Low Risk Of Selection Bias Research Articles

Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1.

Hepatorenal syndrome type 1 (HRS1) is a functional, rapidly progressive, potentially reversible form of acute kidney injury occurring in patients with cirrhosis. Characterised by intense renal arterial vasoconstriction, it carries a very poor prognosis. There is a significant unmet need for a widely approved, safe and effective pharmacological treatment. To re-evaluate efficacy and safety of pharmacological treatments for HRS1, in the light of recently published randomised controlled trials (RCTs). MEDLINE (OvidSP), EMBASE, PubMed and Cochrane registers were searched for RCTs reporting efficacy and adverse events related to pharmacological treatment of HRS1. Search terms included: 'hepatorenal syndrome', 'terlipressin', 'noradrenaline', 'octreotide', 'midodrine', 'vasopressin', 'dopamine', 'albumin' and synonyms. Comparison of vasoactive drugs vs. placebo/no treatment, and two active drugs were included. Meta-analysis was performed for HRS1 reversal, creatinine improvement, mortality and adverse events. Twelve RCTs enrolling 700 HRS1 patients were included. Treatment with terlipressin and albumin led to HRS1 reversal more frequently than albumin alone or placebo (RR: 2.54, 95% CI: 1.51-4.26). Noradrenaline was effective in reversing HRS1, but trials were small and nonblinded. Overall, there was mortality benefit with terlipressin (RR: 0.79, 95% CI: 0.63-1.01), but sensitivity analysis including only trials with low risk of selection bias weakened this relationship (RR: 0.87, 95% CI: 0.71-1.06). Notably, there was a significant risk of adverse events with terlipressin therapy (RR: 4.32, 95% CI: 0.75-24.86). Terlipressin treatment is superior to placebo for achieving HRS1 reversal, but mortality benefit is less clear. Terlipressin is associated with significant adverse events, but infusion regimens may be better tolerated. There is continued need for safe and effective treatment options for hepatorenal syndrome.

Yoga for improving health-related quality of life, mental health and cancer-related symptoms in women diagnosed with breast cancer.

Breast cancer is the cancer most frequently diagnosed in women worldwide. Even though survival rates are continually increasing, breast cancer is often associated with long-term psychological distress, chronic pain, fatigue and impaired quality of life. Yoga comprises advice for an ethical lifestyle, spiritual practice, physical activity, breathing exercises and meditation. It is a complementary therapy that is commonly recommended for breast cancer-related impairments and has been shown to improve physical and mental health in people with different cancer types. To assess effects of yoga on health-related quality of life, mental health and cancer-related symptoms among women with a diagnosis of breast cancer who are receiving active treatment or have completed treatment. We searched the Cochrane Breast Cancer Specialised Register, MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), Indexing of Indian Medical Journals (IndMED), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal and Clinicaltrials.gov on 29 January 2016. We also searched reference lists of identified relevant trials or reviews, as well as conference proceedings of the International Congress on Complementary Medicine Research (ICCMR), the European Congress for Integrative Medicine (ECIM) and the American Society of Clinical Oncology (ASCO). We applied no language restrictions. Randomised controlled trials were eligible when they (1) compared yoga interventions versus no therapy or versus any other active therapy in women with a diagnosis of non-metastatic or metastatic breast cancer, and (2) assessed at least one of the primary outcomes on patient-reported instruments, including health-related quality of life, depression, anxiety, fatigue or sleep disturbances. Two review authors independently collected data on methods and results. We expressed outcomes as standardised mean differences (SMDs) with 95% confidence intervals (CIs) and conducted random-effects model meta-analyses. We assessed potential risk of publication bias through visual analysis of funnel plot symmetry and heterogeneity between studies by using the Chi2 test and the I2 statistic. We conducted subgroup analyses for current treatment status, time since diagnosis, stage of cancer and type of yoga intervention. We included 24 studies with a total of 2166 participants, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias.Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life (pooled SMD 0.22, 95% CI 0.04 to 0.40; 10 studies, 675 participants), reduced fatigue (pooled SMD -0.48, 95% CI -0.75 to -0.20; 11 studies, 883 participants) and reduced sleep disturbances in the short term (pooled SMD -0.25, 95% CI -0.40 to -0.09; six studies, 657 participants). The funnel plot for health-related quality of life was asymmetrical, favouring no therapy, and the funnel plot for fatigue was roughly symmetrical. This hints at overall low risk of publication bias. Yoga did not appear to reduce depression (pooled SMD -0.13, 95% CI -0.31 to 0.05; seven studies, 496 participants; low-quality evidence) or anxiety (pooled SMD -0.53, 95% CI -1.10 to 0.04; six studies, 346 participants; very low-quality evidence) in the short term and had no medium-term effects on health-related quality of life (pooled SMD 0.10, 95% CI -0.23 to 0.42; two studies, 146 participants; low-quality evidence) or fatigue (pooled SMD -0.04, 95% CI -0.36 to 0.29; two studies, 146 participants; low-quality evidence). Investigators reported no serious adverse events.Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce depression (pooled SMD -2.29, 95% CI -3.97 to -0.61; four studies, 226 participants), anxiety (pooled SMD -2.21, 95% CI -3.90 to -0.52; three studies, 195 participants) and fatigue (pooled SMD -0.90, 95% CI -1.31 to -0.50; two studies, 106 participants) in the short term. Very low-quality evidence showed no short-term effects on health-related quality of life (pooled SMD 0.81, 95% CI -0.50 to 2.12; two studies, 153 participants) or sleep disturbances (pooled SMD -0.21, 95% CI -0.76 to 0.34; two studies, 119 participants). No trial adequately reported safety-related data.Three studies that compared yoga versus exercise presented very low-quality evidence showing no short-term effects on health-related quality of life (pooled SMD -0.04, 95% CI -0.30 to 0.23; three studies, 233 participants) or fatigue (pooled SMD -0.21, 95% CI -0.66 to 0.25; three studies, 233 participants); no trial provided safety-related data. Moderate-quality evidence supports the recommendation of yoga as a supportive intervention for improving health-related quality of life and reducing fatigue and sleep disturbances when compared with no therapy, as well as for reducing depression, anxiety and fatigue, when compared with psychosocial/educational interventions. Very low-quality evidence suggests that yoga might be as effective as other exercise interventions and might be used as an alternative to other exercise programmes.

