Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism : a meta-analysis stratified by treatment

Peer reviewed

Risk of Recurrent Stillbirth : Systematic Review and Meta-Analysis

Peer reviewed

Discrete choice experiment response rates : A meta-analysis

Funding: Verity Watson acknowledges financial support from the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Acknowledgements: We thank Marjon van der Pol, Mandy Ryan and Rainer Schulz for helpful comments and suggestions throughout the project. We also thank Karen Gerard and Tim Bolt for comparing the results of our systematic review with a similar systematic review they are conducting at the same time. We would like to thank Douglas Olley for excellent research assistance.

Childhood obesity in relation to poor asthma control and exacerbations : A meta-analysis

Peer reviewed

Prospective risk of stillbirth and neonatal complications in twin pregnancies : systematic review and meta-analysis

Peer reviewed

Risk of Recurrent Stillbirth : Systematic Review and Meta-Analysis

Peer reviewed

The impact of statin use on fetal development:a meta-analysis

INTRODUCTION: Statin use inadvertently during pregnancy and proposed use of statins for the treatment of preeclampsia, led us to question the evidence behind their current contraindicated status. Several studies have evaluated the relationship between statin use in pregnancy with fetal outcome but their results have not been quantitatively assessed by meta-analysis. Our objective was to undertake a systematic review of all published clinical evidence to assess the effects of statin use in pregnancy on subsequent fetal wellbeing. METHODS: A comprehensive search strategy was performed of all electronic databases and the Merck reporting database for studies published from 1966 to 2014. Two reviewers independently screened citations and undertook study quality assessment and data extraction. We obtained summary estimates of adverse fetal events that were classified as potentially fatal, clinically significant morbidity or minor adverse event. We identified 602 titles and reviewed 30 articles for inclusion and exclusion criteria. Meta-analysis was performed on seven studies (3 cohort, 3 case-series and 1 case-control). RESULTS: Of the 922 cases of statin exposure in pregnancy, 27 exposures were associated with lethal or clinically significant fetal morbidity and 10 with minor adverse events. Statin exposure was limited to the first trimester in all but two cases. The pooled rate of lethal or clinically significant fetal abnormalities in pregnant women exposed to statins was 0.01 (95% CI 0.00-0.04), less than the European rate of 0.026 (95% CI 2.54- 2.57)EUROCAT. The rate of fetal abnormality for simvastatin was 0.03 (95% CI 0.00-0.08), atorvostatin 0.11 (95% CI 0.00-0.52), pravastatin 0.01 (95% CI 0.00-0.2) and lovastatin use 0.04 (95% CI 0.00-0.28). Systems based anomalies were also calculated, congenital heart disease was 0.8 (95% CI 0.02-0.12) compared with the background rate of 0.79 (95% CI 0.78- 0.80). CONCLUSIONS: The published data suggests that statins may not be teratogenic when given inadvertently during pregnancy and prospective studies such as The StAmP Trial may provide more data

Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials

Objective: To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. Design: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. Data sources: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. Review methods: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. Results: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9/%year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. Conclusions: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess.

Safety and Use of Anticoagulation After Aortic Valve Replacement With Bioprostheses: A Meta-Analysis.

BACKGROUND: The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding. METHODS AND RESULTS: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79). CONCLUSIONS: Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.

Evaluating the spatial transferability and temporal repeatability of remote-sensing-based lake water quality retrieval algorithms at the European scale: a meta-analysis approach

