Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium.

OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. PARTICIPANTS: 148,731 current, former and never-smokers of European ancestry aged ≥ 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio. RESULTS: The data included up to 66,809 never-smokers, 43,009 former smokers and 38,913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.

Occupational class differences in later life hospital use by women who survived to age 80: the Renfrew and Paisley prospective cohort study.

BACKGROUND: population ageing challenges the sustainability of healthcare provision. OBJECTIVE: to investigate occupational class differences in hospital use in women aged 80+ years. METHODS: a total of 8,353 female residents, aged 45-64, took part in the Renfrew and Paisley prospective cohort study in 1972-76. Information on general and mental health hospital discharges was provided from computerised linkage with the Scottish Morbidity Records data to 31 December 2012. Numbers of admissions and bed-days after the 80th birthday were calculated for all and specific causes. Rate ratios by occupational class were calculated using negative binomial regression analysis, adjusting for age and a range of risk factors. RESULTS: four thousand and four hundred and seven (56%) women survived to age 80 and had 17,563 general admissions thereafter, with a mean stay of 19.4 days. There were no apparent relationships with occupational class for all general admissions, but lower occupational class was associated with higher rate ratios for coronary heart disease and stroke and lower rate ratios for cancer. Adjustment for risk factors could not fully explain the raised rate ratios. Bed-day use was higher in lower occupational classes, especially for stroke. There were strong associations with mental health admissions, especially dementia. Compared with the highest occupational class, admission rate ratios for dementia were higher for the lowest occupational class (adjusted rate ratio = 2.60, 95% confidence interval 1.79-3.77). CONCLUSION: in this population, there were no socio-economic gradients seen in hospital utilisation for general admissions in old age. However, occupational class was associated with mental health admissions, coronary heart disease, stroke and cancer.

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid.

BACKGROUND: Observational studies showed that circulating L-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. OBJECTIVES: We assessed the relation between L-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating L-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-L-ascorbic acid and L-ascorbic acid-outcome associations. DESIGN: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). RESULTS: With the use of a meta-analysis of observational estimates, inverse associations were shown between L-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (-0.13-SD change; 95% CI: -0.20-, -0.07-SD change; P = 0.0001) per SD increase in L-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10⁻6) increase in L-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected. CONCLUSIONS: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of L-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between L-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Explaining the social patterning of lung function in adulthood at different ages: the roles of childhood precursors, health behaviours and environmental factors.

BACKGROUND: Lung function successfully predicts subsequent health. Although lung function is known to decline over age, little is known about changes in association with socioeconomic status (SES) throughout life, and whether explanatory factors for association vary with age or patterns for non smokers. METHODS: Analyses were based on data on 24 500 participants aged ≥18 years from the 1995, 1998 and 2003 Scottish Health Surveys who were invited to provide 1 s forced expiratory volume (FEV1) and forced vital capacity (FVC) lung measurements. Sex-stratified multiple linear regression assessed lung function-SES (occupational social class) associations and attenuation by covariates in three age groups (2003 data (n=7928)). RESULTS: The FEV1-SES patterns were clear (p<0.001) and constant over time. Relative to the least disadvantaged, FEV1 in the most disadvantaged was lower by 0.28 L in men and 0.20 L in women under 40 years compared with differences of 0.51 L in men and 0.25 L in women over 64 years (p(interaction)<0.001 men, p(interaction)=0.004 women). The greatest attenuation of these results was seen by height, parental social class and smoking, especially among the under 65s. Second-hand smoke exposure and urban/rural residence had some impact among older groups. Adjusting for physical activity and weight had little effect generally. Similar patterns were seen for FVC and among never smokers. CONCLUSIONS: We found cross-sectional evidence that SES disparity in lung function increases with age, especially for men. Our findings indicate that early-life factors may predict inequity during younger adulthood, with environmental factors becoming more important at older ages.

In search of the cancer candidate: can lay epidemiology help?

First published in 1991, the ideas embedded in 'Lay epidemiology and the prevention paradox' offered a novel and rational explanation for the lay public's failure to fully engage with the lifestyle messages offered by health educators. During the course of a large ethnographic study in South Wales, Davison and colleagues described the emergence of what they termed the coronary candidate. Candidacy provides a 'cultural mechanism' that facilitates the estimation of risk for coronary heart disease. The model has rarely been applied to other major illnesses. This article presents findings from a study that sought to explore the lay epidemiology model, candidacy and cancer. In a series of in-depth individual interviews, members of the lay public discussed their ideas about cancer, and what emerged was an explanatory hierarchy to account for cancer events. Yet the random and unpredictable nature of cancer was emphasised as well as a general reluctance to accept the idea of cancer candidacy.

Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.

Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4 to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.

Why do males in Scotland die younger than those in England? Evidence from three prospective cohort studies.

