Inequalities in reported use of breast and cervical screening in Great Britain: analysis of cross sectional survey data

Objective To investigate the relation between women’s reported use of breast and cervical screening and sociodemographic characteristics

Reported frequency of physical activity in a large epidemiological study: relationship to specific activities and repeatability over time

BACKGROUND How overall physical activity relates to specific activities and how reported activity changes over time may influence interpretation of observed associations between physical activity and health. We examine the relationships between various physical activities self-reported at different times in a large cohort study of middle-aged UK women. METHODS At recruitment, Million Women Study participants completed a baseline questionnaire including questions on frequency of strenuous and of any physical activity. About 3 years later 589,896 women also completed a follow-up questionnaire reporting the hours they spent on a range of specific activities. Time spent on each activity was used to estimate the associated excess metabolic equivalent hours (MET-hours) and this value was compared across categories of physical activity reported at recruitment. Additionally, 18,655 women completed the baseline questionnaire twice, at intervals of up to 4 years; repeatability over time was assessed using the weighted kappa coefficient (κweighted) and absolute percentage agreement. RESULTS The average number of hours per week women reported doing specific activities was 14.0 for housework, 4.5 for walking, 3.0 for gardening, 0.2 for cycling, and 1.4 for all strenuous activity. Time spent and the estimated excess MET-hours associated with each activity increased with increasing frequency of any or strenuous physical activity reported at baseline (tests for trend, P < 0.003), although the associations for housework were by far the weakest (Spearman correlations, 0.01 and -0.03 respectively for housework, and 0.11-0.37 for all other activities). Repeatability of responses to physical activity questions on the baseline questionnaire declined significantly over time. For strenuous activity, absolute agreement was 64% (κweighted = 0.71) for questionnaires administered less than 6 months apart, and 52% (κweighted = 0.51) for questionnaires more than 2 years apart. Corresponding values for any physical activity were 57% (κweighted = 0.67) and 47% (κweighted = 0.58). CONCLUSIONS In this cohort, responses to simple questions on the frequency of any physical activity and of strenuous activity asked at baseline were associated with hours spent on specific activities and the associated estimated excess MET-hours expended, reported 3 years later. The weakest associations were with housework. Agreement for identical questions asked on two occasions about the frequency of physical activity decreased over time.This work was supported by public funds from Cancer Research UK and the UK Medical Research Council

Body mass index and incident coronary heart disease in women: a population-based prospective study

BACKGROUND A high body mass index (BMI) is associated with an increased risk of mortality from coronary heart disease (CHD); however, a low BMI may also be associated with an increased mortality risk. There is limited information on the relation of incident CHD risk across a wide range of BMI, particularly in women. We examined the relation between BMI and incident CHD overall and across different risk factors of the disease in the Million Women Study. METHODS 1.2 million women (mean age=56 years) participants without heart disease, stroke, or cancer (except non-melanoma skin cancer) at baseline (1996 to 2001) were followed prospectively for 9 years on average. Adjusted relative risks and 20-year cumulative incidence from age 55 to 74 years were calculated for CHD using Cox regression. RESULTS After excluding the first 4 years of follow-up, we found that 32,465 women had a first coronary event (hospitalization or death) during follow-up. The adjusted relative risk for incident CHD per 5 kg/m2 increase in BMI was 1.23 (95% confidence interval (CI) 1.22 to 1.25). The cumulative incidence of CHD from age 55 to 74 years increased progressively with BMI, from 1 in 11 (95% CI 1 in 10 to 12) for BMI of 20 kg/m2, to 1 in 6(95% CI 1 in 5 to 7) for BMI of 34 kg/m2. A 10 kg/m2 increase in BMI conferred a similar risk to a 5-year increment in chronological age. The 20 year cumulative incidence increased with BMI in smokers and non-smokers, alcohol drinkers and non-drinkers, physically active and inactive, and in the upper and lower socioeconomic classes. In contrast to incident disease, the relation between BMI and CHD mortality (n=2,431) was J-shaped. For the less than 20 kg/m2 and ≥35 kg/m2 BMI categories, the respective relative risks were 1.27 (95% CI 1.06 to 1.53) and 2.84 (95% CI 2.51 to 3.21) for CHD deaths, and 0.89 (95% CI 0.83 to 0.94) and 1.85 (95% CI 1.78 to 1.92) for incident CHD. CONCLUSIONS CHD incidence in women increases progressively with BMI, an association consistently seen in different subgroups. The shape of the relation with BMI differs for incident and fatal disease.The Million Women Study is funded by Cancer Research UK, the Medical Research Council, and the NHS Breast Screening Programme. The funding organizations were not involved in the study design or conduct, data analysis or interpretation, manuscript preparation or review, final version approval, or decision to submit the manuscript

