George Davey Smith

Bio: George Davey Smith is an academic researcher from University of Bristol. The author has contributed to research in topics: Population & Mendelian randomization. The author has an hindex of 224, co-authored 2540 publications receiving 248373 citations. Previous affiliations of George Davey Smith include Keele University & Western Infirmary.

High molecular weight adiponectin is not associated with incident coronary heart disease in older women: a nested prospective case-control study.

Abstract: Context: Adiponectin levels appear weakly linked to incident vascular disease, but the high molecular weight (HMW) fraction may be more relevant. Objective: Our objective was to test whether HMW adiponectin, the key biologically active fraction, is linked to incident coronary heart disease (CHD) events. Design, Participants, and Main Outcome Measures: We assessed the association between HMW adiponectin (measured by ELISA) and CHD risk in a prospective (4-yr) case-control study nested within the British Women's Heart and Health Study. All women were postmenopausal. Setting: Women were seen in a primary care setting. Results: Among both cases (n = 167) and controls (n = 333), HMW adiponectin positively correlated with age and high-density lipoprotein cholesterol and inversely correlated with waist to hip ratio, fasting insulin, fasting glucose, homeostasis model assessment for insulin resistance scores, C-reactive protein, and triglycerides, in similar fashion to total adiponectin. The age-adjusted relative...

Trends in blood pressure over 10 years in adolescents: analyses of cross sectional surveys in the Northern Ireland Young Hearts project

Abstract: Objective To examine secular trends in blood pressure over a 10 year period between two representative cohorts of adolescents from Northern Ireland. Design Repeat cross sectional study. Setting Randomly selected post-primary schools from Northern Ireland. Participants 1015 adolescents studied between 1989 and 1990, and 2017 adolescents studied between 1999 and 2001. Participants were aged 12 or 15 years. Main outcome measures Systolic and diastolic blood pressure measured by one observer in each study. Results The four groups for sex and age showed decreases in both systolic blood pressure (mean decrease 7.7 mm Hg to 10.0 mm Hg) and diastolic blood pressure (8.8 mm Hg to 11.0 mm Hg). These decreases were not accounted for by adjustment for potential confounders including age, height, body mass index, smoking, physical activity, aerobic fitness, and stratification of school by education board area and type. The findings were not altered by additional adjustment for social class, pubertal status, birth weight, and infant feeding. No evidence was found of systematic variation between observers. Conclusions Substantial decreases in systolic and diastolic blood pressure over the past decade in adolescents from Northern Ireland are likely to have important benefits to public health and may help offset the increasing risk of cardiovascular disease due to increases in obesity.

Cohort Profile: The Boyd Orr cohort—an historical cohort study based on the 65 year follow-up of the Carnegie Survey of Diet and Health (1937–39)

Abstract: 742 of the children on their health and growth were studied. Around 500 children aged 2–14 received supplements and a similar number of non-supplemented children acted as controls.1,3 The initial aim of establishing the Boyd Orr cohort was to investigate the long-term impact of environmental factors in early life on adult coronary heart disease mortality. Whilst the possible impact of poor childhood nutrition on adult health had been the subject of research and policy interest for many years,4–7 specific interest in the influence of early life exposures on adult cardiovascular disease was re-awakened by a series of studies that began in the 1980s by Professor David Barker and colleagues at the University of Southampton.8,9 These studies demonstrated inverse associations of markers of foetal growth with cardiovascular risk factors and mortality. An important strength of the material collected in the Carnegie Survey/Boyd Orr cohort was the availability of detailed measures of childhood diet; most of the research in this field uses proxy measures of pre-natal and childhood nutrition (e.g. birth weight, height).10 Studies on the cohort to date have investigated a range of disease endpoints, particularly coronary heart disease and cancer in relation to infant and childhood diet, the socio-economic conditions experienced by the children, and markers of childhood nutritional status (body mass index, leg length, and height).

Measuring inconsistency in meta-analyses

Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

Bias in meta-analysis detected by a simple, graphical test

Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration

Abstract: Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

Abstract: Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate