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.

Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans.

Background: South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. Objectives: The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D. Methods: Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Results: Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Conclusions: Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity. Trail registration: NCT02590822.

Inequalities in cancer mortality trends in people with type 2 diabetes: 20 year population-based study in England.

AIMS/HYPOTHESIS: The aim of this study was to describe the long-term trends in cancer mortality rates in people with type 2 diabetes based on subgroups defined by sociodemographic characteristics and risk factors. METHODS: We defined a cohort of individuals aged ≥35 years who had newly diagnosed type 2 diabetes in the Clinical Practice Research Datalink between 1 January 1998 and 30 November 2018. We assessed trends in all-cause, all-cancer and cancer-specific mortality rates by age, gender, ethnicity, socioeconomic status, obesity and smoking status. We used Poisson regression to calculate age- and calendar year-specific mortality rates and Joinpoint regression to assess trends for each outcome. We estimated standardised mortality ratios comparing mortality rates in people with type 2 diabetes with those in the general population. RESULTS: Among 137,804 individuals, during a median follow-up of 8.4 years, all-cause mortality rates decreased at all ages between 1998 and 2018; cancer mortality rates also decreased for 55- and 65-year-olds but increased for 75- and 85-year-olds, with average annual percentage changes (AAPCs) of -1.4% (95% CI -1.5, -1.3), -0.2% (-0.3, -0.1), 1.2% (0.8, 1.6) and 1.6% (1.5, 1.7), respectively. Higher AAPCs were observed in women than men (1.5% vs 0.5%), in the least deprived than the most deprived (1.5% vs 1.0%) and in people with morbid obesity than those with normal body weight (5.8% vs 0.7%), although all these stratified subgroups showed upward trends in cancer mortality rates. Increasing cancer mortality rates were also observed in people of White ethnicity and former/current smokers, but downward trends were observed in other ethnic groups and non-smokers. These results have led to persistent inequalities by gender and deprivation but widening disparities by smoking status. Constant upward trends in mortality rates were also observed for pancreatic, liver and lung cancer at all ages, colorectal cancer at most ages, breast cancer at younger ages, and prostate and endometrial cancer at older ages. Compared with the general population, people with type 2 diabetes had a more than 1.5-fold increased risk of colorectal, pancreatic, liver and endometrial cancer mortality during the whole study period. CONCLUSIONS/INTERPRETATION: In contrast to the declines in all-cause mortality rates at all ages, the cancer burden has increased in older people with type 2 diabetes, especially for colorectal, pancreatic, liver and endometrial cancer. Tailored cancer prevention and early detection strategies are needed to address persistent inequalities in the older population, the most deprived and smokers.

The Cost-Effectiveness of the SMART Work & Life Intervention for Reducing Sitting Time.

Sedentary behaviours continue to increase and are associated with heightened risks of morbidity and mortality. We assessed the cost-effectiveness of SMART Work & Life (SWAL), an intervention designed to reduce sitting time inside and outside of work, both with (SWAL-desk) and without (SWAL-only) a height-adjustable workstation compared to usual practice (control) for UK office workers. Health outcomes were assessed in quality-adjusted life-years (QALY) and costs in pound sterling (2019-2020). Discounted costs and QALYs were estimated using regression methods with multiply imputed data from the SMART Work & Life trial. Absenteeism, productivity and wellbeing measures were also evaluated. The average cost of SWAL-desk was £228.31 and SWAL-only £80.59 per office worker. Within the trial, SWAL-only was more effective and costly compared to control (incremental cost-effectiveness ratio (ICER): £12,091 per QALY) while SWAL-desk was dominated (least effective and most costly). However, over a lifetime horizon, both SWAL-only and SWAL-desk were more effective and more costly than control. Comparing SWAL-only to control generated an ICER of £4985 per QALY. SWAL-desk was more effective and costly than SWAL-only, generating an ICER of £13,378 per QALY. Findings were sensitive to various worker, intervention, and extrapolation-related factors. Based on a lifetime horizon, SWAL interventions appear cost-effective for office-workers conditional on worker characteristics, intervention cost and longer-term maintenance in sitting time reductions.

