Stratified Meta-analysis Research Articles

The incremental benefit of EUS for the identification of malignancy in indeterminate extrahepatic biliary strictures: A systematic review and meta-analysis.

This systematic review aims to assess the literature to determine the impact of EUS for diagnosing malignancy among indeterminate extrahepatic biliary strictures. A systematic review was performed using MEDLINE, EMBASE, Cochrane, and conference proceedings from inception to July 2016. Pooled results were calculated using random-effects model, and heterogeneity was explored using stratified meta-analysis and meta-regression. The main outcome was the incremental benefit of EUS (IBEUS) for the diagnosis of malignancy among patients who have undergone ERCP with brushing cytology for extrahepatic biliary strictures. Of 3131 identified citations, ten met the inclusion criteria and were included in the final analyses (study periods from 1998 to 2014). Pooled IBEUS estimate with the adjustment for publication bias was 14% (95% confidence interval, 7%–20%). Individual studies demonstrate that the IBEUS is greater for distal biliary strictures or when an extrinsic mass is identified on cross-sectional imaging. EUS increases the identification of malignancy for indeterminate biliary strictures following a nondiagnostic ERCP, particularly those that are distal or related to extrinsic compression.

Effect of pharmaceutical care interventions on glycemic control in patients with diabetes: a systematic review and meta-analysis.

PurposeDiabetes is a chronic lifelong condition, and adherence to medications and self-monitoring of blood glucose are challenging for diabetic patients. The dramatic increase in the prevalence of diabetes is largely due to the incidence of type 2 diabetes in low- and middle-income countries (LMIc) besides high-income countries (HIc). We aimed to evaluate whether pharmacist care (PC) service model in LMIc and HIc could improve clinical outcomes in diabetic patients by performing a meta-analysis.MethodsPubMed, Embase, and ProQuest Dissertations Unlimited Published Literature database were searched to find publications pertaining to pharmacist-led intervention in patients with diabetes. The inclusion criteria were as follows: 1) randomized controlled trials, 2) confirmed diabetic patients (type 1 or type 2), 3) pharmaceutical care intervention by clinical pharmacist or/and multidisciplinary team, and 4) reporting HbA1c at baseline and end of study or the mean change in these values.ResultsA total of 37 articles were included in the meta-analysis. The overall result was significant and in favor of PC intervention on HbA1c change (standard difference in mean values [SDM]: 0.379, 95% CI: 0.208–0.550, P<0.001). The stratified meta-analysis showed that PC was significant in both HIc (n=20; SDM: 0.351, 95% CI: 0.207–0.495) and LMIc (n=15; SDM: 0.426, 95% CI: 0.071–0.780). More than 6 months is needed to obtain adequate effects on clinical diabetes parameters.ConclusionOur study presented that an adequate duration of pharmacist-led pharmaceutical care was effective in improving HbA1c in patients with diabetes in both LMIc and HIc.

Association of conflicts of interest with the results and conclusions of goal-directed hemodynamic therapy research: a systematic review with meta-analysis.

The association between conflicts of interest (COI) and study results or article conclusions in goal-directed hemodynamic therapy (GDHT) research is unknown. Randomized controlled trials comparing GDHT with usual care were identified. COI were classified as industry sponsorship, author conflict, device loaner, none, or not reported. The association between COI and study results (complications and mortality) was assessed using both stratified meta-analysis and mixed effects meta-regression. The association between COI and an article's conclusion (graded as GDHT-favorable, neutral, or unfavorable) was investigated using logistic regression. Of the 82 eligible articles, 43 (53%) had self-reported COI, and 50 (61%) favored GDHT. GDHT significantly reduced complications on the basis of the meta-analysis of studies with any type of COI, studies declaring no COI, industry-sponsored studies, and studies with author conflict but not on studies with a device loaner. However, no significant relationship between COI and the relative risk (GDHT vs. usual care) of developing complications was found on the basis of meta-regression (p = 0.25). No significant effect of GDHT was found on mortality. COI had a significant overall effect (p = 0.016) on the odds of having a GDHT-favorable vs. neutral conclusion based on 81 studies. Eighty-four percent of the industry-sponsored studies had a GDHT-favorable conclusion, while only 27% of the studies with a device loaner had the same conclusion grade. The available evidence does not suggest a close relationship between COI and study results in GDHT research. However, a potential association may exist between COI and an article's conclusion in GDHT research.

