Search

Objective: This study aims to create a national ethnicity spine based on all available ethnicity records in linkable anonymised electronic health record and administrative data sources., Design: A longitudinal study using anonymised individual-level population-scale ethnicity data from 26 data sources available within the Secure Anonymised Information Linkage Databank., Setting: The national ethnicity spine is created based on longitudinal national data for the population of Wales-UK over 22 years (between 2000 and 2021)., Procedure and Participants: A total of 46 million ethnicity records for 4 297 694 individuals have been extracted, harmonised, deduplicated and made available within a longitudinal research ready data asset., Outcome Measures: (1) Comparing the distribution of ethnicity records over time for four different selection approaches (latest, mode, weighted mode and composite) across age bands, sex, deprivation quintiles, health board and residential location and (2) distribution and completeness of records against the ONS census 2011., Results: The distribution of the dominant group (white) is minimally affected based on the four different selection approaches. Across all other ethnic group categorisations, the mixed group was most susceptible to variation in distribution depending on the selection approach used and varied from a 0.6% prevalence across the latest and mode approach to a 1.1% prevalence for the weighted mode, compared with the 3.1% prevalence for the composite approach. Substantial alignment was observed with ONS 2011 census with the Latest group method (kappa=0.68, 95% CI (0.67 to 0.71)) across all subgroups. The record completeness rate was over 95% in 2021., Conclusion: In conclusion, our development of the population-scale ethnicity spine provides robust ethnicity measures for healthcare research in Wales and a template which can easily be deployed in other trusted research environments in the UK and beyond., Competing Interests: Competing interests: KK is Director of the University Centre for Ethnic Health Research, Trustee of the South Asian Health Foundation, Chair of the Ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and member of SAGE. RL is a member of the Welsh Government COVID-19 Technical Advisory Group. RKO is a member of the National Institute for Health and Care Excellence (NICE) Technology Appraisal Committee, a member of the NICE Decision Support Unit (DSU) and an associate member of the NICE Technical Support Unit (TSU). She has provided unrelated methodological advice as a paid consultant to the pharmaceutical industry. She reports teaching fees from the Association of British Pharmaceutical Industry (ABPI) and the University of Bristol., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: The aim of the study was to assess the clinical effectiveness of the national cardiovascular disease (CVD) prevention programme-National Health Service Health Check (NHSHC) in reduction of CVD risk., Design: Prospective cohort study., Setting: 147 primary care practices in Leicestershire and Northamptonshire in England, UK., Participants: 27 888 individuals undergoing NHSHC with a minimum of 18 months of follow-up data., Outcome Measures: The primary outcomes were NHSHC attributed detection of CVD risk factors, prescription of medications, changes in values of individual risk factors and frequency of follow-up., Results: At recruitment, 18% of participants had high CVD risk (10%-20% 10-year risk) and 4% very high CVD risk (>20% 10-year risk). New diagnoses or hypertension (HTN) was made in 2.3% participants, hypercholesterolaemia in 0.25% and diabetes mellitus in 0.9%. New prescription of stains and antihypertensive medications was observed in 5.4% and 5.4% of participants, respectively. Total cholesterol was decreased on average by 0.38 mmol/L (95% CI -0.34 to -0.41) and 1.71 mmol/L (-1.48 to -1.94) in patients with initial cholesterol >5 mmol/L and >7.5 mmol/L, respectively. Systolic blood pressure was decreased on average by 2.9 mm Hg (-2.3 to -3.7), 15.7 mm Hg (-14.1 to -17.5) and 33.4 mm Hg (-29.4 to -37.7), in patients with grade 1, 2 and 3 HTN, respectively. About one out of three patients with increased CVD risk had no record of follow-up or treatment., Conclusions: Majority of patients identified with increased CVD risk through the NHSHC were followed up and received effective clinical interventions. However, one-third of high CVD risk patients had no follow-up and therefore did not receive any treatment. Our study highlights areas of focus which could improve the effectiveness of the programme., Trial Registration Number: NCT04417387., Competing Interests: Competing interests: KK was a national advisor for the NHS Health Checks programme., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Older people were at particular risk of morbidity and mortality during COVID-19. Consequently, they experienced formal (externally imposed) and informal (self-imposed) periods of social isolation and quarantine. This is hypothesised to have led to physical deconditioning, new-onset disability and frailty. Disability and frailty are not routinely collated at population level but are associated with increased risk of falls and fractures, which result in hospital admissions. First, we will examine incidence of falls and fractures during COVID-19 (January 2020-March 2022), focusing on differences between incidence over time against expected rates based on historical data, to determine whether there is evidence of new-onset disability and frailty. Second, we will examine whether those with reported SARS-CoV-2 were at higher risk of falls and fractures., Methods and Analysis: This study uses the Office for National Statistics (ONS) Public Health Data Asset, a linked population-level dataset combining administrative health records with sociodemographic data of the 2011 Census and National Immunisation Management System COVID-19 vaccination data for England. Administrative hospital records will be extracted based on specific fracture-centric International Classification of Diseases-10 codes in years preceding COVID-19 (2011-2020). Historical episode frequency will be used to predict expected admissions during pandemic years using time series modelling, if COVID-19 had not occurred. Those predicted admission figures will be compared with actual admissions to assess changes in hospital admissions due to public health measures comprising the pandemic response. Hospital admissions in prepandemic years will be stratified by age and geographical characteristics and averaged, then compared with pandemic year admissions to assess more granular changes. Risk modelling will assess risk of experiencing a fall, fracture or frail fall and fracture, if they have reported a positive case of COVID-19. The combination of these techniques will provide insight into changes in hospital admissions from the COVID-19 pandemic., Ethics and Dissemination: This study has approval from the National Statistician's Data Ethics Advisory Committee (NSDEC(20)12). Results will be made available to other researchers via academic publication and shared via the ONS website., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Uptake of influenza, pneumococcal and shingles vaccines in older adults vary across regions and socioeconomic backgrounds. In this study, we study the coverage and factors associated with vaccination uptake, as well as refusal in the unvaccinated population and their associations with ethnicity, deprivation, household size and health conditions., Design, Setting and Participants: This is a cross-sectional study of adults aged 65 years or older in England, using a large primary care database. Associations of vaccine uptake and refusal in the unvaccinated with ethnicity, deprivation, household size and health conditions were modelled using multivariable logistic regression., Outcome Measure: Influenza, pneumococcal and shingles vaccine uptake and refusal (in the unvaccinated)., Results: This study included 2 054 463 patients from 1318 general practices. 1 711 465 (83.3%) received at least one influenza vaccine, 1 391 228 (67.7%) pneumococcal vaccine and 690 783 (53.4%) shingles vaccine. Compared with White ethnicity, influenza vaccine uptake was lower in Chinese (OR 0.49; 95% CI 0.45 to 0.53), 'Other ethnic' groups (0.63; 95% CI 0.60 to 0.65), black Caribbean (0.68; 95% CI 0.64 to 0.71) and black African (0.72; 95% CI 0.68 to 0.77). There was generally lower vaccination uptake among more deprived individuals, people living in larger household sizes (three or more persons) and those with fewer health conditions. Among those who were unvaccinated, higher odds of refusal were associated with the black Caribbean ethnic group and marginally with increased deprivation, but not associated with higher refusal in those living in large households or those with lesser health conditions., Conclusion: Certain ethnic minority groups, deprived populations, large households and 'healthier' individuals were less likely to receive a vaccine, although higher refusal was only associated with ethnicity and deprivation but not larger households nor healthier individuals. Understanding these may inform tailored public health messaging to different communities for equitable implementation of vaccination programmes., Competing Interests: Competing interests: PST reports previous consultation with AstraZeneca and Duke-NUS outside the submitted work. KK is a Member of the Scientific Advisory Group for Emergencies (SAGE), Member of Independent SAGE, Director of the University of Leicester Centre for Black Minority Health and Trustee of the south Asian Health Foundation. JH-C is a member of several SAGE committees and chair of the risk stratification subgroup of the NERVTAG. She is an unpaid director of QResearch and founder and former medical director of ClinRisk Ltd (outside the submitted work). MP, AKC, HD-M, DS, TAR, FZ, BRS, SJG, CC, CG have no interests to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Peripheral arterial disease (PAD) is a key risk factor for cardiovascular disease, foot ulceration and lower limb amputation in people with diabetes. Early diagnosis of PAD can enable optimisation of therapies to manage these risks. Its diagnosis is fundamental, though challenging in the context of diabetes. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most accurate in routine clinical practice.The aim of this study is to determine the diagnostic performance of a variety of tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of PAD in people with diabetes as determined by a reference test (CT angiography (CTA) or magnetic resonance angiography (MRA)). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan)., Methods and Analysis: A prospective multicentre diagnostic accuracy study (ClinicalTrials.gov Identifier NCT05009602). We aim to recruit 730 people with diabetes from 18 centres across the UK, covering primary and secondary healthcare. Consenting participants will undergo the tests under investigation. Reference tests (CTA or MRA) will be performed within 6 weeks of the index tests. Imaging will be reported by blinded consultant radiologists at a core imaging lab, using a validated scoring system, which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ≥50% stenosis, or tandem lesions with a combined value of ≥50%, will be used as the threshold for the diagnosis of PAD. The primary outcome measure of diagnostic performance will be test sensitivity., Ethics and Dissemination: The study has received approval from the National Research Ethics Service (NRES) (REC reference 21/PR/1221). Results will be disseminated through research presentations and papers., Trial Registration Number: NCT05009602., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Type 2 diabetes mellitus (T2DM) onset before 40 years of age has a magnified lifetime risk of cardiovascular disease. Diastolic dysfunction is its earliest cardiac manifestation. Low energy diets incorporating meal replacement products can induce diabetes remission, but do not lead to improved diastolic function, unlike supervised exercise interventions. We are examining the impact of a combined low energy diet and supervised exercise intervention on T2DM remission, with peak early diastolic strain rate, a sensitive MRI-based measure, as a key secondary outcome., Methods and Analysis: This prospective, randomised, two-arm, open-label, blinded-endpoint efficacy trial is being conducted in Montreal, Edmonton and Leicester. We are enrolling 100 persons 18-45 years of age within 6 years' T2DM diagnosis, not on insulin therapy, and with obesity. During the intensive phase (12 weeks), active intervention participants adopt an 800-900 kcal/day low energy diet combining meal replacement products with some food, and receive supervised exercise training (aerobic and resistance), three times weekly. The maintenance phase (12 weeks) focuses on sustaining any weight loss and exercise practices achieved during the intensive phase; products and exercise supervision are tapered but reinstituted, as applicable, with weight regain and/or exercise reduction. The control arm receives standard care. The primary outcome is T2DM remission, (haemoglobin A1c of less than 6.5% at 24 weeks, without use of glucose-lowering medications during maintenance). Analysis of remission will be by intention to treat with stratified Fisher's exact test statistics., Ethics and Dissemination: The trial is approved in Leicester (East Midlands - Nottingham Research Ethics Committee (21/EM/0026)), Montreal (McGill University Health Centre Research Ethics Board (RESET for remission/2021-7148)) and Edmonton (University of Alberta Health Research Ethics Board (Pro00101088). Findings will be shared widely (publications, presentations, press releases, social media platforms) and will inform an effectiveness trial., Trial Registration Number: ISRCTN15487120., Competing Interests: Competing interests: MGF is board member, shareholder, and consultant of Circle Cardiovascular Imaging. Through the University Hospitals of Leicester NHS Trust, coinvestigator GM has a research agreement with Circle Cardiovascular Imaging. We will be using software from this company to analyse the cardiac MRI images that we will obtain. KK has received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Takeda, Servier, and Pfizer and research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, and Pfizer. MJD has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi, Lilly and Boehringer Ingelheim, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Servier and Gilead Sciences and as a speaker for Napp Pharmaceuticals, Mitsubishi Tanabe Pharma and Takeda Pharmaceuticals International. She has received grants in support of investigator and investigator initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Astrazeneca and Janssen. TY has received investigator initiated funding for obesity-related research from AstraZeneca., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objective: To examine the evidence on the associations between socioeconomic position and young people's physical activity and sedentary behaviours in the UK., Design: Scoping review., Data Sources: PubMed, SCOPUS and Web of Science databases were searched for articles published up to and including January 2021., Eligibility Criteria for Selecting Studies: Observational studies in children and adolescents (aged 5-18 years) from the UK that had assessed associations between at least one indicator of socioeconomic position and at least one outcome of physical activity and/or sedentary behaviour., Data Extraction and Synthesis: Data were extracted by one reviewer and 20% were double checked. Indicators of socioeconomic position were tabulated with domains of physical activity and sedentary behaviour., Results: Fifty-seven publications were included in the review; 37 publications from 19 studies (k=23) of children and 21 publications from 15 studies (k=23) of adolescents. Most studies were cross-sectional. 63% of studies of children, and 40% of studies of adolescents assessed Index of Multiple Deprivation. Eighteen studies measured physical activity in children, 13 measured sedentary behaviour. Eleven studies of adolescents included a measure of physical activity, 10 included a measure of sedentary behaviour. Among children and adolescents, the association between socioeconomic position and measures of either physical activity or sedentary behaviour was highly variable depending on the measure of both socioeconomic position used and the behavioural outcome, with the exception of higher family affluence which was consistently associated with higher reported physical activity among adolescents., Conclusion: Physical activity and sedentary behaviours of children and adolescents in the UK are complex and influenced by multiple indicators of socioeconomic position that are, in most cases, different across age stages, outcomes examined and measurement tools. Greater consistency in the use and measures of socioeconomic position as well as outcomes of behaviour are required for robust country-specific meta-analyses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: (1) To estimate the pooled prevalence of multimorbidity in all age groups, globally. (2) To examine how measurement of multimorbidity impacted the estimated prevalence., Methods: In this systematic review and meta-analysis, we conducted searches in nine bibliographic databases (PsycINFO, Embase, Global Health, Medline, Scopus, Web of Science, Cochrane Library, CINAHL and ProQuest Dissertations and Theses Global) for prevalence studies published between database inception and 21 January 2020. Studies reporting the prevalence of multimorbidity (in all age groups and in community, primary care, care home and hospital settings) were included. Studies with an index condition or those that did not include people with no long-term conditions in the denominator were excluded. Retrieved studies were independently reviewed by two reviewers, and relevant data were extracted using predesigned pro forma. We used meta-analysis to pool the estimated prevalence of multimorbidity across studies, and used random-effects meta-regression and subgroup analysis to examine the association of heterogeneous prevalence estimates with study and measure characteristics., Results: 13 807 titles were screened, of which 193 met inclusion criteria for meta-analysis. The pooled prevalence of multimorbidity was 42.4% (95% CI 38.9% to 46.0%) with high heterogeneity (I 2 >99%). In adjusted meta-regression models, participant mean age and the number of conditions included in a measure accounted for 47.8% of heterogeneity in effect sizes. The estimated prevalence of multimorbidity was significantly higher in studies with older adults and those that included larger numbers of conditions. There was no significant difference in estimated prevalence between low-income or middle-income countries (36.8%) and high-income countries (44.3%), or between self-report (40.0%) and administrative/clinical databases (52.7%)., Conclusions: The pooled prevalence of multimorbidity was significantly higher in older populations and when studies included a larger number of baseline conditions. The findings suggest that, to improve study comparability and quality of reporting, future studies should use a common core conditions set for multimorbidity measurement and report multimorbidity prevalence stratified by sociodemographics. PROSPERO registration number CRD42020172409., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments., Aims: This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies., Methods and Analysis: Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported., Ethics and Dissemination: This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups., Prospero Registration Number: The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Type 2 diabetes mellitus is a major global challenge, including for Thai policy-makers, as an estimated 4 million people in Thailand (population 68 million) have this condition. Premature death and disability due to diabetes are primarily due to complications which can be prevented by good risk factor control. Diabetes Self-Management Education (DSME) programmes provide patients with diabetes with the necessary knowledge and skills to effectively manage their disease. Currently, a trial is being conducted in Thailand to evaluate the effectiveness, defined as HbA1c<7 at 12 months after enrolment, of a culturally tailored DSME in Thailand. A process evaluation can provide further interpretation of the results from complex interventions as well as insight into the success of applying the programme into a broader context., Methods and Analysis: The aim of the process evaluation is to understand how and why the intervention was effective or ineffective and to identify contextually relevant strategies for future successful implementation. For the process evaluation, the design will be a mixed-method study collecting data from nurse providers, and village health volunteers (community health workers) as well as patients. This will be conducted using observations, interviews and focus groups from the three purposively selected groups at the beginning and end of trial. Quantitative data will be collected through surveys conducted at the beginning, during 6-month follow-up, and at the end of trial. The mixed-methods analysis will be triangulated to assess differences and similarities across the various data sources. The overall effectiveness of the intervention will be examined using multilevel analysis of repeated measures., Ethics and Dissemination: Study approved by the Chiang Mai University Research Ethics Committee (326/2018) and the London School of Hygiene & Tropical Medicine (16113/RR/12850). Results will be published in open access, peer-reviewed scientific journals., Trial Registration Number: NCT03938233., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles., Methods and Analysis: The study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals' risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up., Ethics and Dissemination: This study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers., Competing Interests: Competing interests: PB, SO'N, AB, RJS, PC, LAT and LS have nothing to declare. SW is employed by Roche and holds stock in Roche. AB is an economic advisor on DiRECT trial with ongoing responsibility for economic analysis during long-term follow-up phase, and has also acted as consultant to GlaxoSmithKline, Merck, Novo Nordisk and Boehringer Ingelheim in relation to their diabetes products. AIA receives salary from the National Institute for Health Research (NIHR) via the University of Oxford and Addenbrooke’s Hospital, and also chairs an NICE technology appraisal committee, is a member of Diabetes UK, and manages people whose