Self-reported physical functional health predicts future bone mineral density in EPIC-Norfolk cohort.

Using a large population sample from the UK, we found that self-reported physical functional health may be used to predict future bone mineral density especially in women. It may be a useful and inexpensive way to identify individuals before further decline in bone mineral density and the risk of fracture. PURPOSE: Self-reported physical functional health may predict bone mineral density (BMD) and thus provide a method to identify people at risk of low BMD. In this study, the association between the 36-item short-form questionnaire (SF-36) physical component summary (PCS) score and future BMD in participants aged 40-79 years enrolled in the European Prospective Investigation of Cancer-Norfolk study was investigated. METHODS: Associations between a participant's SF-36 PCS score, measured 18 months after baseline health check, and broadband ultrasound attenuation (BUA-a measure of BMD), measured 2-5 years after baseline, were examined using sex-specific linear and logistic regression analyses adjusting for age, BMI, medical co-morbidities, lifestyle and socioeconomic factors. RESULTS: Data from 10,203 participants, mean (standard deviation (SD)) age 61.5 (8.9) years (57.4% women), were analysed from 1993 to 2000. For every five points lower PCS score in men and women, there was approximately a 0.5 dB/MHz lower mean BUA. In women, a PCS score of less than one standard deviation (1SD) below the sex-specific mean was associated with having a low BUA (< 1SD below sex-specific mean) and very low BUA (< 2.5SD below the sex specific mean); odds ratio (OR) (95% confidence interval) 1.53 (1.24, 1.88) and 8.28 (2.67, 25.69), respectively. The relationship was lesser so in men; corresponding OR (95% CI) were 1.34 (0.91, 1.98) and 2.57 (0.72, 9.20), respectively. CONCLUSIONS: Self-reported physical functioning predicts BMD in an apparently healthy population, particularly in women. This could potentially provide an inexpensive, simple screening tool to identify individuals at risk of osteoporosis.

Utility of Genetically Predicted Lp(a) (Lipoprotein [a]) and ApoB Levels for Cardiovascular Risk Assessment.

BACKGROUND: Current lipid guidelines suggest measurement of Lp(a) (lipoprotein[a]) and ApoB (apolipoprotein B) for atherosclerotic cardiovascular disease risk assessment. Polygenic risk scores (PRSs) for Lp(a) and ApoB may identify individuals unlikely to have elevated Lp(a) or ApoB and thus reduce such suggested testing. METHODS: PRSs were developed using least absolute shrinkage and selection operator regression among 273 222 and 356 958 UK Biobank participants of white British ancestry for Lp(a) and ApoB, respectively, and validated in separate sets of 60 771 UK Biobank and 15 050 European Prospective Investigation into Cancer and Nutrition-Norfolk participants. We then assessed the proportion of participants who, based on these PRSs, were unlikely to benefit from Lp(a) or ApoB measurements, according to current lipid guidelines. RESULTS: In the UK Biobank and European Prospective Investigation into Cancer and Nutrition-Norfolk cohorts, the area under the receiver operating curve for the PRS-predicted Lp(a) and ApoB to identify individuals with elevated Lp(a) and ApoB was at least 0.91 (95% CI, 0.90-0.92) and 0.74 (95% CI, 0.73-0.75), respectively. The Lp(a) PRS and measured Lp(a) showed comparable association with atherosclerotic cardiovascular disease incidence, whereas the ApoB PRS was in general less predictive of atherosclerotic cardiovascular disease risk than measured ApoB. In the context of the European Society of Cardiology/European Atherosclerosis Society lipid guidelines, at a 95% sensitivity to identify individuals with elevated Lp(a) and ApoB levels, at least 54% of Lp(a) and 24% of ApoB testing could be reduced by prescreening with a PRS while maintaining a low false-negative rate. CONCLUSIONS: A substantial proportion of suggested testing for elevated Lp(a) and a modest proportion of testing for elevated ApoB could potentially be reduced by prescreening individuals with PRSs.

