Search

Background UK government spending on health has risen on average by 3.7% per year since 1948, outpacing economic growth over the period, with approximately a half of this expenditure used for hospitals. While physical activity interventions have been reported to reduce hospital stays, it is not clear if usual physical activity patterns may be associated with subsequent hospital use independently of other lifestyle factors. We examined the relationship between reported usual physical activity, change in usual physical activity and subsequent admissions to hospital and time spent in hospital for 11 228 men and 13 786 women aged 40–79 years in the general population over two sequential 10-year follow-up period taking into account demographic and lifestyle factors. Methods Participants from EPIC-Norfolk, a British prospective population-based cohort study were followed for 20 years (1999–2019) using record linkage to document hospital usage. Total physical activity was estimated by combining workplace and leisure time activity reported in a baseline lifestyle questionnaire and repeated with independent measures in a subset at a second time point approximately 12 years later. Results Compared to those reporting no physical activity, participants who were the most active had a lower likelihood of spending more than 20 days in hospital odds ratio (OR) 0.75 (95% confidence interval (CI) 0.67–0.83) over the next 10 years after multivariable adjustment for age, sex, smoking status, education, social class and body mass index. Similar results were seen for 10-year follow-up after the second time point OR 0.60 (95% CI 0.50–0.72). Participants reporting any activity had a mean of 0.42 fewer hospital days per year between 1999 and 2009 compared to inactive participants, an estimated potential saving to the National Health Service (NHS) of £247 per person per year, or approximately 7% of UK health expenditure. Participants who remained physically active or became active 12 years later had lower risk of subsequent hospital usage than those who remained inactive or became inactive, p-trend Conclusion Usual physical activity in this middle-aged and older population predicts lower future hospitalisations - time spent in hospital and number of admissions independently of behavioural and sociodemographic factors. Small feasible differences in usual physical activity in the general population may potentially have a substantial impact on hospital usage and costs.

Background Current policies do not support screening for future dementia among apparently healthy individuals. This is due to the lack of certainty of the clinical outcome and effective interventions. Numerous dementia risk models have been developed, currently, all within the research setting only. Studies have shown impairment in multiple cognitive domains several years before a clinical diagnosis of dementia. Methods We examined the utility of an extensive battery assessing a range of specific cognitive abilities as well as a composite global score, to predict dementia. Dementia outcomes were ascertained using electronic health record linkage in 8581 individuals (aged 48–92 years) taking part in the EPIC-Norfolk study. Participants were followed for 15 years (2004–2019). Risk of dementia was estimated using Cox proportional hazard models adjusting for sociodemographic, lifestyle and health variables, evaluating discriminative accuracy of the models by analysing receiver operating characteristic (ROC) curves. Results Poor cognition was predictive of incident dementia, even after adjustment for co-variates. Those with a poor performance score for global cognition (bottom 10%) were almost four times as likely to get a dementia diagnosis than those who performed well (HR=3.51 (95%CI 2.61, 4.71) P Discussion This study provides further insight on poor cognition predicting future dementia. This association was observed for global cognition and specific abilities, particularly for verbal episodic memory. Impairment occurs in multiple domains several years prior to a clinical diagnosis, and the more pervasive and greater the variability, the higher the risk of dementia. Deficits across multiple domains predict over and above individual test scores.

