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Background: People hospitalised for coronavirus disease 2019 (COVID-19) have elevated incidence of diabetes. However, it is unclear whether this is due to shared risk factors, confounding or stress hyperglycaemia in response to acute illness., Methods: We analysed a multicentre prospective cohort study (PHOSP-COVID) of people ≥18 years discharged from NHS hospitals across the United Kingdom following COVID-19. Individuals were included if they attended at least one research visit with a HbA1c measurement within 14 months of discharge and had no history of diabetes at baseline. The primary outcome was new onset diabetes (any type), as defined by a first glycated haemoglobin (HbA1c) measurement ≥6.5% (≥48 mmol/mol). Follow-up was censored at the last HbA1c measurement. Age-standardised incidence rates and incidence rate ratios (adjusted for age, sex, ethnicity, length of hospital stay, body mass index, smoking, physical activity, deprivation, hypertension, hyperlipidaemia/hypercholesterolaemia, intensive therapy unit admission, invasive mechanical ventilation, corticosteroid use and C-reactive protein score) were calculated using Poisson regression. Incidence rates were compared with the control groups of published clinical trials in the United Kingdom by applying the same inclusion and exclusion criteria, where possible., Results: Incidence of diabetes was 91.4 per 1000 person-years and was higher in South Asian (incidence rate ratios [IRR] = 3.60; 1.77, 7.32; p < 0.001) and Black ethnic groups (IRR = 2.36; 1.07, 5.21; p = 0.03) compared with White ethnic groups. When restricted to similar characteristics, the incidence rates were similar to those in UK clinical trials data., Conclusion: Diabetes incidence following hospitalisation for COVID-19 is high, but it remains uncertain whether it is disproportionately higher than pre-pandemic levels., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The benefits of randomised trials are not shared equally, and people from ethnic minority groups are a key constituency under-served by clinical research and clinical care. The STRIDE project aimed to give trialists practical information about how to decide which ethnic groups should be in their trials, and at what proportion., Methods: We considered trials in six clinical areas: cancer, cardiovascular, diabetes, maternal health, mental health, and smoking cessation. We created a summary for each, including participants-intervention-comparators-outcomes, and data on disease prevalence by ethnicity. These were discussed with panels with clinical expertise, trial and methodology expertise, lived experience, funding, and experience of working with and on behalf of ethnic communities. For each trial, we asked panel members to decide which ethnic groups should have been involved and at what proportion., Results: We discussed 23 trials with 40 individual panel members. Panels found our questions difficult to answer. The lack of publicly available data on prevalence by ethnicity was central to this. Where data were available, decision-making was easier but not simple. The discussions led to eight STRIDE recommendations. We recommend that discussions involve diverse teams and that discussions need time, with access to the best available data. In the absence of data or consensus, we recommend the adoption of 'default' minimum rates of inclusion, with oversampling considered. These discussions should inform site selection, and the practical challenges of recruitment and retention should not determine which groups are to be included. We also suggest five policy initiatives to support implementation of the recommendations. Broadly, these are (1) funders need to signal that ethnic diversity is expected, (2) trial teams need access to better data, (3) funders and others need to signal that ethnic diversity means better science, (4) more funding is needed for evaluation, and (5) Good Clinical Practice training should cover ethnic diversity., Conclusions: Agreeing targets for which ethnic groups to involve in a trial is essential but difficult. Our eight recommendations could help to make trials more ethnically diverse if followed, and we suggest five policy initiatives that would create a supportive environment for their implementation., Competing Interests: Declarations Ethics approval and consent to participate Ethics approval was not required for this work. Members of the public who took part did so as patient and public partners helping to drive and shape the work, not as research participants. Consent for publication Not applicable for this article. Competing interests KK is Director for Centre for Ethnic Health Research, University of Leicester, UK. ST is an Editor-in-Chief of Trials. All other authors declare no competing interests., (© 2024. The Author(s).)

Objective: To describe which combinations of long term conditions were associated with a higher risk of hospital admission or death during winter 2021-22 (the third wave of the covid-19 pandemic) in adults in England., Design: Population based cohort study., Setting: Linked primary and secondary care data from the General Practice Extraction Service Data for Pandemic Planning and Research (GDPPR) database, Hospital Episode Statistics, and Office for National Statistics death registry, comprising pseudoanonymised routinely collected electronic medical records from the whole population of England registered at a general practice, 1 December 2021 to 31 March 2022., Participants: 48 253 125 individuals, registered in GDPPR in England, aged ≥18 years, and alive on 1 December 2021., Main Outcomes Measures: All cause hospital admissions and deaths associated with combinations of multiple long term conditions compared with those with no long term conditions, during the winter season (1 December 2021 to 31 March 2022). Overdispersed Poisson regression models were used to estimate the incidence rate ratios after adjusting for age, sex, ethnic group, and index of multiple deprivation., Results: Complete data were available for 48 253 125 adults, of whom 15 million (31.2%) had multiple long term conditions. Rates of hospital admissions and deaths among individuals with no long term conditions were 96.3 and 0.8 per 1000 person years, respectively. Compared with those with no long term conditions, the adjusted incidence rate ratio of hospital admissions were 11.0 (95% confidence interval (CI) 9.4 to 12.7) for those with a combination of cancer, chronic kidney disease, cardiovascular disease, and type 2 diabetes mellitus; 9.8 (8.3 to 11.4) for those with cancer, chronic kidney disease, cardiovascular disease, and osteoarthritis; and 9.6 (8.6 to 10.7) for those with cancer, chronic kidney disease, and cardiovascular disease. Compared with those with no long term conditions, the adjusted rate ratio of death was 21.4 (17.5 to 26.0) for those with chronic kidney disease, cardiovascular disease, and dementia; 23.2 (17.5 to 30.3) for those with cancer, chronic kidney disease, cardiovascular disease, and dementia; and 24.3 (19.1 to 30.4) for those with chronic kidney disease, cardiovascular disease, dementia, and osteoarthritis. Cardiovascular disease with dementia appeared in all of the top five combinations of multiple long term conditions for mortality, and this two disease combination was associated with a substantially higher rate of death than many three, four, and five disease combinations., Conclusions: In this study, rates of hospital admission and death varied by combinations of multiple long term conditions and were substantially higher in those with than in those without any long term conditions. High risk combinations for prioritisation and preventive action by policy makers were highlighted to help manage the challenges imposed by winter pressures on the NHS., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research (NIHR) for the submitted work; KK, CLG, FZ, and SS are supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM), NIHR Global Research Centre for Multiple Long-Term Conditions, the NIHR Leicester Biomedical Research Centre (BRC) and the British Heart Foundation Centre for Excellence; KK and HDM are supported by the Cross NIHR Collaboration for Multiple Long Term Conditions; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: We aimed to estimate regional inequalities in excess deaths and premature mortality in Spain during 2020 and 2021, before high vaccination coverage against COVID-19., Method: With data from the National Institute of Statistics, within each region, sex, and age group, we estimated the excess deaths, the change in life expectancy at birth (e 0 ) and age 65 (e 65 ) and years of life lost as the difference between the observed and expected deaths using a time series analysis of 2015-2019 data and life expectancies based on Lee-Carter forecasting using 2010-2019 data., Results: From January 2020 to June 2021, an estimated 89,200 (men: 48,000; women: 41,200) excess deaths occurred in Spain with a substantial regional variability (highest in Madrid: 22,000, lowest in Canary Islands: -210). The highest reductions in e 0 in 2020 were observed in Madrid (men -3.58 years, women -2.25), Castile-La Mancha (-2.72, -2.38), and Castile and Leon (-2.13, -1.39). During the first half of 2021, the highest reduction in e 0 was observed in Madrid for men (-2.09; -2.37 to -1.84) and Valencian Community for women (-1.63; -1.97 to -1.3). The highest excess years of life lost in 2020 was in Castile-La Mancha (men: 5370; women: 3600, per 100 000). We observed large differences between reported COVID-19 deaths and estimated excess deaths across the Spanish regions., Conclusions: Regions performed highly unequally on excess deaths, life expectancy and years of life lost. The investigation of the root causes of these regional inequalities might inform future pandemic policy in Spain and elsewhere., (Copyright © 2024 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised., Methods: In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital. We excluded individuals with less than 1 year of medical history records in primary or secondary care; admissions to NHS hospitals for which less than 10% of heart failure cases were linkable to the National Heart Failure Audit (NHFA); individuals younger than 18 years at the time of the heart failure hospitalisation; and patients who died in hospital during the index heart failure admission. For patients with new onset heart failure, we assessed incidence rates of 30-day and 1-year all-cause and cause-specific (cardiovascular, non-cardiovascular, and heart failure-related) emergency rehospitalisation and mortality after discharge, and dispensed guideline-recommended medical therapy (GRMT). Follow-up occurred from the index admission to the earliest occurrence of the event of interest, death, or end of data coverage. We estimated adjusted hazard ratios (HRs) to compare HFrEF with HFpEF. We computed population-attributable fractions to quantify the percentage of outcomes attributable to coexisting chronic medical conditions., Findings: Among 233 320 patients identified who survived the index heart failure admission across 335 NHS hospitals between Jan 1, 2019, and Dec 31, 2022, 101 320 (43·4%) had HFrEF, 71 910 (30·8%) had HFpEF, and 60 090 (25·8%) had an unknown classification. In patients with new onset heart failure, there were reductions in all-cause 30-day (-5·2% [95% CI -7·7 to -2·6] in 2019-22) and 1-year rehospitalisation rates (-3·9% [-6·6 to -1·2]). Declining 30-day rehospitalisation rates affected patients with HFpEF (-4·8% [-9·2 to -0·2]) and HFrEF (-6·2% [-10·5 to -1·6]), although 1-year rates were not statistically significant for patients with HFpEF (-2·2% [-6·6 to 2·3] vs -5·7% [-10·6 to -0·5] for HFrEF). There were no temporal trends in incidence rates of 30-day or 1-year mortality after discharge. The rates of all-cause (HR 1·20 [1·18-1·22]) and cause-specific rehospitalisation were uniformly higher in those with HFpEF than those with HFrEF. Patients with HFpEF also had higher rates of 1-year all-cause mortality after discharge (HR 1·07 [1·05-1·09]), driven by excess risk of non-cardiovascular death (HR 1·25 [1·21-1·29]). Rates of rehospitalisation and mortality were highest in patients with coexisting chronic kidney disease, chronic obstructive pulmonary disease, dementia, and liver disease. Chronic kidney disease contributed to 6·5% (5·6-7·4) of rehospitalisations within 1 year for HFrEF and 5·0% (4·1-5·9) of rehospitalisations for HFpEF, double that of any other coexisting condition. There was swift implementation of newer GRMT, but markedly lower dispensing of these medications in patients with coexisting chronic kidney disease., Interpretation: Rates of rehospitalisation in patients with heart failure in England have decreased during 2019-22. Further population health improvements could be reached through enhanced implementation of GRMT, particularly in patients with coexisting chronic kidney disease, who, despite being at high risk, remain undertreated., Funding: Wellcome Trust, Health Data Research UK, British Heart Foundation Data Science Centre., Competing Interests: Declaration of interests RAF received studentship awards from the Health Data Research UK-The Alan Turing Institute Wellcome Trust PhD Programme in Health Data Science (grant 218529/Z/19/Z). PR received a grant from the Dr Johannes and Hertha Tuba Foundation. BLN reports fees for travel support, advisory boards, scientific presentations, and steering committee roles from AstraZeneca, Alexion, Bayer, Boehringer Ingelheim, Cambridge Healthcare Research, Cornerstone Medical Education, Janssen, Limbic, Medscape, Novo Nordisk, and Travere Therapeutics with all honoraria paid to the George Institute for Global Health. CT received a studentship from the University College London UK Research and Innovation Centre for doctoral training in AI-enabled healthcare (EP/S021612/1), Medical Research Council Clinical Top-Up, and a studentship from the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at University College London Hospital NHS Trust. NC received a personal fellowship from the Research Foundation Flanders and a research grant from the European Society of Cardiology. ER is funded by Forte Swedish Research Council for Health, Working Life And Welfare (2022–00882) individual postdoctoral fellowship, and Vetenskapsrådet Swedish Research Council (grant 2023–01982). SD received research funding from GlaxoSmithKline, AstraZeneca, Bayer, and BenevolentAI. CS is a director of the British Heart Foundation Data Science Centre and a chief scientist and deputy director at Health Data Research UK; has codeveloped National Health Service (NHS) England Secure Data Environment; and leads the CVD-COVID UK/COVID-IMPACT Consortium. SEP has a leadership role for the European Association of Cardiovascular Imaging, received consulting fees from Circle Cardiovascular Imaging, and holds an advisory role for the PROTEUS trial (NCT05028179). GMC served on the board of directors of Satellite Healthcare; served as chair or cochair of trial steering committees for Akebia, AstraZeneca, CSL Behring, Sanifit, and Vertex; served as an advisor for Applaud, CloudCath, Durect, Eliaz Therapeutics, Miromatrix, Outset, Physiowave, Renibus, and Unicycive; and served on data safety monitoring boards for Bayer, Mineralys, and ReCor. KK acted as a consultant or speaker and receiving grants for investigator-initiated studies from AstraZeneca, Abbott, Amgen, Bayer, Daiichi-Sankyo, Embecta, Nestle Health Science, Novartis, Novo Nordisk, Roche, Servier, Sanofi-Aventis, Lilly, MSD, Boehringer Ingelheim, Oramed Pharmaceuticals, and Applied Therapeutics; and was a chair of the scientific advisory group for Emergencies Ethnicity Subgroup. JS has direct or indirect stock ownership in Anagram Kommunikation, Sence Research, Symptoms Europe, and MinForskning; and professional services to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Göteborg University, Itrim, Ipsen, Janssen, Karolinska Institutet, LIF, Linköping University, Novo Nordisk, Parexel, Pfizer, Region Stockholm, Region Uppsala, Sanofi, STRAMA, Takeda, TLV, Uppsala University, Vifor Pharma, and WeMind. CA received grants from the National Health Medical Research Council (Medical Research Futures Fund) and NSW Health; and honoraria from AstraZeneca, Novo Nordisk, and Amgen. JGFC reports receipt of personal honoraria for lectures and advisory boards from Pharmacosmos, Vifor, AstraZeneca, Amgen, Bayer, Novartis, and Servier; has received research grants through The University of Glasgow from Pharmacosmos and Vifor; and received funding from the British Heart Foundation Center of Research Excellence (RE/18/6134217). JD reports grants, personal fees, and non-financial support from MSD and Novartis; grants from Pfizer and AstraZeneca; and is part of the International Cardiovascular and Metabolic Advisory Board for Novartis, Steering Committee of UK Biobank, MRC International Advisory Group, MRC High Throughput Science Omics Panel, Scientific Advisory Committee for Sanofi, International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis, AstraZeneca Genomics Advisory Board, Scientific Advisory Board of Nightingale Health, Access Board of Our Future Health, and Scientific Advisory Committee of Leducq Foundation. JJVM received payments through Glasgow University for work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis; personal consultancy fees from Alnylam Pharma, Bayer, BMS, George Clinical, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal; personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharma, JB Pharma, Lupin Pharma, Medscape (Heart.org), ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, and Translational Medicine Academy; and is a director of Global Clinical Trial Partners. MV received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer, Baxter, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for AstraZeneca, Galmed, Novartis, Bayer, Occlutech, and Impulse Dynamics. AMW received funding from the British Heart Foundation Data Science Centre (HDRUK2023.0239) and NIHR (NIHR303137). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Decentralized clinical trials involving the use of digital tools to facilitate remote research are gaining momentum. Rapid advancements in digital technologies have supported the adoption of these trials. These innovations facilitate virtual interactions between clinical trial teams and participants by making it easier to collect, transfer and store electronic data. While some studies have demonstrated the potential for these approaches to reduce barriers to clinical trial participation, they are associated with several challenges that may create or worsen existing health inequalities and limit the generalizability of trial results. Here we review the potential for digitally enabled and decentralized clinical trials to enhance clinical trial participation in an equitable manner. We describe the key barriers individuals from underserved groups may face, and provide recommendations to promote equity, diversity and inclusion., Competing Interests: Competing interests O.L.A. receives funding from the NIHR Birmingham Biomedical Research Centre (BRC), NIHR Blood and Transplant Research Unit (BTRU) in Precision Transplant and Cellular Therapeutics, NIHR Applied Research Collaboration (ARC) West Midlands, UK Research and Innovation (UKRI), LifeArc, Health Foundation, Merck, Gilead, Anthony Nolan, Sarcoma UK and GSK. O.L.A. declares personal fees from Gilead Sciences, Merck and GSK outside the submitted work. S.C.R. receives funding from UK SPINE and Merck, and declares personal fees from Merck. M.J.C. is director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, director of the Centre for the Centre for Patient Reported Outcomes Research and an NIHR Senior Investigator. M.J.C. receives funding from the NIHR, UKRI, NIHR Birmingham BRC, the NIHR Surgical Reconstruction and Microbiology Research Centre, NIHR ARC West Midlands, LifeArc, UK SPINE, European Regional Development Fund—Demand Hub and Health Data Research UK at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Innovate UK (part of UKRI), Macmillan Cancer Support, UCB Pharma, Janssen, GSK and Gilead. M.C. has received personal fees from Astellas, Aparito, CIS Oncology, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK, Pfizer, the Patient-Centered Outcomes Research Institute and Vertex outside the submitted work. In addition, a family member owns shares in GSK. N.A. is an NIHR Senior Research Leader and receives funding from the NIHR, NIHR ARC West Midlands and NIHR Birmingham BRC. S.E.H. receives funding from the NIHR, NIHR BTRU in Precision Transplant and Cellular Therapeutics, NIHR Birmingham BRC, NIHR (ARC) West Midlands, UKRI and UK SPINE. S.E.H. declares personal fees from Cochlear, Pfizer, Rinri Therapeutics, Astra Zeneca, Aparito and CIS Oncology outside the submitted work. K.K. has acted as a consultant, speaker or received grants for investigator-initiated studies for Astra Zeneca, Bayer, Novo Nordisk, Sanofi-Aventis, Servier, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Pfizer, Roche, Daiichi Sankyo, Applied Therapeutics, Embecta and Nestle Health Science. K.K. is supported by the NIHR Applied Research Collaboration East Midlands (ARC EM), the NIHR Leicester BRC and the British Heart Foundation (BHF) Centre of Excellence. D.K. reports grants from the NIHR (CDF-2015-08-074 RATE-AF, NIHR130280 DaRe2THINK, NIHR132974 D2T-NeuroVascular, NIHR203326 Biomedical Research Centre), the BHF (PG/17/55/33087, AA/18/2/34218 and FS/CDRF/21/21032), the EU/EFPIA Innovative Medicines Initiative (BigData@Heart 116074), EU Horizon and UKRI (HYPERMARKER 101095480), UK National Health Service—Data for R&D-Subnational Secure Data Environment programme, UK Department for Business, Energy & Industrial Strategy Regulators Pioneer Fund, the Cook & Wolstenholme Charitable Trust and the European Society of Cardiology supported by educational grants from Boehringer Ingelheim/BMS-Pfizer Alliance/Bayer/Daiichi Sankyo/Boston Scientific, the NIHR/University of Oxford Biomedical Research Centre and BHF/University of Birmingham Accelerator Award (STEEER-AF); in addition, D.K. has received research grants and advisory board fees from Bayer, Amomed and Protherics Medicines Development; all are outside the submitted work. C.M. receives funding from NIHR Surgical Reconstruction and Microbiology Research Centre, UKRI, NIHR, NIHR BTRU in Precision Transplant and Cellular Therapeutics and declares personal fees from Aparito outside the submitted work. A.D. is deputy director of the Birmingham Health Partners Centre for Regulatory Science and Innovation and is an NIHR Senior Investigator. A.D. receives funding from the NIHR, UKRI and NIHR Birmingham BRC. J.M. is chief editor at Nature Medicine and has excused himself from the peer review and editorial process of this article. P.M. is director of the Clinical Practice Research Datalink, a UK government real-world data research service that also provides clinical trial recruitment services. R.H. receives funding from the Leverhulme Trust., (© 2024. Springer Nature America, Inc.)

