Scholarly Works - Public Health and Primary Care

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    Open Access
    Body composition and atrial fibrillation: a Mendelian randomization study.
    (Oxford University Press (OUP), 2019-04-21) Tikkanen, Emmi; Gustafsson, Stefan; Knowles, Joshua W; Perez, Marco; Burgess, Stephen; Ingelsson, Erik; Burgess, Stephen [0000-0001-5365-8760]
    AIMS: Increases in fat-free mass and fat mass have been associated with higher risk of atrial fibrillation (AF) in observational studies. It is not known whether these associations reflect independent causal processes. Our aim was to evaluate independent causal roles of fat-free mass and fat mass on AF. METHODS AND RESULTS: We conducted a large observational study to estimate the associations between fat-free mass and fat mass on incident AF in the UK Biobank (N = 487 404, N events = 10 365). Genome-wide association analysis was performed to obtain genetic instruments for Mendelian randomization (MR). We evaluated the causal effects of fat-free mass and fat mass on AF with two-sample method by using genetic associations from AFGen consortium as outcome. Finally, we evaluated independent causal effects of fat-free mass and fat mass with multivariate MR. Both fat-free mass and fat mass had observational associations with incident AF [hazard ratio (HR) = 1.77, 95% confidence interval (CI) 1.72-1.83; HR = 1.40, 95% CI 1.37-1.43 per standard deviation increase in fat-free and fat mass, respectively]. The causal effects using the inverse-variance weighted method were 1.55 (95% CI 1.38-1.75) for fat-free mass and 1.30 (95% CI 1.17-1.45) for fat mass. Weighted median, Egger regression, and penalized methods showed similar estimates. The multivariate MR analysis suggested that the causal effects of fat-free and fat mass were independent of each other (causal risk ratios: 1.37, 95% CI 1.06-1.75; 1.28, 95% CI 1.03-1.58). CONCLUSION: Genetically programmed increases in fat-free mass and fat mass independently cause an increased risk of AF.
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    Open Access
    Randomised controlled trial of a theory-based behavioural intervention to reduce formula milk intake.
    (BMJ, 2018-11) Lakshman, Rajalakshmi; Sharp, Stephen J; Whittle, Fiona; Schiff, Annie; Hardeman, Wendy; Irvine, Lisa; Wilson, Ed; Griffin, Simon J; Ong, Ken K; Lakshman, Rajalakshmi [0000-0001-6748-5960]; Ong, Ken K [0000-0003-4689-7530]
    OBJECTIVE: To assess the efficacy of a theory-based behavioural intervention to prevent rapid weight gain in formula milk-fed infants. DESIGN: In this single (assessor) blind, randomised controlled trial, 669 healthy full-term infants receiving formula milk within 14 weeks of birth were individually randomised to intervention (n=340) or attention-matched control (n=329) groups. The intervention aimed to reduce formula milk intakes, and promote responsive feeding and growth monitoring to prevent rapid weight gain (≥+0.67 SD scores (SDS)). It was delivered to mothers by trained facilitators up to infant age 6 months through three face-to-face contacts, two telephone contacts and written materials. RESULTS: Retention was 93% (622) at 6 months, 88% (586) at 12 months and 94% attended ≥4/5 sessions. The intervention strengthened maternal attitudes to following infant feeding recommendations, reduced reported milk intakes at ages 3 (-14%; intervention vs control infants), 4 (-12%), 5 (-9%) and 6 (-7%) months, slowed initial infant weight gain from baseline to 6 months (mean change 0.32 vs 0.42 SDS, baseline-adjusted difference (intervention vs control) -0.08 (95% CI -0.17 to -0.004) SDS), but had no effect on the primary outcome of weight gain to 12 months (baseline-adjusted difference -0.04 (-0.17, 0.10) SDS). By 12 months, 40.3% of infants in the intervention group and 45.9% in the control group showed rapid weight gain (OR 0.84, 95% CI 0.59 to 1.17). CONCLUSIONS: Despite reducing milk intakes and initial weight gain, the intervention did not alter the high prevalence of rapid weight gain to age 12 months suggesting the need for sustained intervention. TRIAL REGISTRATION NUMBER: ISRCTN20814693.
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    Open Access
    'Getting to Know Me': the development and evaluation of a training programme for enhancing skills in the care of people with dementia in general hospital settings
    (Taylor & Francis, 2014-05) Elvish, Ruth; Burrow, Simon; Cawley, Rosanne; Harney, Kathryn; Graham, Pat; Pilling, Mark; Gregory, Julie; Roach, Pamela; Fossey, Jane; Keady, John; Pilling, Mark [0000-0002-7446-6597]
    OBJECTIVE: The aims of the study were to report on the development and evaluation of a staff training intervention in dementia care designed for use in the general hospital setting: the 'Getting to Know Me' training programme. The study also aimed to undertake initial psychometric analysis on two new outcome scales designed to measure knowledge and confidence in dementia care. METHODS: The study comprised two phases. The first phase comprised the design of two questionnaires which are shared within this paper: Confidence in Dementia (CODE) Scale and Knowledge in Dementia (KIDE) Scale. In phase two, staff undertook the 'Getting to Know Me' training programme (n=71). The impact of the programme was evaluated using a pre-post design which explored: (1) changes in confidence in dementia; (2) changes in knowledge in dementia; and (3) changes in beliefs about challenging behaviour. RESULTS: The psychometric properties of the CODE and KIDE scales are reported. Statistically significant change was identified pre-post training on all outcome measures. Clinically meaningful change was demonstrated on the CODE scale. CONCLUSIONS: The 'Getting to Know Me' programme was well received and had a significant impact on staff knowledge and confidence. Our findings add to a growing evidence base which will be strengthened by further robust studies, the exploration of the impact of staff training on direct patient outcomes, and further identification of ways in which to transfer principles of care from specialist dementia environments into general hospital settings.