Estimates of years of life lost depended on the method used: tutorial and comparative investigation.

OBJECTIVES: This review aims to summarize key methods for estimating years of life lost (YLL), highlighting their differences and how they can be implemented in current software, and applies them in a real-world example. STUDY DESIGN AND SETTING: We investigated the common YLL methods: (1) Years of potential life lost (YPLL); (2) Global Burden of Disease (GBD) approach; (3) Life tables; (4) Poisson regression; and (5) Flexible parametric Royston-Parmar regression. We used data from UK Biobank and multimorbidity as our example. RESULTS: For the YPLL and GBD method, the analytical procedures allow only to quantify the average YLL within each group (with and without multimorbidity) and, from them, their difference; conversely, for the other methods both the remaining life expectancy within each group and the YLL could be estimated. At 65 years, the YLL in those with vs. without multimorbidity was 1.8, 1.2, and 2.7 years using the life tables approach and the Poisson, and Royston-Parmar regression, respectively; corresponding values were -0.73 and -0.05 years for YPLL and using the GBD approach. CONCLUSION: While deciding among different methods to estimate YLL, researchers should consider the purpose of the research, the type of available data, and the flexibility of the model.

Rates and estimated cost of primary care consultations in people diagnosed with type 2 diabetes and comorbidities: A retrospective analysis of 8.9 million consultations.

AIMS: To determine whether telephone and face-to-face primary care consultation rates, costs, and temporal trends during 2000 to 2018 differed by the number of comorbidities in people with type 2 diabetes (T2DM). METHODS: A total of 120 409 adults with newly diagnosed T2DM between 2000 and 2018 were classified by the number of prevalent and incident comorbidities. Data on face-to-face and telephone primary care consultations with a nurse or physician were obtained. Crude and sex- and age-adjusted annual consultation rates and associated costs were calculated based on the number of comorbidities at the time of consultation. RESULTS: The crude rate of face-to-face primary care consultations for patients without comorbidities was 10.3 (95% confidence interval [CI] 10.3-10.4) per person-year, 12.7 (95% CI 12.7-12.7) for patients with one comorbidity, 15.1 (95% CI 15.1-15.2) for those with two comorbidities, and 18.7 (95% CI 18.7-18.8) for those with three or more comorbidities. The mean annual inflation-adjusted cost for face-to-face consultations was £412.70 per patient without comorbidities, £516.80 for one comorbidity, £620.75 for two comorbidities, and £778.83 for three or more comorbidities. The age- and sex-adjusted face-to-face consultation rate changed by an average of -3.3% (95% CI -4.4 to -2.3) per year from 2000 to 2018 for patients without comorbidities, -2.7% (95% CI -4.0 to -1.3) for those with one comorbidity, -2.2% (95% CI -3.3 to -1.2) for those with two comorbidities, and -4.3% (95% CI -8.7 to +0.3) for those with three or more comorbidities. CONCLUSIONS: Although consultation rates for all patients decreased from 2000 to 2018, there was a significant disparity between the rate for patients with and without comorbidities. Patients with T2DM and comorbidities may require different models of service delivery.

Cardiovascular events and mortality in people with and without type 2 diabetes: An observational study in a contemporary multi-ethnic population.

AIMS/INTRODUCTION: The aim of this study was to examine ethnicity-specific associations between type 2 diabetes mellitus and the risk of a cardiovascular disease (CVD) event as well as risk of specific CVD phenotypes in England. METHODS: We obtained data from the Clinical Practice Research Datalink for adults with and without type 2 diabetes mellitus diagnosed 2000-2006. The outcome was the first CVD event during 2007-2017 and the following components: aortic aneurysm, cerebrovascular accidents, heart failure, myocardial infarction, peripheral vascular disease and other CVD-related conditions. Flexible parametric survival models were used to estimate ethnicity-specific adjusted hazard ratios. RESULTS: A total of 734,543 people with and without type 2 diabetes mellitus (29,847; 4.1%) were included; most were of white ethnicity (93.0% with and 92.3% without type 2 diabetes mellitus) followed by South Asian (3.2 and 4.6%). During a median follow-up period of 11.0 years, 67,218 events occurred (6,156 in individuals with type 2 diabetes mellitus). Type 2 diabetes mellitus was associated with a small increase in CVD events (adjusted hazard ratio 1.06, 95% confidence interval 1.02-1.09) in individuals of white ethnicity; whereas the adjusted hazard ratios were considerably higher in individuals of South Asian ethnicity (1.28, 95% confidence interval 1.09-1.51), primarily due to an increased risk of myocardial infarction (1.53, 95% confidence interval 1.08-2.18). CONCLUSIONS: Despite universal access to healthcare, there are large disparities in CVD outcomes in people with and without type 2 diabetes mellitus. Other non-traditional risk factors might play a role in the higher CVD risk associated with type 2 diabetes mellitus in individuals of South Asian ethnicity.