salaries are partially funded by completed trials involving sitagliptin and exenatide and an ongoing trial of empagliflozin. KK has acted as a consultant, speaker or received grants for investigator-initiated studies for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG/Menarini Group, Janssen, and Napp. IJD holds an unrestricted research grant from GSK and holds shares in GSK. RG sits on the NIHR commissioning committee., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Globally, there are estimated 425 million people with type 2 diabetes (T2D) with 80% from low-middle income countries (LMIC). Diabetes self-management education (DSME) programmes are a vital and core component of the treatment pathway for T2D. Despite LMIC being disproportionally affected by T2D, there are no DSME available that meet international diabetes federation criterion., Methods: The aims were to test the feasibility of delivering a proven effective and cost-effective approach used in a UK population in two urban settings in Malawi and Mozambique by; (1) developing a culturally, contextually and linguistically adapted DSME, the EXTending availability of self-management structured EducatioN programmes for people with type 2 Diabetes in low-to-middle income countries (EXTEND) programme; (2) using a mixed-method approach to evaluate the delivery of training and the EXTEND programme to patients with T2D., Results: Twelve healthcare professionals were trained. Ninety-eight participants received the DSME. Retention was high (100% in Mozambique and 94% in Malawi). At 6 months HbA1c (-0.9%), cholesterol (-0.3 mmol/L), blood pressure (-5.9 mm Hg systolic and -6.1 mm Hg diastolic) improved in addition to indicators of well-being (problem areas in diabetes and self-efficacy in diabetes)., Conclusion: It is feasible to deliver and evaluate the effectiveness of a culturally, contextually and linguistically adapted EXTEND programme in two LMIC. The DSME was acceptable with positive biomedical and psychological outcomes but requires formal testing with cost-effectiveness. Challenges exist in scaling up such an approach in health systems that do not have resources to address the challenge of diabetes., Competing Interests: Competing interests: KK reports grants and or personal fees from Amgen, Astrazeneca, Baye, NAPP, Lilly, Merck Sharp and Dohme, Novartis, Novo Nordisk, Roche, Berlin-Chemie AG/Menarini Group, Sanofi-Aventis, Servier, Bohringer Ingelheim and Pfizer outside the submitted work. MJD reports grants from University of Leicester and international development fund during this work. DH reports non-financial support from Novo Nordisk during this work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The COVID-19 pandemic has resulted in significant morbidity and mortality and devastated economies globally. Among groups at increased risk are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests that HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related outcomes. To date, there has been no large-scale analysis of these risks in UK HCWs or ancillary workers in healthcare settings, stratified by ethnicity or occupation, and adjusted for confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers)., Methods and Analysis: A baseline questionnaire will be administered to a national cohort of UK HCWs and ancillary workers in healthcare settings, and those registered with UK healthcare regulators, with follow-up questionnaires administered at 4 and 8 months. With consent, questionnaire data will be linked to health records with 25-year follow-up. Univariate associations between ethnicity and clinical COVID-19 outcomes, physical and mental health, and key confounders/explanatory variables will be tested. Multivariable analyses will test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables. We will model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings., Ethics and Dissemination: The study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk. We aim to manage the small risk of participant distress about questions on sensitive topics by clearly participant information that the questionnaire covers sensitive topics and there is no obligation to answer these or any other questions, and by providing support organisation links. Results will be disseminated with reports to Government and papers submitted to pre-print servers and peer reviewed journals., Trial Registration Number: ISRCTN11811602; Pre-results., Competing Interests: Competing interests: SC is Deputy Medical Director of the General Medical Council, UK Honorary Professor, University of Leicester. KK is Director of the University of Leicester Centre for Black Minority Ethnic Health, Trustee of the South Asian Health Foundation, Chair of the Ethnicity Subgroup of SAGE and Member of Independent SAGE. LVW receives grant funding from GSK and Orion, outside of the submitted work. KRA has served as a paid consultant, providing unrelated methodological and strategic advice, to the pharmaceutical and life sciences industry generally and has received unrelated research funding from Association of the British Pharmaceutical Industry, European Federation of Pharmaceutical Industries & Associations, Pfizer, Sanofi and Swiss Precision Diagnostics. He is a Partner and Director of Visible Analytics Limited, a healthcare consultancy company., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To examine inequalities in COVID-19 vaccination rates among elderly adults in England., Design: Cohort study., Setting: People living in private households and communal establishments in England., Participants: 6 655 672 adults aged ≥70 years (mean 78.8 years, 55.2% women) who were alive on 15 March 2021., Main Outcome Measures: Having received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted ORs using logistic regression models., Results: By 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of black African and black Caribbean ethnic backgrounds, where only 67.2% and 73.8% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 to 5.16) and 4.85 (4.75 to 4.96) times greater than the white British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socioeconomic position (proxied by living in a rented home), being disabled and living either alone or in a multigenerational household were also associated with higher odds of not having received the vaccine., Conclusion: Research is now urgently needed to understand why disparities exist in these groups and how they can best be addressed through public health policy and community engagement., Competing Interests: Competing interests: KK is Director of the University of Leicester Centre for Black Minority Ethnic Health, Trustee of the South Asian Health Foundation, Chair of the Ethnicity Subgroup of SAGE and Member of Independent SAGE., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Aim: This study's objective was to assess the risk of severe in-hospital complications of patients admitted for COVID-19 and diabetes mellitus (DM)., Design: This was a cross-sectional study., Settings: We used pseudonymised medical record data provided by six general hospitals from the HM Hospitales group in Spain., Outcome Measures: Multiple logistic regression analyses were used to identify variables associated with mortality and the composite of mortality or invasive mechanical ventilation (IMV) in the overall population, and stratified for the presence or absence of DM. Spline analysis was conducted on the entire population to investigate the relationship between glucose levels at admission and outcomes., Results: Overall, 1621 individuals without DM and 448 with DM were identified in the database. Patients with DM were on average 5.1 years older than those without. The overall in-hospital mortality was 18.6% (N=301), and was higher among patients with DM than those without (26.3% vs 11.3%; p<0.001). DM was independently associated with death, and death or IMV (OR=2.33, 95% CI: 1.7 to 3.1 and OR=2.11, 95% CI: 1.6 to 2.8, respectively; p<0.001). In subjects with DM, the only variables independently associated with both outcomes were age >65 years, male sex and pre-existing chronic kidney disease. We observed a non-linear relationship between blood glucose levels at admission and risk of in-hospital mortality and death or IMV. The highest probability for each outcome (around 50%) was at random glucose of around 550 mg/dL (30.6 mmol/L), and the risks flattened above this value., Conclusion: The results confirm the high burden associated with DM in patients hospitalised with COVID-19 infection, particularly among men, the elderly and those with impaired kidney function. Moreover, hyperglycaemia on admission was strongly associated with poor outcomes, suggesting that personalised optimisation could help to improve outcome during the hospital stay., Competing Interests: Competing interests: EO has received advisory and or speaking fees from AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi and Amgen; he received research grants to the institution from MSD and Amgen. RC has received advisory and/or speaking fees from Abbott, Ascensia, Lilly, MSD, Novo Nordisk and Sanofi. MM-C has received advisory honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he received speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, Menarini, MSD, Novartis, Novo Nordisk and Sanofi; he received research grants to the institution from AstraZeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi. JF-N has received advisory and or speaking fees from AstraZeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he received research grants to the institution from AstraZeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. KK has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie AG/Menarini Group, Janssen and Napp. DM has received advisory and/or speaking fees from AstraZeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk and Sanofi; he received research grants to the institution from AstraZeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi and Boehringer. PD has received lecture and Advisory Board fees from Gilead Sciences, Roche, Merck, Sharp & Dohme, ViiV Healthcare, Janssen & Cilag, Theratechnologies, Boehringer Ingelheim and Ferrer International. PD has received research grants from Gilead Sciences, ViiV Healthcare, GSK, Janssen & Cilag and Boehringer Ingelheim. BV, FXCC, JR, RP-T, MG and EC have no conflict of interest to declare., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To systematically learn lessons from the experiences of countries implementing find, test, trace, isolate, support (FTTIS) in the first wave of the COVID-19 pandemic., Design, Data Sources and Eligibility Criteria: We searched MEDLINE (PubMed), Cochrane Library, SCOPUS and JSTOR, initially between 31 May 2019 and 21 January 2021. Research articles and reviews on the use of contact tracing, testing, self-isolation and quarantine for COVID-19 management were included in the review., Data Extraction and Synthesis: We extracted information including study objective, design, methods, main findings and implications. These were tabulated and a narrative synthesis was undertaken given the diverse research designs, methods and implications., Results: We identified and included 118 eligible studies. We identified the core elements of an effective find, test, trace, isolate, support (FTTIS) system needed to interrupt the spread of a novel infectious disease, where treatment or vaccination was