The epidemiology of hospital admissions in a general population: record linkage of hospital episode statistics to the European Prospective Investigation of Cancer (EPIC-Norfolk) cohort

The UK National Health Service (NHS) is primarily funded by taxation free at the point of delivery. Hospitals account for approximately 50% of overall NHS spending. Two-thirds of people admitted to hospital are over 65 with those over 85 accounting for 25% of bed days. This thesis aims to quantify hospital usage in a general population of middle-aged and older men and women over a 20-year follow-up period and to examine related demographic and behavioural factors. Patterns of hospital usage are described using two main hospital usage measures: admission numbers and length of stay. Socioeconomic factors such as education, occupational social class and residential area deprivation that may predict future hospital usage are examined. I assess the relationships between potentially modifiable factors such as cigarette smoking, the consumption of alcohol, body mass index and physical activity and future hospital usage while the implications for clinical and public health planning, policy and practice are also considered. The thesis is based on the European Prospective Investigation of Cancer in Norfolk (EPIC-Norfolk), a community-based cohort of 25,639 men and women aged 40-79 at recruitment between 1993-1997 and followed up to the present. Participants completed a lifestyle questionnaire and attended a clinic where measurements and blood were taken at baseline and again at a second time-point after 12 years. All participants were linked to hospital records using their unique NHS numbers and to census data using their postcode. Episode statistics including admission and discharge dates were used to create numbers of admissions and length of stay outcomes. ICD-10 diagnosis codes were used to construct a hospital multimorbidity outcome using the Charlson Comorbidity Index above the level of 3. Logistic regression was the primary statistical model used throughout the analyses. Exposures were examined prospectively, prior to any hospital admission. The current analyses were conducted on 25,014 participants in the cohort still alive in 1999 when hospital admission data were first available. Over the first 10 years of follow-up, 73% of study participants had at least one admission to hospital, 14% with ≥7 admissions and 20% with >20 hospital days. After 20 years, 90% of participants had a hospital admission, 65% had ≥7 admissions and 59% had >20 hospital days. High numbers of admissions and hospital days were positively associated with male sex, age, manual social class, current cigarette smoking and body mass index (BMI) >30 kg/m². The thesis examined levels of deprivation both at individual level, using education and occupational social class, and residential area level using the Townsend Area Deprivation Index. Compared with those having Townsend Index lower than the average for England and Wales, those with a higher than average deprivation index had a higher likelihood of spending >20 days in hospital. Occupational social class and educational attainment modified the association between area deprivation and hospitalisation; those with manual social class and lower education level were at greater risk of hospitalisation when living in an area with higher deprivation index. The thesis also examined potentially modifiable behavioural factors. Compared with current non-drinkers, men and women who reported any alcohol drinking had a lower risk of spending >20 days in hospital. Participants with a baseline physical activity score of at least moderately inactive had fewer hospital admissions and fewer days in hospital over 10 years, than those who were inactive. Similar associations were observed over 10 years from time-point two (TP2) and similar but attenuated results were observed for 20-year follow-up. Participants who remained physically active or became active between baseline and TP2 had lower risk of subsequent hospital usage than those who remained inactive or became inactive. An additional hospital-based outcome measure, hospital admission with multimorbidity (HAWM), was used to examine incident multimorbidity for participants free of the condition at baseline. Baseline 5-year and 10-year incident HAWM were observed in 11% and 21% of participants, respectively. More men had incident HAWM than women and those aged >75 years had the highest proportion of multimorbid conditions with 29% at 5 years and 47% at 10 years. HAWM rates at TP2 were similar to baseline. Longer duration of hospital stay and number of admissions, age, male sex and prevalent diseases, smoking, physical inactivity, high BMI and low fruit and vegetable intake were associated with incident HAWM. Simple demographic and behavioural indicators are related to the future probability of cumulative hospital admissions, length of stay and hospital admissions with multimorbidity. Increasing age, male sex and modifiable factors such as smoking, body mass index and usual physical activity are all strongly associated with subsequent hospital usage. Modest feasible differences in lifestyles in the general population may potentially mitigate the future impact of long hospital stay and multimorbidity and have a substantial impact on hospital usage and costs. The social determinants of health are well recognised. While some of the socioeconomic gradient in ill health has been attributed to differences in behavioural factors, there is also a socioeconomic gradient in hospital usage for individually measured social class and education and for area level deprivation apparently independently of measured behavioural factors and reported prevalent disease which warrant further exploration

Body Mass Index, Smoking, and Alcohol and Risks of Barrett’s Esophagus and Esophageal Adenocarcinoma: A UK Prospective Cohort Study

