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BACKGROUND: No previous studies have examined the associations between changes in objectively-measured physical behaviours with follow-up QoL in older adults. Based on cross-sectional evidence, it is biologically plausible that such associations exist. If so, this bolsters the case for the commissioning of activity interventions and for including QoL as an outcome in trials of such interventions. METHODS: We assessed physical behaviours (total physical activity, moderate-to-vigorous physical activity (MVPA), light physical activity, total sedentary time and prolonged sedentary bout time) for 7 days using hip-worn accelerometers at baseline (2006-2011) and follow-up (2012-2016) and health-related quality-of-life (QoL) using EQ-5D questionnaires at follow-up in 1433 participants (≥ 60 years) of the EPIC (European Prospective Investigation into Cancer)-Norfolk study. The EQ-5D summary score was used, with 0 as the worst to 1 as best perceived quality-of-life. We evaluated the prospective associations of baseline physical behaviours with follow-up QoL, and of changes in behaviours with follow-up QoL using multi-level regression. RESULTS: On average, MVPA decreased by 4.0 min/day/year (SD 8.3) for men and 4.0 min/day/year for women (SD 12.0) between baseline and follow-up. Total sedentary time increased by an average 5.5 min/day/yr (SD 16.0) for men and 6.4 min/day/yr (SD 15.0) for women between baseline and follow-up. Mean (SD) follow-up time was 5.8 (1.8) years. We found that higher baseline MVPA and lower sedentary time was associated with higher subsequent QoL (e.g. 1 h/day greater baseline MVPA was associated with 0.02 higher EQ-5D score, 95% CI 0.06, 0.36). More pronounced declines in activity were associated with worse Hr-QoL (0.005 (95% CI 0.003, 0.008) lower EQ-5D per min/day/yr decrease in MVPA). Increases in sedentary behaviours were also associated with poorer QoL (0.002 lower EQ-5D, 95% CI -0.003, -0.0007 per hour/day/yr increase in total sedentary time). CONCLUSIONS: Promotion of physical activity and limiting sedentary time among older adults may improve quality-of-life, and therefore this relationship ought to be included in future cost effectiveness analyses so that greater commissioning of activity interventions can be considered.

Introduction: Using risk stratification to determine eligibility for cancer screening is likely to improve the efficiency of screening programmes by targeting resources towards those most likely to benefit. We aimed to explore the implications of this approach from a societal perspective by understanding public views on the most acceptable stratification strategies. Methods: We conducted three online community juries with 9 or 10 participants in each. Participants were purposefully sampled by age (40–79 years), sex, ethnicity, social grade and English region. On the first day, participants were informed of the potential benefits and harms of cancer screening and the implications of different ways of introducing stratification using scenarios based on phenotypic and genetic risk scores. On the second day, participants deliberated to reach a verdict on the research question, ‘Which approach(es) to inviting people to screening are acceptable, and under what circumstances?’ Deliberations and feedback were recorded and analysed using thematic analysis. Results: Across the juries, the principle of risk stratification was generally considered to be an acceptable approach for determining eligibility for screening. Disregarding increasing capacity, the participants considered it to enable efficient resource allocation to high‐risk individuals and could see how it might help to save lives. However, there were concerns regarding fair implementation, particularly how the risk assessment would be performed at scale and how people at low risk would be managed. Some favoured using the most accurate risk prediction model whereas others thought that certain risk factors should be prioritized (particularly factors considered as non‐modifiable and relatively stable, such as genetics and family history). Transparently justifying the programme and public education about cancer risk emerged as important contributors to acceptability. Conclusion: Using risk stratification to determine eligibility for cancer screening was acceptable to informed members of the public, particularly if it included risk factors they considered fair and when communicated transparently. Patient or Public Contribution: Two patient and public involvement representatives were involved throughout this study. They were not involved in synthesizing the results but contributed to producing study materials, co‐facilitated the community juries and commented on the interpretation of the findings and final report.

BACKGROUND/OBJECTIVES: Physical activity energy expenditure (PAEE) represents the total volume of all physical activity. This can be accumulated as different underlying intensity profiles. Although volume and intensity have been studied in isolation, less is known about their joint association with health. We examined this association with body fatness in a population-based sample of middle-aged British adults. METHODS: In total, 6148 women and 5320 men from the Fenland study with objectively measured physical activity from individually calibrated combined heart rate and movement sensing and DXA-derived body fat percentage (BF%) were included in the analyses. We used linear and compositional isocaloric substitution analysis to examine associations of PAEE and its intensity composition with body fatness. Sex-stratified models were adjusted for socio-economic and dietary covariates. RESULTS: PAEE was inversely associated with body fatness in women (beta = -0.16 (95% CI: -0.17; -0.15) BF% per kJ day-1 kg-1) and men (beta = -0.09 (95% CI: -0.10; -0.08) BF% per kJ day-1 kg-1). Intensity composition was significantly associated with body fatness, beyond that of PAEE; the reallocation of energy to vigorous physical activity (>6 METs) from other intensities was associated with less body fatness, whereas light activity (1.5-3 METs) was positively associated. However, light activity was the main driver of overall PAEE volume, and the relative importance of intensity was marginal compared to that of volume; the difference between PAEE in tertile 1 and 2 in women was associated with 3 percentage-point lower BF%. Higher vigorous physical activity in the same group to the maximum observed value was associated with 1 percentage-point lower BF%. CONCLUSIONS: In this large, population-based cohort study with objective measures, PAEE was inversely associated with body fatness. Beyond the PAEE association, greater levels of intense activity were also associated with lower body fatness. This contribution was marginal relative to PAEE. These findings support current guidelines for physical activity which emphasise that any movement is beneficial, rather than specific activity intensity or duration targets., The Fenland study was funded by the Medical Research Council and the Wellcome Trust. The current work was supported by the Medical Research Council (S.B., K.Wi., T.S., K.We, P.C.D., grant number MC_UU_12015/3, MC_UU_00006/4), (S.G., grant number MC_UU_12015/4, MC_UU_00006/6), (N.J.W., grant number MC_UU_12015/1, MC_UU_00006/1), (N.G.F., grant number MC_UU_12015/5, MC_UU_00006/3); the National Institute of Health Research Cambridge (NIHR) Biomedical Research Centre (K.We., E.D.L.R., S.B., N.G.F., and N.J.W., grant number IS-BRC-1215-20014); National Health and Medical Research Council of Australia Research Fellowship (P.C.D., grant number 1142685), and the Cambridge Trust and St Catharine���s College (T.L.). The funders had no role in the design, analysis or writing of this article.

Introduction A number of analytic methods have been used in large datasets to group individuals into clusters by the presence of long-term health conditions. We investigate the reproducibility and validity of these methods in a large simulated dataset and in a dataset derived from electronic primary care records. Methods We selected four clustering algorithms: latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans). Clustering algorithms were first investigated in simulated datasets with 26 diseases of varying prevalence in predetermined clusters and varying prevalence of noise (patients not in a cluster). We compared the derived clusters to known clusters using the adjusted Rand Index (aRI). Methods were then investigated in the medical records of male patients, aged 65 to 84 from 50 UK general practices. Forty-nine long-term health conditions with at least 1% prevalence were considered. Within cluster morbidity profiles were using the Pearson correlation coefficient (PCC). Cluster stability was assessed in 400 bootstrap samples. Results In the simulated datasets, aRI declined as the prevalence of noise increased, approaching zero and when the prevalence of noise approached that of long-term health conditions. LCA and MCA-kmeans algorithms gave the closest agreement (largest aRI) to known clusters. In the patient records dataset, all four algorithms identified one cluster accounting for 20-25% of the study population; LCA and MCA-kmeans found a second cluster of about 7% of the population. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54). About 82% of patients in the large cluster were the same across all four methods. Discussion The amount of noise markedly affects clustering algorithms, suggesting individuals with a single condition should be excluded. LCA achieved higher aRI than other clustering algorithms.

Funder: The University of Cambridge has received salary support in respect of SG from the NHS in the East of England through the Clinical Academic Reserve, Rapid advances in technology and data science have the potential to improve the precision of preventive and therapeutic interventions, and enable the right treatment to be recommended, at the right time, to the right person. There are well-described examples of successful precision medicine approaches for monogenic conditions such as specific diets for phenylketonuria, and sulfonylurea treatments for certain types of MODY. However, the majority of chronic diseases are polygenic, and it is unlikely that the research strategies used for monogenic diseases will deliver similar changes to practice for polygenic traits. Type 2 diabetes, for example, is a multifactorial, heterogeneous, polygenic palette of metabolic disorders. In this non-systematic review I highlight limitations of the evidence, and the challenges that need to be overcome prior to implementation of precision medicine in the prevention and management of type 2 diabetes. Most precision medicine approaches are spuriously precise, overly complex and too narrowly focused on predicting blood glucose levels with a limited set of characteristics of individuals rather than the whole person and their context. Overall, the evidence to date is insufficient to justify widespread implementation of precision medicine approaches into routine clinical practice for type 2 diabetes. We need to retain a degree of humility and healthy scepticism when evaluating novel strategies, and to demand that existing evidence thresholds are exceeded prior to implementation. Graphical abstract

BackgroundGestational diabetes mellitus (GDM) is an important risk factor for developing type 2 diabetes mellitus (T2DM) later in life. Postpartum screening provides an opportunity for early detection and management of T2DM, but uptake is poor.AimTo explore barriers to screening from clinicians’ perspectives to guide future interventions to increase uptake of postpartum screening.Design and settingSystematic review and qualitative synthesis.MethodQualitative studies included in a previous review were assessed, and then five electronic databases were searched from January 2013 to May 2019 for qualitative studies reporting clinicians’ perspectives on postpartum glucose screening after GDM. Study quality was assessed against the Critical Appraisal Skills Programmes checklist. Qualitative data from the studies were analysed using thematic synthesis.ResultsNine studies were included, containing views from 187 clinicians from both community and hospital care. Three main themes were identified: difficulties in handover between primary and secondary care (ambiguous roles and communication difficulties); short-term focus in clinical consultations (underplaying risk so as not to overwhelm patients and competing priorities); and patient-centric barriers such as time pressures.ConclusionBarriers to diabetes screening were identified at both system and individual levels. At the system level, clarification of responsibility for testing among healthcare professionals and better systems for recall are needed. These could be achieved through registers, improved clinical protocols, and automatic flagging and prompts within electronic medical records. At the individual level, clinicians should be supported to prioritise the importance of screening within consultations and better educational resources made available for women. Making it more convenient for women to attend may also facilitate screening.

