat analyses indicated significant improvements in QoL and fatigue in both groups over time but there were no between-group differences. The DEX group had a significantly greater VO(2peak) than the DAL group (mean group difference, +3.0 ml/kg per minute; 95% confidence interval, 1.2-4.7; p = .001) and there were borderline significant differences in favor of the DEX group for Hb response and darbepoetin alfa dosing.\n Aerobic exercise training did not improve QoL or fatigue beyond the established benefits of DAL but it did result in favorable improvements in exercise capacity and a more rapid Hb response with lower dosing requirements. Our results may be useful to clinicians despite the more recent restrictions on the indications for ESAs.", "Lymphoma patients commonly experience declines in physical functioning and quality of life (QoL) that may be reversed with exercise training.\n We conducted a randomized controlled trial in Edmonton, Alberta, Canada, between 2005 and 2008 that stratified 122 lymphoma patients by major disease type and current treatment status and randomly assigned them to usual care (UC; n = 62) or 12 weeks of supervised aerobic exercise training (AET; n = 60). Our primary end point was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia. Secondary end points were overall QoL, psychosocial functioning, cardiovascular fitness, and body composition.\n Follow-up assessment for our primary end point was 96% (117 of 122) at postintervention and 90% (110 of 122) at 6-month follow-up. Median adherence to the supervised exercise program was 92%. At postintervention, AET was superior to UC for patient-rated physical functioning (mean group difference, +9.0; 95% CI, 2.0 to 16.0; P = .012), overall QoL (P = .021), fatigue (P = .013), happiness (P = .004), depression (P = .005), general health (P < .001), cardiovascular fitness (P < .001), and lean body mass (P = .008). Change in peak cardiovascular fitness mediated the change in patient-rated physical functioning. AET did not interfere with chemotherapy completion rate or treatment response. At 6-month follow-up, AET was still borderline or significantly superior to UC for overall QoL (P = .054), happiness (P = .034), and depression (P = .009) without an increased risk of disease recurrence/progression.\n AET significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response. Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients.", "Research suggests that stress-reduction programs tailored to the cancer setting help patients cope with the effects of treatment and improve their quality of life. Yoga, an ancient Eastern science, incorporates stress-reduction techniques that include regulated breathing, visual imagery, and meditation as well as various postures. The authors examined the effects of the Tibetan yoga (TY) practices of Tsa lung and Trul khor, which incorporate controlled breathing and visualization, mindfulness techniques, and low-impact postures in patients with lymphoma.\n Thirty-nine patients with lymphoma who were undergoing treatment or who had concluded treatment within the past 12 months were assigned to a TY group or to a wait-list control group. Patients in the TY group participated in 7 weekly yoga sessions, and patients in the wait-list control group were free to participate in the TY program after the 3-month follow-up assessment.\n Eighty nine percent of TY participants completed at least 2-3 three yoga sessions, and 58% completed at least 5 sessions. Patients in the TY group reported significantly lower sleep disturbance scores during follow-up compared with patients in the wait-list control group (5.8 vs. 8.1; P < 0.004). This included better subjective sleep quality (P < 0.02), faster sleep latency (P < 0.01), longer sleep duration (P < 0.03), and less use of sleep medications (P < 0.02). There were no significant differences between groups in terms of intrusion or avoidance, state anxiety, depression, or fatigue.\n The participation rates suggested that a TY program is feasible for patients with cancer and that such a program significantly improves sleep-related outcomes. However, there were no significant differences between groups for the other outcomes.\n Copyright 2004 American Cancer Society.", "1) To determine the effect of a home-based walking exercise program on the sleep quality and quality of life of cancer patients, as well as 2) to determine if enhanced sleep quality was associated with improvement in quality of life over time.\n This is a prospective, longitudinal, two-armed, randomized clinical trial. Participants were recruited from oncology outpatient clinics in two university-based medical centers and were allocated to either usual care (n = 35) or a home-based walking exercise intervention for 8 weeks (n = 36). Measurements included the Taiwanese version of the Pittsburgh Sleep Quality Index, the Medical Outcomes Study Short Form-36, the Taiwanese Version Ratings of the Perceived Exertion Scale, and a walking exercise log. This study was analyzed on an intention-to-treat basis. Effects of the walking exercise program on sleep quality and quality of life were analyzed by the generalized estimating equation method.\n Patients in the exercise group reported significant improvements in sleep quality (beta = -3.54, p < 0.01) and the mental health dimension of quality of life (beta = 10.48, p < 0.01). Among patients who exercised, enhanced sleep quality also corresponded with reduced bodily pain (beta = 0.98, p = 0.04) and improvements over time in the mental health dimension of quality of life (beta = -3.87, p < 0.01).\n A home-based walking exercise program can be easily incorporated into care for cancer patients who are suffering from sleep disturbances.", "To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy.\n Experimental.\n Breast evaluation clinics of two New England medical centers with comprehensive cancer treatment programs.\n 14 women (mean age = 44 years) receiving adjuvant chemotherapy for breast cancer (86% stage II) following surgical treatment.\n Subjects were assigned randomly to the experimental group or the usual care group. Experimental group members began a structured exercise program of walking and attended support group meetings. All subjects were tested before beginning chemotherapy, during the course of chemotherapy, and one month following chemotherapy completion.\n Performance status, physical functioning, psychosocial adjustment, self-concept and body image, and 12 symptoms (e.g., fatigue, nausea, anxiety).\n Measures of physical performance, psychosocial adjustment, and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program.\n Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy.\n Although more detailed research is necessary to answer some of the questions raised by this study, implementing the walking program and forming a support group are achievable in an outpatient setting.", "This study compares the effects of an integrated yoga program with brief supportive therapy on distressful symptoms in breast cancer outpatients undergoing adjuvant radiotherapy.\n Eighty-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to their radiotherapy treatment. Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days during the course of their adjuvant radiotherapy. Assessments included Rotterdam Symptom Check List and European Organization for Research in the Treatment of Cancer-Quality of Life (EORTC QoL C30) symptom scale. Assessments were done at baseline and after 6 weeks of radiotherapy treatment.\n A GLM repeated-measures ANOVA showed a significant decrease in psychological distress (P = 0.01), fatigue (P = 0.007), insomnia (P = 0.001), and appetite loss (P = 0.002) over time in the yoga group as compared to controls. There was significant improvement in the activity level (P = 0.02) in the yoga group as compared to controls. There was a significant positive correlation between physical and psychological distress and fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, and constipation. There was a significant negative correlation between the activity level and fatigue, nausea and vomiting, pain, dyspnea, insomnia, and appetite loss.\n The results suggest beneficial effects with yoga intervention in managing cancer-and treatment-related symptoms in breast cancer patients.", "Fatigue is the most prevalent and debilitating symptom experienced by breast cancer patients receiving adjuvant chemotherapy or radiation therapy and few evidence-based treatments are available to manage this distressing side-effect. The purpose of this multi-institutional randomized controlled trial was to determine the effects of exercise on fatigue levels during treatment for breast cancer. Sedentary women (N=119) with Stage 0-III breast cancer receiving outpatient adjuvant chemotherapy or radiation therapy were randomized to a home-based moderate-intensity walking exercise program or to usual care for the duration of their cancer treatment. Of participants randomized to exercise, 72% adhered to the exercise prescription; 61% of the usual care group adhered. The intention-to-treat analysis revealed no group differences in part because of a dilution of treatment effect as 39% of the usual care group exercised and 28% of the exercise group did not. When exercise participation was considered using the data analysis method of instrumental variables with principal stratification, a clinically important and statistically significant (p=0.03) effect of exercise on pretest-to-posttest change in fatigue levels was demonstrated. Adherence to a home-based moderate-intensity walking exercise program may effectively mitigate the high levels of fatigue prevalent during cancer treatment.", "This study examined the effect of an integrated yoga programme on chemotherapy-related nausea and emesis in early operable breast cancer outpatients. Sixty-two subjects were randomly allocated to receive yoga (n = 28) or supportive therapy intervention (n = 34) during the course of their chemotherapy. Both groups had similar socio-demographic and medical characteristics. Intervention consisted of both supervised and home practice of yoga sessions lasting for 60 min daily, while the control group received supportive therapy and coping preparation during their hospital visits over a complete course of chemotherapy. The primary outcome measure was the Morrow Assessment of Nausea and Emesis (MANE) assessed after the fourth cycle of chemotherapy. Secondary outcomes included measures for anxiety, depression, quality of life, distressful symptoms and treatment-related toxicity assessed before and during the course of chemotherapy. Following yoga, there was a significant decrease in post-chemotherapy-induced nausea frequency (P = 0.01) and nausea intensity (P = 0.01), and intensity of anticipatory nausea (P = 0.01) and anticipatory vomiting (P = 0.05) as compared with the control group. There was a significant positive correlation between MANE scores and anxiety, depression and distressful symptoms. In conclusion, the results suggest a possible use for stress reduction interventions such as yoga in complementing conventional antiemetics to manage chemotherapy-related nausea and emesis.", "Quality of life (QOL) of cancer patients is often diminished due to the side effects of treatment and symptoms of the disease itself. Medical Qigong (coordination of gentle exercise and relaxation through meditation and breathing exercise based on Chinese medicine theory of energy channels) may be an effective therapy for improving QOL, symptoms and side effects, and longevity of cancer patients. In this pilot study, the feasibility, acceptability, and impact of Medical Qigong (MQ) were evaluated on outcomes in cancer patients. Thirty patients diagnosed with heterogeneous cancers, were randomly assigned to two groups: a control group that received usual medical care and an intervention group who participated in a MQ program for 8 weeks in addition to receiving usual medical care. Randomization was stratified by completion of cancer treatment (n = 14) or under chemotherapy (n = 16). Patients completed measures before and after the program. Quality of life and symptoms were measured by the EORTC QLQ-C 30 and progress of disease by the inflammation biomarker (CRP: c-reactive protein) via a blood test was assessed. The MQ intervention group reported clinically significant improved global QOL scores pre- and post-intervention. The MQ intervention also reduced the symptoms of side effects of cancer treatment and inflammation biomarker (CRP) compare to the control group. Due to the small sample size, however, the results were not statistically significant between treatment and the control groups. Data from the pilot study suggest that MQ with usual medical treatment can enhance the QOL of cancer patients and reduce inflammation. This study needs a further investigation with a larger sample size.", "To assess the influence of physiotherapy performed during radiotherapy (RT) on the quality of life (QL) of women under treatment for breast cancer.\n This was a randomized clinical trial conducted on 55 women under RT treatment, 28 of whom were assigned to a group submitted to physiotherapy (PG) and 27 to the control group receiving no PG (CG). The physiotherapy technique used for PG was kinesiotherapy for the upper limbs using 19 exercises actively performed, with a series of ten rhythmic repetitions or stretching movements involving flexion, extension, abduction, adduction, internal and external shoulder rotation, separate or combined. QL was evaluated using the Functional Assessment of Cancer Therapy-Breast (FACT-B), at the beginning and at the end of RT and six months after the end of RT. The physiotherapy sessions were started concomitantly with RT, 90 days after surgery, on average.\n There was no difference between subgroups regarding the following subscales: physical well-being (p=0.8), social/family well-being (p=0.3), functional well-being (p=0.2) and breast subscale (p=0.2) at the three time points assessed. A comparison of the emotional subscale applied at the three evaluations demonstrated a better behavior of PG as compared to CG (p=0.01), with both groups presenting improvement on the breast subscale between the beginning and the end of RT (PG p=0.0004 and CG p=0.003). There was improvement in FACT-B scores at the end of RT in both groups (PG p=0.0006 and CG p=0.003). However, at the sixth month after RT, this improvement was maintained only in PG (p=0,005). QL assessed along time by the FACT B (p=0.004) and the Trial Outcome Index (TOI) (sums of the physical and functional well-being subscales and of the breast subscale) was better for PG (p=0.006). There was no evidence of negative effects associated with the exercises.\n The execution of exercises for the upper limbs was beneficial for QL during and six months after RT.", "Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer.\n One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks.\n Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P =.04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P =.01) and a more modest difference between the supervised and control groups (6.3 points; P =.09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P =.01) and reduced body weight (-4.8 kg; P <.05) compared with usual care only in participants not receiving chemotherapy.\n Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care.", "Fatigue is a common and often severe problem in cancer patients undergoing chemotherapy. The authors postulated that physical activity training can reduce the intensity of fatigue in this group of patients.\n A group of cancer patients receiving high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group; n = 27) followed an exercise program during hospitalization. The program was comprised of biking on an ergometer in the supine position following an interval training pattern for 30 minutes daily. Patients in the control group (n = 32) did not train. Psychologic distress was assessed at hospital admission and discharge with the Profile of Mood States and Symptom Check List 90.\n By the time of hospital discharge, fatigue and somatic complaints had increased significantly in the control group (P for both < 0.01) but not in the training group. Furthermore, by the time of hospital discharge, the training group had a significant improvement in several scores of psychologic distress (obsessive-compulsive traits, fear, interpersonal sensitivity, and phobic anxiety) (P value for all scores < 0.05); this outcome was not observed in the control group.\n The current study found that aerobic exercise can reduce fatigue and improve psychologic distress in cancer patients undergoing chemotherapy.", "Androgen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue, functional decline, increased body fatness, and loss of lean body tissue. These physical changes can negatively affect health-related quality of life. Resistance exercise may help to counter some of these side effects by reducing fatigue, elevating mood, building muscle mass, and reducing body fat.\n In a two-site study, 155 men with prostate cancer who were scheduled to receive androgen deprivation therapy for at least 3 months after recruitment were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks (82 men) or to a waiting list control group (73 men). The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported questionnaires after 12 weeks. Secondary outcomes were muscular fitness and body composition.\n Men assigned to resistance exercise had less interference from fatigue on activities of daily living (P =.002) and higher quality of life (P =.001) than men in the control group. Men in the intervention group demonstrated higher levels of upper body (P =.009) and lower body (P <.001) muscular fitness than men in the control group. The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight, body mass index, waist circumference, or subcutaneous skinfolds.\n Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving androgen deprivation therapy. This form of exercise can be an important component of supportive care for these patients.", "Androgen suppression therapy (AST) results in musculoskeletal toxicity that reduces physical function and quality of life. This study examined the impact of a combined resistance and aerobic exercise program as a countermeasure to these AST-related toxicities.\n Between 2007 and 2008, 57 patients with prostate cancer undergoing AST (commenced > 2 months prior) were randomly assigned to a program of resistance and aerobic exercise (n = 29) or usual care (n = 28) for 12 weeks. Primary end points were whole body and regional lean mass. Secondary end points were muscle strength and function, cardiorespiratory capacity, blood biomarkers, and quality of life.\n Analysis of covariance was used to compare outcomes for groups at 12 weeks adjusted for baseline values and potential confounders. Patients undergoing exercise showed an increase in lean mass compared with usual care (total body, P = .047; upper limb, P < .001; lower limb, P = .019) and similarly better muscle strength (P < .01), 6-meter walk time (P = .024), and 6-meter backward walk time (P = .039). Exercise also improved several aspects of quality of life including general health (P = .022) and reduced fatigue (P = .021) and decreased levels of C-reactive protein (P = .008). There were no adverse events during the testing or exercise intervention program.\n A relatively brief exposure to exercise significantly improved muscle mass, strength, physical function, and balance in hypogonadal men compared with normal care. The exercise regimen was well tolerated and could be recommended for patients undergoing AST as an effective countermeasure to these common treatment-related adverse effects.", "To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up.\n Pragmatic randomised controlled prospective open trial.\n Three National Health Service oncology clinics in Scotland and community exercise facilities.\n 203 women entered the study; 177 completed the six month follow-up.\n Supervised 12 week group exercise programme in addition to usual care, compared with usual care.\n Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility.\n Mixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95% confidence interval 83 to 176) for metres walked in 12 minutes, 182 (75 to 289) for minutes of moderate intensity activity reported in a week, 2.6 (1.6 to 3.7) for shoulder mobility, 2.5 (1.0 to 3.9) for breast cancer specific subscale of quality of life, and 4.0 (1.8 to 6.3) for positive mood. No significant effect was seen for general quality of life (FACT-G), which was the primary outcome. At the six month follow-up, most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged. No adverse effects were noted.\n Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later. Clinicians should encourage activity for their patients. Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services. Trial registration Current controlled trials ISRCTN12587864 [controlled-trials.com].", "Despite the recognition of fatigue as a common and distressing symptom during cancer treatment, there are few evidence-based interventions available to manage such fatigue. The purpose of this multi-institutional pilot study was to explore the effects of a home-based moderate walking exercise intervention on fatigue, physical functioning, emotional distress, and quality of life (QOL) during breast cancer treatment.\n Fifty-two women were recruited from five university hospital outpatient departments for this pilot study with an experimental design. Subjects were randomly assigned to the walking program or to usual care during adjuvant chemotherapy or radiation therapy for breast cancer. Symptoms, physical functioning, and QOL were measured at baseline, midtreatment, and at the end of treatment.\n Women who exercised at least 90 minutes per week on 3 or more days reported significantly less fatigue and emotional distress as well as higher functional ability and QOL than women who were less active during treatment.\n A home-based walking exercise program is a potentially effective, low-cost, and safe intervention to manage fatigue and to improve QOL during adjuvant chemotherapy or radiation therapy for breast cancer. This health-promoting self-care activity needs further testing in large randomized clinical trials.", "Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental. Aerobic walking improves physical functioning and has been an intervention for chemotherapy-related fatigue. A prospective, randomized, controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma.\n Sixty-six men were randomized before they received radical radiotherapy for localized prostate carcinoma, with 33 men randomized to an exercise group and 33 men randomized to a control group. Outcome measures were fatigue and distance walked in a modified shuttle test before and after radiotherapy.\n There were no significant between group differences noted with regard to fatigue scores at baseline (P = 0.55) or after 4 weeks of radiotherapy (P = 0.18). Men in the control group had significant increases in fatigue scores from baseline to the end of radiotherapy (P = 0.013), with no significant increases observed in the exercise group (P = 0.203). A nonsignificant reduction (2.4%) in shuttle test distance at the end of radiotherapy was observed in the control group; however, in the exercise group, there was a significant increase (13.2%) in distance walked (P = 0.0003).\n Men who followed advice to rest and take things easy if they became fatigued demonstrated a slight deterioration in physical functioning and a significant increase in fatigue at the end of radiotherapy. Home-based, moderate-intensity walking produced a significant improvement in physical functioning with no significant increase in fatigue. Improved physical functioning may be necessary to combat radiation fatigue.", "Radiotherapy for prostate cancer (PCa) may cause unfavorable changes in fatigue, quality of life (QOL), and physical fitness. We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue, QOL, physical fitness, body composition, prostate-specific antigen, testosterone, hemoglobin, and lipid levels in men with PCa receiving radiotherapy.\n Between 2003 and 2006, we conducted a randomized controlled trial in Ottawa, Canada, where 121 PCa patients initiating radiotherapy with or without androgen deprivation therapy were randomly assigned to usual care (n = 41), resistance (n = 40), or aerobic exercise (n = 40) for 24 weeks. Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale.\n The follow-up assessment rate for our primary end point of fatigue was 92.6%. Median adherence to prescribed exercise was 85.5%. Mixed-model repeated measures analyses indicated both resistance (P =.010) and aerobic exercise (P = .004) mitigated fatigue over the short term. Resistance exercise also produced longer-term improvements (P = .002). Compared with usual care, resistance training improved QOL (P = .015), aerobic fitness (P = .041), upper- (P < .001) and lower-body (P < .001) strength, and triglycerides (P = .036), while preventing an increase in body fat (P = .049). Aerobic training also improved fitness (P = .052). One serious adverse event occurred in the group that performed aerobic exercise.\n In the short term, both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy. Resistance exercise generated longer-term improvements and additional benefits for QOL, strength, triglycerides, and body fat.", "To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease.\n Randomised controlled trial.\n Two university hospitals in Copenhagen, Denmark.\n 269 patients with cancer; 73 men, 196 women, mean age 47 years (range 20-65) representing 21 diagnoses. Main exclusion criteria were brain or bone metastases. 235 patients completed follow-up.\n Supervised exercise comprising high intensity cardiovascular and resistance training, relaxation and body awareness training, massage, nine hours weekly for six weeks in addition to conventional care, compared with conventional care.\n European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, muscular strength (one repetition maximum), maximum oxygen consumption (Vo(2)max). Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables.\n Adjusted for baseline score, disease, and demographic covariates, the intervention group showed an estimated improvement at six weeks for the primary outcome, fatigue, of -6.6 points (95% confidence interval -12.3 to -0.9, P=0.02; effect size=0.33, 0.04 to 0.61). Significant effects were seen on vitality (effect size 0.55, 95% CI 0.27 to 0.82), physical functioning (0.37, 0.09 to 0.65), role physical (0.37, 0.10 to 0.64), role emotional (0.32, 0.05 to 0.59), and mental health (0.28, 0.02 to 0.56) scores. Improvement was noted in physical capacity: estimated mean difference between groups for maximum oxygen consumption was 0.16 l/min (95% CI 0.1 to 0.2, P<0.0001) and for muscular strength (leg press) was 29.7 kg (23.4 to 34.9, P<0.0001). No significant effect was seen on global health status/quality of life.\n A supervised multimodal exercise intervention including high and low intensity components was feasible and could safely be used in patients with various cancers who were receiving adjuvant chemotherapy or treatment for advanced disease. The intervention reduced fatigue and improved vitality, aerobic capacity, muscular strength, and physical and functional activity, and emotional wellbeing, but not quality of life.\n Current Controlled trials ISRCTN05322922.", "The aim of this randomized controlled trial was to investigate the effect of a 4- to 6-week multimodal program of exercise, relaxation and psychoeducation on physical capacity, functional performance and quality of life (QOL) in allogeneic hematopoietic cell transplantation (allo-HSCT) adult recipients. In all, 42 patients were randomized to a supervised multimodal intervention or to a control group receiving usual care. The primary end point was on aerobic capacity measured in VO(2) max. Secondary end points were muscle strength, functional performance, physical activity level, QOL, fatigue, psychological well-being and clinical outcomes. The multimodal intervention had a significant effect on physical capacity: VO(2) max (P<0.0001) and muscle strength: chest press (P<0.0001), leg extension (P=0.0003), right elbow flexor (P=0.0009), right knee extensor (P<0.0001) and functional performance (stair test) (0.0008). Moreover, the intervention group showed significantly better results for the severity of diarrhea (P=0.014) and fewer days of total parenteral nutrition (P=0.019). Longitudinal changes in QOL, fatigue and psychological well-being favored the intervention group, but did not reach statistical significance. Assignment of a multimodal intervention during allo-HSCT did not cause untoward events, sustained aerobic capacity and muscle strength and reduced loss of functional performance during hospitalization.", "Healthy lifestyle behaviors could have a role in ameliorating some of the adverse effects of androgen suppression therapy (AST) in men with prostate cancer. The primary aim of this study was to assess the feasibility of a tapered supervised exercise program in combination with dietary advice in men with advanced prostate cancer receiving AST.\n Advanced prostate cancer patients receiving AST for a minimum of 6 months were randomized to a 12-week lifestyle program comprising aerobic and resistance exercise, plus dietary advice (n = 25), or standard care (n = 25). Exercise behavior, dietary macronutrient intake, quality of life, fatigue, functional fitness, and biomarkers associated with disease progression were assessed at baseline, after the intervention, and at 6 months.\n The lifestyle group showed improvements in exercise behavior (P < 0.001), dietary fat intake (P = 0.001), total energy intake (P = 0.005), fatigue (P = 0.002), aerobic exercise tolerance (P < 0.001), and muscle strength (P = 0.033) compared with standard care controls. Although a high rate of attrition (44%) was observed at 6 months, the improvements in key health outcomes were sustained. No effects on clinical prostate cancer disease markers were observed.\n This preliminary evidence suggests that pragmatic lifestyle interventions have potential to evoke improvements in exercise and dietary behavior, in addition to other important health outcomes in men with advanced prostate cancer receiving AST.\n This study shows for the first time that pragmatic lifestyle interventions are feasible and could have a positive impact on health behaviors and other key outcomes in men with advanced prostate cancer receiving AST.", "To examine the effects of a seated exercise program on fatigue and quality of life (QOL) in women with metastatic breast cancer.\n Randomized, controlled, longitudinal trial.\n Outpatient clinic of a comprehensive cancer center.\n Convenience sample of 38 women who were beginning outpatient chemotherapy.\n Subjects were randomized to a control or intervention group; the intervention was performance of a seated exercise program using home videotape three times per week for four cycles of chemotherapy. All subjects completed the Functional Assessment of Chronic Illness Therapy Fatigue Version IV (FACIT F) at baseline and at the time of the next three cycles. Subjects were asked to document the frequency, duration, and intensity of all exercise participation on monthly calendars.\n Exercise, fatigue, and QOL.\n 32 subjects, 16 per group, completed the study follow-up. With a mixed modeling approach, total FACIT F scores for the entire sample declined at a significant rate (p = 0.003) beginning with cycle 3 but at a slower rate for the experimental group (p = 0.02). Fatigue scores indicated less increase and physical well-being subscale scores showed less decline for the experimental group (p = 0.008 and p = 0.02, respectively).\n Women with advanced breast cancer randomized to the seated exercise intervention had a slower decline in total and physical well-being and less increase in fatigue scores starting with the third cycle of chemotherapy.\n Seated exercise may be a feasible exercise program for women with advanced cancer for controlling fatigue and improving physical well-being.", "PURPOSES/OBJECTIVES: To test the hypothesis that women participating in a walking exercise program during radiation therapy treatment for breast cancer would demonstrate more adaptive responses as evidenced by higher levels of physical functioning and lower levels of symptom intensity than women who did not participate.\n Experimental, two-group pretest, post-test.\n Two university teaching hospital outpatient radiation therapy departments.\n 46 women beginning a six-week program of radiation therapy for early stage breast cancer.\n Following random assignment, subjects in the exercise group maintained an individualized, self-paced, home-based walking exercise program throughout treatment. The control group received usual care. Dependent variables were measured prior to and at the end of radiation therapy. In addition, symptoms were assessed at the end of three weeks of treatment.\n Participation in the walking exercise program, physical functioning fatigue, emotional distress, and difficulty sleeping.\n Hypothesis testing by multivariate analysis of covariance, with pretest scores as covariates, indicated significant differences between groups on outcome measures (p < 0.001). The exercise group scored significantly higher than the usual care group on physical functioning (p = 0.003) and symptom intensity, particularly fatigue, anxiety, and difficulty sleeping. Fatigue was the most frequent and intense subjective symptom reported.\n A self-paced, home-based walking exercise program can help manage symptoms and improve physical functioning during radiation therapy.\n Nurse-prescribed and -monitored exercise is an effective, convenient, and low-cost self-care activity that reduces symptoms and facilitates adaptation to breast cancer diagnosis and treatment.", "This paper is a report of a study analysing the effect of a home-based walking exercise program on symptoms and mood distress among breast cancer women receiving chemotherapy postoperatively.\n Treatment-related symptoms, mood distress and decline in physical activity have been identified as major complaints among cancer patients. Studies on the efficacy of home-based walking exercise for symptoms and mood did not fully describe the exercise prescriptions that could be safe and beneficial for women with breast cancer, especially these receiving adjuvant chemotherapy.\n This is a prospective, randomized clinical trial. In 2008-2009, participants were recruited from the oncology outpatient clinic of a medical center in Taiwan, and were assigned to either the exercise group (n=19) or the control group (n=21). Women in the exercise group participated in a moderate-intensity home-based walking program for 12 weeks during their chemotherapy treatments. Symptoms, mood status and physical activity level were measured at baseline, 6- and 12-week follow-up. Data were analysed by two-way repeated-measures analysis of variance.\n Women in the exercise group reported significantly lower symptom severity scores and mood disturbance compared with those in the control group throughout the study period.\n Regular moderate-intensity exercise can play an important role in improving treatment-related symptoms and mood in women with breast cancer. A home-based walking exercise program can be easily incorporated into care for women with breast cancer undergoing chemotherapy.\n © 2010 Blackwell Publishing Ltd.", "This study examined the effects of yoga on quality of life (QOL) and psychosocial outcomes in women with breast cancer undergoing radiotherapy. Sixty-one women were randomly assigned to either a yoga or a wait-list group. Yoga classes were taught biweekly during the 6 weeks of radiotherapy. Participants completed measures of QOL, fatigue, benefit finding (finding meaning in the cancer experience), intrusive thoughts, sleep disturbances, depressive symptoms, and anxiety before radiotherapy and then again 1 week, 1 month, and 3 months after the end of radiotherapy. General linear model analyses revealed that compared to the control group, the yoga group reported significantly better general health perception (p = .005) and physical functioning scores (p = .04) 1 week postradiotherapy; higher levels of intrusive thoughts 1 month postradiotherapy (p = .01); and greater benefit finding 3 months postradiotherapy (p = .01). There were no other group differences in other QOL subscales for fatigue, depression, or sleep scores. Exploratory analyses indicated that intrusive thoughts 1 month after radiotherapy were significantly positively correlated with benefit finding 3 months after radiotherapy (r = .36, p = .011). Our results indicated that the yoga program was associated with statistically and clinically significant improvements in aspects of QOL.", "Substantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients.\n One hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially.\n Regression analysis indicated that the MQ group significantly improved overall QOL (t(144) = -5.761, P < 0.001), fatigue (t(153) = -5.621, P < 0.001), mood disturbance (t(122) =2.346, P = 0.021) and inflammation (CRP) (t(99) = 2.042, P < 0.044) compared with usual care after controlling for baseline variables.\n This study indicates that MQ can improve cancer patients' overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation." ]

[ "17599576", "11998525", "8681614", "16354341", "12502473", "15453553", "17294208", "15293606", "18241718", "12825037", "10591454", "14595277" ]

[ "Expansion sphincter pharyngoplasty: a new technique for the treatment of obstructive sleep apnea.", "[Multi-level treatment for obstructive sleep apnea syndrome: comparative study of four different surgical techniques of palate].", "Nasal-CPAP, surgery, and conservative management for treatment of obstructive sleep apnea syndrome. A randomized study.", "Radiofrequency vs laser in the management of mild to moderate obstructive sleep apnoea: does the number of treatment sessions matter?", "A randomized trial of laser-assisted uvulopalatoplasty in the treatment of mild obstructive sleep apnea.", "Lateral pharyngoplasty versus uvulopalatopharyngoplasty: a clinical, polysomnographic and computed tomography measurement comparison.", "Bipolar radiofrequency treatment for snoring with mild to moderate sleep apnea: a comparative study between the radiofrequency assisted uvulopalatoplasty technique and the channeling technique.", "Laser-assisted uvulopalatoplasty for snoring: does it meet the expectations?", "Palatal implants for the treatment of snoring and obstructive sleep apnea/hypopnea syndrome.", "A randomized trial of temperature-controlled radiofrequency, continuous positive airway pressure, and placebo for obstructive sleep apnea syndrome.", "Effects and adverse events of a dental appliance for treatment of obstructive sleep apnoea.", "Preliminary findings from a prospective, randomized trial of two tongue-base surgeries for sleep-disordered breathing." ]

[ "In this study, we assessed the efficacy of a new method (expansion sphincter pharyngoplasty [ESP]) to treat obstructive sleep apnea.\n We conducted a prospective, randomized controlled trial.\n Forty-five adults with small tonsils, body mass index less than 30 kg/m2, of Friedman stage II or III, of type I Fujita, and with lateral pharyngeal wall collapse were selected for the study.\n The mean body mass index was 28.7 kg/m2. The apnea-hypopnea index improved from 44.2 +/- 10.2 to 12.0 +/- 6.6 (P < 0.005) following ESP and from 38.1 +/- 6.46 to 19.6 +/- 7.9 in the uvulopalatopharyngoplasty group (P < 0.005). Lowest oxygen saturation improved from 78.4 +/- 8.52% to 85.2 +/- 5.1% in the ESP group (P = 0.003) and from 75.1 +/- 5.9% to 86.6 +/- 2.2% in the uvulopalatopharyngoplasty group (P < 0.005). Selecting a threshold of a 50% reduction in apnea-hypopnea index and apnea-hypopnea index less than 20, success was 82.6% in ESP compared with 68.1% in uvulopalatopharyngoplasty (P < 0.05).\n The ESP may offer benefits in a selected group of OSA patients.", "Palatopharyngeal surgery is a therapeutic option for Obstructive Sleep Apnea Syndrome. This surgery is based on the assumption that the soft palate is the principal apneogenic area of the upper airway. We report a comparison of four techniques of palatopharyneal surgery. In the other hand, the effectiveness of palatopharyngeal surgery for correcting other obstructions when present, was also evaluated.", "To assess separately the effectiveness and safety of nasal-continuous positive airway pressure (N-CPAP) and that of surgery in comparison to conservative management in patients with obstructive sleep apnea syndrome (OSAS). DESIGN. A randomized study with 1-year follow-up.\n A university hospital acting as a referral center for OSAS.\n Symptomatic patients with OSAS (72 male and 4 female patients aged 18 to 65 years), who had oxygen desaturations in the overnight recording.\n After the initial diagnostic workup, patients were considered to be candidates for either N-CPAP (44 patients) or surgical treatment (uvulopalatopharyngoplasty [UPPP] with or without mandibular osteotomy) (32 patients). Within the groups, the patients were then randomized to either the assigned treatment or conservative management.\n The number of nocturnal oxygen desaturation events of 4% or more per hour in bed (ODI4); daytime somnolence; side effects.\n N-CPAP Group: Compliance with N-CPAP therapy at 1 year was 13 of 21. The most common reason for noncompliance was general intolerance of CPAP. All compliant patients had a normal ODI4 ( < 10), whereas 1 of 20 of their control subjects had a normal finding. Patients receiving active treatment were significantly less somnolent than their control subjects at 1 year (p < 0.05). SURGERY GROUP: At 1 year, 7 of 18 of the surgically treated and 1 of 14 of the conservatively treated patients had a normal ODI4 (p < 0.001). Daytime somnolence was significantly less severe in the surgically treated patients compared with their control subjects (p < 0.001) both at 3 and 12 months. The overall postoperative complication rate was 22%.\n N-CPAP is an effective therapy for OSAS, but compliance is a problem. Surgical therapy (UPPP with or without mandibular osteotomy) needs further evaluation.", "Obstructive sleep apnea (OSA) is a relatively common and serious problem with many medical and social consequences. Laser and radiofrequency are two recent techniques used to treat OSA and they can be carried out under local anaesthesia, but they need multiple sessions to achieve satisfactory outcome and are associated with better short-term than long-term outcomes. In this work we compare the two modalities as regards the optimal number of treatment sessions needed to achieve a favourable outcome in the short and long term.\n A total of 150 patients with apnoea hypopnoea index (AHI) between 5 and 30 events per hour, no morbid obesity and retropalatal site of obstruction were included in this prospective study.\n Patients were randomly and equally divided into two groups, each comprising 75 patients. The first group was treated with bipolar radiofrequency volumetric tissue reduction of the palate (BRVTR) and the second group was treated with laser-assisted uvulopalatoplasty (LAUP). Each group was further subdivided into five subgroups each consisting of 15 patients. The first group received one treatment session, the second received two sessions, the third received three sessions, the fourth received four sessions and the fifth group received five treatment sessions. Evaluation of efficiency of both techniques in treating OSA was assessed objectively by polysomnography.\n In those treated with BRVTR; at least three sessions were needed to achieve a favourable outcome in OSA in the short and long term. In those treated with LAUP, a single treatment session was enough to achieve a favourable outcome on OSA in the short term, while two sessions were needed to achieve the same long-term outcome.\n In OSA, fewer treatment sessions are needed with LAUP (one session) than with BRVTR (three sessions) to achieve a favourable outcome. In LAUP more treatment sessions (two) are needed to maintain a longer-term favourable outcome than those needed to achieve short-term favourable outcome (one session), which is not the case with BRVTR (three sessions are needed to achieve both short- and long-term favourable results).", "Laser-assisted uvulopalatoplasty (LAUP) is an outpatient surgical treatment for snoring and obstructive sleep apnea (OSA), but to date, no controlled trials have been published. Forty-five subjects with mild OSA (apnea/hypopnea index [AHI], 10-27 per hour) were randomized to LAUP or to no treatment (control group). The AHI post-LAUP was reduced by 21% overall and to 10 or less per hour in 5 of 21 subjects (24%). Four of 24 subjects in the control group (16.7%) had an AHI of 10 or less per hour at outcome. The AHI decreased with the LAUP compared with no change with the control group at outcome. Ten subjects (48%) reported significantly improved snoring after the LAUP. There was no improvement in excessive daytime sleepiness, but there was a small improvement in quality of life (unless side effects were included in the quality of life score). Side effects were common, but serious complications did not occur. LAUP surgery is effective in some subjects with mild OSA for the treatment of snoring, but the reduction in AHI and the level of symptomatic improvement were minor overall.", "To compare the lateral pharyngoplasty procedure with uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS).\n Prospective randomized study.\n Academic tertiary center.\n Twenty-seven adults with OSAHS originally selected for treatment with UPPP.\n Patients were randomly assigned to 2 groups: in one group, we performed the lateral pharyngoplasty (15 cases), and in the other, we did the UPPP (12 cases).\n We compared treatment outcomes through the evaluation of OSAHS-related symptoms and the analysis of polysomnographic tests and computed tomography measurements of pharyngeal airway. The lateral pharyngoplasty group achieved a statistically greater reduction in body weight, excessive daytime sleepiness, and apnea-hypopnea index. In addition, only in this group did we observe a statistically significant increase in the amount of deep sleep stages and improvement in morning headaches. Patients from the UPPP group did not present significant changes in the polysomnographic parameters. Pharyngeal airway measurement outcomes were similar in both groups and did not reflect the clinical and polysomnographic differences we observed.\n Lateral pharyngoplasty produces better clinical and polysomnographic outcomes in the treatment of OSAHS than does UPPP, without resultant differences in the cross-sectional measurements of the pharyngeal airway between these treatments.", "We compared radiofrequency techniques used in the treatment of snoring and obstructive sleep apnea [radiofrequency assisted uvulopalatoplasty (RAUP) and channeling] as regard the efficacy and morbidity. A pilot, prospective randomized single blinded study was conducted on 40 patients in the ENT Department, Kasr Al-Aini Hospital, Cairo University during the period from April to December 2003. Patients were randomized into two groups each consisting of 20 patients. The first group was treated by submucosal channeling of the palate, while the second group was treated by radiofrequency assisted uvulopalatoplasty (RAUP). Patients were followed for 4 months, filling a questionnaire in a standard visual analogue score pattern. Assessment was done prior to the surgery and was repeated 3, 10 days and 3 weeks postoperatively. Visual analogue scores were done for the following parameters: pain, speech deficits, dysphagia, and snoring (by the bed partner). Polysomnography was done pre to intervention and was repeated 4 months postoperatively. This work confirms the favorable effects of radiofrequency in the treatment of patients with snoring and mild to moderate obstructive sleep apnea (OSA) particularly on snoring, confirming the results of the previous studies and highlighting the more rapid relief of snoring and apnea in RAUP group compared to channeling group but with more postoperative pain and morbidity.", "The high prevalence of habitual snoring (35% of the general population) and the increasing demand for an effective treatment have led, in the last decade, to the generalisation of laser-assisted uvulopalatoplasty (LAUP). However, acceptable studies on its effectiveness are lacking. The present randomised, placebo-controlled study included 25 nonapnoeic and mild obstructive sleep apnoea snorers to evaluate LAUP effectiveness for snoring. Group I received a one-stage LAUP treatment and group II a placebo (simulated snore surgery followed by an oral placebo). Before each treatment and 3 months after, the variables and procedures assessed were: body weight; sleepiness (Epworth sleepiness scale); quality of life (SF-36); subjective snoring intensity (0-10 analogue scale); objective snoring intensity (average decibel intensity); snoring index (number of snores per hour); and apnoea/hypopnea index. No differences were observed in body weight, sleepiness, quality of life, subjective and objective intensity, and frequency of snoring, and apnoea/hypopnea index between the groups before and 3 months after treatment. In conclusion, this study provides evidence of the lack of effectiveness of one-stage laser-assisted uvulopalatoplasty for snoring in nonapnoeic and mild obstructive sleep apnoea patients, with the result that it does not meet the expectations generated by the procedure.", "Randomized, double-blinded, placebo-controlled, clinical trial to determine the effectiveness of palatal implants for treatment of mild/moderate obstructive sleep apnea/hypopnea syndrome (OSAHS).\n Sixty-two non-obese adults with history of snoring, daytime sleepiness, and mild/moderate OSAHS, were randomized to receive palatal implants (n = 31) or placebo procedure (n = 31). Complete follow-up including quality of life (QOL, SF-36), snoring visual analog scale (VAS), and Epworth Sleepiness Scale (ESS) data were obtained in 62 patients. Seven patients refused follow-up polysomnography for a total of 55 patients (29 implant and 26 placebo).\n The treatment group (change in score of -7.9 +/- 7.7) was significantly improved compared with the placebo group (change in score of 0.9 +/- 4.3) for apnea/hypopnea index (AHI) (P < 0.0001), QOL, SF-36 (P < 0.0001), snoring VAS (P < 0.0001), and ESS (P = 0.0002).\n Palatal implants improve AHI, QOL, snoring intensity, and daytime sleepiness for selected patients with mild/moderate OSAHS.", "The study goal was to determine the effectiveness of (1) multilevel temperature-controlled radiofrequency tissue ablation (TCRFTA) or (2) continuous positive airway pressure (CPAP) for the treatment of mild to moderate obstructive sleep apnea syndrome (OSAS).\n We conducted a randomized, placebo-controlled, 2-site trial, comparing TCRFTA (n = 30) and CPAP (n = 30) with sham-placebo (n = 30) using intention-to-treat analysis.\n Compared with pretreatment baseline, TCRFTA improved reaction time, OSAS-specific quality of life (QOL), and subjective sleepiness (all P < 0.05). Compared with sham-placebo, TCRFTA improved QOL, airway volume, apnea index, and respiratory arousal index (all P < 0.05). TCRFTA side effects and complications were mild, temporary, and similar to sham-placebo. CPAP improved QOL and sleepiness compared with baseline and QOL when compared with sham-placebo (all P < 0.05). Significant differences were not seen between TCRFTA and CPAP outcomes.\n TCRFTA and CPAP each improve QOL for mild-moderate OSAS patients. TCRFTA improvements may result from changes in airway volume, apnea index, and respiratory arousal index.", "In a prospective study, 95 patients with mild to moderate obstructive sleep apnoea (OSA) were randomised to receive either surgical treatment, uvulopalatopharyngoplasty, (4-6 patients) or treatment with a nocturnal dental appliance for mandibular advancement (49 patients). Of the 49 dental appliance patients, 37 completed the 12-month follow-up. The aim of this study was to evaluate the effects and adverse events of dental appliance treatment from a one-year perspective. Somnography was employed to measure treatment effects before and 12 months post-treatment. At the 12-month control, somnography was performed twice: the first time with the dental appliance and the second time without it. Adverse events were recorded 2 weeks and 3, 6, and 12 months after treatment was initiated. The patients used the dental appliance on average 6 nights/week. After 12 months of treatment, the apnoea, apnoea/hypopnoea, oxygen desaturation, and snoring indices decreased significantly. Ninety-five per cent of the patients reduced their apnoea index by > or = 50% and 78% of the patients were normalised following treatment. At the somnographic registration without the dental appliance, the values were found comparable to what they were before treatment. Mandibular mobility and occlusion were constant throughout the study. The adverse events resulting from using the dental appliance were relatively minor and infrequent, and no serious complications were observed except for two patients who reported pain from the temporomandibular joint. In conclusion, the dental appliance has been shown to be a valuable treatment method for mild to moderate OSA with few adverse events in the stomatognathic system or other complications.", "This study compares the efficacy of 2 tongue-base surgical procedures in the treatment of patients with moderate to severe sleep-disordered breathing.\n We conducted a prospective, randomized crossover surgical trial at a university hospital.\n Seventeen patients with moderate to severe sleep-disordered breathing and Fujita type II upper airway collapse for whom conservative treatment failed were enrolled into an institutional review board-approved surgical protocol. They were randomly assigned to undergo palatopharyngoplasty combined with either tongue advancement (mandibular osteotomy) or tongue suspension. Parameters assessed included severity of sleep-disordered breathing (polysomnography), sleepiness (Epworth Sleepiness Scale), and anatomic changes (upper airway endoscopy), as well as demographic factors. Patients not achieving satisfactory improvement in their condition were offered nonsurgical management or additional surgical treatment that varied based on the postoperative assessment but included crossing over to the other tongue surgical procedure.\n Nine of the 17 patients were randomized to the tongue suspension group, and 8 to the tongue advancement group. In the 9 tongue suspension patients, Epworth Sleepiness Scale scores fell from 12.1 to 4.1 (P = 0.007). Airway collapse for all 9 patients measured on Müller maneuver improved, by a mean of 64% (P = 0.0006) at the palate and 83% (P = 0.0003) at the base of the tongue. In the 8 tongue advancement patients, Epworth Sleepiness Scale scores fell from a mean of 13.3 to 5.4 (P = 0.004). Airway collapse for 5 of 8 patients measured on Müller maneuver improved by a mean of 31% (P = 0.1) at the palate and 75% (P = 0.03) at the base of the tongue.\n Prospective, randomized trials of tongue-base surgery for sleep-disordered breathing are possible. Preliminary findings from the current protocol reveal a slight advantage of tongue suspension over tongue advancement." ]

[ "8869390", "8780092" ]

[ "Double-blind study of the activity and tolerability of cabergoline versus placebo in parkinsonians with motor fluctuations.", "Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease." ]

[ "The use of a dopamine agonist with a long duration of action has theoretical advantages in attempting to reduce the motor fluctuations in Parkinson's disease. We report the results of a double-blind controlled study of adding cabergoline, an ergot derivative with potent long-lasting high affinity for the D2 receptor, to levodopa therapy in 37 patients with severe fluctuations in response to treatment. Increasing dosages of cabergoline (19 patients) or placebo (18 patients) were added to each patient's stable levodopa regime. The two patient groups were similar at baseline in terms of age, disease duration, duration of levodopa treatment, and average hours \"off\" per day. Following incremental dose titration, patients in the cabergoline group had a significant reduction in hours \"off\" per day from 5.0 (SD 2.1) to 3.0 (SD 2.5), but there was no change in this measure in the placebo group [4.0 (2.2) and 3.3 (2.3) respectively]. This was not at the expense of a significant increase in dyskinesia. However, there was no difference between the groups when comparing their average Hoehn and Yahr stage of disease, and Schwab and England activities of daily living index.", "Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the \"on\" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD." ]

[ "11051391", "15288014", "18452482", "12825134" ]

[ "Bezafibrate in the treatment of primary biliary cirrhosis: comparison with ursodeoxycholic acid.", "Prospective randomized crossover trial of combination therapy with bezafibrate and UDCA for primary biliary cirrhosis.", "The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: A prospective, multicenter study.", "Bezafibrate treatment: a new medical approach for PBC patients?" ]

[ "nan", "The aim of this study was to evaluate the effects of the combination therapy with bezafibrate and ursodeoxycholic acid (UDCA) for primary biliary cirrhosis (PBC), compared to UDCA monotherapy. Sixteen patients with compensated PBC were divided randomly into two groups. Group A received treatment with bezafibrate and UDCA for 6 months, while group B received UDCA alone, treatment protocols were then exchanged for another 6 months. The laboratory data was followed every month. The mean levels of alkaline phosphatase (ALP) decreased significantly more in group A than in group B in the first half of the study. Then serum ALP levels were elevated in group A after exchanged the therapy, but fell down in group B. Serum levels of gamma-glutamyl transferase (GGT), immunoglobulin M and triglycerides values were significantly lower in group B than in group A, after changing therapies from monotherapy to combination therapy with bezafibrate and UDCA. The mean levels of ALP, GGT and triglycerides were significantly lower at the end of the combination therapy than those at the end of the monotherapy. The combination therapy with bezafibrate and UDCA significantly improves the laboratory data that specific for PBC in comparison with UDCA monotherapy.", "Aim: Treatment with ursodeoxycholic acid (UDCA) improves the survival of stage I and II primary biliary cirrhosis (PBC) patients. However, new therapeutic options are needed for patients who are refractory to UDCA and for those whose disease is at an advanced stage. Bezafibrate could be useful in PBC treatment, since it increases phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids, which are increased with cholestasis. Methods: We conducted two prospective, multicenter randomized open studies in non-cirrhotic patients with PBC to evaluate the efficacy of bezafibrate. One study compared UDCA and bezafibrate monotherapy (study 1: 45 patients [37 females], mean age 55.9 years), and the other evaluated the addition of bezafibrate to patients who were refractory to UDCA (study 2: 21 patients [18 females], mean age 54.1 years). Results: Study 1 demonstrated that bezafibrate monotherapy was as effective as UDCA and study 2 revealed that bezafibrate combined with UDCA was effective in improving and maintaining biliary enzymes where the ineffectiveness of long-term treatment with UDCA was confirmed. Conclusion: This multicenter, randomized, open study revealed that combination therapy of bezafibrate and UDCA improved biliary enzymes in non-cirrhotic Japanese patients with PBC refractory to UDCA. Further studies are needed to evaluate whether combination therapy improves histological staging and prognosis.", "A new medical approach to primary biliary cirrhosis (PBC) has been desired. We investigated the feasibility of using combination ursodeoxycholic acid (UDCA)-bezafibrate therapy in patients with PBC nonresponsive to UDCA monotherapy.\n During a 6-month period, 22 PBC patients with elevated serum alkaline phosphatase (ALP) despite UDCA monotherapy received either UDCA at 600 mg/day (control group) or UDCA at 600 mg/day plus bezafibrate at 400 mg/day (bezafibrate group). Each patient underwent detailed clinical and biochemical evaluation.\n During treatment, changes in ALP level were greater in the bezafibrate group than in the control group (P< 0.01). During and at the end of treatment, serum ALP levels were significantly lower than those before treatment in patients receiving UDCA plus bezafibrate (P< 0.05). At the end of the 6 months, normalization of serum ALP was observed in 5 of 11 (45.4%) patients given bezafibrate and in 2 of 11 (18.1%) patients not given bezafibrate (P< 0.16). Bile acid proportions during the combination therapy did not change. Pruritus disappeared in 1 of 7 bezafibrate-group patients with this symptom.\n UDCA at 600 mg/day plus bezafibrate at 400 mg/day may be considered as a new therapeutic option for patients with PBC." ]

[ "9532986", "11311761", "16522412", "8532270", "12530483", "16816068", "12634667" ]

[ "A randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection.", "Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding.", "Valacyclovir therapy to reduce recurrent genital herpes in pregnant women.", "Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes.", "Acyclovir suppression to prevent recurrent genital herpes at delivery.", "Valacyclovir prophylaxis to prevent recurrent herpes at delivery: a randomized clinical trial.", "A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery." ]

[ "To evaluate the efficacy and safety of a suppressive course of acyclovir in late pregnancy in women with recurrent genital herpes infection on the incidence of viral shedding, herpes lesion development and caesarean section for recurrent genital herpes.\n Double-blind, randomised placebo controlled clinical trial.\n A department of genitourinary medicine in Sheffield and an antenatal clinic in London.\n Pregnant women with recurrent genital herpes infection at < 36 weeks of gestation.\n Participating women were given acyclovir 200 mg four times a day (or matching placebo) from 36 weeks of gestation until the time of delivery. Women were seen weekly and viral cultures were obtained from the cervix and vulva. Decisions regarding mode of delivery were left to the discretion of the attending obstetrician.\n Delivery by caesarean section for recurrent genital herpes infection. Number of episodes of recurrent genital herpes infection and number of episodes of asymptomatic viral shedding during the treatment period. In addition blood was taken at two weekly intervals to determine acyclovir levels.\n The total number of women recruited was 63 (31 received acyclovir and 32 received placebo). The number of women undergoing delivery by caesarean section for recurrent herpes at the time of delivery was 12 (19%). The odds ratio for delivery by caesarean section in women taking acyclovir, compared with those taking placebo, was 0.44 (95% CI 0.09-1.59). The odds ratio for clinical recurrences during treatment was 0.10 (95% confidence interval 0.00-0.86) and the odds ratio for clinical recurrence or asymptomatic shedding during treatment was 0.32 (95% CI 0.05-1.56).\n This trial was unable to demonstrate that acyclovir can significantly decrease the number of caesarean section deliveries; however, the number of clinical recurrences was significantly reduced. Two episodes of asymptomatic virus shedding both occurred in women taking acyclovir. At the present time there is little evidence to suggest that acyclovir should be used outside randomised controlled trials for the suppression of recurrent genital herpes infection during pregnancy.", "Neonatal herpes affects about 1 in 15,000 newborns and the prognosis for disseminated disease with encephalitis is poor. We investigated whether acyclovir prophylaxis in late pregnancy effectively reduces the risk of viral shedding and, hence, of mother-to-child transmission at delivery. A prospective study was conducted. Pregnant women who had at least one episode of genital herpes during pregnancy were randomly assigned to two groups: group 1 (n=167) received oral acyclovir from 36 weeks of gestation to term; group 2 (n=121) received no treatment. Group 3 (n=201) comprised women not given prophylaxis who had a history of genital herpes, but no active episodes during pregnancy. No specific instruction were set up for obstetrical management except for cesarean section in case of a suspected herpes lesion at the time of labor. The rate of Cesarean section was 8.4% in group 1, 16.5% in group 2, and 9.9% in group 3 (p<0.001). 75% of cesareans in group 2 and 10% in group 3 were done for genital herpes. Percentage of viral shedding was, respectively, 0% (group1), 5% (group2), and 0.5%(group3) (p<0.05). These findings underline the value of antiviral prophylaxis in late pregnancy for women with a known history of genital herpes. Such prophylaxis only partly prevents neonatal herpes infection, because it is not applicable to patients with no known clinical history but may excrete the virus.", "The purpose of this study was to estimate the efficacy of valacyclovir suppressive therapy in pregnant women with recurrent genital herpes.\n At 36 weeks' gestation, herpes simplex virus (HSV)-2 seropositive women were randomized to receive oral valacyclovir 500 mg or placebo twice daily until delivery. Genital tract and neonatal specimens were collected weekly for HSV culture and qualitative polymerase chain reaction (PCR) assay to detect viral DNA from the time of randomization to delivery. Both maternal and neonatal toxicity measures were obtained.\n The 112 enrolled women (57 valacyclovir, 55 placebo) had similar HSV recurrence risks, including mean number of active HSV recurrences before randomization during the index pregnancy (1.1 +/- 1.9 vs 1.5 +/- 2.1, P = .308) and days between randomization and delivery (20.3 +/- 10.2 vs 22.0 +/- 8.9, P = .344). The number of women with clinical HSV recurrences between the time of randomization and delivery was significantly lower in the valacyclovir versus placebo group (10.5% vs 27.3%; P = .023, RR 0.4, 95% CI 0.2-0.9). Shedding of HSV within 7 days of delivery was similar in the valacyclovir and placebo group (10.4% vs 12.0%, P = .804; RR 0.9, 95% CI 0.3-2.7), as was the number of women with clinical HSV lesions at delivery (5.3% vs 14.6%, P = .121; RR 0.4, 95% CI 0.1-1.3). No neonates had symptomatic congenital HSV infection before discharge or up to 2 weeks' postpartum, and no clinical or laboratory safety concerns were identified.\n Administration of valacyclovir beginning at 36 weeks' gestation to women with a history of recurrent genital HSV reduced the number of women with subsequent clinical HSV recurrences.", "To determine if suppressive acyclovir therapy given to term gravidas experiencing a first episode of genital herpes simplex virus (HSV)-infection during pregnancy decreases the need for cesarean delivery for that indication.\n Forty-six pregnant women with first episodes of genital herpes during pregnancy were randomly assigned to receive oral acyclovir 400 mg or placebo, three times per day, from 36 weeks' gestation until delivery as part of a prospective, double-blind trial. Herpes simplex virus cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise, a cesarean was performed. Neonatal HSV cultures were obtained and infants were followed-up clinically.\n None of the 21 patients treated with acyclovir and nine of 25 (36%) treated with placebo had clinical evidence of recurrent genital herpes at delivery (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.002-0.745; P = .002). No woman treated with acyclovir had a cesarean for herpes, compared with nine of 25 (36%) of those treated with placebo (OR 0.04, CI 0.002-0.745; P = .002). No patient in either treatment group experienced asymptomatic genital viral shedding at delivery. No neonate had evidence of herpes infection or adverse effects from acyclovir.\n Suppressive acyclovir therapy reduced the need for cesarean for recurrent herpes in women whose first clinical episode of genital HSV occurred during pregnancy. Suppressive acyclovir treatment did not increase asymptomatic viral shedding and was not harmful to the term fetus.", "To determine if suppressive acyclovir near term decreased the frequency of clinical recurrences at delivery in women with recurrent genital herpes simplex virus (HSV) infection.\n We conducted a prospective, double-blind, randomized trial in 234 women with recurrent genital herpes. Women with genital infection of any frequency were enrolled. Patients received either suppressive oral acyclovir 400 mg three times daily or an identical placebo after 36 weeks' gestation. Clinical lesions were identified, and HSV cultures were obtained at delivery. The frequencies of clinical and subclinical HSV recurrences at delivery were evaluated.\n Six percent of patients treated with acyclovir, and 14% of patients treated with placebo had clinical HSV at delivery (p = 0.046). No patients in the acyclovir group had positive HSV cultures, compared with 6% of placebo-treated patients (p = 0.029). There was no significant difference in subclinical HSV shedding in the acyclovir group (0%) compared with the placebo-treated group (3%) (p = 0.102).\n Suppressive acyclovir therapy significantly decreased the incidence of clinical genital herpes and the overall incidence of HSV excretion at delivery in patients with previous herpes infection.", "To measure the efficacy of valacyclovir suppression in late pregnancy to reduce the incidence of recurrent genital herpes in labor and subsequent cesarean delivery.\n A total of 350 pregnant women with a history of genital herpes were assigned randomly to oral valacyclovir 500 mg twice a day or an identical placebo from 36 weeks of gestation until delivery. In labor, vulvovaginal herpes simplex virus (HSV) culture and polymerase chain reaction (PCR) specimens were collected. Vaginal delivery was permitted if no clinical recurrence or prodromal symptoms were present. Neonatal HSV cultures and laboratory tests were obtained, and infants were followed up for 1 month after delivery. Data were analyzed using chi2 and Student t tests.\n One hundred seventy women treated with valacyclovir and 168 women treated with placebo were evaluated. Eighty-two percent of the women had recurrent genital herpes; 12% had first episode, nonprimary genital herpes; and 6% had first episode, primary genital herpes. At delivery, 28 women (8%) had recurrent genital herpes requiring cesarean delivery: 4% in the valacyclovir group and 13% in the placebo group (P = .009). Herpes simplex virus was detected by culture in 2% of the valacyclovir group and 9% [corrected] of the placebo group (P =.02). No infants were diagnosed with neonatal HSV, and there were no significant differences in neonatal complications. There were no significant differences in maternal or obstetric complications in either group.\n Valacyclovir suppression after 36 weeks of gestation significantly reduces HSV shedding and recurrent genital herpes requiring cesarean delivery.\n I.", "The purpose of this study was to assess the efficacy of acyclovir in the reduction of herpes simplex virus culture and polymerase chain reaction positivity and cesarean delivery.\n Women with recurrent genital herpes simplex virus were randomized to acyclovir 400 mg three times daily or placebo from 36 weeks of gestation until delivery. A subset of daily specimens for herpes simplex virus culture and DNA polymerase chain reaction was self-collected. Analyses used chi(2), Fisher exact, and Mann-Whitney U tests.\n Lesions occurred at delivery among 11 of 78 women (14%) who received placebo and 4 of 84 women (5%) who received acyclovir (P =.08). Herpes simplex virus culture and polymerase chain reaction positivity near delivery occurred in 7% and 34% women in the placebo group and 0 and 2% in the acyclovir group (P =.03 and <.01, respectively). Cesarean delivery for herpes simplex virus occurred in 8 of the women (10%) in the placebo group and in 3 of the women (4%) in the acyclovir group (P =.17). Despite reductions in herpes simplex virus detection, 6% of the women who received acyclovir had herpes simplex virus detected by polymerase chain reaction on >20% of days. Neonatal outcomes were similar between groups.\n Acyclovir significantly reduced, but did not eliminate, herpes simplex virus lesions and detection in late pregnancy." ]

[ "9163285", "8418700", "9163286", "9107241", "3307653", "9352865", "2404448", "3552920", "12195325", "2405792", "7740420", "9362350", "6334234", "1823061", "3491317", "8608893", "11673103", "2001806" ]

[ "Transjugular intrahepatic portosystemic shunts compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized, controlled trial.", "Shunt surgery versus endoscopic sclerotherapy for variceal hemorrhage: late results of a randomized trial.", "Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial.", "Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding.", "Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Early results of a randomized trial.", "Transjugular intrahepatic portosystemic stent shunt versus sclerotherapy plus propranolol for variceal rebleeding.", "Endoscopic variceal sclerosis compared with distal splenorenal shunt to prevent recurrent variceal bleeding in cirrhosis. A prospective, randomized trial.", "Sclerotherapy vs. distal splenorenal shunt in the elective treatment of variceal hemorrhage: a randomized controlled trial.", "Endoscopic variceal ligation plus propranolol vs. transjugular intrahepatic portosystemic stent shunt: a long-term randomized trial.", "Distal splenorenal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding. First stage of a randomized, controlled trial.", "Mesocaval shunt or repeated sclerotherapy: effects on rebleeding and encephalopathy--a randomized trial.", "A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices.", "Endoscopic sclerotherapy versus portacaval shunt in patients with severe cirrhosis and variceal hemorrhage.", "The modified distal splenorenal shunt in the elective treatment of variceal hemorrhage.", "Endoscopic sclerotherapy versus portacaval shunt in patient with severe cirrhosis and acute variceal hemorrhage. Long-term follow-up.", "Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage.", "A randomized clinical trial comparing transjugular intrahepatic portosystemic shunt with endoscopic sclerotherapy in the long-term management of patients with cirrhosis after recent variceal hemorrhage.", "Portacaval shunt versus endoscopic sclerotherapy in the elective treatment of variceal hemorrhage." ]

[ "Transjugular intrahepatic portosystemic shunts (TIPS) have widened the use of portal decompression as therapy for variceal hemorrhage. However, no controlled studies have examined the efficacy of TIPS compared with that of other treatments.\n To compare the efficacy and safety of TIPS with those of endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage.\n Randomized, controlled trial.\n Tertiary-care academic medical center.\n 100 patients with cirrhosis were evaluated a mean of approximately 10 days after an episode of acute variceal bleeding; 20 patients were excluded because of portal venous thrombosis (n = 6), hepatoma (n = 3), florid alcoholic hepatitis (n = 6), and refusal to give consent (n = 5).\n TIPS (n = 41) or sclerotherapy (n = 39). The latter was performed by freehand injections of 5% Na morrhuate at 2- to 3-week intervals. Recurrent variceal hemorrhage was managed by sclerotherapy followed by angiographic assessment of TIPS and dilatation of the stents (TIPS group) or crossover to TIPS (sclerotherapy group).\n Rebleeding and survival were the primary end points. Complications and rates of rehospitalization were secondary end points.\n During a mean follow-up of approximately 1000 days, recurrent gastrointestinal bleeding resulted from variceal hemorrhage (9 patients in the TIPS group and 8 in the sclerotherapy group), portal gastropathy (1 patient in each group), and gastric lipoma (0 and 1 patients, respectively). A higher mortality rate was seen with TIPS (P = 0.03). Death resulted from variceal bleeding (5 patients in the TIPS group and 3 in the sclerotherapy group), sepsis (3 and 2 patients, respectively), liver failure (2 patients in each group), hepatoma (1 and 0 patients, respectively), and hemoperitoneum (1 and 0 patients, respectively). Encephalopathy was the most common complication in the TIPS group (n = 12), and pain developing after sclerotherapy was the most common in the sclerotherapy group (n = 10). The two groups had similar rates of rehospitalization.\n Endoscopic sclerotherapy and TIPS are equivalent with respect to rebleeding developing over the long term. However, sclerotherapy may be superior to TIPS with respect to survival.", "Between September 1982 and April 1988, 60 cirrhotic patients with prior variceal hemorrhage were randomized to undergo the placement of an elective shunt (distal splenorenal: 26; nonselective: 4) or long-term endoscopic sclerotherapy (n = 30). Eighty-six percent of patients had alcoholic cirrhosis, and 33% were classified as Child's class C. After a mean follow-up of 87 months, 60% of patients undergoing sclerotherapy and 17% of shunt patients experienced rebleeding (p < 0.001). Shunt patients have survived longer than those who had sclerotherapy (6-year survival rates of 53% and 26%, respectively; p < 0.05). In part because of the wide geographic distribution of patients, only 4 of 13 patients in whom sclerotherapy failed (31%) could undergo salvage by shunt surgery. Although hepatic portal perfusion was better maintained after sclerotherapy, there were no major differences between the groups in terms of post-therapy hepatic or psychoneurologic function. In a predominantly alcoholic cirrhotic patient population (half non-urban), the results of elective shunt surgery were superior to those of chronic endoscopic sclerotherapy with respect to the prevention of recurrent variceal hemorrhage and survival.", "Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency.\n To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices.\n Randomized, controlled clinical trial.\n Three teaching hospitals.\n 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS.\n Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein.\n Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs.\n Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]).\n In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant.", "The transjugular-intrahepatic-portosystemic shunt is a new interventional treatment for portal hypertension. The aim of our study was to compare the transjugular shunt with endoscopic treatment for the prophylaxis of recurrent variceal bleeding.\n Between March, 1993, and March, 1996, 126 patients with variceal bleeding were randomly assigned either transjugular shunt (n = 61) or endoscopic treatment (n = 65). Patients were followed up for a median of 14 (IQR 8-25) months and 13 (8-25) months, respectively. In 31 (51%) of the shunted patients, simultaneous transjugular-variceal embolisation was done at the time of shunt placement. Endoscopic treatment consisted of sclerotherapy and/or banding ligation and was combined with propranolol medication.\n Technical success was achieved in all patients assigned to the shunt group. During follow-up, the cumulative 1-year variceal rebleeding rates in the shunted and endoscopically treated patients were 15% and 41% and the 2-year rates were 21% and 52% (p = 0.001), respectively. In nine (12%) patients from the endoscopic group treatment failed and the patients received the transjugular-shunt treatment. A total of 19 bleeding episodes from any source occurred in 15 patients in the shunt group compared with 100 episodes in 33 patients in the endoscopic group. There was no difference in survival with estimated 1-year survival rates for shunted and endoscopically treated patients of 90% and 89%, and 2-year survival rates of 79% and 82%, respectively. The incidence of clinically significant hepatic encephalopathy after 1 year was higher in the shunt group (36% vs 18%, p = 0.011).\n These results suggest, that the transjugular shunt is more effective than endoscopic treatment in prevention of variceal rebleeding but has a considerable risk of hepatic encephalopathy. Survival is similar in the two groups.", "In September 1982, a prospective randomized trial comparing shunt surgery and endoscopic sclerotherapy for the elective management of variceal hemorrhage in patients with cirrhosis was initiated. Twenty-seven patients have received shunts (distal splenorenal = 23, nonselective = 4) and 30 patients have had chronic sclerotherapy. Eighty-six per cent of patients had alcoholic cirrhosis and 33% were Child's class C. After a mean follow-up of 25 months, 19% of shunt and 57% of sclerotherapy patients have had rebleeding (p = 0.003). Kaplan-Meier survival analysis reveals similar 2-year survival rates for shunt (65%) and sclerotherapy (61%) groups. Only two of 10 sclerotherapy failures have been salvaged by surgery. Posttherapy quantitative hepatic function, frequency of encephalopathy, and cumulative medical costs were similar for both groups. Hepatic portal perfusion and portal pressure at 1 year were better maintained by sclerotherapy than by distal splenorenal shunt. In conclusion, endoscopic sclerotherapy and shunt surgery provide similar results with respect to survival, hepatic function, frequency of encephalopathy, and costs. Sclerotherapy is an acceptable, but not superior, alternative to shunt surgery for treatment of variceal hemorrhage.", "In patients with cirrhosis of the liver, after the first variceal bleeding episode, transjugular intrahepatic portosystemic stent shunting (TIPS) and endoscopic sclerotherapy plus propranolol (ES) were compared regarding prevention of variceal rebleeding and mortality.\n Eighty-three patients with cirrhosis of the liver were randomized to undergo TIPS (n = 42) or ES (n = 41).\n Median observation time was in 1.6 years in the TIPS group and 1.45 years in the ES group. Cumulative rates of rebleeding were 23% in the TIPS group and 57% in the ES group (P = 0.0001). Hepatic encephalopathy was observed in 29% of the patients in the TIPS group and in 13% of those in the ES group (P = 0.041). Cumulative rates of survival were 69% in the TIPS group and 67% in the ES group (P = 0.62). Mortality rates in both groups were positively correlated with a higher Child's classification.\n Although TIPS significantly reduced the rate of rebleeding, survival rates were not improved. Because TIPS is associated with an increased risk of encephalopathy and high rates of shunt dysfunction, which requires reintervention, the procedure cannot be recommended for elective treatment after the first variceal bleeding episode, but it is an effective therapy in patients in whom endoscopic sclerotherapy fails to control bleeding.", "To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis.\n A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months.\n A private, tertiary-referral university hospital.\n Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval.\n Endoscopic variceal sclerosis or distal splenorenal shunt. MEASUREMENTS and\n Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively).\n Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.", "One hundred and twelve consecutive Child Class A and B cirrhotic patients were included in a prospective controlled trial aimed at investigating the efficacy and safety of endoscopic sclerotherapy vs. distal splenorenal shunt in the elective treatment of hemorrhage from esophagogastric varices. Fifty-seven patients were randomly allocated to splenorenal shunt and 55 to endoscopic sclerotherapy. Since only 4 of the 55 patients assigned to endoscopic sclerotherapy had to be excluded after randomization and before treatment as compared to 14 of the 57 patients assigned to splenorenal shunt, it is suggested that the applicability of endoscopic sclerotherapy is greater than that of splenorenal shunt. One patient in each group died within 30 days of the procedure and two in the endoscopic sclerotherapy group were lost to follow-up just after discharge. Variceal rebleeding during follow-up occurred in 37.5% (18/48) of patients in the endoscopic sclerotherapy group and in 14.3% of those in the splenorenal shunt group (6/42) (p less than 0.02), whereas hepatic encephalopathy was more frequent in patients submitted to splenorenal shunt (10/42, 24%) than in those treated by endoscopic sclerotherapy (4/48, 8%) (p less than 0.05). The therapeutic modality was the only variable with independent predictive value for rebleeding during follow-up, whereas for hepatic encephalopathy, the therapeutic modality, and the presence of encephalopathy related to the bleeding episode each showed independent predictive value. Early and long-term mortality, did not differ between the two therapeutic groups, being the 2-year survival was 71% for splenorenal shunt and 68% for endoscopic sclerotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)", "After a first variceal bleeding episode in patients with cirrhosis of the liver, treatment with transjugular intrahepatic portosystemic stent shunt (TIPS) and endoscopic variceal ligation (EVL) plus propranolol were compared, with regard to prevention of variceal rebleeding, complications, and mortality.\n 85 patients were randomly allocated to receive TIPS (n = 43) or EVL (n = 42). The groups were comparable regarding age, sex, etiology of liver cirrhosis, and liver function.\n The mean observation times were 4.1 years in the TIPS group and 3.6 years in the EVL group. Although the probability of rebleeding was higher in the EVL group (29.9%) than in the TIPS group (19.4%), the difference was not statistically significant. Three of five patients of the EVL group successfully underwent TIPS placement after treatment failure. The probability of TIPS dysfunction requiring shunt revision was 89 %. Hepatic encephalopathy was observed more often in the TIPS group (40.5%) than in the EVL group (20.5%; P < 0.05). The probability of survival was similar in both groups (TIPS group 75.9%, EVL group 82.2%; n.s.).\n In view of its good efficacy and the lower cost of treatment, endoscopic ligation plus propranolol may be recommended as initial procedure for prevention of recurrent variceal hemorrhage, whereas TIPS seems to be the preferable procedure in patients with recurrent bleeding after adequate endoscopic and pharmacological treatment.", "In 1984 we started a prospective controlled trial comparing endoscopic sclerotherapy (ES) with the distal splenorenal shunt (DSRS) in the elective treatment of variceal hemorrhage in cirrhotic patients. The study population included 40 patients with cirrhosis and portal hypertension referred to our department from October 1984 to March 1988. These patients were drawn from a pool of 173 patients who underwent either elective surgery or endoscopic sclerotherapy during this time. Patients were assigned to one of the two groups according to a random-number table: 20 to DSRS and 20 to ES. During the postoperative period, no DSRS patient died, while one ES patient died of uncontrolled hemorrhage. One DSRS patient had mild recurrent variceal hemorrhage despite an angiographically patent DSRS. Four ES patients suffered at least one episode of gastrointestinal bleeding: two from varices and two from esophageal ulcerations. Five ES patients developed transitory dysphagia. Long-term follow-up was complete in all patients. Two-year survival rates for shunt (95%) and ES (90%) groups were similar. One DSRS patient rebled from duodenal ulcer, while three ES patients had recurrent bleeding from esophagogastric sources (two from varices and one from hypertensive gastropathy). One DSRS and two ES patients have evolved a mild chronic encephalopathy; four DSRS and two ES patients suffered at least one episode of acute encephalopathy. Two ES patients had esophageal stenoses, which were successfully dilated. Preliminary data from this trial seem to indicate that DSRS, in a subgroup of patients with good liver function and a correct portal-azygos disconnection, more effectively prevents variceal rebleeding than ES. However no significant difference in the survival of the two treatment groups was noted.", "Sclerotherapy is usually effective in controlling acutely bleeding esophageal varices. It may not be as effective as shunt surgery for prevention of rebleeding; therefore we undertook a prospective study comparing interposition mesocaval shunt (MCS) and repeated sclerotherapy.\n Forty-five patients (mean age, 52.6 +/- 9.8 years) with variceal bleeding were randomized after emergency endoscopic sclerotherapy either to repeat variceal obliteration followed by regular check endoscopy (n = 21) or to elective interposition mesocaval shunting by use of 14 mm polytetrafluoroethylene graft (n = 24). There was an equal distribution of Child's classes in the two groups.\n In the sclerotherapy group 12 patients had recurrent hemorrhages causing five deaths compared with the shunt group, in which four patients had postoperative bleeding but without associated death. No difference was noted in the incidence of encephalopathy despite the development of total shunting 1 year after MCS. The median hospital stay was similar; 34.5 days (MCS) and 33 days (sclerotherapy). The number of intensive care unit days was also similar in the two groups. No difference was noted in survival in patients with Child's A and Child's B disease in the treatment groups. In patients with Child's C cirrhosis there was a statistically significant longer survival in patients undergoing MCS compared with patients undergoing sclerotherapy.\n The results of the study show that the rate of rebleeding is significantly higher after sclerotherapy than after mesocaval shunting. In patients with Child's C cirrhosis MCS may be an alternative to sclerotherapy for the prevention of rebleeding from esophageal varices in patients not suitable for transplantation.", "The aim of this study was to compare transjugular intrahepatic portosystemic stent-shunt (TIPSS) with variceal band ligation (VBL) in the secondary prophylaxis of esophageal variceal hemorrhage in patients with cirrhosis. Fifty-eight patients with cirrhosis who presented with the first episode of esophageal variceal hemorrhage were randomized to TIPSS (31) or VBL (27), 24 hours after control of bleeding. Shunt function was assessed after 1 month and then at 6 monthly intervals thereafter. VBL was performed weekly until variceal eradication, and then at 3 months, 6 months, and yearly thereafter. Mean follow-up in the TIPSS group was 15.7 (+/-10.2) months; in the VBL group, it was 16.8 (+/-10.9) months. Results for rebleeding and mortality were analyzed on an intention-to-treat basis and using the Kaplan-Meier method. The frequency and the severity of variceal rebleeding was significantly lower in the TIPSS group (9.8%), compared with the VBL group (51.9%) (P < .0006). Although mortality rates were not significantly different, 8 of the patients who rebled in the VBL group required TIPSS therapy for uncontrolled bleeding. No significant differences were found in the frequency of other complications such as encephalopathy and sepsis. Patients in the VBL group required significantly greater time in the intensive care unit during the period of this study (<0.03). The total direct cost of treatment incurred was pound sterling 1,373 ($2,200) per patient, the cost being less in the patients treated with TIPSS compared with VBL. The results of this study show that TIPSS is superior to VBL for the secondary prophylaxis of variceal hemorrhage in patients with cirrhosis.", "Fifty-two patients with severe cirrhosis (Child Class C) and variceal hemorrhage requiring six or more units of blood were randomly assigned to either sclerotherapy or portacaval shunt. Of 38 pretreatment characteristics, only the frequency of active alcoholism differed significantly between the groups. During the initial hospitalization, the patients in the shunt group required significantly more blood (21.5 +/- 3.1 units) than did those in the sclerotherapy group (12.3 +/- 1.3 units), although the latter had significantly more rebleeding during hospitalization after the procedure (14 of 28 vs. 5 of 24 patients). There was no difference in short-term survival, with 13 patients in the sclerotherapy group discharged alive, as compared with 10 patients in the shunt group. Patients were followed for a mean of 263 days after the initial discharge (range, 8 to 1117). The sclerotherapy group required significantly more days of hospitalization for rebleeding, but we failed to demonstrate any significant difference in long-term survival between the sclerotherapy and shunt groups. Total health-care costs per patient were significantly higher for the shunt group (+23,957 +/- +3,111) than for the sclerotherapy group (+15,364 +/- +2,220). We conclude that sclerotherapy is less costly than portacaval shunt and as effective for the treatment of esophageal varices associated with severe cirrhosis.", "We report on our experience with a modified version of the distal splenorenal shunt (DSRS) initially described by Warren. Since 1976 more than 150 shunts have been done in the department. The first part of this study shows the long-term results of a series of 100 consecutive patients treated electively. The estimated survival at 80 months was around 30%. On the other hand, the median survival rate (68 months) and the five-year survival (52%) of Child's A patients differed significantly from those of Child's B patients (8 months and 15%, respectively). These results suggested that the modified DSRS was an effective and relatively safe procedure for the elective treatment of variceal bleeding and warranted a prospective and randomized trial to compare DSRS and endoscopic sclerotherapy (ES). In the second part of the study, in which ES was compared with DSRS, both modalities showed a similar survival rate, although patients in the DSRS group had a higher incidence of encephalopathy and patients in the ES group were more prone to rebleed. It was concluded that ES was a good alternative to DSRS for the elective treatment of esophageal variceal bleeding. If orthotopic liver transplant is considered the only definitive mode of treatment for the elective management of portal hypertension, the DSRS should be reserved for patients in whom ES has not been totally effective, or varices are located predominantly in the fundus of the stomach.", "In a continuation of a trial for which preliminary results were reported in the Journal two years ago, a total of 64 patients with Child Class C cirrhosis and variceal hemorrhage requiring six or more units of blood were randomly assigned to receive either a portacaval shunt (32 patients) or endoscopic sclerotherapy (32 patients). The duration of initial hospitalization and the total amount of blood transfused during hospitalization were significantly less in the patients receiving sclerotherapy (P less than 0.001). There was no difference in short-term survival (50 percent of the sclerotherapy group were discharged alive, as compared with 44 percent of the shunt-surgery group). Both groups were followed for a mean of 530 days after randomization. Rebleeding from varices, the duration of rehospitalization for hemorrhage, and transfusions received after discharge were all significantly greater in the sclerotherapy group (P less than 0.001). Forty percent of the sclerotherapy-treated patients discharged alive (7 of 16 patients) ultimately required surgical treatment for bleeding varices, despite a mean of 6.1 treatment sessions. Health care costs and long-term survival did not differ significantly between the groups (P greater than 0.05). We conclude that although endoscopic sclerotherapy is as good as surgical shunting for the acute management of variceal hemorrhage in poor-risk patients with massive bleeding, sclerotherapy-treated patients in whom varices are not obliterated and bleeding continues should be considered for elective shunt surgery.", "Uncontrolled studies suggest that placement of a transjugular intrahepatic portosystemic shunt (TIPS) could be useful in the treatment of variceal bleeding. The aim of this study was to evaluate the efficacy and safety of TIPS in the elective treatment of hemorrhage from esophageal varices in a randomized controlled study that compared the effects of TIPS with those of endoscopic sclerotherapy (ES).\n Sixty-three consecutive cirrhotic patients with hemorrhage from esophageal varices were included. Thirty-two patients were randomly allocated to ES and 31 to TIPS groups.\n One patient in each group died before the therapeutic procedure could be performed. During a mean follow-up period of 15 months, variceal rebleeding occurred in 51.6% of the patients in the ES group and 23% of those in the TIPS group. Uncontrolled rebleeding occurred in 10 of 31 patients in the ES group, whereas rebleeding did not occur in any patient of the TIPS group. Hepatic encephalopathy was more frequent in TIPS patients (33.3%) than in those treated by ES (13%). However, mortality was similar in both treatment groups.\n These preliminary results suggest that TIPS is more effective than ES in the prevention of variceal rebleeding in cirrhotic patients, even though no difference in survival was observed.", "The aim of this study was to compare the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with that of endoscopic sclerotherapy (ES) in the long-term management of patients with cirrhosis after variceal bleeding. Seventy-eight consecutive cirrhotic patients with recent variceal bleeding were randomly allocated to either TIPS (n=38) or ES (n=40). All patients were in good condition at randomization. The mean follow-up was 1116+/-92 days in the TIPS group and 1047+/-102 days in the ES group. Differences in rebleeding from any source (18.4% vs. 32.5%) and esophageal variceal rebleeding (15.7% vs. 27.5%) were not significantly different between the two groups (P>0.05). The mortality rates were similar in both treatment groups. Shunt dysfunction was noted in 27 patients (71%) in the TIPS group. There were more numbers of rehospitalization during follow-up in the TIPS group than in the ES group (2.6+/-0.4 vs. 1.1+/-0.2) (P<0.01). TIPS and ES are equally effective in the prevention of variceal rebleeding. However, TIPS is associated with high incidence of shunt dysfunction, which lead to more rehospitalization. Therefore, TIPS may not be a first-line treatment for the prevention of variceal rebleeding in cirrhotic patients who are in stable condition.", "Eighty-two consecutive Child-Campbell class A and B cirrhotic patients were included in a prospective controlled trial to assess the efficacy and safety of portacaval anastomosis vs. endoscopic sclerotherapy as elective treatment of variceal hemorrhage. Forty-one patients were randomized to portacaval anastomosis and 41 to sclerotherapy. After excluding dropouts, 34 patients were treated with portacaval anastomosis and 35 with sclerotherapy. The incidence of variceal rebleeding during follow-up (mean +/- SD, 20.6 +/- 14.2 months) was significantly higher in the sclerotherapy than in the portacaval groups, either considering the overall treated group or only patients completing sclerotherapy (40% and 25% vs. 2.9%; P = 0.0002 and P = 0.01, respectively). The 2-year probability of suffering from at least one episode of hepatic encephalopathy was significantly higher in patients submitted to portacaval anastomosis than in those treated with endoscopic sclerotherapy (40% vs. 12%; P = 0.04). However, disabling encephalopathy only appeared in 3 of 34 patients who underwent surgery (8.8%). Early and long-term mortality did not differ between the therapeutic groups; 2-year survival rates were 83% for portacaval anastomosis and 79% for sclerotherapy. It is concluded that portacaval anastomosis is more effective than endoscopic sclerotherapy in preventing variceal rebleeding in spite of the greater incidence of hepatic encephalopathy. The role of portacaval anastomosis in the elective treatment of variceal rebleeding should be reassessed." ]

[ "941943" ]

[ "An analysis of the utility of plasma immunoreactive estrogen measurements in determining delivery time of gravidas with a fetus considered at high risk." ]

[ "Although maternal estrogen excretion and plasma estrogen levels are widely used to assess fetal health, the utility of these tests in lowering perinatal mortality rates has not been established. In order to ascertain if, with the help of plasma immunoreactive estrogen measurements, a reduction in perinatal deaths could be achieved, a population of women with a fetus at high risk were randomly divided into two groups and studied prospectively: in 315 gravidas, the estrogen results were reported (Group A); in 307, they were not reported (Group B). Nine perinatal deaths occurred in Group A, 10 in Group B. Ten Group B women whose infant ultimately did well would have been delivered 28 days or more prematurely if management had been based solely on the basis of abnormal immunoreactive estrogen levels. Measurement of estrogen levels is of little value in management of women with a fetus at risk; it may even lead to erroneous premature delivery." ]

[ "19115653", "9846303", "17448057", "21852106", "2679231", "11843736", "734581", "9168215" ]

[ "Lumbar wedge versus pelvic wedge in preventing hypotension following combined spinal epidural anaesthesia for caesarean delivery.", "Lack of benefits of left tilt in emergent cesarean sections: a randomized study of cardiotocography, cord acid-base status and other parameters of the mother and the fetus.", "Manual displacement of the uterus during Caesarean section.", "Hemodynamic effects of a right lumbar-pelvic wedge during spinal anesthesia for cesarean section.", "Incidence of venous air embolism during cesarean section is unchanged by the use of a 5 to 10 degree head-up tilt.", "Maternal cardiovascular consequences of positioning after spinal anaesthesia for Caesarean section: left 15 degree table tilt vs. left lateral.", "Advantages of left over right lateral tilt for caesarean section.", "The effect of head-down tilt position on arterial blood pressure after spinal anesthesia for cesarean delivery." ]

[ "Aortocaval compression is a major cause of maternal hypotension. A randomised controlled clinical trial was designed to compare two wedged supine positions for prevention of hypotension following combined spinal epidural anaesthesia for caesarean delivery. Sixty parturients undergoing elective caesarean delivery were randomly assigned to two different wedged supine positions. After the completion of subarachnoid injection, parturients were placed with either a wedge under the right pelvis (group P pelvic wedge) or under the right lumbar region (group L, lumbar wedge). Systolic blood pressure and heart rate were recorded every minute for 20 minutes from the subarachnoid injection. Hypotension, defined as systolic blood pressure <100 mmHg or 80% of the baseline, was treated with intravenous ephedrine 5 mg. The incidence of hypotension, ephedrine use and neonatal Apgar scores and umbilical arterial pH were recorded. The incidence of hypotension was significantly higher in group P than that in group L (23/30 [77%] vs. 14/30 [47%], P=0.016). Systolic blood pressure decreased significantly in both groups at seven, eight and nine minutes (P < 0.001); moreover it was lower at seven, eight and nine minutes in group P than in group L (P < 0.01). Heart rate did not change significantly in either group. There were no significant differences between the two groups for Apgar score and umbilical arterial pH. A lumbar wedge is more effective than a pelvic wedge in preventing hypotension following combined spinal epidural anaesthesia for caesarean delivery, although it does not eliminate hypotension.", "To assess the benefits of performing the cesarean section in lateral tilt during active labor.\n University Hospital.\n 204 unselected women undergoing cesarean section (21.1% fetal distress, 45.6% cephalo-pelvic disproportion, 26.0% induction failure, 7.4% abnormal presentation) under general (86.8%) or spinal anesthesia (13.2%).\n Randomized study.\n During anesthesia induction and cesarean section 103 women were in partial left lateralization (20 degrees), whereas the remaining 101 remained in the supine position.\n Internal cardiotocography during cesarean section. Umbilical artery acid-base analysis. Newborn evaluation. Maternal hemodynamic parameters.\n Fetal heart rate during cesarean section was similar in both groups, except for a baseline heart rate which was slightly higher in the lateral tilt group (137.5 +/- 19.2 vs 131.1 +/- 20). The umbilical artery pH values, as well as pCO2, base deficit, CO3H and oxygen saturation were similar in both groups. The pO2 value was significantly lower in the lateral tilt group (14.03 +/- 6.04 Hg mm vs 16.02 +/- 7.65). Newborn evaluation was similar in both groups. The blood pressure and heart rate of the mother during the cesarean section were also similar in both groups.\n No benefits were found in performing cesarean section in left lateral tilt.", "Ninety ASA 1 and 2 pregnant women with term singleton pregnancies and no maternal and fetal complications, scheduled for elective or emergency Caesarean section, were randomly allocated to group LT (15 degrees left lateral table tilt, n = 45) and group MD (leftward manual displacement, n = 45). Subarachnoid block was established with a 25-gauge spinal needle at the L3-L4 interspace using 1.5 ml of 0.5% hyperbaric bupivacaine. A median sensory level of T6 was observed in both groups but the incidence of hypotension was markedly lower in group MD when compared to group LT (4.4% vs 40%; p < 0.001) with a significant reduction in mean (SD) ephedrine requirement (6 (0) vs 11.3 (4.9) mg; p < 0.001). The mean (SD) fall in systolic blood pressure was 28.8 (7.3) mmHg in group LT and 20 (12.7) mmHg in group MD. The time to maximum fall in systolic blood pressure was similar in both groups (4.5 min). We conclude that manual displacement of the uterus effectively reduces the incidence of hypotension and ephedrine requirements when compared to 15 degrees left lateral table tilt in parturients undergoing Caesarean section.", "Aortocaval compression is a major cause of maternal hypotension. A randomized controlled trial was designed to determine the effectiveness of a mechanical intervention using a right lumbar-pelvic wedge in preventing hypotension after spinal anesthesia for cesarean delivery.\n Eighty healthy women undergoing elective cesarean section were randomly allocated immediately after spinal blockade to either a lumbar-pelvic wedge positioned under the right posterior-superior iliac crest (Wedge group, n=40) or the complete supine position (Supine group, n=40). Hemodynamic values, vasopressor consumption and adverse effects were collected during the surgical procedure. Hypotension was defined as a reduction in systolic blood pressure of 25% from baseline. Patient allocation, management and data collection were performed by a single unblinded anesthetist.\n There was no difference in the incidence of hypotension between the two groups (42.5% vs. 50%, P=0.51). During the first 5 min, blood pressure decreased less in the Wedge group. There were significant differences in median [interquartile range] vasopressor requirements between the Wedge group and the Supine group (1 [0-2] vs. 3 [1-4] mg, P<0.01) and in nausea during the procedure (6 vs. 22 patients, P<0.01).\n In our study population the use of right lumbar-pelvic wedge was not effective in reducing the incidence of hypotension during spinal anesthesia for cesarean section. Patients in whom the wedge was used had higher systolic blood pressure values during the first 5 min of anesthesia and fewer episodes of nausea. The risk of hypotension remains substantial.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "One hundred healthy parturients were divided at random into two demographically similar groups and were positioned for cesarean section either horizontally or flexed 5 to 10 degrees head up, with a 15 degrees lateral tilt. A Doppler ultrasound transducer was positioned over the fourth intercostal space parasternally. Initially, two patients received spinal, three general, and 95 epidural anesthesia. Two patients subsequently needed general for failed epidural anesthesia. Changes in Doppler heart tones (greater than 15 sec duration) indicative of venous air embolism (VAE) were identified 15 times in 11 patients--seven in supine and four in head-up patients (no statistically significant difference). Six awake patients (three horizontal, three head-up) developed chest tightness or pain during surgery, but only one episode correlated with VAE. No patient developed breathlessness. Moderate hypotension (greater than 10% decrease in systolic arterial pressure [SAP]) occurred in seven of 11 (63.6%) patients with, and in 26 (29.2%) of 89 patients without, VAE (P less than 0.001). More severe hypotension (SAP less than 90 mm Hg) due to bleeding occurred once. We conclude that a modest (5-10 degrees) head-up position does not influence the occurrence of VAE in patients having cesarean section. An 11% incidence of clinically insignificant VAE, although low, is still worrisome, as even small air bubbles in the circulation are potentially harmful, especially if the foramen ovale is patent. VAE during cesarean section should be anticipated and the anesthetic management planned accordingly.", "Sixty healthy women undergoing elective Caesarean section were randomly allocated to either a measured 15 degrees left table tilt position (n = 31) or full left lateral position (n = 29) for a 15-min period after spinal blockade. Arm and leg blood pressure, ephedrine requirements, symptoms, fetal heart rate, cord gases and Apgar scores were recorded. Mean ephedrine requirements and incidence of hypotension were similar in the two groups. Arm systolic arterial pressure over time was similar in both groups, but leg systolic arterial pressure over time was significantly lower in the tilt group (p < 0.001); the mean leg systolic arterial pressure was lower for all 15 sequential recordings in the tilt group, reaching statistical significance (p < 0.05) at 4, 5, 6 and 8 min. Differences in maternal nausea, vomiting and bradycardia and fetal outcome were not statistically significant. Following spinal anaesthesia, even a true 15 degrees left table tilt position is associated with aortic compression.", "The relative merits of right and left lateral tilt were assessed in 75 parturients at elective caesarean section. Significant maternal hypotension (aortocaval occlusion) occurred more frequently with rightward tilt (left hip supported). The clinical and biochemical status of the fetus was generally more favourable with left lateral tilt, as were the maternal-to-fetal blood gas gradients and relationships. The routine use of left lateral tilt is advocated.", "The effect of the head-down tilt position after induction of spinal anesthesia for cesarean delivery on blood pressure and level of sensory block was examined.\n Patients were allocated randomly into two groups, the head-down tilt group (n = 17) and the horizontal group (n = 17). In the head-down tilt group, patients were positioned with a 10 degrees head-down tilt immediately after supine positioning, while those in the horizontal group were maintained in a horizontal position. All patients received 500 mL of lactated Ringer's solution intravenously over 10 minutes prior to spinal injection, a wedge was placed under the patient's right hip, and the operating table was rotated 5 degrees in a counterclockwise direction to provide left uterine displacement. Hypotension (defined as systolic blood pressure below 100 mm Hg) was treated with 5 mg ephedrine intravenously and an increase in the infusion rate of lactated Ringer's solution. The change in systolic blood pressure was expressed as percent change from the baseline value.\n Systolic blood pressure decreased 20% at 3 minutes after spinal block in both groups but recovered to half of this decrease. The incidence of postspinal hypotension was not different between the two groups. The total amount of ephedrine and lactated Ringer's solution administered during the first 20 minutes of spinal block did not differ between the two groups nor did the extent of the cephalad spread of analgesia 20 minutes after spinal block (T4 +/- 2 vs T4 +/- 1 for the head-down and horizontal groups, respectively).\n The head-down position is concluded to have no effect on the incidence of hypotension during spinal anesthesia for cesarean delivery." ]