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    Open Access
    Research data supporting: Genome–wide association study for risk taking propensity indicates shared pathways with body mass index
    Clifton, Emma AD; Perry, John RB; Imamura, Fumiaki; Lotta, Luca A; Brage, Soren; Forouhi, Nita G; Griffin, Simon; Wareham, Nick; Ong, Ken K; Day, Felix R; Perry, John [0000-0001-6483-3771]; Imamura, Fumiaki [0000-0002-6841-8396]; Brage, Soren [0000-0002-1265-7355]; Forouhi, Nita [0000-0002-5041-248X]; Griffin, Simon [0000-0002-2157-4797]; Wareham, Nicholas [0000-0003-1422-2993]; Ong, Kenneth [0000-0003-4689-7530]; Day, Felix [0000-0003-3789-7651]
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    Open Access
    Physical capability predicts mortality in late mid-life as well as in old age: Findings from a large British cohort study.
    (Elsevier BV, 2018-01) Keevil, Victoria L; Luben, Robert; Hayat, Shabina; Sayer, Avan A; Wareham, Nicholas J; Khaw, Kay-Tee; Keevil, Victoria [0000-0001-6148-0640]; Luben, Robert [0000-0002-5088-6343]; Hayat, Shabina [0000-0001-9068-8723]; Wareham, Nicholas [0000-0003-1422-2993]; Khaw, Kay-Tee [0000-0002-8802-2903]
    INTRODUCTION: Low physical capability predicts mortality, perhaps by association with co-morbidity. However, few studies include participants <70years old with lower co-morbidity burdens compared to older adults. We examined relationships between usual walking speed (UWS), timed chair stands speed, grip strength, standing balance and all-cause mortality in 8477 participants aged 48-92years enrolled in the European Prospective Investigation of Cancer-Norfolk study. METHODS: Participants (55.1% female) were followed up for 6.0 years (inter-quartile range 4.6, 7.5). Associations were examined using Cox proportional hazards regression by age-group (<70years versus ≥70years) and then in the whole cohort adjusted for age, sex, anthropometry, history of diabetes/stroke/myocardial infarction/cancer, smoking, alcohol intake, socioeconomic status, television viewing time and physical activity. RESULTS: Age and sex adjusted associations were similar in younger and older participants (Pinteraction all >0.05) and those with lower physical capability had higher mortality risk. For example, in those <70years old hazard ratios (95% confidence interval) for mortality in the third, second and lowest sex-specific quartiles of UWS compared to the highest were 1.21 (0.75, 1.96), 2.11 (1.35, 3.28) and 2.91 (1.84, 4.62) and in participants ≥70years old were 1.19 (0.73, 1.95), 2.09 (1.35, 3.24) and 2.64 (1.73, 4.02) respectively. In the whole cohort, strong associations between all physical capability tests and mortality persisted after multivariable adjustment and after excluding participants with co-morbidity. CONCLUSIONS: Physical capability was independently predictive of future mortality risk with similar associations in late mid-life, when co-morbidity burden is lower, as at older age.
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    Embargo
    The evaluation of physicians’ communication skills from multiple perspectives
    (HighWire, 2018-07) Burt, JA; Abel, Gary; Elliott, Marc; Elmore, Natasha; Newbould, Jennifer; Davey, Antoinette; Llanwarne, Nadia; Maramba, Innocencio; Paddison, Charlotte; Campbell, John; Roland, Martin; Burt, Jenni [0000-0002-0037-274X]; Roland, Martin [0000-0002-8533-3060]
    Purpose To examine how family physicians’, patients’ and trained clinical raters’ assessments of physician-patient communication compare in analysis of individual appointments. Methods Analysis of survey data from patients attending face-to-face appointments with 45 family physicians at 13 practices in England. Immediately post-appointment, patients and physicians independently completed a questionnaire including seven items assessing communication quality. A sample of videoed appointments was assessed by trained clinical raters, using the same seven communication items. Patient-, physician-, and rater-reported communication scores were compared using correlation coefficients. Results 503 physician-patient pairs were included; 55 of these appointments were also evaluated by trained clinical raters. Physicians scored themselves, on average, lower than patients (mean physician score 74.5; mean patient score 94.4); 63.4% (319) of patient-reported scores were the maximum of 100. The mean trained rater scores from 55 rated appointments was 57.3. There was a near-zero correlation coefficient between physician-reported and patient-reported communication scores (0.009, p=0.854), and between physician-reported and trained rater-reported communication scores (-0.006, p=0.69). However, there was a moderate and statistically significant association between patient and trained rater scores (0.35, p=0.042). Conclusions The lack of correlation between physician scores and those of others indicates that physicians’ perceptions of good communication within their appointments may differ from those of external peer raters and patients. Physicians may not be aware of how patients experience their communication practices; peer assessment of communication skills is an important approach in identifying areas for improvement.