BACKGROUND: The timing of the risk factors cigarette smoking, alcohol and obesity in the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) is unclear. AIMS: To investigate these exposures in the aetiology of BE and EAC in the same population. METHODS: The cohort included 24,068 men and women, aged 39–79 years, recruited between 1993 and 1997 into the prospective EPIC-Norfolk Study who provided information on anthropometry, smoking and alcohol intake. The cohort was monitored until December 2008 and incident cases identified. RESULTS: One hundred and four participants were diagnosed with BE and 66 with EAC. A body mass index (BMI) above 23 kg/m(2) was associated with a greater risk of BE [BMI ≥23 vs. 18.5 to <23, hazard ratio (HR) 3.73, 95 % CI 1.37–10.16], and within a normal BMI, the risk was greater in the higher category (HR 3.76, 95 % CI 1.30–10.85, BMI 23–25 vs. 18.5 to >23 kg/m(2)). Neither smoking nor alcohol intake were associated with risk for BE. For EAC, all BMI categories were associated with risk, although statistically significant for only the highest (BMI >35 vs. BMI 18.5 to <23, HR 4.95, 95 % CI 1.11–22.17). The risk was greater in the higher category of a normal BMI (HR 2.73, 95 % CI 0.93–8.00, p = 0.07, BMI 23–25 vs. 18.5 to >23 kg/m(2)). There was an inverse association with ≥7 units alcohol/week (HR 0.51, 95 % CI 0.29–0.88) and with wine (HR 0.49, 95 % CI 0.23–1.04, p = 0.06, drinkers vs. non-drinkers). CONCLUSIONS: Obesity may be involved early in carcinogenesis and the association with EAC and wine should be explored. The data have implications for aetiological investigations and prevention strategies

Predicting admissions and time spent in hospital over a decade in a population-based record linkage study: the EPIC-Norfolk cohort.

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.The design and conduct of the EPIC-Norfolk study and collection and management of the data was supported by programme grants from the Medical Research Council UK (G9502233, G0401527) and Cancer Research UK (C864/A8257, C864/A2883).This is the final version of the article. It first appeared from the BMJ Group via http://dx.doi.org/10.1136/bmjopen-2015-00946

The association between physical activity and the risk of symptomatic Barrett’s oesophagus: a UK prospective cohort study

Background: Physical activity affects the functioning of the gastrointestinal system through both local and systemic effects and may play an important role in the aetiology of gastroesophageal reflux disease, Barrett’s oesophagus and oesophageal adenocarcinoma. We investigated, for the first time in a large prospective cohort study, associations between recreational and occupational levels of physical activity and the incidence of Barrett’s oesophagus. Participants and methods: The European Prospective Investigation of Cancer-Norfolk recruited 30 445 men and women between 1993 and 1997. Occupational and recreational levels of physical activity were measured using a baseline questionnaire. The cohort was followed up until 2015 to identify symptomatic cases of Barrett’s oesophagus. Cox proportional hazard regression estimated hazard ratios (HR) for physical activity and the development of disease. Results: Two hundred and three participants developed Barrett’s oesophagus (mean age: 70.6 years) the majority of whom were men (70.9%). There was an inverse association between standing occupations and disease risk [HR: 0.50, 95% confidence interval (CI): 0.31–0.82, P=0.006] when compared with sedentary jobs. Heavy manual occupations were positively associated with disease risk (HR: 1.66, 95% CI: 0.91–3.00), but conventional statistical significance was not reached (P=0.09). No associations were found between recreational activity and the risk of Barrett’s oesophagus (HR: 1.34, 95% CI: 0.72–2.50, P=0.35, highest vs. lowest levels of activity). Conclusion: Our study suggests that occupational levels of physical activity may be associated with the risk Barrett’s oesophagus. However, further work is required to confirm and describe specific occupations that may be protective

Dietary dairy product intake and incident type 2 diabetes: a prospective study using dietary data from a 7-day food diary