Cardiorespiratory fitness assessment using risk-stratified exercise testing and dose-response relationships with disease outcomes.

Cardiorespiratory fitness (CRF) is associated with mortality and cardiovascular disease, but assessing CRF in the population is challenging. Here we develop and validate a novel framework to estimate CRF (as maximal oxygen consumption, VO2max) from heart rate response to low-risk personalised exercise tests. We apply the method to examine associations between CRF and health outcomes in the UK Biobank study, one of the world's largest and most inclusive studies of CRF, showing that risk of all-cause mortality is 8% lower (95%CI 5-11%, 2670 deaths among 79,981 participants) and cardiovascular mortality is 9% lower (95%CI 4-14%, 854 deaths) per 1-metabolic equivalent difference in CRF. Associations obtained with the novel validated CRF estimation method are stronger than those obtained using previous methodology, suggesting previous methods may have underestimated the importance of fitness for human health.

The global diet and activity research (GDAR) network: a global public health partnership to address upstream NCD risk factors in urban low and middle-income contexts.

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. While upstream approaches to tackle NCD risk factors of poor quality diets and physical inactivity have been trialled in high income countries (HICs), there is little evidence from low and middle-income countries (LMICs) that bear a disproportionate NCD burden. Sub-Saharan Africa and the Caribbean are therefore the focus regions for a novel global health partnership to address upstream determinants of NCDs. PARTNERSHIP: The Global Diet and Activity research Network (GDAR Network) was formed in July 2017 with funding from the UK National Institute for Health Research (NIHR) Global Health Research Units and Groups Programme. We describe the GDAR Network as a case example and a potential model for research generation and capacity strengthening for others committed to addressing the upstream determinants of NCDs in LMICs. We highlight the dual equity targets of research generation and capacity strengthening in the description of the four work packages. The work packages focus on learning from the past through identifying evidence and policy gaps and priorities, understanding the present through adolescent lived experiences of healthy eating and physical activity, and co-designing future interventions with non-academic stakeholders. CONCLUSION: We present five lessons learned to date from the GDAR Network activities that can benefit other global health research partnerships. We close with a summary of the GDAR Network contribution to cultivating sustainable capacity strengthening and cutting-edge policy-relevant research as a beacon to exemplify the need for such collaborative groups.

Using natural experimental studies to guide public health action: turning the evidence-based medicine paradigm on its head.

Despite smaller effect sizes, interventions delivered at population level to prevent non-communicable diseases generally have greater reach, impact and equity than those delivered to high-risk groups. Nevertheless, how to shift population behaviour patterns in this way remains one of the greatest uncertainties for research and policy. Evidence about behaviour change interventions that are easier to evaluate tends to overshadow that for population-wide and system-wide approaches that generate and sustain healthier behaviours. Population health interventions are often implemented as natural experiments, which makes their evaluation more complex and unpredictable than a typical randomised controlled trial (RCT). We discuss the growing importance of evaluating natural experiments and their distinctive contribution to the evidence for public health policy. We contrast the established evidence-based practice pathway, in which RCTs generate 'definitive' evidence for particular interventions, with a practice-based evidence pathway in which evaluation can help adjust the compass bearing of existing policy. We propose that intervention studies should focus on reducing critical uncertainties, that non-randomised study designs should be embraced rather than tolerated and that a more nuanced approach to appraising the utility of diverse types of evidence is required. The complex evidence needed to guide public health action is not necessarily the same as that which is needed to provide an unbiased effect size estimate. The practice-based evidence pathway is neither inferior nor merely the best available when all else fails. It is often the only way to generate meaningful evidence to address critical questions about investing in population health interventions.

Residential area deprivation and risk of subsequent hospital admission in a British population: the EPIC-Norfolk cohort.

