Showing papers in "International Journal of Epidemiology in 2013"

Cohort Profile: The ‘Children of the 90s’—the index offspring of the Avon Longitudinal Study of Parents and Children

Abstract: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective observational study investigating influences on health and development across the life course. It considers multiple genetic, epigenetic, biological, psychological, social and other environmental exposures in relation to a similarly diverse range of health, social and developmental outcomes. Recruitment sought to enroll pregnant women in the Bristol area of the UK during 1990-92; this was extended to include additional children eligible using the original enrollment definition up to the age of 18 years. The children from 14541 pregnancies were recruited in 1990-92, increasing to 15247 pregnancies by the age of 18 years. This cohort profile describes the index children of these pregnancies. Follow-up includes 59 questionnaires (4 weeks-18 years of age) and 9 clinical assessment visits (7-17 years of age). The resource comprises a wide range of phenotypic and environmental measures in addition to biological samples, genetic (DNA on 11343 children, genome-wide data on 8365 children, complete genome sequencing on 2000 children) and epigenetic (methylation sampling on 1000 children) information and linkage to health and administrative records. Data access is described in this article and is currently set up as a supported access resource. To date, over 700 peer-reviewed articles have been published using ALSPAC data.

Cohort Profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort

Abstract: Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

Data Resource Profile: The Survey of Health, Ageing and Retirement in Europe (SHARE)

Abstract: SHARE is a unique panel database of micro data on health, socio-economic status and social and family networks covering most of the European Union and Israel. To date, SHARE has collected three panel waves (2004, 2006, 2010) of current living circumstances and retrospective life histories (2008, SHARELIFE); 6 additional waves are planned until 2024. The more than 150 000 interviews give a broad picture of life after the age of 50 years, measuring physical and mental health, economic and non-economic activities, income and wealth, transfers of time and money within and outside the family as well as life satisfaction and well-being. The data are available to the scientific community free of charge at www.share-project.org after registration. SHARE is harmonized with the US Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA) and has become a role model for several ageing surveys worldwide. SHARE's scientific power is based on its panel design that grasps the dynamic character of the ageing process, its multidisciplinary approach that delivers the full picture of individual and societal ageing, and its cross-nationally ex-ante harmonized design that permits international comparisons of health, economic and social outcomes in Europe and the USA.

Cohort Profile: The English Longitudinal Study of Ageing

Abstract: The English Longitudinal Study of Ageing (ELSA) is a panel study of a representative cohort of men and women living in England aged ≥50 years. It was designed as a sister study to the Health and Retirement Study in the USA and is multidisciplinary in orientation, involving the collection of economic, social, psychological, cognitive, health, biological and genetic data. The study commenced in 2002, and the sample has been followed up every 2 years. Data are collected using computer-assisted personal interviews and self-completion questionnaires, with additional nurse visits for the assessment of biomarkers every 4 years. The original sample consisted of 11 391 members ranging in age from 50 to 100 years. ELSA is harmonized with ageing studies in other countries to facilitate international comparisons, and is linked to financial and health registry data. The data set is openly available to researchers and analysts soon after collection (http://www.esds.ac.uk/longitudinal/access/elsa/l5050.asp).

Cohort Profile: The HUNT Study, Norway

Abstract: The HUNT Study includes large total population-based cohorts from the 1980ies, covering 125 000 Norwegian participants; HUNT1 (1984-86), HUNT2 (1995-97) and HUNT3 (2006-08) The study was primarily set up to address arterial hypertension, diabetes, screening of tuberculosis, and quality of life However, the scope has expanded over time In the latest survey a state of the art biobank was established, with availability of biomaterial for decades ahead The three population based surveys now contribute to important knowledge regarding health related lifestyle, prevalence and incidence of somatic and mental illness and disease, health determinants, and associations between disease phenotypes and genotypes Every citizen of Nord-Trondelag County in Norway being 20 years or older, have been invited to all the surveys for adults Participants may be linked in families and followed up longitudinally between the surveys and in several national health- and other registers covering the total population The HUNT Study includes data from questionnaires, interviews, clinical measurements and biological samples (blood and urine) The questionnaires included questions on socioeconomic conditions, health related behaviours, symptoms, illnesses and diseases Data from the HUNT Study are available for researchers who satisfy some basic requirements (wwwntnuedu/hunt), whether affiliated in Norway or abroad