Background Development of effective strategies to reduce sedentary time among older adults necessitates understanding of its determinants but longitudinal studies of this utilising objective measures are scarce. Methods Among 1536 older adults (≥60 years) in the EPIC-Norfolk study, sedentary time was assessed for seven days at two time-points using accelerometers. We assessed associations of change in total and prolonged bouts of sedentary time (≥ 30 minutes) with change in demographic and behavioural factors using multi-level regression. Results Over follow-up (5.3±1.9 years), greater increases in total sedentary time were associated with older age, being male, higher rate of increase in BMI, lower rate of increase in gardening (0.5 min/day/yr greater sedentary time per hour/week/yr less gardening, 95% CI 0.1, 1.0), a lower rate of increase in walking (0.2 min/day/yr greater sedentary time per hour/week/yr less walking, 95% CI 0.1, 0.3) and a higher rate of increase in television viewing. Correlates of change in prolonged sedentary bouts were similar. Conclusion Individuals in specific sub-groups (older, male, higher BMI) and who differentially participate in certain behaviours (less gardening, less walking and more television viewing) but not others increase their sedentary time at a higher rate than others; utilising this information could inform successful intervention content and targeting.

Funder: Kidney Cancer UK, Funder: Mark Foundation For Cancer Research; Id: http://dx.doi.org/10.13039/100014599, Funder: The Rosetrees Trust, Funder: The Urology Foundation, Funder: Yorkshire Cancer Research; Id: http://dx.doi.org/10.13039/100011703, OBJECTIVE: To review the current state of genetic risk models for predicting the development of kidney cancer, by identifying and comparing the performance of published models. METHODS: Risk models were identified from a recent systematic review and the Cancer-PRS web directory. A narrative synthesis of the models, previous validation studies and related genome-wide association studies (GWAS) was carried out. The discrimination and calibration of the identified models was then assessed and compared in the UK Biobank (UKB) cohort (cases, 452; controls, 487 925). RESULTS: A total of 39 genetic models predicting the development of kidney cancer were identified and 31 were validated in the UKB. Several of the genetic-only models (seven of 25) and most of the mixed genetic-phenotypic models (five of six) had some discriminatory ability (area under the receiver operating characteristic curve >0.5) in this cohort. In general, models containing a larger number of genetic variants identified in GWAS performed better than models containing a small number of variants associated with known causal pathways. However, the performance of the included models was consistently poorer than genetic risk models for other cancers. CONCLUSIONS: Although there is potential for genetic models to identify those at highest risk of developing kidney cancer, their performance is poorer than the best genetic risk models for other cancers. This may be due to the comparatively small number of genetic variants associated with kidney cancer identified in GWAS to date. The development of improved genetic risk models for kidney cancer is dependent on the identification of more variants associated with this disease. Whether these will have utility within future kidney cancer screening pathways is yet to determined.

INTRODUCTION: The cost-effectiveness and long-term health impact of behavioural weight management programmes depends on post-treatment weight-loss maintenance. Growing evidence suggests that interventions using acceptance and commitment therapy (ACT) could improve long-term weight management. We developed an ACT-based, guided self-help intervention to support adults who have recently completed a behavioural weight loss programme. This study will assess the feasibility and acceptability of this type of intervention and findings will inform the development of a full-scale trial. METHODS AND ANALYSIS: This is a pragmatic, randomised, single-blind, parallel group, two-arm, feasibility study with an embedded process evaluation. We will recruit and randomise 60 adults who have recently completed a behavioural weight loss programme to the ACT-based intervention or standard care, using a computer-generated sequence with 2:1 allocation stratified by diabetes status and sex. Baseline and 6-month measurements will be completed using online questionnaires. Qualitative interviews will be conducted with a subsample of participants and coaches about their experiences at 3 (mid-intervention) and 6 (postintervention) months. Feasibility and acceptability of the intervention, and a full-scale trial will be assessed using a number of outcomes, including adherence to, and engagement with the intervention, recruitment and retention rates, proportion of missing data for each outcome measure, participants' experiences of the intervention and study, and coaches' experiences of delivering intervention support. Quantitative and qualitative findings will be integrated and summarised to contribute to the interpretation of the main feasibility evaluation findings. Value of information methods will be used to estimate the decision uncertainty associated with the intervention's cost-effectiveness and determine the value of a definitive trial. ETHICS AND DISSEMINATION: Ethical approval was received from Cambridge South Research Ethics Committee on 15/03/2021 (21/EE/0024). This protocol (V.2) was approved on 19 April 2021. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. TRIAL REGISTRATION NUMBER: ISRCTN12685964., This study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (RP-PG-0216-20010). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

AIMS/HYPOTHESIS: Weight loss is often recommended in the treatment of type 2 diabetes. While evidence has shown that large weight loss may lead to diabetes remission and improvement in cardiovascular risk factors, long-term impacts are unclear. We performed a systematic review of studies of weight loss and other weight changes and incidence of CVD among people with type 2 diabetes. METHODS: Observational studies of behavioural (non-surgical and non-pharmaceutical) weight changes and CVD events among adults with type 2 diabetes, and trials of behavioural interventions targeting weight loss, were identified through searches of MEDLINE, EMBASE, Web of Science, CINAHL, and The Cochrane Library (CENTRAL) until 9 July 2019. Included studies reported change in weight and CVD and/or mortality outcomes among adults with type 2 diabetes. We performed a narrative synthesis of observational studies and meta-analysis of trial data. RESULTS: Of 13,227 identified articles, 17 (14 observational studies, three trials) met inclusion criteria. Weight gain (vs no change) was associated with higher hazard of CVD events (HRs [95% CIs] ranged from 1.13 [1.00, 1.29] to 1.63 [1.11, 2.39]) and all-cause mortality (HRs [95% CIs] ranged from 1.26 [1.12, 1.41] to 1.57 [1.33, 1.85]). Unintentional weight loss (vs no change) was associated with higher risks of all-cause mortality, but associations with intentional weight loss were unclear. Behavioural interventions targeting weight loss showed no effect on CVD events (pooled HR [95% CI] 0.95 [0.71, 1.27]; I2 = 50.1%). Risk of bias was moderate in most studies and was high in three studies, due to potential uncontrolled confounding and method of weight assessment. CONCLUSIONS/INTERPRETATION: Weight gain is associated with increased risks of CVD and mortality, although there is a lack of data supporting behavioural weight-loss interventions for CVD prevention among adults with type 2 diabetes. Long-term follow-up of behavioural intervention studies is needed to understand effects on CVD and mortality and to inform policy concerning weight management advice and support for people with diabetes. PROSPERO registration CRD42019127304., MRC Epidemiology Unit core funding MC_UU_12015/4 and NIHR PGfAR RP PG 0216 20010

Highlights • Conceptualisation of risk is a complex cognitive process. • Individuals tend to overestimate their risk of cancer at baseline. • Immediately after risk information over 80% of people are able to recall the number. • However, less than half believe that to be their risk, thinking their risk is higher. • Risk information has either no effect or reduces worry, anxiety and depression., Objective To synthesize the literature on the effect of provision of personalised cancer risk information to individuals at population level risk on accuracy of risk perception and psychological responses. Methods A systematic review and random effects meta-analysis of articles published from 01/01/2000 to 01/07/2017. Results We included 23 studies. Immediately after provision of risk information 87% of individuals were able to recall the absolute risk estimate. Less than half believed that to be their risk, with up to 71% believing their risk to be higher than the estimate. Provision of risk information increased accuracy of perceived absolute risk immediately after risk information compared with no information (pooled RR 4.16 (95%CI 1.28–13.49), 3 studies). There was no significant effect on comparative risk accuracy (pooled RR 1.39 (0.72–2.69), 2 studies) and either no change or a reduction in cancer worry, anxiety and fear. Conclusion These findings highlight the complex cognitive processes involved in the conceptualisation of risk. Practice implications Individuals who appear to understand and are able to recall risk information most likely do not believe it reflects their own risk.