Many studies have shown the considerable potential for the application of remote-sensing-based methods for deriving estimates of lake water quality. However, the reliable application of these methods across time and space is complicated by the diversity of lake types, sensor configuration, and the multitude of different algorithms proposed. This study tested one operational and 46 empirical algorithms sourced from the peer-reviewed literature that have individually shown potential for estimating lake water quality properties in the form of chlorophyll-a (algal biomass) and Secchi disc depth (SDD) (water transparency) in independent studies. Nearly half (19) of the algorithms were unsuitable for use with the remote-sensing data available for this study. The remaining 28 were assessed using the Terra/Aqua satellite archive to identify the best performing algorithms in terms of accuracy and transferability within the period 2001–2004 in four test lakes, namely Vänern, Vättern, Geneva, and Balaton. These lakes represent the broad continuum of large European lake types, varying in terms of eco-region (latitude/longitude and altitude), morphology, mixing regime, and trophic status. All algorithms were tested for each lake separately and combined to assess the degree of their applicability in ecologically different sites. None of the algorithms assessed in this study exhibited promise when all four lakes were combined into a single data set and most algorithms performed poorly even for specific lake types. A chlorophyll-a retrieval algorithm originally developed for eutrophic lakes showed the most promising results (R2 = 0.59) in oligotrophic lakes. Two SDD retrieval algorithms, one originally developed for turbid lakes and the other for lakes with various characteristics, exhibited promising results in relatively less turbid lakes (R2 = 0.62 and 0.76, respectively). The results presented here highlight the complexity associated with remotely sensed lake water quality estimates and the high degree of uncertainty due to various limitations, including the lake water optical properties and the choice of methods.

Epidemiology of diabetes and complications among adults in the Republic of Ireland 1998-2015: a systematic review and meta-analysis

Background: Accurate estimates of the burden of diabetes are essential for future planning and evaluation of services. In Ireland, there is no diabetes register and prevalence estimates vary. The aim of this review was to systematically identify and review studies reporting the prevalence of diabetes and complications among adults in Ireland between 1998 and 2015 and to examine trends in prevalence over time. Methods: A systematic literature search was carried out using PubMed and Embase. Diabetes prevalence estimates were pooled by random-effects meta-analysis. Poisson regression was carried out using data from four nationally representative studies to calculate prevalence rates of doctor diagnosed diabetes between 1998 and 2015 and was also used to assess whether the rate of doctor diagnosed diabetes changed over time. Results: Fifteen studies (eight diabetes prevalence and seven complication prevalence) were eligible for inclusion. In adults aged 18 years and over, the national prevalence of doctor diagnosed diabetes significantly increased from 2.2 % in 1998 to 5.2 % in 2015 (p trend ≤ 0.001). The prevalence of diabetes complications ranged widely depending on study population and methodology used (6.5–25.2 % retinopathy; 3.2–32.0 % neuropathy; 2.5-5.2 % nephropathy). Conclusions: Between 1998 and 2015, there was a significant increase in the prevalence of doctor diagnosed diabetes among adults in Ireland. Trends in microvascular and macrovascular complications prevalence could not be examined due to heterogeneity between studies and the limited availability of data. Reliable baseline data are needed to monitor improvements in care over time at a national level. A comprehensive national diabetes register is urgently needed in Ireland.

Inventory of SINOPS project data sets

During the SINOPS project, an optimal state of the art simulation of the marine silicon cycle is attempted employing a biogeochemical ocean general circulation model (BOGCM) through three particular time steps relevant for global (paleo-) climate. In order to tune the model optimally, results of the simulations are compared to a comprehensive data set of 'real' observations. SINOPS' scientific data management ensures that data structure becomes homogeneous throughout the project. Practical work routine comprises systematic progress from data acquisition, through preparation, processing, quality check and archiving, up to the presentation of data to the scientific community. Meta-information and analytical data are mapped by an n-dimensional catalogue in order to itemize the analytical value and to serve as an unambiguous identifier. In practice, data management is carried out by means of the online-accessible information system PANGAEA, which offers a tool set comprising a data warehouse, Graphical Information System (GIS), 2-D plot, cross-section plot, etc. and whose multidimensional data model promotes scientific data mining. Besides scientific and technical aspects, this alliance between scientific project team and data management crew serves to integrate the participants and allows them to gain mutual respect and appreciation.