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    Open Access
    Persistent inequalities in Hospice at Home provision.
    (BMJ, 2020-09) Buck, Jackie; Webb, Liz; Moth, Lorraine; Morgan, Lynn; Barclay, Stephen; Buck, Jackie [0000-0002-3598-2329]
    OBJECTIVE: To describe the nature and scope of a new Hospice at Home (H@H) service and to identify its equality of provision. METHODS: Case note review of patients supported by a H@H service for 1 year from September 2012 to August 2013 (n=321). Descriptive analysis to report frequencies and proportions of quantitative data extracted from service logs, referral forms and care records; thematic analysis of qualitative data from care record free text. RESULTS: Demand outstripped supply. Twice as many night care episodes were requested (n=1237) as were provided (n=613). Inequalities in access to the service related to underlying diagnosis and socioeconomic status. 75% of patients using the service had cancer (221/293 with documented diagnosis). Of those who died at home in the areas surrounding the hospice, 53% (163/311) of people with cancer and 11% (49/431) of those without cancer received H@H support. People who received H@H care were often more affluent than the population average for the area within which they lived. Roles of the service identified included: care planning/implementation, specialist end-of-life care assessment and advice, 'holding' complex patients until hospice beds become available and clinical nursing care. CONCLUSION: There is significant unmet need and potentially large latent demand for the H@H service. People without cancer or of lower socioeconomic status are less likely to access the service. Action is needed to ensure greater and more equitable service provision in this and similar services nationally and internationally.
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    Impact of lower strength alcohol labeling on consumption: A randomized controlled trial.
    (American Psychological Association (APA), 2018-07) Vasiljevic, Milica; Couturier, Dominique-Laurent; Frings, Daniel; Moss, Antony C; Albery, Ian P; Marteau, Theresa M; Vasiljevic, Milica [0000-0001-7454-7744]; Couturier, Dominique [0000-0001-5774-5036]; Marteau, Theresa [0000-0003-3025-1129]
    OBJECTIVE: Labels indicating low/light versions of tobacco and foods are perceived as less harmful, which may encourage people to consume more. There is an absence of evidence concerning the impact on consumption of labeling alcohol products as lower in strength. The current study tests the hypothesis that labeling wine and beer as lower in alcohol increases their consumption. METHOD: Weekly wine and beer drinkers (n = 264) sampled from a representative panel of the general population of England were randomized to one of three groups to taste test drinks in a bar-laboratory varying only in the label displayed; Group 1: verbal descriptor Super Low combined with 4% alcohol by volume (ABV) for wine/1% ABV for beer; Group 2: verbal descriptor Low combined with 8% ABV for wine/3% ABV for beer; Group 3: no verbal descriptors of strength (Regular). Primary outcome was total volume (ml) of drink consumed. RESULTS: The results supported the study hypothesis: the total amount of drink consumed increased as the label on the drink denoted successively lower alcohol strength, BLin = .71, p = .015, 95% CI [0.13, 1.30]. Group contrasts showed significant differences between those offered drinks labeled as Super Low (M = 213.77) compared with Regular (M = 176.85), B = 1.43, p = .019, 95% CI [0.24, 2.61]. There was no significant difference in amount consumed between those offered drinks labeled as Low compared with Regular. CONCLUSIONS: These results suggest that labeling drinks as lower in strength increases the amount consumed. Further studies are warranted to test for replication in non-laboratory settings and to estimate whether any effects are at a level with the potential to harm health. TRIAL REGISTRATION: ISRCTN15530806. (PsycINFO Database Record
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    Open Access
    The challenges of interventions to promote healthier food in independent takeaways in England: qualitative study of intervention deliverers' views.
    (Springer Science and Business Media LLC, 2018-01-27) Goffe, Louis; Penn, Linda; Adams, Jean; Araujo-Soares, Vera; Summerbell, Carolyn D; Abraham, Charles; White, Martin; Adamson, Ashley; Lake, Amelia A; Goffe, Louis [0000-0002-3623-2458]
    BACKGROUND: Much of the food available from takeaways, pubs and restaurants particularly that sold by independent outlets, is unhealthy and its consumption is increasing. These food outlets are therefore important potential targets for interventions to improve diet and thus prevent diet related chronic diseases. Local authorities in England have been charged with delivering interventions to increase the provision of healthy food choices in independent outlets, but prior research shows that few such interventions have been rigorously developed or evaluated. We aimed to learn from the experiences of professionals delivering interventions in independent food outlets in England to identify the operational challenges and their suggestions for best practice. METHODS: We used one-to-one semi-structured qualitative interviews to explore the views and experiences of professionals who were either employees of, or contracted by, a local authority to deliver interventions to increase the provision of healthier food choices in independent food outlets. Purposive sampling was used to recruit a sample which included men and women, from a range of professional roles, across different areas of England. Interviews were informed by a topic guide, and proceeded until no new themes emerged. Interviews were recorded, transcribed verbatim and analysed using the Framework method. RESULTS: We conducted 11 individual interviews. Participants focussed on independent takeaways and their unhealthy food offerings, and highlighted the advantages and disadvantages of intervention delivery methods, their evaluation and impact. The main barriers to implementation of interventions in independent takeaways were identified as limited funding and the difficulties of engaging the food outlet owner/manager. Engagement was thought to be facilitated by delivering intensive, interactive and tailored interventions, clear and specific information, and incentives, whilst accounting for practical, primarily financial, constraints of food businesses. Alternative intervention approaches, targeting suppliers or customers, were suggested. CONCLUSIONS: Participants emphasised independent takeaways as particularly challenging, but worthwhile intervention targets. Participants perceived that interventions need to take account of the potentially challenging operating environment, particularly the primacy of the profit motive. Upstream interventions, engaging suppliers, as well as those that drive consumer demand, may be worth exploring. Rigorous, evidence-informed development and evaluation of such interventions is needed.