Aims: To explore the 5-year incidence and relative rates of sleep disorders in younger (16-≤40 years) and middle-older (=>40 years) age adults with and without newly diagnosed type 2 diabetes., Methods: This retrospective, observational cohort study utilised data from the US Collaborative Network within the TriNetX database. We compared 5-year cumulative incidence of sleep disorders in younger (n = 110,088) and middle-older populations (n = 1,185,961)., Results: The absolute risk of developing any type of sleep disorder was greater in individuals with type 2 diabetes vs. those without. Over the 5-year follow-up period, 14.2 % of younger adults and 18.5 % of middle-older age adults with newly diagnosed type 2 diabetes developed any form of sleep disorder, compared to 4.5 % and 7.9 % propensity matched individuals without diabetes. We observed a more pronounced relative rate across the observed sleep disorders in younger adults., Conclusions: The 5-year risk of sleep disorders is higher in those with newly diagnosed type 2 diabetes vs. those without. A higher absolute risk was seen in middle-older adults, but relative rates were consistently higher in younger adults with type 2 diabetes. Sleep should be regularly discussed as part of a holistic approach to diabetes care, particularly in those aged ≤40., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [TY has received research funding from AstraZeneca and Abbott. KK has served as a consultant, speaker or received research grants/support from AstraZeneca, Boehringer Ingelheim, Lilly, and Novo Nordisk. MJD has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk and Sanofi, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Pfizer, Medtronic and ShouTi Pharma Inc and as a speaker for Napp Pharmaceuticals, Novartis 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, AstraZeneca and Janssen. The other authors have no conflicts of interest to declare]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: COVID-19 pandemic restrictions may have influenced behaviours related to weight., Aim: To describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic., Design and Setting: An observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP., Method: Clinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m 2 /year) were investigated using multivariable logistic regression., Results: Data were extracted on adults with T2D ( n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension ( n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = -0.1 kg/m 2 /year [interquartile range {IQR} -0.7-0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60-69 years versus 18-29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m 2 /year [IQR -0.6-0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D., Conclusion: Among adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions., (© The Authors.)

Background: Digital health interventions (DHIs) could support prevention and management of cardiometabolic disease. However, those who may benefit most often experience barriers to awareness and adoption of these interventions., Objective: Among South Asian individuals, we evaluated user experience of DHIs for prevention and management of cardiometabolic disease, aiming to understand barriers and facilitators to initial and ongoing use., Methods: Among South Asian individuals recruited via primary care, community organizations, and snowball methods (n=18), we conducted "think-aloud" interviews using a reflective and reactive approach. Participants included nonusers, as well as those that used a range of DHIs as part of monitoring and improving their health. Participants were asked to think aloud while completing a task they routinely do in a familiar DHI, as well as while setting up and completing a search task in a novel DHI; they were encouraged to behave as if unobserved., Results: Lack of cultural specificity was highlighted as reducing relevance and usability, particularly relating to dietary change. Preferred features reflected individual health beliefs and behaviors, digital skills, and trust in DHIs. For example, tracking blood glucose was considered by some to be positive, while for others it caused distress and anxiety. Similarly, some users found the novel DHI to be extremely simple to set up and use, and others grew frustrated navigating through initial interfaces. Many participants raised concerns about data privacy and needing to agree to terms and conditions that they did not understand. Participants expressed that with information and support from trusted sources, they would be interested in using DHIs as part of self-management., Conclusions: DHIs may support South Asians to prevent and manage cardiometabolic disease, but it is important to consider the needs of specific user groups in DHI development, design, and implementation. Despite motivation to make health changes, digital barriers are common. Cultural appropriateness and trusted sources (such as health care providers and community organizations) have roles in increasing awareness and enabling individuals to access and use DHIs., (© Mel Ramasawmy, Dan Roland Persson, David Sunkersing, Paramjit Gill, Kamlesh Khunti, Lydia Poole, Wasim Hanif, Ann Blandford, Madiha Sajid, Fiona Stevenson, Nushrat Khan, Amitava Banerjee. Originally published in JMIR Human Factors (https://humanfactors.jmir.org).)

