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Clinical trials have shown that bariatric surgery (BS) is associated with better glycemic control and diabetes remission in patients with type 2 diabetes (T2D) compared with routine care.We conducted a real-world population-based study examining the impact of BS on glycemic control and medications in patients with T2D.This was a retrospective, matched, controlled cohort study conducted between January 1, 1990, and January 31, 2018, using IQVIA Medical Research Data, a primary care electronic records database. Adults with body mass index (BMI) ≥30 kg/mA total of 1126 patients in the surgical group and 2219 patients in the control group were analyzed. Mean (standard deviation) age was 50.0 (9.3) years, 67.6% were women, baseline glycocylated hemoglobin (HbA1C) was 7.8% (1.7 mmol/mol), and diabetes duration was 4.7 years (range, 2.0-8.4 years). Over a median (interquartile range) follow-up of 3.6 years (1.7-5.9 years), a higher proportion of patients in the surgical group achieved an HbA1C of ≤6.0% than the control group (65.8% versus 22.8%). The surgical group showed a decrease in mean HbA1C of 1.5% (95% confidence interval [CI]: 1.4%-1.7%), 1.4% (1.2%-1.5%), and 1.3% (1.1%-1.5%) at 1-, 2-, and 3-year follow-up, respectively, whereas HbA1C increased in the control group. The proportion of patients receiving glucose-lowering medications decreased in the surgical group (92.2% to 66.5%) but increased in the control group (85.3% to 90.2%).BS is associated with significant improvement in glycemic control, achievement of normal HbA1C levels, and reduced need for glucose-lowering therapy in patients with T2D.

Background Clinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge. Aim We evaluated post-hospitalisation asthma management in primary care and its associations with patient characteristics. Design and setting A retrospective cohort study was performed using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data. Method Patients with asthma aged ≥5 years who had at least one asthma-related hospitalisation from 1st January 2017 to 31st December 2019 were included. Primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression. Results The study included 17,457 patients. 60% had received the primary outcome within 28 days of hospital discharge. 13% received an asthma review, 8% an asthma management plan, 57% an asthma medication, 8% a demonstration of inhaler technique, and 1.2% (of smokers) smoking cessation counselling. This care was less likely to be received by patients from black ethnic minority groups (27-54% relative reduction, depending on age group). By contrast, previous prescriptions of short-acting bronchodilators were associated with an increased likelihood of the primary outcome. Conclusion A significant proportion of patients do not receive timely follow-up in primary care following asthma-related hospital admissions, particularly among patients from black ethnic groups.

Background Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk. Methods A UK retrospective cohort study (1995–2021) using data from a nationwide database (The Health Improvement Network). Women aged 18–40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls. Results During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00–1.19), IHD 1.18 (1.01–1.37), cerebrovascular disease 1.04 (0.92–1.17), HF 1.30 (1.02–1.65), hypertension 1.07 (1.03–1.11), T2DM 1.37 (1.29–1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02–1.52), IHD 1.13 (0.81–1.57), cerebrovascular disease 1.43 (1.10–1.87), HF 0.99 (0.57–1.75), hypertension 1.31 (1.21–1.43), T2DM 1.74 (1.52–1.98). Conclusions History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health.