OBJECTIVES: To investigate whether residential area deprivation index predicts subsequent admissions to hospital and time spent in hospital independently of individual social class and lifestyle factors. DESIGN: Prospective population-based study. SETTING: The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) study. PARTICIPANTS: 11 214 men and 13 763 women in the general population, aged 40-79 years at recruitment (1993-1997), alive in 1999. MAIN OUTCOME MEASURE: Total admissions to hospital and time spent in hospital during a 19-year time period (1999-2018). 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 >20 days in hospital multivariable adjusted OR 1.18 (95% CI 1.07 to 1.29) and having 7 or more admissions OR 1.11 (95% CI 1.02 to 1.22) after adjustment for age, sex, smoking status, education, social class and body mass index. 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 (p-interaction=0.025 and 0.020, respectively), while the risk for non-manual and more highly educated participants did not vary greatly by area of residence. 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. Conversely, higher education level and social class mitigated the association of area deprivation with hospital usage.

Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial.

BACKGROUND: The multicentre, international ADDITION-Europe study investigated the effect of promoting intensive treatment of multiple risk factors among people with screen-detected type 2 diabetes over 5 years. Here we report the results of a post-hoc 10-year follow-up analysis of ADDITION-Europe to establish whether differences in treatment and cardiovascular risk factors have been maintained and to assess effects on cardiovascular outcomes. METHODS: As previously described, general practices from four centres (Denmark, Cambridge [UK], Leicester [UK], and the Netherlands) were randomly assigned by computer-generated list to provide screening followed by routine care of diabetes, or screening followed by intensive multifactorial treatment. Population-based stepwise screening programmes among people aged 40-69 years (50-69 years in the Netherlands), between April, 2001, and December, 2006, identified patients with type 2 diabetes. Allocation was concealed from patients. Following the 5-year follow-up, no attempts were made to maintain differences in treatment between study groups. In this report, we did a post-hoc analysis of cardiovascular and renal outcomes over 10 years following randomisation, including a 5 years post-intervention follow-up. As in the original trial, the primary endpoint was a composite of first cardiovascular event, including cardiovascular mortality, cardiovascular morbidity (non-fatal myocardial infarction and non-fatal stroke), revascularisation, and non-traumatic amputation, up to Dec 31, 2014. Analyses were based on the intention-to-treat principle. ADDITION-Europe is registered with ClinicalTrials.gov, NCT00237549. FINDINGS: 343 general practices were randomly assigned to routine diabetes care (n=176) or intensive multifactorial treatment (n=167). 317 of these general practices (157 in the routine care group, 161 in the intensive treatment group) included eligible patients between April, 2001, and December, 2006. Of the 3233 individuals with screen-detected diabetes, 3057 agreed to participate (1379 in the routine care group, 1678 in the intensive treatment group), but at the 10-year follow-up 14 were lost to follow-up and 12 withdrew, leaving 3031 to enter 10-year follow-up analysis. Mean duration of follow-up was 9·61 years (SD 2·99). Sustained reductions over 10 years following diagnosis were apparent for bodyweight, HbA1c, blood pressure, and cholesterol in both study groups, but between-group differences identified at 1 and 5 years were attenuated at the 10-year follow-up. By 10 years, 443 participants had a first cardiovascular event and 465 died. There was no significant difference between groups in the incidence of the primary composite outcome (16·1 per 1000 person-years in the routine care group vs 14·3 per 1000 person-years in the intensive treatment group; hazard ratio [HR] 0·87, 95% CI 0·73-1·04; p=0·14) or all-cause mortality (15·6 vs 14·3 per 1000 person-years; HR 0·90, 0·76-1·07). INTERPRETATION: Sustained reductions in glycaemia and related cardiovascular risk factors over 10 years among people with screen-detected diabetes managed in primary care are achievable. The differences in prescribed treatment and cardiovascular risk factors in the 5 years following diagnosis were not maintained at 10 years, and the difference in cardiovascular events and mortality remained non-significant. FUNDING: National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Novo Nordisk, Novo Nordisk Foundation, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, UK National Health Service, Merck, Julius Center for Health Sciences and Primary Care, UK Department of Health, and Nuts-OHRA.

Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT.

BACKGROUND: The treatment of people with diabetes with metformin can reduce cardiovascular disease (CVD) and may reduce the risk of cancer. However, it is unknown whether or not metformin can reduce the risk of these outcomes in people with elevated blood glucose levels below the threshold for diabetes [i.e. non-diabetic hyperglycaemia (NDH)]. OBJECTIVE: To assess the feasibility of the Glucose Lowering In Non-diabetic hyperglycaemia Trial (GLINT) and to estimate the key parameters to inform the design of the full trial. These parameters include the recruitment strategy, randomisation, electronic data capture, postal drug distribution, retention, study medication adherence, safety monitoring and remote collection of outcome data. DESIGN: A multicentre, individually randomised, double-blind, parallel-group, pragmatic, primary prevention trial. Participants were individually randomised on a 1 : 1 basis, blocked within each site. SETTING: General practices and clinical research facilities in Cambridgeshire, Norfolk and Leicestershire. PARTICIPANTS: Males and females aged ≥ 40 years with NDH who had a high risk of CVD. INTERVENTIONS: Prolonged-release metformin (500 mg) (Glucophage® SR, Merck KGaA, Bedfont Cross, Middlesex, UK) or the matched placebo, up to three tablets per day, distributed by post. MAIN OUTCOME MEASURES: Recruitment rates; adherence to study medication; laboratory results at baseline and 3 and 6 months; reliability and acceptability of study drug delivery; questionnaire return rates; and quality of life. RESULTS: We sent 5251 invitations, with 511 individuals consenting to participate. Of these, 249 were eligible and were randomised between March and November 2015 (125 to the metformin group and 124 to the placebo group). Participants were followed up for 0.99 years [standard deviation (SD) 0.30 years]. The use of electronic medical records to identify potentially eligible individuals in individual practices was resource intensive. Participants were generally elderly [mean age 70 years (SD 6.7 years)], overweight [mean body mass index 30.1 kg/m2 (SD 4.5 kg/m2)] and male (88%), and the mean modelled 10-year CVD risk was 28.8% (SD 8.5%). Randomisation, postal delivery of the study drug and outcome assessment using registers/medical records were feasible and acceptable to participants. Most participants were able to take three tablets per day, but premature discontinuation of the study drug was common (≈30% of participants by 6 months), although there were no differences between the groups. All randomised participants returned questionnaires at baseline and 67% of participants returned questionnaires by the end of the study. There was no between-group difference in Short Form questionnaire-8 items or EuroQol-5 Dimensions scores. Compared with placebo, metformin was associated with small improvements in the mean glycated haemoglobin level [-0.82 mmol/mol, 95% confidence interval (CI) -1.39 to -0.24 mmol/mol], mean estimated glomerular filtration rate (2.31 ml/minute/1.73 m2, 95% CI -0.2 to 4.81 ml/minute/1.73 m2) and mean low-density lipoprotein cholesterol level (-0.11 mmol/l, 95% CI -0.25 to 0.02 mmol/l) and a reduction in mean plasma vitamin B12 level (-16.4 ng/l, 95% CI -32.9 to -0.01 ng/l). There were 35 serious adverse events (13 in the placebo group, 22 in the metformin group), with none deemed to be treatment related. LIMITATIONS: Changes to sponsorship reduced the study duration, the limited availability of information in medical records reduced recruitment efficiency and discontinuation of study medication exceeded forecasts. CONCLUSIONS: A large, pragmatic trial comparing the effects of prolonged-release metformin and placebo on the risk of CVD events is potentially feasible. However, changes to the study design and conduct are recommended to enable an efficient scaling up of the trial. Recommendations include changing the inclusion criteria to recruit people with pre-existing CVD to increase the recruitment and event rates, using large primary/secondary care databases to increase recruitment rates, conducting follow-up remotely to improve efficiency and including a run-in period prior to randomisation to optimise trial adherence. TRIAL REGISTRATION: Current Controlled Trials ISRCTN34875079. FUNDING: The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 18. See the NIHR Journals Library website for further project information. Merck KGaA provided metformin and matching placebo.

