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Coronavirus disease (COVID-19) vaccine and its utility in solid organ transplantation (SOT) needs to be revised timely and updated. These guidelines have been formalized by the experts -the apex technical committee members of the National Organ and Tissue Transplant Organization (NOTTO), and the heads of transplant societies for the guidance of transplant communities. In our general recommendations, we recommend that all personnel involved in organ transplantation should get vaccinated as early as possible and continue COVID-19 appropriate behaviour, despite a full course of vaccination. For specific guidelines of recipients, we suggest completing the full schedule before transplantation whenever the clinical condition permits. We also suggest a single dose, rather than proceeding unvaccinated for transplant, in case a complete course is not feasible. In case, vaccination is planned before surgery, we recommend a gap of at least 2 weeks between the last dose of vaccine and surgery. For those not vaccinated prior to transplant, we suggest waiting for 4-12 weeks after transplant. For the potential living donors, we recommend the complete vaccination schedule before transplant. However, if not feasible, we suggest getting at least a single dose of vaccine, 2 weeks prior to donation. We suggest that suitable transplant patients and those on the waiting list should accept a third dose of the vaccine when one is offered to them. In the context of Vaccine-induced thrombotic thrombocytopenia (VITT), we recommend organs from a deceased donor with suspected/proven VITT should be notified and best avoided and are justified only in case of emergency situations with informed consent and counselling.

With the rapid and massive vaccination campaign against coronavirus disease 2019 (COVID-19) taking place across the globe, there are increasing reports of thrombotic complications with various COVID-19 vaccines such as the Pfizer-BioNTech mRNA, Moderna mRNA, AstraZeneca Oxford (serum institute), and JohnsonJohnson/Janssen vaccines. We report a case of successful organ donation from an 18-year-old woman who presented with cerebral venous thrombosis caused by vaccine-induced thrombotic thrombocytopenia following the first dose of the COVID-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India), which caused brain death. Four recipients received 5 organs, kidneys (2), liver (1), and combined heart and lung (1). All 4 recipients had normal graft function without any thrombotic complications after 16 weeks of transplantation. This is first such case being reported from Asian countries.

OBJECTIVE Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS. RESEARCH DESIGN AND METHODS Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs). RESULTS The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78–1.97, P < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59–0.87). CONCLUSIONS In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.

Introduction The externally validated Kidney Failure Risk Equation (KFRE) for predicting risk of end-stage renal disease (ESRD) has been developed, but its potential impact in a population on referrals for patients with chronic kidney disease (CKD) from primary to specialty nephrology care is not known. Methods A cross-sectional population-based study of individuals in United Kingdom primary care registered in The Health Improvement Network database was conducted. National Institute of Health and Care Excellence (NICE) 2014 CKD guidelines versus the 4-variable KFRE set at a >3% risk of ESRD at 5 years were applied to patients identified with CKD stage 3-5 between January 1, 2016, and March 31, 2017. Results In all, 39,476 (36.6%) of 107,962 adults with CKD stage 3-5 had a urine albumin:creatinine ratio (ACR) available and entered into the primary analysis. Of that, 7566 (19.2%) patients fulfilled NICE criteria for referral, 2386 (31.5%) of whom had a ≤3% 5-year risk of ESRD. Also 8663 (21.9%) patients had a >3% 5-year risk of ESRD, 3483 (40.2%) of whom did not fulfill NICE criteria; this represents 8.8% of the primary population. By using the KFRE threshold rather than NICE criteria for referral, 5869 patients (14.9% of the primary analysis population) would have been reallocated between primary and specialist care. Imputational analysis was used for missing ACR measurements and showed similar results. Conclusions A risk-based referral approach would lead to a substantial reallocation of patients between primary care and specialist nephrology care with only a small increase in numbers eligible, ensuring those at higher risk of progression are identified., Graphical abstract

To conduct a pharmacoepidemiological study to explore the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and gout in patients with type 2 diabetes mellitus (T2DM).A retrospective open cohort study using the IQVIA Medical Research Data UK database was performed between November 1, 2012 and December 31, 2018, estimating the risk of gout in patients with T2DM who were new users of SGLT2 inhibitors, compared to propensity-score-matched new users of dipeptidyl peptidase-4 (DPP-4) inhibitors.A total of 85 incident cases of gout were recorded over 30 389 person-years of observation in 13 617 new users of SGLT2 inhibitors and 29 426 new users of DPP-4 inhibitors. Crude incidence rates (IRs) per 1000 person-years were 2.90 and 2.47 for new users of SGLT2 inhibitors and DPP-4 inhibitors, respectively. The unadjusted hazard ratio (HR) was 1.18 (95% confidence interval [CI] 0.76-1.83). The adjusted HR was 1.20 (95% CI 0.77-1.86). In the at-treatment analysis, crude IRs per 1000 person-years were found to be 2.68 and 2.53 for SGLT2 inhibitor and DPP-4 inhibitor users, respectively. In the adjusted model, the adjusted HR was 1.3 (95% CI 0.90-2.29). Sensitivity analyses did not change the findings.In this nationwide study, no difference in the incidence of gout was documented in patients treated with SGLT2 inhibitors compared to DPP-4 inhibitor users. This neutral finding remained consistent in sensitivity analyses.