Background The ageing population and prevalence of long-term disorders with multimorbidity is a major health challenge worldwide. Patients with multimorbidity account for a disproportionately high share of healthcare workload and costs and experience reduced wellbeing and quality of life. The associations between comorbid conditions and mortality risk are well established; however, few prospective community-based studies have reported on prior risk factors for incident hospitalisations with multimorbidity. Our study examines the independent associations for a range demographic, lifestyle and physiological determinants and the likelihood of subsequent hospital incident multimorbidity using a prospective community-based cohort of middle-aged and older men and women resident in Norfolk, UK. We explore demographic, lifestyle and physiological exposures including age and sex, body mass index, cigarette smoking, alcohol intake, educational attainment, occupational social class, physical activity, plasma vitamin C, total cholesterol, systolic blood pressure and common prevalent diseases. Methods Incident hospital admissions with multimorbidity were examined in 25014 men and women aged 40–79 in EPIC-Norfolk, a British prospective population-based study initially recruited in 1993–1997 and followed-up until 2019. The determinants of incident multimorbidity, defined as Charlson Comorbidity Index ≥2, were examined in multivariable models for the 10-year period 1999–2009 and repeated with independent measurements in a second 10-year period 2009–2019. Results Between 1999–2009 18179 participants (73% of the population) had a hospital admission. Baseline 5-year and 10-year incident multimorbidity were observed in 11% and 21% of participants respectively. Age per 10-year increase OR 2.13 (95% CI 2.03–2.23) and male sex OR 1.28 (95% CI 1.17–1.39) predicted incident multimorbidity over 10 years. In the subset free of the most serious diseases at baseline, current smoking OR 1.71 (95% CI 1.53–1.91), BMI >30 kg/m² OR 1.37 (95% CI 1.24–1.51) and physical inactivity OR 1.09 (95% CI 1.00–1.18) were positively associated and plasma vitamin C (a biomarker of plant food intake) per SD increase OR 0.88 (95% CI 0.84–0.91) inversely associated with incident 10-year multimorbidity after multivariable adjustment for age, sex, social class, education, alcohol consumption, systolic blood pressure and cholesterol. Results were similar when re-examined for a further time period 2009–2019. Conclusion Age, male sex and potentially modifiable lifestyle behaviours including smoking, physical inactivity and low fruit and vegetable intake were associated with increased risk of future incident hospital admissions with multimorbidity.

Background Currently used models to predict cardiovascular event risk have limited value. It has been shown repetitively that the addition of single biomarkers has modest impact. Recently we observed that a model consisting of a larger array of plasma proteins performed very well in predicting the presence of vulnerable plaques in primary prevention patients. However, the validation of this protein panel in predicting cardiovascular outcomes remains to be established. Purpose This study investigated the ability of a 384 preselected protein biomarkers to predict acute myocardial infarction, using state-of-the-art machine learning techniques. Secondly, we compared the performance of this multi-protein risk model to traditional risk engines. Methods We selected 822 subjects from the EPIC-Norfolk prospective cohort study, of whom 411 suffered a myocardial infarction during follow-up (median 15 years) compared to 411 controls who remained event-free (median follow-up 20 years). The 384 proteins were measured using proximity extension assay technology. Machine learning algorithms (random forests) were used for the prediction of acute myocardial infarction (ICD code I21–22). Performance of the model was tested against and on top of traditional risk factors for cardiovascular disease (refit Framingham). All performance measurements were averaged over several stability selection routines. Results Prediction of myocardial infarction using a machine-learning model consisting of 50 plasma proteins resulted in a ROC AUC of 0.74±0.14, in comparison to 0.69±0.17 using traditional risk factors (refit Framingham. Combining the proteins and refit Framingham resulted in a ROC AUC of 0.74±0.15. Focussing on events occurring within 3 years after baseline blood withdrawal, the ROC AUC increased to 0.80±0.09 using 50 plasma proteins, as opposed to 0.67±0.22 using refit Framingham (figure). Combining the protein model with refit Framingham resulted in a ROC AUC of 0.82±0.11 for these events. Diagnostic performance events Conclusion High-throughput proteomics outperforms traditional risk factors in prediction of acute myocardial infarction. Prediction of myocardial infarction occurring within 3 years after inclusion showed highest performance. Availability of affordable proteomic approaches and developed machine learning pave the path for clinical implementation of these models in cardiovascular risk prediction. Acknowledgement/Funding This study was funded by an ERA-CVD grant (JTC2017) and EU Horizon 2020 grant (REPROGRAM, 667837)