Background and Aims: Type 2 diabetes prevention programs are effective but costly and intensive, making translation into routine primary care and community settings challenging. Identifying drivers of intervention effectiveness can inform pragmatic future implementation whilst maintaining effectiveness. Translational studies have demonstrated that delivery modalities impact their effectiveness. This systematic review and component network meta-analysis assessed which delivery modality components of non-pharmacological diabetes prevention programs are associated with reductions in type 2 diabetes incidence for individuals at high risk of type 2 diabetes (or pre-diabetes)., Methods: We searched MEDLINE, The Cochrane Library, Opengrey and clinicaltrials.gov from inception to November 17, 2022 for translational studies comparing lifestyle interventions with a minimum 12-month follow-up. Two investigators extracted the data. Random effects network meta-analyses and component network meta-analyses estimated the intervention effects., Results: We identified 50 eligible studies involving 29,286 participants including thirty-six (72.0 %) randomized controlled trials, 10 (20.0 %) cluster randomized controlled trials, and four (8.0 %) observational studies. Component network meta-analyses found in-person (individually) delivery was associated with greater reduction in incidence of type 2 diabetes (hazard ratio: 0.66, 95 % credible interval: 0.41, 0.96) and in-person (group-based) delivery was associated with greater reductions in weight (mean difference: -1.53 kg, 95 % credible interval: -2.18, -0.85) and HbA1c (mean difference: -0.74 mmol/mol, 95 % credible interval: -1.28, -0.17), relative to usual care., Conclusions: This analysis suggests in-person delivery modalities are most effective for diabetes prevention. Future research should focus on improving the effectiveness of digital programs and ensuring preferential delivery for target populations to reduce health inequalities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Background: Pharmacists are uniquely placed with their therapeutic knowledge to manage people with chronic kidney disease (CKD). Data is limited regarding the impact of pharmacist interventions on economic, clinical, and humanistic outcomes (ECHO)., Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) of interventions with pharmacist input was conducted, which included adults with a diagnosis of CKD, including those with and without kidney replacement therapy. Data was extracted on ECHO: economic (e.g. healthcare-associated costs), clinical (e.g. mortality), and humanistic (e.g. patient satisfaction) outcomes. Where appropriate, a random-effects model meta-analysis generated a pooled estimate of effect. A direction of effect plot was used to summarize the overall effects for clinical outcome domains., Results: 32 RCTs reported a total of 10 economic, 211 clinical, and 18 humanistic outcomes. Pharmacist interventions resulted in statistically significant improvements in systolic blood pressure and hemoglobin levels, but not in diastolic blood pressure, estimated glomerular filtration rate, creatinine, and low-density lipoprotein cholesterol levels. Mixed findings were reported for clinical and economic outcomes, whilst pharmacist interventions resulted in an improvement in humanistic outcomes such as patient satisfaction and patient knowledge., Conclusion: Findings showed pharmacist interventions had mixed results for various outcomes. Future studies should be more robustly designed and take into consideration the role of the pharmacist in prescribing and deprescribing, the findings of which will help inform research and clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background/objectives: Saudi Arabia is experiencing a rapid increase in chronic diseases and disabilities. However, there is a dearth of research on these topics in the Arab world. This study aimed to examine the prevalence of multiple long-term chronic conditions (MLTCs) and disabilities and their relationship., Methods: The survey was conducted in Riyadh, Saudi Arabia, in 2023. Convenient sampling was used to select 324 participants aged 50 years and older, using data on disabilities status. The survey collected information on age, sex, body mass index (BMI), MLTCs or multi-morbidity, and activities of daily living (ADL). Disabilities was measured using Arabic versions of basic ADL and the Barthel index., Results: The prevalence of MLTCs among participants was 49.4%. The prevalence of disabilities measured using the ADL and Barthel index was 33.6 and 49.7%, respectively, and these rates increased by 42.5 and 58.1% among participants with MLTCs ( n  = 160). MLTCs were associated with an increased risk of disabilities using ADL [odds ratio (OR) 1.99, p  = 0.037] and the Barthel index (OR 2.27, p  = 0.007)., Conclusion: Approximately half of the participants with disabilities data had MLTCs, and approximately a third to half had a disabilities. MLTCs were significantly associated with various types of disabilities among community-dwelling Saudi adults. Hence, strategies to reduce chronic diseases may result in a reduction in disabilities, and vice versa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alenazi, Alhwoaimel, Alqahtani, Alshehri, Alhowimel and Khunti.)

Aims/hypothesis: The aim of this study was to investigate how diabetes mellitus affects longer term outcomes in individuals presenting to hospital with non-ST segment elevation myocardial infarction (NSTEMI)., Methods: We analysed data from 456,376 adults hospitalised between January 2005 and March 2019 with NSTEMI from the UK Myocardial Ischaemia National Audit Project (MINAP) registry, linked with Office for National Statistics death reporting. We compared outcomes and quality of care by diabetes status., Results: Individuals with diabetes were older (median age 74 vs 73 years), were more often of Asian ethnicity (13% vs 4%) and underwent revascularisation (percutaneous coronary intervention or coronary artery bypass graft surgery) (38% vs 40%) less frequently than those without diabetes. The mortality risk for those with diabetes compared with those without was significantly higher at 30 days (HR 1.19, 95% CI 1.15, 1.23), 1 year (HR 1.28, 95% CI 1.26, 1.31), 5 years (HR 1.36, 95% CI 1.34, 1.38) and 10 years (HR 1.39, 95% CI 1.36, 1.42). In individuals with diabetes, higher quality inpatient care, assessed by opportunity-based quality indicator (OBQI) score category ('poor', 'fair', 'good' or 'excellent'), was associated with lower mortality rates compared with poor care (good: HR 0.74, 95% CI 0.73, 0.76; excellent: HR 0.69, 95% CI 0.68, 0.71). In addition, compared with poor care, excellent care in the diabetes group was associated with the lowest mortality rates in the diet-treated and insulin-treated subgroups (diet-treated: HR 0.64, 95% CI 0.61, 0.68; insulin-treated: HR 0.69, CI 0.66, 0.72)., Conclusion/interpretation: Individuals with diabetes experience disparities during inpatient care following NSTEMI. They have a higher risk of long-term mortality than those without diabetes, and higher quality inpatient care may lead to better long-term survival., Competing Interests: Data availability: The data underlying this article were provided by the National Institute for Cardiovascular Outcomes Research (NICOR). Data will be shared on request to the corresponding author with the permission of NICOR. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: All authors made substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data; and drafting or reviewing the article critically for important intellectual content. All authors approved the final version to be published. MAM is responsible for the integrity of the work as a whole., (© 2024. The Author(s).)