Calculating statistical power in Mendelian randomization studies

Abstract: In Mendelian randomization (MR) studies, where genetic variants are used as proxy measures for an exposure trait of interest, obtaining adequate statistical power is frequently a concern due to the small amount of variation in a phenotypic trait that is typically explained by genetic variants. A range of power estimates based on simulations and specific parameters for two-stage least squares (2SLS) MR analyses based on continuous variables has previously been published. However there are presently no specific equations or software tools one can implement for calculating power of a given MR study. Using asymptotic theory, we show that in the case of continuous variables and a single instrument, for example a single-nucleotide polymorphism (SNP) or multiple SNP predictor, statistical power for a fixed sample size is a function of two parameters: the proportion of variation in the exposure variable explained by the genetic predictor and the true causal association between the exposure and outcome variable. We demonstrate that power for 2SLS MR can be derived using the non-centrality parameter (NCP) of the statistical test that is employed to test whether the 2SLS regression coefficient is zero. We show that the previously published power estimates from simulations can be represented theoretically using this NCP-based approach, with similar estimates observed when the simulation-based estimates are compared with our NCP-based approach. General equations for calculating statistical power for 2SLS MR using the NCP are provided in this note, and we implement the calculations in a web-based application.

Time series regression studies in environmental epidemiology

Abstract: Time series regression studies have been widely used in environmental epidemiology, notably in investigating the short-term associations between exposures such as air pollution, weather variables or pollen, and health outcomes such as mortality, myocardial infarction or disease-specific hospital admissions. Typically, for both exposure and outcome, data are available at regular time intervals (e.g. daily pollution levels and daily mortality counts) and the aim is to explore short-term associations between them. In this article, we describe the general features of time series data, and we outline the analysis process, beginning with descriptive analysis, then focusing on issues in time series regression that differ from other regression methods: modelling short-term fluctuations in the presence of seasonal and long-term patterns, dealing with time varying confounding factors and modelling delayed ('lagged') associations between exposure and outcome. We finish with advice on model checking and sensitivity analysis, and some common extensions to the basic model.

Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis

Abstract: In this contribution we put forward a novel hypothesis concerning the aetiology of Type 2 (non-insulin dependent) diabetes mellitus. The concept underlying our hypothesis is that poor foetal and early post-natal nutrition imposes mechanisms of nutritional thrift upon the growing individual. We propose that one of the major long-term consequences of inadequate early nutrition is impaired development of the endocrine pancreas and a greatly increased susceptibility to the development of Type 2 diabetes. In the first section we outline our research which has led to this hypothesis. We will then review the relevant literature. Finally we show that the hypothesis suggests a reinterpretation of some findings and an explanation of others which are at present not easy to understand.

Why representativeness should be avoided

Abstract: The essence of knowledge is generalisation. That rubbing wood in a certain way can produce fire is a knowledge derived by generalisation from individual experiences; the statement means that rubbing wood in this way will always produce fire. The art of discovery is therefore the art of correct generalisation. What is irrelevant, such as the particular shape or size of the piece of wood used, is to be excluded from the generalisation; what is relevant, for example, the dryness of the wood, is to be included in it. The meaning of the term relevant can thus be defined: that is relevant which must be mentioned for the generalisation to be valid. The separation of relevant from irrelevant factors is the beginning of knowledge. —Hans Reichenbach

