Cost-effectiveness analysis of two interventions to promote physical activity in a multiethnic population at high risk of diabetes: an economic evaluation of the 48-month PROPELS randomized controlled trial.

INTRODUCTION: Physical activity (PA) is protective against type 2 diabetes (T2D). However, data on pragmatic long-term interventions to reduce the risk of developing T2D via increased PA are lacking. This study investigated the cost-effectiveness of a pragmatic PA intervention in a multiethnic population at high risk of T2D. MATERIALS AND METHODS: We adapted the School for Public Health Research diabetes prevention model, using the PROPELS trial data and analyses of the NAVIGATOR trial. Lifetime costs, lifetime quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each intervention (Walking Away (WA) and Walking Away Plus (WA+)) versus usual care and compared with National Institute for Health and Care Excellence's willingness-to-pay of £20 000-£30 000 per QALY gained. We conducted scenario analyses on the outcomes of the PROPELS trial data and a threshold analysis to determine the change in step count that would be needed for the interventions to be cost-effective. RESULTS: Estimated lifetime costs for usual care, WA, and WA+ were £22 598, £23 018, and £22 945, respectively. Estimated QALYs were 9.323, 9.312, and 9.330, respectively. WA+ was estimated to be more effective and cheaper than WA. WA+ had an ICER of £49 273 per QALY gained versus usual care. In none of our scenario analyses did either WA or WA+ have an ICER below £20 000 per QALY gained. Our threshold analysis suggested that a PA intervention costing the same as WA+ would have an ICER below £20 000/QALY if it were to achieve an increase in step count of 500 steps per day which was 100% maintained at 4 years. CONCLUSIONS: We found that neither WA nor WA+ was cost-effective at a limit of £20 000 per QALY gained. Our threshold analysis showed that interventions to increase step count can be cost-effective at this limit if they achieve greater long-term maintenance of effect. TRIAL REGISTRATION NUMBER: ISRCTN registration: ISRCTN83465245: The PRomotion Of Physical activity through structuredEducation with differing Levels of ongoing Support for those with pre-diabetes (PROPELS)https://doi.org/10.1186/ISRCTN83465245.

Are there inequalities in the attendance and effectiveness of behavioural weight management interventions for adults in the UK? Protocol for an individual participant data (IPD) meta-analysis.

INTRODUCTION: It is important to identify whether behavioural weight management interventions work well across different groups in the population so health inequalities in obesity are not widened. Previous systematic reviews of inequalities in the attendance and effectiveness of behavioural weight management interventions have been limited because few trials report relevant analyses and heterogeneity in the categorisation of inequality characteristics prevents meta-analysis. An individual participant data meta-analysis (IPD-MA) allows us to reanalyse all trials with available data in a uniform way. We aim to conduct an IPD meta-analysis of UK randomised controlled trials to examine whether there are inequalities in the attendance and effectiveness of behavioural weight interventions. METHODS AND ANALYSIS: In a recently published systematic review, we identified 17 UK-based randomised controlled trials of primary care-relevant behavioural interventions, conducted in adults living with overweight or obesity and reporting weight outcomes at baseline and 1-year follow-up. The corresponding author of each trial will be invited to contribute data to the IPD-MA. The outcomes of interest are weight at 12-months and intervention attendance (number of sessions offered vs number of sessions attended). We will primarily consider whether there is an interaction between intervention group and characteristics where inequalities occur, such as by gender/sex, socioeconomic status or age. The IPD-MA will be conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses of IPD guidelines. ETHICS AND DISSEMINATION: No further ethical approval was required as ethical approval for each individual study was obtained by the original trial investigators from appropriate ethics committees. The completed IPD-MA will be disseminated at conferences, in a peer-reviewed journal and contribute to the lead author's PhD thesis. Investigators of each individual study included in the final IPD-MA will be invited to collaborate on any publications that arise from the project.

Association between Indicators of Inequality and Weight Change following a Behavioural Weight Loss Intervention.