Vocational and business training to improve women's labour market outcomes in low‐ and middle‐income countries: a systematic review

Vocational and business training to improve women's labour market outcomes in low‐ and middle‐income countries: a systematic review

Interventions to improve adherence to lipid-lowering medication.

Lipid-lowering drugs are widely underused, despite strong evidence indicating they improve cardiovascular end points. Poor patient adherence to a medication regimen can affect the success of lipid-lowering treatment. To assess the effects of interventions aimed at improving adherence to lipid-lowering drugs, focusing on measures of adherence and clinical outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and CINAHL up to 3 February 2016, and clinical trials registers (ANZCTR and ClinicalTrials.gov) up to 27 July 2016. We applied no language restrictions. We evaluated randomised controlled trials of adherence-enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with a variety of measurable outcomes, such as adherence to treatment and changes to serum lipid levels. Two teams of review authors independently selected the studies. Three review authors extracted and assessed data, following criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. We assessed the quality of the evidence using GRADEPro. For this updated review, we added 24 new studies meeting the eligibility criteria to the 11 studies from prior updates. We have therefore included 35 studies, randomising 925,171 participants. Seven studies including 11,204 individuals compared adherence rates of those in an intensification of a patient care intervention (e.g. electronic reminders, pharmacist-led interventions, healthcare professional education of patients) versus usual care over the short term (six months or less), and were pooled in a meta-analysis. Participants in the intervention group had better adherence than those receiving usual care (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.29 to 2.88; 7 studies; 11,204 participants; moderate-quality evidence). A separate analysis also showed improvements in long-term adherence rates (more than six months) using intensification of care (OR 2.87, 95% CI 1.91 to 4.29; 3 studies; 663 participants; high-quality evidence). Analyses of the effect on total cholesterol and LDL-cholesterol levels also showed a positive effect of intensified interventions over both short- and long-term follow-up. Over the short term, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17 to 33.14; 4 studies; 430 participants; low-quality evidence) and LDL-cholesterol decreased by a mean of 19.51 mg/dL (95% CI 8.51 to 30.51; 3 studies; 333 participants; moderate-quality evidence). Over the long term (more than six months) total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95 to 20.19; 2 studies; 127 participants; high-quality evidence). Included studies did not report usable data for health outcome indications, adverse effects or costs/resource use, so we could not pool these outcomes. We assessed each included study for bias using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. In general, the risk of bias assessment revealed a low risk of selection bias, attrition bias, and reporting bias. There was unclear risk of bias relating to blinding for most studies. The evidence in our review demonstrates that intensification of patient care interventions improves short- and long-term medication adherence, as well as total cholesterol and LDL-cholesterol levels. Healthcare systems which can implement team-based intensification of patient care interventions may be successful in improving patient adherence rates to lipid-lowering medicines.

Maintenance Therapy for Patients with Mantle Cell Lymphoma (MCL) - a Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)

Background:MCL is characterized by a dismal long term prognosis with a median overall survival of 3-5 years. Rituximab maintenance treatment (MR) improves survival of patients with follicular lymphoma, and its effect was assessed for MCL patients in several trials with inconsistent results. Other agents as bortezomib were also evaluated as maintenance therapy for MCL.Aims:We performed a systematic review and meta-analysis of RCTs in order to assess the effect of maintenance therapy on clinical outcomes of patients with MCL.Methods:We included RCTs that compared any type of maintenance to no maintenance or a different maintenance for patients with MCL, either in first line or relapsed disease. In July 2016 we searched The CochraneLibrary, MEDLINE, conference proceedings, and databases of ongoing trials. Two reviewers independently assessed the qualityof the trials and extracted data. The primary outcome wasall cause mortality. Secondary outcomes included progression free survival (PFS) and infectious adverse events. Relative risk (RR) for dichotomous data and hazard ratio (HR) for time to event datawere estimated and pooled using random-effects model.ResultsWe identified 6 trials that reported relevant outcomes, conducted between the years 1998 to 2012 and randomizing 857 patients with MCL. Most patients were males, with a median age ranging from 57 to 70 years, and predominantly good performance status. Ninety-six percent of the patients received their first line of treatment. MIPI score was reported in three trials: 20 to 42 percent of patients had a high MIPI score. Induction therapy included rituximab in all trials. In five trials chemotherapy induction was applied and consisted of fludarabine, cyclophosphamide (FC) and mitoxantrone (Forstpointner, Blood 2006), cyclophosphamide, vincristine, adriamycin, prednisone (CHOP) or FC in one trial (Kluin-Nelemans et al.), bendamustine (Rummel et al.), DHAP followed by autologous stem cell transplantation (ASCT) (Le Gouill et al.), and CHOP/cytarabine followed by ASCT (Doorduijn et al.); in one trial rituximab was given alone (Ghielmini et al.). Maintenance consisted of rituximab in five trials and bortezomib in one trial (Doorduijn et al.). The control group received no maintenance in two trials and interferon alfa in one trial. All included trials were judged at low risk of selection bias, none were blinded.No statistically significant effect on mortality rate was shown with rituximab maintenance therapy compared to no maintenance or interferon alfa RR 0.72, 95% CI 0.50 to 1.04, I2 of heterogeneity 57%, 751 patients. The RR of mortality with bortezomib maintenance was 0.67, 95% CI 0.12 to 3.71, but that is based on only 60 patients.PFS improved with rituximab maintenance compared to no maintenance or interferon alfa: HR 0.59, 95% CI 0.46 to 0.75. With bortezomib maintenance vs. no maintenance the HR of event free survival was 0.84, 95% CI 0.32 to 2.20.There was no statistically significant difference in infection rate with or without maintenance (RR 0.80, 95% CI 0.37 to 1.69, 419 patients).ConclusionsMaintenance therapy improved PFS of patients with MCL, but no survival benefit could be shown. The pooled analysis is based mainly on the results of rituximab maintenance as data of the effect of bortezomib maintenance is scarce. The absence of significant increase of infection rate as opposed to maintenance rituximab in follicular lymphoma might be attributed to the small sample size. Based on these results patients treated for both first line and relapsed/refractory MCL should receive rituximab maintenance after achieving response to induction. [Display omitted] DisclosuresDreyling:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Infant position in neonates receiving mechanical ventilation.