Mediation analysis in epidemiology: methods, interpretation and bias

Abstract: In epidemiological studies it is often necessary to disentangle the pathways that link an exposure to an outcome. Typically the aim is to identify the total effect of the exposure on the outcome, the effect of the exposure that acts through a given set of mediators of interest (indirect effect) and the effect of the exposure unexplained by those same mediators (direct effect). The traditional approach to mediation analysis is based on adjusting for the mediator in standard regression models to estimate the direct effect. However, several methodological papers have shown that under a number of circumstances this traditional approach may produce flawed conclusions. Through a better understanding of the causal structure of the variables involved in the analysis, with a formal definition of direct and indirect effects in a counterfactual framework, alternative analytical methods have been introduced to improve the validity and interpretation of mediation analysis. In this paper, we review and discuss the impact of the three main sources of potential bias in the traditional approach to mediation analyses: (i) mediator-outcome confounding;(ii) exposure-mediator interaction and (iii) mediator-outcome confounding affected by the exposure. We provide examples and discuss the impact these sources have in terms of bias.

Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries

Abstract: Background Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30–40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain. Methods Using extant longitudinal birth cohorts (n = 19) with data on birthweight, gestational age and child anthropometry (12–60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth. Results We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5–3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively. Conclusions This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.

Cohort Profile: The Born in Bradford multi-ethnic family cohort study

Abstract: Bradford Institute for Health Research, Bradford Teaching Hospitals Foundation Trust, Bradford, UK, School of Health Studies, University of Bradford, Bradford, UK, Edinburgh Ethnicity and Health Research Group, Centre for Population Health Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK, School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, UK, Medical Research Council Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK, Paediatric Epidemiology Group, Centre for Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK and Department of Health Sciences, University of York, York, UK

Evaluation of inconsistency in networks of interventions

Abstract: Background The assumption of consistency, defined as agreement between direct and indirect sources of evidence, underlies the increasingly popular method of network meta-analysis. No evidence exists so far regarding the extent of inconsistency in full networks of interventions or the factors that control its statistical detection. Methods In this paper we assess the prevalence of inconsistency from data of 40 published networks of interventions involving 303 loops of evidence. Inconsistency is evaluated in each loop by contrasting direct and indirect estimates and by employing an omnibus test of consistency for the entire network. We explore whether different effect measures for dichotomous outcomes are associated with differences in inconsistency, and evaluate whether different ways to estimate heterogeneity affect the magnitude and detection of inconsistency. Results Inconsistency was detected in from 2% to 9% of the tested loops, depending on the effect measure and heterogeneity estimation method. Loops that included comparisons informed by a single study were more likely to show inconsistency. About one-eighth of the networks were found to be inconsistent. The proportions of inconsistent loops do not materially change when different effect measures are used. Important heterogeneity or the overestimation of heterogeneity was associated with a small decrease in the prevalence of statistical inconsistency. Conclusions The study suggests that changing the effect measure might improve statistical consistency, and that an analysis of sensitivity to the assumptions and an estimator of heterogeneity might be needed before reaching a conclusion about the absence of statistical inconsistency, particularly in networks with few studies.

Use of Allele Scores as Instrumental Variables for Mendelian Randomization

Abstract: Background An allele score is a single variable summarizing multiple genetic variants associated with a risk factor. It is calculated as the total number of risk factor-increasing alleles for an individual (unweighted score), or the sum of weights for each allele corresponding to estimated genetic effect sizes (weighted score). An allele score can be used in a Mendelian randomization analysis to estimate the causal effect of the risk factor on an outcome. Methods Data were simulated to investigate the use of allele scores in Mendelian randomization where conventional instrumental variable techniques using multiple genetic variants demonstrate ‘weak instrument’ bias. The robustness of estimates using the allele score to misspecification (for example non-linearity, effect modification) and to violations of the instrumental variable assumptions was assessed. Results Causal estimates using a correctly specified allele score were unbiased with appropriate coverage levels. The estimates were generally robust to misspecification of the allele score, but not to instrumental variable violations, even if the majority of variants in the allele score were valid instruments. Using a weighted rather than an unweighted allele score increased power, but the increase was small when genetic variants had similar effect sizes. Naive use of the data under analysis to choose which variants to include in an allele score, or for deriving weights, resulted in substantial biases. Conclusions Allele scores enable valid causal estimates with large numbers of genetic variants. The stringency of criteria for genetic variants in Mendelian randomization should be maintained for all variants in an allele score.

