Endothelin‐receptor antagonists for diabetic nephropathy: A meta‐analysis

AimEndothelin‐receptor antagonists may be a novel therapeutic strategy for diabetic nephropathy, but their use remains controversial. This meta‐analysis seeks to evaluate the effectiveness and safety of endothelin‐receptor antagonists for patients with diabetic nephropathy.MethodsLiterature reviews of the PubMed, EMBASE and CENTRAL databases were conducted to identify randomized controlled trials (RCTs) comparing endothelin‐receptor antagonist treatment with placebo in patients with diabetic nephropathy. Quality assessment was performed by using the Cochrane Handbook's tools for assessing risk of bias; meta‐analysis was conducted by RevMan 5.3.ResutlsFive RCTs (n = 2034 patients) were included for analysis. Compared with placebo, endothelin‐receptor antagonists showed significant benefits for lowering albuminuria (five trials, n = 2034 patients; SMD 0.66 95% confidence interval (CI) 0.56 to 0.76), but there was no significant difference in the risk of death (two trials, n = 1674 patients; RR 1.49 95% CI 0.81 to 2.76). In addition, risk of cardiovascular events and other serious adverse events were significantly higher in the endothelin‐receptor antagonists group than the placebo group (four trials, n = 1956 patients; RR 1.45 95% CI 1.07 to 1.97; five trials, n = 2034 patients; RR 1.32 95% CI 1.10 to 1.58).ConclusionEndothelin‐receptor antagonists can reduce albuminuria in patients with diabetic nephropathy, although use resulted in more serious adverse events compared with placebo. There is a potential need for further RCTs, which has larger sample size and longer duration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111994/1/nep12442.pd

Educational interventions for improving control of blood pressure in patients with hypertension: a systematic review protocol

peer-reviewedIntroduction: The aim of this review is to evaluate the effectiveness of educational interventions on improving the control of blood pressure in patients with hypertension. Methods: Randomised controlled trials including patients over 18 years of age, regardless of sex and ethnicity, with a diagnosis of hypertension (either treated or not treated with antihypertensive medications) will be assessed in our analysis. We will electronically search four databases: MEDLINE, CINAHL, PEDro and ScienceDirect. There will be no language restrictions in the search for studies. The data will be extracted independently by two authors using predefined criteria. Disagreements will be resolved between the authors. The risk of bias will be assessed using the Cochrane risk of bias tool. After searching and screening of the studies, we will run a meta-analysis of the included randomised controlled trials. We will summarise the results as risk ratio for dichotomous data and mean differences for continuous data. Ethics and dissemination: The review will be published in a journal. The findings from the review will also be disseminated electronically and at conference presentations.PUBLISHEDpeer-reviewe

Do early interventions prevent PTSD? A systematic review and meta-analysis of the safety and efficacy of early interventions after sexual assault

Objective: To review the safety and efficacy of early interventions after sexual assault in reducing or preventing posttraumatic stress disorder (PTSD). Method: Systematic searches were performed on studies (1980–2018) that examined the efficacy of interventions for PTSD within 3 months after sexual assault. Results: The review identified 7 studies (n = 350) with high risk of bias that investigated 5 interventions. Only two studies reported on safety. Contact with the authors of six studies provided no indications for the occurrence of adverse events. Two studies reported the efficacy using PTSD diagnosis as dependent variable but found no difference between groups. All studies reported on efficacy using PTSD severity as dependent variable. For the meta-analysis, 4 studies (n = 293) were included yielding significantly greater reductions of PTSD severity than standard care at 2 to 12 months follow-up (g = −0.23, 95% CI [−0.46, 0.00]), but not at 1 to 6 weeks post-intervention (g = −0.28, 95% CI [−0.57, 0.02]). The heterogeneity of the interventions precluded further analyses. Discussion: Findings suggest that early interventions can lead to durable effects on PTSD severity after sexual assault. However, due to limited availability of data, it is impossible to draw definite conclusions about safety and efficacy of early interventions, and their potential to prevent PTSD

The effect of blue-light blocking spectacle lenses on visual performance, macular health and the sleep-wake cycle: asystematic review of the literature

