Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis.

AIMS The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). METHODS AND RESULTS Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. CONCLUSION We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients.

A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.

Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta-analysis of randomized trials

BACKGROUND & AIMS Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB on HCC by performing a systematic review with meta-analyses of randomized trials. METHODS Electronic and manual searches were combined. Authors were contacted for unpublished data. Included trials assessed NSBB for patients with cirrhosis; the control group could receive any other intervention than NSBB. Fixed and random effects meta-analyses were performed with I(2) as a measure of heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate heterogeneity, bias and the robustness of the results after adjusting for multiple testing. RESULTS Twenty-three randomized trials on 2618 patients with cirrhosis were included, of which 12 reported HCC incidence and 23 reported HCC mortality. The mean duration of follow-up was 26 months (range 8-82). In total, 47 of 694 patients randomized to NSBB developed HCC vs 65 of 697 controls (risk difference -0.026; 95% CI-0.052 to -0.001; number needed to treat 38 patients). There was no heterogeneity (I(2) = 7%) or evidence of small study effects (Eggers P = 0.402). The result was not confirmed in sequential analysis, which suggested that 3719 patients were needed to achieve the required information size. NSBB did not reduce HCC-related mortality (RD -0.011; 95% CI -0.040 to 0.017). CONCLUSIONS Non-selective beta-blockers may prevent HCC in patients with cirrhosis.

Ascertainment, meta-analysis and reporting of adverse reactions in clinical trials of antibiotics

The ascertainment and analysis of adverse reactions to investigational agents presents a significant challenge because of the infrequency of these events, their subjective nature and the low priority of safety evaluations in many clinical trials. A one year review of antibiotic trials published in medical journals demonstrates the lack of standards in identifying and reporting these potentially fatal conditions. This review also illustrates the low probability of observing and detecting rare events in typical clinical trials which include fewer than 300 subjects. Uniform standards for ascertainment and reporting are suggested which include operational definitions of study subjects. Meta-analysis of selected antibiotic trials using multivariate regression analysis indicates that meaningful conclusions may be drawn from data from multiple studies which are pooled in a scientifically rigorous manner. ^

Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: A meta-analysis of individual patient data

Background & Aims: Steatosis is a frequent histologic finding in chronic hepatitis C (CHC), but it is unclear whether steatosis is an independent predictor for liver fibrosis. We evaluated the association between steatosis and fibrosis and their common correlates in persons with CHC and in subgroup analyses according to hepatitis C virus (HCV) genotype and body mass index. Methods: We conducted a meta-analysis on individual data from 3068 patients with histologically confirmed CHC recruited from 10 clinical centers in Italy, Switzerland, France, Australia, and the United States. Results: Steatosis was present in 1561 patients (50.9%) and fibrosis in 2688 (87.6%). HCV genotype was 1 in :1694 cases (55.2%), 2 in 563 (18.4%), 3 in 669 (21.8%), and 4 in :142 (4.6%). By stepwise logistic regression, steatosis was associated independently with genotype 3, the presence of fibrosis, diabetes, hepatic inflammation, ongoing alcohol abuse, higher body mass index, and older age. Fibrosis was associated independently with inflammatory activity, steatosis, male sex, and older age, whereas HCV genotype 2 was associated with reduced fibrosis. In the subgroup analyses, the association between steatosis and fibrosis invariably was dependent on a simultaneous association between steatosis and hepatic inflammation. Conclusions: In this large and geographically different group of CHC patients, steatosis is confirmed as significantly and independently associated with fibrosis in CHC. Hepatic inflammation may mediate fibrogenesis in patients with liver steatosis. Control of metabolic factors (such as overweight, via lifestyle adjustments) appears important in the management of CHC.

Multinationality-performance relationship:a meta-analysis

- We conduct a Meta-analysis of 54 papers that study the relationship between multinationality and firm performance. The aim is to understand if any systematic relationships exist between the characteristics of each study and the reported results of linear and curvilinear regressions to examine the multinationality-performance relationship. - Our main finding, robust to different specifications and to different weights for each observation, is that when analysis is based on non-US data, the reported return to multinationality is higher. However, this relationship for non-US firms is usually U-shaped rather than inverted U-shaped. This indicates that US firms face lower returns to internationalization than other firms but are less likely to incur losses in the early stages of internationalization. - The findings also highlight the differences that are reported when comparing regression and non-regression based techniques. Our results suggest that in this area regression based analysis is more reliable than say ANOVA or other related approaches. - Other characteristics that influence the estimated rate of return and its shape across different studies are: the measure of multinationality used; size distribution of the sample; and the use of market-based indicators to measure firm performance. Finally, we find no evidence of publication bias.

Economic efficiency of smallholder maize producers in Western Kenya:a DEA meta-frontier analysis

Maize is the main staple food for most Kenyan households, and it predominates where smallholder, as well as large-scale, farming takes place. In the sugarcane growing areas of Western Kenya, there is pressure on farmers on whether to grow food crops, or grow sugarcane, which is the main cash crop. Further, with small and diminishing land sizes, the question of productivity and efficiency, both for cash and food crops is of great importance. This paper, therefore, uses a two-step estimation technique (DEA meta-frontier and Tobit Regression) to highlight the inefficiencies in maize cultivation, and their causes in Western Kenya.