BACKGROUND: To examine explanations for the higher rates of male mortality in two Scottish cohorts compared with a cohort in south-east England for which similar data were collected. METHODOLOGY/PRINCIPAL FINDINGS: We compared three cohort studies which recruited participants in the late 1960s and early 1970s. A total of 13,884 men aged 45-64 years at recruitment in the Whitehall occupational cohort (south-east England), 3,956 men in the Collaborative occupational cohort and 6,813 men in the Renfrew & Paisley population-based study (both central Scotland) were included in analyses of all-cause and cause-specific mortality. All-cause mortality was 25% (age-adjusted hazard ratio 1.25, 95% confidence interval (CI)1.21 to 1.30) and 41% (hazard ratio 1.41 (95% CI 1.36 to 1.45) higher in the Collaborative and Renfrew & Paisley cohorts respectively compared to the Whitehall cohort. The higher mortality rates were substantially attenuated by social class (to 8% and 17% higher respectively), and were effectively eliminated upon the further addition of the other baseline risk factors, such as smoking habit, lung function and pre-existing self-reported morbidity. Despite this, coronary heart disease mortality remained 11% and 16% higher, stroke mortality 45% and 37% higher, mortality from accidents and suicide 51% and 70% higher, and alcohol-related mortality 46% and 73% higher in the Collaborative and Renfrew & Paisley cohorts respectively compared with the Whitehall cohort in the fully adjusted model. CONCLUSIONS/SIGNIFICANCE: The higher all-cause, respiratory, and lung cancer male mortality in the Scottish cohorts was almost entirely explained by social class differences and higher prevalence of known risk factors, but reasons for the excess mortality from stroke, alcohol-related causes, accidents and suicide remained unknown.

Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure.

BACKGROUND: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure. METHODS: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730-rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730-rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided. RESULTS: Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730-rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10(-6)) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10(-11)). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730-rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42). CONCLUSIONS: Our data show a stronger association of rs1051730-rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.

Cause specific mortality, social position, and obesity among women who had never smoked: 28 year cohort study.

OBJECTIVE: To investigate the relations between causes of death, social position, and obesity in women who had never smoked. DESIGN: Prospective cohort study. SETTING: Renfrew and Paisley, Scotland. PARTICIPANTS: 8353 women and 7049 men aged 45-64 were recruited to the Renfrew and Paisley Study in 1972-6. Of these, 3613 women had never smoked and were the focus of this study. They were categorised by occupational class (I and II, III non-manual, III manual, and IV and V) and body mass index groups (normal weight, overweight, moderately obese, and severely obese). MAIN OUTCOME MEASURES: All cause and cause specific mortality during 28 years of follow-up by occupational class and body mass index, using Cox proportional hazards models adjusted for age and other confounders. RESULTS: The women in lower occupational classes who had never smoked were on average shorter and had poorer lung function and higher systolic blood pressure than women in the higher occupational classes. Overall, 43% (n = 1555) were overweight, 14% (n = 515) moderately obese, and 5% (n = 194) severely obese. Obesity rates were higher in lower occupational classes and much higher in all occupational classes than in current smokers in the full cohort. Half the women died, 51% (n = 916) from cardiovascular disease and 27% (n = 487) from cancer. Relative to occupational class I and II, all cause mortality rates were more than a third higher in occupational classes III manual (relative rate 1.35, 95% confidence interval 1.16 to 1.57) and IV and V (1.34, 1.17 to 1.55) and largely explained by differences in obesity, systolic blood pressure, and lung function. Similar upward gradients were seen for cardiovascular disease and respiratory disease but not for cancer. Mortality rates were highest in severely obese women in the lowest occupational classes. CONCLUSIONS: Women who had never smoked and were not obese had the lowest mortality rates, regardless of their social position. Where obesity is socially patterned as in this cohort, it may contribute to health inequalities and increase pressure on health and social services serving more disadvantaged populations.

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index.

BACKGROUND: Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. METHODS: We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24,198) and then tested for a genotype × smoking status interaction. RESULTS: There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m(2) [95% confidence interval (95% CI): -0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m(2) (95% CI: 0.13-0.31) lower BMI (P = 8 × 10(-6)). The effect size was larger in current [0.33 kg/m(2) lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10(-5)], than in former smokers [0.16 kg/m(2) (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001). CONCLUSIONS: Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI.

Building on Julian Tudor Hart's example of anticipatory care.