not yet available, as pertained in the initial stages of the COVID-19 pandemic. We report methods used to shorten case finding time, improve accuracy and efficiency of tests, coordinate stakeholders and actors involved in an FTTIS system, support individuals isolating and make appropriate use of digital tools., Conclusions: We identified in our systematic review the key components of an FTTIS system. These include border controls, restricted entry, inbound traveller quarantine and comprehensive case finding; repeated testing to minimise false diagnoses and pooled testing in resource-limited circumstances; extended quarantine period and the use of digital tools for contact tracing and self-isolation. Support for mental or physical health and livelihoods is needed for individuals undergoing self-isolation/quarantine. An integrated system with rolling-wave planning can best use effective FTTIS tools to respond to the fast-changing COVID-19 pandemic. Results of the review may inform countries considering implementing these measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: COVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities., Methods and Analysis: This study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes., Ethics and Dissemination: Ethical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/)., Trial Registration Number: ISRCTN11811602., Competing Interests: Competing interests: LG leads the NIHR ARC EM Data2Health theme. KK is Director for the University of Leicester Centre for BME Health, Trustee of the South Asian Health Foundation, national NIHR ARC lead for Ethnicity and Diversity, and a member of Independent SAGE. He is supported by the NIHR ARC EM and the NIHR Leicester Biomedical Research Centre. CJ holds a Medical Research Council Clinical Research Training Fellowship (MR/P00167X/1)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Recent evidence suggests that ethnic minority groups are disproportionately at increased risk of hospitalisation and death from SARS-CoV-2 infection. Population-based evidence on potential explanatory factors across minority groups and within subgroups is lacking. This study aims to quantify the association between ethnicity and the risk of hospitalisation and mortality due to COVID-19., Methods and Analysis: This is a retrospective cohort study of adults registered across a representative and anonymised national primary care database (QResearch) that includes data on 10 million people in England. Sociodemographic, deprivation, clinical and domicile characteristics will be summarised and compared across ethnic subgroups (categorised as per 2011 census). Cox models will be used to calculate HR for hospitalisation and COVID-19 mortality associated with ethnic group. Potential confounding and explanatory factors (such as demographic, socioeconomic and clinical) will be adjusted for within regression models. The percentage contribution of distinct risk factor classes to the excess risks seen in ethnic groups/subgroups will be calculated., Ethics and Dissemination: The study has undergone ethics review in accordance with the QResearch agreement (reference OX102). Findings will be disseminated through peer-reviewed manuscripts, presentations at scientific meetings and conferences with national and international stakeholders., Competing Interests: Competing interests: JH-C is founder and director of QResearch database, which is a not-for-profit organisation with EMIS (leading commercial supplier of IT for 55% of general practices in the UK). JH-C is co-owner of ClinRisk and was a paid director until June 2019. ClinRisk develops open and closed source software to ensure the reliable and updatable implementation of clinical risk equations within clinical computer systems to help improve patient care, outside the submitted work. KK is national lead for NIHR ARC ethnicity and diversity, Director for the University of Leicester Centre for BME Health, Trustee of the South Asian Health Foundation and member of the Independent SAGE. The authors declare that no support from any organisation and no financial relationships have influenced the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: Using primary care data, develop and validate sex-specific prognostic models that estimate the 10-year risk of people with non-diabetic hyperglycaemia developing type 2 diabetes., Design: Retrospective cohort study., Setting: Primary care., Participants: 154 705 adult patients with non-diabetic hyperglycaemia., Primary Outcome: Development of type 2 diabetes., Methods: This study used data routinely collected in UK primary care from general practices contributing to the Clinical Practice Research Datalink. Patients were split into development (n=109 077) and validation datasets (n=45 628). Potential predictor variables, including demographic and lifestyle factors, medical and family history, prescribed medications and clinical measures, were included in survival models following the imputation of missing data. Measures of calibration at 10 years and discrimination were determined using the validation dataset., Results: In the development dataset, 9332 patients developed type 2 diabetes during 293 238 person-years of follow-up (31.8 (95% CI 31.2 to 32.5) per 1000 person-years). In the validation dataset, 3783 patients developed type 2 diabetes during 115 113 person-years of follow-up (32.9 (95% CI 31.8 to 33.9) per 1000 person-years). The final prognostic models comprised 14 and 16 predictor variables for males and females, respectively. Both models had good calibration and high levels of discrimination. The performance statistics for the male model were: Harrell's C statistic of 0.700 in the development and 0.701 in the validation dataset, with a calibration slope of 0.974 (95% CI 0.905 to 1.042) in the validation dataset. For the female model, Harrell's C statistics were 0.720 and 0.718, respectively, while the calibration slope was 0.994 (95% CI 0.931 to 1.057) in the validation dataset., Conclusion: These models could be used in primary care to identify those with non-diabetic hyperglycaemia most at risk of developing type 2 diabetes for targeted referral to the National Health Service Diabetes Prevention Programme., Competing Interests: Competing interests: BC, LG, FZ and SB: none. MJD has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Janssen, an advisory board member for Servier and as a speaker for Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc. She has received grants in support of investigator and investigator initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim and Janssen. She was a member of the NICE public health guideline for prevention of Type 2 diabetes (NICE PH 38). KK has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp and Dohme. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. He is a member of the External Reference Group of the NHS DPP and was Chair of the NICE public health guideline for prevention of Type 2 diabetes (NICE PH 38)., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Type 2 diabetes mellitus is among the foremost health challenges facing policy makers in Thailand as its prevalence has more than tripled over the last two decades, accounting for considerable death, disability and healthcare expenditure. Diabetes self-management education (DSME) programmes show promise in improving diabetes outcomes, but this is not routinely used in Thailand. This study aims to test a culturally tailored DSME model in Thailand, using a three-arm cluster randomised controlled trial comparing a nurse-led model, a peer-assisted model and standard care. We will test which model is effective and cost effective to improve cardiovascular risk and control of blood glucose among people with diabetes., Methods and Analysis: 21 primary care units in northern Thailand will be randomised to one of three interventions, enrolling a total of 693 patients. The primary care units will be randomised (1:1:1) to participate in a culturally-tailored DSME intervention for 12 months. The three-arm trial design will compare effectiveness of nurse-led, peer-assisted (Thai village health volunteers) and standard care. The primary trial outcomes are changes in haemoglobin A1c and cardiovascular risk score. A process evaluation and cost effectiveness evaluation will be conducted to produce policy relevant guidance for the Thai Ministry of Public Health. The planned trial period will start in January 2020 and finish October 2021., Ethics and Dissemination: Ethical approval has been obtained from Thailand and the UK. We will share our study data with other researchers, advertising via our publications and web presence. In particular, we are committed to sharing our findings and data with academic audiences in Thailand and other low-income and middle-income countries., Trial Registration Number: NCT03938233., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme., Design: DISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019., Setting: Primary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations., Participants: A total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy., Primary and Secondary Outcome Measures: The proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change., Results: Of the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (≥75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe., Conclusions: A substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes., Trial Registration Numbers: NCT02322762 and NCT02226822., Competing Interests: Competing interests: KK, MBG, MK, AN, SP, WR, MVS, IS, HW and LJ are members of the DISCOVER Scientific Committee and received financial support from AstraZeneca to attend DISCOVER planning and update meetings. HC and PF are employees of AstraZeneca. NH is a former employee of AstraZeneca. JC-R is an employee of Evidera. In addition, KK has received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Takeda, Servier and Pfizer, and research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi and Pfizer, and also acknowledges support from the National Institute for Health Research Collaboration for Applied Research Collaboration—East Midlands (NIHR ARC—EM) and the National Institute of Health Research (NIHR) Leicester Biomedical Research Centre. MBG has received honoraria from Merck Serono. MK has received honoraria from Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec Systems, Intarcia, Janssen, Merck (Diabetes), Novartis, Novo Nordisk, Sanofi and Vifor, and research support from AstraZeneca and Boehringer Ingelheim. AN has received honoraria from AstraZeneca, Eli Lilly, Medtronic and Novo Nordisk, and research support from Artsana, Dexcom, Novo Nordisk and Sanofi. WR has received research support from Novo Nordisk. MVS has received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharpe & Dohme, Novo Nordisk, Sanofi and Servier, and research support from Novo Nordisk and Sanofi. IS has received honoraria from Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Kowa, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Novo Nordisk, Ono Pharmaceutical, Sanwa Kagaku Kenkyusho and Takeda Pharmaceutical, and research support from Astellas Pharma, AstraZeneca, Daiichi Sankyo, Eli Lilly, Japan Foundation for Applied Enzymology, Japan Science and Technology Agency, Kowa, Kyowa Hakko Kirin, Midori Health Management Center, Mitsubishi Tanabe Pharma, Novo Nordisk, Ono Pharmaceutical, Sanofi, Suzuken Memorial