Lusting, learning and lasting in school: sexual debut, school performance and dropout among adolescents in primary schools in Karonga district, northern Malawi.

Age at sexual debut is known to have implications for future sexual behaviours and health outcomes, including HIV infection, early pregnancy and maternal mortality, but may also influence educational outcomes. Longitudinal data on schooling and sexual behaviour from a demographic surveillance site in Karonga district, northern Malawi, were analysed for 3153 respondents between the ages of 12 and 25 years to examine the association between sexual debut and primary school dropout, and the role of prior school performance. Time to dropout was modelled using the Fine and Gray survival model to account for the competing event of primary school completion. To deal with the time-varying nature of age at sexual debut and school performance, models were fitted using landmark analyses. Sexual debut was found to be associated with a five-fold increase in rate of subsequent dropout for girls and a two-fold increase in dropout rate for boys (adjusted hazard ratio [aHR] of 5.27, CI 4.22-6.57, and 2.19, CI 1.77-2.7, respectively). For girls who were sexually active by age 16, only 16% ultimately completed primary schooling, compared with 70% aged 18 or older at sexual debut. Prior to sexual debut, girls had primary completion levels similar to those of boys. The association between sexual debut and school dropout could not be explained by prior poor school performance: the effect of sexual debut on dropout was as strong among those who were not behind in school as among those who were overage for their school grade. Girls who were sexually active were more likely to repeat a grade, with no effect being seen for boys. Pathways to dropout are complex and may differ for boys and girls. Interventions are needed to improve school progression so children complete primary school before sexual debut, and to improve sex education and contraception provision.

The influence of school in the development of eating disorders: a record-linkage study.

BACKGROUND: Clinical impression is that rates of eating disorders vary between schools; we are not aware of any previous research on this topic. We aimed to investigate whether rates of eating disorders in 16-20-year-old girls vary between upper secondary schools, and to test the hypothesis that school characteristics are associated with rates of eating disorders, even after accounting for characteristics of individual students. METHODS: This multilevel longitudinal study made use of record-linkage data from Stockholm County, Sweden. Participants were 55 824 Swedish-born girls completing secondary education in 2001-10 at 409 schools. Outcome was any diagnosed eating disorder at 16-20 years, as defined by an ICD (9 or 10) or DSM-IV code, or inferred from an appointment at a specialist eating disorder clinic. Multilevel modelling was used to separate individual and school level effects. The Stockholm Regional Ethical Review Board approved the study. FINDINGS: A 4·4% variation in incidence of eating disorders between schools was seen; after taking individual risk factors into account variation between schools was 2·9% (95% CI 1·5-5·0). Schools with a higher proportions of girls than boys had an increased incidence of eating disorders: for each 10% increase in the proportion of girls at a school, the odds ratio for eating disorders was 1·07 (95% CI 1·01-1·13, p=0·017). For each 10% increase in the proportion of parents with post-secondary education, the odds ratio for eating disorders was 1·14 (1·09-1·19, p<0·0001). INTERPRETATION: Our findings show that the contextual aspects of a school environment are associated with increased incidence of eating disorders. Incidence rates of eating disorders are higher in schools characterised by a high proportion of female students and of students with highly educated parents. To our knowledge, this is the first study to investigate whether rates of eating disorders vary between schools; however, use of registry data means that individuals who did not seek treatment would not have been studied. FUNDING: HB was supported by a Wellcome Trust Institutional Strategic Support Fund (via the Elizabeth Blackwell Institute).

Life-Course Partnership Status and Biomarkers in Midlife: Evidence From the 1958 British Birth Cohort.