[ "10586979", "2675597", "21094553", "16241919" ]

[ "Treatment of women with an abnormal glucose challenge test (but a normal oral glucose tolerance test) decreases the prevalence of macrosomia.", "Management of women with one abnormal oral glucose tolerance test value reduces adverse outcome in pregnancy.", "Effect of a low glycaemic index diet on blood glucose in women with gestational hyperglycaemia.", "Evaluating the therapeutic approach in pregnancies complicated by borderline glucose intolerance: a randomized clinical trial." ]

[ "Infant macrosomia is a serious medical concern. Pregnant women who do not meet the specific diagnosis for gestational diabetes may still have glucose-mediated macrosomia. In Santa Barbara County all pregnant women are screened for gestational diabetes at 24-28 weeks with a 50-g, 1-hr glucose challenge test (GCT). All patients who fail this test are placed on a standard euglycemic diet (40% carbohydrate, 20% protein, 40% fat) and perform home glucose monitoring of fasting and postprandial glucose levels. The objective of this study was to examine the effectiveness of this treatment program in decreasing infant macrosomia, maternal and infant morbidity, maternal complications, and operative delivery. We studied 103 women who had a positive GCT, but a negative 100-g, 3-hr oral glucose tolerance test (OGTT). The women were randomly assigned to either experimental or control groups with experimental women receiving dietary counseling and home glucose monitoring instruction (HBGM). HBGM diaries were reviewed weekly by clinic nurses. All women had hemoglobin A1c (HbA1c) tests at 28 and 32 weeks. Maternal and fetal charts were reviewed to determine delivery type and complications, indications for cesarean section (C-section), and infant gestational age, gender, Apgar scores, birth weight, morbidities, and congenital anomalies. Of the 103 women, 5 women required insulin treatment, 1 woman had an abortion, and 14 women were indeterminate regarding compliance or were control women who received diet counseling and HBGM. The results are based on 83 women--48 control and 35 experimental. There were no significant differences between the groups for age, parity, or weight at 28-30 weeks or 37 weeks to delivery, or HbA1c at 28 weeks. HbA1c was significantly higher in control women at 32 weeks. Birth weight expressed in grams or as a percentile specific for gender, ethnicity, and gestational age was significantly higher in control infants. Birth weight was significantly correlated with maternal intake weight, weight at 28-30 weeks, and weight at delivery and with HbA1c at 32 weeks' gestation. There were no significant differences between groups for maternal complications. Groups were significantly different for mode of delivery with experimental women having more induced vaginal deliveries but fewer repeat C-sections than control women. Groups were not different for primary C-sections. Women who fail the GCT, but not the OGTT and thus do not receive the diagnosis of GDM are still at risk for delivering a macrosomic infant and operative delivery. Our program of treatment for all women who fail the GCT improves outcome by reducing infant birth weight and the number of cesarean sections.", "In this study we sought to test the hypothesis that treatment of women with one abnormal oral glucose tolerance test value will result in reduction of adverse outcome. One hundred twenty-six women with one abnormal oral glucose tolerance test value and 146 women in the control group (normal oral glucose tolerance test values) participated in a prospective study during the third trimester of pregnancy. The subjects with one abnormal test result were randomized into treated (group 1) and untreated groups (group II). Group 1 subjects were treated with a strict diabetic protocol to maintain tight glycemic control by means of diet and insulin therapy. Group 2 subjects tested their capillary blood glucose for a baseline period. The study revealed that the level of glycemic control was similar before initiation of therapy (mean capillary blood glucose 118 +/- 14 vs. 119 +/- 15 mg/dl, p = NS) for groups 1 and 2, respectively. There was a significant difference in mean capillary blood glucose (95 +/- 10 vs. 119 +/- 15 mg/dl, p less than 0.0001), preprandial, and postprandial determinations between the treated and untreated groups. The overall incidence of neonatal metabolic complications (4% vs. 14%, p less than 0.05) and large infants (6% vs. 24%, p less than 0.03) was significantly lower in the treated group. Comparison between the control (normal oral glucose tolerance test) and the untreated groups showed a significantly higher incidence of large infants and metabolic complications. No difference was found between the normal and treated groups. Thus we conclude that treatment of individuals with one abnormal oral glucose tolerance test value will result in significant reduction in adverse outcome in pregnancy.", "The objectives of this pilot study were to determine the feasibility and effect on glycaemic control of a low-glycaemic-index (GI) diet in women with gestational diabetes or impaired glucose tolerance of pregnancy.\n participants, recruited from the Diabetes-in-Pregnancy Clinic of an inner-city teaching hospital serving a predominantly non-Caucasian population, were randomized to a low-GI (n=23) or control (n=24) diet and followed from 28 weeks gestation until delivery. Self-monitored-blood-glucose (SMBG), maternal and infant weight were collected from medical charts. Dietary intakes were assessed using diet records and questionnaires.\n diet GI on control (58, 95% CI: 56,60) was significantly higher than on low-GI (49, 95% CI: 47,51; p=0.001). Glycaemic control improved on both diets, but more postprandial glucose values were within target on low-GI (58.4% of n=1891) than control (48.7% of n=1834; p<0.001). SMBG post-breakfast was directly related to pre-pregnancy BMI in the control, but not the low-GI group (BMI*diet interaction; p=0.021). Participants accepted the study foods and were willing to consume them post-intervention.\n a low-GI diet was feasible and acceptable in this sample and facilitated control of postprandial glucose. A larger study is needed to determine the effect of a low-GI diet on maternal and infant outcomes.\n 2010. Published by Elsevier Ireland Ltd.", "Most studies relating minor gestational metabolic alterations to macrosomia refer to glucose intolerance classified on the basis of the National Diabetes Data Group or previous World Health Organization diagnostic thresholds. Our aim was to evaluate the consequences of very mild forms of gestational glucose intolerance, defined by an elevated 50-g glucose challenge test followed by a normal oral glucose tolerance test, using the more restrictive Carpenter and Coustan's criteria (Borderline Gestational Glucose Intolerance, BGGI).\n Three hundred BGGI women were randomly assigned to: Group A (standard management), Group B (dietary treatment and regular monitoring). A control group (C) was also considered. Newborns were classified as macrosomic, large (LGA), or small for gestational age (SGA).\n The three groups were similar in age, body mass index and parity. Therapy in Group B significantly improved fasting (from 4.68 +/- 0.45 to 4.28 +/- 0.45 mmol/l) and 2-h postprandial glycaemia (from 6.01 +/- 0.57 to 5.13 +/- 0.68 mmol/l). Fasting glycaemia at delivery was significantly lower in B (4.20 +/- 0.38 mmol/l) than in A (4.84 +/- 0.45 mmol/l), and was also lower than in C (4.31 +/- 0.39 mmol/l). Significantly fewer LGA babies were born to Group B (6.0%) than Group A (14.0%) and Group C (9.1%). No difference was found in the SGA rate. The neonatal Ponderal Index was higher (P = 0.030) in group A (2.73 +/- 0.35) than in C (2.64 +/- 0.30) and B (2.64 +/- 0.24).\n Even very mild alterations in glucose tolerance can result in excessive or disharmonious fetal growth, which may be prevented by simple, non-invasive therapeutic measures." ]

[ "15514382", "15249520", "19250151", "18823177", "17227607" ]

[ "Cancer consultation preparation package: changing patients but not physicians is not enough.", "Achieving involvement: process outcomes from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "A treatment decision aid may increase patient trust in the diabetes specialist. The Statin Choice randomized trial.", "Physician and patient communication training in primary care: effects on participation and satisfaction.", "Randomized controlled trial of the effectiveness of an intervention to implement evidence-based patient decision support in a nursing call centre." ]

[ "This study evaluated a cancer consultation preparation package (CCPP) designed to facilitate patient involvement in the oncology consultation.\n A total of 164 cancer patients (67% response rate) were randomly assigned to receive the CCPP or a control booklet at least 48 hours before their first oncology appointment. The CCPP included a question prompt sheet, booklets on clinical decision making and patient rights, and an introduction to the clinic. The control booklet contained only the introduction to the clinic. Physicians were blinded to which intervention patients received. Patients completed questionnaires immediately after the consultation and 1 month later. Consultations were audiotaped, transcribed verbatim, and coded.\n All but one patient read the information. Before the consultation, intervention patients were significantly more anxious than were controls (mean, 42 v 38; P = .04); however anxiety was equivalent at follow-up. The CCPP was reported as being significantly more useful to family members than the control booklet (P = .004). Patients receiving the intervention asked significantly more questions (11 v seven questions; P = .005), tended to interrupt the physician more (1.01 v 0.71 interruptions; P = .08), and challenged information significantly more often (twice v once; P = .05). Patients receiving the CCPP were less likely to achieve their preferred decision making style (22%) than were controls (35%; P = .06).\n This CCPP influences patients' consultation behavior and does not increase anxiety in the long-term. However, this intervention, without physician endorsement, reduced the percentage of patients whose preferred involvement in decision making was achieved.", "A consulting method known as 'shared decision making' (SDM) has been described and operationalized in terms of several 'competences'. One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication'. Few data exist on clinicians' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients.\n The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. Half the consultations were randomly selected for audio-taping, of which 352 patients attended and were audio-taped successfully. After baseline, participating doctors were randomized to receive training in (i) SDM skills or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were allocated randomly to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations were audio-taped from each phase. Raters (independent, trained and blinded to study phase) assessed the audio-tapes using a validated scale to assess levels of patient involvement (OPTION: observing patient involvement), and to analyse the nature of risk information discussed. Clinicians completed questionnaires after each consultation, assessing perceived clinician-patient agreement and level of patient involvement in decisions. Multilevel modelling was carried out with the OPTION score as the dependent variable, and rater, consultation and clinician levels of data, standardized by rater within clinician.\n Following each of the interventions, the clinicians significantly increased their involvement of patients in decision making (OPTION score increased by 10.6 following risk communication training [95% confidence interval (CI) 7.9 -13.3; P < 0.001] and by 12.9 after SDM skill development (95% CI 10 -15.8, P < 0.001), a moderate effect size. The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops (7.7 increase in OPTION score, 95% CI 3.4-12; P < 0.001). The alternative sequence (skills followed by risk communication aids) did not achieve this effect. The use of most risk information formats increased after the provision of specific risk communication aids (P < 0.001). Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment (P < 0.001), patient satisfaction with information (P < 0.01), clinician satisfaction with decision (P < 0.01) and general overall satisfaction with the consultation (P < 0.001) than those who were exposed to SDM skill development workshops.\n These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids. Each intervention provided independent effects. Further progress towards greater patient involvement in health care decision making is possible, and skill development in this area should be incorporated into postgraduate professional development programmes.", "Decision aids in practice may affect patient trust in the clinician, a requirement for optimal diabetes care. We sought to determine the impact of a decision aid to help patients with diabetes decide about statins (Statin Choice) on patients' trust in the clinician.\n We randomized 16 diabetologists and 98 patients with type 2 diabetes referred to a subspecialty diabetes clinic to use the Statin Choice decision aid or a patient pamphlet about dyslipidaemia, and then to receive these materials from either the clinician during the visit or a researcher prior to the visit. Providers and patients were blinded to the study hypothesis. Immediately after the clinical encounter, patients completed a survey including questions on trust (range 0 to total trust = 100), knowledge, and decisional conflict. Researchers reviewed videotaped encounters and assessed patient participation (using the OPTION scale) and visit length.\n Overall mean trust score was 91 (median 97.2, IQR 86, 100). After adjustment for patient characteristics, results suggested greater total trust (trust = 100) with the decision aid [odds ratio (OR) 1.77, 95% CI 0.94, 3.35]. Total trust was associated with knowledge (for each additional knowledge point, OR 1.3, 95% CI 1.1, 1.6), patient participation (for each additional point in the OPTION scale, OR 1.1, 95% CI 1.1, 1.2), and decisional conflict (for every 5-point decrease in conflict, OR 1.5, 95% CI 1.2, 1.9). Total trust was not associated with visit length, which the decision aid did not significantly affect. There was no significant effect interaction across the trial factors.\n Preliminary evidence suggests that decision aids do not have a large negative impact on trust in the physician and may increase trust through improvements in the decision-making process.", "To assess the effects of a communication skills training program for physicians and patients.\n A randomized experiment to improve physician communication skills was assessed 1 and 6 months after a training intervention; patient training to be active participants was assessed after 1 month. Across three primary medical care settings, 156 physicians treating 2,196 patients were randomly assigned to control group or one of three conditions (physician, patient, or both trained).\n Patient satisfaction and perceptions of choice, decision-making, information, and lifestyle counseling; physicians' satisfaction and stress; and global ratings of the communication process.\n The following significant (p < .05) effects emerged: physician training improved patients' satisfaction with information and overall care; increased willingness to recommend the physician; increased physicians' counseling (as reported by patients) about weight loss, exercise, and quitting smoking and alcohol; increased physician satisfaction with physical exam detail; increased independent ratings of physicians' sensitive, connected communication with their patients, and decreased physician satisfaction with interpersonal aspects of professional life. Patient training improved physicians' satisfaction with data collection; if only physician or patient was trained, physician stress increased and physician satisfaction decreased.\n Implications for improving physician-patient relationship outcomes through communication skills training are discussed.\n PsycINFO Database Record (c) 2008 APA, all rights reserved.", "We evaluated the effect of an intervention on call centre nurses' knowledge of decision support and skills in coaching callers facing value-sensitive health decisions. Forty-one registered nurses at a health call centre were randomly assigned to an intervention or control group. The intervention was a coaching protocol, online tutorial, skills building workshop and performance feedback. The main outcome measures were: knowledge test; blinded quality assessment of coaching skills during simulated calls and call duration. Compared with controls, nurses in the intervention group had better knowledge (74 versus 60%, P = 0.007) and decision coaching skills (81 versus 44%, P < 0.001), particularly in assessing decisional needs (information, values clarity, support, stage and timing of decision) and addressing support issues. Call duration did not differ (18.5 versus 16.7 min, P = 0.73). The coaching protocol was rated as compatible with nurses' views on decision-making and more advantageous compared with their usual practices. The intervention improved the quality of nurses' decision coaching without affecting call duration." ]

[ "23195074", "12230594", "3929876" ]

[ "Herbal medicines in migraine prevention Randomized double-blind placebo-controlled crossover trial of a feverfew preparation.", "The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose-response study.", "Efficacy of feverfew as prophylactic treatment of migraine." ]

[ "The efficacy of feverfew capsules on migraine prophylaxis was investigated in a randomized double-blind, placebo-controlled crossover study in which 50 patients, who had not used feverfew before, participated. The capsules were filled with a dried alcoholic extract of feverfew on microcristalline cellulose and contained 0.5 mg parthenolide. The patients used one capsule (feverfew or placebo) a day. Fourty four patients completed the 9 month study. Both treatment groups suffered the same number of migraine attacks. A prophylactic effect could not be demonstrated for our feverfew preparation, but the patients seemed to have a tendency to use fever symptomatic drugs during the period they used feverfew. This result was not in accordance with the results from two other studies. The difference may be explained by the fact that both other studies included patients who previously reported positive experiences with feverfew preparations for migraine prophylaxis.\n Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.", "Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.", "Seventeen patients who ate fresh leaves of feverfew daily as prophylaxis against migraine participated in a double blind placebo controlled trial of the herb: eight patients received capsules containing freeze dried feverfew powder and nine placebo. Those who received placebo had a significant increase in the frequency and severity of headache, nausea, and vomiting with the emergence of untoward effects during the early months of treatment. The group given capsules of feverfew showed no change in the frequency or severity of symptoms of migraine. This provides evidence that feverfew taken prophylactically prevents attacks of migraine, and confirmatory studies are now indicated, preferably with a formulation controlled for sesquiterpene lactone content, in migraine sufferers who have never treated themselves with this herb." ]

[ "15851401" ]

[ "Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial." ]

[ "To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor.\n Prospective, double blind, placebo controlled trial randomised by household.\n 8 villages in rural southern Malawi.\n 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial.\n Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks.\n The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms.\n 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea.\n Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor." ]

[ "2108254", "1907432", "1556523", "8087928", "8299405" ]

[ "A pilot double-blind study of sodium-magnesium EDTA in peripheral vascular disease.", "Arteriographic findings in EDTA chelation therapy on peripheral arteriosclerosis.", "EDTA treatment of intermittent claudication--a double-blind, placebo-controlled study.", "Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial.", "Disodium-ethylene diamine tetraacetic acid (EDTA) has no effect on blood lipids in atherosclerotic patients. A randomized, placebo-controlled study." ]

[ "Ten male patients with peripheral vascular disease, Type 2 (LaFontaine), were randomly assigned in a double-blind study to receive either Na2 ethylene diamine tetra acetic acid (EDTA) plus MgSO4, B complex, and vitamin C, or a placebo of MgSO4, B complex, and vitamin C in Ringer's lactate solution. A total of 20 intravenous infusions were planned for administration to each patient. Clinical and laboratory (noninvasive) tests showed dramatic improvements after 10 infusions in some patients, and thus was broken the code indicating who was receiving EDTA and who was receiving placebo. The group that improved had been receiving EDTA; there was no change in the placebo group. The trial was then completed in a single-blind fashion. Patients originally assigned to receive placebo then received 10 EDTA infusions, while the group originally assigned to EDTA received 20 EDTA infusions. The group that had formerly received placebo showed improvements comparable to those seen in the first EDTA group after 10 treatments.", "In a randomized, double-blind, controlled study, 153 patients with claudication were each given either 20 infusions of Na2EDTA or 20 infusions of saline. Walking distances and ankle/brachial indices were measured before, during, and after treatment. In 30 patients, angiograms and transcutaneous oxygen tensions were obtained before, during, and after treatment. The patients' subjective evaluations of the effect of treatment were also recorded. It is concluded that EDTA chelation therapy has no effect in patients with intermittent claudication in the legs caused by arteriosclerosis.", "A double-blind, randomized multicentre study was undertaken to evaluate the possible effect of chelation treatment with ethylenediamine-tetraacetic acid (EDTA) in patients with severe intermittent claudication. A total of 153 patients received 20 intravenous infusions of either 3 g Na2EDTA or placebo during a period of 5-9 weeks. Vitamin, mineral and trace element supplements were administered orally. The changes observed in the pain-free and maximal walking distances, measured on a treadmill, were similar in the two groups. During the 3-month (n = 149) and 6-month (n = 123) follow-up period, no long-term therapeutic effect of EDTA could be demonstrated. The ankle-brachial blood pressure index remained unchanged throughout the study period. This study failed to demonstrate any effect of EDTA chelation treatment in intermittent claudication.", "The use of repeated intravenous infusions of EDTA, which has become known as \"chelation therapy,\" has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication.\n A double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal proportion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%).\n Chelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication.", "To study whether intravenous disodium-ethylene diamine tetraacetic acid (EDTA) affects blood lipids in patients with intermittent claudication.\n Double-blind, randomized, placebo-controlled trial.\n Twenty-nine patients with intermittent claudication (systolic ankle-brachial blood pressure index < 0.8; pain free walking distance 50-200 m).\n 3 g EDTA or placebo (isotonic saline) per infusion over a period of 5-9 weeks to a total of 57 g EDTA. Patients received vitamins, minerals and trace-elements daily.\n 14 patients received EDTA and 15 placebo. There was no statistically significant difference in the plasma concentration of cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol or triglyceride between the 2 groups.\n Treatment with EDTA does not alter blood lipids in patients with intermittent claudication." ]

[ "15897552", "17116941", "17135639", "16148021", "12637460" ]

[ "Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28.", "Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial.", "Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer.", "Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.", "Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer." ]

[ "The primary aim of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 was to determine whether four cycles of adjuvant paclitaxel (PTX) after four cycles of adjuvant doxorubicin/cyclophosphamide (AC) will prolong disease-free survival (DFS) and overall survival (OS) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes.\n Between August 1995 and May 1998, 3,060 patients were randomly assigned (AC, 1,529; AC followed by PTX [AC --> PTX], 1,531). Patients > or = 50 years and those younger than 50 years with estrogen receptor (ER) or progesterone receptor (PR) -positive tumors also received tamoxifen for 5 years, starting with the first dose of AC. Postlumpectomy radiotherapy was mandated. Postmastectomy or regional radiotherapy was prohibited. Median follow-up is 64.6 months.\n The addition of PTX to AC significantly reduced the hazard for DFS event by 17% (relative risk [RR], 0.83; 95% CI, 0.72 to 0.95; P = .006). Five-year DFS was 76% +/- 2% for patients randomly assigned to AC --> PTX compared with 72% +/- 2% for those randomly assigned to AC. Improvement in OS was small and not statistically significant (RR, 0.93; 95% CI, 0.78 to 1.12; P = .46). Five-year OS was 85% +/- 2% for both groups. Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction (for DFS, P = .30 and P = .44, respectively). Toxicity with the AC --> PTX regimen was acceptable for the adjuvant setting.\n The addition of PTX to AC resulted in significant improvement in DFS but no significant improvement in OS with acceptable toxicity. No significant interaction between treatment effect and receptor status or tamoxifen administration was observed.", "The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer.\n Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS).\n Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose.\n Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.", "The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS).\n Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy.\n Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure.\n At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.", "The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival (DFS) and secondarily on overall survival (OS) in patients with high-risk operable breast cancer.\n From June 1997 until November 2000, 604 patients with T1-3N1M0 or T3N0M0 tumors were randomized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or to four cycles of epirubicin followed by four cycles of CMF, as in group A (group B). All cycles were given every 2 weeks with granulocyte colony-stimulating factor support.\n A total of 595 patients were eligible. Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80% in group A and 77% in group B. Survival rates were 93% and 90%, respectively. The effect of treatment on the hazard of death was different according to hormonal receptor status. More specifically, in patients with negative receptor status the hazard of death was significantly higher for group B (hazard ratio 2.42). Both regimens were well tolerated and severe acute side-effects were infrequent. No cases of severe cardiotoxicity or acute leukemia were recorded.\n The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy.", "This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival.\n After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors.\n There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P =.0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% (+/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest.\n The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer." ]

[ "18256367", "19696520", "20669249", "20437557", "10800878", "11359079", "17055323", "12590375" ]

[ "Use of antihypertensives and the risk of Parkinson disease.", "Antihypertensive agents and risk of Parkinson's disease, essential tremor and dementia: a population-based prospective study (NEDICES).", "Calcium channel blocker use and risk of Parkinson's disease.", "L-type calcium channel blockers and Parkinson disease in Denmark.", "The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's disease.", "Risk factors for parkinson's disease: the leisure world cohort study.", "Calcium channel blockers and beta-blockers in relation to Parkinson's disease.", "[Treatment of sialorrhea in Parkinson's disease patients with clonidine. Double-blind, comparative study with placebo]." ]

[ "Recent studies related angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers to possible neuroprotective effects. Little is known about neuroprotection of angiotensin II (AT II) antagonists or beta-blockers.\n To explore the association between antihypertensive drug use and the risk of developing a first-time diagnosis of Parkinson disease (PD).\n This was a case-control analysis within the UK-based General Practice Research Database. Cases were >or=40 years of age with an incident PD diagnosis between 1994 and 2005. We matched one control to each PD case on age, sex, general practice, index date, and duration of previous history in the database. We assessed antihypertensive drug use by timing and by exposure duration. We calculated ORs using conditional logistic regression, adjusted for body mass index, smoking, and various cardiovascular, metabolic, and psychiatric diseases and dementia.\n We identified 3,637 cases with a first-time diagnosis of idiopathic PD and an equal number of matched controls. As compared to nonuse of antihypertensive drugs, the adjusted OR for current use of >or=30 prescriptions was 1.08 (95% CI 0.85 to 1.37) for ACE inhibitors, 0.91 (95% CI 0.41 to 2.00) for AT II antagonists, 1.16 (95% CI 0.95 to 1.41) for beta-blockers, and 0.77 (95% CI 0.63 to 0.95) for calcium channel blockers.\n Current long-term use of calcium channel blockers was associated with a significantly reduced risk of a Parkinson disease diagnosis, while the risk was not materially altered for users of angiotensin converting enzyme inhibitors or beta-blockers and, with less statistical precision, for users of angiotensin II antagonists.", "Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson's disease (PD) or dementia. There are no data for essential tremor (ET).\n To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease).\n Prospective population-based study in Spain enrolling 5,278 participants at baseline.\n Use of antihypertensive medications (aside from beta-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not associated with prevalent or incident PD. Calcium channel blocker use was marginally reduced in prevalent dementia cases (OR(adjusted) = 0.63, p = 0.06) but was not associated with reduced risk of incident dementia (RR(adjusted) = 1.02, p = 0.95).\n We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders.\n Copyright 2009 S. Karger AG, Basel.", "We investigated whether the use of calcium channel blockers (CCBs) was associated with a reduced risk of Parkinson's disease (PD) in two large prospective cohorts: the Nurses' Health Study (NHS) and Health Professionals' Follow-Up Study (HPFS). Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) to assess the association between use of CCBs and risk of PD adjusting for potential confounders. We identified 514 incident cases of PD during follow-up. No association between baseline use of CCBs (RR = 1.18, 95% CI: 0.73-1.92), frequency of use or duration of use of CCBs and PD risk was observed (P > 0.2 for all). These findings do not support a role for CCBs in providing neuroprotection against development of PD.\n © 2010 Movement Disorder Society.", "This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood-brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk.\n We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis.\n Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54-0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications.\n Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers.", "Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in the substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss.\n We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopril on the clinical features of moderately severe Parkinson's disease.\n After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in 'on phase' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more 'on' periods during their waking day in their movement diary, p=0.007. Perindopril was well tolerated without any significant postural hypotension or renal dysfunction.\n These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study.", "We conducted a case-control study nested within a prospective cohort study of 13,979 residents of Leisure World Laguna Hills, a retirement community in southern California, for etiologic clues for Parkinson's disease (PD). Between 1981 (when first mailed a health survey) and 1998, we identified 395 PD cases from death certificates, hospital discharge diagnoses and a 1992 follow-up questionnaire. Six controls were individually matched on sex, birth date (+/-2 years), vital status and, if dead, death date (+/-1 year) to each case. Baseline characteristics of the 395 cases and 2,320 controls were analyzed as potential PD risk factors. The risk of PD was significantly reduced among smokers, hypertensives, coffee drinkers and alcohol consumers, and significantly increased among those with 3 or more children and with a high intake of total vitamin A and dietary vitamin C. The multivariate odds ratios (95% confidence intervals) were 0.42 (0.22-0.80) for current cigarette smokers of 1+ pack/day, 0.62 (0.48-0.80) for current users of hypertensive medication, 0.71 (0.52-0.95) for coffee drinkers of 2+ cups/day and 0.77 (0.58-1.03) for drinkers of 2+ alcoholic drinks/day. Risk increased with increasing number of children (1.25 for 1, 1.34 for 2 and 1.90 for 3+ children; p for trend = 0.0003). The increased risks among individuals in the highest third of total vitamin A intake and of dietary vitamin C intake were no longer statistically significant after adjusting for the other variables. These findings suggest several environmental factors that may be related to the development of PD and support a multifactorial etiology.\n Copyright 2001 S. Karger AG, Basel.", "We investigated the risk of Parkinson's disease (PD) associated with calcium channel blockers (CCBs) and beta-blockers in a population-based case-control study of 206 men and women between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 controls without PD or other neurodegenerative disorders who were frequency matched on age, sex, duration of GHC enrollment and clinic. The adjusted odds ratio associated with ever use was 0.85 (95% confidence interval [CI]: 0.43, 1.66) for CCBs, and 1.20 (95% CI: 0.71, 2.03) for beta-blockers. We observed no association with PD risk for either class of medication in terms of duration, dose, number of prescriptions or pattern of use. The weakness of these associations and the absence of additional influence of dose or duration of use argue against any causal interpretation.", "sialorrhea is one of the common nonmotor, non-neuropsychiatric symptoms in Parkinson's disease and its pre-sence can cause limitation in the patient's social life. The traditional treatment with anticholinergic medication is capable of triggering important neuropsychiatric complications.\n this is a prospective, double-blind, placebo compared study, which follow-up Parkinson's disease patients for 3 months.\n we measured the efficacy of clonidine in the management of sialorrhea. The study was performed in 32 patients (20 males and 12 females), with a mean age of 70.75 years and mean duration of the disease of 8.84 years. Randomly, 17 patients received clonidine 0.15 mg/day and the remaining 15 patients received placebo. Both groups were made up of subjects with similar characteristics, age, years of illness, sex, stage of disease (H and Y), disability (S and C) and motor score (UPDRS). Likewise, salivation affected both groups in the same intensity. We used the variable analysis and there was a p < 0.05 significance.\n the group which received clonidine showed a significant improvement of the salivation symptoms both at one month as well as at 3 months of treatment (p < 0.00001, respectively). There was no evidence of worsening of the stage of the disease, incapacity or motor score. The side effects were found only in the group that received clonidine (4 patients) without showing statistically significant.\n the use of clonidine can be useful in the management and treatment of sialorrhea in patients with Parkinsońs disease." ]

[ "6713818", "16313377", "11022928", "15564354", "14606735", "8664717", "9133884", "19129262", "12511761", "15514186", "15976500" ]

[ "Social work effectiveness in two-year stroke survivors: a randomised controlled trial.", "Expanding the role of the stroke nurse: a pragmatic clinical trial.", "Family support for stroke: a randomised controlled trial.", "The Families In Recovery From Stroke Trial (FIRST): primary study results.", "A randomized controlled trial of an education and counselling intervention for families after stroke.", "Specialist nurse support for patients with stroke in the community: a randomised controlled trial.", "Evaluation of a stroke family care worker: results of a randomised controlled trial.", "Does behaviour modification affect post-stroke risk factor control? Three-year follow-up of a randomized controlled trial.", "Evaluation of a stroke family support organiser: a randomized controlled trial.", "Multicenter randomized controlled trial of an outreach nursing support program for recently discharged stroke patients.", "A family support organiser for stroke patients and their carers: a randomised controlled trial." ]

[ "nan", "This paper reports a study evaluating whether expanding a specialist nursing role to provide outreach education and support to stroke patients and carers after discharge from hospital is effective in promoting recovery.\n Building therapeutic relationships with patients and carers is a key component of the nursing role in stroke rehabilitation, although this is limited by the constraints of service organization.\n A pragmatic randomized controlled trial was undertaken. Patients with a diagnosis of stroke were randomized to receive continued support from a stroke nurse (n = 87) or usual care and follow-up (n = 89) after discharge from hospital. Patients were recruited from two hospitals in the north-west of England from November 1999 to April 2001. Patient dependence (Barthel Index), general health (Nottingham Health Profile), activities of living (Frenchay Activity of Living Index), depression (Beck Depression Inventory) and carer strain (Carer Strain Index) were assessed at 3 and 12 months after stroke.\n The continued intervention of a stroke nurse after discharge was associated with improved patient perceptions of general health at 12 months (median difference 42.6, P = 0.012), and in particular reduced negative emotional reaction (P = 0.037) and perceived social isolation (P = 0.002). In addition, the intervention reduced carer strain at 3 months (P = 0.045), and reduced deterioration in physical dependence from 3 to 12 months (P = 0.049).\n The provision of continued intervention from a stroke nurse after discharge from hospital, focusing on education and support, has tangible benefits for patients and carers.", "Attention is currently focused on family care of stroke survivors, but the effectiveness of support services is unclear. We did a single-blind, randomised, controlled trial to assess the impact of family support on stroke patients and their carers.\n Patients with acute stroke admitted to hospitals in Oxford, UK, were assigned family support or normal care within 6 weeks of stroke. After 6 months, we assessed, for carers, knowledge about stroke, Frenchay activities index, general health questionnaire-28 scores, caregiver strain index, Dartmouth co-op charts, short form 36 (SF-36), and satisfaction scores, and, for patients, knowledge about stroke and use of services, Barthel index, Rivermead mobility index, Frenchay activities index, London handicap scale, hospital anxiety and depression scales, Dartmouth co-op charts, and satisfaction.\n 323 patients and 267 carers were followed up. Carers in the intervention group had significantly better Frenchay activities indices (p=0.03), SF-36 scores (energy p=0.02, mental health p=0.004, pain p=0.03, physical function p=0.025, and general health perception p=0.02), quality of life on the Dartmouth co-op chart (p=0.01), and satisfaction with understanding of stroke (82 vs 71%, p=0.04) than those in the control group. Patients' knowledge about stroke, disability, handicap, quality of life, and satisfaction with services and understanding of stroke did not differ between groups. Fewer patients in the intervention group than in the control group saw a physiotherapist after discharge (44 vs 56%, p=0.04), but use of other services was similar.\n Family support significantly increased social activities and improved quality of life for carers, with no significant effects on patients.", "Social support and family ties are strong predictors of functional recovery after stroke; however, development of successful psychosocial intervention programs has been difficult. This study examined whether a family-systems intervention designed to influence social support and self-efficacy affects functional outcome in older stroke patients.\n Two hundred ninety-one community-residing survivors of ischemic stroke or nontraumatic cerebral hemorrhage from eight acute-care hospitals and rehabilitation centers were randomized to either psychosocial intervention (PSI) or usual care (UC). PSI involved up to 16 sessions conducted in the home by a mental health worker. Functional recovery (measured by the Barthel Index [BI] at 6 months postrandomization, inability to assess functioning because of illness or death) was the primary end point.\n Functional recovery did not differ between UC and PSI in intention-to-treat analyses. In adjusted logistic regression, the odds of being functionally independent at 6 months was 60% higher in the intervention group, but this difference was not statistically significant (p = .31). Subgroup analyses revealed that PSI may be more effective in subjects with better psychologic and cognitive functioning and who required less inpatient rehabilitation.\n This study does not provide evidence for the efficacy of psychosocial intervention to improve functional recovery in stroke. Although PSI showed greater improvement than UC, the differences were not statistically significant.", "To determine whether education and counselling after stroke leads to improved family functioning and psychosocial outcomes for stroke patients and their spouses, and better functional and social outcomes for patients.\n Two-group randomized controlled trial. Data were collected on admission to and discharge from rehabilitation, and again six months later.\n Rehabilitation units at Repatriation General Hospital and Griffith Hospital, in Adelaide, South Australia.\n Sixty-two stroke patients and their spouses, 32 in the intervention group and 30 in the control group.\n Stroke information package and three visits from a social worker trained in family counselling.\n Family functioning: McMaster Family Assessment Device (FAD); functional status: Barthel Index (BI); social recovery: Adelaide Activities Profile (AAP); depression: Geriatric Depression Scale (GDS); anxiety: Hospital Anxiety and Depression Scale (HADS); mastery: Mastery Scale (MS); health status: SF-36.\n At six months the intervention group had better family functioning for both patients (mean FAD difference 0.19) and spouses (mean difference 0.09). A modest benefit in functional status for intervention patients (mean BI difference 1.3) was related to improved family functioning. Intervention patients reported better social recovery (mean AAP differences: domestic chores 5.7, household maintenance 4.6, social activities 11.5), but there were no significant effects on depression, anxiety, mastery or health status.\n An education and counselling intervention maintained family functioning, and in turn led to improved functional and social patient outcomes. This approach helps patients and their spouses to make the optimal adjustment to living with stroke.", "To evaluate whether specialist nurse visits enhance the social integration and perceived health of patients with stroke or alleviate stress in carers in longer term stroke care.\n Stratified randomised controlled trial; both groups assessed at time of recruitment and at 3, 6, and 12 months.\n Patients with disability related to new stroke who lived in their own homes in the Bradford Metropolitan District.\n 240 patients aged 60 years or over, randomly allocated to control group (n = 120) or intervention group (n = 120). Intervention--Visits by specialist outreach nurses over 12 months to provide information, advice, and support; minimum of six visits during the first six months. The control group received no visits.\n The Barthel index (functional ability), the Frenchay activities index (social activity), the Nottingham health profile (perceived health status). Stress among carers was indicated by the general health questionnaire-28 (28 items). The nurses recorded their interventions in trial diaries.\n There were no significant differences in perceived health, social activities, or stress among carers between the treatment and control groups at any of the assessments points. A subgroup of mildly disabled patients with stroke (Barthel index 15-19) had an improved social outcome at six months (Frenchay activities index, Median difference 3 (95% confidence interval 0 to 6; P = 0.03) and for the full 12 months of follow up (analysis of covariance P = 0.01) compared with the control group.\n The specialist nurse intervention resulted in a small improvement in social activities only for the mildly disabled patients. No proved strategy yet exists that can be recommended to address the psychosocial difficulties of patients with stroke and their families.", "To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers.\n Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation.\n A well organised stroke service in an Edinburgh teaching hospital.\n 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period.\n Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire.\n The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support.\n The introduction of a stroke family care worker improved patients' and their carers' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients' physical wellbeing.", "Little is known about the long-term effectiveness after stroke of interventions for behaviour modification and ensuring concordance with therapies. We describe a follow-up study of a previous randomized controlled trial of a brief period of behaviour modification. The aim of this study was to determine outcomes three years after the initial intervention.\n Survivors of the original cohort were contacted and asked to attend for follow-up interview, within a geriatric day hospital. This study was carried out in the Geriatric Day Hospital at Stobhill Hospital, Balornock Road, Glasgow.\n Details of risk factor control, including blood pressure, cholesterol levels and diabetic control, were assessed. Questionnaires used in the initial study were repeated including the Geriatric Depression Scale score, Euroqol Perceived Health Status and Stroke Services Satisfaction Questionnaire.\n Primary outcome was collective risk factor control. Clinical outcomes including recurrent cerebrovascular events, medication persistence and perceived health status were also recorded.\n Mean length of follow-up was 3.6 years (SD 0.43). Of the 205 patients enrolled in the initial study, 102 patients attended for repeat interview(49 intervention/53 control). There were no significant differences in the percentage of controlled risk factors between groups (intervention 51.7% versus control 55.9%, P = 0.53). Similarities were observed in the number of recurrent clinical events and medication persistence between groups. No overall difference was observed in perceived health status, satisfaction with care or depression scores.\n Brief intervention with respect to behaviour modification and risk factor control does not appear to have any long-term benefit. These results must be cautiously interpreted in light of the small study number and further research is required.", "There is inconclusive evidence of the effectiveness of the Stroke Family Support Organiser (FSO) service. We report the results from a randomized controlled trial of the service.\n Stroke patients admitted to hospital and their informal caregivers were randomly allocated to receive the FSO service (n=126) or standard care (n=124). Outcome assessments were undertaken 4 and 9 months after recruitment with the General Health Questionnaire 12, Carer Strain Index, Barthel Index, Extended Activities of Daily Living scale, and a specially designed questionnaire to determine knowledge of stroke and satisfaction with services.\n There were no significant differences between groups in patients' mood and independence in personal or instrumental activities of daily living or caregivers' mood, strain, or independence. Patients in the intervention group were significantly more knowledgeable about whom to contact for stroke information, reducing the risk of stroke, practical help, community services, and emotional support. Patients in the intervention group were also significantly more satisfied with the stroke information received. Caregivers in the intervention group were significantly more knowledgeable about whom to contact for information on stroke, reducing the risk of stroke, community services, and emotional support. Caregivers in the intervention group were also significantly more satisfied with stroke information.\n The FSO service had no significant effect on mood, independence in activities of daily living, or reduction in caregiver strain, but it did increase knowledge of stroke and satisfaction with that knowledge. The results may not be representative of all FSO services, and the sample was small relative to the heterogeneity of the participants. However, results suggest that the policies and training procedures of FSOs need to be evaluated to ensure that a cost-effective service is being provided to stroke patients and their caregivers.", "Many stroke patients and informal carers experience a decreased quality of life after discharge home and are dissatisfied with the care received. We assessed the effectiveness of an outreach nursing care program.\n In a multicenter trial, 536 stroke patients were randomized at discharge to standard care (n=273) or standard care plus outreach care (n=263). The outreach care consisted of 3 telephone calls and 1 home visit within 5 months after discharge by 1 of 13 stroke nurses. Patients were masked for the trial objectives. Six months after discharge, they assessed the 2 primary outcomes: quality of life (Short Form 36 [SF-36]) and dissatisfaction with care. Secondary measures of outcome were disability, handicap, depression, anxiety, and use of health care services and secondary prevention drugs. Informal carers assessed strain, and social support. Analysis was by intention to treat.\n Twelve patients died before follow-up, 38 declined outcome assessment, and 486 completed the primary outcome assessments. Outreach care patients had better scores on the SF-36 domain \"Role Emotional\" than controls (mean difference 7.9 [95% confidence limit, 0.1 to 15.7]). No statistically significant differences were found on the other primary outcome measures. For secondary outcomes, no statistically significant differences were found, except that intervention patients used fewer rehabilitation services (relative risk, 0.66 [0.44 to 1.00]) and had lower anxiety scores (median difference 1 [0.19 to 2.79]).\n This outreach nursing stroke care was not effective in improving quality of life and dissatisfaction with care of recently discharged patients.", "Previous trials of interventions to support stroke survivors and their families in the community have had contradictory and inconclusive results. Using the MRC Framework for Complex Interventions we developed a family support organiser (FSO) service and refined outcome measures for evaluation. We tested the effects of the intervention in a randomised controlled trial.\n From 1 March 1999 to 1 April 2001 all first-in-a-lifetime strokes (n = 513) were identified and 340 (96%) of eligible strokes randomised to receive FSO or usual care. Patients and their carers were followed up at 3 months and 1 year post-stroke. Outcomes included satisfaction (main outcome) with hospital staff and outpatient services, use of social services, reintegration to normal living (RNLI) and feelings about life after the stroke.\n The mean number of contacts with the FSO was 15 (SD = 9.8) per patient. More intervention than control patients received some social services and had increased patient and carer satisfaction in most aspects, particularly with information about recovery and feeling that someone had listened. There was little evidence at 3 or 12 months of differences in RNLI.\n A meta-analysis of trials in this area is now needed along with further trials of interventions in subgroups of the stroke population to fully identify any benefits of the FSO role.\n Copyright (c) 2005 S. Karger AG, Basel." ]

[ "10874361", "2150642", "11157183", "8825274", "8352673", "10390316", "9669472", "2683557", "2655184", "2358004", "6377803", "8023348", "2195714", "2404768", "1731418", "2298828", "16005902" ]

[ "A randomized double-blind controlled study of nimodipine in acute cerebral ischemic stroke.", "Isradipine in patients with acute ischaemic cerebral infarction. An overview of the ASCLEPIOS Programme.", "Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial.", "Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands.", "Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography.", "Nimodipine and perfusion changes after stroke.", "Effect of nimodipine on memory after cerebral infarction.", "Nimodipine in acute ischemic stroke: a double-blind controlled study.", "A double-blind, randomized trial of PY108-068 in acute ischemic cerebral infarction.", "Flunarizine in acute ischemic stroke: a pilot study.", "The effects of nimodipine on the clinical course of patients with acute ischemic stroke.", "A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke.", "Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction.", "Double-blind study of nimodipine in non-severe stroke.", "Clinical trial of nimodipine in acute ischemic stroke. The American Nimodipine Study Group.", "Effect of nimodipine on regional cerebral glucose metabolism in patients with acute ischemic stroke as measured by positron emission tomography.", "Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial." ]

[ "A randomized placebo controlled double-blind clinical trial of nimodipine was conducted in 31 patients of acute cerebral infarction. Nimodipine was administered in dosage of 120 mg/day for 28 days. Treatment was begun within 48 hours of ischemic stroke. Diagnosis was confirmed by computed tomographic (CT) scan. Similar number of patients (control) received placebo. Neurological assessment was done at the time of entry into the trial, and after 4 weeks, by using Mathew's scale. After four weeks of treatment with nimodipine or placebo, Mathew's scale score improved significantly (< 0.001) in both groups, but difference in mean score between two groups was insignificant (> 0.05). However, significant difference (< 0.05) was noted in relative change in neurological deficit (mean X-value) of two groups. The nimodipine group had higher value in scores on Mathew's scale. No adverse reaction, was observed in either group. The study suggests a beneficial a effect of nimodipine in acute cerebral ischaemia.", "Calcium-related mechanisms are an integral part of metabolic reactions during acute cerebral infarction. In an animal model of stroke, the calcium antagonist isradipine was shown to protect neurons against ischaemia. In order to improve the neurological and functional outcome of human stroke patients, a randomised, double-blind, placebo-controlled multicentre study was started in up to 600 patients with acute ischaemic brain infarction. Since early treatment is considered to be of great importance, patients must be recruited no more than 12 hours after stroke onset. Medical, ECG, laboratory, neurological and functional evaluations are conducted for up to 90 days after stroke.", "The Very Early Nimodipine Use in Stroke (VENUS) trial was designed to test the hypothesis that early treatment with nimodipine has a positive effect on survival and functional outcome after stroke. This was suggested in a previous meta-analysis on the use of nimodipine in stroke. However, in a recent Cochrane review we were unable to reproduce these positive results. This led to the early termination of VENUS after an interim analysis.\n In this randomized, double-blind, placebo-controlled trial, treatment was started by general practitioners or neurologists within 6 hours after stroke onset (oral nimodipine 30 mg QID or identical placebo, for 10 days). Main analyses included comparisons of the primary end point (poor outcome, defined as death or dependency after 3 months) and secondary end points (neurological status and blood pressure 24 hours after inclusion, mortality after 10 days, and adverse events) between treatment groups. Subgroup analyses (on final diagnosis and based on the per-protocol data set) were performed.\n At trial termination, after inclusion of 454 patients (225 nimodipine, 229 placebo), no effect of nimodipine was found. After 3 months of follow-up, 32% (n=71) of patients in the nimodipine group had a poor outcome compared with 27% (n=62) in the placebo group (relative risk, 1.2; 95% CI, 0.9 to 1.6). A treatment effect was not found for secondary outcomes and in the subgroup analyses.\n The results of VENUS do not support the hypothesis of a beneficial effect of early nimodipine in stroke patients.", "An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery.\n The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4-weeks double-blind treatment with either flunarizine (n = 166) or placebo (n = 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3-4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other \"stroke therapies\" were not allowed. Patients were followed up for 24 weeks.\n After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3-5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n = 31; placebo n = 29). Also in this subgroup, no differences were found between the flunarizine and placebo group.\n Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.", "To determine if previously hypertensive patients with acute ischemic stroke should be treated with antihypertensive medication in the immediate poststroke period.\n Randomized double-blind, placebo-controlled trial.\n Sixteen consecutive hypertensive patients (four men and 12 women; mean age, 66 years [age range, 46 to 83 years]) with middle cerebral artery infarction within 72 hours of onset and blood pressure between 170 and 220 mm Hg(systolic) and 95 and 120 mm Hg (diastolic).\n Placebo (n = 6), nicardipine hydrochloride (20 mg [n = 5]), captopril (12.5 mg [n = 3]), or clonidine hydrochloride (0.1 mg [n = 2]) given every 8 hours for 3 days.\n Decline in blood pressure, change in cerebral blood flow as measured by single photon emission computed tomography, and clinical change as determined by the National Institutes of Health Stroke Scale.\n Blood pressure fell significantly in both the drug-treated group as a whole and in those patients receiving placebo (P < .001). There was no difference in blood pressure levels between these two groups throughout the study period. Patients receiving nicardipine had a consistently lower pressure than the other groups. A significant negative relationship was noted between the maximum blood pressure fall and improvement in cerebral blood flow. There were four patients whose blood pressure dropped by more than 16% of the baseline value on any 24 hours in the first 3 days. All either failed to increase or actually decreased their cerebral blood flow to the affected area. Three of these patients were treated with nicardipine. There was no significant difference in clinical course between the placebo-and drug-treated groups as a whole.\n Hypertensive ischemic stroke patients with a moderate elevation of blood pressure in the first few days may not require antihypertensive therapy. Nicardipine and possibly other calcium channel blockers may cause an excessive fall in blood pressure and impair cerebral blood flow in these patients and should therefore be used with caution.", "Meta-analysis of previous trials of oral nimodipine in acute stroke has suggested a benefit when commenced within 12 hours of onset. We sought to study the effect of oral nimodipine on reperfusion after acute stroke and the relation between reperfusion and outcome.\n Fifty patients with acute middle cerebral artery territory cortical infarction were blindly randomized within 12 hours of onset to either oral nimodipine (30 mg every 6 hours) or placebo. Treatment was continued for 2 weeks. Cerebral blood flow was assessed with the use of 99mTc-hexamethylpropyleneamine oxime single-photon emission CT before therapy, 24 hours later, and at 3 months. Hypoperfusion was measured by a validated volumetric technique. Neurological impairment and functional outcome were assessed with the Canadian Neurological Scale and Barthel Index, respectively. Tissue loss was measured with CT at 3 months. Four patients were excluded from analysis for technical reasons.\n Twenty-three patients received nimodipine, and 23 received placebo. In the nimodipine group, there was early reperfusion that was not maintained at outcome (P=0.01). In the placebo group, mean infarct hypoperfusion volumes showed no overall change. Nonnutritional reperfusion in nimodipine-treated patients was associated with adverse neurological (P=0.05) and functional outcome (P=0.06). There was, however, no difference in clinical outcome between the 2 groups.\n Oral nimodipine administered within 12 hours enhanced acute reperfusion, but this was largely nonnutritional. Larger studies using a shorter treatment delay are required to evaluate the clinical efficacy of nimodipine in acute ischemic stroke.", "Epidemiological studies indicate widespread memory impairment in patients with stroke in the early post-ictal stage. Nimodipine may have psychopharmacological properties and may improve memory. We conducted a single-blind randomized controlled trial to determine whether nimodipine given 7-14 days after cerebral infarction improved memory.\n One hundred patients with acute cerebral infarction were consecutively enrolled between D7 to D14. After stratification, patients were randomized to receive oral nimodipine 90 mg daily for 12 weeks, or no drug. Independent assessors administered Mini-Mental State Examination (MMSE) and Fuld Object-Memory Evaluation (FOME) at baseline, 6 weeks, and 12 weeks.\n Patients receiving nimodipine showed greater improvement in FOME mean scores at 12 weeks (P=0.0334), and also in FOME score change across time (P=0.0283). Patients with severe disability who received nimodipine also showed greater MMSE score change across time (P=0.0495).\n Nimodipine given 7-14 days after cerebral infarction for 3 months results in memory improvement.", "Nimodipine (BAY e 9736), a new dihydropyridine derivative, has been shown to reduce neurological deficits and mortality induced by acute cerebral ischemia in experimental studies. We investigated the effects of this calcium antagonist in patients with acute ischemic stroke through a randomized, double-blind, parallel-designed trial in which nimodipine was compared with placebo. Forty-one of 54 screened cases were found to fulfil the inclusion criteria (sudden occurrence of a focal neurological deficit secondary to an acute ischemic event in the carotid area diagnosed after a complete neurological work-up) and entered the study. Nineteen of them were treated with nimodipine (40 mg t.i.d. administered for 28 days) and the remaining 22 with placebo, given in identical tablets. In all patients the treatment started within 12 h after the onset of the symptoms. Course and intensity of the neurological deficit were evaluated by the Mathew Scale (slightly modified). Forty patients concluded the trial. Nimodipine was withdrawn in one case following the occurrence of a skin rash whose causative relation with the test drug could not be clarified. Altogether, however, nimodipine was well tolerated and no severe cardiovascular adverse reactions were observed. In terms of efficacy, the scores obtained by the Mathew Scale showed a higher rate of improvement on nimodipine than on placebo, thus indicating that patients receiving the latter drug did not fare as well as those receiving the test medication. Our data suggest that nimodipine may be beneficial in the treatment of acute stroke.", "A double-blind, randomized, pilot trial of the calcium channel antagonist PY108-068 was completed in patients with acute ischemic cerebral infarction. Nine treated patients received PY108-068 orally (150 mg/day in divided doses) and 10 control patients received placebo within 48 hours of stroke onset for 21 days. The mean age of the treated patients (four men, five women) was 63.7 years and of the control patients (seven men, three women) 64.4 years. Most infarctions were in the territory of the middle cerebral artery. One treated patient died of sudden cardiac death on Day 12; one control patient died of cerebral herniation. Two treated patients had episodes of clinically insignificant hypotension during Day 1 of treatment. Two control patients had myocardial infarctions during the trial. The mean Toronto Stroke Scale scores at stroke onset were 67 and 90 and at Week 12 were 22.5 and 34.7 in the treated and control groups, respectively. There was parallel improvement in the two groups, with no significant difference between groups (p = 0.12). The mean Barthel Index functional scores at stroke onset were 32.8 and 33 and at Week 12 were 90 and 78.8 in the treated and control groups, respectively. There was a trend in favor of the treated group, but differences between groups did not reach significance. In this pilot trial, PY108-068 was found to be safe but not effective in patients with acute ischemic cerebral infarction.", "Twenty-six patients with acute supratentorial brain infarction were randomly allocated to double-blind intravenous treatment with the calcium entry blocker flunarizine (12 patients) or placebo (14 patients) within 24 h. CT scan excluded other significant pathology. Impaired consciousness and gaze deviation were more common in the placebo group. Three patients in the treated group (25%) were either dead or severely disabled after 6 months, whereas this occurred in 8 of the 14 (57%) control patients, a difference of 32%. This difference is not statistically significant and there is an uneven distribution of important prognostic variables, however, the confidence limits of the difference (-4% and +68%) suggest that there may be a clinically important effect.", "60 patients with acute ischemic stroke were enrolled in a prospective single-blind, randomized trial to determine whether treatment with the calcium antagonist nimodipine would reduce their neurological deficit. All patients received a standard treatment. In addition, 29 received a daily dose of 120 mg nimodipine orally as 3 divided doses (treatment group). Evaluation of therapy was assessed with a neurological scoring system ( Mathew scale). Comparison of the Mathew sum scores in the standard group with those of the nimodipine group (analysis of variance) revealed a highly significant difference (P less than 0.0001) in favour of nimodipine during the 4 week period of treatment. Based on the individual items of the Mathew scale, the level of consciousness and disability were significantly improved under the nimodipine-therapy. Side effects were of minor importance and of no clinical relevance.", "A randomized, double-blind, placebo-controlled multicenter trial was conducted to test the hypothesis that nimodipine would improve the functional outcome in acute ischemic hemispheric stroke.\n A total of 350 patients were randomized to nimodipine 120 mg/d PO or matching placebo for 21 days. Randomization was stratified by onset of therapy, age, and stroke severity. Treatment was begun within 48 hours of onset. The patients had neurological evaluation on admission, on days 1, 7, and 21, and at 3 and 12 months. The primary end points were Rankin grade, neurological score, and mobility at 12 months.\n We did not find any differences in the functional outcome between the treatment groups or between the stratified subgroups. We were also unable in post hoc analyses to find any groups of patients who benefited from nimodipine. During the first month and at 3 months the case-fatality rate was higher in the nimodipine-treated patients than in those on placebo (P = .004 and P = .030, respectively), but at the 1-year follow-up this difference had lost statistical significance. During the first week nimodipine had a statistically significant lowering effect on both systolic (P = .005) and diastolic (P = .013) blood pressure.\n Nimodipine did not improve the functional outcome of acute ischemic hemispheric stroke. The early case-fatality rate was higher in the nimodipine group, possibly due to the blood pressure-lowering effect of nimodipine.", "Nimodipine is a 1,4-dihydropyridine derivative that shows a preferential cerebrovascular activity in experimental animals. Clinical data suggest that nimodipine has a beneficial effect on the neurologic outcome of patients suffering an acute ischemic stroke. Our double-blind placebo-controlled multicenter trial was designed to assess the effects of oral nimodipine on the mortality rate and neurologic outcome of patients with an acute ischemic stroke. One hundred sixty-four patients were randomly allocated to receive either nimodipine tablets (30 mg q.i.d.) or identical placebo tablets for 28 days. Treatment was always started less than or equal to 48 hours after the acute event. The Mathew Scale, slightly modified by Gelmers et al, was used for neurologic assessment. Mortality rate and neurologic outcome after 28 days were used as evaluation criteria. We considered 123 patients to be valid for the analysis of efficacy. Mortality rates did not differ significantly between groups. Neurologic outcome after 28 days of therapy did not differ between groups. However, when only those patients most likely to benefit from any intervention (Mathew Scale sum score of less than or equal to 65 at baseline) were analyzed separately in post hoc-defined subgroups, the nimodipine-treated subgroups showed a significantly better neurologic outcome. This result suggests that some patients with acute ischemic stroke will benefit from treatment with nimodipine tablets.", "We evaluated the effect of nimodipine (30 mg q.i.d. orally for 14 days) on acute ischemic stroke of mild or moderate severity in a unicenter, double-blind, randomized, placebo-controlled pilot study. Treatment had to be started after CT, within 48 h of infarct in patients with a Mathew scale sum score between 50 and 75. The duration of follow-up was 4 months. Eight of the 60 randomized patients were excluded because of incorrect diagnosis. For the remaining 52 patients, 24 were allocated to nimodipine and 28 to placebo. Analysis of variance and covariance and repeated measurements of the Mathew scale scores showed no difference between the two groups, who had continuous and parallel improvement. There was no recurrent stroke, but 1 control died 4 weeks after stroke. Treatment with nimodipine was well tolerated (hypotension: 1 treated patient, 3 controls; bradycardia: 1 treated patient, 2 controls; sGPT increase: 1 treated patient, 1 control). The lack of efficacy of nimodipine in this study may be due to: (1) the neurologic deficit not being severe enough, or (2) the delay before treatment was too long.", "A randomized, double-blind, multicenter clinical trial of placebo versus nimodipine was conducted to test the hypothesis that nimodipine would reduce the frequency of death and of worsening by 30% compared with placebo.\n Nimodipine was used in doses of 60 mg, 120 mg, and 240 mg daily in 1,064 patients treated for 21 days. Treatment was begun within 48 hours of stroke due to infarction as inferred by initial computed tomographic scan findings. The Toronto and motor scales were analyzed by analysis of covariance, using covariance-adjusted means, the last-value-carried-forward, to compare the baseline value with the 3 assessment days (days 4, 10, and 21).\n No difference in mortality or neurological outcome was found with any of the rating scales for the overall cohort. Planned but post hoc subgroup analysis showed a reduction in worsening frequency of 30% compared with placebo and significantly better outcome scores with 120 mg nimodipine daily started within 18 hours of stroke as measured by the Toronto scale (p less than 0.005) and when the pretreatment computed tomographic scan was negative (p less than 0.003).\n Nimodipine had no overall effect when treatment was begun within 48 hours. Confirmation of the benefits suggested by post hoc analyses for the subgroup treated with 120 mg nimodipine within 18 hours, and who had negative computed tomographic scans, would require a separate trial.", "In a randomized double-blind placebo-controlled study of 27 patients with acute ischemic stroke, the effect on regional CMRglc (rCMRglc) of the calcium channel blocking agent nimodipine administered in addition to routine treatment was investigated. Following computed tomography-supported diagnosis of focal ischemia in the middle cerebral artery territory, positron emission tomography (PET) of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was performed, and the patients were entered into the study within 48 h after onset of symptoms, randomly receiving either nimodipine (2 mg/h constant i.v. infusion for 5 days, 120 mg/day orally for another 16 days) or carrier/placebo. FDG PET was repeated after completion of therapy. The clinical course was followed during the treatment period and for 6 months after the stroke, using the Mathew Score for early and the Barthel Index for late assessment. During that observation period, five patients died in the nimodipine group and four in the control group. Subsequently, the code was broken, and the clinical and PET data were analyzed in relation to treatment assignment, with the nimodipine group comprising 11 and the control group 12 eligible cases. The two groups were similar with respect to age and sex distribution, initial clinical deficit, and infarct size and location. While the infarct rCMRglc showed comparable slight increases over time in both groups, the metabolic changes in the other evaluated regions (contralateral infarct mirror region, ipsi- and contralateral cerebral gray matter, contra- and ipsilateral cerebellar hemispheres) differed significantly between treatment groups (side x region x treatment interaction p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)", "A multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of fasudil, a Rho-kinase inhibitor (RKI), in the treatment of acute ischemic stroke.\n A total of 160 patients, who were able to receive drug treatment within 48 h of acute ischemic stroke onset were enrolled. Patients received either 60 mg fasudil or a placebo (saline) by intravenous injection over 60 min, twice daily for 14 days. The primary end points were neurological status at 2 weeks after the start of treatment, and clinical outcome at 1 month after the onset of symptoms.\n Fasudil treatment resulted in significantly greater improvements in both neurological functions (p=0.0013), and clinical outcome (p=0.0015). There were no serious adverse events reported in the fasudil group. The average trough value (12 h values) of active metabolite hydroxyfasudil, another RKI, in healthy elderly volunteers receiving 60 mg of fasudil was 0.077 microM-a concentration well above that needed to inhibit Rho-kinase (0.025-0.05 microM).\n Treatment with fasudil within 48 h of acute ischemic stroke onset significantly improved the patient's clinical outcome. This study found fasudil to be a useful and safe drug for patients with acute ischemic stroke. Further evaluations, for example, 3-month functional outcomes in a larger clinical trial, may help to define the efficacy of fasudil in acute ischemic stroke." ]

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[ "Randomised clinical trial of Hydrofiber dressing with silver versus povidone-iodine gauze in the management of open surgical and traumatic wounds.", "Outpatient management of partial-thickness burns: Biobrane versus 1% silver sulfadiazine.", "Prospective comparison of silver sulfadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent (Silvazine) and silver sulfadiazine 1 per cent (Flamazine) as prophylaxis against burn wound infection.", "DuoDERM hydroactive dressing versus silver sulphadiazine/Bactigras in the emergency treatment of partial skin thickness burns.", "Prospective evaluation of topical antibiotics for preventing infections in uncomplicated soft-tissue wounds repaired in the ED.", "A liposome hydrogel with polyvinyl-pyrrolidone iodine in the local treatment of partial-thickness burn wounds.", "Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of partial-thickness burn wounds.", "A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds.", "The use of silver coated dressings on donor site wounds: a prospective, controlled matched pair study.", "Collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine cream in partial-thickness burns: a pilot study.", "Biosynthetic skin substitute vs. 1% silver sulfadiazine for treatment of inpatient partial-thickness thermal burns.", "An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns.", "Wound healing in partial-thickness burn wounds treated with collagenase ointment versus silver sulfadiazine cream.", "Evaluation of Bensal HP for the treatment of diabetic foot ulcers.", "A comparison of topical Phenytoin with Silverex in the treatment of superficial dermal burn wounds.", "A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury.", "Prospective randomized controlled study of Hydrofiber dressing containing ionic silver or calcium alginate dressings in non-ischaemic diabetic foot ulcers.", "Safety and efficacy of TransCyte for the treatment of partial-thickness burns.", "A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine.", "Comparison of a hydrocolloid dressing and silver sulfadiazine cream in the outpatient management of second-degree burns.", "[Treatment of venous ulcera cruris with dry wound dressings. Phase overlapping use of silver impregnated activated charcoal xerodressing].", "Randomized clinical study of Hydrofiber dressing with silver or silver sulfadiazine in the management of partial-thickness burns.", "Prospective clinical study of Hydron, a synthetic dressing, in delivery of an antimicrobial drug to second-degree burns." ]

[ "This prospective, randomised clinical trial compared pain, comfort, exudate management, wound healing and safety with Hydrofiber dressing with ionic silver (Hydrofiber Ag dressing) and with povidone-iodine gauze for the treatment of open surgical and traumatic wounds. Patients were treated with Hydrofiber Ag dressing or povidone-iodine gauze for up to 2 weeks. Pain severity was measured with a 10-cm visual analogue scale (VAS). Other parameters were assessed clinically with various scales. Pain VAS scores decreased during dressing removal in both groups, and decreased while the dressing was in place in the Hydrofiber Ag dressing group (n = 35) but not in the povidone-iodine gauze group (n = 32). Pain VAS scores were similar between treatment groups. At final evaluation, Hydrofiber Ag dressing was significantly better than povidone-iodine gauze for overall ability to manage pain (P < 0.001), overall comfort (P < or = 0.001), wound trauma on dressing removal (P = 0.001), exudate handling (P < 0.001) and ease of use (P < or = 0.001). Rates of complete healing at study completion were 23% for Hydrofiber Ag dressing and 9% for povidone-iodine gauze (P = ns). No adverse events were reported with Hydrofiber Ag dressing; one subject discontinued povidone-iodine gauze due to adverse skin reaction. Hydrofiber Ag dressing supported wound healing and reduced overall pain compared with povidone-iodine gauze in the treatment of open surgical wounds requiring an antimicrobial dressing.", "A randomized, prospective study comparing the use of Biobrane (group 1) with the use of 1% silver sulfadiazine (group 2) in treating 56 partial-thickness burn wounds was carried out in 52 outpatients with burns that comprised less than 10% of their total body surface area. The two groups were similar in age, gender, race, and extent of burn. Wounds of patients in group 1 (30) were compared with those of group 2 (26) for healing time, pain, compliance with scheduled visits, and costs. Infected and skin-grafted wounds were excluded from healing time analysis. Infection rates of the two groups were similar (three of 30 vs two of 26). One patient in each group underwent skin grafting. Healing times of group 1 wounds were significantly less than those of group 2 (10.6 +/- 0.8 vs 15.0 +/- 1.2 days, P less than .01). Using a pain scale of 1 to 5, Biobrane-treated patients averaged lower pain scores at 24 hours after the burn (1.6 +/- 0.8 vs 3.6 +/- 1.3 P less than .001) and used less pain medication. Compliance with scheduled outpatient visits was also improved in the Biobrane-treated group (88.6% vs 63.2% attendance, P less than .001). Idealized total treatment costs averaged $434 for patients in group 1 compared with $504 for patients in group 2. We conclude that when used on properly selected wounds, Biobrane therapy can significantly decrease pain and total healing time without increasing the cost of outpatient burn care. Improved patient compliance may be an added benefit.", "Patients with fresh full-thickness burn wounds were randomly assigned to receive wound treatment with daily applications of either 1 per cent silver sulfadiazine plus 0.2 per cent chlorhexidine digluconate cream (Silvazine) or 1 per cent silver sulfadiazine (Flamazine). Fifty-four patients treated with Silvazine were comparable to 67 treated with Flamazine with respect to extent and distribution of burn, age and all aspects of wound and associated treatment. Overall incidence of wound bacterial colonization was less in the Silvazine treated patients (65 per cent versus 88 per cent; P = 0.002). With Silvazine, wound colonization by Staphylococcus aureus was less (41 per cent versus 64 per cent; P = 0.01). Clinical wound infection with Staph, aureus developed in one Silvazine treated patient and five Flamazine treated patients (P = 0.16). Colonization by and infection due to all other organisms did not differ in the two groups. The incidence of graft failure was similar with both agents. In future increasing the concentration of chlorhexidine digluconate above 0.2 per cent might produce an improved prophylactic effect against Gram negative bacteria reported by other authors using the combined agent in in vitro and clinical trials. Silvazine was effective in reducing the incidence of Staph. aureus burn wound colonization without fostering supervening opportunistic infection.", "The study compared DuoDERM Burn Pack Hydroactive Dressings (DHD) with silver sulphadiazine/Bactigras dressings (SSD/Bactigras) in the outpatient management of small partial skin thickness burns. Forty-eight patients were entered into the study, and randomly allocated into either the DHD or SSD/Bactigras group. Burn wounds were followed until complete re-epithelialization occurred. There were no statistical differences between the groups, either with respect to their composition or characteristics of healing in days, and patients' subjective responses to treatment. However, application was easier in the DHD group (93 per cent), compared with 71 per cent in the SSD/Bactigras group (P = 0.0009), and the SSD/Bactigras were easier to remove (96 per cent) versus DHD (66 per cent, P = 0.0004). Furthermore, the DHD group had significantly less dressing changes; a mean of three changes per subject in the DHD group compared with eight in the SSD/Bactigras group (P = 0.117). Two burn wounds became infected in the DHD group, and one in the SSD/Bactigras group. In this study both modalities were found to be equally suitable and effective for small partial skin thickness burns.", "To determine differences in infection rates among uncomplicated, repaired wounds managed with: topical bacitracin zinc (BAC); neomycin sulfate, bacitracin zinc, and polymyxin B sulfate combination (NEO); silver sulfadiazine (SIL); and petrolatum (PTR).\n This was a prospective, randomized, double-blind, placebo-controlled study conducted at a military community hospital with an emergency medicine residency program. Patients were enrolled if they: presented to the ED within 12 hours of injury and did not have puncture wounds, allergies to the agents used, or a history of immunocompromise; were not receiving antibiotics, chemotherapy, or steroids at the time of presentation; had not taken antibiotics within the preceding seven days; did not have an underlying fracture; and were not pregnant as determined by history. Local anesthetics without epinephrine and high-pressure irrigation with normal saline were used for all patients. Wound scrubbing, débridement, and polyglactin subcutaneous (SQ) suture placement were carried out when necessary. Interrupted simple sutures using a monofilament, nonabsorbable material were used for skin closure. Numbered, randomized vials were given to all patients, with standardized instructions to inspect, clean, and redress their wounds three times a day. The wounds were evaluated for clinical infection at the time of follow-up.\n Among the groups, there was no difference in patient ages; gender; wound location, type, length, or depth; time elapsed from injury to ED treatment; number of wounds scrubbed or necessitating débridement; number of SQ and cutaneous sutures used; and rate of compliance with returning the used vial of dispensed topical agent. The wound infection rates for the treatment groups were: BAC, six of 109 (5.5%); NEO, five of 110 (4.5%); SIL, 12 of 99 (12.1%); and PTR, 19 of 108 (17.6%) (p = 0.0034).\n The use of topical antibiotics resulted in significantly lower infection rates than did the use of a petrolatum control. BAC and NEO had the lowest wound infection rates.", "Local treatment of burn injuries with conventional anti-infective preparations does not provide the moist environment that promotes fast wound healing. In a randomized controlled trial the effects of liposome polyvinyl-pyrrolidone-iodine (PVP-I) hydrogel, a novel formulation of PVP-I in a liposome hydrogel with high water-binding capacity, were investigated in 43 patients with partial-thickness burn wounds in an intraindividual comparison with a conventional silver-sulfadiazine cream. Treatment with liposome PVP-I hydrogel resulted in significantly faster complete healing of the burn wounds compared with silver-sulfadiazine cream (9.9 +/- 4.5 days versus 11.3 +/- 4.9; P < 0.015). The cosmetic result (smoothness, elasticity, appearance) was rated as excellent for 37.0% of study wounds with liposome PVP-I hydrogel compared with 13.0% of wounds treated with silver-sulfadiazine cream. Local tolerability was good; handling and change of dressing were rated as easy. Local treatment with liposome PVP-I hydrogel thus provides fast wound healing with a favorable cosmetic result.", "Acticoat (Smith & Nephew, Hull, UK) is a silver-coated dressing reported to reduce infection and exhibit antimicrobial activity in wounds.\n The purpose of the present study was to compare the efficacy ofacticoat and 1% silver sulfadiazine (1% AgSD) for treatment of partial thickness burn wounds.\n The authors reviewed 50 patients who had partial thickness burn wounds less than 25% admitted to Siriraj Burn Unit from May 2002 to September 2005. All patients were divided into 2 groups: the acticoat treated group (25 patients) and the 1% silver sulfadiazine treated group (25 patients). The 2 groups were compared for the etiology of burn wound, demographic data including age, sex, % Total Body Surface Area burn (TBSA%), cultured organisms, wound infection and outcome of Length Of hospital Stay (LOS) and level of pain.\n The authors found no significant differences in age, TBSA (%) between both groups. 7 patients (28%) developed wound infection. There were no differences in wound infection and LOS between both groups (p > 0.05). All of the patients who developed wound infection responded well to targeted topical and systemic antibiotic treatment. The 1% AgSD treated group (6 of 25, 24%) obtained more split thickness skin graft to close the granulation defects compared to patients who were treated with acticoat (4 of 25, 16%) but no statistical significance, p = 0.32). Average pain scores in the acticoat treated groups were significantly lower than the 1% AgSD treated group (4 +/- 0.6 versus 5 +/- 0.7, respectively).\n The present study confirms the efficacy of acticoat treatment in partial thickness burn wound. The authors conclude that acticoat has an advantage of limiting the frequency of replacement of the dressing and provides a less painful alternative to wound care with 1% AgSD with comparable incidence of burn wound infection. This is due to its long wear time and the ease of application and removal.", "A new silver-coating technology was developed to prevent wound adhesion, limit nosocomial infection, control bacterial growth, and facilitate burn wound care through a silver-coated dressing material. For the purposes of this article, Acticoat (Westaim Biomedical Inc, Fort Saskatchawan, Alberta, Canada) silver-coated dressing was used. After in vitro and in vivo studies, a randomized, prospective clinical study was performed to assess the efficacy and ease of use of Acticoat dressing as compared with the efficacy and ease of our institution's standard burn wound care. Thirty burn patients with symmetric wounds were randomized to be treated with either 0.5% silver nitrate solution or Acticoat silver-coated dressing. The dressing was evaluated on the basis of overall patient comfort, ease of use for the wound care provider, and level of antimicrobial effectiveness. Wound pain was rated by the patient using a visual analog scale during dressing removal, application, and 2 hours after application. Ease of use was rated by the nurse providing wound care. Antimicrobial effectiveness was evaluated by quantitative burn wound biopsies performed before and at the end of treatment. Patients found dressing removal less painful with Acticoat than with silver nitrate, but they found the pain to be comparable during application and 2 hours after application. According to the nurses, there was no statistically significant difference in the ease of use. The frequency of burn wound sepsis (> 10(5) organisms per gram of tissue) was less in Acticoat-treated wounds than in those treated with silver nitrate (5 vs 16). Secondary bacteremias arising from infected burn wounds were also less frequent with Acticoat than with silver nitrate-treated wounds (1 vs 5). Acticoat dressing offers a new form of dressing for the burn wound, but it requires further investigation with greater numbers of patients in a larger number of centers and in different phases of burn wound care.", "Acticoat, a new silver-coated dressing, produces a moist healing environment along with the sustained release of ionic silver for improved microbial control. These properties suggest that Acticoat might be a useful donor site dressing. However, there are no human studies which assess Acticoat for this use. The purpose of this study was to compare the healing of human skin graft donor sites dressed with Acticoat, to the healing of those dressed with Allevyn, an occlusive moist-healing environment material, which is our standard donor site dressing. In burn patients who had undergone burn excision and grafting, identical side-by-side split thickness donor site wound pairs were dressed with Allevyn and Acticoat. Re-epithelialization was directly assessed daily by a single observer from post-operative day 6 onward, and by four independent observers who rated the extent of re-epithelialization by viewing standardized digital images of the wounds that had been obtained on post-operative days 6, 8, 10,and 12. Donor sites were swabbed for bacterial culture on days 3, 6, and 9. Subsequently, each study donor site scar was rated by a blinded observer using the Vancouver Scar Scale at 1, 2, and 3 months. Sixteen paired sites in 15 patients (3 female, 12 male) were studied. Donor sites dressed with Allevyn were >90% re-epithelialized at a mean of 9.1+/-1.6 days while donor sites dressed with Acticoat required a mean of 14.5+/-6.7 days to achieve >90% re-epithelialization (P=0.004). The Allevyn sites had significantly greater estimated re-epithelialization at days 6, 8, 10 and 12 than the Acticoat sites based on the observations of the digital images. There were no significant differences in the incidence of positive bacterial cultures with either dressing at days 3, 6, and 9. Donor sites dressed with Acticoat had significantly worse scars at 1 and 2 months but this difference resolved by 3 months. Our findings do not support the use of Acticoat as a skin graft donor site dressing.", "A multifaceted approach that involves early debridement and control of infection is critical to successful and rapid burn wound healing. This pilot study was conducted in 15 adult patients with burns to assess the usefulness of early enzymatic debridement with a combination of collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine cream in partial-thickness burns. Combination treatment with collagenase and polymyxin B sulfate/bacitracin resulted in significantly shorter time to achieve a clean wound bed than silver sulfadiazine (median 6 vs 12 days; p = 0.0012) and significantly more rapid wound healing than silver sulfadiazine (median 10 vs 15 days; p = 0.0007). These results are encouraging and justify implementation of a larger, multicenter, comparative study.", "When used appropriately on superficial or moderate-depth partial-thickness burns, Biobrane significantly decreased total healing time to complete reepithelialization, reduced pain, and was associated with decreased nursing time and costs when compared to 1% silver sulfadiazine cream. Care must be used in selecting wounds for Biobrane therapy. They must be fresh, noninfected, and free of eschar and debris with a moist, sensate surface that demonstrates capillary blanching and refill. Wounds must be inspected regularly for nonadherence and signs of infection. Early fluid accumulation requires prompt aspiration. Biobrane should be removed if fluid reaccumulates or the Biobrane becomes nonadherent at any time after 48 hours. When used appropriately, Biobrane offers significant advantages over conventional therapy of acute partial-thickness burns.", "Sixty patients with moderate and severe burns were randomly assigned to receive topical silver sulfadiazine (SSD) alone (n=30) or SSD combined with cerium nitrate (SSD-CN) (n=30). There were four deaths in the SSD group and one in the SSD-CN group; more patients with higher risk severity survived in the SSD-CN group. Wound infection did not differ significantly between the groups. The rate of re-epithelialization of partial thickness burns was faster by 8 days in the SSD-CN group. The relatively dry shell-like eschar of the SSD-CN-treated burn allowed planned excisions with immediate autologous grafting and the tissue beneath was ready to accept grafting 11 days earlier than in the SSD group (p=0.03). This resulted in a significantly shorter hospital stay for those in the SSD-CN group than in the SSD group (23.3 vs. 30.7 days; p=0.03) with consequent cost savings. A higher incidence of transient stinging pain was reported with application of SSD-CN, but this was effectively managed with analgesics where necessary. The results of this study confirm the greater efficacy of SSD-CN in the treatment of burns patients.", "During burn care the wounds must be repeatedly debrided of adherent and loose debris until the decision is made to surgically excise and graft the wound or to await epithelialization. Though native proteolytic enzymes in the skin or those produced by colonizing bacteria can speed eschar separation, the use of exogenous enzymes for wound debridement may accelerate wound cleaning and healing. Collagenase digests native and denatured collagen in necrotic tissue. This multicenter trial of 79 patients with partial-thickness wounds compared the efficacy of collagenase ointment applied with polymyxin B sulfate/bacitracin powder with the efficacy of standard topical antimicrobial therapy (control) in which silver sulfadiazine cream (1%) was used to debride paired burn sites. Patients selected for the study had two noncontiguous, partial-thickness, comparably sized, and anatomically similar burn wounds. Ages of patients ranged from 5 to 60 years (mean 33 years). The total body surface area burned ranged from 2% to 30% (mean 13.6%). Mean burn sizes used for study treatment were 366 cm2 (26 to 2310 cm2) for collagenase sites and 355 cm2 (26 to 2394 cm2) for control sites. Sites on each patient were randomly assigned to treatment with either collagenase or control. Endpoints were time to clean wound bed (absence of retained debris) and time to healing (complete epithelialization). The sites treated with collagenase cleaned in less time (mean 9.3 days) than the control sites (mean 11.6 days). Similarly the collagenase sites healed faster than the control sites (mean 19 vs 22.1 days).(ABSTRACT TRUNCATED AT 250 WORDS)", "The extract of oak bark (QRB7) has been used for years as a topical medication with success. QRB7 is the proprietary oak bark extract in Bensal HP. It is indicated as an external treatment for the inflammation and irritation associated with many common forms of dermatitis, including certain eczematoid conditions. These conditions include complications associated with pyodermas, and in the treatment of insect bites, burns, and fungal infections.\n To quantitatively measure the difference in diabetic ulcer size reduction when using Bensal HP versus silver sulfadiazine cream (SSC) for topical treatment as an adjunct to conventional treatment.\n Private office of the primary author.\n Forty diabetic patients with noncellulitic plantar Wagner grade 1 or 2 ulcers and a minimal ankle brachial index of 0.75 were randomly assigned to either the Bensal HP (QRB7) treatment group or SSC control group for 6 weeks of treatment. In addition to either Bensal HP or SSC, all wounds were cultured and treated with debridement at time 0, 2, 4, and 6 weeks and with off-loading.\n The combined wound diameter of the Bensal HP group decreased 72.5% compared to 54.7% for the SSC group. There was a statistical significance between the decreases in wound sizes after 6 weeks of treatment (P = .016). The Cohen effect size for the Bensal HP group was 2.06 compared with 1.03 for the SSC group.\n In this tightly controlled 6-week study in which no patients were lost to follow-up, Bensal HP seems to be an effective treatment for properly treated diabetic ulcers, outperforming an identical control group whose only difference was SSC as a medication.", "To compare topical diphenylhydantion (Phenytoin) with silver sulphadiazine/chlorhexidine (Silverex) in terms of rate of wound healing, analgesic and antibacterial properties in small to moderate-sized (< 30% TBSA) superficial dermal (second degree) burn wounds.\n A prospective randomized controlled study.\n Surgical wards, Muhimbili National Hospital from July 2000 to February 2001.\n Sixty four patients with acute burns, 32 in each group.\n Study group treated by sprinkling Phenytoin powder and control group by sprinkling Silverex powder on the wounds for 14 days or until the wound epithelialised or was ready for skin grafting. The data collected included demographic characteristics of patients, aetiology of burn injury, circumstances of injury, site and extent of burns, pus discharge and smell from the wound, pain and discomfort from the wound, bacterial cultures of wound swabs, rate of reduction in wound size and outcome of treatment.\n The study enrolled 33 male and 31 female patients, 69% being children under five years of age. Hot liquids (80%) and open flames (20%) were the only causes of burns. In 97% of patients injury was due to domestic accidents. In half of the patients burns involved the trunk, and 52% of all patients had less than 15% total body surface burnt. Pus discharge was recorded in 59% of Phenytoin-treated and 75% in Silverex-treated patients while foul smell was noted in 19% and 31% of cases respectively. There were more negative bacterial wound cultures in Phenytoin-than Silverex-treated wounds on day five and day 10 of treatment, the difference being statistically significant (p < 0.01 and 0.001 respectively). There was also a statistically significant difference in wound pain in favour of Phenytoin (p < 0.01). There was no statistically significant difference in the rate of healing in the two groups.\n Phenytoin is a cheap and easy-to-use medicament, effective in suppressing burn wound bacteria and relieving pain thereby promoting healing, and may be advocated for the purpose in resource-scarce environments.", "We prospectively studied 52 consecutive patients who were treated by early tangential excision and grafting following thermal injury. The usefulness of two topical antimicrobial agents--0.5% silver nitrate (Ag) and neomycin (1 gm/liter) plus bacitracin (50,000 units/liter) (NB)--was compared with the effectiveness of Ringer's lactate (RL) for prevention of autogenous skin-graft loss due to infection. Graft loss of 10 percent or more occurred in 17 patients (33 percent)--due to infection in 16. Skin-graft loss was a minor problem in patients with less than 20 percent total body surface area (TBSA) burn (Ag: 0 of 6, NB: 1 of 6, RL: 1 of 5). The use of either antimicrobial (Ag or NB) resulted in less graft loss (1 of 14) than RL (4 of 6; p less than 0.05) in the 20 to 40 percent TBSA burn group. Large burns (greater than 40 percent) had a very high incidence of at least 10 percent graft loss (67 percent) regardless of treatment. Infection in the area of graft loss was caused by antibiotic-resistant organisms or yeast in 50 percent of the Ringer's lactate group and the entire neomycin plus bacitracin group. No graft infections were caused by resistant organisms or yeast in the silver nitrate group. This study demonstrates that topical antimicrobial agents reduce infection-related skin-graft loss in patients with medium-sized (20 to 40 percent TBSA) burns and that neomycin plus bacitracin is associated with rapid emergence of drug-resistant organisms whereas silver nitrate is not.", "Diabetic foot ulcers (DFUs) are at risk of infection and impaired healing, placing patients at risk of lower extremity amputation. DFU care requires debridement and dressings. A prospective, multicentre study compared clinical efficacy and safety of AQUACEL Hydrofiber dressings containing ionic silver (AQAg) with those of Algosteril calcium alginate (CA) dressings in managing out-patients with Type 1 or 2 diabetes mellitus and non-ischaemic Wagner Grade 1 or 2 DFUs.\n Patients stratified by antibiotic use on enrolment were randomly assigned to similar protocols including off-loading, AQAg (n = 67) or CA (n = 67) primary dressings and secondary foam dressings for 8 weeks or until healing. Clinical efficacy measures were healing outcomes and primarily healing speed. Adverse events were recorded.\n AQAg and CA groups were comparable at baseline. All ulcer healing outcomes improved in both groups. The mean time to healing was 53 days for AQAg ulcers and 58 days for CA ulcers (P = 0.34). AQAg-treated ulcers reduced in depth nearly twice as much as CA-treated ulcers (0.25 cm vs. 0.13 cm; P = 0.04). There was more overall ulcer improvement and less deterioration in AQAg subjects (P = 0.058), particularly in the subset initially using antibiotics (P = 0.02). Safety profiles of both groups were similar.\n When added to standard care with appropriate off-loading, AQAg silver dressings were associated with favourable clinical outcomes compared with CA dressings, specifically in ulcer depth reduction and in infected ulcers requiring antibiotic treatment. This study reports the first significant clinical effects of a primary wound dressing containing silver on DFU healing.", "Standard treatment for extensive partial-thickness burns in the United States and in much of the world involves the application of topical antimicrobial agents and repetitive wound débridements and dressing changes. We evaluated a new biologic wound covering, TransCyte (Advanced Tissue Sciences, La Jolla, Calif, formerly marketed as Dermagraft-Transitional Covering), for the treatment of partial-thickness burns. This material is composed of human newborn fibroblasts which are then cultured on the nylon mesh of Biobrane (Dow B. Hickam, Inc, Sugarland, Tex); the thin silicone membrane bonded to the mesh provides a moisture vapor barrier for the wound. A prospective, randomized, comparison study of silver sulfadiazine and TransCyte was performed with the use of paired wound sites on 14 patients. Wounds treated with TransCyte healed more quickly (mean 11.14 days to 90% epithelialization vs 18.14 days, P = .002). A noncomparison evaluation was then done for an additional 18 patients, and it confirmed excellent wound healing and an absence of infections. There were no infections in the 32 wound sites treated with TransCyte. In the first study group, late wound evaluations (3, 6, and 12 months postburn) were performed with use of the Vancouver Scar Scale. The results indicated that wound sites treated with TransCyte healed with less hypertrophic scarring than sites treated with silver sulfadiazine (P < .001 at 3 and 6 months, P = .006 at 12 months).", "Histological and clinical studies of wound healing have been made on comparable fresh partial thickness burns with honey dressing or silver sulfadiazine (SSD) in two groups of 25 randomly allocated patients. Of the wounds treated with honey 84 per cent showed satisfactory epithelialization by the 7th day, and in 100 per cent of the patients by the 21st day. In wounds treated with silver sulfadiazine, epithelialization occurred by the 7th day in 72 per cent of the patients and in 84 per cent of patients by 21 days. Histological evidence of reparative activity was seen in 80 per cent of wounds treated with the honey dressing by the 7th day with minimal inflammation. Fifty two per cent of the silver sulfadiazine treated wounds showed reparative activity with inflammatory changes by the 7th day. Reparative activity reached 100 per cent by 21 days with the honey dressing and 84 per cent with SSD. Thus in honey dressed wounds, early subsidence of acute inflammatory changes, better control of infection and quicker wound healing was observed while in the SSD treated wounds sustained inflammatory reaction was noted even on epithelialization.", "The purpose of this prospective randomized study was to evaluate the use of an occlusive hydrocolloid dressing (Duoderm hydroactive, Squibb) and silver sulfadiazine (Silvadene, Marion) cream in the outpatient management of second-degree burns. The inclusion criteria consisted of burns less than 15% total body surface area that were evaluated within 24 hours of injury and did not require hospital admission. Fifty patients were randomly assigned after having been screened through a list of seven exclusion criteria. On initial evaluation the burns were photographed and screened for causative agent, location, size, depth, tetanus status, and presence of associated burns and injuries. Patients were seen in followup at least biweekly and evaluated for wound bed healing, wound margin healing, pain, number of dressing changes between visits, and ease of dressing application and removal. On final evaluation the burns were photographed and inspected for appearance of the healed burn, repigmentation, wound contraction, approximate time for dressing change, patient compliance, limitation of activity, overall impression of the treatment, and number of days for complete healing. Results were compared using a two-tailed t-test with p less than 0.01. Both groups were statistically similar in age, sex, and size. Duoderm-treated burns had statistically significantly better wound healing, repigmentation, less pain, fewer dressing changes, less time for dressing changes, and less cost. Duoderm-treated patients had statistically significantly less limitation of activity, better patient compliance, greater patient comfort, better overall acceptance, and felt the treatment was more aesthetically pleasing. The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns.", "In a controlled randomized study on 40 patients with venous leg ulcers, monotherapy with a dry wound dressing (silver-impregnated--activated charcoal xerodressing; SIAX) was tested. The xerodressing was applied throughout the entire study and was compared with the conventional phase-adapted therapy using diverse topical modalities, e.g. as granulating ointments, zinc paste. etc. The parameters of wound healing were documented in the two randomized groups over 6 weeks and were statistically evaluated. In the statistical comparison of SIAX therapy (n = 19) and conventional therapy (n = 19) significant differences were found in favour of the SIAX group (increase of epithelialization, reduction of ulcer size; P less than 0.05). In addition, the ulcers of 6/19 patients (= 31.6%) treated with SIAX healed completely within the study period, in contrast to only 2/19 patients (= 10.5%) receiving conventional therapy. Exudate, granulation and colonization of the ulcers as well as odour, necroses, erythema and oedema of the surrounding areas were not significantly different. The study shows that a consistent therapy performed with dry wound dressings such as SIAX is superior to the conventional topical therapy of venous leg ulcers in some cases. Wound dressings provide new therapeutic modalities, being easy to apply and fully efficient, without side-effects.", "This prospective, randomized study compared protocols of care using either AQUACEL Ag Hydrofiber (ConvaTec, a Bristol-Myers Squibb company, Skillman, NJ) dressing with silver (n = 42) or silver sulfadiazine (n = 42) for up to 21 days in the management of partial-thickness burns covering 5% to 40% body surface area (BSA). AQUACEL Ag dressing was associated with less pain and anxiety during dressing changes, less burning and stinging during wear, fewer dressing changes, less nursing time, and fewer procedural medications. Silver sulfadiazine was associated with greater flexibility and ease of movement. Adverse events, including infection, were comparable between treatment groups. The AQUACEL Ag dressing protocol tended to have lower total treatment costs (Dollars 1040 vs. Dollars 1180) and a greater rate of re-epithelialization (73.8% vs 60.0%), resulting in cost-effectiveness per burn healed of Dollars 1,409.06 for AQUACEL Ag dressing and Dollars 1,967.95 for silver sulfadiazine. A protocol of care with AQUACEL(R) Ag provided clinical and economic benefits compared with silver sulfadiazine in patients with partial-thickness burns.", "This clinical trial prospectively evaluates the potential beneficial effects of antimicrobial drug delivery from a synthetic dressing (Hydron-AgSD) formed on second-degree burn wounds. A paste composed of polyethylene glycol-400, poly 2-OH ethylmethacrylate, and silver sulfadiazine (AgSD 1%-3%) matured within one hour to form a solid dressing. In 27 patients, comparable areas of second-degree wounds on the same patient were selected at random for test and control (silver sulfadiazine 1% only) sites. The mean total time of the synthetic dressing application per patient was about nine days, and each dressing remained in place for nearly four days. During this interval the control sites required four dressings changes. In 17 tests for infections, the control areas were contaminated but no bacteria were detected under the synthetic dressing; in three tests, the controls had no bacteria, whereas the synthetic dressing did. Healing of burns was similar under both types of dressing. Benefits of Hydron treatment included increased patient comfort because of the reduced number of dressing changes and, in some cases, greater freedom from contaminating bacteria." ]