Foundation and Takeda Pharmaceutical. HW has received honoraria from Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eli Lilly, Kissei Pharma, Kowa, Kyowa Hakko Kirin, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Novartis, Novo Nordisk, Ono Pharmaceutical, Sanofi, Sanwa Kagaku Kenkyusho and Takeda, and research support from Abbott, Astellas Pharma, AstraZeneca, Bayer, Benefit One Health Care, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eli Lilly, Johnson & Johnson, Kissei Pharma, Kowa, Kyowa Hakko Kirin, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nitto Boseki, Novartis, Novo Nordisk, Ono Pharmaceutical, Pfizer, Sanofi, Sanwa Kagaku Kenkyusho, Taisho Toyama Pharmaceutical, Takeda and Terumo Corp. FT is an employee of the Mid America Heart Institute and has received research support from AstraZeneca. LJ has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Takeda, Sanofi and Roche, and research support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Roche and Sanofi., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To synthesise findings from randomised controlled trials (RCTs) of interventions aimed at increasing medication adherence in individuals with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). And, in a novel approach, to compare the intervention effect of studies which were categorised as being more pragmatic or more explanatory using the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool, to identify whether study design affects outcomes. As explanatory trials are typically held under controlled conditions, findings from such trials may not be relatable to real-world clinical practice. In comparison, pragmatic trials are designed to replicate real-world conditions and therefore findings are more likely to represent those found if the intervention were to be implemented in routine care., Design: Systematic review and meta-analysis., Data Sources: Ovid Medline, Ovid Embase, Web of Science and CINAHL from 1 January 2013 to 31 December 2018., Eligibility Criteria for Selecting Studies: RCTs lasting ≥3 months (90 days), involving ≥200 patients in the analysis, with either established CVD and/or T2DM and which measured medication adherence. From 4403 citations, 103 proceeded to full text review. Studies published in any language other than English and conference abstracts were excluded., Main Outcome Measure: Change in medication adherence., Results: Of 4403 records identified, 34 studies were considered eligible, of which 28, including 30 861 participants, contained comparable outcome data for inclusion in the meta-analysis. Overall interventions were associated with an increase in medication adherence (OR 1.57 (95% CI: 1.33 to 1.84), p<0.001; standardised mean difference 0.24 (95% CI: -0.10 to 0.59) p=0.101). The effectiveness of interventions did not differ significantly between studies considered pragmatic versus explanatory (p=0.598), but did differ by intervention type, with studies that included a multifaceted rather than a single-faceted intervention having a more significant effect (p=0.010). The analysis used random effect models and used the revised Cochrane Risk of Bias Tool to assess study quality., Conclusions: In this meta-analysis, interventions were associated with a significant increase in medication adherence. Overall multifaceted interventions which included an element of education alongside regular patient contact or follow-up showed the most promise. Effectiveness of interventions between pragmatic and explanatory trials was comparable, suggesting that findings can be transferred from idealised to real-word conditions., Prospero Registration Number: CRD42017059460., Competing Interests: Competing interests: MJD reports grants from Novo Nordisk, grants from Sanofi-Aventis, grants from Lilly, grants from Boehringer Ingelheim, grants from Janssen, personal fees from Novo Nordisk, personal fees from Sanofi-Aventis, personal fees from Lilly, personal fees from Merck Sharp & Dohme, personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Servier, personal fees from Mitsubishi Tanabe Pharma, personal fees from Takeda Pharmaceuticals International, outside the submitted work. KK reports personal fees from Amgen, personal fees from AstraZeneca, personal fees from Bayer, personal fees from NAPP, personal fees from Lilly, personal fees from Merck Sharp & Dohme, personal fees from Novartis, personal fees from Novo Nordisk, personal fees from Roche, personal fees from Berlin-Chemie AG/Menarini Group, personal fees from Sanofi-Aventis, personal fees from Servier, personal fees from Boehringer Ingelheim, grants from Pfizer, grants from Boehringer Ingelheim, grants from AstraZeneca, grants from Novartis, grants from Novo Nordisk, grants from Sanofi-Aventis, grants from Lilly, grants from Merck Sharp & Dohme, grants from Servier, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Half of all deaths in custody are due to natural causes, the most common being cardiovascular disease (CVD). National Health Service Healthchecks should be available to all eligible prisoners; it is not clear who receives them. Mental health issues are common in prisoners and may affect how healthcare interventions should be delivered. Current policy is to offer Healthchecks to those serving over 2 years in prison., Objectives, Methods, Setting and Design: An observational cross-sectional survey in six male prisons in England between September 2017 and January 2019 in prisoners aged 35-74 to identify who was eligible for a Healthcheck and compare CVD risk data with those that were not, and factors associated with uptake., Outcome Measures: Characteristics of those accepting a Healthcheck were compared with those declining. Assessments of anxiety and depression were compared with CVD risk factors., Results: 1207 prisoners completed a Healthcheck. 21.8% of prisoners were ineligible due to existing comorbidities. 76.4% of those invited took up a Healthcheck, and of those, 12.1% were found to have new significant CVD comorbidity. CVD risk was similar to community levels but this population was 10 years younger. Definite case-level depression or anxiety was present in 20.7% and 18.0%, respectively, of participants. An association was found between ethnicity and those invited (p=0.023, φ=0.1) and accepting (p=0.008, φ=0.1) a Healthcheck. 9.7% of prisoners serving less than 2 years had CVD risk scores of 10% or more, and had similar CVD risk profiles but much higher levels of anxiety (p<0.001, φ=0.2) or depression (p=0.009, φ=0.2) than those serving 2 years or more., Conclusion: Cardiovascular risk was comparable with community rates and in some prisons, much higher. Rates of anxiety and depression were high. The national policy for selecting prisoners for Healthchecks may leave many high-risk prisoners without appropriate cardiovascular preventative assessments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To identify studies that have investigated the health outcome and treatment priorities of patients with multimorbidity, clinicians or both, in order to assess whether the priorities of the two groups are in alignment, or whether a disparity exists between the priorities of patients with multimorbidity and clinicians., Design: Systematic review., Data Sources: MEDLINE, EMBASE, CINHAL and Cochrane databases from inception to May 2019 using a predefined search strategy, as well as reference lists containing any relevant articles, as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines., Eligibility Criteria: We included studies reporting health outcome and treatment priorities of adult patients with multimorbidity, defined as suffering from two or more chronic conditions, or of clinicians in the context of multimorbidity or both. There was no restriction by study design, and studies using quantitative and/or qualitative methodologies were included., Data Synthesis: We used a narrative synthesis approach to synthesise the quantitative findings, and a meta-ethnography approach to synthesise the qualitative findings., Results: Our search identified 24 studies for inclusion, which comprised 12 quantitative studies, 10 qualitative studies and 2 mixed-methods studies. Twelve studies reported the priorities of both patients and clinicians, 10 studies reported the priorities of patients and 2 studies reported the priorities of clinicians alone. Our findings have shown a mostly low level of agreement between the priorities of patients with multimorbidity and clinicians. We found that prioritisation by patients was mainly driven by their illness experiences, while clinicians focused on longer-term risks. Preserving functional ability emerged as a key priority for patients from across our quantitative and qualitative analyses., Conclusion: Recognising that there may be a disparity in prioritisation and understanding the reasons for why this might occur, can facilitate clinicians in accurately eliciting the priorities that are most important to their patients and delivering patient-centred care., Prospero Registration Number: CRD42018076076., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: A person's chronotype is their entrained preference for sleep time within the 24 hours clock. It is described by the well-known concept of the 'lark' (early riser) and 'owl' (late sleeper). Evidence suggests that the 'owl' is metabolically disadvantaged due to the standard organisation of our society which favours the 'lark' and places physiological stresses on this chronotype. The aim of this study is to explore cardiometabolic health between the lark and owl in a population with an established metabolic condition - type 2 diabetes., Methods: This cross-sectional, multisite study aims to recruit 2247 participants from both secondary and primary care settings. The primary objective is to compare glycaemic control between late and early chronotypes. Secondary objectives include determining if late-chronotype is associated with poorer cardiometabolic health and other lifestyle factors, including well-being, compared with early-chronotype; describing the prevalence of the five different chronotypes in this cohort and examining the trends in glycaemic control, cardiometabolic health, well-being and lifestyle factors across chronotype., Analysis: The primary outcome (glycated haemoglobin (HbA1c)), linear regression analysis will compare HbA1c between early and late chronotypes, with and without adjustment for confounding variables. Chronotype will be modelled as a categorical variable with all five levels (from extreme-morning to extreme-late type), and as a continuous variable to calculate p for trend across the five categories. A number of models will be created; unadjusted through to adjusted with age, sex, ethnicity, body mass index, duration of diabetes, family history of diabetes, current medication and dietary habits. All secondary outcomes will be analysed using the same method., Ethics: Ethical approval from the West Midlands - Black Country Research Ethics Committee (16/WM/0457)., Dissemination: The results will be disseminated through publication in peer-reviewed medical journal, relevant medical/health conferences and a summary report sent to patients., Trial Registration Number: NCT02973412 (Pre-Results)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine at what glycated haemoglobin (HbA1c) level physicians from eight European countries would initiate insulin in type 2 diabetes, which physician