Background Low social economic position is linked to higher rates of mortality and morbidity. Socioeconomic factors are reported to predict admission to hospital for many conditions. It is less clear if residential area deprivation index predicts hospital usage independently of individual social class and lifestyle factors. Methods We examined the relationship between residential Townsend’s Area Deprivation Index and subsequent admissions to hospital and time spent in hospital for 11,214 men and 13,763 women aged 40–79 years in the general population. Participants from the EPIC-Norfolk prospective population-based study were followed for nineteen years (1999–2018) using record linkage. Townsend’s Index from the small area measurements taken at the 1991 UK census was linked to individuals in the EPIC-Norfolk cohort using their postal code. Results Compared to those with residential Townsend Area Deprivation Index lower than the average for England and Wales, those with a higher than average deprivation index had a higher likelihood of spending more than twenty days in hospital multivariable adjusted odds ratio (OR) 1.18 (95% confidence interval (CI) 1.07–1.29) and having 7 or more admissions OR 1.11 (95% CI 1.02–1.22) after adjustment for age, sex, smoking status, education, social class, body mass index and prevalent diseases. Those with manual social class were at greater risk of hospitalisation compared to those with a non-manual social class when living in an area with higher deprivation index (p Interaction=0.025). Similarly, those with a lower education level living in a more deprived area had a higher risk of hospitalisation (p Interaction=0.020) when compared with those with a higher education level. Conclusion Residential area deprivation predicts future hospitalisations - time spent in hospital and number of admissions - independently of individual social class and education level and other behavioural factors. There are significant interactions such that residential area deprivation has greater impact in those with low education level or manual social class.

Cancer Research UK and Ludwig Cancer Research convened an inaugural international Cancer Prevention and Nutrition Conference in London on December 3–4, 2018. Much of the discussion focused on the need for systematic, interdisciplinary approaches to better understand the relationships of nutrition, exercise, obesity and metabolic dysfunction with cancer development. Scientists at the meeting underscored the importance of studying the temporal natural history of exposures that may cumulatively impact cancer risk later in life. A robust dialogue identified obesity as a major risk for cancer, and the food environment, especially high energy and low nutrient processed foods, as strong and prevalent risk factors for obesity. Further engagement highlighted challenges in the post-diagnostic setting, where similar opportunities to understand the complex interplay of nutrition, physical activity, and weight will inform better health outcomes. Going forward, holistic research approaches, encompassing insights from multiple disciplines and perspectives, will catalyze progress urgently needed to prevent cancer and improve public health.

BACKGROUND AND AIM: Obesity is a recognized risk factor for new-onset atrial fibrillation (AF). The association between body fat distribution, which is measured by body mass index (BMI) and waist-hip ratio (WHR), its changes, and new-onset AF is conflicting. METHODS AND RESULTS: Participants of the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort study were included, with exclusion criteria of prevalent AF, rheumatic heart disease, and cancer. AF was confirmed by the International Classification of Diseases-10 hospital discharge code I48. Adjusted sex-specific Cox proportional hazards models were used to quantify the AF risk per 1 standard deviation increase and for quintiles of adiposity indices. A total of 10,885 men and 12,857 women were followed up for a median of 19 years, yielding 451,098 person-years. New-onset AF was diagnosed in 1408 (12.9%) men and 1102 (8.6%) women. Multivariable analyses showed that BMI predicted new-onset AF in all, while WHR predicted only in men. New-onset AF risk gradually increased across the range of adiposity indices: for men in the highest BMI quintile, HR: 1.59 (CI 1.32-1.91, p for trend

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol-metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study-specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol-metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer-specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta-analysed using fixed-effect and random-effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed-effect meta-analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low-grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.