[ "9691162", "1904090" ]

[ "Hyperglycemia in extremely- low-birth-weight infants.", "A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance." ]

[ "The cause of hyperglycemia in extremely-low-birth-weight (ELBW) infants is not well understood. We studied infants weighing <1,000 g to investigate the relationship of hyperglycemia to blood levels of insulin-like growth factor (IGF)-I and IGF-II. We also compared two methods of treatment for hyperglycemia: continuous insulin infusion and reduction of glucose intake. Fifty-six ELBW infants were enrolled on day 2 of life. Intravenous glucose intake was increased incrementally to a maximum of 12 mg/kg/min on day 6. Infants who developed hyperglycemia were randomly assigned to receive reduced glucose intake (n = 11) or insulin infusion (n = 12). Infants whose blood sugar remained normal served as controls (n = 33). Blood was drawn on days 3, 8 and 15 in all infants, and again when they developed hyperglycemia. Nutritional intake and laboratory results for the treatment groups were compared with controls. Hyperglycemic infants had lower birth weights than controls. Hyperglycemic infants treated with glucose reduction remained <60 kcal/kg/day longer than control or insulin infusion groups (8.6 +/- 1.3 days vs. 4.1 +/- 0.2 and 5.5 +/- 0.6 days). No infants became hypoglycemic during insulin infusion. There was no difference in baseline blood levels of IGF-I or IGF-II among the groups, and these growth factors did not change in response to hyperglycemia. Hyperglycemic infants had baseline levels of insulin which were similar to normal controls, and endogenous insulin increased in response to hyperglycemia in 15 of the 23 infants who developed hyperglycemia. IGF-I and IGF-II are not related to hyperglycemia. In our population, hyperglycemic infants did not have baseline insulin deficiency and most had a normal insulin response to hyperglycemia. Insulin infusion appears safe in these infants and helped to maintain normal caloric intake, whereas glucose reduction was associated with a prolonged caloric deprivation.", "To determine whether a continuous insulin infusion improves glucose tolerance in extremely low birth weight infants, we conducted a prospective, randomized trial in 24 neonates 4 to 14 days old (mean birth weight 772.9 +/- 128 gm; mean gestational age 26.3 +/- 1.6 weeks). Infants who had glucose intolerance were randomly assigned to receive either intravenous glucose and total parenteral nutrition with insulin through a microliter-sensitive pump or standard intravenous therapy alone. One infant assigned to receive insulin never required it. The groups were similar in birth weight, gestational age, race, gender, medical condition, and energy intake before the study. The mean duration of therapy was 14.6 days (range 7 to 21 days). During the study, the 11 insulin-treated infants tolerated higher glucose infusion rates (20.1 +/- 2.5 vs 13.2 +/- 3.2 mg/kg/min (1.1 +/- 0.1 vs 0.7 +/- 0.2 mmol/L); p less than 0.01), had greater nonprotein energy intake (124.7 +/- 18 vs 86.0 +/- 6 kcal/kg/day; p less than 0.01), and had better weight gain (20.1 +/- 12.1 vs 7.8 +/- 5.1 gm/kg/day; p less than 0.01) than the 12 control infants. The incidence of hypoglycemia, electrolyte imbalance, chronic lung disease, and death did not differ between groups. We conclude that a controlled insulin infusion improves and sustains glucose tolerance, facilitates provision of calories, and enhances weight gain in glucose-intolerant premature infants." ]

[ "9812111", "10928308", "11087767", "10496251", "9447502" ]

[ "A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.", "Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment.", "Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.", "A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia.", "Pilot study of haloperidol, fluoxetine, and placebo for agitation in Alzheimer's disease." ]

[ "The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease.\n In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol.\n For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects.\n The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.", "The aim of the present study was to compare the efficacy and safety of tiapride versus haloperidol and placebo in the treatment of agitation and aggressiveness in elderly patients with mild or moderate mental impairment.\n This international, multicentre, randomized, double blind, three parallel groups study compared efficacy and safety of a 21 -day regimen of tiapride 100-300 mg/day versus haloperidol 2-6 mg/day and placebo in 306 elderly patients with mild or moderate dementia according to DSM III R and behavioural troubles with the Multidimensional Observation Scale for the Elderly Subjects (MOSES) irritability/aggressiveness subscore ranging from 16 to 30.\n The percentage of responders (defined as patients with at least a 25% MOSES irritability/aggressiveness subscore decrease between the inclusion and the end of the treatment) was significantly greater in the tiapride (63%, P=0.04) and haloperidol (69%, P=0.004) groups than in the placebo group (49%), with no significant difference between the active drugs. Similar results were observed for the mean MOSES irritability/aggressiveness subscores on D7, D21 and at D(end) which were significantly smaller in the tiapride and haloperidol groups than in the placebo group. The decrease between D0 and D(end) was significantly greater in the tiapride (6.57, P=0.009) and haloperidol groups (6.75, P=0.005) than in the placebo group (4.71). The global improvement CGI was significantly better in the tiapride and haloperidol groups than in the placebo group (P=0.03 and P=0.02). No significant difference was observed between the two active drugs or among the three treatment groups for the Folstein's Mini Mental Status scale (MMS) total score, and there was no notable change during treatment. The number of patients with adverse events, assessed on the Udvalg Kliniske Undersogelser scale (UKU), and the number of UKU symptoms were smaller in the tiapride group (62 patients, 61%, 212 events) than in the haloperidol group (77 patients, 76%, 305 events) and identical to that observed in the placebo group (69 patients, 67%, 234 events). Of interest, the number of patients with at least one extrapyramidal symptom was significantly lower (P=0.003) in the tiapride group (16 patients, 16%) than in the haloperidol group (34 patients, 34%) and similar to that of the placebo group (18 patients, 17%); the difference observed between the haloperidol and placebo groups was significant (P=0.008).\n Tiapride is not different from haloperidol in the treatment of agitation and aggressiveness in elderly patients and better tolerated, in particular with significantly fewer extrapyramidal symptoms.", "Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs.\n To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients.\n A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden.\n Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments.\n Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.", "To compare effects of risperidone with placebo (efficacy and tolerability) and haloperidol (tolerability) for treating demented patients with aggression and other behavioral symptoms.\n A 13-week double-blind study involving 344 patients with dementia randomly assigned to receive placebo or flexible doses (0.5 to 4 mg/d) of risperidone or haloperidol. Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression (CGI) scale. Tolerability assessments included the Extrapyramidal Symptom Rating Scale, sedation levels, Functional Assessment Staging, Mini-Mental State Examination, and incidence of adverse events.\n The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Although not significant, a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement (> or =30% reduction from baseline to endpoint in BEHAVE-AD total score) at endpoint and week 12. Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12. In a further analysis of aggression, the most dominant symptom in these patients, BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12. CGI scores were also significantly reduced at endpoint and week 12. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12.\n Low-dose risperidone (mean 1.1 mg/d) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms, particularly aggression, in elderly patients with dementia.", "This pilot study compared haloperidol, fluoxetine, and placebo for reduction of agitation in 15 outpatients with AD. The two drugs were no more effective than placebo at reducing agitation in these subjects; however, both drugs produced more toxicity than did placebo." ]

[ "6346278", "9709721", "6426646" ]

[ "Reactions to booster pneumococcal vaccination in patients with sickle cell disease.", "Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease.", "Prevention of pneumococcal infection in children with homozygous sickle cell disease." ]

[ "Repeat (booster) pneumococcal vaccination was administered to 32 patients with sickle cell disease in a double blind, placebo-controlled crossover study as early as 2.3 years after initial immunization. A significantly greater proportion of patients reported local pain, swelling or redness after booster, as compared to that after placebo (P less than 0.001), and pneumococcal antibody titer before vaccination was the predominant predictive variable for the development of fever, local pain and swelling after booster. A comparison of reaction rates following primary or booster immunization showed no significant differences in the frequency of reported symptoms except for muscle pain which occurred less frequently after booster (P less than 0.005). The concern for adverse reactions after repeat pneumococcal vaccination should not be an obstacle to the pursuit of further studies on the efficacy of pneumococcal vaccine and booster responses.", "We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals > or = 2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine.", "The efficacy of prophylactic penicillin and of 14 valent pneumococcal vaccine in preventing pneumococcal infection in homozygous sickle cell (SS) disease was investigated in 242 children aged 6 months to 3 years at entry. In the first five years of the trial there were 11 pneumococcal infections in the pneumococcal vaccine treated group, 10 by serotypes present in the vaccine. Type 23 accounted for five of these, and there was evidence of higher infection rates in those given the vaccine before age 1. No pneumococcal isolations occurred in the penicillin group while receiving penicillin, although four isolations occurred within one year of stopping penicillin. Probably the most effective prophylaxis against pneumococcal infection requires penicillin beyond the age of 3. The age at which pneumococcal vaccine should be given must await further data on antibody response and clinical efficacy in these patients." ]

[ "6390194", "2875927", "1909085", "8477961" ]

[ "Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone.", "Testosterone treatment of men with alcoholic cirrhosis: a double-blind study. The Copenhagen Study Group for Liver Diseases.", "A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function.", "A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study." ]

[ "A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid (prednisolone) or an anabolic steroid (oxandrolone) in moderate or severe alcoholic hepatitis. One hundred thirty-two patients with moderate disease and 131 with severe disease were randomly assigned to one of three treatments: prednisolone, oxandrolone, or placebo. During the 30 days, mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group. Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died. Although neither steroid improved short-term survival, oxandrolone therapy was associated with a beneficial effect on long-term survival. This was especially true in patients with moderate disease: among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after oxandrolone and 19 to 20 per cent after placebo (P = 0.02). No consistent long-term effect was associated with prednisolone therapy.", "A double-blind, placebo-controlled multicenter trial was conducted to determine the efficacy of oral testosterone treatment (200 mg three times daily) in men with alcoholic cirrhosis. By skewed randomization (3:2), 134 patients received testosterone and 87 placebo. Patients were followed from 8 to 62 months (median = 28 months). In the testosterone group, 33 patients died (25%; 95% confidence limits = 18 to 33%) as compared to 18 (21%; 95% confidence limits = 13 to 31%) in the placebo group. Taking age and significant prognostic variables into consideration, this corresponds with a relative mortality risk of 1.17 (95% confidence limits = 0.65 to 2.15) in the testosterone group vs. the placebo group. Testosterone treatment did not significantly affect liver biochemistry, prevalence of complications to cirrhosis or causes of death. Patients treated with testosterone developed significantly (p less than 0.05) higher serum testosterone and blood hemoglobin concentrations and significantly (p less than 0.05) lower plasma IgM concentrations as compared to the placebo group. The prevalence of gynecomastia decreased significantly (p less than 0.05) in the testosterone group as compared to the placebo group. We conclude that oral testosterone treatment has no beneficial effect on survival and liver biochemistry in men with alcoholic cirrhosis, and adverse effects cannot be excluded.", "The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's-Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35-day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C-leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured.", "A Veterans Affairs cooperative study involving 273 male patients was performed to evaluate efficacy of oxandrolone in combination with an enteral food supplement in severe alcoholic hepatitis. All patients had some degree of protein calorie malnutrition. On an intention-to-treat basis, only minimal changes in mortality were observed. However, in patients with moderate malnutrition mortality on active treatment at 1 mo was 9.4% compared with 20.9% in patients receiving placebo. This beneficial effect was maintained so that after 6 mo on active treatment 79.7% of patients were still alive, compared with 62.7% of placebo-treated patients (p = 0.037). Improvements in both the severity of the liver injury (p = 0.03) and malnutrition (p = 0.05) also occurred. No significant improvement was observed with severe malnutrition. To better determine the effect on therapeutic efficacy, we compared results with those from a nearly identical population (cooperative study 119) treated with oxandrolone but not given the food supplement. Patients were stratified according to their caloric intake (greater than 2,500 kcal/day was considered adequate to supply energy needs and promote anabolism). For patients with moderate malnutrition and adequate caloric intake, oxandrolone treatment reduced 6-mo mortality (4% active treatment vs. 28% placebo [p = 0.002]). For patients with moderate malnutrition and inadequate calorie intake, oxandrolone had no effect on mortality (30% active treatment vs. 33% placebo). In cases of severe malnutrition, oxandrolone had no effect on survival. However, adequate caloric intake was associated with 19% mortality, whereas patients with inadequate intake exhibited 51% mortality (p = 0.0001). These results indicate that nutritional status should be evaluated in patients with alcoholic hepatitis. When malnutrition is present, vigorous nutrition therapy should be provided, and in patients with moderate malnutrition oxandrolone should be added to the regimen." ]

[ "14066183", "14162138", "2358192", "8677772", "14163868", "13545290", "14271801", "1873241", "9236641" ]

[ "INTRAMUSCULAR OXYTOCICS AND CORD TRACTION IN THIRD STATE OF LABOUR.", "OXYTOCIC DRUGS IN FOURTH STAGE OF LABOR.", "Effect of oxytocics on prostaglandin levels in the third stage of labour.", "A placebo-controlled trial of oral ergometrine to reduce postpartum hemorrhage.", "CLINICAL EXPERIENCE WITH SIMULTANEOUS INTRAMUSCULAR INJECTION OF OXYTOCIN AND METHYLERMETRINE.", "A comparison of oxytocic drugs in the management of the placental stage.", "CLINICAL TRIAL OF AN OXYTOCIN-ERGOMETRINE MIXTURE.", "A randomized comparison of oxytocin, sulprostone and placebo in the management of the third stage of labour.", "Routine oxytocin in the third stage of labour: a placebo controlled randomised trial." ]

[ "nan", "nan", "The levels of prostaglandin F2 alpha metabolites (PGFM) in the peripheral blood were measured during third stage in a group of patients not given any oxytocic and this was compared with the levels produced in other groups given different oxytocics. There was a significant rise in PGFM within 5 min of delivery in all groups but there was no statistical difference in the serum concentrations of PGFM between the different groups. This suggests that oxytocics given during third stage do not act through release of prostaglandins.", "Active management with oral ergometrine 0.4 mg was compared with expectant management for the control of blood loss in the third stage of labor in women at low risk of postpartum hemorrhage (PPH).\n A three-arms randomized trial in which 0.4 mg ergometrine (2 tablets of 0.2 mg) was set off against placebo, both groups allowing comparison with a standard oxytocin regimen of 5 IU. Women at low risk for PPH. Of 367 parturients, 146 were randomised to ergometrine 0.4 mg, 143 to placebo and 78 to intramuscular oxytocin in a 2:2:1 design.\n Compared with placebo, ergometrine reduced blood loss with 5% (-5%; Confidence interval: -20% to +13%). Oxytocin reduced blood loss with 9% (-9%; Confidence interval: -26% to +12%) versus placebo.\n Oral ergometrine has too little effect on blood loss after childbirth in order to be a good alternative to parenteral prophylactic management.", "nan", "nan", "nan", "To compare the effect on post partum bloodloss of the postpartum prophylactic administration of oxytocin or sulprostone in low risk women having an expectant management of the third stage.\n Randomized, placebo controlled, double-blind trial.\n Radboud University Hospital, Nijmegen (67 women) and Lievensberg Hospital, Bergen op Zoom (10 women).\n 77 women entered the trial (three were excluded).\n The intramuscular injection, immediately after the birth of the baby, of either oxytocin 5 IU, sulprostone 500 micrograms or 0.9% saline.\n Quantitative postpartum blood loss and length of third stage.\n Postpartum blood loss was reduced almost equally, by about 35%, by oxytocin (P = 0.02), or sulprostone (P = 0.05). The mean length of the third stage was shorter in both groups receiving the active treatment, this effect was significant in the sulprostone group (P = 0.01).\n Prophylactic administration of oxytocin or sulprostone directly after delivery followed by expectant management of the third stage reduces post partum blood loss and shortens the third stage.", "To compare intravenous oxytocin administration (Partocon 10 IU) with saline solution in the management of postpartum haemorrhage in the third stage of labour.\n A double-blind, randomised controlled trial involving 1000 parturients with singleton fetuses in cephalic presentation and undergoing vaginal delivery, randomly allocated to treatment with oxytocin (n = 513) or 0.9% saline solution (n = 487).\n Labour ward at a central county hospital.\n Mean blood loss (total, and before and after placenta delivery); frequencies of blood loss > 800 mL, need of additional oxytocic treatment, postpartum haemoglobin < 10 g/dL; and duration of postpartum hospitalisation.\n As compared with saline solution, oxytocin administration was associated with significant reduction in mean total blood loss (407 versus 527 mL), and in frequencies of postpartum haemorrhage > 800 mL (8.8% versus 5.2%), additional treatment with metylergometrine (7.8% versus 13.8%), and postpartum Hb < 10 g/dL (9.7% versus 15.2%), and a nonsignificant increase in the frequency of manual placenta removal (3.5% versus 2.3%). There was no group difference in the mean duration of postpartum hospitalisation (4.6 versus 4.5 days, respectively).\n Administration of intravenous oxytocin in the third stage of labour is associated with an approximately 22% reduction in mean blood loss, and approximately 40% reductions in frequencies of postpartum haemorrhage (> 500 mL or > 800 mL) and of postpartum haemoglobin < 10 g/dL. Identification of risk groups for oxytocin treatment does not seem worthwhile. Oxytocin is a cheap atoxic drug and should be given routinely after vaginal delivery." ]

[ "20148940", "15162353", "18457329" ]

[ "An exploratory trial of preventative rehabilitation on shoulder disability and quality of life in patients following neck dissection surgery.", "A pilot study of a randomized controlled trial to evaluate the effects of progressive resistance exercise training on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in head and neck cancer survivors.", "Effect of exercise on upper extremity pain and dysfunction in head and neck cancer survivors: a randomized controlled trial." ]

[ "Patients commonly develop shoulder disability and reduction in quality of life (QOL) following neck dissection surgery. There is a lack of studies investigating the impact of preventative rehabilitation to prevent shoulder disability in this population. An exploratory trial was undertaken to investigate this gap in the head and neck cancer literature. Thirty-two subjects were randomly assigned to either one of two groups: early physiotherapy for a period of 3 months following surgery and current routine inpatient care and advice. Blinded measurement of shoulder function and QOL were recorded pre-operatively and at 1 year following surgery. No difference was found using between-group analysis (Mann-Whitney U-Test) for any outcome measures observed. Descriptive data analysis suggests that subjects receiving early physiotherapy had a perception of increased physical well-being when compared with subjects receiving routine care. There may be some clinical significance that subjects receiving a course of physiotherapy did appear to rate their physical well-being higher than those subjects not undergoing rehabilitation. Further research to investigate the preventative effects of physiotherapy on this population should consider the use of head and neck cancer-specific outcome measurement of both shoulder disability and QOL.\n © 2010 Blackwell Publishing Ltd.", "Shoulder dysfunction remains a frequent complication after neck dissection procedures for head and neck cancer.\n We conducted a pilot study to evaluate the effects of progressive resistance exercise training (PRET) on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in patients with head and neck cancer. Twenty patients (mean age, 61 +/- 7.7 years) were randomly assigned to PRET or standard care intervention. Subjects assigned to the PRET group exercised three times per week for 12 weeks. The goal of the exercise program was to enhance scapular stability and strength of the upper extremity. The resistance-training program was progressive in terms of number of sets and repetitions performed, as well as the amount of weight lifted, depending on performance status.\n The completion rate for the trial was 85% (17 of 20). The exercise group completed 93% of scheduled exercise sessions. Significant improvements were found in favor of the PRET group in active shoulder external rotation (p =.001), shoulder pain (p =.038), and overall score for shoulder pain and disability (p =.045).\n The study results demonstrate a high rate of completion and adherence with our PRET program among patients with head and neck cancer. The preliminary findings, although limited, also suggest a potential therapeutic role for resistance exercise as an adjunct to standard physical therapy treatment.\n Copyright 2004 Wiley Periodicals, Inc. Head Neck 26: 518-530, 2004", "Shoulder pain and disability are well recognized complications associated with surgery for head and neck cancer. This study was designed to examine the effects of progressive resistance exercise training (PRET) on upper extremity pain and dysfunction in postsurgical head and neck cancer survivors.\n Fifty-two head and neck cancer survivors were assigned randomly to PRET (n = 27) or a standardized therapeutic exercise protocol (TP) (n = 25) for 12 weeks. The primary endpoint was change in patient-rated shoulder pain and disability from baseline to postintervention. Secondary endpoints were upper extremity strength and endurance, range of motion, fatigue, and quality of life.\n Follow-up assessment for the primary outcome was 92%, and adherence to the supervised PRET and TP programs were 95% and 87%, respectively. On the basis of intention-to-treat analyses, PRET was superior to TP for improving shoulder pain and disability (-9.6; 95% confidence interval [95% CI], -16.4 to -4.5; P = .001), upper extremity strength (+10.8 kg; 95% CI, 5.4-16.2 kg; P < .001), and upper extremity endurance (+194 repetitions x kg; 95% CI, 10-378 repetitions x kg; P = .039). Changes in neck dissection impairment, fatigue, and quality of life favored the PRET group but did not reach statistical significance.\n The PRET program significantly reduced shoulder pain and disability and improved upper extremity muscular strength and endurance in head and neck cancer survivors who had shoulder dysfunction because of spinal accessory nerve damage. Clinicians should consider the addition of PRET in the rehabilitation of postsurgical head and neck cancer survivors.\n (Copyright) 2008 American Cancer Society." ]

[ "3543767" ]

[ "Effect on birth weight of erythromycin treatment of pregnant women." ]

[ "To test the hypothesis that treatment with antibiotics prevents low birth weight, pregnant women whose vaginal cultures contained Ureaplasma urealyticum or Mycoplasma hominis (or both) and who gave written informed consent were treated with one of the following: identical looking capsules containing 250 mg of either erythromycin estolate or stearate (active against U urealyticum), or 150 mg of clindamycin hydrochloride (active against M hominis), or placebo, four times daily for six weeks in a randomized double-blind study. Treatment with clindamycin had no effect. Treatment with erythromycin initiated during the second trimester had no effect on mean birth weight or on the frequency of low-birth-weight infants. In contrast, women whose treatment with erythromycin was initiated in the third trimester gave birth to infants with a heavier mean birth weight (3331 g) than infants born to placebo-treated women (3187 g) (P = .042). Similarly, in women whose erythromycin was begun during the third trimester, the birth rate of infants weighing 2500 g or less was 3%, whereas in women treated with placebo, the birth rate for low-birth-weight infants was 12% (P = .047). These data suggest that treatment with erythromycin during the third trimester prevents low birth weight in mycoplasma-colonized pregnant women. Whether the effect is due solely to the action of erythromycin on U urealyticum is uncertain." ]

[ "16372905", "15515443", "19164402", "16764547", "15963186", "14728633", "18586813", "16594879", "18401810", "8107894", "10647968", "18845605", "12040303", "16888263", "12807578", "14963375", "18678571", "1621796", "11111630", "19652619", "1466871", "19723707", "14991552", "21432349", "17965045", "2792781", "12383143", "12825328", "10568531", "8617897", "17302650", "11186596", "10724076", "17264105", "8831471", "18007119", "5075488", "2317144", "19570158", "8301766", "16813773", "7490386", "2817074", "15233841", "1181361", "15871887", "8190152", "6918434", "8438659", "2399925", "8185457", "17329285", "8184127", "19335676", "15706558", "10404920" ]

[ "The feasibility of Whole Body Vibration in institutionalised elderly persons and its influence on muscle performance, balance and mobility: a randomised controlled trial [ISRCTN62535013].", "Indoor gardening older adults: effects on socialization, activities of daily living, and loneliness.", "An exploratory cluster randomized controlled trial of group exercise on mobility and depression in care home residents.", "High-intensity functional exercise program and protein-enriched energy supplement for older persons dependent in activities of daily living: a randomised controlled trial.", "Effects of Sun-style Tai Chi exercise on physical fitness and fall prevention in fall-prone older adults.", "Muscle strength after resistance training is inversely correlated with baseline levels of soluble tumor necrosis factor receptors in the oldest old.", "A controlled clinical trial on the effects of motor intervention on balance and cognition in institutionalized elderly patients with dementia.", "A randomised controlled trial testing the impact of exercise on cognitive symptoms and disability of residents with dementia.", "Exercise training is beneficial for Alzheimer's patients.", "Promoting activity in the elderly through interdisciplinary linkages.", "A randomized outcome evaluation of group exercise programs in long-term care institutions.", "Does a functional activity programme improve function, quality of life, and falls for residents in long term care? Cluster randomised controlled trial.", "The effects of a walking/talking program on communication, ambulation, and functional status in residents with Alzheimer disease.", "Cluster randomized pilot controlled trial of an occupational therapy intervention for residents with stroke in UK care homes.", "Effectiveness of a group exercise program in a long-term care facility: a randomized pilot trial.", "Changes in postural balance in frail elderly women during a 4-week visual feedback training: a randomized controlled trial.", "A phase II exploratory cluster randomized controlled trial of a group mobility training and staff education intervention to promote urinary continence in UK care homes.", "Comparison of performance in materials-based occupation, imagery-based occupation, and rote exercise in nursing home residents.", "A fall prevention program for elderly individuals. Exercise in long-term care settings.", "The effects of 16-week group exercise program on physical function and mental health of elderly Korean women in long-term assisted living facility.", "A clinical trial of strengthening and aerobic exercise to improve gait and balance in elderly male nursing home residents.", "Effects of a physiotherapy and occupational therapy intervention on mobility and activity in care home residents: a cluster randomised controlled trial.", "An exercise program to improve fall-related outcomes in elderly nursing home residents.", "Randomized controlled trial to evaluate effectiveness of exercise therapy (Takizawa Program) for frail elderly.", "Does functionally based activity make a difference to health status and mobility? A randomised controlled trial in residential care facilities (The Promoting Independent Living Study; PILS).", "Effect of exercise on postural sway in the elderly.", "Translating clinical research into practice: a randomized controlled trial of exercise and incontinence care with nursing home residents.", "Training for muscle power in older adults: effects on functional abilities.", "Nursing rehabilitation and exercise strategies in the nursing home.", "Exercise with physically restrained nursing home residents: maximizing benefits of restraint reduction.", "Exercise program for nursing home residents with Alzheimer's disease: a 1-year randomized, controlled trial.", "Effect of a combined walking and conversation intervention on functional mobility of nursing home residents with Alzheimer disease.", "Exercise training in the debilitated aged: strength and functional outcomes.", "Effect of additional functional exercises on balance in elderly people.", "Outcomes of enhanced physical and occupational therapy service in a nursing home setting.", "The effect of structured strength and balance training on cognitive function in frail, cognitive impaired elderly long-term care residents.", "Physiological effects of training upon institutionalized geriatric men.", "Endurance training in the elderly nursing home patient.", "Nursing home resident outcomes from the Res-Care intervention.", "A randomized trial of physical rehabilitation for very frail nursing home residents.", "Effects of exercise programs on falls and mobility in frail and pre-frail older adults: A multicenter randomized controlled trial.", "Functional Incidental Training, mobility performance, and incontinence care with nursing home residents.", "Added-purpose versus rote exercise in female nursing home residents.", "Effects of resistance and all-round, functional training on quality of life, vitality and depression of older adults living in long-term care facilities: a 'randomized' controlled trial [ISRCTN87177281].", "Response of institutionalized geriatric mental patients to a twelve-week program of regular physical activity.", "Functional Incidental Training: applicability and feasibility in the Veterans Affairs nursing home patient population.", "Exercise training and nutritional supplementation for physical frailty in very elderly people.", "The effect of an exercise program on self-care activities for the institutionalized elderly.", "A controlled trial of exercise by residents of old people's homes.", "Adding purpose to the repetitive exercise of elderly women through imagery.", "Improvements in quadriceps strength with regular seated exercise in the institutionalized elderly.", "Comparison of the effectiveness of two programmes on older adults at risk of falling: unsupervised home exercise and supervised group exercise.", "The effect of skill training on functional abilities of nursing home residents with dementia.", "Tai Chi and health-related quality of life in nursing home residents.", "Controlled whole body vibration to decrease fall risk and improve health-related quality of life of nursing home residents.", "A randomized trial of a combined physical activity and environmental intervention in nursing home residents: do sleep and agitation improve?" ]

[ "Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents. Low-volume exercise interventions with similar training effects might be an alternative. The aim of this randomised controlled trial was to investigate the feasibility of Whole Body Vibration (WBV) in institutionalised elderly, and its impact on functional capacity and muscle performance.\n Twenty-four nursing home residents (15 female, 9 male; mean age 77.5 +/- 11.0 years) were randomised (stratification for age, gender and ADL-category) to 6 weeks static WBV exercise (WBV+, N = 13) or control (only static exercise; N = 11). Outcome measures were exercise compliance, timed up-and-go, Tinetti-test, back scratch, chair sit-and-reach, handgrip strength and linear isokinetic leg extension.\n At baseline, WBV+ and control groups were similar for all outcome variables. Twenty-one participants completed the program and attended respectively 96% and 86% of the exercise sessions for the WBV+ and control groups. Training-induced changes in timed up-and-go and Tinetti-test were better for WBV+ compared to control (p = 0.029 for timed up-and-go, p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively). In an alternative analysis (Worst Rank Score & Last Observation Carried Forward) the differences in change remained significant on the Tinetti body balance and total score. No other significant differences in change between both groups were observed.\n In nursing home residents with limited functional dependency, six weeks static WBV exercise is feasible, and is beneficial for balance and mobility. The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further.", "This study examined the effects of indoor gardening on socialization, activities of daily living (ADLs), and perceptions of loneliness in elderly nursing home residents. A total of 66 residents from two nursing homes participated in this two-phase study. In phase one, experimental group 1 participated once a week for 5 weeks in gardening activities while a control group received a 20-minute visit. While no significant differences were found between groups in socialization or perceptions of loneliness, there were significant pretest-posttest differences within groups on loneliness and guidance, reassurance of worth, social integration, and reliable alliance. The results also demonstrated gardening interventions had a significant effect on three ADLs (transfer, eating, and toileting). Phase two examined differences in the effects of a 5-week versus a 2-week intervention program. Although no significant within-group differences were noted in socialization, loneliness, or ADLs, the 5-week program was more effective in increasing socialization and physical functioning.", "To investigate the feasibility, acceptability and potential efficacy of group exercise for residents in care homes.\n Exploratory cluster randomized controlled trial.\n Five randomly selected care homes in South Birmingham, UK.\n Fifty-six care home residents (mean age 84.5, 71% female), 39 (70%) with cognitive impairments.\n Two homes (n = 28) were randomized to group exercise held twice weekly for five weeks. The remaining three homes (n = 28) formed the control group and received usual care, with no person specifically responsible for exercise training.\n Assessments were conducted at zero (pre-intervention), three (post-intervention) and six months (follow-up) using the Rivermead Mobility Index and Hospital Anxiety and Depression Scale or Stroke Aphasic Depression Questionnaire (depending on cognitive impairment). Adherence to group exercise and retention to the study were also documented.\n No statistically significant improvements in mobility or depression were found in favour of group exercise. Retention to the study was high with 46 (82%) participants completing all assessments. Adherence to group exercise was somewhat lower with participants attending a mean of 3.61 out of 8.5 prescribed sessions (42.5%).\n Group exercise can be delivered to care home residents with reduced mobility but it is not suitable for residents with severe cognitive impairment. An estimated sample size of 240 participants would be required to detect a clinically significant difference in the Rivermead Mobility Index with 90% power.", "The aims of this randomised controlled trial were to determine if a high-intensity functional exercise program improves balance, gait ability, and lower-limb strength in older persons dependent in activities of daily living and if an intake of protein-enriched energy supplement immediately after the exercises increases the effects of the training. One hundred and ninety-one older persons dependent in activities of daily living, living in residential care facilities, and with a Mini-Mental State Examination (MMSE) score of ? 10 participated. They were randomised to a high-intensity functional exercise program or a control activity, which included 29 sessions over 3 months, as well as to protein-enriched energy supplement or placebo. Berg Balance Scale, self-paced and maximum gait speed, and one-repetition maximum in lower-limb strength were followed-up at three and six months and analysed by 2 x 2 factorial ANCOVA, using the intention-to-treat principle. At three months, the exercise group had improved significantly in self-paced gait speed compared with the control group (mean difference 0.04 m/s, p = 0.02). At six months, there were significant improvements favouring the exercise group for Berg Balance Scale (1.9 points, p = 0.05), self-paced gait speed (0.05 m/s, p = 0.009), and lower-limb strength (10.8 kg, p = 0.03). No interaction effects were seen between the exercise and nutrition interventions. In conclusion, a high-intensity functional exercise program has positive long-term effects in balance, gait ability, and lower-limb strength for older persons dependent in activities of daily living. An intake of protein-enriched energy supplement immediately after the exercises does not appear to increase the effects of the training.", "This paper reports a study to determine changes in the physical fitness (knee and ankle muscle strength, balance, flexibility, and mobility), fall avoidance efficacy, and fall episodes of institutionalized older adults after participating in a 12-week Sun-style Tai Chi exercise programme.\n Fall prevention has a high priority in health promotion for older people because a fall is associated with serious morbidity in this population. Regular exercise is effective in fall prevention for older adults because of improvements in strength and balance. Tai Chi exercise is considered to offer great potential for health promotion and rehabilitation, particularly in the maintenance of good mental and physical condition in older people.\n A quasi-experimental design with a non-equivalent control group was used. Data were collected from September 2001 to January 2002. A total of 68 fall-prone older adults with a mean age of 77.8 years participated in the study, and 29 people in the Tai Chi group and 30 controls completed the post-test measures. The Tai Chi exercise programme was provided three times a week for 12 weeks in the experimental group. Data were analysed for group differences using t-tests.\n At post-test, the experimental group showed significantly improved muscle strength in knee and ankle flexors (P < 0.001) and extensors (P < 0.01), and improved flexibility (P < 0.01) and mobility (P < 0.001) compared with the control group. There was no significant group difference in fall episodes, but the relative risk ratio for the Tai Chi exercise group compared with the control group was 0.62. The experimental group reported significantly more confidence in fall avoidance than did the control group.\n The findings reveal that Tai Chi exercise programmes can safely improve physical strength and reduce fall risk for fall-prone older adults in residential care facilities.", "To test the hypothesis that physical exercise induces an antiinflammatory response that is associated with reduced chronic activation of the tumor necrosis factor (TNF)-alpha system in frail elders and that the increase in muscle strength after resistance training is limited by systemic low-grade inflammation.\n A 12-week controlled resistance-training study.\n Nursing homes in Copenhagen, Denmark.\n Twenty-one frail nursing home residents aged 86 to 95 completed the study.\n Ten participants were randomized to a program of resistance training of knee extensors and flexors three times a week for 12 weeks; the remaining 11 participants served as a control group who joined social activities supervised by an occupation therapist.\n Muscle strength, plasma levels of TNF-alpha, soluble TNF receptor (sTNFR)-1, and interleukin (IL)-6 were measured before and at the end of the intervention period.\n The training program improved muscle strength but did not affect plasma levels of TNF-alpha and sTNFR-I or IL-6. However, plasma levels of sTNFR-I at baseline were inversely correlated with the increase in muscle strength.\n Low-grade activation of the TNF system could limit the increase in muscle strength after resistance training in the oldest old. Furthermore, data suggest that the antiinflammatory response induced by 12 weeks of resistance training is not sufficient to reduce chronic activation of the TNF system, but the small sample size limited this interpretation.", "To analyse the effects of two interventions on the cognition and balance of institutionalized elderly people with mixed dementia.\n Fifty-four participants were allocated into three groups. Group 1 was assisted by an interdisciplinary programme comprising physiotherapy, occupational therapy and physical education. A physiotherapist alone carried out the intervention in group 2. Group 3 was considered as control. Assessors were blinded to guarantee the absence of bias. Cognitive functions were analysed with the Mini-Mental State Examination and the Brief Cognitive Screening Battery. Balance was assessed with the Berg Balance Scale and the Timed Get-Up-and-Go Test. Multiple analysis of variance (MANOVA) was used to test possible main effects of the interventions.\n The results showed benefits on the balance of subjects in both groups 1 (F=3.9, P<0.05) and 2 (F=3.1, P<0.05), compared with group 3. MANOVA did not indicate benefits on the cognitive functions between groups 1 and 3 (F=1.1, P>0.05) and groups 2 and 3 (F=1.6, P>0.05). However, univariate analysis indicated some benefits of the interdisciplinary intervention on two specific domains measured by the Brief Cognitive Screening Battery (F=26.5, P<0.05; F=4.4, P<0.05).\n Six months of multidisciplinary or physiotherapeutic intervention were able to improve a person's balance. Although global cognition did not improve through treatment, when the intervention was carried out on a multidisciplinary basis we observed an attenuation in the decline of global cognition on two specific cognitive domains. Exercises applied in different contexts may have positive outcomes for people with dementia.", "A randomized controlled trial was undertaken to measure effects of exercise on: 1) the progression of cognitive symptoms related to dementia using the Clock- Drawing test Shulman et al. 1993); and 2) disability using the Revised Elderly Persons Disabilities Scale (REPDS; Fleming and Bowles 1993). Data was analysed from 75 nursing home residents with dementia who were randomly assigned to one experimental group and two control groups. Group 1 (control) received no intervention, Group 2 (control) received a social visit equivalent in duration and frequency as those undertaking the exercise program in the experimental group, Group 3. A specifically designed, frail aged appropriate, twelve week exercise program was undertaken by the those in the experimental group three times per week, each session lasted for thirty minutes. The findings from: 1) the clock drawing test showed that exercise may slow the rate of progression of the cognitive symptoms related to dementia; and 2) the REPDS showed that exercise slowed and reversed disability in some of the activities of daily living.", "Decreased ability to perform activities of daily living (ADLs) associated with deterioration in physical capacity are key determinants of the poor quality of life and loss of independence of patients with Alzheimer's disease (AD). The purpose of this study was to determine the effects of a 12-week training program (including resistance, flexibility, joint mobility and balance/coordination exercises) for Spanish patients with AD on their i) overall functional capacity (muscle strength and flexibility, agility and balance while moving, and endurance fitness), and ii) ability to perform ADLs. Using a randomized block design, 16 patients were assigned to a training (mean [SD] age: 76 [4] yrs) or control group (73 [4] yrs) (n = 8 subjects [3 male, 5 female] per group). The results showed significant improvements after training (p < 0.05) in upper and lower body muscle strength and flexibility, agility and dynamic balance, and endurance fitness (using the Senior Fitness test), gait and balance abilities (with subsequent decrease in risk of falls) (Tinetti scale) and in the ability to perform ADLs independently (Katz and Barthel scores). No changes (p > 0.05) were found in the control group over the 12-week period. Exercise training could be included in the overall medical/nursing care protocol for patients with AD.", "Interdisciplinary collaboration helped a group of health care providers plan, implement, and evaluate an exercise program for sedentary older adults in a long-term care facility. The program, designed as a research study, can be implemented by paraprofessional care givers with minimal supervision. The synergy resulting from collaboration between the investigator and colleagues in the practice arena was the cornerstone of the program's success. This paper describes the results of a Sit and Get Fit exercise program, a project funded by The University of Akron.", "Physical activity programs in nursing homes typically consist of seated, range of motion (ROM) exercises, regardless of resident abilities. The Functional Fitness for Long-Term Care (FFLTC) Program was designed not only to maintain ROM, but also to improve strength, balance, flexibility, mobility, and function. In addition, it was tailored to meet the needs of both high and low mobility residents.\n The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents (mean age 80) from five institutions. Persons were classified as low or high mobility and randomized into either the FFLTC program or a seated ROM program. Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes, three times per week. Assessments at baseline and 4 months consisted of mobility, balance, gait, flexibility, functional capacity, and several upper and lower extremity strength measures.\n Attendance averaged 86% for the FFLTC and 79% for the ROM classes. Four months of exercise led to significant improvements in mobility (16%), balance (9%), flexibility (36%), knee (55%), and hip (12%) strength for the FFLTC group. Shoulder strength was the only improvement found for the ROM group. The ROM group significantly deteriorated in some areas, particularly hip strength, mobility, and functional ability.\n Institutionalized seniors, even those who are physically frail, incontinent and/or have mild dementia, can respond positively to a challenging exercise program. The FFLTC program demonstrated clear benefits over typical, seated ROM exercises. Moreover, with minimal training, the program can be safely delivered at low cost by institutional staff and volunteers.", "To assess the effectiveness of an activity programme in improving function, quality of life, and falls in older people in residential care.\n Cluster randomised controlled trial with one year follow-up.\n 41 low level dependency residential care homes in New Zealand.\n 682 people aged 65 years or over.\n 330 residents were offered a goal setting and individualised activities of daily living activity programme by a gerontology nurse, reinforced by usual healthcare assistants; 352 residents received social visits.\n Function (late life function and disability instruments, elderly mobility scale, FICSIT-4 balance test, timed up and go test), quality of life (life satisfaction index, EuroQol), and falls (time to fall over 12 months). Secondary outcomes were depressive symptoms and hospital admissions.\n 473 (70%) participants completed the trial. The programme had no impact overall. However, in contrast to residents with impaired cognition (no differences between intervention and control group), those with normal cognition in the intervention group may have maintained overall function (late life function and disability instrument total function, P=0.024) and lower limb function (late life function and disability instrument basic lower extremity, P=0.015). In residents with cognitive impairment, the likelihood of depression increased in the intervention group. No other outcomes differed between groups.\n A programme of functional rehabilitation had minimal impact for elderly people in residential care with normal cognition but was not beneficial for those with poor cognition. Trial registration Australian Clinical Trials Register ACTRN12605000667617.", "The purpose of this study was to investigate the effects of a walking/talking program on residents' communication, ambulation, and level of function when there were two residents to one care provider (2:1). A randomized control trial design was used. Subjects were residents with Alzheimer disease in three geriatric long-term care facilities in Metropolitan Toronto. Residents who met the inclusion criteria were randomly assigned to one of three groups: walk-and-talk group (30 min, 5 times per week for 16 weeks, walking/talking in pairs), talk-only group (30 min, 5 times per week for 16 weeks, talk only in pairs), or no intervention. The outcome measures were the Functional Assessment of Communication Skills for Adults, the 2-min walk test, and London Psychogeriatric Rating Scale. Residents who received the walk-and-talk intervention did not demonstrate statistically significant differences in the outcome variables measured posttest when compared with residents who received the talk-only intervention or no intervention, even after controlling for individual differences. Variability in the outcomes measured posttest is explained by differences in the residents' level of cognitive impairment before the study rather than by study group membership. These findings are contradictory to those of previous studies.", "A pilot evaluation of an occupational therapy intervention to improve self-care independence for residents with stroke-related disability living in care homes was the basis of this study.\n A cluster randomized controlled trial with care home as the unit of randomization was undertaken in Oxfordshire, UK. Twelve homes (118 residents) were randomly allocated to either intervention (6 homes, 63 residents) or control (6 homes, 55 residents). Occupational therapy was provided to individuals but included carer education. The control group received usual care. Assessments were made at baseline, postintervention (3 months) and at 6-months to estimate change using the Barthel Activity of Daily Living Index (BI) scores, \"poor global outcome\", (defined as deterioration in BI score, or death) and the Rivermead Mobility Index.\n At 3 months BI score in survivors had increased by 0.6 (SD 3.9) in the intervention group and decreased by 0.9 (2.2) in the control group; a difference of 1.5 (95% CI allowing for cluster design, -0.5 to 3.5). At 6 months the difference was 1.9 (-0.7 to 4.4). Global poor outcome was less common in the intervention group. At 3 months, 20/63 (32%) were worse/dead in the intervention group compared with 31/55 (56%) in the control group, difference -25% (-51% to 1%). At 6 months the difference was similar, -26% (-48% to -3%). Between-group changes in Rivermead Mobility Index scores were not significantly different.\n Residents who received an occupational therapy intervention were less likely to deteriorate in their ability to perform activities of daily living.", "The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility (LTC) residents would result in improved function.\n A prospective, randomized, controlled, semicrossover trial was designed with participants assigned either to group exercise (EX) or recreational therapy (C). In the EX group, the intervention continued for 1 year. In the C group, recreation continued for 6 months; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months. Functional outcomes were measured at baseline and 3, 6, 9, and 12 months for both groups.\n A LTC facility, which included both assisted living (AL) and nursing home (NH) residents.\n Twenty frail residents (5 from NH, 15 from AL) aged 75 to 99 years at one LTC facility.\n After random group assignment, the EX group met 1 hour three times per week. An exercise physiologist and LTC staff conducted sessions which included seated range of motion (ROM) exercises and strength training using simple equipment such as elastic resistance bands (therabands) and soft weights. The C group met three times per week and participated in activities such as painting during the first 6 months, before crossing over to exercise.\n Objective measures of physical and cognitive function were obtained at baseline and 3, 6, 9, and 12 months using the timed get-up-and-go test (TUG), Berg balance scale, physical performance test (PPT), and mini-mental status exam (MMSE). Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate, a global hypothesis test was used.\n There was a significant overall impact across the four measures of the exercise intervention (P = 0.013). Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds, which represents an effect size (in standard deviation units) of 0.50, increased PPT scores by 1.3, with effect size = 0.40, increased Berg scores by 4.8, with effect size of 0.32, and increased MMSE by 3.1, with effect size = 0.54. Except for the Berg, 90% confidence intervals on these exercise effects excluded 0.\n Frail elderly in a LTC facility were able to participate and benefit from a strength training program. The program was delivered with low-cost equipment by an exercise physiologist and LTC staff. The advantage of such a program is that it provides recreational and therapeutic benefits.", "Balance training programs have not shown consistent results among older adults, and it remains unclear how different training methods can be adapted to frail elderly people.\n The purpose of this study was to investigate the effects of a 4-week visual feedback-based balance training on the postural control of frail elderly women living in residential care homes.\n Elderly women of two residential care facilities were randomized to an exercise group (EG, n = 20) and to a control group (CG, n = 7). The EG participated in training sessions three times/week for 4 weeks. The exercises were carried out with a computerized force platform with visual feedback screen. The dimensions of balance function studied were standing body sway, dynamic weight shifting, and Berg Balance Scale performance.\n The EG showed significant improvement in balance functions. The performance time in dynamic balance tests improved on average by 35.9% compared with a 0.6% increase in the CG (p = 0.025-0.193). The performance distance in these tests decreased on average by 28.2% in the EG as compared with a 9.8% decrease seen in the CG. The Berg Balance Scale performance improved by 6.9% compared with a 0.7% increase in the CG (p = 0.003). The standing balance tests in the more demanding standing positions showed improvements in the EG, whereas similar changes in the CG were not found.\n Our findings suggest that balance training based on visual feedback improves the balance control in frail elderly women living in residential care, also enhancing the performance of functional balancing tasks relevant to daily living. The subjects were motivated to participate in the training, as indicated by the high compliance (97.5%) with the program.\n Copyright 2004 S. Karger AG, Basel", "To assess feasibility, acceptability and potential efficacy of group exercise and staff education intervention to promote continence in older people residing in care homes. To establish measures and information to inform a larger trial.\n Phase II pilot exploratory cluster randomized controlled trial.\n Six purposely selected care homes in the West Midlands, UK.\n Thirty-four care home residents (mean age 86, 29 female), 23 with cognitive impairments.\n Physiotherapy-led group exercise and staff continence and mobility facilitation training.\n Reported continence status, Rivermead Mobility Index. Feasibility was assessed by uptake and compliance, and acceptability by verbal feedback. A staff knowledge questionnaire was used.\n Thirty-three residents, cluster sizes from 3 to 7. The number of residents agreeing with the statement 'Do you ever leak any urine when you don't mean to?' in the intervention group decreased from 12/17 at baseline to 7/17 at six weeks in the intervention group and increased from 9/16 at baseline to 9/15 at six weeks. The Rivermead Mobility Index scores were better in the intervention group (n=17; baseline: 6.1, six weeks: 6.2) compared with controls (n=16; baseline: 5.9, six weeks: 4.75). The intervention was feasible, well received and had good compliance.\n Group mobility training and staff education to promote continence is feasible and acceptable for use with care home residents, including those with cognitive impairment.", "Materials-based occupation, imagery-based occupation, and rote exercise have been examined individually by several researchers. The present study compares all three approaches with one another (i.e., kicking a balloon, imagining kicking a balloon, and a control rote exercise) in nursing home residents. The dependent variable was the number of exercise repetitions. The subjects were 12 women and 3 men between 56 and 93 years of age residing in two nursing homes. All subjects experienced the three approaches but in different orders. One-way analysis of variance for related measures indicated a significant difference among conditions (p = .004). The Tukey procedure (Stevens, 1986) determined that the materials-based occupation condition elicited significantly more repetitions than the other two conditions. The difference between the imagery-based occupation and rote exercise was not statistically significant. These findings support our profession's historical emphasis on the use of physical materials to enhance performance.", "The purpose of this research was to explore the role of exercise in preventing falls, specifically assessing the effectiveness of an ankle strengthening and walking program to improve balance, ankle strength, walking speed, and falls efficacy and to decrease falls and subjects' fear of falling. Sixteen individuals participated in the study which was conducted at two nursing homes. Subjects were assigned randomly to an intervention or control group. The participants in the intervention group completed a 3-month supervised program of ankle strengthening exercises and walking. Descriptive statistics were used to characterize the sample, and differences in the least square means were used to assess the outcome variables (i.e., balance, ankle strength, walking speed, falls, fear of falling, falls efficacy) before the exercise program, and again at 3 months and 6 months after the program for the intervention and control subjects. Findings for the intervention group from pretest to 3-month posttest were, for the most part, maintained or in the predicted direction, suggesting that regular exercise shows promise for preventing deterioration and improving fall-related outcomes for elderly nursing home residents.", "The purpose of this study was to compare the effects of 16-week group exercise program on the physical function (ie, strength, flexibility, and balance) and mental health (ie, self-esteem and depression) of older elderlyl women (>or=75 years old) compared with younger elderly women (<75 years old).\n Exercise is crucial in maintaining older women's health and well-being. However, because most elders have at least one chronic disease, their physical function declines, so their dependence on others for instrumental daily living activities often increases. Older women typically have multiple barriers to participation in physical activities including higher disability rates.\n Of the total of 40 older women (older than 65 years) enrolled, 21 were older elders and 16 were younger elders. Lower body strength (using 30-second chair test), flexibility (sit-and-reach test), and static balance (ability to balance on one leg with open and closed eyes) were assessed. Self-esteem (using Rosenberg's Self-esteem Questionnaire) and depressive symptoms (using Yesavage's Geriatric Depression Scale) were assessed. Two-way analysis of variance was used to examine the differences between the 2 age groups.\n The intervention program was effective in improving body strength, flexibility, static balance, and self-esteem, regardless of age. Furthermore, older elders receiving the intervention program demonstrated greater improvement in self-esteem than younger elders did, although there were intervention effects in both age groups.\n Elderly women can realize benefits from a group exercise program that can improve their functional ability and self-esteem, both important to cardiovascular health.", "The purpose of this study was to determine whether a moderate to high intensity strengthening and aerobic exercise program can improve the strength, exercise capacity, gait and balance of deconditioned male nursing home residents. Ambulatory subjects who scored 30 or less on the modified Tinetti gait and balance assessment scale, who demonstrated less than 80% of age-matched lower extremity strength on isokinetic muscle testing and who gave informed consent were enrolled. Subjects were randomized to either an exercise (n = 8) or a control (n = 6) group. All participants underwent an exercise test to determine maximal oxygen uptake (VO2max) and received quantitative gait and balance measurements. The subjects assigned to the exercise group than completed a 12-wk program of weight training for the lower extremities and stationary cycling. Both the exercise and control groups were then retested. Ten outcome variables were assessed: Tinetti mobility scores, VO2max, isokinetic-tested lower extremity strength and endurance, stride length, gait velocity, stance time, gait duration, cadence and balance. The exercise group, after completion of the program, demonstrated significant improvements in Tinetti mobility scores (P < 0.05), combined right and left quadricep muscle strength (P < 0.01), right and left lower extremity muscular endurance (P < 0.01), left stride length and gait velocity (P < 0.05), although other outcome variables changed insignificantly. The control group revealed no changes of significance with the exception of improvement of the combined right and left hamstring muscle strength (P < 0.05). Nevertheless, for those outcome variables that had improved significantly in the exercise group, the changes amounted to only a 5 to 10% increase over the baseline measurements. These findings showed that an appropriately designed high intensity exercise program can result in significant although limited improvements for clinical mobility scores, strength, muscular endurance and certain gait parameters.", "To compare the clinical effectiveness of a programme of physiotherapy and occupational therapy with standard care in care home residents who have mobility limitations and are dependent in performing activities of daily living.\n Cluster randomised controlled trial, with random allocation at the level of care home.\n Care homes within the NHS South Birmingham primary care trust and the NHS Birmingham East and North primary care trust that had more than five beds and provided for people in the care categories \"physical disability\" and \"older people.\"\n Care home residents with mobility limitations, limitations in activities of daily living (as screened by the Barthel index), and not receiving end of life care were eligible to take part in the study.\n A targeted three month occupational therapy and physiotherapy programme.\n Scores on the Barthel index and the Rivermead mobility index.\n 24 of 77 nursing and residential homes that catered for residents with mobility limitations and dependency for activities of daily living were selected for study: 12 were randomly allocated to the intervention arm (128 residents, mean age 86 years) and 12 to the control arm (121 residents, mean age 84 years). Participants were evaluated by independent assessors blind to study arm allocation before randomisation (0 months), three months after randomisation (at the end of the treatment period for patients who received the intervention), and again at six months after randomisation. After adjusting for home effect and baseline characteristics, no significant differences were found in mean Barthel index scores at six months post-randomisation between treatment arms (mean effect 0.08, 95% confidence interval -1.14 to 1.30; P=0.90), across assessments (-0.01, -0.63 to 0.60; P=0.96), or in the interaction between assessment and intervention (0.42, -0.48 to 1.32; P=0.36). Similarly, no significant differences were found in the mean Rivermead mobility index scores between treatment arms (0.62, -0.51 to 1.76; P=0.28), across assessments (-0.15, -0.65 to 0.35; P=0.55), or interaction (0.71, -0.02 to 1.44; P=0.06).\n The three month occupational therapy and physiotherapy programme had no significant effect on mobility and independence. On the other hand, the variation in residents' functional ability, the prevalence of cognitive impairment, and the prevalence of depression were considerably higher in this sample than expected on the basis of previous work. Further research to clarify the efficacy of occupational therapy and physiotherapy is required if access to therapy services is to be recommended in this population.\n ISRCTN79859980.", "This study tested a 3-month ankle-strengthening and walking program designed to improve or maintain the fall-related outcomes of balance, ankle strength, walking speed, risk of falling, fear of falling, and confidence to perform daily activities without falling (falls efficacy) in elderly nursing home residents. Nursing home residents (N = 81) between the ages of 64 and 100 years participated in the study. Two of the fall-related outcomes, balance and fear of falling, were maintained or improved for the exercise group in comparison to the control group.", "Although exercise therapy intervention for frail elderly people was not of great interest in the past, it has recently drawn attention as a method to prevent and improve conditions requiring care since the enforcement of the Long-Term Care Insurance Law and the revision of the long-term care insurance system. This randomized controlled trial was performed to evaluate the effects of exercise therapy using the Takizawa Program.\n In this randomized controlled trial, we evaluated the effects of exercise therapy on the frail elderly, including those who need a high level of care, in terms of two factors: the range of motion and the functional independence measure. The subjects were 145 females admitted to special nursing homes for the elderly. They were stratified according to their care levels and randomly assigned to either the exercise therapy intervention group or the control group.\n The range of motion values in the flexions of both shoulders, the right knee extension, and the dorsal flexions of both ankles significantly increased only in the exercise therapy intervention group. The functional independence measure score did not improve in the exercise therapy intervention group.\n Exercise therapy should be used for the frail elderly requiring a high level of care.", "to determine whether a repetitive activities of daily living (ADL) activity programme improves health status, life satisfaction and mobility for older people living in residential care.\n cluster randomised controlled trial.\n five low-level dependency residential care homes in Auckland, New Zealand.\n one hundred and forty-nine older residents (mean age 84.7 years).\n trained research staff worked with residents in intervention wards to set a goal and complete a functional assessment for each resident. They then designed an individualised activity programme based on ADL and worked with residential care home staff to implement the programme into daily activities of residents.\n mobility: timed-up-and-go (TUG); life satisfaction: late life satisfaction index (LSI-Z); and health status: SF-36 were assessed at baseline, 3- and 6-months follow-up.\n in the intervention group the SF-36 total physical component summary (PCS) score improved at 3 months in comparison with the control group. There was no difference between groups on mobility measures at any time, nor any measures at 6-months follow-up. Significant contamination is likely to have affected the 6-month follow-up measures.\n a repetitive ADL exercise programme may improve health status in the short term in a group of frail older people living in residential care. Further research is needed to establish sustainability of change.", "Fifty female subjects, aged 72-92 (mean 82) years, were enrolled in a 12-week (36 classes) exercise program aimed at increasing postural stability. Subjects were residents of sheltered apartments, rest homes or nursing homes, well enough and mobile enough to participate in the classes. The subjects were randomized into an exercise or a control group. Their postural sway, standing at rest on a force platform, was measured with eyes open and eyes closed. The groups were well matched in all respects. The results showed no improvement in the postural sway as a result of the exercise program. We hypothesize that increasing postural sway in the elderly represents a deterioration in, for the most part, the nervous system and may at this extreme of life indicate an irreversible loss of function. For this reason no improvement in postural sway may be possible.", "To examine clinical outcomes and describe the staffing requirements of an incontinence and exercise intervention.\n Randomized controlled trial with blinded assessments of outcomes at three points over 8 months.\n Four nursing homes.\n Two hundred fifty-six incontinent residents.\n Research staff provided the intervention, which integrated incontinence care and exercise every 2 hours from 8:00 a.m. to 4:00 p.m. 5 days a week.\n Average and maximum distance walked or wheeled, level of assistance required to stand, maximum pounds lifted by arms, fecal and urinary incontinence frequency, and time required to implement intervention.\n Intervention residents maintained or improved performance whereas the control group's performance declined on 14 of 15 outcome measures. Repeated measures analysis of variance group-by-time significance levels ranged from P <.0001 to.05. The mean time required to implement the intervention each time care was provided was 20.7 +/- 7.2 minutes. We estimate that a work assignment of approximately five residents to one aide would be necessary to provide this intervention.\n The incontinence care and exercise intervention resulted in significant improvement for most residents, and most who could be reliably interviewed expressed a preference for such care. Fundamental changes in the staffing of most nursing homes will be necessary to translate efficacious clinical interventions into everyday practice.", "The purpose of this study was to determine the influence of simple, progressive lower body exercise training, focusing on strength and power, on functional abilities in frail older adults. Twenty-five residents of a long-term care facility (75-94 yrs) participated in this randomized controlled trial of 10-wks duration. The exercise group (Ex, n = 18) underwent simple, progressive lower body resistance exercises, specifically aimed at improving muscle power, 3 times/wk; the control subjects (Con, n = 7) maintained their usual daily activities. Knee extensor strength and power were measured on an isokinetic dynamometer (180 degrees/s), and functional performance was assessed from a 6-m walk timed test, a 30-s chair stand, and an 8-ft up-and-go timed test, before and after the 10-wk intervention period. Significant increases were found in the Ex group for eccentric (44%) and concentric (60%) average power (p < 0.05), and improvements were seen on each functional test: the 8-foot up-and-go, chair stand, and walk time improved by 31%, 66%, and 33%, respectively (p < 0.05). No significant change occurred in the Con group. In conclusion, simple progressive exercise training, even in the 10th decade, increases muscle power and is associated with an improved performance of functional activities using the trained muscles.", "The purpose of this study was to evaluate how weight training or nursing-based rehabilitative care programs in nursing homes impact on resident performance of Activities of Daily Living (ADL) and objectives tests of physical performance.\n This study involved a quasi-experimental control, longitudinal comparison of functional status over a 10-month period, where baseline status was adjusted through a weighting procedure based on functional status, cognitive status, and age. All residents from six residential care nursing home facilities were eligible except those with a terminal prognosis, a projected stay of less than 90 days, or with health complications that prohibited contact. Homes were placed into matched triplets based on patient characteristics: two members of each triplet were randomly designated to be experimental sites, the third became the control site. Baseline data were available for 468 subjects, follow-up for 392. ADL self-performance measures derived from the Minimum Data Set, including indicators of early loss ADL, locomotion, and late loss ADL; a number of objective functional tests (including measures of balance, power, and endurance); and mood state as measured by the Geriatric Depression Scale.\n Mean ADL values in the two experimental groups declined at a significantly lower rate than did rates for the controls. Functional decline was also lower in more specific measures: locomotion, early loss ADL, and late loss ADL.\n With both interventions, facilities were able to implement a broad-based intervention that resulted in a significant reduction in ADL decline rates. A facility-wide nursing rehabilitation program can play a useful role in reversing functional decline, helping residents to maintain their involvement in a broad spectrum of ADL activities.", "To evaluate an exercise protocol designed to improve strength and mobility, and to decrease injury risk factors in physically restrained nursing home residents.\n A randomized controlled trial.\n Ninety-seven residents were randomized into either exercise or control groups. Thirty-five exercise and 37 control group residents completed all post-assessments after a 9-week trial.\n Walking or wheelchair movement training was supplemented by rowing exercise three times per week. Practice in behaviors related to safe movement was provided incidental to the exercise.\n Endurance, speed, and injury risk measures relevant to walking, wheelchair propulsion, and standing were assessed by standardized protocols. Rowing endurance, rowing range of motion, and handgrip strength measures were collected to assess the effect of the rowing component of the exercise protocol.\n Fifty-four percent of the subjects who provided consent did not complete the protocol because of health status changes, lack of cooperation, or physical limitations that precluded exercise. The subjects who completed the exercise program showed significant improvement on injury risk and measures related to upper body strength (handgrip strength, rowing endurance, wheelchair endurance, and speed). Measures related to lower body strength did not significantly improve.\n Physically restrained residents are very frail, and it is difficult to implement a long-term exercise program with many residents because of the frailty. However, a substantial proportion of residents did cooperate well with the exercise program and showed improvement on measures correlated with decreased injury risk. The exercise program could be easily modified to include more lower body exercise, and the resultant protocol would be an important adjunct to restraint reduction programs.", "To investigate the effectiveness of an exercise program in improving ability to perform activities of daily living (ADLs), physical performance, and nutritional status and decreasing behavioral disturbance and depression in patients with Alzheimer's disease (AD).\n Randomized, controlled trial.\n Five nursing homes.\n One hundred thirty-four ambulatory patients with mild to severe AD.\n Collective exercise program (1 hour, twice weekly of walk, strength, balance, and flexibility training) or routine medical care for 12 months.\n ADLs were assessed using the Katz Index of ADLs. Physical performance was evaluated using 6-meter walking speed, the get-up-and-go test, and the one-leg-balance test. Behavioral disturbance, depression, and nutritional status were evaluated using the Neuropsychiatric Inventory, the Montgomery and Asberg Depression Rating Scale, and the Mini-Nutritional Assessment. For each outcome measure, the mean change from baseline to 12 months was calculated using intention-to-treat analysis.\n ADL mean change from baseline score for exercise program patients showed a slower decline than in patients receiving routine medical care (12-month mean treatment differences: ADL=0.39, P=.02). A significant difference between the groups in favor of the exercise program was observed for 6-meter walking speed at 12 months. No effect was observed for behavioral disturbance, depression, or nutritional assessment scores. In the intervention group, adherence to the program sessions in exploratory analysis predicted change in ability to perform ADLs. No adverse effects of exercise occurred.\n A simple exercise program, 1 hour twice a week, led to significantly slower decline in ADL score in patients with AD living in a nursing home than routine medical care.", "Assisted walking and walking combined with conversation were compared to a conversation-only intervention in nursing home residents with Alzheimer disease. Sixty-five subjects randomly assigned to treatment group were tested at baseline and end of treatment. Subjects' mean Mini-Mental State Examination score was 10.83; mean age was 87. Treatment was given for 30 minutes three times a week for 16 weeks. Subjects in the assisted walking group declined 20.9% in functional mobility; the conversation group declined 18.8%. The combined walking and conversation treatment group declined only 2.5%. These differences in outcome were significant and appear to have been affected by differences in treatment fidelity. Subjects in the conversation treatment group completed 90% of intended treatment compared with 75% in the combined group and only 57% in the assisted walking group. Failure to treat was due to subject refusal and physical illness. The conversation component of the combined walking and conversation treatment intervention appears to have improved compliance with the intervention, thereby improving treatment outcome. Results indicate that assisted walking with conversation can contribute to maintenance of functional mobility in institutionalized populations with Alzheimer disease. Staff assigned to this task should be prepared to use effective communication strategies to gain acceptance of the intervention.", "Resistance and endurance training result in gains in fitness in the aged. It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength, endurance, and function in this population.\n Randomized, controlled trial.\n Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home. They were older than 60 yrs with impairment in at least one physical activity of daily living. Seventy-eight subjects volunteered and 58 (mean age, 75 yrs; 9 women, 49 men) completed the intervention and initial posttest. Only one subject withdrew because of injury or disinterest.\n Thrice-weekly resistance training (using an isokinetic dynamometer) and twice-weekly endurance training for 4 to 8 weeks.\n Isometric strength in dominant arm and leg, heart rate response to timed endurance test, and activities of daily living score.\n The mean change in isometric strength across the muscle movements tested was 32.8% in the training group and 10.2% in the control group (difference, 22.6%; 95% confidence interval, 6.2% to 39.0%). No change in heart rate during exercise was seen in the training group. Trained subjects tended to have a greater improvement in functional activity than control subjects, which was statistically significant (p = .04) for those subjects who at enrollment were most dysfunctional (i.e., activities of daily living score less than 13 [maximum score 26]).\n This group of debilitated elderly patients effectively performed resistance training and increased their strength, with the most impaired gaining the most function. Few in the group could effectively perform endurance training.", "To evaluate the additional effect of functional exercises on balance and lower extremity function among hostel-dwelling elderly people partaking in strength,training.\n A randomized two-group parallel controlled trial.\n A senior resident's hostel in Switzerland.\n Thirty-two individuals randomized to either strength or strength and functional exercise groups.\n Both groups received machine-driven strength training for 45 min, twice weekly, for 12 weeks. The strength and functional exercises group received an additional 30 min of functional exercise training, once weekly.\n Tinetti test, balance tests and a physical performance test. Assessments were performed before and after the intervention.\n Improvements for the balance test depended on the type of training (significant interaction effects [F(1,20)= 6.7; P = 0.018]). This test improved from 11.3 +/- 11.7 to 17 +/- 11.2 (P = 0.009) in the combined training group (n = 12) and remained from 7.3 +/- 9.5 to 6.9 +/- 9.2 unchanged (P = 0.821) in the strength training group (n = 13). A significant difference between groups following training was observed (P = 0.031). The Tinetti balance score and the chair stand test of the physical performance assessment improved from 14.3 +/- 1.9 to 15.3 +/- 1.1 (P = 0.026) and 1.8 +/- 1.2 to 2.8 +/- 1.1 (P = 0.012) respectively in the combined training group only.\n Our findings suggest that twice-weekly lower extremity strength training of 12 weeks' duration in hostel-dwelling elderly people only improves task-specific balance performance and lower extremity physical function when additional functional exercises are added.", "The purpose of this study was to determine if 1.0 Full-time Equivalent (FTE) physical therapy (PT) and 1.0 FTE occupational therapy (OT) per 50 beds resulted in differences in functional status for nursing home residents when compared to 1.0 FTE PT and 1.0 FTE OT per 200 beds.\n Randomized control program evaluation, cost analysis.\n Nursing home in the province of Alberta, Canada.\n 115 residents assigned to 1 PT and 1 OT per 50 beds (enhanced group) versus 1 PT and 1 OT per 200 beds (control group) using stratified random allocation by severity of condition.\n Both groups received ongoing treatment, follow-up, and restorative interventions, but enhanced group received more hours of service.\n Functional Independence Measure (FIM), Functional Assessment Measures (FAM), and Clinical Outcome Variables Scale (COVS) recorded at 6-month intervals over a 2-year period.\n Mean score differences favored the enhanced group for the tests over the 2 years. Significance was observed on FIM Total at 6 and 12 months, FIM Self Care at 6 months, FIM Communication at 24 months, and FIM Psychosocial at 6, 12, 18, and 24 months; FAM Total at 6, 12, 18, and 24 months, FAM Self Care at 6 months, FAM Mobility at 12 months, FAM Communication at 6 and 24 months, FAM Psychosocial at 6, 12, 18, and 24 months, and FAM Cognition at 6 and 12 months; and COVS at 6, 12, 18, and 24 months. A cost analysis demonstrated that PT/OT offered at the 1:50 ratio would result in a cost savings in terms of nursing staff dollars for 30 long-term-care beds of $16,973 over the 2 years of the study compared to the 1:200 ratio. This equates to an annual cost savings of $283 per bed.\n Increasing the amount of PT/OT can have a positive effect on the functional status and cost of care of long-term care residents.", "The aim of the study was to assess the effect of structured strength and balance training on cognitive function in frail, geriatric, long-term care facility residents, aged 75 years or older, and additionally to evaluate the influence of training on various functional, physical and psychological parameters.\n Participants were randomly assigned to a training group or a control group. Physical training was performed three times a week for ten weeks in the training group. Muscle function was assessed by manual examination on a scale of 0-5. Cognitive function was tested with the Mini Mental State Examination (MMSE). In addition, scores for activities of daily living, mobility and depression were assessed.\n 30 subjects with a mean age of 86.8 years completed the study. After 10 weeks of intervention in the training group, muscle strength increased from a mean of 3.75 to 4.44 points (p<0.001) and the mean MMSE score increased from 20.9 to 23.9 points (p=0.023). In the training group, the change in the MMSE score correlated significantly with change in muscle function, with a Pearson correlation coefficient of 0.750 (p=0.002). An increase in mean BMI from 23.8 to 25.0 kg/m2 (p=0.013) was also found in the training group, but no significant changes in scores for activities of daily living, mobility or depression. Compared with the control group, the change in the mean scores over the ten-week training period was significantly higher for the trained group with regard to muscle scores, BMI and lean body mass, but not for MMSE scores.\n Our findings reinforce the recommendation that structured strength and balance training should be implemented in long-term care facilities. Besides the well-known benefits of physical training, our findings showed that an improvement in cognitive function may also be possible.", "nan", "Endurance training in nursing home patients was evaluated by selecting 15 of 150 patients for a conditioning program eliminating those patients with dementia and/or significant cardiac disease. After a medical and laboratory screen, all had a symptom-limited exercise test (SLXT) using arm and leg ergometry. Only two patients were able to use the treadmill and many had difficulty with leg cycling. Exercise capacities averaged 2-3METs in most patients. The exercise (E) group included eight randomly selected subjects who participated in a three times weekly upper and lower conditioning program using target heart rates based on the SLXT. The control (C) group continued in the daily nursing home routine. The SLXT was repeated at the end of one year. Two patients in each group expired from unassociated medical problems. Three patients in group E were hospitalized for brief periods. In group E there was a small but significant training effect in the arms (p = 0.05) but not in the legs. It would appear that a small training effect can occur in elderly nursing home patients with a conditioning program. The magnitude is limited by the low intensity of the program as well as the detraining effect of intercurrent illness. Functional limitations of the legs may be responsible for the lack of a training effect in these muscle groups.", "To test the effectiveness of a restorative care (Res-Care) intervention on function, muscle strength, contractures, and quality of life of nursing home residents, with secondary aims focused on strengthening self-efficacy and outcome expectations.\n A randomized controlled repeated-measure design was used, and generalized estimating equations were used to evaluate status at baseline and 4 and 12 months after initiation of the Res-Care intervention.\n Twelve nursing homes in Maryland.\n Four hundred eighty-seven residents consented and were eligible: 256 from treatment sites and 231 from control sites. The majority were female (389, 80.1%) and white (325, 66.8%); 85 (17.4%) were married and the remaining widowed, single, or divorced/separated. Mean age was 83.8 +/- 8.2, and mean Mini-Mental State Examination score was 20.4 +/- 5.3.\n Res-Care was a two-tiered self-efficacy-based intervention focused on motivating nursing assistants and residents to engage in functional and physical activities.\n Barthel Index, Tinetti Gait and Balance, grip strength, Dementia Quality-of-Life Scale, self-efficacy, and Outcome Expectations Scales for Function.\n Significant treatment-by-time interactions (P<.05) were found for the Tinetti Mobility Score and its gait and balance subscores and for walking, bathing, and stair climbing.\n The findings provide some evidence for the utility and safety of a Res-Care intervention in terms of improving function in NH residents.", "Past studies suggest multidisciplinary interventions that include physical therapy (PT) can improve function of nursing home residents. This trial specifically evaluates effects of PT for frail long-stay nursing home residents.\n Randomized, controlled trial.\n One academic nursing home and eight community nursing homes.\n A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months.\n Patients were randomized to individually tailored one-on-one PT sessions or friendly visits (FVs) three times a week for 4 months. Physical therapy included range-of-motion, strength, balance, transfer, and mobility exercises.\n Performance-based physical function assessed by the Physical Disability Index; self-perceived health status assessed with the Sickness Impact Profile; observer-reported activities of daily living; and falls.\n Eighty-nine percent and 92% of PT and FV sessions, respectively, were attended; 5% and 9% of subjects dropped out in the PT group and FV group, respectively. Compared with the FV group, the PT group experienced no significant improvements in overall Physical Disability Index, Sickness Impact Profile, or activities of daily living scores. A 15.5% improvement in the mobility subscale of the Physical Disability Index was seen (95% confidence interval [CI], 6.4% to 24.7%); no benefits in range-of-motion, strength, or balance subscales were found. Compared with the FV group, the PT group used assistive devices for bed mobility tasks less often (P = .06) and were less likely to use assistive devices and wheelchairs for locomotion (P < .005). There were 79 falls in the PT group vs 60 falls in the FV group (P = .11). Charge for the 4-month PT program was $1220 per subject (95% CI, $412 to $1832).\n This standardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions.", "To determine the effects of moderate intensity group-exercise programs on falls, functional performance, and disability in older adults; and to investigate the influence of frailty on these effects.\n A 20-week, multicenter randomized controlled trial, with 52-week follow-up.\n Fifteen homes for the elderly.\n Two hundred seventy-eight men and women (mean age +/- standard deviation, 85+/-6y).\n Two exercise programs were randomly distributed across 15 homes. The first program, functional walking (FW), consisted of exercises related to daily mobility activities. In the second program, in balance (IB), exercises were inspired by the principles of Tai Chi. Within each home participants were randomly assigned to an intervention or a control group. Participants in the control groups were asked not to change their usual pattern of activities. The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks.\n Falls, Performance Oriented Mobility Assessment (POMA), physical performance score, and the Groningen Activity Restriction Scale (GARS) (measuring self-reported disability).\n Fall incidence rate was higher in the FW group (3.3 falls/y) compared with the IB (2.4 falls/y) and control (2.5 falls/y) groups, but this difference was not statistically significant. The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail (hazard ratio [HR] = 2.95; 95% confidence interval [CI], 1.64-5.32). For participants who were classified as being pre-frail, the risk of becoming a faller decreased; this effect became significant after 11 weeks of training (HR = .39; 95% CI, .18-.88). Participants in both exercise groups showed a small, but significant improvement in their POMA and physical performance scores. In the FW group, this held true for the GARS score as well. Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores.\n Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail, but not in frail elderly.", "To determine if an exercise intervention, Functional Incidental Training (FIT), results in improvements in mobility endurance and physical activity when compared with prompted voiding (PV) among cognitively and mobility impaired nursing home residents.\n Residents from four nursing homes were randomized into either a PV only (PV) or a PV plus FIT (FIT) intervention group for 8 weeks. Research staff implemented all intervention and measurement protocols.\n Seventy-six incontinent nursing home residents completed all phases of the trial.\n The standing, walking, and wheelchair endurance, physical activity, and frequency of agitation of all residents were assessed before, during, and after the 8-week intervention.\n The average length of time that subjects could walk or wheel was 2.6 and 4.6 minutes, respectively, at baseline. There was a significant group x time interaction after intervention, with only the FIT group showing improvements in walking, wheelchair, and standing endurance (Manova F = 4.56, 2.62, and 5.98, respectively; P < .05 in all cases). The frequency with which agitation was observed showed a significant drop over time in both groups (F = 14.3, P < .001), with no significant group x time interaction.\n The FIT intervention, which requires 6 minutes more nurses' aide time than does PV, increases both physical activity and mobility endurance in extremely frail and deconditioned nursing home residents. The increased cost of this intervention must be evaluated both in terms of clinical outcomes and by the reality that the target group for this intervention is very frail and will continue to require nursing home care, even assuming an excellent response to the intervention.", "Seven recent experimental and quasi-experimental studies have compared the exercise of subjects instructed to pursue some added goal (often termed purposeful activity) with the exercise of subjects instructed to exercise without the suggestion of an added goal (often termed nonpurposeful activity). This article suggests a new terminology for this type of independent variable and describes an experiment within this developing tradition. An occupational form designed, through materials and instructions, to elicit a rotary arm exercise with the added purpose of stirring cookie dough was compared with an occupational form designed to elicit the rotary arm exercise with no added purpose. The subjects were 30 elderly female nursing home residents randomly assigned to the occupational forms. Results indicated that the added-purpose, occupationally embedded exercise condition elicited significantly more exercise repetitions than did the rote exercise condition (one-tailed p = .012). Exercise duration and exercise stoppages were also recorded. This study provides additional support for the traditional occupational therapy idea of embedding exercise within occupation. Suggestions are made for future research involving the experimental analysis of therapeutic occupation.", "Regular physical activity may improve different aspects of wellbeing in older people, such as quality of life, vitality and depression. However, there is little experimental evidence to support this assumption. Therefore, we examined the effect of different training protocols on quality of life, vitality and depression of older adults living in long-term care facilities.\n Subjects (n = 173, aged 64 to 94 years, living in long-term care facilities), were randomized to six months of three different moderate-intensity group exercise training protocols, or to an 'educational' control condition. Exercise consisted of two 45-60-minute training sessions per week of 1) resistance training; 2) all-round, functional training; or 3) a combination of both. Perceived health, the Geriatric Depression Scale (GDS), the Vitality Plus Scale (VPS) and the Dementia Quality of Life questionnaire (DQoL) were administered at baseline and after six months.\n In the combined training group a small but significant decline was seen in perceived health, DQoL and VPS score compared to the control group.\n We conclude that neither strength training nor all-round, functional training of moderate intensity is effective in improving quality of life, vitality or depression of older people living in long-term care facilities.", "Twenty-three geriatric patients from a mental institution were randomly assigned to three groups-a social group, an exercise group, and a control group. Subjects participated in the study for 12 weeks. Heart rate at rest, exercise and recovery, balancing ability, total daily activity level (diary method), and a self-care inventory were recorded for analysis. Data were collected at the start, the 8th and 12th weeks of the study, and 4 weeks after the termination of treatment. A Groups X Sex X Measurement Period factorial design, using multivariate analysis of variance tested the effect of the three factors. The trials effect was significant, as were several univariate tests for the sex effect and group by sex interaction. Data were discussed in terms of programmed physical activity for geriatrics, its value, and the limitations of evaluating such behavior in geriatric populations.", "To examine the applicability and feasibility of an intervention directed at improving continence, endurance, and strength (Functional Incidental Training [FIT]), for older patients in Veterans Administration (VA) nursing homes.\n Data were collected during a randomized, controlled, crossover trial.\n Four VA nursing homes.\n All 528 patients in the nursing homes were screened, 178 were eligible, and 107 were randomized into the trial. A total of 64 participants completed the intervention phase of the trial.\n Trained research staff provided the FIT intervention, which included prompted voiding combined with individualized, functionally oriented endurance and strength training exercises offered four times per day, 5 days per week, for 8 weeks.\n Descriptive data were collected relevant to the translation of the FIT intervention into everyday practice, including number of patients eligible and reasons for ineligibility, attrition rates and reasons for attrition, participant adherence to and satisfaction with FIT, and the costs of FIT relative to usual care.\n One third of the 528 patients met the eligibility criteria. The major reasons for ineligibility were being continent, age under 60, and a short anticipated length of stay. Of the 146 patients enrolled in the trial, 85 (58%) dropped out during the 9- to 10-month project. Deterioration in health status, death, and discharge accounted for two thirds of the attrition. Adherence to FIT was in general high but variable. Participants completed prompted voiding plus at least one exercise in 75% of the FIT rounds offered. Of the 60 participants who completed the protocol and who could answer simple questions, 75% indicated they enjoyed FIT, but 62% indicated that the exercise was too frequent, and 28% indicated they were offered opportunities to toilet too often. Based on timed observations, the costs of FIT are about four times as high as usual continence care.\n FIT is applicable to a substantial number of patients in VA nursing homes. The FIT protocol tested in this trial can be further refined and individualized based on patient preferences and adherence to various components of FIT in order to make it more feasible, efficient, and cost-effective in practice. The costs of maintaining an intervention such as FIT in all VA nursing home patients who may benefit, however, are high and must be justified largely by potential positive effects on function and quality of life, as opposed to cost savings resulting from the intervention.", "Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied.\n We conducted a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period.\n The mean (+/- SE) age of the 63 women and 37 men enrolled in the study was 87.1 +/- 0.6 years (range, 72 to 98); 94 percent of the subjects completed the study. Muscle strength increased by 113 +/- 8 percent in the subjects who underwent exercise training, as compared with 3 +/- 9 percent in the nonexercising subjects (P < 0.001). Gait velocity increased by 11.8 +/- 3.8 percent in the exercisers but declined by 1.0 +/- 3.8 percent in the nonexercisers (P = 0.02). Stair-climbing power also improved in the exercisers as compared with the nonexercisers (by 28.4 +/- 6.6 percent vs. 3.6 +/- 6.7 percent, P = 0.01), as did the level of spontaneous physical activity. Cross-sectional thigh-muscle area increased by 2.7 +/- 1.8 percent in the exercisers but declined by 1.8 +/- 2.0 percent in the nonexercisers (P = 0.11). The nutritional supplement had no effect on any primary outcome measure. Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation.\n High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people. In contrast, multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty.", "nan", "Regular exercise is widely advocated for the young and middle-aged, but less is heard about its relevance to elderly people. This study reports the findings of a controlled trial of seated exercise in residents of local authority homes for the elderly. Forty-nine residents aged 64-91 years volunteered for the 7-month project, and participated in either twice-weekly exercise or reminiscence sessions. Primary outcome measures were postural sway, flexibility of the spine and knees, hand-grip strength and functional capacity. The average (range of) attendance at the exercise sessions was 91% (64-100%), and at the reminiscence sessions was 86% (46-100%). By the end of the project, the change observed in the exercise group was significantly different from that of the reminiscence group in terms of grip strength (p < 0.02), spinal flexion (p < 0.001), chair-to-stand time (p < 0.001), activities of daily living (p < 0.05), and self-rating of depression (p < 0.01). Even very elderly residents of old peoples homes can benefit from participation in regular seated exercise and improve their functional capacity.", "Many studies have documented the effectiveness of verbally elicited imagery in the enhancement of motor skills in young, nondisabled populations. The present study examined the effects of verbally elicited imagery in the encouragement of two exercises (i.e., reaching up to pick apples and reaching down to pick up coins) in elderly women. The subjects were 27 women between 62 and 96 years of age who were selected from a nursing home, a residential retirement home, and a foster care home. All of the subjects received imagery as well as control conditions, but in a counterbalanced fashion. The Wilcoxon matched-pairs signed rank tests indicated that the imagery condition elicited significantly more repetitions of the reaching-up exercise than did the control condition (z = 2.25, p [one-tailed] = .012). The results in the reaching-down exercise were generally in the same direction but difficult to interpret statistically. The results are discussed in terms of other recent research investigating ways to add purpose to therapeutic exercise through occupation. Clinicians are urged to explore the advantages and disadvantages of imagery-based occupations in treatment.", "The quadriceps strength of a group of residents homes for the elderly (mean age 83 years) was assessed in a randomized controlled trial of seated group exercise versus group reminiscence therapy. Fifty-five of 65 volunteers completed the 6-month study, with 4 dropouts from the exercise group, and 6 dropouts from the reminiscence group. There were no adverse effects. Average of attendance at the exercise sessions was 72% (range, 18% to 98%) and 62% (range, 29% to 100%) at the reminiscence sessions. The reminiscence sessions comprised group interaction and discussion prompted by the use of reminiscence aids. By the end of the study, the change observed in the exercise group was significantly different from the reminiscence group in terms of quadriceps strength (p < 0.01, Mann-Whitney U test). Both groups improved equally in their ability to climb up steps, but neither cognitive function (Mini-Mental State Examination) nor reaction time altered significantly.", "To compare the effectiveness of unsupervised home and supervised group exercise on parameters related to risk of falling among older adults.\n Prospective, single-blind, randomized and controlled trial.\n Nursing home.\n The subjects were selected from 535 independent individuals who resided in a nursing home. Forty-two older adults, aged > 65 years, with risk of falling were recruited, and 32 of them completed the study.\n The 42 subjects were divided into two groups (unsupervised home exercise and supervised exercise group) randomly. Exercise sessions were performed three times a week for a period of eight weeks.\n Measurements were taken at baseline and after the completion of the exercise programme. The fear of falling was evaluated using a visual analogue scale, quadriceps muscle strength was measured with a dynamometer, flexibility was assessed with the sit and reach test, functional mobility was determined using the Timed Up and Go Test, balance was evaluated using one-leg and tandem standing, and Berg Balance Scale and proprioception was assessed with knee position sense.\n Thirty-two subjects (unsupervised home exercise n = 15, supervised group exercise n = 17) completed the exercise programme and all of the measurements. The unsupervised home exercise group showed significant improvement in balance, functional mobility and flexibility (P > 0.05). In addition to balance, functional mobility and flexibility, the supervised exercise group also showed significant improvements in both strength and proprioception (P > 0.05).\n Supervised group exercise is more effective at reducing the risk factors related to falling among older adults living in a nursing home than is unsupervised home exercise.", "The purpose of this experimental study was to compare the effects of skill training, a traditional stimulation approach, and regular care (control group) on the ability to perform the basic activities of daily living of nursing home residents with dementia. Sixty-three subjects were randomly selected and randomly assigned to the three groups. Ability to perform the basic activities of daily living (ADLs) and progress toward meeting individually set ADL-related goals were measured. Significant differences were found in two of the three measures used. In general, the greatest improvement was found in the skill training group, modest improvement in the simulation group, and decline in the control group.", "Health-related quality of life (HRQOL) that is good is regarded as the goal of elderly residential care. However, limited evidence exists indicating a promising intervention that can achieve this goal. The aim of this study is to examine the effect of Tai Chi on HRQOL in nursing home residents.\n A nonequivalent pretest-posttest control-group design.\n A convenience sample of 139 residents from six nursing homes in Hong Kong was used. The experimental group (n=66) joined a 26-week Tai Chi program, while the control group (n=73) continued with usual daily activities. The physical and mental components of HRQOL were designated as the dependent variables. Resident satisfaction was considered as a covariate. Doubly multivariate repeated measures analysis of covariance was done to examine the intervention effect.\n After adjusting for the confounding effect of resident satisfaction, a statistically significant difference (p<0.05) in the physical and mental components of HRQOL between the experimental and control groups was found. Findings showed significant improvement in HRQOL after residents practiced Tai Chi.\n These investigators contribute additional knowledge about the health benefits of Tai Chi among nursing home residents and indicates support for its use in this population to improve HRQOL.\n Tai Chi has unique characteristics as a health exercise that is particularly suitable for nursing home residents. The inclusion of Tai Chi exercise in elderly residential care practice is recommended.", "To investigate the effects of whole body vibration in the elderly.\n Randomized controlled trial.\n Nursing home.\n Forty-two elderly volunteers.\n Six-week vibration intervention plus physical therapy (PT) (n=22) or PT alone (n=20).\n We assessed gait and body balance using the Tinetti test (maximum scores of 12 for gait, 16 for body balance, 28 for global score), motor capacity using the Timed Up & Go (TUG) test, and health-related quality of life (HRQOL) using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36).\n After 6 weeks, the vibration intervention group improved by a mean +/- standard deviation of 2.4+/-2.3 points on the gait score compared with no score change in the control group ( P <.001). The intervention group improved by 3.5+/-2.1 points on the body balance score compared with a decrease of 0.3+/-1.2 points in the control group ( P <.001). TUG test time decreased by 11.0+/-8.6 seconds in the treated group compared with an increase of 2.6+/-8.8 seconds in the control group ( P <.001). The intervention group had significantly greater improvements from baseline on 8 of 9 items on the SF-36 compared with the control group.\n Controlled whole body vibration can improve elements of fall risk and HRQOL in elderly patients.", "The purpose of this study was to test whether an intervention combining increased daytime physical activity with improvement in the nighttime environment improves sleep and decreases agitation in nursing home residents.\n A randomized trial.\n One community nursing home in the Los Angeles, California area.\n Twenty-nine incontinent residents (mean age 88.3 years, 90% female).\n Subjects were randomized to receive either (1) an intervention combining increased daytime physical activity (14 weeks in duration) plus a nighttime program (5 nights in duration) to decrease noise and sleep-disruptive nursing care practices (intervention group), or (2) the nighttime program alone (control group).\n Daytime physical activity monitors and structured physical function assessments; nighttime wrist activity monitors to estimate nighttime sleep; and timed daytime behavioral observations of sleep versus wakefulness, either in or out of bed, and agitation.\n Physical function measures did not change significantly (MANOVA for repeated measures, group by time effect). Wrist actigraphy estimation of nighttime percent sleep (time asleep over time monitored in bed at night) increased in intervention subjects from 51.7% at baseline to 62.5% at follow-up compared with 67.0% at baseline to 66.3% at follow-up in controls (MANOVA, group by time, F = 4.42, P = .045, df = 27). At follow-up, intervention subjects averaged a 32% decrease in the percent of daytime observations in bed compared with baseline, with essentially no change in controls (MANOVA, group by time, F = 5.31, P = .029, df = 27). Seven of 15 intervention subjects had a decrease in observed agitation at follow-up, compared with baseline, versus only 1 of 14 controls with a decrease in observed agitation.\n This study provides preliminary evidence that an intervention combining increased physical activity with improvement in the nighttime nursing home environment improves sleep and decreases agitation in nursing home residents." ]