or practice related factors influenced this level and whether physicians would differentiate between a younger uncomplicated patient and an older patient with comorbidities., Design: Cross-sectional study with data from the Guideline Adherence to Enhance Care study., Setting and Participants: 410 physicians from both primary and secondary care from Belgium, France, Germany, Italy, Ireland, Sweden, the Netherlands and the UK., Outcome Measures: Physicians were asked at which HbA1c level they would initiate insulin for a young, uncomplicated patient (vignette 1) and for an older, complicated patient (vignette 2). We evaluated differences in HbA1c levels between physicians from different countries using analysis of variance. To identify physician and practice related factors associated with HbA1c level at initiation of insulin, we performed multivariable linear regression. Multiple imputation was used to deal with missing data., Results: In Germany, Ireland, Sweden, the Netherlands and the UK, the HbA1c levels for initiating insulin in vignette 2 (range: 60.0 to 66.0 mmol/mol; 7.6% to 8.2%) were higher than for vignette 1 (range: 57.2 to 64.2 mmol/mol; 7.4% to 8.0%). In multivariable analysis, the HbA1c level at which insulin was initiated only differed between countries (vignette 1): Dutch physicians initiated insulin at a lower HbA1c level compared with Belgium, France and the UK. No physician or practice factors were independently associated with HbA1c level at insulin initiation., Conclusions: When deciding on individualised HbA1c targets for insulin initiation, physicians from five countries took patient's age and comorbidity into account. The HbA1c level at which physicians would initiate insulin therapy differed between countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Despite their young age and relatively short duration of disease, younger adults with type 2 diabetes (T2D) already have diastolic dysfunction and may be at risk of incipient heart failure. Whether weight loss or exercise training improve cardiac dysfunction in people with T2D remains to be established., Methods and Analysis: Prospective, randomised, open-label, blind endpoint trial. The primary aim of the study is to determine if diastolic function can be improved by either a meal replacement plan or a supervised exercise programme, compared with guideline-directed care. A total of 90 obese participants with T2D (aged 18-65 years), diabetes duration <12 years and not on insulin treatment will be randomised to either guideline-directed clinical care with lifestyle coaching, a low-energy meal replacement diet (average ≈810 kcal/day) or a supervised exercise programme for 12 weeks. Participants undergo glycometabolic profiling, cardiopulmonary exercise testing, echocardiography and MRI scanning to assesses cardiac structure and function and dual-energy X-ray absorptiometry scanning for body composition. Key secondary aims are to assess the effects of the interventions on glycaemic control and insulin resistance, exercise capacity, blood pressure, changes in body composition and association of favourable cardiac remodelling with improvements in weight loss, exercise capacity and glycometabolic control., Ethics and Dissemination: The study has full ethical approval, and data collection was completed in August 2018. The study results will be submitted for publication within 6 months of completion., Trial Registration Number: NCT02590822; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are two classes of glucose-lowering drugs gaining popularity in the treatment of type 2 diabetes mellitus (T2DM). Current guidelines suggest patient-centred approaches when deciding between available hyperglycaemia drugs with no indication to which specific drug should be administered. Despite systematic reviews and meta-analyses being conducted within SGLT-2is and GLP-1RAs, differences across these classes of drugs have not been investigated. Therefore, this systematic review and network meta-analysis (NMA) will aim to compare the efficacy and safety profiles across and within SGLT-2is and GLP-1RAs., Methods: PubMed, the Cochrane Central Register of Controlled Trials and ISI Web of Science will be searched from inception for published randomised controlled trials conducted in patients with T2DM, with at least two arms consisting of SGLT-2is, GLP-1RAs or control/placebo. Title and abstracts will be screened by two independent reviewers with conflicts resolved by a third. Data will be extracted by the primary researcher, a random sample will be checked by an independent reviewer. Risk of bias will be assessed using the Cochrane Risk of Bias Tool and overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.Study characteristics, participants baseline characteristics, mean change in cardiometabolic outcomes and number of adverse events will be extracted for each study. Primary outcome will be the mean change in glycated haemoglobin (HbA 1c ) (%, mmol/mol). Initial random-effects pairwise meta-analysis will be conducted for each unique treatment comparison where heterogeneity will be assessed. A Bayesian NMA approach will be adopted where random-effects generalised linear models will be fitted in WinBUGS. Sensitivity analysis will be conducted to assess choices of prior distributions and length of burn-in and sample., Ethics and Dissemination: Ethics approval is not required for this study. Results from this study will be published in a peer-review journal., Prospero Registration Number: CRD42018091306., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Optimal glycaemia can reduce type 2 diabetes (T2D) complications. Observing retrospective continuous glucose monitoring (r-CGM) patterns may prompt therapeutic changes but evidence for r-CGM use in T2D is limited. We describe the protocol for a randomised controlled trial (RCT) examining intermittent r-CGM use (up to 14 days every three months) in T2D in general practice (GP)., Methods and Analysis: General Practice Optimising Structured MOnitoring To achieve Improved Clinical Outcomes is a two-arm RCT asking 'does intermittent r-CGM in adults with T2D in primary care improve HbA1c?', Primary Outcome: Absolute difference in mean HbA1c at 12 months follow-up between intervention and control arms., Secondary Outcomes: (a) r-CGM per cent time in target (4-10 mmol/L) range, at baseline and 12 months; (b) diabetes-specific distress (Problem Areas in Diabetes)., Eligibility: Aged 18-80 years, T2D for ≥1 year, a (past month) HbA1c>5.5 mmol/mol (0.5%) above their individualised target while prescribed at least two non-insulin hypoglycaemic therapies and/or insulin (therapy stable for the last four months). Our general glycaemic target is 53 mmol/mol (7%) (patients with a history of severe hypoglycaemia or a recorded diagnosis of hypoglycaemia unawareness will have a target of 64 mmol/mol (8%)).Our trial compares r-CGM use and usual care. The r-CGM report summarising daily glucose patterns will be reviewed by GP and patient and inform treatment decisions. Participants in both arms are provided with 1 hour education by a specialist diabetes nurse.The sample (n=150/arm) has 80% power to detect a mean HbA1c difference of 5.5 mmol/mol (0.5%) with an SD of 14.2 (1.3%) and alpha of 0.05 (allowing for 10% clinic and 20% patient attrition)., Ethics and Dissemination: University of Melbourne Human Ethics Sub-Committee (ID 1647151.1). Dissemination will be in peer-reviewed journals, conferences and a plain-language summary for participants., Trial Registration Number: >ACTRN12616001372471; Pre-results., Competing Interests: Competing interests: JF has received unrestricted educational grants for research support from Roche, Sanofi and Medtronic; JS is a member of the Accu-Check Advisory Board (Roche Diabetes Care) and also served on the advisory boards of Janssen and Medtronic. Her research group has received unrestricted educational grants from AstraZeneca, Medtronic and Sanofi Diabetes; sponsorship to attend educational meetings from Medtronic, Roche Diabetes Care, and Sanofi Diabetes; consultancy income and/or speaker fees from Abbott Diabetes Care, AstraZeneca, Roche Diagnostics Australia and Sanofi Diabetes; DON is on advisory boards to Abbott Diabetes Care, and Novo-Nordisk. DON, DL and JMN have had various financial relationships with pharmaceutical industries outside the submitted work including consultancies, grants, lectures, educational activities and travel. IB has received investigator initiated grant from Medtronic and Sanofi Diabetes. EHT has undertaken research funded by an unrestricted educational grant from Abbott Diabetes Care to ACBRD and has served on an AstraZeneca advisory board. JLB has received consultancy income (paid to the ACBRD) from Sanofi ANZ and Roche Diagnostics, and travel funds from AstraZeneca, and has served on a Sanofi ANZ advisory board. KK has acted as a consultant, speaker or received grants for research from Astra Zeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Janssen, Boehringer Ingelheim and Roche. JF was supported by a National Health and Medical Research Council Career Development Fellowship and then a Translating Research into Practice Fellowship. JS, JLB and EH-T are supported by core funding to the Australian Centre for Behavioural Research in Diabetes from Diabetes Victoria and Deakin University., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Children engage in a high volume of sitting in school, particularly in the classroom. A number of strategies, such as physically active lessons (termed movement integration (MI)), have been developed to integrate physical activity into this learning environment; however, no single approach is likely to meet the needs of all pupils and teachers. This protocol outlines an implementation study of a primary school-based MI intervention: CLASS PAL (Physically Active Learning) programme. This study aims to (A) determine the degree of implementation of CLASS PAL, (B) identify processes by which teachers and schools implement CLASS PAL and (C) investigate individual (pupil and teacher) level and school-level characteristics associated with implementation of CLASS PAL., Methods and Analysis: The intervention will provide teachers with a professional development workshop and a bespoke teaching resources website. The study will use a single group before-and-after design, strengthened by multiple interim measurements. Six state-funded primary schools will be recruited within Leicestershire, UK.Evaluation data will be collected prior to implementation and at four discrete time points during implementation: At measurement 0 (October 2016), school, teacher and pupil characteristics will be collected. At measurements 0 and 3 (June-July 2017), accelerometry, cognitive functioning, self-reported sitting and classroom engagement data will be collected. At measurements 1(December 2016-March 2017) and 3 , teacher interviews (also at measurement 4; September-October 2017) and pupil focus groups will be conducted, and at measurements 1 and 2 (April-May 2017), classroom observations. Implementation will be captured through website analytics and ongoing teacher completed logs., Ethics and Dissemination: Ethical approval was obtained through the Loughborough University Human Participants Ethics Sub-Committee (Reference number: R16-P115). Findings will be disseminated via practitioner and/or research journals and to relevant regional and national stakeholders