A cost comparison of an enhanced primary care diabetes service and standard care.

BACKGROUND: Type 2 diabetes, which contributes 90% of all cases of diabetes mellitus is now mostly managed in the primary care settings in the UK and other advanced health care systems. The UK National Health Service as a whole could potentially benefit if more patients were managed in primary care settings since primary care-based care is likely to be more cost-effective. We initially compared eight larger general practices (Enhanced practices) in Leicester, UK with neighbouring smaller practices (Core practices) matched for comparable demographic characteristics. Even though this initial study did not find any statistically significant differences in terms of clinical outcomes there was trend in favour of the enhanced practices. In this current study, we conducted a cost comparison of enhanced practice model of diabetes care, to standard care delivered in the core practices. METHODS: Data and information were combined from a number of sources and a cost comparison evaluation was carried out in WinBUGs. A probabilistic approach was taken, to allow uncertainty to be included around analysis parameters where appropriate. The analysis evaluated a straight-forward cost comparison of enhanced versus standard care. RESULTS: The cost per person with diabetes per year was £255 (95% CrI 175, 380) in the core practices and £173 (95% CrI 96, 291) in the enhanced practices, resulting in an annual cost saving of -£83 (95% CrI -148, -28) per patient. If the enhanced model of diabetes care were delivered across all the practices in the UK, the cost would be £575,100,000 (95% CrI 320,700,000, 970,700,000), resulting in an annual cost saving of -276,200,000 (95% CrI -495,400,000, -94,480,000). CONCLUSION: A cost comparison analysis of our larger enhanced primary care based diabetes service confirms significant cost saving, probably driven by economies of scale. These benefits could be multiplied manifold if the service was implemented nationally.

Toe gaps and their assessment in footwear for people with diabetes: a narrative review.

BACKGROUND: Adequate footwear fit is critical in preventing diabetes-related foot ulcers. One important element is the toe gap, the difference between foot length and internal footwear length available to the foot. We summarised the literature on toe gaps in studies assessing footwear worn by people with diabetes, the methods used to measure both foot length and internal footwear length and identify ambiguities which may impact on toe gap assessment in clinical practice, and suggest pragmatic solutions. METHODS: The Google Scholar database was searched to April 2020 for peer-reviewed studies using keywords related to incorrectly fitting or ill-fitting and diabetes, foot and ulcer which returned 979 results. Included studies within this narrative review encompassed toe gap measurement to assess footwear worn by people with diabetes. RESULTS: A total of eight studies were included after full paper review. Toe gap ranges as used in assessments of footwear worn by people with diabetes vary, with a minimum of 1.0-1.6 cm and a maximum of 1.5-2.0 cm, as do methods of measuring internal footwear length. Only three published studies suggested possible measuring devices. CONCLUSIONS: Toe gap ranged as used when assessing footwear fit in people with diabetes vary and a gold standard device for internal footwear length measurement has yet to emerge. International guidelines provide welcome standardisation, but further research is needed to evaluate both the effect of toe gap ranges upon pressure, plantar stress response and ulceration and available measuring devices to facilitate development of toe gap measurement protocols that may further enhance consistency in practical assessments.

Reducing sitting at work: process evaluation of the SMArT Work (Stand More At Work) intervention.