Cohort Profile: Generation Scotland: Scottish Family Health Study (GS:SFHS). The study, its participants and their potential for genetic research on health and illness

Abstract: GS:SFHS is a family-based genetic epidemiology study with DNA and socio-demographic and clinical data from about 24 000 volunteers across Scotland, aged 18–98 years, from February 2006 to March 2011. Biological samples and anonymized data form a resource for research on the genetics of health, disease and quantitative traits of current and projected public health importance. Specific and important features of GS:SFHS include the family-based recruitment, with the intent of obtaining family groups; the breadth and depth of phenotype information, including detailed data on cognitive function, personality traits and mental health; consent and mechanisms for linkage of all data to comprehensive routine health-care records; and ‘broad’ consent from participants to use their data and samples for a wide range of medical research, including commercial research, and for re-contact for the potential collection of other data or samples, or for participation in related studies and the design and review of the protocol in parallel with in-depth sociological research on (potential) participants and users of the research outcomes. These features were designed to maximize the power of the resource to identify, replicate or control for genetic factors associated with a wide spectrum of illnesses and risk factors, both now and in the future.

Cohort Profile: TwinsUK and Healthy Ageing Twin Study

Abstract: The UK's largest registry of adult twins, or TwinsUK Registry, started in 1992 and encompasses about 12000 volunteer twins from all over the United Kingdom. More than 70% of the registered twins have filled at least one detailed health questionnaire and about half of them undergone a baseline comprehensive assessment and two follow-up clinical evaluations. The most recent follow-up visit, known as Healthy Ageing Twin Study (HATS), involved 3125 female twins aged >40 years with at least one previous clinical assessment to enable inspection of longitudinal changes in ageing traits and their genetic and environmental components. The study benefits from several state-of-the-art OMICs studies including genome-wide association, next-generation genome and transcriptome sequencing, and epigenetic and metabolomic profiles. This makes our cohort as one of the most deeply phenotyped and genotyped in the world. Several collaborative projects in the field of epidemiology of complex disorders are ongoing in our cohort and interested researchers are encouraged to get in contact for future collaborations.

Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study

Abstract: Background Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking. Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy. Results The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12–0.51], communication (β 0.20, 95% CI 0.01–0.39), externalizing behaviour (β 0.28, 95% CI 0.15–0.42), internalizing behaviour (β 0.14, 95% CI 0.01–0.28), and higher activity levels (β 0.24, 95% CI 0.11–0.38). Children exposed prenatally to short-term use of paracetamol (1–27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02–0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes. Conclusion Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age.

Metabolomic markers reveal novel pathways of ageing and early development in human populations

Abstract: Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2 = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10−157) and lung function (FEV1 beta = −0.04, SE = 0.008, P = 1.8 × 10−8 adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = −0.01, SE = 0.002, P = 1.9 × 10−6) and birthweight (beta = −0.06, SE = 0.01, P = 2.5 × 10−9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10−6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = −0.20, SE = 0.04, P = 2.9 × 10−8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing.

Cohort Profile: The National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0

Abstract: In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) c ...

Cohort Profile: The Dongfeng-Tongji cohort study of retired workers

Abstract: China has seen rapid socio-economic and epidemiolo-gical changes over the past several decades. Economicgrowth plus shifts in environment, lifestyles and diethave increased life expectancy, but they have also ledto a higher burden of chronic, non-communicablediseases. Stroke, coronary heart disease (CHD), cancerand diabetes account for 80% of the deaths and 70%of the disability-adjusted life-years lost in China.