INTRODUCTION: Weight loss through behavioural weight management interventions can have important health benefits for people with obesity. However, to maximise the health benefits, weight loss must be maintained. Evidence suggests that behavioural weight loss interventions do not exacerbate inequalities in the short term. However, no study has yet considered whether inequalities exist in long-term weight change following intervention. We aimed to investigate if there are inequalities in weight change following weight loss intervention. METHODS: We conducted a cohort analysis of data from the Weight Loss Referrals for Adults in Primary Care (WRAP) trial (N = 1,267). WRAP randomised participants to receive a brief intervention information booklet or vouchers for 12-weeks or 52-weeks of WW (formerly WeightWatchers) and followed them for 5 years. Multiple linear regression estimated the association between exposures (indicators of inequality) and outcomes (change in weight between 1- and 5-years). Each model was adjusted for the intervention group, baseline weight, weight change between baseline and 1-year, research centre, and source of the 5-year weight data. RESULTS: Of the 1,267 participants in WRAP, 708 had weight change data available. Mean weight change between 1- and 5-years was +3.30 kg (SD 9.10 kg). A 1 year difference in age at baseline was associated with weight change of 0.11 kg ((95% CI 0.06, 0.16), p < 0.001). We did not find evidence of associations between ethnicity, gender, education, indices of multiple deprivation, household income, or other family members participating in a weight loss programme and weight change. CONCLUSION: Except for age, we did not find evidence of inequalities in weight change following a behavioural intervention. Findings further support the use of behavioural weight management interventions as part of a systems-wide approach to improving population health.

Effectiveness and cost-effectiveness of referral to a commercial open group behavioural weight management programme in adults with overweight and obesity: 5-year follow-up of the WRAP randomised controlled trial.

BACKGROUND: There is evidence that commercially available behavioural weight management programmes can lead to short-term weight loss and reductions in glycaemia. Here, we aimed to provide the 5-year impact and cost-effectiveness of these interventions compared with a brief intervention. METHODS: WRAP was a non-blinded, parallel-group randomised controlled trial (RCT). We recruited from primary care practices in England and randomly assigned participants to one of three interventions (brief intervention, 12-week open-group behavioural programme [WW, formerly Weight Watchers], or a 52-week open-group WW behavioural programme) in an uneven (2:5:5) allocation. Participants were followed up 5 years after randomisation using data from measurement visits at primary care practices or a research centre, review of primary care electronic medical notes, and self-report questionnaires. The primary outcome was change in weight at 5 years follow-up, assessed using analysis of covariance. We also estimated cost-effectiveness of the intervention. This study is registered at Current Controlled Trials, ISRCTN64986150. FINDINGS: Between Oct 18, 2012, and Feb 10, 2014, we recruited 1269 eligible participants (two participants were randomly assigned but not eligible and therefore excluded) and 1040 (82%) consented to be approached about additional follow-up and to have their medical notes reviewed at 5 years. The primary outcome (weight) was ascertained for 871 (69%) of 1267 eligible participants. Mean duration of follow-up was 5·1 (SD 0·3) years. Mean weight change from baseline to 5 years was -0·46 (SD 8·31) kg in the brief intervention group, -1·95 (9·55) kg in the 12-week programme group, and -2·67 (9·81) kg in the 52-week programme. The adjusted difference in weight change was -1·76 (95% CI -3·68 to 0·17) kg between the 52-week programme and the brief intervention; -0·80 (-2·13 to 0·54) kg between the 52-week and the 12-week programme; and -0·96 (-2·90 to 0·97) kg between the 12-week programme and the brief intervention. During the trial, the 12-week programme incurred the lowest cost and produced the highest quality-adjusted life-years (QALY). Simulations beyond 5 years suggested that the 52-week programme would deliver the highest QALYs at the lowest cost and would be the most cost-effective. No participants reported adverse events related to the intervention. INTERPRETATION: Although the difference in weight change between groups was not statistically significant, some weight loss was maintained at 5 years after an open-group behavioural weight management programme. Health economic modelling suggests that this could have important implications to reduce the incidence of weight-related disease and these interventions might be cost-saving. FUNDING: The UK National Institute for Health and Care Research Programme Grants for Applied Research and the Medical Research Council.