In patients of various ages undergoing mechanical ventilation (MV), it has been observed that positions other than the standard supine position, such as the prone position, may improve respiratory parameters. The benefits of these positions have not been clearly defined for critically ill newborns receiving MV.This is an update of a review first published in 2005 and last updated in 2013. Primary objectiveTo assess the effects of different positioning of newborn infants receiving MV (supine vs prone, lateral decubitus or quarter turn from prone) in improving short-term respiratory outcomes. Secondary objectiveTo assess the effects of different positioning of newborn infants receiving MV on mortality and neuromotor and developmental outcomes over the long term, and on other complications of prematurity. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE via PubMed (1966 to 22 August 2016), Embase (1980 to 22 August 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 22 August 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised clinical trials comparing different positions in newborns receiving mechanical ventilation. Three unblinded review authors independently assessed trials for inclusion in the review and extracted study data. We used standard methodological procedures as expected by The Cochrane Collaboration and assessed the quality of the evidence using the GRADE approach. If the meta-analysis was not appropriate owing to substantial clinical heterogeneity between trials, we presented review findings in narrative format. We included in this review 19 trials involving 516 participants. Seven of the included studies (N = 222) had not been evaluated in the previous review. Investigators compared several positions: prone versus supine, prone alternant versus supine, prone versus lateral right, lateral right versus supine, lateral left versus supine, lateral alternant versus supine, lateral right versus lateral left, quarter turn from prone versus supine, quarter turn from prone versus prone and good lung dependent versus good lung uppermost.Apart from two studies that compared lateral alternant versus supine, one comparing lateral right versus supine and two comparing prone or prone alternant versus the supine position, all included studies had a cross-over design. In five studies, infants were ventilated with continuous positive airway pressure (CPAP); in the other studies, infants were treated with conventional ventilation (CV).Risks of bias did not differ substantially for different comparisons and outcomes. This update detects a moderate to high grade of inconsistency, similar to previous versions. However, for the analysed outcomes, the direction of effect was the same in all studies. Therefore, we consider that this inconsistency had little effect on the conclusions of the meta-analysis. When comparing prone versus supine position, we observed an increase in arterial oxygen tension (PO2) in the prone position (mean difference (MD) 5.49 mmHg, 95% confidence interval (CI) 2.92 to 8.05 mmHg; three trials; 116 participants; I2= 0). When percent haemoglobin oxygen saturation was measured with pulse oximetry (SpO2), improvement in the prone position was between 1.13% and 3.24% (typical effect based on nine trials with 154 participants; I2= 89%). The subgroup ventilated with CPAP (three trials; 59 participants) showed a trend towards improving SpO2 in the prone position compared with the supine position, although the mean difference (1.91%) was not significant (95% CI -1.14 to 4.97) and heterogeneity was extreme (I2= 95%).Sensitivity analyses restricted to studies with low risk of selection bias showed homogeneous results and verified a small but significant effect (MD 0.64, 95% CI 0.26 to 1.02; four trials; 92 participants; I2= 0).We also noted a slight improvement in the number of episodes of desaturation; it was not possible to establish whether this effect continued once the intervention was stopped. Investigators studied few adverse effects from the interventions in sufficient detail. Two studies analysed tracheal cultures of neonates after five days on MV, reporting lower bacterial colonisation in the alternating lateral position than in the supine posture. Other effects - positive or negative - cannot be excluded in light of the relatively small numbers of neonates studied. This update of our last review in 2013 supports previous conclusions. Evidence of low to moderate quality favours the prone position for slightly improved oxygenation in neonates undergoing mechanical ventilation. However, we found no evidence to suggest that particular body positions during mechanical ventilation of the neonate are effective in producing sustained and clinically relevant improvement.

Topiramate for acute affective episodes in bipolar disorder in adults.

Topiramate for acute affective episodes in bipolar disorder in adults.

Comparison of soft tissue balancing, femoral component rotation, and joint line change between the gap balancing and measured resection techniques in primary total knee arthroplasty: A meta-analysis.