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    Open Access
    Impairments in Hemodynamic Responses to Orthostasis Associated with Frailty: Results from TILDA
    (Wiley-Blackwell, ) Romero-Ortuno, R; O'Connell, Matthew; Savva, George; Finucane, Ciaran; Fan, Chie; Kenny, Rose Anne; Romero-Ortuno, Roman [0000-0002-3882-7447]
    Background: Dysregulated homeostatic response to stressors may underlie frailty in older adults. Orthostatic hypotension results from impairments in cardiovascular homeostasis and is implicated in falls and other adverse outcomes. This study aimed to characterise the relationships between orthostatic BP and heart rate recovery and frailty in an older population. Design: Cross-sectional study. Setting: Two health centres in the Republic of Ireland. Participants: 4334 adults aged 50 and older enrolled in The Irish Longitudinal Study on Ageing. Measurements: Continuous non-invasive blood pressure (BP) responses during active standing were captured by Finometer®. Frailty was assessed using the Cardiovascular Health Study criteria. Linear mixed models (random intercept) with piecewise splines were used to model differences in the rate of BP and heart rate recovery. Results: 93 (2.2%) participants were frail and 1366 (31.5%) were prefrail. Adjusting for age and sex, frailty was associated with a reduced rate of systolic BP recovery between 10-20 seconds post stand (frailty*time = -4.12 95%CI: -5.53 - -2.72) and with subsequent deficits in BP between 20-50 seconds. Similar results were seen for diastolic BP and heart rate. Further adjustment for health behaviours, morbidities, and medications reduced, but did not attenuate these associations. Of the 5 frailty criteria, only slow gait speed was consistently related to impaired BP and heart rate responses in the full models. Conclusions: Frailty, and particularly slow gait speed, was associated with reduced rate of recovery in BP and heart rate recovery following active standing. Impaired BP recovery may represent a marker of physiological frailty.
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    Open Access
    Frail-VIG index: a concise frailty evaluation tool for rapid geriatric assessment. Results of a 24-months prospective follow-up
    (BioMed Central, ) Romero-Ortuno, R; Amblàs-Novellas, Jordi; Martori, Joan Carles; Espaulella, Joan; Oller, Ramon; Molist-Brunet, Núria; Inzitari, Marco; Romero-Ortuno, Roman [0000-0002-3882-7447]
    Background: Demographic changes have led to an increase in the number of elderly frail persons and, consequently, systematic geriatric assessment is more important than ever. Frailty Indexes (FI) may be particularly useful to discriminate between various degrees of frailty but are not routinely assessed due, at least in part, to the large number of deficits assessed (from 30 to 70). Therefore, we have developed a new, more concise FI for rapid geriatric assessment (RGA)—the Frail-VIG index ("VIG" is the Spanish/Catalan abbreviation for Comprehensive Geriatric Assessment), which contains 22 simple questions that assess 25 different deficits. Here we describe this FI and report its ability to predict mortality at 24 months.
 Methods: Prospective, observational, longitudinal study of geriatric patients followed for 24 months or until death. The study participants were patients (n=590) admitted to the Acute Geriatric Unit at the at the University Hospital of Vic (Barcelona)
during the year 2014. Participants were classified into one of seven groups based on their Frail-VIG score (0-0.15; 0.16-0.25; 0.26-0.35; 0.36-0.45; 0.46-0.55; 0.56-0.65; and 0.66-1). Survival curves for these groups were compared using the log-rank test. ROC curves were used to assess the index's capacity to predict mortality at 24 months. Results: Mean (standard deviation) patient age was 86.4 (5.6) years. The 24-month mortality rate was 57.3% for the whole sample. Significant between-group (deceased vs. living) differences (p<0.05) were observed for most index variables. Survival curves for the seven Frail-VIG groups differed significantly (X2= 433.4, p<0.001), with an area under the ROC curve (confidence interval) of 0.90 (0.88-0.92) at 12 months and 0.85 (0.82-0.88) at 24 months. Administration time for the Frail-VIG index ranged from 5 to 10 minutes. Conclusions: The Frail-VIG index, which requires less time to administer than previously validated FIs, presents a good discriminative capacity for the degree of frailty and a high predictive capacity for mortality in the present cohort. Although more research is needed to confirm the validity of this instrument in other populations and settings, the Frail-VIG may provide clinicians with a RGA method and also a reliable tool to assess frailty in routine practice.