Background:\ud Domestic abuse is a global public health issue. The association between the development of central sensitivity syndromes (CSS) and previous exposure to domestic abuse has been poorly understood particularly within European populations.\ud \ud Methods:\ud A retrospective cohort study using the ‘The Health Improvement Network,’ (UK primary care medical records) between 1st January 1995–31st December 2018. 22,604 adult women exposed to domestic abuse were age matched to 44,671 unexposed women. The average age at cohort entry was 36 years and the median follow-up was 2.5 years. The outcomes of interest were the development of a variety of syndromes which demonstrate central nervous system sensitization. Fibromyalgia, chronic fatigue syndrome and temporomandibular joint disorder outcomes have been reported previously. Outcomes were adjusted for the presence of mental ill health.\ud \ud Results:\ud During the study period, women exposed to domestic abuse experienced an increased risk of developing chronic lower back pain (adjusted incidence rate ratio [aIRR] 2.28; 95% CI 1.85–2.80), chronic headaches (aIRR 3.15; 95% CI 1.07–9.23), irritable bowel syndrome (aIRR 1.41; 95% CI 1.25–1.60) and restless legs syndrome (aIRR 1.89; 95% CI 1.44–2.48). However, no positive association was seen with the development of interstitial cystitis (aIRR 0.52; 95% CI 0.14–1.93), vulvodynia (aIRR 0.42; 95% CI 0.14–1.25) and myofascial pain syndrome (aIRR 1.01; 95% CI 0.28–3.61).\ud \ud Conclusion:\ud This study demonstrates the need to consider a past history of domestic abuse in patients presenting with CSS; and also consider preventative approaches in mitigating the risk of developing CSS following exposure to domestic abuse.\ud \ud Significance:\ud Domestic abuse is a global public health issue, with a poorly understood relationship with the development of complex pain syndromes. Using a large UK primary care database, we were able to conduct the first global cohort study to explore this further. We found a strong pain morbidity burden associated with domestic abuse, suggesting the need for urgent public health intervention to not only prevent domestic abuse but also the associated negative pain consequences.

Objective To compare the incident risk of RA in patients with type 2 diabetes mellitus (T2DM) and to explore the role of glycaemic control and associated therapeutic use in the onset of RA. Methods This study was a retrospective cohort study using patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 1995 and 2019. A total of 224 551 newly diagnosed patients with T2DM were matched to 449 101 patients without T2DM and followed up to assess their risk of RA. Further analyses investigated the effect of glycaemic control, statin use and anti-diabetic drugs on the relationship between T2DM and RA using a time-dependent Cox regression model. Results During the study period, the incidence of RA was 8.1 and 10.6 per 10 000 person-years in the exposed and unexposed groups, respectively. The adjusted hazard ratio (aHR) was 0.73 (95% CI 0.67, 0.79). In patients who had not used statins in their lifetime, the aHR was 0.89 (95% CI 0.69, 1.14). When quantifying the effects of glycaemic control, anti-diabetic drugs and statins using time-varying analyses, there was no association with glycaemic control [aHR 1.00 (95% CI 0.99, 1.00)], use of metformin [aHR 1.00 (95% CI 0.82, 1.22)], dipeptidyl peptidase-4 inhibitors [DPP4is; aHR 0.94 (95% CI 0.71, 1.24)] and the development of RA. However, statins demonstrated a protective effect for progression of RA in those with T2DM [aHR 0.76 (95% CI 0.66, 0.88)], with evidence of a duration–response relationship. Conclusion There is a reduced risk of RA in patients with T2DM that may be attributable to the use of statins.

Organ donation following circulatory determination of death (DCDD) has contributed significantly to the donor pool in several countries. In India, majority of deceased donations happen following brain death (BD). While existing legislation allows for DCDD, there have been only few reports of kidney transplantation following DCDD from India. This document, prepared by a multidisciplinary group of experts, reviews international best practices in DCDD and outlines the path for DCDD in India. Ethical, medical, legal, economic, procedural, and logistic challenges unique to India have been addressed. The practice of withdrawal of life-sustaining treatment (WLST) in India, laid down by the Supreme Court of India, is time-consuming, possible only in patients in a permanent vegetative state, and too cumbersome for day-to-day practice. In patients where continued medical care is futile, the procedure for WLST is described. In controlled DCDD (category-III), decision for WLST is independent of and delinked from the subsequent possibility of organ donation. Families that are inclined toward organ donation are explained the procedure including the timing and location of WLST, consent for antemortem measures, no-touch period, and the possibility of stand-down and return to the intensive care unit (ICU) without donation. In donation following neurologic determination of death (DNDD), if cardiac arrest occurs during the process of BD declaration, the protocol for DCDD category-IV has been described in detail. In DCDD category-V, organ donation may be possible following unsuccessful cardiopulmonary resuscitation of cardiac arrest in the ICU. An outline of organ-specific requisites for kidney, liver, heart, and lung transplantation following DCDD and techniques, such as normothermic regional perfusion (nRP) andSeth AK, Mohanka R, Navin S, Gokhale AGK, Sharma A, Kumar A

ObjectiveTo investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.DesignObservational controlled interrupted time series study.SettingUK primary and secondary care.Participants515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.InterventionFetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.Main outcome measuresThe primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.ResultsProphylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.ConclusionsThis study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.