Objectives: There is insufficient evidence to support national screening programmes for atrial fibrillation (AF). Nevertheless, some practitioners, policymakers and special interest groups have encouraged introduction of opportunistic screening in primary care in order to reduce the incidence of stroke through earlier detection and treatment of AF. The attitudes of the public towards AF screening are unknown. We aimed to explore why AF screening participants took part in the screening. Design: Semi-structured longitudinal interview study of participant engagement in the SAFER study (Screening for Atrial Fibrillation with ECG to Reduce stroke). We undertook initial interviews face-to-face, with up to two follow-up telephone interviews during the screening process. We thematically analysed and synthesised this data to understand shared views of screening participation. Setting: 5 primary care practices in the East of England, UK. Participants: 23 people taking part in the SAFER study first feasibility phase. Results: Participants were supportive of screening for AF, explaining their participation in screening as a ‘good thing to do’. Participants suggested screening could facilitate earlier diagnosis, more effective treatment, and a better future outcome, despite most being unfamiliar with AF. Participating in AF screening helped attenuate participants’ concerns about stroke and demonstrated their commitment to self-care and being a ‘good patient’. Participants felt that the screening test was non-invasive, and they were unlikely to have AF; they therefore considered engaging in AF screening was low risk, with few perceived harms. Conclusions: Participants assessed the SAFER AF screening programme to be a legitimate, relevant, and safe screening opportunity, and complied obediently with what they perceived to be a recommendation to take part. Their unreserved acceptance of screening benefit and lack of awareness of potential harms suggests that uptake would be high but reinforces the importance of ensuring participants receive balanced information about AF screening initiatives., National Institute for Health Research (NIHR) Programme Grants for Applied Research (grant reference number RP-PG-0217-20007) and School for Primary Care Research (SPCR-2014-10043, project 410). Health Foundation

Background There is a need to develop cost-effective weight loss maintenance interventions to prolong the positive impact of weight loss on health outcomes. Conducting pre-trial health economic modelling is recommended to inform the design and development of behavioural interventions. We aimed to use health economic modelling to estimate the maximum cost per-person (justifiable cost) of a cost-effective behavioural weight loss maintenance intervention, given an estimated intervention effect for individuals with: i) a Body Mass Index (BMI) of 28 kg/m2 or above without diabetes and ii) a diagnosis of type 2 diabetes prescribed a single non-insulin diabetes medication. Methods The School for Public Health Research Diabetes prevention model was used to estimate the lifetime Quality-adjusted life year (QALY) gains, healthcare costs, and maximum justifiable cost associated with a weight loss maintenance intervention. Based on a meta-analysis, the estimated effect of a weight loss maintenance intervention following a 9 kg weight loss, was a regain of 1.33 kg and 4.38 kg in years one and two respectively compared to greater regain of 2.84 kg and 5.6 kg in the control group. Sensitivity analysis was conducted around the rate of regain, duration of effect and initial weight loss. Results The justifiable cost for a weight loss maintenance intervention at an ICER of £20,000 per QALY was £104.64 for an individual with a BMI of 28 or over and £88.14 for an individual with type 2 diabetes. Within sensitivity analysis, this varied from £36.42 to £203.77 for the former, and between £29.98 and £173.05 for the latter. Conclusions Researchers developing a weight loss maintenance intervention should consider these maximum justifiable cost estimates and the potential impact of the duration of effect and initial weight loss when designing intervention content and deciding target populations. Future research should consider using the methods demonstrated in this study to use health economic modelling to inform the design and budgetary decisions in the development of a behavioural interventions.

Introduction: Diabetes and related metabolic disorders such as obesity and cardiovascular diseases (CVD) are a growing global issue. Equipping individuals with the necessary ‘knowledge, skills and confidence to self-manage their health’ (i.e. patient activation [PAct]) may lead to improvements in health outcomes. It is unclear whether existing evidence allows us to assume a causal relationship. We aim to synthesise and critically appraise evidence on the relationship between PAct and self-management behaviours and clinical outcomes of people living with diabetes and related metabolic disorders. Methods and analysis: The protocol is based on guidance on Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will search Medline, Embase, CENTRAL, PsycInfo, Web of Science, and CINAHL using search terms related to patient activation, diabetes, prediabetes, obesity, and cardiovascular disease. Any quantitative study design is eligible provided studies assess the association between PAct and clinical outcomes and/or self-management behaviours of diabetes and related metabolic disorders. Outcomes include behavioural (e.g. diet) and clinical (e.g. blood pressure) outcomes. Two reviewers will independently screen titles/abstracts and full texts and assess risk of bias using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). One reviewer will extract data, with independent checking by a second reviewer. We will critically assess the level of evidence available for assuming a causal association between PAct and outcomes. Data permitting, we will use the Hunter-Schmidt random-effects method to meta-analyse correlations across studies. Ethics and dissemination: Ethical approval is not required. The review will be disseminated in the form of a peer-reviewed journal article, at conferences and other presentations. The findings of the review will be of interest to clinical commissioning groups, policy makers and intervention deliverers/developers. Registration: Prospero registration number: CRD42021230727, This work was supported by the Medical Research Council [grant number MC_UU_00006/6] and the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (RP-PG-0216-20010).

Background Type 2 diabetes is a leading cause of mortality globally and accounts for significant health resource expenditure. Increased physical activity can reduce the risk of diabetes. However, the longer-term clinical effectiveness and cost-effectiveness of physical activity interventions in those at high risk of type 2 diabetes is unknown. Objectives To investigate whether or not Walking Away from Diabetes (Walking Away) – a low-resource, 3-hour group-based behavioural intervention designed to promote physical activity through pedometer use in those with prediabetes – leads to sustained increases in physical activity when delivered with and without an integrated mobile health intervention compared with control. Design Three-arm, parallel-group, pragmatic, superiority randomised controlled trial with follow-up conducted at 12 and 48 months. Setting Primary care and the community. Participants Adults whose primary care record included a prediabetic blood glucose measurement recorded within the past 5 years [HbA1c ≥ 42 mmol/mol (6.0%), Interventions Participants were randomised (1 : 1 : 1) using a web-based tool to (1) control (information leaflet), (2) Walking Away with annual group-based support or (3) Walking Away Plus (comprising Walking Away, annual group-based support and a mobile health intervention that provided automated, individually tailored text messages to prompt pedometer use and goal-setting and provide feedback, in addition to biannual telephone calls). Participants and data collectors were not blinded; however, the staff who processed the accelerometer data were blinded to allocation. Main outcome measures The primary outcome was accelerometer-measured ambulatory activity (steps per day) at 48 months. Other objective and self-reported measures of physical activity were also assessed. Results A total of 1366 individuals were randomised (median age 61 years, median body mass index 28.4 kg/m2, median ambulatory activity 6638 steps per day, women 49%, black and minority ethnicity 28%). Accelerometer data were available for 1017 (74%) and 993 (73%) individuals at 12 and 48 months, respectively. The primary outcome assessment at 48 months found no differences in ambulatory activity compared with control in either group (Walking Away Plus: 121 steps per day, 97.5% confidence interval –290 to 532 steps per day; Walking Away: 91 steps per day, 97.5% confidence interval –282 to 463). This was consistent across ethnic groups. At the intermediate 12-month assessment, the Walking Away Plus group had increased their ambulatory activity by 547 (97.5% confidence interval 211 to 882) steps per day compared with control and were 1.61 (97.5% confidence interval 1.05 to 2.45) times more likely to achieve 150 minutes per week of objectively assessed unbouted moderate to vigorous physical activity. In the Walking Away group, there were no differences compared with control at 12 months. Secondary anthropometric, biomechanical and mental health outcomes were unaltered in either intervention study arm compared with control at 12 or 48 months, with the exception of small, but sustained, reductions in body weight in the Walking Away study arm (≈ 1 kg) at the 12- and 48-month follow-ups. Lifetime cost-effectiveness modelling suggested that usual care had the highest probability of being cost-effective at a threshold of £20,000 per quality-adjusted life-year. Of 50 serious adverse events, only one (myocardial infarction) was deemed possibly related to the intervention and led to the withdrawal of the participant from the study. Limitations Loss to follow-up, although the results were unaltered when missing data were replaced using multiple imputation. Conclusions Combining a physical activity intervention with text messaging and telephone support resulted in modest, but clinically meaningful, changes in physical activity at 12 months, but the changes were not sustained at 48 months. Future work Future research is needed to investigate which intervention types, components and features can help to maintain physical activity behaviour change over the longer term. Trial registration Current Controlled Trials ISRCTN83465245. Funding This 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. 25, No. 77. See the NIHR Journals Library website for further project information.

Aims/hypothesis Weight reduction is fundamental for type 2 diabetes management and remission, but uncertainty exists over which diet type is best to achieve and maintain weight loss. We evaluated dietary approaches for weight loss, and remission, in people with type 2 diabetes to inform practice and clinical guidelines. Methods First, we conducted a systematic review of published meta-analyses of RCTs of weight-loss diets. We searched MEDLINE (Ovid), PubMed, Web of Science and Cochrane Database of Systematic Reviews, up to 7 May 2021. We synthesised weight loss findings stratified by diet types and assessed meta-analyses quality with A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. We assessed certainty of pooled results of each meta-analysis using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (PROSPERO CRD42020169258). Second, we conducted a systematic review of any intervention studies reporting type 2 diabetes remission with weight-loss diets, in MEDLINE (via PubMed), Embase and Cochrane Central Register of Controlled Trials, up to 10 May 2021. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies – of Interventions [ROBINS-I]), with GRADE applied (PROSPERO CRD42020208878). Results We identified 19 meta-analyses of weight-loss diets, involving 2–23 primary trials (n = 100–1587), published 2013–2021. Twelve were ‘critically low’ or ‘low’ AMSTAR 2 quality, with seven ‘high’ quality. Greatest weight loss was reported with very low energy diets, 1.7–2.1 MJ/day (400–500 kcal) for 8–12 weeks (high-quality meta-analysis, GRADE low), achieving 6.6 kg (95% CI −9.5, −3.7) greater weight loss than low-energy diets (4.2–6.3 MJ/day [1000–1500 kcal]). Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI −3.3, −1.4) greater weight loss over 12–52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3–2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate). For type 2 diabetes remission, of 373 records, 16 met inclusion criteria. Remissions at 1 year were reported for a median 54% of participants in RCTs including initial low-energy total diet replacement (low-risk-of-bias study, GRADE high), and 11% and 15% for meal replacements and Mediterranean diets, respectively (some concerns for risk of bias in studies, GRADE moderate/low). For ketogenic/very low-carbohydrate and very low-energy food-based diets, the evidence for remission (20% and 22%, respectively) has serious and critical risk of bias, and GRADE certainty is very low. Conclusions/interpretation Published meta-analyses of hypocaloric diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets. Programmes including a hypocaloric formula ‘total diet replacement’ induction phase were most effective for type 2 diabetes remission. Most of the evidence is restricted to 1 year or less. Well-conducted research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications. Graphical abstract

