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AIMS: Antihypertensive drugs have been implicated in coronavirus disease 2019 (COVID-19) susceptibility and severity, but estimated associations may be susceptible to bias. We aimed to evaluate antihypertensive medications and COVID-19 diagnosis and mortality, accounting for healthcare-seeking behaviour. METHODS: A population-based case-control study was conducted including 16 866 COVID-19 cases and 70 137 matched controls from the UK Clinical Practice Research Datalink. We evaluated all-cause mortality among COVID-19 cases. Exposures were angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (B), calcium-channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). Analyses were adjusted for covariates and consultation frequency. RESULTS: ACEIs were associated with lower odds of COVID-19 diagnosis (adjusted odds ratio [AOR] 0.82, 95% confidence interval [CI] 0.77-0.88) as were ARBs (AOR 0.87, 95% CI 0.80-0.95) with little attenuation from adjustment for consultation frequency. C and D were also associated with lower odds of COVID-19 diagnosis. Increased odds of COVID-19 for B (AOR 1.19, 95% CI 1.12-1.26) were attenuated after adjustment for consultation frequency (AOR 1.01, 95% CI 0.95-1.08). Patients treated with ACEIs or ARBs had similar odds of mortality (AOR 1.00, 95% CI 0.83-1.20) to patients treated with classes B, C, D or O or patients receiving no antihypertensive therapy (AOR 0.99, 95% CI 0.83-1.18). CONCLUSIONS: There was no evidence that antihypertensive therapy is associated with increased risk of COVID-19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID-19 diagnosis.

BackgroundChildren and young people (CYP) with attention-deficit/hyperactivity disorder (ADHD) face delays in diagnosis and barriers to accessing appropriate interventions. Evidence is limited on how these barriers are perceived by their parents and carers.MethodsFocus group in South London with parents/carers of CYP with ADHD. Data were thematically analysed using an inductive/deductive hybrid approach.ResultsParticipants (n=8) described the challenge of accessing services within a disjointed, multiagency system for their CYP’s ADHD and broader health needs. They described feeling judged and overlooked by healthcare professionals, which could negatively impact the health, relationships and educational progress of their children. Pragmatic solutions were proposed, including providing parents with information on navigating services at an early stage of ADHD symptom recognition.ConclusionsParents/carers sought improved continuity of care within and between services. They are a key group for consultation on the development of interventions to improve access for CYP with ADHD.

BackgroundThe COVID-19 pandemic has altered the context for antimicrobial stewardship in primary care.AimTo assess the effect of the pandemic on antibiotic prescribing, accounting for changes in consultations for respiratory and urinary tract infections (RTIs/UTIs).Design and settingPopulation-based cohort study using the UK Clinical Practice Research Datalink (CPRD) GOLD database from January 2017 to September 2020.MethodInterrupted time-series analysis evaluated changes in antibiotic prescribing and RTI/UTI consultations adjusting for age, sex, season, and secular trends. The authors assessed the proportion of COVID-19 episodes associated with antibiotic prescribing.ResultsThere were 253 655 registered patients in 2017 and 232 218 in 2020, with 559 461 antibiotic prescriptions, 216 110 RTI consultations, and 36 402 UTI consultations. Compared with prepandemic months, March 2020 was associated with higher antibiotic prescribing (adjusted rate ratio [ARR] 1.13; 95% confidence interval [CI] = 1.11 to 1.16). Antibiotic prescribing fell below predicted rates between April and August 2020, reaching a minimum in May (ARR 0.73; 95% CI = 0.71 to 0.75). Pandemic months were associated with lower rates of RTI/UTI consultations, particularly in April for RTIs (ARR 0.23; 95% CI = 0.22 to 0.25). There were small reductions in the proportion of RTI consultations with antibiotic prescribed and no reduction for UTIs. Among 25 889 COVID-19 patients, 2942 (11%) had antibiotics within a COVID-19 episode.ConclusionPandemic months were initially associated with increased antibiotic prescribing, which then fell below expected levels during the national lockdown. Findings are reassuring that antibiotic stewardship priorities have not been neglected because of COVID-19. Research is required into the effects of reduced RTI/UTI consultations on incidence of serious bacterial infections.

