Moderate Between-study Heterogeneity Research Articles

The association between obstructive sleep apnea and metabolic syndrome: a systematic review and meta-analysis.

BackgroundObstructive sleep apnea (OSA) is characterized by repeated episodes of obstruction of the upper airway. Numerous studies have indicated a relationship between OSA and metabolic syndrome (MS), but the results remain debatable. We aimed to perform a systematic review and meta-analysis to evaluate the association between OSA and MS.MethodsWe searched electronic databases (PubMed, EMBASE, and ISO Web of Knowledge) up to September 2014 with English-language restriction. Cross-sectional, case–control, and cohort studies in which the presence of OSA was assessed by objective measurements, the exposure of interest was OSA, and the outcome of interest was the presence (or incidence) of MS were included. The adjusted odds ratios (ORs) (or relative risk) and 95 % confidence intervals (CIs) were extracted and pooled. Sensitivity analyses were conducted, and heterogeneity and publication bias were assessed.ResultsOverall, 15 cross-sectional (2456 patients with OSA and 1705 subjects without OSA), five case–control (1156 OSA patients and 404 controls), and no cohort studies were included. The pooled ORs of MS in individuals with OSA for cross-sectional and case–control studies were 2.87 (95 % CI: 2.41–3.42) and 2.56 (95 % CI: 1.98–3.31), respectively. There was clinically unimportant (I2 = 20 %) and moderate (I2 = 35 %) between-study heterogeneity of the analysis. The pooled crude ORs of MS in individuals with mild and moderate-to-severe OSA was 2.39 (95 % CI: 1.65–3.46) and 3.45 (95 % CI: 2.33–5.12), respectively, and there was substantial heterogeneity in the meta-analyses (I2 = 53 % and I2 = 63 %, respectively). However, no evidence of publication bias was detected.ConclusionsOSA is shown to be associated with MS, although causality between these two factors has not been demonstrated yet. Future cohort and randomized controlled studies are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0102-3) contains supplementary material, which is available to authorized users.

Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis

Background and objectiveWhile paracetamol exposure in pregnancy and early infancy has been associated with asthma, it remains unclear whether this is confounded by respiratory tract infections, which have been suggested...

Does drug-eluting bead transcatheter arterial chemoembolization improve the management of patients with hepatocellular carcinoma? A meta-analysis.

BackgroundDrug eluting beads (DEB) are relatively new embolic agents that allow sustained release of chemotherapeutic agents in a localized fashion to the tumor. This technique is associated with reduced systemic side effects relative to systemic chemotherapy and an increase in the dose of antineoplastic agent delivered to the lesion. The meta-analysis was undertaken to assess the effectiveness of DEB-transcatheter arterial chemoembolization (TACE) in the management of hepatocellular cancer.MethodsWe searched the Web of Science, PubMed, EBSCO, EMBASE, the Wiley Library and Google Scholar for studies on DEB-TACE in the management of hepatocellular cancer from 1979 to April 2013. The risk of bias was assessed using RevMan 5·1. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. Disease control, complications and severe complications were recorded.ResultsFive studies met the selection criteria, three RCTs and two case-control studies, published from 2010 to 2012, included 217 patients in the DEB-TACE group and 237 in the conventional-TACE group. There was no significance over disease control (OR 2.27, 95% CI 0.78–6.63) with moderate between-study heterogeneity (χ2 = 6.83, degrees of freedom [df] = 3; p<0.08; I2 = 56%). Complications in both groups were assessed and no significant difference was observed (χ2 = 6.34, degrees of freedom [df] = 4; p<0.18; I2 = 37%). Severe complications were also assessed and no significant difference was observed (χ2 = 6.47, degrees of freedom [df] = 4; p<0.17; I2 = 38%). No publication bias relating to the above outcomes was detected by funnel plot. DEB-TACE benefited disease control without an increase in complications and severe complications.

Fetal death and preterm birth associated with maternal influenza vaccination: systematic review.

