Baseline anticholinergic burden from medications predicts incident fatal and non-fatal stroke in the EPIC-Norfolk general population.

BACKGROUND: Stroke is primarily a disease of older age, with a substantial impact on global mortality and morbidity. Medications with anticholinergic effects are widely used, but no studies have been conducted to examine the relationship between anticholinergic burden (ACB) and stroke in a general population. METHOD: The sample was drawn from the EPIC-Norfolk cohort. Baseline assessments were carried out during 1993-97 and participants were followed up until March 2016. Participants were divided into four groups according to their total ACB score at baseline; these groups were those with a total ACB score of 0, 1, 2-3 and >3. After exclusion, Cox proportional hazards models were constructed to determine the associations between the ACB score groups and the risk of incident stroke and stroke mortality. Sensitivity analysis and propensity score matched analyses were performed. RESULTS: In total 25 639 participants attended the first health check; 3917 participants were excluded, leaving 21 722 participants to be included. Participants had a mean age [standard deviation (SD)] of 58.9 (9.2) years (54.4% women). Of these, 2131 suffered incident stroke and 562 died from stroke. Mean follow-up was approximately 18 years for both outcomes. In the fully adjusted model, those with an ACB of >3 had 59% relative risk of incident stroke {hazard ratio [HR] [95% confidence interval (CI) 1.59 [1.34-1.89]} and 86% relative risk of stroke mortality [1.86 (1.37-2.53)] compared with those in ACB 0 category. Sensitivity analyses and propensity score matched analyses showed similar results. CONCLUSIONS: Our results provide an incentive for the cautious use of medications with anticholinergic properties, to help reduce the global burden of stroke

Dimension of pain-related quality of life and self-reported mental health in men and women of the European Prospective Investigation into Cancer–Norfolk cohort : a population-based cross-sectional study

Acknowledgement: The authors thank Prof. Gary J Macfarlane, Head of Epidemiology Group, University of Aberdeen, for discussions and constructive comments during manuscript preparation. We also wish to thank the participants of the EPIC-Norfolk cohort, staff, co-PIs, and the funders. The EPIC-Norfolk study was supported by grants from the Cancer Research UK and Medical Research Council (UK). Funders have no role in study design and interpretation of the results. Funding Sources: The EPIC-Norfolk study was supported by grants from the Cancer Research UK (CRUK 14136) and Medical Research Council UK (MRC: G1000143). Funders have no role in study design and interpretation of the results.Peer reviewedPostprin

Hypertensive Disorders of Pregnancy (HDP) and the Risk of Common Cancers in Women: Evidence from the European Prospective Investigation into Cancer (EPIC)-Norfolk Prospective Population-Based Study.

PURPOSE: The purpose was to determine the association between HDP and cancer in a UK cohort. METHODS: Between 1993 and 1997, participants from the EPIC-Norfolk cohort attended baseline health-checks and completed questionnaires, where a history of HDP was collected. Incident cancer cases were identified through NHS record linkage until March 2016. Univariable and multivariable logistic regression analyses were employed to determine the association between HDP and odds of cancer, with adjustment for potential confounders including co-morbidities, sociodemographic, lifestyle and reproductive factors. RESULTS: 13,562 women were included after excluding prevalent cancer cases and women with no pregnancies. 2919 (21.5%) reported HDP and 2615 incident cancers occurred during mean follow up of 19 years. Median age (IQR) at baseline for incident cancer was 60.8 (±14.8) years. Among incident cancer cases, 578 (22.1%) had HDP. In multivariable analyses, HDP had odds ratio (OR) 1.06; 95% CI 0.95-1.18 for incident cancer. The ORs (95% CIs) for common site-specific cancers including breast, colorectal, lung, ovarian and endometrial cancers were 1.06 (0.88-1.28), 1.15 (0.92-1.45), 0.96 (0.68-1.35), 1.30 (0.93-1.83) and 1.16 (0.80-1.67). CONCLUSION: We found no association between HDP and cancer risk. Further studies are required to confirm and account for any underlying genetic factors involved in pregnancy-related exposures and cancer risk