[ "6341388", "10801172", "8105213", "16219950", "14715820" ]

[ "Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: comparison with systemic corticosteroids alone.", "Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study.", "Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy.", "Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: a preliminary study.", "A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy." ]

[ "The effects of different methods of treatment of Graves' ophthalmopathy were evaluated in a series of 48 patients. Thirty-six patients were given combined treatment with orbital cobalt irradiation and systemic 6 alpha-methylprednisolone (methylprednisolone). Included in this group were 12 of 24 consecutive patients who were randomly assigned to either combined therapy or systemic methylprednisolone alone. The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index) and clinical assessment. Of the 36 patients treated by combined therapy, 12 (33%) showed excellent responses, 14 (39%) showed good responses, 9 (25%) showed slight responses, and 1 (3%) had no response. Treatment was more effective for soft tissue involvement, newly developed ophthalmoplegia, and optic neuropathy, while proptosis and longstanding ophthalmoplegia were less responsive. There was an inverse relationship between the duration of ophthalmopathy and the efficacy of treatment, more favorable results being observed when symptoms had been present for less than 2 yr. Treatment with systemic methylprednisolone alone was also effective, but, in general, responses were less satisfactory; 4 of the 12 patients of this group (33%) had good responses, 6 (50%) had slight responses, and 2 (17%) had no response. The results obtained in the 24 patients randomly assigned to combined therapy or steroid treatment alone were compared by evaluating changes in the ophthalmopathy index. Mean initial ophthalmopathy indices (6.4 vs. 6.2, respectively) showed no significant differences between the 2 groups, whereas the mean decrease in the group receiving combined therapy (4.8) was significantly greater (P less than 0.05) than that in the other group (3.2). In conclusion, the present study indicates that both orbital cobalt irradiation combined with systemic methylprednisolone treatment and systemic methylprednisolone therapy alone are valuable methods of treatment for Graves' ophthalmopathy, but the combined therapy proved to be more effective.", "The best treatment (steroids, irradiation, or both) for moderately severe Graves' orbitopathy, a self-limiting disease is not known. We tested the efficacy of external beam irradiation compared with sham-irradiation.\n In a double-blind randomised clinical trial, 30 patients with moderately severe Graves' orbitopathy had radiotherapy (20 Gy in ten fractions), and 30 were assigned sham-irradiation (ten fractions of 0 Gy). Treatment outcome was measured qualitatively by changes in major and minor criteria and quantitatively in several ophthalmic and other variables, such as eyelid aperture, proptosis, eye movements, subjective eye score, and clinical-activity score at 24 weeks.\n The qualitative treatment outcome was successful in 18 of 30 (60%) irradiated patients versus nine of 29 (31%) sham-irradiated patients at week 24 (relative risk [RR]=1.9 [95% CI 1.0-3.6], p=0.04). This difference was caused by improvements in diplopia grade, but not by reduction of proptosis, nor of eyelid swelling. Quantitatively, elevation improved significantly in the radiotherapy group, whereas all other variables remained unchanged. The field of binocular single vision was enlarged in 11 of 17 patients after irradiation compared with two of 15 after sham-irradiation. Nevertheless, only 25% of the irradiated patients were spared from additional strabismus surgery.\n In these patients with moderately severe Graves' orbitopathy, radiotherapy should be used only to treat motility impairment.", "Corticosteroids are usually given for management of Graves' ophthalmopathy, but they have many and serious side-effects. By comparison, retrobulbar irradiation is well tolerated, although its efficacy has been evaluated only in uncontrolled studies. Therefore, we did a double-blind randomised trial, in which 28 patients with moderately severe Graves' ophthalmopathy were treated with a 3-month course of oral prednisone and sham irradiation, and 28 received retrobulbar irradiation (20 Gy) and placebo capsules. Therapeutic outcome, assessed twenty-four weeks after the start of treatment, was determined by the change in the highest NOSPECS class. A successful outcome was observed in 14 prednisone-treated and in 13 irradiated patients. Responders to treatment (but not nonresponders) in both groups showed improvements in total and subjective eye score and a decrease in eye-muscle volume. Response to either treatment was due largely to changes in soft-tissue involvement and eye-muscle motility. Mean elevation in responders to radiotherapy increased from 18.5 degrees (95% CI 14.8-22.2) at baseline to 21.8 degrees (18.6-25.0) at week twenty-four (p = 0.003), but did not change in prednisone responders. Side-effects were more frequent and severe during prednisone than during radiotherapy. Radiotherapy and oral prednisone appear to be equally effective as initial treatment in patients with moderately severe Graves' ophthalmopathy. In view of its better tolerability, radiotherapy should be considered the treatment of first choice.", "To assess the efficacy and safety of combined orbital irradiation and systemic steroids in the management of moderate-to-severe Graves' ophthalmopathy.\n Single-blind randomised prospective study.\n Regional hospital, Hong Kong.\n Sixteen patients with active moderate-to-severe Graves' ophthalmopathy who were randomly assigned to steroid therapy (ST group) or combination therapy of orbital irradiation and systemic steroids (SRT group) between June 2000 and June 2003.\n NOSPECS scoring system, total eye score, subjective eye score, and extra-ocular muscle thickness as determined by either computed tomographic or magnetic resonance imaging scans.\n The study was completed by 15 of 16 patients. Both groups experienced improvement in total eye score, soft tissue swelling, ocular motility, visual acuity, and subjective eye score at 52-week follow-up. Total eye score improved earlier in the SRT group, achieving statistical significance (P<0.05) at as early as 4 weeks of follow-up. Improvement in ocular parameters was greater and led to a significantly greater reduction in total eye score than in the ST group at weeks 16, 24, and 52. Maximum extra-ocular muscle thickness was significantly reduced in the SRT group only. No change was observed in proptosis in either group. No serious adverse effect was observed with the addition of orbital irradiation to steroid therapy.\n A combination of orbital irradiation and systemic steroids is well tolerated and more effective than steroids alone in the treatment of active moderate-to-severe Graves' ophthalmopathy. It achieves greater and more rapid improvement in soft tissue swelling, ocular motility, and visual acuity.", "Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs." ]

[ "10698876", "11237160", "10440303" ]

[ "Domiciliary occupational therapy for patients with stroke discharged from hospital: randomised controlled trial.", "A multicentre randomized controlled trial of leisure therapy and conventional occupational therapy after stroke. TOTAL Study Group. Trial of Occupational Therapy and Leisure.", "Occupational therapy for stroke patients not admitted to hospital: a randomised controlled trial." ]

[ "To establish if a brief programme of domiciliary occupational therapy could improve the recovery of patients with stroke discharged from hospital.\n Single blind randomised controlled trial.\n Two hospital sites within a UK teaching hospital.\n 138 patients with stroke with a definite plan for discharge home from hospital.\n Six week domiciliary occupational therapy or routine follow up.\n Nottingham extended activities of daily living score and \"global outcome\" (deterioration according to the Barthel activities of daily living index, or death).\n By eight weeks the mean Nottingham extended activities of daily living score in the intervention group was 4.8 points (95% confidence interval -0.5 to 10.0, P=0.08) greater than that of the control group. Overall, 16 (24%) intervention patients had a poor global outcome compared with 30 (42%) control patients (odds ratio 0.43, 0.21 to 0.89, P=0.02). These patterns persisted at six months but were not statistically significant. Patients in the intervention group were more likely to report satisfaction with a range of aspects of services.\n The functional outcome and satisfaction of patients with stroke can be improved by a brief occupational therapy programme carried out in the patient's home immediately after discharge. Major benefits may not, however, be sustained.", "To evaluate the effects of leisure therapy and conventional occupational therapy (OT) on the mood, leisure participation and independence in activities of daily living (ADL) of stroke patients 6 and 12 months after hospital discharge.\n Multicentre randomized controlled trial.\n Four hundred and sixty-six stroke patients from five UK centres.\n The General Health Questionnaire (12 item), the Nottingham Extended ADL Scale and the Nottingham Leisure Questionnaire, assessed by post, with telephone clarification.\n Four hundred and forty (94%) and 426 (91%) subjects were alive at 6 and 12 months, respectively. Three hundred and seventy-four (85% of survivors) and 311 (78% of survivors) responded at 6 and 12 month follow-up respectively. At six months and compared to the control group, those allocated to leisure therapy had nonsignificantly better GHQ scores (-1.2: 95% CI -2.9, +0.5), leisure scores (+0.7, 95% CI -1.1, +2.5) and Extended ADL scores (+0.4: 95% CI -3.8, +4.5): the ADL group had nonsignificantly better GHQ scores (-0.1: 95% CI -1.8, +1.7) and Extended ADL scores (+1.4: 95% CI -2.9, +5.6) and nonsignificantly worse leisure scores (-0.3: 95% CI -2.1, +1.6). The results at 12 months were similar.\n In contrast to the findings of previous smaller trials, neither of the additional OT treatments showed a clear beneficial effect on mood, leisure activity or independence in ADL measured at 6 or 12 months.", "Patients who have a stroke are not always admitted to hospital, and 22-60% remain in the community, frequently without coordinated rehabilitation. We aimed to assess the efficacy of an occupational therapy intervention for patients with stroke who were not admitted to hospital.\n In this single-blind randomised controlled trial, consecutive stroke patients on a UK community register in Nottingham and Derbyshire were allocated randomly to up to 5 months of occupational therapy at home or to no intervention (control group) 1 month after their stroke. The aim of the occupational therapy was to encourage independence in personal and instrumental activities of daily living. Patients were assessed on outcome measures at baseline (before randomisation) and at 6 months. The primary outcome measure was the score on the extended activities of daily living (EADL) scale at 6 months. Other outcome measures included the Barthel index, the general health questionnaire 28, the carer strain index, and the London handicap scale. All assessments were done by an independent assessor who was unaware of treatment allocation. The analysis included only data from completed questionnaires.\n 185 patients were included: 94 in the occupational therapy group and 91 in the control group. 22 patients were not assessed at 6 months. At follow-up, patients who had occupational therapy had significantly higher median scores than the controls on: the EADL scale (16 vs 12, p<0.01, estimated difference 3 [95% CI 1 to 4]); the Barthel index (20 vs 18, p<0.01, difference 1, [0-1]); the carer strain index (1 vs 3, p<0.05, difference 1 [0 to 2]); and the London handicap scale (76 vs 65, p<0.05, difference 7, [0.3 to 13.5]). There were no significant differences on the general health questionnaire between the patient or carer.\n Occupational therapy significantly reduced disability and handicap in patients with stroke who were not admitted to hospital." ]

[ "15679718", "16685007", "16337447", "16615971", "17587425", "17885859", "15875528", "16024244", "16629781", "17587424", "16860173", "16443353" ]

[ "Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma.", "Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma.", "Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma.", "Once-daily ciclesonide in children: efficacy and safety in asthma.", "Efficacy and safety of inhaled ciclesonide compared with chlorofluorocarbon beclomethasone dipropionate in adults with moderate to severe persistent asthma.", "Similar efficacy of ciclesonide once daily versus fluticasone propionate twice daily in patients with persistent asthma.", "Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma.", "Once-daily ciclesonide 80 or 320 microg for 12 weeks is safe and effective in patients with persistent asthma.", "Anti-inflammatory effects of once daily low dose inhaled ciclesonide in mild to moderate asthmatic patients.", "Efficacy and safety of once-daily inhaled ciclesonide in adults with mild to moderate asthma: a double-blind, placebo-controlled study.", "A multinational, 12-week, randomized study comparing the efficacy and tolerability of ciclesonide and budesonide in patients with asthma.", "Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with mild allergic asthma." ]

[ "Inhaled corticosteroids (ICS) are recommended therapy for persistent asthma, although side effects can limit appropriate use. Ciclesonide, a novel ICS, is activated in the lung, thereby reducing systemic activity and side effects. This 12-week, double-blind, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma.\n After a 2-week baseline period in which current ICS treatment was continued, 329 patients were randomized to receive ciclesonide 160 microg (n = 107) or 640 microg (n = 112) (ex-actuator doses, equivalent to 200 and 800 microg ex-valve, respectively), or placebo (n = 110) once daily in the morning. Efficacy was monitored by asthma symptom scores, rescue medication use, morning and evening peak expiratory flow (PEF) measurements, spirometry, and probability of study completion without experiencing lack of efficacy.\n Morning PEF remained stable with either ciclesonide dose but decreased with placebo; the differences were significant (P < 0.0001) for both ciclesonide doses vs placebo. The forced expiratory volume in 1 s and forced vital capacity decreased significantly with placebo (P < 0.005), but were unchanged with ciclesonide. Lack of efficacy was significantly greater for patients switched to placebo (63%) than it was for those treated with ciclesonide 160 microg (30%) (P < 0.0001 vs placebo) or ciclesonide 640 microg (31%) (P < 0.0001 vs placebo). There were no significant differences between the two tested doses of ciclesonide with respect to efficacy and safety. Serum and 24-h urine cortisol were unaffected by ciclesonide treatment. Both doses of ciclesonide were well tolerated with no cases of oral candidiasis.\n Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma.", "Oral corticosteroids (OCS) may be associated with systemic adverse events (AEs), which can be reduced by replacing OCS with inhaled corticosteroids (ICS). The potential of ciclesonide, a novel ICS, to reduce OCS use in patients with severe, persistent asthma was evaluated in this study.\n A phase III, 12-week, international, multicenter, double-blind, placebo-controlled, parallel-group study.\n Adult and adolescent patients (> or = 12 years old; n = 141) with severe, persistent, oral steroid (prednisone)-dependent asthma.\n Patients were randomized to receive ciclesonide (640 mug/d or 1,280 microg/d [ex-actuator]) bid or placebo for 12 weeks. Weekly evaluations determined eligibility for prednisone dose reduction based on predetermined criteria.\n The prednisone dose was significantly reduced by 47% and 63% in the groups receiving ciclesonide, 640 microg/d, and ciclesonide, 1,280 microg/d, respectively, vs an increase of 4% in the placebo group (both p < or = 0.0003) at week 12. By week 12, prednisone was discontinued by approximately 30% of patients in the ciclesonide-treated groups, vs 11% of patients in the placebo group (both p < or = 0.04). FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo (p < 0.03). The occurrence of local and systemic AEs was comparable between all treatment groups.\n Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe, persistent asthma, while maintaining asthma control.", "Inhaled corticosteroids are recommended as first-line therapy for persistent asthma.\n We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma.\n An integrated analysis of 2 identical, multicenter, double-blind, randomized, parallel-group, placebo-controlled trials was conducted. Patients (n = 1015; aged > or =12 years) with mild-to-moderate asthma (FEV1 of 60% to 85% of predicted value) were randomized to ciclesonide 80 microg (CIC80), 160 microg (CIC160), or 320 microg (CIC320), once daily (exactuator doses) in the morning or placebo for 12 weeks.\n All ciclesonide groups showed significant improvements from baseline to week 12 in FEV1 compared with the placebo group (CIC80, 0.12 L [P = .0007]; CIC160, 0.13 L [P = .0004]; and CIC320, 0.14 L [P < .0001]). Likewise, FEV1 percent predicted, morning and evening peak expiratory flow, 24-hour asthma symptom score, daily albuterol use, and nighttime awakenings were significantly improved in all ciclesonide groups compared with the placebo group. Overall ciclesonide safety profile and rates of oropharyngeal adverse events for all groups were low and similar to those of the placebo group. Fewer ciclesonide-treated patients exhibited asthma-aggravated adverse events, and fewer ciclesonide-treated patients discontinued the study for any reason or because of a lack of efficacy compared with those in the placebo group. No suppression of hypothalamic-pituitary-adrenal-axis function (as assessed by means of 24-hour urinary cortisol levels corrected for creatinine and peak serum cortisol levels after stimulation with low-dose [1 microg] cosyntropin) was observed with any dose of ciclesonide.\n In this integrated analysis, ciclesonide once daily administered in the morning is effective and well tolerated.", "To compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug (CIC40), 80 mug (CIC80), and 160 mug (CIC160) with placebo in children with persistent asthma of all severities.\n Overall, 1031 children age 4 to 11 years were randomized into 2 identical double-blinded, placebo-controlled, parallel group studies consisting of a run-in phase followed by 12 weeks of treatment. Both studies were designed to allow for a prespecified integrated analysis. The primary outcome variable was change in forced expiratory volume in 1 second (FEV(1)) percent predicted between baseline and study end; treatment comparisons were assessed using analysis of covariance. Additional endpoints included asthma symptom scores, daily albuterol use, and safety, including hypothalamic-pituitary-adrenal (HPA) axis function.\n Baseline characteristics were comparable; 59.4% of patients had moderate asthma, and 24.1% had severe asthma. All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1) percent predicted versus placebo (CIC40, 11.97; CIC80, 13.58, P <.05; CIC160, 14.17, P < .01). Significant improvements in asthma symptoms (P < .01) and reductions in albuterol use were reported. Ciclesonide was well tolerated with no effect on HPA axis function.\n In this integrated analysis, ciclesonide was effective and well tolerated in children with persistent asthma.", "Inhaled corticosteroids are recognized as first-line therapy in the management of asthma; however, their use may be limited by systemic and local side-effects. Ciclesonide, a novel pro-drug inhaled corticosteroid, is activated in the lungs and is expected to have less systemic and local side-effects. This study evaluated the efficacy and safety of ciclesonide in hydrofluoroalkane (HFA) compared with beclomethasone dipropionate (BDP) in a chlorofluorocarbon (CFC) formulation in adult patients with moderate to severe asthma.\n This was a multicentre, randomized, open-label, parallel-group comparative study. The patients were given 800 microg/day of CFC-BDP in the four-week baseline period. After the baseline period, 319 patients were randomly allocated into three groups which, respectively, received HFA-ciclesonide 400 microg/day (without a spacer), HFA-ciclesonide 800 microg/day (without spacer) and CFC-BDP 800 microg/day (with spacer) for the eight-week treatment period. The primary efficacy variable was morning PEF.\n The morning PEF increased by 16.02 L/min in the 400 microg HFA-ciclesonide group, 23.98 L/min in the 800 microg HFA-ciclesonide group and 5.91 L/min in the 800 microg CFC-BDP group. Better outcomes were achieved by the use of 800 microg/day of HFA-ciclesonide compared with 800 microg/day of CFC-BDP (P = 0.001). There was no difference in adverse events between the groups.\n In adult patients with moderate to severe asthma, 800 microg/day of HFA-ciclesonide was significantly more effective than 800 microg/day of CFC-BDP. Ciclesonide at doses of 400 microg/day and 800 microg/day was safe and well tolerated.", "This 12-week, double-blind, parallel-group study compared the efficacy and safety of once daily ciclesonide and twice daily fluticasone propionate in patients aged 12-75 years with persistent asthma. Patients were randomized to once-daily ciclesonide 80 micro g (n = 278) or 160 micro g (n = 271), or twice daily fluticasone propionate 88 micro g (n = 259) (all ex-actuator). Significant improvements from baseline were seen in all three treatment groups for forced expiratory volume in 1 second, asthma symptom scores and rescue medication use (all p < 0.0001). Asthma exacerbation rates were low (each ciclesonide group, n = 2; fluticasone group, n = 1). Adverse event reporting indicated good tolerability. Once daily ciclesonide 80 micro g or 160 micro g showed comparable efficacy and tolerability to twice daily fluticasone propionate 88 micro g in persistent asthma.", "Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events.\n To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma.\n This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator.\n For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate.\n These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.", "The efficacy and safety of ciclesonide was assessed in this randomized, placebo-controlled study in patients with persistent asthma (randomized n=360) maintained on low to moderate doses of inhaled corticosteroids. Patients were randomized to receive ciclesonide 80 or 320 microg (ex-actuator doses, equivalent to 100 and 400 microg ex-valve, respectively) or placebo once daily in the morning via metered-dose inhaler for 12 weeks. Morning peak expiratory flow was maintained throughout the treatment period in patients treated with ciclesonide and decreased significantly in patients treated with placebo (P=0.0003). Ciclesonide (80 and 320 microg) significantly increased forced expiratory volume in 1s from baseline (0.13 and 0.19 L increases, respectively; P<0.01); improvements were superior versus placebo (P=0.0044 for 80 microg ciclesonide; P<0.0001 for 320 microg ciclesonide). The probability of losing efficacy decreased in a dose-dependent manner (55% for placebo, 38% for ciclesonide 80 microg, 23% for ciclesonide 320 microg). Asthma symptom scores and rescue medication use were unchanged with ciclesonide and significantly worsened with placebo. The incidence of adverse events was comparable in all treatment groups and no cortisol suppression was observed. Therefore, ciclesonide 80 and 320 microg administered once daily was a safe and effective maintenance treatment for patients with persistent asthma.", "Ciclesonide exhibits clinical efficacy at 160 microg (ex-actuator) once daily but the anti-inflammatory effects at this dose are not known. We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 microg once daily in the morning exhibited significant anti-inflammatory effects.\n Seventeen patients with mild persistent asthma (FEV(1) 3.35 l) were recruited into a double-blind placebo-controlled randomized crossover study. Measurements were made after ciclesonide and placebo treatment as well as after run-in and washout periods, for adenosine monophosphate (AMP) bronchial challenge (primary variable), exhaled nitric oxide (NO) and induced sputum (in a subgroup).\n The mean (SEM) AMP bronchial challenge PC(20) following ciclesonide (140 (63) mg/ml) was significantly (P < 0.001) increased compared with placebo (17 (8) mg/ml), run-in (13 (5) mg/ml) and washout (9 (3) mg/ml) periods. This amounted to an eightfold (CI: 5.3-12.0) for ciclesonide vs placebo. Likewise, there were significant improvements in exhaled NO levels and a significant reduction in induced sputum eosinophil cell counts.\n We have shown that inhaled ciclesonide given at 160 microg once daily in the morning exhibits significant anti-inflammatory effects that are in keeping with the previously described clinical effects.", "Inhaled corticosteroids are recommended as first-line therapy for the management of asthma, although side-effects may limit their use. Ciclesonide, a novel pro-drug inhaled corticosteroid, exerts potent and prolonged local anti-inflammatory effects in the lungs, and is considered to have an improved safety and tolerability profile. The aim of this study was to evaluate the efficacy and safety of ciclesonide in adult patients with mild to moderate asthma.\n A placebo-controlled, multicentre, randomized, double-blind, parallel-group study was conducted. During the 4-week baseline period, patients were given 400 microg/day of beclomethasone dipropionate in a chlorofluorocarbon formulation. After the baseline period, 311 patients were given once-daily 100, 200 or 400 microg of ciclesonide or placebo for an 8-week treatment period without the use of a spacer. The primary efficacy variable was morning PEF.\n Changes in the morning PEF (least squares mean) at the end of the study were 4.23 L/min (P < 0.001) in the 100 microg group, 3.75 L/min (P < 0.001) in the 200 microg group, -0.40 L/min (P < 0.001) in the 400 microg group, as compared with -24.95 L/min in the placebo group. In the ciclesonide groups, the PEF remained at the same level as the baseline period. No large differences were observed between the placebo group and the ciclesonide groups regarding safety.\n Once-daily administration of ciclesonide at doses of 100, 200 or 400 microg was shown to be effective in adult patients with mild to moderate asthma. Ciclesonide is considered to have favourable safety profiles and be well tolerated.", "Ciclesonide is a new lung-activated inhaled corticosteroid (ICS) that has shown efficacy in previous placebo-controlled and comparative studies in patients with persistent asthma. It is important to compare new treatments with existing ICSs to obtain relative data concerning their efficacy and tolerability.\n This study compared the efficacy and tolerability of ciclesonide QD with budesonide BID in patients with asthma.\n This 12-week, randomized study was conducted at 62 study sites across Europe. Male and female patients aged 12 to 75 years with primarily mild to moderate asthma were enrolled. This study was double blind with respect to the ciclesonide dose and open label for budesonide, as placebofor budesonide was not available. Patients were randomly assigned to receive inhaled ciclesonide 80 or 320 microg QD (morning) or budesonide 200 microg BID for 12 weeks. Efficacy and tolerability assessments were performed at weeks 0 (baseline), 4, 8, and 12. The primary end point was the change from baseline in forced expiratory volume in 1 second (FEV1) at 12 weeks. Secondary end points were changes from baseline in morning peak expiratory flow (PEF), asthma symptom scores, and rescue medication use. Tolerability was assessed throughout the study by monitoring of standard laboratory variables (hematology and biochemistry); physical examination, including vital signs; reporting of adverse events (AEs); and 24-hour urinary cortisol as a measure of hypothalamic-pituitary-adrenal-axis function.\n Five hundred fifty-four patients were randomized (301 men, 253 women; mean age, 41.3 years; ciclesonide 80 microg QD, 182 patients; ciclesonide 320 microg QD, 195; budesonide 200 microg BID, 177). Demographic and baseline clinical characteristics, including age, sex, weight, and (FEV1) were similar between the 3 groups. Compared with baseline values, week-12 FEV1 (least squares mean [LSM] [SEM] A, +0.267 [0.035], +0.256 [0.033], and +0.355 [0.034] L, respectively; all, P<0.001) and morning PEF (LSM [SEM] Delta, +12 [5], +17 [4], and +21 [4] L/min, respectively; all, P<or=0.008) were significantly improved with ciclesonide 80 and 320 microg QD and budesonide 200 microg BID. At 12 weeks, ciclesonide was found to be noninferior to budesonide with regard to mean changes from baseline in (FEV1) (intent to treat [ITT]: 97.5% CI for ciclesonide 80 microg QD vs budesonide 200 microg BID, -0.192 to 0.015; 97.5 CI for ciclesonide 320 microg QD vs budesonide 200 microg BID, -0.200 to 0.001) and morning PEF (ITT. 97.5% CI for ciclesonide 80 microg QD vs budesonide 200 microg BID, -22 to 5; 97.5% CI for ciclesonide 320 microg QD vs budesonide 200 microg BID, -17 to 10). Similar findings were seen in the per-protocol population. Week-12 daily, daytime, and nighttime asthma symptom scores and rescue medication use were significantly decreased from baseline in all 3 treatment groups (all, P<0.001). The prevalences of AEs were similar across all 3 treatment groups. Week-12 mean urinary cortisol excretion was statistically similar to baseline with both ciclesonide doses (Delta, -0.54 and +0.16 nmol/mmol creatinine with ciclesonide 80 and 320 microg QD, respectively) but was significantly reduced from baseline with budesonide (Delta, -1.42 nmol/mmol creatinine; P<0.05).\n The results of this study in patients with primarily mild to moderate asthma suggest that ciclesonide 80 and 320 microg QD were similar to budesonide 200 microg BID in improving pulmonary function, controlling asthma symptoms, and reducing the need for rescue medication use. Unlike budesonide, ciclesonide was not associated with significant urinary cortisol suppression in these patients.", "Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily efficacy and potent anti-inflammatory activity. The aim of the study was to compare the effect of ciclesonide and fluticasone propionate on exhaled nitric oxide (FENO), pulmonary function, and other parameters used in clinical evaluation of patients with mild allergic asthma. The study indicates that ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster and stronger decrease of FENO in comparison with fluticasone (100 microg twice daily). In both groups of patients treated with ciclesonide, the highest decrease in FENO levels was observed after 2 weeks of treatment. In the group of patients treated with fluticasone, this maximum effect was not observed till 8 weeks. An improvement in spirometric indices was observed in all groups studied. Statistical differences between the groups were not found; however, there was a trend toward higher increase in the group receiving 160 microg of ciclesonide. In all groups studied we observed clinical improvement (asthmatic symptoms and consumption of rescue medication were reduced), but there were no significant differences between these groups. Our results indicate that ciclesonide, compared with fluticasone, has stronger anti-inflammatory activity in patients with mild allergic asthma." ]

[ "16333556", "4603119", "3516299", "1793781", "3299678", "1871540", "2316883", "16952918", "394267", "3551119", "7048956", "16626607", "8424422", "9459225", "8211620", "17445634", "6398510", "6892625", "15906123", "1678650", "8143997", "7851167", "10365879", "3554490", "2979233", "3911699", "3907073", "7970045", "10733114", "15383800", "12568180", "11528141", "2036922", "11575284", "8239200", "6345045" ]

[ "Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study.", "Does pantothenic acid accelerate the return of bowel motility in post-operative patients?", "Negative effect of Metoclopramide in postoperative adynamic ileus. A prospective, randomized, double blind study.", "Cisapride in the treatment of post-operative ileus.", "Effect of combined blockade of beta-adrenoceptors and acetylcholinesterase in the treatment of postoperative ileus after cholecystectomy.", "Treatment of postoperative paralytic ileus with cisapride.", "Treatment of postoperative paralytic ileus by intravenous lidocaine infusion.", "Comparison of the effects of thoracic epidural analgesia and i.v. infusion with lidocaine on cytokine response, postoperative pain and bowel function in patients undergoing colonic surgery.", "[Evaluation of the use of caerulein (ceruletide) in the postoperative of abdominal surgery].", "Cisapride does not reduce postoperative paralytic ileus.", "Double-blind study of the treatment of the adynamic ileus with fructose-1,6-diphosphate.", "A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy.", "Effect of intravenous erythromycin on postoperative ileus.", "Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy.", "The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative study with conventional cholecystectomy and sympathetic blockade treatment.", "Treatment of postoperative ileus after bowel surgery with low-dose intravenous erythromycin.", "Modulation of the adrenergic system in the treatment of postoperative bowel atonia.", "Usefulness of caerulein in the treatment of post-operative intestinal atony.", "Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery.", "Lack of effect of metoclopramide on colonic motility after cholecystectomy.", "Small bowel motility following major intra-abdominal surgery: the effects of opiates and rectal cisapride.", "Effect of cisapride on distal colonic motility in the early postoperative period following left colonic anastomosis.", "A prospective, randomized, double-blinded, placebo-controlled trial of cisapride after colorectal surgery.", "Beta-adrenoceptor blockade in the treatment of postoperative adynamic ileus.", "Pharmacological manipulation of adynamic ileus: controlled randomized double-blind study of ceruletide on intestinal motor activity after elective abdominal surgery.", "The effect of cholecystokinin on postoperative bowel function.", "[Postoperative intestinal atony and vasopressin. A randomized study of the effect of administration of vasopressin on the duration of postoperative intestinal atony].", "[A double-blind study of neostigmine versus placebo in paralytic ileus as a result of surgical interventions].", "Prokinetic effect of erythromycin after colorectal surgery: randomized, placebo-controlled, double-blind study.", "Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus.", "The effect of erythromycin on bile excretion and proximal small bowel motility following divided gastric bypass surgery: a prospective randomized placebo-controlled trial.", "Effects of propranolol on human postoperative ileus.", "Does metoclopramide reduce the length of ileus after colorectal surgery? A prospective randomized trial.", "Selective postoperative inhibition of gastrointestinal opioid receptors.", "Oncotic pressure, albumin and ileus: the effect of albumin replacement on postoperative ileus.", "Dihydroergotamine in postoperative ileus." ]

[ "Alvimopan is a peripherally acting mu-opioid receptor (PAM-OR) antagonist for accelerating gastrointestinal recovery after surgery.\n Patients undergoing open laparotomy (bowel resection, n = 418; hysterectomy, n = 197) were randomized to receive alvimopan 6 or 12 mg or placebo orally > or = 2 h before surgery and then b.i.d. until hospital discharge (up to 7 days). The primary efficacy endpoint was time to gastrointestinal (GI) recovery (measured by toleration of solid food and passage of flatus/stool; GI-3). Secondary endpoints included time to GI-2 recovery (toleration of solid food and passage of stool) and hospital discharge order written (DCO).\n Alvimopan did not significantly accelerate GI-3 compared with placebo [6 mg: hazard ratio (HR) = 1.20, p = 0.080; 12 mg: HR = 1.24, p = 0.038). However, after adjustment for significant covariates (sex/surgical duration), benefits were significant for both doses (6 mg: HR = 1.24, p = 0.037; 12 mg: HR = 1.26, p = 0.028). Alvimopan also significantly accelerated time to GI-2 (6 mg: HR = 1.37, p = 0.008; 12 mg: HR = 1.33, p = 0.018) and DCO (6 mg: HR = 1.31, p = 0.008; 12 mg: HR = 1.28, p = 0.015). Adverse events were similar between groups.\n Alvimopan (6 or 12 mg) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy.", "nan", "In a double blind controlled study including 60 patients it was found that Metoclopramide has a negative effect upon the resolution of postoperative adynamic ileus. Metoclopramide causes a delay in the time from operation to the first passage of flatus.", "The effect of cisapride on duration of post-operative ileus after surgery was investigated in a randomized, double-blind, placebo-controlled study. Patients undergoing elective upper gastrointestinal (n = 47) or colonic (n = 22) surgery were pre-operatively randomly allocated to treatment with either cisapride 30 mg t.d.s., by rectal administration, or placebo. Treatment started exactly 48 h after surgery if the patient at this time had not passed stool. Time to passage of first stool after surgery was estimated. Mean time to passage of stool was 85 (32) h (s.d.) for cisapride-treated and 91 (43) h for placebo-treated patients. No difference between the treatment groups was noted. Treatment with cisapride did not shorten the duration of postoperative ileus after either upper gastrointestinal or colonic surgery.", "The effect of treatment with a non-selective beta-adrenoceptor blocker (propranolol) and an acetylcholinesterase blocker (neostigmine) on the duration of postoperative ileus after cholecystectomy was investigated in a double-blind, randomized study comprising 51 patients. Propranolol (P), 10 mg intravenously twice daily was, together with neostigmine (N), 0.5 mg subcutaneously twice daily, administered to 16 patients. Eighteen patients were treated with neostigmine, 0.5 mg subcutaneously twice daily only, and 17 patients were placebo-treated controls (C). The medical treatment started in the evening of the day of operation. The time to first passage of stool after operation was determined and used as a measure of duration of the postoperative ileus. The mean time was 68 +/- 6 h in the P + N-treated group, 82 +/- 6 h in the N group, and 90 +/- 7 h in the C group. The difference between the P + N group and controls was significant (p less than 0.01). P + N was effective in patients older than 60 years (p less than 0.01), whereas no effect was seen in patients younger than 60 years. In conclusion, treatment with a combination of propranolol and neostigmine shortened the duration of postoperative paralytic ileus after cholecystectomy. This effect was not seen after treatment with neostigmine only. The effect of P + N was most marked in patients older than 60 years.", "The effect of cisapride on postoperative colonic motility was studied in 40 patients undergoing cholecystectomy under randomized, double-blind conditions. The patients received 10 mg of cisapride or placebo by intravenous injection starting on the day of surgery and repeated every 12 h until the 3rd postoperative day. The return of propagative motility in the colon was visualized by means of radiopaque markers and serial abdominal radiographs. Cisapride induced a significantly earlier return of propulsive motility in the right colon, as indicated by the propagation of markers from the ascending colon to the transverse colon (p less than 0.05). Radiopaque markers reached the descending colon (p less than 0.05) and the rectosigmoid colon (p less than 0.05) significantly earlier in the cisapride group than in controls. The first passage of feces occurred significantly earlier in cisapride-treated patients than in controls (p less than 0.05). The first passage of gas after surgery did not differ significantly between the groups. Our results suggest that cisapride can be used to induce earlier return of propagative motility in the colon after major abdominal surgery.", "The effects of continuous intravenous infusion of lidocaine on postoperative paralytic ileus in cholecystectomized patients was investigated in this double-blind study. An infusion of lidocaine (3 mg/min, n = 15) or an infusion of an equal volume of saline (n = 15) was started 30 min before induction of anesthesia and continued for 24 h after surgery. Postoperative colonic motility was evaluated by radiopaque markers and serial abdominal radiographs. A record was kept of the first passage of gas and feces. Results showed significantly earlier return of propulsive motility in the colon of lidocaine-treated patients. Radiopaque markers in the lidocaine group were propelled significantly earlier from the cecum/ascending colon to the transverse colon (P less than 0.05) and appeared significantly earlier in the descending colon (P less than 0.05) and the rectosigmoid colon (P less than 0.05) than in saline-treated patients. Despite the fact that the mean time for postoperative defecation occurred 17 h earlier in lidocaine-treated patients, differences between the groups were not statistically significant--a fact due, perhaps, to great individual variations in defecation habits. The time to first passage of gas, a variable representative of changes in anorectal or colonic tone rather than propagative motility, also did not differ significantly between the groups. No adverse reactions to lidocaine were reported. The results suggest that continuous intravenous infusion of lidocaine during the first postoperative day shortens the duration of paralytic ileus in the colon after abdominal surgery. Suppression of inhibitory gastrointestinal reflexes by reduction of postoperative peritoneal irritation is suggested as the mechanism of action.", "Both thoracic epidural analgesia (TEA) and i.v. lidocaine were able to decrease postoperative pain and duration of ileus. We compared TEA and i.v. lidocaine (IV) regarding their effects on cytokines, pain and bowel function after colonic surgery.\n Sixty patients were randomly allocated to one of the three groups. TEA group had lidocaine 2 mg kg(-1) followed by 3 mg kg(-1) h(-1) epidurally and an equal volume of i.v. normal saline. The IV group received the same amount of lidocaine i.v. and normal saline epidurally. The control group received normal saline via both routes. These regimens were started 30 min before surgery and were continued throughout. Blood cytokines were measured at scheduled times within 72 h.\n Both TEA and IV groups had better pain relief. The total consumptions using patient-controlled epidural analgesia were 81.6 (6.5), 55.0 (5.3) and 45.6 (3.9) ml (P<0.01) and the times of flatus passage were 50.2 (4.9), 60.2 (5.8) and 71.7 (4.7) h (P<0.01) in the TEA, IV and control groups, respectively. The TEA group exhibited the best postoperative pain relief and the least cytokine surge. The IV group experienced better pain relief and less cytokine release than the control group.\n The TEA lidocaine had better pain relief, lower opioid consumption, earlier return of bowel function and lesser production of cytokines than IV lidocaine during 72 h after colonic surgery; IV group was better than the control group.", "In order to evaluate the efficacy of Caerulein in the postoperative stage of abdominal surgery, 25 patients received 0.3 mcg/kg intravenously every 4 hours. Bowel Movements, passage of gases, first evacuation and general improvement were compared to 25 patients in similar conditions who didn't receive the drug. The study group showed an earlier appearance of intestinal motility as compared to the control group. This contributed in a relevant matter to an earlier discharge from the hospital. The differences with the control group were statistically significative. The benefits of the drug in the management of the postoperative stage of abdominal surgery are discussed.", "nan", "nan", "The purpose of this study was to investigate the safety and efficacy of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy.\n Women (n = 519) were randomized (4:1) to receive alvimopan 12 mg (n = 413) or placebo (n = 106) > or = 2 hours before the operation then twice daily for 7 days (hospital and home). Adverse events were monitored up to 30 days after the last dose of study drug was administered. Efficacy was assessed for 7 postoperative days.\n Overall, the most common adverse events were nausea, vomiting, and constipation; < 5% of patients discontinued use because of adverse events. Alvimopan significantly accelerated the time to first bowel movement (hazard ratio, 2.33; P <.001). Average time to first bowel movement was reduced by 22 hours, with more frequent bowel movement and better bowel movement quality found in the treatment cohort.\n Alvimopan has a safety profile that is similar to that of placebo and provides significantly improved lower gastrointestinal recovery in women who undergo simple total abdominal hysterectomy.", "We attempted to determine whether the administration of erythromycin shortens the period of postoperative ileus by a prospective, double-blind, placebo-controlled study. Seventy-seven patients were randomized and included in the statistical calculations. The patients were stratified according to the operation performed (cholecystectomy, celiotomy, or other major abdominal operations). Forty-one patients (group 1) received 250 mg erythromycin intravenously every 8 h for nine doses upon admission to the recovery room. Thirty-six patients (group 2) received placebo. The time (in hours) to first passage of flatus, first liquid meal, first bowel movement, and total length of hospital stay was recorded. There was no significant difference between group 1 and group 2 in time to first flatus (54.9 +/- 29 vs. 53.9 +/- 27 h, respectively), first meal (70.4 +/- 44 vs. 71.7 +/- 65), first bowel movement (81.8 +/- 32 vs. 80.1 +/- 28), or length of hospital stay (185.2 +/- 183 vs. 182.1 +/- 163). Erythromycin, in the dosage tested in this study, does not seem to alter clinical parameters of gastrointestinal motility after an abdominal operation. New prokinetic agents may deserve further studies.", "Postoperative ileus is a concern among surgical patients. Epidural anesthesia and analgesia with local anesthetics can decrease the duration of ileus. Significant systemic absorption of local anesthesia occurs during epidural use. In this study, we examined whether many of the beneficial effects on bowel function seen with epidural lidocaine are also present when the drug is given parenterally. Forty patients undergoing radical retropubic prostatectomy were studied with one half of the patients receiving a lidocaine bolus (1.5 mg/kg) and infusion (3 mg/min, unless weight <70 kg, then 2 mg/min); the other half received a saline infusion. A blind observer recorded the patient's daily pain score, the time the patient first experienced flatulence and had the first bowel movement, and the total use of analgesics. Lidocaine-treated patients first experienced flatulence in a significantly shorter time (P < 0.01) than control patients. Lidocaine patients' hospital stay was also significantly shorter (P < 0.05); on average, they spent 1.1 fewer days in the hospital. I.V. lidocaine initiated before anesthesia and continued 1 h postoperatively significantly sped up the return of bowel function. Lidocaine patients were also more comfortable postoperatively. Many of the bowel function benefits attributed to epidural lidocaine are also present when the drug is administered parenterally. Additionally, the length of hospital stay was reduced in lidocaine-treated patients. Implications: This study prospectively examined whether I.V. lidocaine could affect the return of bowel function after radical prostate surgery. Lidocaine-treated patients had shorter hospital stays, less pain, and faster return of bowel function. In this population, lidocaine infusion can be a useful adjunct in anesthetic management.", "Our study is prompted by the arrival of laparoscopic cholecystectomy in connection with the evolution of postoperative ileus (PI) and by its avoidance of the intraabdominal handling implied in conventional cholecystectomy. With this aim a prospective, controlled, randomized, and blind clinical trial was designed using 100 patients divided into five groups (n = 20): I, conventional cholecystectomy (CC): II, CC+injection of 20 ml bupivacaine 0.5% into the mesentery root; III, CC + 7.5 mg propranolol i.v. and 0.5 mg neostigmine s.c., postoperatively until the first defecation; IV, II+III; and V, laparoscopic cholecystectomy. The shortest period of PI was observed in group V. This period increases notably in group IV (53 h), group II (72 h), and group III (84 h) relative to the control group with (89 h). This reduction in PI time runs parallel with an improvement in the patient's general state of well-being. We concluded that after laparoscopic cholecystectomy PI is nonexistent. Furthermore, this study confirms the correlation between the avoidance of intraabdominal manipulation and the evolution of postoperative ileus.", "Treatment of postoperative ileus remains unsatisfactory. Erythromycin (EM), a macrolide antibiotic, has prokinetic effects on the gut. We investigated whether intravenous erythromycin decreases the time to the return of normal bowel function after bowel surgery in patients with bladder cancer and interstitial cystitis who have undergone cystectomy and urinary diversion.\n We conducted a double-blind, randomized, placebo-controlled study of 22 volunteers. On the first postoperative day, patients began receiving intravenous erythromycin (125 mg) or placebo every 8 hours (maximum of 21 doses). The patients' ability to tolerate a general diet and return of bowel function was monitored.\n A general diet was tolerated at a median of 9 days postoperatively for the EM arm and 8 for the placebo arm (P = 0.60). The first bowel sounds were detected at an average of 2 postoperative days for the EM arm and 3 for the placebo arm (P = 0.88). First flatus was present an average of 5 days postoperatively for both study arms (P = 0.35). The first bowel movement was present an average of 6 days postoperatively for the EM arm and 5 for the placebo arm (P = 0.98).\n No significant difference was found between EM and placebo with regard to the onset of bowel sounds, passage of flatus, passage of the first bowel movement, and the time to tolerate a general diet. These data indicate that erythromycin is not useful in improving postoperative bowel function.", "Sympathetic hyperactivity is considered to be the most important factor in the development of postoperative bowel atonia. In a double-blind study we evaluated the gut motor effects of dihydroergotamine, which predominantly acts as a sympatholytic agent in the gastrointestinal tract. Forty-six patients undergoing cholecystectomy received either 0.5 mg dihydroergotamine + 5000 U heparin or 5000 U heparin alone (controls) twice daily in a randomized order starting on the morning of the operation. The first postoperative bowel movement occurred 57 +/- 4 h (means +/- SEM) after operation in the patients receiving dihydroergotamine, compared with 102 +/- 4 h in the control patients (p less than 0.001). Electromyography performed in the stomach and upper small bowel on the 3rd postoperative day showed an increase in the number of activity fronts of the interdigestive migrating motor complex and in the duration of spike activity under the influence of dihydroergotamine compared with the controls (p less than 0.001). It is concluded that dihydroergotamine stimulates depressed gut motility after abdominal surgery and that sympatholysis is the likely mechanism of action.", "We conducted a controlled clinical trial designed to test caerulein for tolerability and effectiveness in post-operative patients recovering from abdominal surgery. The test product was administered 24 hours after surgery, by intravenous drip infusion, at the rate of 2 nanograms/kg/minute. The results were compared with parallel observations made in a matched group of patients receiving no drugs or manipulation likely to promote intestinal peristalsis with the exception of the application of a nasogastric tube for aspiration and the water and electrolyte replenishment customary in the post-operative period. The results of this study evince a clear-cut difference between the two groups of patients in regard to the restoration of intestinal peristalsis and the passing of flatus and faeces, as confirmed by statistical analysis (Cochran's test) demonstrating the significant (p less than 0.01) superiority of caerulein treatment relative to the untreated control group. Likewise, the study revealed the excellent tolerability of the test drug at the dosage employed.", "Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay, contribute to readmission, and increase morbidity. There is no approved treatment for postoperative ileus. Alvimopan is a novel, peripherally acting, mu opioid receptor antagonist currently in development for the management of postoperative ileus.\n Patients undergoing partial colectomy or simple or radical hysterectomy were randomized to receive alvimopan 6 mg (n = 152), alvimopan 12 mg (n = 146), or placebo (n = 153) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days. The primary efficacy end point, time to return of gastrointestinal function, was a composite measure of passage of flatus or stool and tolerating solid food. Secondary end points included time to the hospital discharge order written. Adverse events were monitored throughout the study.\n Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo (hazard ratio = 1.45; P = 0.003), with a smaller reduction seen with alvimopan 12 mg (hazard ratio = 1.28; P = 0.059). Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg (hazard ratio = 1.50; P < 0.001). The most common treatment-emergent adverse events across all treatment groups were nausea, vomiting, and hypotension; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group.\n In patients undergoing major abdominal surgery, alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated.", "The effect of metoclopramide on postoperative colonic ileus was evaluated in a randomised, double-blind study in 20 patients after cholecystectomy. The start of propulsive colonic motility and colonic transit time after operation were measured by radio-opaque markers and serial abdominal radiographs. Metoclopramide 20 mg given intravenously three times a day until the fourth postoperative day (n = 10) did not significantly reduce the duration of postoperative colonic paralysis compared with control patients (n = 10), nor were there any differences between the groups when the time of first postoperative passage of gas and faeces were compared. In conclusion, the use of metoclopramide in the postoperative period did not result in a quicker return of propulsive motility in the right or left colon as judged by the radio-opaque markers and serial abdominal radiographs.", "Human small bowel motility is altered after laparotomy. Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy.\n Continuous proximal small bowel manometry was performed for up to 92 hours in 23 patients after major intra-abdominal surgery. They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus. Small bowel manometry was performed for 30 hours in 5 volunteers receiving 1 mg/kg meperidine over 3 hours.\n Phase III activity was present within 3 hours of the end of surgery in all patients. Initially, the migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but gradually increased. Phase II activity was absent until a median of 40 hours had elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum, in contrast to that in the duodenum, presumably as a result of dilatation and/or altered tone, increasing to normal by 72 hours. In the volunteer group, although the MMC period was reduced by meperidine, it remained significantly greater than that of the placebo patient group for approximately 48 hours and phase II was reduced but not eliminated. Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility. Clinical outcome, assessed by the return of bowel sounds and passage of flatus, was accelerated by cisapride, but the trend was not significant (P = 0.11).\n This is the first published study using prolonged manometry to show the gradual evolution of small bowel motor activity after major intra-abdominal surgery. The findings suggest that surgery decreases the MMC period to the equivalent of the absolute refractory period, thereby eliminating phase II, which returns as the MMC period lengthens. Cisapride, at the dosage given, confers only modest benefit.", "This study was designed to investigate the modulatory effect of cisapride on colonic motility in the postoperative period.\n A prospective, double-blind, randomized, placebo-controlled trial of 14 patients undergoing left colonic anastomosis was carried out. Manometric probes were positioned with transducers on either side of the anastomosis, and colonic activity was recorded continuously for a median of 98 (range, 72-144) hours using an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program.\n Isolated waveform activity returned at a median of 1.8 (interquartile range, 1-3) hours and motor complex activity at 24 (interquartile range, 19-30) hours in the placebo group and at similar times in the cisapride group. All motility variables except mean amplitude increased significantly with time in both groups. In the cisapride group the motility index was significantly increased compared with the placebo group (P = 0.03), resulting from an increase in percentage duration of activity (P = 0.002). Activity index, mean amplitude of waveforms, and number of waves greater than 50 cm H2O did not differ between groups. In contrast to placebo, cisapride significantly increased the median number of waves greater than 13 cm H2O and percentage duration of activity distal to the anastomosis compared with proximally. The return of bowel sounds (median, 43, interquartile range, 24-48 hours vs. 67, 29-69 hours; P = 0.2) or first passage of flatus (78, 54-94 hours vs. 94, 81-105 hours; P = 0.1) did not differ between groups.\n Although cisapride may have a differential effect on the colon proximal and distal to an anastomosis and significantly increases some indices of motility in the early postoperative period, these are unlikely to be of any clinical relevance.", "The predominant factor prolonging hospitalization and delaying oral intake after colorectal surgery continues to be return of large bowel function. We investigated the effect of the cisapride on postoperative bowel motility.\n Patients were started on cisapride versus a placebo on postoperative day 1 after colorectal surgery. Endpoints included the time to patients' first bowel movement, time of advancement to regular diet, time of hospitalization, and cost analysis. Results were analyzed using a Mann-Whitney test.\n Thirty-five patients were entered in the study, consisting of 17 in the cisapride group and 18 in the placebo group. The median time to first bowel movement, advancement of diet, and hospital discharge was 1 day less in the cisapride group compared with the placebo group (P <0.05). There was a substantial cost savings in the study group.\n Cisapride use results in statistically significant improvement in postoperative bowel motility. Cisapride should be added as adjunct treatment in postoperative care after colorectal surgery.", "Abdominal trauma, such as surgery and peritonitis, leads to inhibition of intestinal motility, partly mediated by alpha- and beta-adrenoceptors. To investigate the effect of nonselective beta-blockade on adynamic ileus, propranolol was compared with placebo in the postoperative course after elective colonic surgery in a double-blind randomized study. Ten patients received 4 mg propranolol intravenously twice daily, and ten received 10 mg intravenously twice daily. Nineteen patients received placebo. The time to first passage of stool was 110 +/- 9 h in the placebo group and 82 +/- 11 h in the 4-mg propranolol group. In the 10-mg propranolol group, the time was 79 +/- 8 h. The difference between the placebo-treated group and the propranolol-treated groups was significant (p less than 0.01). The effect of propranolol was most marked in older patients and after surgery on the distal colon. In patients older than 60 years the time to first stool in the placebo group was 127 +/- 13 h (n = 8), compared with 73 +/- 8 h (n = 11) in the propranolol group (p less than 0.01). In patients who had undergone surgery on the distal colon the time to first stool was 125 +/- 13 h (n = 8) in the placebo group and 76 +/- 8 h (n = 11) for propranolol (p less than 0.01). Adverse effects on the respiratory or cardiovascular system were not seen during medication. It is concluded that propranolol shortens the period of adynamic ileus after colonic surgery.", "In a double-blind placebo-controlled trial of patients undergoing elective abdominal surgery (n = 91), a single intravenous infusion of ceruletide (2.5 ng kg-1 min-1 for 1 hour) resulted in audible bowel sounds in 42/47 patients as opposed to 30/44 receiving placebo (P less than 0.025). Excessive bowel sounds were noted in 16 patients in the ceruletide group and four receiving placebo (P less than 0.01). Significantly more patients (P less than 0.01) in the ceruletide group (22/45 versus 9/44) passed flatus per rectum between the second and third post-operative day. Ceruletide infusion was accompanied by a significant increase in the incidence of nausea and vomiting (P less than 0.005, P less than 0.0025) but these side effects were short-lived. These results indicate that ceruletide is likely to be a useful therapeutic agent for acute intestinal adynamic motility disorders.", "Cholecystokinin (CCK) was used in a randomized double-blind trial to evaluate its effect on post-operative paralytic ileus. Sixty patients were admitted to the study. The return of postoperative intestinal motility was registered with subjective and/or objective methods. No differences were found between the CCK group and the placebo group.", "nan", "A fully randomized double-blind study, stratified according to diagnosis, was carried out in order to assess the effect of endonasal neostigmine in the treatment of post-laparotic paralytic ileus. A total of 40 patients (16 M, 24 F), aged between 22 and 76 years old, were admitted to the study; of these 20 were cholecystectomized and 20 had undergone emergency surgery. According to a special randomization list, 10 patients from each pathological group were treated with 6% neostigmine en (1 puff = 5.4 mg) and the other ten were treated with placebo. Both treatments were administered at a dose of 2 puffs, one per nostril, at the end of surgery and then repeated every 4 hours up to a maximum of 6 puffs/day. Treatment was continued for 4 days or until canalization of feces and gas was achieved. The mean daily dose of endonasal neostigmine found to be efficacious was 4 puffs/day, equivalent to 24.7 mg in cholecystectomized patients and 23.5 mg in patients undergoing emergency surgery. In over-all terms the canalization of gas and feces was observed in 74% of patients treated with neostigmine and in 45% of those receiving placebo and the difference was statistically significant.", "Nausea and vomiting three to seven days after an elective operation on the colon and rectum remain a persistent clinical problem. Erythromycin, a safe, inexpensive drug that stimulates intestinal motilin receptors, has previously been shown to accelerate gastric emptying significantly after upper gastrointestinal surgery. We aimed to evaluate the effect of postoperative intravenous erythromycin on postoperative ileus in patients undergoing elective surgery for primary colorectal cancer.\n Between May 1998 and April 1999, 150 patients undergoing primary resection of colon or rectal cancer were enrolled in this prospective, randomized, placebo-controlled trial. One hundred thirty-four patients completed the study. Patients were excluded if they had extensive metastatic disease, were taking medications known to interact with erythromycin, or if they required an ileostomy. Patients received either 200 mg of intravenous erythromycin or placebo every six hours. Clinical endpoints were recorded and continuous end-points are presented as mean +/- standard deviation.\n There were no significant complications related to erythromycin. The erythromycin (n = 65) and placebo (n = 69) groups were comparable regarding demographic and operative factors. The erythromycin group had a slightly shorter length of time to passage of flatus (4.1 +/- 1.3 vs. 4.4 +/- 1.1 days; P = 0.03). There was no significant difference between erythromycin and placebo in time to first solid food (5.6 +/- 1.9 vs. 5.4 +/- 1.8 days), time to first bowel movement (5.2 +/- 1.9 vs. 5.4 +/- 1.3 days), or time to discharge from hospital (7.5 +/- 2.0 vs. 7.6 +/- 2.8 days). There was no difference in the rate of clinically significant nausea (26 vs. 26 percent; P = 0.99), vomiting (17 vs. 16 percent; P = 0.88), or nasogastric tube placement (9 vs. 7 percent; P = 0.68).\n Erythromycin does not seem to alter clinically important outcomes related to postoperative ileus in patients undergoing resection for colorectal cancer.", "To demonstrate that alvimopan (6 or 12 mg) accelerates recovery of gastrointestinal (GI) function in patients undergoing laparotomy for bowel resection or radical hysterectomy.\n Postoperative ileus (POI) following laparotomy may increase morbidity and extend hospitalization. Opioids can contribute to the duration of POI. Alvimopan is a novel opioid receptor antagonist in development for the management of POI.\n A total of 510 patients scheduled for bowel resection or radical hysterectomy were randomized (1:1:1) to receive alvimopan 6 mg, alvimopan 12 mg, or placebo orally > or =2 hours before surgery, then twice a day (b.i.d.) until hospital discharge or for up to 7 days. The primary efficacy end point was a composite of time to recovery of upper and lower GI function. An associated secondary end point was time to hospital discharge order written.\n The modified intent-to-treat population included 469 patients (451 bowel resection and 18 radical hysterectomy patients). Time to recovery of GI function was accelerated for the alvimopan 6 mg (hazard ratio [HR] = 1.28; P < 0.05) and 12 mg (HR = 1.54; P < 0.001) groups with a mean difference of 15 and 22 hours, respectively, compared with placebo. The time to hospital discharge order written was also accelerated in the alvimopan 12 mg group (HR = 1.42; P = 0.003) with a mean difference of 20 hours compared with placebo. The incidence of adverse events was similar among treatment groups.\n Alvimopan accelerated GI recovery and time to hospital discharge order written compared with placebo in patients undergoing laparotomy and was well tolerated.", "No conclusive data exists supporting the use of any prokinetic agent in the postoperative setting. The study was designed to examine the effect of erythromycin on small bowel motility in a placebo-controlled trial of post gastric bypass patients utilizing a standardized nuclear medicine test.\n A consecutive series of 21 patients undergoing elective gastric bypass surgery for morbid obesity between September 1999 and March 2001 were enrolled in this prospective double-blind randomized controlled trial. Standard open, divided gastric bypass was performed. Patients were randomized to receive either erythromycin 250 mg i. v. (11 patients) or placebo (10 patients) every 8 hours. On postoperative day 2, a hepatic iminodiacetic acid (HIDA) scan was obtained. Tracer movement through the biliary tree and proximal small bowel was quantified and compared.\n Tracer clearance from the liver and biliary tree was no different between groups from time of injection through 1 hour. Tracer material clearance from the duodenum into the jejunum was no different between the erythromycin and control groups at 1 hour, 37% +/- 13% and 37% +/- 22% respectively (P = 0.95). At 4 hours, clearance was greater in the erythromycin group, 77% +/- 6%, compared to control, 60% +/- 20% (P = 0.036). The rate of tracer change between hour 1 and 4 (slope) was steeper in the erythromycin group (P = 0.048).\n Erythromycin increases intestinal transit in the postoperative setting.", "The sympathetic nervous hyperactivity present in response to surgical stress has been implicated as an important component of the postoperative paralytic ileus. A randomized and prospective study was conducted, evaluating the effects of the preoperative beta-adrenergic blockade with propranolol in schistosomotic patients during the period of postoperative ileus.\n The study compared schistosomotic patients submitted, or not, to beta-adrenergic blockade. Basal cardiac frequency was determined and propranolol was used in a dose of 40 mg twice a day. The dose was adjusted weekly until a minimum decrease of 20% in cardiac frequency was achieved. Three coupled bipolar electrodes were placed in the left colon in both groups, and registration of myoelectric activity of the left colon was made twice a day during the period of postoperative ileus using a system of data collection (DATA Q Series 200). The electric signals were previously amplified, filtered and separated into Electric Control Activity (ECA) and Electric Response Activity (ERA).\n The dose of propranolol varied from 80 to 160 mg/day. The proportional decrease in basal heart frequency varied from 20 to 33%, with an average of 25.4 +/- 3.9% in the propranolol group, maintaining a mean of 24.3 +/- 3.6% decrease in the postoperative period. Differences on clinical recovery of the postoperative ileus were not found. Significant differences on electromyographic patterns were not observed between the groups, except for the presence of a greater number of short-duration contractions in the second postoperative day in the beta-blocked group.\n The authors suggest that the preoperative beta-adrenergic blockade with propranolol does not determine myoelectric activity changes that could contribute to an earlier resolution of postoperative ileus.\n Copyright 2001 S. Karger AG, Basel", "Between August 1988 and September 1989, 100 consecutive patients who underwent elective abdominal colorectal surgical procedures were prospectively randomized to receive or not to receive metoclopramide. Metoclopramide was intravenously administered every 8 hours from the completion of surgery until a solid food diet was able to be tolerated. Seven patients were not included in the final tabulations because of one death, one small bowel obstruction requiring laparotomy, one anastomotic leak requiring laparotomy, and four protocol violations. Ninety-three patients, 37 men and 56 women (mean age, 59.5; range, 14-89 years) underwent 40 segmental colectomies, 13 total abdominal colectomies, 8 abdominoperineal resections, 8 ileoanal pouch procedures, 7 small bowel resections, and 17 other colorectal procedures. The 40 patients who received postoperative metoclopramide were in Group 1, and the 53 who did not were in Group 2. The mean length of time between laparotomy and commencement of oral fluid and oral solid intake in Groups 1 and 2 were 3.5 and 4.8 days, and 3.5 and 5.0 days, respectively. These differences were not statistically significant (P greater than 0.05). Prolonged ileus was seen in seven patients in Group 1 and in eight patients in Group 2. These differences were also not statistically significant (P greater than 0.05). Prolonged ileus was defined as the need for nasogastric tube reinsertion or discontinuation of oral intake. We conclude that metoclopramide does not significantly alter the course of postoperative ileus.", "Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function.\n We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients--including 1 whose surgery was canceled--to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated the outcomes.\n Fifteen patients underwent partial colectomy and 63 underwent total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly faster recovery of gastrointestinal function than those given placebo. The median time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the median time to the first bowel movement decreased from 111 to 70 hours (P=0.01), and the median time until patients were ready for discharge decreased from 91 to 68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were less pronounced.\n Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization.", "The effect of decreased colloid oncotic pressure, as seen in hypoalbuminemia and hypoproteinemia, upon intestinal function has been well delineated in the surgical literature. Patients undergoing abdominal aortic aneurysm resection or aortoiliac or aortofemoral bypass grafts are almost uniformly hypoalbuminemic postoperatively; with these two facts in mind, a prospective, randomized clinical study was undertaken to identify the role of serum albumin concentration on the length of postoperative ileus in this population. The main hypothesis was that patients whose albumin levels dropped below 3.5 gm/dL would have a more prolonged postoperative hospital course as a result of delay in return of bowel function when compared with those patients in whom the low albumin levels were exogenously acutely replenished to > 3.5 gm/dL. Albumin was replaced to a level greater-than or equal to 3.5 g/dL in one group of 37 patients (AR), with a control group of 32 patients (NR) not receiving any albumin. Return of bowel function was measured by the postoperative day that flatus was documented, as well as the postoperative day oral intake was resumed. Mean values were determined for each group, and t tests did not reveal a significant difference in postoperative day of flatus (AR mean = 4.06 days, NR mean = 4.16 days) or postoperative day of oral intake (AR mean = 4.0, NR mean = 3.75). Additional comparisons between the groups involving the number of postoperative days until a regular diet was begun (AR mean = 6.06, NR mean = 5.48) and length of postoperative hospital stay (AR mean = 9.16, NR mean = 8.43) failed to reveal significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effects of dihydroergotamine (DHE) on postoperative ileus after major abdominal surgery were studied. Forty-one patients received 0.5 mg DHE subcutaneously twice a day from the day of surgery to the seventh postoperative day. Thirty-three patients served as controls. There were no significant differences in the time to the first postoperative passage of flatus or delivery of stools nor in the quantity of laxatives given. It is concluded that DHE does not reduce the duration of postoperative ileus." ]

[ "7983954", "1548825", "3523718", "3204081", "6385838", "8268363", "8527539", "1482152", "3524436", "3541724", "9815469", "2668252", "1538160", "2403603", "1603387", "2012354", "1493985" ]

[ "Randomised trial of single-dose ciprofloxacin for travellers' diarrhoea.", "Oral aztreonam, a poorly absorbed yet effective therapy for bacterial diarrhea in US travelers to Mexico.", "Antimicrobial therapy for travelers' diarrhea.", "Treatment of travellers' diarrhoea with pivmecillinam.", "Furazolidone versus ampicillin in the treatment of traveler's diarrhea.", "Short-term treatment of traveler's diarrhea with norfloxacin: a double-blind, placebo-controlled study during two seasons.", "Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent.", "Optimal dosing of trimethoprim-sulfamethoxazole when used with loperamide to treat traveler's diarrhea.", "Role of a novel antidiarrheal agent, BW942C, alone or in combination with trimethoprim-sulfamethoxazole in the treatment of traveler's diarrhea.", "Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial.", "Single Dose Ofloxacin plus Loperamide Compared with Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea.", "Short-term self-treatment of travellers' diarrhoea with norfloxacin: a placebo-controlled study.", "Treatment of traveler's diarrhea with ciprofloxacin and loperamide.", "Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide.", "Norfloxacin compared to trimethoprim/sulfamethoxazole for the treatment of travelers' diarrhea among U.S. military personnel deployed to South America and West Africa.", "Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial.", "Ecological effects of short-term ciprofloxacin treatment of travellers' diarrhoea." ]

[ "Diarrhoea is the most common illness affecting travellers to developing countries. Our study was designed to compare the efficacy of a single 500 mg dose of ciprofloxacin with placebo for treatment of acute diarrhoea in travellers. British troops who were within their first 8 weeks of deployment in Belize and who presented within 24 h of the onset of diarrhoea, were randomized to receive either ciprofloxacin 500 mg or placebo. Every subject recorded the number and consistency of stools and presence of any other associated symptoms for 72 h or until recovery. Of 88 subjects enrolled, 83 were evaluable, of whom 45 received ciprofloxacin and 38 placebo. Groups did not differ with regard to duration or severity of diarrhoea at randomisation. Mean (SE) duration of diarrhoea, as assessed by time to the last liquid and last unformed stool, was reduced from 50.4 (4.5) h and 53.5 (4.4) h, respectively, in the placebo group to 20.9 (3.4) h and 24.8 (3.8) h in those receiving ciprofloxacin (p < 0.0001). Mean number of liquid stools was reduced from 11.4 (1.2) in the placebo group to 5.0 (0.7) in the ciprofloxacin-treated group (p < 0.0001). The cumulative percentages of subjects with no unformed stool after 24 h, 48 h, and 72 h were, respectively, 64%, 82%, and 93% in the ciprofloxacin group and 11%, 42%, and 79% in the placebo group (p < 0.0001, p < 0.001, and not significant, respectively). A single 500 mg dose of ciprofloxacin was an effective empirical treatment for reducing the duration and severity of diarrhoea in travellers. The regimen should maximise compliance and reduce the cost and duration of therapy.", "To evaluate a poorly absorbed antimicrobial with in vitro activity against all major bacterial enteropathogens in oral therapy for bacterial diarrhea.\n One hundred ninety-one US students with diarrhea acquired in Mexico received 100 mg of aztreonam or matching placebo three times a day for 5 days. Stools were cultured for bacterial enteropathogens before and after therapy.\n We studied US students who acquired diarrhea in Mexico (travelers' diarrhea) in view of the high frequency of bacterial agents in this setting.\n We examined time of clinical recovery, treatment failures, adverse experiences, and microbiologic eradication from stool of the etiologic agent in subjects randomized to receive aztreonam or placebo.\n Aztreonam reduced the average duration of diarrhea compared with the placebo: for all cases, by 40 hours (P much less than .01); for those with enterotoxigenic Escherichia coli diarrhea, by 50 hours (P less than .01); for those with shigellosis, by 90 hours (P, not significant [small sample size]); for all bacterial agents, by 57 hours (P much less than .01). Clinical failures during the 5 days of therapy were seen in six patients (6%) receiving aztreonam and 25 (27%) receiving placebo (P less than .01). Pathogen eradication occurred in 95% of those receiving aztreonam and in 70% of those receiving the placebo (P less than .01). All bacterial enteropathogens were susceptible in vitro to aztreonam. The drug was well tolerated.\n Oral aztreonam, which is poorly absorbed, was well tolerated and was an effective therapy for bacterial diarrhea in US adults in Mexico.", "Three clinical trials were carried out to examine the efficacy of various antimicrobial agents in the treatment of travelers' diarrhea among students from the United States in Mexico. Thirty-seven subjects received twice daily for five days 160 mg of trimethoprim (TMP) and 800 mg of sulfamethoxazole (SMZ), 38 received 200 mg of TMP, and 35 received a placebo. Another group of students were given 100 mg of furazolidone (47 students) or ampicillin (47 students) four times a day for five days. In the third study, 500 mg of bicozamycin (72 students) or a placebo (68 students) was given four times a day for three days. Most students who received TMP-SMZ (78%), TMP (84%), or bicozamycin (85%) had recovered by 48 hr after initiation of treatment, as compared with 14% and 47% in the corresponding placebo groups and 55% in the furazolidone group. The agents had a positive effect for all etiologic categories, including diarrhea due to enterotoxigenic Escherichia coli and Shigella strains and illness without any established etiologic agents. Treatment failures were unusual with TMP-SMZ, TMP, and bicozamycin therapy (5% vs. 39% for the placebo-treated students). The drugs were well tolerated. The use of TMP-SMZ or TMP alone in the empiric treatment of moderate to severe travelers' diarrhea is advocated.", "nan", "Ninety-four U.S. students who acquired diarrhea in Mexico were treated with furazolidone (47 subjects) or ampicillin (47 subjects) on a double-blind random basis. Of 47 students, 26 (55%) who received furazolidone (100 mg four times daily for 5 days) recovered from illness within 48 h after initiation of therapy, in contrast to 15 of 47 (32%) who received ampicillin (500 mg four times daily for 5 days) (P less than 0.05). Altogether, 74% of students treated with furazolidone and 49% of those receiving ampicillin were well within 72 h (P less than 0.05). When furazolidone was compared with ampicillin, clinical illness was shortened on the average from 65 to 61 h for enterotoxigenic Escherichia coli diarrhea, from 83 to 58 h for shigellosis, from 82 to 51 h for diarrhea unassociated with a detectable agent, and from 72 to 57 h for all cases irrespective of etiology. Although not dramatically effective in the current trial, the broad spectrum of activity of furazolidone is of interest. Because of in vitro activity against Campylobacter strains and known effectiveness in treating giardiasis, furazolidone should be considered in therapy for diarrhea of unknown etiology in certain settings when laboratory processing of stools for etiological agent is not feasible.", "Clinical efficacy of norfloxacin for treatment of traveler's diarrhea in 106 Finnish tourists vacationing in Morocco was evaluated during two different seasons. When the criteria for diagnosis of traveler's diarrhea were fulfilled, norfloxacin (400 mg) or a placebo was given orally, twice daily for 3 days. All symptoms and signs subsided sooner in the norfloxacin group. The clearest difference was observed in the duration of diarrhea: 1.2 days in the norfloxacin group vs. 3.3 days in the placebo group (P < .001). The duration of diarrhea due to particular species was as follows for the two groups: in cases due to Salmonella enterica, 1.1 vs 4.1 days (P < .01); in cases due to Campylobacter jejuni, 1.8 vs. 5.0 days (P < .01); and in cases due to enterotoxigenic Escherichia coli, 1.0 day vs. 3.1 days (P < .01). The rate of full recovery during administration of norfloxacin or a placebo was also greater among the norfloxacin recipients: 84% vs. 47% (P < .001). No significant adverse effects were reported. Norfloxacin proved to be safe and effective in therapy for traveler's diarrhea.", "We evaluated the use of azithromycin (500 mg) or ciprofloxacin (500 mg) daily for 3 days for the treatment of acute diarrhea among United States military personnel in Thailand. Stool cultures were obtained and symptoms were recorded on study days 0, 1, 2, 3, and 10. Campylobacter species were the most common pathogen isolated (44 isolates from 42 patients). All Campylobacter isolates were susceptible to azithromycin; 22 were resistant to ciprofloxacin. Among the 42 patients with campylobacter infection, there were 2 clinical and 6 bacteriologic treatment failures in the ciprofloxacin group and no treatment failures in the azithromycin group (P = .021 for bacteriologic failures). Overall, azithromycin was as effective as ciprofloxacin in decreasing the duration of illness (36.9 hours vs. 38.2 hours, respectively) and the number of stools (6.4 vs. 7.8, respectively). Among those not infected with Campylobacter species (n = 30), the duration of illness was 32.9 hours vs. 20.7 hours (P = .03) for the azithromycin and ciprofloxacin groups, respectively. Azithromycin is superior to ciprofloxacin in decreasing the excretion of Campylobacter species and as effective as ciprofloxacin in shortening the duration of illness. Azithromycin therapy may be an effective alternative to ciprofloxacin therapy in areas where ciprofloxacin-resistant Campylobacter species are prevalent.", "To explore the optimal dosing regimen for trimethoprim-sulfamethoxazole (TMP-SMX) when used in combination with loperamide to treat traveler's diarrhea, 190 U.S. adults with acute diarrhea were enrolled in a double-blind, randomized trial in Guadalajara, Mexico. All patients received loperamide (4-mg loading dose; 2 mg after each loose stool, not to exceed 16 mg/day for 3 days) and were randomized to receive a 3-day course of TMP-SMX (160:800 mg twice daily for six doses) (group A), a single large dose of TMP-SMX (320:1,600 mg) (group B), or a large loading dose (320:1,600 mg) followed by standard doses for 3 days (160:800 mg twice daily for five doses) (group C). Patients in group C responded best (P < 0.01), with 75% of subjects recovered from diarrhea in 12 h compared with 34 h (group A) and 33 h (group B). Similar differences in favor of group C were noted in the subset of patients who presented with moderate to severe diarrhea. On average, patients in group C took significantly (P < 0.05) less loperamide (1.2 mg) after the 4-mg loading dose compared with patients in group A (2.4 mg) or group B (2.0 mg). We conclude that the most efficacious treatment of traveler's diarrhea in the interior of Mexico is to take loperamide in usual doses to control symptoms in combination with a single large dose of TMP-SMX, which should then be continued for 3 days in standard doses.", "The efficacy of BW942C, a novel enkephalinlike pentapeptide antidiarrheal agent, was compared with the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of the two agents in a placebo-controlled trial of the 72-h treatment of acute diarrhea. Subjects with diarrhea but without bloody stools or fever greater than 102 degrees F (38.9 degrees C) were enrolled. Administered to 134 U.S. adults with diarrhea that developed shortly after their arrival in Guadalajara, Mexico, BW942C was more efficacious than TMP-SMX in relieving diarrhea and cramps in the first 12 h of therapy, especially among subjects with diarrhea caused by enterotoxigenic E. coli. In the BW942C treatment group, 25% of subjects eventually took additional therapy because their diarrhea did not respond to BW942C alone. Neurological side effects such as dizziness and light-headedness occurred more frequently among BW942C-treated subjects. Therapy for 3 days with TMP-SMX provided lasting relief comparable with previously reported 5-day therapy. Use of the combination of both agents provided the benefits of prompt relief afforded by BW942C and lasting relief afforded by TMP-SMX. BW942C might prove to be an agent suitable for the treatment of acute diarrhea, with TMP-SMX reserved for treatment of those who do not respond adequately. The empiric use of the combination of BW942C and TMP-SMX appears appropriate for the treatment of severe nondysenteric disease.", "The efficacy of ciprofloxacin was compared with that of trimethoprim-sulfamethoxazole in a placebo-controlled trial of the 5-day treatment of acute diarrhea among 181 adults recently arrived in Guadalajara, Mexico. Both antimicrobial agents were significantly (p less than 0.0001) more efficacious than placebo in the treatment of diarrhea, with the average duration of diarrhea being 29, 20, and 81 hours, respectively, in the ciprofloxacin, trimethoprim-sulfamethoxazole, and placebo treatment groups. The antimicrobial agents were also more efficacious than placebo in treating diarrhea caused by enterotoxigenic Escherichia coli, invasive enteropathogens, and unknown pathogens. Both antimicrobials were effective in treating mild-to-moderate and moderate-to-severe disease, and both were well tolerated. Ciprofloxacin appears to be a logical alternative to trimethoprim-sulfamethoxazole in the initial treatment of acute travelers' diarrhea.", "Background: Although the use of the antimicrobial, trimethoprim-sulfamethoxazole, in combination with the antisecretory and antimotility agent, loperamide, has been shown to be efficacious in the treatment of traveler's diarrhea, the use of fluoroquinolone antimicrobials in combination with loperamide has less support in the literature. The present study was designed to compare the efficacy of ofloxacin versus ofloxacin plus loperamide in the treatment of acute traveler's diarrhea. Method: This prospective, randomized, evaluator-blinded treatment trial was conducted in Guadalajara, Mexico, during the summers of 1992-1994. Adults newly arrived in Mexico from the United States who developed acute diarrhea of less than 2 weeks' duration were randomized to receive orally either: A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose stool, not to exceed 16 mg per day, for 3 days. The duration of illness was the number of hours elapsed from the beginning of therapy to the passage of the last unformed stool. Results: Ofloxacin and loperamide were well tolerated. Combination therapy with single dose ofloxacin plus loperamide was significantly more efficacious in reducing the duration of diarrhea than single dose ofloxacin or ofloxacin given for 3 days (p <.00001). Furthermore, combination therapy was more efficacious when enterotoxigenic Escherichia coli (ETEC) was the pathogen (p <.01) or when no pathogen was isolated (p <.001). Sixty-three percent of subjects passed no further unformed stools after the initial doses of combination therapy, and 91% were well by the end of the first 24 hours. Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone.", "In a randomized, double blind, placebo-controlled, multicentre trial, 447 travellers to Africa, Asia or Latin America started three days treatment with norfloxacin 400 mg bd or placebo within 24 h after the onset of travellers' diarrhoea. One hundred and four subjects developed diarrhoea and of those 94 (46 in the norfloxacin group and 48 in the placebo group) could be analysed for efficacy. By the last treatment day, 34 patients in the norfloxacin and 18 in the placebo group were cured (P = 0.0001), four and three improved and five and 19, respectively, were failures. Recurrences were seen in three patients on norfloxacin and eight on placebo. The mean time to cure was 3.2 days in the norfloxacin group and 4.4 days in the placebo group (P less than 0.005). The number of loose stools was significantly lower in the norfloxacin group. Nine adverse events were reported; seven in the placebo and two in the norfloxacin group. Pre- and post-travel faecal samples were studied in 19 patients treated with norfloxacin, 21 treated with placebo and 21 untreated subjects without diarrhoea. In treated subjects, increased frequencies of Escherichia coli resistant to ampicillin, co-trimoxazole, doxycycline and chloramphenicol were found in both groups, though more frequently in the placebo one. No subject had norfloxacin resistant Esch. coli pre- and post-travel.", "To determine the efficacy of loperamide given with long- and short-course quinolone therapy for treating traveler's diarrhea, 142 US military personnel were randomized to receive a single 750-mg dose of ciprofloxacin with placebo, 750 mg of ciprofloxacin with loperamide, or a 3-day course of 500 mg of ciprofloxacin twice daily with loperamide. Culture of pretreatment stool specimens revealed campylobacters (41%), salmonellae (18%), enterotoxigenic Escherichia coli (ETEC, 6%), and shigellae (4%). Of the participants, 87% completely recovered within 72 h of entry. Total duration of illness did not differ significantly among the three treatment groups, but patients in the 3-day ciprofloxacin plus loperamide group reported a lower cumulative number of liquid bowel movements at 48 and 72 h after enrollment compared with patients in the single-dose ciprofloxacin plus placebo group (1.8 vs. 3.6, P = .01; 2.0 vs. 3.9, P = .01). While not delivering a remarkable therapeutic advantage, loperamide appears to be safe for treatment of non-ETEC causes of traveler's diarrhea. Two of 54 patients with Campylobacter enteritis had a clinical relapse after treatment that was associated with development of ciprofloxacin resistance.", "In a randomized, double-blind, placebo-controlled trial, 227 US adults with acute diarrhea in Mexico received a single dose of sulfamethoxazole and trimethoprim (1600/320 mg) or 3 days of therapy with loperamide hydrochloride (4-mg loading dose, then 2 mg orally after each loose stool), sulfamethoxazole-trimethoprim (800/160 mg orally twice daily), or the combination of both. Subjects treated with the combination had the shortest average duration of diarrhea compared with the placebo group (1 hour vs 59 hours), took the least amount of loperamide after the loading dose (3.8 mg), and had the shortest duration of diarrhea associated with fecal leukocytes or blood-tinged stools (4.5 hours). A single dose of sulfamethoxazole-trimethoprim was also efficacious (28 vs 59 hours), but loperamide alone was significantly effective only when treatment failures were treated with antibiotics (33 vs 58 hours). The combination of sulfamethoxazole-trimethoprim plus loperamide can be highly recommended for the treatment of most patients with traveler's diarrhea.", "A randomized treatment trial of travelers' diarrhea was carried out among U.S. military personnel participating in routine exercises in several port cities in South America and West Africa. A 5-day, twice daily course of either norfloxacin (400 mg) or trimethoprim/sulfamethoxazole (TMP/SMX, 160/800 mg) was given to 142 volunteers. At the end of 5 days of treatment, diarrhea had resolved in 100% of 73 patients receiving norfloxacin and 97.1% (67/69) receiving TMP/SMX. A probable bacterial pathogen was determined in 44% of 142 subjects: 49% of the norfloxacin group and 39% of the TMP/SMX group. The most common pathogens detected were enterotoxigenic Escherichia coli in 20% of cases and rotavirus in 15%. Resistance to TMP/SMX was present in 20 (27%) bacterial isolates, while no resistance to norfloxacin was found. Eight of 10 patients in the TMP/SMX treatment group who had TMP/SMX-resistant bacterial enteropathogens improved clinically. Both norfloxacin and TMP/SMX were clinically effective in the treatment of travelers' diarrhea in this military population.", "To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea.\n Double-blind, placebo-controlled, randomized clinical trial.\n United States Army hospital in Egypt.\n United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded.\n All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo.\n Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common.\n After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19).\n In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe.", "Forty-two subjects travelling to Mexico for 11 days were enrolled in a randomized, double-blind, placebo-controlled trial comparing ciprofloxacin 250 mg twice daily for three days or placebo for treatment of travellers' diarrhoea. Seventeen (41%) subjects were randomized to treatment. By the last treatment day, all seven evaluable subjects in the ciprofloxacin group, and three of eight evaluable subjects in the placebo group were cured (P = 0.04). The mean time to cure was 26 h for ciprofloxacin and 60 h for placebo-treated patients (P = 0.03). Faecal specimen were collected pre-travel, after four days in Mexico, 48 h post-travel and four weeks post-travel. Potentially pathogenic Escherichia coli strains carrying diarrhoeagenic virulence genes were detected by DNA hybridization tests, during or after travel, in 41% of treated and 31% of asymptomatic travellers. Travel, irrespective of diarrhoea and type of treatment, had a minor impact on the aerobic and anaerobic microflora. In travellers with ongoing diarrhoea, a suppression of the numbers of anaerobic bacteria was found, but the microflora was otherwise virtually unaffected. Significantly increased frequencies of E. coli resistant to ampicillin, doxycycline, chloramphenicol and co-trimoxazole were found during and after travel in all categories of travellers, though more frequently in subjects who experienced diarrhoea. The susceptibility of Bacteroides spp. remained unchanged. The sensitivity of E. coli to ciprofloxacin was not affected by travel, except in four ciprofloxacin-treated subjects who acquired multiresistant E. coli with ciprofloxacin MICs of > or = 0.125 mg/L post-travel. Bacteroides strains with MICs of > or = 64 mg/L were isolated post-travel from four ciprofloxacin-treated patients, and from one of the other 34 travellers not treated with ciprofloxacin." ]

[ "10411037", "10705194", "10799197", "11125353" ]

[ "Sacral nerve stimulation for treatment of refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group.", "Sacral root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized clinical trial.", "Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.", "Efficacy of sacral nerve stimulation for urinary retention: results 18 months after implantation." ]

[ "A prospective, randomized study was performed to evaluate sacral nerve stimulation for the treatment of refractory urinary urge incontinence.\n Primary outcome variables were obtained from voiding diaries. After baseline evaluation candidates who satisfied inclusion criteria were enrolled into the study. Test stimulation results determined eligibility for randomization into a stimulation (treatment) or delay (control) group. The stimulation group included 34 patients who underwent implantation and were followed for 6 months. The delay group comprised 42 patients who received standard medical therapy for 6 months and then were offered implantation. The stimulation group completed a therapy evaluation test (on versus off) after 6 months.\n At 6 months the number of daily incontinence episodes, severity of episodes and absorbent pads or diapers replaced daily due to incontinence were significantly reduced in the stimulation compared to the delay group (all p<0.0001). Of the 34 stimulation group patients 16 (47%) were completely dry and an additional 10 (29%) demonstrated a greater than 50% reduction in incontinence episodes 6 months after implantation. Efficacy appeared to be sustained for 18 months. During the therapy evaluation test the group returned to baseline levels of incontinence when stimulation was inactivated. Urodynamic testing confirmed that sacral nerve stimulation did not adversely affect voiding function. Complications included implantable pulse generator site pain in 15.9% of the patients, implant site pain in 19.1% and lead migration in 7.0%. Surgical revision was required in 32.5% of patients with implants to resolve a complication. There were no reports of permanent injury or nerve damage.\n Sacral nerve stimulation is safe and effective in treating refractory urinary urge incontinence.", "To compare the effectiveness of sacral root neuromodulation with that of conservative management in ameliorating symptoms of refractory urinary urge incontinence and enhancing quality of life, to assess the objective response to neuromodulation as revealed by urodynamic testing, and to delineate the long-term outcomes of neuromodulation.\n Forty-four patients with refractory urge incontinence were randomized to undergo neuromodulation with an implantable impulse generator (n = 21) or to continue their prior conservative management (n = 23). At 6 months the control group was eligible for crossover to implant. Patient evaluation included voiding diaries, quality of life questionnaires, urodynamic testing, and documentation of adverse events. Long-term follow-up evaluations were conducted at 6-month intervals up to 36 months.\n At 6 months mean leakage episodes, leakage severity and pad usage in the implant group were significantly lower by 88% (p < 0.0005), 24% (p = 0.047) and 90% (p < 0.0005), respectively, than the corresponding control group mean values. Improvements in leakage episodes and pad usage of >/=90% were attained by 75 and 85% of the implant group, respectively, but none of the control group. One third of implant patients, but none of the control patients, achieved >/=50% improvement in leakage severity. Over half of the implant patients (56%) were completely dry compared with 1 control patient (4%). Implant patients, but not control patients, exhibited significant improvement with respect to two quality of life measures. Neuromodulation resulted in increases of 220% (p < 0.0005) and 39% (p = 0.013), respectively, in urodynamically assessed bladder volume at first contraction and maximum fill. At 36 months the actuarial rate of treatment failure was 32.4% (95% CI, 17.0-56.0%). Adverse events most frequently involved pain at the implant site, and the incidence of serious complications was low.\n Neuromodulation is markedly more effective than conservative management in alleviating symptoms of refractory urge incontinence. Quality of life and urodynamic function are also improved by neuromodulation. The effects of neuromodulation are long-lasting, and associated morbidity is low.", "Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency.\n A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void.\n Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months.\n Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.", "We investigate the efficacy of sacral neurostimulation in patients with idiopathic urinary retention in a prospective, randomized multicenter trial.\n A total of 177 patients with urinary retention refractory to standard therapy were enrolled in the study. Greater than 50% improvement in baseline voiding symptoms during a 3 to 7-day percutaneous test stimulation qualified a patient for surgical implantation of an InterStim parallel system. Of the patients who qualified for implantation 37 were randomly assigned to a treatment and 31 to a control group. Patients in the treatment group underwent early surgical implantation of the sacral nerve stimulation system, while implantation was delayed in the control group for 6 months. Followup evaluations, including voiding diary analysis and temporary deactivation of the stimulator at 6 months, were conducted at 1, 3, 6, 12 and 18 months after implantation in the treatment group, and after 3 and 6 months in the control group.\n Compared to the control group, patients implanted with the InterStim system had statistically and clinically significant reductions in the catheter volume per catheterization (p <0.0001). Of the patients treated with implants 69% eliminated catheterization at 6 months and an additional 14% had a 50% or greater reduction in catheter volume per catheterization. Therefore, successful results were achieved in 83% of the implant group with retention compared to 9% of the control group at 6 months. Temporary inactivation of sacral nerve stimulation therapy resulted in a significant increase in residual volumes (p <0.0001) but effectiveness of sacral nerve stimulation was sustained through 18 months after implant.\n Results of this prospective, randomized clinical study demonstrate that sacral nerve stimulation is effective for restoring voiding in patients with retention who are refractory to other forms of treatment." ]

[ "12413994", "9853844", "15493565", "11157827", "10813100", "17681325", "16873892", "10527965", "15925050", "18367182", "19572228", "16600226", "11432109", "8567765", "10920087", "8822422", "10783345", "9402268", "12773445", "11172835", "12930572", "11532479", "18583332", "11172834", "14619648" ]

[ "Effect of highly purified urinary follicle-stimulating hormone on oocyte and embryo quality.", "A prospective randomized clinical trial comparing recombinant follicle stimulating hormone (Puregon) and human menopausal gonadotrophins (Humegon) in non-down-regulated in-vitro fertilization patients.", "Efficacy of recombinant human follicle-stimulating hormone in improving oocyte quality in assisted reproductive techniques.", "HMG is as good as recombinant human FSH in terms of oocyte and embryo quality: a prospective randomized trial.", "A prospective and randomized study of ovarian stimulation for ICSI with recombinant FSH versus highly purified urinary FSH.", "Effectiveness of highly purified human menopausal gonadotropin vs. recombinant follicle-stimulating hormone in first-cycle in vitro fertilization-intracytoplasmic sperm injection patients.", "Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial.", "A prospective, randomized clinical trial comparing 150 IU recombinant follicle stimulating hormone (Puregon((R))) and 225 IU highly purified urinary follicle stimulating hormone (Metrodin-HP((R))) in a fixed-dose regimen in women undergoing ovarian stimulation.", "The effect of HMG and recombinant human FSH on oocyte quality: a randomized single-blind clinical trial.", "Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized, multicenter, investigator-blind trial.", "Efficacy of recombinant versus human derived follicle stimulating hormone on the oocyte and embryo quality in IVF-ICSI cycles: Randomised, controlled, multi-centre trial.", "Urinary follicle-stimulating hormone (FSH) is more effective than recombinant FSH in older women in a controlled randomized study.", "Comparison of recombinant and urinary follicle-stimulating hormone preparations in short-term gonadotropin releasing hormone agonist protocol for in vitro fertilization-embryo transfer.", "A prospective, randomized, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization.", "Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. On behalf of The Feronia and Apis study group.", "Efficacy and safety of recombinant follicle stimulating hormone (Puregon) in infertile women pituitary-suppressed with triptorelin undergoing in-vitro fertilization: a prospective, randomized, assessor-blind, multicentre trial.", "Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP).", "Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques.", "A prospective, randomized, controlled trial comparing highly purified hMG with recombinant FSH in women undergoing ICSI: ovarian response and clinical outcomes.", "Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome.", "Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction.", "Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in normogonadotropic women down-regulated with a gonadotropin-releasing hormone agonist who were undergoing in vitro fertilization and intracytoplasmic sperm injection: a prospective randomized study.", "Highly purified hMG versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists--a randomized study.", "A randomized prospective assessor-blind evaluation of luteinizing hormone dosage and in vitro fertilization outcome.", "Recombinant FSH vs. urinary FSH for ovarian stimulation in in vitro fertilization." ]