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    The current and potential health benefits of the National Health Service Health Check cardiovascular disease prevention programme in England: A microsimulation study.
    (Public Library of Science (PLoS), 2018-03) Mytton, Oliver T; Jackson, Christopher; Steinacher, Arno; Goodman, Anna; Langenberg, Claudia; Griffin, Simon; Wareham, Nick; Woodcock, James; Mytton, Oliver T [0000-0003-3218-9912]; Wareham, Nick [0000-0003-1422-2993]; Woodcock, James [0000-0003-4769-5375]
    BACKGROUND: The National Health Service (NHS) Health Check programme was introduced in 2009 in England to systematically assess all adults in midlife for cardiovascular disease risk factors. However, its current benefit and impact on health inequalities are unknown. It is also unclear whether feasible changes in how it is delivered could result in increased benefits. It is one of the first such programmes in the world. We sought to estimate the health benefits and effect on inequalities of the current NHS Health Check programme and the impact of making feasible changes to its implementation. METHODS AND FINDINGS: We developed a microsimulation model to estimate the health benefits (incident ischaemic heart disease, stroke, dementia, and lung cancer) of the NHS Health Check programme in England. We simulated a population of adults in England aged 40-45 years and followed until age 100 years, using data from the Health Survey of England (2009-2012) and the English Longitudinal Study of Aging (1998-2012), to simulate changes in risk factors for simulated individuals over time. We used recent programme data to describe uptake of NHS Health Checks and of 4 associated interventions (statin medication, antihypertensive medication, smoking cessation, and weight management). Estimates of treatment efficacy and adherence were based on trial data. We estimated the benefits of the current NHS Health Check programme compared to a healthcare system without systematic health checks. This counterfactual scenario models the detection and treatment of risk factors that occur within 'routine' primary care. We also explored the impact of making feasible changes to implementation of the programme concerning eligibility, uptake of NHS Health Checks, and uptake of treatments offered through the programme. We estimate that the NHS Health Check programme prevents 390 (95% credible interval 290 to 500) premature deaths before 80 years of age and results in an additional 1,370 (95% credible interval 1,100 to 1,690) people being free of disease (ischaemic heart disease, stroke, dementia, and lung cancer) at age 80 years per million people aged 40-45 years at baseline. Over the life of the cohort (i.e., followed from 40-45 years to 100 years), the changes result in an additional 10,000 (95% credible interval 8,200 to 13,000) quality-adjusted life years (QALYs) and an additional 9,000 (6,900 to 11,300) years of life. This equates to approximately 300 fewer premature deaths and 1,000 more people living free of these diseases each year in England. We estimate that the current programme is increasing QALYs by 3.8 days (95% credible interval 3.0-4.7) per head of population and increasing survival by 3.3 days (2.5-4.1) per head of population over the 60 years of follow-up. The current programme has a greater absolute impact on health for those living in the most deprived areas compared to those living in the least deprived areas (4.4 [2.7-6.5] days of additional quality-adjusted life per head of population versus 2.8 [1.7-4.0] days; 5.1 [3.4-7.1] additional days lived per head of population versus 3.3 [2.1-4.5] days). Making feasible changes to the delivery of the existing programme could result in a sizable increase in the benefit. For example, a strategy that combines extending eligibility to those with preexisting hypertension, extending the upper age of eligibility to 79 years, increasing uptake of health checks by 30%, and increasing treatment rates 2.5-fold amongst eligible patients (i.e., 'maximum potential' scenario) results in at least a 3-fold increase in benefits compared to the current programme (1,360 premature deaths versus 390; 5,100 people free of 1 of the 4 diseases versus 1,370; 37,000 additional QALYs versus 10,000; 33,000 additional years of life versus 9,000). Ensuring those who are assessed and eligible for statins receive statins is a particularly important strategy to increase benefits. Estimates of overall benefit are based on current incidence and management, and future declines in disease incidence or improvements in treatment could alter the actual benefits observed in the long run. We have focused on the cardiovascular element of the NHS Health Check programme. Some important noncardiovascular health outcomes (e.g., chronic obstructive pulmonary disease [COPD] prevention from smoking cessation and cancer prevention from weight loss) and other parts of the programme (e.g., brief interventions to reduce harmful alcohol consumption) have not been modelled. CONCLUSIONS: Our model indicates that the current NHS Health Check programme is contributing to improvements in health and reducing health inequalities. Feasible changes in the organisation of the programme could result in more than a 3-fold increase in health benefits.