Fever worsens outcomes in animal models of ischaemic stroke: A systematic review and meta-analysis.

BackgroundSubfebrile temperatures and fever in the first days after stroke are associated with a greater risk of a poor outcome. If this relation is causal, prevention of hyperthermia may improve outcome. Causality can be tested in animal models. We therefore assessed the effects of hyperthermia on outcomes in animal models of ischaemic stroke and explored under which conditions prevention of hyperthermia could be most effective.MethodsWe performed a systematic review and meta-analysis of data from animal experiments testing the effect of spontaneous or induced hyperthermia on outcome after focal cerebral ischaemia. Our primary outcome measure was infarct size. Normalised mean differences were combined using the random effects model and stratified meta-analysis was used to explore the impact of study characteristics.ResultsWe included 19 publications, reporting on 49 comparisons involving 603 animals. Overall, hyperthermia increased infarct size by 43.4% (95% confidence interval, 29.8–56.9%) and worsened neurobehavioral outcomes by 48.5% (17.2–79.8%). The increase in infarct size was larger with higher temperatures. Hyperthermia was most harmful if present for more than 2 h and when started at the time of artery occlusion rather than later.ConclusionHyperthermia substantially increased infarct size in animal models of ischaemic stroke, suggesting that the relation between fever and poor outcome observed in patients is at least in part causal. These data provide support to trials testing the effect of the prevention of fever with antipyretic drugs in patients with acute stroke.

Prevalence of depression or depressive symptoms among people living with HIV/AIDS in China: a systematic review and meta-analysis

BackgroundThe number of people living with HIV/AIDS (PLHA) in China continues to increase. Depression, a common mental disorder in this population, may confer a higher likelihood of worse health outcomes. An estimate of the prevalence of this disorder among PLHA is required to guide public health policy, but the published results vary widely and lack accuracy in China. The goal of this study was to estimate the pooled prevalence of depression or depressive symptoms among PLHA in China.MethodsA systematic literature search of several databases was conducted from inception to June 2017, focusing on studies reporting on depression or depressive symptoms among PLHA in China. The risk of bias of individual studies was assessed using a modified version of the Newcastle-Ottawa scale. The overall prevalence estimates were pooled using random-effects meta-analysis. Differences according to study-level characteristics were examined using stratified meta-analysis and meta-regression.ResultsSeventy-four observational studies including a total of 20,635 PLHA were included. The pooled prevalence of depression or depressive symptoms was 50.8% (95% CI: 46.0–55.5%) among general PLHA, 43.9% (95% CI: 36.2–51.9%) among HIV-positive men who have sex with men, 85.6% (95% CI: 64.1–95.2%) among HIV-positive former blood/plasma donors, and 51.6% (95% CI: 31.9–70.8%) among other HIV-positive populations. Significant heterogeneity was detected across studies regarding these prevalence estimates. Heterogeneity in the prevalence of depression among the general population of PLHA was partially explained by the geographic location and baseline survey year.ConclusionsBecause of the significant heterogeneity detected across studies regarding these prevalence estimates of depression or depressive symptoms, the results must be interpreted with caution. Our findings suggest that the estimates of depression or depressive symptoms among PLHA in China are considerable, which highlights the need to integrate screening and providing treatment for mental disorders in the treatment package offered to PLHA, which would ultimately lead to better health outcomes in PLHA.

A Stratified Meta-Analysis of the Association between Exposure to Environmental Tobacco Smoke during Childhood and Adulthood and Urothelial Bladder Cancer Risk.