[ "To determine the effects of ovarian stimulation with highly purified urofollitropin on oocyte and embryo quality.\n Parallel randomized open-label clinical study.\n Assisted reproduction centers.\n Two hundred sixty-seven infertile couples undergoing IVF/ICSI.\n All participants underwent standard down-regulation with GnRH analogue. One hundred thirty-three participants received highly purified urinary FSH and 134 controls received recombinant FSH.\n Primary end points were number of morphologically mature oocytes retrieved, embryo quality, and pregnancy and implantation rates. Secondary end points were: total number of days of FSH stimulation, total dose of gonadotropin administered, fertilization rate per number of retrieved oocytes, embryo cleavage rate, live birth and miscarriage rates, endometrial thickness and estradiol level on the day of hCG administration, cancellation rate, and incidence of moderate or severe ovarian hyperstimulation syndrome.\n Pregnancy and implantation rates were nonsignificantly higher in the urinary FSH group than the recombinant FSH group (46.5% vs. 36.8% and 22.1% vs. 15.8%, respectively). The grade 1 embryo score was significantly higher in the urinary FSH group than the recombinant FSH (42.1% vs. 33.5%), and the live birth rate was nonsignificantly higher in the former group.\n Highly purified urinary FSH is as effective, efficient, and safe for clinical use as recombinant FSH.", "A randomized clinical trial was performed comparing recombinant follicle stimulating hormone (rFSH, Puregon, n = 54) and human menopausal gonadotrophin (HMG, Humegon, n = 35) in infertile women undergoing in-vitro fertilization without the use of a gonadotrophin-releasing hormone (GnRH) agonist. Most patients had a tubal or idiopathic infertility, the latter always longer than 4 years' duration. Patients with sperm abnormalities were excluded. None of the between-group differences in treatment outcome was statistically significant. In the rFSH group, a mean number of 11.2 oocytes was retrieved compared with 8.3 in the HMG group. Ongoing pregnancy rates per started cycle were higher in the rFSH group (22.2%) than in the HMG group (17.1%). Implantation rates were 27.5% in the rFSH group in comparison with 16.7% in the HMG group. In the rFSH group, a mean total dose of 1410 IU during 6.2 days was administered compared with 1365 IU in 6.0 days in the HMG group. Oestradiol concentrations on the day of human chorionic gonadotrophin administration were 3889 pmol/l in the rFSH group and 3145 pmol/l in the HMG group. In 15 subjects (rFSH: n = 9, 16.7%; HMG: n = 6, 17.1%) luteinizing hormone concentrations higher than 10 IU/l were seen during stimulation. In two of them, both from the rFSH group, ongoing pregnancies were achieved. The results indicate that rFSH (Puregon) is at least as efficacious as HMG and that acceptable pregnancy rates can be achieved without the use of a GnRH agonist.", "To estimate the efficacy of recombinant human follicle-stimulating hormone (rFSH) versus highly purified urinary human FSH (uFSH) in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET).\n This prospective, randomized, quality of retrieved double-blind study compared uFSH with rFSH in IVF-ET rFSh cycles. A total of 254 cycles from 241 patients who attended the infertility clinic at Samsung Cheil Hospital from January to August 2001 were included in the study. With pituitary desensitization using gonadotropin-releasing hormone agonist and a short protocol, rFSH was administered in 131 cycles; uFSH was administered in 123 cycles. We analyzed ovarian response, oocyte quality, fertilization rate, embryo quality, pregnancy rate and live birth rate in the uFSH and rFSH groups.\n Total FSH dosage (1322.3 +/- 526.2 vs. 2124.4 +/- 881.9 i.u.) and dosage per retrieved oocyte (90.6 +/- 36.0 vs. 138.0 +/- 57.2 i.u.) were significantly lower in the rFSH group than those in the uFSH group (P < .001). The proportion of good-quality oocytes (grade 1 and 2) was higher in the rFSH group (68.2% vs. 64.8%, P = .024). Moreover, the proportion of atretic oocytes (grade 5) was lower in the rFSH group (7.5% vs. 10.3%, P = .002). The fertilization rate, quality of transferred embryos, clinical pregnancy rate and live birth rate were not significantly differ between the 2 groups.\n In women undergoing COH, rFSH revealed more efficient ovarian response and better quality of oocytes than did uFSH.", "Previous studies have demonstrated that the use of recombinant human follicle stimulating hormone (rhFSH) for ovarian stimulation may be associated with a better outcome than human menopausal gonadotrophin (HMG), probably due to the absence of LH, higher FSH bioactivity and better quality of oocytes and embryos when rhFSH is used. Very few studies have examined the effects of different gonadotrophins on oocyte and embryo quality. In this prospective study, 40 women undergoing ovarian stimulation for intracytoplasmic sperm injection were randomized to receive a standard protocol of either HMG or rhFSH in down-regulated cycles. Prior to microinjection, each denuded oocyte was videotaped to assess nuclear maturity, morphology of zona pellucida, oocyte and polar body and the zona thickness, and diameters of oocyte and ooplasma. Fertilization and subsequent embryo development of each oocyte were followed. The embryologists were blind to the type of gonadotrophin each patient had received for stimulation. No significant differences were found between the two groups with regard to the demographic data, the ovarian responses and pregnancy/implantation rates. The percentage of metaphase II oocytes in the HMG and rhFSH groups were similar (86.9 versus 87.4% respectively). All other parameters assessing oocyte and embryo quality were also comparable between the two groups.", "A prospective and randomized study of ovarian stimulation with human recombinant follicle-stimulating hormone (r-FSH; Gonal-F) versus highly purified urinary FSH (u-FSH-HP; Metrodin-HP) was conducted on patients submitted to an intracytoplasmic sperm injection (ICSI) program. A total of 120 patients aged 37 years or less were stimulated in a randomized manner with r-FSH (group I = 60 patients) or u-FSH-HP (group II = 60 patients). All received a fixed dose of FSH for 7 days and on the 8th day of stimulation the doses started to be adapted according to ovarian response. Human chorionic gonadotropin (hCG) at the dose of 5000 IU to 10,000 IU was administered to both groups when at least one follicle presented a diameter > or = 17 mm. The ovarian response did not differ significantly between groups I and II in terms of number of follicles > or = 16 mm (group I = 6.2 +/- 3.2; group II = 6.7 +/- 2.9; p = 0.26), number of oocytes collected (group I = 10.7 +/- 6.8; group II = 10.5 +/- 5.7; p = 0.91), number of oocytes in metaphase II (group I = 9.2 +/- 5.8; group II = 8.2 +/- 4.8; p = 0.56) or number of immature oocytes (group I = 1.8 +/- 0.9; group II = 1.9 +/- 1.7; p = 0.62). The normal fertilization rate after ICSI did not differ significantly between treatments (group I = 69.4 +/- 25; group II = 66.5 +/- 23; p = 0.38). No cases of cancellation of ovarian stimulation or of severe ovarian hyperstimulation syndrome occurred in either group. The total number of embryos obtained from patients who used r-FSH (group I = 6.3 +/- 4.5) was similar (p = 0.46) to the number obtained from patients who used u-FSH-HP (group II = 5.5 +/- 3.7), as also was the number of transferred embryos (group I = 2.8 +/- 0.8; group II = 2.6 +/- 0.9; p = 0.27). Implantation rate (26.1%) and clinical pregnancy rates per puncture (36.7%) and per embryo transfer (37.9%) were higher in patients who used r-FSH than in patients who used u-FSH-HP (19.5%, 31.7% and 32.2%, respectively), but the differences were not statistically significant. The abortion rate (p = 0.32) did not differ between groups (group I = 4.5%, n = 1 versus group II = 15.7%, n = 3). Thus far, the data do not demonstrate significant differences in ovary stimulation with r-FSH versus u-FSH in patients whose indication for assisted reproduction was the male factor.", "To compare the effectiveness of highly purified hMG with recombinant FSH (rFSH) in IVF-intracytoplasmic sperm injection patients who were treated with a GnRH agonist.\n An open-label, prospective, randomized comparison of fixed gonadotropin regimens.\n Eighteen Dutch IVF centers.\n Six hundred twenty-nine patients who were selected for IVF-intracytoplasmic sperm injection.\n Patients were randomized to receive either highly purified hMG or rFSH in a fixed dosage of 150 IU/d after GnRH-agonist suppression (long protocol).\n Ongoing pregnancy rate per started cycle. Difference between the two treatment groups was tested by using odds ratios, including the 95% confidence limits (intention-to-treat sample), and by using the Fisher's exact test (per-protocol sample).\n The ongoing pregnancy rates per started cycle were 26.3% and 25.2% for highly purified hMG and rFSH, respectively (no statistically significant difference). Treatment with highly purified hMG resulted in statistically significantly fewer oocytes (n = 7.8) than did treatment with rFSH (n = 10.6). There were no differences with respect to fertilization rates and implantation rates. Cycles with highly purified hMG were statistically significantly less often canceled as a result of ovarian hyperresponse (2.0% vs. 6.0% for highly purified hMG and rFSH, respectively).\n Compared with rFSH, highly purified hMG did not result in superiority in ongoing pregnancy rates in first-cycle IVF-intracytoplasmic sperm injection patients who were treated with a fixed dosage of 150 IU of gonadotropin per day. Compared with rFSH, treatment with highly purified hMG resulted in retrieval of fewer oocytes, a lower incidence of hyperresponse, and comparable pregnancy rates.", "LH activity may influence treatment response and outcome in IVF cycles.\n A randomized, assessor-blind, multinational trial compared ongoing pregnancy rates (primary end-point) in 731 women undergoing IVF after stimulation with highly purified menotrophin (HP-hMG) (n = 363) or recombinant FSH (rFSH) (n = 368) following a long GnRH agonist protocol. Patients received identical pre- and post-randomization interventions. One or two embryos were transferred on day 3.\n More oocytes were retrieved (P < 0.001) after rFSH treatment (11.8) compared with HP-hMG treatment (10.0), but a higher proportion developed into top-quality embryos (P = 0.044) with HP-hMG (11.3%) than with rFSH (9.0%). At the end of stimulation, lower estradiol (E(2)) (P = 0.031) and higher progesterone (P < 0.001) levels were found with rFSH, even after adjusting for follicular response. The distribution of hypo-, iso- and hyper-echogenic endometrium showed a significant (P = 0.023) shift towards the hyperechogenic pattern after rFSH treatment. The ongoing pregnancy rate per cycle was 27% with HP-hMG and 22% with rFSH [odds ratio (95% confidence interval): 1.25 (0.89-1.75)].\n Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study, but non-inferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality, endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations, which may be relevant for treatment outcome.", "A prospective, randomized, open, multicentre (n = 3) study was conducted to compare the efficacy and efficiency of a fixed daily dose of 150 IU (3x50 IU) recombinant follicle stimulating hormone (recFSH, Puregon((R))) and 225 IU (3x75 IU) highly purified urinary FSH (uFSH-HP, Metrodin-HP((R))) in women undergoing ovarian stimulation prior to in-vitro fertilization treatment. A total of 165 women were treated with FSH, 83 subjects with recFSH and 82 subjects with uFSH-HP. In the recFSH group a mean number of 8.8 oocytes were retrieved, compared with 9.8 in the uFSH-HP group (not statistically significant). In the recFSH group, a significantly lower total dose was required compared to the uFSH-HP group, 1479 versus 2139 IU, respectively (P < 0.0001; 95% confidence interval -747 to -572). Treatment with recFSH resulted in a significantly higher embryo development rate (69.6 versus 56.2%; P = 0.003) and more embryos accessible for the embryo freezing programme (3.3 versus 2.0; P = 0.02) compared to uFSH-HP. The vital pregnancy rate per cycle started was 30.2 versus 28.3% in the recombinant and urinary FSH group, respectively. It is concluded that treatment outcome of a fixed daily dose of 150 IU recFSH is comparable to a fixed daily dose of 225 IU uFSH-HP. However, a significantly lower total dose was needed in the recFSH group (nearly 700 IU less).", "To compare the effect of HMG and rhFSH on oocyte quality in ICSI cycle.\n Vali-e-Asr university teaching hospital.\n Prospective single-blind randomized clinical trial.\n Sixty women undergoing ovarian stimulation for ICSI were randomized to receive a standard protocol of either HMG or rhFSH in down-regulation cycles.\n Prior to microinjection, each oocyte was assessed regarding the nuclear maturity, morphology of zona plucida, cytoplasmic appearance and polar body morphology. Fertilization rate was followed.\n The percentage of metaphase II oocytes in HMG and rhFSH groups.\n Statistical analyses were carried out by the Mann-Whitney, Fisher's exact, chi2 tests and Student's t-test.\n No significant differences were found between two groups in regard to the demographic data, the ovarian response and pregnancy/implantation rates (P>0.05). The percentage of metaphase II oocytes in HMG and rhFSH groups were 81.3% versus 80.6%, respectively.\n There were no significant differences between parameters such as, oocyte quality and percentage of metaphase II oocytes between these two groups.", "To compare the efficacy of highly purified human urinary follicle stimulating hormone (HP-hFSH) versus human recombinant follitropin-alpha (rFSH) in volunteers undergoing controlled ovarian stimulation for IVF.\n A randomized, controlled, investigator-blind trial.\n Four assisted reproductive technology centers.\n One hundred fifty-two IVF patients.\n Volunteers, aged 18-39, were randomized to HP-hFSH (n = 76) versus rFSH (n = 76) at a starting dose of 300 IU in down-regulated cycles.\n Number of oocytes, clinical pregnancy rate, and live birth rate with HP-hFSH versus rFSH.\n The total IU of gonadotropin used did not differ between the two groups. There was no difference in number of oocytes retrieved with HP-hFSH (mean = 16.3) compared with rFSH (mean = 17.1), confidence interval (CI) of difference = -3.79 to +2.18. Clinical pregnancy rate, as defined by the presence of a gestational sac, was 48.7% (CI = 37.0%-60.4%) with HP-hFSH versus 44.7% (CI = 33.3%-56.6%) with rFSH (CI of difference = -11.9% to +19.8%). Live birth rate was 38.2% (29 of 76) in both groups (CI = 27.2%-50.0%), for a difference between groups of 0.0% (CI of the difference = -15.4% to +15.4%).\n There were no statistically significant differences in mean oocyte number, clinical pregnancy rate, or live birth rate between HP-hFSH versus rFSH.", "The aim of this trial, comparing human follicle stimulating hormone (hFSH) and recombinant FSH (rFSH) was to evaluate the efficacy on oocyte and embryo quality in in vitro fertilisation/intracytoplasmic sperm injection cycles. Four-hundred and one women were randomised in two groups to receive or hFSH or rFSH in stimulation protocols. The primary end point of this study was the oocyte/embryo quality. No significant difference in oocyte/embryo quality was observed between the two groups. The number of oocytes retrieved was significantly higher in the hFSH group (6 +/- 2.8 in hFSH group vs. 5 +/- 2.6 in rFSH group; P = 0.003). A less amounts of gonadotropins consumed (2106 +/- 719 IU in hFSH group vs. 3536 +/- 1099 IU in rFSH group; P < 0.0001) and shorter duration of stimulation (human chorionic gonadotropin day of administration: Day 12.3 +/- 1.0 in hFSH and Day 13.3 +/- 1.2 in rFSH group, respectively; P < 0.0001) was registered in hFSH group. Fertilisation, cleavage and implantation rates, pregnancy and abortion rates were similar in both groups. However, lower clinical abortion rate (not significant) in hFSH group might be noteworthy. In our study, we demonstrated that hFSH and rFSH products are equivalent in terms of clinical efficacy.", "The following study was conducted to determine which FSH, recombinant or urinary, works better in older women.\n We conducted a controlled randomized study in a single university IVF center.\n University IVF center.\n Women (N = 257) over 39 years old undergoing IVF.\n The patients were randomized into two study groups at their first IVF cycle: 121 patients were treated with recombinant FSH, and 120 patients were treated with urinary FSH. Both groups were suppressed with a long GnRH analog protocol.\n Days of stimulation, E2 at the day of hCG, total amount of FSH administered, number of oocytes collected, amount of FSH per oocyte, and number of embryos obtained.\n Patients treated with urinary FSH required a significantly lower total amount of FSH, and a lower amount of FSH per oocyte than women treated with recombinant FSH. The other measures evaluated did not show any statistically significant differences.\n Our study showed that urinary FSH performed better in older women than recombinant FSH when associated with the long protocol.", "To compare the efficiency and efficacy of two recombinant human FSH (r-FSH) and urinary (u-FSH) preparations in patients undergoing superovulation for IVF-ET using a short-term gonadotropin releasing hormone agonist (GnRH-a) (Triptorelin) protocol.\n A total of 88 women undergoing IVF-ET were included in this prospective study. They were randomized to receive u-FSH (150 IU/d), follitropin-alpha (100 IU/d), or follitropin-beta (100 IU/d) for 2 days, and dosages were subsequently adjusted according to the ovarian response.\n The FSH dose required for the overall stimulation was significantly lower in patients treated with r-FSH than in those treated with u-FSH while serum FSH values were higher in the latter group. There were no statistically significant differences in ovarian response and IVF outcome between r-FSH preparations.\n Recombinant FSH preparations have a higher efficiency than urinary ones in patients undergoing IVF-ET using a short-term GnRH-a protocol. In this situation, the two recombinant follitropins have comparable effectiveness.", "Urinary follicle stimulating hormone (FSH) is being used for the treatment of human infertility. Recently, FSH manufactured by means of recombinant DNA technology with a much higher purity (> 99%) has become available. A prospective, randomized, assessor-blind, multicentre (n = 18) study was conducted in infertile women undergoing in-vitro fertilization comparing recombinant FSH (Org 32489, Puregon) and urinary FSH (Metrodin). Eligible subjects were randomized (recombinant versus urinary FSH = 3:2) and pretreated with buserelin for pituitary suppression. FSH was given until three or more follicles with a diameter of at least 17 mm were seen. After oocyte retrieval, fertilization routines were applied according to local procedures. No more than three embryos were replaced. In all, 585 subjects received recombinant FSH and 396 urinary FSH. Significantly more oocytes were retrieved after recombinant FSH treatment (mean adjusted for centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancy rates per attempt and transfer in the recombinant FSH group were 22.17 and 25.97% respectively, and in the urinary FSH group, 18.22 and 22.02% respectively (not significant). Ongoing pregnancy rates including pregnancies resulting from frozen-thawed embryo cycles were 25.7% for recombinant and 20.4% for urinary FSH (P = 0.05). Compared to urinary FSH, the total dose of FSH was significantly lower with recombinant FSH (2138 versus 2385 IU, P < 0.0001) in a significantly shorter treatment period (10.7 versus 11.3 days, P < 0.0001). No clinically relevant differences between recombinant and urinary FSH were seen with respect to safety variables. It is concluded that recombinant FSH (Puregon) is more effective than urinary FSH in inducing multifollicular development and achieving an ongoing pregnancy.", "This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development.", "The objective of this study was to compare the efficacy and safety of a recombinant follicle stimulating hormone (FSH) preparation (Org 32489, Puregon) with a urinary FSH preparation (Metrodin) in infertile women undergoing in-vitro fertilization (IVF and embryo transfer and who were pituitary-suppressed with triptorelin. In an assessor-blind, group-comparative, multicentre study, 60 women were randomized to Org 32489 and 39 to urinary FSH. An evaluation of the main parameter, the mean total number of oocytes recovered, indicated a similar efficacy for the two preparations: 9.7 with Org 32489 versus 8.9 with urinary FSH. In addition, there were no significant between-group differences with respect to other efficacy variables such as the total dose used, the duration of the treatment, the number of follicles > or = 17 mm in diameter and embryo quality. The ongoing pregnancy rates per attempt (30.2 versus 17.4%) and per transfer (34.0 versus 18.8%) were higher with Org 32489, but this difference was not statistically significant. No clinically relevant differences between Org 32489 and urinary FSH were seen with respect to safety variables. Serum antibodies were not detected in any of the subjects. It is concluded that Org 32489 compares favourably with urinary FSH in the treatment of infertile pituitary-suppressed women undergoing IVF and embryo transfer.", "This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs.", "A prospective, randomized, comparative, assessor-blind study was carried out in two centres to compare the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (u-hFSH HP; Metrodin HP), both administered s.c. in women undergoing ovarian stimulation for in-vitro fertilization including intracytoplasmic sperm injection (ICSI). A total of 235 patients started a long gonadotrophin-releasing hormone agonist protocol: 119 received r-hFSH and 114 received u-hFSH HP (150 IU/day) for the first 6 days. Two patients were excluded from the study because they mistakenly received the incorrect treatment combination. Human chorionic gonadotrophin (HCG; 10000 IU, s.c.) was administered once there was at least one follicle 18 mm in diameter and two others > or = 16 mm. In all, 119 (100%) and 102 (89%) of the patients respectively in the r-hFSH and u-hFSH HP groups achieved the criteria for HCG. The mean numbers (+/- SD) of oocytes recovered (the primary endpoint) were 12.2 +/- 5.5 and 7.6 +/- 4.4 in the r-hFSH and u-hFSH HP groups respectively (P < 0.0001). However, the number of FSH treatment days (11.0 +/- 1.6 versus 13.5 +/- 3.7) and the number of 75 IU ampoules (21.9 +/- 5.1 versus 31.9 +/- 13.4) used were significantly less (P < 0.0001) in the r-hFSH group than in the u-hFSH HP group. In patients treated using ICSI (63 patients in each group), no difference in oocyte maturation was observed. The mean numbers of embryos obtained were 8.1 +/- 4.2 and 4.7 +/- 3.5 (P < 0.0001), in favour of the r-hFSH group. In the majority of patients (96 and 99% respectively) only one or two embryos were replaced (mean 2.0 +/- 0.2 and 1.9 +/- 0.1 respectively) in the r-hFSH and u-hFSH HP groups. The clinical pregnancy rates per started cycle and per embryo transfer were 45 and 36%, and 48 and 47%, respectively in the r-hFSH and u-hFSH HP groups (not significant). There were six (5.1%) and two (1.7%) cases of ovarian hyperstimulation syndrome respectively. In conclusion, it was found that r-hFSH was more effective than u-hFSH at inducing multiple follicular development. However, the high rate of low ovarian response in the u-hFSH group compared with our general experience was unexpected. The availability of a gonadotrophin with less inter-batch variation would be beneficial for clinicians. r-hFSH seems to fulfil such a requirement.", "To assess the clinical profile and efficacy in assisted reproductive treatment of a new human-derived highly purified (HP) menotropin, we compared HP hMG and recombinant (r) FSHalpha use in ICSI within a prospective, randomized, controlled study.\n 100 infertile women were treated with HP hMG (50 patients) or rFSHalpha (50 patients). All patients received the same daily gonadotrophin dose (150 IU) following GnRH agonist suppression (long regimen) until more than three follicles >17 mm and estradiol (E(2)) levels >600 pg/ml were reached. Patients were monitored with daily LH, FSH, hCG, estradiol (E(2)), progesterone, and testosterone measurements; and alternate day pelvic ultrasound.\n Treatment duration (11.1 +/- 0.4 versus 12.9 +/- 0.5 days, P < 0.05) and gonadotrophin dose (22.4 +/- 1.0 versus 27.0 +/- 1.5 ampoules, P < 0.05) were lower in the HP hMG group. Conversely, peak pre-ovulatory E(2) (1342 +/- 127 versus 933 +/- 109 pg/ml, P < 0.005); and area under the curve of E(2) (3491 +/- 350 versus 2602 +/- 349 pg/ml.day, P < 0.05), immunoreactive serum FSH (65.9 +/- 2.1 versus 48.8 +/- 1.8 IU/l.day, P < 0.001). and hCG (1.7 +/- 0.3 versus 0.0 +/- 0.0 IU/l/day, P < 0.001) during treatment were higher in the HP hMG group. Cycle cancellation rates, transferred embryo number, pregnancy rates per started cycle (30 versus 28%) and per embryo transfer (35 versus 35%) and miscarriage rates (6 versus 6%) were not significantly different.\n HP hMG treatment was associated with: (i) a more efficient patient response, as reflected by reduced treatment duration and gonadotrophin requirements; (ii) increased serum levels of hCG, E(2), and immunoreactive FSH during treatment; (iii) an ICSI outcome indistinguishable from rFSHalpha.", "To investigate possible differences between using recombinant FSH (rFSH) and hMG for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles.\n Parallel group design. Prospective, randomized clinical study.\n A tertiary care infertility clinic.\n A total of 578 patients of our IVF/ICSI routine were recruited.\n Treatment with hMG was used for 282 patients (282 cycles), whereas 296 patients (296 cycles) were treated with rFSH. The number of cycles leading to an embryo transfer were 248 and 259, respectively.\n Primary: clinical pregnancy rate. Secondary: treatment days, total dose of gonadotropin administered, number of oocytes retrieved, number of mature oocytes, and embryo quality.\n Of the cycles with embryo transfer, the pregnancy rates were 30.1% and 32.3% in the rFSH and the hMG groups, respectively. This difference is not statistically significant (P=0.798). Treatment with rFSH resulted in a significantly higher number of recovered oocytes compared with the hMG group but was also associated with a higher number of ampoules needed to reach the criterion for hCG administration. No significant differences were found with regard to the number of mature oocytes, the number of treatment days, and the embryo quality.\n In terms of the clinical pregnancy rate, no significant differences between the two stimulation regimens can be stated.", "At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.", "To evaluate clinical and endocrinological effects of intranasal (IN) vs. subcutaneous (SC) GnRH-a for pituitary down-regulation combined with hMG vs. rFSH.\n Prospective, randomized study.\n University hospital, IVF unit.\n Three hundred seventy-nine normogonadotropic women eligible for IVF or ICSI.\n Randomization to intranasal (IN) or SC GnRH-a and to hMG or rFSH.\n Oocytes retrieved, embryos developed, clinical pregnancy, and delivery rates. Serum hormone concentrations on stimulation days 1 (S1) and 8 (S8), and oocyte pick-up (OPU) day.\n After randomization, four groups were formed: IN/hMG (n = 100), IN/FSH (n = 98), SC/hMG (n = 89), and SC/FSH (n = 92). Mean number of oocytes retrieved and of transferable and transferred embryos were similar in the four groups. Clinical pregnancy rate per started cycle was significantly higher in the IN/HMG group than in the SC/FSH group (P<.05) and was intermediate in the two remaining groups. Se-LH on S8 in the two SC groups was significantly lower than in the two IN groups. Se-E2 on S8 in the SC/FSH group was significantly lower than in the other three groups.\n The clinical and endocrinological outcome in IVF and ICSI-treated normogonadotropic women is significantly influenced by mode of down-regulation as well as gonadotropin formulation.", "Highly purified hMG (hp-hMG) has recently shown better cycle outcome than the recombinant FSH (rFSH) when compared in GnRH agonist long protocol cycles. However, they have not yet been compared in GnRH antagonist cycles.\n A RCT comparing the ongoing pregnancy rate (primary end-point) in 280 patients undergoing IVF/ICSI after stimulation with hp-hMG or rFSH controlled with a GnRH antagonist.\n No significant differences were observed between hp-hMG and rFSH in terms of the ongoing pregnancy rate per started cycle (35.0 versus 32.1%, respectively; P = 0.61); relative risk: 1.09 (95% confidence interval: 0.78-1.51; risk difference: 2.9%). No differences were observed for implantation, clinical pregnancy and pregnancy loss rates. More oocytes were obtained from patients receiving rFSH then hMG (14.4 +/- 8.1 versus 11.3 +/- 6.0, respectively; P = 0.001). Estradiol was higher at the end of stimulation in the hp-hMG group (P = 0.02), whereas progesterone was higher in patients stimulated with rFSH (P < 0.001).\n A similar outcome was observed for hp-hMG and rFSH when used for stimulation in GnRH antagonist cycles. However, some differences were found in ovarian response in terms of oocyte yield and hormonal profile. Clinical Trials.gov Trial registration number: NCT00669786.", "To determine the effect of exogenous LH dosage on IVF outcome.\n Single-blinded (assessor-blinded) study with random assignment of treatment groups.\n Human Assisted Reproduction Unit, Rotunda Hospital, Dublin, Ireland.\n Infertile normogonadotropic women undergoing their first cycle of IVF were studied.\n Patients were randomized to gonadotropin drugs with varying doses of LH per ampule: recombinant FSH containing no LH (group 0, n = 39), urinary FSH containing <1 IU of LH per ampule (group 1, n = 30), hMG containing 25 IU of LH per ampule (group 25, n = 30), and hMG containing 75 IU of LH per ampule (group 75, n = 29). The FSH dose was kept constant at 75 IU per ampule. A long-protocol GnRH-analog regimen was used.\n Dose and duration of gonadotropin stimulation, follicle and oocyte numbers, implantation rate, and pregnancy rate.\n The median duration of ovarian stimulation; median number of gonadotropin ampules used; serum E2 levels; and numbers of follicles, oocytes, and embryos were similar among the four groups. Median LH levels on the day of hCG administration, however, differed significantly. Live birth rates per cycle differed markedly, but statistical significance was not achieved (23%, 7%, 20%, and 31% for groups 0, 1, 25, and 75, respectively). A significant trend in implantation rates was noted with increasing LH dosage of the urinary preparations (19%, 10%, 18%, and 28% for groups 0, 1, 25, and 75, respectively).\n In the present study, although the residual endogenous LH after down-regulation was adequate for ovarian response and E2 synthesis, the addition of exogenous LH improved implantation. An FSH/LH ratio of 75/75 IU per ampule appeared to be the optimum dose.", "To compare ovarian stimulation with recombinant FSH (rFSH) vs. urinary FSH (uFSH) in terms of hormonal events within ovarian follicles and the outcome of in vitro fertilization.\n A prospective randomized comparative study of rFSH (n = 70) vs. uFSH (n = 61) ovarian stimulation. Hormone determinations were serum estradiol (E2) on the day of human chorionic gonadotropin (hCG) administration, and E2, androstenedione (A) and testosterone (T) at the time of follicular aspiration in the follicular fluid and serum.\n The total dose of gonadotropins required and the length of ovarian stimulation were the same in the 2 groups. In follicular fluid the E2 and the A levels were significantly higher in the rFSH group (3,065 +/- 1,646 vs. 2,368 +/- 1,240 nmol/L, P = .004, and 103.7 +/- 51.6 vs. 89.0 +/- 42.3 nmol/L, P = .042, respectively), whereas A:E2 and T:E2 ratios were significantly lower (39.6 +/- 22.5 vs. 52.3 +/- 59.6, P = .042, and 9.1 +/- 4.7 vs. 17.6 +/- 26.9, P = .006, respectively). Serum hormonal levels, number of oocytes retrieved and pregnancy rates did not differ significantly between the groups.\n rFSH provides results similar to those of uFSH. rFSH enhances steroidogenesis and provokes different androgen/estrogen ratios than does uFSH without influencing the outcome of in vitro fertilization." ]

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[ "A comparison of artificial saliva and chewing gum in the management of xerostomia in patients with advanced cancer.", "Efficacy of pilocarpine lozenge for post-radiation xerostomia in patients with head and neck cancer.", "Comparison between saliva stimulants and saliva substitutes in patients with symptoms related to dry mouth. A multi-centre study.", "A double-blind, crossover study of Biotène Oralbalance and BioXtra systems as salivary substitutes in patients with post-radiotherapy xerostomia.", "Salivary stimulation by chewing gum and lozenges in rheumatic patients with xerostomia.", "Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer.", "Effects of mouthrinses with linseed extract Salinum without/with chlorhexidine on oral conditions in patients with Sjögren's syndrome. A double-blind crossover investigation.", "The cholinesterase inhibitor physostigmine for the local treatment of dry mouth: a randomized study.", "Improvement of oral mucosa with mucin containing artificial saliva in geriatric patients.", "Comparing Moi-Stir to lemon-glycerin swabs.", "Comparison between saliva stimulants and a saliva substitute in patients with xerostomia and hyposalivation.", "Comparison between new saliva stimulants in patients with dry mouth: a placebo-controlled double-blind crossover study.", "Patient preferences in a preliminary study comparing an intra-oral lubricating device with the usual dry mouth lubricating methods.", "Chewing gum and a saliva substitute alleviate thirst and xerostomia in patients on haemodialysis.", "Treatment of xerostomia: a double-blind trial in 108 patients with Sjögren's syndrome.", "Effect of Saliment on parotid salivary gland secretion and on xerostomia caused by Sjögren's syndrome.", "Buffering effect of a prophylactic gel on dental plaque in institutionalised elderly.", "The effect of a chewing gum on salivary secretion, oral mucosal friction, and the feeling of dry mouth in xerostomic patients.", "Effects of a betaine-containing toothpaste on subjective symptoms of dry mouth: a randomized clinical trial.", "Treatment of xerostomia with polymer-based saliva substitutes in patients with Sjögren's syndrome.", "Subjective assessment of a new moisturizing mouth spray for the symptomatic relief of dry mouth.", "Efficacy of a novel lubricating system in the management of radiotherapy-related xerostomia.", "Mucin-containing lozenges in the treatment of intraoral problems associated with Sjögren's syndrome. A double-blind crossover study in 42 patients.", "Efficacy of a new oral lubricant solution in the management of psychotropic drug-induced xerostomia: a randomized controlled trial.", "Management of xerostomia in older patients : a randomised controlled trial evaluating the efficacy of a new oral lubricant solution.", "A double-blind crossover trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with xerostomia following radiation therapy.", "Different saliva substitutes for treatment of xerostomia following radiotherapy. A prospective crossover study.", "Clinical trial of a mucin-containing oral spray for treatment of xerostomia in hospice patients.", "A double-blind cross-over trial of a mucin-containing artificial saliva.", "Use of a mucoadhesive disk for relief of dry mouth: a randomized, double-masked, controlled crossover study.", "Comparison of the effect of the linseed extract Salinum and a methyl cellulose preparation on the symptoms of dry mouth.", "Safety and effectiveness of topical dry mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for polypharmacy-induced dry mouth.", "Evaluation of the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lysozyme and lactoferrin in elderly patients with dry mouth--a pilot study.", "Subjective and clinical evaluation of oral lubricants in xerostomic patients.", "The efficacy of Xialine in patients with xerostomia resulting from radiotherapy for head and neck cancer: a pilot-study.", "Randomized-controlled trial: effect of a reservoir biteguard on quality of life in xerostomia." ]

[ "This was a prospective, randomized, open, crossover study comparing a mucin-based artificial saliva (Saliva Orthana) with a low-tack, sugar-free chewing gum (Freedent) in the management of xerostomia in patients with advanced cancer. The conclusions of this study were that both Saliva Orthana and Freedent are effective in the management of xerostomia in patients with advanced cancer, that both Saliva Orthana and Freedent cause some side-effects in this group of patients, and that patients with cancer think that chewing gum is an acceptable treatment. Sixty-nine per cent of the patients preferred the chewing gum to the artificial saliva. Furthermore, the chewing gum scored better than the artificial saliva on every measure of efficacy. However, none of these results reached statistical significance.", "Patients with radiation-induced xerostomia produce little or no saliva. Several studies have demonstrated the efficacy of systemic administration of pilocarpine hydrochloride in individuals with post-radiation xerostomia. However, analysis of pilocarpine lozenges for treatment of post-radiation xerostomia in patients with head and neck cancer has not been reported.\n The aim of this study was to quantify improvement in clinical symptoms and salivary function after treatment of post-radiation xerostomia with pilocarpine lozenges. In a double-blinded, placebo-controlled trial, 33 head and neck cancer patients were assigned randomly to receive Salagen tablet, pilocarpine hydrochloride lozenge (3 or 5 mg) or placebo lozenge every 10 days. At each visit, a subjective evaluation was undertaken through the use of visual analog scales before and at 180 minutes after treatment. Whole resting saliva was collected before and at 0, 30, 60, 90, 120, 150 and 180 minutes after treatment.\n The percentage of patients with decreased feeling of oral dryness, sore mouth or speaking difficulties after taking 5-mg pilocarpine lozenge was greater than Salagen or placebo. There were statistically significant increases in salivary production in pilocarpine treatment groups vs. placebo (P < 0.05).\n The 5-mg pilocarpine lozenge produced the best clinical results, but further investigation with a larger group of patients is required.", "Five saliva stimulants (Salivin, V6, Mucidan, Ascoxal-T and Nicotinamide) and three saliva substitutes (Saliment, Salisynt and an ex témpore solution) were evaluated in 106 patients with a low salivay flow rate and a long history of dry mouth. The study was carried out as a multi-centre study in collaboration with ten different hospital dental clinics. The participants were interviewed about their complaints related to dry mouth. Each patient was then asked to use the eight saliva stimulants and substitutes for 14 days in a randomized order with one week intervals. After the 14-day-periods, the patients were interviewed about the effect of the various products by a dentist using a standardized questionnaire. Paraffin-stimulated whole saliva samples were collected after each test period. The most serious complaints among the patients were, besides dryness of the mouth, difficulty to talk and difficulty to swallow. The results showed that all eight tested saliva stimulants and substitutes relieved the symptoms of dry mouth to some extent. However, V6 chewing gum and Salivin lozenge were ranked as the two best products by the patients. No long-term effect was found with any of the eight products on the flow rate of paraffin-stimulated whole saliva.", "This study assessed the efficacy of the Bioxtra (BX) and Biotène Oralbalance (OB) systems in the treatment of post-radiotherapy xerostomia. In a double-blind, crossover study, 20 patients with post-radiotherapy xerostomia were randomly allocated to receive either OB then BX, or vice versa, each product for 2 weeks, with a 1 week wash-out period in between. Subject-based dry mouth scores derived from 100-mm visual analogue scales were recorded at days 0 and 14 of each 2-week period, together with subjective perception of changes in dry mouth symptoms. Both treatments were effective, resulting in reduction of visual analogue scale scores from day 0-14. Between-groups comparisons identified that BX achieved significantly better improvements compared with OB for the perception of dry mouth and improvements in speech and was also rated as more pleasant to use than OB (P < 0.05). In conclusion, both treatments were effective in alleviating the symptoms of post-radiotherapy xerostomia, although BX achieved superiority in some of the outcomes assessed compared with OB.", "The effect of chewing gum and lozenges in relieving the signs and symptoms of xerostomia was studied in a 2-wk cross-over clinical trial in 18 rheumatic patients with dry mouth symptoms and low salivary flow rates. Resting flow was measured before (PRESTIM) a chewing stimulated flow rate test (STIM), and also 5 min after (POSTSTIM). STIM flow (mean 1.0 ml/min) was not affected by the test regimens. In the lozenge regimen, mean PRESTIM flow in the group increased from 0.11 to 0.14 ml/min and POSTSTIM from 0.10 to 0.13. In the chewing gum regimen, PRESTIM flow (mean 0.13 ml/min) did not change, whereas POSTSTIM flow increased from 0.13 to 0.16 ml/min. In terms of patients' preferences, chewing gum and lozenges were ranked equal. Both these physiologic stimuli had few side-effects. Subjective symptoms were relieved in about one-third of the subjects, but relief was not always verified by improved flow rates. The regimens were not found to influence buffering capacity; salivary counts of mutans streptococci, lactobacilli, and candida; or oral sugar clearance time.", "The aim of this study was to determine if radiotherapy induces hyposalivation altering oral microbial flora. The purpose of this placebo-controlled, single-blind study was to determine beneficial effects of a saliva substitute and an oral hygiene product on irradiated patients with oropharyngeal cancer. Eighteen patients were assigned to the test group (Biotène Oral Balance gel [Lacléde Incorporated Healthcare Products, Gardena, CA] and toothpaste used daily), and another 18 were put on a conventional daily regimen (carboxymethylcellulose gel and Oral-B toothpaste [Laclede Pharmaceuticals, Gardena, CA]). Cultures for identifying and quantitating microorganisms, whole unstimulated saliva, and visual analog measurements for comfort were obtained before mucositis occurred and after treatment. Daily use of Biotène products enhanced control of microbial flora, improved salivary flow, and increased oral comfort as compared with control subjects. Four weeks after mucositis, some aerobic isolates disappeared in the test group; periodontal-associated bacteria were markedly decreased in the test group; and candidal species were significantly lowered in the test group. Although baseline saliva was lower in the test group (P = 0.001), after 4 weeks, no difference between groups existed; comfort was greater in the test group (P = 0.007). Use of enzyme-engineered Biotène products that assist in control of the oral microbial flora as well as supporting oral comfort through lubrication appear to be useful aids for irradiated patients with oropharyngeal cancer.", "To study the effect of mouthrinses with salivary replacement substances on oral conditions in patients with primary Sjögren's syndrome.\n Cross-over, double-blind study.\n Facilities at the Centre for Oral Health Sciences, Malmö University and at Malmö University Hospital, Malmö, Sweden.\n Twenty-two patients with Sjogren's syndrome.\n Linseed extract Salinum alone (Sal) or with addition of chlorhexidine (Sal/Chx) was used for mouthrinsing during 3-week periods of rinsings separated by a 3-week \"wash-out\" period.\n Recordings of percentages of sites with dental plaque and bleeding on probing, mirror friction test and microbiological analyses. Questionnaire on oral symptoms due to reduced salivation.\n Dental plaque and bleeding on probing were reduced after Sal and after Sal/Chx. Friction was reduced after both treatments. No significant differences for counts of studied microbial groups were seen after Sal but the total anaerobically cultured microorganisms and of mutans streptococci fell after Sal/Chx (p<0.05 and p<0.001). Symptoms of oral dryness improved following Sal and Sal/Chx (p<0.05 and p<0.001 respectively). Speaking problems and burning mouth symptoms improved after use of Sal (p<0.05).\n Positive effects on symptoms in patients with Sjögren's syndrome were seen after use of Salinum without or with chlorhexidine.", "Application of physostigmine to the oromucosal surface with the aim of stimulating underlying mucin-producing glands while reducing cholinergic systemic effects might be a strategy for treating dry mouth. Subjects suffering from dry mouth and with hyposalivation participated in a crossover, double-blind, randomized study. A gel containing physostigmine (0.9, 1.8, 3.6, and 7.2 mg) or placebo was applied to the inside of the lips and distributed with the tongue. The feeling of dryness was assessed using a visual analogue scale (VAS) (where a score of 100 = extremely dry) and systemic effects were registered. Based on assessments of efficacy and safety, the dose of 1.8 mg of physostigmine was selected for use in the second part of the study to make objective measurements of saliva volumes. Physostigmine (1.8 mg) produced long-lasting (120 min) relief (evident as a score reduction of 25 on the VAS) in the feeling of dryness. Judging from AUC values related to baseline over 180 min, the improvement for both mouth and lips in response to physostigmine was six times greater than that to placebo. At higher doses of physostigmine, gastrointestinal discomfort predominantly occurred. The volume of saliva collected in response to physostigmine was five times higher over 180 min than that collected in response to placebo. Physostigmine, applied locally, therefore appears to be a promising modality for dry-mouth treatment.", "In elderly individuals the saliva production is often decreased, leading to dry mucosal membranes and predisposition to local infections, as well as other oral problems. Eighty-five hospitalized geriatric patients, with a multitude of disabling diseases, participated in a double blind placebo-controlled study when mucin-containing artificial saliva and a placebo liquid was given. In the patients treated with the artificial saliva a considerable improvement in the condition of oral mucosa was seen. Also, in one quarter of the patients treated with the placebo liquid, the oral candida infection disappeared, possibly due to improved oral hygiene. It is reasonable to assume that general well-being increases when the condition of the oral mucosa improves. If factors causing dry mouth cannot be removed, i.e. due to diseases or ageing factors, treatment with artificial saliva could be of benefit, but the importance of good oral hygiene must not be overlooked.", "nan", "The purpose of this study was to assess patient preference and product efficacy of three non-prescription products for the symptomatic relief of xerostomia. The study group consisted of 80 individuals with a complaint of chronic (> six months) xerostomia and an unstimulated salivary flow rate of < 0.1 mL/min. The three products--a sorbitol/xylitol-sweetened chewing gum, a sorbitol-sweetened sour lemon lozenge, and a sorbitol/xylitol-sweetened artificial saliva substitute spray--were assigned in a permuted block randomization scheme. Each product was used for two weeks with an interval of one week between trials. The study did not identify any product to be statistically significant in terms of patient preference. Kruskal-Wallis testing revealed no statistical significance (P > 0.589) among the products. No product demonstrated marked efficacy in stimulating salivary output. ANOVA analysis followed by Tukey HSD testing revealed no significant difference between the baseline paraffin-stimulated mean flow rate and the gum- and lozenge-stimulated flow rates.", "Two new saliva stimulants: V6 and a mucin containing chewing gum were tested in this placebo-controlled double-blind crossover study. Forty-three patients (mean age 63 yr) complaining of dry mouth participated. The products were administered in a randomized order, and used for 2 wk each. The effect was evaluated by interviews and by determining changes in stimulated and unstimulated saliva flow rates. A positive effect was reported by 64%, 44%, and 26% of the patients using the mucin chewing gum, V6, and the placebo, respectively. More than 2/3 of the patients found the mucin chewing gum efficient at various times and situations. Sixty-one percent of the patients preferred the mucin chewing gum, 21% V6, and 5% the placebo product. Fifty percent of the patients had an increase in unstimulated salivary secretion rate from all products after 14 days regular use indicating a long-term effect.", "To compare an intra-oral device to relieve oral dryness with the other methods of lubricating the mouth at night.\n Multidisciplinary single blind randomised cross over study.\n The subjects were drawn from patients attending a dry mouth clinic.\n Thirty-four dentate subjects attended on five occasions at intervals of 4 weeks. At the first visit the teeth were scaled and impressions were recorded. The device was fitted either on the second or the fourth visit. At all visits samples were taken of the resting and stimulated saliva for volumetric analysis and the dry mouth score recorded. Data were collected from the lubrication timings and the questionnaire.\n Ten water, nine saliva substitute and ten sugar-free chewing gum lubricators completed the study. There were 27 female and two male subjects with an average age of 62 years. Nine out of 10 of those lubricating with chewing gum preferred wearing the device (P = 0.037). After the device wearing period the subjects' self assessment of mouth dryness (P = 0.056), speech (P = 0.009) and swallowing (P = 0.031) were more favourable when compared with the alternative lubrication with 66% preferring the intra-oral device to their alternative method of lubrication.\n The majority of the subjects preferred wearing the device at night compared with their normal method of lubrication. Subjects' perception of dryness, speech and swallowing became closer to the clinician's assessment after wearing the device.", "Most patients on haemodialysis (HD) have to maintain a fluid-restricted diet to prevent a high interdialytic weight gain (IWG). The prevalence of xerostomia (the feeling of a dry mouth) is higher in HD patients than in controls. Recently, we demonstrated that xerostomia and thirst were positively correlated with IWG in HD patients. Thus, this may play a role as a stimulus for fluid intake between dialysis sessions. The aim of the present study was to investigate the effect of chewing gum or a saliva substitute on xerostomia, thirst and IWG.\n This study was a randomized two-treatment crossover design with repeated measures. After the use of chewing gum or saliva substitute for 2 weeks, a wash-out period of 2 weeks was introduced and hereafter the other regimen was carried out. Xerostomia and thirst were assessed by validated questionnaires as xerostomia inventory (XI) and dialysis thirst inventory (DTI), at baseline and after each treatment period, as were IWG and salivary flow rates.\n Sixty-five HD patients (42 men, 54.6+/-14.1 years; 23 women, 54.7+/-16.3 years) participated in this study. Chewing gum decreased XI from 29.9+/-9.5 to 28.1+/-9.1 (P<0.05). Chewing gum as well as a saliva substitute reduced DTI significantly (P<0.05), but no differences occurred for the average IWG or salivary flow rates.\n The use of chewing gum and, to a lesser extent, a saliva substitute may alleviate thirst and xerostomia in some HD patients.", "The first-ever controlled study of a therapeutic modality for xerostomia is reported. A recently described formulation for saliva substitute (SS) has been tested against a glycerine mouthwash as a control saliva substitute (placebo) in a double-blind clinical trial in 108 patients with varying grades of xerostomia of Sjögren's syndrome. The results indicate that SS offered significant relief of nocturnal oral discomfort (p less than 0.02) and more patients reported \"excellent\" improvement (p less than 0.01) on a five-point graded response. In all other respects, the SS was not significantly better than the placebo. Significant adverse effects were not reported. It is suggested that any such current and future therapeutic modalities for Sjögren's syndrome be subjected to similar critical appraisal of their worth.", "The stimulatory effect of a recently introduced saliva substitute (Saliment) on the parotid salivary secretion was experimentally investigated in 10 healthy individuals without signs or symptoms of xerostomia and in 11 patients with xerostomia due to Sjögren's syndrome. Further, in 15 patients with Sjögren's syndrome, the effect of Saliment on the sensation of xerostomia was examined in a double-blind clinical study with cross-over. The use of Saliment was followed by a significant stimulation in the parotid salivary secretion (P less than 0.01) and the subjection sensation of xerostomia was significantly reduced (P less than 0.01).", "The effect of multiple daily applications of a prophylactic gel, with buffering substances, on plaque acidogenicity in elderly institutionalised individuals was evaluated.\n Many elderly suffer from reduced salivary flow, poor oral hygiene and increased levels of cariogenic bacteria and are considered to be at an increased risk for coronal and root caries. Reinforcing the buffering capacity of dental plaque by the addition of substances such as bicarbonate and phosphates may decrease their caries activity.\n Fourteen elderly, with subjective dry mouth, were treated for 16-day-periods at random with: (i) Profylin fluoride gel with buffering components; (ii) Profylin fluoride gel without buffering components and (iii) rinsing with water. Applications were made four times a day and each period was followed by a 2-week wash-out period. The plaque pH was registered after a carbohydrate challenge and the following were recorded before and after each test period: stimulated salivary secretion rate, buffer capacity, number Colony Farming Units (CFU) mutans streptococci, lactobacilli and a sample of Candida albicans on oral mucosa.\n Eleven participants (mean age 76.6 years) fulfilled the study. Changes in plaque pH measurements, when calculated as area under the curve (AUC(6.2) and AUC(5.7)) values (pH x min), before and after each of the three treatments, showed no significant differences. A tendency to a higher plaque acidogenicity and amount of cariogenic microorganisms was found after the gel treatments. C. albicans was found in low levels.\n Frequent applications of the gel did not result in an improved neutralising effect in the elderly. This may be caused by a combination of several factors, such as the level of oral dryness of the individuals and low solubility, release and retention of the gel substances in plaque. Instead, an increased plaque acidogenicity was noted.", "A new chewing gum (PTC) with the ability to release flavoring substances for a rather long time was tested for its ability to stimulate saliva secretion. The chewing gum is mildly flavored and contains non-cariogenic sweeteners (xylitol and sorbitol). Measurements of saliva secretion rate and oral mucosal sliding friction and subjective evaluations on visual analog scales were made in relation to chewing and compared with those when chewing a commercially available gum (V6). The study was a randomized, crossover comparison with blind evaluation. Both chewing gums stimulated saliva secretion and decreased oral mucosal friction. The PTC gum gave consistently higher mean values of saliva secretion rate and lower oral mucosal friction values than V6. The difference was statistically significant for the saliva secretion rate and most pronounced after 5-10 min of chewing. There was also a statistically significant difference between the subjective evaluations of V6 and PTC with regard to saliva-stimulating ability and taste in favor of the PTC gum.", "Our aim was to study the effects of mildly flavoured sodium lauryl sulphate (SLS)-containing and detergent-free toothpastes with and without betaine (BET) on subjective symptoms of dry mouth in a randomised clinical trial. BET is an osmoprotectant that reacts with molecules to supply the surface with a water coating that protects cells from surfactants. Twenty-seven xerostomic patients and 18 healthy controls took part in the randomised, double-blind clinical trial with a crossover design. Three mildly flavoured toothpastes: (1) 4% BET, (2) 1% SLS and 4% BET, and (3) 1% SLS were used for six weeks each. The reference or washout paste contained neither SLS nor BET. The subjects' dental appointments were at the beginning of the trial and before and after the use of each toothpaste. At each appointment, the subjects were interviewed about subjective sensations of dry mouth (Visual Assessment Scoring (VAS) Index). The subjects did not report any adverse effects in connection with the use of the toothpastes. The VAS scores for lip dryness and eating difficulties were significantly lower for the BET paste (lip dryness: BET<BET+SLS; p < 0.005 and eating difficulties: BET<BET+SLS; p = 0.02; BET<reference; p = 0.003). The BET paste relieved dry mouth symptoms in 44% of the xerostomic patients, the corresponding figures for the other pastes being BET+SLS 22% (p = 0.002 as compared with BET), SLS 18% (p = 0.022), and reference 7% (p = 0.000). In conclusion, all the mildly flavoured toothpastes used in this study were well accepted by the xerostomic subjects. Thus, other toothpaste components may be more mucosa-irritating than just SLS, or else they enhance the effect of SLS. The detergent-free, BET-containing toothpaste appeared to be associated with relief of some symptoms of dry mouth.", "To determine the efficacy of 3 types of polymer-based saliva substitutes in reducing oral dryness in patients with Sjögren's syndrome (SS).\n Subjective efficacy of 3 different saliva substitutes (determined by self-administered questionnaire) was evaluated in a double-blind, placebo-controlled trial in 43 patients with primary and secondary SS. High-viscosity versus low-viscosity xanthan gum-based saliva substitutes were also compared in 33 SS patients. Salivary flow rates (SFR) were determined to examine correlations between the SFR and the subjective efficacy of the saliva substitute.\n Neither the saliva substitutes nor the placebo was truly effective. Preference for a particular saliva substitute over placebo was equally distributed among the 3 types of substitutes. The SFR of patients who preferred polyacrylic acid-based saliva substitutes was lower than that in patients who preferred the porcine mucin-based substitute (P < 0.05). Patients whose oral dryness was reduced by low-viscoelastic substitutes had a low stimulated SFR ( < 0.20 ml/minute; P < 0.05).\n The optimal properties of a saliva substitute are not the same for all patients with SS, but are dependent on such parameters as the individual SFR. Thus, to determine the best saliva substitute for a particular patient, it is necessary to have the patient try a number of substitutes of different viscoelastic properties.", "A randomized clinical trial (Study 1) and consumer usage test (Study 2) were conducted to evaluate the acceptability and efficacy of OASIS Mouth Moisturizing Spray in subjects experiencing dry mouth.\n Study 1: A randomized, single-blind, four-arm crossover clinical trial was conducted in 24 subjects, ranging from 50-84 years of age, to evaluate OASIS Mouth Moisturizing Spray and two experimental mouth spray formulations, and compare their performance to a reference (marketed) mouth spray, SALIVEZE. Following a three-day acclimatization phase, subjects used all four products at home for three days. Each treatment phase was separated by a three-day washout period. Study 2: One-hundred twenty subjects participated in a three-week home usage consumer test using OASIS Mouth Moisturizing Spray, after which they completed a 52-question online survey exploring sensory, efficacy, and resultant quality of life attributes of the product.\n Study 1: On average, subjects used the four test products 2-3 times per day. OASIS Mouth Moisturizing Spray was found to be effective in relieving dry mouth in the study population, as evidenced by a statistically significant feeling of coating the mouth (p < 0.05), and statistically significantly longer dry mouth relief (p < 0.005) than the commercial control. The OASIS Mouth Moisturizing Spray was statistically significantly (p < 0.05) better and preferred over the other product tested. All the products used in the study were well-tolerated. Study 2: On a five-point scale, 73% of respondents perceived the OASIS Mouth Moisturizing Spray as \"very good\" or \"excellent,\" and more than 60% gave the product an \"excellent\" or \"very good\" rating on sensory, efficacy, and quality of life attributes.\n These studies show that OASIS Mouth Moisturizing Spray helped provide dry mouth relief and was well liked by the study population.", "A comparison was made of Oral Balance gel delivered by slow release via a novel intra-oral device versus an oral bolus of gel on the oral health condition and oral health-related quality of life (OHRQoL) in patients who had received standard head and neck irradiation for nasopharyngeal carcinoma. Twenty-two participants took part in a randomized single-blind crossover clinical study. Each treatment lasted 4 weeks with an intervening 4 weeks washout period. The GOHAI, Xerostomia Inventory and patient satisfaction measures were self-completed and oral health condition assessed objectively at baseline (week 0) and weeks 4, 8 and 12. Oral Balance gel, in bolus and slow-release forms, was effective in improving aspects of oral health, notably a reduction in oral cariogenic micro-organisms. Slow release of gel via the intra-oral device did not appear to improve OHRQoL whereas gel alone reduced the severity of xerostomia symptoms and was the treatment of choice.", "Irreversible hyposalivation is a common sequela of Sjögren's syndrome and may lead to a decreased quality of the patient's life. The aim of this study was to evaluate the efficacy and therapeutic value of mucin-containing lozenges in reducing patients' complaints of hyposalivation. In a double-blind crossover trial in 42 patients with Sjögren's syndrome, the efficacy and therapeutic value of both a mucin-containing and placebo lozenge were assessed by means of self-administered questionnaires, which had to be completed before and after the use of each type of lozenge for a period of 2 weeks. Seventy-six percent of the patients preferred the mucin lozenge, 10% preferred the placebo, and 14% had no preference. In reducing patients' complaints, sucking the mucin lozenge resulted in a larger improvement of the total pattern of complaints and the sensation of oral dryness, and in a longer moistening of the oral cavity than the placebo. Oral functioning was improved after the use of the placebo, and the patients reported the taste of the placebo to be better than the mucin lozenge. From the responses it was concluded that the use of the mucin lozenges can be recommended in the treatment of oral symptoms of xerostomia.", "Xerostomia is a subjective sensation of mouth dryness often occurring as an unwanted effect of psychotropic drugs.\n The clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray (1 or 2 sprays up to 4 times daily) in the treatment of xerostomia was compared with those of a commercially available artificial saliva substitute (ASS [Saliveze]) in a 2-week, open-labeled, randomized, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness by means of a 10-cm-long visual analog scale, objective blinded assessment of the oral tissue condition by a dental hygienist by means of a 4-point ordinal scale, and subjective patient-based assessment of dry mouth symptoms by means of dichotomous responses to a questionnaire. [Day 14 - baseline] patient-based mouth dryness score was the primary end point.\n Seventy-four patients (41 women and 33 men, 44 +/- 15 years) undergoing long-term psychotropic drug treatment were consecutively enrolled. At day 14, OGT resulted in better efficacy than ASS in mouth dryness score (mean difference, 1.2 +/- 0.4; P = 0.006), speech difficulties (mean difference, 1.2 +/- 0.4; P = 0.005), taste (mean difference, 1.1 +/- 0.4; P = 0.02), and overall mouth condition (mean difference, 1.4 +/- 0.9; P = 0.005). Taste of OGT was better than that of ASS (mean difference, 1.4 +/- 0.6; P = 0.04), as was OGT acceptability (mean difference, 1.4 +/- 0.9; P = 0.005).\n Oxygenated glycerol triester lubricant oral spray was superior to a commercially available ASS in improving xerostomia and overall condition of the oral tissue.", "Xerostomia is a subjective sensation of mouth dryness that may frequently occur in older patients.\n To compare the clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray taken five times daily with that of a commercially available saliva substitute Saliveze in the treatment of xerostomia.\n Forty-one institutionalised patients (28 women, 13 men; mean age 84 +/- 7 years) were randomly assigned to receive either OGT or Saliveze in a 2-week, randomised, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness using a self-rated, 10cm long visual analogue scale (VAS), objective assessment of oral tissue condition using a four-point ordinal scale and subjective assessment of symptoms of xerostomia using dichotomous responses to a questionnaire. The primary endpoint was the day (D) 14 patient-based mouth dryness score measured on a self-rated VAS.\n At D14, OGT resulted in significantly greater efficacy with respect to mouth dryness (mean between-treatment difference 2.1 +/- 0.1, 95% CI 1.9, 2.3; p = 0.001), swallowing difficulty (1.8 +/- 0.3, 95% CI 1.5, 2.1; p = 0.001), speech difficulty (1.1 +/- 0.2, 95% CI 1.0, 2.4; p = 0.04) and overall sensation of symptom relief (2.7 +/- 1.2, 95% CI 1.9, 3.8; p = 0.001). Objective assessment of oral tissues also showed significantly better improvement with OGT spray with respect to dryness (p = 0.01), stickiness (p = 0.005) and dullness (p = 0.001) of oral mucosa; severity of mucositis (p = 0.01); and thickening of the tongue (p = 0.03). A significant difference in taste acceptability was also noted in favour of OGT (1.4 +/- 0.6, 95% CI 1.2, 1.9; p = 0.04).\n OGT lubricant oral spray was superior to Saliveze in improving xerostomia and oral tissue condition in older institutionalised patients.", "Following therapeutic irradiation of the head and neck, patients with profound xerostomia have complaints associated with oral dryness, effects upon use of oral prosthesis, speech, and taste. In addition, xerostomia may lead to risk of oral infections and rampant demineralization of teeth. The use of topical Oral Balance gel and Biotene toothpaste (Laclede Professional Products, Gardena, CA) versus carboxymethylcellulose gel and commercial toothpaste applications was assessed in a 2-week double-blind, crossover design. The palliative effects of Oral Balance gel and Biotene toothpaste were superior to the effects of a placebo. No effect on oral colonization by Candida species and cariogenic oral microflora was seen with use of the topical agents.", "Xerostomia is an important chronic side effect of radiotherapy in the head and neck area. The authors investigated the efficacy of different artificial saliva compounds in patients with postirradiation xerostomia.\n In 120 patients with xerostomia after radiotherapy for head and neck cancer, four different saliva substitute compounds (gel, carmellose spray, oil, mucin spray) were tested in a prospective crossover design. Xerostomia at baseline and under treatment with each compound was measured with a questionnaire approved in a pilot trial.\n All compounds significantly improved xerostomia when compared to baseline situation (p < 0.0001). The gel was rated best, the carmellose spray was rated worst by the patients, but the single compounds did not differ significantly in their effects. In spite of this result, most patients chose the carmellose spray as their favorite compound. This is due to its good taste and easy handling, which play an important role for the acceptance of the products. Big individual differences in the preference of the single compounds were found.\n For most patients considerable relief from xerostomia can be reached by saliva substitutes. Thus, every patient with xerostomia should be given different artificial saliva compounds for a test period. This will help to find the individually best way to cope with the dry mouth.", "Thirty-five hospice patients complaining of dry mouth entered a double-blind, single-phase placebo-controlled trial of a mucin-containing oral spray (Saliva Orthana) for the relief of xerostomia. The sprays were administered ad libitum for two weeks by the patients themselves, with nursing help as necessary. A detailed history and examination were undertaken, together with collection of microbiological specimens, at entry and after seven and 14 days of spray usage, respectively. Thirty-one patients were available for follow-up at seven days and 26 patients after 14 days. Relief of oral dryness during the day was reported by 9/15 patients on Saliva Orthana and 10/16 patients on placebo by day 7, with a similar degree of improvement maintained to day 14. The corresponding figures by day 7 for relief of dryness at night were 8/15 for Saliva Orthana and 8/16 for placebo. There were no statistically significant differences between those on active and those on placebo spray for any of the oral symptoms recorded. Neither spray had any major impact on the oral microflora. However, the majority of patients in both treatment groups wished to continue using a mouth spray at the end of their involvement in the trial. Whilst the data from this study provide no evidence for increased benefit of a mucin-containing spray over a mucin-free placebo among xerostomic hospice patients, it is clear that both sprays provided worthwhile symptomatic relief of oral dryness for many of the participants.", "A double-blind, five phase, cross-over clinical trial was used to compare a mucin-based artificial saliva (Saliva Orthana) with its non-mucin base and water. Thirty patients, acting as their own controls, took part. Saliva Orthana offered significantly greater relief from xerostomia compared with its base or water, and was significantly better at relieving soreness than water. In terms of overall preference, it was ranked significantly higher than either alternative.", "Dry mouth is a frequent complaint of adults worldwide. In those who experience dry mouth, therapeutic options include the use of salivary substitutes and sialogogues.\n The authors compared the efficacy and safety of mucoadhesive disks (OraMoist, Axiomedic, Zurich; distributed by Quantum Health, Eugene, Ore.) applied three times daily with those of placebo mucoadhesive disks in a double-masked, randomized, controlled crossover study. The primary end point of interest was within-participant differences in subjective (visual analog scale) ratings of dry mouth according to the New York University Bluestone Mouthfeel Questionnaire. The secondary end point was within-participant differences in salivary flow rates.\n Twenty-seven participants completed the single-site study. The results showed no significant difference between the two types of mucoadhesive disks, both of which were associated with a statistically significant improvement in the subjective experience of moistness across the 60-minute period after application and compared with baseline measures after two weeks of use. Furthermore, both disks were associated with a statistically significant improvement in salivary flow rates across the 60-minute period after application and compared with baseline measures after one and two weeks of use. The disks were well tolerated, and participants did not report any adverse events.\n The mucoadhesive disks used in this study were safe and provided symptomatic relief from dry mouth. Practice Implications. Patients with dry mouth may benefit from this novel delivery system.", "The effect of a linseed extract Salinum and a sodium carboxymethyl cellulose preparation called MAS-84 was compared with regard to its effect on the symptoms of dry mouth. Twenty patients with xerostomia, who had been treated for cancer in the head and neck by radiation were recruited from the clinic for maxillofacial surgery, Malmo University Hospital. Following radiation treatment the salivation was severely reduced. The symptoms of a general feeling of a dry mouth, difficulties in chewing and swallowing, taste disturbances, problems with speech and mouth burning were registered on a subjective verbal rating scale. In addition plaque index and gingival bleeding were determined. The study design was crossover and performed single blind. The experimental period was 7 weeks. The patients were randomly divided into 2 groups. One group used Salinum and the other MAS-84 for 3 weeks. The fourth week was a wash out period and for the next three weeks the patients shifted preparation. Each of the preparations was used ad libitum. Registrations of the various parameters were undertaken on days 0, 7 and 21 of the respective period. At the initial examination all patients reported considerable disturbances from mouth-dryness. These symptoms were reduced in 15 patients during the Salinum period and in 9 during the MAS-84 period. The relief was significantly more pronounced during the use of Salinum compared to that during the use of the methyl cellulose preparation. On day 21 plaque and gingival bleeding were significantly reduced during the Salinum period but not during the MAS-84 period. The results of the present study confirm those of a previous pilot study and indicate that the linseed mucilage significantly reduced the symptoms of dry mouth. This effect increased with increasing time of saliva substitute use. The linseed mucilage Salinum appeared to be a suitable saliva replacement in mouth dry patients.", "Polypharmacy is a common cause of salivary hypofunction, producing symptoms of dry mouth or xerostomia, especially among older populations. As the number of older people continues to increase, polypharmacy-induced salivary hypofunction is becoming an increasing problem. Many over-the-counter products are available for relieving symptoms of dry mouth, but few have been tested in controlled clinical investigations. The purpose of this investigation was to evaluate the safety and efficacy of a group of topical dry mouth products (toothpaste, mouth rinse, mouth spray and gel) containing olive oil, betaine and xylitol. Forty adults were entered into this single-blinded, open-label, cross-over clinical study and 39 completed all the visits. Subjects were randomly assigned at baseline to using the novel topical dry mouth products daily for 1 week, or to maintain their normal dry mouth routine care. After 1 week, they were crossed over to the other dry mouth regimen. The results demonstrated that the use of the novel topical dry mouth products increased significantly unstimulated whole salivary flow rates, reduced complaints of xerostomia and improved xerostomia-associated quality of life. No clinically significant adverse events were observed. These data suggest that the daily use of topical dry mouth products containing olive oil, betaine and xylitol is safe and effective in relieving symptoms of dry mouth in a population with polypharmacy-induced xerostomia.", "To evaluate the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lactoferrin and lysozyme, in a sample of elderly individuals with dry mouth.\n Twenty elderly institutionalised subjects with dry mouth and with a certain degree of independence for daily life activities were included in this pilot study. A randomised, double blind and cross-over design was used. The study variables comprised subjective dry mouth sensation, the severity of discomfort assessed by means of a visual analogical scale (VAS), the Oral Health Impact Profile (OHIP), the presence of signs and symptoms of dry mouth, sialometry and Candida albicans culture. All the variables were recorded before and after each of the two periods of the study.\n The 20 selected subjects we made up of 16 women and four men, with a mean age of 81.3 years. Improvement was observed on analysing the data between the first and second intervention period in terms of the OHIP values, the presence of dry mouth, and the need to drink fluids to swallow. However, the improvement in certain variables before and after treatment did not take a positive course in all cases, and some subjects even improved with placebo.\n The evaluated mouthwash and oral gel improved some subjective and clinical aspects in elderly individuals with dry mouth, though a placebo effect cannot be entirely discarded.", "The purpose of this investigation was to evaluate and compare four oral lubricants in relation to oral mucosal status, perceived relief of dry mouth symptoms, and patient acceptance. Three commercial oral lubricants--two sprays and one gel--and a home remedy of margarine were evaluated. Twenty-five xerostomic/salivary gland dysfunctional patients demonstrating < 0.20 mL/min of unstimulated whole saliva participated in the randomized, four-phase, cross-over study. Each phase included a ten-day use of oral lubricants, followed by a four-day washout period. On the first and tenth days of use, lip and buccal mucosa dryness and perceived oral dryness were evaluated. Patient acceptance of the oral lubricant was evaluated at the end of each ten-day period. The Wilcoxon matched-pairs signed-rank test was used to analyze data over time and between-group differences. The gel group reported a statistically significant improvement in perceived oral dryness from Day 1 to Day 10. No other significant within-group differences were found. Subjects rated the gel significantly better than margarine for convenience, perceived value, minutes of relief, and in the \"overall\" rating. No other significant between-group differences were noted.", "Changes in subjective sensations due to xerostomia before and after administration of Xialine, a xanthan gum-based saliva substitute, were evaluated in 30 patients with radiation-induced xerostomia using the QLQ-H&N35. Xerostomia in general decreased with both Xialine and placebo to almost the same degree. A trend was seen for Xialine to improve problems with speech and senses.", "To assess the effect of a reservoir biteguard for artificial saliva on the oral health-related quality of life of patients with xerostomia.\n Double-blind randomized placebo-controlled trial among 86 adults with xerostomia. Study group received the trial biteguard. Control group received a conventional biteguard. Outcomes were number of impacts and total scores as recorded by oral impacts on daily performances (OIDP).\n At 1-month follow up 84 people remained in the trial. The median number of impacts in the study and control groups was 3 and 4 respectively. The median total score was 6 and 12 respectively. In ANCOVA receipt of the reservoir biteguard reduced the number of impacts recorded by OIDP but there was no difference in the total score.\n Reservoir biteguards improved the quality of life of people with xerostomia by reducing the number of impacts on daily life." ]

[ "12359854", "16049976" ]

[ "Randomized trial of breast self-examination in Shanghai: final results.", "Outcome of screening by clinical examination of the breast in a trial in the Philippines." ]

[ "Among women who practice breast self-examination (BSE), breast cancers may be detected when they are at an earlier stage and are smaller than in women who do not practice BSE. However, the efficacy of breast self-examination for decreasing breast cancer mortality is unproven. This study was conducted to determine whether an intensive program of BSE instruction will reduce the number of women dying of breast cancer.\n From October 1989 through October 1991, 266,064 women associated with 519 factories in Shanghai were randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women). Initial instruction in BSE was followed by reinforcement sessions 1 and 3 years later, by BSE practice under medical supervision at least every 6 months for 5 years, and by ongoing reminders to practice BSE monthly. The women were followed through December 2000 for mortality from breast cancer. Cumulative risk ratios of dying from breast cancer were estimated using Cox proportional hazards models. All statistical tests were two-sided.\n There were 135 (0.10%) breast cancer deaths in the instruction group and 131 (0.10%) in the control group. The cumulative breast cancer mortality rates through 10 to 11 years of follow-up were similar (cumulative risk ratio for women in the instruction group relative to that in the control group = 1.04, 95% confidence interval = 0.82 to 1.33; P =.72). However, more benign breast lesions were diagnosed in the instruction group than in the control group.\n Intensive instruction in BSE did not reduce mortality from breast cancer. Programs to encourage BSE in the absence of mammography would be unlikely to reduce mortality from breast cancer. Women who choose to practice BSE should be informed that its efficacy is unproven and that it may increase their chances of having a benign breast biopsy.", "The value of screening by Clinical Examination of the Breast (CBE) as a means of reducing mortality from breast cancer (BC) is not established. The issue is relevant, as CBE may be a suitable option for countries in economic transition, where incidence rates are on the increase but limited resources do not permit screening by mammography. Our aims were to assess whether mass screening by CBE carried out by trained para-medical personnel is feasible in an urban population of a low-income country, and its efficacy in reducing BC mortality. Our study was designed as a randomised controlled trial of the effect on BC mortality of 5 annual CBE carried out by trained nurses. The target population was women aged 35-64 years, resident in 12 municipalities of the National Capital Region of Manila, Philippines. The units of randomization were the 202 health centres (HC) within the selected municipalities. During 1995 nurses and midwives were recruited and trained in performing CBE. The first round of screening took place in 1996-1997. The intervention however showed a refractory attitude of the population with respect to clinical follow-up and was discontinued after the completion of the first screening round. Cases of breast cancer occurring in the study population during 1996-1999 were identified by the 2 local population-based registries. In the single screening round 151,168 women were interviewed and offered CBE, 92% accepted (138,392), 3,479 were detected positive for a lump and referred for diagnosis. Of these only 1220 women (35%) completed diagnostic follow-up, whereas 42.4% actively refused further investigation even with home visits, and 22.5% were not traced. Of 53 cases that occurred among screen-positive women in the 2 years after CBE only 34 were diagnosed through the intervention. Eighty cases occurred among screen-negative women. The test sensitivity for CBE repeated annually was 53.2%. The actual sensitivity of the programme was 25.6% and positive predictive value 1%. Screen-detected cases were non-significantly less advanced than the others. Previous studies have shown that most breast cancer cases in the Philippines present at advanced stages and have an unfavourable outcome. Although CBE undertaken by health workers seems to offer a cost-effective approach to reducing mortality, the sensitivity of the screening programme in the real context was low. Moreover, in this relatively well-educated population, cultural and logistic barriers to seeking diagnosis and treatment persist and need to be addressed before any screening programme is introduced.\n Copyright 2005 Wiley-Liss, Inc." ]

[ "10529932", "22000272", "22094303", "10090431", "20852438", "22688429", "8979657", "16386090", "8930426", "22419858" ]

[ "The dorzolamide/timolol combination versus timolol plus pilocarpine: patient preference and impact on daily life. United States Patient Preference Study Group. International Patient Preference Study Group.", "The influence of health literacy level on an educational intervention to improve glaucoma medication adherence.", "Individualised patient care as an adjunct to standard care for promoting adherence to ocular hypotensive therapy: an exploratory randomised controlled trial.", "Patient preference, efficacy, and compliance with timolol maleate ophthalmic gel-forming solution versus timolol maleate ophthalmic solution in patients with ocular hypertension or open-angle glaucoma.", "Measurement of adherence to brimonidine therapy for glaucoma using electronic monitoring.", "Impact of a health communication intervention to improve glaucoma treatment adherence. Results of the interactive study to increase glaucoma adherence to treatment trial.", "The effect of a medication alarm device on patient compliance with topical pilocarpine.", "Comparison of latanoprost monotherapy and combined therapy of 0.5% timolol and 1% dorzolamide in chronic primary angle-closure glaucoma (CACG) in Japanese patients.", "Dorzolamide versus pilocarpine as adjunctive therapies to timolol: a comparison of patient preference and impact on daily life.", "Comparison of the latanoprost 0.005%/timolol 0.5% + brinzolamide 1% versus dorzolamide 1%/timolol 0.5% + latanoprost 0.005%: a 12-week, randomized open-label trial." ]

[ "To compare the 2.0% dorzolamide/0.5% timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5% timolol plus 2.0% pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP).\n Two multi-center, randomized, cross-over, observer masked studies were conducted, one in the United States (97 patients) and one in Europe (93 patients). The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from study medications. Intraocular pressure was measured before and 2 hours after the morning dose of study medication (hour 0 and hour 2).\n In both studies, among patients with a preference, the combination was preterred to timolol plus pilocarpine by a ratio of 4 to 1. The most commonly cited reason for this preference was side effects. Patients in both studies also reported that the combination interfered significantly less with daily life in terms of side effects and activity limitations. They also reported missing significantly fewer doses of study medication while taking the combination and being significantly more satisfied with it. The efficacy of these two treatments was not significantly different, based on IOP measurements at hour 0 and 2 hours after administration. Patients reported significantly more adverse events while receiving timolol plus pilocarpine in both studies, and in the U.S. study, significantly more patients discontinued therapy while receiving timolol plus pilocarpine than while receiving the combination.\n Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.", "To test an educational intervention targeted to health literacy level with the goal of improving glaucoma medication adherence.\n One hundred and twenty-seven veterans with glaucoma were randomized to glaucoma education or standard care. The intervention included a video scripted at a 4th, 7th, or 10th grade level, depending on the subject's literacy level. After six months, the number of days without glaucoma medicine (DWM) according to pharmacy records for the intervention and control groups was compared.\n The number of DWM in the six months following enrollment was similar for control and intervention groups (intervention, n=67, DWM=63 ± 198; standard care, n=60, DWM=65 ± 198; p=0.708). For each subgroup of literacy (adequate, marginal, inadequate), subjects in the intervention group experienced less mean DWM than subjects in the control group and the effect size (ES) increased as literacy decreased: adequate literacy, ES 0.069; marginal, ES 0.183, inadequate, ES 0.363. Decreasing health literacy skills were associated with decreasing self-reported satisfaction with care (slope=0.017, SE=0.005, p=0.002).\n Patients with decreased health literacy skills may benefit from educational efforts tailored to address their health literacy level and learning style.\n Providers should consider health literacy skills when engaging in glaucoma education.\n Published by Elsevier Ireland Ltd.", "To evaluate the impact of individualised patient care, as an adjunct to standard care, on adherence to ocular hypotensive therapy.\n A two-arm, single-masked exploratory randomised controlled trial recruited patients newly prescribed ocular hypotensive therapy. The intervention involved an individual assessment of health-care needs and beliefs and a 1-year follow-up period according to need. The primary outcome was refill adherence, measured by collating prescription and dispensing data for 12 months. Secondary outcomes included self-reported adherence, glaucoma knowledge, beliefs about illness and medicines, quality of care, intraocular pressure (IOP) fluctuation, and changes in clinical management assessed at 12 months. The strength of the intervention was measured following withdrawal by reviewing clinical outcomes for a further 12 months.\n In all, 127 patients were recruited (91% response rate). Intervention-arm patients collected significantly more prescriptions than control-arm patients. Self-report adherence was significantly better in the intervention-arm for patients who forgot drops and those who intentionally missed drops. The intervention group demonstrated significantly more glaucoma knowledge, expressed a significantly stronger belief in the necessity of eye drops and believed that they had more personal control over managing their condition. Control-arm patients had more IOP fluctuation and changes in clinical management. However, this finding only reached significance at 24 months.\n Modelling patient care according to health-care needs and beliefs about illness and medicines can have a significant impact on improving adherence to therapy for this patient group, with the potential benefit of improving clinical outcomes.", "This study was designed to compare timolol maleate ophthalmic gel-forming solution 0.5% (timolol gel) once daily with timolol maleate ophthalmic solution 0.5% (timolol solution) twice daily with respect to patient preference, intraocular pressure (IOP)-lowering effect, and tolerability. A total of 202 patients with ocular hypertension or open-angle glaucoma and an IOP > or = 22 mm Hg were enrolled in this 12-week, randomized, observer-masked, two-period crossover study. Significantly more patients preferred timolol gel to timolol solution (P < 0.001). Ninety-two percent of patients preferring timolol gel strongly agreed or agreed that once-daily dosing was a reason for their preference. Those who preferred timolol solution did so because of fewer side effects. The mean IOP-lowering effects of the 2 treatments were similar at both morning trough and peak time points. The incidence of drug-related adverse experiences was similar (timolol gel 11.4% vs timolol solution 10.9%). Because both treatments were well tolerated and effective in lowering IOP, timolol gel, with its once-daily dosing regimen, should be considered in patients who are candidates for therapy with an ophthalmic beta-blocking agent.", "To assess the patient adherence and behavior with brimonidine twice daily (bid) or 3 times daily (tid) in patients used to topical glaucoma medication.\n Seventy-five patients with glaucoma or ocular hypertension were enrolled in a prospective, observational cohort study. Consenting patients were randomly assigned to brimonidine bid or tid and received conventional brimonidine eye drops with attached electronic monitoring devices for 4 weeks. Patients were not explicitly informed on the compliance monitoring.\n The study was completed by 67 patients (89%). In 65 patients (97%), at least 1 dosing interval exceeded 24 hours. The mean adherence rates were better in the brimonidine bid group (72 ± 19% vs. 62 ± 16%, P=0.04), although dosing frequency was higher in the tid group (1.9 ± 0.5 vs. 1.4 ± 0.4 per day; P<0.001). On average medication coverage was 70% for the bid group and 67% for the tid group; 19 patients (28%) had a coverage rate above 75%, 42 patients (63%) 50% to 75%, and 6 (9%) below 50%. Patients with normal-tension glaucoma had lower coverage rates than patients with primary open-angle glaucoma and ocular hypertension (P<0.05). Data also showed that on average 20% of the glaucoma medication was wasted owing to inefficient drug delivery by using more than 1 drop per dosing.\n Individual adherence with brimonidine was highly variable and pharmacologically insufficient for more than two-third of the patients. Special attention should be paid to compliance of patients with normal-tension glaucoma. Our findings underline the need to improve individual adherence and drug delivery in topical glaucoma therapy.", "To determine the efficacy of an automated, interactive, telephone-based health communication intervention for improving glaucoma treatment adherence among patients in 2 hospital-based eye clinics.\n A total of 312 patients with glaucoma (18-80 years of age) were enrolled in a randomized controlled trial at 2 eye clinics located in hospitals in the southeastern United States. These patients were considered nonadherent because they did not take their medication, refill their medication, and/or keep their appointments. The treatment group received an automated, interactive, tailored, telephone-based health communication intervention and tailored print materials. The control group received usual care.\n Adherence with medication taking, prescription refills, and appointment keeping measured by interviews, medical charts, appointment records, and pharmacy data.\n A statistically significant increase was found for all adherence measures in both the intervention and control groups. Interactive telephone calls and tailored print materials did not significantly improve adherence measures compared with controls.\n During the study period, patient adherence to glaucoma treatment and appointment keeping improved in both study arms. Participation in the study and interviews may have contributed. Strategies that address individuals' barriers and facilitators may increase the impact of telephone calls, especially for appointment keeping and prescription refills.\n Glaucoma patient care should include reminders about consistent use of medication and the importance of keeping appointments. More frequent, and personalized, telephone contact may be helpful to patients who are known to be nonadherent. Trial Registration: clinicaltrials.gov Identifier:NCT00794170.", "This study was performed to investigate the use of an electronic medication alarm device (Prescript TimeCap) to enhance compliance in glaucoma patients taking pilocarpine.\n Thirteen subjects were selected who had been diagnosed with open-angle glaucoma and were receiving 1 drop of pilocarpine solution 4 times a day in both eyes. For each subject, the study was divided into 2 30-day phases, one with the medication alarm device and the other without. Thus, each subject served as his or her own control. Compliance was measured based on the amount of pilocarpine used and by patient questionnaire. In addition, the subjects completed a post-study questionnaire regarding the ease of use of the TimeCap and whether it helped them remember to take their medication.\n When subjects used the TimeCap, they administered an average of 2.867 g (P < 0.0001) more pilocarpine over the 30 days than during the period without it. Subjects also estimated a significant difference in compliance level, 95.8 percent with the alarm device versus 83.1 percent without it (p < 0.01). All subjects reported no difficulty using the TimeCap, and all reported that it helped them remember to take their medication.\n These results are highly suggestive that the TimeCap is an effective compliance aid for glaucoma patients on pilocarpine.", "To compare the efficacy, adverse effects, and patient compliance of latanoprost monotherapy with unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of chronic primary angle-closure glaucoma (CACG), 36 Japanese patients with CACG following laser iridotomy (LPI) were treated for 12 weeks with instillation of latanoprost alone or with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. After 12 weeks of treatment, latanoprost reduced intraocular pressure (IOP) from 22.2 +/- 2.0 mmHg to 14.8 +/- 1.9 mmHg (33% reduction); timolol maleate and dorzolamide hydrochloride also reduced IOP from 22.5 +/- 2.2 mmHg to 17.1 +/- 2.7 mmHg (24% reduction). Latanoprost monotherapy significantly lowered IOP compared with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. Furthermore, a systemic adverse effect of bradycardia was not observed in the latanoprost monotherapy group. Concerning compliance, no significant difference was observed between the two groups. Thus, latanoprost monotherapy is more effective than unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of CACG following relief of pupillary block in Japanese patients.", "The purpose of this study was to compare 2% dorzolamide three times daily with 2% pilocarpine four times daily to determine patient preference, tolerability, and impact on daily life in patients concurrently receiving 0.5% timolol twice daily for treatment of elevated intraocular pressure (IOP). Seventy-five patients were enrolled in this 4-week, randomized, two-period, crossover study. The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from the study medications. IOP measurements were obtained 2 hours after drops were instilled and visual field tests were performed at baseline and at the end of each crossover period. Significantly more patients receiving pilocarpine than dorzolamide reported adverse experiences and discontinued the drug because of these adverse experiences. Similarly, patients reported more interference with their daily life because of side effects and activity limitations when receiving pilocarpine. Vision difficulties, accommodation difficulties, and brow ache were reported more often and were considered more bothersome by patients receiving pilocarpine. Bitter/unusual taste was reported more frequently and was considered more bothersome by patients receiving dorzolamide. Patients also reported missing fewer doses and were more satisfied with their medication when receiving dorzolamide. All of these changes were considered statistically significant. IOP control was not significantly different with either dorzolamide or pilocarpine. However, patients experienced a significant worsening of the mean defect of automated visual field examinations when receiving pilocarpine. At the end of the study, among patients with a preference, dorzolamide was preferred to pilocarpine by a ratio of more than 9:1. Overall, 81.9% of patients preferred dorzolamide. Thus dorzolamide demonstrated better tolerability and less adverse impact on daily life than pilocarpine.", "To compare the safety and effectiveness of fixed-combination regimes (latanoprost- timolol and brinzolamide 1% compared to dorzolamide 1%/timolol and latanoprost) in open-angle glaucoma patients after switching from a combination of three topical antiglaucoma eye drops.\n We conducted an open, randomized 12-week multicenter prospective study. We randomly allocated 39 patients who had been treated with three antiglaucoma eye drops (prostaglandin F(2α) analogues plus beta-blockers and carbonic anhydrase inhibitors) into two groups. Group A (n = 20) were treated with latanoprost-timolol and brinzolamide 1% therapy and Group B (n = 16) were treated with dorzolamide 1%/timolol and latanoprost. Thirty-six patients completed all 12 weeks of this study. The major clinical parameters measured were intraocular pressure (IOP), conjunctive hyperemia, superficial punctate keratopathy and hyperpigmentation of eyelid at baseline, 4, and 12 weeks. Additionally noted were adverse events and patient preferences, measured using a questionnaire at study initiation and at 12 weeks.\n AT BASELINE, IOPS WERE (GROUP A: 14.1 ± 2.9 mmHg, B: 14.5 ± 2.9 mmHg; P = 0.658), (Group A: 13.8 ± 2.6 mmHg, B: 14.3 ± 2.8 mmHg; P = 0.715) at 4 weeks, and (Group A: 14.1 ± 2.7 mmHg, B: 14.2 ± 2.7 mmHg; P = 0.538) at 12 weeks. Among the groups, there was no significant difference at any time point after baseline (P = 0.923, 0.951, respectively). All adverse events were not remarkably different after therapy. In regards to patient preference before and after switching therapy, 10 patients (50%) in Group A and 10 patients (63%) in Group B preferred using fixed-combination eye drop therapy.\n Effectiveness and safety were maintained in both groups after switching therapy. Overall, patients generally preferred using a fixed-combination therapy." ]

[ "15723895" ]

[ "Evaluation of the UCL diabetes self-management programme (UCL-DSMP): a randomized controlled trial." ]

[ "Self-management has been described as the cornerstone of care for diabetes. Many self-management studies are limited by poor methodology and poor descriptions of the intervention. The current study developed a theoretically based self-management programme for patients with type 2 diabetes, which was evaluated via a randomized controlled trial. At immediate post-intervention and three-month follow-up the intervention group showed significant improvement relative to controls on self-management behaviours, quality of life and illness beliefs. A trend towards improved HbA1c was also observed. Documentation in a manual and development of a training programme for facilitators ensures the programme is replicable." ]

[ "8134777", "16481707", "16836502", "19565120", "10642678", "12609786", "7926408", "12174005", "11205591", "10376691", "1375206", "14700144", "1862029", "11603388", "20177574", "1689135", "2188239", "2431015", "3828029" ]

[ "Comparison of ivermectin and benzyl benzoate for treatment of scabies.", "Comparison of the efficacy of topical 1% lindane vs 5% permethrin in scabies: a randomized, double-blind study.", "Efficacy and tolerability of a new synergized pyrethrins thermofobic foam in comparison with benzyl benzoate in the treatment of scabies in convicts: the ISAC study (Studio Della scabbia in ambiente carcerario).", "Ivermectin versus benzyl benzoate applied once or twice to treat human scabies in Dakar, Senegal: a randomized controlled trial.", "A comparative study of oral ivermectin and topical permethrin cream in the treatment of scabies.", "Efficacy and tolerability of natural synergised pyrethrins in a new thermo labile foam formulation in topical treatment of scabies: a prospective, randomised, investigator-blinded, comparative trial vs. permethrin cream.", "[The treatment of scabies with oral ivermectin].", "Ivermectin is better than benzyl benzoate for childhood scabies in developing countries.", "Successful treatment of scabies with oral ivermectin in Nigeria.", "Equivalent therapeutic efficacy and safety of ivermectin and lindane in the treatment of human scabies.", "Permethrin versus crotamiton and lindane in the treatment of scabies.", "A comparative study between 10 per cent sulfur ointment and 0.3 per cent gamma benzene hexachloride gel in the treatment of scabies in children.", "Therapeutic efficacy, secondary effects, and patient acceptability of 10% sulfur in either pork fat or cold cream for the treatment of scabies.", "Oral ivermectin in scabies patients: a comparison with 1% topical lindane lotion.", "Comparison of safety, efficacy, and cost effectiveness of benzyl benzoate, permethrin, and ivermectin in patients of scabies.", "Comparative study of 5% permethrin cream and 1% lindane lotion for the treatment of scabies.", "Comparison of crotamiton 10% cream (Eurax) and permethrin 5% cream (Elimite) for the treatment of scabies in children.", "Permethrin 5% dermal cream: a new treatment for scabies.", "[Treatment of scabies with a dermatological lotion of decamethrin at 0.02%. Study of 127 patients using 2 therapeutic regimens]." ]