Dietary cost associated with adherence to the Mediterranean diet, and its variation by socio-economic factors in the UK Fenland Study.

High cost of healthy foods could be a barrier to healthy eating. We aimed to examine the association between dietary cost and adherence to the Mediterranean diet in a non-Mediterranean country. We evaluated cross-sectional data from 12 417 adults in the UK Fenland Study. Responses to 130-item FFQ were used to calculate a Mediterranean diet score (MDS). Dietary cost was estimated by matching food consumption data with retail prices of five major supermarkets. Using multivariable-adjusted linear regression, we examined the association of MDS and individual foods with dietary cost in absolute and relative scales. Subsequently, we assessed how much the association was explained by education, income, marital status and occupation, by conducting mediation analysis and testing interaction by these variables. High compared with low MDS (top to bottom third) was associated with marginally higher cost by 5·4 % (95 % CI 4·4, 6·4) or £0·20/d (95 % CI 0·16, 0·25). Participants with high adherence had higher cost associated with the healthier components (e.g. vegetables, fruits and fish), and lower cost associated with the unhealthy components (e.g. red meat, processed meat and sweets) (P for trend<0·001 each). In total, 20·7 % (95 % CI 14·3, 27·0) of the MDS-cost association was explained by the selected socio-economic factors, and the MDS-cost association was of greater magnitude in lower socio-economic groups (P interaction<0·005). Overall, greater adherence to the Mediterranean diet was associated with marginally higher dietary cost, partly modified and explained by socio-economic status, but the potential economic barriers of high adherence might be offset by cost saving from reducing unhealthy food consumption.

Interplay of Socioeconomic Status and Supermarket Distance Is Associated with Excess Obesity Risk: A UK Cross-Sectional Study.

U.S. policy initiatives have sought to improve health through attracting neighborhood supermarket investment. Little evidence exists to suggest that these policies will be effective, in particular where there are socioeconomic barriers to healthy eating. We measured the independent associations and combined interplay of supermarket access and socioeconomic status with obesity. Using data on 9702 UK adults, we employed adjusted regression analyses to estimate measured BMI (kg/m²), overweight (25 ≥ BMI < 30) and obesity (≥30), across participants' highest educational attainment (three groups) and tertiles of street network distance (km) from home location to nearest supermarket. Jointly-classified models estimated combined associations of education and supermarket distance, and relative excess risk due to interaction (RERI). Participants farthest away from their nearest supermarket had higher odds of obesity (OR 1.33, 95% CI: 1.11, 1.58), relative to those living closest. Lower education was also associated with higher odds of obesity. Those least-educated and living farthest away had 3.39 (2.46-4.65) times the odds of being obese, compared to those highest-educated and living closest, with an excess obesity risk (RERI = 0.09); results were similar for overweight. Our results suggest that public health can be improved through planning better access to supermarkets, in combination with interventions to address socioeconomic barriers.

Sociodemographic, lifestyle and behavioural factors associated with consumption of sweetened beverages among adults in Cambridgeshire, UK: the Fenland Study.

