The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance.
The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27 720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).
The Amsterdam Growth and Health Longitudinal Study (AGHLS) is a unique, multidisciplinary cohort study that was initially set up to examine growth and health among teenagers. Throughout the years, the AGHLS has aimed to answer research questions dealing with the relationships between the (natural) development of anthropometry, lifestyle and health from adolescence into adulthood. The AGHLS specifically focuses on anthropometrics, physical activity and fitness, cardiovascular disease risk, lifestyle, musculoskeletal health, psychological health and well-being. Besides this, many methodological issues related to the analysis of longitudinal data were also explored within the framework of the AGHLS. In 1976, students from two secondary schools from the greater Amsterdam area were included in the study. Between 1976 and 2006, 10 rounds of measurement were performed covering an age range between 13 and 43 years. The huge database collected so far has been primarily used to answer relevant research questions regarding the longitudinal relationship between lifestyle and health. Further information about the study can be obtained from the principal investigator Jos Twisk (firstname.lastname@example.org), and up-to-date information on AGHLS can be found by visiting the website www.aggo.nl.
The Themba Lethu Clinical Cohort was established in 2004 to allow large patient-level analyses from a single HIV treatment site to evaluate National Treatment Guidelines, answer questions of national and international policy relevance and to combine an economic and epidemiologic focus on HIV research. The current objectives of the Themba Lethu Clinical Cohort analyses are to: (i) provide cohort-level information on the outcomes of HIV treatment; (ii) evaluate aspects of HIV care and treatment that have policy relevance; (iii) evaluate the cost and cost-effectiveness of different approaches to HIV care and treatment; and (iv) provide a platform for studies on improving HIV care and treatment. Since 2004, Themba Lethu Clinic has enrolled approximately 30 000 HIV-positive patients into its HIV care and treatment programme, over 21 000 of whom have received anti-retroviral therapy since being enrolled. Patients on treatment are typically seen at least every 3 months with laboratory monitoring every 6 months to 1 year. The data collected include demographics, clinical visit data, laboratory data, medication history and clinical diagnoses. Requests for collaborations on analyses can be submitted to our data centre.
What are the implications for population health of the demographic trend toward increasing paternal age at conception (PAC) in modern societies? We propose that the effects of older PAC are likely to be broad and harmful in some domains of health but beneficial in others. Harmful effects of older PAC have received the most attention. Thus, for example, older PAC is associated with an increased risk of offspring having rare conditions such as achondroplasia and Marfan syndrome, as well as with neurodevelopmental disorders such as autism. However, newly emerging evidence in the telomere field suggests potentially beneficial effects, since older PAC is associated with a longer leukocyte telomere length (LTL) in offspring, and a longer LTL is associated with a reduced risk of atherosclerosis and with increased survival in the elderly. Thus, older PAC may cumulatively increase resistance to atherosclerosis and lengthen lifespan in successive generations of modern humans. In this paper we: (i) introduce these novel findings; (ii) discuss potential explanations for the effect of older PAC on offspring LTL; (iii) draw implications for population health and for life course; (iv) put forth an evolutionary perspective as a context for the multigenerational effects of PAC; and (v) call for broad and intensive research to understand the mechanisms underlying the effects of PAC. We draw together work across a range of disciplines to offer an integrated perspective of this issue.
Background The present study investigated whether single nucleotide polymorphisms (SNPs) in the alpha-protein kinase 1 (ALPK1) gene are associated with gout in aboriginal and Han Chinese Taiwanese.
Methods A total of 1351 aborigines from the community (511 cases and 840 controls) and 511 Han people from hospital (104 cases and 407 controls) were recruited. SNPs in potentially functional regions of the 38 genes within 4q25 were identified and genotypes determined by direct sequencing. Quantitation of blood ALPK1 mRNA expression levels and luciferase assay of gout-associated rs231253 pGL3-SNP constructs cotransfected with hsa-miR-519e were examined.
Results We found that ALPK1 gene was the most determinant of gout. Three SNPs of rs11726117 M861T [C], rs231247 [G] and rs231253 [G] were most associated with gout risk [odd ratios (OR) ≥1.44, P ≤ 3.78 x 10–6) in aborigines. A replication set using Han people had risk at rs11726117 and rs231247 (OR ≥1.72, P ≤ 4.08 x 10–3). From pooled analysis (Breslow-Day test, P > 0.33) assuming an additive model, each increasing copy of the risk allele of rs11726117 [C], rs231247 [G] and rs231253 [G] showed significantly elevated OR for gout ≥1.42 (P ≥ 1.53 x 10–6). Consistently, the composite homozygous of linked 3 SNPs (versus wild-type, OR = 1.83, P = 8.21 x 10–4) had strong associations with ALPK1 mRNA expression. Luciferase showed reduced hybridization between hsa-miR-519e and construct carrying gout-associated rs231253 [G] than the wild-type [C] (P = 6.19 x 10–4).