OBJECTIVES: We examined the association between trajectories of partnership status over the life course and objectively measured health indicators in midlife. METHODS: We used data from 4 waves (1981, 1991, 2000, and 2002-2004) of the British National Child Development Study (NCDS), a prospective cohort study that includes all people born in Britain during 1 week in March 1958 (n = 18 558). RESULTS: After controlling for selection attributable to early-life and early-adulthood characteristics, we found that life-course trajectories of partnership status were associated with hemostatic and inflammatory markers, the prevalence of metabolic syndrome and respiratory function in midlife. Never marrying or cohabiting was negatively associated with health in midlife for both genders, but the effect was more pronounced in men. Women who had married in their late 20s or early 30s and remained married had the best health in midlife. Men and women in cohabiting unions had midlife health outcomes similar to those in formal marriages. CONCLUSIONS: Partnership status over the life course has a cumulative effect on a wide range of objectively measured health indicators in midlife.

Parental mental illness and eating disorders in offspring.

OBJECTIVE: To investigate which parental mental illnesses are associated with eating disorders in their offspring. METHOD: We used data from a record-linkage cohort study of 158,679 children aged 12-24 years at the end of follow-up, resident in Stockholm County from 2001 to 2007, to investigate whether different parental mental illnesses are risk factors for eating disorders in their offspring. The outcome measure was diagnosis of any eating disorder, either from an ICD or DSM-IV code, or inferred from an appointment at a specialist eating disorder clinic. RESULTS: Mental illness in parents is a risk factor for eating disorders in female offspring (Adjusted Hazard Ratio (AHR) 1.57 (95% CI 1.42, 1.92), p < 0.0001). Risk of eating disorders is increased if there is a parental diagnosis of bipolar affective disorder (AHR 2.28 (95% CI 1.39, 3.72), p = 0.004), personality disorder (AHR 1.57 (95% CI 1.01, 2.44), p = 0.043) or anxiety/depression (AHR 1.57 (95% CI 1.32, 1.86), p < 0.0001). There is a lack of statistical evidence for an association with parental schizophrenia (AHR 1.41 (95% CI 0.96, 2.07), p = 0.08), and somatoform disorder (AHR 1.25 (95% CI 0.74, 2.13), p = 0.40). There is no support for a relationship between parental substance misuse and eating disorders in children (AHR 1.08 (95% CI 0.82, 1.43), p = 0.57). DISCUSSION: Parental mental illness, specifically parental anxiety, depression, bipolar affective disorder, and personality disorders, are risk factors for eating disorders in their offspring.

Health differentials in the older population of England: an empirical comparison of the materialist, lifestyle and psychosocial hypotheses.

BACKGROUND: In developed countries with old age structures most deaths occur at older ages and older people account for the majority of those in poor health, which suggests a particular need to investigate health inequalities in the older population. METHODS: We empirically compared the materialist, psychosocial and lifestyle/behavioural theoretical mechanisms of explanation for socio-economic variation in health using data from two waves of the English Longitudinal Study of Ageing (ELSA), a nationally representative multi-purpose sample of the population aged 50 and over living in England. Three dimensions of health were examined: somatic health, depression and well-being. RESULTS: The materialist and lifestyle/behavioural paths had the most prominent mediating role in the association between socio-economic position and health in the older population, whereas the psychosocial pathway was less influential and exerted most of its influence on depression and well-being, with part of its effect being due to the availability of material resources. CONCLUSIONS: From a policy perspective there is therefore an indication that population interventions to reduce health differentials and thus improve the overall health of the older population should focus on material circumstances and population based interventions to promote healthy lifestyles.

Are active children and young people at increased risk of injuries resulting in hospital admission or accident and emergency department attendance? Analysis of linked cohort and electronic hospital records in Wales and Scotland.