Background: Active smoking is a major risk factor for urothelial bladder cancer (UBC). However, the evidence that exposure to environmental tobacco smoke (ETS) either in childhood or adult life is also associated with UBC risk is ambiguous. With this meta-analysis, we aim to summarise how exposure to ETS is associated with UBC risk. Methods: In total, 11 studies (3 cohort studies, 8 case-control studies) were included in this meta-analysis and summary odds ratios (SORs) for UBC risk were calculated for never smokers who were exposed to ETS during childhood at home, during adulthood at home, or during adulthood in a work environment compared to never smokers who were never exposed to ETS. Sensitivity analyses were conducted to test the robustness of findings. Results: Never smokers exposed to ETS during childhood (SOR = 1.04, 95% confidence interval (CI) = 0.82–1.26), during adulthood at work (SOR = 0.98, 95% CI = 0.78–1.18) or at home (SOR = 0.99, 95% CI = 0.83–1.15) were at a similar risk of UBC compared to never smokers who were never exposed to ETS. Results for males and females were similar. Also, when pooling all estimates during both childhood and adulthood, no effect was observed (SOR = 1.00, 95% CI = 0.89–1.10). Conclusions: Although measurement of exposure to ETS was imprecise, there does not seem to be an association between UBC risk and exposure to ETS during childhood or adulthood. However, the current body of evidence mostly overlooks the duration and intensity of exposure to ETS.

Screening for distress in patients with primary brain tumor using distress thermometer: a systematic review and meta-analysis

BackgroundPatients with primary brain tumors are reported to have an elevated level of distress prevalence, due to the functional sequelae and the unfavorable prognosis, but the estimated prevalence of this disorder varies among studies. The Distress Thermometer (DT) is widely used distress screening tools to identify patients suffering from elevated psychosocial distress. The objective of this meta-analysis is to get a summarized estimate of distress prevalence in adult primary brain tumor patients screened by the DT instrument to identify distress in brain tumor patients.MethodWe searched studies published in PubMed, PsycINFO, and Cochrane library through August 2017 and checked related reviews and meta-analyses for eligible studies. Studies were eligible if they were published in the peer-reviewed literature and evaluated distress level by Distress Thermometer. The prevalence of distress symptoms in patients with the intracranial tumor was estimated by study-level characteristics using stratified meta-analysis. The prevalence of distress level or symptoms during the follow-up examination at different time points was detected by secondary analysis of the longitudinal studies included.ResultsTwelve studies including a total of 2145 brain tumor patients were included in this analysis. Eight used a cross-sectional design and four were longitudinal. The pooled prevalence of distress was 38.2% (95% confidence interval (CI) 28.7%–47.7%) for the overall sample. The pooled prevalence of distress DT ≥4 was 41.1% (642/1686, 95% CI 28.6%–53.5%) and the pooled prevalence of distress by DT ≥6 was 29.7% (137/459, 95% CI 19.5%–39.9%). The distress symptom did not decrease in follow-up studies (Relative Increase Ratio:1.02, 95% CI, (0.78, 1.35)). A huge heterogeneity in different studies was detected, and different screening scales were not compared.ConclusionThe high prevalence of distress becomes an enormous challenge for primary brain tumor patients. Routine screening and evaluation of distress in brain tumor patients may assist medical workers to develop proper interventions, which may lead to better quality of life and oncology management.

A comparison of meta-analytic methods for synthesizing evidence from explanatory and pragmatic trials

BackgroundThe pragmatic–explanatory continuum indicator summary version 2 (PRECIS-2) tool has recently been developed to classify randomized clinical trials (RCTs) as pragmatic or explanatory based on their design characteristics. Given that treatment effects in explanatory trials may be greater than those obtained in pragmatic trials, conventional meta-analytic approaches may not accurately account for the heterogeneity among the studies and may result in biased treatment effect estimates. This study investigates if the incorporation of PRECIS-2 classification of published trials can improve the estimation of overall intervention effects in meta-analysis.MethodsUsing data from 31 published trials of intervention aimed at reducing obesity in children, we evaluated the utility of incorporating PRECIS-2 ratings of published trials into meta-analysis of intervention effects in clinical trials. Specifically, we compared random-effects meta-analysis, stratified meta-analysis, random-effects meta-regression, and mixture random-effects meta-regression methods for estimating overall pooled intervention effects.ResultsOur analyses revealed that mixture meta-regression models that incorporate PRECIS-2 classification as covariate resulted in a larger pooled effect size (ES) estimate (ES = − 1.01, 95%CI = [− 1.52, − 0.43]) than conventional random-effects meta-analysis (ES = − 0.15, 95%CI = [− 0.23, − 0.08]).ConclusionsIn addition to the original intent of PRECIS-2 tool of aiding researchers in their choice of trial design, PRECIS-2 tool is useful for explaining between study variations in systematic review and meta-analysis of published trials. We recommend that researchers adopt mixture meta-regression methods when synthesizing evidence from explanatory and pragmatic trials.