Convergence of non-communicable and infectious diseases in low- and middle-income countries

Abstract: The convergence of non-communicable disease (NCD) and infectious disease (ID) in low- and middle-income countries (LMICs) presents new challenges and new opportunities to enact responsive changes in policy and research. Most LMICs have significant dual disease burdens of NCDs such as cardiovascular disease, diabetes and cancer, and IDs including tuberculosis, HIV/AIDS and parasitic diseases. A combined strategy is needed in surveillance and disease control; yet, experts, institutions and policies that support prevention and control of these two overarching disease categories have limited interaction and alignment. NCDs and IDs share common features, such as long-term care needs and overlapping high-risk populations, and there are also notable direct interactions, such as the association between certain IDs and cancers, as well as evidence of increased susceptibility to IDs in individuals with NCDs. Enhanced simultaneous surveillance of NCD and ID comorbidity in LMIC populations would generate the empirical data needed to better understand the dual burden, and to target coordinated care. Where IDs and NCDs are endemic, focusing on vulnerable populations by strengthening social protections and improving access to health services is crucial, as is the re-alignment of efforts to combine NCD and ID screening, treatment programmes, and the assessment of their impact. Integrating public health activities for ID and NCD should extend beyond health care services to prevention, which is widely seen as crucial to successful NCD and ID control campaigns alike. The convergence of NCD and ID in LMICs has the potential to overstretch already strained health systems. With some LMICs now focused on major health system reforms, a unique opportunity is available to address NCD and ID challenges with newfound urgency and novel approaches.

Cohort profile of the CARTaGENE study: Quebec's population-based biobank for public health and personalized genomics

Abstract: Accepted 20 August 2012The CARTaGENE (CaG) study is both a population-based biobankand the largest ongoing prospective health study of men andwomen in Quebec. In population-based cohorts, participants arenot recruited for a particular disease but represent a random selec-tion among the population, minimizing the need to correct for biasin measured phenotypes. CaG targeted the segment of the popula-tion that is most at risk of developing chronic disorders, that is40–69 years of age, from four metropolitan areas in Quebec. Over20000 participants consented to visiting 1 of 12 assessment siteswhere detailed health and socio-demographic information, physio-logical measures and biological samples (blood, serum and urine)were captured for a total of 650 variables. Significant correlations ofdiseases and chronic conditions are observed across these regions,implicating complex interactions, some of which we describe formajor chronic conditions. The CaG study is one of the fewpopulation-based cohorts in the world where blood is stored notonly for DNA and protein based science but also for gene expressionanalyses, opening the door for multiple systems genomicsapproaches that identify genetic and environmental factors asso-ciated with disease-related quantitative traits. Interested researchersare encouraged to submit project proposals on the study website(www.cartagene.qc.ca).

Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis

Abstract: Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, −0.59; 95% CI, −0.86 to −0.31), BMI (SMD, −0.32; 95% CI, −0.45 to −0.18), SBP (SMD, −0.40; 95% CI, −0.55 to −0.25) and DBP (SMD, −0.34; 95% CI, −0.51 to −0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, −0.34; 95% CI, −0.62 to −0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

Markov Chain Monte Carlo: an introduction for epidemiologists

Abstract: Markov Chain Monte Carlo (MCMC) methods are increasingly popular among epidemiologists. The reason for this may in part be that MCMC offers an appealing approach to handling some difficult types of analyses. Additionally, MCMC methods are those most commonly used for Bayesian analysis. However, epidemiologists are still largely unfamiliar with MCMC. They may lack familiarity either with he implementation of MCMC or with interpretation of the resultant output. As with tutorials outlining the calculus behind maximum likelihood in previous decades, a simple description of the machinery of MCMC is needed. We provide an introduction to conducting analyses with MCMC, and show that, given the same data and under certain model specifications, the results of an MCMC simulation match those of methods based on standard maximum-likelihood estimation (MLE). In addition, we highlight examples of instances in which MCMC approaches to data analysis provide a clear advantage over MLE. We hope that this brief tutorial will encourage epidemiologists to consider MCMC approaches as part of their analytic tool-kit.