The consumption of specific dairy types may be beneficial for the prevention of diabetes. Abstract: The aim of this study was to investigate the association between total and types of dairy product intake and risk of developing incident type 2 diabetes, using a food diary. Methods: A nested case-cohort within the EPIC-Norfolk Study was examined, including a random subcohort (n=4,000) and cases of incident diabetes (n=892, including 143 cases in the subcohort) followed-up for 11 years. Diet was assessed using a prospective 7-day food diary. Total dairy intake (g/day) was estimated and categorised into high-fat (≥3.9%) and low-fat (&lt;3.9% fat) dairy, and by subtype into yoghurt, cheese and milk. Combined fermented dairy product intake (yoghurt, cheese, sour cream) was estimated and categorised into high- and low-fat. Prentice-weighted Cox regression HRs were calculated. Results: Total dairy, high-fat dairy, milk, cheese and high-fat fermented dairy product intakes were not associated with the development of incident diabetes. Low-fat dairy intake was inversely associated with diabetes in age- and sex-adjusted analyses (tertile [T] 3 vs T1, HR 0.81 [95% CI 0.66, 0.98]), but further adjustment for anthropometric, dietary and diabetes risk factors attenuated this association. In addition, an inverse association was found between diabetes and low-fat fermented dairy product intake (T3 vs T1, HR 0.76 [95% CI 0.60, 0.99]; ptrend=0.049) and specifically with yoghurt intake (HR 0.72 [95% CI 0.55, 0.95]; ptrend=0.017) in multivariable adjusted analyses. Conclusions/interpretation: Greater low-fat fermented dairy product intake, largely driven by yoghurt intake, was associated with a decreased risk of type 2 diabetes development in prospective analyses. These findings suggest that the consumption of specific dairy types may be beneficial for the prevention of diabetes, highlighting the importance of food group subtypes for public health messages

The Relationship Between Cognitive Performance Using Tests Assessing a Range of Cognitive Domains and Future Dementia Diagnosis in a British Cohort: A Ten-Year Prospective Study.

BACKGROUND: Exploring the domains of cognitive function which are most strongly associated with future dementia may help with understanding risk factors for, and the natural history of dementia. OBJECTIVE: To examine the association of performance on a range of cognitive tests (both global and domain specific) with subsequent diagnosis of dementia through health services in a population of relatively healthy men and women and risk of future dementia. METHODS: We examined the association between performance on different cognitive tests as well as a global score and future dementia risk ascertained through health record linkage in a cohort of 8,581 individuals (aged 48-92 years) between 2004-2019 with almost 15 years follow-up (average of 10 years) before and after adjustment for socio-demographic, lifestyle, and health characteristics. RESULTS: Those with poor performance for global cognition (bottom 10%) were almost four times as likely to receive a dementia diagnosis from health services over the next 15 years than those who performed well HR = 3.51 (95% CI 2.61, 4.71 p < 0.001) after adjustment for socioeconomic, lifestyle, and biological factors and also prevalent disease. Poor cognition performance in multiple tests was associated with 10-fold increased risk compared to those not performing poorly in any test HR = 10.82 (95% CI 6.85, 17.10 p < 0.001). CONCLUSION: Deficits across multiple cognitive domains substantially increase risk of future dementia over and above neuropsychological test scores ten years prior to a clinical diagnosis. These findings may help further understanding of the natural history of dementia and how such measures could contribute to strengthening future models of dementia.This work was supported by the Medical Research Council, UK (MRC) http://www.mrc.ac.uk/ (Ref: MR/N003284/1) Cancer Research UK http://www.cancerresearchuk. org/ (CRUK, Ref: C864/A8257) and NIHR https://www.nihr.ac.uk (Ref: NF-SI-0616-10090 to [CB]). The clinic for EPIC- Norfolk 3HC was funded by Research into Aging, now known as Age UK http://www.ageuk.org.uk/ (Grant Ref: 262). The pilot phase was supported by MRC (Ref: G9502233) and CRUK (Ref: C864/ A2883)

Cross-sectional and prospective relationship between occupational and leisure time inactivity and cognitive function in an ageing population. The European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) Study.

Background: The current evidence for higher physical activity and better cognitive function and lower risk of dementia is strong but not conclusive. More robust evidence is needed to inform public health policy. We provide further insight to discrepancies observed across studies, reporting on habitual inactivity including that during work. Methods: We examined cross-sectional and prospective relationships of physical inactivity during leisure and occupation time, with cognitive performance using a validated physical activity index in a cohort of 8585 men and women aged 40-79 years at baseline (1993-1997) for different domains using a range of cognitive measures. Cognitive testing was conducted between 2006-2011 (including pilot phase 2004-2006). Associations were examined using multinomial logistic regression adjusting for socio-demographic and health variables as well total habitual physical activity. Results: Inactivity during work was inversely associated with poor cognitive performance (bottom tenth percentile of a composite cognition score); Odds Ratio (OR) = 0·68 (95% Confidence Interval (CI) 0.54, 0·86) P=0·001. Results were similar cross-sectionally; OR = 0·65 (95% CI 0·45, 0·93) P=0·02. Manual workers had increased risk of poor performance compared to those with an occupation classified as inactive. Inactivity during leisure time was associated with increased risk of poor performance in the cross-sectional analyses only. Conclusions: The relationship between inactivity and cognition is strongly confounded by education, social class and occupation. Physical activity during leisure may be protective for cognition, but work related physical activity is not protective. A greater understanding of the mechanisms and confounding underlying these paradoxical findings is needed.This work was supported by the Medical Research Council, UK (MRC) http://www.mrc.ac.uk/ (Ref: MR/N003284/1, MC-UU_12015/1 to N.W.); Cancer Research UK, http://www.cancerresearchuk.org/ (CRUK, Ref: C864/A8257) and NIHR, https://www.nihr.ac.uk (Ref: NF-SI-0616–10090 to C.B.). The clinic for EPIC- orfolk 3HC was funded by Research into Ageing, now known as Age UK, http://www.ageuk.org.uk/ (Grant Ref: 262). The pilot phase was supported by MRC (Ref: G9502233) and CRUK (Ref: C864/A2883

Physical activity trajectories and mortality: population based cohort study.