The burden of allergic diseases (ADs) such as asthma and rhinitis and autoimmune disorders (AIDs) such as rheumatoid arthritis (RA) are relatively low/moderate in low and low-middle income countries and there is some evidence regarding higher incidence rates of these conditions amongst immigrant population settled in high income countries . The burden of ADs are particularly high in high income countries such as UK, Republic of Ireland and New Zealand . Studies in immigrants have been limited by several factors including relatively small sample size, shorter duration, and methodological issues such as selection bias, survey or questionnaire-based data, focus on a single or limited number of ADs or AIDs, and some not accounting for important disease confounders such as smoking history.

Background Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated. Aims To investigate incidence and prevalence of Crohn's disease and ulcerative colitis and risk of colorectal cancer and all-cause mortality in these diseases. Methods Inflammatory bowel disease cases between 2000 and 2018 were identified from a national primary care database. Inflammatory bowel disease prevalence was forecast until 2025. The association between inflammatory bowel disease and colorectal cancer and all-cause mortality was investigated using age/sex-matched retrospective cohort studies. Hazard ratios were adjusted for age, sex, deprivation, comorbidity, smoking status and body mass index. Results Ulcerative colitis prevalence increased from 390 to 570 per 100 000 population from 2000 to 2017. Prevalence of Crohn's disease increased from 220 to 400 per 100 000. In 2017 male Crohn's disease prevalence was 0.35% (95% confidence interval 0.34-0.36); female prevalence was 0.44% (0.43-0.45). Prevalence of inflammatory bowel disease is predicted to be 1.1% by 2025. Incidence of ulcerative colitis and Crohn's disease was 23.2 (22.8-23.6) and 14.3 (14.0-14.7) per 100 000 person-years respectively. Subjects with ulcerative colitis were more likely to develop colorectal cancer than controls (adjusted Hazard Ratio 1.40 [1.23-1.59]). Colorectal cancer rates remained stable in inflammatory bowel diseases over time. Ulcerative colitis and Crohn's disease were associated with increased risk of all-cause mortality (1.17 [1.14-1.21] and 1.42 [1.36-1.48] respectively). Conclusions The UK prevalence of inflammatory bowel disease is greater than previous reports suggest and we predict an 11% increase in prevalence by the year 2025. Mortality risk in inflammatory bowel disease and colorectal cancer risk in ulcerative colitis are increased compared to matched controls.

Objectives The epidemiology of Behçet’s disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. Methods We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). Results The prevalence of BD was 14.61 (95% CI 13.35–15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28–7.44)], venous thrombosis [aHR 4.80 (2.42–9.54)] and mortality [aHR 1.40 (1.07–1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66–8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). Conclusion BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

IntroductionIndividuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4–12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.Methods and analysisA cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.Ethics and disseminationEthical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.Trial registration number1567490.