INTRODUCTION: Children and young people (CYP) are encouraged to increase time spent being physically active, especially in moderate and vigorous intensity pursuits. However, there is limited evidence on the prospective association of activity levels with injuries resulting in use of hospital services. We examined the relationship between objectively-measured physical activity (PA) and subsequent injuries resulting in hospital admissions or accident and emergency department (A&E) attendances, using linked electronic hospital records (EHR) from a nationally representative prospective cohort of CYP in Wales and Scotland. METHODS: We analysed accelerometer-based estimates of moderate to vigorous (MVPA) and vigorous PA (VPA) from 1,585 (777 [46%] boys) seven-year-old Millennium Cohort Study members, living in Wales or Scotland, whose parents consented to linkage of cohort records to EHRs up until their 14th birthday. Negative binomial regression models adjusted by potential individual, household and area-level confounders, were fitted to estimate associations between average daily minutes of MVPA, and VPA (in 10-minute increments), and number of injury-related hospital admissions and/or A&E attendances from age nine to 14 years. RESULTS: CYP spent a median of 59.5 and 18.1 minutes in MVPA and VPA/day respectively, with boys significantly more active than girls; 47.3% of children experienced at least one injury-related admission or A&E attendance during the study period. Rates of injury-related hospital admission and/or A&E attendance were positively associated with MVPA and VPA in boys but not in girls: respective adjusted incidence rate ratios (95% CI) for boys: 1.09 (1.01, 1.17) and 1.16 (1.00, 1.34), and for girls: 0.94 (0.86, 1.03) and 0.85 (0.69, 1.04). CONCLUSION: Boys but not girls who engage in more intense PA at age seven years are at higher risk of injury-related hospital admission or A&E attendance when aged nine to 14 years than their less active peers. This may reflect gender differences in the type and associated risks of activities undertaken. EHRs can make a useful contribution to injury surveillance and prevention if routinely augmented with information on context and setting of the injuries sustained. Injury prevention initiatives should not discourage engagement in PA and outdoor play given their over-riding health and social benefits.

Exploratory study of the impact of perceived reward on habit formation.

BACKGROUND: Habits (learned automatic responses to contextual cues) are considered important in sustaining health behaviour change. While habit formation is promoted by repeating behaviour in a stable context, little is known about what other variables may contribute, and whether there are variables which may accelerate the habit formation process. The aim of this study was to explore variables relating to the perceived reward value of behaviour - pleasure, perceived utility, perceived benefits, and intrinsic motivation. The paper tests whether reward has an impact on habit formation which is mediated by behavioural repetition, and whether reward moderates the relationship between repetition and habit formation. METHODS: Habit formation for flossing and vitamin C tablet adherence was investigated in the general public following an intervention, using a longitudinal, single-group design. Of a total sample of 118 participants, 80 received an online vitamin C intervention at baseline, and all 118 received a face-to-face flossing intervention four weeks later. Behaviour, habit, intention, context stability (whether the behaviour was conducted in the same place and point in routine every time), and reward variables were self-reported every four weeks, for sixteen weeks. Structured equation modelling was used to model reward-related variables as predictors of intention, repetition, and habit, and as moderators of the repetition-habit relationship. RESULTS: Habit strength and behaviour increased for both target behaviours. Intrinsic motivation and pleasure moderated the relationship between behavioural repetition and habit. Neither perceived utility nor perceived benefits predicted behaviour nor interacted with repetition. Limited support was obtained for the mediation hypothesis. Strong intentions unexpectedly weakened the repetition-habit relationship. Context stability mediated and for vitamin C, also moderated the repetition-habit relationship. CONCLUSIONS: Pleasure and intrinsic motivation can aid habit formation through promoting greater increase in habit strength per behaviour repetition. Perceived reward can therefore reinforce habits, beyond the impact of reward upon repetition. Habit-formation interventions may be most successful where target behaviours are pleasurable or intrinsically valued.

Early school failure predicts teenage pregnancy and marriage: A large population-based cohort study in northern Malawi.