BACKGROUND: Office-based workers accumulate high amounts of sitting time. Stand More At Work (SMArT Work) aimed to reduce occupational sitting time and a cluster randomised controlled trial demonstrated it was successful in achieving this aim. The purpose of this paper is to present the process evaluation of the SMArT Work intervention. METHODS: Questionnaire data were collected from intervention participants at 6 months (n = 58) and 12 months (n = 55). Questionnaires sought feedback on the different components of the intervention (education, height-adjustable desk, Darma cushion, behaviour feedback, progress chats (coaching) with research team, action planning/goal setting diary) and experiences of evaluation measures. Control participants (n = 37) were asked via questionnaire at 12-month follow-up about the impact of the study on their behaviour and any lifestyle changes made during the study. Participants from both arms were invited to focus groups to gain a deeper understanding of their experiences on completion of 12-month follow-up. RESULTS: Focus group and questionnaire data showed a positive attitude towards the height-adjustable workstation with a high proportion of participants using it every day (62%). Most participants (92%) felt the education seminar increased their awareness of the health consequences of too much sitting and motivated them to change their behaviour. Receiving feedback on their sitting time and support from the research team also encouraged behaviour change. The Darma cushion and action planning/goal setting diary were seen to be less helpful for behaviour change. Benefits experienced included fewer aches and pains, improved cognitive functioning, increased productivity, more energy and positive feelings about general health. CONCLUSIONS: Key elements of the programme identified as facilitating behaviour change were the educational seminar, the height-adjustable workstation, behavioural feedback and regular contact with research staff through regular progress chats. TRIAL REGISTRATION: ISRCTN: ISRCTN10967042. Registered on 2 February 2015.

A Cost and Cost-Benefit Analysis of the Stand More AT Work (SMArT Work) Intervention.

This study conducted a cost and cost-benefit analysis of the Stand More AT (SMArT) Work workplace intervention, designed to reduce sitting time. The study was a cluster two-armed randomised controlled trial involving 37 office clusters (146 desk-based workers) in a National Health Service Trust. The intervention group received a height-adjustable workstation with supporting behaviour change strategies. The control group continued with usual practice. Self-report absenteeism, presenteeism and work productivity were assessed at baseline, 3, 6 and 12 months; and organisational sickness absence records 12 months prior to, and 12 months of the intervention. Mean per employee costs associated with SMArT Work were calculated. Absenteeism, presenteeism and work productivity were estimated, and employer-recorded absence data and employee wage-banding were used to provide a human-capital-based estimate of costs to the organisation. The return-on-investment (ROI) and incremental cost-efficacy ratios (ICER) were calculated. Intervention cost was £692.40 per employee. Cost-benefit estimates show a net saving of £1770.32 (95%CI £-354.40, £3895.04) per employee as a result of productivity increase. There were no significant differences in absence data compared to the control group. SMArT Work provides supporting evidence for policy-makers and employers on the cost benefits of reducing sitting time at work.

Effectiveness and cost of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in obesity services (STRIVE study): study protocol of an open-label, real-world, randomised, controlled trial.

INTRODUCTION: In the UK and Ireland, severe and complex obesity is managed in specialist weight management services (SWMS), which provide multicomponent lifestyle interventions to support weight loss, and use of medication if available. Liraglutide 3 mg (LIRA 3 mg) is an effective weight-loss medication, but weight loss in individual patients is variable, and its efficacy has not been assessed in SWMS. This study aims to investigate whether a targeted prescribing pathway for LIRA 3 mg with multiple prespecified stopping rules could help people with severe obesity and established complications achieve ≥15% weight loss in order to determine whether this could be considered a clinically effective and cost-effective strategy for managing severe and complex obesity in SWMS. METHODS AND ANALYSIS: In this 2-year, multicentre, open-label, real-world randomised controlled trial, 384 adults with severe and complex obesity (defined as body mass index ≥35 kg/m2 plus either prediabetes, type 2 diabetes, hypertension or sleep apnoea) will be randomised via a 2:1 ratio to receive either standard SWMS care (n=128) or standard SWMS care plus a targeted prescribing pathway for LIRA 3 mg with prespecified stopping rules at 16, 32 and 52 weeks (n=256).The primary outcome is to compare the proportion of participants achieving a weight loss of ≥15% at 52 weeks with a targeted prescribing pathway versus standard care. Secondary outcomes include a comparison of (1) the weight loss maintenance at 104 weeks and (2) the budget impact and cost effectiveness between the two groups in a real-world setting. ETHICS AND DISSEMINATION: The Health Research Authority and the Medicines and Healthcare products Regulatory Authority in UK, the Health Products Regulatory Authority in Ireland, the North West Deanery Research Ethics Committee (UK) and the St Vincent's University Hospital European Research Ethics Committee (Ireland) have approved the study. The findings of the study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov-Identifier: NCT03036800.European Clinical Trials Database-Identifier: EudraCT Number 2017-002998-20.