This meta-analysis was designed to compare the accuracy of soft tissue balancing and femoral component rotation as well as change in joint line positions, between the measured resection and gap balancing techniques in primary total knee arthroplasty. Studies were included in the meta-analysis if they compared soft tissue balancing and/or radiologic outcomes in patients who underwent total knee arthroplasty with the gap balancing and measured resection techniques. Comparisons included differences in flexion/extension, medial/lateral flexion, and medial/lateral extension gaps (LEGs), femoral component rotation, and change in joint line positions. Finally, 8 studies identified via electronic (MEDLINE, EMBASE, and the Cochrane Library) and manual searches were included. All 8 studies showed a low risk of selection bias and provided detailed demographic data. There was some inherent heterogeneity due to uncontrolled bias, because all included studies were observational comparison studies. The pooled mean difference in gap differences between the gap balancing and measured resection techniques did not differ significantly (-0.09 mm, 95% confidence interval [CI]: -0.40 to +0.21 mm; P = 0.55), except that the medial/LEG difference was 0.58 mm greater for measured resection than gap balancing (95% CI: -1.01 to -0.15 mm; P = 0.008). Conversely, the pooled mean difference in femoral component external rotation (0.77°, 95% CI: 0.18° to 1.35°; P = 0.01) and joint line change (1.17 mm, 95% CI: 0.82 to 1.52 mm; P < 0.001) were significantly greater for the gap balancing than the measured resection technique. The gap balancing and measured resection techniques showed similar soft tissue balancing, except for medial/LEG difference. However, the femoral component was more externally rotated and the joint line was more elevated with gap balancing than measured resection. These differences were minimal (around 1 mm or 1°) and therefore may have little effect on the biomechanics of the knee joint. This suggests that the gap balancing and measured resection techniques are not mutually exclusive.

Out‐of‐Home Care versus In‐home Care for Children Who Have Been Maltreated: A Systematic Review of Health and Wellbeing Outcomes

We systematically reviewed quantitative research that compared developmental health or wellbeing outcomes for maltreated children placed in out‐of‐home care (OoHC) with those cared for in their home. Randomised, quasi‐randomised and cohort studies that met detailed criteria were eligible. Study results and bias risk information were extracted by two authors using predefined data fields. Narrative synthesis was used because of the diversity of studies. No randomised studies were found. Thirty‐one papers from 11 cohort studies were included. The studies covered 15 developmental health or wellbeing outcomes (63 distinct comparisons). Of 40 significance‐tested comparisons, 29 were consistent with no evidence of benefit or harm of OoHC, seven were consistent with harm and four with benefit. Three studies with low risk of selection bias showed no evidence of significant differences, or found worse outcomes for OoHC. Overall, evidence from cohort studies shows limited evidence of improved outcomes, and some evidence of worse outcomes associated with OoHC. These results may be explained by selection bias favouring placement of children likely to have worse outcomes in OoHC rather than in‐home care. Further research, including randomised controlled trials and carefully matched data‐sets, is needed to determine the effectiveness of OoHC. Copyright © 2016 John Wiley &amp; Sons, Ltd.‘Studies covered 15 developmental health or wellbeing outcomes’Key Practitioner Messages Most research has high bias risk, as children who enter OoHC have more disadvantaged backgrounds and higher risk for poor outcomes than other maltreated children. Even allowing for significant bias risk in the studies, there are mixed results for children entering OoHC, and the three highest-quality studies showed no difference or worse outcomes for OoHC.

Ultrasound versus 'clinical touch' for catheter guidance during embryo transfer in women.

Many women undergoing an assisted reproductive technology (ART) cycle will not achieve a live birth. Failure at the embryo transfer stage may be due to lack of good-quality embryo/s, lack of uterine receptivity, or the transfer technique itself. Numerous methods, including the use of ultrasound guidance for proper catheter placement in the endometrial cavity, have been suggested as more effective techniques of embryo transfer. This review evaluates the efficacy of ultrasound-guided embryo transfer (UGET) compared with 'clinical touch' (CTET), which is the traditional method of embryo transfer and relies on the clinician's tactile senses to judge when the transfer catheter is in the correct position. To determine whether ultrasound guidance compared with clinical touch improves pregnancy outcomes in women undergoing embryo transfer during ART cycles. For the 2016 update of this review, we ran updated searches in the Cochrane Gynaecology and Fertility Group trials register (May 2015), the Cochrane Central Register of Controlled Trials (the Cochrane Library, May 2015), MEDLINE (2009 to May 2015), and EMBASE (2009 to May 2015). We also handsearched relevant conference proceedings: American Society for Reproductive Medicine (ASRM), European Society for Human Reproduction and Embryology (ESHRE), and International Federation of Gynecology and Obstetrics (FIGO). There were no language restrictions. We included only randomised controlled trials. Two review authors independently assessed eligibility and quality of trials and extracted data from those selected. We calculated odds ratio (OR) and 95% confidence interval (CI) for dichotomous outcomes. No outcomes were reported using continuous data. We assessed the overall quality of the evidence for the main findings using the GRADE working group methods. This systematic review now has 21 included studies (four of which we added in the 2016 update), two studies awaiting assessment, and 47 excluded studies. In total, data for meta-analyses were available in 21 trials (n = 6218 women), of which only four reported live births.UGET was associated with an increased chance of a live birth/ongoing pregnancy compared with CTET (OR 1.47, 95% CI 1.30 to 1.65; 13 trials; n = 5859 women; I(2) = 74%; low-quality evidence). Sensitivity analysis by including only trials with low risk of selection bias or by using a random-effects model did not alter the effect. We estimate that for women with a chance of a live birth/ongoing pregnancy of 23% using CTET, this would increase to between 28% and 33% using UGET. We considered the quality of the evidence using GRADE methodology to be low.UGET was associated with an increase in the chance of a clinical pregnancy (OR 1.31, 95% CI 1.17 to 1.45; 20 trials; n = 6711 women; I(2) = 42%; moderate-quality evidence). We identified no differences between groups for the incidence of adverse events including multiple pregnancy, ectopic pregnancy, or miscarriage. These events were relatively rare, and sample sizes limited the ability to detect such differences. The evidence suggests ultrasound guidance improves the chance of live birth/ongoing and clinical pregnancies compared with clinical touch, without increasing the chance of multiple pregnancy, ectopic pregnancy, or miscarriage. Methodological limitations included: only four studies reporting details of both computerised randomisation techniques and adequate allocation concealment, only four studies reported on the outcome of live birth, and none of the nine studies that reported on ongoing pregnancy reported on live birth, suggesting possible reporting bias. Adequate reporting of randomisation and allocation concealment will improve the quality of future studies. The primary outcome measure of future studies should be the reporting of live births per woman randomised.