Tubal ligation and risk of ovarian cancer subtypes: a pooled analysis of case-control studies

Abstract: Background Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes. Methods We pooled primary data from 13 population-based case-control studies, including 10 157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13 904 control women. Invasive cases were analysed by histological type, grade and stage, and borderline cases were analysed by histological type. Pooled odds ratios were estimated using conditional logistic regression to match on site, race/ethnicity and age categories, and to adjust for age, oral contraceptive use duration and number of full-term births. Results Tubal ligation was associated with significantly reduced risks of invasive serous (OR, 0.81; 95% CI, 0.74-0.89; P < 0.001), endometrioid (OR, 0.48; 95% CI, 0.40-0.59; P < 0.001), clear cell (OR, 0.52; 95% CI, 0.40-0.67; P < 0.001) and mucinous (OR, 0.68; 95% CI, 0.52-0.89; P = 0.005) cancers. The magnitude of risk reduction was significantly greater for invasive endometrioid (P < 0.0001) and clear cell (P = 0.0018) than for serous cancer. No significant associations were found with borderline serous or mucinous tumours. Conclusions We found that the protective effects of tubal ligation on ovarian cancer risk were subtype-specific. These findings provide insights into distinct aetiologies of ovarian cancer subtypes and mechanisms underlying the protective effects of tubal ligation.

Consistently high estimates for the proportion of human exposure to malaria vector populations occurring indoors in rural Africa

Abstract: BACKGROUND: Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are highly effective tools for controlling malaria transmission in Africa because the most important vectors, from the Anopheles gambiae complex and the A. funestus group, usually prefer biting humans indoors at night. METHODS: Matched surveys of mosquito and human behaviour from six rural sites in Burkina Faso, Tanzania, Zambia, and Kenya, with ITN use ranging from 0.2% to 82.5%, were used to calculate the proportion of human exposure to An. gambiae sensu lato and An. funestus s.l. that occurs indoors (πi), as an indicator of the upper limit of personal protection that indoor vector control measures can provide. This quantity was also estimated through use of a simplified binary analysis (π(i)(B)) so that the proportions of mosquitoes caught indoors (Pi), and between the first and last hours at which most people are indoors (Pfl) could also be calculated as underlying indicators of feeding by mosquitoes indoors or at night, respectively. RESULTS: The vast majority of human exposure to Anopheles bites occurred indoors (π(i)(B)= 0.79-1.00). Neither An. gambiae s.l. nor An. funestus s.l. strongly preferred feeding indoors (P(i) = 0.40-0.63 and 0.22-0.69, respectively), but they overwhelmingly preferred feeding at times when most humans were indoors (P(fl) = 0.78-1.00 and 0.86-1.00, respectively). CONCLUSIONS: These quantitative summaries of behavioural interactions between humans and mosquitoes constitute a remarkably consistent benchmark with which future observations of vector behaviour can be compared. Longitudinal monitoring of these quantities is vital to evaluate the effectiveness of ITNs and IRS and the need for complementary measures that target vectors outdoors.

Cohort Profile: The Young Lives Study

Abstract: Young Lives is an international longitudinal study investigating the changing nature of childhood poverty in four low-income countries [Ethiopia, India (Andhra Pradesh), Peru and Vietnam] over a 15-year period. In each country, the cohort is comprised of ≈ 2000 children aged between 6 and 18 months and up to 1000 children aged between 7 and 8 years, recruited in 2002 and sampled from 20 sentinel sites. The first survey data collection from primary caregivers and older children took place in 2002, the second in 2006-07 and the third in 2009-10. Data on the community contexts were collected to complement the household surveys. To elaborate and extend the quantitative data, longitudinal qualitative research with a subgroup of the children was carried out in 2007, 2008 and 2010-11. Topic areas covered included nutrition, health and well-being, cognitive and physical development, health behaviours and education, as well as the social, demographic and economic status of the household. Survey data from the study are archived in the International Section of the UK Public Data Archive.