Introduction: Adults with overweight and obesity are vulnerable to weight gain and mental health deterioration during the COVID-19 pandemic. We developed a web-based, guided self-help intervention based on Acceptance and Commitment Therapy (ACT) that aims to support adults with overweight and obesity to prevent weight gain by helping them to manage their eating behaviours, be more physically active and protect their emotional wellbeing (“SWiM-C”). SWiM-C is a guided self-help programme using non-specialist guides to enhance scalability and population reach while minimising cost. This study evaluated the effect of SWiM-C on bodyweight, eating behaviour, physical activity and mental wellbeing in adults with overweight and obesity over 4 months during the COVID-19 pandemic in the UK. Methods: We randomised adults (BMI≥25kg/m2) to SWiM-C or to a wait-list standard advice group. Participants completed outcome assessments online at baseline and 4 months. The primary outcome was self-measured weight; secondary outcomes were eating behaviour, physical activity, experiential avoidance/psychological flexibility, depression, anxiety, stress, and wellbeing. We estimated differences between study groups in change in outcomes from baseline to 4 months using linear regression, adjusted for outcome at baseline and the randomisation stratifiers (BMI, sex). The trial was pre-registered (ISRCTN12107048). Results: 486 participants were assessed for eligibility; 388 participants were randomised (196 standard advice, 192 SWiM-C) and 324 were analysed. The adjusted difference in weight between SWiM-C and standard advice was -0.60kg (-1.67 to 0.47, p=0.27). SWiM-C led to improvements in uncontrolled eating (-3.61 [-5.94 to -1.28]), cognitive restraint (5.28 [2.81 to 7.75]), experiential avoidance (-3.39 [-5.55 to -1.23]), and wellbeing (0.13 [0.07 to 0.18]). Conclusions: SWiM-C improved several psychological determinants of successful weight management and had a protective effect on wellbeing during the pandemic. However, differences in weight and some other outcomes were compatible with no effect of the intervention, suggesting further refinement of the intervention is needed.

Introduction: On average, aspects of mental health improve following behavioural weight management programmes, yet this is not the case for all participants. It is important to identify those at risk of harm to provide more effective psychological support. We aimed to identify participant characteristics associated with changes in depression and anxiety in participants of a behavioural weight management programme. Methods: In the Weight loss Referrals for Adults in Primary care trial, 1,267 adults with body mass index ≥28 kg/m2 were randomized to brief intervention, or WW (formerly weight watchers) for 12-weeks or 52-weeks and followed for 5 years. We used linear and multinomial regression to explore the association between participant characteristics and changes in depression and anxiety (measured by the hospital anxiety and depression scale). Where possible, the impact of missing data was investigated using multiple imputation. Results: Higher baseline anxiety was associated with decreases in anxiety symptoms and increases in depression symptoms from baseline to follow-up. Higher baseline depression was associated with decreases in depression symptoms and increases in anxiety symptoms from baseline to follow-up. The magnitude of the associations was small. No further characteristics were consistently associated with changes in mental health. Discussion: Evidence suggests that baseline depression and anxiety may indicate how depression and anxiety symptoms change during and after attending WW. Measurement of depression and anxiety at the start of a behavioural weight management programme and subsequent monitoring may facilitate timely psychological support if a deterioration in mental health is identified. Further research in large and diverse participant samples is required to clarify the findings.

OBJECTIVE: To systematically identify and compare the performance of prognostic models providing estimates of survival or recurrence of localized renal cell cancer (RCC) in patients treated with surgery with curative intent. MATERIALS AND METHODS: We performed a systematic review (PROSPERO CRD42019162349). We searched Medline, EMBASE and the Cochrane Library from 1 January 2000 to 12 December 2019 to identify studies reporting the performance of one or more prognostic model(s) that predict recurrence-free survival (RFS), cancer-specific survival (CSS) or overall survival (OS) in patients who have undergone surgical resection for localized RCC. For each outcome we summarized the discrimination of each model using the C-statistic and performed multivariate random-effects meta-analysis of the logit transformed C-statistic to rank the models. RESULTS: Of a total of 13 549 articles, 57 included data on the performance of 22 models in external populations. C-statistics ranged from 0.59 to 0.90. Several risk models were assessed in two or more external populations and had similarly high discriminative performance. For RFS, these were the Sorbellini, Karakiewicz, Leibovich and Kattan models, with the UCLA Integrated Staging System model also having similar performance in European/US populations. All had C-statistics ≥0.75 in at least half of the validations. For CSS, they the models with the highest discriminative performance in two or more external validation studies were the Zisman, Stage, Size, Grade and Necrosis (SSIGN), Karakiewicz, Leibovich and Sorbellini models (C-statistic ≥0.80 in at least half of the validations), and for OS they were the Leibovich, Karakiewicz, Sorbellini and SSIGN models. For all outcomes, the models based on clinical features at presentation alone (Cindolo and Yaycioglu) had consistently lower discrimination. Estimates of model calibration were only infrequently included but most underestimated survival. CONCLUSION: Several models had good discriminative ability, with there being no single 'best' model. The choice from these models for each setting should be informed by both the comparative performance and availability of factors included in the models. All would need recalibration if used to provide absolute survival estimates.

Background: The long-term impact and cost-effectiveness of weight management programmes depends on post-treatment weight maintenance. There is growing evidence that interventions based on third-wave cognitive behavioural therapy (3wCBT), specifically acceptance and commitment therapy (ACT), could improve long-term weight management however these interventions are typically delivered face-to-face by psychologists, which limits the scalability of this type of intervention. Objective: To use an evidence-, theory- and person-based approach to develop an ACT-based intervention for weight-loss maintenance that uses digital technology and non-specialist guidance to minimise resources needed for delivery at scale. Methods: Intervention development was guided by the Medical Research Council framework for the development of complex interventions in healthcare, Intervention Mapping Protocol, and the person-based approach for enhancing the acceptability and feasibility of interventions. Two phases of work were conducted: phase one consisted of collating and analysing existing and new primary evidence, and phase two consisted of theoretical modelling and intervention development. Phase one included a synthesis of existing evidence on weight-loss maintenance from previous research, a systematic review and network meta-analysis of 3wCBT interventions for weight management, a qualitative interview study of experiences of weight-loss maintenance, and the modelling of a justifiable cost for a weight-loss maintenance programme. Phase two included iterative development of guiding principles, a logic model and the intervention design and content. Target user and stakeholder panels were established to inform each phase of development and user-testing of successive iterations of the prototype intervention were conducted. Results: This process resulted in a guided self-help ACT-based intervention called SWiM (Supporting Weight Management). SWiM is a 4-month programme, consisting of weekly web-based sessions for 13 consecutive weeks, followed by a 4-week break for participants to reflect and practice their new skills, and a final session at week 17. Each session consists of psychoeducational content, reflective exercises, and behavioural experiments. SWiM includes specific sessions on key determinants of weight-loss maintenance, including developing skills to manage high-risk situations for lapses, creating new helpful habits, breaking old unhelpful habits, and learning to manage interpersonal relationships and their impact on weight-management. A trained, non-specialist coach provides guidance for participants through the programme with four scheduled 30-minute telephone calls and three further optional calls. Conclusions: This comprehensive approach facilitated the development of an intervention that is based on scientific theory and evidence of how to support people with weight-loss maintenance, and is grounded in the experiences of the target users and the context in which it is intended to be delivered. The intervention will be refined based on findings of a planned pilot randomised controlled trial. Keywords: weight management; eHealth; acceptance and commitment therapy; third wave cognitive behavioural therapy; guided self-help

BACKGROUND: Low attendance and engagement in behavioural weight management trials are common. Mental health may play an important role, however previous research exploring this association is limited with inconsistent findings. We aimed to investigate whether mental health was associated with attendance and engagement in a trial of behavioural weight management programmes. METHODS: This is a secondary data analysis of the Weight loss referrals for adults in primary care (WRAP) trial, which randomised 1267 adults with overweight or obesity to brief intervention, WW (formerly Weight Watchers) for 12-weeks, or WW for 52-weeks. We used regression analyses to assess the association of baseline mental health (depression and anxiety (by Hospital Anxiety and Depression Scale), quality of life (by EQ5D), satisfaction with life (by Satisfaction with Life Questionnaire)) with programme attendance and engagement in WW groups, and trial attendance in all randomised groups. RESULTS: Every one unit of baseline depression score was associated with a 1% relative reduction in rate of WW session attendance in the first 12 weeks (Incidence rate ratio [IRR] 0.99; 95% CI 0.98, 0.999). Higher baseline anxiety was associated with 4% lower odds to report high engagement with WW digital tools (Odds ratio [OR] 0.96; 95% CI 0.94, 0.99). Every one unit of global quality of life was associated with 69% lower odds of reporting high engagement with the WW mobile app (OR 0.31; 95% CI 0.15, 0.64). Greater symptoms of depression and anxiety and lower satisfaction with life at baseline were consistently associated with lower odds of attending study visits at 3-, 12-, 24-, and 60-months. CONCLUSIONS: Participants were less likely to attend programme sessions, engage with resources, and attend study assessments when reporting poorer baseline mental health. Differences in attendance and engagement were small, however changes may still have a meaningful effect on programme effectiveness and trial completion. Future research should investigate strategies to maximise attendance and engagement in those reporting poorer mental health. TRIAL REGISTRATION: The original trial ( ISRCTN82857232 ) and five year follow up ( ISRCTN64986150 ) were prospectively registered with Current Controlled Trials on 15/10/2012 and 01/02/2018., The WRAP trial was funded by the National Prevention Research Initiative through research grant MR/J000493. The intervention was provided by WW (formerly Weight Watchers) at no cost via an MRC Industrial Collaboration Award. Five year follow up of the WRAP trial was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (RP-PG-0216-20010). RAJ, ALA, SJG, and SJS are supported by the Medical Research Council (MRC) (Grant MC_UU_00006/6). The University of Cambridge has received salary support in respect of SJG from the National Health Service in the East of England through the Clinical Academic Reserve. All funding bodies had no role in the design of the study and collection, analysis and interpretation of the data, and in the writing of the manuscript.