[ "A randomized investigator-blinded trial of oral ivermectin 100 micrograms/kg single dose vs. benzyl benzoate 10% application in the treatment of scabies, was conducted in 1992 in French Polynesia. In total, 44 patients aged 5-56 years were included in the study: 23 in the group ivermectin (IVER) and 21 in the group benzyl benzoate (BB). At day 30 after treatment, the cumulative recovery rates were 70% (16/23) in the group IVER, and 48% (10/21) in the group BB, 95% confidence intervals 51-87% and 29-70% respectively. The rates of recovery were greater in the group IVER at day 7, 14 and 30, but the difference was not statistically significant. Our results show that oral ivermectin is a valuable alternative to benzyl benzoate local treatment.", "Permethrin, a pyrethroid insecticide, is not yet available in Iran and may be a useful substitute for the control of scabies in Iran.\n To compare the efficacy of topical lindane with topical permethrin in the treatment of scabies in a population in Iran.\n In a double-blind, randomized study, all consecutive patients with scabies were randomized into two groups. One group and their family contacts received 1% lindane cream, and the other group and their family contacts were treated with topical 5% permethrin cream. Subsequently, patients were followed up at 2- and 4-week post-treatment.\n Of the 99 patients enrolled in the study, 47 patients received 1% lindane cream, and 52 patients were treated topically with 5% permethrin cream. Permethrin provided an improvement rate of 84.6% after two weeks, whereas lindane was effective only in 48.9% of patients.\n Permethrin (5%) cream was found to be significantly more effective in the treatment of scabies in comparison with lindane in this study, and it seems that it could be an alternative treatment.", "Scabies is a very common skin infection in convicts. The SIMSPE Society (Società Italiana di Medicina e Sanità Penitenziaria) has organized and conducted a multicentre, randomized, comparative, parallel group, investigator-blinded trial to evaluate the efficacy and tolerability of synergized pyrethrins foam (PF) in comparison with benzyl benzoate (BB) lotion.\n A total of 240 convicted patients, enrolled in eight National Jail Institutions, with a clinical diagnosis of scabies, were treated with PF (n = 120) for three consecutive days or BB (n = 120) for five consecutive days. Primary study endpoints were the clinical cure rate and the local tolerability. Secondary endpoints were clinical evolution of scabietic lesions and itching intensity. Study outcomes were assessed using appropriate semiquantitative scores at baseline and after 2 and 4 weeks. A second treatment cycle was applied if after 2 weeks the patient was not judged clinically cured.\n At week 2, a total of 75% (95% CI: 66-82%) and 71% (95% CI: 62-78%) of patients showed a complete clinical cure rate in the PF and BB groups, respectively. At week 4, the percentage of totally cured patients increased up to 95% (95% CI: 89-97%) and 91% (95% CI: 83-94%) in the PF and BB groups, respectively (P = NS between groups). At week 4, 5% in the PF group and 9% in the BB group complained of itching. Burning and irritation after treatment applications were more common in the BB group in comparison with the PF group. The tolerability score was better in the PF group in comparison with to BB group (2.9 vs. 2.2; P = 0.0001). A total of 95% of patients in the PV group had a good tolerability score (i.e. = 3) in comparison with 41% in the BB group.\n Our results show that a 3-day treatment with pyrethrins thermofobic foam is at least as effective as a 5-day treatment with benzyl benzoate lotion in convicted subjects with scabies. The foam formulation is better tolerated than the benzyl benzoate lotion.", "To compare the effectiveness of oral ivermectin (IV) and two different modalities of topical benzyl benzoate (BB) for treating scabies in a community setting.\n The trial included patients aged 5-65 years with scabies who attended the dermatology department at the Institut d'Hygiène Sociale in Dakar, Senegal. The randomized, open trial considered three treatments: a single application of 12.5% BB over 24 hours (BB1 group), two applications of BB, each over 24 hours (BB2 group), and oral IV, 150-200 microg/kg (IV group). The primary endpoint was the disappearance of skin lesions and itching at day 14. If necessary, treatment was repeated and patients were evaluated until cured. Results were analysed on an intention-to-treat basis. A pre-planned intermediate analysis was carried out after the BB1, BB2 and IV groups had recruited 68, 48 and 65 patients, respectively.\n At day 14, 33 patients (68.8%) in the BB2 group were cured versus 37 (54.4%) in the BB1 group and 16 (24.6%) in the IV group (P < 10-6). Bacterial superinfection occurred more often in the IV group than in the BB1 and BB2 groups combined (28% versus 7.8%, respectively; P = 0.006). At day 28, 46 patients (95.8%) in the BB2 group were cured versus 52 (76.5%) in the BB1 group and 28 (43.1%) in the IV group (P < 10-5). These clear findings prompted early study cessation.\n Topical BB was clearly more effective than oral IV for treating scabies in a Senegalese community.", "The conventional antiscabietics have poor compliance. Ivermectin, an oral antiparasitic drug, has been shown to be an effective scabicide and could be a useful substitute.\n This study compares the efficacy of oral ivermectin with topical permethrin cream in the treatment of scabies.\n Eighty-five consecutive patients were randomized into 2 groups. Forty patients and their family contacts received 200 microg/kg body weight of ivermectin, and another 45 patients and their family contacts received a single overnight topical application of 5% permethrin cream. Patients were followed up at intervals of 1, 2, 4, and 8 weeks.\n A single dose of ivermectin provided a cure rate of 70%, which increased to 95% with 2 doses at a 2-week interval. A single application of permethrin was effective in 97.8% of patients. One (2.2%) patient responded to 2 applications at a 2-week interval. Permethrin-treated patients recovered earlier.\n A single application of permethrin is superior to a single dose of ivermectin. Two doses of ivermectin is as effective as a single application of permethrin. The temporal dissociation in clinical response suggests that ivermectin may not be effective against all the stages in the life cycle of the parasite.", "We compared in a prospective, randomised, investigator-blinded trial, the efficacy and tolerability of a new synergised-pyrethrins thermo-labile foam (F) formulation with permethrin 5 % cream (P) in 40 patients with scabies. Clinical evolution of scabetic lesions (Clinical grading = CG) and itching intensity (IS) were assessed, using a 5-point semi-quantitative score, at baseline, at week 2 and 4. F and P were equally effective in the clinical resolution of scabetic lesions. As compared to baseline, P reduced CG and IS from 3.4 0.7 and 3.1 0.4 to 0.2 0.6 and 1.4 1, at week 2, and to 0.0 0.0 and 0.1 0.3 at week 4, respectively (P < 0.001). F reduced CG and IS from 3.3 0.5 and 3.2 0.4 to 0.05 0.2 and 0.4 0.6 (week 2) and to 0.0 0.0 and 0.0 0.0 (week 4), respectively (P < 0.0001). As compared to P group, the IS in F group, at week 2, was significantly lower (0.4 0.6 vs. 1.4 1.1) (P < 0.0013). This foam formulation was at least as effective as permethrin 5 % cream in the treatment of scabies. In comparison with permethrin the foam induced a more rapid and complete resolution of itching.", "To evaluate the efficacy and safety of a single 200 mcg/Kg dose of ivermectine as compared with placebo in the treatment of scabies was settled. Fifty five patients with the diagnosis of scabies were randomized to a single oral dose of ivermectine or placebo. The study informed that 26 (79.3%) patients were cured with ivermectine on their first follow-up visit, as compared to only four (16%) in the placebo group (X2 = 77.07, p < 0.001). Overall, 37 of 50 (74%) patients treated with ivermectine cured, as compared to only four of 26 (16%) treated with placebo, this difference was still significant (X2 = 23.66, p < 0.001). We concluded that ivermectine is a safe and effective treatment for scabies.", "To compare single dose oral ivermectin with topical benzyl benzoate for the treatment of paediatric scabies.\n An observer-blinded randomized controlled trial was undertaken at Vila Central Hospital, Vanuatu. One hundred and ten children aged from 6 months to 14 years were randomized to receive either ivermectin 200 micro g/kg orally or 10% benzyl benzoate topically. Follow up was at 3 weeks post-treatment. Primary outcome measures were the number of scabies lesions, the itch visual analogue score and nocturnal itch. Secondary outcome measures were the skin's reaction to treatment, the passage of worms in stool and other side effects.\n Eighty patients completed the study protocol. There was no significant difference between the two treatments; both produced a significant decrease in the number of scabies lesions seen at follow up. Ivermectin cured 24 out of 43 patients (56%), and benzyl benzoate 19 out of 37 patients (51%) at 3 weeks post-treatment. No serious side effects were noted with either treatment, but benzyl benzoate was more likely to produce local skin reactions (P = 0.004, OR 6.4, 95% CI 1.6-25.0)\n Ivermectin is cheap and effective in the treatment of paediatric scabies. Ivermectin has minimal observed toxicity and has the additional beneficial effects of antiparasitic action in onchocerciasis, filariasis and strongyloidiasis. Ivermectin is better than benzyl benzoate for the treatment of paediatric scabies in developing countries.", "Currently, several topical scabicides are available but there is yet no oral or parenteral drug which has been established for the treatment of scabies in Nigeria. Ivermectin which is a modified avermectin, known to be an ectoparasiticidal agent in animals, has been used in adults for systemic parasitosis. In Nigeria, 25% benzyl benzoate is being extensively used for the treatment of scabies in adults. It is effective and readily available. The present study was carried out to evaluate the efficacy and safety of ivermectin in the treatment of patients with scabies at the skin clinic of the University of Nigeria Teaching Hospital, Enugu. Fifty-eight patients with scabies were recruited for the study; 13 (22.4%) were children aged between 5-14 years. Oral ivermectin was given in a single dose of 200 [microg/kg body weight to 29 patients. The remaining 29 patients had to apply 25% benzyl benzoate emulsion. All patients received a full physical and dermatological examination prior to onset of treatment and weekly for 4 weeks. Skin scrapings were taken to confirm the diagnosis of scabies. There was a 93% resolution of pruritus with ivermectin and 48% with benzyl benzoate. No side effects were observed with ivermectin. Our results show that oral ivermectin is a promising, effective and safe alternative in both children and adults of Nigeria when compared to 25% benzyl benzoate topical application.", "To compare the therapeutic efficacy and safety of ivermectin and lindane for the treatment of human scabies.\n Randomized, prospective, controlled, double-blind, \"double-dummy,\" and parallel clinical study.\n A single department of dermatology at a hospital in Buenos Aires, Argentina.\n Patients were outpatients, hospitalized patients, and those referred to our hospital from nursing homes and asylums. Fifty-three patients had clinical signs and symptoms compatible with scabies.\n Patients received either a single oral dose of ivermectin (150-200 microg/kg of body weight) or a topical application of 1% lindane solution. Treatment was repeated after 15 days if clinical cure had not occurred.\n Clinical healing and adverse effects.\n Of 53 patients, 43 (81%) completed the study, 19 in the group treated with ivermectin and 24 in the group treated with lindane. At day 15, 14 patients (74%; 95% confidence interval, 48.8%-90.8%) in the group receiving ivermectin showed healing of their scabies and 13 patients (54%; 95% confidence interval, 32.8%-74.4%) in the group treated with lindane were healed. At 29 days, both treatments resulted in statistically equivalent therapeutic efficacy: 18 patients (95%; 95% confidence interval, 74.0%-99.9%) were healed with ivermectin and 23 patients (96%; 95% confidence interval, 78.9%, 99.9%) were healed with lindane (P<.02). Adverse effects from the treatments were few, mild, and transient. Results from laboratory tests showed no major abnormalities and no difference between treatments.\n Ivermectin is as effective as lindane for the treatment of scabies. Ivermectin is simpler to use and, therefore, is a promising tool to improve compliance and to control infestations.", "nan", "Scabies is a common contagious skin disease in children. Treatment of scabies in infants and children is the subject of worldwide concern because of risk and benefit of the variety of scabicides.\n To compare the efficacy of 10 per cent sulfur ointment and 0.3 per cent gamma benzene hexachloride gel for the treatment of scabies in children.\n A randomized investigator blind study was conducted to compare the efficacy of 10 per cent sulfur ointment and 0.3 per cent gamma benzene hexachloride (GBH) for the treatment of scabies in children at Queen Sirikit National Institute of Child Health from December 1999 to May 2000. Diagnosis was made by the clinical signs of excoriated papules in the classic distribution with nocturnal pruritus and family history of similar symptoms. Diagnosis for all patients was confirmed by positive skin scrapings for eggs, larva, mites or fecal pellets by light microscopy. Patients were followed-up at intervals of 2 and 4 weeks.\n One hundred children with an age range from 6 months to 13 years were randomized into 2 groups, 10 per cent sulfur group (50 cases) and 0.3 per cent GBH (50 cases). Age, sex, history of contact cases and clinical manifestations were not statistically different between the two groups. After 4 weeks of treatment, there were no statistical differences between the two groups in patients assessed cured (92% vs 94%), clinical cure (92% vs 91%) and parasitic cure (83% vs 84%). The adverse effect of foul odor in the sulfur group was more common than in the GBH group (p < 0.05).\n 10 per cent sulfur ointment is as safe and efficacious as 0.3 per cent GBH for the treatment of scabies in children.", "Twenty-six children with scabies and 32 contacts were treated with 10% sulfur in cold cream. A 100% clinical cure rate was observed, although 56.8% of patients experienced some kind of mild, transient cutaneous reaction. An additional 25 children with scabies and 28 contacts were treated with 10% sulfur and 1% salicylic acid in pork fat. Of these, 88% were clinically cured and 73.5% had some cutaneous adverse effects. In both groups, most adverse effects were related to skin dryness or postscabetic reaction. The cold cream base was more acceptable to patients than the pork fat base. However, the pork fat base was significantly cheaper and easier to obtain than the cold cream base, and 238 times less expensive than the cheapest commercial scabicidal medication available in the United States.", "Scabies. which constitutes a significant proportion of the outpatient attendance in tropical dermatology clinics, has so far been treated with lindane, crotamiton, sulphur, permethrin, etc. Ivermectin, an orally administered drug, was tried in scabies patients and compared with 1% topical lindane lotion to evaluate its effects and toxicity profile. Two hundred scabies patients were randomly allocated to one of two groups. One group received oral invermectin in a single dose of 200 micrograms/kg body weight. The other received 1% lindane lotion for topical application overnight. Patients were assessed after 48 hours, two weeks and four weeks. After a period of four weeks, 82.6% of the patients in the ivermectin group showed marked improvement; only 44.44% of the patients in the lindance group showed a similar response. A side effects in the form of severe headache were noted in one patient in group A. Oral ivermectin is an easy drug to administer. It is given as a single oral dose, unlike lindane, which has to be applied topically. The compliance is accordingly increased. Moreover, ivermectin induces an early and effective improvement in signs and symptoms. Thus, it may be a better option for scabies than the traditional topical linlane lotion.", "To compare three treatment modalities in scabies for safety, efficacy, and economy in a local population of Nagpur.\n This was a prospective, randomized, comparative clinical trial conducted in 103 participants, randomly allocated to three groups. First group received benzyl benzoate (BB) 25% lotion, second group received permethrin 5% cream, whereas third group received tablet ivermectin 200 mug/kg as a single dose. The participants were recalled after one week for follow-up evaluation. If there were no signs of cure, the same intervention was repeated. The participants were followed up for two weeks for cure rate, adverse drug reaction (ADR) monitoring, and postintervention observation. The follow-up was stopped after two weeks.\n Fischer's exact test using Graph pad Instat v 3.05.\n Ivermectin showed 100% cure rate after two weeks of treatment. Permethrin decreased pruritus by 76% at the end of one week and had significantly better cure rate than ivermectin. At the end of two weeks treatment, this finding was reversed, that is, cure rate in ivermectin group was 100%. For cost-effectiveness analysis, treatment regimens were formulated hypothetically for comparison from Markov population tree for decision analysis. It was found that BB and ivermectin each consecutively for two weeks were most cost effective regimens giving complete cure in four weeks, while ivermectin was the fastest regimen giving the same results in two weeks.\n Benzyl benzoate as first line intervention and ivermectin in the remaining gave best cost-effective results in the study patients of scabies.", "A multicenter, randomized, investigator-blind controlled trial was conducted to compare the safety and efficacy of a single, whole-body application of 5% permethrin cream with that of 1% lindane lotion for the treatment of scabies in 467 patients. At 14 +/- 3 days after treatment, the mean active lesion count decreased from pretreatment levels of 85 (range, 4 to 600) in both treatment groups to 14 (range, 0 to 133) in the permethrin group and to 15 lesions (range, 0 to 500) in the lindane group. At 28 +/- 7 days after treatment, complete resolution had occurred in 181 (91%) of 199 patients treated with permethrin and in 176 (86%) of 205 patients given lindane. Pruritus due to scabies persisted at 28 +/- 7 days in 14% of the permethrin group and in 25% of the lindane group. The most frequent adverse effects were new or increased pruritus and mild, transient burning or stinging; the latter was slightly more frequent following permethrin treatment and appeared to be related to severity of infestation. Because of a lower potential for neurologic toxicity, permethrin may be preferable to lindane for the treatment of scabies particularly in children.", "Permethrin 5% cream (Elimite) was approved as a treatment for scabies by the U.S. Food and Drug Administration in September 1989. In a double-blinded, randomized study, it was compared with crotamiton 10% cream (Eurax) for the treatment of scabies in children 2 months to 5 years of age. Two weeks after a single overnight treatment, 14 (30%) of 47 children were cured with permethrin 5% cream, in contrast to only 6 of 47 (13%) of subjects treated with Eurax. Four weeks after treatment the figures were 89% and 60% cured for the two agents, respectively. In 10 of the 19 patients whose treatment failed, the condition became worse after therapy. The difference in efficacy in favor of permethrin was significant (P = 0.002). That agent also demonstrated greater effectiveness in reducing pruritus and secondary bacterial infections. Elimite offers a safe, efficacious, and cosmetically elegant alternative to Eurax in the treatment of scabies in children.", "Permethrin 5% dermal cream (Burroughs Wellcome Co.) was compared in an investigator-blinded, randomized study against lindane 1% lotion (Kwell) for the treatment of microscopically confirmed scabies. Eleven of twenty-three patients treated with permethrin cream were cured in 2 weeks (48%). Only two patients had scabies 1 month following a single treatment with this product, giving a cure rate of 91%. One of these two patients was considered to have a reinfestation. Only three of twenty-three (13%) patients treated with 1% lindane lotion (Kwell) were free of scabies 2 weeks after a single treatment and fifteen of twenty-three (65%) were cured at 1 month. The unusually high percentage of treatment failures (35%) following lindane therapy may have been related to extensive use of this agent for head lice and scabies in this village during the preceding 5 years. The higher cure rate at 1 month seen with permethrin cream was significant (p less than 0.025). Permethrin 5% dermal cream offers a new, cosmetically elegant alternative to lindane therapy and was effective in a community in which lindane demonstrated an unacceptable level of treatment failures.", "nan" ]

[ "11215597", "6508992", "2206966" ]

[ "Changes in vocal loudness following intensive voice treatment (LSVT) in individuals with Parkinson's disease: a comparison with untreated patients and normal age-matched controls.", "Speech therapy in Parkinson's disease: a study of the efficacy ad long term effects of intensive treatment.", "Speech therapy and Parkinson's disease: a review and further data." ]

[ "This study assessed the impact of the Lee Silverman Voice Treatment (LSVT) on vocal loudness [sound pressure level (SPL)] in a group of dysarthric individuals with idiopathic Parkinson's disease (IPD). Pre- to post-treatment changes in SPL in the treated group were compared with changes in voice SPL during the same time in two control groups: individuals with IPD not treated with the LSVT and in non-disordered individuals, age-matched to the patients. All subjects produced the same voice and speech tasks--sustaining vowel phonation, reading the \"Rainbow Passage,\" producing a short monologue, and describing a picture. These tasks were recorded at three different occasions: just prior to treatment, just after treatment, and 6 months following treatment. The individuals treated with LSVT increased voice SPL from baseline to post-treatment by an average of 8 dB and from baseline to 6 months follow-up by an average of 6 dB. These changes were statistically significant and perceptibly audible. No significant changes in SPL were observed in the control groups during the time corresponding to the treatment and follow-up. Differences in SPL between the treated and untreated patients at post-treatment and follow-up were statistically significant for all voice and speech tasks. These findings, along with others, provide additional support for the efficacy of the LSVT.", "nan", "A review is undertaken of recent experimental studies of the effects of speech therapy offered to patients with Parkinson's disease. In contrast to earlier opinions based upon clinical impressions, the results of these studies indicate that the immediate gains from therapy measured within the clinical setting are readily detected, that these are perceived by patient's relatives and that there is reasonable evidence that benefits persist for some period after treatment. A further study is reported which tests the effects of a less intensive treatment regimen. This also gave positive results. Although questions remain regarding the most efficient form of treatment and the extent of its benefits outside the clinic, the existing results warrant greater optimism about the benefits of speech therapy offered to patients with Parkinson's disease." ]

[ "7779349", "2702862" ]

[ "Early intervention for low birthweight, premature infants: participation and intellectual development.", "Type of day-care and preschool intellectual development in disadvantaged children." ]

[ "The Infant Health and Development Program was an eight-site randomized controlled trial of comprehensive early intervention for low birthweight, premature infants during the first 3 years of life in which intellectual development was an outcome of major importance. At 24 and 36 months, but not at 12 months, higher Mental Development Index and IQ were associated with higher levels of participation in the intervention. In a longitudinal analysis of these data, we found that the intellectual development of children in the intervention group was associated with each of the three intervention modalities (the number of home visits received, days attended at child centers, and the number of parent meetings attended) but not with children's background characteristics (i.e., maternal education, birthweight). We suggest that these findings represent a dose-response relation between intervention and outcome.", "Levels and patterns of intellectual development of 3 groups of socioeconomically disadvantaged children were compared. The groups consisted of (1) children who were randomly assigned to receive extensive university-based intervention group day-care, (2) children whose parents placed them in community day-care centers for varying amounts of time, or (3) children whose parents chose little to no center-based day-care for their children. Two repeated-measures analyses of variance were performed to identify possible day-care effects on IQ level and on patterns of infant and preschool cognitive development. The results suggest that quality community day-care, as well as intervention day-care, may positively change both the level and pattern of preschool intellectual development of socioeconomically disadvantaged children." ]

[ "2669935", "1950351", "2223676", "2864530", "6726592", "1967729" ]

[ "Preterm labour in twin pregnancies: can it be prevented by hospital admission?", "The effects of hospitalization for bed rest on duration of gestation, fetal growth and neonatal morbidity in triplet pregnancy.", "The effects of hospitalization for rest on fetal growth, neonatal morbidity and length of gestation in twin pregnancy.", "The effects of hospital admission for bed rest on the duration of twin pregnancy: a randomised trial.", "Is routine hospitalization needed in antenatal care of twin pregnancy?", "Routine hospital admission in twin pregnancy between 26 and 30 weeks' gestation." ]

[ "Women attending a twin pregnancy antenatal clinic underwent cervical palpation to calculate a cervical score by subtracting dilatation from length. Those with a score of -2 or less at or before 34 weeks are at especially high risk of preterm labour. A total of 139 such women were randomly allocated either to receive bed-rest in hospital or to continue conventional outpatient management. No beneficial effect of bed-rest could be identified in prolonging twin pregnancy or improving fetal outcome.", "Nineteen women attending a special multiple pregnancy antenatal clinic with a triplet pregnancy were randomly allocated to either bed rest in hospital from 24 weeks gestation onwards until delivery, or to continue conventional outpatient management. Conclusions are limited by the trial size, but the study suggests that routine hospitalization for bed rest decreases the incidence of preterm delivery and light-for-gestational age infants and reduces the need for intensive neonatal care. Although still compatible with change variation, the observations, if confirmed in a larger randomized study, would have considerable implications for clinical practice. The policy needs further evaluation in a large multicentered collaborative study.", "To test whether a policy of hospitalization for bed rest, from 28-30 weeks gestation until delivery, lengthens the duration of gestation, improves fetal growth and decreases neonatal morbidity in twin pregnancy.\n A randomized controlled trial.\n Harare Maternity Hospital, Zimbabwe.\n 118 women with an uncomplicated twin pregnancy between 28 and 30 weeks gestation.\n Hospitalization for bed rest. Encouraged to rest in bed as much as possible, although voluntary ambulation was allowed.\n Gestational age at delivery and number of infants delivered preterm (less than 37 weeks); birthweight and number of small-for-gestational age (SGA) infants; neonatal morbidity was assessed by number of infants requiring admission to the neonatal unit and the length of stay.\n There was no effect on duration of gestation or the occurrence of preterm delivery. Mean birthweight was greater in the hospitalized group (t = -2.28, df 234, P = 0.02) and there were fewer SGA infants (OR 0.57, 95% CI 0.33-0.96). No differences were found in neonatal morbidity.\n Hospitalization for bed rest does not prolong pregnancy but can improve fetal growth, although this was not reflected in improved neonatal morbidity. Whether twin fetal growth can be enhanced similarly in other populations should be investigated.", "212 women with twin pregnancies were randomly allocated either to receive advice to rest in hospital from 32 weeks' gestation until delivery, or to be part of a control group in which hospital admission was offered selectively (and, on average, 5 weeks later). Preterm delivery was more common among women admitted routinely for bed rest than among controls, and this difference was unlikely to have occurred by chance. There is at present no scientifically acceptable evidence that this common, disruptive, and expensive obstetric policy does more good than harm.", "A prospective study was carried out to evaluate the significance and efficacy of routine hospital bed rest in prevention of premature birth and pregnancy complications compared to specialized antenatal care at the outpatient clinic of 73 twin pregnancies. The twin pregnancies were screened in health centers by means of symphysis-fundus measurement, and the diagnosis was confirmed by ultrasound examination at the outpatient clinic. On the average the ultrasonic diagnosis was performed during the 23rd gestational week; at this visit the women were divided into two groups with similar follow-up to the end of the 29th gestational week. At this stage one of the groups was hospitalized unless there had been indications for earlier admission. In the hospital group, the mean for gestational week at delivery was 36.7 (+/- 2.4) and in the outpatient group 37.4 (+/- 1.8) respectively (N.S.). There was no difference in the rate of pregnancy complications between the groups too. No statistical differences in the perinatal mortality (7.1% and 1.1% respectively) or birthweights of the newborns were found, either. Present results do not support the idea of using routine hospital bed rest. It could not be proved to have positive effects on the gestational age, birth weight and perinatal mortality of the newborns, nor to the pregnancy complications. In our opinion early diagnosis of twin pregnancy is of decisive importance and specialized ambulatory follow-up could be employed instead of routine bed rest in antenatal care of twin pregnancy.", "Of 141 women with twin pregnancies, 72 were randomly assigned to outpatient care and 69 to hospital admission between 26 and 30 weeks' gestation. There were no differences between the groups in the frequencies of major maternal complications in pregnancy and labour but more of those admitted to hospital than of the outpatient group had to be admitted after 30 weeks. There were no differences between the groups in the mean birthweights of the twins by birth order, or in their mean gestation at birth whether analysed by intention to treat or by the treatment given. 22 infants were delivered before 32 weeks' gestation in the inpatient group compared with 10 in the outpatient group. With the exception of small-for-dates infants, any trend towards greater morbidity or mortality was seen in the inpatient group. The policy of routine hospital admission of women with twin pregnancies from 26 weeks' gestation is not beneficial to mother or babies and should be abandoned." ]

[ "9291399", "2571469", "6918343", "3304515", "3881968" ]

[ "Prevention of urinary retention after general surgery: a controlled trial of carbachol/diazepam versus alfusozine.", "The use of anxiolytic and parasympathomimetic agents in the treatment of postoperative urinary retention following anorectal surgery. A prospective, randomized, double-blind study.", "[Intravesical prostaglandin E2 and placebo in urinary retention after gynaecological surgery (author's transl)].", "Intravesical prostaglandin F2 for promoting bladder emptying after surgery for female stress incontinence.", "Is prostaglandin E2 really of therapeutic value for postoperative urinary retention? Results of a prospectively randomized double-blind study." ]

[ "Postoperative urinary retention is a common complication after surgical procedures. It can cause bladder dilatation, infection, and even sepsis. Carbachol/diazepam and alfusozine have been reported to lower the incidence of postoperative urinary retention, but no study showed the benefits of these drugs in a randomized, placebo-controlled trial.\n We used a double blind, placebo-controlled trial in which 249 patients with postoperative urinary retention were randomly assigned to receive carbachol/diazepam (n = 72), alfusozine (n = 82), or placebo (n = 95). The primary endpoint was miction within 2 hours after taking the medication.\n There was no significant difference in miction frequency after taking the medication among the three groups (p = 0.31). The miction rate was 60% for patients in the alfusozine group, 61% in the carbachol/diazepam group, and 51% in the placebo group.\n Alfusozine and carbachol/diazepam had no apparent benefit on the incidence of postoperative urinary retention.", "Approximately 30 percent of patients undergoing anorectal surgery will develop acute urinary retention. The cause of this complication is poorly understood. Anxiety, anal distention, bladder distention as a result of vigorous hydration during surgery, and reflex inhibition of the urinary bladder detrusor muscle secondary to pain have been postulated as contributing factors. A four-armed prospective, double-blind, randomized trial was carried out to determine whether an anxiolytic agent (midazolam, 5 mg intramuscularly) and/or a parasympathomimetic agent (bethanechol, 10 mg subcutaneously) reduce the incidence of postoperative urinary retention following anorectal surgery. One hundred thirty-two patients (ages, 18 to 50 years), in acute urinary retention 6 to 12 hours following anorectal surgery, were enrolled. Sixty-nine percent of patients responded to bethanechol. Side effects were minimal. Midazolam alone had no effect on retention. Bethanechol and midazolam in combination resulted in less retention than midazolam and a placebo (P less than 0.05). Bethanechol alone was better than a placebo (P less than 0.002). Mean intraoperative intravenous fluid volume for the entire study group was 900 cc. Initial postoperative urinary volumes of patients who failed the treatment protocol were significantly higher than in those responding to bethanechol (mean of 527 cc vs. 241 cc, P less than 0.001). The use of an anxiolytic agent was not effective in the treatment of postoperative urinary retention. Bladder distention may increase the incidence of urinary retention. Bethanechol, in a dose of 10 mg subcutaneously, significantly lowered the incidence of postoperative urinary catheterization and should be considered as initial treatment of postoperative urinary retention following anorectal surgery.", "In a randomized single blind trial we studied the effectiveness of intravesical prostaglandin E2 in the treatment of postoperative urinary retention after vaginal hysterectomy with colposuspension. One group of patients (n = 8) received 1.5 mg prostaglandin E2 in 50 ml 0.9% NaCl on the 9th postoperative day (72 hours after removal of the Foley catheter) and 50 ml NaCl without prostaglandin E2 on the following day. In the second group (n = 12) NaCl was instilled on the first day of treatment and prostaglandin E2 on the following day. Four hours after the instillation of prostaglandin E2 5 out of 8 women were able to void spontaneously, while after the instillation of NaCl spontaneous micturition occurred in only 2 out of 12 women (p less than 0.05). In both groups the average time period until patients were free of residual urine was 4 days after the initiation of therapy. Compared to placebo intravesical prostaglandin E2 is significantly more effective in achieving spontaneous voiding after gynaecological surgery.", "Prostaglandin F2 alpha 10 mg was administered intravesically in a double-blind placebo-controlled study to promote micturition in cases of urinary retention after operative treatment of urinary stress incontinence in women. Fifteen of 18 patients (83%) succeeded in voiding after treatment with prostaglandin F2 alpha, but the placebo was ineffective in all 18 patients (P less than 0.001). Although the effect of prostaglandin F2 alpha on bladder muscle contraction was short-lived, it seemed to enhance the restoration of bladder motor function with no serious side effects, and thus to be clinically useful in the treatment of post-operative urinary retention.", "In a prospectively randomized double-blind study 28 patients with urinary retention after anterior colporrhaphy were administered either placebo or prostaglandin E2 in different doses (0.75 mg, 1.5 mg, or 2.25 mg) intravesically on postoperative days 6 and 7. Urodynamic assessment was performed before and after treatment. A moderate but not significant decrease of maximum bladder capacity, bladder compliance, and maximum urethral closure pressure was found in patients treated with 2.25 mg of prostaglandin E2. These urodynamic changes did not correspond to the clinical outcome: Residual urine decreased and effective bladder capacity increased significantly in all four groups uninfluenced by the type of therapy. The rate of success (defined by the amounts of residual urine after therapy) was similar in the four groups. A long-term effect of prostaglandin E2 could also be excluded, since the mean time interval from operation to the first day without residual urine was similar in the four groups. Therefore the therapeutic value of intravesically administered prostaglandin E2 in doses from 0.75 to 2.25 mg must be seriously questioned." ]

[ "11697833", "16921033", "9060525", "9667265", "9294465", "12118018", "8381164" ]

[ "Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG).", "Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis.", "Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.", "Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083.", "Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group.", "Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104.", "Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group." ]

[ "Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy.\n To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response.\n 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded.\n Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.", "To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC).\n Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-naïve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks.\n TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17).\n This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.", "To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).\n Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.\n The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.\n Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.", "To provide a 10-year update of the experience of the Cancer and Leukemia Group B (CALGB) in the addition of thoracic radiation therapy to chemotherapy in limited-stage small-cell lung cancer.\n Three hundred ninety-nine patients with limited-stage small-cell lung cancer were randomized to receive thoracic radiation therapy that started on day 1 (arm I) or day 64 of chemotherapy treatment (arm II), or chemotherapy alone with cyclophosphamide, vincristine, and etoposide (later, doxorubicin). Thoracic radiation therapy consisted of 4,000 rad to the tumor and mediastinum with a 1,000-rad boost. All patients received prophylactic cranial radiation to a dose of 3,000 rad.\n Arm I patients had a median survival of 13.04 months, arm II patients 14.54 months, and arm III patients 13.58 months (log-rank test, P = .0072). Median time to clinical failure was 11 months in arm I, 11.21 months in arm II, and 8.7 months in arm III (log-rank test, P = .0004).\n With 10 years of follow-up, the two arms that included thoracic radiation therapy remain superior to chemotherapy alone. The addition of thoracic radiation therapy to combination chemotherapy improved both complete response rates and survival, with increased but acceptable toxicity.", "To evaluate if the timing of chest irradiation with respect to chemotherapy would influence survival and local and distant control in patients with limited-stage small-cell lung cancer (LSCLC).\n From 1981 to 1989, 199 consecutive patients with LSCLC were randomly allocated to receive initial chest irradiation (ICI; n = 99) or late chest irradiation (LCI; n = 100) given 18 weeks delayed. Both groups received the same nine cycles of combination chemotherapy: three cycles of cisplatin and etoposide and six cycles of cyclophosphamide, doxorubicin, and vincristine. In the first part of the study, prophylactic cranial irradiation (PCI) was only given to patients randomized to ICI, but after inclusion of 42 patients in the LCI arm, the protocol was changed, so that all patients received PCI independent of the timing of the chest irradiation (CI). A total of 157 patients received PCI with a radiation dose of 25 Gy in 11 fractions.\n The timing of radiotherapy had no significant effect on the 2-year overall survival rate (20% after ICI v 19% after LCI, P = .4) or the 2-year in-field recurrence rate (72% after ICI v 68% after LCI, P = .2). Median survival durations were 10.5 (ICI) and 12.0 (LCI) months. Similarly, no difference in the 2-year incidence of CNS recurrences was found between the 2 arms in patients who received PCI (19% after ICI v 13% after LCI, P = .24). Bone marrow toxicity was acceptable, as 15% developed World Health Organization (WHO) grade 4 leukocytopenia and 4% grade 4 thrombocytopenia. Grade 4 leukocytopenia was more pronounced in the ICI group. There was no difference in the frequency and severity of other toxicities between the 2 groups.\n Timing of CI did not significantly influence the incidence of in-field recurrences, CNS recurrences, or overall survival.", "To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT.\n We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm.\n Concurrent radiotherapy yielded better survival than sequential radiotherapy (P =.097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm.\n This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.", "The importance of the timing of thoracic irradiation (TI) in the combined modality therapy of limited-stage small-cell lung cancer (SCLC) was assessed in a randomized trial.\n All 308 eligible patients received cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each chemotherapy regimen. Patients randomized to early TI received 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP (week 3), and late TI patients received the same radiation concurrent with the last cycle of EP (week 15). After completion of all chemotherapy and TI, patients without progressive disease received prophylactic cranial irradiation (25 Gy in 10 fractions over 2 weeks).\n Although complete remission rates were not significantly different between the two arms, progression-free survival (P = .036) and overall survival (P = .008) were superior in the early TI arm. Patients in the late TI arm had a higher risk of brain metastases (P = .006).\n The early administration of TI in the combined modality therapy of limited-stage SCLC is superior to late or consolidative TI." ]

[ "11303205", "15916656", "19624440", "11004357", "12175715", "17688611", "16580290" ]

[ "Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: a randomized controlled trial to determine effects on maternal and fetal hemodynamics.", "Evaluation of glyceryl trinitrate, misoprostol, and prostaglandin E2 gel for preinduction cervical ripening in term pregnancy.", "Randomised placebo-controlled trial of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour--clinical trial with analyses of efficacy and acceptability. The IMOP study.", "Randomized comparison of glyceryl trinitrate and prostaglandin E2 for cervical ripening at term.", "Randomized trial of isosorbide mononitrate versus misoprostol for cervical ripening at term.", "Nitric oxide donor isosorbide mononitrate for pre-induction cervical ripening at 41 weeks' gestation: A randomized controlled trial.", "The \"PRIM\" study: a randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term." ]

[ "Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term.\n We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes.\n Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination-only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination-only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination-only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index.\n Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant.", "To compare the efficacy of glyceryl trinitrate (GTN), dinoprostone and misoprostol for preinduction cervical ripening in primigravida at term.\n Sixty-five term primigravida, each with an unfavorable cervix (Bishop score </=5), were randomized to receive GTN (0.5 mg perivaginally, n = 21), dinoprostone gel (0.5 mg intracervically, n = 21) and misoprostol (50 microg perivaginally, n = 23) for a maximum of two doses, 6 h apart. Statistical analysis included paired t-tests to compare pre- and post-treatment Bishop scores, one-way analysis of variance (anova) tests to compare quantitative variables and chi-squared tests to compare the proportion of subjects achieving favorable Bishop scores.\n Baseline Bishop scores were similar in the GTN (3.4 +/- 0.9), dinoprostone (3.4 +/- 1.0) and misoprostol groups (3.2 +/- 1.2). The final outcome was favorable (Bishop score >6) in a greater proportion of subjects in the misoprostol (n = 18, 81.8%) and dinoprostone (n = 14, 66.7%) groups compared with the GTN group (n = 11, 55%). In subjects with a severely unfavorable cervix (Bishop score </=3), treatment with misoprostol led to a favorable response in 61.6% of patients compared with 45.6% in the misoprostol group and 33.3% in the GTN group. A significant improvement was noted in the Bishop score of all three groups (P < 0.001) but the increase in Bishop score was greater in misoprostol (3.5 +/- 2.1) and dinoprostone groups (2.8 +/- 1.5), compared with the GTN group (2.0 +/- 1.0, ANOVA F = 4.8, P = 0.01). Hyperstimulation and tachysystole were observed only in the misoprostol (9% and 4.3%) and dinoprostone groups (4.7% and 16.2%). The most common adverse effect in the GTN group was headache, which was observed in 47.6% of this group's subjects.\n The findings of the present study suggest that GTN is safer, but less efficacious, compared with prostaglandins for preinduction cervical ripening at term.", "To determine whether isosorbide mononitrate (IMN), self-administered vaginally by women at home, improves the process of induction of labour.\n Randomised double blind placebo-controlled trial.\n Large UK maternity hospital.\n Nulliparous women with a singleton pregnancy, cephalic presentation > or = 37 weeks gestation, requiring cervical ripening prior to induction of labour.\n IMN (n = 177) or placebo (n = 173) self-administered vaginally at home at 48, 32 and 16 hours prior to the scheduled time of admission for induction.\n Admission to delivery interval and women's experience of induction of labour.\n IMN did not shorten the admission to delivery interval as compared with placebo [mean difference of -1.6 hours (95% CI -5.1,1.9, P = 0.37)], despite being more effective than placebo in inducing a change in Bishop score [mean difference of 0.65 (95% CI 0.14,1.17, P = 0.013)]. While both groups found the overall experience of home treatment to be positive, (mean score of 3.8/10 +/- 2.3/10 for the IMN group, where 1 = extremely good and 10 = not at all good) women in the placebo group found it marginally more positive than those in the IMN group (just over half a unit on a 10-point scale, P = 0.043). There were no differences between the groups in the pain or anxiety experienced or willingness to take the treatment in a subsequent pregnancy.\n IMN self-administered vaginally at home does not shorten admission to delivery interval despite a significant effect on cervical ripeness assessed using the Bishop score. However, women report positive views on cervical ripening at home, and the setting deserves further investigation.", "To estimate the adverse effects of glyceryl trinitrate compared with prostaglandin (PG) E2 vaginal tablet for cervical ripening in term pregnancy.\n One hundred ten women with term pregnancies referred for induction of labor with Bishop scores of 6 or less were randomly assigned to receive a 500-microg glyceryl trinitrate tablet vaginally (n = 54) or a 3-mg PGE2 tablet vaginally (n = 56), every 6 hours for maximum of two doses. Subjects were sent to the labor ward for amniotomy or oxytocin if their Bishop scores were more than 6 or their cervices were not ripe 24 hours after treatment. Adverse effects, changes in the Bishop scores, progress, and outcomes of labor were assessed.\n Glyceryl trinitrate was associated with fewer episodes of uterine tachysystole (0% versus 9%; P =.02). The median Bishop score after 12 hours was lower in women given glyceryl trinitrate compared with those given PGE2. Adverse effects, including headache and palpitations, were more frequent with glyceryl trinitrate than with PGE2. The cesarean rate was not significantly different between groups.\n Cervical ripening with glyceryl trinitrate resulted in fewer episodes of tachysystole, but there were significantly more minor side effects. It can be used for cervical ripening at term, but it was not as effective as PGE2.", "To assess the adverse effects of isosorbide mononitrate (IMN) compared with misoprostol for cervical ripening at term.\n One hundred and seven women with term pregnancies referred for induction of labor with Bishop scores of 6 or less were randomly allocated to receive either a 40-mg IMN tablet vaginally (n = 55) or 50 microg misoprostol vaginally (n = 52) every 6 h for a maximum of three doses. They were sent to the labor ward for amniotomy or oxytocin if either their Bishop scores were more than 6 or their cervices were not ripe 24 h after the treatment. Adverse effects, progress, and outcomes of labor were assessed.\n Isosorbide mononitrate was associated with fewer adverse effects especially uterine tachysystole (0 vs. 19.2%, P < 0.01) and hyperstimulation (0 vs. 15.4%, P < 0.01). The time from start of medication to vaginal delivery in IMN group was significantly longer (25.6 +/- 6.1 vs. 14 +/- 6.9 h, P < 0.01). Oxytocin was needed in 51 women (92%) of the isosorbide mononitrate group and six women (11%) of the misoprostol group (P < 0.001). The cesarean rate was not significantly different between the groups, but the major indications were different: dystocia (45%) in the IMN group vs. persistent non-reassuring fetal heart rate pattern (56%) in the misoprostol group.\n Cervical ripening with IMN resulted in fewer adverse effects, but was less effective than misoprostol.", "Nitric oxide donors have been shown to cause cervical ripening. The aim of this study was to determine whether sustained release isosorbide mononitrate (ISMN-SR) 60 mg administered vaginally is effective for pre induction cervical ripening at 41 weeks' gestation.\n A double-blind randomised controlled trial was carried out at the University Obstetric Unit, Galle, Sri Lanka for a period of 9 months, commencing 1st August 2003. One hundred and fifty-six consecutive women with uncomplicated singleton pregnancies at 41 weeks' gestation with a modified Bishop Score <5 were allocated by stratified (primip/multip) block randomization to receive either ISMN-SR 60 mg (n = 78) or vitamin C 100 mg (n = 78) vaginally. Modified Bishop Score at 41 weeks + 2 days' gestation and the proportions establishing spontaneous labor or becoming favorable for induction of labor (IOL) by 41 weeks + 2 days' gestation were evaluated in each group.\n At the commencement of the study there were no differences between the mean age, parity or modified Bishop Score of the two groups. In the ISMN-SR group, there was a marked increase in the proportion establishing spontaneous labor (28% vs 7.5%, P < 0.01) and being favorable for IOL (40% vs 9% P < 0.001), 2 days after therapy. In the ISMN-SR group, there was a significantly higher increase in the mean modified Bishop Score (3.8, 95% CI 2.3-5.3 vs 1.3, 95% CI 0.3-2.2, P < 0.01) and a marked decrease in the proportion of subjects requiring further ripening of the cervix with a Foley catheter. (32% vs 79%, P < 0.001). The cesarean section rates were similar in both groups.\n Sustained release ISMN administered vaginally is effective for preinduction cervical ripening.", "The purpose of this study was to compare the efficacy and safety profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term.\n Primigravid women were assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery. Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening.\n Prostaglandin E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score. Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostaglandin E2. There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7% of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal satisfaction was significantly higher in the isosorbide mononitrate group.\n Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis." ]

[ "4047540", "7884757", "15587828", "1580171" ]

[ "Comparison of glucose polymer and glucose for screening and tolerance tests in pregnancy.", "Carbohydrate sources for gestational diabetes mellitus screening. A comparison.", "Diagnosis of gestational diabetes mellitus in Nigerian pregnant women--comparison between 75G and 100G oral glucose tolerance tests.", "Screening for gestational diabetes mellitus: comparison of a glucose polymer and a glucose monomer test beverage." ]

[ "Forty-eight of 100 pregnant women received a 100-g (nonfasting) glucose screening test at about 28 weeks' gestation, followed by a 100-g glucose tolerance test. Another 52 received a 100-g (nonfasting) glucose polymer screening test followed by a 100-g glucose polymer tolerance test. Mean plasma glucose one hour after the glucose screening test was significantly lower than after the glucose polymer screening test. A further 178 women received a glucose polymer screening test and a glucose polymer tolerance test (230 in total). These women and the infants they delivered were studied to derive diagnostic criteria for the 100-g glucose polymer tolerance test by correlating maternal carbohydrate tolerance with indexes of neonatal metabolic performance, and to determine an adequate method of screening for carbohydrate intolerance of pregnancy (gestational diabetes). Diagnostic criteria similar to those of O'Sullivan and Mahan were also developed for the glucose polymer tolerance test. These values are up to 5% lower than those recommended by the National Diabetes Data Group (1979) for the 100-g glucose tolerance test.", "One hundred eight patients were prospectively randomized to receive 50 g of a glucose polymer, d-glucose or a candy bar during a one-hour gestational diabetes mellitus (GDM) screening. The polymer had a mean serum glucose similar to that of d-glucose, with significantly fewer side effects, allowing an increased rate of examination completion. The candy bar produced a significantly lower mean serum glucose but had the highest rating for flavor. The polymer was an inexpensive and well-tolerated alternative for GDM screening, while the use of a candy bar needs more study.", "To compare the diagnostic performances of 75g and 100g oral glucose tolerance tests in detecting Gestational Diabetes Mellitus in Nigerian pregnant women.\n 248 women in 3rd trimester attending antenatal clinic of the Lagos University Teaching Hospital, Lagos, between November 1997 and July 1999 were randomly subjected to standard oral glucose tolerance tests (OGTT). 110 had 100g OGTT while 138 had 75g OGTT. The plasma glucose response (PGR) was assessed and glucose tolerance status of each patient was determined using WHO (1985) criteria to interpret 75g OGTT and National Diabetes Data Group (NDDG) (1979) criteria for 100g OGTT. The PGR in the two study groups were compared. The prevalence rates of GDM using either of the two criteria were evaluated and compared. Incidences of foetal macrosomia in GDM cases diagnosed by either set of criteria were also compared.\n The mean age of the study subjects was 30.7(+/-4.2) years while the BMI was 25.4(+/-4.9) kg/m2. The mean parity was 1.33. Traditional risk factors for GDM were found in 47.5% of them. The plasma glucose response (PGR) to 100g OGTT was found to be higher than that of 75g OGTT at 1 hour, 2hour and 3 hour sampling times but the difference was only significant at 3rd hour (p values = 0.68, 0.137, 0.007 respectively). The total area under the glucose response curve (AUC) for 75g OGTT was 345.1 (+/-49.5) AAU while for 100g OGTT, it was 363.4(+/-61.4) AAU. The difference was not statistically significant (p value >0.05). The prevalence rate of GDM diagnosed by 75g OGTT was 11.6% while that of 100g OGTT was 4.5 %. The difference was significant (p value = 0.04). The incidence rate of foetal macrosomia among GDM cases diagnosed by 100g OGTT was 66.7% as against 23.1% among those diagnosed by 75g OGTT. Statistical difference could not be determined because of the small number.\n Plasma glucose response to OGTT among Nigerian pregnant women has little or no respect for the load of the glucose administered. 100g OGTT- based NDDG criteria was more stringent than 75g OGTT-based WHO criteria in identifying GDM. However it appears to be more specific for detecting the complications associated with the condition though it will require a larger study to validate this claim.", "The current test for gestational diabetes mellitus (GDM) uses a glucose monomer test beverage, which frequently causes gastrointestinal symptoms, and venipuncture. We investigated a simplified test using a beverage of glucose polymer and a capillary whole blood glucose measurement.\n In a randomized, double-blind clinical trial, women at 24 to 28 weeks' gestation received a 50-g glucose monomer (n = 41) or glucose polymer (n = 35) beverage. Venous and capillary blood samples were obtained 1 hour later. The women then completed standardized questionnaires about their symptoms.\n The glucose polymer beverage was associated with significantly fewer symptoms than was the glucose monomer drink: the mean was 1.1 symptoms per test with the glucose monomer drink and 0.4 symptoms per test with the glucose polymer drink (P less than 0.05), 51 percent of the women developed symptoms after drinking the glucose monomer beverage, and 27 percent of the women developed symptoms after drinking the glucose polymer beverage (P less than 0.05). Glucose type did not affect the 1-hour plasma glucose level, mean 5.94 mmol/L (107 mg/dL) for the glucose monomer and 5.76 mmol/L (103.8 mg/dL) for the glucose polymer (P = 0.79). For the capillary test, sensitivity was 0.75 and specificity was 0.82 in detecting a screening test positive by the venous plasma glucose criterion.\n The results of this study indicate that a glucose polymer beverage is better tolerated than a glucose monomer beverage during GDM screening, but capillary glucose measurement might be of limited use in clinics where many personnel perform the capillary blood glucose testing." ]

[ "7871564", "8350886", "1496538", "7879202", "14621869", "2271089", "8704119", "11134724", "9589380", "1465872", "9351079" ]

[ "Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study.", "Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants.", "The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients.", "Results of a 1-year randomized controlled trial with omega-3 fatty acid fish oil in renal transplantation under triple immunosuppressive therapy.", "Decrease of erythrocyte deformability in cyclosporine-treated renal transplant patients: correction with fish oil as well as corn oil.", "Dietary supplementation with fish oil modifies renal reserve filtration capacity in postoperative, cyclosporin A-treated renal transplant recipients.", "Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown.", "Effects of fish oil in cyclosporine-treated renal transplant recipients.", "Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in kidney graft recipients: a randomized placebo-controlled study.", "One-year randomized controlled trial with omega-3 fatty acid-fish oil in clinical renal transplantation.", "Therapy of post-renal transplantation hyperlipidaemia: comparative study with simvastatin and fish oil." ]

[ "An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits.", "Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in cyclosporine-treated recipients of renal transplants.\n In a randomized, double-blind trial, 33 recipients of first cadaveric kidney transplants who were treated with cyclosporine and prednisolone ingested 6 g of fish oil daily during the first postoperative year (the fish-oil group), whereas another 33 renal-graft recipients treated with cyclosporine and prednisolone ingested 6 g of coconut oil daily for three months after which time it was stopped (the control group).\n One year after transplantation, the fish-oil group had higher median values than the controls for glomerular filtration rate (53 vs. 40 ml per minute per 1.73 m2, P = 0.038) and effective renal plasma flow (214 vs. 178 ml per minute per 1.73 m2, P = 0.023) and lower mean arterial pressure (103 vs. 118 mm Hg, P = 0.0011). The cyclosporine doses in the two groups were similar. The cumulative number of rejection episodes was 20 in the controls, as compared with 8 in the fish-oil group (P = 0.029). One-year graft survival also tended to be better in the fish-oil group, (97 vs. 84 percent, P = 0.097).\n The daily administration of 6 g of fish oil during the first postoperative year has a beneficial effect on renal hemodynamics and blood pressure in renal-transplant recipients treated with cyclosporine. Although the fish-oil group had significantly fewer rejection episodes than the control group, graft survival at one year was not significantly better in the fish-oil group.", "In a randomized prospective coconut oil (daily 6g[63% C8:0 and 36% C10:0] [EPA-] [n = 48])-controlled trial, we investigated the effect of a one-month dietary supplementation with daily 6 g fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3 as their methyl esthers [EPA+] [n = 40]) on the incidence and course of early postoperative rejection in 88 first cadaveric, cyclosporine-treated renal transplant recipients. At one month there were no differences in renal function and incidence of rejection episodes. When analyzed separately for rejection (re+) or nonrejection (re-), the rejecting and fish oil-treated patients showed a significant better recovery of renal function after a histologically confirmed rejection episode, creatinine clearance being 43 ml/min/1.73m2 in the EPA+re+group versus 27 ml/min/1.73 m2 in the EPA-re+group (P less than 0.05), and serum creatinine being 183 and 283 mumol/l (P less than 0.05), respectively. The prerejection renal function and the decline of renal function during the rejection episode did not differ significantly between the EPA+re+ and the EPA-re+ groups. The nonrejecting fish oil-treated patients showed no better renal function than the nonrejecting coconut oil-treated patients. However, cyclosporine trough levels were significantly higher in the fish oil-treated group (EPA+re- 251 versus EPA-re- 200 ng/ml [P less than 0.05]). From these results we conclude that dietary supplements with fish oil favorably influence renal function in the recovery phase following a rejection episode in cyclosporine-treated renal transplant recipients. We further conclude that one month after grafting there is no difference in the incidence of rejection episodes between the fish- and coconut oil-treated patients. The same holds true for renal function in the absence of rejection, and for the decline in renal function during a rejection episode.", "nan", "Twenty-nine renal transplant recipients with good, stable transplant function were included in a double-blind cross-over study to investigate the effects of different immunosuppressive treatment modalities and also the effects of fish oil and corn oil supplementation on erythrocyte deformability. Ten patients were treated with cyclosporine (CyA) only, 10 patients with CyA and prednisolone, and 9 patients with azathioprine and prednisolone. Erythrocyte deformability, as measured by an ektacytometric technique, was significantly decreased in both CyA-treated groups compared with the azathioprine-prednisolone-treated group, and this decrease was corrected with fish oil and with corn oil. The cause and the clinical significance of less deformable erythrocytes due to CyA are not yet clear. However, less deformable erythrocytes could play a role in the genesis of the complications of CyA.", "The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 = EPA and 20% C22:6 omega-3 = DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA+). Renal function tests were performed using the simultaneous determination of 125I-iothalamate and 131I-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA- and EPA+ groups. Filtration fraction (FF) differed significantly, being 0.21 in the EPA- group versus 0.26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA + re - and EPA - re -. These two groups were comparable in age, donor age, and GFR. The EPA + re-group had a significantly lower ERPF (164 ml/min per 1.73 m2) than the EPA-re- group (262 ml/min per 1.73 m2). FF was significantly higher in the EPA+ re-group (0.26) than in the EPA-re-group (0.21).(ABSTRACT TRUNCATED AT 250 WORDS)", "This study aimed to determine whether dietary supplementation with fish oil has a beneficial effect on graft function and the incidence of rejection in renal allograft recipients treated with cyclosporin A (CsA). Renal function, blood pressure, the incidence of acute rejection episodes, graft survival, and renal histology and immunochemistry were investigated. In a randomized, placebo-controlled, double-blind trial, groups of 25 recipients of primary cadaveric renal allografts who had been treated with CsA took fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3) or coconut oil (63% C8:0 and 36% C10:0) at 6 g/day for 3 months. There were no differences between the two patient groups with regard to HLA matching, panel-reactive antibody titers, or the demographic characteristics of donors or recipients. The GFR and effective RPF were determined at 1, 3, and 12 months after transplantation by simultaneous measurement of (125I-)iothalamate and (131I-)hippuran clearances. At 1 yr after transplantation, patients treated with fish oil showed better renal function than did the control patients, but this difference was not statistically significant. Blood pressure and antihypertensive drug use were similar in both groups. The number of rejection episodes was also similar, and renal histopathological and immunohistochemical studies showed no significant differences between the fish-oil group and the control patients. It is concluded that fish oil, at a dose of 6 g/day, has no beneficial effect after renal transplantation within the time scale of the study.", "nan", "Highly concentrated marine polyunsaturated fatty acids (n-3 PUFA), affecting the lipids and lipophilic drugs metabolism, can interfere with cyclosporine (CyA) pharmacokinetics. This prospective, randomized and placebo-controlled, double-blind study involved 42 kidney graft recipients. From day +1, 21 pts (E) received 6 g n-3 PUFA (85% EPA + DHA, Esapent, Pharmacia) and 21 pts (P) received placebo (olive oil), both reduced to 3 g from day +30 on. A quadruple immunosuppressive regimen was employed. Plasma creatinine, lipids and CyA pharmacokinetics were investigated 1, 3, 6, 9 and 12 months after graft. The two groups were comparable for age, weight, M/F ratio, hypertension prevalence and baseline lipids. Active treatment did not affect total and HDL-cholesterol, but significantly lowered triglycerides (E:120 +/- 12 vs P:166 +/- 21 mg/dl, p < 0.0001). At one year, E pts had lower creatinine than P (1.26 +/- 0.06 vs. 1.88 +/- 0.2 mg/dl, p < 0.05), comparable CyA dosage, and a larger CyA area under the curve (AUC) (n.s.), with a higher blood peak level (Cmax) (p < 0.04) and less variance in time to peak (n.s.). The larger AUC in the E group at all intervals and the better pattern of plasma creatinine, with no rise in blood pressure, provided evidence of better CyA absorption and metabolism in n-3 PUFA supplemented kidney graft recipients.", "nan", "Recipients of renal transplantation (RT) exhibit disturbances of serum lipids and apoproteins that may contribute to their cardiovascular morbidity and mortality. In our renal transplant department the hypercholesterolaemia prevalence at the first and fifth year of RT is 70.0% and 81.2%, respectively. Lipid-lowering therapy has been utilized in many Transplant Units. The aim of our study was to evaluate post-RT hyperlipidaemia control with simvastatin or fish oil.\n Forty-three RT patients (26 men and 17 women) with persistent hypercholesterolaemia and stable graft function which were resistant to a lipid-lowering diet (American Heart Association Step Two) were randomized into two groups and treated for 3 months with simvastatin (S) (10mg/day; n = 25) and fish oil (F) (6 g/day; n = 18). Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), lipoprotein a (Lp(a)), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were monitored and at the study baseline they were similar between the two groups.\n No side effects were detected after 3 months of therapy. In group S, the concentrations of TC (271 +/- 46 mg% vs 228 +/- 49 mg%; P < 0.001), TG (180 +/- 78 vs 134 +/- 45; P < 0.01), LDL-C (177 +/- 40 vs 144 +/- 43; P < 0.01) and Apo B (96 +/- 18 vs 82 +/- 16; P < 0.001) were significantly reduced, and Apo A1 concentration had increased (135 +/- 24 vs 149 +/- 30; P < 0.01). In group F, the concentrations of TC (266 +/- 25 vs 240 +/- 31; P < 0.001), TG (203 +/- 105 vs 156 +/- 72; P = 0.02) and HDL-C (63 +/- 15 vs 53 +/- 12; P < 0.01) were significantly reduced.\n We concluded that low-dose simvastatin and fish oil are both effective and safe in correcting post-RT hyperlipidaemia. Further prospective studies with larger follow-up are needed to clarify whether this therapy has an impact on cardiovascular morbidity and mortality in RT patients." ]

[ "6441523", "17585011" ]

[ "Prospective, controlled study of a polyvalent pseudomonas vaccine in cystic fibrosis--three year results.", "A double-blind randomized placebo-controlled phase III study of a Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients." ]

[ "Thirty four children with cystic fibrosis allocated to pseudomonas vaccine and control groups were studied for three years. No significant differences were observed in the numbers colonised by Pseudomonas aeruginosa or in the overall disease progress of the two groups.", "Pseudomonas aeruginosa causes life-threatening lung infections in patients with cystic fibrosis. We hypothesized that vaccination may prevent P. aeruginosa lung infection. In a double-blind, placebo-controlled, multicenter trial, 483 European patients, 2-18 years of age without P. aeruginosa colonization were randomly assigned to receive four intramuscular injections of a bivalent P. aeruginosa flagella vaccine or placebo over a 14-month period. Patients were evaluated quarterly for P. aeruginosa-positive throat cultures and antipseudomonal serum antibody titers during the study period of 2 years. The vaccine was well tolerated, and the patients developed high and long-lasting serum antiflagella IgG titers. In the intention-to-treat group (all patients enrolled), 82 of 239 vaccinated patients had P. aeruginosa infection and/or antipseudomonal serum titers compared with 105 of 244 patients in the placebo group (P = 0.05; relative risk: 0.80; 95% CI: 0.64-1.00). Analysis of the 381 patients in the per-protocol group, who received all four vaccinations or placebo treatments, revealed 37 of 189 patients with infection episodes in the vaccine group compared with 59 of 192 patients with such episodes in the placebo group (P = 0.02; relative risk: 0.66; 95% CI: 0.46-0.93). P. aeruginosa strains, exhibiting flagella subtypes included in the vaccine, were significantly less frequently isolated from vaccinates than from placebo controls (P = 0.016, relative risk: 0.319; 95% CI: 0.12-0.86). Chronic P. aeruginosa infection was rare because of recent institution of early antibiotic eradication regimes. Active immunization of patients with cystic fibrosis lowers the risk for infection with P. aeruginosa and therefore may contribute to a longer survival of these patients." ]

[ "9659643", "11779098", "8540930", "9509504", "10048613", "15526012", "19635302", "8740313", "12061670", "8346946", "8466265", "9175950", "7770284", "1372652", "2040933", "7549303", "14517513", "10709119", "8737229", "12091844", "8190577", "11134438", "9297428", "8757567" ]

[ "Recombinant human erythropoietin therapy for treatment of anemia of prematurity in very low birth weight infants: a randomized, double-blind, placebo-controlled trial.", "Effect of recombinant human erythropoietin administration on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants.", "Recombinant human erythropoietin in the treatment of anemia of prematurity.", "Erythropoietin (rHuEPO) administration to premature infants for the treatment of their anemia.", "Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants.", "Effect of short-term erythropoietin therapy in anemic premature infants.", "Erythropoietin increases reticulocyte counts and maintains hematocrit in neonates requiring surgery.", "Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity.", "Does early erythropoietin therapy decrease transfusions in anemia of prematurity?", "Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity.", "Double blind trial of recombinant human erythropoietin in preterm infants.", "Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease.", "Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants.", "Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study.", "Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study.", "Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother's milk during anaemia of prematurity.", "Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates.", "Recombinant human erythropoietin in anemia of prematurity.", "Effects of recombinant human erythropoietin in infants with very low birth weights.", "Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g.", "Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study.", "Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants.", "[Randomized multi-center trial of the administration of erythropoietin in anemia of prematurity].", "Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions." ]

[ "To evaluate the efficacy and safety of recombinant human erythropoietin (rHuEPO) in very low birth weight infants with anemia of prematurity.\n Thirty infants were randomly assigned to receive either rHuEPO (300 U/kg per dose) or placebo twice a week. Hematologic parameters, transfusion requirements, caloric intake, and growth were monitored.\n The number and volume of erythrocyte transfusions were significantly lower in infants treated with rHuEPO. Serum ferritin levels, similar in both groups at study entry, fell and were significantly lower in rHuEPO-group infants at the completion of the study. An inverse correlation was observed between reticulocyte count and absolute neutrophil count both at entry and at completion of the study.\n Twice-a-week administration of rHuEPO significantly reduces the need for erythrocyte transfusion in very low birth weight infants in stable condition. A significant decrease in serum ferritin levels in infants receiving rHuEPO suggests the need to determine the optimal dose of iron supplementation in these infants.", "In the present investigation, we studied the effect of recombinant human erythropoietin (r-HuEPO) on serum malondialdehyde (MDA) as an index of lipid peroxidation, related to iron-catalyzed free radical reaction and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities in very-low-birth weight (VLBW) infants. Forty premature infants, at gestational ages were less than 33 weeks and birthweights were less than 1,500 g, were enrolled in the study. The study population was randomly divided into 2 groups. Twenty infants in Group 1 (treatment group) were given r-HuEPO, and 20 infants in Group 2 served as the control. r-HuEPO treatment (750 U/kg a week) was initiated on the 10th day of life and continued for 6 weeks. Preterm infants given erythrocyte transfusions during the study were excluded from the results. Serum ferritin and MDA levels, and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were analyzed at the end of the first week of life (at the beginning of the study). Subsequently, serum ferritin, and MDA levels were measured at the end of the 3rd and the 6th week. SOD, CAT, and GPX activities in the hemolysate were analyzed at the end of the 4th week. Six infants in the control group and 1 infant in the r-HuEPO group received transfusions through the end of the study, and these infants were excluded from the results. Significantly decreased serum ferritin concentrations were found in the r-HuEPO group compared to those in the control group both at the end of the 3rd and the 6th week (P < 0.05, and P < 0.01, respectively). In addition, serum MDA levels were also significantly reduced in Group 1 compared to control both at the end of the 3rd and the 6th week (P < 0.01 and P < 0.05, respectively). A good correlation was found between serum MDA and ferritin levels in Group 1. When the 2 groups were compared with respect to activities of SOD, CAT, and GPX at the end of the 4th week, no differences were observed. Our findings in this study show that administration of r-HuEPO significantly decreases lipid peroxidation, but does not affect erythrocyte antioxidant enzyme(s) activities in preterm infants. The mechanism responsible for the r-HuEPO-induced decrease in lipid peroxidation may concern inhibition to iron-catalyzed free radical reactions.", "Seventy premature infants (birthweight 1.75 kg or less, gestational age 33 weeks or less) with hemoglobin less than 10 g/dL and hematocrit less than 30% were studied and randomly divided into three groups. All of them received oral elemental iron 3 mg/kg/day and vitamin E 5 mg/kg/day during the study period. Recombinant human erythropoietin (rHuEPO) 150 U/kg was administered intravenously twice a week for 4 weeks in group A (26 infants). Infants in group A received a total of 4 erythrocyte transfusions because of frequent apnea. Infants in group B (25 infants) received erythrocyte transfusion when their hemoglobin levels was less than 10 g/dL with signs and symptoms (including tachycardia, tachypnea, poor feeding, apnea, poor weight gain) attributed to anemia or who had a hemoglobin less than 8 g/dL even if asymptomatic. Infants in group B received a total of 36 erythrocyte transfusions. Infants in group C (19 infants) were assigned to a non-rHuEPO and nontransfusion group. Three of the 19 premature infants in group C received erythrocyte transfusions later because of frequent and prolonged apneic episodes and were excluded from this study. Our data revealed that reticulocyte and serum erythropoietin values were higher (p < 0.01) in rHuEPO-treated group than transfusion group and hemoglobin and hematocrit values were lower in group C than the other two groups during the rHuEPO treatment period. No significant difference (p > 0.05) was found in neutrophil and platelet counts among these three groups. Serum ferritin values were found lower in the rHuEPO-treated group than the other two groups. Lower weight gain was found in infants in group C. We conclude that rHuEPO administration can reduce the need for blood transfusion. Poor weight gain can be found in infants with anemia of prematurity who do not receive rHuEPO or blood transfusion therapy.", "In an attempt to stimulate erythrocyte production and thereby decrease the requirement for red blood transfusions, recombinant human erythropoietin (rHuEPO) was administered to 16 premature infants with birth weights less than 1000 g and to 18 with birth weights of 1000-1300 g; two corresponding groups, who did not receive rHuEPO, were used as control groups. The rHuEPO was administered subcutaneously in a dose of 300 IU/kg three times a week for 6-8 weeks. The erythropoietin decreased the red blood requirement in both groups of infants, and the increment of hemoglobin following rHuEPO administration was not statistically significant. No correlation was observed between gestational age, number of transfusions, and reticulocyte percentage. The effect of rHuEPO was higher in the group of infants with birth weights of 1000-1300 g than in those of less than 1000 g. No significant side effects were observed during rHuEPO administration.", "The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8-7.2 mg/l to 10.5-11.3 mg/l.\n In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron.", "To determine the effectiveness of a 10-day subcutaneous erythropoietin (rHuEpo) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness.\n Prospective, randomized trial performed at a 40-bed, teaching, referral, level III, neonatal intensive care unit. Infants with a gestational age at birth of less than 32 weeks, hematocrit of less than or equal to 28% with a corrected reticulocyte count of less than or equal to 5%, postconceptual age of less than 48 weeks or 5 months chronological age, and a diagnosis of anemia of prematurity were considered for inclusion. Major outcome parameters included hematocrit, corrected reticulocyte count and red cell transfusion requirements.\n A total of 60 infants were enrolled (n=30 per group). Infants randomized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group (p<0.001). There was a trend towards fewer red cell requirements in the rHuEpo group.\n The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts. This study did not demonstrate a statistically significant decrease in transfusion therapy, in part related to increased subsequent use of rHuEpo in the control group. Taken together, these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants.", "Limited erythropoietin (Epo) production diminishes neonates' ability to regenerate blood removed by phlebotomy. Neonates requiring surgery are at risk to receive multiple transfusions. We sought to determine if recombinant Epo administration to neonates requiring surgery would stimulate erythropoiesis.\n Infants were randomized in double-masked fashion to receive Epo (200 units kg(-1) d(-1)) or placebo for 14 days. Complete blood count, absolute reticulocyte count (ARC), phlebotomy losses, and transfusions were measured during the study period. Infants were transfused using a strict transfusion protocol.\n In the Epo group (n = 10, 2034 +/- 308 g, 8 +/- 2 days old; mean +/- SEM), ARC increased significantly, whereas in the placebo group (n = 10, 2400 +/- 184 g, 7 +/- 2 days old), ARC remained low. Hematocrits in the Epo group trended upward from 34.4 1.7% to 37.3 1.9% (although not statistically significant) despite phlebotomy losses of 53 +/- 12 mL/kg. Hematocrits in the placebo group were 35.9 1.8% and 33.2 1.6% on days 1 and 15, respectively, with phlebotomy losses of 27 +/- 5 mL/kg. There were no differences in absolute neutrophil counts or platelet counts between groups at the end of the study. No adverse effects were noted.\n Infants randomized to Epo increased reticulocyte counts and hematocrits without adverse effects. Erythropoietin administration may provide an adjunct to present care in decreasing or eliminating erythrocyte transfusions in surgical neonates.", "Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin (microgram 1-1) and iron (mumol l-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus 6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/- 191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l-1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.", "To investigate the effect of early erythropoietin treatment on induction of erythropoiesis and the need for transfusion in Very Low Birth Weight (VLBW) infants with acute neonatal problems.\n The study group consisted of 14 VLBW prematures with gestational ages less than 32 weeks who were given subcutaneous erythropoietin (600 U/kg per week) and oral iron (3 mg/kg per day) during the first 7-8 weeks of their life, while 13 other VLBW prematures that were given placebo constituted the control group. Weekly hematocrit, (Hct) reticulocyte (Ret) values and the volume of blood drawn and transfused were recorded in the both groups.\n The groups were comparable regarding with birth weights and gestational ages. The volume of the blood drawn (76.8 +/- 42.5 and 37.0 +/- 15.2) was higher and the volume of the transfusions (51.84 +/- 49.30 and 68.84 +/- 41.2) was lower in the study group but the differences between the groups were not significant (p>0.05). The hematocrit, the reticulocyte and the ferritin values were similar in both the groups at the end of the therapy.\n Under the neonatal intensive care circumstances of developing countries where blood volumes needed for laboratory analysis are still very high, phlebotomy losses can not be avoided. Thus early erythropoietin and iron therapy at these doses are not effective in decreasing the need for transfusion and induction of endogenous erythropoiesis.", "The effectiveness of recombinant human erythropoietin (r-HuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose r-HuEpo can produce significant gains in red cell production that may be clinically useful.", "Twenty four infants between 27 and 33 weeks' gestation were recruited into a double blind study to investigate the use of recombinant human erythropoietin (r-HuEpo) for the prevention of anaemia of prematurity. Between 50 and 150 U of r-HuEpo (n = 16) or placebo was administered subcutaneously twice a week from 7 days of age until discharge. There was a significant increase in the reticulocyte count in infants receiving r-HuEpo sustained from the second week of treatment until discharge compared with placebo. There was a reduction in the number of transfusions required in the r-HuEpo group with only 47% requiring a transfusion compared with 87% in the placebo group. During treatment with r-HuEpo there was a significant rise in the red cell folate concentration, a significant fall in the ferritin concentration, and a significantly higher percentage of haemoglobin F at discharge suggesting active erythropoiesis. The study provides strong evidence for the efficacy of r-HuEpo in stimulating erythropoiesis and reducing the requirement for transfusions for anaemia of prematurity.", "To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease.\n A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required.\n Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months -0.50, 95% confidence interval -1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0). The study was stopped early because of failure to recruit babies at the expected rate.\n R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.", "We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines.\n Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups.\n We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.", "We randomly assigned eight concurrently symptom-free premature infants (birth weight less than or equal to 1250 gm) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved. All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4% in babies who received r-HuEPO versus 33.6% in the control subjects, and were 31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of treatment. One r-HuEPO-treated and three control babies received transfusions during the study; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects. The percentage of hemoglobin F increased in infants not given transfusions. We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy. A controlled multicenter trial has been undertaken to confirm these promising preliminary observations.", "Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin (r-HuEPO) might be used to treat or prevent it. We therefore randomly assigned 20 small premature infants (birth weight less than or equal to 1250 gm) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO (at a dose of 100 units/kg twice each week) or a placebo. Hematologic measurements, transfusion requirements, and growth were followed during therapy and for 6 months thereafter. Treated (EPO) and control babies did not differ with respect to weight, hematocrit, overall mean absolute reticulocyte count, calculated erythrocyte mass, or rate of growth. However, reticulocyte counts increased earlier in patients given r-HuEPO. Six of ten babies in the EPO group, and 8 of 10 assigned to the control group, received at least one erythrocyte transfusion during treatment. For all infants the amount of blood sampled for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused (r = 0.890; p = 0.0001). Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests, none of four given r-HuEPO received a transfusion, whereas three of five infants assigned to the placebo group received one. No toxic effects were attributable to r-HuEPO, and no significant changes in leukocyte or platelet counts occurred during treatment. Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups. We conclude that r-HuEPO administration is safe and feasible at the dose studied. Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified.", "Twenty-four premature infants, < 32 weeks gestational age, were randomly assigned in a double-blind, placebo-controlled trial to 6 weeks of treatment with either recombinant human erythropoietin (rHuEpo) 150 U/kg three times per week given sc (n = 12) or placebo (n = 12). The infants were fed a diet rich in protein (3.2 g/kg/day) and energy (130 kcal/kg/day) based on their own mother's milk fortified with bovine protein together with moderate iron supplementation (4 mg/kg/day). During the treatment (rHuEpo versus placebo) significant differences in mean (+/- SD) reticulocyte count (4.8 +/- 1.2 versus 2.7 +/- 1.4%; p < 0.01), mean packed red cell volume (PCV) (0.38 +/- 0.03 versus 0.34 +/- 0.04, p < 0.05) and mean haemoglobin concentration (12.6 +/- 1.1 versus 11.5 +/- 1.2 g/100 ml; p < 0.05) were found. Within the rHuEpo group, PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group. No indications of iron deficiency were seen. We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity. High iron supplementation does not seem to be essential for a significant erythropoietic response. No adverse effect attributable to rHuEpo was observed.", "Human fetuses and neonates ingest erythropoietin (Epo) when they swallow amniotic fluid, colostrum, and human milk. This study was designed to determine whether enterally dosed recombinant Epo (rEpo) stimulates erythropoiesis in preterm neonates.\n Preterm infants (<1500 g birth weight) were randomly assigned to receive feedings supplemented with either rEpo (1000 U/kg per day) or placebo for 14 days (n=36). Reticulocyte counts, serum Epo concentrations, hematocrit, and zinc protoporphyrin to heme ratios were measured at baseline and after 7 and 14 days of study drug administration. Transfusion guidelines were followed. Transfusion requirements, medications, feeding tolerance, and clinical diagnoses were documented.\n Enteral rEpo was well tolerated. There were no differences in erythropoietic indexes based on treatment group. Serum Epo concentrations were not different in the treatment versus placebo group, nor were transfusion requirements.\n Enterally dosed rEpo (1000 U/kg/day) does not significantly influence erythropoiesis or iron utilization when given for a 2-week period, nor does it elevate the serum Epo concentration in preterm or term infants. Oral administration of rEpo is not an effective substitute for parenteral administration.", "To evaluate safety and efficacy of recombinant human erythropoietin (r-HuEPO)in reducing the need for red cell transfusions in anemia of prematurity.\n forty -two preterm infants (gestational age <32 weeks) were randomly assigned to a \"treatment\" group (r-HuEPO 400 units/kg every alternate day * 10 doses) or \"no treatment\" (control) group. All infants on enteral feeds received oral iron 3 mg/kg/day, graded up to 6 mg/kg/day.\n Higher reticulocyte counts in week 2 and 3 and higher hemoglobin levels in week 4 were noted after treatment with r-HuEPO. Despite stumulated erythropoiesis, the frequency of transfusions could not be reduced with r-HuEPO therapy.Overall, Phlebotomy losses, frequency and volume of redcell transfusions were significantly more in neonates with birthweight <1000 grams compared with those with birthweight >1000 grams (p<0.05). Associated side effects of r-HuEPO such as neutropenia,sepsis, hypertension or increased risk of late death did not occur.\n r-HuEPO therapy was safe without any side effects. Inability of r-HuEPO therapy to minimize red cell transfusions for anemia of prematurity may be explained by a relatively strict red-cell transfusion policy and the desired degree of treatment effect.", "Anaemia of prematurity, a postnatal fall in haemoglobin concentration and haematocrit, is particularly common in those born at less than 32 weeks of gestation. Experimental and clinical data implicate inadequate erythropoietin production as an important reason. In this study recombinant human erythropoietin (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions. Premature infants (birth weight < or = 1250 g and gestational age < or = 32 weeks), who were likely to need transfusions, were randomly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12), three times weekly. All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at the end of treatment. The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment. There were no toxic effects attributable to r-HuEpo. The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte transfusions.", "To investigate whether recombinant erythropoietin (rhEPO) reduces the need for transfusion in extremely low birth weight (ELBW) infants (birth weight 500-999 g) and to determine the optimal time for treatment.\n In a blinded multicenter trial, 219 ELBW infants were randomized on day 3 to one of 3 groups: early rhEPO group (rhEPO from the first week for 9 weeks, n = 74), late rhEPO group (rhEPO from the fourth week for 6 weeks, n = 74), or control group (no rhEPO, n = 71). All infants received enteral iron (3-9 mg/kg/day) from the first week. The rhEPO beta dose was 750 IU/kg/week. Success was defined as no transfusion and hematocrit levels never below 30%.\n Success rate was 13% in the early rhEPO group, 11% in the late rhEPO group, and 4% in the control group (P =.026 for early rhEPO versus control group). Median transfusion volume was 0.4 versus 0.5 versus 0.7 mL/kg/day (P =.02) and median donor exposure was 1.0 versus 1.0 versus 2.0 (P =.05) in the early rhEPO group, the late rhEPO group, and the control group, respectively. Infection risk was not increased and weight gain was not delayed with rhEPO beta.\n Early rhEPO beta treatment effectively reduces the need for transfusion in ELBW infants.", "To assess the efficacy of recombinant human erythropoietin (rHuEpo) in the treatment of the anemia of prematurity.\n A double-blind, placebo-controlled study was conducted on 80 preterm infants (< or = 32 weeks; postnatal age, 2 to 8 weeks; central hematocrit < or = 35%). Patients were randomly assigned to receive subcutaneous rHuEpo (Eprex, 600 U/kg per week) or an equivalent volume of placebo, for up to 6 weeks. All patients received supplements of vitamin E (25 IU) and iron (3 mg/kg per day). The iron supplement was increased if declining serum ferritin measurements were noted.\n Treatment and placebo groups did not differ significantly with respect to mean gestational age, birth weight, hematocrit, or reticulocyte count at study entry. Fewer transfusions were administered to those receiving erythropoietin (7 compared with 21; P = .002). Compared with the placebo group, the infants receiving rHuEpo had a higher mean hematocrit (32.3 +/- 4% vs 29.3 +/- 6.2%; P = .014) and absolute reticulocyte count (223 +/- 73 vs 124.9 +/- 73 x 10(9)/L; P < .001) at the end of the study. The mean neutrophil count was not significantly reduced at study exit (P = .8), nor at any other period during the trial in the rHuEpo group. Intercurrent events (mostly infections) were not increased in the treatment group, although there was one case of sudden infant death syndrome at age 4 months.\n Using a dose of rHuEpo of 600 U/kg per week, this study has shown a clear reduction in the requirement for blood transfusion in preterm infants.", "To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants.\n A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine.\n At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing.\n In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity.", "The purpose of this study was to test the therapeutic effect of human recombinant erythropoietin (rH-EPO) on anemia of prematurity.\n Fifty-eight preterm infants less than 34 weeks of gestational age from three different hospitals were studied. Transfusional policies were similar in all three centers. Infants with ABO or Rh incompatibility were excluded. At 28 days after birth, 28 infants (48.3%) had hemoglobin levels under 10.5 g/dL and were randomized to receive rH-EPO or standard care. Those infants ascribed to the treatment group received 200 U/kg of body weight of rH-EPO subcutaneously once a day, three days a week for 4 weeks together with oral supplements of ferrous sulfate at a dosage of 4 mg/kg/day. Both groups received daily doses of 50 micrograms of folic acid and 5U of vitamin E per os. Erythropoietin and ferritin were determined at randomization and at 60 days of age. Hemoglobin, reticulocytes, leucocytes, granulocytes and platelets were measured once a week, from the beginning of the treatment until 60 days of age.\n At randomization into treatments, there were no significant differences between the groups with respect to weight, gestational age, hemoglobin (9.42 +/- 0.73 vs 9.26 +/- 0.68 g/dL), reticulocytes (61.7 +/- 32.2 vs 68.0 +/- 61.0 x 10(9)/L), ferritin, EPO1 leucocytes or platelets. At 60 days of age, the treatment group showed higher hemoglobin values (10.5 +/- 1.73 vs 9.1 +/- 1.0 g/dL, p < 0.05). There were no significant differences between reticulocyte counts (176.4 +/- 91.1 vs 112.6 +/- 85.0 x 10(9)/L), granulocytes (2,351 +/- 868 vs 2,075 +/- 856 x 10(9)/L), platelets (400 +/- 138 vs 316 +/- 164 x 10(9)/L) or ferritin (209 +/- 177 vs 393 +/- 328 micrograms/mL). Of the infants in the nontreated group, 13.3% received blood transfusions between 30 and 60 days of age, while only 6.7% of the treatment group did (p = 0.31).\n We have been able to find 11 controlled studies in the medical literature which deal with the clinical usage of rH-EPO in newborns. Six use the hormone in an early phase and 5 in a posterior one. Our study should be included in the later and, as happens in most of them, demonstrates the efficacy of rH-EPO in the treatment of late anemia of the preterm newborn as shown by an increment in the hemoglobin levels and a trend towards the diminution in the use of blood transfusions. We have not observed substantial adverse effects.", "To determine whether treatment with recombinant human erythropoietin (r-HuEPO) reduces transfusion requirements in premature neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions.\n A double-blind, randomized, controlled trial.\n Fifty-five infants appropriate in weight for gestational age (less than 1250 gm birth weight) who, at 10 days of age, were predicted to have a greater than 75% probability of having bronchopulmonary dysplasia. This criterion had previously been shown to identify infants requiring multiple transfusions. Twenty-seven infants were randomly assigned to receive r-HuEPO therapy and 28 to a control group. r-HuEPO was administered in a dosage of 20 U/kg body weight, subcutaneously, three times a week for 6 weeks. Control infants received sham treatment.\n Infants treated with r-HuEPO required significantly fewer transfusions than control infants during their entire hospital stay (mean 3.48 +/- 1.58 vs 5.68 +/- 2.30; p = 0.0001) and had a higher mean reticulocyte count (p < or = 0.0005) and a higher mean hemoglobin concentration (p < or = 0.005) during the treatment period. At follow-up, 4 months after term, there were no significant differences between the groups in mean reticulocyte count (p = 0.86) or mean hemoglobin concentration (p = 0.56). However, two infants in each group had low serum ferritin values indicative of depleted iron stores.\n Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants at high risk of having bronchopulmonary dysplasia and requiring multiple transfusions; the result was a reduction in transfusion requirements. This treatment, together with other strategies to reduce the need for transfusions, is appropriate in this population. Unrelated to r-HuEPO treatment, these infants may be at risk of having iron deficiency later in infancy." ]

[ "12002243" ]

[ "The test of time: predictors and effects of duration in youth mentoring relationships." ]

[ "The effects and predictors of duration in youth mentor relationships were examined. The study included 1,138 young, urban adolescents (Mean age 12.25), all of whom applied to Big Brothers Big Sisters programs. The adolescents were randomly assigned to either the treatment or control group, and administered questions at baseline and 18 months later Adolescents in relationships that lasted a year or longer reported the largest number of improvements, with progressively fewer effects emerging among youth who were in relationships that terminated earlier. Adolescents who were in relationships that terminated within a very short period of time reported decrements in several indicators of functioning. Older adolescents, as well as those who had been referred for services or had sustained emotional, sexual or physical abuse, were most likely to be in early terminating relationships, as were married volunteers aged 26-30 and those with lower incomes. Several dyadic factors were also found to be related to earlier terminations, including race, gender, and relationship quality." ]

[ "17088142", "18953552", "18284860", "15208594", "15637558", "16222197" ]

[ "Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis.", "Postoperative application of amphotericin B nasal spray in chronic rhinosinusitis with nasal polyposis, with a review of the antifungal therapy.", "Amphotericin B irrigation for the treatment of chronic rhinosinusitis without nasal polyps: a randomized, placebo-controlled, double-blind study.", "Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: a randomized, double-blind clinical trial.", "Treatment of chronic rhinosinusitis with intranasal amphotericin B: a randomized, placebo-controlled, double-blind pilot trial.", "Treatment of chronic rhinosinusitis with high-dose oral terbinafine: a double blind, placebo-controlled study." ]

[ "Chronic rhinosinusitis (CRS) is one of the most common chronic diseases. Recently, it has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of the disease. On the basis of this hypothesis, intranasal treatment with amphotericin B should benefit patients with CRS. Data from 2 uncontrolled and 2 controlled trials are conflicting, however.\n To clarify the role of intranasal antifungal drugs in the treatment of CRS, we conducted a large, double-blind, placebo-controlled, multicenter study comparing the effectiveness of amphotericin B nasal lavages with placebo.\n A total of 116 randomly selected patients with CRS were instructed to instill 25 mL amphotericin B (100 microg/mL) or placebo to each nostril twice daily for 3 months. Primary outcomes included a reduction in total visual analog scale (VAS) score and nasal endoscopy score. Secondary outcome measures included peak nasal inspiratory flow, polyp score, quality of life (Short Form-36, Rhinosinusitis Outcome Measure-31), and individual VAS scores.\n Analysis was based on intention to treat and involved all patients randomly assigned. Mean VAS scores, Short Form-36 and Rhinosinusitis Outcome Measure-31 data, peak nasal inspiratory flow values, nasal endoscopy scores, and polyp scores were similar in both treatment groups at the time of randomization, and no significant differences were observed after 13 weeks of treatment.\n Amphotericin B nasal lavages in the described dosing and time schedule do not reduce clinical signs and symptoms in patients with CRS.\n Amphotericin B nasal lavages in the described dosing and time schedule are ineffective and therefore not advised in the treatment of patients with CRS.", "Chronic rhinosinusitis (CRS) affects 1-4% of the adult population. The etiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade, it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE-type) immune response against fungal organisms in the nasal mucus. If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases. To check on this assumption, we conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; group A (14 randomly selected patients) were treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group B (16 randomly selected patients) received a nasal spray lacking amphotericin B. We evaluated our results with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which assesses changes in the symptoms), a quality of life test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and 1 year postoperatively. The CT scores of the group A patients 1 year after the operation exhibited wide scattering, without signs of recovery. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant relative to group A. Both the SNAQ-11 test and the quality of life test revealed a significant improvement in each group, but the degrees of change in these tests did not differ significantly between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation. These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in either CT score, clinical symptoms, or quality of life. The more favorable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms. In connection with the conclusions drawn from this study, the authors discuss the controversial data available on the fungal etiology of CRS. They critically analyze the contradictory observations and conclusions of seven recent clinical studies.", "Fungus-driven inflammation is proposed to play an important role in the pathogenesis of chronic rhinosinusitis (CRS). Previous studies tested the efficacy of intranasal antifungal agents for patients with nasal polyps. The purpose of this study was to evaluate the efficacy of intranasal amphotericin B (AMB) in patients who have CRS without nasal polyps (CRSsNP).\n Patients diagnosed with CRSsNP were enrolled in this study. They were assigned randomly to receive irrigation with AMB solution (20 mg of AMB in 500 mL of normal saline) or placebo (yellowish dye in 500 mL of normal saline) for 4 weeks. The outcome measures included the Chinese version of the Rhinosinusitis Outcome Measure 31 (CRSOM-31), nasal endoscopy, and bacterial and fungal cultures.\n Seventy patients were enrolled and 64 patients completed this study. There was significant improvement in the AMB group (n = 32) both in endoscopic (p = 0.013) and CRSOM-31 scores (p < 0.0001). The placebo group (n = 32) showed significant improvement in CRSOM-31 scores (p < 0.0001). CRSOM-31 scores were significantly lower in the AMB group than in the placebo group after 2-week treatment (p = 0.018) and remained lower after 4-week treatment, although the difference was not significant (p = 0.091). There were no significant differences in endoscopic scores and bacterial or fungal culture rates between two groups after treatment.\n Our results showed that AMB irrigation improved symptoms and endoscopic scores but did not show superiority to saline irrigation alone in patients who have CRSsNP.", "Recently, fungal elements were suspected to be the causative agent of chronic rhinosinusitis, and benefits of topical amphotericin B therapy have been reported.\n The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind, randomized clinical trial.\n Patients with chronic rhinosinusitis were administered 200 microL per nostril amphotericin B (3 mg/mL) or saline nasal spray 4 times daily over a period of 8 weeks. The response rate, defined as a 50% reduction of pretreatment computed tomography score, was the primary outcome variable. Additional outcome variables included a symptom score, a quality of life score, and an endoscopy score. Before and after treatment, nasal lavages were pretreated with dithiothreitol and examined for fungal elements by PCR and standard culture techniques.\n Seventy-eight patients were included, and 60 patients finished the study per protocol. In the control group, no positive response (0 of 32) was observed, and 2 of 28 patients responded in the amphotericin B group (P>.2). The symptom scores were distinctly worse after amphotericin B therapy (P <.005). The other parameters investigated did not differ remarkably between the treatment groups.\n Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms.", "Chronic rhinosinusitis (CRS) is one of the most common chronic diseases. Its etiology is unknown, and there is a paucity of effective medical treatments.\n We tested the hypothesis that intranasal antifungal treatment improves the objective computed tomography (CT) findings (inflammatory mucosal thickening), nasal endoscopy stages, and symptoms of CRS.\n A randomized, placebo-controlled, double-blind, single-center trial used amphotericin B to treat 30 randomly selected patients with CRS. Patients were instructed to instill 20 mL amphotericin B (250 mug/mL) or placebo to each nostril twice daily for 6 months. The primary outcome was a quantitative reduction in inflammatory mucosal thickening on CT scans of a standardized coronal cut. Secondary outcome measures were endoscopic scores, patient symptom scores, and levels of intranasal inflammatory mediators.\n Twenty-four patients completed the 6 months of treatment. Patients receiving amphotericin B achieved a relative reduction in the percentage of mucosal thickening on CT scans (n = 10; -8.8%) compared with placebo (n = 14; +2.5%; P = .030). Likewise, the changes in the endoscopic scores improved in the amphotericin B group compared with placebo ( P = .038). Between-group comparisons of the changes in the intranasal mucus levels of eosinophil-derived neurotoxin showed a reduction in the amphotericin B group and an increase in the placebo group ( P = .046); levels of IL-5 showed similar tendencies ( P = .082).\n Intranasal amphotericin B reduced inflammatory mucosal thickening on both CT scan and nasal endoscopy and decreased the levels of intranasal markers for eosinophilic inflammation in patients with CRS.", "To evaluate antifungal terbinafine in patients with chronic rhinosinusitis.\n Randomized, double-blind, placebo-controlled multicenter pilot study.\n Fifty-three adults with chronic rhinosinusitis received terbinafine 625 mg/day (n = 25) or placebo (n = 28) once daily for 6 weeks. Sinus secretions were collected at screening for mycology. Computed tomography was graded for extent of opacification at baseline and at week 6 using a modification of the Lund-Mackay scoring system. Patients recorded rhinosinusitis symptoms on a visual analogue scale and completed the Rhinosinusitis Disability Index.\n Positive fungal cultures were found in 41 of 53 patients (17 terbinafine, 24 placebo). (Two subjects from the Terbinafine group and one subject from the control group had no week 6 data). The mean opacification scores pre- and posttreatment for the entire study group improved from 24.2 to 22.5 in placebo (n = 26) and from 26.3 to 24.2 in terbinafine group (n = 23). The least squares means for percent change from baseline (SE) were -6.0 (8.7) for placebo compared with -7.2 (8.1) for terbinafine; 95% confidence interval for treatment difference (-18.9, 21.1); P = .91. Results were similar when only patients with positive fungal cultures were evaluated in the efficacy analysis. Investigator therapeutic evaluations and sinus symptom scores were not significantly different between the two groups at baseline or at treatment completion.\n Treatment with terbinafine failed to improve the symptoms or radiographic appearance of chronic rhinosinusitis even when nasal irrigation samples were positive for fungus on culture. One consideration is that the fungi isolated were not a major pathologic factor in this cohort. It is also possible that, even at high dose, terbinafine may not have maintained therapeutic levels in the nasal secretions." ]