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    Tele-First. Evaluation of a ‘telephone first’ approach to demand management in English general practice: observational study
    (BMJ Publishing Group, 2017-09-27) Newbould, J; Abel, G; Ball, S; Corbett, J; Elliott, M; Exley, J; Martin, A; Saunders, C; Wilson, E; Winpenny, E; Yang, M; Roland, M; Saunders, Catherine [0000-0002-3127-3218]; Wilson, Ed [0000-0002-8369-1577]; Winpenny, Eleanor [0000-0003-1933-0168]; Roland, Martin [0000-0002-8533-3060]
    Objective. To evaluate a ‘telephone first’ approach, in which all patients wanting to see a GP are asked to speak to a GP on the phone before being given an appointment for a face to face consultation. Design Time-series and cross-sectional analysis of routine healthcare data, data from national surveys, and primary survey data. Participants 147 general practices adopting the ‘telephone first’ approach compared to a 10% random sample of other practices in England. Intervention Management support for workload planning and introduction of the ‘telephone first’ approach provided by two commercial companies. Main outcome measures Number of consultations, total time consulting (59 ‘telephone first’ practices, no controls). Patient experience (GP Patient Survey, ‘telephone first’ practices plus controls). Secondary care utilisation and costs (Hospital Episode Statistics, ‘telephone first’ practices plus controls). The main analysis was intention to treat, with sensitivity analyses restricted to practices believed to be closely following the companies’ protocols. Results Following the introduction of the ‘telephone first’ approach, face-to-face consultations decreased considerably (adjusted within-practice change -38% 95% CI -45%,-29%, p<0.001). An average practice experienced a 12-fold increase in telephone consultations (adjusted within-practice change 1204% , 95% CI 633%, 2290%, p<0.001). The average duration of both telephone and face-to-face consultations decreased, but there was an overall increase of 8% in the mean time spent consulting by GPs, albeit with large uncertainty on this estimate (95%CI -1%,17%, p=0.088). These average workload figures mask wide variation between practices, with some practices experiencing a substantial reduction in workload and others a large increase. Comparing practices using the ‘telephone first’ approach to other English practices in the national GP Patient Survey, there was a large (20.0 percentage point, 95%CI 18.2,21.9, p<0.001) improvement in length of time to be seen. In contrast, other GP Patient Survey scores were slightly more negative. Introduction of the ‘telephone first’ approach was followed by a small (2.0%) increase in hospital admissions (95%CI 1%,3%, p=0.006), no initial change in A&E attendance but a small (2% per year) decrease in the subsequent rate of rise of A&E attendance (95%CI 1%,3%, p=0.005). There was a small net increase in secondary care costs. Conclusions The ‘telephone first’ approach shows that many problems in general practice can be dealt with on the phone. The approach does not suit all patients or practices and is not a panacea for meeting demand. We found no evidence to support claims that the approach would, on average, be cost-saving or reduce secondary care utilisation.
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    Open Access
    A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.
    (American Diabetes Association, 2013-01) Li, Huaixing; Gan, Wei; Lu, Ling; Dong, Xiao; Han, Xueyao; Hu, Cheng; Yang, Zhen; Sun, Liang; Bao, Wei; Li, Pengtao; He, Meian; Sun, Liangdan; Wang, Yiqin; Zhu, Jingwen; Ning, Qianqian; Tang, Yong; Zhang, Rong; Wen, Jie; Wang, Di; Zhu, Xilin; Guo, Kunquan; Zuo, Xianbo; Guo, Xiaohui; Yang, Handong; Zhou, Xianghai; DIAGRAM Consortium; AGEN-T2D Consortium; Zhang, Xuejun; Qi, Lu; Loos, Ruth JF; Hu, Frank B; Wu, Tangchun; Liu, Ying; Liu, Liegang; Yang, Ze; Hu, Renming; Jia, Weiping; Ji, Linong; Li, Yixue; Lin, Xu; Loos, Ruth [0000-0002-8532-5087]
    Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility.
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    Open Access
    Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.
    (American Diabetes Association, 2013-03) Tabassum, Rubina; Chauhan, Ganesh; Dwivedi, Om Prakash; Mahajan, Anubha; Jaiswal, Alok; Kaur, Ismeet; Bandesh, Khushdeep; Singh, Tejbir; Mathai, Benan John; Pandey, Yogesh; Chidambaram, Manickam; Sharma, Amitabh; Chavali, Sreenivas; Sengupta, Shantanu; Ramakrishnan, Lakshmi; Venkatesh, Pradeep; Aggarwal, Sanjay K; Ghosh, Saurabh; Prabhakaran, Dorairaj; Srinath, Reddy K; Saxena, Madhukar; Banerjee, Monisha; Mathur, Sandeep; Bhansali, Anil; Shah, Viral N; Madhu, Sri Venkata; Marwaha, Raman K; Basu, Analabha; Scaria, Vinod; McCarthy, Mark I; DIAGRAM; INDICO; Venkatesan, Radha; Mohan, Viswanathan; Tandon, Nikhil; Bharadwaj, Dwaipayan; Scaria, Vinod [0000-0001-7644-7181]
    Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.
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    Open Access
    Current and future cardiovascular disease risk assessment in the European Union: an international comparative study.