Abstract TP72: Transcranial Direct Current Stimulation (tDCS) for Neuroprotection in Acute Cerebral Ischemia: Meta-analysis of Preclinical Studies and Implications for Human Clinical Trials

Introduction: Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique safe and promising in early human studies of nonacute disorders (depression, OCD, stroke recovery), and also reported to confer direct neuroprotection and vasodilation in animal models of acute cerebral ischemia. Systematic review of preclinical acute cerebral ischemia studies would aid planning for potential initial human clinical trials. Method: A systematic Medline search identified controlled, preclinical studies of tDCS in acute ischemic stroke. Studies were categorized according to stimulation type (hemispheric cathodal; hemispheric anodal; targeted cerebellar fastigial nucleus). Stratified meta-analysis assessed effect of tDCS on final infarct volume. Results: The systematic search identified 17 controlled comparisons of tDCS in preclinical acute cerebral ischemia models, including a total of 256 animals, all with middle cerebral artery occlusion. Hemispheric cathodal stimulation was used in 3 experiments (32 animals), hemispheric anodal stimulation in 1 experiment (8 animals) and fastigial nucleus stimulation in 13 experiments (91 animals). Overall, tDCS reduced final infarct volume by 27.5 cc (95% CI 25.33-29.74, P&lt;0.00001). Heterogeneity of effect by stimulation type was noted (I 2 =90.5%), with the greatest infarct reduction with cathodal - 34.9 cc (95% CI 30.60-39.18, P&lt; 0.00001), followed by targeted fastigial nucleus - 26.8 cc (95% CI 25.33-29.53, P&lt; 0.00001), and anodal - 17.8 cc (95% CI 11.42-24.18, P&lt; 0.00001). In the cathodal studies, stimulation was started 30-45 minutes after ischemia onset. Conclusions: Transcranial direct current stimulation reduces final infarct volume across animal preclinical studies. The greatest neuroprotective effect is observed with hemispheric cathodal stimulation, with treatment initiation in a time frame achievable in human prehospital clinical trials. Human clinical trials of hemispheric cathodal tDCS are warranted.

Effectiveness of fixed-dose combination therapy in hypertension: systematic review and meta-analysis.

IntroductionClinical studies have revealed that fixed-dose combinations (FDCs) of drugs can have a better effect on blood pressure than free-equivalent combinations (FECs). Our objectives were to perform an up-to-date assessment of the effectiveness of FDCs and FECs in antihypertensive therapy, to provide more accurate results by using a stratified meta-analysis.Material and methodsA systematic review was performed in PubMed, Web of Science, and Cochrane databases according to PRISMA guidelines. The outcomes were adherence (compliance), persistence to medication, reduction of blood pressure and the safety profile. We used the Newcastle Ottawa scale or the Delphi list for the assessment of the quality of cohort studies or clinical trials, respectively. Heterogeneity was assessed using the Cochrane Q test and I 2 statistic.ResultsOf 301 abstracts screened, 26 primary studies and 2 other meta-analyses were identified, of which 12 studies were included in the meta-analyses and 3 studies were included in the narrative review. The FDC treatment is associated with a significant improvement in adherence and persistence in comparison with FEC treatment, e.g., the average medicine possession ratio increased with FDC by 13.1% (p < 0.001). For endpoints correlated with higher adherence (e.g., a reduction in blood pressure), a nonsignificant benefit was observed for FDCs. Moreover, it was demonstrated that higher adherence can lead to a lower risk of cardiovascular events.ConclusionsIn comparison with FECs, the FDC treatment is associated with a significant improvement in the cooperation between a doctor and a patient and with increased patients’ adherence to the treatment schedule.

Flat Epithelial Atypia on Core Biopsy and Upgrade to Cancer: a Systematic Review and Meta-Analysis.