BACKGROUND: School dropout has been linked to early pregnancy and marriage but less is known about the effect of school performance. We aimed to assess whether school performance influenced age at sexual debut, pregnancy and marriage, and from what age school drop-out and performance were associated with these later life events. METHODS: Data from 2007-2016 from a demographic surveillance site in northern Malawi with annual updating of schooling status and grades, and linked sexual behaviour surveys, were analysed to assess the associations of age-specific school performance (measured as age-for-grade) and status (in or out of school) on subsequent age at sexual debut, pregnancy and marriage. Landmark analysis with Cox regression was used to estimate hazard ratios of sexual debut, pregnancy and marriage by schooling at selected (landmark) ages, controlling for socio-economic factors. RESULTS: Information on at least one outcome was available for >16,000 children seen at ages 10-18. Sexual debut was available on a subset aged ≥15 by 2011. For girls, being out of school was strongly associated with earlier sexual debut, pregnancy and marriage. For example, using schooling status at age 14, compared to girls in primary, those who had dropped out had adjusted hazard ratios of subsequent sexual debut, pregnancy and marriage of 5.39 (95% CI 3.27-8.86), 2.39 (1.82-3.12), and 2.76 (2.08-3.67) respectively. For boys, the equivalent association with sexual debut was weak, 1.92 (0.81-4.55), but that with marriage was strong, 3.74 (2.28-6.11), although boys married later. Being overage-for-grade was not associated with sexual debut for girls or boys. For girls, being overage-for-grade from age 10 was associated with earlier pregnancy and marriage (e.g. adjusted hazard ratio 2.84 (1.32-6.17) for pregnancy and 3.19 (1.47-6.94) for marriage, for those ≥3 years overage compared to those on track at age 10). For boys, overage-for-grade was associated with earlier marriage from age 12, with stronger associations at older ages (e.g. adjusted hazard ratio 2.41 (1.56-3.70) for those ≥3 years overage compared to those on track at age 14). For girls ≥3 years overage at age 14, 39% were pregnant before they were 18, compared to 18% of those who were on track. The main limitation was the use of reported ages of sexual debut, pregnancy and marriage. CONCLUSIONS: School progression at ages as young as 10 can predict teenage pregnancy and marriage, even after adjusting for socio-economic factors. Early education interventions may reduce teenage pregnancy and marriage as well as improving learning.

Does early linear growth failure influence later school performance? A cohort study in Karonga district, northern Malawi.

INTRODUCTION: Stunting or linear growth retardation in childhood is associated with delayed cognitive development due to related causes (malnutrition, illness, poor stimulation), which leads to poor school outcomes at later ages, although evidence of the association between the timing and persistence of stunting and school outcomes within the sub-Saharan African context is limited. METHODS: Anthropometric data around birth (0-4 months), early (11-16 months) and late childhood (ages 4-8 years) along with school outcomes up until the age of 11 were analysed for a cohort of 1,044 respondents, born between 2002-2004 in Karonga district, northern Malawi. The schooling outcomes were age at school enrolment, grade repetition in Standard 1 and age-for-grade by age 11. Height-for-Age Z-scores (HAZ) and growth trajectories were examined as predictors, based on stunting (<-2SD HAZ) and on trajectories between early and late childhood (never stunted, improvers, decliners or persistently stunted). Multinomial and logistic regression were used to estimate the association between stunting/trajectories and schooling, adjusted for socioeconomic confounders. RESULTS: The effects of stunting on schooling were evident in early childhood but were more pronounced in late childhood. Children who were stunted in early childhood (9.3%) were less likely to be underage at enrolment, more likely to repeat Standard 1 and were 2-3 times more likely to be overage for their grade by the age of 11, compared to their non-stunted peers. Those persistently stunted between early and late childhood (7.3%) faced the worst consequences on schooling, being three times as likely to enrol late and 3-5 times more likely to be overage for their grade by the age of 11, compared to those never stunted. Compared to improvers, those persistently stunted were three times as likely to be overage by two or more years by the age of 11, with no effect on enrolment or repetition. CONCLUSION: Our findings confirm the importance of early childhood stunting on schooling outcomes and suggest some mitigation by improvements in growth by the age of starting school. The nutritional and learning needs of those persistently stunted may need to be prioritised in future interventions.

How good is probabilistic record linkage to reconstruct reproductive histories? Results from the Aberdeen Children of the 1950s study.