Introduction To describe the incidence and prevalence of pelvic inflammatory disease (PID) and to estimate the risk of cardiometabolic outcomes among women with PID compared to women without PID. Methods A UK retrospective matched cohort study using data from The Health Improvement Network. To assess cardiometabolic risk, women (aged ≥ 16 years) with PID were compared to matched controls without PID. Annual prevalence and incidence of PID (1998–2017) were estimated among women aged 16–50 years using annual cross-sectional and cohort analyses, respectively. Adjusted hazard ratios (aHR) and 95% CI for cardiometabolic outcomes were estimated using Cox proportional hazards models. The primary outcome was composite cardiovascular disease (CVD) and its subtypes, including ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were hypertension, and type 2 diabetes mellitus (T2DM). Results Among the 715 recorded composite CVD events, the crude incidence rate per 1000 person-years was 1.5 among women with history of PID compared to 1.3 in matched controls. Compared to women without PID (N = 73,769), the aHRs for cardiometabolic outcomes among women with PID (N = 19,804) were: composite CVD 1.10 (95% CI 0.93–1.30); IHD 1.19 (95% CI 0.93–1.53); cerebrovascular disease 1.13 (95% CI 0.90–1.43); HF 0.92 (95% CI 0.62–1.35) hypertension 1.10 (95% CI 1.01–1.20); and T2DM 1.25 (95% CI 1.09–1.43). The prevalence (per 10,000 population) of PID was 396.5 in 1998 and 237 in 2017. The incidence (per 10,000 person-years) of PID was 32.4 in 1998 and 7.9 in 2017. Conclusion There was no excess risk of composite CVD or its subtypes among women with history of PID compared to matched controls. Findings from our study suggest that history of PID was associated with an increased risk of hypertension and type 2 diabetes mellitus, two major risk factors for CVD. Additional studies are required to support these findings.

ObjectivesTo assess the association between demographic and clinical risk factors and asthma-related hospital and intensive care admissions in children, adolescents, and adults, and to estimate the proportion of hospital admissions attributable to modifiable risk factors.DesignCohort study using routinely collected primary and secondary care data.SettingA large UK-based primary care database, the Clinical Practice Research Datalink (CPRD) Aurum, and linked Hospital Episode Statistics Admitted Patient Care (HES APC) data.ParticipantsPatients were eligible for the study if they were aged five years and older and had an asthma diagnosis with linked data to the HES APC database. This included 90,989 children aged 5-11 years, 114,927 adolescents aged 12-17 years, and 1,179,410 adults aged 18 years or older.Primary and secondary outcome measuresPrimary outcome: asthma-related hospital admissions recorded from 1stJanuary 2017 to 31stDecember 2019. Secondary outcome: asthma-related intensive care unit (ICU) admissions. Incidence rate ratios (IRR) adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) amongst those with asthma was estimated for modifiable risk factors that were statistically significantly associated with the primary outcome.ResultsIn children, the risk factors for asthma-related hospital admission were belonging to an ethnic minority group, increasing socioeconomic deprivation, allergies (PAF 11.4%, 95% CI 6.8 to 15.8), and atopic eczema (6.8%, 3.6 to 9.9). In adolescents, the risk factors were being female, belonging to an ethnic minority group, increasing socioeconomic deprivation, former smoking (PAF 6.8%, 0.9 to 12.3), and allergic rhinitis. In adults, the risk factors were younger age, being female, belong to an ethnic minority group, increasing socioeconomic deprivation, being underweight, overweight or obese (PAF 23.3%, 95% CI 20.5 to 26.1 for obesity), current smoking (4.3%, 3.0 to 5.7), depression (11.1%, 9.1 to 13.1), allergies (6.2%, 4.4 to 8.0), gastro-oesophageal reflux disease (2.3%, 1.2 to 3.4), anxiety (2.0%, 0.5 to 3.6), and chronic rhinosinusitis (0.8%, 0.3 to 1.3%). In all age groups, increasing medication burden was associated with an increased risk in the primary outcome.Risk factors for asthma-related ICU admissions in children were black or mixed ethnicity and high levels of socioeconomic deprivation; in adolescents, they were female sex and black ethnicity; and in adults, they were younger age, female sex, black, mixed, or Asian ethnicity, and depression. In all age groups, increasing medication burden was associated with an increased risk in the secondary outcome.ConclusionsThere are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating atopic conditions in all age groups should be considered an integral part of asthma management. Adults have a wide range of potentially treatable risk factors that contribute substantially to asthma-related hospital admissions, including obesity, smoking, depression, anxiety and gastro-oesophageal reflux disease. Treating these risk factors could significantly reduce the rate of avoidable hospital admissions. Overall asthma medication burden is an important reflection of disease severity and prognostic marker of asthma outcomes, which should be monitored in all patients.WHAT IS ALREADY KNOWN ON THIS TOPICAsthma is one of the most common chronic diseases and remains an important cause of avoidable hospital and intensive care admissions.Risk factors for asthma have previously been described but there are a lack of large population scale analyses stratifying these risk factors among children, adolescents, and adults, or providing estimates of the key modifiable risk factors that most contribute to avoidable hospital admissions.WHAT THIS STUDY ADDSThere are significant sociodemographic inequalities in asthma-related hospital and intensive care admissions in children, adolescents, and adults.Atopic disorders and smoking are key addressable risk factors in all age groups, while obesity, depression, and anxiety are important treatment targets more specific to adults.Overall asthma medication burden is strongly associated with the risk of asthma-related hospital and ICU admissions and should be used for assessing disease severity and monitoring asthma control and prognosis.