[ "9002332", "15582060", "17954538", "18996423" ]

[ "Maximizing immunization coverage through home visits: a controlled trial in an urban area of Ghana.", "Monetary incentives in primary health care and effects on use and coverage of preventive health care interventions in rural Honduras: cluster randomised trial.", "Informing resource-poor populations and the delivery of entitled health and social services in rural India: a cluster randomized controlled trial.", "Redesigned immunization card and center-based education to reduce childhood immunization dropouts in urban Pakistan: a randomized controlled trial." ]

[ "A strategy of home visits to maximize children's immunization coverage was implemented in three towns in Ghana. The strategy was tested in town 1 in a controlled trial where clusters of children were allocated to the intervention and control groups. A total of 200 mothers in the intervention group were visited at home by non-health workers and their children were referred to a routine under-fives' clinic. Subsequent home visits targeted at those who failed to complete immunization schedules were made by nurses. After 6 months, coverage had risen from 60% to 85%, which was 20% higher than in the town 1 control group of 219 age-matched children (P < 0.005). A similar home-visiting strategy in a neighbouring town resulted in a rise in coverage from 38% to 91% (n = 55), mainly through home immunizations. Children were more likely to complete the schedule if their fathers were interviewed and participated in the decision to send them to the clinic. Countries with national service programmes can use a home-visiting strategy to supplement and strengthen their routine immunization programmes. A wide range of other community-based primary health care interventions could also be tested and implemented using this methodology.", "Scaling-up of effective preventive interventions in child and maternal health is constrained in many developing countries by lack of demand. In Latin America, some governments have been trying to increase demand for health interventions by making direct payments to poor households contingent on them keeping up-to-date with preventive health services. We undertook a public health programme effectiveness trial in Honduras to assess this approach, contrasting it with a direct transfer of resources to local health teams.\n 70 municipalities were selected because they had the country's highest prevalence of malnutrition. They were allocated at random to four groups: money to households; resources to local health teams combined with a community-based nutrition intervention; both packages; and neither. Evaluation surveys of about 5600 households were undertaken at baseline and roughly 2 years later. Pregnant women and mothers of children younger than 3 years old were asked about use of health services (primary outcome) and coverage of interventions such as immunisation and growth monitoring (secondary outcome). Reports were supplemented with data from children's health cards and government service utilisation data. Analysis was by mixed effects regression, accounting for the municipality-level randomisation.\n The household-level intervention had a large impact (15-20 percentage points; p<0.01) on the reported coverage of antenatal care and well-child check-ups. Childhood immunisation series could thus be started more opportunely, and the coverage of growth monitoring was markedly increased (15-21 percentage points; p<0.01. Measles and tetanus toxoid immunisation were not affected. The transfer of resources to local health teams could not be implemented properly because of legal complications.\n Conditional payments to households increase the use and coverage of preventive health care interventions.", "A lack of awareness about entitled health and social services may contribute to poor delivery of such services in developing countries, especially among individuals of low socioeconomic status.\n To determine the impact of informing resource-poor rural populations about entitled services.\n Community-based, cluster randomized controlled trial conducted from May 2004 to May 2005 in 105 randomly selected village clusters in Uttar Pradesh state in India. Households (548 intervention and 497 control) were selected by a systematic sampling design, including both low-caste and mid- to high-caste households.\n Four to 6 public meetings were held in each intervention village cluster to disseminate information on entitled health services, entitled education services, and village governance requirements. No intervention took place in control village clusters.\n Visits by nurse midwife; prenatal examinations, tetanus vaccinations, and prenatal supplements received by pregnant women; vaccinations received by infants; excess school fees charged; occurrence of village council meetings; and development work in villages.\n At baseline, there were no significant differences in self-reported delivery of health and social services. After 1 year, intervention villagers reported better delivery of several services compared with control villagers: in a multivariate analysis, 30% more prenatal examinations (95% confidence interval [CI], 17%-43%; P < .001), 27% more tetanus vaccinations (95% CI, 12%-41%; P < .001), 24% more prenatal supplements (95% CI, 8%-39%; P = .003), 25% more infant vaccinations (95% CI, 8%-42%; P = .004), and decreased excess school fees of 8 rupees (95% CI, 4-13 rupees; P < .001). In a difference-in-differences analysis, 21% more village council meetings were reported (95% CI, 5%-36%; P = .01). There were no improvements in visits by a nurse midwife or in development work in the villages. Both low-caste and mid- to high-caste intervention households reported significant improvements in service delivery.\n Informing resource-poor rural populations in India about entitled services enhanced the delivery of health and social services among both low- and mid- to high-caste households. Interventions that emphasize educating resource-poor populations about entitled services may improve the delivery of such services.\n clinicaltrials.gov Identifier: NCT00421291.", "In Pakistan during 2000-2004, about 11-13% of children who received the first dose of diphtheria-pertussis-tetanus (DPT1) failed to complete its third dose (DPT3). We assessed the effect of a redesigned immunization card and center-based education to mothers on DPT3 completion. We enrolled 1500 mother-child units at DPT1, randomized them to three intervention and one standard care groups, and recorded their DPT3 visits during a 90-day follow-up. In multivariable analysis, a significant increase of 31% (adjusted RR=1.31, 95% CI=1.18-1.46) in DPT3 completion was estimated in the group that received both redesigned card and center-based education compared with the standard care group." ]

[ "10705425", "16079444", "16904773" ]

[ "Effects of 3 analgesic regimens on the perception of pain after removal of femoral artery sheaths.", "Randomized, controlled study of long-acting local anesthetic (levobupivacaine) in femoral artery sheath management during and after percutaneous coronary intervention.", "Effect of local anesthesia and intravenous sedation on pain perception and vasovagal reactions during femoral arterial sheath removal after percutaneous coronary intervention." ]

[ "Effective pain management after removal of femoral artery sheaths after percutaneous transluminal coronary angioplasty is highly individualized and requires frequent, accurate assessment and administration of analgesics as needed.\n To determine which of 3 analgesic regimens is most effective in decreasing patients' perception of pain with the fewest side effects after removal of a femoral artery sheath.\n 130 adult who had undergone percutaneous transluminal coronary angioplasty and were in an 8-bed cardiac short-stay unit in a 1400-bed acute care hospital.\n Patients were randomized to receive either intravenous morphine, intravenous fentanyl, subcutaneous lidocaine around the sheath site, or an intravenous placebo before sheath removal. Rescue analgesia (intravenous fentanyl) was made available to all groups. Patients used a visual analog scale to assess pain within 10 minutes before, 1 minute after, and 20 minutes after sheath removal. Pain levels, frequency of side effects, and use of rescue analgesia were compared among groups.\n Age, sex, number of stents, and frequency of hematomas did not differ significantly among groups. Pain ratings, use of rescue analgesia, and side effects (nausea, vomiting, or vasovagal symptoms) were not significantly different among treatment groups. Ratings of pain were slightly higher immediately after sheath removal in all groups.\n For most patients, removal of femoral artery sheaths and manual compression for hemostasis are relatively pain-free. Pain scores among patients given analgesia with subcutaneous lidocaine, intravenous morphine, or intravenous fentanyl were not significantly different from pain scores among control patients.", "To assess the effect of long-acting local anesthetic (levobupivacaine) in addition to lidocaine for the management of femoral artery sheaths during and after percutaneous coronary intervention (PCI).\n Femoral artery sheaths are commonly used during PCI. Sheath removal is often delayed after the procedure by which time short-acting local anesthetic agents may no longer be effective.\n Sixty patients were randomized to either usual care or the administration of local levobupivacaine after PCI. Patients were asked to report their pain experienced on a visual analogue score.\n Thirty patients received additional levobupivacaine (0.5%) and 30 received standard care. There were no procedural differences between the groups, except that more patients in the control group received intravenous (IV) morphine at the time of sheath removal. There was no difference between the control group and levobupivacaine group in pain scores at the time of sheath insertion. (2.0 +/- 0.4 versus 1.8 +/- 0.3; p = 0.80). Both groups recorded low pain scores while waiting for sheath removal, and the score was slightly (but not significantly) lower in the levobupivacaine group (1.3 +/- 0.2 versus 0.8 +/- 0.2; p = 0.09). Pain scores were lower in the levobupivacaine group during sheath removal 2.2 +/- 0.4 versus 1.1 +/- 0.2; p = 0.02). There were no differences in terms of blood pressure between the groups at any time point.\n Levobupivacaine reduced the need for IV opiate and provided better analgesia than lidocaine alone in patients undergoing PCI.", "There is no consensus with respect to the use of analgesia during femoral arterial sheath removal after percutaneous coronary intervention (PCI). We performed a randomized controlled trial to assess the impact of intravenous sedation and local anesthesia during femoral sheath removal after PCI on patient comfort and the incidence of vasovagal reactions.\n All patients undergoing PCI whose femoral sheaths were to be removed with assisted manual compression were eligible. Patients were randomized to receive either intravenous sedation (Fentanyl and Midazolam) or local anesthesia (1% lignocaine) infiltrated around the sheath site or both or neither. The primary endpoint of the study was the patients reported worst pain according to a Visual Analogue scale (VAS) after sheath removal. The incidence and predictors of vasovagal reactions during sheath removal and occurrence of vascular complications was also determined.\n A total of 611 patients were randomized into this study. The mean pain score was highest in the local anesthesia only arm as compared to the sedation only arm, the combined local and sedation arm and the neither sedation or local arm (p=0.001). vasovagal reactions were experienced by 35 patients (5.1%) with the highest percentage in the local anesthesia only group (9.8%). Multivariate logistic regression analysis identified a higher pain score (OR 1.18, 95% CI 1.12-1.24, p=0.001), use of glyceryl trinitrate during sheath removal (OR 9.05, 95% CI 5.06-16.1, p<0.001), a lower body mass index (OR 1.12, 95% CI 1.08-1.18, p=0.009) and the left anterior descending artery as the treated vessel (OR 5.2, 95% CI 3.41-7.87, p<0.001) as independent predictors of the occurrence of a vasovagal reaction. There was no significant difference in vascular complications between the 4 study groups.\n The routine use of fentanyl and midazolam prior to sheath removal leads to a reduction in pain perception and vasovagal incidence, whilst the routine use of local infiltration during sheath removal should be discouraged as it leads to more pain and a trend to more vasovagal reactions." ]

[ "11122219" ]

[ "Intranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo-controlled study." ]

[ "In a recent placebo-controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non-allergic non-infectious rhinitis. In this study the therapeutic effect lasted more than 9 months. This effect was not based on modulation of inflammation. To evaluate the effect of repeated application of capsaicin to patients with a nasal allergy to house dust mites (HDM), using the same treatment protocol as recently introduced in the treatment of non-allergic patients. Twenty-six patients with rhinitis, 15 females and 11 males (range: 20-46 years; mean 30.5), allergic to HDM were treated with either capsaicin or placebo in a double-blind, placebo-controlled, parallel group design. Nasal reactivity to HDM expressed as nasal symptoms, albumin and leukotriene levels in nasal lavage fluid and responsiveness to histamine, assessed as symptoms before and 6 weeks after treatment, were used to compare both treatment groups. In addition, visual analogue scales and rhinitis quality of life (RQL) assessment before, 6 weeks after and 3 months after treatment were used as outcome variables. No significant effect of capsaicin on nasal challenge tests with HDM (nasal symptoms, albumin and leukotriene levels), on VAS or RQL outcome 6 weeks or 3 month's after treatment, was demonstrated. Capsaicin did have a small effect on the area of the curve (AUC) of histamine dose response curves (P = 0.03). Desensitization with capsaicin in doses sufficient to control symptoms in patients with severe non-allergic rhinitis is lacking therapeutic effect in perennial allergic rhinitis." ]

[ "1970284", "7914759", "9625131", "2202199", "3278942", "8287749", "10925979", "9536943" ]

[ "Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis.", "5-ASA enema versus oral sulphasalazine in maintaining remission in ulcerative colitis.", "Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group.", "5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial.", "5-Aminosalicylic acid enemas: effective agent in maintaining remission in left-sided ulcerative colitis.", "Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains remission in ulcerative proctitis and proctosigmoiditis.", "Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis.", "Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study." ]

[ "Sixty patients who had presented recently with a relapse of mild to moderate ulcerative colitis with rectosigmoid involvement were randomly assigned to treatment with either 5-aminosalicylic acid enemas (N = 29) or oral sulfasalazine (N = 31). All patients were in remission, which was documented by clinical, histologic, and endoscopic criteria. Five-aminosalicylic acid treatment was administered on an intermittent schedule, consisting of 4 gm daily for the first seven days of each month; sulfasalazine was given as continuous therapy (2 gm daily as oral tablets). The study period was 2 years. Overall, 9 relapses occurred in the 5-aminosalicylic acid group and 12 occurred in the sulfasalazine group. The actuarial relapse rate at 12 months was 20 percent in the 5-aminosalicylic acid group and 24 percent in the sulfasalazine group; at 24 months, these rates were 37 and 43 percent, respectively. The actuarial relapse curves of the two groups were very similar. The relapse severity was also similar between the two groups. These results show that the authors proposed schedule of maintenance treatment with high-dose 5-aminosalicylic acid enemas is effective in subjects with rectosigmoiditis. This form of intermittent therapy may therefore be proposed for maintaining remission in patients who are refractory to oral and/or rectal treatment with sulfasalazine and steroids or who are intolerant or allergic to sulfasalazine. Treatment with 5-aminosalicylic acid enemas for seven days each month can also constitute an alternative for patients who favor the intermittent schedule over the classic continuous regimen of oral administrations.", "This prospective trial in patients with left-sided ulcerative colitis evaluated the efficacy and acceptability of biweekly high-dose 5-aminosalicylic acid (5-ASA) enemas (4g/100ml) in maintaining a remission recently induced using daily 5-ASA enemas. Thirty-one patients were randomly assigned, 16 to 5-ASA and 15 to oral sulphasalazine (2g/day), and examined monthly. Sigmoidoscopy was performed \"blind\" at six months or at clinical relapse. Twelve patients on 5-ASA (75%) and nine on sulphasalazine (60%) remained in clinical and endoscopic remission throughout the study (NS), and the survival curve for 5-ASA was better at all points (NS). No patient stopped therapy due to side effects, and all those on 5-ASA chose to continue rectal maintenance therapy after the study. It was concluded that biweekly 5-ASA enemas is at least as effective as oral sulphasalazine in maintaining remission in unselected patients whose remission has been achieve using local therapy.", "A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis.\n From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (< or = 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurrence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features.\n The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0-21) in the mesalazine b.i.d. group, 32% (95% CI: 16-49) in the mesalazine u.i.d. group, and 47% (95% CI: 29-65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up.\n The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.", "Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5-ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis.", "The efficacy of 5-aminosalicylic acid enemas in maintaining remission in left-sided ulcerative colitis was studied. Twenty-five patients in remission for at least 2 mo were randomized to receive either 1-g 5-aminosalicylic acid or placebo enemas daily and were followed up for 1 yr. Eleven of 13 patients randomized to placebo relapsed after a mean of 16 wk. Nine of 12 patients randomized to 5-aminosalicylic acid remained in remission for 1 yr, 2 others in remission withdrew by request, and 1 relapsed at 10 wk. The difference between relapse rate on 1-g 5-aminosalicylic acid versus placebo was significant (p less than 0.005). Seven patients entered the blinded trial a second time. Three of 4 patients randomized to 5-aminosalicylic acid remained in remission and 1 relapsed. Three randomized to placebo relapsed at a mean of 14 wk. One-gram 5-aminosalicylic acid enemas are safe and effective in maintaining remission in patients with left-sided ulcerative colitis.", "The aim of this study was to compare the efficacy of intermittent therapy with mesalazine enemas and continuous oral mesalazine to maintain remission of distal ulcerative colitis or proctitis.\n Thirty-eight patients with distal ulcerative colitis (n = 17) or ulcerative proctitis (n = 21) in clinical, endoscopic, and histologic remission were randomly assigned to receive either oral mesalazine (0.5 g three times/day, Eudragit L coating, n = 19) or intermittent therapy with mesalazine enemas (4 g of 5-aminosalicylic acid enema every third night, n = 19). Both groups were comparable in regard to sex, age, age at disease onset, extent and duration of disease, number and mode of treatment of previous attacks, and time in remission. Patients were reviewed at the beginning of the study and, subsequently, at two-month intervals for 24 months or until a relapse occurred. At each visit, diaries were reviewed and clinical and laboratory assessments were performed. Sigmoidoscopy was carried out and biopsies were obtained by a blinded observer. Histology was assessed without knowledge of the patient's clinical state or treatment category.\n At the end of the study, 6 of 19 patients on oral mesalazine (32 percent) and 14 of 19 patients on mesalazine enemas (74 percent) were still in full remission (log rank test: 15.28, P < 0.001). Differences in relapse rates between groups were significant even when data were stratified by extent of disease (P < 0.01). In the oral group, six and seven patients relapsed at 12 and 24 months, respectively. In the enema group, three and two relapses occurred in the first and second year of the study, respectively. All patients complied with the treatment satisfactorily and there were no dropouts.\n These results suggest that intermittent therapy with mesalazine enemas is more effective than continuous oral mesalazine in maintaining remission in patients with distal ulcerative colitis and proctitis.", "The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission.\n In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy).\n Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events.\n The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.", "Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis. Maintenance of remission with lower doses would be an advantage.\n The efficacy of mesalazine suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied.\n Ninety five patients with cryptogenetic proctitis were randomised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa (n = 48) or placebo (n = 47). In the case of a relapse, the patients received one suppository/day.\n It was found that 25 of 48 subjects v 18 of 47 remained in remission in the mesalazine and placebo groups respectively. The relapse rate was lower in the mesalazine group for the following time intervals: 0-90 days (19% v 38%, p = 0.035), 0-180 days (29% v 54%, p = 0.017), 0-270 days (38% v 60%, p = 0.031), and 0-365 days (48% v 62%, p = 0.18). Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively (p = 0.001). Overall, 61% v 28% patients remained in the protocol and were in remission at one year (p = 0.001). Tolerance was good.\n Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis. Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed." ]

[ "16101852" ]

[ "Effects of resident-oriented care on quality of care, wellbeing and satisfaction with care." ]

[ "In a resident-oriented care model applied in nursing homes, the residents are assigned to primary nurses. These primary nurses are responsible for the total care of the residents assigned to them. The purpose of the present study, using a pretest, post-test and control group quasi-experimental design, was to evaluate the effects of the implementation of resident-oriented care on the following aspects of quality of care: coordination of care, instrumental aspects, expressive aspects, resident wellbeing and satisfaction with care, and family satisfaction with care. The study was carried out on somatic and psycho-geriatric wards in three nursing homes in the Netherlands. Data were collected by questionnaires, interviews and observations. The results of the study showed that the intervention was partly successful in the experimental group. Some aspects of the resident-oriented care model were not clearly evident. Moreover, the effects on quality-of-care aspects were limited. The results revealed that the 'coordination of care' increased on half of the experimental wards. Furthermore, there was an indication that 'expressive aspects' changed in favour of the experimental wards. The implementation of resident-oriented care had no effect on resident wellbeing and satisfaction or on family satisfaction. Finally, the results are discussed in the light of some methodological limitations that often go together with intervention studies in the real world." ]

[ "17389293", "16263978", "18725823" ]

[ "Web-based proactive system to improve breast cancer screening: a randomized controlled trial.", "Using the internet to provide information prescriptions.", "Implementing an intervention to promote colon cancer screening through e-mail over the Internet: lessons learned from a pilot study." ]

[ "Screening mammography is recommended for early detection of breast cancer but screening rates remain suboptimal.\n A primary care portal for a large academic primary practice was developed for all preventive services. Another Web-based system (PRECARES [PREventive CAre REminder System]) was developed for appointment secretaries to manage proactive breast cancer screening. Female patients aged 40 to 75 years were randomly assigned to a control group (usual care) and an intervention group. For the intervention group, 2 monthly letters inviting patients to undergo mammography were sent starting 3 months before they were due for annual screening, followed by a telephone call to nonresponding patients. A subgroup of women employees was further randomized to receive a reminder by either US mail or e-mail.\n Of the total eligible population of 6665 women identified as having consented to participate in research, 3339 were randomly assigned to the control group and 3326 to the intervention group. The screening rate for annual mammography was 64.3% for the intervention group and 55.3% for the control group (P <.001). There were no significant differences between the 2 groups for any of the other adult preventive services. For the employee subgroup, the screening rate was 57.5% for the control group, 68.1% for the US mail group, and 72.2% for the e-mail group (intervention vs control, P <.001; e-mail vs US mail; P = .24).\n The breast cancer screening rate improved significantly with the practice redesign of having appointment secretaries proactively manage breast cancer screening needs.", "An information prescription is the provision of specific information to a patient on how to help manage a health problem. The Internet is being used increasingly as a source for information prescriptions, with clinicians directing patients to specific Web sites. As with any health care intervention, patients' lack of compliance is a barrier to the effectiveness of Web-based information prescriptions (WebIPs). WebIPs cannot be helpful if patients do not review the information prescribed for them.\n The main objective of this study was to quantify the percentage of families who visit a Web site that was specifically prescribed by their physician. In addition, the use of an e-mail reminder was used to determine if it increases the likelihood that families will visit the prescribed Web site. Finally, barriers to accessing the prescribed Web site were identified.\n Children were eligible if they presented to the pediatric gastroenterology clinic with chronic constipation and/or encopresis and their family had an active e-mail account and access to the Internet in their home. During their clinic visit, physicians instructed families to visit a Web site that provided educational information pertinent to their child's problem. Families were given a form with the Web-site address and a log-in identification number. Two days after their clinic visit, half of the families received an e-mail reminding them to visit the Web site. Families were contacted 1 week after their clinic visit to identify barriers to accessing the Web site.\n Eighty-three families participated in the study. Of the 83 families, 54 (65%) visited the prescribed Web site within 1 week of their clinic visit. Families who received e-mail reminders were significantly more likely to visit the Web site than families who did not receive an e-mail reminder (77% vs 53%). This difference could not be explained by the type or speed of Internet connection or how frequently they accessed the Internet or e-mail. The most common reasons that families cited for not accessing the Web site were \"I forgot\" and \"I didn't have time.\" Few families cited technical reasons for not accessing the Web site.\n Almost two thirds of the families given a WebIP logged on to the prescribed Web site. The probability that families would access the site was increased by 45% with an e-mail reminder. Clearly, e-mail prompts improve compliance to WebIPs. As content and treatment programs continue to proliferate on the Web, it is important to identify barriers and solutions to them to improve overall compliance.", "Colon cancer screening (CRCS) tests are underused. Multiple CRCS options may confuse patients and lead to inaction. E-mail between patients and physicians may raise awareness about CRCS and allow physicians to answer questions about test options.\n To develop and implement an electronic intervention, the InterNet LETter (NetLET), to increase interest in and use of CRCS among patients with and without e-mail access at home or work.\n During 2004-2005, 97 patients over 49 years old were recruited during a clinic visit. Patients with e-mail at home or work were assigned to the private access arm; patients without e-mail but willing to use the public library system were assigned to the public access arm. Within each arm, patients were randomized to the NetLET or control group. The NetLET consisted of a personalized e-mail from the physician reminding the patient to undergo CRCS and providing a link to a webpage with information about CRCS. Control groups were mailed a reminder letter from their physician. All were mailed a fecal occult blood test (FOBT) kit.\n In the public access intervention group, only 1 of 11 patients viewed the NetLET. In the private access intervention group, 10 of 42 viewed it. Eleven of 42 (26%) private access intervention group participants, and 8 of 35 (23%) private access control group participants returned an FOBT. No public access intervention group patients, but 3 of 9 control group patients, returned an FOBT.\n We concluded that it was not feasible to implement the NetLET, but reasons for lack of success differed for the private and public access arms." ]

[ "15265847", "9917116", "12915827", "12390953", "12505222", "8726243", "16140708" ]

[ "Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial.", "Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial.", "Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial.", "Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin.", "Early statin therapy restores endothelial function in children with familial hypercholesterolemia.", "Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia.", "Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia." ]

[ "Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children.\n To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia.\n Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years.\n Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands.\n After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108).\n The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels.\n Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], -0.010 [0.048] mm; P =.049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P =.28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P =.02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (-24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups.\n Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.", "Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).\n To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH.\n One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994.\n Fourteen pediatric outpatient clinics in the United States and Finland.\n Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively.\n Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo.\n The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development.\n Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation.\n This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.", "To determine the safety and efficacy of atorvastatin (10 to 20 mg) in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia.\n Subjects (n=187) were randomly assigned to 26 weeks of treatment with atorvastatin (10 mg) or placebo. Dosage was increased to 20 mg if LDL cholesterol (LDL-C) levels remained >3.4 mmol/L (130 mg/dL) at week 4. At week 26, subjects received 10 mg of atorvastatin for an additional 26 weeks. Efficacy variables included percent changes in LDL-C, total cholesterol, triglycerides, HDL cholesterol, and apolipoprotein B from baseline to week 26.\n Atorvastatin caused a highly significant reduction in LDL-C compared with placebo (-40% vs -0.4%, respectively; P<.001). Percent changes at week 26 also significantly favored atorvastatin for total cholesterol (-32% vs -1.5%; P<.001), triglycerides (-12% vs +1.0%; P=0.03), and apolipoprotein B (-34% vs +0.7%; P<.001), with a significantly greater increase in HDL cholesterol with atorvastatin compared with placebo (+2.8% vs -1.8%; P=.02). Atorvastatin was as well-tolerated as placebo.\n Treatment with atorvastatin for 12 months was effective and safe for pediatric subjects with known familial hypercholesterolemia or severe hypercholesterolemia.", "A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH).\n A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. After 48 weeks of simvastatin therapy, there were significant reductions of LDL cholesterol (-41%), total cholesterol (-31%), apolipoprotein B (-34%), VLDL cholesterol (-21%), and triglyceride (-9%) levels. HDL cholesterol and apolipoprotein A-I levels were increased by 3.3% and 10.4%, respectively (not significant). No safety issues became evident. Except for small decreases in dehydroepiandrosterone sulfate compared with placebo, there were no significant changes from baseline in adrenal, gonadal, and pituitary hormones in either treatment group.\n Simvastatin significantly reduced LDL cholesterol, total cholesterol, triglyceride, VLDL cholesterol, and apolipoprotein B levels and was well tolerated in children with heFH. There was no evidence of any adverse effect of simvastatin on growth and pubertal development. Therefore, simvastatin at doses up to 40 mg is a well-tolerated and effective therapy for heFH children.", "This study was designed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia (FH).\n Endothelial function measured by flow-mediated dilation of the brachial artery (FMD) is used as a surrogate marker of cardiovascular disease (CVD). Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD.\n The study included 50 children with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed at baseline and at 28 weeks of treatment.\n At baseline, FMD was impaired in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH group, FMD improved significantly, whereas the FMD remained unaltered in the placebo FH group throughout the study period (absolute increase 3.9% +/- 4.3% vs. 1.2% +/- 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level similar to the non-FH controls (15.6% +/- 6.8% vs. 15.5% +/- 5.4%, p = 0.958). Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (-2.16 +/- 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (-2.13 +/- 0.99 mmol/l, 39.8%). The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC (r = -0.31, p < 0.05) and LDL-C (r = -0.31, p < 0.05).\n Our data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH. These results emphasize the relevance of statin therapy in patients with FH at an early stage, when the atherosclerotic process is still reversible.", "The safety, tolerability, and efficacy of a 12-wk treatment with pravastatin, 5, 10, and 20 mg/d, was evaluated in 72 children with heterozygous familial hypercholesterolemia (FH) in a double-blind, randomized and placebo-controlled study. The results show that pravastatin was well tolerated and that adverse events were mild and equally distributed among the three treatment groups. Plasma total and LDL cholesterol levels were significantly reduced in all pravastatin treatment groups, in comparison with the control group; -24.6% (-28.1 to 21.0) and -32.9% (-37.0 to -28.6), for mean change and 95% confidence interval, respectively. In four children plasma LDL cholesterol levels were reduced within normal limits for sex and age. HDL cholesterol increased in the pravastatin 20-mg group, +10.8% (+3.4 to +18.8), whereas plasma apo B100 and very LDL (VLDL) cholesterol levels were reduced within all pravastatin-treated groups -26.8% (-31.2 [corrected] to -21.7) and -24.5% (-35.0 to -12.3). These data show that short-term pravastatin treatment of children with FH is safe and effective, although long-term dose titration studies with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors need to be performed, to reduce plasma LDL cholesterol levels below a predefined level. The results of these studies have to be awaited before new treatment strategies are to be considered in these children.", "The present study was designed to evaluate the lipid-altering efficacy, safety, and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia.\n A total of 54 postmenarchal girls, aged 10 to 17 years, were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. After a 4-week diet/placebo run-in period, patients were randomized to 1 of 2 groups: (1) treatment with diet plus lovastatin 20 mg/day for 4 weeks, followed by diet plus lovastatin 40 mg/day for 20 weeks, or (2) diet plus placebo for 24 weeks.\n Baseline values of lipids, lipoproteins, and apolipoproteins (apo) were comparable between treatment groups. Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23% to 27%, total cholesterol by 17% to 22%, and apo B by 20% to 23% at weeks 4 and 24, respectively. Between-treatment group differences were not statistically significant for triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apo A-I. Lovastatin was generally safe and well tolerated. There were no clinically significant alterations in vital signs (blood pressure and pulse rate), anthropomorphic measurements (height, weight, and BMI), hormone levels (luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, estradiol, and cortisol), menstrual cycle length, or tests of liver and muscle function.\n Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia." ]

[ "9870832", "9081359", "2182447", "12447954", "10865914", "8156515", "8172437", "7935568", "9462438", "10808206", "8922787" ]

[ "A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia.", "Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial.", "Management of fungal infection in neutropenic patients with fluconazole.", "Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation.", "Early empiric antifungal therapy of infections in neutropenic patients comparing fluconazole with amphotericin B/flucytosine.", "Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B.", "Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B.", "Fluconazole versus oral amphotericin B in preventing fungal infection in chemotherapy-induced neutropenic patients with haematological malignancies.", "Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer.", "Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group.", "Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature." ]

[ "Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated.\n We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection.\n Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia.\n These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.", "Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.", "Fluconazole is a new orally absorbed antifungal azole which is effective in the treatment of mucosal and systemic infections caused by Candida, cryptococci and other fungi. In view of its favourable efficacy, safety and pharmacokinetic profile it was considered appropriate to evaluate its use prophylactically in patients undergoing a period of neutropenia. Two hundred and forty-eight patients receiving chemotherapy and/or bone marrow transplantation for the treatment of acute leukaemia, lymphoma or aplastic anaemia, and expected to be rendered temporarily neutropenic, have been entered into an ongoing multicentre comparative clinical study to compare the prophylactic efficacy of 50 mg daily oral fluconazole with that of widely used regimens of oral polyenes. The incidence of suspected fungal infection was less in the fluconazole group (27%) than in the polyene group (45%), the difference being statistically significant (P less than 0.05). Only one of the suspected infections in the fluconazole group was confirmed mycologically compared with 17 in the polyene group. Fluconazole prophylaxis was well tolerated and it therefore offers a promising new approach to the management of fungal infection in the neutropenic patient. Further studies are warranted to define the optimum dosage for use in this situation.", "Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.\n Copyright 2002 Wiley-Liss, Inc.", "We compared the efficacy and tolerability of fluconazole (FCA) with amphotericin B/flucytosine (ABF) in neutropenic patients with haematological malignancies. Antifungal therapy started on day 4 when fever was unresponsive to antibiotics or on day 1 together with the antibiotics, if there was evidence of mycosis. If patients did not respond to FCA after 7 days they switched to ABF. 98 patients, 51 FCA and 47 ABF were included in the study. Response to fever was achieved in 28/51 FCA patients and in another 16 after switching to ABF. So in overall 44/51 (86.2%) of the FCA and 37/47 (78.8%) of the ABF group defervescence was observed. 46 patients (21 FCA, 25 ABF) developed radiological signs of pneumonia. Resolution of infiltrates was achieved in 5/21 FCA and 20/25 ABF patients, and another 10 of 15 initially not responding patients showed regression when switched to ABF, 5 of these had highly suspected aspergillosis. Adverse events occurred in 19.6% of FCA and 97.9% of ABF patients. In conclusion fluconazole and amphotericin B/flucytosine seem to be equally effective. In view of its lower toxicity fluconazole may be preferred as first line empiric antifungal agent, but in case of nonresponse, pneumonia or aspergillosis it may be replaced by amphotericin B combined with flucytosine.", "Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis.\n Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity.\n Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02).\n At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.", "To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.\n A randomized, controlled, multicenter trial.\n 30 hematologic units in tertiary care or university hospitals.\n 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.\n Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.\n An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.\n Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).\n Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.", "This open, randomized, controlled study was designed to assess the efficacy of fluconazole in comparison with oral amphotericin B in preventing clinically suspected fungal infection. A total of 178 chemotherapy-induced neutropenic episodes expected to last more than 10 days in 51 patients with haematological malignancies were randomly treated with fluconazole, 200 mg once a day, or amphotericin B, 800 mg three times a day orally. Defining the end points as (1) documented fungal infection or (2) use of empiric intravenous amphotericin B for suspected fungal infection including an episode of fever lasting more than 5 days or fever developed during the use of broad-spectrum antibiotics, no difference was observed between the two groups.", "An open, prospective, randomized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing candida infections in 50 children undergoing remission induction or consolidation therapy for cancer. In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful. Mild and transient oropharyngeal candidosis was observed in two and three patients in the fluconazole and nystatin groups respectively. One patient randomized to fluconazole and two patients randomized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven candida colitis. Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms. Initially colonized patients stayed colonized throughout treatment although at the end of the study, more patients randomized to nystatin were still harbouring yeasts (P = 0.05). Almost exclusively, Candida albicans (95%) was isolated. A change in species was observed in one patient in each arm of the study. Candida krusei or Candida glabrata were not encountered. Transient elevations of hepatic transaminases were more common in the fluconazole group, although not statistically significant (28% vs 12%, P = 0.15). Reversible grade I gastrointestinal and skin symptoms were observed in four patients randomized to fluconazole (16 vs 0%, P < 0.05). Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive candida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer.", "Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.", "We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections." ]

[ "367511", "2285001", "3537823" ]

[ "New approach to treatment of recent stroke.", "A randomized double-blind controlled trial of naftidrofuryl in acute stroke.", "Towards a model stroke trial. The single-centre naftidrofuryl study." ]

[ "Ninety-one patients with acute stroke participated in a double-blind, placebo-controlled trial of naftidrofuryl. Treatment was allocated at random and given over 12 weeks, neurological and neurophysical scores being obtained before treatment and at weeks 2, 4, 8, and 12. Both treatment groups greatly improved over the 12 weeks, but the naftidrofuryl-treated patients made greater neurological progress. Of the patients eventually discharged, those given naftidrofuryl spent only half as long in hospital as the controls. Deaths attributable to stroke were significantly fewer in the active-treatment group.", "There is evidence to support the use of naftidrofuryl in acute stroke with claims of increased recovery, reduced fatality and reduced bed occupancy in patients treated with either oral or intravenous preparations. One hundred patients presenting with acute hemisphere stroke (less than 72 hours) were randomized to receive either a new oral formulation of naftidrofuryl or placebo on a double-blind basis. Treatment was given for a total of 12 weeks and patients followed for 26 weeks with serial neurological and functional assessments by a single observer. Cumulative fatality and hospital-bed occupancy were determined at each assessment interval. No significant difference was demonstrated in cumulative fatality, hospital-bed occupancy or recovery of motor function in patients treated with either naftidrofuryl or placebo. There is no evidence from this study to support the use of oral naftidrofuryl in acute stroke.", "It has been questionable whether the lack of proven pharmacological treatments in acute cerebral infarction (ACI) reflects ineffective drugs or only inadequacies in their assessment. The difficulties in developing a rationale for drug therapy in this condition favoured the former, although the latter possibility was supported by re-evaluation of most published trials. In this paper, a plausible rationale, in terms of our current understanding of both the drug and the condition, is expounded for treatment of ACI with naftidrofuryl. Guidelines for the design and conduct of clinical trials in acute stroke are discussed in relation to the particular problems posed: need for early initiation of treatment; need for, and difficulties of, diagnostic confirmation; matching of treatment groups by prognostic indicators of uncertain significance, and requirements for large numbers of patients and long-term follow-up. The practical application of these guidelines is tested in a clinical trial of naftidrofuryl conducted in a single centre on 100 patients with proven diagnoses. Rigorous attention to all aspects of selection, treatment and follow-up, with an explanatory approach to the trial design, was predicted to produce a positive result if the drug was effective. The findings were that naftidrofuryl treatment was associated with no change in death rate but with clinically and statistically significant improvements in neurological recovery and bed-occupancy. Better functional recovery was also noted, so that the trial result was coherent. It was concluded that a beneficial effect had been recorded, and consistency of this outcome with those of previous studies is demonstrated. A case is made for further studies to define exactly the role of this drug in the management of ACI." ]

[ "12785023", "10917577", "12614412", "4608096", "7943585", "371740" ]

[ "Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).", "Endovascular sclerotherapy, surgery, and surgery plus sclerotherapy in superficial venous incompetence: a randomized, 10-year follow-up trial--final results.", "Ambulatory phlebectomy versus compression sclerotherapy: results of a randomized controlled trial.", "Surgery and sclerotherapy in the treatment of varicose veins. A random trial.", "Randomized trial of stripping versus high ligation combined with sclerotherapy in the treatment of the incompetent greater saphenous vein.", "The value of different forms of treatment for varicose veins." ]

[ "The study compared, by a prospective, randomized method, 6 treatment options: A: Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclerotherapy; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occurrence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. \"Standard,\" low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.", "The study was planned to evaluate efficacy and costs of endovascular sclerotherapy (ES) in comparison with surgery and surgery associated with sclerotherapy in a prospective (10-year follow-up), good-clinical-practice study. Patients with varicose veins and pure, superficial venous incompetence were included. Of the patients randomized into the three groups 39 (group A) were treated with ES, 40 (B) with surgery + sclerotherapy, and 42 with surgery only (C). Surgery consisted of ligation of the SFJ (saphenofemoral junction) and of incompetent veins detected with color duplex. Of the preselected 150 patients, 121 subjects entered the study; 96 completed the 10-year follow-up (mean age 52.6 +/- 6 years; 51 men, 45 women). Dropouts were due to nonmedical problems. At 10 years no incompetence was observed in subjects treated with SPJ ligation (B and C). In the ES group 18.8% of the SFJs were patent and incompetent and in 43.8% of limbs the distal (below-knee) venous system was still incompetent [16.1% in the surgery + sclerotherapy group (p < 0.05) and 36% in the group treated with surgery only (p < 0.05 vs B and 0.05 vs A)]. Color duplex of the long saphenous vein indicated atrophy or obstruction of a segment (average 6.7 cm) after SFJ ligation (4.2 cm after ES). The cost of ES was 68% of surgery while the cost of surgery and sclerotherapy was 122% of surgery only. Endovascular sclerotherapy is an effective, cheaper treatment option, but surgery after 10 years is superior.", "Although no randomized controlled trial has assessed the effects of either compression sclerotherapy or ambulatory phlebectomy, both techniques are used to treat varicose veins worldwide. We performed a randomized controlled trial to compare recurrence rates of varicose veins and complications after compression sclerotherapy and ambulatory phlebectomy.\n From September 1996 to October 1998, we randomly allocated 49 legs to compression sclerotherapy and 49 legs to ambulatory phlebectomy. Our primary outcome parameters were as follows: recurrence rates at 1 and 2 years and complications related to therapy. Eighty-two patients were included, of whom 16 were included with both of their legs. The number of treated legs was therefore 98, but two patients were lost to follow-up.\n One year recurrence amounted to 1 out of 48 for phlebectomy and 12 out of 48 for compression sclerotherapy (P<0.001); at 2 years, six additional recurrences were found, but then solely for compression sclerotherapy (P<0.001). Significant differences in complications occurring more in phlebectomy than in compression sclerotherapy therapy were blisters, teleangiectatic matting, scar formation, and bruising from bandaging.\n Our results show that ambulatory phlebectomy is an effective therapy for varicose veins of the leg. Recurrence rates are significantly lower than for compression sclerotherapy therapy. If varicose veins persist 4 weeks after compression sclerotherapy, it can be argued that to reduce the risk of future recurrence ambulatory phlebectomy should be considered as the better treatment option.", "nan", "This prospective randomized study compared the treatment of greater saphenous vein insufficiency by stripping and local avulsions of varicose veins with high ligation of the saphenofemoral junction (crossectomy) combined with sclerocompression therapy. Of 156 consecutive patients, 89 legs were randomly allocated to stripping and 92 to high ligation. At follow-up of 3 months and 1, 2, and 3 years after treatment, clinical and Doppler ultrasound results, and complaints and cosmetic results, as judged by the patient and the surgeon, were scored. At 3 years, 69 limbs in the stripping group (78%) and 73 limbs in the ligation group (79%) were available to follow-up. The cosmetic results, both judged by the patient and the surgeon, were significantly better (P < 0.05) in the stripped limbs than in the limbs with high ligation and sclerotherapy. Clinical and Doppler ultrasound evidence of reverse flow in the saphenous vein was significantly less (P < 0.001) after the stripping operation. The results of treatment of isolated saphenous vein insufficiency by stripping operation, therefore, were superior to those obtained by high ligation combined with sclerotherapy.", "nan" ]

[ "13030591", "14933493", "14771191", "13104505" ]

[ "Effect of stilbestrol on pregnancy compared to the effect of a placebo.", "The use of diethylstilbestrol in threatened abortion.", "The management of threatened abortion: A study of 100 cases.", "Does the administration of diethylstilbestrol during pregnancy have therapeutic value?" ]

[ "nan", "nan", "nan", "nan" ]

[ "3539028", "1560798" ]

[ "Respiratory distress syndrome and inositol supplementation in preterm infants.", "Inositol supplementation in premature infants with respiratory distress syndrome." ]

[ "We report a randomised double blind trial of myo-inositol (inositol) supplementation for 10 days in 74 preterm infants with a birth weight less than 2000 g (mean gestational age 29.5 weeks and mean birth weight 1266 g). All infants required artificial ventilation for treatment of respiratory distress syndrome. Inositol (120-160 mg/kg/day) was administered by the ingastric or intravenous route. The 37 infants who received inositol supplementation required less mechanical ventilation during days 4-10, had less failures of indomethacin to close ductus arteriosus, and had less deaths or bronchopulmonary dysplasia, or both, than the infants treated with placebo. There were no detectable adverse effects. These preliminary results suggest that inositol is an important nutrient in immature preterm infants.", "Inositol influences cellular function and organ maturation. Feeding premature infants inositol-rich breast milk increases their serum inositol concentrations. Whether inositol supplementation benefits infants receiving fluids for parenteral nutrition, which are inositol-free, is not known.\n We carried out a placebo-controlled, randomized, double-blind trial to determine the effects of administering inositol (80 mg per kilogram of body weight per day) during the first five days of life to 221 infants with respiratory distress syndrome who were receiving parenteral nutrition (gestational age, 24 to 32 weeks; birth weight, less than 2000 g). All the infants were treated with mechanical ventilation and some with surfactant as well. The primary end point was survival at 28 days without bronchopulmonary dysplasia.\n The 114 patients given inositol had significantly lower mean requirements for inspiratory oxygen (P less than 0.01) and mean airway pressure (P less than 0.05) from the 12th through the 144th hour of life than did the 107 infants given placebo. Eighty-one infants given inositol and 51 given placebo survived without bronchopulmonary dysplasia (71 vs. 55 percent; P = 0.005). In the 65 infants given surfactant, however, inositol had no effect on the degree of respiratory failure. Thirteen infants given inositol and 21 given placebo had retinopathy of prematurity (13 vs. 26 percent; P = 0.022); none of the infants given inositol had stage 4 disease, whereas 7 of those given placebo did (0 vs. 9 percent; P = 0.012). Among the infants given placebo, those who had poor outcomes (death, bronchopulmonary dysplasia, or stage 4 retinopathy of prematurity) had lower serum inositol concentrations during days 2 through 7 than those who had good outcomes (P less than 0.01).\n The administration of inositol to premature infants with respiratory distress syndrome who are receiving parenteral nutrition during the first week of life is associated with increased survival without bronchopulmonary dysplasia and with a decreased incidence of retinopathy of prematurity." ]

[ "4264387", "8219559", "8090293", "8911400", "2647051", "15234692", "16325694", "1835704" ]

[ "Aortoiliofemoral thromboendarterectomy vs bypass graft. A randomized study.", "Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial. Principal investigators and their Associates of Veterans Administration Cooperative Study Number 199.", "[Spinal cord electric stimulation vs. femoro-distal bypass in critical ischemia of the legs. Preliminary results in a randomized prospective study].", "Surgical revascularization versus thrombolysis for nonembolic lower extremity native artery occlusions: results of a prospective randomized trial. The STILE Investigators. Surgery versus Thrombolysis for Ischemia of the Lower Extremity.", "Intermittent claudication--surgical reconstruction or physical training? A prospective randomized trial of treatment efficiency.", "Angioplasty or bypass for superficial femoral artery disease? A randomised controlled trial.", "Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial.", "Chronic lower limb ischaemia. A prospective randomised controlled study comparing the 1-year results of vascular surgery and percutaneous transluminal angioplasty (PTA)." ]

[ "nan", "Surgical revascularization and angioplasty (PTA) are effective therapies for patients with peripheral arterial disease, but there are no data on long-term survival, limb salvage, and hemodynamic status from a randomized study of such patients. A multicenter, prospective trial compared PTA with bypass surgery (BP) in 263 men who had iliac, femoral, or popliteal artery obstruction.\n Lesions in the iliac versus the femoropopliteal artery and rest pain versus claudication were separately randomized to the two treatment interventions. One hundred twenty-six patients underwent BP, 129 patients underwent PTA, and eight patients were not treated for lower extremity ischemia.\n Three operative deaths occurred in the BP group and none in the PTA group. For the entire study, average annual mortality was higher in the BP group, but survival was not significantly different on life-table analysis (P = .08). Primary success favored BP, while limb salvage favored PTA, but differences were not statistically significant (P = .08 and .35, respectively). Patients with iliac disease or claudication fared better, but there was no statistical difference in response to PTA or BP.\n Patients in both treatment groups had prompt and sustained increases in hemodynamics and quality of life. This study of patients randomly assigned to BP or PTA shows no significant difference in outcomes during a median follow-up of 4 years.", "In the last few years the development of new and improved surgical procedures caused a more aggressive approach, by femoro-distal bypass, to the limb affected by critical ischaemia. A good surgical result is related to the crural vessel patency, the presence of an adequate autologous vein and the possibility to visualize inframalleolar and foot arteries by selective angiograms. Should all these conditions not be present, an outflow procedure might be at high risk for failure. On the other hand, several studies show that SCS relieves rest pain and improves trophic lesion healing although there is no evident increase in peripheral blood flow, but these studies refer to heterogeneous non-randomized patients. In order to evaluate the effectiveness of SCS compared to distal arterial reconstruction, we started this prospective and randomized study. In a period of 15 months, 12 patients affected by critical limb ischaemia at 4th stage of Fontaine with angiographic multilevel distal lesions were randomised for SCS (7 cases: group A) and distal bypass (5 cases: group B). The result of the therapy was judged as good or fair when either complete or evident pain regression and trophic lesion healing were obtained; otherwise the result was considered as poor. Actually the study is in progress, the follow-up is partial (3-12 months), the results are preliminary. In the patients of group A the results were good or fair in 5 cases (72%) and poor in 2 (28%). In the patients of group B the results were good or fair in 2 cases (40%) and poor in 3 (60%).(ABSTRACT TRUNCATED AT 250 WORDS)", "Early results of a prospective study that compared surgical revascularization and thrombolysis for lower extremity arterial and graft occlusions have been published. This report details the final results in patients who have native artery occlusions.\n Two hundred thirty-seven patients who had lower extremity ischemia as a result of iliac-common femoral (IF; 69 patients) or superficial femoral-popliteal (FP; 168 patients) occlusion, and had symptomatically deteriorated within the past 6 months were randomized to catheter-directed thrombolysis (150 patients) or surgical revascularization (87 patients). After diagnostic arteriographic examination but before randomization, the optimal surgical procedure was determined. Lytic patients were randomized to recombinant tissue plasminogen activator (rt-PA; 84 patients) or urokinase (UK; 66 patients). Recurrent ischemia, morbidity, amputation, and death rates were determined at 30 days, 6 months, and 1 year, and were analyzed on an intent-to-treat basis.\n For patients randomized to lysis, a catheter was properly positioned and the lytic agent delivered in 78%. This provided a reduction in the predetermined surgical procedure in 58% of patients who had an FP occlusion and 51% of those who had an IF occlusion. rt-PA and UK were equally effective and safe, but lysis time was shorter with rt-PA (8 vs 24 hr; p < 0.05). At 1 year, the incidence of recurrent ischemia (64% vs 35%; p < 0.0001) and major amputation (10% vs 0%; p = 0.0024) was increased in patients who were randomized to lysis. Factors associated with a poor lytic outcome included FP occlusion, diabetes, and critical ischemia. No differences in mortality rates were observed at 1 year between the lysis and surgical groups.\n Surgical revascularization for lower extremity native artery occlusions is more effective and durable than thrombolysis. Thrombolysis used initially provides a reduction in the surgical procedure for a majority of patients; however, long-term outcome is inferior, particularly for patients who have an FP occlusion, diabetes, or critical ischemia.", "This study reports the initial evaluation of treatment efficiency in 75 patients with intermittent claudication who were randomized to three treatment groups: 1) reconstructive surgery, 2) reconstructive surgery with subsequent physical training, and 3) physical training alone. Before treatment, there were no statistically significant differences between the groups in age, sex, smoking habits, symptom duration of claudication, ankle-arm blood pressure quotient (ankle-index), maximal plethysmographic calf blood flow, symptom-free and maximal walking distance, the history of other atherosclerotic manifestations or in the medical treatment. The walking performance was improved in all three groups at follow-up 13 +/- 0.5 months after randomization. Surgery was most effective, but the addition of training to surgery improved the symptom-free walking distance even further. In pooled observations of the three groups, age, symptom duration, and a history of myocardial ischemic disease correlated negatively with walking performance after treatment. In the operated group, the duration of claudication and a history of myocardial ischemic disease correlated negatively with the walking performance. This was not the case when patients were censored if limited by other symptoms than intermittent claudication after treatment. In the trained group, the duration of claudication correlated negatively to symptom-free and maximal walking distance. Ankle-index and maximal plethysmographic calf blood flow after treatment and the change of these variables with treatment correlated positively with both symptom-free and maximal walking distance when results were pooled for all patients. Although this mainly was a consequence of the improved blood flow after surgery, the change of maximal plethysmographic calf blood flow also correlated with symptom-free but not with maximal walking distance in the trained group. The results demonstrate that, compared with physical training alone, operation alone or in combination with subsequent training are superior treatment modalities in patients with intermittent claudication.", "To evaluate whether angioplasty or above-knee bypass is the best treatment for symptomatic superficial femoral artery occlusive lesions, we performed a multicentre randomised trial.\n Between October 1995 and August 1998, 56 patients were enrolled, all with symptoms related to a 5-15 cm long occlusive lesion of the superficial femoral artery. Thirty-one patients were randomly assigned to percutaneous transluminal angioplasty (PTA); 25 patients to bypass surgery. All patients were followed at 1, 6 and 12 months after the procedure. The primary outcome of our study was re-occlusion of the femoral artery.\n Thirty patients underwent the allocated PTA and 24 patients underwent bypass surgery. Cumulative 1-year primary patency after PTA was 43 and 82% after bypass surgery. After PTA more than half of the patients had a re-occlusion with an absolute risk reduction of 31% (CI: 6-56%) in favour of bypass surgery. The hazard ratio for occlusion comparing PTA with bypass surgery is 2.24 (95% CI: 0.9-5.58).\n Despite 18 participating centres only 56 patients were randomised to PTA our bypass surgery. Based on our results, for every three patients treated with bypass surgery instead of PTA, one additional re-occlusion is prevented. Therefore, we conclude that with respect to patency, for long superficial femoral artery (SFA) stenoses or occlusions, surgery is better than PTA.", "The treatment of rest pain, ulceration, and gangrene of the leg (severe limb ischaemia) remains controversial. We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty in such patients.\n We randomly assigned 452 patients, who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease, to receive a surgery-first (n=228) or an angioplasty-first (n=224) strategy. The primary endpoint was amputation (of trial leg) free survival. Analysis was by intention to treat. The BASIL trial is registered with the National Research Register (NRR) and as an International Standard Randomised Controlled Trial, number ISRCTN45398889.\n The trial ran for 5.5 years, and follow-up finished when patients reached an endpoint (amputation of trial leg above the ankle or death). Seven individuals were lost to follow-up after randomisation (three assigned angioplasty, two surgery); of these, three were lost (one angioplasty, two surgery) during the first year of follow-up. 195 (86%) of 228 patients assigned to bypass surgery and 216 (96%) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median (IQR) of 6 (3-16) and 6 (2-20) days after randomisation, respectively. At the end of follow-up, 248 (55%) patients were alive without amputation (of trial leg), 38 (8%) alive with amputation, 36 (8%) dead after amputation, and 130 (29%) dead without amputation. After 6 months, the two strategies did not differ significantly in amputation-free survival (48 vs 60 patients; unadjusted hazard ratio 1.07, 95% CI 0.72-1.6; adjusted hazard ratio 0.73, 0.49-1.07). We saw no difference in health-related quality of life between the two strategies, but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy.\n In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty, a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angioplasty.", "In a prospective randomised study, performed over a 6-year period, 102 patients with severe lower limb ischaemia or claudication resistant to exercise training were randomised either to percutaneous transluminal angioplasty (PTA) or vascular surgery. Only patients who could be treated by both methods were included, constituting only 5% of the total number of patients treated during this period. The two groups were similar regarding age, severity of symptoms and diabetes. The immediate and 1-year results showed similar success and complication rates. There was, however, a significantly shorter hospital stay for patients treated with PTA. Due to early complications and initial failures PTA should, however, only be used in institutions where vascular surgical facilities are available since PTA demands access to such treatment." ]

[ "10791373", "11252361", "15629605", "2064591" ]

[ "Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group.", "A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma.", "Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency.", "Local thermo-radiotherapy in carcinoma cervix: improved local control versus increased incidence of distant metastasis." ]

[ "Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy.\n The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat.\n Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up.\n Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.", "To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas, both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated. Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis, combined with iridium 192 high-dose-rate intracavitary brachytherapy. All patients were divided randomly into the following two groups: the radiotherapy (RT) group of 20 patients, who underwent radiotherapy alone; and the thermoradiotherapy (TRT) group of 20 patients, who underwent three sessions of hyperthermia in addition to radiotherapy. The primary endpoint of this study was local complete response and survival. A complete response was achieved in 50% (10 of 20) in the RT group versus 80% (16 of 20) in the TRT group (p = 0.048). The 3-year overall survival and disease-free survival of the patients who were treated with TRT (58.2 and 63.6%) were better than those of the patients treated with RT (48.1 and 45%), but these differences were not significant. The 3-year local relapse-free survival of the patients who were treated with TRT (79.7%) was significantly better than that of the patients treated with RT (48.5%) (p = 0.048). TRT, as delivered in this trial, was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone. TRT resulted in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma.", "Hyperthermia can be used to enhance the effects of radiation, and a combined treatment may, in some circumstances, be an advantage. Uterine cervical cancer is very common in developing countries. The control of locally advanced pelvic tumors is difficult with conventional treatment modalities. Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques, radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospective randomized trial sponsored by the International Atomic Energy Agency. The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control, compared with radiotherapy alone.\n A total of 110 patients with biopsy-proven, locally advanced carcinoma of the uterine cervix were randomized to treatment by radiotherapy with or without hyperthermia. The patients were stratified by institution, stage, and histologic type. Each patient received external beam radiation therapy and brachytherapy. For the patients randomized to receive hyperthermia, a minimum of five sessions (60 min each, once per week) were administered, employing a radiofrequency (RF) capacitive heating device. Intratumoral temperature was measured at the first hyperthermic treatment, and at least once more during the course of treatment. The equipment and the policies and procedures at each participating institution except one (Pusan) were personally inspected at least once by the corresponding author, to ensure that quality assurance procedures were in place and were followed for treatment according to the protocol guidelines. The median follow-up period was 466 days for all the patients and 512 days for the surviving patients.\n The two arms were well balanced with regard to the patient factors, tumor factors, and treatment factors. The overall survival rate at 3 years was 73.2%, and the local control rate was 68.5%. There were no significant differences between the patients treated with or without hyperthermia, either with regard to the survival (p = 0.1893) or the rate of local control (p = 0.58). The survival was significantly worse among the patients with Stage IIb disease who received hyperthermia (p = 0.0162) although there was no difference in their rate of local control (p = 0.7988). Further analysis is necessary to determine if the difference in survival is due to a greater incidence of distant metastases or some other cause. Acute Grade 2-3 toxicity was seen in 10/55 patients (18%) treated by hyperthermia and in 2/55 of the patients (4%) treated without hyperthermia (p = 0.01). There was no significant difference in the late toxicity observed in the two arms.\n This prospective randomized study failed to show any benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced carcinoma of the uterine cervix. The acute toxicity was significantly greater among the patients receiving hyperthermia, and the survival was significantly worse among the Stage IIb patients receiving hyperthermia even though there was no difference in the local control rate.", "In 1986, 50 patients with stages II and III carcinoma of the cervix were entered into this prospective randomized study. Twenty-five cases (Group I) were treated only by radical radiation whereas remaining 25 cases (Group II) received local hyperthermia in addition to radical radiation. Hyperthermia was delivered by intracavitary brachyhyperthermia approach using an endotract applicator. Both the groups were followed up for a minimum period of 18 months. Group II patients achieved better local control (14 out of 20 evaluable cases) than the Group I patients (11 out of 22 evaluable cases). A disturbing observation was the increased incidence of distant metastasis in Group II (4 out of 23 cases) as compared to Group I (1 out of 23 cases), though most of them remained disease free locally. The increasing use of hyperthermia in the management of various cancers needs to be reviewed in this context." ]

[ "15379121", "17374742", "15044693", "17649720", "21385856", "20018913", "12393590", "12384411" ]

[ "[Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias].", "A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARalpha transcript after consolidation therapy: the Japan Adult Leukemia Study Group (JALSG) APL97 study.", "All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia.", "[Application of all-trans retinoic acid combining chemotherapy and As4S4 in the maintenance treatment of patients with acute promyelocytic leukemia].", "AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance.", "Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience.", "All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol.", "Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up." ]

[ "To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial.\n The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant.\n 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03).\n The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.", "To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RARalpha at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n = 89) or observation (n = 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P = .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P = .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RARalpha fusion transcript after 3 courses of intensive consolidation therapy.", "Both all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, As(2)O(3), and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RAR alpha (promyelocytic leukemia-retinoic acid receptor alpha) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high (> or =90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RAR alpha transcripts at CR decreased more significantly in combined therapy as compared with ATRA or As(2)O(3) mono-therapy (P < 0.01). This difference persisted after consolidation (P < 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed (P < 0.05) after a follow-up of 8-30 months (median: 18 months). Synergism of ATRA and As(2)O(3) on apoptosis and degradation of PML-RAR alpha oncoprotein might provide a plausible explanation for superior efficacy of combination therapy in clinic. In conclusion, the ATRA/As(2)O(3) combination for remission/maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival.", "To compare the efficacy of all-trans retinoic acid (ATRA) combining chemotherapy and As4S4 with ATRA combining chemotherapy for the maintenance treatment of patients with acute promyelocytic leukemia (APL).\n Sixty patients with APL induced to complete remission by ATRA and consolidated by chemotherapy were randomly divided into two groups. Thirty patients as As4S4 group received ATRA + As4S4 + chemotherapy, and another thirty patients as non-As4S4 group were treated only with ATRA + chemotherapy as maintenance therapy. The therapeutic effects, side effects and PML-RARalpha gene expression were analyzed.\n The three-year continuous complete remission (CCR) rate was 90.0% for As4S4 group and 61.1% for non-As4S4 group, the difference being statistically significant. Significant difference was also found in the positive rate of PML-RARalpha fusion gene between the two groups. The side effects were mild.\n APL patients in maintenance therapy with ATRA + 6-MP + MTX + As4S4 can obtain a higher CCR.", "All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed acute promyelocytic leukemia patients received ATRA plus idarubicin as induction, followed by 3 intensive consolidation courses. Thereafter, patients reverse-transcribed polymerase chain reaction-negative for the PML-RARA fusion gene were randomized into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); and no further therapy (arm 4). Starting from February 1997, randomization was limited to ATRA-containing arms only (arms 2 and 3). Complete remission was achieved in 761 of 807 (94.3%) patients, and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML-RARA fusion gene, and 586 of 646 (90.7%) who tested reverse-transcribed polymerase chain reaction-negative were randomized to maintenance. The event-free survival estimate at 12 years was 68.9% (95% confidence interval, 66.4%-71.4%), and no differences in disease-free survival at 12 years were observed among the maintenance arms.", "Acute promyelocytic leukemia (APL) is highly curable with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy (CT), but very long-term results of this treatment, when CT should be added to ATRA and the role of maintenance treatment, remain uncertain. In our APL93 trial that included 576 newly diagnosed APL patients, with a median follow-up of 10 years, 10-year survival was 77%. Maintenance treatment significantly reduced 10-year cumulative incidence of relapses, from 43.2% to 33%, 23.4%, and 13.4% with no maintenance, maintenance using intermittent ATRA, continuous 6 mercaptopurine plus methotrexate, and both treatments, respectively (P < .001). Maintenance particularly benefited patients with white blood cell (WBC) count higher than 5 x 10(9)/L (5000/microL). Early addition of CT to ATRA significantly improved 10-year event-free survival (EFS), but without significant effect on overall survival (OS). The 10-year cumulative incidence of deaths in complete response (CR), resulting mainly from myelosuppression, was 5.7%, 15.4%, and 21.7% in patients younger than 55, 55 to 65, and older than 65 years, respectively, supporting the need for less myelosuppressive treatments, particularly for consolidation therapy. This study is registered at http://clinicaltrials.gov as NCT00599937.", "We previously reported a benefit for all-trans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American Intergroup APL trial is reported. A total of 350 patients with newly diagnosed APL were randomized to either daunorubicin and cytarabine (DA) or ATRA for induction and then either ATRA maintenance or observation following consolidation chemotherapy. The complete remission (CR) rates were not significantly different between the ATRA and DA groups (70% and 73%, respectively). However, the 5-year disease-free survival (DFS) and overall survival (OS) were longer with ATRA than with DA for induction (69% vs 29% and 69% vs 45%, respectively). Based on both induction and maintenance randomizations, the 5-year DFS was 16% for patients randomized to DA and observation, 47% for DA and ATRA, 55% for ATRA and observation, and 74% for ATRA and ATRA. There was no advantage of either induction regimen among any subgroups when CR alone was considered. However, female sex, classical M3 morphology (vs the microgranular variant [M3v]), and treatment-white blood cell count (WBC) interaction (ATRA/WBC below 2 x 10(9)/L [2000/microL] best, DA/WBC above 2 x 10(9)/L worst) were each significantly associated with improved DFS (P <.05). Treatment with ATRA, WBC below 2 x 10(9)/L, and absence of bleeding disorder were each significantly associated with improved OS. Age more than 15 years, female sex, and treatment-morphology interaction (DA/M3v worst, ATRA best regardless of morphology) were each significantly associated with improved DFS based on maintenance randomization. The improvement in outcome with ATRA in APL was maintained with long-term follow-up.", "Shortly before the all-trans retinoic acid (ATRA) era, the GIMEMA cooperative group initiated a randomized study comparing idarubicin (IDA) alone with IDA plus arabinosylcytosine (Ara-C) as induction treatment in patients with newly diagnosed hypergranular acute promyelocytic leukemia (APL). Of the 257 patients evaluable for induction treatment, 131 were randomized to receive IDA alone (arm A) and 126 to receive IDA + Ara-C (arm B). Treatment in arm A consisted of 10 mg/m(2) IDA daily for 6 consecutive days, whereas in arm B it consisted of 12 mg/m(2) IDA daily for 4 days combined with 200 mg/m(2) Ara-C daily in continuous infusion for 7 days. Once in complete remission (CR), patients received 3 consolidation courses of standard chemotherapy, and those still in CR at the end of the consolidation were randomized to receive or not receive 1 mg/kg 6-mercaptopurine daily and intramuscular injections of 0.25 mg/kg methotrexate weekly for 2 years. Overall, 100 (76.3%) patients in arm A and 84 (66.6%) patients in arm B achieved CR (P = NS). Event-free survival (EFS) rates were 35% and 23% for patients in arm A and arm B, respectively (P =.0352). Multivariate analysis revealed that EFS was favorably influenced by induction treatment with IDA alone (P =.0352) and unfavorably influenced by white blood cell (WBC) counts greater than 3000/microL (P =.0001) and increasing age (P =.0251). These results indicate that anthracycline monochemotherapy with IDA favorably influences the EFS of patients with newly diagnosed hypergranular APL." ]

[ "2918333", "8951510", "8653332", "2461141", "3181441", "7311555", "2477316", "2475912", "1718211", "7553472", "7677982", "7833134", "7457527", "2022140", "3344898", "7835798", "6823374" ]

[ "Results of surgery for obstructing carcinomatosis of gastrointestinal, pancreatic, or biliary origin.", "Rectal cancer recurrence after prior resection and radiotherapy: palliation following additional surgery.", "Management of intestinal obstruction after gastrectomy for carcinoma.", "Intestinal obstruction in patients with gynaecological malignancies.", "Survival following intestinal obstruction in ovarian cancer.", "Ovarian carcinoma complicated by gastric outlet obstruction.", "Bowel obstruction in patients with ovarian carcinoma: analysis of prognostic factors.", "Intestinal obstruction in patients with advanced carcinoma of the ovaries treated with combination chemotherapy.", "Palliative gastrojejunostomy for advanced carcinoma of the stomach.", "Benefit of palliative surgery for bowel obstruction in advanced ovarian cancer.", "Results of surgery for malignant bowel obstruction in advanced, unresectable, recurrent colorectal cancer.", "Management of bowel obstruction in patients with advanced ovarian cancer.", "Intestinal operations in patients with ovarian carcinoma.", "Small bowel obstruction after colon resection for benign and malignant diseases.", "Treatment of bowel obstruction after operation for colorectal carcinoma.", "Follow-up after primary therapy: management of the symptomatic patient-surgery.", "Surgical management of bowel obstruction in advanced ovarian carcinoma." ]

[ "Results of operation for obstructing carcinomatosis of gastrointestinal (GI), pancreatic, or biliary origin were reviewed to assess relief of symptoms, management of re-obstruction, and duration of hospitalization. A retrospective review (1977 to 1986) identified 89 patients, 59 (66%) of whom had tumors originating in the colon, and 19 (21%) in the stomach. Normal bowel function was restored for a median of 102 days in 66 patients (74%) and all but four (94%) were discharged. Forty-one (46%) patients remained unobstructed until death. Twenty-three (26%) were not relieved by operation and died a median of 33 days later (P less than .005). Forty-eight (81.4%) of the 59 colon cancer patients and ten (52.6%) of 19 with gastric cancer (P less than .05) were benefited by the operation, although comparison of duration of function was less striking (P less than .1). In-hospital mortality was 13% and complications occurred in 44%. Obstruction recurred in 38% of those relieved by the initial operation. Normal bowel function was restored in six (46%) of 13 patients undergoing a second laparotomy (median, 158 days) and in six of 13 (46%) treated with nasogastric suction. Obstruction recurred again in four of the latter six patients (median, 39 days). Hospitalization averaged 31 days (median, 25 days) for the first procedure and 41 days (median, 39 days) for patients operated for recurrent obstruction. These results justify laparotomy for intestinal obstruction in known or suspected carcinomatosis, particularly of colonic origin, if performance status is compatible with a reasonable quality of life.", "Patients with rectal cancer may develop local recurrence despite cancer resection plus treatment with high dose radiation therapy. In this report, symptomatic patients received benefit from repeat resection. The morbidity and mortality can be maintained at an acceptable level with meticulous dissections and consistent use of reconstructive procedures.\n The primary treatment of rectal carcinoma is surgical excision to remove the primary tumor and its draining lymphatic systems. Postoperative radiotherapy may be recommended if tumor has penetrated through the full thickness of the bowel wall, and where there is lymph node involvement. Despite such treatments, tumor may recur locally, producing symptoms relieved by palliative surgery.\n Between 1989 and 1995, twenty patients underwent 21 reoperations for locally recurrent rectal cancer. All patients previously had not only surgical resection but also radiotherapy as treatment. The clinical data available on these patients was critically evaluated.\n Eighty-nine dissections (4.5 per patient) and 39 reconstructive procedures (2.0 per patient) were required on these 20 patients to re-resect rectal cancer in an irradiated site. Major complications occurred in 4 of 21 reoperative procedures (19%). There were no mortalities. Palliative benefits from pain control (8 of 9 patients), resolution of uncontrolled hemorrhage (2 of 2 patients), resolution of pelvic sepsis (2 of 2 patients), and reversal of intestinal obstruction (2 of 2 patients) were clearly demonstrated. The median survival following repeat resection was 24 months.\n Surgical cure following reoperation for recurrent rectal cancer treated initially with resection radiotherapy was uncommon. However, the morbidity and mortality of the procedures were acceptable, the survival was extensive and the palliative effects were substantial. The results of treatment suggest that repeat resection combined with aggressive reconstruction, is an important part of the treatment of symptomatic rectal cancer patients who recur locally, after resection combined with radiation therapy.", "nan", "Bowel obstruction developing in patients with gynaecological malignancies may present as a therapeutic dilemma. The causes, and results of surgical and conservative management of 92 patients are analysed. The causes of obstruction in the 64 patients who were treated surgically were: tumour recurrence in 42, adhesions in 12, radiation stricture in 9 and pelvic abscess in 1. Surgical palliation was effective in 45 patients in this group, with another 12 patients being palliated initially but subsequently developing further obstructive symptoms. Surgical palliation was ineffective in 7. Conservative management was effective only in 12 of the 41 patients, and even in this group 8 developed further obstructive episodes within the first month of discharge. The median survival in the surgically treated group for benign and malignant causes is 57 and 10 weeks respectively; while it is 4 weeks for those treated conservatively.", "A retrospective survey of 38 ovarian cancer patients who developed radiologically confirmed intestinal obstruction was performed. Twenty-six patients underwent surgery. In the surgical treatment group, obstruction was not due to recurrent disease in six cases. The median survival for the group as a whole was 56 days. Patients in the operative group survived significantly longer than those in the non-operative group. There was an operative mortality of 15% and major postoperative morbidity was seen in 42%. Neither the site of the obstruction nor the type of operation influenced survival. No postoperative chemotherapy responses were seen in previously treated patients.", "nan", "A retrospective study was performed in which patients with both bowel obstruction and ovarian carcinoma admitted to the gynecologic oncology service at the Milton S. Hershey Medical Center between July 1, 1980, and June 30, 1987, were examined. Thirty-three patients were identified who fulfilled the inclusion criteria for bowel obstruction that did not occur in the postoperative period. Historical, physical, nutritional, and laboratory variables thought to contribute to patient survival were evaluated by a retrospective chart review. Survival time was not significantly related to presence or absence of tumor at obstruction, type of intervention whether medical or surgical, patient age, or interval from initial diagnosis of ovarian cancer to obstruction. Survival time was found to be significantly related to the prognostic index initially proposed by H. B. Krebs and D. R. Goplerud [Obstet. Gynecol. 61, 327-330 (1983)], P = 0.002. This prognostic index incorporates a multifactorial assessment of patient status including age, nutritional status, tumor spread, ascites, and prior chemotherapy and radiotherapy and can be used to evaluate patients at the time of presentation with intestinal obstruction and to help select optimal treatment for palliation.", "An analysis of incidence, risk factors and treatment results of intestinal obstruction caused by carcinoma of the ovaries was performed in 310 consecutive patients with carcinoma of the ovaries, The International Federation of Gynecology and Obstetrics stage IIB to IV, treated with combination chemotherapy. With a median observation time of 46 months, the incidence was 14 per cent and the cumulated risk was estimated to be 26 per cent at five years after treatment was begun. Risk factors were stages IIIB and IV, residual primary tumor size greater than 2 centimeters and presence of intestinal carcinomatosis at primary laparotomy. There was no difference in the survival time between 16 conservatively treated patients and 25 surgically treated patients (a median of 30 and 68 days, respectively, p greater than 0.30). The complication risk of surgical treatment was high (64 per cent), and surgical benefit--defined as survival greater than 60 days with total palliation of intestinal symptoms--was achieved in only 32 per cent.", "The outcome of 51 patients who underwent gastrojejunostomy for unresectable gastric cancer with outlet obstruction was studied to evaluate the palliative benefit. The operative mortality and postoperative complication rates were 22% and 55% respectively. The mean duration of postoperative hospital stay was 13 days and median survival period 14 weeks. Delayed gastric emptying occurred in 21%, mostly in patients with extensive tumour involvement of the stomach and was associated with a poor outcome. Among the survivors, 87.5% were able to take a soft diet by the eighth postoperative day and 60% could cope with the progression of the disease at home. We conclude that gastrojejunostomy offers satisfactory palliation in patients with advanced gastric cancer.", "To determine the benefit of palliative surgery for patients with advanced ovarian cancer and bowel obstruction and to identify criteria for selecting patients who are most likely to benefit from palliation.\n A retrospective study of patients treated between 1982 and 1992.\n A university-affiliated hospital.\n Fifty-three patients with complete and unresolved bowel obstruction caused by ovarian cancer.\n Surgery for relief of bowel obstruction.\n Postoperative survival longer than 60 days, return home and relief of bowel obstruction for longer than 60 days, factors associated with failure of palliative surgery.\n Successful palliation was achieved in 27 (51%) patients and was associated with the absence of four prognostic factors: palpable abdominal and pelvic masses, ascites exceeding 3 L, multiple obstructive sites and preoperative weight loss greater than 9 kg. Age, time interval between diagnosis of ovarian cancer and bowel obstruction, stage of disease at initial diagnosis, tumour type and grade, site and degree of obstruction, presence of gross residual tumour after initial operation and preoperative use of chemotherapy or radiotherapy did not indicate the success or failure of palliative surgery.\n Palliative surgery for bowel obstruction in advanced ovarian cancer can be worthwhile, and there are four prognostic factors that indicate the likely failure of palliation.", "When conservative treatment fails in the management of patients with malignant bowel obstruction secondary to advanced, recurrent colorectal cancer, the attitude toward surgery is often less than enthusiastic because of the limited life expectancy. We report a retrospective review of 30 patients with unresectable intra-abdominal disease who underwent laparotomy for the relief of bowel obstruction. Normal bowel function was restored in 19 patients (63 percent). The failures included five patients (17 percent) who died as a result of surgical complications and six patients (20 percent) who despite the surgery had continuing obstruction. Postoperative complications occurred in eight patients (27 percent). The median survival was significantly improved in those who benefited from the operation (192 days vs. 26 days; P = 0.0001). Whether the obstruction occurred at one site or more than one site appeared not to influence the outcome of surgery. Obstruction recurred after a mean symptom-free interval of 120 days in eight of those relieved by the initial operation. Half of these patients responded to conservative treatment, and surgery was again beneficial in three of the remaining four. Our results justify a more positive approach toward this problem, and, when conservatism fails, laparotomy should be undertaken in those who are not terminally ill.", "In a retrospective study, 58 patients with bowel obstruction due to advanced ovarian cancer were analysed. In a forward stepwise proportional hazard regression analysis, we looked for factors influencing bowel obstruction-free survival. Patients who presented with bowel obstruction as the first sign of ovarian cancer and those with a longer interval between last cancer treatment and bowel obstruction did better. Patients with ascites did worse. No other independent factors were found. Based on these data, we classified patients into a favourable prognosis group (no previous treatment or interval since last treatment exceeding 6 months; no ascites) and a poor prognosis group (interval since last treatment shorter than 6 months; ascites). Patients from the favourable prognosis group had a median bowel obstruction-free survival of 8 months, compared to 1 month for the poor prognosis group (P < 0.001). Surgery had a marginally significant positive effect on bowel obstruction-free survival when compared to medical treatment in the favourable prognosis group (P = 0.052). Surgery had no effect at all in the poor prognosis patients.", "Forty-two patients with epithelial ovarian carcinoma underwent intestinal operations at the University of California, Los Angeles, and the City of Hope National Medical Center during the course of the disease. The patients were divided into three groups for purposes of this analysis. The first group had intestinal surgery during their initial laparotomy. Patients in the second group underwent intestinal operation at the time of re-exploration for recurrent disease but had no preoperative signs or symptoms of intestinal tract dysfunction, while those in the third group underwent re-exploration for symptomatic intestinal involvement by tumor. Operative complications, postoperative morbidity, and effect of the resection on disease outcome are analyzed for each group in an attempt to define the indications for intestinal resection or bypass in patients with epithelial ovarian cancer.", "To determine the etiology and outcome of patients with small bowel obstruction after a colon resection for benign and malignant diseases, the medical records of 118 patients who underwent 120 laparotomies for small bowel obstruction were reviewed. Contrary to previous reports, benign adhesions were responsible for the obstruction in all patients with a history of benign colon disease, 82.6 percent of patients with a history of adenocarcinoma of the colon without known recurrence, and 30.1 percent of patients with known recurrent malignancy. The morbidity and mortality was more related to the etiology of the obstruction rather than the preoperative delay or operative procedure performed. Considering the high likelihood of adhesive obstruction in patients with a history of, or known, metastatic colorectal carcinoma, it is suggested that these not deter surgeons from aggressive early surgical intervention in these patients who develop small bowel obstruction.", "Operative therapy is beneficial in patients with bowel obstruction after operation for colorectal carcinoma. The cause of the bowel obstruction is more likely to be benign following colorectal carcinoma than following other malignancies. Also, the period of preoperative nasogastric suction can safely be extended to 3 to 4 days in these patients, since a resolution rate of 28 percent can be achieved with minimal risk of strangulation.", "The benefit of secondary surgery in patients (pts) recurring after a negative second look is still a matter of controversy. Twenty-seven patients underwent this procedure: 5 were stage I at primary surgery and 22 stage IIIC. All 5 stage I pts had a pelvic recurrence: 3 were left with no visible tumor and were then treated with cisplatin chemotherapy. Two are alive and with no evidence of disease (NED) at 45 and 62 months. In stage IIIC pts, optimal debulking (< 2 cm) was achieved in 59% (13/22), and 8 of them had no macroscopic residual tumor. All pts were then treated with cisplatin chemotherapy. Only 3 pts are still alive and NED at 56, 61, and 67 months. The most important prognostic parameters regarding secondary surgery seem to be residual tumor volume both at primary and secondary surgery, time interval between negative second-look surgery and recurrence, histology (serous) and degree of differentiation, and response to second-line chemotherapy. Finally, surgery can have a true palliative role in pts who present with bowel obstruction; in our center, most patients who had a definitive procedure did benefit from the quality of life viewpoint.", "The surgical management of 118 instances of bowel obstruction associated with advanced ovarian cancer in 98 patients is reviewed. In 12% of the treatment episodes, patients were found to have inoperable disease at laparotomy. Surgical correction of the intestinal obstruction was associated with an operative mortality of 12%. In 35% of the cases, patients did not benefit from surgical treatment, as they died within 8 weeks of the operation. Patients' age, nutritional status, tumor spread, presence of ascites, and the type and amount of prior chemotherapy and/or radiation therapy correlate well with the patients' prognosis. A simple prognostic index based upon these 6 criteria is suggested as a means of predicting the possible benefit from surgical intervention." ]

[ "11139861", "21429079" ]

[ "A randomised controlled trial to compare the effectiveness of ice-packs and Epifoam with cooling maternity gel pads at alleviating postnatal perineal trauma.", "Perineal analgesia with an ice pack after spontaneous vaginal birth: a randomized controlled trial." ]

[ "To evaluate the effectiveness of standard regimes (ice packs and Epifoam) at relieving perineal trauma and compare these with a new cooling device (maternity gel pad).\n A randomised controlled trial involving three treatment groups. The women were free to choose the time of initial application (within four hours after delivery) in all treatment groups and the number of subsequent treatments up to 48 hours after suturing.\n A midwifery unit in the north of England and then continued in the women's own homes.\n 120 women who had undergone an instrumental delivery and had a 48 hours post-delivery stay in a postnatal ward.\n The ordinal scale of none, mild, moderate and severe was used to determine the levels of perineal oedema and bruising at initial assessment (less than 4 hours), 24 hours and at 48 hours, by use of a newly developed visual evaluating tool. Self-assessed pain was recorded using a 10-point visual analogue scale within four hours, at 24 hours, 48 hours, and finally at five days after suturing. Women's opinions as to the effectiveness of their treatment was rated by use of a 5-point scale describing the categories; poor, fair, good, very good and excellent. A high proportion of women had some perineal oedema at initial assessment. A statistically significant difference in the proportion of women with oedema was found between treatment groups at 48 hours (p = 0.01), which was in favour of the maternity gel pad group. This was particularly noticeable for women with initial levels of mild oedema (p = 0.017). Localised treatment with the gel pad caused a significant decrease in reported pain at 48 hours in women who initially demonstrated moderate or severe pain (p = 0.048). A significant increase in the proportion of women with some bruising was seen across all treatment groups from initial assessment, through 24 hours to 48 hours (p < 0.0005). The bruising was significantly less in the gel-pad group in women who initially had no bruising (p = 0.021). There was no statistically significant effect of treatment at other initial levels of severity for oedema, bruising or pain at 24 hours, 48 hours and five days (for pain). Women in the gel-pad group rated the effectiveness of their localised treatment to be significantly higher than women in the other two treatment groups (p < 0.0005).\n This trial demonstrated that a high proportion of women experience perineal oedema, bruising and pain following an instrumental delivery, which continues for at least five days for perineal pain, despite oral analgesia. Maternity gel pads, which were specially designed to cool the perineal region, were more effective in alleviating perineal trauma when compared with hospital standard regimens and were more highly rated by women.", "This study evaluated the effectiveness of an ice pack applied for 20 minutes to alleviate perineal pain after spontaneous vaginal birth.\n We conducted a randomized controlled trial at the Amparo Maternal Birth Center in São Paulo, Brazil. Study participants included 114 nulliparous women divided into 3 groups (n = 38 per group): experimental (ice packs on the perineum), placebo (water packs at set temperature), and control (no treatment).\n A numerical scale (0 to 10) was used for pain assessment. A comparison of the average pain at the beginning and after 20 minutes showed a significant reduction of pain (P < .001) in the 3 groups, and the experimental group had a lower average score for pain compared with the control group (1.6 versus 3.3, P = .032).\n The use of ice packs for 20 minutes was effective for perineal pain relief after vaginal birth.\n © 2011 by the American College of Nurse-Midwives." ]

[ "10904462", "11840224", "12409965", "12836810", "11887193", "15287931" ]

[ "Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial.", "Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors.", "Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension.", "Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension.", "Effects of sibutramine on the treatment of obesity in patients with arterial hypertension.", "Effects of orlistat on obesity-related diseases - a six-month randomized trial." ]

[ "Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension. This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension, including a subset analysis of African American patients.\n Obese patients with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker (with or without concomitant thiazide diuretic treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74) with minimal behavioral intervention for 52 weeks. African Americans constituted 36% of enrolled patients. Efficacy assessments were body weight and related parameters (BMI and waist and hip circumferences), metabolic parameters (serum levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric acid), and quality-of-life measures. Safety assessments included recording of blood pressure, pulse rate, adverse events, and reasons for discontinuation.\n For patients receiving sibutramine, weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of body weight (5% responders) and 13.4% lost 10% or more of body weight (10% responders) compared with 8.7% and 4.3% of patients in the placebo group, respectively (P<.05). Changes in body weight were similar among African Americans and whites. Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid. Waist circumference and quality-of-life measures also improved significantly in patients receiving sibutramine. Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure (2.0 mm Hg) and pulse rate (4.9 beats/min) compared with placebo-treated patients (-1.3 mm Hg and 0.0 beats/min; P<.05); these changes were similar among African Americans and whites. Most adverse events were mild to moderate in severity and transient. The most common adverse event resulting in discontinuation among patients receiving sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of patients receiving placebo).\n In obese patients with controlled hypertension, sibutramine was an effective and well-tolerated treatment for weight loss and maintenance. Sibutramine-induced weight loss resulted in improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and in waist circumference and quality-of-life measures. Blood pressure and heart rate increased by a small amount. Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar.", "Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control.", "To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension. DESIGN This was a 1-year, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives.\n Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed.\n Patients on orlistat experienced greater weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001) and greater reduction in body mass index (-1.9 +/- 2.3 versus -0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04).\n A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction.", "This 6-month randomized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension. Following a 2-week washout to confirm the diagnosis of hypertension, antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day. A body mass index in excess of 27 kg/m2 was required for entry. At study end, weight had changed from 75.4+/-9.6 to 70.0+/-9.5 kg in the sibutramine group and from 77.9+/-9.0 to 74.5+/-9.4 kg in the placebo group. In the sibutramine group, systolic blood pressure was 127.8+/-5.8 mm Hg after stabilization and 125.2+/-8.5 mm Hg after completion of the trial; respective values for diastolic blood pressure were 82.4+/-3.7 and 81.5+/-4.6 mm Hg. With placebo, blood pressure dropped from 129.0+/-7.1/80.9+/-4.9 mm Hg to 122.8+/-9.7/80.3+/-5.4 mm Hg at the same timepoints. In the sibutramine group, 14 patients reported 21 adverse events, most frequently headache (n=5), constipation (n=4), and dry mouth (n=4). In the placebo group, 13 patients had 20 adverse events. Sibutramine is safe and effective in overweight Hispanic patients with hypertension, but monitoring of blood pressure and titration of antihypertensive medication are necessary.", "To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months.\n The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo.\n The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3 +/- 7.3 to 82 +/- 7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105 +/- 29.3 versus 96.6 +/- 28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change.\n The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy.", "To assess the effect of orlistat on body weight and concomitant diseases in patients with body mass index (BMI) of > 28 kg/m2 and poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia.\n This trial was a six-month, randomized, double-blind, placebo-controlled study of orlistat 120 mg three times daily plus a mildly reduced-calorie diet. 1004 obese patients (BMI 28-40 kg/m2) were included by 253 private endocrinologists and received orlistat (n = 499) or placebo (n = 505). Patients were stratified by concomitant disorder (type 2 diabetes, n = 193; hypertension, n = 614; hypercholesterolaemia, n = 197). Body weight, anthropometry, lipid and glycaemic control parameters and blood pressure.\n After six months, orlistat produced a significantly greater weight loss than placebo in type 2 diabetes (-4.2% vs. -1.4%), hypertension (-6.2% vs. -1.9%) and hypercholesterolaemia (-5.5% vs. -2.3%) groups (p < 0.0001 for all). There was a greater decrease in HbA(1c) in the type 2 diabetes group (-0.54 vs. -0.18%; p = 0.002) and low-density lipoprotein (LDL)-cholesterol in the hypercholesterolaemia group (-11.7% vs. -4.5%; p = 0.004) with orlistat vs. placebo. Early weight loss (> or = 5% at 12 weeks) was associated with the highest weight loss in each group, and the highest decreases in HbA1c, LDL-cholesterol and diastolic blood pressure in patients with type 2 diabetes, hypercholesterolaemia and hypertension, respectively, at six months. The incidence of adverse events was similar for orlistat and placebo, except for certain generally well-tolerated gastrointestinal events that were more common with orlistat.\n Orlistat plus a mildly reduced-calorie diet produced clinically meaningful weight loss and improvements in risk factors in overweight and obese patients with poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia.\n Copyright 2004 Blackwell Publishing Ltd" ]

[ "17899572", "7443111", "6682631", "12592250", "17671253", "18275573", "12802023" ]

[ "Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.", "Inefficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy.", "The effect of 17 alpha-hydroxyprogesterone caproate on pregnancy outcome in an active-duty military population.", "Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.", "A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins.", "Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial.", "Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate." ]