A systematic review of inequalities in the uptake of, adherence to, and effectiveness of behavioral weight management interventions in adults.

The extent to which behavioral weight management interventions affect health inequalities is uncertain, as is whether trials of these interventions directly consider inequalities. We conducted a systematic review, synthesizing evidence on how different aspects of inequality impact uptake, adherence, and effectiveness in trials of behavioral weight management interventions. We included (cluster-) randomized controlled trials of primary care-applicable behavioral weight management interventions in adults with overweight or obesity published prior to March 2020. Data about trial uptake, intervention adherence, attrition, and weight change by PROGRESS-Plus criteria (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) were extracted. Data were synthesized narratively and summarized in harvest plots. We identified 91 behavioral weight loss interventions and 12 behavioral weight loss maintenance interventions. Fifty-six of the 103 trials considered inequalities in relation to at least one of intervention or trial uptake (n = 15), intervention adherence (n = 15), trial attrition (n = 32), or weight outcome (n = 34). Most trials found no inequalities gradient. If a gradient was observed for trial uptake, intervention adherence, and trial attrition, those considered "more advantaged" did best. Alternative methods of data synthesis that enable data to be pooled and increase statistical power may enhance understanding of inequalities in behavioral weight management interventions.

Cluster randomised controlled trial of screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the pilot study for the SAFER trial.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures. METHODS AND ANALYSIS: SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective. ETHICS AND DISSEMINATION: The London-Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

The impact of participant mental health on attendance and engagement in a trial of behavioural weight management programmes: secondary analysis of the WRAP randomised controlled trial.

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.

Should colorectal cancer screening start at different ages for men and women? Cost-effectiveness analysis for a resource-constrained service.

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 modeling 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 Fecal Immunochemical Test (FIT) threshold of 120 µg/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 = £1392), and to reduce CRC cases and mortality by 25 and 19 per 100 000 people respectively, while 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 impact of information about different absolute benefits and harms on intention to participate in colorectal cancer screening: A think-aloud study and online randomised experiment.

BACKGROUND: There is considerable heterogeneity in individuals' risk of disease and thus the absolute benefits and harms of population-wide screening programmes. Using colorectal cancer (CRC) screening as an exemplar, we explored how people make decisions about screening when presented with information about absolute benefits and harms, and how those preferences vary with baseline risk, between screening tests and between individuals. METHOD: We conducted two linked studies with members of the public: a think-aloud study exploring decision making in-depth and an online randomised experiment quantifying preferences. In both, participants completed a web-based survey including information about three screening tests (colonoscopy, sigmoidoscopy, and faecal immunochemical testing) and then up to nine scenarios comparing screening to no screening for three levels of baseline risk (1%, 3% and 5% over 15 years) and the three screening tests. Participants reported, after each scenario, whether they would opt for screening (yes/no). RESULTS: Of the 20 participants in the think-aloud study 13 did not consider absolute benefits or harms when making decisions concerning CRC screening. In the online experiment (n = 978), 60% expressed intention to attend at 1% risk of CRC, 70% at 3% and 77% at 5%, with no differences between screening tests. At an individual level, 535 (54.7%) would attend at all three risk levels and 178 (18.2%) at none. The 27% whose intention varied by baseline risk were more likely to be younger, without a family history of CRC, and without a prior history of screening. CONCLUSIONS: Most people in our population were not influenced by the range of absolute benefits and harms associated with CRC screening presented. For an appreciable minority, however, magnitude of benefit was important.

Incorporating a brief intervention for personalised cancer risk assessment to promote behaviour change into primary care: a multi-methods pilot study.