Objectives: To describe the direct impact of coronavirus disease 2019 (COVID-19) infection on morbidity and mortality in people with multiple long-term conditions (MLTCs)., Design: A systematic review and meta-analysis including observational studies., Setting: Studies conducted between 1 January 2020 and 4 May 2023 across 51 countries were identified from five databases., Participants: A total of 4,084,469 patients with confirmed COVID-19 infection., Main Outcome Measures: Pooled risk ratios (RRs) for mortality, hospitalisation, severe disease, intensive care unit (ICU) admission and mechanical ventilation were estimated with random effect meta-analysis models., Results: A total of 38,356 studies were identified and 111 included. In most (74%) of the studies, MLTCs referred to having two or more long-term conditions. Others described MLTCs by high weighted indices: the Charlson Comorbidity Index in 11% and the Clinical Frailty Score in 7%. Using the National Institutes of Health quality assessment tool for observational studies, the risk of bias was judged as low and moderate in 86 and 25 studies, respectively. Having MLTCs was associated with increased mortality (RR: 2.61 [95% CI: 2.27 to 3.0]); hospitalisation (2.4 [1.92 to 2.99]); severe disease (2.61 [1.92 to 3.54]); ICU admission (1.22 [1.07 to 1.39]) and mechanical ventilation (1.83 [1.18 to 2.84]) compared with those with no MLTCs. Pooled RRs for adverse outcomes were higher in children and young people compared with all age groups. In meta-regression analyses, men were more likely to need ICU admission ( p  = 0.013) and mechanical ventilation ( p  = 0.002)., Conclusions: Public health policies, clinical and preventative interventions should prioritise people with MLTCs to minimise direct adverse outcomes from COVID-19 disease.

Cardiovascular clinical trials continue to under-represent children, older adults, females and people from ethnic minority groups relative to population disease distribution. Here we describe strategies to foster trial representativeness, with proposed actions at the levels of trial funding, design, conduct and dissemination. In particular, trial representativeness may be increased through broad recruitment strategies and site selection criteria that reflect the diversity of patients in the catchment area, as well as limiting unjustified exclusion criteria and using pragmatic designs that minimize research burden on patients (including embedded and decentralized trials). Trial communications ought to be culturally appropriate; engaging diverse people with lived experience in the co-design of some trial elements may foster this. The demographics of trialists themselves are associated with participant demographics; therefore, trial leadership must be actively diversified. Funding bodies and journals increasingly require the reporting of sociodemographic characteristics of trial participants, and regulatory bodies now provide guidance on increasing trial diversity; these steps may increase the momentum towards change. Although this Perspective focuses on the cardiovascular trial context, many of these strategies could be applied to other fields., (© 2024. Springer Nature America, Inc.)

Aim: To investigate the relationship between age at diagnosis of type 2 diabetes and the risk of macrovascular disease, heart failure, and microvascular disease., Methods: In August 2022, PubMed/EMBASE were searched for articles reporting (i) coronary artery disease, cerebrovascular disease, peripheral vascular disease, amputation; (ii) heart failure; and (iii) retinopathy, neuropathy, nephropathy (albuminuria, chronic kidney disease [CKD], end-stage renal disease) by age at diagnosis of type 2 diabetes. Random effects, non-linear dose-response meta-analysis was undertaken for each outcome to assess the association with age at diagnosis (40 years = reference), using both crude and maximally adjusted odds ratios separately, with and without adjustment for current age (age at sampling)., Results: We identified 42 articles (230,003 to 3,465,590 participants; 1035 to 391,140 events). Age at diagnosis was positively associated with the risk of macrovascular diseases, heart failure, and CKD, independent of current age, and negatively associated with retinopathy. For other microvascular outcomes, when adjusting for current age, a "reverse U" relationship was observed (peak risk = 55-60 years)., Discussion: Retinopathy was negatively associated with age at diagnosis, highlighting the importance of retinopathy screening in early-onset type 2 diabetes. The implications of other associations were unclear due to the heterogeneity in methodologies and findings., Competing Interests: Declaration of competing interest KK has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim and Bayer. MJD has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk and Sanofi, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Pfizer, Medtronic and ShouTi Pharma Inc. and as a speaker for Napp Pharmaceuticals, Novartis 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, AstraZeneca and Janssen. JAS received a grant for an investigator-initiated study for AstraZeneca. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Early-stage (stage 1-3) chronic kidney disease (CKD) has an asymptomatic presentation such that most people with CKD are unaware of their disease status and remain undiagnosed. CKD is associated with multiple long-term conditions (MLTC), or multimorbidity, the most common of these being cardiovascular disease, hypertension, and type 2 diabetes. Primary care practitioners (PCPs) are crucial in the early identification and management of patients with CKD. For individuals at high risk of CKD, measurements of estimated glomerular filtration rate, urine albumin-creatinine ratio, and blood pressure should be obtained regularly and recorded in a timely manner. The importance of lifestyle changes in the prevention and management of CKD should also be highlighted. A recent addition to the treatment of CKD in people with and without type 2 diabetes has been the recommendation by clinical practice guidelines of a sodium-glucose co-transporter 2 (SGLT2) inhibitor alongside a renin-angiotensin-aldosterone system inhibitor as foundational therapy. SGLT2 inhibitors prevent CKD progression and reduce fatal and non-fatal kidney and cardiovascular events, hospitalization for heart failure, and all-cause mortality, and they have a favorable safety and tolerability profile. However, uptake has been slow, particularly in people with CKD without type 2 diabetes. A multifaceted approach is required to ensure that people with CKD receive optimal kidney protection. Measures to raise awareness of the importance of early identification and intervention include local/national campaigns via social media and practice-based education; clinical education programs; integration of clinical decision support tools into electronic health records; detection programs built around electronic health records; and good interdisciplinary communication. PCPs at the forefront of multidisciplinary care are best placed to implement the evidence-based clinical practice CKD guidelines for lifestyle modification and guideline-directed medical therapy., (© 2024. The Author(s).)

Hypertension is the leading modifiable risk factor for cardiovascular disease, but less than 50% have their blood pressure controlled. A possible avenue to support hypertension management is a holistic approach, using non-pharmacological interventions. Since hypertension is mediated in part by dysregulation of the autonomic nervous system (ANS), biofeedback may help improve hypertension management by targeted self-regulation and self-awareness of parameters that regulate the ANS. This systematic review aimed to assess the effectiveness of biofeedback on blood pressure in hypertensive patients. The review was pre-registered on PROSPERO and followed the PICO strategy. A total of 1782 articles were retrieved, 20 met the inclusion criteria. Sample sizes ranged from 15 to 301 participants; with a median age of 49.3 (43.3-55.0) years and 45% were female. There was a significant effect of biofeedback on systolic (-4.52, Z = 2.31, P = 0.02, CI [-8.35, -0.69]) and diastolic blood pressure (-5.19, Z = 3.54, P = 0.0004, CI [-8.07, -2.32]). Six different biofeedback modalities were used, with biofeedback delivered by psychologists, trained therapists and research assistants. There was no publication bias, heterogeneity was rated as substantial and data quality was rated to be poor. This review demonstrated that biofeedback had a significant effect on blood pressure. However, this should be viewed in the context of included studies being limited by heterogeneity and dated literature, meaning the research does not reflect the current biofeedback technology such as wearable devices. Future research should incorporate these technologies with robust methodology to fully understand the effect of biofeedback on hypertension., (© 2024. The Author(s).)