BackgroundTimely diagnosis of bladder and kidney cancer is key to improving clinical outcomes. Given the challenges of early diagnosis, models incorporating clinical symptoms and signs may be helpful to primary care clinicians when triaging at-risk patients.AimTo identify and compare published models that use clinical signs and symptoms to predict the risk of undiagnosed prevalent bladder or kidney cancer.Design and settingSystematic review.MethodA search identified primary research reporting or validating models predicting the risk of bladder or kidney cancer in MEDLINE and EMBASE. After screening identified studies for inclusion, data were extracted onto a standardised form. The risk models were classified using TRIPOD guidelines and evaluated using the PROBAST assessment tool.ResultsThe search identified 20 661 articles. Twenty studies (29 models) were identified through screening. All the models included haematuria (visible, non-visible, or unspecified), and seven included additional signs and symptoms (such as abdominal pain). The models combined clinical features with other factors (including demographic factors and urinary biomarkers) to predict the risk of undiagnosed prevalent cancer. Several models (n = 13) with good discrimination (area under the receiver operating curve >0.8) were identified; however, only eight had been externally validated. All of the studies had either high or unclear risk of bias.ConclusionModels were identified that could be used in primary care to guide referrals, with potential to identify lower-risk patients with visible haematuria and to stratify individuals who present with non-visible haematuria. However, before application in general practice, external validations in appropriate populations are required.

BackgroundAssociations between driving and physical-activity (PA) intensities are unclear, particularly among older adults. We estimated prospective associations of travel modes with total PA, sedentary time (ST), light-intensity PA (LPA), and moderate-to-vigorous intensity PA (MVPA) among adults aged 39–70 years.MethodsWe studied 90 810 UK Biobank participants (56.1 ± 7.8 years). Driving status, specific travel modes (non-work travel; commuting to/from work) and covariates were assessed by questionnaire (2006–10). PA was assessed over 7 days by wrist-worn accelerometers (2013–15). We estimated associations using overall and age-stratified multivariable linear-regression models.ResultsDrivers accumulated 1.4% more total PA (95% confidence interval: 0.9, 1.9), 11.2 min/day less ST (–12.9, –9.5), 12.2 min/day more LPA (11.0, 13.3) and 0.9 min/day less MVPA (–1.6, –0.2) than non-drivers. Compared with car/motor-vehicle users, cyclists and walkers had the most optimal activity profiles followed by mixed-mode users (e.g. for non-work travel, cyclists: 10.7% more total PA, 9.0, 12.4; 20.5 min/day less ST, –26.0, –15.0; 14.5 min/day more MVPA, 12.0, 17.2; walkers: 4.2% more total PA, 3.5, 5.0; 7.5 min/day less ST –10.2, –4.9; 10.1 min/day more MVPA, 8.9, 11.3; mixed-mode users: 2.3% more total PA, 1.9, 2.7; 3.4 min/day less ST –4.8, –2.1; 4.9 min/day more MVPA, 4.3, 5.5). Some associations varied by age (p interaction ConclusionsAssessing specific travel modes rather than driving status alone may better capture variations in activity. Walking, cycling and, to a lesser degree, mixed-mode use are associated with more optimal activity profiles in adults of all ages.

The PAM intervention is a behavioural intervention to support adherence to anti-hypertensive medications and therefore to lower blood pressure. This feasibility trial recruited 101 nonadherent patients (54% male, mean age 65.8 years) with hypertension and high blood pressure from nine general practices in the UK. The trial had 15.5% uptake and 7.9% attrition rate. Patients were randomly allocated to two groups: the intervention group (n = 61) received the PAM intervention as an adjunct to usual care; the control group (n = 40) received usual care only. At 3 months, biochemically validated medication adherence was improved by 20% (95% CI 3–36%) in the intervention than control, and systolic blood pressure was reduced by 9.16 mmHg (95% CI 5.69–12.64) in intervention than control. Improvements in medication adherence and reductions in blood pressure suggested potential intervention effectiveness. For a subsample of patients, improvements in medication adherence and reductions in full lipid profile (cholesterol 1.39 mmol/mol 95% CI 0.64–1.40) and in glycated haemoglobin (3.08 mmol/mol, 95% CI 0.42–5.73) favoured the intervention. A larger trial will obtain rigorous evidence about the potential clinical effectiveness and cost-effectiveness of the intervention.Trial registration Trial date of first registration 28/01/2019. ISRCTN74504989. https://doi.org/10.1186/ISRCTN74504989.

Background Remission of Type 2 diabetes is achievable through dietary change and weight loss. In the UK, lifestyle advice and referrals to weight loss programmes predominantly occur in primary care where most Type 2 diabetes is managed. Objective To quantify the association between primary care experience and remission of Type 2 diabetes over 5-year follow-up. Methods A prospective cohort study of adults with Type 2 diabetes registered to 49 general practices in the East of England, UK. Participants were followed-up for 5 years and completed the Consultation and Relational Empathy measure (CARE) on diabetes-specific primary care experiences over the first year after diagnosis of the disease. Remission at 5-year follow-up was measured with HbA1c levels. Univariable and multivariable logistic regression models were constructed to quantify the association between primary care experience and remission of diabetes. Results Of 867 participants, 30% (257) achieved remission of Type 2 diabetes at 5 years. Six hundred twenty-eight had complete data at follow-up and were included in the analysis. Participants who reported higher CARE scores in the 12 months following diagnosis were more likely to achieve remission at 5 years in multivariable models; odds ratio = 1.03 (95% confidence interval = 1.01–1.05, P = 0.01). Conclusion Primary care practitioners should pay greater attention to delivering optimal patient experiences alongside clinical management of the disease as this may contribute towards remission of Type 2 diabetes. Further work is needed to examine which aspects of the primary care experience might be optimized and how these could be operationalized.

Introduction Around 23% of adults worldwide are insufficiently active. Wearable devices paired with virtual coaching software could increase physical activity. The effectiveness of 3 minimal contact interventions (paper-based physical activity diaries, activity trackers, and activity trackers coupled with virtual coaching) in increasing physical activity energy expenditure and cardiorespiratory fitness were compared over 12 weeks among inactive adults. Methods This was an open label, parallel-group RCT. Inactive adults (aged ≥18 years, N=488) were randomized to no intervention (Control; n=121), paper-based diary (Diary; n=124), activity tracker (Activity Band; n=122), or activity tracker plus virtual coaching (Activity Band PLUS; n=121) groups. Coprimary outcomes included 12-week changes in physical activity energy expenditure and fitness (May 2012–January 2014). Analyses were conducted in 2019–2020. Results There were no differences between groups overall (physical activity energy expenditure: p=0.114, fitness: p=0.417). However, there was a greater increase in physical activity energy expenditure (4.21 kJ/kg/day, 95% CI=0.42, 8.00) in the Activity Band PLUS group than in the Diary group. There were also greater decreases in BMI and body fat percentage in the Activity Band PLUS group than in the Control group (BMI= −0.24 kg/m2, 95% CI= −0.45, −0.03; body fat= −0.48%, 95% CI= −0.88, −0.08) and in theActivity Band PLUS group than in the Diary group (BMI= −0.30 kg/m2, 95% CI= −0.50, −0.09; body fat= −0.57%, 95% CI= −0.97, −0.17). Conclusions Coupling activity trackers with virtual coaching may facilitate increases in physical activity energy expenditure compared with a traditional paper‒based physical activity diary intervention and improve some secondary outcomes compared with a traditional paper‒based physical activity diary intervention or no intervention. Trial registration This study is registered at www.clinicaltrials.gov ISRCTN31844443.

Background Men have a greater risk of colorectal cancer (CRC) than women, but population screening currently starts at the same age for both sexes. Aim This analysis investigates whether, in a resource constrained setting, it would be more effective and cost-effective for men and women to start screening for CRC at different ages. Methods and Results An economic modelling analysis was carried out using the Microsimulation Model in Cancer of the Bowel to compare sex-stratification against screening everyone from the same age, taking an English National Health Service perspective. Screening men from age 56 and women from age 60, rather than screening everyone from age 58 using a Faecal Immunochemical Test (FIT) threshold of 120µg/g is expected to produce an additional 0.0004 QALYs for a cost of £0.55 per person at model start (Incremental Cost-effectiveness Ratio = £1,392), and to reduce CRC cases and mortality by 25 and 19 per 100,000 people respectively, whilst using a similar amount of screening resources. Probabilistic sensitivity analysis indicates a 61% probability that sex-stratification is more cost-effective than screening everyone at age 58. Similar benefits of sex-stratification are found at other FIT thresholds, but become negligible if mean screening start age is reduced to 50. Conclusion Where resources are constrained and it is not feasible to screen everyone from the age of 50, starting screening earlier in men than women is likely to be more cost-effective and gain more health benefits overall than strategies where men and women start screening at the same age.