BACKGROUND: Approximately 40% of cancers could be prevented if people lived healthier lifestyles. We have developed a theory-based brief intervention to share personalised cancer risk information and promote behaviour change within primary care. This study aimed to assess the feasibility and acceptability of incorporating this intervention into primary care consultations. METHOD: Patients eligible for an NHS Health Check or annual chronic disease review at five general practices were invited to participate in a non-randomised pilot study. In addition to the NHS Health Check or chronic disease review, those receiving the intervention were provided with their estimated risk of developing the most common preventable cancers alongside tailored behaviour change advice. Patients completed online questionnaires at baseline, immediately post-consultation and at 3-month follow-up. Consultations were audio/video recorded. Patients (n = 12) and healthcare professionals (HCPs) (n = 7) participated in post-intervention qualitative interviews that were analysed using thematic analysis. RESULTS: 62 patients took part. Thirty-four attended for an NHS Health Check plus the intervention; 7 for a standard NHS Health Check; 16 for a chronic disease review plus the intervention; and 5 for a standard chronic disease review. The mean time for delivery of the intervention was 9.6 min (SD 3) within NHS Health Checks and 9 min (SD 4) within chronic disease reviews. Fidelity of delivery of the intervention was high. Data from the questionnaires demonstrates potential improvements in health-related behaviours following the intervention. Patients receiving the intervention found the cancer risk information and lifestyle advice understandable, useful and motivating. HCPs felt that the intervention fitted well within NHS Health Checks and facilitated conversations around behaviour change. Integrating the intervention within chronic disease reviews was more challenging. CONCLUSIONS: Incorporating a risk-based intervention to promote behaviour change for cancer prevention into primary care consultations is feasible and acceptable to both patients and HCPs. A randomised trial is now needed to assess the effect on health behaviours. When designing that trial, and other prevention activities within primary care, it is necessary to consider challenges around patient recruitment, the HCP contact time needed for delivery of interventions, and how best to integrate discussions about disease risk within routine care.

Inequalities in the uptake of, adherence to and effectiveness of behavioural weight management interventions: systematic review protocol.

INTRODUCTION: It has been suggested that interventions focusing on individual behaviour change, such as behavioural weight management interventions, may exacerbate health inequalities. These intervention-generated inequalities may occur at different stages, including intervention uptake, adherence and effectiveness. We will synthesise evidence on how different measures of inequality moderate the uptake, adherence and effectiveness of behavioural weight management interventions in adults. METHODS AND ANALYSIS: We will update a previous systematic literature review from the United States Preventive Services Taskforce to identify trials of behavioural weight management interventions in adults aged 18 years and over that were, or could feasibly be, conducted in or recruited from primary care. Medline, Cochrane database (CENTRAL) and PsycINFO will be searched. Only randomised controlled trials (RCTs) and cluster-RCTs will be included. Two investigators will independently screen articles for eligibility and conduct risk of bias assessment. We will curate publication families for eligible trials. The PROGRESS-Plus acronym (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) will be used to consider a comprehensive range of health inequalities. Data on trial uptake, intervention adherence, weight change and PROGRESS-Plus-related data will be extracted. Data will be synthesised narratively. We will present a Harvest plot for each PROGRESS-Plus criterion and whether each trial found a negative, positive or no health inequality gradient. We will also identify potential sources of unpublished original research data on these factors which can be synthesised through a future individual participant data meta-analysis. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data are being collected. The completed systematic review will be disseminated in a peer-reviewed journal, at conferences, and contribute to the lead author's PhD thesis. Authors of trials included in the completed systematic review may be invited to collaborate on a future individual participant data meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42020173242.

Clinical and cost-effectiveness of a diabetes education and behavioural weight management programme versus a diabetes education programme in adults with a recent diagnosis of type 2 diabetes: study protocol for the Glucose Lowering through Weight management (GLoW) randomised controlled trial.