Conclusions Our study found that a newly identified ALPK1 gene can effectively interfere with microRNA target recognition and modulates the mRNA expression; and the varying distribution of the implicated SNPs among cases and controls in the two studied populations suggests a significant role in gout susceptibility.
Background At the APOE gene, encoding apolipoprotein E, genotypes of the 2/3/4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.
Methods We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT).
Results The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84–1.43) for 2/2; 0.85 (95% CrI: 0.78–0.92) for 2/3; 1.05 (95% CrI: 0.89–1.24) for 2/4; 1.05 (95% CrI: 0.99–1.12) for 3/4; and 1.12 (95% CrI: 0.94–1.33) for 4/4 using the 3/3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 x 10–152), apolipoprotein B (P-trend: 8.7 x 10–06) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 x 10–26) and HDL-C (P-trend: 1.6 x 10–12). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear.
Conclusions In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE 2/2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
Objectives Using a statistical modelling approach, our study aim is to determine reliable age-related estimates of the risk of all-cause tubal factor infertility (TFI) following past or current chlamydial infection in women in Scotland.
Method Using data from several sources, a Markov-Chain Monte Carlo model was used to estimate the age-related risk of TFI given genital chlamydia infection at any time. The analysis is based on the probability of a woman ever having chlamydial infection, ever having TFI and ever having a previous chlamydial infection given a diagnosis of TFI. The model was programmed and evaluated using WinBugs14.
Results By the age 44 years, the overall risk of a woman having at least a single chlamydial infection is estimated at 42.9% (95% credible interval 30.0, 59.0%). The risk of a woman having TFI increased from 0.5% in those aged 16–19 years to 0.8% in those aged 40–44. The overall estimated probability of TFI, based on lifetime infertility, given a past or current chlamydial infection, is relatively consistent across all five age groups from 16–44 years, being 0.9% among those aged 25–29 and 1.4% in those aged 35–39; The estimates were found to be sensitive to the definition of infertility, with the estimate increasing from 1.3% in the youngest age group to 2.8% and 4.5% for 24-month primary infertility and primary or secondary infertility, respectively.
Conclusions At the population level, the likelihood of all-cause TFI in those with past or current chlamydial infection is low. These findings have relevance both at the policy level, in the development of control programmes, and also at an individual level, particularly for clinicians supporting women undergoing testing or with a positive diagnosis.
Background Maternal pre-pregnancy obesity may be associated with impaired infant neuropsychological development; however, there are few studies and it is unclear if reported associations are due to intrauterine mechanisms.
Methods We assessed whether maternal pre-pregnancy overweight and obesity were associated with cognitive and psychomotor development scores (mean 100 ± 15) of children aged 11–22 months in two birth cohorts: Environment and Childhood (INMA, Spain; n = 1967) and Mother-Child (RHEA, Greece: n = 412). Paternal body mass index (BMI) was used as a negative control exposure.
Results The percentage of overweight and obese mothers was 18% and 8%, respectively, in INMA and 20% and 11% in RHEA, respectively. Maternal pre-pregnancy obesity was associated with reduced infant cognitive development scores in both INMA (score reduction: –2.72; 95% CI: –5.35, –0.10) and RHEA (score reduction: –3.71; 95% CI: –8.45, 1.02), after adjusting for socioeconomic variables and paternal BMI. There was evidence in both cohorts of a dose-response relationship with continuous maternal BMI. Paternal overweight/obesity was not associated with infant cognitive development. Associations with psychomotor scores were not consistent between cohorts, and were stronger for paternal than maternal BMI in RHEA.
Conclusions This study in two birth cohorts with moderately high obesity prevalence suggests that maternal pre-pregnancy obesity is associated with reduced child cognitive development at early ages. This association appears more likely to be due to maternal than shared family and social mechanisms, but further research is needed to disentangle a direct intrauterine effect from other maternal confounding factors.
Progress towards the Millennium Development Goals (MDGs) has been uneven. Inequalities in child health are large and effective interventions rarely reach the most in need. Little is known about how to reduce these inequalities. We describe and explain the equity impact of a women’s group intervention in India that strongly reduced the neonatal mortality rate (NMR) in a cluster-randomised trial. We conducted secondary analyses of the trial data, obtained through prospective surveillance of a population of 228 186. The intervention effects were estimated separately, through random effects logistic regression, for the most and less socio-economically marginalised groups. Among the most marginalised, the NMR was 59% lower in intervention than in control clusters in years 2 and 3 (70%, year 3); among the less marginalised, the NMR was 36% lower (35%, year 3). The intervention effect was stronger among the most than among the less marginalised (P-value for difference = 0.028, years 2-3; P-value for difference = 0.009, year 3). The stronger effect was concentrated in winter, particularly for early NMR. There was no effect on the use of health-care services in either group, and improvements in home care were comparable. Participatory community interventions can substantially reduce socio-economic inequalities in neonatal mortality and contribute to an equitable achievement of the unfinished MDG agenda.