Before 2012, few studies had addressed pregnancy outcomes following maternal influenza vaccination; however, the number of publications on this topic has increased recently. To review comparative studies evaluating fetal death or preterm birth associated with influenza vaccination during pregnancy. We searched bibliographic databases from inception to April 2014. Experimental or observational studies assessing the relationship between influenza vaccination during pregnancy and fetal death or preterm birth. Two reviewers independently abstracted data from studies meeting the inclusion criteria. We included one randomised clinical trial and 26 observational studies. Meta-analyses were not considered appropriate because of high clinical and statistical heterogeneity. Three studies of fetal death at any gestational age reported adjusted effect estimates in the range 0.56-0.79, and four of five studies of fetal death at <20 weeks reported adjusted estimates between 0.89 and 1.23, all with confidence intervals including 1.0. Adjusted effect estimates for four of five studies of fetal death at ≥20 weeks ranged from 0.44 to 0.77 (two with confidence intervals not crossing 1.0), whereas a fifth reported a non-significant effect in the opposite direction. Among 19 studies of preterm birth, there was no strong evidence suggesting any increased risk, and meta-regression did not explain the moderate between-study heterogeneity (I(2) = 57%). Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness.

Meta-Analysis of Sequencing Studies With Heterogeneous Genetic Associations

Recent advances in sequencing technologies have made it possible to explore the influence of rare variants on complex diseases and traits. Meta-analysis is essential to this exploration because large sample sizes are required to detect rare variants. Several methods are available to conduct meta-analysis for rare variants under fixed-effects models, which assume that the genetic effects are the same across all studies. In practice, genetic associations are likely to be heterogeneous among studies because of differences in population composition, environmental factors, phenotype and genotype measurements, or analysis method. We propose random-effects models which allow the genetic effects to vary among studies and develop the corresponding meta-analysis methods for gene-level association tests. Our methods take score statistics, rather than individual participant data, as input and thus can accommodate any study designs and any phenotypes. We produce the random-effects versions of all commonly used gene-level association tests, including burden, variable threshold, and variance-component tests. We demonstrate through extensive simulation studies that our random-effects tests are substantially more powerful than the fixed-effects tests in the presence of moderate and high between-study heterogeneity and achieve similar power to the latter when the heterogeneity is low. The usefulness of the proposed methods is further illustrated with data from National Heart, Lung, and Blood Institute Exome Sequencing Project (NHLBI ESP). The relevant software is freely available.

Alcohol Consumption Over Time and Risk of Death: A Systematic Review and Meta-Analysis

The results from the few cohort studies that have measured usual alcohol consumption over time have not been summarized. We therefore conducted a systematic review and meta-analysis to quantify mortality risk. Pertinent studies were identified by searching the Medline, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Scopus databases through August 2012 using broad search criteria. Studies reporting relative mortality risks for quantitatively defined categories of alcohol consumption over time were eligible. Nine cohort studies published during 1991-2010 (comprising 62,950 participants and 10,490 deaths) met the inclusion criteria. For men, there was weak evidence of lower mortality risk with low levels of alcohol intake over time but higher mortality risk for those with intakes over 40 g/day compared with abstainers using a random-effects model (P for nonlinearity = 0.02). The pooled relative risks were 0.90 (95% confidence interval: 0.81, 0.99) for 1-29 g/day, 1.19 (95% confidence interval: 0.89, 1.58) for 30-59 g/day, and 1.52 (95% confidence interval: 0.78, 2.98) for 60 or more g/day compared with abstention. There was moderate between-study heterogeneity but no evidence of publication bias. Studies including women were extremely scarce. Our findings include a curvilinear association between drinking over time and mortality risk for men overall and widespread disparity in methods used to capture exposure and report results.

