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Hasso Plattner Institute 20

BACKGROUND Hyperuricemia has been associated with the development of high blood pressure (BP). We studied the effects of allopurinol therapy in hyperuricemic hemodialysis (HD) patients with high BP. MATERIALS AND METHODS This single-blind, randomized cross-over clinical study involved 55 HD patients with serum uric acid level > 6.5 (men) and > 5.5 mg/dL (women). They were randomly divided in two groups, each of which went through two phases. Group-1 in phase-1 received 100 mg/day orally of allopurinol for three months; while Group-2 was given whatever medication they received prior to the study. After two months of washing period, the groups were crossed-over. The BP levels were measured before and after HD during the eight months study period. RESULTS Fifty-three patients completed the study (33 men and 20 women, with mean age of 55.8 years). Uric acid levels decreased significantly during the12 weeks of allopurinol therapy (7.71 ± 1.53 to 5.2 ± 1.2 P < 0.005). Overall, after the 12 weeks of allopurinol therapy, systolic and diastolic BP also significantly decreased in allopurinol group, 15.8% (139 to 117, P < 0.0005) and 8.6% (81 to 74, P <.0005), respectively. There were not significant changes in body mass index, blood urea nitrogen, creatinine, albumin, cholesterol, triglyceride, hemoglobin, liver enzymes and serum electrolytes level after treatment. Patients treated with allopurinol had a significant increase in the quality of dialysis (KT/V) (P: 0.043). CONCLUSIONS In HD patients, allopurinol treatment reduced BP. The results indicate a new potential therapeutic approach for controlling BP in HD patients.

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BACKGROUND Interventional studies on the effect of alcohol-based hand rub on ventilator-associated pneumonia (VAP) among neurosurgical patients are scarce. AIM To observe the effect of alcohol-based hand rub on tracheobronchial colonization and VAP after elective neurosurgical procedures. MATERIALS AND METHODS An interventional study using a "before-after" design in a tertiary care center in Kerala. Two 9-month study periods were compared; between these periods, an infection control protocol incorporating an alcohol-based hand rub was implemented for a period of 3 months and continued thereafter. Consecutive patients who required mechanical ventilation after neurosurgery between January and September 2006 and 2007, respectively, were included. Outcome measures included VAP rate, tracheobronchial colonization rate, profile of microorganisms and patient survival. RESULTS A total of 352 patients were on mechanical ventilator for a varying period of 1-125 days. The patients in the control and intervention groups were similar with regard to sex, age and type of neurosurgery. Tracheobronchial colonization was seen in 86 (48.6%) of 177 in the control group and 73 (41.7%) of 175 among the intervention group (P = 0.195). The VAP rates in the control and intervention groups were 14.03 and 6.48 per 1000 ventilator days (P = 0.08). The predominant organisms causing VAP and tracheobronchial colonization were Klebsiella and Pseudomonas aeruginosa, respectively, in both groups. Patient survival rates were 87.6% (control) and 92% (intervention). CONCLUSION Clinical results indicated a better outcome, showing a reduction in tracheobronchial colonization rate and VAP rate, although this was not statistically significant.

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PURPOSE To evaluate postoperative pain, corneal epithelial healing, development of corneal haze, refractive outcomes, and corneal aberrations in a novel one-step, modified transepithelial photorefractive keratectomy (PRK), termed All-surface laser ablation (ASLA), compared to conventional, alcohol-assisted PRK. MATERIALS AND METHODS Sixty eyes of 30 myopic patients were prospectively recruited to a randomized fellow eye study. Patients underwent conventional alcohol-assisted PRK in one eye (control group) and ASLA-modified transepithelial PRK in the other (30 eyes in each treatment arm). Primary endpoints were postoperative pain and haze scores at 1 day, 3 days, 1 week, and 1, 3, 6, and 12 months. Secondary endpoints included visual acuity at 1, 3, 6, and 12 months, corneal aberrations at 3, 6, and 12 months, and early and late onset haze. Refractive predictability, safety, and efficacy of the two methods were considered. RESULTS The average age of the cohort was 29 years (standard deviation [SD]: 9; range: 18-46), and the average spherical equivalent refractive error was -4.18 diopters (SD: 1.9). At 3 days after surgery, the average pain score was 64% lower in the ASLA group (P < 0.0005). At this point, 96% of ASLA eyes had no epithelial defect, whereas 43% in the alcohol-assisted group did not achieve complete epithelial healing, and required replacement of bandage contact lens. The haze level was consistently lower in the ASLA group at all time points from 1 to 6 months. CONCLUSION This study shows that the ASLA technique may have a future role in refractive surgery, due to the fact that it offers faster epithelial healing, lower pain scores, and significantly less haze formation.

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BACKGROUND: Infants usually respond differently to a neuromuscular relaxant compared to children or adults. Isoflurane is commonly used as an anesthetic gas in infants. In an RCT design, we investigated whether a dose of mivacurium 250 &mgr;g/kg results in faster onset of action than 200 &mgr;g/kg in infants under isoflurane anesthesia. Spontaneous recovery times and cardiovascular response were also evaluated. METHODS: Twenty-four low surgical risk children, aged 6-24 months, undergoing an elective surgery and requiring tracheal intubation were selected. After anesthetic induction, patients randomly received an iv bolus dose of mivacurium 200 or 250 &mgr;g/kg. After maximal relaxation, the patient was intubated. Isoflurane was administered to maintain anesthetic level during the surgical procedure. Neuromuscular function was monitored by accelerometry (TOF-Guard) at the adductor pollicies. The first twitch (T) of the TOF and the T4/T1 were measured. The time-course of heart rate and systolic and diastolic blood pressure were analysed by transforming them into their respective areas under the curve. RESULTS: Mivacurium 250 &mgr;g/kg produced a maximal T block faster than 200 &mgr;g/kg, i.e. 2.4 +/- 1.1 vs. 3.5 +/- 1.4 min (p < 0.05). Spontaneous recovery times were similar in both groups. Heart rate was similar between doses while systolic and diastolic blood pressures were lower with the higher dose (p < 0.05). Flushing was observed in two cases, one in each group. CONCLUSIONS: The maximal effect of mivacurium 250 &mgr;g/kg, in infants under isoflurane anesthesia, was present one minute faster than 200 &mgr;g/kg. However, it produced a significant cardiovascular response.

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BACKGROUND Primary dysmenorrhea is a common and sometimes disabling condition. In recent years, some studies aimed to improve the treatment of dysmenorrhea, and therefore, introduced several therapeutic measures. This study was designed to compare the analgesic effect of iron chip containing heat wrap with ibuprofen for the treatment of primary dysmenorrhea. METHODS In this randomized (IRCT201107187038N2) controlled trial, 147 students (18-30 years old) with the diagnosis of primary dysmenorrhea were enrolled considering the CONSORT guideline. Screening for primary dysmenorrhea was done by a two-question screening tool. The participants were randomly assigned into one of the intervention groups (heat Patch and ibuprofen). Data regarding the severity and emotional impact of the pain were recorded by a shortened version of McGill Pain Questionnaire (SF-MPQ). Student's t test was used for statistical analysis. RESULTS The maximum and minimum pain severities were observed at 2 and 24 hours in both groups. The severity of sensual pain at 8, 12, and 24 hours was non-significantly less in the heat Patch group. There was also no significant difference between the groups regarding the emotional impact of pain at the first 2, 4, 8, 12 and 12 hours of menstruation. CONCLUSIONS Heat patch containing Iron chip has comparable analgesic effects to ibuprofen and can possibly be used for primary dysmenorrhea. TRIAL REGISTRATION IRCT201107187038N2.

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BACKGROUND Environmental enteropathy (EE) is an asymptomatic abnormality of small bowel structure and function, which may underlie vaccine inefficacy in the developing world. HIV infection co-exists in many of these populations. There is currently no effective treatment. We conducted a secondary analysis of a randomised controlled trial of high dose multiple micronutrient (MM) supplementation on small bowel architecture in EE in participants with or without HIV infection. METHODS In a double-blind parallel-group trial of the effect of MM on innate immune responses to oral vaccines, consenting Zambian adults were randomised to receive 6 weeks of 24 micronutrients as a daily capsule or placebo. HIV status was established after randomisation. Proximal jejunal biopsies were obtained after the supplementation period. Villous height, crypt depth, villous width, villous perimeter per 100 μm muscularis mucosa (a measure of epithelial surface area), and villous cross sectional area per 100 μm muscularis mucosa (a measure of villous compartment volume) were measured in orientated biopsy sections using semi-automated image analysis. Analysis was by intention to treat. RESULTS 18 patients received MM and 20 placebo. 6/18 MM and 9/20 placebo patients had HIV. In HIV negative patients given MM compared to placebo, mean villous height was 24.0% greater (293.3 v. 236.6 μm; 95% CI of difference 17.7-95.9 μm; P = 0.006), mean villous area was 27.6% greater (27623 v. 21650 μm2/100 μm; 95% CI of difference 818-11130 μm2/100 μm; P = 0.03), and median villous perimeter was 29.7% greater (355.0 v. 273.7 μm/100 μm; 95% CI of difference 16.3-146.2 μm/100 μm; P = 0.003). There was no significant effect on crypt depth or villous width. No effect was observed in HIV positive patients. There were no adverse events attributable to MM. CONCLUSIONS MM improved small bowel villous height and absorptive area, but not crypt depth, in adults with EE without HIV. Nutritional intervention may therefore selectively influence villous compartment remodelling. In this small study, there was a clear difference in response depending on HIV status, suggesting that EE with superimposed HIV enteropathy may be a distinct pathophysiological condition.

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BACKGROUND Leukemia is the most common and fatal cancer among young adults. Among all malignancies, it has the greatest effects on emotional and mental aspects of the patients. While 25-33% of patients with non-hematological malignancies suffer from anxiety disorder, some studies have reported the rate among patients with leukemia as high as 50%. Anxiety can negatively affect other important characteristics and parameters in patients with cancer. Furthermore, cancer increases the patients' spiritual needs. Therefore, spirituality has a significant role in adapting to leukemia and coping with its consequent mental disorders such as anxiety. This study was hence performed to determine the effects of a spiritual care program on anxiety of patients with leukemia. MATERIALS AND METHODS This randomized clinical trial was conducted in Sayyed-Al-Shohada Hospital affiliated to Isfahan University of Medical Sciences (Isfahan, Iran) in 2012. Sixty four adult patients with leukemia were randomly divided into the experiment and control groups. The spiritual care program including supportive presence and support for religious rituals was implemented for 3 days. Anxiety subscale from the 42-item depression, anxiety and stress scale was completed before and after the intervention for both groups. Data was analyzed using descriptive and inferential statistical methods (Chi-square, paired and independent t-tests) in SPSS18. RESULTS There was no significant difference between the two groups before the intervention. However, after the intervention, mean score of anxiety were significantly lower in the experiment group than in the control group (P < 0.01). There was also a significant difference in the scores of the experiment group before and after the intervention (P < 0.01). Such a difference was absent in the control group. CONCLUSIONS Our spiritual care program could successfully decrease anxiety levels in patients with leukemia. Therefore, in cases of refractory diseases such as cancer, nurses have to apply a holistic care approach with emphasis on spiritual care.

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BACKGROUND AND AIMS Intrathecal bupivacaine results in complete anaesthetic block of longer duration than ropivacaine. Fentanyl as an adjuvant may improve the quality of spinal block of ropivacaine while maintaining its advantage of early motor recovery. In this study, we proposed to compare the efficacy and safety of intrathecal ropivacaine-fentanyl (RF) with bupivacaine-fentanyl (BF) for major lower limb orthopaedic surgeries. METHODS Sixty patients were randomly allocated to receive either intrathecal 15 mg 0.5% ropivacaine with 25 mcg fentanyl (Group RF) or 15 mg 0.5% bupivacaine with 25 mcg fentanyl (Group BF). The onset, duration, spread of sensory and motor block, haemodynamic parameters and side effects were recorded. Statistical Package for Social Sciences 20 software was used for statistical analysis. RESULTS Time to reach highest sensory level and complete motor block were comparable. Sensory regression to L1 dermatome was 226 ± 46.98 min in Group RF and 229.33 ± 50.51 min in Group BF, P = 0.36. The motor recovery to Bromage scale 1 was faster in Group RF (242.8 ± 47.06 min) than Group BF (268 ± 49.9 min) P = 0.023. Time for rescue analgesia was prolonged in Group BF (263.33 ± 63 min) when compared to Group RF (234.44 ± 58.76 min), P = 0.021. The haemodynamic stability was better in Group RF than Group BF. CONCLUSION Intrathecal RF provided satisfactory anaesthesia with haemodynamic stability for major lower limb orthopaedic surgery. It provided similar sensory but shorter duration of motor block compared to BF which is a desirable feature for early ambulation, voiding and physiotherapy.

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INTRODUCTION Nausea and vomiting are the most common complications after minor head trauma that increases the risk of intracranial pressure rising. Therefore, the present study was aimed to compare the antiemetic effects of metoclopramide and ondansetron in the treatment of post-traumatic nausea and vomiting. METHODS The study was a controlled, randomized, double blind clinical trial, which was conducted in the first 6 months of 2014 in emergency department Al-Zahra and Kashani Hospitals in Isfahan, Iran. The patients with minor head trauma associated with nausea and vomiting were randomly divided into 2 groups: treatment with metoclopramide (10mg/2ml, slow injection) and treatment with ondansetron (4mg/2ml, slow injection). The comparison between the 2 groups was done regarding antiemetic efficacy and side effects using SPSS 21 statistical software. RESULTS 120 patients with minor head trauma were distributed and studied into two groups of 60 patients (mean age 35.6±14.1 years; 50.0% male). Administration of both ondansetron and metoclopramide significantly reduced the severity of nausea (P<0.001). Changes in the severity of nausea in both groups before and after the treatment revealed that nausea had been decreased significantly in both groups (P < 0.001). The incidence of fatigue (p=0.44), headache (p=0.58) and dystonia (p=0.06) had no significant difference in the two groups but the incidence of drowsiness and anxiety in the metoclopramide group was significantly higher (P < 0.001). CONCLUSION The present study indicated that the treatment effectiveness of ondansetron and metoclopramide are similar. However, incidence of drowsiness and anxiety in the metoclopramide was considerably higher. Since these complications can have adverse effects on the treatment of patients with brain injury, it is suggested that it may be better to use ondansetron in these patients.

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BACKGROUND Antihypertensive drugs are used to control blood pressure (BP) and reduce macro- and microvascular complications in hypertensive patients with diabetes. OBJECTIVES The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. METHODS Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day) or losartan (100 mg/day). Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV), and flow-mediated dilation (FMD) of the brachial artery. RESULTS A total of 42 patients were evaluated (21 in each group), with a predominance of women (71%) in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years), with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic) and 84 ± 8 mmHg (diastolic); losartan group: 153 ± 19 mmHg (systolic) and 90 ± 9 mmHg (diastolic)]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025) and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045) were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. CONCLUSIONS Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.

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BACKGROUND The importance of 2-yr postradiotherapy prostate biopsy status remains uncertain. OBJECTIVE To assess the value of 2 year post treatment biopsies in a randomised trial of radiotherapy dose escalation. DESIGN, SETTING, AND PARTICIPANTS Between 1998 and 2001, 843 men with localised prostate cancer were randomised to receive either control-64Gy or escalated-74Gy conformal radiotherapy (CFRT) in the MRC RT01 trial in combination with 3-6-mo neoadjuvant androgen deprivation therapy. Prostate biopsies were planned at 2 yr from start of CFRT in suitable men. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Prostate biopsy results and prostate-specific antigen (PSA) levels performed at 2 yr post-CFRT were evaluated with long-term biochemical progression free survival (bPFS) and overall survival. Outcome measures were timed from the 2-yr biopsy using a landmark approach. RESULTS AND LIMITATIONS A 2-yr biopsy was performed in 312/843 patients. One hundred and seventy-seven patients were included in the per-protocol group with median follow-up of 7.8 yr from biopsy. Median PSA at biopsy was 0.5ng/ml. Sixty-four bPFS events were reported: 46/145 (32%) in patients with negative, 6/18 (33%) suspicious, and 12/14 (86%) positive biopsies. A positive biopsy was prognostic of worse bPFS, going forward, compared with negative and suspicious biopsies, hazard ratio (HR)=4.81 (95% confidence interval [CI]: 2.50-9.26, p<0.001). The estimate for survival was HR=1.58 (95% CI: 0.52-4.78, p=0.42). PSA values at 2 yr between 1.01ng/ml and 2.09ng/ml were also associated with subsequent PSA failures (HR=2.71, 95% CI: 1.98-3.71), bPFS events (HR=2.45, 95% CI: 1.81-3.32), and prostate cancer-specific survival (HR=2.87, 95% CI: 1.08-7.64) compared with PSA ≤1.0ng/ml. CONCLUSIONS Two-year postradiotherapy prostate biopsies have limited value in patients with PSA control but both positive biopsy and higher PSA status are strongly associated with future bPFS events. A policy of selected biopsy may provide an opportunity for early salvage interventions. PATIENT SUMMARY Routine 2-yr postradiotherapy biopsy is not recommended but can be considered in selected patients with unfavourable post-treatment prostate-specific antigen levels who are suitable for early salvage treatments.

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BACKGROUND Most women delivering in South African State Maternity Hospitals do not have a childbirth companion; in addition, the quality of care could be better, and at times women are treated inhumanely. We piloted a multi-faceted intervention to encourage uptake of childbirth companions in state hospitals, and hypothesised that lay carers would improve the behaviour of health professionals. METHODS We conducted a pilot randomised controlled trial of an intervention to promote childbirth companions in hospital deliveries. We promoted evidence-based information for maternity staff at 10 hospitals through access to the World Health Organization Reproductive Health Library (RHL), computer hardware and training to all ten hospitals. We surveyed 200 women at each site, measuring companionship, and indicators of good obstetric practice and humanity of care. Five hospitals were then randomly allocated to receive an educational intervention to promote childbirth companions, and we surveyed all hospitals again at eight months through a repeat survey of postnatal women. Changes in median values between intervention and control hospitals were examined. RESULTS At baseline, the majority of hospitals did not allow a companion, or access to food or fluids. A third of women were given an episiotomy. Some women were shouted at (17.7%, N = 2085), and a few reported being slapped or struck (4.3%, N = 2080). Despite an initial positive response from staff to the childbirth companion intervention, we detected no difference between intervention and control hospitals in relation to whether a companion was allowed by nursing staff, good obstetric practice or humanity of care. CONCLUSION The quality and humanity of care in these state hospitals needs to improve. Introducing childbirth companions was more difficult than we anticipated, particularly in under-resourced health care systems with frequent staff changes. We were unable to determine whether the presence of a lay carer impacted on the humanity of care provided by health professionals. TRIAL REGISTRATION Current Controlled Trials ISRCTN33728802.