OBJECTIVE: To assess the prospective associations of baseline and long term trajectories of physical activity on mortality from all causes, cardiovascular disease, and cancer. DESIGN: Population based cohort study. SETTING: Adults from the general population in the UK. PARTICIPANTS: 14 599 men and women (aged 40 to 79) from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, assessed at baseline (1993 to 1997) up to 2004 for lifestyle and other risk factors; then followed to 2016 for mortality (median of 12.5 years of follow-up, after the last exposure assessment). MAIN EXPOSURE: Physical activity energy expenditure (PAEE) derived from questionnaires, calibrated against combined movement and heart rate monitoring. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular disease, and cancer. Multivariable proportional hazards regression models were adjusted for age, sex, sociodemographics, and changes in medical history, overall diet quality, body mass index, blood pressure, triglycerides, and cholesterol levels. RESULTS: During 171 277 person years of follow-up, 3148 deaths occurred. Long term increases in PAEE were inversely associated with mortality, independent of baseline PAEE. For each 1 kJ/kg/day per year increase in PAEE (equivalent to a trajectory of being inactive at baseline and gradually, over five years, meeting the World Health Organization minimum physical activity guidelines of 150 minutes/week of moderate-intensity physical activity), hazard ratios were: 0.76 (95% confidence interval 0.71 to 0.82) for all cause mortality, 0.71 (0.62 to 0.82) for cardiovascular disease mortality, and 0.89 (0.79 to 0.99) for cancer mortality, adjusted for baseline PAEE, and established risk factors. Similar results were observed when analyses were stratified by medical history of cardiovascular disease and cancer. Joint analyses with baseline and trajectories of physical activity show that, compared with consistently inactive individuals, those with increasing physical activity trajectories over time experienced lower risks of mortality from all causes, with hazard ratios of 0.76 (0.65 to 0.88), 0.62 (0.53 to 0.72), and 0.58 (0.43 to 0.78) at low, medium, and high baseline physical activity, respectively. At the population level, meeting and maintaining at least the minimum physical activity recommendations would potentially prevent 46% of deaths associated with physical inactivity. CONCLUSIONS: Middle aged and older adults, including those with cardiovascular disease and cancer, can gain substantial longevity benefits by becoming more physically active, irrespective of past physical activity levels and established risk factors. Considerable population health impacts can be attained with consistent engagement in physical activity during mid to late life.The EPIC-Norfolk study is supported by programme grants from the Medical Research CouncilandCancer Research UKwith additional support from the Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and the Wellcome Trust. Alexander Mok was supported by the National Science Scholarship from Singapore, A*STAR (Agency for Science, Technology and Research).The work of Nick Wareham and Soren Brage was funded by the Medical Research Council UK [MC_UU_12015/1 and MC_UU_12015/3].The funders had no role in the study design; the collection, analysis, and interpretation of data; the writing of the manuscript; or the decision to submit the article for publication

Dietary Fiber and the Risk of Pancreatic Cancer

Objectives: High dietary fiber may protect against pancreatic ductal adenocarcinoma (PDAC). We investigated associations between fiber intake and the risk of PDAC using for the first time 7-day food diaries. Methods: Participants in the European Prospective Investigation Into Cancer–Norfolk completed the 7-day food diaries at recruitment. The cohort was followed up for 17 years to identify those who developed PDAC. Participants were divided into quintiles of fiber intake, and hazard ratios (HR) were estimated with their 95% confidence intervals (CIs). Fiber was tested for effect modification of high red and processed meat intake and smoking and the risk of PDAC. Results: No significant associations for any quintiles of intake (HR Q5 vs Q1, 1.08; 95% CI, 0.56–2.08) were detected with no trend across quintiles. A high-fiber diet modified positive associations between red and processed meats with the development of PDAC (HR trends, 0.89 [95% CI, 0.47–1.69] and 1.02 [95% CI, 0.55–1.88], respectively) but not those with lower fiber intake. Fiber intake did not modify the risk of PDAC in past and current smokers. Conclusion: The findings do not suggest that fiber protects against PDAC, although it may decrease potential deleterious effects of meats