The prevention and delay of chronic disease is an increasing priority in all advanced health-care systems, but sustainable, effective and equitable approaches remain elusive. In a famous pioneering example in the UK, Julian Tudor Hart combined reactive and anticipatory care within routine consultations in primary medical care, while applying a population approach to delivery and audit. This approach combined the structural advantages of UK general practice, including universal coverage and the absence of user fees, with his long-term commitment to individual patients, and was associated with a 28% reduction in premature mortality over a 25-year period. The more recent, and comprehensively evaluated Scottish National Health Service demonstration project, 'Have a Heart Paisley', took a different approach to cardiovascular prevention and health improvement, using population screening for ascertainment, health coaches and referral to specific health improvement programmes for diet, smoking and exercise. We draw from both examples to construct a conceptual framework for anticipatory care, based on active ingredients, programme pathways and whole system approaches. While the strengths of a family practice approach are coverage, continuity, co-ordination and long-term relationships, the larger health improvement programme offered additional resources and expertise. As theory and evidence accrue, the challenge is to combine the strengths of primary medical care and health improvement, in integrated, sustainable systems of anticipatory care, addressing the heterogeneity of individual needs and solutions, while achieving high levels of coverage, continuity, co-ordination and outcome.

The combined effect of smoking tobacco and drinking alcohol on cause-specific mortality: a 30 year cohort study.

BACKGROUND: Smoking and consuming alcohol are both related to increased mortality risk. Their combined effects on cause-specific mortality were investigated in a prospective cohort study. METHODS: Participants were 5771 men aged 35-64, recruited during 1970-73 from various workplaces in Scotland. Data were obtained from a questionnaire and a screening examination. Causes of death were all cause, coronary heart disease (CHD), stroke, alcohol-related, respiratory and smoking-related cancer. Participants were divided into nine groups according to their smoking status (never, ex or current) and reported weekly drinking (none, 1-14 units and 15 or more). Cox proportional hazards models were used to obtain relative rates of mortality, adjusted for age and other risk factors. RESULTS: In 30 years of follow-up, 3083 men (53.4%) died. Compared with never smokers who did not drink, men who both smoked and drank 15+ units/week had the highest all-cause mortality (relative rate = 2.71 (95% confidence interval 2.31-3.19)). Relative rates for CHD mortality were high for current smokers, with a possible protective effect of some alcohol consumption in never smokers. Stroke mortality increased with both smoking and alcohol consumption. Smoking affected respiratory mortality with little effect of alcohol. Adjusting for a wide range of confounders attenuated the relative rates but the effects of alcohol and smoking still remained. Premature mortality was particularly high in smokers who drank 15 or more units, with a quarter of the men not surviving to age 65. 30% of men with manual occupations both smoked and drank 15+ units/week compared with only 13% with non-manual ones. CONCLUSIONS: Smoking and drinking 15+ units/week was the riskiest behaviour for all causes of death.

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study.

BACKGROUND: Antioxidant vitamins are often described as having "independent" associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors. METHODS AND FINDINGS: Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30-59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (alpha-carotene, beta-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3-6.0] to 38.8% [49.9-25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7-13.5]) and waist hip ratio for vitamin E (9.5% [4.8-14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels. CONCLUSIONS: Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.

Record rewards: the effects of targeted quality incentives on the recording of risk factors by primary care providers.

Financial incentives may increase performance on targeted activities and have unintended consequences for untargeted activities. An innovative pay-for-performance scheme was introduced for UK general practices in 2004. It incentivised particular quality indicators for targeted groups of patients. We estimate the intended and unintended consequences of this Quality and Outcomes Framework (QOF) using dynamic panel probit models estimated on individual patient records from 315 general practices over the period 2000/1-2005/6. We focus on annual rates of recording of blood pressure, smoking status, cholesterol, body mass index and alcohol consumption. The recording of each risk factor is designated as incentivised or unincentivised for each individual based on whether they have one of the diseases targeted by the QOF. The effect on incentivised factors was substantially larger on the targeted patient groups (+19.9 percentage points) than on the untargeted groups (+5.3 percentage points). There was no obvious evidence of effort diversion but there was evidence of substantial positive spillovers (+10.9 percentage points) onto unincentivised factors for the targeted groups. Moreover, provider responses were larger on those indicators for which more stringent standards were set and greater rewards offered. We conclude that the incentives induced providers to improve targeted quality and make investments in quality that extended beyond the scheme. We estimate that the average provider was paid pound20 500 for recording 410 additional items of information on the risk factors targeted by the financial incentives. Allowance for the positive spillovers reduces the estimated average reward from pound50 to pound25 per additional record.

Effect of tobacco smoking on survival of men and women by social position: a 28 year cohort study.