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INTRODUCTION The aim of the research was to compare the dynamics of venous ulcer healing when treated with the use of compression stockings as well as original two- and four-layer bandage systems. MATERIAL AND METHODS A group of 46 patients suffering from venous ulcers was studied. This group consisted of 36 (78.3%) women and 10 (21.70%) men aged between 41 and 88 years (the average age was 66.6 years and the median was 67). Patients were randomized into three groups, for treatment with the ProGuide two-layer system, Profore four-layer compression, and with the use of compression stockings class II. In the case of multi-layer compression, compression ensuring 40 mmHg blood pressure at ankle level was used. RESULTS In all patients, independently of the type of compression therapy, a few significant statistical changes of ulceration area in time were observed (Student's t test for matched pairs, p < 0.05). The largest loss of ulceration area in each of the successive measurements was observed in patients treated with the four-layer system - on average 0.63 cm2/per week. The smallest loss of ulceration area was observed in patients using compression stockings - on average 0.44 cm(2)/per week. However, the observed differences were not statistically significant (Kruskal-Wallis test H = 4.45, p > 0.05). CONCLUSIONS A systematic compression therapy, applied with preliminary blood pressure of 40 mmHg, is an effective method of conservative treatment of venous ulcers. Compression stockings and prepared systems of multi-layer compression were characterized by similar clinical effectiveness.

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BACKGROUND The data comparing daily versus intermittent iron supplementation during pregnancy remain controversial. This study was undertaken to compare the efficacy of daily versus two different intermittent iron supplementation regimes on hematologic markers and birth outcomes in nonanemic pregnant women. METHODS Two hundred and ten women with singleton pregnancies, no known disease, and hemoglobin levels >11.0 g/dL were randomly assigned to one of three groups, ie, Group A consuming two iron supplementation tablets once weekly (100 mg iron per week, n = 70), Group B consuming one tablet twice weekly (100 mg iron per week, n = 70) and Group C, consuming one tablet daily (50 mg iron per day, n = 70). No additional micronutrients were supplied. Hemoglobin and serum ferritin levels were measured at 20, 28, and 38 weeks. Pregnancy and birth outcomes (pregnancy termination, method of delivery, birth weight, stillbirth) were analyzed. RESULTS In total, 201 women completed the protocol. There was a significant difference in mean hemoglobin and ferritin levels in Group B at 38 weeks (P = 0.018 and P = 0.035, respectively) but this difference was not clinically significant (hemoglobin >12 g/dL, ferritin >19 μg/L). There was a significant increase in ferritin in Group C (P = 0.03) at 28 weeks. No significant difference was observed with respect to pregnancy or birth outcome across the groups. All regimens prevented the occurrence of hemoglobin <10.5 g/dL, but weekly supplementation was associated with development of a hemoglobin level <11.0 g/dL (risk ratio 0.044). CONCLUSION Twice-weekly supplementation is as effective as daily supplementation, and may represent an acceptable compromise in iron supplementation regimens for nonanemic pregnant women.

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OBJECTIVE The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. RESULTS The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. CONCLUSION The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.

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BACKGROUND The objective of this randomized prospective study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every nine hours for a maximum of three doses, for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation. MATERIAL AND METHODS One hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed. The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours. Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome. RESULTS The induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group (11.9 h vs. 15.5 h, p < 0.001). With misoprostol, more women delivered within 12 hours (57.5% vs. 32.5%, p < 0.01) and 24 hours (98.7% vs. 91.4%, p < 0.05), spontaneous rupture of the membranes occurred more frequently (38.8% vs. 20.5%, p < 0.05), there was less need for oxytocin augmentation (65.8% vs. 81.5%, p < 0.05) and fewer additional doses were required (7.5% vs. 22%, p < 0.05). Although not statistically significant, a lower Caesarean section (CS) rate was observed with misoprostol (7.5% vs. 13.3%, p > 0.05) but with the disadvantage of higher abnormal fetal heart rate (FHR) tracings (22.5% vs. 12%, p > 0.05). From the misoprostol group more neonates were admitted to the intensive neonatal unit, than from the dinoprostone group (13.5% vs. 4.8%, p > 0.05). One woman had an unexplained stillbirth following the administration of one dose of dinoprostone. CONCLUSIONS Vaginal misoprostol, compared with dinoprostone in the regimens used, is more effective in elective inductions of labor beyond 40 weeks of gestation. Nevertheless, this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit, indicating that the faster approach is not necessarily the better approach to childbirth.

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BACKGROUND 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? METHOD 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. RESULTS 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. CONCLUSION 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.

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INTRODUCTION Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication. METHODS In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24. RESULTS Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively). CONCLUSIONS Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies.

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OBJECTIVE To determine whether glargine is noninferior to detemir regarding the percentage of patients reaching A1C <7% without symptomatic hypoglycemia <or=3.1 mmol/l. RESEARCH DESIGN AND METHODS In this 24-week trial, 973 insulin-naive type 2 diabetic patients on stable oral glucose-lowering drugs with A1C 7.0-10.5% were randomized to glargine once daily or detemir twice daily. Insulin doses were systematically titrated. RESULTS 27.5 and 25.6% of patients reached the primary outcome with glargine and detemir, respectively, demonstrating the noninferiority of glargine. Improvements in A1C were -1.46 +/- 1.09% for glargine and -1.54 +/- 1.11% for detemir (P = 0.149), with similar proportions of patients achieving A1C <7% (P = 0.254) but more detemir-treated patients reaching A1C <6.5% (P = 0.017). Hypoglycemia risk was similar. Weight gain was higher for glargine (difference: 0.77 kg, P < 0.001). Glargine doses were lower than detemir doses: 43.5 +/- 29.0 vs. 76.5 +/- 50.5 units/day (P < 0.001). CONCLUSIONS In insulin-naive type 2 diabetic patients, glargine reached similar control as detemir, with more weight gain, but required significantly lower doses.

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INTRODUCTION Ashwagandha (Withania somnifera [L.] Dunal) has been traditionally used for various actions ranging from vitalizer, improve endurance and stamina, promote longevity, improve immunity, and male and female fertility. However, clinical studies are needed to prove the clinical efficacy of this herb, especially in cardiovascular endurance and physical performance. AIMS This prospective, double-blind, randomized, and placebo-controlled study evaluated the efficacy of Ashwagandha roots extract in enhancing cardiorespiratory endurance and improving the quality of life (QOL) in 50 healthy male/female athletic adults. MATERIALS AND METHODS Cardiorespiratory endurance was assessed by measuring the oxygen consumption at peak physical exertion (VO2 max) levels during a 20 m shuttle run test. The World Health Organization self-reported QOL questionnaire (physical health, psychological health, social relationships, and environmental factors) was used to assess the QOL. Student's t-test was used to compare the differences in a mean and change from baseline VO2 max levels, whereas Wilcoxon signed-rank test was used to assess changes in QOL scores from baseline in the two groups. RESULTS There was a greater increase from baseline (P < 0.0001) in the mean VO2 max with KSM-66 Ashwagandha (n = 24) compared to placebo (n = 25) at 8 weeks (4.91 and 1.42, respectively) and at 12 weeks (5.67 and 1.86 respectively). The QOL scores for all subdomains significantly improved to a greater extent in the Ashwagandha group at 12 weeks compared to placebo (P < 0.05). CONCLUSION The findings suggest that Ashwagandha root extract enhances the cardiorespiratory endurance and improves QOL in healthy athletic adults.

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BACKGROUND Headache is a highly prevalent disorder. Irrespective of the headache diagnosis it is often accompanied with neck pain and -stiffness. Due to this common combination of headache and neck pain, physical treatments of the cervical spine are often considered. The additional value of these treatments to standard medical care or usual care (UC) is insufficiently documented.We therefore wanted to compare the treatment effects of UC alone and in combination with manual therapy (MT) in patients with a combination of headache and neck pain. UC consisted of a stepped treatment approach according to the Dutch General Practitioners Guideline for headache, the additional MT consisted of articular mobilisations and low load exercises.Due to insufficient enrolment the study was terminated prematurely. We aim to report not only our preliminary clinical findings but also to discuss the encountered difficulties and to formulate recommendations for future research. METHODS A randomised clinical trial was conducted. Thirty-seven patients were included and randomly allocated to one of both treatment groups. The treatment period was 6 weeks, with follow-up measurements at weeks 7, 12 and 26. Primary outcome measures were global perceived effect (GPE) and the impact of the headache using the Headache Impact Test (HIT-6). Reduction in headache frequency, pain intensity, medication intake, absenteeism and the use of additional professional help were secondary outcome measures RESULTS Significant improvements on primary and secondary outcome measures were recorded in both treatment groups. No significant differences between both treatment groups were found. The number of recruited patients remained low despite various strategies. CONCLUSION It appears that both treatment strategies can have equivalent positive influences on headache complaints. Additional studies with larger study populations are needed to draw firm conclusions. Recommendations to increase patient inflow in primary care trials, such as the use of an extended network of participating physicians and of clinical alert software applications, are discussed. TRIAL REGISTRATION NUMBER NCT00298142.

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BACKGROUND This study reports on the effects of botulinum toxin A (BoNT-A) injections in the upper extremity (UE) in children with unilateral Cerebral Palsy (uCP) combined with bimanual task-oriented therapy (BITT) or either treatment modality performed separately. Bimanual activities were measured with the Assisting Hand Assessment (AHA), the ABILHand-Kids questionnaire (AK), the Observational Skills Assessment Score (OSAS). Goal achievement was measured with Goal Attainment Scaling (GAS), using blind video assessment, and the Canadian Occupational Performance Measure (COPM). METHODS Thirty-five children, mean age 7.14 years (SD 2.63), 11 Manual Ability Classification Score (MACS) I, 15 MACS II and 9 MACS III, participated. The trial started with four study groups: BoNT-A-only (n = 5), BITT-only (n = 11), BoNT-A + BITT (n = 13), and control (n = 6). Twenty-two children were randomised, 13 children received their parents' preferred treatment: BoNT-A + BITT or BITT-only. Three comparisons were analysed: BITT (BoNT-A + BITT and BITT-only; n = 24) versus no BITT (BoNT-A-only and control; n = 11), BoNT-A (BoNT-A-only and BoNT-A + BITT; n = 18) versus no BoNT-A (BITT-only and control; n = 17), and the additional effect of BoNT-A (BoNT-A + BITT versus BITT-only). Follow-up time: 24 weeks. RESULTS No significant differences between the groups were found on the AHA. The amount of use of both hands on the OSAS was significantly better in the BoNT-A group in the beading and sandwich-making task. The BoNT-A group also showed significant improvement in the quality scores of the OSAS: the wrist position during grasping and holding, especially in the younger children. The BITT group improved significantly on the AK and significantly more on the performance and satisfaction scores of the COPM at 12 and 24 weeks regarding several goals. BoNT-A showed a significant negative effect at 12 and 24 weeks in the most important goal. BITT, more than BoNT-A + BITT, showed positive effects on the GAS score at 12 (significant), 18 and 24 weeks. CONCLUSIONS BoNT-A has a positive effect on quality of movement and amount of use of the affected UE during the 3 months' working time. BoNT-A has no additional effect on bimanual performance and goal achievement. BITT has a positive effect on goal achievement and bimanual performance, even up to 6 weeks after therapy had stopped. TRIAL REGISTRATION Current Controlled Trials ISRCTN69541857.

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AIM The aim of the study was to evaluate the effect of different irrigating solutions used in final irrigation on depth of sealer penetration into dentinal tubules. MATERIALS AND METHODS Thirty recently extracted, human mandibular premolar teeth with single canals were randomly divided into two groups, and one of the two irrigants was used in each group - Group A (Chitosan) and Group B (Ethylenediaminetetraacetic acid). All the teeth were obturated with gutta-percha and AH 26 ® sealer labeled with fluorescent dye. The teeth were sectioned at distances 2, 5, and 8 mm from the root apex. Maximum depth of sealer penetration was measured using confocal laser scanning microscopy. STATISTICAL ANALYSIS Statistical analysis used One-way analysis of variance and t -test. RESULTS At coronal third depth, the sealer penetration was greater in ethylenediaminetetraacetic acid (EDTA) group; however, depth of sealer penetration was greater at apical third in chitosan group. CONCLUSION Final irrigation with EDTA and chitosan after the use of sodium hypochlorite affected sealer penetration.

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BACKGROUND The purpose is to assess cardiopulmonary function outcomes and quality of life values in inactive people that participated in the Physical Activity Promotion Programme (PAPP) against the control group that did not perform this program. METHOD A total of 100 subjects of both genders participated in the randomized controlled trial with systematic random sampling; all were aged 55 and older, from Torremolinos, Spain. Participants either received (n = 50) the PAPP for 60 minutes, twice a week during three months or (n = 50) they received health education. The effectiveness of the intervention was measured by general state of health the Short Form 12 health survey questionnaire, and the quality of life was determined with the EuroQoL-5D questionnaire. Cardiopulmonary function was measured with a spirometry and a walking test according to the Bruce protocol. RESULTS This pilot study had a significant impact on the quality of life (p = 0.05) in men, which increased. However, the quality of life in women did not improve. The average changes in the lung and cardiovascular function was not significant between groups. CONCLUSIONS Changes in the quality of life measured with EQ-5D in the group of men who carried out the PAPP were statistically significant when comparing between groups. However changes in cardiopulmonary function were not as relevant when comparing between groups. There was a significant effect within each group in the pulmonary outcomes of values in men, within the experimental group. TRIAL REGISTRATION Developed by the University of Málaga. ClinicalTrials.gov ID: NCT01172483.

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OBJECTIVE The present study aims to evaluate intravenous ketamine and inhalation sedation in children, their unwanted side-effects and surgeon satisfaction. METHODS In this study, data of 922 children aged between 1-18 who underwent tooth extraction under sedoanalgesia in our department between September 2015-January 2016 were gathered and anesthesia approaches, unwanted side effects and surgical satisfaction was investigated. Postoperative recovery emergence agitation or delirium was evaluated with Watcha Behavior Scale (WBS). RESULTS Patients were grouped and compared according to acceptance of intravenous line placement (Group-1) or not (Group- 2). Group 1 received intravenous ketamine anesthesia (n=822), Group 2 received inhalation anesthesia with sevoflurane (n=100). Number of patients, age, weight and gender was significantly different in two groups. When side effects were investigated nausea was observed in 30 patients (3.6%), skin rashes were observed in 26 patients (3.2%) in Group-1 while skin rashes were observed in one patient (1%) in Group 2. 95% of surgeons reported intravenous anesthesia, 18% of surgeons reported inhalation anesthesia to be the anesthesia of choice. Emergence of postoperative recovery agitation (WBS≥3) was observed more frequent in Group 2 (p<0.05) than Group 1. CONCLUSION Ketamine, which has analgesic, hypnotic and amnestic effects and which does not alter pharyngeal and laryngeal reflexes thus minimizes aspiration possibility, is a safe and effective anesthetic agent for tooth extractions of the pediatric population under sedoanalgesia.

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BACKGROUND The outcomes of hospitalization anxiety are mental health disorders. One of the methods of anxiety reduction is massage, which can cause reduction of pain and changes in physiological parameters. OBJECTIVES This study aimed to investigate the effects of slow-stroke back massage (SSBM) on hospitalization anxiety and physiological parameters in school-age children. METHODS This clinical trial study included 80 school-aged children from Ali Ebne Abi Taleb hospital, located in Zahedan, who were selected using sequential sampling and randomly divided into two groups: a massage group (40) and a control group (40). Data were collected using a demographic questionnaire and the state-trait anxiety inventory for children (STAIC). Subjects in the massage group received SSBM, using sesame oil, for 3 days. Massage was given three times a day, and each massage session lasted for 15 - 20 minutes. Physiological parameters and hospitalization anxiety were determined from the second to fifth days. T-test and Chi-square were used for analysis data. RESULTS There was a statistically significant difference (P < 0.05) between the mean of systolic blood pressure (SBP), diastolic blood pressures (DBP), and pulse rate (PR) in the massage group prior to intervention (97.05 ± 20.7, 60.35 ± 16.69 and 95.45 ± 13.02 respectively) and on the fifth day (88.32 ± 16.58, 55.95 ± 12.7 and 90.45 ± 15.1 respectively). However, no difference was observed in mean respiratory rate (RR) in the massage group from the second day (17.55 ± 3.6) to fifth day (17.62 ± 3.27) (P = 0.096). The mean of state of anxiety, which was 36.4 ± 5.1 before intervention, was reduced by the fifth day to 31.2 ± 5.1 in the massage group (P < 0.0001, t = 5.2). CONCLUSIONS The results suggest that massage reduced hospitalization anxiety, PR, and BP. Therefore, we propose that nurses can use massage to reduce anxiety in school-age children in hospital. This method has no side-effects and is easily applicable.

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BACKGROUND Glucocorticoids (GCs), such as prednisone, are the standard of care for several inflammatory and immunologically mediated diseases, but their chronic systemic administration is severely limited by serious adverse effects that are both dose and time dependent. Short-term treatment (7-14 days) with oral prednisone is used for many acute inflammatory and allergic conditions. This study was conducted to characterize the safety and pharmacodynamic (PD) dose-response of a 7-day course of oral prednisone on biomarkers of GC receptor agonism. METHODS In this randomized, single-blind, placebo-controlled, crossover study (A9001309), 37 healthy subjects received placebo or a prednisone dose from 2.5-60 mg daily over 7 days in each of three treatment periods. White blood cell counts and plasma samples for measuring cortisol, osteocalcin and procollagen type 1 N-propeptide (P1NP) were obtained at 2, 4, 8, and 12 h post-dose on Day 1, immediately prior to dosing on Days 1, 2, and 4, and at nominal dosing time on Days 0 and 8. Urine samples for urinary N-terminal cross-linked telopeptide of type 1 collagen (uNTX) were collected on Days 0, 1, 2, 4, and 8. Serum samples for adiponectin were obtained prior to dosing on days 0, 1, 4 and 8. RESULTS Daily doses of prednisone up to 60 mg resulted in dose- and time-dependent decreases in plasma osteocalcin, plasma P1NP, serum cortisol, and absolute blood eosinophil counts. Absolute blood neutrophil counts increased, while blood lymphocyte counts rebounded to an increased level following an initial rapid decrease after dosing. An increase was observed for uNTX and adiponectin. The incidence of adverse effects with prednisone was not dose related, and nervous system disorders, mainly headache, were the most frequently reported adverse effects. CONCLUSIONS This characterization provides important and relevant information on safety and PD responses of short-term prednisone dosing over the commonly-used clinical dose range, and also provides a reference for early clinical development of dissociated agents targeting a differentiated PD profile. TRIAL REGISTRATION NUMBER NCT02767089 (retrospectively registered: 21 April 2016).