Cost-effectiveness of intensive interventions compared to standard care in individuals with type 2 diabetes: A systematic review and critical appraisal of decision-analytic models.

AIMS: The objective of this systematic review is to identify and assess the quality of published decision-analytic models evaluating the long-term cost-effectiveness of target-driven intensive interventions for single and multifactorial risk factor control compared to standard care in people with type 2 diabetes. METHODS: We searched the electronic databases MEDLINE, the National Health Service Economic Evaluation Database, Web of Science and the Cochrane Library from inception to October 31, 2019. Articles were eligible for inclusion if the studies had used a decision-analytic model evaluating both the long-term costs and benefits associated with intensive interventions for risk factor control compared to standard care in people with type 2 diabetes. Data were extracted using a standardised form, while quality was assessed using the decision-analytic model-specific Philips-criteria. RESULTS: Overall, nine articles (11 models) were identified, four models evaluated intensive glycaemic control, three evaluated intensive blood pressure control, two evaluated intensive lipid control, and two evaluated intensive multifactorial interventions. Six reported using discrete-time simulations modelling approach, whereas five reported using a Markov modelling framework. The majority, seven studies, reported that the intensive interventions were dominant or cost-effective, given the assumptions and analytical perspective taken. The methodological and reporting quality of the studies was generally weak, with only four studies fulfilling more than 50% of their applicable Philips-criteria. CONCLUSIONS: This is the first systematic review of decision-analytic models of target-driven intensive interventions for single and multifactorial risk factor control in individuals with type 2 diabetes. Identified shortcomings are lack of transparency in data identification and evidence synthesis as well as for the selection of the modelling approaches. Future models should aim to include greater evaluation of the quality of the data sources used and the assessment of uncertainty in the model.

activPAL and ActiGraph Assessed Sedentary Behavior and Cardiometabolic Health Markers.

PURPOSE: To establish whether associations between sedentary behavior and cardiometabolic health differ when assessed by thigh-worn and waist-worn accelerometry. METHODS: Participants were recruited from several areas in the United Kingdom. Sedentary behavior was assessed using the activPAL worn on the thigh and ActiGraph worn on the waist. Average total (TST), prolonged (bouts ≥30 min; PST) and breaks (BST) in sedentary time were calculated. Cardiometabolic health markers included: adiposity (body fat) and surrogate markers of adiposity ((waist circumference, body mass index [BMI]), lipids (total, low density lipoprotein, and high-density lipoprotein [HDL] cholesterol, triglycerides), blood pressure, and glucose (fasting, 2 h and glycated hemoglobin A1c). A clustered cardiometabolic risk score was calculated. Linear regression analysis examined the associations with cardiometabolic health. RESULTS: There were 1457 participants (mean age [± standard deviation], 59.38 ± 11.85 yr; 51.7% male; mean BMI, 30.19 ± 5.59 kg·m) included in the analyses. ActivPAL and ActiGraph sedentary variables were moderately correlated (0.416-0.511, P < 0.01); however, all variables were significantly different from each other (P < 0.05). Consistency was observed across devices in the direction and magnitude of associations of TST and PST with adiposity, surrogate markers of adiposity, HDL, triglycerides, and cardiometabolic risk score and for BST with adiposity, surrogate markers of adiposity, and cardiometabolic risk. Differences across devices were observed in associations of TST and PST with diastolic blood pressure, for TST with 2-h glucose and for BST with HDL. No other associations were observed for any other health marker for either device. CONCLUSIONS: Results suggest that associations with cardiometabolic health are largely comparable across the two common assessments of sedentary behavior but some small differences may exist for certain health markers.