Aim: To assess mortality and complication trends in people with type 1 diabetes during the 11 years before the SARS-CoV2 pandemic (2009-2019)., Materials and Methods: Sequential cohorts of people in England with type 1 diabetes aged ≥20 years from the National Diabetes Audit (2006/2007 to 2016/2017) were analysed. Discretized Poisson regression models, adjusted for age, sex, ethnicity, socioeconomic deprivation and duration of diabetes, were used to calculate mortality and hospitalization rates., Results: Demographic characteristics changed little; average diabetes duration increased. All-cause mortality was unchanged. Cardiovascular and kidney disease mortality declined. Mortality from respiratory disease, diabetes and dementia increased in younger people (aged 20-74 years) as did mortality from liver disease and dementia in the elderly (aged ≥75 years). Younger Asian and Black people had lower all-cause mortality than those of White ethnicity; elderly Mixed, Asian and Black people had lower all-cause mortality. People from more deprived areas had higher all-cause mortality. The deprivation gradient for mortality was steeper at younger ages. In younger people, rates of hospitalization increased for myocardial infarction, stroke, heart failure and kidney disease but only for kidney disease in the elderly. Rates of a composite measure of cardiovascular hospitalizations increased in younger people (rate ratio [RR] 1.07, 95% confidence interval [CI] 1.03-1.11) but declined in the elderly (RR 0.91, 95% CI 0.86-0.95)., Conclusion: Between 2009 and 2019, hospitalizations for cardiovascular disease increased at younger ages (20-74 years) and hospitalizations for kidney disease increased at all ages, but mortality from cardiovascular and kidney disease declined. All-cause mortality rates were unchanged., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: Research in diabetes-related foot conditions (DRFC) often focuses on ulcer-related care, whilst the patient experience and influence of sociodemographic factors are under-researched. This systematic review investigated patient-reported outcomes and experience in people with DRFC., Methods: Multiple databases were searched from inception to 16 August 2023. All original articles that assessed any patient-reported outcome or experience in DRFC and reported participant ethnicity were included. Data were synthesized using a sequential contingent approach. Study quality was assessed using study design-specific tools., Results: Twenty-three studies were included (11 qualitative, 11 quantitative and one mixed-methods). DRFC had a largely negative impact on various life dimensions, including social and daily life, work, emotional and psychological well-being, necessitating dependence on others in the form of emotional, social and/or religious support, which were experienced differently by different groups. Patient DRFC knowledge and self-care habits were typically suboptimal, and levels of hope and feeling of control over their condition varied between groups. Outcomes varied slightly between ethnicities across studies, with some ethnicity-specific themes identified such as beliefs about disease cause and footwear habits. Quantitative and qualitative findings were mostly congruent., Conclusions: DRFC profoundly and negatively impacts patient-reported outcomes and experience, with limited evidence suggesting an influence of ethnicity., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Diabetes mellitus is a central driver of multiple long-term conditions (MLTCs), but population-based studies have not clearly characterized the burden across the life course. We estimated the age of onset, years of life spent and loss associated with diabetes-related MLTCs among 46 million English adults. We found that morbidity patterns extend beyond classic diabetes complications and accelerate the onset of severe MLTCs by 20 years earlier in life in women and 15 years earlier in men. By the age of 50 years, one-third of those with diabetes have at least three conditions, spend >20 years with them and die 11 years earlier than the general population. Each additional condition at the age of 50 years is associated with four fewer years of life. Hypertension, depression, cancer and coronary heart disease contribute heavily to MLTCs in older age and create the greatest community-level burden on years spent (813 to 3,908 years per 1,000 individuals) and lost (900 to 1,417 years per 1,000 individuals). However, in younger adulthood, depression, severe mental illness, learning disabilities, alcohol dependence and asthma have larger roles, and when they occur, all except alcohol dependence were associated with long periods of life spent (11-14 years) and all except asthma associated with many years of life lost (11-15 years). These findings provide a baseline for population monitoring and underscore the need to prioritize effective prevention and management approaches., (© 2024. The Author(s).)

Objectives: This study examines clinically confirmed long-COVID symptoms and diagnosis among individuals with COVID in England, aiming to understand prevalence and associated risk factors using electronic health records. To further understand long COVID, the study also explored differences in risks and symptom profiles in three subgroups: hospitalised, non-hospitalised, and untreated COVID cases., Methods: A population-based longitudinal cohort study was conducted using data from 1,554,040 individuals with confirmed SARS-CoV-2 infection via Clinical Practice Research Datalink. Descriptive statistics explored the prevalence of long COVID symptoms 12 weeks post-infection, and Cox regression models analysed the associated risk factors. Sensitivity analysis was conducted to test the impact of right-censoring data., Results: During an average 400-day follow-up, 7.4% of individuals with COVID had at least one long-COVID symptom after acute phase, yet only 0.5% had long-COVID diagnostic codes. The most common long-COVID symptoms included cough (17.7%), back pain (15.2%), stomach-ache (11.2%), headache (11.1%), and sore throat (10.0%). The same trend was observed in all three subgroups. Risk factors associated with long-COVID symptoms were female sex, non-white ethnicity, obesity, and pre-existing medical conditions like anxiety, depression, type II diabetes, and somatic symptom disorders., Conclusions: This study is the first to investigate the prevalence and risk factors of clinically confirmed long-COVID in the general population. The findings could help clinicians identify higher risk individuals for timely intervention and allow decision-makers to more efficiently allocate resources for managing long-COVID., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Christina Van Der Feltz-Cornelis received travel and accommodation in UK for lectures from The Lloyd Register Foundation and honoraries from Janssen UK and royalties for books on psychiatry. Prof. Christina Van Der Feltz-Cornelis has also received grants from the National Institute for Health Research, British Medical Association, European Union’s Horizon 2020 research programme and the Netherlands Organisation for Health Research and Development. Prof. Amitava Banerjee has received grants and/or fees from the National Institute for Health Research, British Medical Association, UK Research and Innovation, European Union’s Horizon 2020 research and innovation programme and EFPIA, and AstraZeneca. Dr. Michael G Crooks has received grants, fees and/or non-financial support from the National Institute for Health and Care Research, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Philips, and Pfizer. Prof. Kamlesh Khunti was chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and has acted as a consultant, speaker or received grants for investigator-initiated studies from Astra Zeneca and Pfizer. K.K. (chair) and A.B. are members of the National Long Covid Research Group that informs the chief medical officer for England. All other authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity., Materials and Methods: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other., Results: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m 2 , 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide., Conclusions: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs., (© 2024 John Wiley & Sons Ltd.)

Aims: Health education is integral to cardiometabolic disease (CMD) management. This study aimed to assess whether and how education preferences have changed over time, and whether trends differ by sociodemographic characteristics (education status, age, ethnicity, and sex)., Methods: A cross-sectional questionnaire was deployed across five counties in the East Midlands, UK between 2017 and 2022 to adults with CMD (type 2 diabetes, cardiovascular disease or cerebrovascular disease). Respondent demographic data were collected alongside health education preferences. Statistical analyses ascertained whether demographic characteristics influenced preferences. The distribution of preferences over time was charted to identify trends., Results: A total of 4301 eligible responses were collected. Face-to-face one-to-one education was preferred (first choice for 75.1% of participants) but popularity waned over the five-year period. Trends were similar amongst demographic groups. Online education showed a U-shaped trend: In 2017, 44% of respondents ranked it as acceptable, peaking at 53% in 2019, but declining again, to below base line, 43%, by 2022. This modality was more popular with participants aged younger than 65 years, but popularity in people older than 65 years increased over the study period. The popularity of printed information also declined over time across all demographic groups except those of South Asian ethnicity, for whom it remained static., Conclusions: The overwhelming preference for face-to-face one-to-one health education from a doctor or nurse highlights the importance of preserving access to this modality, even in the face of current NHS pressures and trends towards digitalisation. Trends are changing, and should continue to be monitored, including between different sociodemographic groups., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes., Competing Interests: Declaration of competing interest None of the Task Force members received monetary renumeration for their contributions to the creation or writing of this consensus document. See the Supplementary Appendix for full declarations of competing interests for each author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown., Methods: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone., Results: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores., Conclusions: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Higher accelerometer-assessed volume and intensity of physical activity (PA) have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA. We aimed to: (a) improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity; (b) inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity., Methods: 92,480 UK Biobank participants aged 43-80 years with wrist-worn accelerometer data were included. Average acceleration and intensity gradient were derived as proxies for PA volume and intensity. We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape (GAMLSS) and modeled the effect of adding moderate (walking) or vigorous (running) activity on the combined change in the volume and intensity centiles (change in PA profile)., Results: In men, volume was lower as age increased while intensity was lower after age 55; in women, both volume and intensity were lower as age increased. Adding 150 min of moderate PA weekly (5 × 30 min walking) increased the PA profile by 4 percentage points. Defining moderate PA as brisk walking approximately doubled the increase (9 percentage points) while 75 min of vigorous PA weekly (5 × 15 min running) trebled the increase (13 percentage points)., Conclusion: These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data. Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile (volume and intensity) than longer duration moderate activity., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Objectives: Globally, there is a growing number of people who are living with multiple long-term conditions (MLTCs). Due to complex management needs, it is imperative that research consists of participants who may benefit most from interventions. It is well documented that ethnic minority groups and lower socioeconomic status (SES) groups are at an increased risk of developing MLTCs. Therefore, the aim of this systematic review was to determine the level of reporting and representation of underserved groups (ethnic minority and low SES) in intervention studies addressing MLTCs., Design: Systematic review. Four databases including Cochrane Library, MEDLINE, CINAHL and Scopus were searched for intervention studies from North America or Europe published between January 1990 and July 2023., Setting: Hospital and community-based interventions. We included interventional studies focusing on improving MLTC-related outcomes., Participants: Patients with MLTCs., Main Outcome Measures: Total number of studies reporting on ethnicity and SES. Number and proportion of studies reporting by ethnic/SES group., Results: Thirteen studies met the inclusion criteria. Only 4 of 13 studies (31%) recorded and reported ethnicity information. Of these four studies that reported on ethnicity, three studies consisted of primarily White participants. Ethnic minority groups were underrepresented, but one study included a majority of African American participants. Moreover, 12 of 13 studies (92%) reported on SES with income and educational level being the primary measures used. SES representation of higher deprivation groups was varied due to limited data., Conclusions: For ethnicity, there was a lack of reporting, and ethnic minority groups were underrepresented in intervention studies. For SES, there was a high level of reporting but the proportion of study samples from across the spectrum of SES varied due to the variety of SES measures used. Findings highlight a need to improve the reporting and representation of ethnic minority groups and provide more detailed information for SES through using consistent measures (e.g. education, income and employment) to accurately determine the distribution of SES groups in intervention studies of people with MLTCs.