OBJECTIVE: To assess the impact of tobacco smoking on the survival of men and women in different social positions. DESIGN: A cohort observational study. SETTING: Renfrew and Paisley, two towns in west central Scotland. PARTICIPANTS: 8353 women and 7049 men aged 45-64 years recruited in 1972-6 (almost 80% of the population in this age group). The cohort was divided into 24 groups by sex (male, female), smoking status (current, former, or never smokers), and social class (classes I + II, III non-manual, III manual, and IV + V) or deprivation category of place of residence. MAIN OUTCOME MEASURE: Relative mortality (adjusted for age and other risk factors) in the different groups; Kaplan-Meier survival curves and survival rates at 28 years. RESULTS: Of those with complete data, 4387/7988 women and 4891/6967 men died over the 28 years. Compared with women in social classes I + II who had never smoked (the group with lowest mortality), the adjusted relative mortality of smoking groups ranged from 1.7 (95% confidence interval 1.3 to 2.3) to 4.2 (3.3 to 5.5). Former smokers' mortalities were closer to those of never smokers than those of smokers. By social class (highest first), age adjusted survival rates after 28 years were 65%, 57%, 53%, and 56% for female never smokers; 41%, 42%, 33%, and 35% for female current smokers; 53%, 47%, 38%, and 36% for male never smokers; and 24%, 24%, 19%, and 18% for male current smokers. Analysis by deprivation category gave similar results. CONCLUSIONS: Among both women and men, never smokers had much better survival rates than smokers in all social positions. Smoking itself was a greater source of health inequality than social position and nullified women's survival advantage over men. This suggests the scope for reducing health inequalities related to social position in this and similar populations is limited unless many smokers in lower social positions stop smoking.

Determinants of birthweight: gender based analysis.

The objective of this cross sectional study is to look at determinants of birth weight and their association with the gender of the baby in 2,795 full term children living in the occupied Palestinian territory, derived from a stratified random sample of 2,994 households in the West Bank and 2,234 households in the Gaza Strip. The response rate was 85%. Multivariable analysis using analysis of variance for mixed models showed that sex and birth order, maternal age and education and to a lesser extent region were determinants of birth weight for all children. The effect of maternal education on birth weight differed for female and male infants, tending to be relatively unchanged for male infants and with mean birth weights increasing with maternal education in female infants. The effect of birth order differed by maternal age, with mean birth weight increasing with maternal age for first and second births; but being unaffected by maternal age for infants of birth order greater than two. We conclude that birth weight is influenced by common biological determinants across cultures, but is also influenced by social, ethnic, and environmental factors that are culture specific, of which some might be gender related.

The impact of consent on observational research: a comparison of outcomes from consenters and non consenters to an observational study.

BACKGROUND: Public health benefits from research often rely on the use of data from personal medical records. When neither patient consent nor anonymisation is possible, the case for accessing such records for research purposes depends on an assessment of the probabilities of public benefit and individual harm. METHODS: In the late 1990s, we carried out an observational study which compared the care given to affluent and deprived women with breast cancer. Patient consent was not required at that time for review of medical records, but was obtained later in the process prior to participation in the questionnaire study. We have re-analysed our original results to compare the whole sample with those who later provided consent. RESULTS: Two important findings emerged from the re-analysis of our data which if presented initially would have resulted in insufficient and inaccurate reporting. Firstly, the reduced dataset contains no information about women presenting with locally advanced or metastatic cancer and we would have been unable to demonstrate one of our initial key findings: namely a larger number of such women in the deprived group. Secondly, our re-analysis of the consented women shows that significantly more women from deprived areas (51 v 31%, p = 0.018) received radiotherapy compared to women from more affluent areas. Previously published data from the entire sample demonstrated no difference in radiotherapy treatment between the affluent and deprived groups. CONCLUSION: The risk benefit assessment made regarding the use of medical records without consent should include the benefits of obtaining research evidence based on 100% of the population and the possibility of inappropriate or insufficient findings if research is confined to consented populations.

Contribution of Midparental BMI and other determinants of obesity in adult offspring.

The aim of this study was to evaluate midparental BMI among intergenerational factors associated with obesity in adult offspring. The data was from an unusual two-generational observational design of 1,477 married couples from Renfrew and Paisley in Scotland who were aged 45-64 years when screened in 1972-1976, and 1,040 sons and 1,298 daughters aged 30-59 years when screened in 1996. BMI was categorized as normal (< 25 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (> or = 30 kg/m(2)) in offspring and parents. Midparental BMI was defined as the mean of the mother's and father's BMI. Low physical activity, nonsmoking status, higher cholesterol level, and manual social class were all associated with increased BMI in offspring. The effect of reported dietary intake was less clear. Offspring of obese parents (defined by midparental BMI) were over four times more likely to be obese than offspring of normal weight parents. Midparental BMI had a strong effect on offspring BMI, independent of social class, smoking habit, physical activity, and reported dietary intake. Adding midparental BMI to the regression model more than doubled the explained variation of offspring BMI from 7.7 to 17%. Every 1 kg/m(2) increment in midparental BMI was associated with a BMI greater by 0.51 kg/m(2) in offspring. We conclude that midparental BMI is a useful simple tool to predict offspring BMI. Whether it represents genetic or environmental family effects, it is easily ascertained by the individual and could be used in health promotion and clinical settings to target individuals who are at increased risk of becoming obese.