The impact of an intervention to increase uptake to structured self-management education for people with type 2 diabetes mellitus in primary care (the embedding package), compared to usual care, on glycaemic control: study protocol for a mixed methods study incorporating a wait-list cluster randomised controlled trial.

BACKGROUND: Approximately 425 million people globally have diabetes, with ~ 90% of these having Type 2 Diabetes Mellitus (T2DM). This is a condition that leads to a poor quality of life and increased risk of serious health complications. Structured self-management education (SSME) has been shown to be effective in improving glycaemic control and patient related outcome measures and to be cost-effective. However, despite the demonstrated benefits, attendance at SSME remains low. An intervention has been developed to embed SSME called the 'Embedding Package'. The intervention aims to address barriers and enhance enablers to uptake of SSME at patient, healthcare professional and organisational levels. It comprises a marketing strategy, user friendly and effective referral pathways, new roles to champion SSME and a toolkit of resources. METHODS: A mixed methods study incorporating a wait-list cluster randomised trial and ethnographic study, including 66 UK general practices, will be conducted with two intervention start times (at 0 and 9 months), each followed by an active delivery phase. At 18 months, the intervention will cease to be actively delivered and a 12 month observational follow-up phase will begin. The intervention, the Embedding Package, aims to increase SSME uptake and subsequent improvements in health outcomes, through a clear marketing strategy, user friendly and effective referral pathways, a local clinical champion and an 'Embedder' and a toolkit of resources for patients, healthcare professionals and other key stakeholders. The primary aim is, through increasing uptake to and attendance at SSME, to reduce HbA1c in people with T2DM compared with usual care. Secondary objectives include: assessing whether there is an increase in referral to and uptake of SSME and improvements in biomedical and psychosocial outcomes; an assessment of the sustainability of the Embedding Package; contextualising the process of implementation, sustainability of change and the 'fit' of the Embedding Package; and an assessment of the cost-effectiveness of the Embedding Package. DISCUSSION: This study will assess the effectiveness, cost-effectiveness and sustainability of the Embedding Package, an intervention which aims to improve biomedical and psychosocial outcomes of people with T2DM, through increased referral to and uptake of SSME. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number ISRCTN23474120. Assigned 05/04/2018. The study was prospectively registered. On submission of this manuscript practice recruitment is complete, participant recruitment is ongoing and expected to be completed by the end of 2019.

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.

20-year trends in cause-specific heart failure outcomes by sex, socioeconomic status, and place of diagnosis: a population-based study.