Rising rates of obesity-associated cardiometabolic disorders allied to ageing populations are driving increases in cardiovascular morbidity and mortality. These adverse trends present challenges for healthcare systems that are struggling to prevent and manage the burgeoning cardiometabolic nexus of multiple long-term conditions. While potent new medications and non-pharmacological interventions have ushered in a promising new therapeutic era, translating clinical trial data to real-world clinical practice is often suboptimal. Postgraduate training and narrowly focused clinical specialisations reflect the traditional siloed approach to managing cardiovascular-metabolic disease that appears increasingly outmoded in the 21st century. It is our contention that greater inter-disciplinary collaboration allied to increased awareness of the continuum of cardiometabolic disease should enable clinicians to address this global public health threat more effectively. With this aim in mind, we have established an International Cardiometabolic Working Group. It is our hope to stimulate the interest of clinicians and clinical researchers across a range of medical specialties who share the vision of better care for people living with cardiometabolic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD)., Methods: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions., Results: Hospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively., Interpretation: Prior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions., Funding: NIHR. HDR UK., Competing Interests: Declarations of competing interest KK is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. KK (Chair) and AB are members of the LC Research Group that reports to the Chief Medical Officer for England. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The COVID-19 pandemic disrupted healthcare delivery and increased cardiovascular morbidity and mortality. This study assesses whether cardiovascular mortality rates in the US have recovered post-pandemic and examines the equity of this recovery across different populations., Methods: We analyzed data from the CDC WONDER database, covering US residents' mortality from 2018-2023. We focused on cardiovascular diseases, categorized by ischemic heart disease (IHD), heart failure (HF), hypertensive diseases (HTN), and cerebrovascular disease. Age-adjusted mortality rates were calculated for three periods: pre-COVID (2018-2019), during COVID (2020-2021), and post-COVID (2022-2023), stratified by demographic and geographic variables., Results: Cardiovascular age-adjusted mortality rates increased by 5.9% during the pandemic but decreased by 3.4% post-pandemic, resulting in a net increase of 2.4% compared to pre-COVID levels. When compared to pre COVID age-adjusted mortality rates, post COVID IHD mortality age-adjusted mortality rates decreased by 5.0%, while cerebrovascular and HTN age-adjusted mortality rates increased by 5.9% and 28.5%, respectively. Men and younger populations showed higher increases in cardiovascular Age-adjusted mortality rates. Geographic disparities were notable, with significant reductions in cardiovascular mortality in the Northeast and increases in states like Arizona and Oregon., Conclusion: The COVID-19 pandemic led to a surge in cardiovascular mortality, with partial recovery post-pandemic. Significant differences in mortality changes highlight the need for targeted healthcare interventions to address inequities across demographic and geographic groups., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KK has acted as a consultant, speaker or received grants for investigator-initiated studies for Astra Zeneca, Bayer, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Pfizer, Roche, Daiichi-Sankyo and Applied Therapeutics. SM has received speaker Honoraria from Lilly and Sanofi, UK., (© 2024 The Authors. Published by Elsevier Inc.)

Background: There is a lack of research examining the interplay between objectively measured physical activity volume and intensity with life expectancy., Methods: Individuals from UK Biobank with wrist-worn accelerometer data were included. The average acceleration and intensity gradient were extracted to describe the physical activity volume and intensity profile. Mortality data were obtained from national registries. Adjusted life expectancies were estimated using parametric flexible survival models., Results: 40,953 (57.1%) women (median age = 61.9 years) and 30,820 (42.9%) men (63.1 years) were included. Over a median follow-up of 6.9 years, there were 1719 (2.4%) deaths (733 in women; 986 in men). At 60 years, life expectancy was progressively longer for higher physical activity volume and intensity profiles, reaching 95.6 years in women and 94.5 years in men at the 90th centile for both volume and intensity, corresponding to 3.4 (95% confidence interval (95%CI): 2.4-4.4) additional years in women and 4.6 (95%CI: 3.6-5.6) additional years in men compared to those at the 10th centiles. An additional 10-min or 30-min daily brisk walk was associated with 0.9 (95%CI: 0.5-1.3) and 1.4 (95%CI: 0.9-1.9) years longer life expectancy, respectively, in inactive women; and 1.4 (95%CI: 1.0-1.8) and 2.5 (95%CI: 1.9-3.1) years in inactive men., Conclusion: Higher physical activity volumes were associated with longer life expectancy, with a higher physical activity intensity profile further adding to a longer life. Adding as little as a 10-min brisk walk to daily activity patterns may result in a meaningful benefit to life expectancy., Competing Interests: Competing interests The authors declare that they have no other competing interests., (Copyright © 2024. Production and hosting by Elsevier B.V.)

A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes., (© 2024. The Author(s).)

Background and Aims: Although extreme cardiac adaptions mirroring phenotypes of cardiomyopathy have been observed in endurance athletes, adaptions to high levels of physical activity within the wider population are under-explored. Therefore, in this study, associations between device-measured physical activity and clinically relevant cardiac magnetic resonance volumetric indices were investigated., Methods: Individuals without known cardiovascular disease or hypertension were included from the UK Biobank. Cardiac magnetic resonance data were collected between 2015 and 2019, and measures of end-diastolic chamber volume, left ventricular (LV) wall thickness, and LV ejection fraction were extracted. Moderate-to-vigorous-intensity physical activity (MVPA), vigorous-intensity physical activity (VPA), and total physical activity were assessed via wrist-worn accelerometers., Results: A total of 5977 women (median age and MVPA: 62 years and 46.8 min/day, respectively) and 4134 men (64 years and 49.8 min/day, respectively) were included. Each additional 10 min/day of MVPA was associated with a 0.70 [95% confidence interval (CI): 0.62, 0.79] mL/m2 higher indexed LV end-diastolic volume (LVEDVi) in women and a 1.08 (95% CI: 0.95, 1.20) mL/m2 higher LVEDVi in men. However, even within the top decile of MVPA, LVEDVi values remained within the normal ranges [79.1 (95% CI: 78.3, 80.0) mL/m2 in women and 91.4 (95% CI: 90.1, 92.7) mL/m2 in men]. Associations with MVPA were also observed for the right ventricle and the left/right atria, with an inverse association observed for LV ejection fraction. Associations of MVPA with maximum or average LV wall thickness were not clinically meaningful. Results for total physical activity and VPA mirrored those for MVPA., Conclusions: High levels of device-measured physical activity were associated with cardiac remodelling within normal ranges., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The STEP-HFpEF DM trial 1 showed that semaglutide improved body weight, systemic inflammation, and heart failure symptoms in people with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. By addressing both metabolic and cardiovascular risk, semaglutide is a promising therapeutic option for HFpEF in addition to SGLT2i., Competing Interests: Declaration of interests L.-L.L. has acted as a consultant, speaker, or received research grants via her institution from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Roche, Servier, Viatris, and Zuellig Pharma Therapeutics. K.K. has acted as a consultant, speaker, or received grants for investigator-initiated studies for AstraZeneca, Bayer, Novo Nordisk, Sanofi-Aventis, Servier, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Pfizer, Roche, Daiichi-Sankyo, Applied Therapeutics, Embecta, and Nestle Health Science., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