Adiponectin and Risk of Stroke

The favorable cardiovascular effects attributed to adiponectin may lower risk of stroke. We investigated this in a prospective study and meta-analysis. A case-cohort study nested within the Potsdam cohort of the European Prospective Investigation into Cancer was performed, with 170 incident cases of ischemic stroke and a randomly selected subcohort of 2155 participants without major cardiovascular disease at baseline. A random-effects dose-response meta-analysis was performed on prospective studies reporting on adiponectin and incident stroke in healthy populations up to April 2013, identified through MEDLINE and EMBASE. In European Prospective Investigation into Cancer-Potsdam, after adjustment for cardiovascular risk factors, the hazard ratio of ischemic stroke per 5-µg/mL higher total-adiponectin was 1.10 (95% confidence interval, 0.89-1.37). Participants with higher total-adiponectin had higher high-density lipoprotein-cholesterol and lower high-sensitivity C-reactive protein and triglyceride levels, and had less often diabetes mellitus. Additional adjustment for these putative mediators yielded a hazard ratio of 1.31 (95% confidence interval, 1.04-1.64). Nine studies (19,259 participants, 2960 cases), including European Prospective Investigation into Cancer-Potsdam, were meta-analyzed. Pooling relative risks adjusted for cardiovascular risk factors not including putative mediators indicated moderate between-study heterogeneity (I2=52.2%). This was explained by the smallest study, and the pooled relative risk (95% confidence interval) before and after its exclusion was 1.03 (0.98-1.08) and 0.99 (0.96-1.01) per 5 µg/mL, respectively. The pooled relative risk (95% confidence interval) additionally adjusted for potential mediators was 1.08 (1.01-1.15) and 1.05 (1.00-1.11) before and after excluding the same study, respectively. Adiponectin is not associated with risk of stroke. If anything, adiponectin relates directly to stroke risk after controlling for risk factors that favorably correlate with adiponectin.

Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants

Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight (LBW) infants. Preterm infants are deficient in immunoglobulin G (IgG); therefore, administration of intravenous immunoglobulin (IVIG) may have the potential of preventing or altering the course of nosocomial infections. To use systematic review/meta-analytical techniques to determine whether IVIG administration (compared with placebo or no intervention) to preterm (< 37 weeks' postmenstrual age (PMA) at birth) or LBW (< 2500 g birth weight) infants or both is effective/safe in preventing nosocomial infection. For this update, MEDLINE, EMBASE, CINAHL, The Cochrane Library, Controlled Trials, ClinicalTrials.gov and PAS Abstracts2view were searched in May 2013. We selected randomised controlled trials (RCTs) in which a group of participants to whom IVIG was given was compared with a control group that received a placebo or no intervention for preterm (< 37 weeks' gestational age) and/or LBW (< 2500 g) infants. Studies that were primarily designed to assess the effect of IVIG on humoral immune markers were excluded, as were studies in which the follow-up period was one week or less. Data collection and analysis was performed in accordance with the methods of the Cochrane Neonatal Review Group. Nineteen studies enrolling approximately 5000 preterm and/or LBW infants met inclusion criteria. No new trials were identified in May 2013.When all studies were combined, a significant reduction in sepsis was noted (typical risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74 to 0.98; typical risk difference (RD) -0.03, 95% CI 0.00 to -0.05; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 20 to infinity), and moderate between-study heterogeneity was reported (I(2) 54% for RR, 55% for RD). A significant reduction of one or more episodes was found for any serious infection when all studies were combined (typical RR 0.82, 95% CI 0.74 to 0.92; typical RD -0.04, 95% CI -0.02 to -0.06; NNTB 25, 95% CI 17 to 50), and moderate between-study heterogeneity was observed (I(2) 50% for RR, 62% for RD). No statistically significant differences in mortality from all causes were noted (typical RR 0.89, 95% CI 0.75 to 1.05; typical RD -0.01, 95% CI -0.03 to 0.01), and no heterogeneity for RR (I(2) = 21%) or low heterogeneity for RD was documented (I(2) = 28%). No statistically significant difference was seen in mortality from infection; in incidence of necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) or intraventricular haemorrhage (IVH) or in length of hospital stay. No major adverse effects of IVIG were reported in any of these studies. IVIG administration results in a 3% reduction in sepsis and a 4% reduction in one or more episodes of any serious infection but is not associated with reductions in other clinically important outcomes, including mortality. Prophylactic use of IVIG is not associated with any short-term serious side effects.The decision to use prophylactic IVIG will depend on the costs and the values assigned to the clinical outcomes. There is no justification for conducting additional RCTs to test the efficacy of previously studied IVIG preparations in reducing nosocomial infections in preterm and/or LBW infants.

Miscarriage and future maternal cardiovascular disease: a systematic review and meta-analysis

ContextThe 2011 American Heart Association guidelines identified pregnancy complications as a risk factor for cardiovascular disease in women. However, miscarriage was not mentioned within the guidelines, and there is no...