Body size from birth to middle age and the risk of hip and knee replacement

Background: Information regarding the effects of body size in childhood and early adulthood on the risk of hip and knee replacement in later life is inconsistent. We aimed to assess their effect, taking into account body mass index (BMI) in middle-age. Methods: Prospective cohort (Million Women Study) of 791,034 women with information on birth weight, body size at age 10 and age 20, and current BMI (at mean age 59.5 years) were followed for 6.82 million person-years. Adjusted relative risks (RRs) and absolute risks of hospitalisations for hip or knee replacement surgery for osteoarthritis were estimated. Results: After a mean of 8.6 years follow-up, 17,402 women had a hip replacement and 18,297 a knee replacement. Between the ages of 50 and 79 years, absolute risks for women with current BMIs of <22.5 kg/m2 and 35 + kg/m2 were respectively 5.6 and 13.2 % for hip replacement; and 2.6 and 35.1 % for knee replacement. Within each category of current BMI, increasing body size at age 10 and at age 20 had comparatively small effects; there were no significant associations with birth weight. We estimate that 40 % of UK women with a BMI 35 + kg/m2 have either a hip or knee replacement between the ages of 50–79 years; this compares to just 10 % of UK women with a healthy BMI (<25 kg/m2). Conclusions: The effects of body size in childhood and early adulthood on the absolute risks of either a hip or knee replacement are minimal compared to the effect of adiposity in middle ag

Linear law for the logarithms of the Riemann periods at simple critical zeta zeros

Each simple zero 1/2 + iγn of the Riemann zeta function on the critical line with γn > 0 is a center for the flow s˙ = ξ(s) of the Riemann xi function with an associated period Tn. It is shown that, as γn →∞, log Tn ≥ π/4 γn + O(log γn). Numerical evaluation leads to the conjecture that this inequality can be replaced by an equality. Assuming the Riemann Hypothesis and a zeta zero separation conjecture γn+1 − γn≥ γn-θ for some exponent θ > 0, we obtain the upper bound log Tn ≤ γn2 + θ Assuming a weakened form of a conjecture of Gonek, giving a bound for the reciprocal of the derivative of zeta at each zero, we obtain the expected upper bound for the periods so, conditionally, log Tn = π/ 4 γn +O(log γn). Indeed, this linear relationship is equivalent to the given weakened conjecture, which implies the zero separation conjecture, provided the exponent is sufficiently large. The frequencies corresponding to the periods relate to natural eigenvalues for the Hilbert–Polya conjecture. They may provide a goal for those seeking a self-adjoint operator related to the Riemann hypothesis

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort

Objective To examine the hypothesis that risk of oesophageal, but not of gastric or colorectal, cancer is increased in users of oral bisphosphonates

Tobacco smoking and all-cause mortality in a large Australian cohort study: findings from a mature epidemic with current low smoking prevalence

This study finds that up to two-thirds of deaths in current smokers&nbsp; in Australia can be attributed to smoking. Abstract Background The smoking epidemic in Australia is characterised by historic levels of prolonged smoking, heavy smoking, very high levels of long-term cessation, and low current smoking prevalence, with 13% of adults reporting that they smoked daily in 2013. Large-scale quantitative evidence on the relationship of tobacco smoking to mortality in Australia is not available despite the potential to provide independent international evidence about the contemporary risks of smoking. Methods This is a prospective study of 204,953 individuals aged ≥45&nbsp;years sampled from the general population of New South Wales, Australia, who joined the 45 and Up Study from 2006–2009, with linked questionnaire, hospitalisation, and mortality data to mid-2012 and with no history of cancer (other than melanoma and non-melanoma skin cancer), heart disease, stroke, or thrombosis. Hazard ratios (described here as relative risks, RRs) for all-cause mortality among current and past smokers compared to never-smokers were estimated, adjusting for age, education, income, region of residence, alcohol, and body mass index. Results Overall, 5,593 deaths accrued during follow-up (874,120 person-years; mean: 4.26&nbsp;years); 7.7% of participants were current smokers and 34.1% past smokers at baseline. Compared to never-smokers, the adjusted RR (95% CI) of mortality was 2.96 (2.69–3.25) in current smokers and was similar in men (2.82 (2.49–3.19)) and women (3.08 (2.63–3.60)) and according to birth cohort. Mortality RRs increased with increasing smoking intensity, with around two- and four-fold increases in mortality in current smokers of ≤14 (mean 10/day) and ≥25 cigarettes/day, respectively, compared to never-smokers. Among past smokers, mortality diminished gradually with increasing time since cessation and did not differ significantly from never-smokers in those quitting prior to age 45. Current smokers are estimated to die an average of 10&nbsp;years earlier than non-smokers. Conclusions In Australia, up to two-thirds of deaths in current smokers can be attributed to smoking. Cessation reduces mortality compared with continuing to smoke, with cessation earlier in life resulting in greater reductions