Corticosteroids for treating sepsis.

Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment (SOFA) score of two or higher. Sepsis may be complicated by impaired corticosteroid metabolism. Giving corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and again in 2015. To examine the effects of corticosteroids on death at one month in patients with sepsis, and to examine whether dose and duration of corticosteroids influence patient response to this treatment. We searched the Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (October 2014), EMBASE (October 2014), Latin American Caribbean Health Sciences Literature (LILACS; October 2014) and reference lists of articles, and we contacted trial authors. The original searches were performed in August 2003 and in October 2009. We included randomized controlled trials of corticosteroids versus placebo or supportive treatment in patients with sepsis. All review authors agreed on the eligibility of trials. One review author extracted data, which were checked by the other review authors, and by the primary author of the paper when possible. We obtained some missing data from trial authors. We assessed the methodological quality of trials. We identified nine additional studies since the last update, for a total of 33 eligible trials (n = 4268 participants). Twenty-three of these 33 trials were at low risk of selection bias, 22 were at low risk of performance and detection bias, 27 were at low risk of attrition bias and 14 were at low risk of selective reporting.Corticosteroids reduced 28-day mortality (27 trials; n = 3176; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 1.00; P value = 0.05, random-effects model). The quality of evidence for this outcome was downgraded from high to low for imprecision (upper limit of 95% CI = 1) and for inconsistency (significant heterogeneity across trial results). Heterogeneity was related in part to the dosing strategy. Treatment with a long course of low-dose corticosteroids significantly reduced 28-day mortality (22 trials; RR 0.87, 95% CI 0.78 to 0.97; P value = 0.01, fixed-effect model). The quality of evidence was downgraded from high to moderate for inconsistency (owing to non-significant effects shown by one large trial). Corticosteroids also reduced mortality rate in the intensive care unit (13 trials; RR 0.82, 95% CI 0.68 to 1.00; P value = 0.04, random-effects model) and at the hospital (17 trials; RR 0.85, 95% CI 0.73 to 0.98; P value = 0.03, random-effects model). Quality of the evidence for in-hospital mortality was downgraded from high to moderate for inconsistency and imprecision (upper limit of 95% CI for RR approaching 1). Corticosteroids increased the proportion of shock reversal by day seven (12 trials; RR 1.31, 95% CI 1.14 to 1.51; P value = 0.0001) and by day 28 (seven trials; n = 1013; RR 1.11, 95% CI 1.02 to 1.21; P value = 0.01) and reduced the SOFA score by day seven (eight trials; mean difference (MD) -1.53, 95% CI -2.04 to -1.03; P value < 0.00001, random-effects model) and survivors' length of stay in the intensive care unit (10 trials; MD -2.19, 95% CI -3.93 to -0.46; P value = 0.01, fixed-effect model) without inducing gastroduodenal bleeding (19 trials; RR 1.24, 95% CI 0. 92 to 1.67; P value = 0.15, fixed-effect model), superinfection (19 trials; RR 1.02, 95% CI 0.87 to 1.20; P value = 0.81, fixed-effect model) or neuromuscular weakness (three trials; RR 0.62, 95% CI 0.21 to 1.88; P value = 0.40, fixed-effect model). Corticosteroid increased the risk of hyperglycaemia (13 trials; RR 1.26, 95% CI 1.16 to 1.37; P value < 0.00001, fixed-effect model) and hypernatraemia (three trials; RR 1.64, 95% CI 1.28 to 2.09; P value < 0.0001, fixed-effect model). Overall, low-quality evidence indicates that corticosteroids reduce mortality among patients with sepsis. Moderate-quality evidence suggests that a long course of low-dose corticosteroids reduced 28-day mortality without inducing major complications and led to an increase in metabolic disorders.

Associated Factors and Consequences of Risk of Bias in Randomized Controlled Trials of Yoga: A Systematic Review.

BackgroundBias in randomized controlled trials (RCTs) of complementary therapy interventions seems to be associated with specific factors and to potentially distort the studies’ conclusions. This systematic review assessed associated factors of risk of bias and consequences for the studies’ conclusions in RCTs of yoga as one of the most commonly used complementary therapies.MethodsMedline/PubMed, Scopus, IndMED and the Cochrane Library were searched through February 2014 for yoga RCTs. Risk of selection bias was assessed using the Cochrane tool and regressed to a) publication year; b) country of origin; c) journal type; and d) impact factor using multiple logistic regression analysis. Likewise, the authors’ conclusions were regressed to risk of bias.ResultsA total of 312 RCTs were included. Impact factor ranged from 0.0 to 39.2 (median = 1.3); 60 RCT (19.2%) had a low risk of selection bias, and 252 (80.8%) had a high or unclear risk of selection bias. Only publication year and impact factor significantly predicted low risk of bias; RCTs published after 2001 (adjusted odds ratio (OR) = 12.6; 95% confidence interval (CI) = 1.7, 94.0; p<0.001) and those published in journals with impact factor (adjusted OR = 2.6; 95%CI = 1.4, 4.9; p = 0.004) were more likely to have low risk of bias. The authors’ conclusions were not associated with risk of bias.ConclusionsRisk of selection bias was generally high in RCTs of yoga; although the situation has improved since the publication of the revised CONSORT statement 2001. Pre-CONSORT RCTs and those published in journals without impact factor should be handled with increased care; although risk of bias is unlikely to distort the RCTs’ conclusions.