ObjectivesTo explore population patterns of sex-based incidence and prevalence of peripheral arterial disease (PAD), guideline-directed best medical therapy prescriptions and its relationship with all-cause mortality at 1 year.DesignA retrospective cohort study.SettingAnonymised electronic primary care from 787 practices in the UK, or approximately 6.2% of the UK population.ParticipantsAll registered patients over 40 with a documented diagnosis of peripheral arterial disease.Outcome measurePopulation incidence and prevalence of PAD by sex. Patterns of guideline-directed therapy, and correlation with all-cause mortality at 1 year (defined as death due to any outcome) in patients with and without an existing diagnosis of cardiovascular disease. Covariates included Charlson comorbidity, sex, age, body mass index, Townsend score of deprivation, smoking status, diabetes, hypertension, statin and antiplatelet prescription.ResultsSequential cross-sectional studies from 2010 to 2017 found annual PAD prevalence (12.7–14.3 vs 25.6 per 1000 in men) and incidence were lower in women (11.6–12.4 vs 22.7–26.8 per 10 000 person years in men). Cox proportional hazards models created for PAD patients with and without cardiovascular disease over one full year analysed 25 121 men and 13 480 women, finding that following adjustment for age, women were still less likely to be on a statin (OR 0.69; 95% CI 0.66 to 0.72; pConclusionsWomen with a new diagnosis of PAD were not prescribed guideline-directed therapy at the same rate as men. However once adjusted for factors including age, all-cause mortality in men and women was similar.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) infection is frequently associated with a wide range of persistent symptoms, now referred to as post-COVID-19 condition, or Long COVID. The objectives of this study were to assess which symptoms are associated with confirmed SARS CoV-2 beyond 12 weeks post-infection in non-hospitalised individuals, and the risk factors associated with developing persistent symptoms. We undertook a retrospective matched cohort study between 31st January 2020 and 15th April 2021 using data from a large database of UK-based primary care electronic health records, Clinical Practice Research Datalink (CPRD) Aurum. We selected 486,149 adult patients with a confirmed diagnosis of SARS CoV-2 infection that had not been hospitalised within 28 days of the diagnosis (infected cohort). We propensity score matched them to 1,944,580 patients without a coded record of either confirmed or suspected COVID-19 (uninfected cohort). Outcomes were the presence of 115 separate symptoms at ≥12 weeks post-infection, and Long COVID, defined as having at least one of the symptoms included in the World Health Organisation case definition. Separate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) for individual symptoms and Long Covid. 62 symptoms were significantly associated with prior exposure to SARS CoV-2 after 12 weeks. The largest adjusted hazard ratios (aHR) were for anosmia (aHR 6.49, 95% CI 5.02 to 8.39), hair loss (3.99, 3.63 to 4.39), sneezing (2.77, 1.40 to 5.50), difficulties with ejaculation (2.63, 1.61 to 4.28), reduced libido (2.36, 1.61 to 3.47), shortness of breath at rest (2.20, 1.57 to 3.08), fatigue (1.92, 1.81 to 2.03), pleuritic chest pain (1.86, 1.41 to 2.46), hoarse voice (1.78, 1.44 to 2.20), and fever (1.75, 1.54 to 1.98). Among the infected cohort, risk factors for Long COVID included younger age (aHR 0.75, 95% CI 0.70 to 0.81, for those aged ≥70 years compared to those aged 18 to 30 years), female sex (1.52, 1.48 to 1.56), belonging to an ethnic minority group (1.14 [1.07 to 1.22] for mixed race, 1.21 [1.10 to 1.34] for black ethnic groups, and 1.06 [1.03 to 1.10] for other ethnic minority groups, compared to white ethnic groups), socioeconomic deprivation (1.11 [1.07 to 1.16] for the most compared to the least socioeconomically deprived quintile), smoking (1.12, 1.08 to 1.15), obesity (1.10, 1.07 to 1.14), and a wide range of comorbidities such as COPD. SARS CoV-2 in non-hospitalised individuals is associated with a plethora of symptoms being reported at ≥12 weeks post-infection, with a higher risk associated with younger age, female sex, ethnic minority groups, socioeconomic deprivation, smoking, obesity, and several comorbidities.

Introduction To assess if in adults with COVID‐19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM‐NC) and those without diabetes. Methods Service‐level data was used from 996 adults with laboratory confirmed COVID‐19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM‐NC, and non‐diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality. Results Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM‐NC and 597 (59.9%) non‐diabetes. There were 309 (31.0%) in‐hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM‐NC and 170 (17.0%) non‐diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM‐NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95–2.03, p = 0.093) and 1.18 (95% CI 0.90–1.54, p = 0.226) in DM+C and DM‐C, respectively. Conclusions Those with COVID‐19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study., As people with diabetes are disproportionately affected by COVID‐19, there is a need to identify diabetes sub‐groups who could be at high risk of adverse outcomes when presenting to hospitals.Our real world study of people with diabetes and laboratory confirmed diagnoses of COVID‐19 uses service level data including biochemical markers for initial assessment. We compared these values and mortality levels in people with and without diabetes and hyperglycaemic complications.We found people with COVID‐19 and diabetes with existing complications presented with a more severe clinical and biochemical profile.However, the association between diabetic/hyperglycemic state in COVID‐19 and all cause‐mortality was not statistically significant in this study.

