Explore the vast range of titles available.

High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. 5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. National Institute for Health Research, Wellcome Trust, and Medical Research Council.

This Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomised controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment. Large-scale evidence from randomised trials shows that statin therapy reduces the risk of major vascular events (ie, coronary deaths or myocardial infarctions, strokes, and coronary revascularisation procedures) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about £2 per month) for 5 years in 10 000 patients would typically prevent major vascular events from occurring in about 1000 patients (ie, 10% absolute benefit) with pre-existing occlusive vascular disease (secondary prevention) and in 500 patients (ie, 5% absolute benefit) who are at increased risk but have not yet had a vascular event (primary prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. The only serious adverse events that have been shown to be caused by long-term statin therapy—ie, adverse effects of the statin—are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50–100 new cases of diabetes, and 5–10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50–100 patients (ie, 0·5–1·0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms. It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.

The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. During 5·2 years median follow-up, we recorded 83 098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32–1·58]), subarachnoid haemorrhage (1·43 [1·25–1·63]), and stable angina (1·41 [1·36–1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00–1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86–0·98]) and strongest for peripheral arterial disease (1·23 [1·20–1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9–63·8) compared with 46·1% (45·5–46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8–5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. Medical Research Council, National Institute for Health Research, and Wellcome Trust.

The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps. For this population-based cohort study, we used linked primary care, hospital, and cancer registry data from the UK Clinical Practice Research Datalink to identify cohorts of survivors of the 20 most common cancers who were 18 years or older and alive 12 months after diagnosis and controls without history of cancer, matched for age, sex, and general practice. We compared risks for a range of cardiovascular disease outcomes using crude and adjusted Cox models. We fitted interactions to investigate effect modification, and flexible parametric survival models to estimate absolute excess risks over time. Between Jan 1, 1990, and Dec 31, 2015, 126 120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630 144 controls. After exclusions, 108 215 cancer survivors and 523 541 controls were included in the main analyses. Venous thromboembolism risk was elevated in survivors of 18 of 20 site-specific cancers compared with that of controls; adjusted hazard ratios (HRs) ranged from 1·72 (95% CI 1·57–1·89) in patients after prostate cancer to 9·72 (5·50–17·18) after pancreatic cancer. HRs decreased over time, but remained elevated more than 5 years after diagnosis. We observed increased risks of heart failure or cardiomyopathy in patients after ten of 20 cancers, including haematological (adjusted HR 1·94, 1·66–2·25, with non-Hodgkin lymphoma; 1·77, 1·50–2·09, with leukaemia; and 3·29, 2·59–4·18, with multiple myeloma), oesophageal (1·96, 1·46–2·64), lung (1·82, 1·52–2·17) kidney (1·73, 1·38–2·17) and ovarian (1·59, 1·19–2·12). Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies. HRs for heart failure or cardiomyopathy and venous thromboembolism were greater in patients without previous cardiovascular disease and in younger patients. However, absolute excess risks were generally greater with increasing age. Increased risks of these outcomes seemed most pronounced in patients who had received chemotherapy. Survivors of most site-specific cancers had increased medium-term to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between cancer sites. Wellcome Trust and Royal Society.

PurposeThere is limited high-quality evidence on quality of life, anxiety, and depressive symptoms in breast cancer survivors and women with no history of cancer. We aimed to address this by comparing patient-reported outcomes between breast cancer survivors and women with no history of breast cancer.MethodsBreast cancer survivors and women with no prior cancer were selected from the UK Clinical Practice Research Datalink GOLD primary care database, which includes population-based primary care electronic health record data. Breast cancer survivors and controls were frequency matched by age and primary care practice. Outcomes were assessed with validated instruments via postal questionnaire. Linear and logistic regression models were fitted to estimate adjusted associations between breast cancer survivorship and outcomes.ResultsA total of 356 breast cancer survivors (8.1 years post diagnosis) and 252 women with no prior cancer participated in the study. Compared with non-cancer controls, breast cancer survivors had poorer QoL in the domains of cognitive problems (adjusted β (aβ) = 1.4, p = 0.01), sexual function (aβ = 1.7, p = 0.02) and fatigue (aβ = 1.3, p = 0.01), but no difference in negative feelings, positive feelings, pain, or social avoidance. Breast cancer survivors had higher odds of borderline-probable anxiety (score ≥ 8) (adjusted OR = 1.47, 95%CI:1.15–1.87), but no differences in depression. Advanced stage at diagnosis and chemotherapy treatment were associated with poorer QoL.ConclusionsCompared with women with no history of cancer, breast cancer survivors report more problems with cognition, sexual function, fatigue, and anxiety, particularly where their cancer was advanced and/or treated with chemotherapy.Implications for Cancer SurvivorsBreast cancer survivors with more advanced disease and/or treated with chemotherapy should be closely monitored and, when possible, offered evidence-based intervention for fatigue, cognitive dysfunction, and sexual problems.