OBJECTIVE: We aimed to identify sociodemographic, lifestyle and behavioural determinants of consumption of sugar-sweetened beverages (SSB) and artificially sweetened beverages (ASB) among adults in Cambridgeshire, UK. DESIGN: Cross-sectional data were obtained from a cohort of 9991 adults born between 1950 and 1975. An FFQ was used to assess consumption of beverages and other dietary factors. Multivariable logistic regression was used to examine potential determinants of consuming SSB and ASB (≥1 serving/d). SETTING: Recruitment from general practice surgeries to participate in the ongoing population-based Fenland Study. SUBJECTS: Adults (n 9991) aged 30-64 years from three areas of Cambridgeshire, UK. RESULTS: Prevalence estimates for daily SSB and ASB consumption were 20·4 % (n 2041) and 8·9 % (n 893), respectively. SSB consumption (OR; 95 % CI) was more common in men than women (1·33; CI 1·17, 1·50) and among those reporting lower income (£40 000/year; 1·31; 1·09, 1·58). In contrast, daily ASB consumption was more common among women than men (1·62; 1·34, 1·96), those on weight-loss diets than those who were not (2·58; 2·05, 3·24) and those reporting higher income than lower income (1·53; 1·16, 2·00). Factors associated with higher consumption of each of SSB and ASB included being a younger adult, being overweight/obese, having shorter education, eating meals or snack foods while watching television, and skipping breakfast (P<0·05 each). CONCLUSIONS: Frequent consumers of SSB and ASB differ by several sociodemographic characteristics. However, increased BMI, younger age and unhealthy eating behaviours are common to both groups.

Accessibility and Affordability of Supermarkets: Associations With the DASH Diet.

INTRODUCTION: It is unknown whether there is an interplay of affordability (economic accessibility) and proximity (geographic accessibility) of supermarkets in relation to having a Dietary Approaches to Stop Hypertension (DASH)-accordant diet. METHODS: Data (collected: 2005-2015, analyzed: 2016) were from the cross-sectional, population-based Fenland Study cohort: 9,274 adults aged 29-64 years, living in Cambridgeshire, United Kingdom. Dietary quality was evaluated using an index of DASH dietary accordance, based on recorded consumption of foods and beverages in a validated 130-item, semi-quantitative food frequency questionnaire. DASH accordance was defined as a DASH score in the top quintile. Dietary costs (£/day) were estimated by attributing a food price variable to the foods consumed according to the questionnaire. Individuals were classified as having low-, medium-, or high-cost diets. Supermarket affordability was determined based on the cost of a 101-item market basket. Distances between home address to the nearest supermarket (geographic accessibility) and nearest economically-appropriate supermarket (economic accessibility) were divided into tertiles. RESULTS: Higher-cost diets were more likely to be DASH-accordant. After adjustment for key demographics and exposure to other food outlets, individuals with lowest economic accessibility to supermarkets had lower odds of being DASH-accordant (OR=0.59, 95% CI=0.52, 0.68) than individuals with greatest economic accessibility. This association was stronger than with geographic accessibility alone (OR=0.85, 95% CI=0.74, 0.98). CONCLUSIONS: Results suggest that geographic and economic access to food should be taken into account when considering approaches to promote adherence to healthy diets for the prevention of cardiovascular diseases and other chronic disease.

Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study.

BACKGROUND: Physical activity has not been objectively measured in prospective cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes. Technological advances now make this possible. We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study, and report variation by age, sex, day, time of day, and season. METHODS: Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them. Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration, removal of gravity and sensor noise, and identification of wear / non-wear episodes. We report age- and sex-specific wear-time compliance and accelerometer measured physical activity, overall and by hour-of-day, week-weekend day and season. RESULTS: 103,712 datasets were received (44.8% response), with a median wear-time of 6.9 days (IQR:6.5-7.0). 96,600 participants (93.3%) provided valid data for physical activity analyses. Vector magnitude, a proxy for overall physical activity, was 7.5% (2.35mg) lower per decade of age (Cohen's d = 0.9). Women had a higher vector magnitude than men, apart from those aged 45-54yrs. There were major differences in vector magnitude by time of day (d = 0.66). Vector magnitude differences between week and weekend days (d = 0.12 for men, d = 0.09 for women) and between seasons (d = 0.27 for men, d = 0.15 for women) were small. CONCLUSIONS: It is feasible to collect and analyse objective physical activity data in large studies. The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening. This work lays the foundation for studies of physical activity and its health consequences. Our summary variables are part of the UK Biobank dataset and can be used by researchers as exposures, confounding factors or outcome variables in future analyses.

Estimation of Physical Activity Energy Expenditure during Free-Living from Wrist Accelerometry in UK Adults.