    (Oxford University Press (OUP), 2018-08-01) Mossakowska, Teresa J; Saunders, Catherine L; Corbett, Jennie; MacLure, Calum; Winpenny, Eleanor M; Dujso, Elma; Payne, Rupert A; Saunders, Catherine [0000-0002-3127-3218]; Winpenny, Eleanor [0000-0003-1933-0168]
    BACKGROUND: Risk assessment is central to primary prevention of cardiovascular disease (CVD), but there remains a need to better understand the use of evidence-based interventions in practice. This study examines: (i) the policies and guidelines for risk assessment in Europe, (ii) the use of risk assessment tools in clinical practice and (iii) the barriers to, and facilitators of, risk assessment. METHODS: Data were collected from academics, clinicians and policymakers in an online questionnaire targeted at experts from all European Union member states, and in 8 in-depth country case studies that were developed from a targeted literature review and 36 interviews. RESULTS: The European Society of Cardiology (ESC) produces European guidelines for CVD risk assessment and recommends the Systematic COronary Risk Evaluation tool, which is the most widely used risk assessment tool in Europe. The use of risk assessment tools is variable. Lack of time and resources are important barriers. Integrating risk assessment tools into clinical systems and providing financial incentives to carry out risk assessments could increase implementation. Novel biomarkers would need to be supported by evidence of their clinical effectiveness and cost-effectiveness to be introduced in clinical practice. These findings were consistent across Europe. CONCLUSIONS: Efforts to improve the assessment of CVD risk in clinical practice should be carried out by or in collaboration with, the ESC. Increasing the use of existing risk assessment tools is likely to offer greater gains in primary prevention than the development of novel biomarkers.
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    Open Access
    Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.
    (Springer Science and Business Media LLC, 2016-11-22) Moskal, Aurélie; Freisling, Heinz; Byrnes, Graham; Assi, Nada; Fahey, Michael T; Jenab, Mazda; Ferrari, Pietro; Tjønneland, Anne; Petersen, Kristina En; Dahm, Christina C; Hansen, Camilla Plambeck; Affret, Aurélie; Boutron-Ruault, Marie-Christine; Cadeau, Claire; Kühn, Tilman; Katzke, Verena; Iqbal, Khalid; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Naska, Androniki; Masala, Giovanna; de Magistris, Maria Santucci; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Peeters, Petra H; Bueno-de-Mesquita, Bas H; Engeset, Dagrun; Licaj, Idlir; Skeie, Guri; Ardanaz, Eva; Buckland, Genevieve; Castaño, José M Huerta; Quirós, José R; Amiano, Pilar; Molina-Portillo, Elena; Winkvist, Anna; Myte, Robin; Ericson, Ulrika; Sonestedt, Emily; Perez-Cornago, Aurora; Wareham, Nick; Khaw, Kay-Tee; Huybrechts, Inge; Tsilidis, Konstantinos K; Ward, Heather; Gunter, Marc J; Slimani, Nadia; Wareham, Nicholas [0000-0003-1422-2993]; Khaw, Kay-Tee [0000-0002-8802-2903]
    BACKGROUND: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. RESULTS: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. CONCLUSIONS: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.
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    Insights into the clinical management of the syndrome of supine hypertension--orthostatic hypotension (SH-OH): the Irish Longitudinal Study on Ageing (TILDA).
    (Springer Science and Business Media LLC, 2013-07-15) Romero-Ortuno, Roman; O'Connell, Matthew DL; Finucane, Ciaran; Soraghan, Christopher; Fan, Chie Wei; Kenny, Rose Anne; Romero-Ortuno, Roman [0000-0002-3882-7447]
    BACKGROUND: Our previously proposed morphological classification of orthostatic hypotension (MOH) is an approach to the definition of three typical orthostatic hemodynamic patterns using non-invasive beat-to-beat monitoring. In particular, the MOH pattern of large drop/non-recovery (MOH-3) resembles the syndrome of supine hypertension-orthostatic hypotension (SH-OH), which is a treatment challenge for clinicians. The aim of this study was to characterise MOH-3 in the first wave of The Irish Longitudinal Study of Ageing (TILDA), with particular attention to concurrent symptoms of orthostatic intolerance (OI), prescribed medications and association with history of faints and blackouts. METHODS: The study included all TILDA wave 1 participants who had a Finometer® active stand. Automatic data signal checks were carried out to ensure that active stand data were of sufficient quality. Characterisation variables included demographics, cardiovascular and neurological medications (WHO-ATC), and self-reported information on comorbidities and disability. Multivariable statistics consisted of logistic regression models. RESULTS: Of the 4,467 cases, 1,456 (33%) were assigned to MOH-1 (small drop, overshoot), 2,230 (50%) to MOH-2 (medium drop, slower but full recovery), and 781 (18%) to MOH-3 (large drop, non-recovery). In the logistic regression model to predict MOH-3, statistically significant factors included being on antidepressants (OR = 1.99, 95% CI: 1.50 - 2.64, P < 0.001) and beta blockers (OR = 1.60, 95% CI: 1.26 - 2.04, P < 0.001). MOH-3 was an independent predictor of OI after full adjustment (OR = 1.47, 95% CI: 1.25 - 1.73, P < 0.001), together with being on hypnotics or sedatives (OR = 1.83, 95% CI: 1.31 - 2.54, P < 0.001). In addition, OI was an independent predictor of history of falls/blackouts after full adjustment (OR = 1.27, 95% CI: 1.09 - 1.48, P = 0.003). CONCLUSIONS: Antidepressants and beta blockers were independently associated with MOH-3, and should be used judiciously in older patients with SH-OH. Hypnotics and sedatives may add to the OI effect of MOH-3. Several trials have demonstrated the benefits of treating older hypertensive patients with cardiovascular medications that were not associated with adverse outcomes in our study. Therefore, the evidence of benefit does not necessarily have to conflict with the evidence of potential harm.