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

Childhood maltreatment affects over one in three children worldwide and is associated with a substantial disease burden. This study explores the association between childhood maltreatment and the development of atopic disease.We did a population-based retrospective matched open cohort study using participating general practices between 1st January 1995 and 30th September 2019. Read codes were utilised to identify patients exposed to childhood maltreatment (either suspected or confirmed) who were matched to up to four unexposed patients by age, sex, general practice, and Townsend deprivation quintile. Cox regression analysis was used to calculate adjusted (age, sex, Townsend deprivation quintile) hazard ratios (aHR) for development of atopy (asthma, atopic dermatitis, or allergic rhino conjunctivitis) during follow up in those without atopy at study entry.183,897 exposed patients were matched to 621,699 unexposed patients. During the follow up period, 18,555 patients (incidence rate (IR) 28.18 per 1000 person-years) in the exposed group developed atopic disease compared to the 68,368 (IR 23.58 per 1000 person-years) in the unexposed group, translating to an adjusted HR of 1.14 (95% CI 1.12-1.15). Notably, the risk of developing asthma was aHR 1.42 (95% CI 1.37-1.46). Associations were more pronounced in analyses restricted to females and confirmed cases of childhood maltreatment only.Considering the substantial health burden associated with childhood maltreatment, it is important to implement public health policies aimed at enhancing: 1) detection and primary prevention of childhood maltreatment, 2) secondary and tertiary prevention interventions to reduce the burden of ill health associated with exposure to maltreatment and 3) clinical awareness of such associations and subsequent knowledge of management.None.

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.

Objective To describe the prevalence and incidence of endometriosis and to estimate the risk of cardiovascular outcomes in women with endometriosis. Design Population-based cohort study using The Health Improvement Network database. Setting UK primary care. Population Women aged 16-50 years were followed from 1995 to 2018. Methods Adjusted hazard ratios (aHR) for cardiovascular outcomes comparing women with endometriosis with those without endometriosis were estimated using multivariable Cox regression models. Prevalence and incidence of endometriosis were estimated using annual (1998-2017) sequential cross-sectional and cohort studies, respectively. Main outcome measure The primary outcome was composite cardiovascular disease (CVD) including, ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were arrhythmia, hypertension and all-cause mortality. Results In all, 56 090 women with endometriosis and 223 669 matched controls without endometriosis were included in the analysis of cardiovascular risk. Compared with women without endometriosis, the aHR for cardiovascular outcomes among women with endometriosis were: composite CVD 1.24 (95% CI 1.13-1.37); IHD 1.40 (95% CI 1.22-1.61); cerebrovascular disease 1.19 (95% CI 1.04-1.36); HF 0.76 (95% CI 0.54-1.07); arrhythmia 1.26 (95% CI 1.11-1.43); hypertension 1.12 (95% CI 1.07-1.17) and all-cause mortality 0.66 (95% CI 0.59-0.74). The incidence of endometriosis was 12.3 per 10 000 person-years in 1998 and 11.5 per 10 000 person-years in 2017. The prevalence of endometriosis increased from 119.7 per 10 000 population in 1998 to 201.3 per 10 000 population in 2017. Conclusion Endometriosis is associated with an increased risk of cardiovascular outcomes. Young women with endometriosis are a potential target for CVD risk assessment and prevention. Tweetable abstract Endometriosis is associated with increased risk of cardiovascular outcomes: a UK retrospective matched cohort study.