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BACKGROUND AND PURPOSE Adjuvant lymphatic radiotherapy (LNRT) is recommended for selected axillary node positive women with early breast cancer. We investigated whether hypofractionated LNRT is safe combined with similarly-hypofractionated breast/chest wall radiotherapy (RT). MATERIAL AND METHODS The Standardisation of Breast Radiotherapy (START) pilot, A and B trials randomised women with early breast cancer to schedules of 2.67-3.3 Gy versus 2.0 Gy fractions (control). RT adverse effects were assessed by patients using the EORTC QLQ-BR23 and protocol-specific questions, and by physicians. Rates of arm/shoulder effects were compared between schedules for patients given LNRT. RESULTS 864/5861 (14.7%) patients received LNRT (385 START-pilot, 318 START-A, 161 START-B). Prevalences of moderate/marked arm/shoulder effects were low up to 10 years. There were no significant differences between the hypofractionated and control groups for patient- and physician-assessed symptoms in START-A or START-B. In START-pilot, adverse effect rates were higher after 13 fractions of 3.3 Gy, consistent with effects reported in the breast/chest wall (significant for shoulder stiffness, HR 3.07, 95%CI 1.62-5.83, p = 0.001). CONCLUSIONS The START trial results suggest that appropriately-dosed hypofractionated LNRT is safe in the long-term, according to patient and physician-assessed arm and shoulder symptoms. These findings are consistent with those reported after the same schedules delivered to the breast/chest wall.

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BACKGROUND This study investigated the effect of combining oral dexamethasone with either nebulized racemic epinephrine or salbutamol compared to bronchodilators alone for the treatment of infants with bronchiolitis. MATERIALS AND METHODS This was a double-blind, randomized controlled trial on infants (1 to 12 months) who were diagnosed in the emergency department with moderate-to-severe bronchiolitis. The primary outcome was the rate of hospital admission within 7 days of the first dose of treatment, and the secondary outcomes were changes in respiratory distress assessment instrument score, heart rate, respiratory rate, and oxygen saturation (O2 Sat) over a 4-hour observation period. Infants (n = 162) were randomly assigned to four groups: A (dexamethasone + racemic epinephrine) = 45, B (placebo and racemic epinephrine) =39, C (dexamethasone and salbutamol) = 40, or D (placebo and salbutamol) = 38. RESULTS Patients who had received dexamethasone + epinephrine exhibited similar admission rates compared to placebo + epinephrine or salbutamol (P = 0.64). Similarly, no statistically significant difference was observed in the rate of hospitalization for patients who received dexamethasone + salbutamol compared to those who received placebo + epinephrine or salbutamol (P = 0.51). Clinical parameters were improved at the end of the 4-hour observation period for all treatment groups. Treatment with dexamethasone + epinephrine resulted in a statistically significant change in HR over time (P < 0.005) compared to the other groups. CONCLUSIONS This study adds to a body of evidence suggesting that corticosteroids have no role in the management of bronchiolitis for young infants who are first time wheezers with no risk of atopy.

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OBJECTIVE Ibuprofen - a non-steroidal anti-inflammatory drug (NSAID)- and glucosamine sulfate - a natural compound and a food supplement- are two therapeutic agents which have been widely used for treatment of patients with temporomandibular joint (TMJ) disorders. This study was aimed to compare the effectiveness and safety of these two medications in the treatment of patients suffering from TMJ disorders. METHODS After obtaining informed consent, 60 patients were randomly allocated to two groups. Patients with painful TMJ, TMJ crepitation or limitation of mouth opening entered the study. Exclusion criteria were history of depressive disorders, cardiovascular disease, musculoskeletal disorders, asthma, gastrointestinal problems, kidney or liver dysfunction or diabetes mellitus, dental diseases needing ongoing treatment; taking aspirin or warfarin, or concomitant treatment of TMJ disorder with other agents or methods. Thirty patients were treated with ibuprofen 400 mg twice a day, (mean age 27.12 ± 10.83 years) and 30 patients (mean age 26.60 ± 10) were treated with glucosamine sulfate 1500 mg daily. Patients were visited 30, 60 and 90 days after starting the treatment, pain and mandibular opening were checked and compared within and between two groups. FINDINGS Comparing with baseline measures, both groups had significantly improved post-treatment pain (P < 0.0001 for both groups) and mandibular opening (P value: 0.001 for glucosamine sulfate and 0.03 for ibuprofen). Post treatment pain and mandibular opening showed significantly more improvement in the glucosamine treated patients (P < 0.0001 and 0.01 respectively). Rate of adverse events was significantly lower in the P value glucosamine sulfate group (P < 0.0001). CONCLUSION This investigation demonstrated that comparing with a commonly prescribed NSAID - ibuprofen-, glucosamine sulfate is a more effective and safer therapeutic agent for treatment of patients with TMJ degenerative join disorder.

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OBJECTIVE Psychotherapeutic intervention combined with pharmacotherapy is helpful for achieving remission of depressive disorder. We developed and tested the effect of cognitive behavior therapy (CBT)-based psychotherapy applied in a forest environment on major depressive disorder. METHODS We performed 4 sessions during 4 weeks (3 hours/session) in patients with major depressive disorder during pharmacotherapy. For the forest group, sessions were performed in the forest; for the hospital group, sessions were performed in the hospital. The control group was treated with the usual outpatient management. RESULTS A total of 63 patients completed the study: 23 in the forest group, 19 in the hospital group, and 21 in the control group. Hamilton Rating Scales for Depression (HRSD) scores of the forest group were significantly decreased after 4 sessions compared with controls. Montgomery-Asberg Depression Rating Scales (MADRS) scores of the forest group were significantly decreased compared with both the hospital group and the controls. The remission rate (7 and below in HRSD) of the forest group was 61% (14/23), significantly higher than both the hospital group (21%, 4/19) and the controls (5%, 1/21). In heart rate variability (HRV) analysis, some measurements representing HRV and parasympathetic nerve tone were increased in the forest group after 4 sessions. The salivary cortisol levels of the forest group were significantly decreased. CONCLUSION CBT-based psychotherapy applied in the forest environment was helpful in the achievement of depression remission, and its effect was superior to that of psychotherapy performed in the hospital and the usual outpatient management. A good environment such as a forest helps improve the effect of psychotherapeutic intervention because it includes various natural instruments and facilitators in the treatment of depression.

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PURPOSE This report provides the 3-year clinical outcomes from the randomized, controlled US Food and Drug Administration Investigational Device Exemption trial of the Superion(®) for the treatment of moderate degenerative lumbar spinal stenosis. PATIENTS AND METHODS The Superion(®) was evaluated in the treatment of subjects aged 45 years or older suffering from symptoms of intermittent neurogenic claudication, secondary to a confirmed diagnosis of moderate degenerative lumbar spinal stenosis at one or two contiguous levels from L1 to L5. Patients were treated between June 2008 and December 2011 at 31 investigational sites. Three hundred ninety-one subjects were included in the randomized study group consisting of 190 Superion(®) and 201 X-STOP(®) control subjects. The primary composite endpoint was individual patient success based on four components: improvement in two of three domains of the Zurich Claudication Questionnaire, no reoperations at the index level, no major implant/procedure-related complications, and no clinically significant confounding treatments. RESULTS At 3 years, the proportion of subjects achieving the primary composite endpoint was greater for Superion(®) (63/120, 52.5%) than for X-STOP(®) (49/129, 38.0%) (P=0.023) and the corresponding success rates exceeded 80% for each of the individual components of the primary endpoint in the Superion(®) group (range: 81%-91%). Improvements in back and leg pain severity as well as back- and disease-specific functional outcomes were also maintained through 36 months. CONCLUSION The 3-year outcomes from this randomized controlled trial demonstrate durable clinical improvement consistently across all clinical outcomes for the Superion(®) in the treatment of patients with moderate degenerative lumbar spinal stenosis.

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BACKGROUND Cognitive impairment is common in multiple sclerosis (MS), with cognitive processing speed being the most frequently affected domain. OBJECTIVE Examine the effects of daclizumab beta versus intramuscular (IM) interferon (IFN) beta-1a on cognitive processing speed as assessed by Symbol Digit Modalities Test (SDMT). METHODS In DECIDE, patients with relapsing-remitting multiple sclerosis (RRMS) (age: 18-55 years; Expanded Disability Status Scale (EDSS) score 0-5.0) were randomized to daclizumab beta ( n = 919) or IM IFN beta-1a ( n = 922) for 96-144 weeks. SDMT was administered at baseline and at 24-week intervals. RESULTS At week 96, significantly greater mean improvement from baseline in SDMT was observed with daclizumab beta versus IM IFN beta-1a ( p = 0.0274). Significantly more patients treated with daclizumab beta showed clinically meaningful improvement in SDMT (increase from baseline of ⩾3 points ( p = 0.0153) or ⩾4 points ( p = 0.0366)), and significantly fewer patients showed clinically meaningful worsening (decrease from baseline of ⩾3 points ( p = 0.0103)). Odds representing risk of worsening versus stability or improvement on SDMT were significantly smaller for daclizumab beta ( p = 0.0088 (3-point threshold); p = 0.0267 (4-point threshold)). In patients completing 144 weeks of treatment, the effects of daclizumab beta were generally sustained. CONCLUSION These results provide evidence for a benefit of daclizumab beta versus IM IFN beta-1a on cognitive processing speed in RRMS. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT01064401 (Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon β 1a in Participants With Relapsing-Remitting Multiple Sclerosis (DECIDE)): https://clinicaltrials.gov/ct2/show/NCT01064401 .

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INTRODUCTION The use of dipeptidyl peptidase-4 inhibitors in combination with metformin is increasing in Japanese patients with type 2 diabetes mellitus (T2DM), but no single-pill combination (SPC) is currently available in Japan. The objective of this study was to assess the efficacy and safety of vildagliptin/metformin SPC in Japanese patients with T2DM inadequately controlled with vildagliptin monotherapy. METHODS This was a 14-week, randomized, double-blind, parallel-group, placebo-controlled trial. 171 patients with T2DM inadequately controlled [HbA1c (glycosylated hemoglobin) 7.0-10.0%] with vildagliptin 50 mg twice daily (bid) were randomized (2:1) to receive either a vildagliptin/metformin SPC (n = 115) or matching vildagliptin/placebo SPC (n = 56). RESULTS Baseline demographics and background characteristics were generally comparable between the treatment groups. The change in HbA1c [mean ± standard error (SE)] was -0.8 ± 0.1% in the vildagliptin/metformin SPC (baseline HbA1c, 7.9 ± 0.1%) group and 0.1 ± 0.1% in the vildagliptin/placebo SPC (baseline HbA1c, 8.0 ± 0.1%) group, with a between-treatment difference of -1.0 ± 0.1% (P <0.001) in favor of the vildagliptin/metformin SPC group. The proportion of patients achieving target HbA1c <7.0% was significantly higher with vildagliptin/metformin SPC compared with vildagliptin/placebo SPC (45.8% vs. 13.5%, P <0.001). The overall incidences of adverse events (AEs) were 43.5% in the vildagliptin/metformin SPC and 67.9% in the vildagliptin/placebo SPC group. The incidences of serious AEs were low in both the treatment groups (0.9% vs. 3.6%, respectively). Body weight remained constant throughout the study in both the treatment groups. There were no deaths or hypoglycemic events during the study. CONCLUSIONS Switching Japanese patients with T2DM requiring treatment intensification, from vildagliptin monotherapy to a vildagliptin/metformin SPC (50/250 or 50/500 mg) was efficacious and safe, eliciting significant reduction in HbA1c without increased risk of hypoglycemia and weight gain.

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BACKGROUND Process evaluation is important for improving theories of behavior change and behavioral intervention methods. The present study reports on the process outcomes of a pilot test of the theoretical model (the Process Model for Lifestyle Behavior Change; PMLBC) underpinning an evidence-informed, theory-driven, group-based intervention designed to promote healthy eating and physical activity for people with high cardiovascular risk. METHODS 108 people at high risk of diabetes or heart disease were randomized to a group-based weight management intervention targeting diet and physical activity plus usual care, or to usual care. The intervention comprised nine group based sessions designed to promote motivation, social support, self-regulation and understanding of the behavior change process. Weight loss, diet, physical activity and theoretically defined mediators of change were measured pre-intervention, and after four and 12 months. RESULTS The intervention resulted in significant improvements in fiber intake (M between-group difference = 5.7 g/day, p < .001) but not fat consumption (-2.3 g/day, p = 0.13), that were predictive of weight loss at both four months (M between-group difference = -1.98 kg, p < .01; R(2) = 0.2, p < 0.005), and 12 months (M difference = -1.85 kg, p = 0.1; R(2) = 0.1, p < 0.01). The intervention was successful in improving the majority of specified mediators of behavior change, and the predicted mechanisms of change specified in the PMBLC were largely supported. Improvements in self-efficacy and understanding of the behavior change process were associated with engagement in coping planning and self-monitoring activities, and successful dietary change at four and 12 months. While participants reported improvements in motivational and social support variables, there was no effect of these, or of the intervention overall, on physical activity. CONCLUSIONS The data broadly support the theoretical model for supporting some dietary changes, but not for physical activity. Systematic intervention design allowed us to identify where improvements to the intervention may be implemented to promote change in all proposed mediators. More work is needed to explore effective mechanisms within interventions to promote physical activity behavior.

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BACKGROUND The additional benefit of lifestyle interventions in patients receiving cardioprotective drug treatment to improve cardiovascular risk profile is not fully established.The objective was to evaluate the effectiveness of a target-driven multidisciplinary structured lifestyle intervention programme of 6 months duration aimed at maximum reduction of cardiovascular risk factors in patients with cardiovascular disease (CVD) compared with usual care. METHODS A single centre, two arm, parallel group randomised controlled trial was performed. Patients with stable established CVD and at least one lifestyle-related risk factor were recruited from the vascular and cardiology outpatient departments of the university hospital. Blocked randomisation was used to allocate patients to the intervention (n = 71) or control group (n = 75) using an on-site computer system combined with allocations in computer-generated tables of random numbers kept in a locked computer file. The intervention group received the comprehensive lifestyle intervention offered in a specialised outpatient clinic in addition to usual care. The control group continued to receive usual care. Outcome measures were the lifestyle-related cardiovascular risk factors: smoking, physical activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL cholesterol concentrations, BMI, waist circumference, and changes in medication. RESULTS The intervention led to increased physical activity/fitness levels and an improved cardiovascular risk factor profile (reduced BMI and waist circumference). In this setting, cardiovascular risk management for blood pressure and lipid levels by prophylactic treatment for CVD in usual care was already close to optimal as reflected in baseline levels. There was no significant improvement in any other risk factor. CONCLUSIONS Even in CVD patients receiving good clinical care and using cardioprotective drug treatment, a comprehensive lifestyle intervention had a beneficial effect on some cardiovascular risk factors. In the present era of cardiovascular therapy and with the increasing numbers of overweight and physically inactive patients, this study confirms the importance of risk factor control through lifestyle modification as a supplement to more intensified drug treatment in patients with CVD. TRIAL REGISTRATION ISRCTN69776211 at http://www.controlled-trials.com.

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BACKGROUND In Burkina Faso, it is not uncommon for mothers to drink alcohol, even during pregnancy. We aimed to study the association between maternal alcohol consumption during pregnancy and the child's cognitive performance using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) and the Children's Category Test Level 1 (CCT-1) in rural Burkina Faso. METHODS We conducted a follow-up study of a community cluster-randomised Exclusive breastfeeding trial, and re-enrolled the children in rural Burkina Faso. A total of 518 children (268 boys and 250 girls) aged 6-8 years were assessed using the KABC-II and the CCT-1. We examined the effect size difference using Cohen's d and conducted a linear regression analysis to examine the association. RESULTS Self-reported alcohol consumption during pregnancy was 18.5% (96/518). Children whose mothers reported alcohol consumption during pregnancy performed significantly poorly for memory and spatial abilities tests from small effect size difference for 'Atlantis' (0.27) and 'Triangle' (0.29) to moderate effect size difference for 'Number recall' (0.72) compared to children whose mothers did not consume alcohol during pregnancy; the exposed children scored significantly higher errors with a small effect size (0.37) at problem solving (CCT-1) test compared to unexposed children. At unstandardized and standardized multivariable analysis, children whose mothers reported alcohol consumption during pregnancy performed significantly poorer for memory-'Atlantis' ( p  = 0.03) and 'Number recall' ( p  = 0.0001), and spatial ability tests-'Triangle' ( p  = 0.03); they scored significantly higher errors at problem solving CCT-1 test ( p  = 0.002); all the results were adjusted for age, sex, schooling, stunting, father's education, mother's employment and the promotion of exclusive breastfeeding. No statistical association was found for visual abilities-'Conceptual Thinking', 'Face recognition', 'Story completion', and reasoning tests-'Rover', 'Block counting', and 'Pattern Reasoning'. CONCLUSION Maternal alcohol consumption during pregnancy is associated with poorer cognitive performance for memory, spatial ability, and problem solving tests in the offspring in rural Burkina Faso. Futures studies needs to assess in more detail the maternal alcohol consumption patterns in Burkina Faso and possible preventive strategies.

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BACKGROUND This study was to compare the effect of a stimulant laxative alone and in combination with traditional Japanese medicine Daikenchuto (TJ-100) in improving stool frequency and in alleviating bloating and abdominal pain in patients with chronic constipation. METHODS Twenty-two patients with chronic constipation who required sennoside (24 - 60 mg daily) were allocated to two groups for treatment with 7.5 g /day (N = 14) or with 15 g/day (N = 8) of TJ-100. The study period was 12 weeks and consisted of 4 weeks (pretreatment phase) before the administration of TJ-100, 6 weeks (treatment phase) for the administration of TJ-100, and 2 weeks (washout period) after cessation of TJ-100. The bowel movement frequency and the dose of sennoside required were recorded during the study period. Bloating and abdominal pain and gastrointestinal symptoms rating scale were evaluated at 0, 4, 6, and 8 weeks. The gas volume score was measured at 0 week and 6 weeks. RESULTS The addition of TJ-100 to sennoside resulted in significant improvement in bloating (P < 0.01) and abdominal pain (P < 0.05). Its effects for abdominal pain were dose-dependent. There was no significant change in frequency of bowel movements or the dose of sennoside used. The gas volume score was significantly decreased after the addition of TJ-100 (P < 0.05). CONCLUSIONS The addition of a traditional Japanese medicine, TJ-100, reduced bloating and abdominal pain in patients with chronic constipation receiving stimulant laxatives, possibly by decreasing the bowel gas volume.