Omega-3 fatty acids for depression in adults.

Omega-3 fatty acids for depression in adults.

Psychosocial interventions for smoking cessation in patients with coronary heart disease.

This is an update of a Cochrane review previously published in 2008. Smoking increases the risk of developing atherosclerosis but also acute thrombotic events. Quitting smoking is potentially the most effective secondary prevention measure and improves prognosis after a cardiac event, but more than half of the patients continue to smoke, and improved cessation aids are urgently required. This review aimed to examine the efficacy of psychosocial interventions for smoking cessation in patients with coronary heart disease in short-term (6 to 12 month follow-up) and long-term (more than 12 months). Moderators of treatment effects (i.e. intervention types, treatment dose, methodological criteria) were used for stratification. The Cochrane Central Register of Controlled Trials (Issue 12, 2012), MEDLINE, EMBASE, PsycINFO and PSYNDEX were searched from the start of the database to January 2013. This is an update of the initial search in 2003. Results were supplemented by cross-checking references, and handsearches in selected journals and systematic reviews. No language restrictions were applied. Randomised controlled trials (RCTs) in patients with CHD with a minimum follow-up of 6 months. Two authors independently assessed trial eligibility and risk of bias. Abstinence rates were computed according to an intention to treat analysis if possible, or if not according to completer analysis results only. Subgroups of specific intervention strategies were analysed separately. The impact of study quality on efficacy was studied in a moderator analysis. Risk ratios (RR) were pooled using the Mantel-Haenszel and random-effects model with 95% confidence intervals (CI). We found 40 RCTs meeting inclusion criteria in total (21 trials were new in this update, 5 new trials contributed to long-term results (more than 12 months)). Interventions consist of behavioural therapeutic approaches, telephone support and self-help material and were either focused on smoking cessation alone or addressed several risk factors (eg. obesity, inactivity and smoking). The trials mostly included older male patients with CHD, predominantly myocardial infarction (MI). After an initial selection of studies three trials with implausible large effects of RR > 5 which contributed to substantial heterogeneity were excluded. Overall there was a positive effect of interventions on abstinence after 6 to 12 months (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.13 to 1.32, I² 54%; abstinence rate treatment group = 46%, abstinence rate control group 37.4%), but heterogeneity between trials was substantial. Studies with validated assessment of smoking status at follow-up had similar efficacy (RR 1.22, 95% CI 1.07 to 1.39) to non-validated trials (RR 1.23, 95% CI 1.12 to 1.35). Studies were stratified by intervention strategy and intensity of the intervention. Clustering reduced heterogeneity, although many trials used more than one type of intervention. The RRs for different strategies were similar (behavioural therapies RR 1.23, 95% CI 1.12 to 1.34, I² 40%; telephone support RR 1.21, 95% CI 1.12 to 1.30, I² 44%; self-help RR 1.22, 95% CI 1.12 to 1.33, I² 40%). More intense interventions (any initial contact plus follow-up over one month) showed increased quit rates (RR 1.28, 95% CI 1.17 to 1.40, I² 58%) whereas brief interventions (either one single initial contact lasting less than an hour with no follow-up, one or more contacts in total over an hour with no follow-up or any initial contact plus follow-up of less than one months) did not appear effective (RR 1.01, 95% CI 0.91 to 1.12, I² 0%). Seven trials had long-term follow-up (over 12 months), and did not show any benefits. Adverse side effects were not reported in any trial. These findings are based on studies with rather low risk of selection bias but high risk of detection bias (namely unblinded or non validated assessment of smoking status). Psychosocial smoking cessation interventions are effective in promoting abstinence up to 1 year, provided they are of sufficient duration. After one year, the studies showed favourable effects of smoking cessation intervention, but more studies including cost-effectiveness analyses are needed. Further studies should also analyse the additional benefit of a psychosocial intervention strategy to pharmacological therapy (e.g. nicotine replacement therapy) compared with pharmacological treatment alone and investigate economic outcomes.

Melatonin for pre- and postoperative anxiety in adults.