Pronounced reduction of postprandial glucagon by lixisenatide:a meta-analysis of randomized clinical trials

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. Methods: Six randomized, placebo-controlled studies of lixisenatide 20μg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. Results: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9mmol/l, p<0.001) and glucose excursion (LS mean difference vs. placebo: -4.5mmol/l, p<0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0ng/l, p<0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p<0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. Conclusions: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion. © 2014 John Wiley and Sons Ltd.

Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1- 18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention.

Emotional intelligence and leadership in organizations: A meta-analytic test of process mechanisms

The present study—employing psychometric meta-analysis of 92 independent studies with sample sizes ranging from 26 to 322 leaders—examined the relationship between EI and leadership effectiveness. Overall, the results supported a linkage between leader EI and effectiveness that was moderate in nature (ρ = .25). In addition, the positive manifold of the effect sizes presented in this study, ranging from .10 to .44, indicate that emotional intelligence has meaningful relations with myriad leadership outcomes including effectiveness, transformational leadership, LMX, follower job satisfaction, and others. Furthermore, this paper examined potential process mechanisms that may account for the EI-leadership effectiveness relationship and showed that both transformational leadership and LMX partially mediate this relationship. However, while the predictive validities of EI were moderate in nature, path analysis and hierarchical regression suggests that EI contributes less than or equal to 1% of explained variance in leadership effectiveness once personality and intelligence are accounted for. ^

Emotional Intelligence and Leadership in Organization: A Meta-analytic Test of Process Mechanisms

The present study – employing psychometric meta-analysis of 92 independent studies with sample sizes ranging from 26 to 322 leaders – examined the relationship between EI and leadership effectiveness. Overall, the results supported a linkage between leader EI and effectiveness that was moderate in nature (ρ = .25). In addition, the positive manifold of the effect sizes presented in this study, ranging from .10 to .44, indicate that emotional intelligence has meaningful relations with myriad leadership outcomes including effectiveness, transformational leadership, LMX, follower job satisfaction, and others. Furthermore, this paper examined potential process mechanisms that may account for the EI-leadership effectiveness relationship and showed that both transformational leadership and LMX partially mediate this relationship. However, while the predictive validities of EI were moderate in nature, path analysis and hierarchical regression suggests that EI contributes less than or equal to 1% of explained variance in leadership effectiveness once personality and intelligence are accounted for.

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.

A Validation Study of Vascular Cognitive Impairment Genetics Meta-Analysis Findings in an Independent Collaborative Cohort

Vascular cognitive impairment (VCI), including its severe form, vascular dementia (VaD), is the second most common form of dementia. The genetic etiology of sporadic VCI remains largely unknown. We previously conducted a systematic review and meta-analysis of all published genetic association studies of sporadic VCI prior to 6 July 2012, which demonstrated that APOE (ɛ4, ɛ2) and MTHFR (rs1801133) variants were associated with susceptibility for VCI. De novo genotyping was conducted in a new independent relatively large collaborative European cohort of VaD (nmax = 549) and elderly non-demented samples (nmax = 552). Where available, genotype data derived from Illumina's 610-quad array for 1210 GERAD1 control samples were also included in analyses of genes examined. Associations were tested using the Cochran-Armitage trend test: MTHFR rs1801133 (OR = 1.36, 95% CI 1.16-1.58, p = <0.0001), APOE rs7412 (OR = 0.62, 95% CI 0.42-0.90, p = 0.01), and APOE rs429358 (OR = 1.59, 95% CI 1.17-2.16, p = 0.003). Association was also observed with APOE epsilon alleles; ɛ4 (OR = 1.85, 95% CI 1.35-2.52, p = <0.0001) and ɛ2 (OR = 0.67, 95% CI 0.46-0.98, p = 0.03). Logistic Regression and Bonferroni correction in a subgroup of the cohort adjusted for gender, age, and population maintained the association of APOE rs429358 and ɛ4 allele.

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis

BACKGROUND: The aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association.

METHODS: A cohort of 8391 patients with newly diagnosed Dukes' A-C CRC (2009-2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality.

RESULTS: In the Scottish cohort, statin use before diagnosis (HR=0.84, 95% CI 0.75-0.94), but not after (HR=0.90, 95% CI 0.77-1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I(2)=0%,heterogeneity P=0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n=86,622, pooled HR=0.82, 95% CI 0.79-0.86) but this association was less apparent and more heterogeneous (I(2)=67%,heterogeneity P=0.03) with statin use after diagnosis in 4 studies (n=19,152, pooled HR=0.84, 95% CI 0.68-1.04).

CONCLUSION: In a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies.

Dipyridamole plus aspirin versus aspirin alone in the secondary prevention after TIA or stroke: a meta-analysis by risk

Objectives: Our aim was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D. Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on the comparison of A+D versus ASA were excluded. Review methods: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification. Results: A total of 7,612 patients (5 trials) were included in the analyses, 3,800 allocated to A+D and 3,812 to ASA alone. The trial-adjusted hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke, HR 0.78 (95% CI 0.68 – 0.90). Conclusion: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk. ---------------------------7dc3521430776 Content-Disposition: form-data; name="c14_creators_1_name_family" Halkes