Purpose: Blue-blocking (BB) spectacle lenses, which attenuate short-wavelength light, are being marketed to alleviate eyestrain and discomfort when using digital devices, improve sleep quality and potentially confer protection from retinal phototoxicity. The aim of this review was to investigate the relative benefits and potential harms of these lenses. Methods: We included randomised controlled trials (RCTs), recruiting adults from the general population, which investigated the effect of BB spectacle lenses on visual performance, symptoms of eyestrain or eye fatigue, changes to macular integrity and subjective sleep quality. We searched MEDLINE, EMBASE, the Cochrane Library and clinical trial registers, until 30 April 2017. Risk of bias was assessed using the Cochrane tool. Results: Three studies (with 136 participants) met our inclusion criteria; these had limitations in study design and/or implementation. One study compared the effect of BB lenses with clear lenses on contrast sensitivity (CS) and colour vision (CV) using a pseudo-RCT crossover design; there was no observed difference between lens types (log CS; Mean Difference (MD) = −0.01 [−0.03, 0.01], CV total error score on 100-hue; MD = 1.30 [−7.84, 10.44]). Another study measured critical fusion frequency (CFF), as a proxy for eye fatigue, on wearers of low and high BB lenses, pre- and post- a two-hour computer task. There was no observed difference between low BB and standard lens groups, but there was a less negative change in CFF between the high and low BB groups (MD = 1.81 [0.57, 3.05]). Both studies compared eyestrain symptoms with Likert scales. There was no evidence of inter-group differences for either low BB (MD = 0.00 [−0.22, 0.22]) or high BB lenses (MD = −0.05 [−0.31, 0.21]), nor evidence of a difference in the proportion of participants showing an improvement in symptoms of eyestrain or eye fatigue. One study reported a small improvement in sleep quality in people with self-reported insomnia after wearing high compared to low-BB lenses (MD = 0.80 [0.17, 1.43]) using a 10-point Likert scale. A study involving normal participants found no observed difference in sleep quality. We found no studies investigating effects on macular structure or function. Conclusions: We find a lack of high quality evidence to support using BB spectacle lenses for the general population to improve visual performance or sleep quality, alleviate eye fatigue or conserve macular health

Image-guided versus blind corticosteroid injections in adults with shoulder pain: A systematic review

<p>Abstract</p> <p>Background</p> <p>Corticosteroid injections can be performed blind (landmark-guided) or with image guidance, and this may account for variable clinical outcomes. The objective of this study was to assess the effectiveness and safety of image-guided versus blind corticosteroid injections in improving pain and function among adults with shoulder pain.</p> <p>Methods</p> <p>MEDLINE, the Cochrane Controlled Trials Register and EMBASE were searched to May 2010. Additional studies were identified by searching bibliographies of shortlisted articles. Search items included blind, landmark, anatomical, clinical exam, image-guided, ultrasound, fluoroscopy, steroid injection, frozen shoulder, random allocation, randomized controlled trial (RCT) and clinical trial.</p> <p>Randomized controlled studies comparing image-guided versus blind (landmark-guided) corticosteroid shoulder injections that examined pain, function and/or adverse events were included. Independent extraction was done by two authors using a form with pre-specified data fields, including risk of bias appraisal. Conflicts were resolved by discussion. The decision to pool data was based on assessment of clinical design homogeneity. When warranted, studies were pooled under a random-effects model.</p> <p>Results</p> <p>Two RCTs for pain, function and adverse events (n = 101) met eligibility criteria. No serious threats to validity were found. Both trials compared ultrasound-guided versus landmark-guided injections and were judged similar in clinical design. Low to moderate heterogeneity was observed: shoulder pain I²= 60%, function I²= 22%. A meta-analysis demonstrated greater improvement with ultrasound-guided injections at 6 weeks after injection in both pain (mean difference = 2.23 [95% CI: 1.27, 3.18]), as assessed with a 0 to 10 visual analogue scale, and shoulder function (standardised mean difference = 1.09 [95% CI: 0.61, 1.57]) as assessed with shoulder function scores. Although more adverse events (all mild) were reported with landmark-guided injections, the difference was not statistically significant (risk ratio = 0.20 [95% CI: 0.04, 1.13]).</p> <p>This review was only based on two moderate-sized trials. Blinding of patients was not performed in both trials, causing some risk of bias in outcome assessment since primary endpoints were wholly or partially patient-reported.</p> <p>Conclusion</p> <p>There is a paucity of RCTs on image-guided versus landmark-guided corticosteroid shoulder injections examining pain, function and adverse events. In this review, patients who underwent image-guided (ultrasound) injections had statistically significant greater improvement in shoulder pain and function at 6 weeks after injection. Image-guided (ultrasound) corticosteroid injections potentially offer a significantly greater clinical improvement over blind (landmark-guided) injections in adults with shoulder pain. However, this apparent benefit requires confirmation from further studies (adequately-powered and well-executed RCTs).</p

Comprehensive literature review and statistical considerations for GWAS meta-analysis