through print and online media and dissemination event(s)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Assess the longitudinal association between polypharmacy and falls and examine the differences in this association by different thresholds for polypharmacy definitions in a nationally representative sample of adults aged over 60 years from England., Design: Longitudinal cohort study., Setting: The English Longitudinal Study of Ageing waves 6 and 7., Participants: 5213 adults aged 60 or older., Main Outcome Measures: Rates, incidence rate ratio (IRR) and 95% CI for falls in people with and without polypharmacy., Results: A total of 5213 participants contributed 10 502 person-years of follow-up, with a median follow-up of 2.02 years (IQR 1.9-2.1 years). Of the 1611 participants with polypharmacy, 569 reported at least one fall within the past 2 years (rate: 175 per 1000 person-years, 95% CI 161 to 190), and of the 3602 participants without polypharmacy 875 reported at least one fall (rate: 121 per 1000 person-years, 95% CI 113 to 129). The rate of falls was 21% higher in people with polypharmacy compared with people without polypharmacy (adjusted IRR 1.21, 95% CI 1.11 to 1.31). Using ≥4 drugs threshold the rate of falls was 18% higher in people with polypharmacy compared with people without (adjusted IRR 1.18, 95% CI 1.08 to 1.28), whereas using ≥10 drugs threshold polypharmacy was associated with a 50% higher rate of falls (adjusted IRR 1.50, 95% CI 1.34 to 1.67)., Conclusions: We found almost one-third of the total population using five or more drugs, which was significantly associated with 21% increased rate of falls over a 2-year period. Further exploration of the effects of these complex drug combinations in the real world with a detailed standardised assessment of polypharmacy is greatly required along with pragmatic studies in primary care, which will help inform whether the threshold for a detailed medication review should be lowered., Competing Interests: Competing interests: KK has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. KK has received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme and Novo Nordisk. MJD has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Janssen, and as a speaker for Mitsubishi Tanabe Pharma Corporation. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis and Lilly., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: The aim of this systematic review is to explore the association of South Asian (SA) ethnicity on comorbidities, microvascular and macrovascular complications and mortality compared with other ethnic groups in people with type 1 diabetes mellitus (T1DM)., Design: Systematic review., Method: A systematic literature search strategy was designed and carried out using Medline and Embase for full-text and abstract studies published in English from 1946 to February 2016. The initial search identified 4722 papers. We assessed 305 full-text articles in detail for potential inclusion. Ten papers met the inclusion criteria for review and an additional one paper was included from our secondary search strategy using the bibliography of included studies. In total, 11 studies were included., Eligibility Criteria for Selecting Studies: Studies were included if they were published in English, involved SA participants with T1DM and compared them with non-SA participants and assessed one of the outcomes of comorbidities, microvascular complications, macrovascular complications and mortality., Results: SA with T1DM have higher mortality compared with white Europeans (WE), mainly contributed to by excess cardiovascular disease. SA have significantly higher glycated haemoglobin (HbA1c), lower high-density lipoprotein (HDL) and lower rates of neuropathy compared with WE. There were no differences in rates of retinopathy and nephropathy. Compared with Africans, SA had lower levels of microalbuminuria, HbA1c and systolic blood pressure and higher HDL levels. There were no significant differences in the remaining outcomes: cardiovascular disease, retinopathy, neuropathy and body mass index. Furthermore, SA have higher HbA1c levels than Malay and Chinese and higher waistâ€"hip ratio and lower HDL levels compared with Chinese only., Conclusion: Our analysis highlights ethnic disparity in macrovascular outcomes that is so evident for type 2 diabetes mellitus may also be present for SA patients with T1DM. We highlight the need for a large, prospective, cohort study exploring the effect of ethnicity in a uniform healthcare setting., Competing Interests: Competing interests: KK (co-chair), PS and PN are the members of the South Asian Health Foundation Working group on diabetes., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Patients with type 2 diabetes (T2DM) on insulin therapy are less satisfied with their diabetes treatment than those on oral hypoglycaemic therapies or lifestyle advice only. Determinants of satisfaction in patients with T2DM on insulin therapy are not clearly known. The aim of this study was to determine the association of treatment satisfaction with demographic and clinical characteristics of patients with T2DM., Design: For this study we used data from the GUIDANCE (Guideline Adherence to Enhance Care) study, a cross-sectional study among 7597 patients with T2DM patients from Belgium, France, Germany, Ireland, Italy, Sweden, the Netherlands and the UK. The majority of patients were recruited from primary care. Treatment satisfaction was assessed by the Diabetes Treatment Satisfaction Questionnaire (DTSQ, score 0-36; higher scores reflecting higher satisfaction). To determine which patient characteristics and laboratory values were independently associated with treatment satisfaction, a linear mixed model analysis was used., Participants: In total, 1984 patients on insulin were analysed; the number of included patients per country ranged from 166 (the Netherlands) to 384 (Italy)., Results: The mean DTSQ score was 28.50±7.52 and ranged from 25.93±6.57 (France) to 30.11±5.09 (the Netherlands). Higher DTSQ scores were associated with having received diabetes education (β 1.64, 95% CI 0.95 to 2.32), presence of macrovascular complications (β 0.76, 95% CI 0.21 to 1.31) and better health status (β 0.08 for every one unit increase on a 0-100 scale, 95% CI 0.07 to 0.10). Lower DTSQ scores were associated with more frequently perceived hyperglycaemia (β -0.32 for every 1 unit increase on a seven-point Likert scale, 95% CI -0.50 to -0.13), and higher glycated haemoglobin (β -0.52 for every percentage increase, 95% CI -0.75 to -0.29)., Conclusions: A number of factors including diabetes education, perceived and actual hyperglycaemia and macrovascular complications are associated with treatment satisfaction. Self-management education programmes should incorporate these factors for ongoing support in patients with T2DM., Competing Interests: Competing interests: AMB reports an unrestricted grant from Sanofi-Aventis for a study in type 2 diabetes patients on insulin therapy (support of self-management by mHealth), outside the submitted work. RCV reports an unrestricted grant from Sanofi-Aventis for a study in type 2 diabetes patients on insulin therapy (support of self-management by mHealth). Also an unrestricted grant is received from European Foundation for the Study of Diabetes for a study on the long-term effects of a self-management education course for patients with type 2 diabetes. Both outside the submitted work. TGTH, NPAZ and NM have nothing to disclose. KK is supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care, East Midlands (NIHR CIAHRC, EM) and the NIHR Leicester–Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University and the University of Leicester, UK (outside the submitted work). GEHMR received an unrestricted research grant from Sanofi-Aventis and fees from Novo Nordisk for consultancy and lecturing, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To describe low-density lipoprotein (LDL) cholesterol management and lipid-lowering treatment patterns in patients with a cardiovascular (CV) event., Design: Retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data., Setting: Routine clinical practice in the UK from 2006 to 2012., Participants: Individuals ≥18 years were selected at their first CV-related hospitalisation (first event cohort) if they had received ≥2 lipid-lowering therapy prescriptions within 180 days beforehand. Patients were stratified into four mutually exclusive subgroups based on the presence or absence of vascular disease and of diabetes. Those with a second CV hospitalisation within 36 months were included in a separate cohort (second event cohort)., Primary and Secondary Outcome Measures: LDL levels in the year prior to the CV event and 12 months later as well as measures of adherence to lipid-lowering therapy during the 12 months after the CV hospitalisation., Results: There were 24 093 patients in the first event cohort, of whom 5274 were included in the second event cohort. Most received moderate intensity statins at baseline and 12 months. Among the four first event cohort subgroups at baseline, the proportions with an LDL of <1.8 mmol/L was similar between the two diabetic cohorts (36% to 38%) and were higher than those in the two non-diabetic cohorts (17% to 22%) and in the second event cohort (31%). An incremental 5% to 9% had an LDL below 1.8 mmol/L at 12 months, suggesting intensification of therapy. The proportion of adherent patients (medication possession ratio of≥0.8) was highest for statins, ranging from 68% to 72%. For ezetimibe, the range was 65% to 70%, and for fibrates, it was 48% to 62%., Conclusions: Despite the existence of effective therapies for lowering cholesterol, patients do not reach achievable LDL targets., Competing Interests: Competing interests: MD, MG, and RG work with Outcomes Insights, Inc., which was funded to conduct this study. LK is an employee of Amgen, Inc. KK has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Janssen, Astra Zeneca and Boehringer Ingelheim. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim, Merck Sharp & Dohme, Janssen and Roche and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme, Novo Nordisk, Boehringer Ingelheim, Janssen and Astra Zeneca. SRKS has provided consulting to Amgen and received grants from Kowa and Sanofi. KKR has provided consultancy to Amgen, Sanofi, Pfizer, Regeneron, Astra Zeneca, Kowa, Aegerion, Merck Sharp & Dohme, Lilly and ISIS, and received grants from Sanofi, Regeneron, Amgen, Pfizer and Merck Sharp & Dohme through his institution., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To investigate the associations of objectively measured moderate-to-vigorous-intensity physical activity (MVPA) and body mass index (BMI) with glycated haemoglobin (HbA1c) in a national sample of English adults., Methods: The 2008 Health Survey for England data were used with 1109 participants aged ≥18 providing complete data. MVPA time was assessed using an accelerometer. Weighted linear regression models, adjusted for several confounders, quantified the associations between continuous measures of MVPA and BMI with HbA1c. Interaction analyses were implemented to observe whether the association of MVPA with HbA1c was modified by BMI or vice versa. Further weighted linear regression models examined the differences in HbA1c across four mutually exclusive categories of MVPA and BMI: (1) 'physically active and non-obese', (2) 'physically active and obese', (3) 'physically inactive and non-obese' and (4) 'physically inactive and obese'. 