BACKGROUND: Probabilistic record linkage is widely used in epidemiology, but studies of its validity are rare. Our aim was to validate its use to identify births to a cohort of women, being drawn from a large cohort of people born in Scotland in the early 1950s. METHODS: The Children of the 1950s cohort includes 5868 females born in Aberdeen 1950-56 who were in primary schools in the city in 1962. In 2001 a postal questionnaire was sent to the cohort members resident in the UK requesting information on offspring. Probabilistic record linkage (based on surname, maiden name, initials, date of birth and postcode) was used to link the females in the cohort to birth records held by the Scottish Maternity Record System (SMR 2). RESULTS: We attempted to mail a total of 5540 women; 3752 (68%) returned a completed questionnaire. Of these 86% reported having had at least one birth. Linkage to SMR 2 was attempted for 5634 women, one or more maternity records were found for 3743. There were 2604 women who reported at least one birth in the questionnaire and who were linked to one or more SMR 2 records. When judged against the questionnaire information, the linkage correctly identified 4930 births and missed 601 others. These mostly occurred outside of Scotland (147) or prior to full coverage by SMR 2 (454). There were 134 births incorrectly linked to SMR 2. CONCLUSION: Probabilistic record linkage to routine maternity records applied to population-based cohort, using name, date of birth and place of residence, can have high specificity, and as such may be reliably used in epidemiological research.

Association of violence with emergence of persecutory delusions in untreated schizophrenia.

OBJECTIVE: Psychosis is considered an important risk factor for violence, but studies show inconsistent results. The mechanism through which psychotic disorders influence violence also remains uncertain. The authors investigated whether psychosis increased the risk of violent behavior among released prisoners and whether treatment reduced this risk. They also explored whether active symptoms of psychosis at the time of violent behavior explained associations between untreated psychosis and violence. METHOD: The U.K. Prisoner Cohort Study is a prospective longitudinal study of prisoners followed up in the community after release. Adult male and female offenders serving sentences of 2 or more years for a sexual or violent offense were classified into four groups: no psychosis (N=742), schizophrenia (N=94), delusional disorder (N=29), and drug-induced psychosis (N=102). Symptoms of psychosis, including hallucinations, thought insertion, strange experiences, and delusions of persecution, were measured before and after release. Information on violence between release and follow-up was collected through self-report and police records. RESULTS: Schizophrenia was associated with violence but only in the absence of treatment (odds ratio=3.76, 95% CI=1.39-10.19). Untreated schizophrenia was associated with the emergence of persecutory delusions at follow-up (odds ratio=3.52, 95% CI=1.18-10.52), which were associated with violence (odds ratio=3.68, 95% CI=2.44-5.55). The mediating effects of persecutory delusions were confirmed in mediation analyses (ß=0.02, 95% CI=0.01-0.04). CONCLUSIONS: The results indicate that the emergence of persecutory delusions in untreated schizophrenia explains violent behavior. Maintaining psychiatric treatment after release can substantially reduce violent recidivism among prisoners with schizophrenia. Better screening and treatment of prisoners is therefore essential to prevent violence.

Acute alcohol-related dysfunction as a predictor of employment status in a longitudinal study of working-age men in Izhevsk, Russia.