ObjectiveThis study aimed to estimate the incidence of new diabetes mellitus (DM) and cardiovascular diseases (CVD) up to one year after Covid-19 compared with matched controls.MethodsA cohort study was conducted using electronic records for 1,473 family practices with a population of 14.9 million. Covid-19 patients without DM or CVD were individually matched with controls and followed up to October 2021. A difference-in-difference analysis estimated the net effect of Covid-19 allowing for baseline differences and covariates.ResultsThere were 372,816 Covid-19 patients, with 2,935 CVD and 3,139 DM events, and 372,816 matched controls with 1,193 CVD and 1,861 DM events following the index date. Net incidence of DM increased in acute Covid-19 up to four weeks from index date (adjusted rate ratio, RR 1.71, 1.40 to 2.10) and remained elevated in post-acute (five to 12 weeks from index date; RR 1.17, 1.01 to 1.36) and long-Covid-19 (13 to 52 weeks, 1.20, 1.09 to 1.31). Acute Covid-19 was associated with net increased CVD incidence (RR 6.02, 95% confidence interval 4.84 to 7.47) including pulmonary embolism (RR 14.5, 7.72 to 27.4), atrial arrythmias (6.58, 3.78 to 11.4) and venous thromboses (5.44, 3.22 to 9.17). CVD incidence declined in post-acute Covid-19 (1.68, 1.41 to 2.01) and showed no net increase in long Covid-19 (0.95, 0.85 to 1.06).ConclusionsDM incidence remains elevated up to one year following Covid-19. CVD is increased early after Covid-19 mainly from pulmonary embolism, atrial arrhythmias and venous thromboses.

Purpose of Review This review summarises epidemiological research using electronic health records (EHR) for antimicrobial stewardship. Recent Findings EHRs enable surveillance of antibiotic utilisation and infection consultations. Prescribing for respiratory tract infections has declined in the UK following reduced consultation rates. Reductions in prescribing for skin and urinary tract infections have been less marked. Drug selection has improved and use of broad-spectrum antimicrobics reduced. Diagnoses of pneumonia, sepsis and bacterial endocarditis have increased in primary care. Analytical studies have quantified risks of serious bacterial infections following reduced antibiotic prescribing. EHRs are increasingly used in interventional studies including point-of-care trials and cluster randomised trials of quality improvement. Analytical and interventional studies indicate patient groups for whom antibiotic utilisation may be more safely reduced. Summary EHRs offer opportunities for surveillance and interventions that engage practitioners in the effects of improved prescribing practices, with the potential for better outcomes with targeted study designs.

BackgroundThis study presents the theory of change underpinning an intervention to provide online contraceptive care in an inner London area with high rates of unplanned pregnancy. It aims to suggest attributes of an effective service and to identify key questions for its evaluation.MethodsThematic analysis of an online sexual and reproductive health programme funding application and 21 semi-structured interviews with a purposive sample of stakeholders selected to provide expertise in contraception and online health.ResultsA theory of change model summarised the positive processes of change which could be initiated through increased access to contraceptive supplies, online information and remote interaction and support. Stakeholders predicted that perceptions of convenience and anonymity of online access would vary across the target population. They stressed the importance of trusting service-users’ capabilities for autonomous contraceptive decision-making, but expressed concerns that online access could be detrimental for those requiring more complex care. Concerns were alleviated by the prospect of responsive support through text messaging and phone calls, and when the online service was positioned as part of a broader system of provision including physical services.ConclusionsThis study has revealed priority areas for the ongoing development of an online contraception service and pertinent evaluation questions. Evaluative research should test assumptions within the theory of change model, exploring the characteristics and circumstances of those preferring online access over existing services and the value of convenience, anonymity, autonomous access and responsive support in executing effective contraceptive choices within a new landscape of contraceptive delivery.