INTRODUCTION: People with type 2 diabetes (T2D) can improve glycaemic control or even achieve remission through weight loss and reduce their use of medication and risk of cardiovascular disease. The Glucose Lowering through Weight management (GLoW) trial will evaluate whether a tailored diabetes education and behavioural weight management programme (DEW) is more effective and cost-effective than a diabetes education (DE) programme in helping people with overweight or obesity and a recent diagnosis of T2D to lower their blood glucose, lose weight and improve other markers of cardiovascular risk. METHODS AND ANALYSIS: This study is a pragmatic, randomised, single-blind, parallel group, two-arm, superiority trial. We will recruit 576 adults with body mass index>25 kg/m2 and diagnosis of T2D in the past 3 years and randomise them to a tailored DEW or a DE programme. Participants will attend measurement appointments at a local general practitioner practice or research centre at baseline, 6 and 12 months. The primary outcome is 12-month change in glycated haemoglobin. The effect of the intervention on the primary outcome will be estimated and tested using a linear regression model (analysis of covariance) including randomisation group and adjusted for baseline value of the outcome and the randomisation stratifiers. Participants will be included in the group to which they were randomised, under the intention-to-treat principle. Secondary outcomes include 6-month and 12-month changes in body weight, body fat percentage, systolic and diastolic blood pressure and lipid profile; probability of achieving good glycaemic control; probability of achieving remission from diabetes; probability of losing 5% and 10% body weight and modelled cardiovascular risk (UKPDS). An intention-to-treat within-trial cost-effectiveness analysis will be conducted from NHS and societal perspectives using participant-level data. Qualitative interviews will be conducted with participants to understand why and how the programme achieved its results and how participants manage their weight after the programme ends. ETHICS AND DISSEMINATION: Ethical approval was received from East of Scotland Research Ethics Service on 15 May 2018 (18/ES/0048). This protocol (V.3) was approved on 19 June 2019. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. TRIAL REGISTRATION NUMBER: ISRCTN18399564.

Evaluation of a very brief pedometer-based physical activity intervention delivered in NHS Health Checks in England: The VBI randomised controlled trial.

BACKGROUND: The majority of people do not achieve recommended levels of physical activity. There is a need for effective, scalable interventions to promote activity. Self-monitoring by pedometer is a potentially suitable strategy. We assessed the effectiveness and cost-effectiveness of a very brief (5-minute) pedometer-based intervention ('Step It Up') delivered as part of National Health Service (NHS) Health Checks in primary care. METHODS AND FINDINGS: The Very Brief Intervention (VBI) Trial was a two parallel-group, randomised controlled trial (RCT) with 3-month follow-up, conducted in 23 primary care practices in the East of England. Participants were 1,007 healthy adults aged 40 to 74 years eligible for an NHS Health Check. They were randomly allocated (1:1) using a web-based tool between October 1, 2014, and December 31, 2015, to either intervention (505) or control group (502), stratified by primary care practice. Participants were aware of study group allocation. Control participants received the NHS Health Check only. Intervention participants additionally received Step It Up: a 5-minute face-to-face discussion, written materials, pedometer, and step chart. The primary outcome was accelerometer-based physical activity volume at 3-month follow-up adjusted for sex, 5-year age group, and general practice. Secondary outcomes included time spent in different intensities of physical activity, self-reported physical activity, and economic measures. We conducted an in-depth fidelity assessment on a subsample of Health Check consultations. Participants' mean age was 56 years, two-thirds were female, they were predominantly white, and two-thirds were in paid employment. The primary outcome was available in 859 (85.3%) participants. There was no significant between-group difference in activity volume at 3 months (adjusted intervention effect 8.8 counts per minute [cpm]; 95% CI -18.7 to 36.3; p = 0.53). We found no significant between-group differences in the secondary outcomes of step counts per day, time spent in moderate or vigorous activity, time spent in vigorous activity, and time spent in moderate-intensity activity (accelerometer-derived variables); as well as in total physical activity, home-based activity, work-based activity, leisure-based activity, commuting physical activity, and screen or TV time (self-reported physical activity variables). Of the 505 intervention participants, 491 (97%) received the Step it Up intervention. Analysis of 37 intervention consultations showed that 60% of Step it Up components were delivered faithfully. The intervention cost £18.04 per participant. Incremental cost to the NHS per 1,000-step increase per day was £96 and to society was £239. Adverse events were reported by 5 intervention participants (of which 2 were serious) and 5 control participants (of which 2 were serious). The study's limitations include a participation rate of 16% and low return of audiotapes by practices for fidelity assessment. CONCLUSIONS: In this large well-conducted trial, we found no evidence of effect of a plausible very brief pedometer intervention embedded in NHS Health Checks on objectively measured activity at 3-month follow-up. TRIAL REGISTRATION: Current Controlled Trials (ISRCTN72691150).