BACKGROUND: Wrist-worn accelerometers are emerging as the most common instrument for measuring physical activity in large-scale epidemiological studies, though little is known about the relationship between wrist acceleration and physical activity energy expenditure (PAEE). METHODS: 1695 UK adults wore two devices simultaneously for six days; a combined sensor and a wrist accelerometer. The combined sensor measured heart rate and trunk acceleration, which was combined with a treadmill test to yield a signal of individually-calibrated PAEE. Multi-level regression models were used to characterise the relationship between the two time-series, and their estimations were evaluated in an independent holdout sample. Finally, the relationship between PAEE and BMI was described separately for each source of PAEE estimate (wrist acceleration models and combined-sensing). RESULTS: Wrist acceleration explained 44-47% between-individual variance in PAEE, with RMSE between 34-39 J•min-1•kg-1. Estimations agreed well with PAEE in cross-validation (mean bias [95% limits of agreement]: 0.07 [-70.6:70.7]) but overestimated in women by 3% and underestimated in men by 4%. Estimation error was inversely related to age (-2.3 J•min-1•kg-1 per 10y) and BMI (-0.3 J•min-1•kg-1 per kg/m2). Associations with BMI were similar for all PAEE estimates (approximately -0.08 kg/m2 per J•min-1•kg-1). CONCLUSIONS: A strong relationship exists between wrist acceleration and PAEE in free-living adults, such that irrespective of the objective method of PAEE assessment, a strong inverse association between PAEE and BMI was observed.

A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study.

BACKGROUND: Intensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain. OBJECTIVE: To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes. DESIGN: Pragmatic, multicentre, cluster-randomised, parallel-group trial. SETTING: Three hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK. PARTICIPANTS: Individuals aged 40-69 years with screen-detected diabetes. INTERVENTIONS: Screening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol. MAIN OUTCOME MEASURES: The primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3; (©) Isis Innovation Ltd 2010; see www.dtu.ox.ac.uk/outcomesmodel (accessed 27 January 2016)]. RESULTS: We included 3055 (RC, n = 1377; IT, n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient. CONCLUSIONS: Compared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00237549. FUNDING DETAILS: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 64. See the NIHR Journals Library website for further project information.

Dietary Diversity, Diet Cost, and Incidence of Type 2 Diabetes in the United Kingdom: A Prospective Cohort Study.

BACKGROUND: Diet is a key modifiable risk factor for multiple chronic conditions, including type 2 diabetes (T2D). Consuming a range of foods from the five major food groups is advocated as critical to healthy eating, but the association of diversity across major food groups with T2D is not clear and the relationship of within-food-group diversity is unknown. In addition, there is a growing price gap between more and less healthy foods, which may limit the uptake of varied diets. The current study had two aims: first, to examine the association of reported diversity of intake of food groups as well as their subtypes with risk of developing T2D, and second, to estimate the monetary cost associated with dietary diversity. METHODS AND FINDINGS: A prospective study of 23,238 participants in the population-based EPIC-Norfolk cohort completed a baseline Food Frequency Questionnaire in 1993-1997 and were followed up for a median of 10 y. We derived a total diet diversity score and additional scores for diversity within each food group (dairy products, fruits, vegetables, meat and alternatives, and grains). We used multivariable Cox regression analyses for incident diabetes (892 new cases), and multivariable linear regression for diet cost. Greater total diet diversity was associated with 30% lower risk of developing T2D (Hazard ratio [HR] 0.70 [95% CI 0.51 to 0.95]) comparing diets comprising all five food groups to those with three or fewer, adjusting for confounders including obesity and socioeconomic status. In analyses of diversity within each food group, greater diversity in dairy products (HR 0.61 [0.45 to 0.81]), fruits (HR 0.69 [0.52 to 0.90]), and vegetables (HR 0.67 [0.52 to 0.87]) were each associated with lower incident diabetes. The cost of consuming a diet covering all 5 food groups was 18% higher (£4.15/day [4.14 to 4.16]) than one comprising three or fewer groups. Key limitations are the self-reported dietary data and the binary scoring approach whereby some food groups contained both healthy and less healthy food items. CONCLUSIONS: A diet characterized by regular consumption of all five food groups and by greater variety of dairy, fruit, and vegetable subtypes, appears important for a reduced risk of diabetes. However, such a diet is more expensive. Public health efforts to prevent diabetes should include food price policies to promote healthier, more varied diets.