Background The threat of antimicrobial resistance has led to intensified efforts to reduce antibiotic utilisation, but serious bacterial infections are increasing in frequency. Objectives To estimate the risks of serious bacterial infections in association with lower antibiotic prescribing and understand stakeholder views with respect to safe antibiotic reduction. Design Mixed-methods research was undertaken, including a qualitative interview study of patient and prescriber views that informed a cohort study and a decision-analytic model, using primary care electronic health records. These three work packages were used to design an application (app) for primary care prescribers. Data sources The Clinical Practice Research Datalink. Setting This took place in UK general practices. Participants A total of 706 general practices with 66.2 million person-years of follow-up from 2002 to 2017 and antibiotic utilisation evaluated for 671,830 registered patients. The qualitative study included 31 patients and 30 health-care professionals from primary care. Main outcome measures Sepsis and localised bacterial infections. Results Patients were concerned about antimicrobial resistance and the side effects, as well as the benefits, of antibiotic treatment. Prescribers viewed the onset of sepsis as the most concerning potential outcome of reduced antibiotic prescribing. More than 40% of antibiotic prescriptions in primary care had no coded indication recorded across both Vision® and EMIS® practice systems. Antibiotic prescribing rates varied widely between general practices, but there was no evidence that serious bacterial infections were less frequent at higher prescribing practices (adjusted rate ratio for 20% increase in prescribing 1.03, 95% confidence interval 1.00 to 1.06; p = 0.074). The probability of sepsis was lower if an antibiotic was prescribed at an infection consultation, and the number of antibiotic prescriptions required to prevent one episode of sepsis (i.e. the number needed to treat) decreased with age. For those aged 0–4 years, the number needed to treat was 29,773 (95% uncertainty interval 18,458 to 71,091) in boys and 27,014 (95% uncertainty interval 16,739 to 65,709) in girls. For those aged > 85 years, the number needed to treat was 262 (95% uncertainty interval 236 to 293) in men and 385 (95% uncertainty interval 352 to 421) in women. Frailty was associated with a greater risk of sepsis and a smaller number needed to treat. For severely frail patients aged 55–64 years, the number needed to treat was 247 (95% uncertainty interval 156 to 459) for men and 343 (95% uncertainty interval 234 to 556) for women. At all ages, the probability of sepsis was greatest for urinary tract infection, followed by skin infection and respiratory tract infection. The numbers needed to treat were generally smaller for the period 2014–17, when sepsis was diagnosed more frequently. The results are available using an app that we developed to provide primary care prescribers with stratified risk estimates during infection consultations. Limitations Analyses were based on non-randomised comparisons. Infection episodes and antibiotic prescribing are poorly documented in primary care. Conclusions Antibiotic treatment is generally associated with lower risks, but the most serious bacterial infections remain infrequent even without antibiotic treatment. This research identifies risk strata in which antibiotic prescribing can be more safely reduced. Future work The software developed from this research may be further developed and investigated for antimicrobial stewardship effect. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 9. See the NIHR Journals Library website for further project information.

BackgroundOnline contraception services increasingly provide information, clinical assessment and home-delivered oral contraceptives (OCs). Evidence is lacking on the effects of online contraceptive service use on short-term contraceptive continuation.MethodsCohort study comparing contraceptive continuation between new users of a free-to-access online OC service in South East London with those from other, face-to-face services in the same area. Online questionnaires collected data on participants’ sociodemographic characteristics, motivations for OC access, service ratings, OC knowledge and contraceptive use. Contraceptive use in the 4-month study period was measured using health service records. Unadjusted and multivariable logistic regression models compared outcomes between the online service group and those using other services.ResultsOnline service-users (n=138) were more likely to experience short-term continuation of OCs compared with participants using other services (n=98) after adjusting for sociodemographic and other characteristics (adjusted OR 2.94, 95% CI 1.52 to 5.70). Online service-users rated their service more highly (mean 25.22, SD 3.77) than the other services group (mean 22.70, SD 4.35; pConclusionsFree-to-access, online contraception has the potential to improve short-term continuation of OCs. Further research using a larger study population and analysis of longer-term outcomes are required to understand the impact of online services on unintended pregnancy.