With increasing numbers of randomized controlled trials (RCTs) investigating potential health events of vitamin D supplementation, a better understanding is required of the risk factors for adverse events and for study withdrawals. This analysis aimed to identify baseline risk factors of reporting an adverse event in a multi-year randomized double-blinded placebo-controlled trial of vitamin D supplementation. The secondary aim was to investigate if adverse events were associated with study withdrawals. We analyzed data from the Vitamin D Assessment (ViDA) study: 5110 adults, aged 50–84 years, living in Auckland, New Zealand. Monthly doses of 100,000 IU vitamin D3 or placebo were mailed to participants homes, with a questionnaire to collect data on adverse events and adherence to the study capsule (initially monthly, then 4-monthly). Median follow-up was 3.3 years. Data were analysed using multivariable log-binomial regression and Cox-regression. During the follow-up period, 818 people reported adverse events and 412 withdrew or stopped returning questionnaires. Vitamin D was not associated with reporting of adverse events. Of sociodemographic factors, ethnicity was associated with reporting adverse events: compared to European participants, Maori and Pacific Islander people were more likely to report an adverse event. Non-smokers were more likely to report an adverse event, compared to smokers (adjusted hazard ratio (HR) = 1.80; 95%CI = 1.24, 2.62); as were those who had reported a history of depression (adjusted HR = 1.27; 95%CI = 1.01, 1.60) or a recent cough or cold (adjusted HR = 1.22; 95%CI = 1.03, 1.44) at baseline. Reporting of adverse events was not associated with withdrawals (adjusted HR = 1.12; 95%CI = 0.86, 1.46). These data did not identify any clear pattern in the factors associated with self-reported adverse events, which themselves did not increase risk of withdrawals.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from 375 incident pancreatic cancer cases and 375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval]=0.41-0.98; Ptrend =0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 =0.60; 95%CI=0.39-0.92; Ptrend =0.02) and docosapentaenoic acid (ORT3-T1 =0.52; 95%CI=0.32-0.85; Ptrend =0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 =3.00; 95%CI=1.13-7.99; Ptrend =0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 =0.37; 95%CI=0.17-0.81; Ptrend =0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 =3.40; 95%CI=1.39-8.34; Ptrend =0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking. This article is protected by copyright. All rights reserved.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

Udgivelsesdato: 2010-Nov-2 Background:Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.Methods:We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.Results:After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.Conclusion:Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.British Journal of Cancer advance online publication, 2 November 2010; doi:10.1038/sj.bjc.6605965 www.bjcancer.com.

Objective To quantify hospital use in a general population over 10 years follow-up and to examine related factors in a general population-based cohort. Design A prospective population-based study of men and women. Setting Norfolk, UK. Participants 11 228 men and 13 786 women aged 40–79 years in 1993–1997 followed between 1999 and 2009. Main outcomes measures Number of hospital admissions and total bed days for individuals over a 10-year follow-up period identified using record linkage; five categories for admissions (from zero to highest ≥7) and hospital bed days (from zero to highest ≥20 nights). Results Over a period of 10 years, 18 179 (72.7%) study participants had at least one admission to hospital, 13.8% with 7 or more admissions and 19.9% with 20 or more nights in hospital. In logistic regression models with outcome ≥7 admissions, low education level OR 1.14 (1.05 to 1.24), age OR per 10-year increase 1.75 (1.67 to 1.82), male sex OR 1.32 (1.22 to 1.42), manual social class 1.22 (1.13 to 1.32), current cigarette smoker OR 1.53 (1.37 to 1.71) and body mass index >30 kg/m² OR 1.41 (1.28 to 1.56) all independently predicted the outcome with p30 kg/m², estimated percentages of the cohort in the categories of admission numbers and hospital bed days in stratified age bands with twofold to threefold differences in future hospital use between those with high-risk and low-risk scores. Conclusions The future probability of cumulative hospital admissions and bed days appears independently related to a range of simple demographic and behavioural indicators. The strongest of these is increasing age with high body mass index and smoking having similar magnitudes for predicting risk of future hospital usage.