ObjectivesExisting UK prognostic models for patients admitted to hospital with COVID-19 are limited by reliance on comorbidities, which are under-recorded in secondary care, and lack of imaging data among the candidate predictors. Our aims were to develop and externally validate novel prognostic models for adverse outcomes (death, intensive therapy unit (ITU) admission) in UK secondary care; and externally validate the existing 4C score.DesignCandidate predictors included demographic variables, symptoms, physiological measures, imaging, laboratory tests. Final models used logistic regression with stepwise selection.SettingModel development was performed in data from University Hospitals Birmingham (UHB). External validation was performed in the CovidCollab dataset.ParticipantsPatients with COVID-19 admitted to UHB January-August 2020 were included.Main outcome measuresDeath and ITU admission within 28 days of admission.Results1040 patients with COVID-19 were included in the derivation cohort; 288 (28%) died and 183 (18%) were admitted to ITU within 28 days of admission. Area under the receiver operating curve (AUROC) for mortality was 0.791 (95%CI 0.761-0.822) in UHB and 0.767 (95%CI 0.754-0.780) in CovidCollab; AUROC for ITU admission was 0.906 (95%CI 0.883-0.929) in UHB and 0.811 (95%CI 0.795-0.828) in CovidCollab. Models showed good calibration. Addition of comorbidities to candidate predictors did not improve model performance. AUROC for the 4C score in the UHB dataset was 0.754 (95%CI 0.721-0.786).ConclusionsThe novel prognostic models showed good discrimination and calibration in derivation and external validation datasets, and outperformed the existing 4C score. The models can be integrated into electronic medical records systems to calculate each individual patient’s probability of death or ITU admission at the time of hospital admission. Implementation of the models and clinical utility should be evaluated.Article SummaryStrengths and limitations of this studyWe developed novel prognostic models predicting mortality and ITU admission within 28 days of admission for patients hospitalised with COVID-19, using a large routinely collected dataset gathered at admission with a wide range of possible predictors (demographic variables, symptoms, physiological measures, imaging, laboratory test results).These novel models showed good discrimination and calibration in both derivation and external validation cohorts, and outperformed the existing ISARIC model and 4C score in the derivation dataset. We found that addition of comorbidities to the set of candidate predictors included in model derivation did not improve model performance.If integrated into hospital electronic medical records systems, the model algorithms will provide a predicted probability of mortality or ITU admission for each patient based on their individual data at, or close to, the time of admission, which will support clinicians’ decision making with regard to appropriate patient care pathways and triage. This information might also assist clinicians in explaining complex prognostic assessments and decisions to patients and their relatives.A limitation of the study was that in the external validation cohort we were unable to examine all of the predictors included in the original full UHB model due to only a reduced set of candidate predictors being available in CovidCollab. Nevertheless, the reduced model performed well and the results suggest it may be applicable in a wide range of datasets where only a reduced set of predictor variables is available.Furthermore, it was not possible to carry out stratified analysis by ethnicity as the UHB dataset contained too few patients in most of the strata, and no ethnicity data was available in the CovidCollab dataset.

IntroductionIndividuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.Methods and analysisA cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink (CPRD) and invited by their general practitioners to participate on a digital platform (Atom5™). Individuals will report symptoms, quality of life, work capability, and patient reported outcome measures. Data will be collected monthly for one year.Statistical clustering methods will be used to identify distinct Long COVID symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear sub-study which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for post-viral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.Ethics and disseminationEthical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). The study is registered on the ISRCTN Registry (1567490). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.Article SummaryStrengths and limitations of the studyThe study will generate a nationally representative cohort of individuals with Long COVID recruited from primary care.We will recruit controls matched on a wide range of demographic and clinical factors to assess differences in symptoms between people with Long COVID and similar individuals without a history of COVID-19.We will use a newly developed electronic patient reported outcome measure (Symptom Burden Questionnaire™) for Long COVID to comprehensively assess a wide range of symptoms highlighted by existing literature, patients, and clinicians.Immunological, proteomic, genetic, and wearable data captured in the study will allow deep phenotyping of Long COVID syndromes to help better target therapies.A limitation is that a significant proportion of non-hospitalised individuals affected by COVID-19 in the first wave of the pandemic will lack confirmatory testing and will be excluded from recruitment to the study.

Clinical outcomes for patients with COVID-19 are heterogeneous and there is interest in defining subgroups for prognostic modeling and development of treatment algorithms. We obtained 28 demographic and laboratory variables in patients admitted to hospital with COVID-19. These comprised a training cohort (n = 6099) and two validation cohorts during the first and second waves of the pandemic (n = 996; n = 1011). Uniform manifold approximation and projection (UMAP) dimension reduction and Gaussian mixture model (GMM) analysis was used to define patient clusters. 29 clusters were defined in the training cohort and associated with markedly different mortality rates, which were predictive within confirmation datasets. Deconvolution of clinical features within clusters identified unexpected relationships between variables. Integration of large datasets using UMAP-assisted clustering can therefore identify patient subgroups with prognostic information and uncovers unexpected interactions between clinical variables. This application of machine learning represents a powerful approach for delineating disease pathogenesis and potential therapeutic interventions.

BackgroundCannabis use is a global public health issue associated with increased risks of developing mental health disorders, especially in young people. We aimed to investigate the relationships between cannabis exposure and risks of receiving mental illness diagnoses or treatment as outcomes.MethodsA population based, retrospective, open cohort study using patients recorded in ‘IQVIA medical research data’, a UK primary care database. Read codes were used to confirm patients with recorded exposure to cannabis use who were matched up to two unexposed patients. We examined the risk of developing three categories of mental ill health: depression, anxiety or serious mental illness (SMI).ResultsAt study entry, the exposed cohort had an increased likelihood of having experienced mental ill health [odds ratio (OR) 4.13; 95% confidence interval (CI) 3.99–4.27] and mental ill health-related prescription (OR 2.95; 95% CI 2.86–3.05) compared to the unexposed group. During the study period we found that exposure to cannabis was associated with an increased risk of developing any mental disorder [adjusted hazard ratio (aHR) 2.73; 95% CI 2.59–2.88], also noted when examining by subtype of disorder: anxiety (aHR 2.46; 95% CI 2.29–2.64), depression (aHR 2.34; 95% CI 2.20–2.49) and SMI (aHR 6.41; 95% CI 5.42–7.57). These results remained robust in sensitivity analyses.ConclusionThese findings point to the potential need for a public health approach to the management of people misusing cannabis. However, there is a gross under-recording of cannabis use in GP records, as seen by the prevalence of recorded cannabis exposure substantially lower than self-reported survey records.