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BACKGROUND Iron deficiency anemia is highly prevalent in patients with chronic kidney disease and is often treated with intravenous iron. There are few trials directly comparing the safety and efficacy of different intravenous iron products. METHODS This post-hoc analysis pooled data from 767 patients enrolled in two randomized, controlled, open-label trials of similar design comparing the treatment of iron deficiency anemia with ferumoxytol and iron sucrose across patients with all stages of renal function. One trial was conducted in adults with CKD either on or not on dialysis and the second in adults with IDA of any underlying cause and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used who had normal to no worse than moderately impaired renal function. Patients were categorized by chronic kidney disease stage (i.e., estimated glomerular filtration rate), and the primary efficacy endpoint was the mean change in hemoglobin from Baseline to Week 5. RESULTS The overall incidence of adverse events was numerically lower in ferumoxytol-treated patients compared to those treated with iron sucrose (42.4 vs. 50.2 %, respectively); the incidence of treatment-related adverse events was generally similar between the two treatment groups (13.6 vs. 16.0 %, respectively). Adverse events of Special Interest (i.e., hypotension, hypersensitivity) occurred at lower rates in those treated with ferumoxytol compared to those treated with iron sucrose (2.5 vs. 5.3 %, respectively). Overall, mean hemoglobin increased in both treatment groups, regardless of degree of renal insufficiency, although greater increases were seen among those with less severe kidney damage. Mean increases in hemoglobin from Baseline to Week 5 were significantly greater with ferumoxytol than with iron sucrose treatment in the subgroup with an estimated glomerular filtration rate ≥90 mL/min (Least Squares mean difference = 0.53 g/dL; p < 0.001). There were no other consistent, significant differences in hemoglobin levels between treatment groups for the other chronic kidney disease categories except for isolated instances favoring ferumoxytol. CONCLUSIONS The efficacy and safety of ferumoxytol is at least comparable to iron sucrose in patients with varying degrees of renal function. TRIAL REGISTRATION (CKD-201; ClinicalTrials.gov identifier: NCT01052779; registered 15 January, 2010), (IDA-302; ClinicalTrials.gov identifier: NCT01114204; registered 29 April, 2010).

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INTRODUCTION This study aimed to compare the incidence of dentinal crack formation by instrumentation with ProTaper Universal system (rotary, multi-file system), SafeSider (reciprocation movement, multi-file system) and Neolix (rotary, single-file system). METHODS AND MATERIALS In this in vitro study, 60 freshly extracted mandibular first molars were randomly divided into three experimental groups ( n =15) and a control group containing unprepared teeth ( n =15). Instrumentation in different groups was accomplished using either ProTaper, Neolix or SafeSider systems up to 25/0.08. The teeth were then sectioned at 3, 6 and 9 mm from the apex, and observed under a stereomicroscope for presence of dentinal cracks. Data were analyzed with Chi square test, Fisher's exact test and Bonferroni correction. RESULTS Micro cracks were seen in all experimental groups (13.3% in ProTaper, 26.7% in SafeSider and 40% in Neolix). There was a significant difference between Neolix and the control groups in microcrack formation ( P =0.042). Micro cracks mainly occurred in the coronal section (9 mm). No microcrack occurred in the control group. CONCLUSION Neolix rotary single-file system caused more dentinal cracks compared to the unprepared roots. All the instrumentation systems increased the number of micro cracks compared to unprepared teeth.

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BACKGROUND Liver stem cell therapy (SCT) has been suggested as a promising means to improve liver regeneration in advanced liver disease. However, data from trials are heterogeneous, with no systematic histological evaluation. The aim of this study is to specifically analyze the effect of autologous SCT on liver regeneration and on gene expression changes. METHODS Individuals in the randomized controlled trial of SCT in alcoholic hepatitis with paired liver biopsies were included (n = 58). Immunohistochemistry (Ki67, K7, and CD68), in situ hybridization (SPINK1), and global gene expression analysis were performed on liver biopsies (30 control patients and 28 patients with transarterial administration of bone marrow-derived stem cells) both at baseline and after 4 weeks of follow-up. RESULTS No difference between the two groups could be observed regarding the proliferative hepatocyte number, proliferative K7-positive cells, or total K7-positive cells at the 4-week follow-up liver biopsy. However, patients who received SCT showed a more important liver macrophagic expansion as compared to standard treatment. Transcriptome data revealed changes in genes linked with inflammation (CD68 and SAA), regeneration (SPINK1 and HGF), fibrosis (COL1A1), and stem cells (CD45). No changes in gene pathways involved in liver growth and cell cycle proteins were evident. SPINK1 mRNA was present by in situ hybridization at week 4 in SCT patients in the liver parenchyma areas adjacent to macrophage recruitment and liver cell proliferation. CONCLUSIONS The analysis of liver tissue after SCT demonstrated an expansion of macrophages concurrent with an upregulated expression of genes involved in inflammatory and regenerative pathways. With the negative results from the clinical trial, the impact of the SCT has to be interpreted as weak, and it is not able to modify the clinical course of this severe liver disease.

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OBJECTIVES We compared hemodynamic responses and upper airway morbidity following tracheal intubation via conventional laryngoscopy or intubating laryngeal mask airway in hypertensive patients. METHODS Forty-two hypertensive patients received a conventional laryngoscopy or were intubated with a intubating laryngeal mask airway. Anesthesia was induced with propofol, fentanyl, and cis-atracurium. Measurements of systolic and diastolic blood pressures, heart rate, rate pressure product, and ST segment changes were made at baseline, preintubation, and every minute for the first 5 min following intubation. The number of intubation attempts, the duration of intubation, and airway complications were recorded. RESULTS The intubation time was shorter in the conventional laryngoscopy group than in the intubating laryngeal mask airway group (16.33 ± 10.8 vs. 43.04 ± 19.8 s, respectively) (p<0.001). The systolic and diastolic blood pressures in the intubating laryngeal mask airway group were higher than those in the conventional laryngoscopy group at 1 and 2 min following intubation (p<0.05). The rate pressure product values (heart rate x systolic blood pressure) at 1 and 2 min following intubation in the intubating laryngeal mask airway group (15970.90 ± 3750 and 13936.76 ± 2729, respectively) were higher than those in the conventional laryngoscopy group (13237.61 ± 3413 and 11937.52 ± 3160, respectively) (p<0.05). There were no differences in ST depression or elevation between the groups. The maximum ST changes compared with baseline values were not significant between the groups (conventional laryngoscopy group: 0.328 mm versus intubating laryngeal mask airway group: 0.357 mm; p = 0.754). The number and type of airway complications were similar between the groups. CONCLUSION The intense and repeated oropharyngeal and tracheal stimulation resulting from intubating laryngeal mask airway induces greater pressor responses than does stimulation resulting from conventional laryngoscopy in hypertensive patients. As ST changes and upper airway morbidity are similar between the two techniques, conventional laryngoscopy, which is rapid and safe to perform, may be preferred in hypertensive patients with normal airways.

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BACKGROUND Knowledge acquisition and skill maintenance are important in learning neonatal resuscitation. Traditionally this is taught by using low fidelity mannequins. Technological advancement enabled a move towards high fidelity mannequins. In a low resources setting, it is incumbent to ensure reasonable cost benefit ratio before investing in technology. METHODS A randomized control trial was conducted in 101 undergraduate students who were assigned to conventional Resusci(®) Baby Basic or SimNewB group over a period of 3 days. The lectures were the same for both groups but the hands on training was on different mannequins. There were five experienced and accredited teachers who were standardized for training the students. Both the groups received a written test and a Megacode before and after the training, and 3 months later a post-test. RESULTS The baseline written exam score (p = 0.07), Megacode assessment score (p = 0.19) and sex distribution (p = 0.17) were similar in both groups. Both groups showed significant improvement in the written exam score as well as in the Megacode assessment score at post-test and 3 months (retention) period. However there was no significant difference in the "improvement" between both the groups with respect to written exam (p = 0.38) or Megacode assessment (p = 0.92). Further the post-test and 3 month scores were comparable for the skills as well as content components suggesting that the skills were retained in 3 months with an opportunity of self learning them. CONCLUSIONS Due diligence is a caveat before contemplating the acquisition of high fidelity mannequins by educational centers for neonatal resuscitation.

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OBJECTIVE Laryngoscopy and intratracheal intubation may cause acute hemodynamic instabilities due to catecholamine release. Magnesium sulfate (MgSO4) prevents catecholamine release and results in bradycardia and vasodilatation, so can be used to diminish complications of laryngoscopy and intubation in doses > 50 mg/kg. The aim of this study was to compare the different doses of MgSO4 used to improve cardiovascular instabilities due to laryngoscopy and intratracheal intubation. METHODS In this double-blind randomized controlled trial, 120 patients undergoing elective surgery were divided equally into four groups (n = 30) and received different doses of MgSO4 as case groups (Group I: 30 mg/kg, Group II: 40 mg/kg, Group III: 50 mg/kg) or the equal volume of normal saline as a control group. The patients' hemodynamic status was recorded at baseline, before laryngoscopy and in 1, 3, 5, and 10 minutes after laryngoscopy. Bradycardia, tachycardia, hypertension, hypotension, ST-T changes, arrhythmias, and duration of extubation and laryngoscopy were also recorded. FINDINGS There was no significant difference in heart rate between four groups (Pbaseline = 0.46, Ppreoperation = 0.55, P1 min = 0.86, P3 min = 0.30, P5 min = 0.63, P10 min = 0.74). Systolic, diastolic and mean arterial pressures were statistically significant less at 1, 3, and 5 minutes after intubation in comparison with other times of following-up in the three groups received MgSO4 than the control group. CONCLUSION The use of MgSO4 in doses less than 50 mg/kg can be effective to reduce cardiovascular instability related to laryngoscopy and tracheal intubation.

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BACKGROUND In recent decades, shared decision-making (SDM) models have been developed to increase patient involvement in treatment decisions. The purpose of this study was to examine the effect of a shared decision-making intervention (SDMI) for substance-dependent patients on patients' and clinicians' perceptions of therapeutic alliance. METHODS Clinicians were randomly assigned to SDMI or usual procedures to reach a treatment agreement. SDMI is a structured, manualized, 5-session procedure to facilitate treatment agreement and consists of five standardized sessions. RESULTS Patients' perceptions of the therapeutic alliance were very favorable at start of treatment, and no differences were found between intervention groups. Clinicians' scores on perceived helpfulness and on the overall therapeutic alliance were higher in the SDMI group than in the controls, after 8 weeks of treatment and at the end of treatment. CONCLUSION The present study has shown that a specific intervention to enhance shared decision-making results in favorable changes in clinicians' perceptions of the therapeutic alliance.

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BACKGROUND Bioelectrical impedance analysis (BIA) is often used to estimate total body water (TBW), intracellular body water (ICW), extracellular body water (ECW), and body fat percentage (BF%). A common restriction for BIA analysis is abstinence from caffeine 12-h prior to testing. However, research has yet to determine whether the consumption of caffeine influences BIA testing results. The purpose of this study was to determine if the consumption of caffeine influences BIA-derived BF% and body water values in habitual caffeine users. METHODS Twenty apparently healthy males (26.6 ± 4.1 years) identified as habitual caffeine consumers (≥ one 95 mg serving per day ≥ four days per week) participated in this study. Participants came to the lab on three occasions, the first visit serving as the control (CON) with no supplementation. The remaining two visits were performed in a randomized double-blind, cross-over fashion. Participants consumed 200 mg of dextrose (PLA) or caffeine (CAF) in capsule form. During each visit, seven multi-frequency BIA measurements were conducted before (PRE) and after (15-min, 30-min, 45-min, 60-min, 75-min, 90-min) consumption. RESULTS Repeated measures ANOVA revealed BF% for CAF was lower than the CON and PLA conditions at PRE and 15-min ( p  < 0.001, p  = 0.004), but not statistically significant for the remaining time points (i.e., 30-, 45-, 60-, 75-, and 90-min). However, the effect size (ES) of the BF% differences were trivial. The CON, PLA, and CAF conditions had higher PRE ICW values than their associated post time points (i.e., 15-, 30-, 45-, 60-, 75-, and 90-min). Similar to BF%, ES of the mean differences for ICW were trivial. No other differences were observed. CONCLUSION Caffeine consumption in habitual users produced trivial changes in TBW, ECW, ICW, or BF%. Therefore, the pre-testing guidelines for caffeine consumption may not be necessary in habitual caffeine consumers.

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OBJECTIVE Overestimating patients' medication adherence diminishes the ability of psychiatric care providers to prescribe the most effective treatment and to identify the root causes of treatment resistance in schizophrenia. This study was conducted to determine how credible patient drug adherence information (PDAI) might change prescribers' treatment decisions. METHODS In an online survey containing 8 clinical case vignettes describing patients with schizophrenia, health care practitioners who prescribe antipsychotics to patients with schizophrenia were instructed to choose a preferred treatment recommendation from a set of predefined pharmacologic and non-pharmacologic options. The prescribers were randomly assigned to an experimental or a control group, with only the experimental group receiving PDAI. The primary outcome was the prescribers' treatment choice for each case. Between-group differences were analyzed using multinomial logistic regression. RESULTS A convenience sample (n=219) of prescribers completed the survey. For 3 nonadherent patient vignettes, respondents in the experimental group were more likely to choose a long-acting injectable antipsychotic compared with those in the control group (77.7% experimental vs 25.8% control; P <0.001). For 2 adherent but poorly controlled patient vignettes, prescribers who received PDAI were more likely to increase the antipsychotic dose compared with the control group (49.1% vs 39.1%; P <0.001). For the adherent and well-controlled patient vignette, respondents in both groups made similar treatment recommendations across all choices ( P =0.099), but respondents in the experimental arm were more likely to recommend monitoring clinical stability (87.2% experimental vs 75.5% control, reference group). CONCLUSION The results illustrate how credible PDAI can facilitate more appropriate clinical decisions for patients with schizophrenia.

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BACKGROUND AND AIMS Post-operative nausea and vomiting (PONV) is highly distressing and unpleasant symptom. Dexamethasone and palonosetron are effective antiemetics with minimal side effect profile. This study compares the efficacy of palonosetron or dexamethasone alone and their combination (palonosetron plus dexamethasone) for prevention of PONV after laparoscopic cholecystectomy. METHODS This prospective, randomised, double-blind trial was done on 187 adults, American Society of Anesthesiologists Grade I and II patients, aged 18-75 years undergoing laparoscopic cholecystectomy. They were allocated to three groups which were to receive either of the three treatment regimens: dexamethasone 8 mg (Group D, n = 57), palonosetron 0.075 mg (Group P, n = 66) or dexamethasone 8 mg plus palonosetron 0.075 mg (Group PD, n = 64). The primary outcome was incidence of PONV in 24 h and the secondary outcome was a number of rescue antiemetic required. One-way ANOVA test was used to compare the means amongst three groups. To compare the proportions in the groups, Chi-square test/Fisher's exact test/Two proportions Z-test was applied as appropriate. RESULTS Overall incidences of PONV in the study 24 h postoperatively were 23.4% in PD, 27.2% in P group and 56.14% in D group ( P < 0.001). Requirement of rescue antiemetic was more in dexamethasone group than other two groups (PD = 1 time, P = 1.38 times and D = 1.5 times). CONCLUSION Palonosetron alone and palonosetron-dexamethasone combination were equally effective in the prevention of PONV. Dexamethasone alone was least effective amongst the three groups. There is no difference between palonosetron and palonosetron-dexamethasone for PONV prevention.

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BACKGROUND Despite being present in up to 1% of the population, few controlled trials have examined the efficacy of treatments for bipolar II depression. Pooled data are presented from four placebo-controlled studies (BOLDER I [5077US/0049] and II [D1447C00135]; EMBOLDEN I [D1447C00001] and II [D1447C00134]) that evaluated the efficacy of quetiapine monotherapy for depressive episodes in patients with bipolar II disorder. METHODS All studies included an 8-week, double-blind treatment phase in which patients were randomly assigned to treatment with quetiapine 300 mg/day, quetiapine 600 mg/day, or placebo. Outcome measures included the change from baseline in MADRS total score at week 8, effect sizes, and MADRS response and remission rates. RESULTS AND DISCUSSION Improvements in mean MADRS total scores from baseline to week 8 were significantly greater with quetiapine 300 and 600 mg/day (-15.58 [n = 283] and -14.88 [n = 289]; p < 0.001) compared with placebo (-11.61 [n = 204]). The MADRS effect sizes were 0.44 for quetiapine 300 mg/day and 0.47 for 600 mg/day (p < 0.001 vs placebo). Significantly higher proportions of patients receiving quetiapine, at both doses, than placebo-treated patients achieved response and remission at week 8 (p < 0.01). Common adverse events associated with quetiapine (both doses) included dry mouth, somnolence, sedation, dizziness, and headache. Rates of mania and hypomania were similar for quetiapine and placebo. Quetiapine monotherapy demonstrated significant efficacy compared with placebo and was generally well tolerated in the treatment of bipolar II depression.

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BACKGROUND Cholecystectomy can be associated with considerable postoperative pain. While the benefits of paravertebral block (PVB) on pain after thoracotomy and mastectomy have been demonstrated, not enough investigations on the effects of PVB on pain after open cholecystectomy have been conducted. We tested the hypothesis that a single-injection thoracic PVB reduces pain scores, decreases opioid consumption, and prolongs analgesic request time after cholecystectomy. METHODS Of 52 patients recruited, 50 completed the study. They were randomly allocated into two groups: the paravertebral group and the control group. The outcome measures were the severity of pain measured on numeric pain rating scale, total opioid consumption, and first analgesic request time during the first postoperative 24 hours. RESULT The main outcomes recorded during 24 hours after surgery were Numerical Rating Scale (NRS) pain scores (NRS, 0-10), cumulative opioid consumption, and the first analgesic request time. Twenty four hours after surgery, NRS at rest was 4 (3-6) vs 5 (5-7) and at movement 4 (4-7) vs 6 (5-7.5) for the PVB and control groups, respectively. The difference between the groups over the whole observation period was statistically significant ( P <0.05). Twenty-four hours after surgery, median (25th-75th percentile) cumulative morphine consumption was 0 (0-2) vs 2.5 (2-4) mg ( P <0.0001) and cumulative tramadol consumption was 200 (150-250) mg vs 300 (200-350) mg in the paravertebral and in the control group, respectively ( P =0.003). After surgery, the median (25th-75th percentile) first analgesic requirement time was prolonged in the PVB group in statistically significant fashion ( P <0.0001). CONCLUSION AND RECOMMENDATIONS Single-shot thoracic PVB as a component of multi-modal analgesic regimen provided superior analgesia when compared with the control group up to 24 postoperative hours after cholecystectomy, and we recommend this block for post cholecystectomy pain relief.

