Many routinely used summary methods provide widely ranging estimates when applied to sparse data with high imbalance between the size of the studies' arms. A sensitivity analysis using several methods and continuity correction factors is advocated for routine practice.

SummaryBackgroundLow-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.MethodsWe did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies.FindingsIn the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively.InterpretationIn current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being ...

BackgroundCoronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes.ObjectivesThis study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention.MethodsUsing a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1.7 million genetic variants. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22,242 CAD cases and 460,387 noncases from the UK Biobank.ResultsThe hazard ratio (HR) for CAD was 1.71 (95% confidence interval [CI]: 1.68 to 1.73) per SD increase in metaGRS, an association larger than any other externally tested genetic risk score previously published. The metaGRS stratified individuals into significantly different life course trajectories of CAD risk, with those in the top 20% of metaGRS distribution having an HR of 4.17 (95% CI: 3.97 to 4.38) compared with those in the bottom 20%. The corresponding HR was 2.83 (95% CI: 2.61 to 3.07) among individuals on lipid-lowering or antihypertensive medications. The metaGRS had a higher C-index (C = 0.623; 95% CI: 0.615 to 0.631) for incident CAD than any of 6 conventional factors (smoking, diabetes, hypertension, body mass index, self-reported high cholesterol, and family history). For men in the top 20% of metaGRS with >2 conventional factors, 10% cumulative risk of CAD was reached by 48 years of age.ConclusionsThe genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screening in early life to complement conventional risk prediction.

UK National Institute for Health Research, Camelia Botnar Arterial Research Foundation.

There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.

No abstract

INSTEAD trial and the known adverse affects of a patent false lumen after aortic dissection, studies such as this focusing on variables that can be identified after dissection as possible indicators for early endovascular therapy are clearly needed. Although patients with Marfan syndrome are not thought to be optimal candidates for endovascular treatments, non-Marfan patients with large proximal aortic tears and large aortas would seem to be two subgroups that would benefit from further study for "prophylactic" endovascular thoracic aortic repair after acute thoracic aortic resection. Meta-Analysis of Individual Patient Data to Examine Factors Affecting Growth and Rupture of Small Abdominal Aortic AneurysmsSweeting MJ, Thompson SG, Brown LC, et al; RESCAN collaborators. Br J Surg 2012;99:655-65. Conclusion: Risk factors differ for growth and rupture of small abdominal aortic aneurysms (AAAs). In addition to aneurysm diameter, diabetes and smoking may need to be considered in developing schedules for surveillance of small AAAs. No single drug for cardiovascular risk reduction has a pronounced affect on rupture or growth of small AAAs.Summary: It is now well established that screening for AAAs can reduce aneurysm-related mortality. Individual aneurysm and patient-specific factors affecting small AAA growth rate and rupture potential are not well established. Rupture of a small AAA is infrequent, and because most studies are small, there are little convincing data about factors that might affect risk of rupture of a small AAA. In addition, studies of growth rates of small AAAs have made minimal attempts to adjust for the multiplicity of potential risk factors in patients with AAA or to identify modifiers of aneurysm growth rate such as diabetes or smoking (Bergqvist D, Eur J Vasc Endovasc Surg 2011;41:663-1; and Powel JT et al, Br J Surg 2011;98:609-19; and Brady AR et al, Circulation 2004;110:16-21). In this report the authors used individual patient data from Ͼ15,000 people under follow-up for a small AAA to identify whether any of the common cardiovascular risk factors or classes of drugs used by patients with aneurysms influence growth and rupture rates of small AAAs. The authors requested individual patient data from corresponding authors of 25 studies that included Ͼ100 patients with a small AAA. Eighteen studies provided data to the RESCAN collaborators and 15,475 people were entered into the database. The effects of covariables (patient demographics, medical, and drug history) on AAA growth rate were summarized in an individual patient meta-analysis. Analysis used longitudinal random-affects modeling and survival analysis adjusted for aneurysm diameter. The mean AAA growth rate was 2.21 mm/y. AAA growth was independent of age and sex. The growth rate in smokers was increased by 0.35 mm/y, and the growth rate in patients with diabetes was decreased by 0.51 mm/y. Cardioprotective medications, mean arterial pressure, or use of antihypertensive medications had no significant effects on AAA growth. Calendar...

This report should be referenced as follows:Thompson SG, Brown LC, Sweeting MJ, Bown MJ, Kim LG, Glover MJ, et al. Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic aneurysms: implications for surveillance intervals and their cost-effectiveness. Health Technol Assess 2013;17(41). Health Technology Assessment is indexed in MEDLINE, CINAHL, EMBASE, The Cochrane Library and the ISI Science Citation Index and is assessed for inclusion in the Database of Abstracts of Reviews of Effects. Health Technology Assessment is indexed and abstracted inThis journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www.publicationethics.org/).Editorial contact: nihredit@southampton.ac.ukThe full HTA archive is freely available to view online at www.journalslibrary.nihr.ac.uk/hta. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www.journalslibrary.nihr.ac.uk Criteria for inclusion in the Health Technology Assessment journalReports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors.Reviews in Health Technology Assessment are termed 'systematic' when the account of the search appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA programmeThe HTA programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.The journal is indexed in NHS Evidence via its abstracts included in MEDLINE and its Technology Assessment Reports inform National Institute for Health and Care Excellence (NICE) guidance. HTA research is also an important source of evidence for National Screening Committee (NSC) policy decisions.For more information about the HTA programme please visit the website: www.hta.ac.uk/ This reportThe research reported in this issue of the journal was funded by the HTA programme as project number 08/30/02. The contractual start date was in November 2009. The draft report began editorial review in July 2012 and was accepted for publication in November 2012. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research...