Summary Background Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health. Methods In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients. Findings The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6–4·3) versus 3·2 years (1·3–6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08–2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40–2·48). Interpretation Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health. Funding None.

Aim To determine whether the Diabetes Inpatient Care and Education (DICE) programme, a whole-systems approach to managing inpatient diabetes, reduces length of stay, in-hospital mortality and readmissions. Research design and methods Diabetes Inpatient Care and Education initiatives included identification of all diabetes admissions, a novel DICE care-pathway, an online system for prioritizing referrals, use of web-linked glucose meters, an enhanced diabetes team, and novel diabetes training for doctors. Patient administration system data were extracted for people admitted to Ipswich Hospital from January 2008 to June 2016. Logistic regression was used to compare binary outcomes (mortality, 30-day readmissions) 6 months before and after the intervention; generalized estimating equations were used to compare lengths of stay. Interrupted time series analysis was performed over the full 7.5-year period to account for secular trends. Results Before-and-after analysis revealed a significant reduction in lengths of stay for people with and without diabetes: relative ratios 0.89 (95% CI 0.83, 0.97) and 0.93 (95% CI 0.90, 0.96), respectively; however, in interrupted time series analysis the change in long-term trend for length of stay following the intervention was significant only for people with diabetes (P=0.017 vs P=0.48). Odds ratios for mortality were 0.63 (0.48, 0.82) and 0.81 (0.70, 0.93) in people with and without diabetes, respectively; however, the change in trend was not significant in people with diabetes, while there was an apparent increase in those without diabetes. There was no significant change in 30-day readmissions, but interrupted time series analysis showed a rising trend in both groups. Conclusion The DICE programme was associated with a shorter length of stay in inpatients with diabetes beyond that observed in people without diabetes.

Objective\ud To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.\ud \ud Methods\ud We performed a propensity score–matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.\ud \ud Results\ud During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score–matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62–1.10) and 0.79 (95% CI 0.57–1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75–1.27) and 0.85 (95% CI 0.61–1.20), respectively. There was no effect modification by age or sex.\ud \ud Conclusion\ud No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

Objective Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. Research Design and Methods We performed a propensity score–matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF−). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. Results There were 29 558 and 10 271 patients in the MF+ and MF− groups, respectively, who met the inclusion criteria. In the propensity score–matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. Conclusion Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.

OBJECTIVE To investigate the relationship between social deprivation and incident diabetes-related foot disease (DFD) in newly diagnosed patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A population-based open retrospective cohort study using The Health Improvement Network (1 January 2005 to 31 December 2019) was conducted. Patients with type 2 diabetes free of DFD at baseline were stratified by Townsend deprivation index, and risk of developing DFD was calculated. DFD was defined as a composite of foot ulcer (FU), Charcot arthropathy, lower-limb amputation (LLA), peripheral neuropathy (PN), peripheral vascular disease (PVD), and gangrene. RESULTS A total of 176,359 patients were eligible (56% men; mean age 62.9 [SD 13.1] years). After excluding 26,094 patients with DFD before/within 15 months of type 2 diabetes diagnosis, DFD incidentally developed in 12.1% of the study population over 3.27 years (interquartile range 1.41–5.96). Patients in the most deprived Townsend quintile had increased risk of DFD compared with those in the least deprived (adjusted hazard ratio [aHR] 1.22; 95% CI 1.16–1.29) after adjusting for sex, age at type 2 diabetes diagnosis, ethnicity, smoking, BMI, HbA1c, cardiovascular disease, hypertension, retinopathy, estimated glomerular filtration rate, insulin, glucose/lipid-lowering medication, and baseline foot risk. Patients in the most deprived Townsend quintile had higher risk of PN (aHR 1.18; 95% CI 1.11–1.25), FU (aHR 1.44; 95% CI 1.17–1.77), PVD (aHR 1.40; 95% CI 1.28–1.53), LLA (aHR 1.75; 95% CI 1.08–2.83), and gangrene (aHR 8.49; 95% CI 1.01–71.58) compared with those in the least. CONCLUSIONS Social deprivation is an independent risk factor for the development of DFD, PN, FU, PVD, LLA, and gangrene in newly diagnosed patients with type 2 diabetes. Considering the high individual and economic burdens of DFD, strategies targeting patients in socially deprived areas are needed to reduce health inequalities.