Development and usability testing of a very brief intervention for personalised cancer risk assessment to promote behaviour change in primary care using normalisation process theory.

BACKGROUND: Cancer is the second leading cause of death worldwide. Lifestyle choices play an important role in the aetiology of cancer with up to 4 in 10 cases potentially preventable. Interventions delivered by healthcare professionals (HCPs) that incorporate risk information have the potential to promote behaviour change. Our aim was to develop a very brief intervention incorporating cancer risk, which could be implemented within primary care. METHODS: Guided by normalisation process theory (NPT), we developed a prototype intervention using literature reviews, consultation with patient and public representatives and pilot work with patients and HCPs. We conducted focus groups and interviews with 65 HCPs involved in delivering prevention activities. Findings were used to refine the intervention before 22 HCPs completed an online usability test and provided further feedback via a questionnaire incorporating a modified version of the NoMAD checklist. RESULTS: The intervention included a website where individuals could provide information on lifestyle risk factors view their estimated 10-year risk of developing one or more of the five most common preventable cancers and access lifestyle advice incorporating behaviour change techniques. Changes incorporated from feedback from the focus groups and interviews included signposting to local services and websites, simplified wording and labelling of risk information. In the usability testing, all participants felt it would be easy to collect the risk information. Ninety-one percent felt the intervention would enable discussion about cancer risk and believed it had potential to be easily integrated into National Health Service (NHS) Health Checks. However, only 36% agreed it could be delivered within 5 min. CONCLUSIONS: With the use of NPT, we developed a very brief intervention that is acceptable to HCPs in primary care and could be potentially integrated into NHS Health Checks. However, further work is needed to assess its feasibility and potential effectiveness.

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

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

Impact of sit-stand desks at work on energy expenditure, sitting time and cardio-metabolic risk factors: Multiphase feasibility study with randomised controlled component.

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 office-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.

Delivery and impact of the NHS Health Check in the first 8 years: a systematic review.

BACKGROUND: Since 2009, all eligible persons in England have been entitled to an NHS Health Check. Uncertainty remains about who attends, and the health-related impacts. AIM: To review quantitative evidence on coverage (the proportion of eligible individuals who attend), uptake (proportion of invitees who attend), and impact of NHS Health Checks. DESIGN AND SETTING: A systematic review and quantitative data synthesis. Included were studies or data reporting coverage or uptake and studies reporting any health-related impact that used an appropriate comparison group or before- and-after study design. METHOD: Eleven databases and additional internet sources were searched to November 2016. RESULTS: Twenty-six observational studies and one additional dataset were included. Since 2013, 45.6% of eligible individuals have received a health check. Coverage is higher among older people, those with a family history of coronary heart disease, those living in the most deprived areas, and some ethnic minority groups. Just under half (48.2%) of those invited have taken up the invitation. Data on uptake and impact (especially regarding health-related behaviours) are limited. Uptake is higher in older people and females, but lower in those living in the most deprived areas. Attendance is associated with small increases in disease detection, decreases in modelled cardiovascular disease risk, and increased statin and antihypertensive prescribing. CONCLUSION: Published attendance, uptake, and prescribing rates are all lower than originally anticipated, and data on impact are limited, with very few studies reporting the effect of attendance on health-related behaviours. High-quality studies comparing matched attendees and non-attendees and health economic analyses are required.