ObjectiveTo estimate mortality of care home (CH) residents, and matched community-dwelling controls, during the Covid-19 pandemic from primary care electronic health records.DesignMatched cohort studySettingGeneral practices contributing to the Clinical Practice Research Datalink Aurum Database in England.ParticipantsThere were 83,627 CH residents contributing data in 2020, with 26,923 deaths; 80,730 (97%) were matched on age, gender and general practice with 300,445 community-dwelling adults.Main outcome measuresAll-cause mortality. Adjusted rate ratios (RR) by negative binomial regression were adjusted for age, gender, number of long-term conditions (LTCs), frailty category, region, calendar month or week, and clustering by general practice.ResultsDuring April 2020, the mortality rate of CH residents was 27.2 deaths per 1,000 patients per week, compared with 2.31 per 1,000 for controls, RR 11.1 (95% confidence interval 10.1 to 12.2). Compared with CH residents, LTCs and frailty were differentially associated with greater mortality in community-dwelling controls. During April 2020, mortality rates per 1,000 patients per week for persons with 9+ LTCs were: CH, 37.9; controls 17.7; RR 2.14 (1.18 to 3.89). In severe frailty, mortality rates were: CH, 29.6; controls 5.1; RR 6.17 (5.74 to 6.62).ConclusionsIndividual-patient data from primary care electronic health records may be used to estimate mortality in care home residents. Mortality is substantially higher than for community-dwelling comparators and showed a disproportionate increase in the first wave of the Covid-19 pandemic. Multiple morbidity and frailty were associated with greater absolute risks but lower relative risks because community-dwelling frail or multi-morbid patients also experienced high mortality.

ObjectivesSepsis is a growing concern for health systems, but the epidemiology of sepsis is poorly characterised. We evaluated sepsis recording across primary care electronic records, hospital episodes and mortality registrations.Methods and FindingsCohort study including 378 general practices in England from Clinical Practice Research Datalink (CPRD) GOLD database from 2002 to 2017 with 36,209,676 patient-years of follow-up with linked Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality registrations. Incident sepsis episodes were identified for each source. Concurrent records from different sources were identified and age-standardised and age-specific incidence rates compared. Logistic regression analysis evaluated associations of gender, age-group, fifth of deprivation and period of diagnosis with concurrent sepsis recording.There were 20,206 first episodes of sepsis from primary care, 20,278 from HES and 13,972 from ONS. There were 4,117 (20%) first HES sepsis events and 2,438 (17%) mortality records concurrent with incident primary care sepsis records within 30 days. Concurrent HES and primary care records of sepsis within 30 days before or after first diagnosis were higher at younger or older ages and for patients with the most recent period of diagnosis with those diagnosed during 2007:2011 less likely to have a concurrent HES record given CPRD compared to those diagnosed during 2012 to 2017 (odd ratio 0.65, 95% confidence interval 0.60 to 0.70). At age 85 and older, primary care incidence was 5.22 per 1,000 patient years (95% CI 1.75 to 11.97) in men and 3.55 (0.87 to 9.58) in women which increased to 10.09 (4.86 to 18.51) for men and 7.22 (2.96 to 14.72) for women after inclusion of all three sources.ConclusionExplicit recording of sepsis is inconsistent across healthcare sectors with a high proportion of non-concurrent records. Incidence estimates are higher when linked data are analysed.

ObjectivesTo evaluate antihypertensive medications and COVID-19 diagnosis and mortality, accounting for healthcare seeking behaviour.DesignA population-based case control study with additional cohort analysis.SettingPrimary care patients from the UK Clinical Practice Research Datalink (CPRD).Participants16 866 patients with COVID-19 events in the CPRD from 29th January to June 25th 2020 and 70 137 matched controls.Main outcome measuresWe explored associations between COVID-19 diagnosis and prescriptions for angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (B), calcium-channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). We evaluated all-cause mortality among COVID-19 cases. Analyses were adjusted for covariates and consultation frequency.ResultsIn covariate adjusted analyses, ACEIs were associated with lower odds of COVID-19 diagnosis (0.82, 95% confidence interval 0.77 to 0.88) as were ARBs, 0.87 (0.80 to 0.95) with little attenuation from adjustment for consultation frequency. In fully adjusted analyses, C and D were also associated with lower odds of COVID-19. Increased odds of COVID-19 for B (1.19, 1.12 to 1.26), were attenuated after adjustment for consultation frequency (1.01, 0.95 to 1.08). In adjusted analyses, patients treated with ACEIs or ARBs had similar mortality to patients treated with classes B, C, D or O (1.00, 0.83 to 1.20) or patients receiving no antihypertensive therapy (0.99, 0.83 to 1.18).ConclusionsAssociations were sensitive to adjustment for confounding and healthcare seeking, but there was no evidence that antihypertensive therapy is associated with increased risk of COVID-19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID-19 diagnosis.