OBJECTIVE To assess the impact of bariatric surgery (BS) on incident microvascular complications of diabetes-related foot disease (DFD), sight-threatening diabetic retinopathy (STDR), and chronic kidney disease (CKD) in patients with type 2 diabetes and obesity. RESEARCH DESIGN AND METHODS A retrospective matched, controlled population-based cohort study was conducted of adults with type 2 diabetes between 1 January 1990 and 31 January 2018 using IQVIA Medical Research Data (IMRD), a database of primary care electronic records. Each patient with type 2 diabetes who subsequently had BS (surgical group) was matched on the index date with up to two patients with type 2 diabetes who did not have BS (nonsurgical group) within the same general practice by age, sex, preindex BMI, and diabetes duration. RESULTS Included were 1,126 surgical and 2,219 nonsurgical participants. In the study population 2,261 (68%) were women. Mean (SD) age was 49.87 (9.3) years vs. 50.12 (9.3) years and BMI was 46.76 (7.96) kg/m2 vs. 46.14 (7.49) kg/m2 in the surgical versus nonsurgical group, respectively. In the surgical group, 22.1%, 22.7%, 52.2%, and 1.1% of patients had gastric band, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and duodenal switch, respectively. Over a median follow-up of 3.9 years (interquartile range 1.8–6.4), BS was associated with reduction in incident combined microvascular complications (adjusted hazard ratio 0.53, 95% CI 0.43–0.66, P < 0.001), DFD (0.61, 0.50–0.75, P < 0.001), STDR (0.66, 0.44–1.00, P = 0.048), and CKD (0.63, 0.51–0.78, P < 0.001). Analysis based on the type of surgery showed that all types of surgery were associated with a favorable impact on the incidence of composite microvascular complications, with the greatest reduction for RYGB. CONCLUSIONS BS was associated with a significant reduction in incident diabetes-related microvascular complications.

There is a gap in the literature investigating the impact of obstetric complications on subsequent mental ill health outcomes. The aim of this study was to establish the association between post-partum haemorrhage (PPH) and mental ill health. We conducted a retrospective open cohort study utilizing linked primary care (The Health Improvement Network (THIN)) and English secondary care (Hospital Episode Statistics (HES)) databases, from January 1, 1990 to January 31, 2018. A total of 42,327 women were included: 14,109 of them were exposed to PPH during the study period and 28,218 unexposed controls were matched for age and date of delivery. Hazard ratios (HRs) for mental illness among women with and without exposure to PPH were estimated after controlling for covariates. Women who had had PPH were at an increased risk of developing postnatal depression (adjusted HR: 1·10, 95%CI: 1·01–1·21) and post–traumatic stress disorder (PTSD) (adjusted HR: 1·17, 95%CI: 0·73–1·89) compared to women unexposed to PPH. When restricting the follow–up to the first year after childbirth, the adjusted HR for PTSD was 3·44 (95% CI 1·31–9·03). No increase in the overall risk was observed for other mental illnesses, including depression (adjusted HR: 0·94, 95%CI: 0·87–1·01), severe mental illness (adjusted HR: 0·65, 95%CI: 0·40–1·08, p = 0·239) and anxiety (adjusted HR: 0·99, 95%CI: 0·90–1·09). PPH is associated with a significant increase in the risk of developing postnatal depression and PTSD in the first year after delivery. Active monitoring for mental illness should form an integral part of the follow–up in women who suffered a PPH.

Objective Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection. Design Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN). Methods The main outcome was the incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS. Results We identified 21 292 women with a coded diagnosis of PCO/PCOS and randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 (95% CI: 1.27–1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14–1.63)], P = 0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 (1.05–1.56), P = 0.015). Conclusion Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic. Significance statement Women with polycystic ovary syndrome (PCOS) have an increased risk of cardio-metabolic disease, which have been identified as a risk factor for COVID-19. To investigate whether the increased metabolic risk in PCOS translates into an increased risk of COVID-19 infection, we carried out a population-based closed cohort study in the UK during its first wave of the SARS-CoV-2 pandemic (January to July 2020), including 21 292 women with PCOS and 78 310 controls matched for sex, age and general practice location. Results revealed a 52% increased risk of COVID-19 infection in women with PCOS, which remained increased at 28% above controls after adjustment for age, BMI, impaired glucose regulation and other explanatory variables.