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BACKGROUND Care during pregnancy and performing consultation for delivery preparation play an important role in improving pregnant women's knowledge. OBJECTIVE The purpose of this study was to investigate the effect of consultation and instruction in the preparation classes for delivery on pregnancy consequences, including choosing the type of delivery, the performed type of delivery, and infant's weight. METHODS This study was conducted in 2015 on 170 pregnant women who had been referred to the prenatal clinic in Hamedan. The participants were randomly divided into intervention and control groups. Eight sessions of consultation for delivery preparation were held for the women in 20 to 36 weeks of pregnancy. The control group received only the routine care. After 37 weeks of pregnancy, the participants answered a questionnaire. The infant's weight was measured after birth. Data were analyzed Using SPSS-21 and McNemar-Bowker Test, independent t-test, chi-square test, and Fisher exact test. RESULTS Results showed a significant statistical difference between the two groups concerning their selective and performed delivery (p<0.001). The weight of infants in the intervention group was significantly higher than that of those in the control group (p<0.001). CONCLUSION The findings of this study showed that the consultation for delivery preparation had a positive effect on some pregnancy consequences such as selecting the type of delivery performed and infant's weight. TRIAL REGISTRATION The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCTID: IRCT2015012513405N9. FUNDING The authors received no financial support for the research, authorship, and/or publication of this article.

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PURPOSE To evaluate the efficacy and safety of once-daily ciclesonide in comparison to both levocetirizine alone, and a ciclesonide/levocetirizine combination in patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS Subjects exhibiting moderate to severe allergic rhinitis for longer than 1 year were randomized in an open-label, 3-arm, parallel group, multicenter study. Subjects received 200 µg ciclesonide, 5 mg levocetirizine, or a combination of both. Changes from baseline until the end-of-study visit (2 weeks following) were evaluated by reflective total nasal symptom scores (rTNSSs), reflective total ocular symptom scores (rTOSSs), physician-assessed overall nasal signs and symptoms severity (PANS), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). RESULTS Significant improvements in rTNSS, PANS, and RQLQ in the ciclesonide monotherapy group were observed in comparison to the levocetirizine alone group. Three individual symptoms of rTNSS, including runny nose, nasal itching, and congestion, were improved in the ciclesonide-treated group. rTOSS scores for ciclesonide monotherapy improved from baseline, but no superiority over levocetirizine was shown. The absolute score and changes in rTNSS and PANS were positively correlated. Ciclesonide spray was more effective than levocetirizine in reducing nasal symptoms in both SAR and PAR patients. Ciclesonide and levocetrizine were well tolerated alone and in combination. CONCLUSIONS Our results provide support for an AR and its Impact on Asthma (ARIA) recommendation stipulating that ciclesonide is superior to levocetirizine for the treatment of AR, with tolerable safety. Addition of levocetirizine to ciclesonide did not give further clinical benefit over monotherapy.

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PURPOSE We previously showed that a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is not superior to FOLFOX4 in patients at advanced stage of colorectal cancer with liver metastases. Here we aimed to determine whether time to health-related quality of life (HRQoL) score definitive deterioration (TUDD) differs by study arm. METHODS HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline and every 4 cycles until the end of the study or death. Functional scale, symptom scale, global health status, and financial difficulties were analyzed. The TUDD was defined as the time interval between randomization and the first decrease in HRQoL score ≥ 5-point with no further improvement in HRQoL score ≥ 5 points or any further HRQoL data. TUDD was estimated using the Kaplan-Meier method and the long-rank test. Cox regression analyses were used to identify HRQoL items influencing TUDD. Sensitivity analyses were done using a multiple imputation method and different definitions of TUDD. RESULTS Of the 284 patients, 171 (60.2%) completed HRQoL questionnaires. Cox multivariate analysis showed no statistically significant difference in TUDD for most of the QLQ-C30 scales between treatments. Patients with dyspnea and those without symptoms at baseline had a significantly longer TUDD when there was a delay >12 months between diagnosis of the primary tumor and metastases (HR 0.48 [0.26-0.89]) and when there was diarrhea (HR 0.59 [0.36-0.96]), respectively. CONCLUSION This study shows that TUDD does not differ significantly according to type of treatment. The TUDD method produces meaningful longitudinal HRQoL results that may facilitate effective clinical decision making in patients with mCRC. TRIAL REGISTRATION ClinicalTrials.gov NCT00268398.

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AIM To investigate whether the use of an oxidizing mouth rinse as an adjunct to chlorhexidine is efficacious in reducing stains and plaque. MATERIALS AND METHODS This study had a single-blind, three-group (n = 35 each) parallel design, including a 21 days experimental period during which group I rinsed with chlorhexidine (CHX) 0.2% alone, group II used chlorhexidine (CHX) followed by hydrogen peroxide (H2O2) 1.5%. Group III rinsed with the same mouthwashes in reverse order. Patients were randomly assigned to one of the three groups. The examination for plaque, and stains was done after 1, 2, and 3 weeks of rinsing. RESULTS Group II showed significantly less stain intensity in comparison with group I after 14 and 21 days (P values 0.025 and 0.005, respectively). The proportion of stained surfaces was less in the group II than in the group I and was significant at the end of 1 week. The plaque formation was significantly less in groups II and III than group I at 7, 14, and 21 days. CONCLUSION The adjunctive use of hydrogen peroxide to chlorhexidine proved to be superior to chlorhexidine alone with regard to the inhibition of plaque and development of stains.

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BACKGROUND Postoperative hypothermia is a common cause of complications in patients who underwent laparoscopic cholecystectomy. Hypothermia is known to elicit electrophysiological, biochemical, and cellular alterations thus leading to changes in the active and passive membrane properties. These changes might influence the bioelectrical impedance (BI). Our aim was to determine whether the BI depends on the core temperature. METHODS We studied 60 patients (52 female and 8 male) age 40 to 80 years with an ASA I-II classification that had undergone laparoscopic cholecystectomy under balanced inhalation anesthesia. The experimental group (n = 30) received active core rewarming during the transanesthetic and postanesthesic periods. The control group (n = 30) received passive external rewarming. The BI was recorded by using a 4-contact electrode system to collect dual sets of measurements in the deltoid muscle. The body temperature, hemodynamic variables, respiratory rate, blood-gas levels, biochemical parameters, and shivering were also measured. The Mann-Whitney unpaired t-test was used to determine the differences in shivering between each group at each measurement period. Measurements of body temperature, hemodynamics variables, respiratory rate, and BI were analyzed using the two-way repeated-measures ANOVA. RESULTS The gradual decrease in the body temperature was followed by the BI increase over time. The highest BI values (95 ± 11 Ω) appeared when the lowest values of the temperature (35.5 ± 0.5°C) were reached. The active core rewarming kept the body temperature within the physiological range (over 36.5°C). This effect was accompanied by low stable values (68 ± 3 Ω) of BI. A significant decrease over time in the hemodynamic values, respiratory rate, and shivering was seen in the active core-rewarming group when compared with the controls. The temporal course of shivering was different from those of body temperatue and BI. The control patients showed a significant increase in the serum-potassium levels, which were not seen in the active-core rewarming group. CONCLUSIONS The BI analysis changed as a function of the changes of core temperature and independently of the shivering. In addition, our results support the beneficial use of active core rewarming to prevent accidental hypothermia.

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BACKGROUND The complexity of medication therapy in older adults with multiple comorbidities often leads to inappropriate prescribing. Drugs with anticholinergic properties are of particular interest because many are not recognized for this property; their use may lead to increased anticholinergic burden resulting in significant health risks, as well as negatively impacting cognition. Medication therapy management (MTM) interventions showed promise in addressing inappropriate medication use, but the effectiveness of targeted multidisciplinary team interventions addressing anticholinergic medications in older populations is yet to be determined. METHODS We conducted an 8-week, parallel-arm, randomized trial to evaluate whether a targeted patient-centered pharmacist-physician team MTM intervention ("targeted MTM intervention") reduced the use of inappropriate anticholinergic medications in older patients enrolled in a longitudinal cohort at University of Kentucky's Alzheimer's Disease Center. Study outcomes included changes in the medication appropriateness index (MAI) targeting anticholinergic medications and in the anticholinergic drug scale (ADS) score from baseline to the end of study. RESULTS Between October 1, 2014 and September 30, 2015 we enrolled and randomized 50 participants taking at least one medication with anticholinergic properties. Of these, 35 (70%) were women, 45 (90%) were white, and 33 (66%) were cognitively intact (clinical dementia rating [CDR] = 0); mean age was 77.7 ± 6.6 years. At baseline, the mean MAI was 12.6 ± 6.3; 25 (50%) of the participants used two or more anticholinergics, and the mean ADS score was 2.8 ± 1.6. After randomization, although no statistically significant difference was noted between groups, we identified a potentially meaningful imbalance as the intervention group had more participants with intact cognition, and thus included CDR in all of the analyses. The targeted MTM intervention resulted in statistically significant CDR adjusted differences between groups with regard to improved MAI (change score of 3.6 (1.1) for the MTM group as compared with 1.0 (0.9) for the control group, p = 0.04) and ADS (change score of 1.0 (0.3) for the MTM group as compared with 0.2 (0.3) for the control group, p = 0.03). CONCLUSIONS Our targeted MTM intervention resulted in improvement in anticholinergic medication appropriateness and reduced the use of inappropriate anticholinergic medications in older patients. Our results show promise in an area of great importance to ensure optimum outcomes for medications used in older adults. TRIAL REGISTRATION ClinicalTrials.gov NCT02172612 . Registered 20 June 2014.

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OBJECTIVE To identify factors that predict medication adherence and to examine relationships among adherence, glycemic control, and indices of insulin action in TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth). RESEARCH DESIGN AND METHODS A total of 699 youth 10-17 years old with recent-onset type 2 diabetes and ≥80% adherence to metformin therapy for ≥8 weeks during a run-in period were randomized to receive one of three treatments. Participants took two study pills twice daily. Adherence was calculated by pill count from blister packs returned at visits. High adherence was defined as taking ≥80% of medication; low adherence was defined as taking <80% of medication. Depressive symptoms, insulin sensitivity (1/fasting insulin), insulinogenic index, and oral disposition index (oDI) were measured. Survival analysis examined the relationship between medication adherence and loss of glycemic control. Generalized linear mixed models analyzed trends in adherence over time. RESULTS In this low socioeconomic cohort, high and low adherence did not differ by sex, age, family income, parental education, or treatment group. Adherence declined over time (72% high adherence at 2 months, 56% adherence at 48 months, P < 0.0001). A greater percentage of participants with low adherence had clinically significant depressive symptoms at baseline (18% vs. 12%, P = 0.0415). No adherence threshold predicted the loss of glycemic control. Longitudinally, participants with high adherence had significantly greater insulin sensitivity and oDI than those with low adherence. CONCLUSIONS In the cohort, the presence of baseline clinically significant depressive symptoms was associated with subsequent lower adherence. Medication adherence was positively associated with insulin sensitivity and oDI, but, because of disease progression, adherence did not predict long-term treatment success.

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BACKGROUND Psychostimulants are considered first-line pharmacotherapy for youth with attention-deficit/hyperactivity disorder (ADHD), but questions remain regarding the comparative efficacy of amphetamine- and methylphenidate-based agents. OBJECTIVE Our objective was to describe two acute randomized, double-blind, placebo-controlled, head-to-head studies of lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) in adolescents with ADHD. METHODS Adolescents (13-17 years) diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were enrolled in an 8-week flexible-dose study [LDX 30-70 mg/day (n = 186 randomized); OROS-MPH 18-72 mg/day (n = 185 randomized); placebo (n = 93 randomized)] or a 6-week forced-dose study [LDX 70 mg/day (n = 219 randomized); OROS-MPH 72 mg/day (n = 220 randomized); placebo (n = 110 randomized)]. Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV) total score changes from baseline (primary endpoint) at week 8 (flexible-dose study) or week 6 (forced-dose study) were assessed with mixed-effects models for repeated measures. Secondary endpoints included improvement on the dichotomized Clinical Global Impressions-Improvement scale (CGI-I; key secondary endpoint) and changes from baseline on the ADHD-RS-IV subscales. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs. RESULTS Least squares (LS) mean ± standard error of the mean (SEM) ADHD-RS-IV total score changes from baseline to end of treatment were -17.0 ± 1.03 with placebo, -25.4 ± 0.74 with LDX, and -22.1 ± 0.73 with OROS-MPH in the forced-dose study and -13.4 ± 1.19 with placebo, -25.6 ± 0.82 with LDX, and -23.5 ± 0.80 with OROS-MPH in the flexible-dose study. LS mean ± SEM treatment difference for the change from baseline significantly favored LDX over OROS-MPH in the forced-dose [-3.4 ± 1.04, p = 0.0013, effect size (ES) -0.33] but not the flexible-dose (-2.1 ± 1.15, p = 0.0717, ES -0.20) study. The percentage of improved participants on the dichotomized CGI-I at end of treatment was significantly greater with LDX than with OROS-MPH in the forced-dose study (81.4 vs. 71.3%, p = 0.0188) but not the flexible-dose study (LDX 83.1%, OROS-MPH 81.0%, p = 0.6165). The LS mean ± SEM treatment differences for change from baseline on the ADHD-RS-IV hyperactivity/impulsivity and inattentiveness subscales nominally favored LDX in the forced-dose study (hyperactivity/impulsivity subscale -1.3 ± 0.49, nominal p = 0.0081, ES -0.27; inattentiveness subscale -2.0 ± 0.63, nominal p = 0.0013, ES -0.33), but there were no significant differences between active treatments in the flexible-dose study. In both studies, LDX and OROS-MPH were superior to placebo for all efficacy-related endpoints (all nominal p < 0.0001; ES range -0.43 to -1.16). The overall frequency of TEAEs for LDX and OROS-MPH, respectively, were 66.5 and 58.9% in the forced-dose study and 83.2 and 82.1% in the flexible-dose study. TEAEs occurring in ≥ 5% of participants that were also reported at two or more times the rate of placebo were decreased appetite, decreased weight, insomnia, initial insomnia, dry mouth, and nasopharyngitis (LDX and OROS-MPH), irritability and dizziness (LDX only), and increased heart rate (OROS-MPH only) in the forced-dose study and decreased appetite, decreased weight, insomnia, and dizziness (LDX and OROS-MPH) and dry mouth and upper abdominal pain (LDX only) in the flexible-dose study. Mean ± standard deviation (SD) increases from baseline in vital signs (systolic and diastolic blood pressure, pulse) were observed in the forced-dose study [LDX 1.6 ± 9.65 and 3.3 ± 8.11 mmHg, 6.7 ± 12.78 beats per minute (bpm); OROS-MPH 2.6 ± 10.15 and 3.3 ± 9.13 mmHg, 7.6 ± 12.47 bpm] and the flexible-dose study (LDX 2.4 ± 9.46 and 2.8 ± 8.41 mmHg, 4.7 ± 11.82 bpm; OROS-MPH 0.4 ± 9.90 and 2.2 ± 8.64 mmHg, 6.0 ± 10.52 bpm) at the last on-treatment assessment. CONCLUSIONS LDX was superior to OROS-MPH in adolescents with ADHD in the forced-dose but not the flexible-dose study. Safety and tolerability for both medications was consistent with previous studies. These findings underscore the robust acute efficacy of both psychostimulant classes in treating adolescents with ADHD. CLINICALTRIALS. GOV REGISTRY NUMBERS NCT01552915 and NCT01552902.

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INTRODUCTION Percutaneous nephrolithotomy (PCNL) is the treatment of choice for large renal calculi. Pain around the nephrostomy tube is a clinical problem and we have previously reported alleviation of pain by peritubal block with bupivacaine, which lasted for 14 hours. The present study aimed to investigate the role of buprenorphine and bupivacaine combination in prolonging the duration of analgesia in peritubal block. MATERIALS AND METHODS A prospective, randomized controlled study was undertaken in 40 American Society of Anesthesiologists (ASA) grade I and II patients who were scheduled for PCNL. Group I patients received 20 mL of 0.25% bupivacaine and group II patients received 20 mL of 0.25% bupivacaine with 100 μg of buprenorphine. Peritubal infiltration was given under fluoroscopic guidance along the nephrostomy tube from the renal capsule to the skin. Post-operative pain was assessed by Visual Analog Score (VAS), dynamic VAS (DVAS), sedation score, duration of analgesia and number of rescue analgesic demands. Rescue analgesia was inj tramadol 1 mg/kg IV if pain score exceeded 3. RESULTS Demographic data were comparable between the groups. Median duration of analgesia was 16 h in group I and 20 h in group II (P = 0.002). The maximum median VAS was 4 in group I and 2 in group II (P = 0.002). The median area under curve (AUC) for VAS was 7 and 5 in groups I and II, respectively (P = 0.047). The median maximum DVAS in group I was 6 and 4 in group II. The median AUC for DVAS in 24 h was 16 in group I and 15 in group II (P = 0.017). CONCLUSIONS Peritubal infiltration of 0.25% bupivacaine with 100 μg buprenorphine around a nephrostomy tube increased the duration of analgesia following PCNL without any side-effects.

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BACKGROUND Cuff pressure (P cuff) control is mandatory to avoid leakage of oral secretions passing the tracheal tube and tracheal ischemia. The aim of the present trial was to determine the efficacy of a mechanical device (PressureEasy®) in the continuous control of P cuff in patients intubated with polyvinyl chloride (PVC)-cuffed tracheal tubes, compared with routine care using a manometer. METHODS This is a prospective, randomized, controlled, cross-over study. All patients requiring intubation with a predicted duration of mechanical ventilation ≥48 h were eligible. Eighteen patients randomly received continuous control of P cuff with PressureEasy® device for 24 h, followed by discontinuous control (every 4 h) with a manual manometer for 24 h, or vice versa. P cuff and airway pressure were continuously recorded. P cuff target was 25 cmH2O during the two periods. RESULTS The percentage of time spent with P cuff 20-30 cmH2O (median (IQR) 34 % (17-57) versus 50 % (35-64), p = 0.184) and the percentage of time spent with P cuff <20 cmH2O (23 % (5-63) versus 43 % (16-60), p = 0.5) were similar during continuous control of P cuff and routine care, respectively. However, the percentage of time spent with P cuff >30 cmH2O was significantly higher during continuous control compared with routine care of tracheal cuff (26 % (14-39) versus 7 % (1-18), p = 0.002). No significant difference was found in P cuff (25 (18-28) versus 21 (18-26), p = 0.17), mean airway pressure (14 (10-17) versus 14 (11-16), p = 0.679), or coefficient of variation of P cuff (19 % (11-26) versus 20 % (11-25), p = 0.679) during continuous control compared with routine care of tracheal cuff, respectively. CONCLUSIONS PressureEasy® did not demonstrate a better control of P cuff between 20 and 30 cmH2O, compared with routine care using a manometer. Moreover, the device use resulted in significantly higher time spent with overinflation of tracheal cuff, which might increase the risk for tracheal ischemic lesions. TRIAL REGISTRATION Clinicaltrial.gov: NCT02109003.