Anxiety in relation to surgery is a well-known problem. Melatonin offers an atoxic alternative to benzodiazepines in ameliorating this condition in the pre- and postoperative period. To assess the effect of melatonin on pre- and postoperative anxiety in adults when comparing melatonin with placebo or when comparing melatonin with benzodiazepines. The following databases were searched on 19 April 2013: CENTRAL, MEDLINE, EMBASE, CINAHL and Web of Science. For ongoing trials and protocols we searched clinicaltrials.gov, Current Controlled Trials and the World Health Organization (WHO) International Clinical Trials Registry Platform. We reran the search in October 2014. We will deal with any studies of interest when we update the review. Randomized, placebo-controlled or standard treatment-controlled, or both, studies that evaluated the effect of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both genders (15 to 90 years of age) undergoing any kind of surgical procedure in which it was necessary to use general, regional or topical anaesthesia. Data were extracted independently by two review authors. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimen, preoperative anxiety outcome measures and postoperative anxiety outcome measures. This systematic review identified 12 randomized controlled trials (RCTs) including 774 patients that assessed melatonin for treating preoperative anxiety, postoperative anxiety or both. Four of the 12 studies compared melatonin, placebo and midazolam, whereas the remaining eight studies compared melatonin and placebo only.The quality of the evidence for our primary outcome (melatonin versus placebo for preoperative anxiety) was high. More than half of the included studies had a low risk of selection bias and at least 75% of the included studies had a low risk of attrition, performance and detection bias. Most of the included studies had an unclear risk of reporting bias.Eight out the 10 studies that assessed the effect of melatonin on preoperative anxiety using a visual analogue scale (VAS) (ranging from 0 to 100 mm, higher scores indicate greater anxiety) showed a reduction compared to placebo. The reported estimate of effect (relative effect -13.36, 95% confidence interval (CI) -16.13 to -10.58; high quality evidence) was based on a meta-analysis of seven studies. Two studies did not show any difference between melatonin and placebo. Two studies comparing melatonin with midazolam using a VAS found no evidence of a difference in preoperative anxiety between the two groups (relative effect -1.18, 95% CI -2.59 to 0.23; low quality evidence).Eight studies assessed the effect of melatonin on postoperative anxiety. Four of these studies measuring postoperative anxiety 90 minutes postoperatively using a VAS did not find any evidence of a difference between melatonin and placebo (relative effect -3.71, 95% CI -9.26 to 1.84). Conversely, two studies showed a reduction of postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) when comparing melatonin with placebo (relative effect -5.31, 95% CI -8.78 to -1.84; moderate quality evidence). Two studies comparing melatonin with midazolam using a VAS did not find any evidence of a difference between the two groups in postoperative anxiety (relative effect -2.02, 95% CI -5.82 to 1.78). When compared to placebo, melatonin given as premedication (tablets or sublingually) can reduce preoperative anxiety in adults (measured 50 to 100 minutes after administration). Melatonin may be equally as effective as standard treatment with midazolam in reducing preoperative anxiety in adults (measured 50 to 100 minutes after administration). The effect of melatonin on postoperative anxiety (measured 90 minutes and 6 hours after surgery) in adults is mixed but suggests an overall attenuation of the effect compared to preoperatively.

Outcomes of intraventricular hemorrhage and posthemorrhagic hydrocephalus in a population-based cohort of very preterm infants born to residents of Nova Scotia from 1993 to 2010.

OBJECT Intraventicular hemorrhage (IVH) is a common complication of preterm birth, and the prognosis of IVH is incompletely characterized. The objective of this study was to describe the outcomes of IVH in a population-based cohort with minimal selection bias. METHODS All very preterm (≥ 30 completed weeks) patients born in the province of Nova Scotia were included in a comprehensive database. This database was screened for infants born to residents of Nova Scotia from January 1, 1993, to December 31, 2010. Among very preterm infants successfully resuscitated at birth, the numbers of infants who died, were disabled, developed cerebral palsy, developed hydrocephalus, were blind, were deaf, or had cognitive/language scores assessed were analyzed by IVH grade. The relative risk of each outcome was calculated (relative to the risk for infants without IVH). RESULTS Grades 2, 3, and 4 IVH were significantly associated with an increased overall mortality, primarily in the neonatal period, and the risk increased with increasing grade of IVH. Grade 4 IVH was significantly associated with an increased risk of disability (RR 2.00, p < 0.001), and the disability appeared to be primarily due to cerebral palsy (RR 6.07, p < 0.001) and cognitive impairment (difference in mean MDI scores between Grade 4 IVH and no IVH: -19.7, p < 0.001). No infants with Grade 1 or 2 IVH developed hydrocephalus, and hydrocephalus and CSF shunting were not associated with poorer outcomes when controlling for IVH grade. CONCLUSIONS Grades 1 and 2 IVH have much better outcomes than Grades 3 or 4, including a 0% risk of hydrocephalus in the Grade 1 and 2 IVH cohort. Given the low risk of selection bias, the results of this study may be helpful in discussing prognosis with families of very preterm infants diagnosed with IVH.