OBJECTIVE To estimate 22-year trends in the prevalence and incidence of scleritis, and the associations of scleritis with infectious and immune-mediated inflammatory diseases (I-IMIDs) in the UK. METHODS The retrospective cross-sectional and population cohort study (1997-2018) included 10,939,823 patients (2,946 incident scleritis cases) in The Health Improvement Network, a nationally representative primary care records database. The case-control and matched cohort study (1995-2019) included 3,005 incident scleritis cases and 12,020 control patients matched by age, sex, region, and Townsend deprivation index. Data were analyzed using multivariable Poisson regression, multivariable logistic regression, and Cox proportional hazards multivariable models adjusted for age, sex, Townsend deprivation index, race/ethnicity, smoking status, nation within the UK, and body mass index. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS Scleritis incidence rates per 100,000 person-years declined from 4.23 (95% CI 2.16-6.31) to 2.79 (95% CI 2.19-3.39) between 1997 and 2018. The prevalence of scleritis per 100,000 person-years was 93.62 (95% CI 90.17-97.07) in 2018 (61,650 UK patients). Among 2,946 patients with incident scleritis, 1,831 (62.2%) were female, the mean ± SD age was 44.9 ± 17.6 years (range 1-93), and 1,257 (88.8%) were White. Higher risk of incident scleritis was associated with female sex (adjusted IRR 1.53 [95% CI 1.43-1.66], P < 0.001), Black race/ethnicity (adjusted IRR 1.52 [95% CI 1.14-2.01], P = 0.004 compared to White race/ethnicity), or South Asian race/ethnicity (adjusted IRR 1.50 [95% CI 1.19-1.90], P < 0.001 compared to White race/ethnicity), and older age (peak adjusted IRR 4.95 [95% CI 3.99-6.14], P < 0.001 for patients ages 51-60 years versus those ages ≤10 years). Compared to controls, scleritis patients had a 2-fold increased risk of a prior I-IMID diagnosis (17 I-IMIDs, P < 0.001) and significantly increased risk of subsequent diagnosis (13 I-IMIDs). The I-IMIDs most strongly associated with scleritis included granulomatosis with polyangiitis, Behcet's disease, and Sjogren's syndrome. CONCLUSION From 1997 through 2018, the UK incidence of scleritis declined from 4.23 to 2.79/100,000 person-years. Incident scleritis was associated with 19 I-IMIDs, providing data for rational investigation and cross-specialty engagement.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.

Background There appears to be an inequality in the risk of cardio-metabolic disease between those from a South Asian (SA) background when compared to those of White Europeans (WE) descendance, however, this association has not been explored in a large European cohort. This population-based open retrospective cohort explores the incidence of cardio-metabolic disease in those without pre-existing cardiometabolic disease taken from a large UK primary care database from 1st January 2007 to 31st December 2017. Methods A retrospective open cohort matched population-based study using The Health Improvement Network (THIN) database. The outcomes of this study were the incidences of cardio-metabolic events (type 2 diabetes mellitus, hypertension, ischemic heart disease, stroke, heart failure, and atrial fibrillation). Results A total of 94,870 SA patients were matched with 189,740 WE patients. SA were at an increased risk of developing: T2DM (adjusted hazard ratio (aHR) 3.1; 95% CI 2.97–3.23); HTN (1.34; 95% CI: 1.29–1.39); ischaemic heart disease (IHD) (1.81; 95% CI: 1.68–1.93) and heart failure (HF) (1.11; 95% CI: 1.003–1.24). However, they were at a lower risk of atrial fibrillation (AF) (0.53; 95% CI: 0.48–0.59) when compared to WE. Of those of SA origin, the Bangladeshi community were at the greatest risk of T2DM, HTN, IHD and HF, but were at the lowest risk of AF in when compared to Indians and Pakistanis. Conclusion Considering the high risk of cardio-metabolic diseases in the SA cohort, differential public health measures should be considered in these patients to reduce their risk of disease, which may be furthered tailored depending on their country of origin.

OBJECTIVE To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA. RESEARCH DESIGN AND METHODS This age-, sex-, BMI-, and diabetes duration–matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA. RESULTS A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3–5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed. CONCLUSIONS Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.

Background Childhood maltreatment remains a significant public health issue associated with a number of poor health outcomes. This study explores the association between childhood maltreatment and the subsequent development of cardiometabolic disease and all‐cause mortality. Methods and Results Using a UK primary care database between January 1, 1995 and December 31, 2018, we conducted a population‐based open retrospective cohort study. We matched 80 657 adult patients with a historic recording of childhood maltreatment or maltreatment‐related concerns (exposed group) to 161 314 unexposed patients. Outcomes of interest were the development of cardiovascular disease, hypertension, type 2 diabetes mellitus, and risk of all‐cause mortality. During the study period there were 243 new diagnoses of cardiovascular disease (incidence rate 8.3 per 10 000 person‐years) in the exposed group compared with 254 in the unexposed group (incidence rate 4.6 per 10 000 person‐years). Following adjustment for key covariates, this translated to an adjusted incidence rate ratio of 1.71 (95% CI 1.42–2.06). Additionally, the exposed group had an increased risk of hypertension (adjusted incidence rate ratio 1.42; 95% CI , 1.26–1.59), type 2 diabetes mellitus (adjusted incidence rate ratio 2.13; 95% CI , 1.86–2.45) and all‐cause mortality (adjusted incidence rate ratio 1.75; 95% CI , 1.52–2.02) during the study period compared with the unexposed group. Conclusions Considering the high prevalence of exposure to childhood maltreatment, we have demonstrated the substantial associated burden of preventable cardiometabolic disease. There is a clear need to ensure that public health approaches are implemented to prevent the adverse consequences following exposure to childhood maltreatment.