OBJECTIVE Cardiovascular disease (CVD) is a major complication and cause of mortality in Takayasu arteritis (TAK), but population-based controlled studies from the UK are lacking. We undertook the present study to investigate the frequency of morbidity and mortality related to CVD, as well as to cerebrovascular and kidney disease, among patients with TAK in the UK. METHODS Yearly cohort and cross-sectional studies were performed from 2000 to 2017 to estimate annual incidence and prevalence, respectively, of TAK. Using a UK primary care database (IQVIA Medical Research Data), an open retrospective matched cohort study was conducted to estimate risk of hypertension, diabetes, cardiovascular morbidity, chronic kidney disease (CKD), and all-cause mortality in TAK. Risk (adjusted hazard ratio [HR]) of the assessed comorbidities among patients with TAK compared to age- and sex-matched controls was estimated. Changes in medication prescription over time were examined in both groups. RESULTS One hundred forty-two patients with TAK (median age 53.4 years [interquartile range 33.8-70.7]) and 1,371 matched controls were included. The annual incidence and prevalence of TAK were 0.8 per million and 7.5 per million respectively. All-cause mortality was increased in TAK (adjusted HR 1.88 [95% confidence interval 1.29-2.76]). Patients with TAK had an increased risk of developing ischemic heart disease, stroke/transient ischemic attack, combined CVD, and peripheral vascular disease compared to controls, but no increase in risk of hypertension, CKD, heart failure, or diabetes. Only ~50% of patients with TAK requiring secondary CVD prevention were prescribed statins or antiplatelet agents within 1 year after study entry. CONCLUSION Cardiovascular morbidity was increased among patients with TAK receiving primary care services in the UK. Treatment with statins and antiplatelet agents in these patients was suboptimal.

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.

Surgery is required for most patients with Crohn's disease (CD) and further surgery may be necessary if medical treatment fails to control disease activity. The aim of this study was to characterize the risk of, and factors associated with, further surgery following a first resection for Crohn's disease.Hospital Episode Statistics from England were examined to identify patients with CD and a first recorded bowel resection between 2007 and 2016. Multivariable logistic regression was used to examine risk factors for further resectional surgery within 5 years. Prevalence-adjusted surgical rates for index CD surgery over the study period were calculated.In total, 19 207 patients (median age 39 years, interquartile range 27-53 years; 55% women) with CD underwent a first recorded resection during the study period. 3141 (16%) underwent a further operation during the study period. The median time to further surgery was 2.4 (interquartile range 1.2-4.6) years. 3% of CD patients had further surgery within 1 year, 14% by 5 years and 23% by 10 years. Older age (≥58), index laparoscopic surgery and index elective surgery (adjusted OR 0.65, 95% CI 0.54-0.77; 0.77, 0.67-0.88; and 0.77, 0.69-0.85; respectively) were associated with a reduced risk of further surgery by 5 years. Prior surgery for perianal disease (1.60, 1.37-1.87), an extraintestinal manifestation of CD (1.51, 1.22-1.86) and index surgery in a high-volume centre for CD surgery (1.20, 1.02-1.40) were associated with an increased risk of further surgery by 5 years. A 25% relative and 0.3% absolute reduction in prevalence-adjusted index surgery rates for CD was observed over the study period.Further surgery following an index operation is common in CD. This risk was particularly seen in patients with perianal disease, extraintestinal manifestations and those who underwent index surgery in a high-volume centre.

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.