AIMS: To investigate longitudinally the effect of alcohol consumption and related acute alcohol-related dysfunction on employment status. DESIGN, SETTING AND PARTICIPANTS: A total of 1143 men aged 25-55 years in regular paid employment and resident in the city of Izhevsk, Russia were interviewed between 2003-06 and then re-interviewed (2008-09) and their employment status ascertained. MEASUREMENTS: Exposures of interest were baseline alcohol intake (yearly total volume of ethanol consumed and non-beverage alcohols) and alcohol-related dysfunction, measured by a latent variable defined in terms of frequency of alcohol-related dysfunctional behaviours and by one or more episodes of zapoi (a period of continuous drunkenness lasting 2 or more days). The outcome of interest was whether or not men were still in regular paid employment at follow-up. The inter-relationship between these variables was investigated using structural equation modelling. FINDINGS: Total volume of ethanol consumed had no substantive effect on future employment status; however, taking into account education and other socio-demographic factors, there was strong evidence that loss of regular paid employment at follow-up was influenced by non-beverage alcohol consumption [odds ratio = 2.30 for non-beverage drinkers compared with beverage-only drinkers, 95% confidence interval (CI) = 1.21, 4.40)], latent acute alcohol-related dysfunction (odds ratio = 1.50 per standard deviation increase in dysfunction score, 95% CI = 1.20, 1.88) and zapoi (odds ratio = 3.08, 95% CI = 1.71, 5.55). Acute alcohol-related dysfunction was an important mediator of the relationship between non-beverage alcohol use and employment status. CONCLUSIONS: Acute alcohol-related dysfunction is an important factor in determining whether men remain in employment and an important mediator of the effects of alcohol intake.

Lifelong Socio Economic Position and biomarkers of later life health: testing the contribution of competing hypotheses.

The relative contribution of early or later life Socio Economic Position (SEP) to later life health is not fully understood and there are alternative hypotheses about the pathways through which they may influence health. We used data from the English Longitudinal Study of Ageing with a formal approach for the identification of mediating factors in order to investigate alternative hypotheses about life course influences on biomarkers of later life health. We found that early life SEP predicts physical health at least 65 years later. However, a more complicated pattern of associations than that implied by previous findings was also observed. Age group specific effects emerged, with current SEP dominating the effect on later life physical health and fibrinogen levels in participants under 65, while early life SEP had a more prominent role in explaining inequalities in physical health for men and women over 75. We extend previous findings on mid adulthood and early old age, to old age and the beginnings of late old age. The complexity of our findings highlights the need for further research on the mechanisms that underlie the association between SEP and later life health.

Activities of daily living associated with acquisition of melioidosis in northeast Thailand: a matched case-control study.

BACKGROUND: Melioidosis is a serious infectious disease caused by the Category B select agent and environmental saprophyte, Burkholderia pseudomallei. Most cases of naturally acquired infection are assumed to result from skin inoculation after exposure to soil or water. The aim of this study was to provide evidence for inoculation, inhalation and ingestion as routes of infection, and develop preventive guidelines based on this evidence. METHODS/PRINCIPAL FINDINGS: A prospective hospital-based 1∶2 matched case-control study was conducted in Northeast Thailand. Cases were patients with culture-confirmed melioidosis, and controls were patients admitted with non-infectious conditions during the same period, matched for gender, age, and diabetes mellitus. Activities of daily living were recorded for the 30-day period before onset of symptoms, and home visits were performed to obtain drinking water and culture this for B. pseudomallei. Multivariable conditional logistic regression analysis based on 286 cases and 512 controls showed that activities associated with a risk of melioidosis included working in a rice field (conditional odds ratio [cOR] = 2.1; 95% confidence interval [CI] 1.4-3.3), other activities associated with exposure to soil or water (cOR = 1.4; 95%CI 0.8-2.6), an open wound (cOR = 2.0; 95%CI 1.2-3.3), eating food contaminated with soil or dust (cOR = 1.5; 95%CI 1.0-2.2), drinking untreated water (cOR = 1.7; 95%CI 1.1-2.6), outdoor exposure to rain (cOR = 2.1; 95%CI 1.4-3.2), water inhalation (cOR = 2.4; 95%CI 1.5-3.9), current smoking (cOR = 1.5; 95%CI 1.0-2.3) and steroid intake (cOR = 3.1; 95%CI 1.4-6.9). B. pseudomallei was detected in water source(s) consumed by 7% of cases and 3% of controls (cOR = 2.2; 95%CI 0.8-5.8). CONCLUSIONS/SIGNIFICANCE: We used these findings to develop the first evidence-based guidelines for the prevention of melioidosis. These are suitable for people in melioidosis-endemic areas, travelers and military personnel. Public health campaigns based on our recommendations are under development in Thailand.