Validation of a model to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD: The rotterdam ischemic heart disease and stroke computer simulation (RISC) model

Background: We developed a Monte Carlo Markov model designed to investigate the effects of modifying cardiovascular disease (CVD) risk factors on the burden of CVD. Internal, predictive, and external validity of the model have not yet been established.Methods: The Rotterdam Ischemic Heart Disease and Stroke Computer Simulation (RISC) model was developed using data covering 5 years of follow-up from the Rotterdam Study. To prove 1) internal and 2) predictive validity, the incidences of coronary heart disease (CHD), stroke, CVD death, and non-CVD death simulated by the model over a 13-year period were compared with those recorded for 3,478 participants in the Rotterdam Study with at least 13 years of follow-up. 3) External validity was verified using 10 years of follow-up data from the European Prospective Investigation of Cancer (EPIC)-Norfolk study of 25,492 participants, for whom CVD and non-CVD mortality was compared.Results: At year 5, the observed incidences (with simulated incidences in brackets) of CHD, stroke, and CVD and non-CVD mortality for the 3,478 Rotterdam Study participants were 5.30% (4.68%), 3.60% (3.23%), 4.70% (4.80%), and 7.50% (7.96%), respectively. At year 13, these percentages were 10.60% (10.91%), 9.90% (9.13%), 14.20% (15.12%), and 24.30% (23.42%). After recalibrating the model for the EPIC-Norfolk population, the 10-year observed (simulated) incidences of CVD and non-CVD mortality were 3.70% (4.95%) and 6.50% (6.29%). All observed incidences fell well within the 95% credibility intervals of the simulated incidences.Conclusions: We have confirmed the internal, predictive, and external validity of the RISC model. These findings provide a basis for analyzing the effects of modifying cardiovascular disease risk factors on the burden of CVD with the RISC model

The Accuracy and Reliability of Crowdsource Annotations of Digital Retinal Images

Purpose: Crowdsourcing is based on outsourcing computationally intensive tasks to numerous individuals in the online community who have no formal training. Our aim was to develop a novel online tool designed to facilitate large-scale annotation of digital retinal images, and to assess the accuracy of crowdsource grading using this tool, comparing it to expert classification. Methods: We used 100 retinal fundus photograph images with predetermined disease criteria selected by two experts from a large cohort study. The Amazon Mechanical Turk Web platform was used to drive traffic to our site so anonymous workers could perform a classification and annotation task of the fundus photographs in our dataset after a short training exercise. Three groups were assessed: masters only, nonmasters only and nonmasters with compulsory training. We calculated the sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) plots for all classifications compared to expert grading, and used the Dice coefficient and consensus threshold to assess annotation accuracy. Results: In total, we received 5389 annotations for 84 images (excluding 16 training images) in 2 weeks. A specificity and sensitivity of 71% (95% confidence interval [CI], 69%-74%) and 87% (95% CI, 86%-88%) was achieved for all classifications. The AUC in this study for all classifications combined was 0.93 (95% CI, 0.91-0.96). For image annotation, a maximal Dice coefficient (~0.6) was achieved with a consensus threshold of 0.25. Conclusions: This study supports the hypothesis that annotation of abnormalities in retinal images by ophthalmologically naive individuals is comparable to expert annotation. The highest AUC and agreement with expert annotation was achieved in the nonmasters with compulsory training group. Translational Relevance: The use of crowdsourcing as a technique for retinal image analysis may be comparable to expert graders and has the potential to deliver timely, accurate, and cost-effective image analysis

The clustering of health behaviours in Ireland and their relationship with mental health, self-rated health and quality of life