Randomised controlled trial of a theory-based behavioural intervention to reduce formula milk intake.

OBJECTIVE: To assess the efficacy of a theory-based behavioural intervention to prevent rapid weight gain in formula milk-fed infants. DESIGN: In this single (assessor) blind, randomised controlled trial, 669 healthy full-term infants receiving formula milk within 14 weeks of birth were individually randomised to intervention (n=340) or attention-matched control (n=329) groups. The intervention aimed to reduce formula milk intakes, and promote responsive feeding and growth monitoring to prevent rapid weight gain (≥+0.67 SD scores (SDS)). It was delivered to mothers by trained facilitators up to infant age 6 months through three face-to-face contacts, two telephone contacts and written materials. RESULTS: Retention was 93% (622) at 6 months, 88% (586) at 12 months and 94% attended ≥4/5 sessions. The intervention strengthened maternal attitudes to following infant feeding recommendations, reduced reported milk intakes at ages 3 (-14%; intervention vs control infants), 4 (-12%), 5 (-9%) and 6 (-7%) months, slowed initial infant weight gain from baseline to 6 months (mean change 0.32 vs 0.42 SDS, baseline-adjusted difference (intervention vs control) -0.08 (95% CI -0.17 to -0.004) SDS), but had no effect on the primary outcome of weight gain to 12 months (baseline-adjusted difference -0.04 (-0.17, 0.10) SDS). By 12 months, 40.3% of infants in the intervention group and 45.9% in the control group showed rapid weight gain (OR 0.84, 95% CI 0.59 to 1.17). CONCLUSIONS: Despite reducing milk intakes and initial weight gain, the intervention did not alter the high prevalence of rapid weight gain to age 12 months suggesting the need for sustained intervention. TRIAL REGISTRATION NUMBER: ISRCTN20814693.

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

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

Effect of screening for type 2 diabetes on healthcare costs: a register-based study among 139,075 individuals diagnosed with diabetes in Denmark between 2001 and 2009.

AIMS/HYPOTHESIS: Trials have not demonstrated benefits to the population of screening for type 2 diabetes. However, there may be cost savings for those found to have diabetes. We therefore aimed to compare healthcare costs among individuals with incident type 2 diabetes in a screened group with those in an unscreened group. METHODS: In this register-based, non-randomised controlled trial, eligible individuals were men and women aged 40-69 years without known diabetes who were registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk-score questionnaire. Individuals with a moderate-to-high risk were invited to visit their family doctor for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other practices in Denmark constituted the retrospectively constructed no-screening (control) group. In this post hoc analysis, we identified individuals from the screening and no-screening groups who were diagnosed with diabetes between 2001 and 2009 (n = 139,075). Using national registry data, we quantified the cost of healthcare services in these two groups between 2001 and 2012. From a healthcare sector perspective, we estimated the potential healthcare cost savings for individuals with diabetes that were attributable to the screening programme. RESULTS: In the screening group, 27,177 of 153,107 individuals (18% of those sent a risk-score questionnaire) attended for screening, 1533 of whom were diagnosed with diabetes. Between 2001 and 2009, 13,992 people were newly diagnosed with diabetes in the screening group (including those diagnosed by screening) and 125,083 in the no-screening group. Healthcare costs were significantly lower in the screening group compared with the no-screening group (difference in mean total annual healthcare costs -€889 per individual with incident diabetes; 95% CI -€1196, -€581). The screening programme was associated with a cost saving per person with incident diabetes over a 5-year period of €2688 (95% CI €1421, €3995). CONCLUSIONS/INTERPRETATION: Healthcare costs were lower among individuals with incident type 2 diabetes in the screened group compared with the unscreened group. The relatively modest cost of screening per person discovered to have developed diabetes was offset within 2 years by savings in the healthcare system.