The environments in which young and middle-aged adults live may influence their physical activity (PA) behaviours. These associations are less clear among older adults. We estimated cross-sectional and prospective associations of population density, junction density, and land use mix and perceived active living environments with accelerometer-assessed PA in a cohort of older adults. Adults living in more dense and mixed neighbourhoods had less optimal activity profiles at baseline and less optimal changes in activity. Better perceptions were associated with more overall PA at baseline. Interventions for older adults may wish to target individuals living in more dense and mixed neighbourhoods., Highlights • Older adults living in more dense/mixed areas are more sedentary and less active. • More dense/mixed areas are associated with less optimal changes in activity. • Adults who perceive living in more activity-friendly accumulate more total activity. • There was no evidence of associations between perceptions and changes in activity.

Population-based screening for colorectal cancer is an effective and cost-effective way of reducing colorectal cancer incidence and mortality. Many genetic and phenotypic risk factors for colorectal cancer have been identified, leading to development of colorectal cancer risk scores with varying discrimination. However, these are not currently used by population screening programs. We performed an economic analysis to assess the cost-effectiveness, clinical outcomes, and resource impact of using risk-stratification based on phenotypic and genetic risk, taking a UK National Health Service perspective. Biennial fecal immunochemical test (FIT), starting at an age determined through risk-assessment at age 40, was compared with FIT screening starting at a fixed age for all individuals. Compared with inviting everyone from age 60, using a risk score with area under the receiver operating characteristic curve of 0.721 to determine FIT screening start age, produces 418 QALYs, costs £247,000, and results in 218 fewer colorectal cancer cases and 156 fewer colorectal cancer deaths per 100,000 people, with similar FIT screening invites. There is 96% probability that risk-stratification is cost-effective, with net monetary benefit (based on £20,000 per QALY threshold) estimated at £8.1 million per 100,000 people. The maximum that could be spent on risk-assessment and still be cost-effective is £114 per person. Lower benefits are produced with lower discrimination risk scores, lower mean screening start age, or higher FIT thresholds. Risk-stratified screening benefits men more than women. Using risk to determine FIT screening start age could improve the clinical outcomes and cost effectiveness of colorectal cancer screening without using significant additional screening resources. Prevention Relevance: Colorectal cancer screening is essential for early detection and prevention of colorectal cancer, but implementation is often limited by resource constraints. This work shows that risk-stratification using genetic and phenotypic risk could improve the effectiveness and cost-effectiveness of screening programs, without using substantially more screening resources than are currently available.

Background Increasing physical activity, improving diet, and performing brain training exercises are associated with reduced cognitive decline in older adults. Objective In this paper, we describe a feasibility trial of the Active Brains intervention, a web-based digital intervention developed to support older adults to make these 3 healthy behavior changes associated with improved cognitive health. The Active Brains trial is a randomized feasibility trial that will test how accessible, acceptable, and feasible the Active Brains intervention is and the effectiveness of the study procedures that we intend to use in the larger, main trial. Methods In the randomized controlled trial (RCT), we use a parallel design. We will be conducting the intervention with 2 populations recruited through GP practices (family practices) in England from 2018 to 2019: older adults with signs of cognitive decline and older adults without any cognitive decline. Trial participants were randomly allocated to 1 of 3 study groups: usual care, the Active Brains intervention, or the Active Brains website plus brief support from a trained coach (over the phone or by email). The main outcomes are performance on cognitive tasks, quality of life (using EuroQol-5D 5 level), Instrumental Activities of Daily Living, and diagnoses of dementia. Secondary outcomes (including depression, enablement, and health care costs) and process measures (including qualitative interviews with participants and supporters) will also be collected. The trial has been approved by the National Health Service Research Ethics Committee (reference 17/SC/0463). Results Results will be published in peer-reviewed journals, presented at conferences, and shared at public engagement events. Data collection was completed in May 2020, and the results will be reported in 2021. Conclusions The findings of this study will help us to identify and make important changes to the website, the support received, or the study procedures before we progress to our main randomized phase III trial. Trial Registration International Standard Randomized Controlled Trial Number 23758980; http://www.isrctn.com/ISRCTN23758980 International Registered Report Identifier (IRRID) DERR1-10.2196/18929

AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial.METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis.RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)].CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.

Context Early detection of kidney cancer improves survival; however, low prevalence means that population-wide screening may be inefficient. Stratifying the population into risk categories could allow for the introduction of a screening program tailored to individuals. Objective This review will identify and compare published models that predict the risk of developing kidney cancer in the general population. Evidence Acquisition A search identified primary research reporting or validating models predicting the risk of kidney cancer in Medline and EMBASE. After screening identified studies for inclusion, we extracted data onto a standardised form. The risk models were classified using TRIPOD guidelines and evaluated using the PROBAST assessment tool. Evidence Synthesis The search identified 15,281 articles. Sixty-two satisfied the inclusion criteria; performance measures were provided for 11 models. Some models predicted the risk of prevalent undiagnosed disease and others future incident disease. Six of the models had been validated, two using external populations. The most commonly included risk factors were age, smoking status and BMI. Most of the models had acceptable-to-good discrimination (AUROC>0.7) in development and validation. Many also had high specificity; however, several had low sensitivity. The highest performance was seen for the models using only biomarkers to detect kidney cancer; however, these were developed and validated in small case-control studies. Conclusion We identified a small number of risk models that could be used to stratify the population according to risk of kidney cancer. Most exhibit reasonable discrimination but few have been externally validated in population-based studies. Patient Summary In this review, we looked at mathematical models predicting the likelihood of an individual developing kidney cancer. We found several suitable models, using a range of risk factors (such as age and smoking) to predict individual risk. Most of the models identified require further testing in the general population to confirm their usefulness.

BACKGROUND The efficacy of a highly tailored digital intervention to support medication adherence and feasibility to support clinical effectiveness as an adjunct to the primary care setting has not been evaluated. OBJECTIVE This trial aimed to assess the behavioral efficacy of a highly tailored digital intervention to support medication adherence and to evaluate the feasibility of its clinical effectiveness, in patients with either or both hypertension and type 2 diabetes. We also examined quality of life and mechanisms of behavior change. Intervention fidelity, engagement, and satisfaction were also explored. METHODS This was a multicenter, individually randomized controlled trial of 2 parallel groups: an intervention group that received a highly tailored text message and interactive voice response intervention for 12 weeks, and a control group that received usual care. Medication adherence was measured using self-reports and assessor-blinded practice records of a repeat prescription. Systolic blood pressure and glucose levels were assessed by nurses blinded to group allocation during practice visits at 3 months follow-up. Questionnaires obtained data to assess intervention mechanisms of action and satisfaction and digital log files captured data to evaluate fidelity and engagement. RESULTS A total of 135 nonadherent patients (62/135, 46% female; 122/135, 90.3%; aged above 50 years) were randomly allocated in the intervention (n=79) or in the control group (n=56); of whom 13% (18/135) were lost at follow-up. Medication adherence was significantly improved in the intervention group compared with the control group (t116=2.27; P=.02, 2-tailed). Systolic blood pressure was 0.6 mmHg (95% CI −7.423 to 6.301), and hemoglobin A1c was 4.5 mmol/mol (95% CI −13.099 to 4.710) lower in the intervention group compared with the control group. Changes in intentional nonadherence and nonintentional nonadherence explained the improvements in medication adherence in the intervention group (beta=.074, SE=0.464; P=.04), but not in the control group (beta=.00, SE 1.35; P=.37). The intervention had 100% fidelity, a median of 12 days of engagement, and 76% overall satisfaction. CONCLUSIONS Our trial is the first that has been conducted in the United Kingdom and showed that among nonadherent patients with either or both hypertension and type 2 diabetes, a highly tailored digital intervention was effective at improving treatment adherence and feasible to obtain clinically meaningful outcomes. Changes in intentional and nonintentional nonadherence predicted the improvements in medication adherence. The intervention had high fidelity, engagement, and satisfaction. Future research using a rigorous design is needed to evaluate the clinical effectiveness and cost-effectiveness of the intervention in primary care. CLINICALTRIAL International Standard Randomized Controlled Trial Number (ISRCTN) 10668149; http://www.controlled-trials.com/ISRCTN10668149.

Summary 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.

Summary Background & aims Associations of dietary sugars with metabolic and inflammatory markers may vary according to the source of the sugars. The aim of this study was to examine the association of dietary sugars from different sources [beverages (liquids), foods (solids), extrinsic (free) or intrinsic (non-free)] with metabolic and inflammatory markers. Methods Population-based cross-sectional study of adults in the East of England (n = 9678). Sugar intakes were estimated using food frequency questionnaires. Fasting glycated haemoglobin, glucose, insulin, and C-Reactive Protein (CRP) were measured and indices of metabolic risk were derived (homeostatic model of insulin resistance, HOMA-IR and metabolic risk z-score). Results In multiple linear regression analyses adjusted for potential confounders including BMI and TEI, sugars from liquids were positively associated with ln-CRP [b-coefficient (95%CI), 0.14 (0.05,0.22) per 10%TEI] and metabolic risk z-score [0.13 (0.07,0.18)]. Free sugars were positively associated with ln-HOMA-IR [0.05 (0.03,0.08)] and metabolic risk z-score [0.09 (0.06,0.12)]. Sugars from solids were not associated with any outcome. Among major dietary contributors to intakes (g/d), sugars in fruit, vegetables, dairy products/egg dishes, cakes/biscuits/confectionary and squash/juice drinks were not associated, but sugar added to tea, coffee, cereal was significantly positively associated with all outcomes. Sugars in 100% juice [0.16 (0.06,0.25) per 10%TEI] and other non-alcoholic beverages [0.13 (0.03,0.23)] were positively associated with metabolic risk z-score. Conclusion Higher intakes of sugars from non-alcoholic beverages and sugar added to tea, coffee, cereal were associated with glycaemia and inflammatory markers. Sugars from solids were not associated, irrespective of whether they were intrinsic or extrinsic. Positive associations of free sugars were largely explained by contribution of beverages to intake.