No consensus exists on whether flat epithelial atypia (FEA) diagnosed percutaneously should be surgically excised. A systematic review and meta-analysis of the frequency of upgrade to cancer or an atypical ductal hyperplasia (ADH) at surgical excision of FEA was performed. Embase, MEDLINE, Scopus, and Web of Science databases from January 2003 to November 2015 were searched. The inclusion criteria required a manuscript in English with original data on FEA diagnosed percutaneously, data including the presence or absence of other concurrent high-risk lesions, and data including outcome of cancer at surgical excision. Studies were assessed for quality, and two reviewers extracted data. Random-effects meta-analysis was used to pool estimates. The impact of study-level characteristics was assessed by stratified meta-analysis and meta-regression. The inclusion criteria was met by 32 studies. A total of 1966 core needle biopsies showed pure FEA, and 1517 (77%) showed surgical excision. The proportions of patients with upgrade to cancer varied from 0 to 42%, with an overall pooled estimate of 11.1%. Heterogeneity was observed, with the greatest impact based on whether a study included cases of FEA diagnosed before 2003. With restriction of the investigation to 16 higher-quality studies, the cancer upgrade pooled estimate was 7.5% (95% confidence interval [CI], 5.4-10.4%), and the rate of invasive cancer was 3% (95% CI 1.9-4.5%). For upgrade to ADH, data from 22 studies including 937 patients were analyzed. The proportion of patients upgraded to ADH ranged from 0 to 60%, with a pooled estimate of 17.9% overall and 18.6% among high-quality studies. With patient management change potential for approximately 25% of patients, this analysis supports a general recommendation for surgical excision of FEA diagnosed by core biopsy.

Diagnostic ability of intraoperative ultrasound for identifying tumor residual in glioma surgery operation.

Achieving total glioma resection represents a major challenge to neurosurgeons with no distinct margin between tumor and surrounding brain tissue. Many imaging methods are employed in surgery visualization and resection control. We performed this meta-analysis to assess the diagnosis value of intraoperative ultrasound and judged whether ultrasound is a suitable tool in detecting glioma residual. The databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu were systematically searched to find out relevant studies and published up to May 5, 2017. A total of 14 studies involving 542 participants met the selection criteria and bivariate mixed effects models were used for analysis. The parameters and their corresponding 95% confidence interval (CI) were computed on Stata 12.0 software. The pooled sensitivity was 0.75 (95%CI: 0.62–0.84), specificity was 0.88 (95%CI: 0.79–0.94), positive likelihood ratios was 6.27 (95%CI: 3.76–10.47), negative likelihood ratios was 0.29 (95%CI: 0.20–0.42), diagnostic odds ratios was 21.83 (95%CI: 14.20–33.55) and area under the curve of summary receiver operator characteristic was 0.89. Stratified meta-analysis showed sensitivity and area under the curve in low-grade glioma were both higher than high-grade glioma. The Deek's plot showed no significant publication bias (t = −1.03, P = 0.33). Intraoperative ultrasound has high overall diagnostic value to identify glioma remnants, especially in low-grade glioma, which shows a benefit for prognosis and life quality of patients. In general, Intraoperative ultrasound is an effective tool for maximizing the extent of glioma resection.

Association between depression and brain tumor: a systematic review and meta-analysis.

BackgroundPatients with brain tumor are in risk of depression or depressive symptoms, but the estimated prevalence varies between studies. The aim of this study is to get a proper summarized estimate of depression prevalence in brain tumor patients.MethodsLiterature search on Pubmed, PsycINFO, and Cochrane library from January 1981 through October 2016. The prevalence of depression or depressive symptoms in brain tumor patients was estimated by screening scales and analyzed using stratified meta-analysis and subgroup analysis. The prevalence of depression level or symptoms during the follow-up periods was detected by secondary analysis.ResultsAmong the 37 studies included in this meta-analysis, 25 used a cross-sectional design and 12 used longitudinal study. The pooled prevalence was 21.7% (971/4518 individuals, 95 % confidence interval (CI) 18.2%–25.2%) for overall sample. Lower prevalence was detected in studies with sample size ≥100 than <100, lower grade tumor than high grade tumor, studies using clinician-rated depression scales than self-rated or non-depression-specific ones, and in patients from UK, Germany and Italy than USA. After analyzing 6 longitudinal studies, prevalence of depression remained no change in the follow-up periods. No significant differences were observed between study designs and tumor types.ConclusionsThe estimated prevalence of depression or depressive symptoms among brain tumor patients was 21.7%, affected by depression assessment type, sample size, tumor grade and country. Diagnosis and treatment of co-morbid depression in brain tumor patients need to be addressed in future studies for better life quality and oncology management.