Background We investigate associations of self-reported and objectively assessed walking activity with measures of glucose regulation in a multi-ethnic population at high risk of type 2 diabetes.
Methods This study reports data from a 2009–2011 screening programme for impaired glucose regulation (IGR) within a high-risk primary care population in Leicestershire, UK; 2532 participants (38% women, 8% South Asian) with a mean age of 64 ± 8 years and an average BMI of 32.1 ± 5.6 kg/m2 were included. Walking activity was measured by self-report (International Physical Activity Questionnaire) and objectively (pedometer). Glucose regulation assessments included 2h post-challenge glucose, fasting glucose and HbA1c.
Results Higher levels of self-reported walking activity and pedometer steps were associated with lower 2h post-challenge glucose after controlling for several known confounding variables, including BMI. Similarly, when categorized in tertiles, both measures were associated with a lower odds of having any form of IGR; odds ratio for lowest vs highest tertile was 0.64 (0.51–0.80) for self-report and 0.69 (0.55–0.87) for pedometer steps. There was no significant difference between self-reported and objective measures in the strength of associations with glucose regulation; associations with self-report were maintained when further adjusted for pedometer steps. Stronger associations between self-reported walking activity and glucose regulation were observed in South Asians compared with White Europeans.
Conclusions Self-reported and objectively measured walking activity were equally associated with indices of glucose regulation. Associations with self-reported walking activity were maintained when further adjusted for pedometer steps, suggesting that self-reported walking activity may measure facets of physical activity that are beyond total volume.
Background Certain sites have gained notoriety as ‘hotspots’ for suicide by jumping. Structural interventions (e.g. barriers and safety nets) have been installed at some of these sites. Individual studies examining the effectiveness of these interventions have been underpowered.
Method We conducted a meta-analysis, pooling data from nine studies.
Results Following the interventions, there was an 86% reduction in jumping suicides per year at the sites in question (95% CI 79% to 91%). There was a 44% increase in jumping suicides per year at nearby sites (95% CI 15% to 81%), but the net gain was a 28% reduction in all jumping suicides per year in the study cities (95% CI 13% to 40%).
Conclusions Structural interventions at ‘hotspots’ avert suicide at these sites. Some increases in suicide are evident at neighbouring sites, but there is an overall gain in terms of a reduction in all suicides by jumping.
Background The German East-West mortality difference narrowed rapidly after the 1990 unification, particularly for women. We analyse recent trends for women aged 50–89 years and document for the first time lower mortality in the East. We study how smoking contributes to this cross-over.
Methods We analyse mortality by cause for women aged 50–89 over the years 1992–2009 for the East and West Germany, excluding Berlin. We compare the East-West mortality rate ratio (MRR) for total mortality and after removing smoking-attributable mortality using the indirect Preston-Glei-Wilmoth method.
Results In the early 1990s mortality was higher in the East. By 2000 mortality for ages 50–64 had declined below that of the West and remained lower thereafter. For example, from 1992–94 to 2005–09 the MRR for ages 55–59 declined from 1.27 to 0.87. Smoking explains a third of the MRR change for ages 50–64, and when smoking-attributable deaths are removed the mortality cross-over vanishes. For example, non-smoking-attributable MRR for ages 55–59 is 1.03 in 2005–09. For ages 65–89 smoking matters less, and mortality remains higher in the East.
Conclusions We show for the first time that mortality for middle-aged women is lower in the former East Germany than in the West. Prior studies have documented convergence and suggested improving living standards and medical care as mechanisms. We show that much of the convergence, and the cross-over, are attributable to smoking. The seeds for the female East-West mortality cross-over were planted before the unification, when the women now aged 50–64 adopted their smoking behaviours.
Background Living arrangements have changed markedly in recent decades, so we wanted to provide an up-to-date assessment of mortality as a function of marital status and cohabitation status in a complete population.
Methods We studied mortality in a national cohort of 6.5 million Danes followed for 122.5 million person-years during 1982–2011, using continuously updated individual-level information on living arrangements, socio-demographic covariates and causes of deaths. Hazard ratios (HRs) estimated relative mortality in categories of marital status, cohabitation status and combinations thereof.
Results HRs for overall mortality changed markedly over time, most notably for persons in same-sex marriage. In 2000–2011, opposite-sex married persons (reference, HR = 1) had consistently lower mortality than persons in other marital status categories in women (HRs 1.37–1.89) and men (HRs 1.37–1.66). Mortality was particularly high for same-sex married women (HR = 1.89), notably from suicide (HR = 6.40) and cancer (HR = 1.62), whereas rates for same-sex married men (HR = 1.38) were equal to or lower than those for unmarried, divorced and widowed men. Prior marriages (whether opposite-sex or same-sex) were associated with increased mortality in both women and men (HR = 1.16–1.45 per additional prior marriage).