The British Society of Gastroenterology has recommended the Edinburgh Dysphagia Score (EDS) to risk-stratify dysphagia referrals during the endoscopy COVID recovery phase.External validation of the diagnostic accuracy of EDS and exploration of potential changes to improve its diagnostic performance.A prospective multicentre study of consecutive patients referred with dysphagia on an urgent suspected upper gastrointestinal (UGI) cancer pathway between May 2020 and February 2021. The sensitivity and negative predictive value (NPV) of EDS were calculated. Variables associated with UGI cancer were identified by forward stepwise logistic regression and a modified Cancer Dysphagia Score (CDS) developed.1301 patients were included from 19 endoscopy providers; 43% male; median age 62 (IQR 51-73) years. 91 (7%) UGI cancers were diagnosed, including 80 oesophageal, 10 gastric and one duodenal cancer. An EDS ≥3.5 had a sensitivity of 96.7 (95% CI 90.7-99.3)% and an NPV of 99.3 (97.8-99.8)%. Age, male sex, progressive dysphagia and unintentional weight loss3 kg were positively associated and acid reflux and localisation to the neck were negatively associated with UGI cancer. Dysphagia duration6 months utilised in EDS was replaced with progressive dysphagia in CDS. CDS ≥5.5 had a sensitivity of 97.8 (92.3-99.7)% and NPV of 99.5 (98.1-99.9)%. Area under receiver operating curve was 0.83 for CDS, compared to 0.81 for EDS.In a national cohort, the EDS has high sensitivity and NPV as a triage tool for UGI cancer. The CDS offers even higher diagnostic accuracy. The EDS or CDS should be incorporated into the urgent suspected UGI cancer pathway.

Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively).We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.

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.

Background Granulomatosis with polyangiitis (GPA) is small vessel vasculitis with heterogeneous clinical presentation. In the present population-based cohort study, we classified patients with GPA based on clinical features at presentation using an unsupervised clustering approach and compared their mortality, infections and frequency of comorbidities. Methods In this open cohort study, de-identified primary care data of patients with GPA included in the IQVIA Medical Research Data database between 1 January 1995 and 25 September 2019 was analysed retrospectively. Latent class analysis was performed to create symptom clusters of patients based on 16 categories of symptoms representing various organ involvement. All-cause mortality of resultant clusters was compared after adjusting for age, sex, Townsend deprivation quintile and smoking status at index date using extended Cox proportional hazards models. Prescription of antibiotics, considered as an indirect indicator of recurrent bacterial infection, was compared using a recurrent event model, after adjusting for quarterly use of steroid as a time-dependent covariate. Cumulative frequencies of common comorbidities were compared among the clusters at index visit, 1-year and 3-year follow-up. Results Altogether, 649 patients with GPA [median age 60.0 (IQR: 49.6–70.1)] were included. Three clusters were identified: patients with limited disease mainly with involvement of ENT and cough were classified into cluster 1 (n = 426); cluster 2 had generalised non-renal disease (n = 176); while patients in cluster 3 had renal-predominant disease (n = 47). Many patients in cluster 1 developed generalised disease at the end of 1 year. Mortality in clusters 2 and 3 was higher compared with cluster 1. Mortality in cluster 1 itself was 68% higher than the general population without GPA. The duration of antibiotics prescription and frequency of coexisting medical illnesses was also higher in clusters 2 and 3. Conclusions In a primary care setting, patients with GPA can be classified into three distinct clusters with different prognosis, susceptibility to recurrent infections and presence of comorbidities. The tendency of cluster 1 to evolve into a more generalised disease raises questions about current immunosuppressive treatment approaches in these patients.

Periodontal disease and domestic abuse (DA) are significant public health problems. Previous cross-sectional evidence indicates an association between DA exposure and development of periodontal disease. There have been no large-scale cohort studies exploring this relationship in a UK-setting. Our aim was to conduct a population-based retrospective open cohort study to explore the association between DA exposure and the subsequent development of general practitioner (GP)-coded periodontal disease.We undertook a retrospective open-cohort study using the IQVIA Medical Research Database (IMRD) UK database between the 123429 exposed patients were matched to 69815 unexposed patients. During the study period, 78 exposed patients had developed GP-recorded periodontal disease compared to 154 in the unexposed group, translating to an IR of 94.18 per 100,000 person years (py) and 54.67 per 100,000 py respectively. Following adjustment for key covariates, this translated to an aHR of 1.74 (95% CI 1.31-2.32), which was robust during our sensitivity analysis.Our results provide further evidence that DA exposure is associated with increased risk of developing periodontal disease. There is a need for swift implementation of public health policies to improve surveillance, reporting, and prevention of DA.

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.