Objectives Many health promotion campaigns and interventions focussing on improving health-related behaviours have been based on targeting response efficacy. This is based on the assumption that response efficacy is an important modifiable determinant of behaviour change. This study aimed to quantify the association between response efficacy and objective and subjective measures of physical activity and diet. Study design Prospective cohort analysis of data from a randomised controlled trial. Methods A total of 953 participants were assessed for response efficacy at baseline and 12 weeks following randomisation to interventions to increase physical activity and improve diet. Subjective measures were collected via a self-report questionnaire that included two questions used to derive the Cambridge Index of physical activity and questions about daily or weekly fruit and vegetable, whole grain, meat and fish intake, based on the dietary guidelines to lower cardiovascular risk. Objective measures were quantified using accelerometers and plasma carotenoids. Results The mean change in response efficacy for physical activity was +0.5 (standard deviation [SD] 2.0) and for diet was +0.5 (SD 2.1).There were no clinically or statistically significant associations between baseline or change in response efficacy and objective and subjective measures of physical activity or objective measures of diet. There was a small statistically significant association between baseline response efficacy and change in self-reported wholegrain consumption, but this is unlikely to be clinically significant. Conclusions Response efficacy is not a fundamental determinant of diet and physical activity and should not be the main focus of interventions targeting these behaviours., Highlights • Response efficacy alone is not associated with change in physical activity or diet. • This was seen for both subjective and objective measures of physical activity and diet. • Targeting response efficacy alone is unlikely to achieve behaviour change.

Background: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. Methods: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. Results: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. Conclusions: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening.

This study aimed to assess the association between achievement, and within-person change in achievement, of lifestyle recommendations in middle-age and incidence of the most common potentially preventable cancers. We used data from 44,572 participants from the Swedish Västerbotten Intervention Programme who had attended at least two health checks 9–11 years apart. We assessed the association between the mean number of healthy lifestyle recommendations achieved (lifestyle score), and change in lifestyle score between the health checks, and risk of one or more of the eight most common potentially preventable cancers using Cox regression. Participants were followed-up for 11.0 (SD 4.9) years. A higher mean lifestyle score was associated with a lower hazard of cancer in men (HR 0.81 (95%CI 0.74–0.90) per unit increase) and women (HR 0.90 (0.84–0.96)). There was no evidence of a linear association between change in lifestyle score and risk (HR 0.93 (0.85–1.03) and HR 1.004 (0.94–1.07) per unit change for men and women respectively). When comparing those with an increase in lifestyle score of ≥2 with those who improved less or declined in achievement the HR was 0.74 (0.54–1.00) and 1.02 (0.84–1.24) for men and women respectively. These findings support the inclusion of lifestyle recommendations in cancer prevention guidelines. They further suggest that interventions to change health behaviours in middle-age may reduce risk of the most common preventable cancers in men, but this association was not observed in women. Strategies to encourage healthy lifestyles earlier in the life course may be more effective., Highlights • Meeting more lifestyle recommendations in middle-age reduces cancer incidence. • Each additional recommendation met is associated with a 10–19% decrease in rate. • Change in middle-age to achieve ≥2 more recommendations may reduce cancer rate in men. • Up to 23% of chosen cancers might be prevented if all men achieved ≥2 more recommendations. • Change in middle-age is not associated with incident cancer in women.

Background The NHS Health Check programme is a prevention initiative offering cardiovascular risk assessment and management advice to adults aged 40–74 years across England. Its effectiveness depends on uptake. When it was introduced in 2009, it was anticipated that all those eligible would be invited over a 5-year cycle and 75% of those invited would attend. So far in the current cycle from 2013 to 2018, 33.8% of those eligible have attended, which is equal to 48.5% of those invited to attend. Understanding the reasons why some people do not attend is important to maximise the impact of the programmes. Aim To review why people do not attend NHS Health Checks. Design and setting A systematic review and thematic synthesis of qualitative studies. Method An electronic literature search was carried out of MEDLINE, Embase, Health Management Information Consortium, Cumulative Index to Nursing and Allied Health Literature, Global Health, PsycINFO, Web of Science, OpenGrey, the Cochrane Library, NHS Evidence, Google Scholar, Google, ClinicalTrials.gov, and the ISRCTN registry from 1 January 1996 to 9 November 2016, and the reference lists of all included papers were also screened manually. Inclusion criteria were primary research studies that reported the views of people who were eligible for but had not attended an NHS Health Check. Results Nine studies met the inclusion criteria. Reasons for not attending included lack of awareness or knowledge, misunderstanding the purpose of the NHS Health Check, aversion to preventive medicine, time constraints, difficulties with access to general practices, and doubts regarding pharmacies as appropriate settings. Conclusion The findings particularly highlight the need for improved communication and publicity around the purpose of the NHS Health Check programme and the personal health benefits of risk factor detection., This work was funded by a grant from Public Health England. Juliet A Usher-Smith was funded by a National Institute for Health Research (NIHR) Clinical Lectureship and Fiona M Walter by an NIHR Clinician Scientist award (RG 68235). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. All researchers were independent of the funding body and the funder had no role in data collection, analysis and interpretation of data; in the writing of the report; or decision to submit the article for publication.

ObjectiveWe 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.DesignCross-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).SettingRecruitment from general practice surgeries to participate in the ongoing population-based Fenland Study.SubjectsAdults (n 9991) aged 30–64 years from three areas of Cambridgeshire, UK.ResultsPrevalence 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 (PConclusionsFrequent consumers of SSB and ASB differ by several sociodemographic characteristics. However, increased BMI, younger age and unhealthy eating behaviours are common to both groups.

Maintaining physical activity in later life is important for maintaining health and function. Activity outdoors, such as walking, jogging and cycling, may provide an accessible, sociable and practical solution, but maintaining outdoor mobility may be a challenge in later life. Providing green environments which are supportive of physical activity may facilitate this, yet research into how greenspace could be best used is inconclusive. This study evaluates the role of greenspace in protecting against decline in physical activity over time in older adults.Data from the European Prospective Investigation of Cancer Norfolk, UK, cohort 1993–2009 (N=15,672) was used. Linear regression modelling was used to examine the association between exposure to greenspace in the home neighbourhood and change in overall, recreational and outdoor physical activity measured in terms of metabolic equivalent cost (MET) in hours/week. Mediation analysis was conducted to assess if dog walking explained the relationship between greenspace and physical activity change. Models were adjusted for known and hypothesised confounders.People living in greener neighbourhoods experienced less of a decline in physical activity than those living in less green areas. Comparing change for those living in the greenest versus least green quartiles, participants showed a difference in overall physical activity of 4.21 MET hours/week (trend P=0.001), adjusted for baseline physical activity, age, sex, BMI, social class and marital status. This difference was 4.03 MET hours/week for recreational physical activity (trend P

Appetitive traits influence food intake and weight gain throughout the life-course. Here, we investigated whether maternal attitudes to following healthy infant feeding guidelines could modify this association. Baseline data from 544 mother-infant formula-feeding dyads recruited to the Baby Milk Trial were included in this observational, cross-sectional analysis. Infant appetitive traits (food responsiveness and satiety responsiveness), maternal attitudes to following healthy infant feeding guidelines (self-efficacy, outcome-expectancy, intentions) and infant milk intakes were reported by mothers through questionnaires. Infant weight was measured using standard procedures. Associations between the maternal attitudes score or infant appetitive traits with infant milk intake and infant weight were evaluated in linear regression models adjusted for infant sex and age. To identify effect modification, the interaction term between the maternal attitudes score and infant appetitive trait was added to the model. Infants’ mean age and weight were 2.3 months (SD = 0.9) and 5.5 kg (SD = 0.9), respectively. The mean daily infant milk intake reported by mothers was 895 ml/day (SD = 215). Higher maternal attitudes score was associated with lower infant milk intake (Beta = −68.4 ml/day/unit (95% CI: 96.6, −40.2)) and infant weight (Beta = −0.13 SD/unit (−0.25, −0.02)). The maternal attitudes score showed interactions with infant food responsiveness on infant milk intake (p = 0.049), and with infant satiety responsiveness on infant weight (p = 0.01). In both cases, a higher maternal attitudes score attenuated the associations between infant appetitive traits and those outcomes. This analysis provides evidence that positive maternal attitudes to following healthy infant feeding guidelines attenuate the effects of infant appetitive traits on infant milk intake and body weight.

When looking for an answer to a question, in most cases, hundreds, if not thousands of research papers have been published in that area. A systematic review attempts ‘to collate all empirical evidence that fits pre-specified eligibility criteria in order to answer a specific research question. It uses explicit, systematic methods that are selected with a view of minimizing bias, thus providing more reliable findings from which conclusions can be drawn and decisions made’ (Antman, Lau, Kupelnick, Mosteller, Chalmers 1992; Oxman and Guyatt 1993). As systematic reviews aim to collate all of the relevant information (Higgins and Green, 2011), clinicians or researchers can be confident that most of, it not all, the relevant papers have been considered. Systematic reviews are the most highly regarded research evidence (Murad, Asi, Alsawas and Alahdab, 2016) and therefore used to inform guidelines, summarise existing evidence and provide appropriate justification for commencing a randomised controlled trial.