BACKGROUND: Heart failure is an important public health issue affecting about 1 million people in the UK, but contemporary trends in cause-specific outcomes among different population groups are unknown. METHODS: In this retrospective, population-based study, we used the UK Clinical Practice Research Datalink and Hospital Episodes Statistics databases to identify a cohort of patients who had a diagnosis of incident heart failure between Jan 1, 1998, and July 31, 2017. Patients were eligible for inclusion if they were aged 30 years or older with a first code for heart failure in their primary care or hospital record during the study period. We assessed cause-specific admission to hospital (ie, hospitalisation) and mortality, by age, sex, socioeconomic status, and place of diagnosis (ie, hospital vs community diagnosis). We calculated outcome rates separately for the first year (first-year rates) and for the second-year onwards (subsequent-year rates). Patients were followed up until death or study end. This study is registered with Clinical Practice Research Datalink Independent Scientific Advisory Committee, protocol number 18_037R. FINDINGS: We identified 88 416 individuals with incident heart failure over the study period, of whom 43 461 (49%) were female. The mean age was 77·8 years (SD 11·3) and median follow-up was 2·4 years (IQR 0·5 to 5·7). Age-adjusted first-year rates of hospitalisation increased by 28% for all-cause admissions, from 97·1 (95% CI 94·3 to 99·9) to 124·2 (120·9 to 127·5) per 100 person-years; by 28% for heart failure-specific admissions, from 17·2 (16·2 to 18·2) to 22·1 (20·9 to 23·2) per 100 person-years; and by 42% for non-cardiovascular admissions, from 59·2 (57·2 to 61·2) to 83·9 (81·3 to 86·5) per 100 person-years. 167 641 (73%) of 228 113 hospitalisations were for non-cardiovascular causes and annual rate increases were higher for women (3·9%, 95% CI 2·8 to 4·9) than for men (1·4%, 0·6 to 2·1; p<0·0001); and for patients diagnosed with heart failure in hospital (2·4%, 1·4 to 3·3) than those diagnosed in the community (1·2%, 0·3 to 2·2). Annual increases in hospitalisation due to heart failure were 2·6% (1·9 to 3·4) for women compared with stable rates in men (0·6%, -0·9 to 2·1), and 1·6% (0·6 to 2·6) for the most deprived group compared with stable rates for the most affluent group (1·2%, -0·3 to 2·8). A significantly higher risk of all-cause hospitalisation was found for the most deprived than for the most affluent (incident rate ratio 1·34, 95% CI 1·32 to 1·35) and for the hospital-diagnosed group than for the community-diagnosed group (1·76, 1·73 to 1·80). Age-adjusted first-year rates of all-cause mortality decreased by 6% from 24·5 (95% CI 23·4 to 39·2) to 23·0 (22·0 to 24·1) per 100 person-years. Annual change in mortality was -1·4% (95% CI -2·3 to -0·5) in men but was stable for women (0·3%, -0·5 to 1·1), and -2·7% (-3·2 to -2·2) for the community-diagnosed group compared with -1·1% (-1·8 to -0·4) in the hospital-diagnosed group (p<0·0001). A significantly higher risk of all-cause mortality was seen in the most deprived group than in the most affluent group (hazard ratio 1·08, 95% CI 1·05 to 1·11) and in the hospital-diagnosed group than in the community-diagnosed group (1·55, 1·53 to 1·58). INTERPRETATION: Tailored management strategies and specialist care for patients with heart failure are needed to address persisting and increasing inequalities for men, the most deprived, and for those who are diagnosed with heart failure in hospital, and to address the worrying trends in women. FUNDING: Wellcome Trust.

Micro-costing and a cost-consequence analysis of the 'Girls Active' programme: A cluster randomised controlled trial.

Physical inactivity has been identified as a leading risk factor for premature mortality globally, and adolescents, in particular, have low physical activity levels. Schools have been identified as a setting to tackle physical inactivity. Economic evidence of school-based physical activity programmes is limited, and the costs of these programmes are not always collected in full. This paper describes a micro-costing and cost-consequence analysis of the 'Girls Active' secondary school-based programme as part of a cluster randomised controlled trial (RCT). Micro-costing and cost-consequence analyses were conducted using bespoke cost diaries and questionnaires to collect programme delivery information. Outcomes for the cost-consequence analysis included health-related quality of life measured by the Child Health Utility-9D (CHU-9D), primary care General Practitioner (GP) and school-based (school nurse and school counsellor) service use as part of a cluster RCT of the 'Girls Active' programme. Overall, 1,752 secondary pupils were recruited and a complete case sample of 997 participants (Intervention n = 570, Control n = 427) was used for the cost-consequence analysis. The micro-costing analysis demonstrated that, depending upon how the programme was delivered, 'Girls Active' costs ranged from £1,054 (£2 per pupil, per school year) to £3,489 (£7 per pupil, per school year). The least costly option was to absorb 'Girls Active' strictly within curriculum hours. The analysis demonstrated no effect for the programme for the three main outcomes of interest (health-related quality of life, physical activity and service use).Micro-costing analyses demonstrated the costs of delivering the 'Girls Active' programme, addressing a gap in the United Kingdom (UK) literature regarding economic evidence from school-based physical activity programmes. This paper provides recommendations for those gathering cost and service use data in school settings to supplement validated and objective measures, furthering economic research in this field. Trial registration: -ISRCTN, ISRCTN10688342.