Over the last decade, genome-wide association studies (GWAS) have become the standard tool for gene discovery in human disease research. While debate continues about how to get the most out of these studies and on occasion about how much value these studies really provide, it is clear that many of the strongest results have come from large-scale mega-consortia and/or meta-analyses that combine data from up to dozens of studies and tens of thousands of subjects. While such analyses are becoming more and more common, statistical methods have lagged somewhat behind. There are good meta-analysis methods available, but even when they are carefully and optimally applied there remain some unresolved statistical issues. This article systematically reviews the GWAS meta-analysis literature, highlighting methodology and software options and reviewing methods that have been used in real studies. We illustrate differences among methods using a case study. We also discuss some of the unresolved issues and potential future directions

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

The management of menopause in women with a history of endometriosis: a systematic review

BACKGROUND Endometriosis is typically regarded as a premenopausal disease, resolving after natural or iatrogenic menopause due to declining oestrogen levels. Nonetheless, case reports over the years have highlighted the incidence of recurrent postmenopausal endometriosis. It is now clear that both recurrence and malignant transformation of endometriotic foci can occur in the postmenopausal period. Postmenopausal women are commonly treated with hormone replacement therapy (HRT) to treat climacteric symptoms and prevent bone loss; however, HRT may reactivate endometriosis and stimulate malignant transformation in women with a history of endometriosis. Given the uncertain risks of initiating HRT, it is difficult to determine the best menopausal management for this group of women. OBJECTIVE AND RATIONAL The aim of this study was to systematically review the existing literature on management of menopausal symptoms in women with a history of endometriosis. We also aimed to evaluate the published literature on the risks associated with HRT in these women, and details regarding optimal formulations and timing (i.e. initiation and duration) of HRT. SEARCH METHODS Four electronic databases (MEDLINE via OVID, Embase via OVID, PsycINFO via OVID and CINAHL via EbscoHost) were searched from database inception until June 2016, using a combination of relevant controlled vocabulary terms and free-text terms related to ‘menopause’ and ‘endometriosis’. Inclusion criteria were: menopausal women with a history of endometriosis and menopausal treatment including HRT or other preparations. Case reports/series, observational studies and clinical trials were included. Narrative review articles, organizational guidelines and conference abstracts were excluded, as were studies that did not report on any form of menopausal management. Articles were assessed for risk of bias and quality using GRADE criteria. OUTCOMES We present a synthesis of the existing case reports of endometriosis recurrence or malignant transformation in women undergoing treatment for menopausal symptoms. We highlight common presenting symptoms, potential risk factors and outcomes amongst the studies. Sparse high-quality evidence was identified, with few observational studies and only two randomized controlled trials. Given this paucity of data, no definitive conclusions can be drawn concerning risk. WIDER IMPLICATIONS Due to the lack of high-quality studies, it remains unclear how to advise women with a history of endometriosis regarding the management of menopausal symptoms. The absolute risk of disease recurrence and malignant transformation cannot be quantified, and the impact of HRT use on these outcomes is not known. Multicentre randomized trials or large observational studies are urgently needed to inform clinicians and patients alike

Success or failure of critical steps in community case management of malaria with rapid diagnostic tests: a systematic review

Background: Malaria still causes high morbidity and mortality around the world, mainly in sub-Saharan Africa. Community case management of malaria (CCMm) by community health workers (CHWs) is one of the strategies to combat the disease by increasing access to malaria treatment. Currently, the World Health Organization recommends to treat only confirmed malaria cases, rather than to give presumptive treatment. Objectives. This systematic review aims to provide a comprehensive overview of the success or failure of critical steps in CCMm with rapid diagnostic tests (RDTs). Methods. The databases of Medline, Embase, the Cochrane Library, the library of the \u27Malaria in Pregnancy\u27 consortium, and Web of Science were used to find studies on CCMm with RDTs in SSA. Studies were selected according to inclusion and exclusion criteria, subsequently risk of bias was assessed and data extracted. Results: 27 articles were included. CHWs were able to correctly perform RDTs, although specificity levels were variable. CHWs showed high adherence to test results, but in some studies a substantial group of RDT negatives received treatment. High risk of bias was found for morbidity and mortality studies, therefore, effects on morbidity and mortality could not be estimated. Uptake and acceptance by the community was high, however negative-tested patients did not always follow up referral advice. Drug or RDT stock-outs and limited information on CHW motivation are bottlenecks for sustainable implementation. RDT-based CCMm was found to be cost effective for the correct treatment of malaria in areas with low to medium malaria prevalence, but study designs were not optimal. Discussion. Trained CHWs can deliver high quality care for malaria using RDTs. However, lower RDT specificity could lead to missed diagnoses of non-malarial causes of fever. Other threats for CCMm are non-adherence to negative test results and low referral completion. Integrated CCM may solve some of these issues. Unfortunately, morbidity and mortality are not adequately investigated. More information is needed about influencing sociocultural aspects, CHW motivation and stock supply. Conclusion: CCMm is generally well executed by CHWs, but there are several barriers for its success. Integrated CCM may overcome some of these barriers