Aims/hypothesis People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes. Methods We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis. Results In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19–10.11), and the mean BMI was 25.82 kg/m2 (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p Conclusions/interpretation Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs. Graphical abstract

Background Miscarriages affect up to a fifth of all pregnancies and are associated with substantial psychological morbidity. However, their relationship with cardiometabolic risk factors is not well known. Therefore, in this study we aimed to estimate the burden of cardiovascular risk factors including diabetes mellitus (type 1 or 2) and hypertension in women with miscarriage compared to women without a record of miscarriage. Methods A population-based retrospective cohort study was conducted using IVQIA Medical Research Data UK (IMRD-UK) between January 1995 and May 2016, an anonymised electronic health records database that is representative of the UK population. A total of 86,509, 16–50-year-old women with a record of miscarriage (exposed group) were matched by age, smoking status, and body mass index to 329,865 women without a record of miscarriage (unexposed group). Patients with pre-existing hypertension and diabetes were excluded. Adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95% CI) for diabetes and hypertension were estimated using multivariable Poisson regression models offsetting for person-years follow-up. Results The mean age at cohort entry was 31 years and median follow up was 4.6 (IQR 1.7–9.4) years. During the study period, a total of 792 (IR 1.44 per 1000 years) and 2525 (IR 1.26 per 1000 years) patients developed diabetes in the exposed and unexposed groups, respectively. For hypertension, 1995 (IR 3.73 per 1000 years) and 1605 (IR 3.39 per 1000 years) new diagnoses were recorded in the exposed and unexposed groups, respectively. Compared to unexposed individuals, women with a record miscarriage were more likely to develop diabetes (aIRR = 1.25, 95% CI: 1.15–1.36; p Conclusions Women diagnosed with miscarriage were at increased risk of developing diabetes mellitus and hypertension. Women with history of miscarriage may benefit from periodic monitoring of their cardiometabolic health.

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 This study compared the incidence of obstructive sleep apnea (OSA) in patients with and without type 2 diabetes and investigated risk factors for OSA in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was performed to compare OSA incidence between adult patients with and without type 2 diabetes matched for age, sex, and BMI. Patients with a prevalent OSA diagnosis were excluded. The study cohort was derived from The Health Improvement Network (THIN), a U.K. primary care database, from 1 January 2005 to 31 December 2017. RESULTS There were 3,110 (0.88%) and 5,968 (0.46%) incident OSA cases identified in the 360,250 exposed and 1,296,489 unexposed patient cohorts, respectively. Adjusted incidence rate ratio (aIRR) of OSA in patients with type 2 diabetes compared with those without was 1.48 (95% CI 1.42–1.55; P < 0.001). In a multivariate regression analysis of patients with type 2 diabetes, significant predictors of OSA were diabetes-related foot disease (1.23 [1.06–1.42]; P = 0.005), being prescribed insulin in the last 60 days (1.58 [1.42–1.75]; P < 0.001), male sex (2.27 [2.09–2.46]; P < 0.001), being overweight (2.02 [1.54–2.64]; P < 0.001) or obese (8.29 [6.42–10.69]; P < 0.001), heart failure (1.41 [1.18–1.70]; P < 0.001), ischemic heart disease (1.22 [1.11–1.34]; P < 0.001), atrial fibrillation (1.23 [1.04–1.46]; P = 0.015), hypertension (1.32 [1.23–1.43]; P < 0.001), and depression (1.75 [1.61–1.91]; P < 0.001). CONCLUSIONS When considered alongside previous evidence, this study indicates that the association between type 2 diabetes and OSA is bidirectional. In addition to known predictors of OSA, diabetes-related foot disease and insulin treatment were identified as risk factors in patients with type 2 diabetes.