Background We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. Methods and results We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993–1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66–0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71–1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66–1.01). Conclusions Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure., Highlights • Whether chocolate consumption increases or decreases the risk of heart failure remains controversial. • Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure. • Our meta-analysis found consistent findings across all studies that chocolate consumption does not increase the risk of incident heart failure. • Evidence suggests that chocolate consumption does not increase risk of heart failure at the general population level.

Background Objectively measured physical activity between older individuals and between populations has been poorly described. We aimed to describe and compare the variation in accelerometry data in older UK (EPIC-Norfolk) and American (NHANES) adults. Methods Physical activity was measured by uniaxial accelerometry in 4,052 UK (49–91 years) and 3459 US older adults (49–85 years). We summarized physical activity as volume (average counts/minute), its underlying intensity distribution, and as time spent 809 counts/minute is used 18.7 % of people reached the 30 min/day threshold. By comparison, 2.5 % and 9.5 % of American older adults accumulated activity at these levels, respectively. Conclusion As assessed by objectively measured physical activity, the majority of older adults in this UK study did not meet current activity guidelines. Older adults in the UK were more active overall, but also spent more time being sedentary than US adults. Electronic supplementary material The online version of this article (doi:10.1186/s12966-015-0316-z) contains supplementary material, which is available to authorized users.

Background Anti-citrullinated protein antibody (ACPA) immune response occurs several years prior to the diagnosis of rheumatoid arthritis (RA). However, limited data are available on ACPA status in the general population compared to those who develop RA or inflammatory polyarthritis (IP) in the future. Objectives The aim of this study was to examine ACPA status in the general population and in patients developing IP/RA. Methods ACPA was measured by ELISA (Euro-Diagnostica) in stored serum samples collected at baseline in people participating in the European Prospective Investigation of Cancer in Norfolk, (EPIC-Norfolk), a prospective population-based study in the UK. In addition, data on ACPA status (positive >25 U/ml) age, gender, socio-economic status (i.e. manual/unskilled worker, manager/skilled non-manual worker, professional), smoking status (i.e. never, former, current) were also collected at inclusion. Individuals who subsequently developed IP/RA were identified by linkage with the Norfolk Arthritis Register (NOAR), a primary-care based cohort with an overlapping catchment area in the UK. Logistic regression analyses were used to assess the association between demographic characteristics and ACPA positivity in the general population. Cox regression analyses were performed to assess the association between ACPA and the development of IP, adjusting for age and gender. Patients with a symptom onset prior to inclusion in EPIC-Norfolk were excluded from the Cox regression analysis (N=104). In addition, the interaction between ACPA and smoking was tested. People were followed until development of IP/RA or censored at date of death or May 2014, whichever came first. Results ACPA was measured in 18,628 EPIC participants aged 40-79 years. ACPA was positive in 429 subjects (2.30%) of the whole EPIC population including 104 patients with prevalent IP/RA (35.6% ACPA positive, median titre 6.95 [IQR 3.75 – 121.2] U/ml) and 173 (16.8% ACPA positive, median titre 5.14 [IQR 3.37 – 9.41] U/ml) subjects who developed IP during 311,051 person years of follow-up. Cross-sectionally, current and former smokers (OR 1.60, 95%CI 1.95 to 2.13 and OR 1.29 95%CI 1.02 to 1.55, respectively) and older age (OR 1.01 95%CI 1.00 to 1.03) were associated with ACPA positivity. Gender and socio-economic status were not associated with ACPA. Of 173 patients who developed IP and were notified to NOAR, 85 (49.4%) fulfilled the 2010 ACR/EULAR criteria for RA at entry to the NOAR cohort. ACPA status was predictive for the development of IP/RA (adjHR 10,3 95%CI 6.90 to 15.34). The interaction between ACPA and smoking was not significant. Conclusions ACPA was positive in 2.1% of a general population sample aged 40-79 years old. People who were ACPA positive were 10 times more likely to develop IP/RA in the next 3-10 years than those ACPA negative subjects. ACPA may be a useful adjunct to other screening approaches to identify people at higher risk of developing IP/RA. Disclosure of Interest None declared

