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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.

Background The COVID-19 pandemic presented new diagnostic and management challenges to primary care alongside rapid changes in service delivery. The purpose of this study was to describe the characteristics of patients with symptoms of COVID-19 in primary care, explore which characteristics were associated with a clinical diagnosis of COVID-19 and referrals to secondary care, and to describe secondary care referral decisions with reference to national guidance. Methods An observational study using routinely collected data from the Birmingham Out-of-hours Research Database. The study uses consultation data from the Birmingham and Solihull COVID Referral Centre (CRC) between 21st April and 24th July. All CRC consultations were examined to extract patient demographics, free text consultations, prescriptions, observation and onward referrals. The National Early Warning Score (NEWS2) was calculated and the clinical diagnosis of COVID-19 was established. The population was described and univariate logistic regression was used to identify characteristics associated with clinical diagnosis of COVID-19 and referral decisions. Results 681 patients were seen at the CRC and 56.3% were identified to have a clinical diagnosis of COVID-19. 14.0% of all patients were referred to secondary care, but 59% of patients classified as most severe according to national criteria were not referred. Referral was associated with increasing age, shortness of breath, tachycardia, tachypnoea and hypoxia but patients with a clinical COVID-19 diagnosis were less likely to be referred than those with other diagnoses. Conclusion Just over half of patients seen in the CRC were clinically diagnosed with COVID-19 and most patients were managed in the community. Guidelines developed in the absence of service delivery data for the management of COVID-19 were inconsistent with community urgent care delivery.

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.

Additional file 1: Supplementary Table 1. Read codes used for the ascertainment of the primary outcome (confirmed/suspected COVID-19)

Additional file 2: Supplementary Table 2. The RECORD statement for pharmacoepidemiology (RECORD-PE) checklist of items, extended from the STROBE and RECORD statements, which should be reported in non-interventional pharmacoepidemiological studies using routinely collected health data

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.

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 Although maternal death is rare in the UK, 90% (510 of 566 deaths) of women who died during or within a year after pregnancy in 2016–18 had multiple health and social problems (MBRRACE-UK). This study aims to estimate the prevalence of pre-existing multimorbidity in pregnant women in the UK. Methods Pregnant women aged 15–49 years with a conception date between Jan 1 and Dec 31, 2018, were included in this cross-sectional study, using routine health-care datasets: Clinical Practice Research Datalink (CPRD) GOLD (UK, n=37 641), Secure Anonymised Information Linkage (SAIL) databank (Wales, n=27 782), and Scottish Morbidity Records (SMR, secondary care) with linked community prescribing data (Tayside and Fife, n=6099). We defined pre-existing multimorbidity (two or more morbidities) preconception from 79 long-term physical and mental health conditions. This definition was identified from the literature and prioritised by the multidisciplinary research advisory group, including patient representatives. The association of women's characteristics preconception with multimorbidity was examined with logistic regression. The University of St Andrews School of Medicine Ethics Committee approved this project. Participant consent was not required as the data used are anonymised. Interpretation Prevalence of multimorbidity was 44·2% (95% CI 43·7–44·7) in CPRD, 46·2% (45·6–46·8) in SAIL, and 19·8% (18·8–20·8) in SMR. Mental health conditions were highly prevalent and involved 70% of multimorbidity (CPRD: prevalence of multimorbidity with one or more mental health conditions 31·3% [30·8–31·8]). Pregnant women with conditions that were leading causes of maternal deaths had a high prevalence of multimorbidity (CPRD: 745 [2·0%] of 37 641 women had cardiovascular disease, of whom 597 [80·1%] had multimorbidity). Higher maternal age (CPRD: adjusted odds ratio 1·81 [95% CI 1·04–3·17] for 45–49 years vs 15–19 years), gravidity (1·68 [1·50–1·89] for ≥5 vs 1), BMI (1·59 [1·44–1·76], for ≥30 vs 18·5–24·9) and smoking (1·61 [1·46–1·77] for smoker vs non-smoker) were significantly associated with multimorbidity. Ethnicity and deprivation were not significantly associated with multimorbidity. Interpretation A significant proportion of women enter pregnancy with pre-existing multimorbidity, especially mental health conditions. Pregnant women with multimorbidity were more likely to smoke and have a raised BMI and support may be required to address this. There may be health-care access inequalities for some health conditions, especially mental health conditions in pregnant women from deprived or ethnic minority groups. Secondary care and linked community prescription dataset captured severe conditions and might underestimate the prevalence of multimorbidity. Urgent research is needed to quantify the consequences of maternal multimorbidity for mother and child. Funding This work was supported by the joint UKRI-NIHR Strategic Priorities Fund consolidator grant (grant number MR/V005243/1). BT was funded by the National Institute for Health Research (NIHR) West Midlands Applied Research Collaboration. AA and SIL were funded as NIHR Academic Clinical Fellows. The views expressed are those of the author and not necessarily those of the funders, the NIHR or the UK Department of Health and Social Care.

The first-line therapy for patients with center-involving diabetic macular edema (DME) is with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with or without adjunctive macular laser treatment. However, a significant proportion of patients have persistent and recurrent edema despite repeated anti-VEGF injections. The fluocinolone acetonide (FA) 190 μg intravitreal implant has been shown in pivotal clinical trials to be efficacious for the treatment of DME and has been approved in many countries for use in patients who have not responded to first-line therapy. In this report, we have collated the latest data from the increasing number of studies to illustrate the pattern of usage of the Iluvien FA implant for DME during the current anti-VEGF era. We have shown that there is now a wealth of published evidence from real-world studies to support the clinical utility of the FA implant in achieving further resolution of edema and improving visual acuity outcomes in this challenging group of patients.

The first-line therapy for patients with center-involving diabetic macular edema (DME) is with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with or without adjunctive macular laser treatment. However, a significant proportion of patients have persistent and recurrent edema despite repeated anti-VEGF injections. The fluocinolone acetonide (FA) 190 μg intravitreal implant has been shown in pivotal clinical trials to be efficacious for the treatment of DME and has been approved in many countries for use in patients who have not responded to first-line therapy. In this report, we have collated the latest data from the increasing number of studies to illustrate the pattern of usage of the Iluvien FA implant for DME during the current anti-VEGF era. We have shown that there is now a wealth of published evidence from real-world studies to support the clinical utility of the FA implant in achieving further resolution of edema and improving visual acuity outcomes in this challenging group of patients.