Conclusion Our study provides a detailed account of living arrangements and their associations with mortality over three decades, thus yielding accurate and statistically powerful analyses of public health relevance to countries with marriage and cohabitation patterns comparable to Denmark’s. Of note, mortality among same-sex married men has declined markedly since the mid-1990s and is now at or below that of unmarried, divorced and widowed men, whereas same-sex married women emerge as the group of women with highest and, in recent years, even further increasing mortality.
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.
Background Age at menarche is an important determinant of hormonal-related neoplasia and other chronic diseases. Spatial and temporal variations in age at menarche have been observed in industrialised countries and several environmental factors were reported to have an influence.
Method We examined geographical variations in self-reported age at menarche and explored the effects of both latitude and ultraviolet radiation (UVR) dose on the onset of menarche in 88 278 women from the French E3N cohort (aged 40–65 years at inclusion).
Results The mean age at menarche was 12.8 years. After adjustment for potential confounders (birth cohort, prematurity, birth weight and length, father’s income index, body silhouette in childhood, food deprivation during World War II, population of birthplace, number of siblings, breastfeeding exposure and indoor exposure to passive smoking during childhood), latitude and UVR dose (annual or spring/summer) in county of birth were significantly associated with age at menarche (Ptrend < 0.0001). Women born at lower latitudes or in regions with higher annual or spring/summer UVR dose had a 3- to 4-month earlier menarche than women born at higher latitudes or in regions with lower UVR. On a continuous scale, a 1° increment in latitude resulted in a 0.04-year older age at menarche [95% confidence interval (CI): 0.03, 0.05], whereas a 1-kJ/m2 increment in annual UVR dose resulted in a 0.42-year younger age at menarche (95% CI: –0.55, –0.29).
Conclusion These data further suggest that light exposure in childhood may influence sexual maturation in women.
Background Only a limited number of studies have investigated the correlation between haematocrit (HCT) and mortality in the general population, and few of those studies have had data on a wide range of low and high levels of HCT. We investigated the association between baseline HCT and mortality in a prospective cohort study of 49 983 adult subjects in Iran with a broad spectrum of HCT values.
Methods Data on socio-demographic and life-style factors, past medical history, and levels of HCT were collected at enrollment. During a mean follow-up of 5 years (follow-up success rate ~99%), 2262 deaths were reported. Cox proportional hazards regression models were used to estimate hazard ratios and corresponding 95% confidence intervals.
Results There was a U-shaped relationship between categories of HCT and mortality in both sexes: both low and high levels of HCT were associated with increased overall mortality and mortality from cardiovascular disease. The U-shaped relationship persisted after several sensitivity analyses were done, including analyses restricted to non-smokers and non-users of opium; analyses excluding deaths from accidents and other external causes as well as deaths of persons with self-reported ischemic heart disease at the baseline interview for the study; and analyses excluding the first 2 years of follow-up. Self-reported past medical history and lack of data about lipids and other cellular blood components were the major limitations of the study.
Conclusions Low and high levels of HCT are associated with increased mortality in the general population. The findings in the present study can be of particular importance for low- and middle-income countries in which a substantial proportion of the population lives with suboptimal levels of HCT.
Background This article aims at providing an overview of the current epidemiological situation in the heterogeneous Eastern Mediterranean Region (EMR). It is one in a series of eight articles appointed by the International Epidemiological Association to improve the epidemiological situation.
Methods Several resources were used to extract morbidity, mortality and risk factors data that contribute mostly to the burden of disease and highlight health inequalities. Medline search was used to estimate epidemiological publications output by country. Indexing status of Index Medicus for the Eastern Mediterranean (IMEMR) journals in Medline/PubMed was checked. A questionnaire was designed to collect data from epidemiological associations on type of work and workforce. Authors’ knowledge and networks were used to get a perspective on the training, research and funding sources.
Results Large inequalities exist between EMR nations especially ones pertaining to social conflicts. The EMR age-standardized disability-adjusted life years rate per 1000 population is higher than the global one, with most contribution of communicable diseases in low- and middle-income countries (45%) and non-communicable diseases in high-income countries (64%). Iran and Pakistan have the highest number of publications from 1996–2012, but Kuwait has the highest rate of publications per 100 000 population. The majority of IMEMR journals are not indexed in Medline/PubMed. Masters in Public Health is the most common form of training.
Conclusions Efforts are required to ameliorate the epidemiological situation. There is a dire need for health evidence-based policy change and for field training of epidemiologists.
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.