Introduction The development of both Barrett’s oesophagus (BO) and oesophageal adenocarcinoma (OAC) may involve oxidative stress. We investigated whether the antioxidants vitamins C and E, selenium, zinc and carotene were associated with a decreased risk of BO and OAC, in the same population, using nutritional information from 7-day food diaries, the most accurate questionnaire-based methodology. Method A cohort of 23,658 initially well individuals, aged 40–74 years, enrolled in the European Prospective Investigation of Cancer-Norfolk Study completed 7-day food diaries. Serum vitamin C levels were measured. They were monitored till December 2008 to identify those diagnosed with BO and OAC, confirmed through reviewing medical records. Hazard ratios (HRs) for these two conditions were estimated for each quintile of intake, corrected for age, gender, BMI and smoking. The analyses were repeated in participants younger and older than 65 years at recruitment, the mid-point of the peak prevalence of BO. Results 92 participants who developed BO and 61 OAC were compared with 3712 randomly selected controls. In the whole cohort, and in those aged above 65 years at recruitment, there were no associations between any antioxidant and the risk of developing BO or OAC. However, in participants aged less than 65 years at recruitment, for BO statistically non-significant inverse associations were observed between all quintiles of food-diary assessed vitamin C intake (highest vs lowest quintile HR = 0.49, 95% CI = 0.20–1.22), with a significant inverse trend across quintiles for serum vitamin C and BO risk (Trend HR = 0.76; CI = 0.59–0.97; P = 0.03). For the development of OAC in participants recruited when less than 65 years, there were significant inverse trends across quintiles for both dietary vitamin C intake (Trend HR = 0.65; CI = 0.44–0.96; P = 0.03) and serum vitamin C (Trend HR = 0.54; CI = 0.33–0.89; P = 0.02). In this group there was a borderline significant inverse trend between vitamin E intake and OAC (Trend HR = 0.70; CI = 0.48–1.01; P = 0.06), but no associations with zinc, selenium or carotenes. Conclusion Vitamin C deficiency may be involved in the aetiology of BO and possibly OAC, and may influence carcinogenesis below 65 years of age. Vitamin E may prevent the malignant progression of BO to OAC, again in younger individuals. Vitamins C and E levels should be measured in future aetiological studies for these conditions and randomised controlled trials of their use to prevent the malignant progression of BO may be justified. Disclosure of interest None Declared.