Cochrane review: community‐wide interventions for increasing physical activity

Abstract BACKGROUND: Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown. OBJECTIVES: To evaluate the effects of community wide, multi-strategic interventions upon population levels of physical activity. SEARCH STRATEGY: We searched the Cochrane Public Health Group Specialised Register, The Cochrane Library, MEDLINE, MEDLINE in Process, EMBASE, CINAHL, LILACS, PsycINFO, ASSIA, The British Nursing Index, Chinese CNKI databases, EPPI Centre (DoPHER, TRoPHI), ERIC, HMIC, Sociological Abstracts, SPORTDiscus, Transport Database and Web of Science (Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index). We also scanned websites of the EU Platform on Diet, Physical Activity and Health; Health-Evidence.ca; the International Union for Health Promotion and Education; the NIHR Coordinating Centre for Health Technology (NCCHTA) and NICE and SIGN guidelines. Reference lists of all relevant systematic reviews, guidelines and primary studies were followed up. We contacted experts in the field from the National Obesity Observatory Oxford, Oxford University; Queensland Health, Queensland University of Technology, the University of Central Queensland; the University of Tennessee and Washington University; and handsearched six relevant journals. The searches were last updated to the end of November 2009 and were not restricted by language or publication status. SELECTION CRITERIA: Cluster randomised controlled trials, randomised controlled trials (RCT), quasi-experimental designs which used a control population for comparison, interrupted time-series (ITS) studies, and prospective controlled cohort studies (PCCS) were included. Only studies with a minimum six-month follow up from the start of the intervention to measurement of outcomes were included. Community wide interventions had to comprise at least two broad strategies aimed at physical activity for the whole population. Studies which randomised individuals from the same community were excluded. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted the data and assessed the risk of bias of each included study. Non-English language papers were reviewed with the assistance of an epidemiologist interpreter. Each study was assessed for the setting, the number of included components and their intensity. Outcome measures were grouped according to whether they were dichotomous (physically active, physically active during leisure time and sedentary or physically inactive) or continuous (leisure time physical activity, walking, energy expenditure). For dichotomous measures we calculated the unadjusted and adjusted risk difference, and the unadjusted and adjusted relative risk. For continuous measures we calculated net percentage change from baseline, unadjusted and adjusted risk difference, and the unadjusted and adjusted relative risk. MAIN RESULTS: After the selection process had been completed 25 studies were included in the review. Of the included studies, 19 were set in high income countries, using the World Bank economic classification, and the remaining six were in low income countries. The interventions varied by the number of strategies included and their intensity. Almost all of the interventions included a component of building partnerships with local governments or non-governmental organisations (NGOs) (22 studies). None of the studies provided results by socio-economic disadvantage or other markers of equity consideration. However of those included studies undertaken in high income countries, 11 studies were described by the authors as being provided to deprived, disadvantaged, or low socio-economic communities.Fifteen studies were identified as having a high risk of bias, 10 studies were unclear, and no studies had a low risk of bias. Selection bias was a major concern with these studies, with only one study using randomisation to allocate communities (Simon 2008). No studies were judged as being at low risk of selection bias although 16 studies were considered to have an unclear risk of bias. Eleven studies had a high risk of detection bias, 10 with an unclear risk and four with no risk. Assessment of detection bias included an assessment of the validity of the measurement tools and quality of outcome measures. The effects reported were inconsistent across the studies and the measures. Some of the better designed studies showed no improvement in measures of physical activity. Publication bias was evident. AUTHORS' CONCLUSIONS: Although numerous studies have been undertaken, there is a noticeable inconsistency of the findings of the available studies and this is confounded by serious methodological issues within the included studies. The body of evidence in this review does not support the hypothesis that multi-component community wide interventions effectively increase population levels of physical activity. There is a clear need for well-designed intervention studies and such studies should focus on the quality of the measurement of physical activity, the frequency of measurement and the allocation to intervention and control communities. PMID: 21491409

Community wide interventions for increasing physical activity.

Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown. The objective of this review is to evaluate the effects of community wide, multi-strategic interventions upon population levels of physical activity.

Rituximab Maintenance (MR) for Patients with Mantle Cell Lymphoma (MCL) – a Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)

BackgroundMCL is characterized by a dismal long term prognosis with a median overall survival of 3-5 years. The addition of rituximab to induction chemotherapy improved significantly response rates of patients with MCL. MR treatment for these patients has the potential to further improve disease control and overall survival (OS). The few trials that addressed that question showed inconsistent results.AimsWe performed a systematic review and meta-analysis of RCTs in order to assess the effect of MR on clinical outcomes of patients with MCL.MethodsWe included RCTs that compared MR to no treatment or other treatment for patients with MCL, either in first line or relapsed disease. In March 2014 we searched The Cochrane Library, MEDLINE, conference proceedings, and databases of ongoing trials. Two reviewers independently assessed the quality of the trials and extracted data. The primary outcome was all cause mortality. Secondary outcomes included progression free survival (PFS) and infectious adverse events. Relative risk (RR) for dichotomous data and hazard ratio (HR) for time to event datawere estimated and pooled using random-effects model.ResultsWe identified 3 trials, conducted between the years 1998 to 2010 and randomizing 434 adult patients with MCL. Most patients were males, with a median age ranging from 61 to 70 years, and predominantly good performance status. Seventy-nine percent of the patients received their first line of treatment. MIPI score was reported in one trial. Induction therapy included rituximab in all three trials. In two trials additional chemotherapy induction was applied consisting of fludarabine, cyclophosphamide (FC) and mitoxantrone in one trial (Forstpointner, Blood 2006), and cyclophosphamide, vincristine, adriamycin, prednisone (CHOP) or FC in the other (Kluin-Nelemans, NEJM 2012); in the third trial rituximab was given alone (Ghielmini, JCO 2005). The control group received no maintenance in two trials and interferon alfa in one trial. All included trials are judged at low risk of selection bias, none were blinded.Mortality rate decreased with MR compared to no MR or interferon alfa RR 0.67, 95% CI 0.46 to 0.98, I2 of heterogeneity 54%, 392 patients (Figure).PFS improved with MR compared to no MR or interferon alfa: HR 0.60, 95% CI 0.44 to 0.82, I2 of heterogeneity = 0.There was no statistically significant difference in infection rate with or without MR (RR 0.80, 95% CI 0.37 to 1.69, 419 patients).ConclusionsThe results of this meta-analysis support a survival benefit of MR in patients with first line or relapsed/refractory MCL who responded to induction therapy. Additionally, there is a significant improvement of PFS benefit of MR. The absence of significant increase of infection rate as opposed to MR in follicular lymphoma may be attributed to the small sample size. Based on these results patients treated for both first line and relapsed/refractory MCL should receive MR after achieving response to induction. [Display omitted] DisclosuresVidal:Roche: unrestricted grant Other. Ghielmini:Roche: Research Funding, Speakers Bureau. Unterhalt:Roche: Travel Support Other. Shpilberg:Roche: Consultancy, Research Funding.

Interventions for treating femoral shaft fractures in children and adolescents.

Interventions for treating femoral shaft fractures in children and adolescents.