Objectives: The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and ethnic groups are not well defined. By conducting a systematic review and meta-analysis of all randomised, placebo-controlled, cardiovascular disease (CVD) outcomes trials (CVOTs), we aimed to compare racial/ethnic as well as regional patterns in the effects of SGLT2-Is and GLP1-RAs on cardiovascular and renal outcomes in patients with type 2 diabetes (T2D)., Design: Trials were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to 7 July 2023. Setting North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa., Setting: North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa., Participants: people with type 2 diabetes enrolled in cardiovascular outcome trials of SGLT2-Is and GLP1-RAs., Main Outcome Measures: Outcomes were (i) major adverse cardiovascular events (MACE), (ii) composite CVD death/heart failure (HF) hospitalization; (iii) composite renal outcome; and (iv) their components. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled., Results: In total, 14 unique CVOTs (7 comparing SGLT2-Is vs placebo and 7 comparing GLP1-RAs vs placebo) were eligible. The proportion of participants enrolled in the trials ranged from 66.6-93.2% for White populations, 1.2-21.6% for Asian populations, 2.4-8.3% for Black populations and 0.9-23.1% for Other populations. The HR (95% CI) for MACE comparing SGLT2-Is vs placebo was 0.92 (0.86-0.98), 0.69 (0.53-0.92) and 0.70 (0.54-0.91) for White, Asian and Hispanic/Latino populations, respectively. Comparing GLP1-RAs vs placebo, the corresponding HR (95% CI) was 0.88 (0.80-0.97), 0.76 (0.63-0.93) and 0.82 (0.70-0.95), respectively. SGLT2-Is reduced the risk of all other cardiorenal outcomes in White and Asian populations, except for HF hospitalizations in Asians. No effects were observed in Black populations except for a reduced risk of HF hospitalizations by SGLT2-I. SGLT1-Is reduced the risk of composite CVD death/HF hospitalization in North America and Europe, whereas GLP1-RAs reduced the risk of MACE in Europe. GRADE certainty of evidence ranged from moderate to high., Conclusions: There appears to be substantial racial/ethnic differences in the cardiorenal effects of SGLT2-Is and GLP1-RAs in patients with T2D, with consistent benefits observed among White and Asian populations and consistent lack of benefits in Black populations. Whether the differences are due to issues with under-representation of Black populations and low statistical power or racial/ethnic variations in the pharmacokinetics, pharmacodynamics and safety of SGLT2-Is and GLP1-RAs need further investigation.PROSPERO Registration: CRD42023401734.

Aim: To assess the differential association of risk factors with severe and non-severe hypoglycaemia., Materials and Methods: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia., Results: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen., Conclusions: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data., (© 2024 Diabetes UK.)

The first dose of COVID-19 vaccines led to an overall reduction in cardiovascular events, and in rare cases, cardiovascular complications. There is less information about the effect of second and booster doses on cardiovascular diseases. Using longitudinal health records from 45.7 million adults in England between December 2020 and January 2022, our study compared the incidence of thrombotic and cardiovascular complications up to 26 weeks after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs., (© 2024. The Author(s).)

Diabetic Foot Ulcers (DFUs) are a major complication of diabetes, with treatment requiring offloading. This study aimed to capture how the accelerometer-assessed physical activity profile differs in those with DFUs compared to those with diabetes but without ulceration (non-DFU). Participants were requested to wear an accelerometer on their non-dominant wrist for up to 8days. Physical activity outcomes included average acceleration (volume), intensity gradient (intensity distribution), the intensity of the most active sustained (continuous) 5-120 min of activity (MX CONT ), and accumulated 5-120 min of activity (MX ACC ). A total of 595 participants (non-DFU = 561, DFU = 34) were included in the analysis. Average acceleration was lower in DFU participants compared to non-DFU participants (21.9 mg [95%CI:21.2, 22.7] vs. 16.9 mg [15.3, 18.8], p < 0.001). DFU participants also had a lower intensity gradient, indicating proportionally less time spent in higher-intensity activities. The relative difference between DFU and non-DFU participants was greater for sustained activity (MX CONT ) than for accumulated (MX ACC ) activity. In conclusion, physical activity, particularly the intensity of sustained activity, is lower in those with DFUs compared to non-DFUs. This highlights the need for safe, offloaded modes of activity that contribute to an active lifestyle for people with DFUs.

Background: Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of UK adults., Methods: This prospective cohort study included 144,288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorised PA and diet indicators (diet quality score (DQS) and energy intake (EI)) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension)., Results: A total of 14,003(7.1%) participants developed T2D, 28,075(19.2%) developed hypertension, and 30,529(21.2%) developed T2D or hypertension over a mean follow-up of 10.9(3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet, e.g. among high DQS group, hazard ratios in middle and high MVPA group were 0.90 (95%CI:0.86-0.94), and 0.88(95%CI:0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR: 0.84, 95%CI:0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes., Conclusion: Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Ethnic inequalities in acute health acute care are not well researched. We examined how attendee ethnicity influenced outcomes of emergency care in unselected patients presenting with a gastrointestinal (GI) disorder., Methods: A descriptive, retrospective cohort analysis of anonymised patient level data for University Hospitals of Leicester emergency department attendees, from 1 January 2018 to 31 December 2021, receiving a diagnosis of a GI disorder was performed. The primary exposure of interest was self-reported ethnicity, and the two outcomes studied were admission to hospital and whether patients underwent clinical investigations. Confounding variables including sex and age, deprivation index and illness acuity were adjusted for in the analysis. Chi-squared and Kruskal-Wallis tests were used to examine ethnic differences across outcome measures and covariates. Multivariable logistic regression was used to examine associations between ethnicity and outcome measures., Results: Of 34,337 individuals, median age 43 years, identified as attending the ED with a GI disorder, 68.6% were White. Minority ethnic patients were significantly younger than White patients. Multiple emergency department attendance rates were similar for all ethnicities (overall 18.3%). White patients had the highest median number of investigations (6, IQR 3-7), whereas those from mixed ethnic groups had the lowest (2, IQR 0-6). After adjustment for age, sex, year of attendance, index of multiple deprivation and illness acuity, all ethnic minority groups remained significantly less likely to be investigated for their presenting illness compared to White patients (Asian: aOR 0.80, 95% CI 0.74-0.87; Black: 0.67, 95% CI 0.58-0.79; mixed: 0.71, 95% CI 0.59-0.86; other: 0.79, 95% CI 0.67-0.93; p < 0.0001 for all). Similarly, after adjustment, minority ethnic attendees were also significantly less likely to be admitted to hospital (Asian: aOR 0.63, 95% CI 0.60-0.67; Black: 0.60, 95% CI 0.54-0.68; mixed: 0.60, 95% CI 0.51-0.71; other: 0.61, 95% CI 0.54-0.69; p < 0.0001 for all)., Conclusions: Significant differences in usage patterns and disparities in acute care outcomes for patients of different ethnicities with GI disorders were observed in this study. These differences persisted after adjustment both for confounders and for measures of deprivation and illness acuity and indicate that minority ethnic individuals are less likely to be investigated or admitted to hospital than White patients., (© 2024. The Author(s).)