GSTT1andGSTM1polymorphisms and myelodysplastic syndrome risk: a systematic review and meta‐analysis

Glutathione-S-transferace polymorphisms may make hematopoietic lineage cells susceptible to genotoxicity following exposure to heavy metals or benzene. We conducted a systematic review and meta-analysis to define the effect of GSTM1 and GSTT1 null polymorphisms on MDS risk. We searched the PubMed and SCOPUS databases to identify peer-reviewed published case-control studies investigating the association between GSTT1 and/or GSTM1 null genotypes and development of MDS. Between-study heterogeneity was assessed using Cochran's Q statistic and the I(2) statistic. Odds ratios from individual studies were pooled using fixed and random effects models. Thirteen studies were considered eligible for the GSTT1 meta-analysis (1471 cases, 1907 controls) and 10 were considered eligible for the GSTM1 meta-analysis (1161 cases, 1668 controls). For the GSTT1 polymorphism, there was moderate between study heterogeneity (p(Q) = 0.01; I(2) = 52.3%) and the null genotype was significantly associated with increased risk of MDS development, random effects OR = 1.43 (95% CI, 1.09-1.89); p = 0.01. For the GSTM1 polymorphisms there was moderate between-study heterogeneity (p = 0.07; I(2) = 43.1%) and the random effects OR = 1.02 (95% CI, 0.82-1.28) was non-significant (p = 0.85). The GSTT1 null genotype is a significant risk factor for MDS development. Gene-environment interactions need to be further explored.

HLA–B51/B5 and the risk of Behçet's disease: A systematic review and meta‐analysis of case–control genetic association studies

To quantify by meta-analysis the genetic effect of the HLA-B5 or HLA-B51 (HLA-B51/B5) allele on the risk of developing Behçet's disease (BD) and to look for potential effect modifiers. Relevant studies were identified using the PubMed Medline database and manual searches of the literature. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by using the random-effects model. Subgroup meta-analyses and meta-regression analyses were undertaken to investigate the effects of selected study-level parameters on the pooled OR. Heterogeneity was assessed using the I2 statistic. Pooled results were used to calculate population-attributable risks (PAR) for BD in relationship to HLA-B51/B5. A total of 4,800 patients with BD and 16,289 controls from 78 independent studies (published 1975-2007) were selected. The pooled OR of HLA-B51/B5 allele carriers to develop BD compared with noncarriers was 5.78 (95% CI 5.00-6.67), with moderate between-study heterogeneity (I2 = 61%). The subgroup analyses stratifying studies by geographic locations (Eastern Asia, Middle East/North Africa, Southern Europe, Northern/Eastern Europe) yielded consistent OR ranges (5.31-7.20), with I2 ranges of 52-70%. Univariate random-effects meta-regression indicated the percentage of male BD cases (P = 0.008) as a source of heterogeneity. The PAR within the various geographic areas were estimated at 32-52%. The strength of the association between BD and HLA-B51/B5, and its consistency across populations of various ethnicities, lends further support to this allele being a primary and causal risk determinant for BD. Variations according to sex support an interaction of this allele with BD characteristics.

Lifestyle factors and colorectal cancer risk (2): a systematic review and meta‐analysis of associations with leisure‐time physical activity

Increased physical activity may decrease the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we performed a systematic review and meta-analysis of prospective observational studies to quantify gender-specific risk associated with increased leisure-time physical activity (LT-PA). We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. We used random-effects meta-analyses to estimate summary risk ratios (RR) and 95% confidence intervals (95% CI) for uppermost vs lowermost categories of physical activity. To investigate dose-response, we explored risks ratios as a function of cumulative percentiles of physical activity distribution. Fifteen datasets from 14 articles, including 7873 incident cases, were identified. For colon cancer, there were inverse associations with LT-PA for men (RR: 0.80; 95% CI: 0.67-0.96) and women (0.86; 0.76-0.98). LT-PA did not influence risk of rectal cancer. The dose-response analysis was consistent with linear pattern reductions in risk of colon cancer in both genders. There was evidence of moderate between-study heterogeneity but summary estimates were broadly consistent across potential confounding factors. Increased LT-PA is associated with a modest reduction in colon but not rectal cancer risk; a risk reduction, which previously may have been overstated. LT-PA only interventions in public health cancer prevention strategies are unlikely to impact substantially on colorectal cancer incidences.