Team Building Interventions in Sport: A Meta-Analysis

A meta-analysis of team building interventions in sport was completed. Seventeen studies containing 180 effect sizes were retrieved. The overall effect (Hedges g) was .427. Analyses of possible moderator variables showed the largest effect sizes were in interventions where: (a) non-experimental designs were used (g=.474); (b) the data were unpublished (g=.539); (c) goal setting only was used (g=.714); (d) the coach/manager directed the delivery (g=.446); and (e) the teams were at the university level (g=.482). Finally, team building had the greatest influence on cognitions (g=.799

Effects of introspection on meta and structural attitude bases

Introspection is the process by which individuals question their attitudes; either questioning why they hold their attitudes (Why introspection), or how they feel about a particular attitude object (How introspection). Previous research has suggested that Why-introspection induces attitude change, and that Why and How introspection influence attitude-behaviour consistency,persuasion, and other effects. Generally, psychologists have assumed that affective and cognitive attitude bases are the mechanism by which introspection leads to these effects. Leading perspectives originating from these findings suggest that either Why introspection changes the content of cognitive attitude bases (the skewness hypothesis), or increases the salience of cognitive attitude bases (the dominance hypothesis); whereas How introspection may increase the salience of affective attitude bases (another part of the dominance hypothesis). However, direct evidence for these mechanisms is lacking, and the distinction between structural and meta bases has not been considered. Two studies investigated this gap in the existing literature. Both studies measured undergraduate students’ attitudes and attitude bases (both structural and meta, affective and cognitive) before and after engaging in an introspection manipulation (Why introspection / How introspection / control), and after reading a (affective / cognitive) persuasive passage about the attitude object. No evidence was found supporting either the skewness or dominance hypotheses. Furthermore, previous introspection effects were not replicated in the present data. Possible reasons for these null findings are proposed, and several unexpected effects are examined.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis

Background: Esophageal adenocarcinoma (EA) is one of the fastest rising cancers in western countries. Barrett’s Esophagus (BE) is the premalignant precursor of EA. However, only a subset of BE patients develop EA, which complicates the clinical management in the absence of valid predictors. Genetic risk factors for BE and EA are incompletely understood. This study aimed to identify novel genetic risk factors for BE and EA.Methods: Within an international consortium of groups involved in the genetics of BE/EA, we performed the first meta-analysis of all genome-wide association studies (GWAS) available, involving 6,167 BE patients, 4,112 EA patients, and 17,159 representative controls, all of European ancestry, genotyped on Illumina high-density SNP-arrays, collected from four separate studies within North America, Europe, and Australia. Meta-analysis was conducted using the fixed-effects inverse variance-weighting approach. We used the standard genome-wide significant threshold of 5×10-8 for this study. We also conducted an association analysis following reweighting of loci using an approach that investigates annotation enrichment among the genome-wide significant loci. The entire GWAS-data set was also analyzed using bioinformatics approaches including functional annotation databases as well as gene-based and pathway-based methods in order to identify pathophysiologically relevant cellular pathways.Findings: We identified eight new associated risk loci for BE and EA, within or near the CFTR (rs17451754, P=4·8×10-10), MSRA (rs17749155, P=5·2×10-10), BLK (rs10108511, P=2·1×10-9), KHDRBS2 (rs62423175, P=3·0×10-9), TPPP/CEP72 (rs9918259, P=3·2×10-9), TMOD1 (rs7852462, P=1·5×10-8), SATB2 (rs139606545, P=2·0×10-8), and HTR3C/ABCC5 genes (rs9823696, P=1·6×10-8). A further novel risk locus at LPA (rs12207195, posteriori probability=0·925) was identified after re-weighting using significantly enriched annotations. This study thereby doubled the number of known risk loci. The strongest disease pathways identified (P<10-6) belong to muscle cell differentiation and to mesenchyme development/differentiation, which fit with current pathophysiological BE/EA concepts. To our knowledge, this study identified for the first time an EA-specific association (rs9823696, P=1·6×10-8) near HTR3C/ABCC5 which is independent of BE development (P=0·45).Interpretation: The identified disease loci and pathways reveal new insights into the etiology of BE and EA. Furthermore, the EA-specific association at HTR3C/ABCC5 may constitute a novel genetic marker for the prediction of transition from BE to EA. Mutations in CFTR, one of the new risk loci identified in this study, cause cystic fibrosis (CF), the most common recessive disorder in Europeans. Gastroesophageal reflux (GER) belongs to the phenotypic CF-spectrum and represents the main risk factor for BE/EA. Thus, the CFTR locus may trigger a common GER-mediated pathophysiology.