'Physically active' was defined as: ≥150 min/week of MVPA. 'Obese' was defined as: BMI ≥30.0 kg/m 2 . A wide range of sensitivity analyses were also implemented., Results: Every 30 min/day increment in MVPA was associated with a 0.7 mmol/mol (0.07% (p<0.001)) lower HbA1c level. Each 1 kg/m 2 increment in BMI was associated with a 0.2 mmol/mol (0.02% (p<0.001)) higher HbA1c level. The association of MVPA with HbA1c was stronger in obese individuals (-1.5 mmol/mol (-0.13% (p<0.001))) than non-obese individuals (-0.7 mmol/mol (-0.06% (p<0.001))); p=0.004 for interaction. The association of BMI with HbA1c remained stable across MVPA categories. Compared with individuals categorised as 'physically inactive and obese', only those categorised as 'physically active and obese' or 'physically active and non-obese' had lower HbA1c levels by 2.1 mmol/mol (0.19% (p=0.005)) and 3.5 mmol/mol (0.32% (p<0.001)), respectively. Sensitivity analyses indicated robustness and stability., Conclusions: This study emphasises the importance of physical activity as a determinant of HbA1c, and suggests that the associations may be stronger in obese adults., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To quantify associations between sitting time and glucose, insulin and insulin sensitivity by considering reallocation of time into standing or stepping., Design: Cross-sectional., Setting: Leicestershire, UK, 2013., Participants: Adults aged 30-75 years at high risk of impaired glucose regulation (IGR) or type 2 diabetes. 435 adults (age 66.8±7.4 years; 61.7% male; 89.2% white European) were included., Methods: Participants wore an activPAL3 monitor 24 hours/day for 7 days to capture time spent sitting, standing and stepping. Fasting and 2-hour postchallenge glucose and insulin were assessed; insulin sensitivity was calculated by Homeostasis Model Assessment of Insulin Secretion (HOMA-IS) and Matsuda-Insulin Sensitivity Index (Matsuda-ISI). Isotemporal substitution regression modelling was used to quantify associations of substituting 30 min of waking sitting time (accumulated in prolonged (≥30 min) or short (<30 min) bouts) for standing or stepping on glucose regulation and insulin sensitivity. Interaction terms were fitted to assess whether the associations with measures of glucose regulation and insulin sensitivity was modified by sex or IGR status., Results: After adjustment for confounders, including waist circumference, reallocation of prolonged sitting to short sitting time and to standing was associated with 4% lower fasting insulin and 4% higher HOMA-IS; reallocation of prolonged sitting to standing was also associated with a 5% higher Matsuda-ISI. Reallocation to stepping was associated with 5% lower 2-hour glucose, 7% lower fasting insulin, 13% lower 2-hour insulin and a 9% and 16% higher HOMA-IS and Matsuda-ISI, respectively. Reallocation of short sitting time to stepping was associated with 5% and 10% lower 2-hour glucose and 2-hour insulin and 12% higher Matsuda-ISI. Results were not modified by IGR status or sex., Conclusions: Reallocating a small amount of short or prolonged sitting time with standing or stepping may improve 2-hour glucose, fasting and 2-hour insulin and insulin sensitivity. Findings should be confirmed through prospective and intervention research., Trial Registration Number: ISRCTN31392913, Post-results., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: To characterise the costs to the UK National Health Service of cardiovascular (CV) events among individuals receiving lipid-modifying therapy., Design: Retrospective cohort study using Clinical Practice Research Datalink records from 2006 to 2012 to identify individuals with their first and second CV-related hospitalisations (first event and second event cohorts). Within-person differences were used to estimate CV-related outcomes., Setting: Patients in the UK who had their first CV event between January 2006 and March 2012., Participants: Patients ≥18 years who had a CV event and received at least 2 lipid-modifying therapy prescriptions within 180 days beforehand., Primary and Secondary Outcome Measures: Direct medical costs (2014 £) were estimated in 3 periods: baseline (pre-event), acute (6 months afterwards) and long-term (subsequent 30 months). Primary outcomes included incremental costs, resource usage and total costs per period., Results: There were 24 093 patients in the first event cohort of whom 5274 were included in the second event cohort. The mean incremental acute CV event costs for the first event and second event cohorts were: coronary artery bypass graft/percutaneous transluminal coronary angioplasty (CABG/PTCA) £5635 and £5823, myocardial infarction £4275 and £4301, ischaemic stroke £3512 and £4572, heart failure £2444 and £3461, unstable angina £2179 and £2489 and transient ischaemic attack £1537 and £1814. The mean incremental long-term costs were: heart failure £848 and £2829, myocardial infarction £922 and £1385, ischaemic stroke £973 and £682, transient ischaemic attack £705 and £1692, unstable angina £328 and £677, and CABG/PTCA £-368 and £599. Hospitalisation accounted for 95% of acute and 61% of long-term incremental costs. Higher comorbidity was associated with higher long-term costs., Conclusions: Revascularisation and myocardial infarction were associated with the highest incremental costs following a CV event. On the basis of real-world data, the economic burden of CV events in the UK is substantial, particularly among those with greater comorbidity burden., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: We investigate differences between White and South Asian (SA) populations in levels of objectively measured and self-reported physical activity., Design: Cross-sectional study., Setting: Leicestershire, UK, 2010-2011., Participants: Baseline data were pooled from two diabetes prevention trials that recruited a total of 4282 participants from primary care with a high risk score for type 2 diabetes. For this study, 2843 White (age=64±8, female=37%) and 243 SA (age=58±9, female=34%) participants had complete physical activity data and were included in the analysis., Outcome Measures: Moderate-intensity to vigorous-intensity physical activity (MVPA) and walking activity were measured using the International Physical Activity Questionnaire (IPAQ), and a combination of piezoelectric pedometer (NL-800) and accelerometer (Actigraph GT3X) were used to objectively measure physical activity., Results: Compared to White participants, SA participants self-reported less MVPA (30 vs 51 min/day; p<0.001) and walking activity (11 vs 17 min/day; P=0.001). However, there was no difference in objectively measured ambulatory activity (5992 steps/day vs 6157 steps/day; p=0.75) or in time spent in MVPA (18.0 vs 21.5 min/day; p=0.23). Results were largely unaffected when adjusted for age, sex and social deprivation. Compared to accelerometer data, White participants overestimated their time in MVPA by 51 min/day and SA participants by 21 min/day., Conclusions: SA and White groups undertook similar levels of physical activity when measured objectively despite self-reported estimates being around 40% lower in the SA group. This emphasises the limitations of comparing self-reported lifestyle measures across different populations and ethnic groups., Trial Registration Number: Reports baseline data from: Walking Away from Type 2 Diabetes (ISRCTN31392913) and Let's Prevent Diabetes (NCT00677937)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To investigate the relationship between neighbourhood greenspace and type 2 diabetes., Design: Cross-sectional., Setting: 3 diabetes screening studies conducted in Leicestershire, UK in 2004-2011. The percentage of greenspace in the participant's home neighbourhood (3 km radius around home postcode) was obtained from a Land Cover Map. Demographic and biomedical variables were measured at screening., Participants: 10,476 individuals (6200 from general population; 4276 from high-risk population) aged 20-75 years (mean 59 years); 47% female; 21% non-white ethnicity., Main Outcome Measure: Screen-detected type 2 diabetes (WHO 2011 criteria)., Results: Increased neighbourhood greenspace was associated with significantly lower levels of screen-detected type 2 diabetes. The ORs (95% CI) for screen-detected type 2 diabetes were 0.97 (0.80 to 1.17), 0.78 (0.62 to 0.98) and 0.67 (0.49 to 0.93) for increasing quartiles of neighbourhood greenspace compared with the lowest quartile after adjusting for ethnicity, age, sex, area social deprivation score and urban/rural status (Ptrend=0.01). This association remained on further adjustment for body mass index, physical activity, fasting glucose, 2 h glucose and cholesterol (OR (95% CI) for highest vs lowest quartile: 0.53 (0.35 to 0.82); Ptrend=0.01)., Conclusions: Neighbourhood greenspace was inversely associated with screen-detected type 2 diabetes, highlighting a potential area for targeted screening as well as a possible public health area for diabetes prevention. However, none of the risk factors that we considered appeared to explain this association, and thus further research is required to elicit underlying mechanisms., Trial Registration Number: This study uses data from three studies (NCT00318032, NCT00677937, NCT00941954)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To explore the relative association of admission blood glucose levels and antecedent diabetes on early and long-term survival in a contemporary UK population of patients with ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI)., Design: Retrospective cohort study based on the Myocardial Ischaemia National Audit Project dataset., Setting: Tertiary care centre., Participants: 4111 (20.3% known diabetes) consecutive patients admitted with acute myocardial infarction (58.3% STEMI) between October 2002 and September 2008., Primary and Secondary Outcome Measures: All-cause mortality at 30 days and 1 year. The relative association of admission blood glucose and of antecedent diabetes with mortality was assessed using multivariate Cox regression analysis. Furthermore, we compared these relationships in patients with STEMI to those with NSTEMI., Results: By 30 days and 1 year, 409 (9.9%) and 677 (16.5%) of patients died. After adjusting for covariates, diabetes did not show independent association with mortality at any time point, in the entire cohort (HR 30 days 0.93 (95% CI 0.63 to 1.38); 1 year 1.00 (0.77 to 1.30)) or in subgroups of STEMI (HR 30 days 1.03 (0.65 to 1.64); 1 year 1.08 (0.77 to 1.51)) and NSTEMI (HR 30 days 0.62 (0.26 to 1.50); 1 year 0.87 (0.56 to 1.36)). In contrast, after adjusting for covariates, admission glucose showed robust and independent association with mortality in the entire cohort (HR: 30 days 1.07 (1.04 to 1.10); 1 year 1.05 (1.03 to 1.08)), and in the subgroup of STEMI (30 days 1.07 (1.03 to 1.10); 1 year 1.07 (1.04 to 1.10)), and NSTEMI (HR 30 days 1.07 (1.00 to 1.14); 1 year 1.02 (0.97 to 1.06))., Conclusions: Admission glucose is strongly associated with mortality in all presentations of acute myocardial infarction (AMI), irrespective of established diabetes diagnosis. The increased risk is maintained up to 1 year. Future studies are required to assess the impact of active management of elevated blood glucose in improving mortality in individuals admitted with AMI.