To systematically review current smoking prevalence among adults in sub-Saharan Africa from 2007 to May 2014 and to describe the context of tobacco control strategies in these countries. Five databases, Medline, Embase, Africa-wide Information, Cinahl Plus, and Global Health were searched using a systematic search strategy. There were no language restrictions. 26 included studies measured current smoking prevalence in nationally representative adult populations in sub-Saharan African countries. Study details were independently extracted using a standard datasheet. Data on tobacco control policies, taxation and trends in prices were obtained from the Implementation Database of the WHO FCTC website. Studies represented 13 countries. Current smoking prevalence varied widely ranging from 1.8% in Zambia to 25.8% in Sierra Leone. The prevalence of smoking was consistently lower in women compared to men with the widest gender difference observed in Malawi (men 25.9%, women 2.9%). Rwanda had the highest prevalence of women smokers (12.6%) and Ghana had the lowest (0.2%). Rural, urban patterns were inconsistent. Most countries have implemented demand-reduction measures including bans on advertising, and taxation rates but to different extents. Smoking prevalence varied widely across sub-Saharan Africa, even between similar country regions, but was always higher in men. High smoking rates were observed among countries in the eastern and southern regions of Africa, mainly among men in Ethiopia, Malawi, Rwanda, and Zambia and women in Rwanda and rural Zambia. Effective action to reduce smoking across sub-Saharan Africa, particularly targeting population groups at increased risk remains a pressing public health priority.

Objective To inform potential pathophysiological mechanisms of air pollution effects on cardiovascular disease (CVD), we investigated short-term associations between ambient air pollution and a range of cardiovascular events from three national databases in England and Wales. Methods Using a time-stratified case-crossover design, over 400 000 myocardial infarction (MI) events from the Myocardial Ischaemia National Audit Project (MINAP) database, over 2 million CVD emergency hospital admissions and over 600 000 CVD deaths were linked with daily mean concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter less than 10 μm in aerodynamic diameter (PM10), particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) and sulfur dioxide (SO2), and daily maximum of 8-hourly running mean of O3 measured at the nearest air pollution monitoring site to the place of residence. Pollutant effects were modelled using lags up to 4 days and adjusted for ambient temperature and day of week. Results For mortality, no CVD outcome analysed was clearly associated with any pollutant, except for PM2.5 with arrhythmias, atrial fibrillation and pulmonary embolism. With hospital admissions, only NO2 was associated with a raised risk: CVD 1.7% (95% CI 0.9 to 2.6), non-MI CVD 2.0% (1.1 to 2.9), arrhythmias 2.9% (0.6 to 5.2), atrial fibrillation 2.8% (0.3 to 5.4) and heart failure 4.4% (2.0 to 6.8) for a 10th–90th centile increase. With MINAP, only NO2 was associated with an increased risk of MI, which was specific to non-ST-elevation myocardial infarction (non-STEMIs): 3.6% (95% CI 0.4 to 6.9). Conclusions This study found no clear evidence for pollution effects on STEMIs and stroke, which ultimately represent thrombogenic processes, though it did for pulmonary embolism. The strongest associations with air pollution were observed with selected non-MI outcomes.

Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting.

In pharmacoepidemiology, routinely collected data from electronic health records (including primary care databases, registries, and administrative healthcare claims) are a resource for research evaluating the real world effectiveness and safety of medicines. Currently available guidelines for the reporting of research using non-randomised, routinely collected data—specifically the REporting of studies Conducted using Observational Routinely collected health Data (RECORD) and the Strengthening the Reporting of OBservational studies in Epidemiology (STROBE) statements—do not capture the complexity of pharmacoepidemiological research. We have therefore extended the RECORD statement to include reporting guidelines specific to pharmacoepidemiological research (RECORD-PE). This article includes the RECORD-PE checklist (also available on www.record-statement.org) and explains each checklist item with examples of good reporting. We anticipate that increasing use of the RECORD-PE guidelines by researchers and endorsement and adherence by journal editors will improve the standards of reporting of pharmacoepidemiological research undertaken using routinely collected data. This improved transparency will benefit the research community, patient care, and ultimately improve public health.