BackgroundIgA vasculitis (IgAV, Henoch-Schönlein purpura) is a small-vessel vasculitis most common in children but also occurring in adults. Case series have suggested that IgAV may be associated with cardiovascular disease and venous thromboembolism, but this has not been evaluated in population-based studies. Renal disease and hypertension are possible complications of the disease with unknown incidence.MethodsUsing a large UK primary care database, we conducted an open retrospective matched cohort study of cardiovascular, venous thrombotic and renal outcomes in adult-onset and childhood-onset IgAV. Control participants were selected at a 2:1 ratio, matched for age and sex. Adjusted HRs (aHRs) were calculated using Cox proportional hazards models.Results2828 patients with adult-onset IgAV and 10 405 patients with childhood-onset IgAV were compared with age-matched and sex-matched controls. There was significantly increased risk of hypertension (adult-onset aHR 1.42, 95% CI 1.19 to 1.70, p < 0.001; childhood-onset aHR 1.52, 95% CI 1.22 to 1.89, p < 0.001) and stage G3–G5 chronic kidney disease (adult-onset aHR 1.54, 95% CI 1.23 to 1.93, p < 0.001; childhood-onset aHR 1.89, 95% CI 1.16 to 3.07, p=0.010). There was no evidence of association with ischaemic heart disease, cerebrovascular disease or venous thromboembolism. All-cause mortality was increased in the adult-onset IgAV cohort compared with controls (aHR 1.27, 95% CI 1.07 to 1.50, p=0.006).ConclusionsPatients with IgAV are at increased risk of hypertension and chronic kidney disease (CKD) compared with individuals without IgAV; analysis restricted to adult-onset IgAV patients showed increased mortality. Appropriate surveillance and risk factor modification could improve long-term outcomes in these patients.

Due to the relatively small number of outcomes in our study, we decided that it was best to be conservative in the number of covariates we included in the Cox regression models. We therefore restricted to age, sex, BMI, Townsend deprivation quintile and smoking status. We provided information on statin use, steroid use and comorbidities in the exposed and unexposed groups in the baseline table.

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.

BackgroundBariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.AimTo investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.Design and settingRetrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).MethodParticipants were adults who had had bariatric surgery with a minimum of 3 years’ follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.ResultsA total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2–7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.ConclusionThis study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.

Background People with diabetes have longer hospital stays and poorer clinical outcomes. Diabetes inpatient specialist nurses have been introduced to improve care. Aims To assess the evidence for the benefit of diabetes specialist nurses in the inpatient setting. Methods A systematic search of MEDLINE (ovid), Embase (ovid), CINAHL (EBSCO) and Web of Science core collection from January 1998 to September 2019 was performed using key terms for diabetes specialist nurses and hospital setting. Studies measuring patient care using any standardised or validated outcome measures after introduction of a dedicated diabetes specialist nurse or nursing team were eligible for inclusion and findings reported by narrative synthesis. Results There were 10 studies which met the inclusion criteria. One was a randomised controlled study and the remaining nine studies were before and after studies with three of them using a time series analysis methodology. The majority reported length of stay (LOS) and showed a reduction in median LOS by between 0.5 and 3 days. Reductions in bed occupancy ranged from 39% to 47%. There was a paucity of evidence for outcomes related to patient care with some measures limited to single studies. These included a 52% reduction in total drug errors, improved patient knowledge, higher patient satisfaction and improved glycaemic control post-discharge. There was no reduction of mortality observed. Conclusions These studies suggest a reduction in LOS and improved clinical care for patients with diabetes after the introduction of diabetes inpatient specialist nurses. Future research should examine a range of benefits associated with diabetes inpatient specialist nurse delivered services, including reduction of inpatient complications such as infections and cardiovascular events.

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.

BACKGROUND Remission of type 2 diabetes following bariatric surgery is well established, but identifying patients who will go into remission is challenging. PURPOSE To perform a systematic review of currently available diabetes remission prediction models, compare their performance, and evaluate their applicability in clinical settings. DATA SOURCES A comprehensive systematic literature search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) was undertaken. The search was restricted to studies published in the last 15 years and in the English language. STUDY SELECTION All studies developing or validating a prediction model for diabetes remission in adults after bariatric surgery were included. DATA EXTRACTION The search identified 4,165 references, of which 38 were included for data extraction. We identified 16 model development and 22 validation studies. DATA SYNTHESIS Of the 16 model development studies, 11 developed scoring systems and 5 proposed logistic regression models. In model development studies, 10 models showed excellent discrimination with area under the receiver operating characteristic curve ≥0.800. Two of these prediction models, ABCD and DiaRem, were widely externally validated in different populations, in a variety of bariatric procedures, and for both short- and long-term diabetes remission. Newer prediction models showed excellent discrimination in test studies, but external validation was limited. LIMITATIONS While the key messages were consistent, a large proportion of the studies were conducted in small cohorts of patients with short duration of follow-up. CONCLUSIONS Among the prediction models identified, the ABCD and DiaRem models were the most widely validated and showed acceptable to excellent discrimination. More studies validating newer models and focusing on long-term diabetes remission are needed.