Introduction Processed, red and white meat intake may be involved in the aetiology of pancreatic cancer as they can contain carcinogens including nitrosamines, which may influence the natural history of the cancer at different ages. The data from epidemiological studies are conflicting, possibly due to lack of generalisability and inaccurate measures of diet. We investigated associations between processed, red and white meat intake and pancreatic cancer, for the first time using data from 7-day food diaries (7-DFDs), the most accurate questionnaire-based nutritional assessment. Method 23,658 participants recruited into the EPIC-Norfolk Study completed 7-DFDs and were followed up over 17 years to identify incident cases of pancreatic cancer. Meat intakes were divided into quintiles and compared with a sample of 3970 controls. Hazard ratios (HR) were calculated for developing pancreatic cancer for each quintile and for trends across quintiles, adjusted for age, sex, smoking, diabetes, and energy intake. A sub-group analysis was performed in participants younger and older than 60 years at recruitment. Results During follow-up, 86 participants (0.36%) were diagnosed with pancreatic cancer (56% women). The median age at diagnosis was 73.4 years with a median survival of 4 months (inter-quartile range= 2–7 months). In the whole cohort, there were no associations with any quintiles of processed, red or white meats or for trends across quintiles. However, in participants younger than 60 years at recruitment, all quintiles of processed and red meat intakes were borderline significantly positively associated with risk (Q1 vs Q5, HR=3.73, 95% CI=0.95–14.66, p = 0.06 and Q1 vs Q5, HR=4.62, 95% CI=0.96–22.30, p = 0.06) respectively, with trends across quintiles for both (HR trend =1.37, 95% CI=1.04–1.82 and HR trend =1.33, 95% CI=1.00–1.77). For participants older than 60, there were no significant effects for either processed or red meats. For white meat, there was a positive association for all ages in quintiles two (HR=2.44, 95% CI=1.12–4.91) and four (HR=2.47, 95% CI=1.25–4.91), but no trend. There were no associations for white meat intake in those younger than 60 but the effects remained if older than 60. Conclusion The findings suggest that processed and red meats may be involved in the aetiology of pancreatic cancer. As the associations are related to consumption before the age of 60 years, these meats may influence the development of precursor lesions for pancreatic cancer, such as pancreatic intraepithelial neoplasia (PanINs). The effects of white meat are uncertain. Processed and red meat intakes should be measured in aetiological studies, and reducing intake could reduce the incidence of pancreatic cancer. Disclosure of interest None Declared.

Background Linkage of the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk) population and the Norfolk Arthritis Register (NOAR), the EPIC-2-NOAR study, has enabled investigation of potential lifestyle predictors of incident inflammatory polyarthritis (IP) [1]. However, potential metabolic predictors of IP have not been as well investigated in this population and have not been considered alongside lifestyle factors. Objectives To assess the addition of metabolic factors to an established multivariate lifestyle factor model for incident IP [1], with updated record linkage in EPIC-2-NOAR. Methods Data on lifestyle factors (pack-years of smoking (adjusted for never being a smoker), smoking status, alcohol consumption (adjusted for being a teetotaller), body mass index, socio-economic status, self-reported diabetes mellitus (DM), parity and duration of breast feeding) was collected by questionnaire at entry to EPIC-Norfolk. Metabolic factors (serum uric acid, HDL-C, Apo-A1, Apo-B and HbA1c) were measured using a non-fasting blood sample taken at the same time. EPIC-Norfolk participants who subsequently developed IP were identified via linkage with NOAR, a primary care based inception cohort study of early IP. Associations between the metabolic predictors and incident IP were assessed using Cox regression: univariately, adjusting for age and gender, and by adding individual predictors to the existing multivariate Cox models [1], one for all participants (with an interaction term for gender and pack years of smoking) and one for females only. Subjects were followed until development of IP, death, loss to follow-up or May 2014, whichever came first. Results Data was available on 25 636 subjects (55% female), including 231 incident cases of IP (66% female). Median (IQR) age at entry to EPIC-Norfolk was 59 (51-67) years, median follow-up was 214 (198-230) months and median time to onset of IP was 79 (34-136) months. No significant association was observed between incident IP and serum uric acid, HDL-C, Apo-A or Apo-B. Baseline HbA1c was positively associated with incident IP in univariate analysis (HR 1.22, 95% CI (1.03, 1.44)), when adjusted for sex and age (HR 1.27 (1.08, 1.49)) and when added to the existing multivariate lifestyle factor models for all (HR 1.26 (1.07, 1.47)) and for females only (HR 1.23 (1.00, 1.52)). Inclusion of HbA1c in the multivariate models led to self-reported DM no longer being significantly associated with IP. Conclusions Baseline HbA1c was significantly associated with incident IP, at the expense of self-reported DM in an established multivariate lifestyle factor model. While DM is an established risk factor for IP, HbA1c levels may capture additional information on those in a prediabetic state and could prove a more sensitive marker of future IP. References Lahiri et al. Ann Rheum Dis 2014; 73: 219 Disclosure of Interest None declared

Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.