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BACKGROUND Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), as pre-exposure prophylaxis (PrEP) for reducing the risk of HIV acquisition. Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women (FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study), but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials. METHODS We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites (Bondo, Kenya; Bloemfontein, South Africa; and Pretoria, South Africa) to examine adherence levels over time and to assess factors associated with adherence, based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals. RESULTS We observed drug concentrations consistent with good adherence in 28.5% of all visit intervals when drug was available to use, but only 12% of participants achieved good adherence throughout their study participation. In multivariate analysis, the Bloemfontein site [odds ratio (OR): 2.43; 95% confidence interval (CI): 1.32 to 4.48] and liking the pill color (OR: 2.93; 95% CI: 1.18 to 7.27) were positively associated with good adherence, whereas using oral contraceptive pills at enrollment was negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74). CONCLUSIONS Most participants did not regularly adhere to the study product throughout their trial participation, although a small minority did. Few factors associated with good adherence to the study product were identified in FEM-PrEP.

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BACKGROUND The cardiometabolic effects of SRT2104, a novel SIRT1 activator, were investigated in people with type 2 diabetes mellitus (T2DM). METHODS Fifteen adults with T2DM underwent a randomised, double-blind, placebo-controlled cross-over trial and received 28 days of oral SRT2104 (2.0 g/day) or placebo. Forearm vasodilatation (measured during intrabrachial bradykinin, acetylcholine and sodium nitroprusside infusions) as well as markers of glycaemic control, lipid profile, plasma fibrinolytic factors, and markers of platelet-monocyte activation, were measured at baseline and at the end of each treatment period. RESULTS Lipid profile and platelet-monocyte activation were similar in both treatment arms (p>0.05 for all). Forearm vasodilatation was similar on exposure to acetylcholine and sodium nitroprusside (p>0.05, respectively). Bradykinin-induced vasodilatation was less during treatment with SRT2104 versus placebo (7.753vs9.044, respectively, mean difference=-1.291,(95% CI -2.296 to -0.285, p=0.012)). Estimated net plasminogen activator inhibitor type 1 antigen release was reduced in the SRT2104 arm versus placebo (mean difference=-38.89 ng/100 mL tissue/min, (95% CI -75.47, to -2.305, p=0.038)). There were no differences in other plasma fibrinolytic factors (p>0.05 for all). After 28 days, SRT2104 exposure was associated with weight reduction (-0.93 kg (95% CI -1.72 to -0.15), p=0.0236), and a rise in glycated haemoglobin (5 mmol/mol or 0.48% (0.26 to 0.70), p=0.004). CONCLUSIONS In people with T2DM, SRT2104 had inconsistent, predominantly neutral effects on endothelial and fibrinolytic function, and no discernible effect on lipids or platelet function. In contrast, weight loss was induced along with deterioration in glycaemic control, suggestive of potentially important metabolic effects. CLINICAL TRIAL REGISTRATION NCT01031108; Results.

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OBJECTIVE To assess the efficacy of surgical decompression <24 (early) versus 24-72 hours (late) in thoracic/thoracolumbar traumatic spinal cord injury (TSCI). METHODS A randomized controlled trial (RCT) of 35 T1-L1 TSCI patients including early (n=16) and late (n=19) surgical decompression was conducted in the neurosurgery department of Shahid Rajaee Hospital from September 2010. Pre- and postoperative American Spinal Injury Association (ASIA) Impairment Scale (AIS), ASIA motor/sensory scores, length of hospitalization, complications, postoperative vertebral height restoration/rebuilding and angle reduction, and 12-month loss of height restoration/rebuilding and angle reduction were evaluated. RESULTS Sixteen patients (46%) had complete TSCI. No AIS change was seen in 17 (52%) patients. Complete TSCI patients had no motor improvement. The AIS change in this group was solely due to increased sensory scores. For incomplete TSCI, the mean motor score improved from 77 (± 22) to 92 (± 12) in early, and from 68 (± 22) to 82 (± 16) in late surgery. One deep vein thrombosis was observed in each group. There were 2 wound infections, one CSF leak, one case of meningitis, and one decubitus ulcer in the late surgery group. Six screw revisions were required. CONCLUSION Our primary results show overall AIS and motor score improvement in both groups. Motor improvement was only observed in incomplete TSCI. Two-grade improvements in AIS were seen in 3 early, and one late surgery patient.

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BACKGROUND It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. RESULTS D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. CONCLUSION It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. TRIAL REGISTRATION UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

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PURPOSE Laparoscopic techniques have allowed surgeons to perform complicated intra-abdominal surgery with minimal trauma. Single incision laparoscopic surgery (SILS) was developed with the aim of reducing the invasiveness of conventional laparoscopy. In this study we aimed to compare results of SILS cholecystectomy and three port conventional laparoscopic (TPCL) cholecystectomy prospectively. METHODS In this prospective study, 100 patients who underwent laparoscopic cholecystectomy for gallbladder disease were randomly allocated to SILS cholecystectomy (group 1) or TPCL cholecystectomy (group 2). Demographics, pathologic diagnosis, operating time, blood loss, length of hospital stay, complications, pain score, conversion rate, and satisfaction of cosmetic outcome were recorded. RESULTS Forty-four SILS cholesystectomies (88%) and 42 TPCL cholecystectomies (84%) were completed successfully. Conversion to open surgery was required for 4 cases in group 1 and 6 cases in group 2. Operating time was significantly longer in group 1 compared with group 2 (73 minutes vs. 48 minutes; P < 0.05). Higher pain scores were observed in group 1 versus group 2 in postoperative day 1 (P < 0.05). There was higher cosmetic satisfaction in group 1 (P < 0.05). CONCLUSION SILS cholecystectomy performed by experienced surgeons is at least as successful, feasible, effective and safe as a TPCL cholecystectomy. Surgeons performing SILS should have a firm foundation of advanced minimal access surgical skills and a cautious, gradated approach to attempt the various procedures. Prospective randomized studies comparing single access versus conventional multiport laparoscopic cholecystectomy, with large volumes and long-term follow-up, are needed to confirm our initial experience. (ClinicalTrials.gov Identifier: NCT01772745.).

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BACKGROUND Anal sphincter defects are a major cause of fecal incontinence causing negative effects on daily life, social interactions, and mental health. Because human adipose-derived stromal/stem cells (hADSCs) are easier and safer to access, secrete high levels of growth factor, and have the potential to differentiate into muscle cells, we investigated the ability of hADSCs to improve anal sphincter incontinence. METHODS The present randomized double-blind clinical trial was performed on patients with sphincter defects. They were categorized into a cell group (n = 9) and a control group (n = 9). Either 6 × 10 6 hADSCs per 3 ml suspended in phosphate buffer saline (treatment) or 3 ml phosphate buffer saline (placebo) was injected. Two months after surgery, the Wexner score, endorectal sonography, and electromyography (EMG) results were recorded. RESULTS Comparing Wexner scores in the cell group and the control group showed no significant difference. In our EMG and endorectal sonography analysis using ImageJ/Fiji 1.46 software, the ratio of the area occupied by the muscle to total area of the lesion showed a 7.91% increase in the cell group compared with the control group. CONCLUSION The results of the current study show that injection of hADSCs during repair surgery for fecal incontinence may cause replacement of fibrous tissue, which acts as a mechanical support to muscle tissue with contractile function. This is a key point in treatment of fecal incontinence especially in the long term and may be a major step forward. TRIAL REGISTRATION Iranian Registry of Clinical Trials IRCT2016022826316N2 . Retrospectively registered 7 May 2016.

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BACKGROUND Most research on how to enhance response rates in physician surveys has been done using paper surveys. Uncertainties remain regarding how to enhance response rates in Internet-based surveys. OBJECTIVE To evaluate the impact of a low-cost nonmonetary incentive and paper mail reminders (formal letter and postcard) on response rates in Internet-based physician surveys. METHODS We executed a factorial-design randomized experiment while conducting a nationally representative Internet-based physician survey. We invited 3966 physicians (randomly selected from a commercial database of all licensed US physicians) via email to complete an Internet-based survey. We used 2 randomly assigned email messages: one message offered a book upon survey completion, whereas the other did not mention the book but was otherwise identical. All nonrespondents received several email reminders. Some physicians were further assigned at random to receive 1 reminder via paper mail (either a postcard or a letter) or no paper reminder. The primary outcome of this study was the survey response rate. RESULTS Of the 3966 physicians who were invited, 451 (11.4%) responded to at least one survey question and 336 (8.5%) completed the entire survey. Of those who were offered a book, 345/2973 (11.6%) responded compared with 106/993 (10.7%) who were not offered a book (odds ratio 1.10, 95% CI 0.87-1.38, P=.42). Regarding the paper mail reminder, 168/1572 (10.7%) letter recipients, 148/1561 (9.5%) postcard recipients, and 69/767 (9.0%) email-only recipients responded (P=.35). The response rate for those receiving letters or postcards was similar (odds ratio 1.14, 95% CI 0.91-1.44, P=.26). CONCLUSIONS Offering a modest nonmonetary incentive and sending a paper reminder did not improve survey response rate. Further research on how to enhance response rates in Internet-based physician surveys is needed.

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OBJECTIVE To evaluate the safety and efficacy of a plasmid (VM202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy. METHODS In a double-blind, placebo-controlled study, patients were randomized to receive injections of 8 or 16 mg VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density. RESULTS There were no significant adverse events attributable to VM202. Eighty-four patients completed the study. Patients receiving 8 mg VM202 per leg improved the most in all efficacy measures including a significant (P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain. INTERPRETATION VM202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM202 may be particularly beneficial for patients not taking gabapentin or pregabalin.

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OBJECTIVES To investigate the feasibility of recruitment, adherence and likely effectiveness of an e-learning intervention for managers to improve employees' well-being and reduce sickness absence. METHODS The GEM Study (guided e-learning for managers) was a mixed methods pilot cluster randomised trial. Employees were recruited from four mental health services prior to randomising three services to the intervention and one to no-intervention control. Intervention managers received a facilitated e-learning programme on work-related stress. Main outcomes were Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), 12-item GHQ and sickness absence <21 days from human resources. 35 in-depth interviews were undertaken with key informants, managers and employees, and additional observational data collected. RESULTS 424 of 649 (65%) employees approached consented, of whom 350 provided WEMWBS at baseline and 284 at follow-up; 41 managers out of 49 were recruited from the three intervention clusters and 21 adhered to the intervention. WEMWBS scores fell from 50.4-49.0 in the control (n=59) and 51.0-49.9 in the intervention (n=225), giving an intervention effect of 0.5 (95% CI -3.2 to 4.2). 120/225 intervention employees had a manager who was adherent to the intervention. HR data on sickness absence (n=393) showed no evidence of effect. There were no effects on GHQ score or work characteristics. Online quiz knowledge scores increased across the study in adherent managers. Qualitative data provided a rich picture of the context within which the intervention took place and managers' and employees' experiences of it. CONCLUSIONS A small benefit from the intervention on well-being was explained by the mixed methods approach, implicating a low intervention uptake by managers and suggesting that education alone may be insufficient. A full trial of the guided e-learning intervention and economic evaluation is feasible. Future research should include more active encouragement of manager motivation, reflection and behaviour change. TRIAL REGISTRATION NUMBER ISRCTN58661009.

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BACKGROUND Therapy that combines repetitive training with non-invasive brain stimulation is a potential avenue to enhance upper limb recovery after stroke. This study aimed to investigate the feasibility of transcranial Random Noise Stimulation (tRNS), timed to coincide with the generation of voluntary motor commands, during reaching training. METHODS A triple-blind pilot RCT was completed. Four stroke survivors with chronic (6-months to 5-years) and severe arm paresis, not taking any medications that had the potential to alter cortical excitability, and no contraindications to tRNS or MRI were recruited. Participants were randomly allocated to 12 sessions of reaching training over 4-weeks with active or sham tRNS delivered over the lesioned hemisphere motor representation. tRNS was triggered to coincide with a voluntary movement attempt, ceasing after 5-s. At this point, peripheral nerve stimulation enabled full range reaching. To determine feasibility, we considered adverse events, training outcomes, clinical outcomes, corticospinal tract (CST) structural integrity, and reflections on training through in-depth interviews from each individual case. RESULTS Two participants received active and two sham tRNS. There were no adverse events. All training sessions were completed, repetitive practice performed and clinically relevant improvements across motor outcomes demonstrated. The amount of improvement varied across individuals and appeared to be independent of group allocation and CST integrity. CONCLUSION Reaching training that includes tRNS timed to coincide with generation of voluntary motor commands is feasible. Clinical improvements were possible even in the most severely affected individuals as evidenced by CST integrity. TRIAL REGISTRATION This study was registered on the Australian and New Zealand Clinical Trials Registry (ANZCTR) http://www.ANZCTR.org.au/ACTRN12614000952640.aspx . Registration date 4 September 2014, first participant date 9 September 2014.

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BACKGROUND To study the longer term effects of an internet-based CBT intervention for relapse prevention (RP) in anorexia nervosa. METHODS 210 women randomized to the RP intervention group (full and partial completers) or the control group were assessed for eating and general psychopathology. Multiple regression analysis identified predictors of favorable course concerning Body Mass Index (BMI). Logistic regression analysis identified predictors of adherence to the RP program. RESULTS Most variables assessed showed more improvement for the RP than for the control group. However, only some scales reached statistical significance (bulimic behavior and menstrual function, assessed by expert interviewers blind to treatment condition). Very good results (BMI) were seen for the subgroup of "full completers" who participated in all nine monthly RP internet-based intervention sessions. "Partial completers" and controls (the latter non-significantly) underwent more weeks of inpatient treatment during the study period than "full completers", indicating better health and less need for additional treatment among the "full completers". Main long-term predictors for favorable course were adherence to RP, more spontaneity, and more ineffectiveness. Main predictors of good adherence to RP were remission from lifetime mood and lifetime anxiety disorder, a shorter duration of eating disorder, and additional inpatient treatment during RP. CONCLUSIONS Considering the high chronicity of AN, internet-based relapse prevention following intensive treatment appears to be promising.

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BACKGROUND Quality of life is a concept, which in recent years is considered as a measure for health in chronic diseases such as kidney diseases. Complications of chronic diseases can affect the quality of life in children and their families over time. Therefore, empowerment programs are necessary to improve their quality of life. This study aimed to investigate the impact of the family empowerment model on the quality of life in children with chronic kidney diseases. MATERIALS AND METHODS This quasi-experimental study was conducted on 64 children with chronic kidney diseases and their families. The research tools included the questionnaire of demographic characteristics and the quality of life questionnaire 4(th) edition. After data collection in the first phase, the family empowerment model was implemented in the intervention group and the test was repeated after 1 month. For comparison of data between the two groups and within each group, independent t-test and paired t-test were used, respectively. RESULTS Independent t-test showed that the mean score of quality of life was not significantly different in the two groups before intervention. However, after intervention, the differences were significant. Paired t-test showed a significant difference in the quality of life before and after intervention in the study group. CONCLUSIONS The findings showed that family empowerment model was effective in increasing the quality of life of children with chronic kidney diseases. Thus, we suggest this model to be used in inpatient and outpatient children's health care.

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BACKGROUND According to a World Health Organization (WHO) report, the prevalence of smoking in Iranian individuals aged 15-64 is up to 12%. OBJECTIVE The aim of the current study was to determine the durability of smoking cessation behavior based on a trans-theoretical model. METHODS This educational experimental study was conducted on smokers in Khomein City, Iran, in 2015. Sampling was done through a public announcement and then a random allocation of participants into two study group (50 persons) and control group (60 persons). Tools to gather data were as follows: an individual characteristics form and DiClemente's stages of change, Velicer's self-efficacy, Prochaska's processes of change, Velicer's decisional balance, and Fagerstrom's nicotine dependency questionnaires. The study group received five sessions of 45-minute individual counseling each and were followed-up three and six months later. Data were analyzed by SPSS version 16, using paired-samples t-test, independent-samples t-test, and chi-square. RESULTS Within six months of follow-up, 20 persons (40%) of the intervention group reached the maintenance stage of smoking cessation, while no one from controls managed to do that. Except for the perceived barriers and benefits of smoking cessation, all other constructs of the trans-theoretical model (cognitive and behavioral processes and smoking temptation) showed significant changes among the intervention group during six months' follow-up (p<0.05). There was no significant relationship between variables of having smoker friends, occupation, marital status, education status, and success or failure in cigarette smoking cessation (p>0.05). CONCLUSION According to our study, selection of cigarette smokers who are willing to quit, delivery of individual counseling according to specific personal characteristics, and also provision of free nicotine replacement therapies should be taken into account in cigarette smoking cessation programs.

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STATEMENT OF THE PROBLEM Self-etch adhesives can activate matrix metalloproteinase (MMP) which hydrolyzes organic matrix of demineralized dentin. Epigallocatechin gallate (EGCG), especially found in green tea, could inhibit the activation of MMP. PURPOSE The aim of this study was to evaluate the effect of adding Epigallocatechin gallate (EGCG) into two types of adhesives on dentin bond strength. MATERIALS AND METHOD In this experimental study, 64 extracted third molars were randomly divided into 16 groups. Clearfil SE Bond and Filtek Silorane System with 0 µM, 25µM, 50µM, and 100µM concentration of 95% EGCG were used for bonding. Following the bonding and fabrication of beams (1±0.1 mm(2)) and storage in distilled water, the specimens were subjected to thermal cycles. Microtensile bond strengths of 8 groups were examined after 24 hours and others were tested after 6 months. The fracture modes of specimens were evaluated by stereomicroscope and SEM. Data were analyzed by three-way ANOVA and t-test (α = 0.05). RESULTS The results of the three- way ANOVA test showed that types of bonding, storage time and interactive effect of EGCG concentration and bonding influenced the bond strength of specimens significantly (p<0.05). The results of the t-test indicated that storage time only had significant effect on bond strength of Clearfil SE Bond with no EGCG (p= 0.017). The most common failure modes in Filtek Silorane System groups and Clearfil SE Bond groups were adhesive and mixed/cohesive, respectively. The results of SEM at different magnifications showed that most fractures have occurred in the hybrid layer. CONCLUSION Although adding 100 µM volume of EGCG to Clearfil SE Bond can preserve the dentin bond, incorporation of EGCG in the silorane system, especially in high concentrations, decreases the bond strength after 6 months.