Introduction Death after upper gastrointestinal (GI) bleeding is commonly due to cardiovascular disease and early re-initiation of anti-platelet therapy after haemostasis is associated with a reduction in all-cause and cardiovascular mortality. 2012 NICE upper GI bleeding guidelines advocate early re-initiation of antiplatelet agents for primary or secondary prevention of cardiovascular disease. Methods The Health Improvement Network (THIN) is a UK primary care database containing data from over 15 million subjects. Subjects were identified with an existing diagnosis of ischaemic heart disease (IHD) or stroke, who were taking antiplatelet agents (aspirin, clopidogrel, ticagrelor, prasugrel or dipyridamole) and had an upper GI bleed between 2000 and 2017. Re-initiation of antiplatelet agents (defined as a record of at least one prescription after the upper GI bleeding event) within 28, 56 and 90 days was examined. Interrupted time series analysis (ITS) was performed to investigate changes in prescribing practices before and after the 2012 NICE guidelines, with prescription of statins over the same time period used as a negative control. Results 6,372 subjects prescribed antiplatelet agents and 9,615 prescribed statins with a clinical code for upper GI bleeding and IHD or stroke were identified. Between 2000 and 2017, the proportion of subjects who had their antiplatelet agents re-initiated post-upper GI bleed increased from 33.9 to 55.6% (p Conclusions There has been a progressive and statistically significant increase in early re-initiation of antiplatelet agents after upper GI bleeding in the UK between 2000 and 2017. However, the 2012 NICE upper GI bleeding guidelines appeared to have no significant effect on prescribing practices.

Introduction Skin diseases including erythema nodosum (EN), pyoderma gangrenosum (PG), Sweet’s syndrome (SS) and aphthous stomatitis (AS) can occur with inflammatory bowel disease (IBD). We examined the risk of later developing IBD in these skin disorders and the time to IBD diagnosis. Methods A large UK primary care database was examined between 1995–2018. Cases of EN (excluding sulfasalazine history), PG and all skin disorders associated with IBD combined were matched to controls on age, sex and GP registration. Pre-existing IBD cases were excluded. Subjects were followed until a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) and incident rate ratio (IRR) modelled, adjusting for age, sex, body mass index, comorbidity, deprivation level and smoking status. The time to a later diagnosis of IBD in cases and controls was compared using the Mann-Whitney U test. Results 5,349 EN cases (median age 36 (IQR 23–51), 78% female) were matched to 21,100 controls. Median time to UC diagnosis was reduced in EN compared to control subjects (224 and 1,856 days respectively p 863 PG cases (age 57 (39–73), 40% male) were matched to 3,404 controls. Few IBD diagnoses were made during the study period (16 in PG cases and 6 in controls). Time to IBD diagnosis in PG cases was reduced compared to controls p=0.047. The rate of IBD was 13-fold that of controls (13.21 (5.07–34.41) p When skin disorders combined (EN, PG, SS and AS) were examined, 7,340 cases (median age 36 (23–50), female 74%) were matched to 21,764 controls. 133 cases of IBD were observed in the skin disorder group compared to 53 in controls. The rate of UC was more than 3-fold higher in the skin disorder group (3.63 (2.17–6.08) p Conclusions Skin disorders associated with IBD are not unique to IBD and clinicians who diagnose these conditions may not consider IBD leading to a delayed diagnosis. The relative risk of IBD is high in such skin disorders and symptoms suggestive of IBD should be sought, and screening investigations and gastroenterology referral considered.

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.

Background Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet’s syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM. Methods A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis. Results We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn’s disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86). Conclusions Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.