Vascular disease in women: comparison of diagnoses in hospital episode statistics and general practice records in England

BACKGROUND Electronic linkage to routine administrative datasets, such as the Hospital Episode Statistics (HES) in England, is increasingly used in medical research. Relatively little is known about the reliability of HES diagnostic information for epidemiological studies. In the United Kingdom (UK), general practitioners hold comprehensive records for individuals relating to their primary, secondary and tertiary care. For a random sample of participants in a large UK cohort, we compared vascular disease diagnoses in HES and general practice records to assess agreement between the two sources. METHODS Million Women Study participants with a HES record of hospital admission with vascular disease (ischaemic heart disease [ICD-10 codes I20-I25], cerebrovascular disease [G45, I60-I69] or venous thromboembolism [I26, I80-I82]) between April 1st 1997 and March 31st 2005 were identified. In each broad diagnostic group and in women with no such HES diagnoses, a random sample of about a thousand women was selected for study. We asked each woman's general practitioner to provide information on her history of vascular disease and this information was compared with the HES diagnosis record. RESULTS Over 90% of study forms sent to general practitioners were returned and 88% of these contained analysable data. For the vast majority of study participants for whom information was available, diagnostic information from general practice and HES records was consistent. Overall, for 93% of women with a HES diagnosis of vascular disease, general practice records agreed with the HES diagnosis; and for 97% of women with no HES diagnosis of vascular disease, the general practitioner had no record of a diagnosis of vascular disease. For severe vascular disease, including myocardial infarction (I21-22), stroke, both overall (I60-64) and by subtype, and pulmonary embolism (I26), HES records appeared to be both reliable and complete. CONCLUSION Hospital admission data in England provide diagnostic information for vascular disease of sufficient reliability for epidemiological analyses.The Million Women Study is funded by Cancer Research UK and the UK Medical Research Council. The study is registered with the NHS National Institute of Health Research Portfolio (study number 6862). General practices were reimbursed for conducting the data collection through NHS Service Support Cost funding of the National Institute of Health Research

Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy

Background: Although breast cancer risk is greater in users of estrogen-progestin than estrogen-only formulations of menopausal hormonal therapy, reports on their effects have been somewhat inconsistent. We investigated whether the timing of these therapies affected breast cancer incidence. Methods: A total of 1 129 025 postmenopausal UK women provided prospective information on hormonal therapy use and other factors relevant for breast cancer risk. We used Cox regression to estimate adjusted relative risks (RRs) of breast cancer in hormonal therapy users vs never users and calculated standardized incidence rates. All statistical tests were two-sided. Results: During 4.05 million woman-years of follow-up, 15 759 incident breast cancers occurred, with 7107 in current users of hormonal therapy. Breast cancer incidence was increased in current users of hormonal therapy, returning to that of never users a few years after use had ceased. The relative risks for breast cancer in current users were greater if hormonal therapy was begun before or soon after menopause than after a longer gap (Pheterogeneity <. 001, for both estrogen-only and estrogen-progestin formulations). Among current users of estrogen-only formulations, there was little or no increase in risk if use began 5 years or more after menopause (RR = 1.05, 95% confidence interval [CI] = 0.89 to 1.24), but risk was statistically significantly increased if use began before or less than 5 years after menopause (RR = 1.43, 95% CI = 1.35 to 1.51). A similar pattern was observed among current users of estrogen-progestin formulations (RR = 1.53, 95% CI = 1.38 to 1.70, and RR = 2.04, 95% CI = 1.95 to 2.14, respectively). At 50-59 years of age, annual standardized incidence rates for breast cancer were 0.30% (95% CI = 0.29% to 0.31%) among never users of hormone therapy and 0.43% (95% CI = 0.42% to 0.45%) and 0.61% (95% CI = 0.59% to 0.64%), respectively, among current users of estrogen-only and estrogen-progestin formulations who began use less than 5 years after menopause. Conclusions: There was substantial heterogeneity in breast cancer risk among current users of hormonal therapy. Risks were greater among users of estrogen-progestin than estrogen-only formulations and if hormonal therapy started at around the time of menopause than later

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

B Background Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. Methods Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. Findings During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use. Interpretation If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.Central data collection, checking, analysis, and manuscript preparation was supported by the core funding of the Cancer Epidemiology Unit by CR-UK (C570/A16491) and the MRC (MR/K02700X/1)