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OBJECTIVE This study proposes more objective methods for deciding the appropriate direction of the sylvian fissure dissection during surgical clipping in middle cerebral artery (MCA) bifurcation aneurysms. METHODS We reviewed data of 36 consecutive patients with MCA bifurcation aneurysms. We measured 2 indices preoperatively on 3-dimensional computed tomography angiography (3D-CTA). Analysis of the calculated data allowed us to select the appropriate direction of sylvian fissure dissection for ease of proximal control of M1. Statistically, Mann-Whitney test was used. RESULTS We classified subjects into 2 groups based on the technical level of M1 exposure during surgical clipping. When it was difficult to expose M1, subjects were assigned to Group I, and Group II were subjects in whom M1 exposure was easy. The mean difference between the distances extending from the limbus sphenoidale (LS) line to the internal carotid artery bifurcation and extending from the LS line to the MCA bifurcation was 1.00 ± 0.42 mm in group I and 4.39 ± 2.14 mm in group II. The mean M1 angle was 9.36 ± 3.73° in the group I and 34.05 ± 16.71° in the group II (M1 slope gap p < 0.05, M1 angle p < 0.05). CONCLUSION We have found an objective method for preoperatively verifying ease of exposure of M1 artery during surgical clipping. Therefore, we suggest use of the preoperative M1 slope gap and M1 angle as indicators in 3D-CTA selecting the direction of sylvian fissure dissection for easy proximal control of M1.

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BACKGROUND Whilst evidence suggests cognitive behaviour therapy (CBT) may be effective for depressed older people in a primary care setting, few studies have examined its cost-effectiveness. The aim of this study was to compare the cost-effectiveness of cognitive behaviour therapy (CBT), a talking control (TC) and treatment as usual (TAU), delivered in a primary care setting, for older people with depression. METHODS Cost data generated from a single blind randomised controlled trial of 204 people aged 65 years or more were offered only Treatment as Usual, or TAU plus up to twelve sessions of CBT or a talking control is presented. The Beck Depression Inventory II (BDI-II) was the main outcome measure for depression. Direct treatment costs were compared with reductions in depression scores. Cost-effectiveness analysis was conducted using non-parametric bootstrapping. The primary analysis focussed on the cost-effectiveness of CBT compared with TAU at 10 months follow up. RESULTS Complete cost data were available for 198 patients at 4 and 10 month follow up. There were no significant differences between groups in baseline costs. The majority of health service contacts at follow up were made with general practitioners. Fewer contacts with mental health services were recorded in patients allocated to CBT, though these differences were not significant. Overall total per patient costs (including intervention costs) were significantly higher in the CBT group compared with the TAU group at 10 month follow up (difference £427, 95% CI: £56 - £787, p < 0.001). Reductions in BDI-II scores were significantly greater in the CBT group (difference 3.6 points, 95% CI: 0.7-6.5 points, p = 0.018). CBT is associated with an incremental cost of £120 per additional point reduction in BDI score and a 90% probability of being considered cost-effective if purchasers are willing to pay up to £270 per point reduction in the BDI-II score. CONCLUSIONS CBT is significantly more costly than TAU alone or TAU plus TC, but more clinically effective. Based on current estimates, CBT is likely to be recommended as a cost-effective treatment option for this patient group if the value placed on a unit reduction in BDI-II is greater than £115. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN18271323.

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BACKGROUND Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant ( amenable ) forms of α-Gal to facilitate normal lysosomal trafficking. METHODS The main objective of the 18-month, randomised, active-controlled ATTRACT study was to assess the effects of migalastat on renal function in patients with Fabry disease previously treated with ERT. Effects on heart, disease substrate, patient-reported outcomes (PROs) and safety were also assessed. RESULTS Fifty-seven adults (56% female) receiving ERT (88% had multiorgan disease) were randomised (1.5:1), based on a preliminary cell-based assay of responsiveness to migalastat, to receive 18 months open-label migalastat or remain on ERT. Four patients had non-amenable mutant forms of α-Gal based on the validated cell-based assay conducted after treatment initiation and were excluded from primary efficacy analyses only. Migalastat and ERT had similar effects on renal function. Left ventricular mass index decreased significantly with migalastat treatment (-6.6 g/m 2 (-11.0 to -2.2)); there was no significant change with ERT. Predefined renal, cardiac or cerebrovascular events occurred in 29% and 44% of patients in the migalastat and ERT groups, respectively. Plasma globotriaosylsphingosine remained low and stable following the switch from ERT to migalastat. PROs were comparable between groups. Migalastat was generally safe and well tolerated. CONCLUSIONS Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations. TRIAL REGISTRATION NUMBER NCT00925301; Pre-results.

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BACKGROUND Recent studies provide evidence for the effectiveness of Internet-based maintenance treatments for mental disorders. However, it is still unclear which participants might or might not profit from this particular kind of treatment delivery. OBJECTIVE The study aimed to identify moderators of treatment outcome in a transdiagnostic Internet-based maintenance treatment (TIMT) offered to patients after inpatient psychotherapy for mental disorders in routine care. METHODS Using data from a randomized controlled trial (N=400) designed to test the effectiveness of TIMT, we performed secondary analyses to identify factors moderating the effects of TIMT (intervention) when compared with those of a treatment-as-usual control condition. TIMT involved an online self-management module, asynchronous patient-therapist communication, a peer support group, and online-based progress monitoring. Participants in the control condition had unstructured access to outpatient psychotherapy, standardized outpatient face-to-face continuation treatment, and psychotropic management. Self-reports of psychopathological symptoms and potential moderators were assessed at the start of inpatient treatment (T1), at discharge from inpatient treatment/start of TIMT (T2), and at 3-month (T3) and 12-month follow-up (T4). RESULTS Education level, positive outcome expectations, and diagnoses significantly moderated intervention versus control differences regarding changes in outcomes between T2 and T3. Only education level moderated change differences between T2 and T4. The effectiveness of the intervention (vs control) was more pronounced among participants with a low (vs high) education level (T2-T3: B=-0.32, SE 0.16, P=.049; T2-T4: B=-0.42, SE 0.21, P=.049), participants with high (vs low) positive outcome expectations (T2-T3: B=-0.12, SE 0.05, P=.02) and participants with anxiety disorder (vs mood disorder) (T2-T3: B=-0.43, SE 0.21, P=.04). Simple slope analyses revealed that despite some subgroups benefiting less from the intervention than others, all subgroups still benefited significantly. CONCLUSIONS This transdiagnostic Internet-based maintenance treatment might be suitable for a wide range of participants differing in various clinical, motivational, and demographic characteristics. The treatment is especially effective for participants with low education levels. These findings may generalize to other Internet-based maintenance treatments.

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BACKGROUND Mesalamine has been used as the first-line medication for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two different mesalamine formulations in the maintenance of remission in patients with UC. METHODS In a multicenter, double-blind, randomized study, 131 patients with quiescent UC were assigned to two groups: 65 to receive a pH-dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time-2.25 g). Both formulations were administered three times daily for 48 weeks. The primary endpoint was the proportion of patients without bloody stools. RESULTS In the full analysis set (n = 130), the proportion of patients without bloody stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant difference in time to bloody stools was found between the two formulations (P = 0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4 g compared to Time-2.25 g, and a similar trend was observed with regard to the time to relapse. No differences were observed between the safety profiles of the two formulations. CONCLUSIONS The pH- and time-dependent release of mesalamine formulations were similarly safe and effective. Interestingly, the remission phase tended to be longer in the group that received the pH-dependent formulation compared to the group that received the time-dependent formulation (UMIN Clinical Trials Registry, no. C000000289).

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BACKGROUND Recently, there has been an increased interest in the effects of essential oils on athletic performances and other physiological effects. This study aimed to assess the effects of Citrus sinensis flower and Mentha spicata leaves essential oils inhalation in two different groups of athlete male students on their exercise performance and lung function. METHODS Twenty physical education students volunteered to participate in the study. The subjects were randomly assigned into two groups: Mentha spicata and Citrus sinensis (ten participants each). One group was nebulized by Citrus sinensis flower oil and the other by Mentha spicata leaves oil in a concentration of (0.02 ml/kg of body mass) which was mixed with 2 ml of normal saline for 5 min before a 1500 m running tests. Lung function tests were measured using a spirometer for each student pre and post nebulization giving the same running distance pre and post oils inhalation. RESULTS A lung function tests showed an improvement on the lung status for the students after inhaling of the oils. Interestingly, there was a significant increase in Forced Expiratory Volume in the first second and Forced Vital Capacity after inhalation for the both oils. Moreover significant reductions in the means of the running time were observed among these two groups. The normal spirometry results were 50 %, while after inhalation with M. spicata oil the ratio were 60 %. CONCLUSION Our findings support the effectiveness of M. spicata and C. sinensis essential oils on the exercise performance and respiratory function parameters. However, our conclusion and generalisability of our results should be interpreted with caution due to small sample size and lack of control groups, randomization or masking. We recommend further investigations to explain the mechanism of actions for these two essential oils on exercise performance and respiratory parameters. TRIAL REGISTRATION ISRCTN10133422, Registered: May 3, 2016.

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OBJECTIVE The aim of this study was to determine the effect of oral ondansetron in decreasing the vomiting due to acute gastroenteritis in children. METHODS In a single center, randomized, double blind, controlled trial, the effect of oral ondansetron was compared with placebo on 176 patients between 1 and 10 years old with acute gastroenteritis. 30 minutes after drug administration, oral rehydration therapy (ORT) was initiated. Severity of vomiting was evaluated during emergency department (ED) stay and 48 hours follow up. Data were collected and analyzed by SPSS16. FINDINGS Fifty two of children (58.5%) were males with the mean age of 3.12 (±2.30) years. Ten patients in ondansetron and 14 in placebo group had persistent vomiting during ED stay. After analyzing, there was no significant relation between vomiting in 4 and 48 hours and need for intra venous fluid therapy between the two groups although ondansetron generally decreased ORT failure (P=0.03). CONCLUSION Although administrayion of oral ondansetron in gastroenteritis could decrease failure of ORT, it seems that further well-conducted clinical studies are needed to determine effects of oral ondansetron precisely.

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BACKGROUND Clinical guidelines recommend knee muscle strengthening exercises to improve physical function. However, the amount of knee muscle strength increase needed for clinically relevant improvements in physical function is unclear. Understanding how much increase in knee muscle strength is associated with improved physical function could assist clinicians in providing appropriate strength gain targets for their patients in order to optimise outcomes from exercise. The aim of this study was to investigate whether an increase in knee muscle strength is associated with improved self-reported physical function following exercise; and whether the relationship differs according to physical function status at baseline. METHODS Data from 100 participants with medial knee osteoarthritis enrolled in a 12-week randomised controlled trial comparing neuromuscular exercise to quadriceps strengthening exercise were pooled. Participants were categorised as having mild, moderate or severe physical dysfunction at baseline using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Associations between 12-week changes in physical function (dependent variable) and peak isometric knee extensor and flexor strength (independent variables) were evaluated with and without accounting for baseline physical function status and covariates using linear regression models. RESULTS In covariate-adjusted models without accounting for baseline physical function, every 1-unit (Nm/kg) increase in knee extensor strength was associated with physical function improvement of 17 WOMAC units (95% confidence interval (CI) -29 to -5). When accounting for baseline severity of physical function, every 1-unit increase in knee extensor strength was associated with physical function improvement of 24 WOMAC units (95% CI -42 to -7) in participants with severe physical dysfunction. There were no associations between change in strength and change in physical function in participants with mild or moderate physical dysfunction at baseline. The association between change in knee flexor strength and change in physical function was not significant, irrespective of baseline function status. CONCLUSIONS In patients with severe physical dysfunction, an increase in knee extensor strength and improved physical function were associated. TRIAL REGISTRATION ANZCTR 12610000660088 . Registered 12 August 2010.

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BACKGROUND Subcutaneous specific immunotherapy (SCIT) is an effective treatment attenuating the progression of allergic asthma. To date, there is a lack of studies investigating the economic consequences of SCIT on health care expenditures. METHODS A health-economic piggy-back analysis of SCIT was conducted based on a RCT that enrolled 65 children and adolescents with allergic asthma. Patients were allocated into two groups: A group receiving SCIT with a high-dose hypoallergenic house dust mite preparation plus asthma medication and a control group receiving only asthma medication. For both groups asthma control was achieved before the start of the SCIT treatment and was maintained during the study. Both, costs and cost-effectiveness of SCIT with the high-dose hypoallergenic house dust mite preparation were investigated based on total medication costs, incremental medication costs and treatment effects (measured as lung function), respectively. A bootstrap analysis was performed to validate the results. RESULTS A steady decline in medication costs could be observed in the SCIT group one year after treatment start compared to the control group. This cost trend became statistically significant 3 years after SCIT started. The calculated potential savings in the SCIT group correlated with an improved lung function. The distribution of the bootstrap results revealed that the probability of SCIT having a superior effectiveness compared to the control group is around 90%. CONCLUSION SCIT with a high-dose hypoallergenic preparation received by children and adolescents suffering from mite induced allergic asthma reduces the allergic medication intake and has cost-saving effects. Additional costs associated with SCIT may be completely compensated by drug cost savings 4 years after end of SCIT. Additionally, SCIT is superior compared to routine care as measured by the lung function that improved in SCIT-treated patients. TRIAL REGISTRATION (EudraCT no. 2004 - 003892 - 35).

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BACKGROUND The aim of the present study was to examine the postprandial calcium and phosphate concentrations after supplementation with pentacalcium hydroxy-triphosphate (CaP). METHODS Ten men participated in this double-blind, placebo-controlled, cross-over study. The participants were divided into two groups. One group consumed bread enriched with CaP (plus 1 g calcium/d) and the other group a placebo product for three weeks. After a two week wash-out, the intervention was switched between the groups for another three weeks. Blood samples were drawn at the beginning (single administration) and at the end (repeated administration) of the intervention periods at 0, 30, 60, 120, 180 and 240 min. Between 0 and 30 min, a test meal, with or without CaP was consumed. The plasma concentrations of calcium and phosphate were examined. One participant dropped out due to personal reasons. RESULTS CaP supplementation resulted in a significantly higher plasma calcium concentration after 240 min compared to placebo. After repeated CaP administration, the AUC for the increment in plasma calcium concentration was significantly higher compared to placebo.After single and repeated CaP supplementation, plasma phosphate concentration significantly decreased after 30, 60, 120 and 180 min compared to 0 min. The placebo administration resulted in significant decreases after 30, 60 and 120 min compared to 0 min. CONCLUSION Our results show that CaP contributes to an adequate calcium supply, but without increasing the plasma concentration of phosphate. TRIAL REGISTRATION www.clinicaltrials.gov; NCT01296997.

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BACKGROUND Current medical daily practice relies on guidelines, protocols and procedures (GPPs), which require exploitation. However, diagnosis, treatment, risk management and process improvements require exploration. Physician are often unable to switch between exploitation and exploration. This study tested a new approach to facilitate switching that included (1) a new 'thinking protocol' that encouraged leaping from exploitation to exploration and (2) a GPP that encouraged leaping from exploration to exploitation. METHOD Two hundred students were divided into four groups. The groups received a set of tasks that required switching between exploitation and exploration. Three groups received the thinking protocol, the GPP, or both, and the fourth group served as control. RESULTS With each additional task, all groups increased exploitative tendency(p<0.0001). The two groups with the thinking protocol leaped from exploitation to exploration (p<0.0001); the other two groups remained in exploitation (p=0.1173, p=0.0758). For the groups that employed exploration learning, the group that received the GPP switched back to exploitation (p<0.0001), but the other group remained in exploration (p=0.2363). CONCLUSION Despite the importance of timely leaping between exploration and exploitation, in some events, medical teams fail to make the appropriate leap. We suggest to use our novel approach and to encourage the leaping between exploration and exploitation in daily medical practice, to enable the prevention of medical errors and to enhance the effectiveness of risk managements and process improvements.

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PURPOSE To identify hypoxia-related biomarkers indicative of response and resistance to epirubicin treatment in patients with locally advanced breast cancer. PATIENTS AND METHODS One hundred seventy-six women with T2-4 N0-1 breast tumours were randomly assigned to receive epirubicin 120 mg/m2/1-21 (EPI ARM), epirubicin 120 mg/m2/1-21 + erythropoietin 10.000 IU sc three times weekly (EPI-EPO ARM) and epirubicin 40 mg/m2/w-q21 (EPI-W ARM). Sixteen tumour proteins involved in cell survival, hypoxia, angiogenesis and growth factor, were assessed by immunohistochemistry in pre-treatment samples. A multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization. RESULTS VEGF and GLUT-1 expression were significantly positively associated with complete response (CR) to treatment in all leave-one-out iterations. Bcl-2 expression was inversely correlated with pCR, whilst EPO expression was positively correlated with pathological complete response (pCR). Haemaglobin and HIF-1a nuclear expression were inversely correlated with pCR. HB and HIF-1a expression were associated with a higher risk of relapse and overall survival. CONCLUSION Hypoxic biomarkers determines the epirubicin resistance in breast cancer. Assessment of such biomarkers, may be useful for predicting chemosensitivity and also anthracycline-based treatment outcome.

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AIMS AND OBJECTIVES The main objective of this study was to evaluate the duration of stimulation over the parotid salivary flow following the use of transcutaneous electric nerve stimulation (TENS) in different age groups. MATERIALS AND METHODS The study was carried out in three different age groups. Under group A individuals from 21 to 35 years of age, group B 36-50 years and group C above 51 years were considered. In each group 30 subjects were taken of whom 15 were males and 15 were females. The placement of pads was approximated bilaterally over the parotid glands. The working parameters of TENS unit were fixed at 50 Hz and the unit was in normal mode. RESULTS Subjects belonging to group B were showing statistically significant increases in the duration of stimulated parotid salivary flow following the use of TENS. CONCLUSION TENS can be considered as a non-pharmacological alternative to improve salivation for longer period in xerostomia patients.