Does neighborhood fast-food outlet exposure amplify inequalities in diet and obesity? A cross-sectional study.

BACKGROUND: Greater exposures to fast-food outlets and lower levels of education are independently associated with less healthy diets and obesity. Little is known about the interplay between these environmental and individual factors. OBJECTIVE: The purpose of this study was to test whether observed differences in fast-food consumption and obesity by fast-food outlet exposure are moderated by educational attainment. DESIGN: In a population-based cohort of 5958 adults aged 29-62 y in Cambridgeshire, United Kingdom, we used educational attainment-stratified regression models to estimate the food-frequency questionnaire-derived consumption of energy-dense "fast foods" (g/d) typically sold in fast-food restaurants and measured body mass index (BMI; in kg/m(2)) across geographic information system-derived home and work fast-food exposure quartiles. We used logistic regression to estimate the odds of obesity (BMI ≥30) and calculated relative excess risk due to interaction (RERI) on an additive scale. Participant data were collected during 2005-2013 and analyzed in 2015. RESULTS: Greater fast-food consumption, BMI, and odds of obesity were associated with greater fast-food outlet exposure and a lower educational level. Fast-food consumption and BMI were significantly different across education groups at all levels of fast-food outlet exposure (P < 0.05). High fast-food outlet exposure amplified differences in fast-food consumption across levels of education. The relation between fast-food outlet exposure and obesity was only significant among those who were least educated (OR: 2.05; 95% CI: 1.08, 3.87; RERI = 0.88), which suggested a positive additive interaction between education and fast-food outlet exposure. CONCLUSION: These findings suggest that efforts to improve diets and health through neighborhood-level fast-food outlet regulation might be effective across socioeconomic groups and may serve to reduce observed socioeconomic inequalities in diet and obesity.

Repeat Cardiovascular Risk Assessment after Four Years: Is There Improvement in Risk Prediction?

BACKGROUND: Framingham risk equations are widely used to predict cardiovascular disease based on health information from a single time point. Little is known regarding use of information from repeat risk assessments and temporal change in estimated cardiovascular risk for prediction of future cardiovascular events. This study was aimed to compare the discrimination and risk reclassification of approaches using estimated cardiovascular risk at single and repeat risk assessments. METHODS: Using data on 12,197 individuals enrolled in EPIC-Norfolk cohort, with 12 years of follow-up, we examined rates of cardiovascular events by levels of estimated absolute risk (Framingham risk score) at the first and second health examination four years later. We calculated the area under the receiver operating characteristic curve (aROC) and risk reclassification, comparing approaches using information from single and repeat risk assessments (i.e., estimated risk at different time points). RESULTS: The mean Framingham risk score increased from 15.5% to 17.5% over a mean of 3.7 years from the first to second health examination. Individuals with high estimated risk (≥20%) at both health examinations had considerably higher rates of cardiovascular events than those who remained in the lowest risk category (<10%) in both health examinations (34.0 [95%CI 31.7-36.6] and 2.7 [2.2-3.3] per 1,000 person-years respectively). Using information from the most up-to-date risk assessment resulted in a small non-significant change in risk classification over the previous risk assessment (net reclassification improvement of -4.8%, p>0.05). Using information from both risk assessments slightly improved discrimination compared to information from a single risk assessment (aROC 0.76 and 0.75 respectively, p<0.001). CONCLUSIONS: Using information from repeat risk assessments over a period of four years modestly improved prediction, compared to using data from a single risk assessment. However, this approach did not improve risk classification.