[ "Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth.\n This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at </= 32 weeks of gestation. The trial was analyzed using an intent-to-treat strategy.\n Baseline characteristics were similar in the two treatment groups. Progesterone did not decrease the frequency of preterm birth at </= 32 weeks. There was no difference between the groups with respect to the mean gestational age at delivery, infant morbidity or mortality or other maternal or neonatal outcome measures. Adverse events during the course of treatment were similar for the two groups.\n Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth (</= 32 weeks) in women with a history of spontaneous preterm birth. The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone (e.g. sonographic cervical length) requires further investigation.\n Copyright (c) 2007 ISUOG", "There are indications that prophylactic administration of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHP-C) could be beneficial in the treatment of women at risk for preterm delivery. Since twin pregnancy is commonly associated with prematurity, 77 women with twin pregnancy were treated during the last trimester until the 37th gestational week with weekly injections of either 17 alpha-OHP-C or a placebo, following double-blind principles. The gestational length and birth weight and the outcome of the neonates were similar in both groups. The administration of 17 alpha-OHP-C thus seems ineffective in the prevention of prematurity risks associated with twin pregnancy.", "A prior report suggested that active-duty pregnant women are at increased risk for low-birth weight infants and a higher perinatal mortality rate. The present double-blind investigation was designed to prospectively evaluate that risk and to test the efficacy of 17 alpha-hydroxyprogesterone caproate to prevent reported complications. Three groups of active-duty women were studied, beginning between 16 and 20 weeks' gestation. They were similar for parity, previous abortion, race, cigarette smoking, and marital status. Of these, 80 were given 17 alpha-hydroxyprogesterone caproate, 88 received placebo, and 78 declined to participate in the protocol. There was no significant differences in the three groups when comparisons were made for low-birth weight infants and for perinatal mortality. However, when comparison was made to a military dependent population, they had a significantly worse outcome with regard to both perinatal mortality (p = 0.001) and infants with a birth weight less than 2,500 gm (p = 0.01). We concluded that pregnant military personnel were at increased risk for adverse pregnancy outcome, but that this risk was not altered by therapy with 17 alpha-hydroxyprogesterone caproate.", "The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population.\n A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test.\n The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05).\n Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity.", "In singleton gestations, 17 alpha-hydroxyprogesterone caproate (17P) has been shown to reduce the rate of recurrent preterm birth. This study was undertaken to evaluate whether 17P would reduce the rate of preterm birth in twin gestations.\n We performed a randomized, double-blind, placebo-controlled trial in 14 centers. Healthy women with twin gestations were assigned to weekly intramuscular injections of 250 mg of 17P or matching placebo, starting at 16 to 20 weeks of gestation and ending at 35 weeks. The primary study outcome was delivery or fetal death before 35 weeks of gestation.\n Six hundred sixty-one women were randomly assigned to treatment. Baseline demographic data were similar in the two study groups. Six women were lost to follow-up; data from 655 were analyzed (325 in the 17P group and 330 in the placebo group). Delivery or fetal death before 35 weeks occurred in 41.5% of pregnancies in the 17P group and 37.3% of those in the placebo group (relative risk, 1.1; 95% confidence interval [CI], 0.9 to 1.3). The rate of the prespecified composite outcome of serious adverse fetal or neonatal events was 20.2% in the 17P group and 18.0% in the placebo group (relative risk, 1.1; 95% CI, 0.9 to 1.5). Side effects of the injections were frequent in both groups, occurring in 65.9% and 64.4% of subjects, respectively (P=0.69), but were generally mild and limited to the injection site.\n Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with twin gestations. (ClinicalTrials.gov number, NCT00099164 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "Women with preterm labour that is arrested with tocolytic therapy are at increased risk of recurrent preterm labour. The efficacy of maintenance tocolytic therapy after successful arrest of preterm labour remains controversial.\n The purpose of this study was to determine whether supplementation of vaginal progesterone after inhibition of preterm labour is associated with an increased latency period and a decreased recurrent of preterm labour.\n This trial was conducted in 70 women who presented with symptoms of threatened preterm labour, who after arrest of uterine activity were then randomised to progesterone therapy or no treatment. Treatment group received progesterone suppository (400 mg) daily until delivery and control group received no treatment.\n Longer mean latency until delivery (36/11 +/- 17/9 vs 24/52 +/- 27/2) (mean + standard deviation) days; respiratory distress syndrome 4 (10.8%) vs 12 (36.4%) P = 0.021; low birthweight 10 (27%) vs 17 (51.5%) P = 0.04; and birthweight (3101.54 +/- 587.9 g vs r 2609.39 +/- 662.9 g, P = 0.002), were significantly different between the two groups. No significant differences were found between recurrent preterm labour 13 (35.1%) vs 19 (57.6%), P = 0.092; admission to intensive care unit 9 (24.3%) vs 13 (39.4%), P= 0.205 ; and neonatal sepsis 2 (5.4%) vs 6 (18.2%) P = 0.136, for the progesterone and control groups, respectively.\n The use of vaginal progesterone suppository after successful parenteral tocolysis associated with a longer latency preceding delivery but failed to reduce the incidence of readmission for preterm labour.", "Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery.\n We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle.\n Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen.\n Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.\n Copyright 2003 Massachusetts Medical Society" ]

[ "7985832", "15788475", "17642061", "12270988", "12506149", "9621293", "1762298" ]

[ "Prevalence of infection from subclavian dialysis catheters with two different postinsertion catheter cares: a randomized comparative study.", "Randomized, controlled trial of topical exit-site application of honey (Medihoney) versus mupirocin for the prevention of catheter-associated infections in hemodialysis patients.", "A prospective, randomized trial comparing a transparent dressing and a dry gauze on the exit site of long term central venous catheters of hemodialysis patients.", "A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters.", "Hemodialysis infection prevention with polysporin ointment.", "Staphylococcus aureus prophylaxis in hemodialysis patients using central venous catheter: effect of mupirocin ointment.", "Prevention of hemodialysis subclavian vein catheter infections by topical povidone-iodine." ]

[ "A comparison of the outcome of two different protocols concerning the postinsertion catheter care are reported and the literature of the subject is reviewed. Forty patients had the \"Quinton\" double-lumen catheter in the subclavian vein for hemodialysis. These catheters were kept in place for a total of 1392 days. The patients were divided randomly into two groups (A and B), each consisting of 20 patients. The care of group A catheters was done by the hospital intravenous (IV) team using heparin flushing three times/day. The care of group B catheters was done by dialysis nurses using heparin 1 mL of 2500 units in each lumen only after dialysis, ie, three times/week. The bacteremia rate of group A was 15% while that of group B was 5%. In conclusion, flushing the catheter with heparin 1 mL/2500 units in each lumen of the catheter at the end of dialysis, ie, three times/week along with changing the dressing once per week were found valuable in decreasing the rate of bacteremia from catheter infection.", "The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.", "The objective of this study was to assess the risk of bacteremia, estimate the cost and evaluate the quality of life by using a transparent dressing (TD) versus (vs) a dry gauze (DG) on the exit site of long term central I.V. catheters (LTCC) of hemodialysis patients. This 6-months preliminary study was conducted on 58 patients (pts) randomized to receive DG replaced 3 times/week (29 pts) or TD replaced every 7 days (29 pts). Data on patients, conditions of the exit site, local infection, bacteremia, quality of life and cost related to each type of dressing were collected. Two pts in the DG group experienced bacteremia related to their LTCC vs 1 pt in the group TD. A total of 7 (DG) vs 13 (TD) pts experienced skin condition changes at the catheter exit site. Some skin reactions, erythema and pruritus, did occur initially in the group TD and was due in part to insufficient drying time of the skin preparation solution. The estimated individual, weekly costs for using the DG was $7.60 vs $4.72 Canadian dollars for the TD. The SF-36trade mark scores did not show a significant difference between the 2 groups during the study (3.8 (PCS), 6.4 (MCS) at study end). Although this study was statistically underpowered, it suggests that the incidence of bacteremia was not increased with the use of a TD. Moreover, the use of a TD allowed fewer dressing changes, lowered total treatment costs, with no observed unfavorable impact on the quality of life and without significant local complications of the exit site. Based on the positive results observed in this pilot study, further study is warranted to examine the cost effectiveness of long-term use of TD dressings on dialysis catheter exit sites.", "Central venous catheters are frequently needed for the provision of haemodialysis, but their clinical usefulness is severely limited by infectious complications. The risk of such infections can be reduced by topical application of mupirocin to the exit sites of non-cuffed catheters or by the use of tunnelled, cuffed catheters. Whether mupirocin offers any additional protection against infection in patients with tunnelled, cuffed haemodialysis catheters has not been studied.\n An open-label, randomized controlled trial was performed comparing the effect of thrice-weekly exit site application of mupirocin (mupirocin group) vs no ointment (control group) on infection rates and catheter survival in patients receiving haemodialysis via a newly inserted, tunnelled, cuffed central venous catheter. All patients were followed until catheter removal and were monitored for the development of exit site infections and catheter-associated bacteraemias.\n Fifty patients were enrolled in the study. Both the mupirocin (n=27) and control (n=23) groups were similar at baseline with respect to demographic characteristics, comorbid illnesses and causes of renal failure. Compared with controls, mupirocin-treated patients experienced significantly fewer catheter-related bacteraemias (7 vs 35%, P<0.01) and a longer time to first bacteraemia (log rank score 8.68, P<0.01). The beneficial effect of mupirocin was entirely attributable to a reduction in staphylococcal infection (log rank 10.69, P=0.001) and was still observed when only patients without prior nasal Staphylococcus aureus carriage were included in the analysis (log rank score 6.33, P=0.01). Median catheter survival was also significantly longer in the mupirocin group (108 vs 31 days, log rank score 5.9, P<0.05). Mupirocin use was not associated with any adverse patient effects or the induction of antimicrobial resistance.\n Thrice-weekly application of mupirocin to tunnelled, cuffed haemodialysis catheter exit sites is associated with a marked reduction in line-related sepsis and a prolongation of catheter survival.", "Hemodialysis patients in whom permanent vascular access cannot be achieved are dependent on a central venous catheter. In such patients, catheter-related infections are a common and serious complication. This study was a randomized clinical trial to determine if topical Polysporin Triple antibiotic ointment applied to the central venous catheter insertion site could reduce the incidence of catheter-related infections. A total of 169 patients receiving hemodialysis through a central venous catheter were randomized to receive Polysporin Triple or placebo using a double-blind study design. In the 6-mo study period, infections were observed in more patients in the placebo group than in the Polysporin Triple group (34 versus 12%; relative risk, 0.35; 95% CI, 0.18 to 0.68; P = 0.0013). The number of infections per 1000 catheter days (4.10 versus 1.02; P < 0.0001) and the number of bacteremias per 1000 catheter days (2.48 versus 0.63; P = 0.0004) were also greater in the placebo group. Within the 6-mo study period, there were 13 deaths in the placebo group as compared with 3 deaths in the Polysporin Triple group (P = 0.0041). When all available follow-up information was included, the difference in survival remained significant (19 versus 9 deaths; P = 0.0027). Within the first 6 mo, infections were observed in 7 of the 13 placebo subjects who died (54%) as compared with no infections in the three Polysporin Triple subjects who died. The prophylactic application of topical Polysporin Triple antibiotic ointment to the central venous catheter insertion site reduced the rate of infections and was associated with improved survival in hemodialysis patients.", "Central venous catheterization is a common technique to establish rapid and temporary access for hemodialysis. However, it is a known risk factor for Staphylococcus aureus infection and bacteremia. Mupirocin is a topical antibiotic with high in vitro anti-staphylococcal activity. A randomized prospective trial was conducted to assess the effectiveness of mupirocin ointment in the prevention of Staphylococcus aureus skin and catheter colonization, and episodes of bacteremia in 136 end-stage renal disease patients. Of these, 67 received skin disinfection at the venous catheter insertion site with povidone iodine (control group), and 69 received the same treatment followed by application of 2% mupirocin ointment at the cannula site after catheter placement and at the end of each dialysis session. Patients were followed until catheter removal and were monitored for the development of Staphylococcus aureus skin/catheter colonization and episodes of bacteremia. Median duration of catheter use was greater in the mupirocin than in the control group (37 versus 20 d, P < 0.01). Patients in the mupirocin group had a significantly lower rate of Staphylococcus aureus isolation from the pericatheter skin (1.76 per 1000 versus 14.27 per 1000 patient-days, P < 0.001) and from the catheter surface (3.17 per 1000 versus 14.27 per 1000 patient-days, P < 0.001). The proportion of patients with Staphylococcus aureus skin infection at the insertion site was lower in the mupirocin group (4.3% versus 23.9%, P = 0.001). Staphylococcus aureus-associated bacteremia was observed in 17 patients (two in the mupirocin group [0.71 episodes per 1000 patient-days] and 15 in the control group [8.92 per 1000 patient-days], P < 0.001). The hazard ratio of developing Staphylococcus aureus bacteremia was 7.2 (95% confidence interval, 1.6 to 31.6) times greater in patients not receiving mupirocin. Mupirocin applied to the insertion site significantly reduces the risk of Staphylococcus aureus skin and catheter colonization, exit-site infection, and Staphylococcus aureus bacteremia in hemodialysis patients.", "Subclavian catheter (SCC) related infections are a major cause of morbidity in hemodialysis patients, the vast majority due to staphylococci species. Povidone-iodine (PI) has proven anti-staphylococcal activity. Therefore, a randomized controlled trial of topical PI ointment was undertaken to evaluate the impact of this prophylactic intervention on the incidence of SCC related infections in hemodialysis patients. The role of S. aureus nasal carrier state in the acquisition of infection was also evaluated. Patients requiring SCC for temporary hemodialysis access were randomized to receive the treatment (T; N = 63) or sterile gauze dressings alone (C; N = 66). Catheter duration ranged from 2 to 210 days in both groups, with a mean of 38.6 days in T and 36.2 days in C (NS). Exit site (ES) infections were significantly less in T (5%) versus C (18%) (P less than 0.02); tip colonization (TC) was 17% in T versus 36% in C (P less than 0.01), while the incidence of septicemia (S) was also significantly less in T (2%) versus C (17%; P less than 0.01). S. aureus nasal carriers were at a threefold higher risk of SCC related septicemia (0.009/day) than noncarriers (0.003/day; P less than 0.05). The beneficial effect of PI ointment was most evident in this high risk group of S. aureus carriers: ES = 0% T versus 24% C, TC = 12% T versus 42% C, S = 0% T versus 29% C, P less than 0.05. There were no adverse effects of the treatment. The routine application of topical PI ointment to temporary hemodialysis catheter exit sites is effective in reducing SCC related infections." ]

[ "21641021", "21856336", "18096677", "21636820", "21586821" ]

[ "Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients.", "Electrical stimulation over the left inferior frontal gyrus (IFG) determines long-term effects in the recovery of speech apraxia in three chronic aphasics.", "Improved naming after transcranial direct current stimulation in aphasia.", "Short-term anomia training and electrical brain stimulation.", "Improved picture naming in aphasia patients treated with cathodal tDCS to inhibit the right Broca's homologue area." ]

[ "Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernicke's area) or the right Wernicke's area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernicke's area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects the performance of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS for the recovery of apraxia of speech in 3 patients with stroke-induced aphasia. Over 2 weeks, three aphasic subjects participated in a randomized double-blinded experiment involving intensive language training for their articulatory difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over the left inferior frontal gyrus (referred to as Broca's area) while they performed a repetition task. By the end of each week, a significant improvement was found in both conditions. However, all three subjects showed greater response accuracy in the anodic than in the sham condition. Moreover, results for transfer of treatment effects, although different across subjects, indicate a generalization of the recovery at the language test. Subjects 2 and 3 showed a significant improvement in oral production tasks, such as word repetition and reading, while Subjects 1 and 2 had an unexpected significant recovery in written naming and word writing under dictation tasks. At three follow-ups (1 week, 1 and 2 months after the end of treatment), response accuracy was still significantly better in the anodic than in sham condition, suggesting a long-term effect on the recovery of their articulatory gestures.\n Copyright © 2011 Elsevier B.V. All rights reserved.", "Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant technique to improve functional recovery after ischaemic stroke. This study evaluated the effect of tDCS over the left frontotemporal areas in eight chronic non-fluent post-stroke aphasic patients. The protocol consisted of the assessment of picture naming (accuracy and response time) before and immediately after anodal or cathodal tDCS (2 mA, 10 minutes) and sham stimulation. Whereas anodal tDCS and sham tDCS failed to induce any changes, cathodal tDCS significantly improved the accuracy of the picture naming task by a mean of 33.6% (SEM 13.8%).", "Language training success in chronic aphasia remains only moderate. Electric brain stimulation may be a viable way to enhance treatment efficacy.\n In a randomized, double-blind, sham-controlled crossover trial, we assessed if anodal transcranial direct current stimulation compared to cathodal transcranial direct current stimulation and sham stimulation over the right temporo-parietal cortex would improve the success of short-term high-frequency anomia training. Twelve chronic poststroke aphasia patients were studied. Naming outcome was assessed after training and 2 weeks later.\n All training conditions led to a significant increase in naming ability, which was retained for at least 2 weeks after the end of the training. Application of anodal transcranial direct current stimulation significantly enhanced the overall training effect compared to sham stimulation. Baseline naming ability significantly predicted anodal transcranial direct current stimulation effects.\n Anodal transcranial direct current stimulation applied over the nonlanguage dominant hemisphere can enhance language training outcome in chronic aphasia. Clinical Trial Registration- URL: www.clinicaltrials.gov/. Unique identifier: NCT00822068.", "Previous reports have suggested that noninvasive cortical stimulation could influence speech production in patients with chronic stroke. Here, we evaluated the hypothesis that cathodal transcranial DC stimulation (ctDCS), a technique that decreases excitability of stimulated cortical sites, applied over a healthy right Broca's homologue area could improve picture naming in patients with post-stroke aphasia.\n Ten right-handed patients with post-stroke aphasia were enrolled in this double blind, counterbalanced sham-controlled, crossover study. Each patient received an intervention of ctDCS (2 mA for 20 min) and of sham tDCS (2 mA for 1 min) daily for 5 consecutive days in a randomized crossover manner with a minimum interval of one week between interventions, over a healthy right Broca's homologue area using a left supraorbital anode and simultaneous daily sessions of conventional word-retrieval training. The primary endpoint measure of this study was a standardized, validated Korean version of the Boston Naming Test, which is a measure of picture naming skills.\n ctDCS was not found to have any adverse effects. Furthermore, significantly improved picture naming (p = 0.02) was observed at 1 hour following the last (5th) ctDCS treatment session, but no changes were observed after sham tDCS.\n These results demonstrate that cathodal tDCS over the right healthy Broca's homologue area with a left supraorbital anodal location can improve picture naming task performance in post-stroke aphasia." ]

[ "17310863", "14694248", "11003974", "8776785", "9603132", "3067313", "12958052", "3708186", "1736753", "9923569", "2526721", "20614859", "10607087", "18548827", "6142508", "22281004", "1541143", "3294213", "18198262", "21269278", "20297950", "18710420", "9989366", "11898120", "2040719", "3300449", "6750396" ]

[ "Efficacy of mirtazapine in obstructive sleep apnea syndrome.", "Intranasal corticosteroid therapy for obstructive sleep apnoea in patients with co-existing rhinitis.", "The therapeutic effect of theophylline in mild obstructive sleep Apnea/Hypopnea syndrome: results of repeated measurements with portable recording devices at home.", "A double-blind, randomized trial of sabeluzole--a putative glutamate antagonist--in obstructive sleep apnea.", "Surface tension forces in sleep apnea: the role of a soft tissue lubricant: a randomized double-blind, placebo-controlled trial.", "Role of protriptyline and acetazolamide in the sleep apnea/hypopnea syndrome.", "Reduction of sleep-disordered breathing after physostigmine.", "Effect of doxapram on obstructive sleep apnea.", "Effect of clonidine in obstructive sleep apnea.", "Cardiovascular effects of mibefradil in hypertensive patients with obstructive sleep apnea.", "Indices of severity of obstructive sleep apnea syndrome do not change during medroxyprogesterone acetate therapy.", "Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome.", "Naltrexone improves blood gas patterns in obstructive sleep apnoea syndrome through its influence on sleep.", "Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea.", "[Effect of oral almitrine on the sleep apnea syndrome].", "Beneficial effect of donepezil on obstructive sleep apnea: a double-blind, placebo-controlled clinical trial.", "Theophylline in obstructive sleep apnea. A double-blind evaluation.", "A double-blind trial of protriptyline in the treatment of sleep apnea syndrome.", "Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study.", "Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold.", "Proof of concept study: does fenofibrate have a role in sleep apnoea syndrome?", "Does nasal decongestion improve obstructive sleep apnea?", "Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea.", "Obstructive Sleep Apnea and Hypopnea Efficacy and Safety of a Long-Acting beta2-Agonist.", "Buspirone administration to sleep apnea patients.", "The effects of aminophylline on sleep and sleep-disordered breathing in patients with obstructive sleep apnea syndrome.", "Protriptyline in obstructive sleep apnea: a double-blind trial." ]

[ "Decreased serotonergic facilitation of upper-airway motor neurons during sleep has been postulated as an important mechanism rendering the upper airway vulnerable to obstruction in patients with obstructive sleep apnea syndrome (OSA). Although serotonin reuptake inhibitors have been shown to produce modest reductions in the apnea-hypopnea index (AHI) during non-rapid eye movement (NREM) sleep, they have not been proven to be generally effective as treatments for OSA. Conversely, antagonists of type 3 (5-HT3) serotonin receptors effectively have been shown to reduce the frequency of central apneas during rapid eye movement (REM) sleep in a rodent model of sleep-related breathing disorder. We sought to determine whether mirtazapine, a mixed 5-HT2/5-HT3 antagonist that also promotes serotonin release in the brain would effectively reduce AHI during both NREM and REM sleep in patients with OSA.\n A randomized, double-blind, placebo-controlled, 3-way crossover study of mirtazapine in patients with OSA.\n Laboratory studies were conducted in the Center for Sleep and Ventilatory Disorders at the University of Illinois Medical Center.\n Seven adult men and 5 adult women with newly diagnosed (treatment-naïve) and medically uncomplicated OSA were randomized into the study.\n Each subject self-administered oral medications 30 minutes before bedtime each night for 3 consecutive 7-day treatment periods. These treatments comprised (1) placebo, (2) 4.5 mg per day of mirtazapine, and (3) 15 mg per day of mirtazapine. The order of treatments was randomized for each subject, and orders were counterbalanced for the overall study.\n Each subject charted his or her sleep-wake schedule throughout the study and completed the Stanford Sleepiness Scale every 2 hours during the seventh day of each treatment period. Subjects were studied by laboratory polysomnography on the seventh night of each treatment period. With respect to placebo treatment, 4.5 mg of mirtazapine significantly reduced the AHI in all sleep stages to 52%, with 11 of 12 subjects showing improvement over placebo; 15 mg of mirtazapine reduced the AHI to 46%, with 12 of 12 subjects showing improvement over placebo. Sleep fragmentation was reduced only by the higher dose of mirtazapine. Gross changes in sleep architecture were unremarkable.\n Daily administration of 4.5 to 15 mg of mirtazapine for 1 week reduces AHI by half in adult patients with OSA. This represents the largest and most consistent drug-treatment effect demonstrated to date in a controlled trial. These findings suggest the therapeutic potential of mixed-profile serotonergic drugs in OSA and provide support for future studies with related formulations. Mirtazapine also is associated with sedation and weight gain-2 negative side effects in patients with OSA. In view of the above, we do not recommend use of mirtazapine as a treatment for OSA.", "Increased nasal airflow resistance (NAR) may contribute to the pathophysiology of obstructive sleep apnoea syndrome (OSAS) but studies investigating the effects of relieving nasal obstruction in OSAS have produced differing results. There are no reports of intranasal corticosteroid therapy in adult OSAS patients with reversible nasal obstruction.\n We evaluated an intranasal corticosteroid, fluticasone propionate, in 24 consecutive snorers with associated rhinitis using a randomised, placebo controlled, crossover design. Patients underwent polysomnography, snoring noise, and NAR measurements at baseline and after each 4 week treatment period.\n Twenty three patients completed the protocol and were divided into an apnoeic group (group A; 13 patients) and a non-apnoeic snoring group (group S; 10 patients) based on an apnoea-hypopnoea frequency (AHI) of > or =10/h or <10/h. AHI was significantly lower following treatment with fluticasone than with placebo in the total population (median (quartile range) 11.9 (22.6) v 20 (26.3); p<0.05) and in group A (23.3 (21.3) v 30.3 (31.9); p<0.05). Median (95% confidence interval) within subject differences for AHI were -3.2 (-17.7 to -0.2) in the total population and -6.5 (-29.5 to 1.8) in group A. NAR was also lower on fluticasone (2.74 (1.21) v 3.27 (1.38), p<0.01), within subject difference being -0.45 (95% CI -0.87 to -0.21). The changes in AHI and NAR in group A were significantly correlated (r=0.56; p<0.05). Snoring noise and sleep quality were unchanged but daily diary records indicated subjective improvements in nasal congestion and daytime alertness with fluticasone (p<0.02).\n Intranasal fluticasone is of benefit to some patients with OSAS and rhinitis. The data suggest that this form of nasal obstruction may contribute to the pathophysiology of OSAS.", "Theophylline has been recommended in the literature as a therapeutic option in mild OSAHS. In mild obstructive sleep apnea/hypopnea syndrome (OSAHS), night-to-night variability of parameters of sleep-disordered breathing has been determined rarely, we therefore compared the results of serial measurements of sleep apnea/hypopnea parameters under the effects of placebo and theophylline. To this end, we measured the individual variability of the apnea-hypopnea index (AHI) for seven consecutive nights using a portable sleep apnea recording device, in 14 subjects (2 women, 12 men, mean age +/- [standard deviation] 50 +/- 8 years), treated with placebo or theophylline in a double blind, randomized crossover fashion, whose polysomnographically measured AHI was 13 +/- 5 /hour. Under theophylline treatment in comparison with placebo we observed a small but significant decrease in mean (of seven days) AHI at home (9.2 +/- 7.7 to 6.7 +/- 6.1 /hour), which was independent of body position. The night-to-night variability of AHI at home was high (9. 2 +/- 8.9 /hour; range: 0-31.4 /hour) and proved to be independent of body position and alcohol consumption. - In mild OSAHS, repeated measurements of sleep related breathing events should be performed. Theophylline showed a small but clinically insignificant potencial to reduce AHI.", "The effect of sabeluzole (SAB), an agent with anti-excitatory amino acid activity, on sleep, breathing and daytime symptoms was investigated in 13 patients with obstructive sleep apnea (OSA). There was marked interindividual variation in both the effect on sleep and breathing and the plasma concentration of SAB. However, individual plasma drug concentration was highly correlated (r = 0.82, p = 0.02) with a reduction of the oxygen desaturation index during sleep (ODI) after treatment with SAB. Further investigation of this and agents of this type are warranted in patients with OSA.", "Upper airway obstruction in patients with sleep apnea may occur in the absence of a negative intraluminal upper airway pressure. We hypothesized that surface tension forces may play a role in the pathogenesis of obstructive sleep apnea (OSA), and that a topical soft tissue lubricant might reduce the severity of OSA. Ten male patients (age 49 +/- 10 yr [mean +/- SD]; body mass index [BMI] 31 +/- 5 kg/m2) with OSA (apnea-hypopnea index [AHI] 17 +/- 9) were studied. The arousal index was lower with the lubricant treatment than with placebo (mean difference 8; 95% CI 4 to 11 arousals/h; p = 0.001). The AHI was lower, in each of the 10 patients, on the lubricant treatment than the placebo (mean change 10, 95% CI 6 to 13; p = 0.0003). The lower AHI with lubricant as compared with placebo was present in both supine (mean difference 13; 95% CI 5 to 20; p = 0.006) and nonsupine (mean difference 6; 95% CI 0 to 12; p = 0.05) positions. There was no significant difference in sleep architecture between the lubricant and placebo treatments. Application of a topical lubricant consistently reduced the severity of OSA. This implies a pathogenetic role for surface tension forces in OSA, and a potential role for surface tension-reducing agents in the treatment of OSA.", "The role of drug therapy in the treatment of the sleep apnea/hypopnea syndrome is unclear. In a randomised, double-blind, placebo-controlled study, we investigated the value of 14-day therapy with protriptyline (20 mg daily) or acetazolamide (250 mg 4 times per day) on symptoms and on the frequency of apneas, hypopneas, arousals, and 4% desaturations in 10 patients with obstructive sleep apnea/hypopnea syndrome. Overall, protriptyline did not have a significant effect either on symptoms or on any of the above polysomnographic criteria. Acetazolamide reduced the apnea/hypopnea frequency [placebo 50 +/- 26 (SD); acetazolamide 26 +/- 20/h of sleep, p less than 0.03] and tended to decrease the frequency of 4% desaturations (placebo 29 +/- 20; acetazolamide 19 +/- 16/h of sleep, p = 0.06). Despite these physiological improvements, acetazolamide did not significantly improve symptoms and paraesthesiae were common. Contrary to earlier studies, we conclude that protriptyline may have a limited role in the treatment of the sleep apnea syndrome. The reason why acetazolamide produced a physiological, but not a symptomatic, response requires further investigation.", "The cholinesterase inhibitor physostigmine (PHYS) was investigated in a double-blind, placebo-controlled, randomized, crossover trial of 10 male patients with moderate to severe obstructive sleep apnea. PHYS (0.12 microg/minute/kg, 7-hour infusion) reduced mean apnea/hypopnea index (AHI) by 13.6 (95% confidence interval [CI], 2.2-25.1) corresponding to 21.4% (95% CI, -5.5 to 47.9) and increased minimum SaO2 by 8.7% (95% CI, -0.3 to 17.7) corresponding to 23.2% (95% CI, 4.8-41.3). During the last third of the night, coinciding with predicted plasma concentration steady state, non-REM sleep AHI decreased by 19.2 (95% CI, 0.1-38.3) or 14.9% (95% CI, -43.6 to 77.7) and REM AHI by 33.8 (95% CI, 13.7-54.0) or 67.5% (95% CI, 49.7-85.3). Mean total sleep time was reduced by 74 minutes (95% CI, 33.9-114.9), but patients with the least pronounced sleep shortening had the largest reduction of AHI (r = 0.73, p < 0.02). The nocturnal decline in heart rate was reduced by PHYS. Moreover, resting (early-night placebo heart rate) was positively correlated with proportional reduction of REM apnea index (r = 0.69, p < 0.02). Body mass index was negatively correlated with reduction of REM AHI (r = 0.77, p < 0.02). This, predominantly REM-related, reduction of obstructive sleep apnea after PHYS may provide a new treatment option if the effects are maintained in long-term studies.", "To determine whether treatment with a respiratory stimulant, doxapram hydrochloride, would improve obstructive sleep apnea, we administered the drug to four patients with this disease. Subjects were given a bolus of doxapram, 0.5 mg X kg-1 lean body mass, followed by a 1 mg X min-1 infusion throughout the night on one night and placebo another night. Doxapram produced improvement in the average oxyhemoglobin desaturation during apneic and hypopneic episodes and decreased average apnea length, but did not change the average number of oxyhemoglobin desaturations per hour of sleep or sleep efficiency. We conclude that doxapram, when administered at levels known to increase ventilatory drive, does not decrease the number of disordered breathing events during sleep but does cause termination of these events at higher levels of oxyhemoglobin saturation.", "The current treatment of choice for obstructive sleep apnea is continuous positive airway pressure. However, not all patients tolerate this form of therapy. We evaluated the effect of clonidine hydrochloride, an alpha 2-adrenergic agonist with REM-suppressant activity, in eight male patients with obstructive sleep apnea. In each patient, sleep-stage distribution and breathing pattern in two all-night sleep studies performed during a 10-day course of clonidine were compared with those of two control and two placebo nights. A dose of 0.2 mg of clonidine administered orally at bedtime totally suppressed REM sleep in two patients. In the other six patients, the same dose decreased percent time spent in REM sleep from a control of 13.4 +/- 1.0 to 8.6 +/- 1.4% (mean +/- SEM, p less than 0.05). The latency to REM sleep increased in the latter group from a control of 129 +/- 9 to 308 +/- 24 min (p less than 0.001). Clonidine had no effect on the frequency and duration of non-REM breathing abnormalities. Under clonidine, the level of nocturnal hypoxemia improved in six patients. This was due to a total suppression of REM and the consequent lack of REM apneas in two patients. In four patients, upper airway obstruction disappeared during period of unsuppressed REM sleep, and SaO2 remained above 90% throughout this sleep stage. Clonidine transformed the pattern of sleep-disordered breathing during unsuppressed REM in the other two patients from that of repetitive obstructive hypopneas associated with persistent hypoxemia to occlusive apneas and cyclical hypoxemia. These results were observed consistently in all patients during both clonidine-sleep studies.(ABSTRACT TRUNCATED AT 250 WORDS)", "Hypertension is often seen in obstructive sleep apnea (OSA) and is characterized by increased sympathetic activity, depressed baroreflex and accentuated vascular responsiveness. The objective of this study was to investigate the effects of the new T-selective calcium channel blocker mibefradil on invasively measured blood pressure (BP) and heart rate in hypertensive patients with OSA.\n The present study was a double-blind, randomized and placebo-controlled before and after trial in two parallel groups. Fifty-three men aged 23 69 years with systemic hypertension and OSA were recruited from the Outpatient Department of the Marburg University Sleep Laboratory and hospitalized for 10 days. Mibefradil (50 mg) or placebo were given orally in the morning for 8 days. The main outcome measure was the mean arterial (radial) BP monitored continuously during nocturnal sleep and during standardized daytime physical and psychological performance testing.\n Mibefradil lowered mean arterial BP and heart rate with (SD) during the entire measurement period compared with placebo: -7.25 (9.59) vs -2.11 (8.43) mmHg (P=0.039) and -4.83 (5.94) vs -1.34 (4.13) bpm (P=0.022), respectively. Both effects were observed during nocturnal sleep and performance testing, including graded exercise. Adverse events did not differ compared with placebo.\n Mibefradil is an effective but well-tolerated antihypertensive that also lowers heart rate over 24 h in OSA, in conditions known to increase BP.", "Medroxyprogesterone acetate (MPA) could change the frequency and/or duration of disordered breathing events (DBEs) in patients with the obstructive sleep apnea (OSA) syndrome by altering pharyngeal muscle function relative to diaphragm and external intercostal function. Ten male patients with OSA syndrome underwent an initial polysomnogram with monitoring of EEG, EOG, myohyoid EMG, oral and nasal airflow, abdominal and thoracic movement, and SaO2. The patients were then entered into a randomized, double-blind crossover study using MPA, 150 mg/day, and MPA placebo. Each patient took tablets for one week and then had a second polysomnogram. After a three week washout, the patient again took tablets for a week prior to the third and final sleep study. There was no significant difference between drug and placebo for DBE time (expressed as a percentage of sleep time), DBE frequency, DBE mean duration or mean fall in O2 saturation during DBEs. We conclude that treatment with MPA does not alter indices of severity of the OSA syndrome.", "Incremental withdrawal of serotonin during wake to sleep transition is postulated as a key mechanism that renders the pharyngeal airway collapsible. While serotonin promotion with reuptake inhibitors have demonstrated modest beneficial effects during NREM sleep on obstructive sleep apnea (OSA), animal studies suggest a potential therapeutic role for selective serotonin receptor antagonists (5-HT3) in REM sleep. We aimed to test the hypothesis that a combination of ondansetron (Ond) and fluoxetine (Fl) may effectively reduce expression of disordered breathing during REM and NREM sleep in patients with OSA.\n A prospective, parallel-groups, single-center trial in patients with OSA.\n 35 adults with apnea hypopnea index (AHI) > 10; range 10-98.\n Subjects were randomized to placebo, n = 7; Ond (24 mg QD), n = 9; Fl (5 mg QD) + Ond (12 mg QD), n = 9; and Fl (10 mg QD) + Ond (24 mg QD), n = 10.\n AHI was measured by in-lab polysomnography after a 7-day no-treatment period (Baseline) and on days 14 and 28 of treatment. The primary endpoint was AHI reduction at days 14 and 28. OND+FL resulted in approximately 40% reduction of baseline AHI at days 14 and 28 (unadjusted P < 0.03 for each) and improved oximetry trends. This treatment-associated relative reduction in AHI was also observed in REM and supine sleep.\n Combined treatment with OND+FL is well-tolerated and reduces AHI, yielding a potentially therapeutic response in some subjects with OSA.", "Endogenous opiates have been shown to depress ventilation, and could therefore play a role in sleep apnoea syndrome (SAS). Hence, opiate antagonists have been used to treat SAS. The improvement they seem to give in blood-gas monitoring could derive either from a direct blocking of endorphins that inhibit respiration or else, indirectly, through an influence on sleep patterns. The present study used a double blind cross-over protocol to investigate the relationships between the effects on blood-gas and on sleep patterns of the oral opiate antagonist naltrexone in obstructive SAS. Sleep patterns and transcutaneous blood gas (tcPO2 and tcPCO2) were recorded in parallel. Control recordings, without treatment, were carried out over two nights, followed by two nights of recording after administration either of naltrexone followed by a placebo or of a placebo followed by naltrexone. The number of obstructive apnoea and hypopnoea events per hour of sleep (Apnoea-Hypopnoea Index: AHI), of hypoxic events (defined as a tcPO2 fall of at least 10, 15 or 20 mm Hg) and of hypercapnic events (defined as a tcPCO2 increase of at least 5 mm Hg) were counted. A Metabolic Suffering Index (MSI) was calculated, defined as the product of the number, duration and magnitude of hypoxic and hypercapnic events. Compared to placebo, naltrexone resulted in significant improvements in blood-gas patterns for the duration and MSI of hypoxic events and for the number, duration and MSI of hypercapnic events. Likewise, compared to placebo, naltrexone induced significant decreases in total sleep time, slow-wave sleep and rapid eye movement (REM) sleep, and, on the other hand, significant increases in total wake time and in the number of wakenings per hour of sleep (Nw h-1). Certain naltrexone-linked blood-gas improvements were closely correlated with certain of the sleep pattern changes: the decrease in number and duration of hypoxic events correlated with REM-time decrease and the decrease in number and duration of hypercapnic events correlated with the increase in Nwh-1. These findings suggest that the improvement in blood-gas patterns induced by naltrexone in SAS may be mediated by sleep pattern effects: i.e. a decrease in REM-time and an increase in intra-sleep wakening.", "Mirtazapine is an a2A antagonist and mixed 5-HT2/5-HT3 antagonist that has been proposed as a potential treatment for obstructive sleep apnea (OSA). A small, randomized, controlled trial has previously found an approximate halving in the severity of OSA with daily doses of 4.5 and 15 mg. We aimed to confirm and extend these findings in 2 randomized placebo-controlled, proof-of-concept trials.\n Two randomized, double-blind, placebo-controlled trials of mirtazapine for OSA (apnea-hypopnea index 10-40/h). Study 1: 3-way crossover, dose-finding study testing the self-administration of mirtazapine (7.5, 15, 30, and/or 45 mg) or placebo 30 minutes prior to bedtime for 2 weeks at each dose. Twenty patients were randomly assigned to 1 of 6 different dose-sequence groups, with each patient exposed to a maximum of 3 doses. Study 2: 3-arm, randomized, parallel-group trial of mirtazapine at 15 mg or mirtazapine 15 mg + Compound CD0012 or placebo for 4 weeks in 65 patients with OSA.\n Two patients withdrew from Study 1 after complaints of unacceptable lethargy. Fifteen patients were withdrawn from study 2, 7 after complaints of unacceptable lethargy or other side-effects. No measurement of sleep apnea improved due to mirtazapine in either study. Weight gain was significantly greater on mirtazapine than on placebo in both trials.\n Mirtazapine did not improve sleep apnea in either trial. Mirtazapine caused weight gain, which may further worsen OSA. Therefore, mirtazapine is not recommended for the treatment of OSA.", "Almitrine stimulates breathing by activating peripheral chemoreceptors and was given orally in a dose of 200 mg/day to nine patients with sleep apnoea syndrome, after a single blind placebo sequence. No reduction in the number of respiratory events per hour of sleep was observed. On the other hand Almitrine led to a significant fall in the mean duration of respiratory events (p less than 0.02). This fall occurred principally in the obstructive apnoea group and in those with mixed apnoea only during light slow wave sleep. These results are in agreement with the hypothesis that the arousal response to hypoxia mediated by the chemoreceptors could be responsible for the termination of sleep apneas.", "Previous publications have shown beneficial effects of cholinergic medication on obstructive sleep apnea (OSA) in Alzheimer's disease (AD) patients. We hypothesized that cholinergic medication could also improve OSA in non-AD patients. The present study evaluated the effects of donepezil on OSA in non-AD patients.\n A randomized, double-blind, placebo-controlled study was conducted. The final sample consisted of 21 male patients with mild to severe OSA and AHI >10 divided into two groups, a donepezil-treated group (n=11) and a placebo-treated group (n=10). The dosage was one tablet/day (5 mg) for the first two weeks and two tablets/day (10 mg) for the last two weeks. Polysomnography and sleepiness evaluations were performed at baseline and after one month of treatment. Groups were compared using two-way ANOVA for repeated measures with treatment-group and treatment-time as the main factors and time-treatment as an interaction effect.\n Considering the effect of the interaction with time-treatment, there was a significant improvement in the obstructive apnea/hypopnea index, desaturation index, percentage of time with O(2) saturation ≤3% lower than baseline, lowest oxygen saturation, and the Epworth Sleepiness Scale (ESS) scores with donepezil treatment (p<0.05). Sleep efficiency significantly decreased (p<0.01).\n Donepezil treatment improved obstructive sleep apnea index, oxygen saturation, and sleepiness in parallel with a reduction in sleep efficiency. Our findings support the concept that cholinergic transmission may influence breathing regulation in OSA patients.\n Copyright © 2011 Elsevier B.V. All rights reserved.", "Twelve patients with documented obstructive sleep apnea were enrolled in a double-blind placebo controlled crossover trial of oral theophylline, (Uniphyllin) 800 mg, taken at night for four weeks. Overnight polysomnography, using standard techniques, was performed at the end of each treatment period. The total number of apneas (A) and hypopneas (H) decreased significantly while receiving theophylline compared to placebo, from 398 (69), mean (SEM), to 283 (72), p less than 0.01. Sleep quality was, however, significantly worse while receiving theophylline. Obstructive A and H were very much decreased with theophylline (p less than .001), and even when the data were adjusted for the more disturbed sleep with theophylline, this decrease remained significant; the obstructive A and H index fell from 49 (8.7) on placebo to 40 (9) while receiving theophylline, p = 0.02. There was no difference in the numbers of central or mixed A and H, and mean A and H duration was unchanged on the two study nights. Oxygen desaturations greater than 4 percent were less with theophylline treatment (p = 0.02), but mean overnight SaO2 was unchanged. We conclude that theophylline may be beneficial in patients with OSA, but part of the improvement is due to a deterioration in sleep quality.", "nan", "There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease.\n Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance.\n AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01).\n Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. Trial registration: ClinicalTrials.gov Identifier: NCT00480870.", "Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to -15 cm H(2)O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO(2) (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study. Compared with placebo, eszopiclone significantly increased the arousal threshold [-14.0 (-19.9 to -10.9) compared with -18.0 (-22.2 to -15.1) cm H(2)O; P<0.01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25±6 compared with 14±4 events/h of sleep; P<0.01). In conclusion, eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are probably required to achieve elimination of apnoea.", "To investigate the effect of fenofibrate on sleep apnoea indices.\n Proof-of-concept study comprising a placebo run-in period (1 week, 5 weeks if fibrate washout was required) and a 4-week randomized, double-blind treatment period. Thirty-four subjects (mean age 55 years, body mass index 34 kg/m 2 , fasting triglycerides 3.5 mmol/L) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and randomized to once daily treatment with fenofibrate (145 mg NanoCrystal(R) tablet) or placebo. Overnight polysomnography, computerized attention/vigilance tests and blood sampling for measurement of lipids, insulin, fasting plasma glucose and fibrinogen were performed at the end of each study period.\n NCT00816829.\n As this was an exploratory study, a range of sleep variables were evaluated. The apnoea/hypopnoea index (AHI) and percentage of time spent with arterial oxygen saturation (SpO(2)) <90% were relevant as they have been evaluated in other clinical trials. Other variables included total apnoeas, hypopnoeas and oxygen desaturations, and non-cortical micro-awakenings related to respiratory events per hour.\n Fenofibrate treatment significantly reduced the percentage of time with SpO(2) <90% (from 9.0% to 3.5% vs. 10.0% to 11.5% with placebo, p = 0.007), although there was no significant change in the AHI (reduction vs. control 14% (95%CI -47 to 40%, p = 0.533). Treatment reduced obstructive apnoeas (by 44%, from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo, p = 0.048), and non-cortical micro-awakenings per hour (from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo, p = 0.004). Other sleep variables were not significantly influenced by fenofibrate. KEY LIMITATIONS: Exploratory study in patients with mild to moderate sleep apnoea, limited treatment duration; concomitant hypnotic treatment (35%); lack of correction for multiplicity of testing.\n The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome.", "Whether nasal congestion promotes obstructive sleep apnea is controversial. Therefore, we performed a randomized placebo-controlled cross-over trial on the effects of topical nasal decongestion in patients with obstructive sleep apnea syndrome (OSA) and nasal congestion. Twelve OSA patients with chronic nasal congestion (mean +/- SD age 49.1 +/- 11.1 years, apnea/hypopnea index 32.6 +/- 24.5/h) were treated with nasal xylometazoline or placebo for 1 week each. At the end of treatment periods, polysomnography including monitoring of nasal conductance by an unobtrusive technique, vigilance by the OSLER test, and symptom scores were assessed. Data from xylometazoline and placebo treatments were compared. Mean nocturnal nasal conductance on xylometazoline was significantly higher than on placebo (8.6 +/- 5.3 versus 6.3 +/- 5.8 mL s(-1)Pa(-1), P < 0.05) but the apnea/hypopnea index was similar (29.3 +/- 32.5/h versus 33.2 +/- 32.8/h, P = NS). However, 30-210 min after application of xylometazoline, at the time of the maximal pharmacologic effect, the apnea/hypopnea index was slightly reduced (27.3 +/- 30.5/h versus 33.2 +/- 33.9/h, P < 0.05). Xylometazoline did not alter sleep quality, sleep resistance time (33.6 +/- 8.8 versus 33.4 +/- 10.1 min, P = NS) and subjective sleepiness (Epworth score 10.5 +/- 3.8 versus 11.8 +/- 4.4, P = NS). The reduced apnea/hypopnea index during maximal nasal decongestion by xylometazoline suggests a pathophysiologic link but the efficacy of nasal decongestion was not sufficient to provide a clinically substantial improvement of OSA.", "Pharmacologic enhancement of serotonergic transmission by serotonin uptake inhibition has been suggested as one approach to improve upper-airway patency and thus nocturnal breathing in patients with obstructive sleep apnea (OSA). To test this hypothesis, we performed a double-blind, randomized, placebo-controlled crossover study testing the effect of paroxetine (20 mg od) on polysomnographic and psychopathologic outcomes in 20 male OSA patients (mean age 52.1 years, mean BMI 28.7 kg/m2, mean oxygen desaturation index on a previous screening 25.4/hour). The two treatment periods of 6 weeks and the separating washout period of 4 weeks were completed by 17 patients. Paroxetine reduced the apnea index during NREM sleep (-35%, p = 0.003), but not during REM sleep. No significant effect on hypopnea indices was found. With the exception of a previously described REM-postponing effect (p = 0.05), sleep architecture was not significantly influenced by paroxetine. Similarly, the effect of paroxetine on apnea was not associated with a significant overall alleviation of psychopathologic symptoms as rated on the Comprehensive Psychopathological Rating Scale or OSA-related daytime complaints assessed by visual analog scales. We conclude that enhanced serotonergic transmission improves breathing during NREM sleep in OSA. This effect is poorly related to effects on sleep architecture or daytime symptoms.", "The effect of inhaled long-acting beta2-agonists in obstructive sleep apnea syndrome (OSAS) is unknown, although from the pharmacological point of view both therapeutic and adverse effects need to be considered. The purpose of this study was to obtain data on the efficacy and safety of salmeterol in patients with OSAS. In a randomized, double-blind, placebo-controlled, cross-over study, effects of salmeterol on respiration during sleep and sleep quality were investigated in 20 patients with OSAS. Of these, 4 patients were female, 16 male; the average age was 53.0 +/- 7.8 years, with average body mass index 28.0 +/- 3.0 kg small middle dot m(-2) and average apnea hypopnea index 35.6 +/- 17.8 h(-1). Patients with asthma, chronic obstructive pulmonary disease (COPD), and left heart failure were excluded. Placebo or verum (50 &mgr;g salmeterol) was administered at 7 pm by meter dose inhaler and spacer device. All patients underwent full polysomnography during baseline, placebo, and verum night. Statistical analysis was performed by StudentOs t-test (p > 0.05). Between the placebo and verum there were no differences in total sleep time, sleep stages, apnea index (AI), apnea hypopnea index (AHI), and nadir oxygen saturation. There was, however, 1) a significant deterioration of mean oxygen saturation (SaO2m; placebo 93.1 +/- 2.0 vs. verum 92.5 +/- 2.2%; p = 0.01), 2) of percent of time spent with an oxygen saturation (SaO2) </= 90% (placebo 13.1 +/- 14.5 vs. verum 19.5 +/- 20.8%; p = 0.02), and 3) a significant increase in heart rate (placebo 63.1 +/- 9.2 vs. verum 65.6 +/- 9.3 h(-1); p = 0.01). In patients with OSAS, salmeterol had no adverse effect on quality of sleep, AI or AHI. The slight increase in heart rate and the deterioration of oxygen saturation probably have no clinical relevance; the latter condition might be due to ventilation-perfusion-mismatch. This study excluded any influence of salmeterol on obstructive sleep apnea and hypopnea; on the other hand, salmeterol turned out to be safe in terms of OSAS. This might be of special importance in patients suffering from both OSAS and obstructive airway disease.", "nan", "The methylxanthine derivatives are known to have respiratory stimulant properties. To determine whether these drugs would improve obstructive sleep apnea, 10 male patients with obstructive sleep apnea (OSA) (Apnea Index greater than 15/h) were given infusions of aminophylline and a saline placebo on 2 separate nights a week apart, using a randomized crossover design. There was a significant decrease during aminophylline infusion in the frequency of those apneas, which contained periods of complete respiratory inactivity (central and mixed apneas; placebo, 4.3 +/- 1.8/h; aminophylline, 0.7 +/- 0.5/h; p less than 0.05). There was no change in either the frequency (placebo, 31.8 +/- 5.9/h; aminophylline, 28.7 +/- 8.7/h; NS) or duration of obstructive apneas. Mean and minimal arterial oxygen saturation values were also unchanged. Sleep architecture was markedly disturbed by aminophylline. There was a reduction in sleep efficiency (placebo, 84.8 +/- 2.0%; aminophylline, 60.2 +/- 5.0%; p less than 0.005), an increase in sleep fragmentation (sleep stage shifts/h: placebo, 11.6 +/- 1.3: aminophylline, 21.0 +/- 2.9; p less than 0.05) and less Stage 2 and more Stage 1 non-REM sleep. We conclude that aminophylline reduces central apnea and the central component of mixed apneas but has no effect on obstructive apnea. Theophylline is therefore unlikely to be therapeutically useful in patients with OSA, and because it leads to marked sleep disruption, its long-term use could conceivably increase the propensity to upper airway occlusion during sleep.", "We evaluated protriptyline, a nonsedating tricyclic antidepressant, as a treatment for obstructive sleep apnea in a double-blind crossover study of five men. After two weeks of treatment, with no change in body weight, daytime somnolence was markedly reduced and nocturnal oxygenation was improved, although apnea duration and frequency were not significantly decreased. Rapid-eye-movement (REM) stage time as a fraction of the total sleep time was reduced during treatment from 0.231 +/- 0.031 to 0.107 +/- 0.013 (mean +/- S.E.M.) (P less than 0.05). REM apnea time as a fraction of total sleep time was reduced from 0.145 +/- 0.022 to 0.054 +/- 0.006 (P less than 0.05). REM reduction during treatment with protriptyline can account for decreased REM apnea time. Similar decreases in REM stage time and REM apnea duration and similar improvement in oxygenation continued after six months of treatment. In addition, body weight, apnea, and arousal frequency were decreased at this time. Although the obstructive sleep apnea was not resolved, it was reduced. Protriptyline can be effective in patients with sleep apnea when the disorder is not life-threatening." ]

[ "11084569", "16411999" ]

[ "A randomized clinical trial comparing primary overlap with approximation repair of third-degree obstetric tears.", "How to repair an anal sphincter injury after vaginal delivery: results of a randomised controlled trial." ]

[ "We compared, in a prospective, randomized clinical trial, the subjective and objective outcomes after primary anal sphincter overlap or approximation repair of third-degree obstetric tears.\n In a prospective, randomized clinical trial at our university teaching hospital, we studied 112 primiparous women who sustained a third-degree tear during a 1-year period (July 1998-June 1999); they were randomly selected, at diagnosis, to receive either an overlap or an approximation repair. Obstetric personnel, trained in both methods, carried out the repairs immediately after delivery. Fifty-five women underwent an overlap procedure, and 57 women underwent an approximation repair. Outcome measures assessed were symptoms of fecal incontinence, abnormal findings on anal manometry, and abnormal findings on endoanal ultrasonography at 3 months post partum.\n Obstetric factors, including mode of delivery, birth weight, duration of labor, and episiotomy incidence, did not differ significantly between the 2 groups. Experience of the operator, analgesia used, and place of repair were similar in both groups. The median incontinence scores were 0/20 after overlap repair and 2/20 after approximation repair (difference not significant). Eleven women (20%) complained of fecal urgency after overlap repair, in comparison with 17 (30%) after approximation repair (difference not significant). There were no significant differences in either anal manometry or endoanal ultrasonographic results between the 2 groups. Six women (11%) had a significant (>1 quadrant) anal sphincter defect after primary overlap repair, compared with 3 (5%) after approximation repair (difference not significant). Overall, 66% of women had ultrasonographic evidence of a residual full-thickness defect in the external anal sphincter after primary repair.\n The outcome after primary repair of third-degree obstetric tear was similar whether an approximation or an overlap technique was used. Overall symptomatic outcome was good, although two thirds of women had ultrasonographic evidence of residual anal sphincter damage irrespective of the method of repair.", "To compare two surgical techniques and two types of suture material for anal sphincter repair after childbirth-related injury.\n Factorial randomised controlled trial.\n Tertiary referral maternity unit.\n Women with an anal sphincter injury sustained during childbirth.\n Women were randomised into four groups: overlap repair with polyglactin (Vicryl); end-to-end repair with polyglactin (Vicryl); overlap repair with polydioxanone (PDS); and end-to-end repair with PDS. All repairs were completed as a primary procedure by staff trained in both methods.\n Suture-related morbidity at six weeks. Bowel symptoms at 3, 6 and 12 months. Anorectal physiology at three months. Quality of life scores at 3 and 12 months.\n One hundred and fifty women (1.5% of deliveries) were eligible and 112 (75%) were randomised. One hundred and three (92%) attended follow up visit at 6 weeks, 89 (80%) at 3 months, 79 (71%) at 6 months and 60 (54%) at 12 months. At six weeks, there was no difference in suture-related morbidity between groups (P=0.11) and 70% patients were completely asymptomatic. Incidence of bowel symptoms and quality of life disturbances were low, with no differences between the four groups.\n Obstetric anal sphincter repair carried out by appropriately trained staff is associated with low morbidity, irrespective of the suture material and repair method used." ]

[ "11932561", "17545356", "14670773", "21905270" ]

[ "Effect of growth hormone on exercise tolerance in children with cystic fibrosis.", "A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the metabolic and respiratory effects of growth hormone in children with cystic fibrosis.", "Prospective randomised treatment with recombinant human growth hormone in cystic fibrosis.", "A multi-center controlled trial of growth hormone treatment in children with cystic fibrosis." ]

[ "The effect of growth hormone (GH) treatment on exercise tolerance in children with cystic fibrosis was investigated.\n 10 prepubertal children (mean +/- SD; age: 12.1 +/- 1.7 yr; height: 137.4 +/- 9.2 cm; body mass: 27.8 +/- 4.2 kg; forced expiratory volume in 1 s (FEV1): 68 +/- 22% predicted) were randomly assigned to either control period (CON, standard therapy) or recombinant human growth hormone (GH) period (additional GH treatment, 0.11-0.14 IU.kg-1, daily, s.c.) for the first 6 months, and then assigned to the other period for the next 6 months. At study entry and after each period, anthropometric data, pulmonary function, and exercise capacity (peak exercise capacity, .VO(2peak), and isokinetic muscle strength) were measured.\n Changes in height (+4.3 +/- 1.0 cm), total body mass (+2.2 +/- 0.8 kg), and lean body mass (LBM, +2.9 +/- 0.7 kg) were significantly higher (P < 0.01) after GH treatment compared with CON. Pulmonary function did not significantly change in either of the periods. In contrast to CON, GH treatment improved absolute .VO(2peak) (+19%, P < 0.01), peak ventilation (+14%, P < 0.01), and peak oxygen pulse (+18%, P < 0.01). Analysis of variance revealed that most of the changes (71%) in .VO(2peak) could be explained by those in LBM and FEV1 (P = 0.001).\n GH treatment clearly improved exercise tolerance, presumably resulting from the combined effects of GH on the muscular, cardiovascular, and pulmonary capacity.", "Positive effects of growth hormone therapy on growth, nutritional status, and lung function have been observed in patients with cystic fibrosis, but the current evidence is based on unblinded studies that involved a small number of patients. This trial was designed as a multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy and safety of 2 dosages of growth hormone in cystic fibrosis.\n Sixty-three dystrophic patients with cystic fibrosis were randomly assigned for 24 weeks to 1 of 3 treatment arms: growth hormone dosage of 0.11 IU/kg body weight per day, growth hormone dosage of 0.21 IU/kg body weight per day, or placebo. The 24-week double-blind period was followed by an open treatment period of 24 weeks. The primary outcome measure was the change in forced expiratory volume in 1 second in percentage predicted from baseline. Secondary outcome measures were changes in height, weight, and exercise tolerance.\n Height, growth velocity, and growth factors (insulin-like growth factor 1 and insulin-like growth factor-binding protein 3) increased significantly in both treatment groups, whereas weight gain did not differ between the growth hormone groups and placebo. A trend toward improvement in absolute forced vital capacity was observed in patients who received the higher growth hormone dosage, whereas forced expiratory volume in 1 second did not change significantly with growth hormone treatment. Maximal oxygen uptake during peak exercise increased significantly in treated patients. There were no significant differences in the frequency or severity of adverse effects or in the incidence of abnormalities in glucose metabolism.\n These data suggest that in the group investigated, growth hormone therapy was well tolerated and had positive metabolic effects but did not result in short-term improvement of lung function in patients with cystic fibrosis.", "To evaluate the efficacy and safety of treatment with recombinant growth hormone (rGH) in patients with cystic fibrosis (CF).\n Twenty patients with CF (aged 10-23 years) were randomised to age and sex matched treatment and control groups. The treatment group received daily subcutaneous injections of 1 IU/kg/wk rGH for 12 months. Pulmonary function (forced expiratory volume in one second (FEV1) and airway resistance), exercise capacity measured with a bicycle ergometer, body composition (dual energy x ray absorptiometry), and weight were assessed at the beginning of the study and after 6 and 12 months.\n rGH treatment did not improve weight and pulmonary function, but lean body mass increased significantly in the treatment group. Exercise capacity increased in the treatment group from 143 (16) W (mean (SD)) to 164 (19) W after 12 months of rGH treatment.\n Treatment of CF patients with rGH for one year improved the exercise capacity significantly but not pulmonary function. The improved exercise capacity needs confirmation in a larger population before such an expensive treatment is justified.", "We evaluated safety and efficacy of recombinant human growth hormone (rhGH) for improving growth, lean body mass (LBM), pulmonary function, and exercise tolerance in children with cystic fibrosis (CF) and growth restriction.\n Multicenter, open-label, controlled clinical trial comparing outcomes in prepubertal children <14 years with CF, randomized in a 1:1 ratio to receive daily rhGH (Nutropin AQ) or no treatment (control) for 12 months, followed by a 6-month observation (month 18). Safety was monitored at each visit, including assessments of glucose tolerance.\n Sixty-eight subjects were randomized (control n = 32; rhGH n = 36). Mean height standard deviation score (SDS) in the rhGH group increased by 0.5 ± 0.4 at 12 months (mean ± SD, P < 0.001); the control group height SDS remained unchanged. Weight increased by 3.8 ± 1.8 versus 2.8 ± 1.5 kg, (mean ± SD, P = 0.0356) and LBM increased by 3.8 ± 1.8 versus 2.1 ± 1.4 kg (P = 0.0002) in the rhGH group versus controls, respectively. Forced vital capacity increased by 325 ± 319 in the rhGH group compared with 178 ± 152 ml in controls (mean ± SD, P = 0.032). Forced expiratory volume in 1 sec improved in both groups with a significant difference between groups after adjustment for baseline severity (LS mean ± SE: rhGH, 224 ± 37, vs. controls, 108 ± 40 ml; P = 0.04). There was no difference between groups in exercise tolerance (6-min walk distance) at 1 year. Changes in glucose tolerance for the two groups were similar over the 12-month study period, with three subjects developing IGT and one CFRD in each group. One rhGH-treated patient developed increased intracranial pressure.\n Treatment with rhGH in prepubertal children with CF was effective in promoting growth, weight, LBM, lung volume, and lung flows, and had an acceptable safety profile.\n Copyright © 2011 Wiley Periodicals, Inc." ]

[ "17577461", "11293556", "10566562", "17933588", "18164917", "12462285", "15117090", "12162474" ]

[ "A randomized, double-blind, celecoxib- and placebo-controlled study of the effectiveness of CS-706 in acute postoperative dental pain.", "Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults.", "Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial.", "Lumiracoxib 400 mg compared with celecoxib 400 mg and placebo for treating pain following dental surgery: a randomized, controlled trial.", "Analgesic efficacy of celecoxib in postoperative oral surgery pain: a single-dose, two-center, randomized, double-blind, active- and placebo-controlled study.", "A comparison of rofecoxib versus celecoxib in treating pain after dental surgery: a single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study using the dental impaction pain model.", "Analgesic efficacy of a single dose of lumiracoxib compared with rofecoxib, celecoxib and placebo in the treatment of post-operative dental pain.", "Efficacy and tolerability of nonprescription ibuprofen versus celecoxib for dental pain." ]

[ "CS-706 is a cyclooxygenase-2 (COX-2)-selective inhibitor with an in vitro selectivity ratio (COX-1:COX-2) similar to that of celecoxib. It has exhibited analgesic, anti-inflammatory, and antitumor properties in animal models.\n This study evaluated the tolerability of single doses of CS-706 and compared the analgesic efficacy of CS-706 with that of celecoxib and placebo in the dental pain model.\n This was a randomized, double-blind, double-dummy, active- and placebo-controlled study. Healthy male and female subjects with moderate to severe pain intensity (PI) after dental surgery were randomized ( approximately 50 per group) to receive a single oral dose of CS-706 10, 50, 100, or 200 mg; celecoxib 400 mg; or placebo. PI and pain relief (PR) were measured on categorical and visual analog scales through 24 hours after the dose. The primary efficacy variable was the time-weighted sum of PR scores at 4 hours after the dose (TOPAR4). The onset of analgesia was assessed by calculating the pain intensity difference (PID). Perceptible and meaningful pain relief were assessed using a 2-stopwatch method.\n The majority of subjects were female (62.0%) and white (59.5%). Subjects' mean (SD) age was 22.6 (3.9) years, and their mean body mass index was 25.3 (5.1) kg/m(2). All doses of CS-706 were associated with significant analgesic efficacy compared with placebo based on the primary end point, TOPAR4 (P<0.001), and on all secondary end points (P<0.05, comparisons of all CS-706 doses vs placebo) with the exception of time to 100% PR for CS-706 10 mg. Single 50-, 100-, and 200-mg doses of CS-706 also were significantly more effective than celecoxib for TOPAR4 (P=0.036, P=0.004, and P=0.006, respectively). The onset of analgesia (PID >or= 1) for all CS-706 doses occurred within 1 hour after dosing (P<0.001 vs placebo). The median duration of analgesia, measured as the time to administration of rescue medication, was significantly greater for all doses of CS-706 compared with placebo (5.7 hours for CS-706 10 mg, >24 hours for CS-706 50, 100, and 200 mg, and 1.7 hours for placebo; P<0.001 for CS-706 50, 100, and 200 mg). These data suggest that once-daily administration of CS-706 may be effective in providing relief of acute pain. The incidence of adverse events was similar among all treatment groups. Adverse events occurring in >or= 5 % of subjects in any treatment group were nausea, vomiting, dry socket, dizziness, headache, and paresthesia.\n Single doses of CS-706 had significant analgesic efficacy compared with celecoxib and placebo in the relief of postoperative dental pain in the healthy subjects enrolled in this study.", "Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, both types of medications are associated with side effects that can limit their usefulness in the outpatient setting.\n Two studies with identical protocols assessed the single- and multiple-dose analgesic efficacy and tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the treatment of acute pain after orthopedic surgery.\n These were multicenter, randomized, placebo- and active-controlled, double-blind, parallel-group trials conducted between January and June 1998. Both consisted of a single-dose assessment period (SDAP) and a multiple-dose assessment period (MDAP). In the SDAP, patients who had undergone orthopedic surgery received a single oral dose of celecoxib 200 mg, hydrocodone 10 mg/acetaminophen 1000 mg, or placebo within 24 hours after the end of anesthesia, with pain assessments conducted over the following 8-hour period. In the MDAP, extending from 8 hours after the first dose of study medication up to 5 days, patients who had received < or =1 dose of rescue medication during the SDAP continued on study medication (placebo recipients were rerandomized to active treatment), which could be taken up to 3 times a day as needed.\n A total of 418 patients were enrolled in the 2 trials. During the SDAP, 141 patients received celecoxib, 136 received hydrocodone/acetaminophen, and 141 received placebo. During the MDAP, 185 patients received celecoxib and 181 received hydrocodone/acetaminophen. When the combined data were analyzed, mean pain intensity difference (PID) scores generally favored the active treatments over placebo from 1 to 6 hours (with the exception of 1.5 hours) after dosing (P < or = 0.016) and favored celecoxib over the other treatments at 7 and 8 hours after dosing (P < 0.001). The active treatments demonstrated superior summed PID scores through 8 hours (P < 0.001), significantly shorter median times to onset of analgesia (P < 0.05), and significantly longer median times to first use of rescue medication (P < 0.05). During the MDAP, more hydrocodone/acetaminophen-treated patients (20%) than celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the celecoxib group had significantly lower maximum pain intensity scores (P < 0.001, days 2-5), required fewer doses of study medication (P < or = 0.01, days 3-5), and had superior scores on a modified American Pain Society Patient Outcome Questionnaire (P < or = 0.013). In addition, a significantly lower proportion of celecoxib-treated patients experienced adverse events (43%) compared with hydrocodone/acetaminophen-treated patients (89%; P < 0.001).\n Over 8 hours, patients with moderate to severe pain after orthopedic surgery experienced comparable analgesia with single doses of celecoxib and hydrocodone/acetaminophen. Over a 5-day period, oral doses of celecoxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerability compared with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day. Most patients required no more than 2 daily doses of celecoxib 200 mg for the control of their postorthopedic surgical pain.", "Pain is a common complaint, often occurring in conjunction with inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic agents in ambulatory patients. In recent studies, the cyclooxygenase-2 (COX-2) inhibitor rofecoxib demonstrated analgesic effects similar to those of NSAIDs in the treatment of acute pain and primary dysmenorrhea. The present randomized, single-dose, double-blind, double-dummy, placebo- and active-comparator-controlled, parallel-group study was undertaken to compare the analgesic efficacy of the COX-2 inhibitors rofecoxib 50 mg and celecoxib 200 mg with that of ibuprofen 400 mg and placebo in patients with postoperative dental pain. Two hundred and seventy-two patients experiencing pain after the removal of > or =2 third molars were randomized according to pain severity (moderate vs severe) to receive a single dose of placebo (n = 45), rofecoxib 50 mg (n = 90), celecoxib 200 mg (n = 91), or ibuprofen 400 mg (n = 46). Using a patient diary, patients recorded pain intensity, pain relief, and global evaluations throughout the 24-hour period after dosing. The overall analgesic effect, onset of action, peak effect, and duration of effect were evaluated, with the primary end point being total pain relief over 8 hours (TOPAR8). The safety profile was assessed on the basis of physical findings, laboratory results, and spontaneous reports of adverse experiences. The results showed that compared with celecoxib, rofecoxib had superior analgesic effects on all measures of analgesic efficacy, including overall analgesic effect (TOPAR8, 18.3 vs. 12.5; P<0.001), time to onset of effect (30 vs. 60 minutes; P = 0.003), peak pain relief (score, 2.8 vs 2.3; P<0.05), and duration of effect (>24 vs. 5.1 hours; P<0.001). In addition, rofecoxib's analgesic efficacy was similar to that of ibuprofen (TOPAR8, 18.3 vs. 17.0; P = 0.460), but the duration was longer (P<0.05); with ibuprofen, the time to on set was 24 minutes, peak pain relief score was 2.9, and duration of analgesic effect was 8.9 hours. The safety profile was similar across all treatment groups. Thus rofecoxib provided analgesic efficacy superior to that of celecoxib and comparable to that of ibuprofen in the treatment of patients with acute postoperative dental pain.", "This randomized, double-blinded, double-dummy, parallel-group, single-center study compared a single dose of the novel selective COX-2 inhibitor lumiracoxib (400 mg), with celecoxib (400 mg) or placebo in dental pain. Patients > or =17 years with moderate-to-severe dental pain were recruited after surgical extraction of 2 or more partially or fully bony impacted molars. Pain intensity was measured using the categorical scale and the primary efficacy variable was the summed pain intensity difference over 8 hours after dosing (SPID-8). Patient disposition and demographics were comparable between lumiracoxib 400 mg (n = 156), celecoxib 400 mg (n = 156), and placebo (n = 52) groups. Lumiracoxib was statistically superior (P < .001) to both celecoxib and placebo in reducing pain intensity (SPID-8; least-squares means: 8.31, lumiracoxib; 4.26, celecoxib; -1.87, placebo). Significantly more patients treated with lumiracoxib (58.9%) considered treatment to be good or excellent compared with celecoxib and placebo (42.3% and 5.7%, respectively; P = .001). Lumiracoxib was superior to celecoxib and placebo for all other secondary efficacy variables. All treatments were well-tolerated. In conclusion, 400 mg lumiracoxib was well-tolerated and provided significantly superior analgesia to 400 mg celecoxib or placebo in patients with moderate-to-severe pain after dental surgery.\n In a randomized, double-blinded, double-dummy, parallel-group, single-center study, a single dose of the novel selective COX-2 inhibitor lumiracoxib (400 mg) was well-tolerated and provided significantly superior analgesia to 400 mg celecoxib or placebo in patients with moderate-to-severe dental pain after surgical extraction of impacted molars.", "Celecoxib 200 mg has been reported to reduce pain following dental extraction but to offer poorer pain relief than active comparators.\n The aim of this study was to compare the efficacy and tolerability of celecoxib 400 mg, the recommended loading dose for treatment of acute pain, with that of ibuprofen 400 mg and placebo following oral surgery.\n This was a single-dose, 2-center, randomized, double-blind, active- and placebo-controlled study in which patients with moderate to severe pain following third molar extraction were randomized to receive a single dose of celecoxib 400 mg, ibuprofen 400 mg, or placebo. Pain assessments were completed using a 4-point pain intensity scale where 0=no pain and 3=severe pain and a 5-point pain relief scale where 0=no pain relief and 4= complete pain relief at baseline and 18 time points over 24 hours. Primary efficacy outcome measures were time to onset of analgesia (the median time to perceptible pain relief in those patients who achieved meaningful pain relief), time-specific pain intensity difference (PID), time-specific pain relief (PR), time-specific sum of PID and PR, and time to use of rescue medication. Times to perceptible and meaningful pain relief (secondary efficacy outcome measures) were recorded using 2 stopwatches. Tolerability was assessed through recording of adverse events, clinical laboratory tests, and physical examinations (including collection of vital signs).\n One hundred seventy-one patients were randomized to celecoxib 400 mg (30 women and 27 men; mean [SD] age, 21.4 [4.2] years); ibuprofen 400 mg (30 women and 27 men; mean [SD] age, 22.0 [4.7] years); or placebo (34 women and 23 men; mean [SD] age, 21.6 [5.0] years). Mean times to onset of analgesia with celecoxib 400 mg and ibuprofen 400 mg were rapid and comparable (median 28 minutes and 26 minutes, respectively) and were significantly shorter than with placebo (>24 hours) (both, P<0.05 vs placebo). Compared with placebo, mean time-specific PID scores were significantly greater with celecoxib from 0.5 to 24 hours and with ibuprofen from 0.5 to 16 hours (all, P<0.05 vs placebo). Time-specific PR scores with celecoxib and ibuprofen were significantly greater from 0.75 and 0.5 hour, respectively, compared with placebo (all, P<0.05 vs placebo). PID was significantly greater with celecoxib compared with ibuprofen beginning at 11 hours (all, P<0.05). PR scores were significantly higher with celecoxib versus ibuprofen beginning at 9 hours (all, P<0.05). Median (95% CI) time to use of rescue medication with celecoxib (>24 hours) was significantly longer than with ibuprofen (10 hours, 58 minutes [8 hours, 30 minutes- 14 hours, 34 minutes]) or placebo (1 hour, 51 minutes [1 hour, 40 minutes-2 hours, 22 minutes]) (both, P<0.05). The 3 most common adverse events experienced in the celecoxib group were headache (9 [15.8%] patients), nausea (9 [15.8%] patients), and dizziness (6 [10.5%] patients).\n In this postsurgical dental pain study, the onset and magnitude of pain relief with celecoxib 400 mg and ibuprofen 400 mg were found to be comparable. In addition, patients who received celecoxib 400 mg as a single dose had a significantly longer time to use of rescue medication and had higher pain relief scores later in the study than those who received ibuprofen 400 mg. Celecoxib was well tolerated compared with placebo.", "Rofecoxib and celecoxib, selective cyclooxygenase-2 inhibitors, have analgesic efficacy similar to that of nonselective nonsteroidal anti-inflammatory drugs.\n This study was designed to confirm earlier findings that the overall analgesic efficacy of rofecoxib 50 mg was superior to that of celecoxib 200 mg and to extend the comparison to include celecoxib 400 mg.\n In this single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study, patients who experienced moderate or severe pain after surgical extraction of at least 2 third molars received a single oral dose of either rofecoxib 50 mg, celecoxib 400 mg, celecoxib 200 mg, ibuprofen 400 mg, or placebo. Patients recorded scores of pain intensity, pain relief, and global assessment at prespecified time intervals throughout the 24-hour period after dosing. The end points were total pain relief (TOPAR) score over 8 hours (TOPAR8; primary end point), TOPAR score over 12 hours (TOPAR12), sum of pain intensity difference (SPID) over 8 and 12 hours (SPID8 and SPID12), patient's global assessment of study drug at 8 hours, time to confirmed perceptible pain relief (ie, time to onset of analgesic effect), peak pain intensity difference (PID), peak pain relief, time to first dose of rescue medication (ie, duration of analgesic effect), and percentage of patients using rescue medication.\n A total of 482 patients (358 females, 124 males; mean age, 22.1 years) were enrolled. Rofecoxib 50 mg (n = 151 patients) demonstrated significantly greater overall analgesic efficacy compared with celecoxib 400 mg (n = 151), as measured by TOPAR8 (least squares mean [SE] 17.2 [0.8] vs 15.0 [0.8]; P < 0.05) and TOPAR12 (25.3 [1.2] vs 21.0 [1.2]; P < 0.05), as well as a significantly longer duration of analgesic effect (P < 0.05). Time to onset of analgesic effect and peak analgesic effect were similar for rofecoxib 50 mg and celecoxib 400 mg. Rofecoxib also showed significantly greater overall analgesic efficacy than did celecoxib 200 mg (n = 90), including greater TOPAR8 scores (17.2 [0.8] vs 11.5 [1.1]; P < 0.001), faster onset of analgesic effect (P < 0.001), greater peak analgesic effect (P < 0.001 for peak pain relief and peak PID), and longer duration of analgesic effect (P < 0.001). The overall analgesic efficacy of rofecoxib 50 mg was similar to that of ibuprofen 400 mg (n = 45), except that the duration of analgesic effect of rofecoxib 50 mg was significantly longer (P < 0.001). All active treatments produced significantly greater overall analgesic efficacy compared with that of placebo (P < 0.001 for all scores [TOPAR8, TOPAR12, SPID8, SPID12, and patient's global assessment] for all study drugs). The adverse-events (AE) profile was generally similar in all treatment groups. The 3 most common AEs were nausea, postextraction alveolitis, and vomiting.\n In this study, rofecoxib 50 mg provided generally superior overall analgesic efficacy compared with that of celecoxib 400 and 200 mg, including a significantly longer duration of analgesic effect. The overall analgesic efficacy of rofecoxib 50 mg was generally similar to that of ibuprofen 400 mg, except for a significantly longer duration of analgesic effect.", "This randomised, double-blind, placebo-controlled, parallel-group study compared the efficacy and tolerability of lumiracoxib (a novel COX-2 selective inhibitor) with rofecoxib, celecoxib and placebo in patients with moderate-to-severe post-operative dental pain. Following third molar extraction, patients received single oral doses of lumiracoxib 400 mg, rofecoxib 50 mg, celecoxib 200 mg or placebo (n = 355). Additional patients from a similar study, assigned to lumiracoxib, rofecoxib or placebo (n = 155), were included for analysis of the primary variable, Summed Pain Intensity Difference over the first 8 h post dose (SPID-8). For SPID-8, lumiracoxib was superior to rofecoxib (p < 0.05), celecoxib (p < 0.001) and placebo (p < 0.001). Lumiracoxib demonstrated the fastest onset of analgesia and the longest time to rescue medication use. Patient global evaluation of lumiracoxib was comparable to rofecoxib and superior to celecoxib and placebo. All treatments were well tolerated. Lumiracoxib 400 mg provides rapid, effective and sustained relief of post-operative dental pain, comparable or superior to rofecoxib.", "Many clinicians appear confused about the purported clinical advantages of the new generation COX-2 inhibitors compared to both over-the-counter and prescription nonsteroidal anti-inflammatory analgesic agents (NSAIDs). Infact, there is a paucity of published information comparing the safety and efficacy of these two classes of drugs when used to treat acute pain. This study was designed to compare the safety and analgesic efficacy of an over-the-counter (OTC) analgesic, ibuprofen (Advil Liqui-Gels), to the leading prescription COX-2 inhibitor celecoxib (Celebrex). Ibuprofen liquigel is an encapsulated, solubilized potassium salt of ibuprofen that has a higher Cmax and shorter tmax than traditional ibuprofen solid-dosage formulations. This trial evaluated the maximum approved OTC dosing regimen (400 mg x 3, q4-6h) of ibuprofen liquigels compared to a single dose of celecoxib (200 mg) and placebo in 174 patients with moderate orsevere pain following surgical extraction of impacted third molars. The study design was multiple dose, randomized (stratified by baseline pain and gender), placebo controlled, double blind, double dummy, and parallel group. The onset of pain relief was determined using a two-stopwatch procedure. Treatments were also compared using standard indices of pain intensity and pain relief. The study demonstrated assay sensitivity in that both active medications were significantly more effective than placebo for all efficacy measures. In comparing the two active medications, the time to meaningful relief was significantly shorter, and the mean 4-, 8-, and 12-hour summed pain relief combined with pain intensity difference scores were significantly higher for ibuprofen liquigels compared with celecoxib (p < 0.001). Analyses of other key efficacy variables, including the time to rescue medication and the patients' overall assessment of study medication, confirmed the superior efficacy of ibuprofen liquigels over celecoxib. Both active treatments were well tolerated, with no differences in incidence or severity of adverse events. Of particular interest, there were no differences in gastrointestinal-related side effects when comparing these doses of ibuprofen liquigels to celecoxib. In conclusion, ibuprofen liquigels were a significantly more effective analgesic and provided relief significantly faster compared with celecoxib in the treatment of postsurgical pain." ]

[ "8457123", "3918495" ]

[ "Erythromycin in acute laryngitis in adults.", "Inefficacy of penicillin V in acute laryngitis in adults. Evaluation from results of double-blind study." ]

[ "Moraxella catarrhalis and Hemophilus influenzae are isolated from the nasopharynx in 50% to 55% and 8% to 15%, respectively, of cases of acute laryngitis in adults. This finding indicates that these organisms, M catarrhalis in particular, are in some way involved in the pathogenesis of the disorder. In the present double-blind, placebo-controlled trial, the effect of erythromycin ethylsuccinate (0.5 g twice a day for 5 days) on the elimination of nasopharyngeal pathogens and reduction of clinical signs of upper respiratory tract infection, as well as on subjective complaints, was evaluated in 106 adults with acute laryngitis. The bacterial isolation rates at presentation were M catarrhalis 50%, H influenzae 18%, and Streptococcus pneumoniae 4%. In the 99 patients who completed the study, the elimination of M catarrhalis after 1 week was better in the erythromycin group (25 of 30 cases) than in the placebo group (6 of 19 cases; p < or = .00038). The elimination of H influenzae was unaffected by erythromycin. Otolaryngologic examination did not reveal any significant group differences regarding laryngitis, pharyngitis, or rhinitis. Voice quality was improved after 1 week, irrespective of treatment. However, as compared to the placebo group, the erythromycin group reported fewer voice complaints after 1 week and fewer coughing complaints after 2 weeks. As acute laryngitis in adults is self-limiting, and subjective symptoms are spontaneously reduced after 1 week in most cases, antibiotic treatment does not seem warranted as a general policy. However, erythromycin may be justified in patients who are professionally dependent on voice function.", "Patients with acute laryngitis following an upper respiratory tract infection are often treated with antibiotics for their voice complaints, although, to our knowledge, the effect of such therapy has not been examined. In the present study, comprising 100 adults with laryngitis, the rate of resolution of vocal symptoms, as estimated from voice recordings or subjectively by the patients, was the same in patients who received penicillin V (pcV) as in those who received placebo. Similarly, the degree of rhinorrhea/nasal congestion and cough was not significantly influenced by pcV treatment. At the acute visit, nasopharyngeal cultures revealed Branhamella catarrhalis in 50%, Hemophilus influenzae in 15% and Streptococcus pneumoniae in 1% of the patients; the rate of elimination of these bacteria was the same in the pcV as in the placebo group. Thus, while suggesting that B catarrhalis and H influenzae are important for the pathogenesis of the disorder, our results do not provide support for the use of pcV in acute laryngitis." ]

[ "19953579", "19884591", "12576370", "17719935", "19674354", "16599051", "12475841" ]

[ "High volume normal saline alone is as effective as nebulized salbutamol-normal saline, epinephrine-normal saline, and 3% saline in mild bronchiolitis.", "A randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department.", "Nebulized 3% hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis.", "Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants.", "Nebulized hypertonic saline/salbutamol solution treatment in hospitalized children with mild to moderate bronchiolitis.", "Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay: 2 years experience.", "Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms." ]

[ "The objective of this study was to investigate the effectivenesses of nebulized salbutamol, epinephrin, 3% saline, and normal saline (0.9% NaCl) in the treatment of mildly affected infants with acute bronchiolitis. We enrolled 186 children (mean age 9.5 +/- 5.3 months, range 1.5-24 months, 65.1% male) with a first episode of wheezing diagnosed as mild bronchiolitis in emergency department. Patients were randomized in a double-blind fashion to receive 4 ml dose either of 1.5 mg epinephrine plus normal saline (group 1; n = 38) or 1.5 mg epinephrine plus 3% saline (group 2; n = 39) or 2.5 mg salbutamol plus normal saline (group 3; n = 36) or 2.5 mg salbutamol plus 3% saline (group 4; n = 36) or normal saline alone (group 5; n = 37) at 0 and 30 min. Thus, all treatment modalities included high amount of NaCl (72-240 mg). Clinical score, oxygen saturation and heart rate were assessed at 0, 30, 60, and 120 min. After discharge, patients were reassessed by telephone contact at 48 hr and 6 months. The baseline characteristics were similar in all groups (P > 0.05). The outcome of patients at 120 min was found significantly better than the baseline values (P < 0.05). There were no significant differences between the outcome variables of the groups (P > 0.05). No adverse effects attributable to nebulized therapy were seen. In conclusion, all treatment modalities used in this study, including a total of 8 ml normal saline inhalation at 30-min interval showed clinically significant and swift improvement in mildly affected ambulatory infants with acute bronchiolitis.\n (c) 2009 Wiley-Liss, Inc.", "To determine whether nebulized 3% hypertonic saline with epinephrine is more effective than nebulized 0.9% saline with epinephrine in the treatment of bronchiolitis in the emergency department.\n Randomized, double-blind, controlled trial.\n Single-center urban pediatric emergency department.\n Infants younger than 12 months with mild to moderate bronchiolitis.\n Patients were randomized to receive nebulized racemic epinephrine in either hypertonic or normal saline.\n The primary outcome measure was the change in respiratory distress, as measured by the Respiratory Assessment Change Score (RACS) from baseline to 120 minutes. The change in oxygen saturation was also determined. Secondary outcome measures included the rates of hospital admission and return to the emergency department.\n Forty-six patients were enrolled and evaluated. The 2 study groups had similar baseline characteristics. The RACS from baseline to 120 minutes demonstrated no improvement in respiratory distress in the hypertonic saline group compared with the normal saline control group. The change in oxygen saturation in the hypertonic saline group was not significant when compared with the control group. Rates of admission and return to the emergency department were not different between the 2 groups.\n In the treatment of acute bronchiolitis, hypertonic saline and epinephrine did not improve clinical outcome any more than normal saline and epinephrine in the emergency setting. This differs from previously published results of outpatient and inpatient populations and merits further evaluation.\n isrctn.org Identifier: ISRCTN66632312.", "To determine the utility of inhaled hypertonic saline solution to treat infants hospitalized with viral bronchiolitis.\n Randomized, double-blind, controlled trial. Fifty-two hospitalized infants (mean +/- SD age, 2.9 +/- 2.1 months) with viral bronchiolitis received either inhalation of epinephrine, 1.5 mg, in 4 mL of 0.9% saline solution (group 1; n = 25) or inhalation of epinephrine, 1.5 mg, in 4 mL of 3% saline solution (group 2; n = 27). This therapy was repeated three times every hospitalization day until discharge.\n The percentage improvement in the clinical severity scores after inhalation therapy was not significant in group 1 on the first, second, and third days after hospital admission (3.5%, 2%, and 4%, respectively). In group 2, significant improvement was observed on these days (7.3%, 8.9%, and 10%, respectively; p < 0.001). Also, the improvement in clinical severity scores differed significantly on each of these days between the two groups. Using 3% saline solution decreased the hospitalization stay by 25%: from 4 +/- 1.9 days in group 1 to 3 +/- 1.2 days in group 2 (p < 0.05).\n We conclude that in nonasthmatic, nonseverely ill infants hospitalized with viral bronchiolitis, aerosolized 3% saline solution/1.5 mg epinephrine decreases symptoms and length of hospitalization as compared to 0.9% saline solution/1.5 mg epinephrine.", "To investigate the use of nebulized 3% hypertonic saline (HS) for treating viral bronchiolitis in moderately ill hospitalized infants by a prospective, randomized, double-blinded, controlled, multicenter trial.\n A total of 96 infants (mean age, 4.7 months; range, 0.3 to 18 months) admitted to the hospital for treatment of viral bronchiolitis were recruited from 3 regional pediatric centers over 3 bronchiolitis seasons (December 2003 to May 2006). Patients were randomized to receive, in a double-blind fashion, repeated doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group), in addition to routine therapy ordered by the attending physician. The principal outcome measure was hospital length of stay (LOS).\n On an intention-to-treat basis, the infants in the HS group had a clinically relevant 26% reduction in LOS to 2.6 +/- 1.9 days, compared with 3.5 +/- 2.9 days in the NS group (P = .05). The treatment was well tolerated, with no adverse effects attributable to the use of HS.\n The use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis.", "The objective of this study was to determine the efficacy and safety of nebulized 3% hypertonic saline solution and salbutamol in the treatment of mild to moderate bronchiolitis.\n In a randomized controlled trial, 93 infants with mild to moderate bronchiolitis were divided into two groups. The infants received inhalation of 2.5 mg (0.5 mL) salbutamol dissolved in either 4.0 mL normal (0.9%) saline (control group, n= 43) or 4.0 mL hypertonic (3%) saline (treatment group, n= 50). The therapy was repeated three times daily until discharge. Cough, wheezing, pulmonary physical signs, and the length of hospital stay were recorded.\n Wheezing remission time was 3.8 + or - 1.1 days in the control group and 2.7 + or - 0.9 days in the treatment group (P < 0.01). Cough remission time was 6.3 + or - 0.9 days in the control group and 5.3 + or - 0.8 days in the treatment group (P < 0.01). The moist crackles disappeared at 5.4 + or - 0.8 days in the treatment group versus 6.2 + or - 0.9 days in the control group (P < 0.01). Furthermore, the average length of hospital stay decreased from 7.4 + or - 1.5 days in the control group to 6.0 + or - 1.2 days in the treatment group (P < 0.01). No obvious adverse effects were observed.\n Inhalation of nebulized 3% hypertonic saline solution and salbutamol is a safe and effective therapy for patients with mild to moderate bronchiolitis.", "We recently published preliminary evidence on the effectiveness of hypertonic saline in infants with viral bronchiolitis.\n To further establish the efficacy of nebulized hypertonic saline in these infants.\n In a continuing, second-year randomized, doubleblind controlled trial, an additional 41 infants (age 2.6 +/- 1 months) hospitalized with viral bronchiolitis were recruited during the winter of 2001-2002. The infants received inhalation of 1.5 mg epinephrine dissolved either in 4 ml normal (0.9%) saline (Group I, n=20) or 4 ml hypertonic (3%) saline (Group II, n=22). The therapy was repeated three times daily until discharge. Pooling our 2 years of experience (2000-2002), a total of 93 hospitalized infants with viral bronchiolitis were recruited; 45 were assigned to Group I and 48 to Group II.\n The clinical scores at baseline were 7.6 +/- 0.7 for Group I vs. 7.4 +/- 1.3 for Group II (P = NS). However, the clinical scores at days 1 and 2 after inhalation differed significantly between the two groups, invariably favoring Group II: 7 +/- 1 vs. 6.25 +/- 1.1 (P< 0.05), 6.45 +/- 1 vs. 5.35 +/- 1.35 (P< 0.05), respectively. Adding aerosolized 3% saline to 1.5 mg epinephrine reduced the hospitalization stay from 3.5 +/- 1.7 days in Group I to 2.6 +/- 1.4 in Group II (P< 0.05). The pooled data of both years revealed that adding 3% saline to the inhalation mixture decreased hospitalization stay from 3.6 +/- 1.6 to 2.8 +/- 1.3 days (P< 0.05).\n This second-year experience and our 2 year pooled data analysis strengthen the evidence that the combination of 3% saline/1.5 mg epinephrine benefits hospitalized infants with viral bronchiolitis.", "To determine the utility of inhaled hypertonic saline solution to treat ambulatory infants with viral bronchiolitis.\n Randomized, double-blind, controlled trial. Sixty-five ambulatory infants (mean +/- SD age, 12.5 +/- 6 months) with viral bronchiolitis received either of the following: inhalation of 0.5 mL (5 mg) terbutaline added to 2 mL of 0.9% saline solution as a wet nebulized aerosol (control; group 1; n = 32) or 0.5 mL (5 mg) terbutaline added to 2 mL of 3% saline solution administered in the same manner as above (treatment; group 2; n = 33). This therapy was repeated three times every day for 5 days.\n The clinical severity (CS) scores at baseline on the first day of treatment were 6.4 +/- 1.8 in group 1 and 6.6 +/- 1.5 in group 2 (not significant). After the first day, the CS score was significantly lower (better) in group 2 as compared to group 1 on each of the treatment days (p < 0.005; Fig 1 ). On the first day, the percentage decrease in the CS score after inhalation therapy was significantly better for group 2 (33%) than for group 1 (13%) [p < 0.005; Fig 1 ]. On the second day, the percentage improvement was better in the hypertonic saline solution-treated patients (group 2) as compared to the 0.9% saline solution-treated patients (group 1) [p = 0.01; Fig 1 ].\n We conclude that in nonasthmatic, nonseverely ill ambulatory infants with viral bronchiolitis, aerosolized 3% saline solution plus 5 mg terbutaline is effective in decreasing symptoms as compared to 0.9% saline solution plus 5 mg terbutaline." ]