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AIM The aim of this study was to analyse the effect of an 8-week multimodal physiotherapy programme (MPP), integrating physical land-based therapeutic exercise (TE), adapted swimming and health education, as a treatment for patients with chronic non-specific neck pain (CNSNP), on disability, general health/mental states and quality of life. METHODS 175 CNSNP patients from a community-based centre were recruited to participate in this prospective study. INTERVENTION 60-minute session (30 minutes of land-based exercise dedicated to improving mobility, motor control, resistance and strengthening of the neck muscles, and 30 minutes of adapted swimming with aerobic exercise keeping a neutral neck position using a snorkel). Health education was provided using a decalogue on CNSNP and constant repetition of brief advice by the physiotherapist during the supervision of the exercises in each session. STUDY OUTCOMES primary: disability (Neck Disability Index); secondary: physical and mental health states and quality of life of patients (SF-12 and EuroQoL-5D respectively). Differences between baseline data and that at the 8-week follow-up were calculated for all outcome variables. RESULTS Disability showed a significant improvement of 24.6% from a mean (SD) of 28.2 (13.08) at baseline to 16.88 (11.62) at the end of the 8-week intervention. All secondary outcome variables were observed to show significant, clinically relevant improvements with increase ranges between 13.0% and 16.3% from a mean of 0.70 (0.2) at baseline to 0.83 (0.2), for EuroQoL-5D, and from a mean of 40.6 (12.7) at baseline to 56.9 (9.5), for mental health state, at the end of the 8-week intervention. CONCLUSION After 8 weeks of a MPP that integrated land-based physical TE, health education and adapted swimming, clinically-relevant and statistically-significant improvements were observed for disability, physical and mental health states and quality of life in patients who suffer CNSNP. The clinical efficacy requires verification using a randomised controlled study design. TRIAL REGISTRATION ClinicalTrials.gov NCT02046876.

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BACKGROUND Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. METHODS AND FINDINGS A5164 was a randomized strategy trial of "early ART"--given within 14 days of starting acute OI treatment versus "deferred ART"--given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) >or=50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. THE DIFFERENCE IN THE PRIMARY ENDPOINT DID NOT REACH STATISTICAL SIGNIFICANCE: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27-0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30-0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. CONCLUSIONS Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications. TRIAL REGISTRATION ClinicalTrials.gov NCT00055120.

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BACKGROUND Tube thoracostomy (TT) is the most commonly performed surgical procedure in thoracic surgery clinics. The procedure might have to be repeated due to ineffective drainage in patients with tube malposition (TM), in whom the drain is not directed to the apex or located in the fissure. Trocar technique, which is used to prevent TM, is not recommended because of its potential for severe complications. METHODS The study involved 180 patients who required TT application for any etiology within one year. The patients were divided into two groups as Group A, who had undergone classical surgical technique (n = 90) and Group B, who had undergone a combination of surgery and trocar techniques (n = 90). The groups were compared for TM, the effect of TM on the drain removal, and other insertion related complications. RESULTS In Group A, 23 patients had TM, 4 of whom developed associated ineffective drainage, while the patients in Group B had no insertion related complications (p = 0.001). The mean drain removal time of the patients with TM was 5 +/- 2.25 days. In the patients who did not develop TM, it was 3.39 +/- 1.18 days (p = 0.001). CONCLUSIONS The modified combination technique is a reliable method in preventing TM and its potential complications.

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BACKGROUND Paracrine disruption of growth factors in women with polycystic ovarian syndrome (PCOS) results in production of low quality oocyte, especially following ovulation induction. The aim of this study was to investigate the effects of metformin (MET), N-acetylcysteine (NAC) and their combination on the hormonal levels and expression profile of GDF-9, BMP-15 and c-kit, as hallmarks of oocyte quality, in PCOS patients. MATERIALS AND METHODS This prospective randomized, double-blind, placebo controlled trial aims to study the effects of MET, NAC and their combination (MET+NAC) on expression of GDF-9, BMP-15 and c-kit mRNA in oocytes [10 at the germinal vesicle (GV) stage, 10 at the MI stage, and 10 at the MII stage from per group] derived following ovulation induction in PCOS. Treatment was carried out for six weeks, starting on the third day of previous cycle until oocyte aspiration. The expression of GDF9, BMP15 and c-kit were determined by quantitative real time polymerase chain reaction (RT-qPCR) and western blot analysis. Data were analyzed with one-way ANOVA. RESULTS The follicular fluid (FF) level of c-kit protein significantly decreased in the NAC group compared to the other groups. Significant correlations were observed between the FF soluble c-kit protein with FF volume, androstenedione and estradiol. The GDF-9 expression in unfertilized mature oocytes were significantly higher in the NAC group compared to the other groups (P<0.001). Similar difference was not observed between the MET, NAC+MET and control groups. The c-kit expression in unfertilized mature oocytes were significantly lower in the NAC group compared to the other groups (P<0.001). Similar difference was not observed between the MET, NAC+MET and control groups (Registration number: IRCT201204159476N1). CONCLUSION We concluded that NAC can improve the quality of oocytes in PCOS.

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OBJECTIVE To evaluate the long-term intervention effects of oral insulin on the development of type 1 diabetes and to assess the rate of progression to type 1 diabetes before and after oral insulin treatment was stopped in the Diabetes Prevention Trial-Type 1 (DPT-1). RESEARCH DESIGN AND METHODS The follow-up included subjects who participated in the early intervention of oral insulin (1994-2003) to prevent or delay type 1 diabetes. A telephone survey was conducted in 2009 to determine whether diabetes had been diagnosed and, if not, an oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), and autoantibody levels were obtained on all subjects who agreed to participate. RESULTS Of 372 subjects randomized, 97 developed type 1 diabetes before follow-up; 75% of the remaining 275 subjects were contacted. In the interim, 77 subjects had been diagnosed with type 1 diabetes and 54 of the remainder have had an OGTT; 10 of these were diagnosed with type 1 diabetes, subsequently. Among individuals meeting the original criteria for insulin autoantibodies (IAAs) (≥80 nU/mL), the overall benefit of oral insulin remained significant (P=0.05). However, the hazard rate in this group increased (from 6.4% [95% CI 4.5-9.1] to 10.0% [7.1-14.1]) after cessation of therapy, which approximated the rate of individuals treated with placebo (10.2% [7.1-14.6]). CONCLUSIONS Overall, the oral insulin treatment effect in individuals with confirmed IAA≥80 nU/mL appeared to be maintained with additional follow-up; however, once therapy stopped, the rate of developing diabetes in the oral insulin group increased to a rate similar to that in the placebo group.

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BACKGROUND Rates of cardiovascular disease are higher among HIV-infected patients as a result of the complex interplay between traditional risk factors, HIV-related inflammatory and immunologic changes, and effects of antiretroviral therapy (ART). This study prospectively evaluated changes in cardiovascular biomarkers in an underrepresented, racially diverse, HIV-1-infected population receiving abacavir/lamivudine as backbone therapy. METHODS This 96-week, open-label, randomized, multicenter study compared once-daily fosamprenavir/ritonavir 1400/100 mg and efavirenz 600 mg, both with ABC/3TC 600 mg/300 mg, in antiretroviral-naïve, HLA-B*5701-negative adults without major resistance mutations to study drugs. We evaluated changes from baseline to weeks 4, 12, 24, 48, and 96 in interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), d-dimer, plasminogen, and fibrinogen. Biomarker data were log-transformed before analysis, and changes from baseline were described using geometric mean ratios. RESULTS This study enrolled 101 patients (51 receiving fosamprenavir/ritonavir; 50 receiving efavirenz): 32% female, 60% African American, and 38% Hispanic/Latino; 66% (67/101) completed 96 weeks on study. At week 96, levels of IL-6, sVCAM-1, d-dimer, fibrinogen, and plasminogen were lower than baseline in both treatment groups, and the decrease was statistically significant for sVCAM-1 (fosamprenavir/ritonavir and efavirenz), d-dimer (fosamprenavir/ritonavir and efavirenz), fibrinogen (efavirenz), and plasminogen (efavirenz). Values of hs-CRP varied over time in both groups, with a significant increase over baseline at Weeks 4 and 24 in the efavirenz group. At week 96, there was no difference between the groups in the percentage of patients with HIV-1 RNA <50 copies/mL (fosamprenavir/ritonavir 63%; efavirenz 66%) by ITT missing-equals-failure analysis. Treatment-related grade 2-4 adverse events were more common with efavirenz (32%) compared with fosamprenavir/ritonavir (20%), and median lipid concentrations increased in both groups over 96 weeks of treatment. CONCLUSIONS In this study of underrepresented patients, treatment with abacavir/lamivudine combined with either fosamprenavir/ritonavir or efavirenz over 96 weeks, produced stable or declining biomarker levels except for hs-CRP, including significant and favorable decreases in thrombotic activity (reflected by d-dimer) and endothelial activation (reflected by sVCAM-1). Our study adds to the emerging data that some cardiovascular biomarkers are decreased with initiation of ART and control of HIV viremia. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT00727597.

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BACKGROUND Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited. METHOD This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted. RESULTS The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R2 = 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora. CONCLUSIONS Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism. TRIAL REGISTRATION CLINICAL TRIAL REGISTRATION NUMBER NCT01225198.

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INTRODUCTION A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) found reduction of antioxidants and substrates for energy generation. These metabolic alterations may underlie one of the most common features of SLE--fatigue. The metabolomic studies also noted reduced omega-3 fatty acids, which are powerful anti- oxidants. This deficiency may be causally related to oxidative stress, inflammation, disease activity, and fatigue in SLE. Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies. The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue, quality of life, and disease activity as part of a randomized clinical trial. METHODS Fifty SLE patients recruited in outpatient clinics were randomized 1:1 to fish oil supplementation or olive oil placebo, and blinded to their treatment group. At baseline and after 6 months of treatment, RAND Short Form-36 (RAND SF-36), Fatigue Severity Scale (FSS), SLE Disease Activity Index (SLEDAI), and Physician Global Assessment (PGA) were completed; serum was also collected for soluble mediator analysis. RESULTS Thirty-two patients completed the study. PGA improved significantly in the fish oil group compared with the placebo group (p = 0.015). The RAND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends (p = 0.092 and 0.070). No clear difference was seen in FSS and SLEDAI (p = 0.350 and p = 0.417). Erythrocyte sedimentation rate and serum IL-12 were reduced (p = 0.008 and p = 0.058); while serum IL-13 was increased by fish oil supplementation (p = 0.033). CONCLUSIONS In this randomized, placebo-controlled 6-month trial, SLE patients randomized to fish oil supplementation demonstrated improvement in their PGA, RAND SF-36, and some circulating inflammatory markers. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02021513 (registered 13 December 2013).

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AIM The aim of this study was to investigate the immediate effect of bitter gourd, Knol-khol, and ash gourd juices on blood glucose level among Type II diabetes mellitus patients. METHODS In 2015, pilot study was conducted randomly enrolling 30 patients with type 2 diabetes mellitus into three groups in SRK college, India. The first group received bitter gourd juice at FBS range between 120 to 300 mg per dl. The second, third group received Knol-khol, ash gourd juice respectively in the same range of fasting blood sugar level. Blood sugar level was evaluated ½ hour interval till 2 h after received respective juices. Data were collected for statistical analysis. RESULTS The mean blood glucose concentration in bitter gourd group was not statistically significant between time points, (P = .176). However, 90 min after the intake of bitter gourd juice shows statistical significant reduction of blood glucose level when compare with fasting level, (p = .049). After Knol khol juice the mean blood glucose level differed statistically significant between time points, shown in (p = .029). But no statistical changes seen in ash gourd group. As a result bitter gourd juice is immediately reducing the blood glucose level, while Knol khol juice reduces the blood sugar level gradually for longer period of 120 min. CONCLUSION This study shows the significance of hypoglycemic effects of bitter gourd and Knol khol juices among the type 2 Diabetic patients. Hence Bitter gourd juice, Knol khol juices may be beneficial in Diabetes patients to reduce the blood glucose level.

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INTRODUCTION Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine, passes into breast milk, and may produce unwanted side effects in neonates; therefore, alternatives to opioids are being sought. Reiki is an ancient Japanese form of healing where practitioners transfer healing energy through light touch and positive healing intention. Although 1.2 million Americans use reiki to reduce pain or depression, there is a lack of strong evidence supporting its effectiveness. A recent systematic review showed existing studies to be of poor methodological quality, with the common limitation of lack of blinding. To overcome this issue, the authors used distant reiki to assess its effectiveness in reducing pain following an elective C-section. METHODS In this randomised, double-blinded study, women who underwent an elective C-section were allocated to either usual care (control, n=40) or three distant reiki sessions in addition to usual care (n=40). Pain was assessed using a visual analogue scale (VAS). The primary endpoint was the Area Under the VAS-Time Curve (AUC) for days 1-3. Secondary measures included: the proportion of women who required opioid medications and dose consumed, rate of healing and vital signs. RESULTS AUC for pain was not significantly different in the distant reiki and control groups (mean ± SD; 212.1 ± 104.7 vs 223.1 ± 117.8; p=0.96). There were no significant differences in opioid consumption or rate of healing; however, the distant reiki group had a significantly lower heart rate (74.3 ± 8.1 bpm vs 79.8 ± 7.9 bpm, p=0.003) and blood pressure (106.4 ± 9.7 mmHg vs 111.9 ± 11.0 mmHg, p=0.02) post surgery. CONCLUSION Distant reiki had no significant effect on pain following an elective C-section. Clinical Trial Registration Number ISRCTN79265996.

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BACKGROUND In considering the importance of postoperative pain management and its consequences on its related secondary outcomes including nausea, vomiting, and operation-related complications, we aimed to compare the effectiveness of the three analgesic agents including ketamine, paracetamol, and magnesium sulfate for postoperative pain relief and associated consequences in this trial. MATERIALS AND METHODS In this double-blinded randomized control clinical trial, patients scheduled for elective lower extremity orthopedic surgery under general anesthesia were enrolled and randomized into four groups for receiving intravenous ketamine (0.25 mg/kg), paracetamol (15 mg/kg), magnesium sulfate (7.5 mg/kg), and placebo (normal saline), immediately after the induction of anesthesia. Postoperative pain scores, analgesic, and metoclopramide use, and frequency of vomiting and satisfaction score of studied patients in the four studied groups during the 6 h, 6-12 h, and 12-24 h after recovery were recorded and compared. RESULTS In this trial, thirty patients randomized in each studied groups. Mean of postoperative pain score was significantly lower in ketamine group than others during 24 h after recovery ( P < 0.001). Mean of additive analgesic use was significantly lower in ketamine group during 12 h after recovery ( P < 0.001), but it was not significantly different during 12-24 h after recovery ( P = 0.12). Mean of vomiting frequency and metoclopramide use was not different between groups ( P > 0.05). Excellent and good satisfaction score were significantly higher in ketamine group than other groups ( P = 0.04). CONCLUSIONS Ketamine has more superior effect for during recovery and postoperative pain controlling and analgesic use than paracetamol and magnesium sulfate.

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BACKGROUND The purpose of the present study was to determine the effect of additional calcium carbonate treatment on fibroblast growth factor 23 (FGF23) levels in patients treated with calcitriol. METHODS In this randomized, open-labeled, and parallel-group study, a total of 30 patients with early chronic kidney disease (CKD) and vitamin D deficiency were randomly assigned to two groups and received interventions for 8 weeks: 1) a combination of calcium carbonate and calcitriol group; and 2) calcitriol only group. The primary outcome was the difference in percentage change of serum FGF23 levels from baseline between the two groups. Secondary end points included the changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), and 25-hydroxyvitamin D 3 (25(OH)D) from baseline. RESULTS Serum FGF23 levels were more elevated in the combination group than in the calcitriol-alone group. However, both mean change and percentage change in the serum FGF23 levels during the 8-week period were not significantly different between the two groups. Serum calcium level was increased significantly only in the combination treatment group. There was no significant difference in percentage change of serum calcium levels between the two groups. In addition, changes in serum levels of phosphate, 25(OH)D, or PTH were not significantly different between the two groups. In correlation analysis, changes in serum FGF23 levels were positively correlated with changes in serum calcium and phosphate levels, but not with changes in 25(OH)D or PTH levels. No serious adverse events were observed, however, there was one case of mild gastrointestinal discomfort. CONCLUSION This study revealed that additional calcium carbonate treatment significantly increased serum FGF23 levels in patients treated with calcitriol, with their synergistic effect in promoting intestinal calcium absorption. This suggests that serum FGF23 levels should be monitored regularly, especially in those who use combination of vitamin D and calcium carbonate from the early stages of CKD.

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BACKGROUND Various sedative and analgesic techniques have been used for pain relief during oocyte retrieval which is the most painful part of in vitro fertilization (IVF) procedures. AIM This study aimed at comparing dexmedetomidine and midazolam for conscious sedation in women undergoing transvaginal oocyte retrieval during an IVF program. SETTINGS AND DESIGN Prospective randomized double-blinded comparative study. PATIENTS AND METHODS Fifty-two patients undergoing oocyte retrieval in their first IVF cycle were randomly allocated into two equal groups. The intervention started with giving fentanyl1 mcg/kg intravenous (IV) followed by paracervical block in both groups. Then, subjects in group (D) received dexmedetomidine at a loading dose of 1 μg/kg IV over 10 min followed by 0.5 μg/kg/h infusion until Ramsay Sedation Scale (RSS) reached 3-4. Patients in group (M) received a loading dose of midazolam 0.06 mg/kg IV over 10 min followed by 0.5 mg incremental doses until RSS reached 3-4. STATISTICAL ANALYSIS Statistical analysis was performed using SPSS program version 19 and EP 16 program. RESULTS Visual analog scale scores significantly decreased in group D than group M at 5 and 10 min during the procedure ( P = 0.03 and 0.01, respectively), and at 20 min during postanesthesia care unit (PACU) time ( P = 0.04). Intraoperative rescue sedation by propofol and postoperative rescue analgesia by acetaminophen showed a highly significant decrease ( P < 0.01) in group D compared with group M. Furthermore, the time of PACU stay was significantly less ( P < 0.01) in group D (49.03 ± 12.8 min) compared to group M (62.5 ± 18.34 min). Although significant bradycardia was noted in group D (23% of patients) during the procedure ( P = 0.02), no cases were reported in group M. Patient satisfaction was significantly higher in group D ( P < 0.1). CONCLUSION Dexmedetomidine is an effective analgesic alternative to midazolam during oocyte retrieval for IVF. It offered not only a shorter PACU stay without significant side effects, but also better overall patient satisfaction scores.

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