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    A frailty instrument for primary care: findings from the Survey of Health, Ageing and Retirement in Europe (SHARE).
    (Springer Science and Business Media LLC, 2010-08-24) Romero-Ortuno, Roman; Walsh, Cathal D; Lawlor, Brian A; Kenny, Rose Anne; Romero-Ortuno, Roman [0000-0002-3882-7447]
    BACKGROUND: A frailty paradigm would be useful in primary care to identify older people at risk, but appropriate metrics at that level are lacking. We created and validated a simple instrument for frailty screening in Europeans aged ≥50. Our study is based on the first wave of the Survey of Health, Ageing and Retirement in Europe (SHARE, http://www.share-project.org), a large population-based survey conducted in 2004-2005 in twelve European countries. SUBJECTS: SHARE Wave 1 respondents (17,304 females and 13,811 males). MEASURES: five SHARE variables approximating Fried's frailty definition. Analyses (for each gender): 1) estimation of a discreet factor (DFactor) model based on the frailty variables using LatentGOLD. A single DFactor with three ordered levels or latent classes (i.e. non-frail, pre-frail and frail) was modelled; 2) the latent classes were characterised against a biopsychosocial range of Wave 1 variables; 3) the prospective mortality risk (unadjusted and age-adjusted) for each frailty class was established on those subjects with known mortality status at Wave 2 (2007-2008) (11,384 females and 9,163 males); 4) two web-based calculators were created for easy retrieval of a subject's frailty class given any five measurements. RESULTS: Females: the DFactor model included 15,578 cases (standard R2 = 0.61). All five frailty indicators discriminated well (p < 0.001) between the three classes: non-frail (N = 10,420; 66.9%), pre-frail (N = 4,025; 25.8%), and frail (N = 1,133; 7.3%). Relative to the non-frail class, the age-adjusted Odds Ratio (with 95% Confidence Interval) for mortality at Wave 2 was 2.1 (1.4 - 3.0) in the pre-frail and 4.8 (3.1 - 7.4) in the frail. Males: 12,783 cases (standard R2 = 0.61, all frailty indicators had p < 0.001): non-frail (N = 10,517; 82.3%), pre-frail (N = 1,871; 14.6%), and frail (N = 395; 3.1%); age-adjusted OR (95% CI) for mortality: 3.0 (2.3 - 4.0) in the pre-frail, 6.9 (4.7 - 10.2) in the frail. CONCLUSIONS: The SHARE Frailty Instrument has sufficient construct and predictive validity, and is readily and freely accessible via web calculators. To our knowledge, SHARE-FI represents the first European research effort towards a common frailty language at the community level.
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    Open Access
    Analysis of protein-coding genetic variation in 60,706 humans.
    (Springer Science and Business Media LLC, 2016-08-18) Lek, Monkol; Karczewski, Konrad J; Minikel, Eric V; Samocha, Kaitlin E; Banks, Eric; Fennell, Timothy; O'Donnell-Luria, Anne H; Ware, James S; Hill, Andrew J; Cummings, Beryl B; Tukiainen, Taru; Birnbaum, Daniel P; Kosmicki, Jack A; Duncan, Laramie E; Estrada, Karol; Zhao, Fengmei; Zou, James; Pierce-Hoffman, Emma; Berghout, Joanne; Cooper, David N; Deflaux, Nicole; DePristo, Mark; Do, Ron; Flannick, Jason; Fromer, Menachem; Gauthier, Laura; Goldstein, Jackie; Gupta, Namrata; Howrigan, Daniel; Kiezun, Adam; Kurki, Mitja I; Moonshine, Ami Levy; Natarajan, Pradeep; Orozco, Lorena; Peloso, Gina M; Poplin, Ryan; Rivas, Manuel A; Ruano-Rubio, Valentin; Rose, Samuel A; Ruderfer, Douglas M; Shakir, Khalid; Stenson, Peter D; Stevens, Christine; Thomas, Brett P; Tiao, Grace; Tusie-Luna, Maria T; Weisburd, Ben; Won, Hong-Hee; Yu, Dongmei; Altshuler, David M; Ardissino, Diego; Boehnke, Michael; Danesh, John; Donnelly, Stacey; Elosua, Roberto; Florez, Jose C; Gabriel, Stacey B; Getz, Gad; Glatt, Stephen J; Hultman, Christina M; Kathiresan, Sekar; Laakso, Markku; McCarroll, Steven; McCarthy, Mark I; McGovern, Dermot; McPherson, Ruth; Neale, Benjamin M; Palotie, Aarno; Purcell, Shaun M; Saleheen, Danish; Scharf, Jeremiah M; Sklar, Pamela; Sullivan, Patrick F; Tuomilehto, Jaakko; Tsuang, Ming T; Watkins, Hugh C; Wilson, James G; Daly, Mark J; MacArthur, Daniel G; Exome Aggregation Consortium; Danesh, John [0000-0003-1158-6791]
    Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.