Patient education in the management of coronary heart disease.

Patient education in the management of coronary heart disease.

Effect of Pharmacy-Supported Transition-of-Care Interventions on 30-Day Readmissions: A Systematic Review and Meta-analysis.

To describe pharmacy-supported transition-of-care (TOC) interventions and determine their effect on 30-day all-cause readmissions. MEDLINE/PubMed, EMBASE, International Pharmaceutical Abstracts, ABI Inform Complete, PsychINFO, Web of Science, Academic Search Complete, CINHAL, Cochrane library, OIASTER, ProQuest Dissertations & Theses, ClinicalTrials.gov , and relevant websites were searched from January 1, 1995, to December 31, 2015. PICOS+E criteria were utilized. Eligible studies reported pharmacy-supported TOC interventions compared with usual care in adult patients discharged to home within the United States. Studies were required to evaluate postdischarge outcomes (eg, rate of readmissions, hospital utilization). Randomized controlled trials, cohort studies, or controlled before-and-after studies were included. Two reviewers independently extracted data and evaluated study quality. A total of 56 articles were included in the systematic review (n = 61 858), of which 32 reported 30-day all-cause readmissions and were included in the meta-analysis. A taxonomy was developed to categorize targeted patients, intervention types, and pharmacy personnel as sole intervener. The meta-analysis demonstrated about a 32% reduction in the odds of readmission (odds ratio [OR] = 0.68; 95% CI = 0.61 to 0.75) observed for pharmacy-supported TOC interventions compared with usual care. Heterogeneity was identified ( I2 = 55%; P < 0.001). A stratified meta-analysis showed that interventions with patient-centered follow-up reduced 30-day readmissions relative to studies without follow-up (OR = 0.70; CI = 0.63 to 0.78). Pharmacy-supported TOC programs were associated with a significant reduction in the odds of 30-day readmissions.

Lifestyle interventions based on the diabetes prevention program delivered via eHealth: A systematic review and meta-analysis.

The objective was to describe Diabetes Prevention Program (DPP)-based lifestyle interventions delivered via electronic, mobile, and certain types of telehealth (eHealth) and estimate the magnitude of the effect on weight loss. A systematic review was conducted. PubMed and EMBASE were searched for studies published between January 2003 and February 2016 that met inclusion and exclusion criteria. An overall estimate of the effect on mean percentage weight loss across all the interventions was initially conducted. A stratified meta-analysis was also conducted to determine estimates of the effect across the interventions classified according to whether behavioral support by counselors post-baseline was not provided, provided remotely with communication technology, or face-to-face. Twenty-two studies met the inclusion/exclusion criteria, in which 26 interventions were evaluated. Samples were primarily white and college educated. Interventions included Web-based applications, mobile phone applications, text messages, DVDs, interactive voice response telephone calls, telehealth video conferencing, and video on-demand programing. Nine interventions were stand-alone, delivered post-baseline exclusively via eHealth. Seventeen interventions included additional behavioral support provided by counselors post-baseline remotely with communication technology or face-to-face. The estimated overall effect on mean percentage weight loss from baseline to up to 15months of follow-up across all the interventions was -3.98%. The subtotal estimate across the stand-alone eHealth interventions (-3.34%) was less than the estimate across interventions with behavioral support given by a counselor remotely (-4.31%), and the estimate across interventions with behavioral support given by a counselor in-person (-4.65%). There is promising evidence of the efficacy of DPP-based eHealth interventions on weight loss. Further studies are needed particularly in racially and ethnically diverse populations with limited levels of educational attainment. Future research should also focus on ways to optimize behavioral support.