Gang membership, violence, and psychiatric morbidity.

OBJECTIVE: Gang members engage in many high-risk activities associated with psychiatric morbidity, particularly violence-related ones. The authors investigated associations between gang membership, violent behavior, psychiatric morbidity, and use of mental health services. METHOD: The authors conducted a cross-sectional survey of 4,664 men 18-34 years of age in Great Britain using random location sampling. The survey oversampled men from areas with high levels of violence and gang activities. Participants completed questionnaires covering gang membership, violence, use of mental health services, and psychiatric diagnoses measured using standardized screening instruments. RESULTS: Violent men and gang members had higher prevalences of mental disorders and use of psychiatric services than nonviolent men, but a lower prevalence of depression. Violent ruminative thinking, violent victimization, and fear of further victimization accounted for the high levels of psychosis and anxiety disorders in gang members, and with service use in gang members and other violent men. Associations with antisocial personality disorder, substance misuse, and suicide attempts were explained by factors other than violence. CONCLUSIONS: Gang members show inordinately high levels of psychiatric morbidity, placing a heavy burden on mental health services. Traumatization and fear of further violence, exceptionally prevalent in gang members, are associated with service use. Gang membership should be routinely assessed in individuals presenting to health care services in areas with high levels of violence and gang activity. Health care professionals may have an important role in promoting desistence from gang activity.

Development and evaluation of a semi-quantitative food frequency questionnaire for use in urban and rural India.

The objective of this study was to develop and evaluate a semi-quantitative food frequency questionnaire (FFQ) for use in urban and rural India. A single FFQ was developed for use in cities and rural areas of four regions of India. To assess validity, the FFQ was administered to 530 factory workers and rural dwellers, and subsequently three 24 hour recalls were administered on different days. Nutrient and food group intake calculated from these two methods were compared using medians, kappa statistics, Spearman's correlation coefficients and Bland- Altman plots. Dietary intake was overestimated by the FFQ compared to the 24 hour recalls (mean difference in energy intake = 1743 kJ), with kappa statistics ranging from 0.07 (egg) to 0.51 (carbohydrate). The results showed acceptable validity for measuring intakes of groups, and demonstrated that it is feasible to measure dietary intake in diverse regions of India with a single FFQ.

Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women.

OBJECTIVE: To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy). DESIGN: Multicentre, randomised, placebo controlled, double blind trial. SETTING: General practices in UK (384), Australia (91), and New Zealand (24). PARTICIPANTS: Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56,583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22,300) started treatment. INTERVENTIONS: Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned. PRIMARY OUTCOMES: major cardiovascular disease, osteoporotic fractures, and breast cancer. SECONDARY OUTCOMES: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life. RESULTS: The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women's health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 v 0, P=0.016) and venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences. CONCLUSIONS: Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause. The results are consistent with the findings of the women's health initiative study and secondary prevention studies. Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause, when the effect may be different. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 63718836.

Limits to causal inference based on Mendelian randomization: a comparison with randomized controlled trials.

"Mendelian randomization" refers to the random assortment of genes transferred from parent to offspring at the time of gamete formation. This process has been compared to a randomized controlled trial of genetic variants. This could greatly aid observational epidemiology by potentially allowing an unbiased estimate of the effects of gene products on disease outcomes. However, studies utilizing Mendelian randomization to estimate effects of gene products on outcomes should be interpreted with caution. In this paper, the authors discuss some of the challenges facing epidemiologists in the analysis and interpretation of Mendelian randomization studies, particularly those that become apparent when the analogy with randomized controlled trials is closely examined. The authors conclude that Mendelian randomization is a powerful addition to etiologic research tools. However, care must be taken, because drawing valid causal inferences from its application depends upon more extensive assumptions than are required in randomized controlled trials.