Health behaviours do not occur in isolation. Rather they cluster together. It is important to examine patterns of health behaviours to inform a more holistic approach to health in both health promotion and illness prevention strategies. Examination of patterns is also important because of the increased risk of mortality, morbidity and synergistic effects of health behaviours. This study examines the clustering of health behaviours in a nationally representative sample of Irish adults and explores the association of these clusters with mental health, self-rated health and quality of life

Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies

<p>Background: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.</p> <p>Methods and Findings: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.</p> <p>Conclusions: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions.</p&gt

Television Viewing and Incident Cardiovascular Disease: Prospective Associations and Mediation Analysis in the EPIC Norfolk Study

Background: Although television viewing time is detrimentally associated with intermediate cardiovascular risk factors, the relationship with incident total (i.e. combined fatal and non-fatal) cardiovascular disease (CVD), non-fatal CVD and coronary heart disease is largely unknown. This study examined whether television viewing time is associated with these three outcomes, independently of physical activity energy expenditure and other confounding variables. Methodology/Principal Findings: A population-based cohort of 12,608 men and women (aged 61.4 +/- 9.0), free from stroke, myocardial infarction and cancer at baseline in 1998-2000 were followed up until 2007 (6.9 +/- 1.9 years). Participants self-reported education, smoking, alcohol use, antihypertensive, lipid lowering and antidepressant medication, disease history, total energy intake, sleep duration, physical activity and television viewing. BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol and glycated haemoglobin (HbA(1c)) were measured by standardized procedures; a clustered metabolic risk score was constructed. Every one hour/day increase in television viewing was associated with an increased hazard for total (HR = 1.06, 95% CI = 1.03-1.08; 2,620 cases), non-fatal CVD (HR = 1.06, 95% CI = 1.03-1.09; 2,134 cases), and coronary heart disease (HR = 1.08, 95% CI = 1.03-1.13; 940 cases), independent of gender, age, education, smoking, alcohol, medication, diabetes status, CVD family history, sleep duration and physical activity energy expenditure. Energy intake, BMI, waist circumference, blood pressure, triglycerides, HDL cholesterol, HbA(1c) and the clustered metabolic risk score only partially mediated these associations. Conclusions: These results indicate that the most prevalent leisure time (sedentary) behaviour, television viewing, independently contributes to increased CVD risk. Recommendations on reducing television viewing time should be considered

Measured adiposity in relation to head and neck cancer risk in the European Prospective Investigation into Cancer and Nutrition

BACKGROUND: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer (HNC). However, most studies have used self-reported anthropometry which is prone to error. METHODS: Among 363 094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of HNC. HNC risk was examined in relation to body mass index (BMI) [lean: 30 kg/m²], waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR) using Cox proportional hazards models. RESULTS: Among men, a BMI < 22.5 kg/m² was associated with higher HNC risk [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.23 - 2.12)]; BMI was not associated with HNC among women. WC and WHR were associated with greater risk of HNC among women, (WC per 5 cm: HR 1.08, 95% CI 1.02 - 1.15; WHR per 0.1 unit: HR 1.64, 95% CI 1.38 - 1.93). After stratification by smoking status, the association for WHR was present only among smokers (p interaction 0.004). Among men, WC and WHR were associated with HNC only upon additional adjustment for BMI (WC per 5 cm: HR 1.16, 95% CI 1.07 - 1.26; WHR per 0.1 unit: HR 1.42, 95% CI 1.21 - 1.65). CONCLUSION: Central adiposity, particularly among women, may have a stronger association with HNC risk than previously estimated. IMPACT: Strategies to reduce obesity may beneficially impact HNC incidence.The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC- 2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; , PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to K.T. Khaw, N.J. Wareham; C570/A16491 to R.C. Travis and C8221/A19170 to Tim Key (EPIC-Oxford), Medical Research Council (1000143 to K.T. Khaw, N.J. Wareham, MR/M012190/1 to Tim Key (EPIC-Oxford)) (United Kingdom)