A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer's disease: A metal meta-analysis (AMMA study-I)

BackgroundAvailable studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. AimThe objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients. MethodsAll major databases were searched for eligible studies. We included 12 case–control/observational studies reporting selenium concentrations in AD and controls. Pooled-overall effect size as standardized mean difference (SMD) and pooled r-values were generated using Review Manager 5.3 and MedCalc 15.8 software. ResultsRandom-effects meta-analysis indicated a decrease in circulatory (SMD=−0.44), erythrocellular (SMD=−0.52) and CSF (SMD=−0.14) selenium levels in AD patients compared to controls. Stratified meta-analysis demonstrated that the selenium levels were decreased in both the subgroups with (SMD=−0.55) and without (SMD=−0.37) age matching between AD and controls. Our results also demonstrated a direct association between decreased selenium levels and GPx in AD. ConclusionThis meta-analysis suggests that circulatory selenium concentration is significantly lower in AD patients compared to controls and this decrease in selenium is directly correlated with an important antioxidant enzyme, the GPx, in AD.

The incremental benefit of EUS for identifying unresectable disease among adults with pancreatic adenocarcinoma: A meta-analysis

Background and study aimsIt is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma.Patients and methodsWe searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression.ResultsAmong 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10–33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8–24%) after a CT scan was performed.LimitationsThe majority of the included studies were retrospective.ConclusionsEUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma.

The role of muscle strengthening in exercise therapy for knee osteoarthritis: A systematic review and meta-regression analysis of randomized trials.

To analyze if exercise interventions for patients with knee osteoarthritis (OA) following the American College of Sports Medicine (ACSM) definition of muscle strength training differs from other types of exercise, and to analyze associations between changes in muscle strength, pain, and disability. A systematic search in 5 electronic databases was performed to identify randomized controlled trials comparing exercise interventions with no intervention in knee OA, and reporting changes in muscle strength and in pain or disability assessed as standardized mean differences (SMD) with 95% confidence intervals (95% CI). Interventions were categorized as ACSM interventions or not-ACSM interventions and compared using stratified random effects meta-analysis models. Associations between knee extensor strength gain and changes in pain/disability were assessed using meta-regression analyses. The 45 eligible trials with 4699 participants and 56 comparisons (22 ACSM interventions) were included in this analysis. A statistically significant difference favoring the ACSM interventions with respect to knee extensor strength was found [SMD difference: 0.448 (95% CI: 0.091-0.805)]. No differences were observed regarding effects on pain and disability. The meta-regressions indicated that increases in knee extensor strength of 30-40% would be necessary for a likely concomitant beneficial effect on pain and disability, respectively. Exercise interventions following the ACSM criteria for strength training provide superior outcomes in knee extensor strength but not in pain or disability. An increase of less than 30% in knee extensor strength is not likely to be clinically beneficial in terms of changes in pain and disability (PROSPERO: CRD42014015344).

Hyperbaric oxygen for experimental intracerebral haemorrhage: Systematic review and stratified meta-analysis

ABSTRACTObjective: Hyperbaric oxygen (HBO) is widely used in treating various neurological diseases. However, HBO for treatment of intracerebral haemorrhage (ICH) remains controversial, in either animal or clinical studies. Therefore, we conducted this systematic review and meta-analysis on studies describing the efficacy of HBO in animal models of ICH.Methods: Studies were identified by searching mainstream databases through November 2015. The efficacy of HBO in animal models of ICH was assessed by changes in the brain water content (BWC), neurobehavioural outcome (NO) or both. Subgroup analyses were performed according to different design characteristics.Results: In total 15 studies met our inclusion criteria. HBO can reduce the BWC (−0.982, 95% CI, −1.148 to −0.817; P < 0.01; 57 comparisons), and improve NO (−0.767, 95% CI, −1.376 to −0.159; P < 0.01; eight comparisons). HBO was most effective in reducing BWC when given 72 h after ICH for a 4- to 5-day consecutive treatment at the chamber pressure of 3.0 atmosphere absolute. Efficacy was higher with phenobarbital anaesthesia, the blood infusion model and in rabbits.Conclusion: Although HBO was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality and the limited number of studies conducting clinical trials.