Objective: To determine whether provision of web-based lifestyle advice and coronary heart disease risk information either based on phenotypic characteristics or phenotypic plus genetic characteristics affects changes in objectively measured health behaviours. Methods: A parallel-group, open randomised trial including 956 male and female blood donors with no previous history of cardiovascular disease (mean [SD] age = 56.7 [8.8] years) randomised to four study groups: control group (no information provided); web-based lifestyle advice only (lifestyle group); lifestyle advice plus information on estimated 10-year coronary heart disease risk based on phenotypic characteristics (phenotypic risk estimate) (phenotypic group); and lifestyle advice plus information on estimated 10-year coronary heart disease risk based on phenotypic (phenotypic risk estimate) and genetic characteristics (genetic risk estimate) (genetic group). The primary outcome was change in physical activity from baseline to 12 weeks assessed by wrist-worn accelerometer. Results: 928 (97.1%) participants completed the trial. There was no evidence of intervention effects on physical activity (difference in adjusted mean change from baseline): lifestyle group vs control group 0.09 milligravity (mg) (95%CI: -1.15 to 1.33); genetic group vs phenotypic group -0.33 mg (-1.55 to 0.90); phenotypic group and genetic group vs control group -0.52 mg (-1.59 to 0.55); and vs lifestyle group -0.61 mg (-1.67 to 0.46). There was no evidence of intervention effects on secondary biological, emotional and health-related behavioural outcomes except self-reported fruit and vegetable intake. Conclusions: Provision of risk information, whether based on phenotypic or genotypic characteristics, alongside web-based lifestyle advice did not importantly affect objectively measured levels of physical activity, other health-related behaviours, biological risk factors or emotional well-being. Clinical Trial Registration: Current Controlled Trials ISRCTN17721237. Prospectively registered 12 January 2015. http://www.isrctn.com/ISRCTN17721237. Key words: cardiovascular disease; genetics; primary prevention; risk assessment; risk reduction behaviour, This work was supported by a European Commission Framework 7 EPIC-CVD Grant agreement no: 279233. NHS Blood and Transplant funded the INTERVAL trial. DNA extraction and genotyping in INTERVAL/INFORM was funded by the National Institute for Health Research. The coordinating team for INTERVAL/INFORM at the Cardiovascular Epidemiology Unit of the University of Cambridge was supported by core funding from: UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence and UK National Institute for Health Research Cambridge Biomedical Research Centre. BS was supported by the Medical Research Council [MC_UU_12015/4].

Whilst frailty and ageing are inherently linked, we agree with O' Hanlon and Rechner that frailty is likely to be more useful for assessing perioperative risk in older people [1]. Physical inactivity is a defining feature of frailty, and a target of numerous frailty intervention studies [2]. Health benefits from a physically active lifestyle are well-documented; increased physical activity can delay the onset and slow the progression from a non-frail to frail state [3]. Furthermore, there is growing evidence of the association between physical activity and perioperative outcomes [4]. Such considerations have prompted the incorporation of promotion of activity into prehabilitation in this population. Whilst sustained change in habitual, environmentally-cued behaviours such as physical activity is notoriously difficult to achieve, it is plausible that the preoperative period may represent a “teachable moment” in which motivation may be elevated. However, the impact that increasing preoperative physical activity has on frail elderly patients, the optimal type, duration and intensity of physical activity for prehabilitation programmes and the mutable determinants of activity in this population are poorly understood. Consequently, parameters that are likely to be important in the design and evaluation of complex interventions targeting preoperative physical activity remain uncertain.

Context Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism. Objective To compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3. Methods We measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups. Results Vitamin D2 was less effective than vitamin D3 in elevating total serum 25(OH)D concentration. Vitamin D2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and mean ratios of 25(OH)D3 to D3 and 1α,25(OH)2D3 to 25(OH)D3, while increasing the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Vitamin D3 increased mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Participants receiving vitamin D2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D3 and 1α,25(OH)2D3 to 25(OH)D3 than those receiving vitamin D3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D3 and 4β,25(OH)2D3 to 25(OH)D3 did not differ between groups. Conclusions Bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration. Administration of vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, while increasing 24R-hydroxylation of 25(OH)D3., Data from this randomized controlled trial show that vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, and increases 24R-hydroxylation of 25(OH)D3.

Uncertainties remain about the overall effect of sit-stand desks for reducing prolonged sitting among office-based workers. This study assessed the feasibility of a randomised controlled trial of the impact of workplace sit-stand desks on overall energy expenditure, sitting time and cardio-metabolic outcomes. It involved four phases: Phase I: online survey; Phase II: workspace auditing; Phase III: randomised intervention (provision of sit-stand desks at work for 3 months); Phase IV: qualitative component. Participants were offıce-based employees of two companies in Cambridge, England. Among Phase I participants interested in the trial, 100 were randomised to Phase II. Of those with workspaces suitable for sit-stand desks, 20 were randomised to Phase III. Those allocated to the intervention completed Phase IV. Outcomes included: trial participation interest, desk-type (full desks/desk mounts) and assessment location (work/laboratory/home) preferences (Phase I); proportion of workspaces permitting sit-stand desk installation (Phase II); energy expenditure, sitting time and cardio-metabolic outcomes (Phase III); study participation experiences (Phase IV). Data were collected between May 2015 and December 2016. Recruitment and trial implementation were feasible: 92% of survey respondents expressed participation interest; 80% of workspaces could accommodate sit-stand desks; assessments were done in workplaces, preferred by 71%. Sit-stand desk provision reduced workplace sitting time by 94 min/day (95% CI 17.7–170.7). Their impact on energy expenditure and cardio-metabolic outcomes is unclear. The results confirm the feasibility of a trial assessing sit-stand desks' impact on energy expenditure, sitting time and cardio-metabolic outcomes, which should reduce uncertainty concerning the intervention's potential to reduce the health risks of prolonged sitting.Trial registration ISRCTN44827407. Keywords: Sit-stand desks, Standing desks, Height-adjustable desks, Sitting, Standing, Energy expenditure, Sedentary behaviour, Feasibility study

Aims To estimate development of type 2 diabetes (T2DM) in women with previous gestational diabetes (GDM) and investigate characteristics associated with higher diagnoses, building on previous meta-analyses and exploring heterogeneity. Methods Systematic literature review of studies published up to October 2019. We included studies reporting progression to T2DM ≥6 months after pregnancy, if diagnostic methods were reported and ≥50 women with GDM participated. We conducted random-effects meta-analyses and meta-regression of absolute and relative T2DM risk. PROSPERO ID: CRD42017080299. Results In 129 included studies, the percentage diagnosed with T2DM was 12% (95% confidence interval 8–16%) higher for each additional year after pregnancy, with a third developing diabetes within 15 years. Development was 18% (5–34%) higher per unit BMI at follow-up, and 57% (39–70%) lower in White European populations compared to others (adjusted for ethnicity and follow-up). Women with GDM had a relative risk of T2DM of 8.3 (6.5–10.6). 17.0% (15.1–19.0%) developed T2DM overall, although heterogeneity between studies was substantial (I2 99.3%), and remained high after accounting for various study-level characteristics. Conclusions Percentage developing T2DM after GDM is highly variable. These findings highlight the need for sustained follow-up after GDM through screening, and interventions to reduce modifiable risk factors.

BACKGROUND: Mechanisms linking changes to the environment with changes in physical activity are poorly understood. Insights into mechanisms of interventions can help strengthen causal attribution and improve understanding of divergent response patterns. We examined the causal pathways linking exposure to new transport infrastructure with changes in cycling to work. METHODS: We used baseline (2009) and follow-up (2012) data (N=469) from the Commuting and Health in Cambridge natural experimental study (Cambridge, UK). Exposure to new infrastructure in the form of the Cambridgeshire Guided Busway was defined using residential proximity. Mediators studied were changes in perceptions of the route to work, theory of planned behaviour constructs and self-reported use of the new infrastructure. Outcomes were modelled as an increase, decrease or no change in weekly cycle commuting time. We used regression analyses to identify combinations of mediators forming potential pathways between exposure and outcome. We then tested these pathways in a path model and stratified analyses by baseline level of active commuting. RESULTS: We identified changes in perceptions of the route to work, and use of the cycle path, as potential mediators. Of these potential mediators, only use of the path significantly explained (85%) the effect of the infrastructure in increasing cycling. Path use also explained a decrease in cycling among more active commuters. CONCLUSION: The findings strengthen the causal argument that changing the environment led to changes in health-related behaviour via use of the new infrastructure, but also show how some commuters may have spent less time cycling as a result.

OBJECTIVE: To identify the proportion of individuals with an accurate perception of their risk of type 2 diabetes (T2D) prior to, immediately after and eight weeks after receiving a personalised risk estimate. Additionally, we aimed to explore what factors are associated with underestimation and overestimation immediately post-intervention. METHODS: Cohort study based on the data collected in the Diabetes Risk Communication Trial. We included 379 participants (mean age 48.9 (SD 7.4) years; 55.1% women) who received a genotypic or phenotypic risk estimate for T2D. RESULTS: While only 1.3% of participants perceived their risk accurately at baseline, this increased to 24.7% immediately after receiving a risk estimate and then dropped to 7.3% at eight weeks. Those who overestimated their risk at baseline continued to overestimate it, whereas those who underestimated their risk at baseline improved their risk accuracy. We did not identify any other characteristics associated with underestimation or overestimation immediately after receiving a risk estimate. CONCLUSION: Understanding a received risk estimate is challenging for most participants with many continuing to have inaccurate risk perception after receiving the estimate. PRACTICE IMPLICATIONS: Individuals who overestimate or underestimate their T2D risk before receiving risk information might require different approaches for altering their risk perception.