Mobile phone use and risk of brain neoplasms and other cancers: prospective study

Abstract: Background Results from some retrospective studies suggest a possible increased risk of glioma and acoustic neuroma in users of mobile phones. Methods The relation between mobile phone use and incidence of intracranial central nervous system (CNS) tumours and other cancers was examined in 791,710 middle-aged women in a UK prospective cohort, the Million Women Study. Cox regression models were used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Women reported mobile phone use in 1999 to 2005 and again in 2009. Results During 7 years' follow-up, 51,680 incident invasive cancers and 1,261 incident intracranial CNS tumours occurred. Risk among ever vs never users of mobile phones was not increased for all intracranial CNS tumours (RR = 1.01, 95% CI = 0.90-1.14, P = 0.82), for specified CNS tumour types nor for cancer at 18 other specified sites. For long-term users compared with never users, there was no appreciable association for glioma (10+ years: RR = 0.78, 95% CI = 0.55-1.10, P = 0.16) or meningioma (10+ years: RR = 1.10, 95% CI = 0.66-1.84, P = 0.71). For acoustic neuroma, there was an increase in risk with long term use vs never use (10+ years: RR = 2.46, 95% CI = 1.07-5.64, P = 0.03), the risk increasing with duration of use (trend among users, P = 0.03). Conclusions In this large prospective study, mobile phone use was not associated with increased incidence of glioma, meningioma or non-CNS cancers.

Cohort Profile: Growing Up in New Zealand

Abstract: Centre for Longitudinal Research – He Ara ki Mua, University of Auckland, Auckland, New Zealand, Growing Up in New Zealand, University of Auckland, Auckland, New Zealand, School of Medicine, University of Auckland, Auckland, New Zealand, Starship Children’s Hospital, Auckland District Health Board, Auckland, New Zealand, School of Population Health, University of Auckland, Auckland, New Zealand, Department of Public Health, School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand, Office of the Deputy Vice-Chancellor (Māori), Massey University, Wellington, New Zealand, Bioinformatics Institute, University of Auckland, Auckland, New Zealand, Ministry of Pacific Island Affairs, Auckland Office, Auckland, New Zealand, Department of Psychology, University of Auckland, Auckland, New Zealand, Roy McKenzie Centre for the Study of Families, Victoria University, Wellington, New Zealand, Department of Psychology, University of Otago, Dunedin, New Zealand and School of Medical Sciences, University of Auckland, Auckland, New Zealand

Cohort Profile: The Helsinki Health Study

Abstract: The Helsinki Health Study cohort was set up to enable longitudinal studies on the social and work related determinants of health and well-being, making use of self-reported as well as objective register data. The target population is the staff of the City of Helsinki, Finland. Baseline data for the cohort were derived from questionnaire surveys conducted in 2000, 2001 and 2002 among employees reaching 40, 45, 50, 55 or 60 years of age in each year. The number of responders at baseline was 8960 (80% women, response rate 67%). Additional age-based health examination data were available. A follow up survey was conducted in 2007 yielding 7332 responders (response rate 83%). Measures of health include health behaviours, self-rated health, common mental disorders, functioning, pain, sleep problems, angina symptoms and major diseases. Social determinants include socio-demographics, socio-economic circumstances, working conditions, social support, and work-family interface. Further register linkages include sickness absence, hospital discharge, prescribed drugs, and retirement updated at the end of 2010. The cohort allows comparisons with the Whitehall II study, London, UK, and the Japanese Civil Servants Study from western Japan. The cohort data are available for collaborative research at Hjelt Institute, Department of Public Health, University of Helsinki, Finland.