Background In January 2017, the first free service providing oral contraceptive pills (OCPs) ordered online and posted home became available in the London boroughs of Lambeth and Southwark – ethnically and socioeconomically diverse areas with high rates of unplanned pregnancy. There are concerns that online services can increase health inequalities; therefore, we aimed to describe service-users according to age, ethnicity and Index of Multiple Deprivation (IMD) quintile of area of residence and to examine the association of these with repeated use. Methods We analysed routinely collected data from January 2017 to April 2018 and described service-users using available sociodemographic factors and information on patterns of use. Logistic regression analysis examined factors associated with repeat ordering of OCPs. Results The service was accessed by 726 individuals; most aged between 20 and 29 years (72.5%); self-identified as being of white ethnic group (58.8%); and residents of the first and second most deprived IMD quintiles (79.2%). Compared with those of white ethnic group, those of black ethnic group were significantly less likely to make repeat orders (adjusted OR 0.53, 95% CI 0.31 to 0.89; p=0.001), as were those of Asian and mixed ethnic groups. Conclusions These are the first empirical findings on free, online contraception and suggest that early adopters broadly reflect the population of the local area in terms of ethnic diversity and deprivation as measured by IMD. Ongoing service development should prioritise the identification and removal of barriers which may inhibit repeat use for black and minority ethnic groups.

Introduction STI self-sampling accessed via the internet (e-STI testing) is recommended to expand access to services. There is limited evidence on its effectiveness. This is the first RCT to evaluate an e-STI testing service for chlamydia, gonorrhoea, HIV and syphilis. Methods Single-blind RCT with allocation concealment. Eligibility: aged 16–30, resident in 2 boroughs of London, having at least one sexual partner in the last 12 months, willing to take an STI test. Participants were randomly allocated to (1) an e-STI testing service or (2) to a website with signposting to local sexual health clinics. Primary outcomes were: 1) diagnosis of any STI 2) completion of any STI test All analyses were intention-to-treat. We used multivariate imputation using chained equations (MICE) for the primary analyses. We explored heterogeneity by age, gender, ethnicity, deprivation, number of sexual partners in the last 12 months, and sexuality. Results 2072 participants were randomised. The response rate was 84%. At 6 weeks, 50.0% of the intervention group completed an STI test compared to 26.6% in the control group (RR 1.87, 95% confidence interval 1.63 to 2.15, p v 0.7% in the control (RR 1.72, 95% confidence interval 0.71 to 4.16, p=0.231). No heterogeneity was observed in the pre-specified sub group analyses. Time-to-test was lower in the intervention arm compared to the control arm (28.8 days vs 36.5 days; p Data cleaning and data collection were still underway late 2016. Conclusion e-STI testing increased testing uptake and may yield a small increase in STI diagnoses. Service innovations may be needed so that gains in testing and diagnoses translate into similar gains in cases treated. e-STI testing could be a valuable option in high prevalence contexts where expanding access is priority.

Background In January, 2017, the first free service offering 3 or 6 months’ supplies of oral contraceptive pills (OCPs) ordered online and posted home became available in the London boroughs of Lambeth and Southwark—an ethnically and socioeconomically diverse area with high rates of unplanned pregnancy. There are concerns that online services may only benefit more advantaged groups; therefore, we aimed to describe service users according to age, ethnicity, and index of multiple deprivation (IMD) quintile of area of residence, and determine whether these factors were associated with repeat use of the service. Methods We analysed routinely collected data from all 1186 requests for OCPs from January, 2017, to April, 2018, describing service users and their patterns of use. The primary outcome was two or more orders of OCPs from the online service during these 15 months, excluding those whose index prescription had not expired. Logistic regression analysis examined factors associated with this outcome at the bivariate and multivariable level, adjusting for age, IMD quintile, and ethnic group. Ethics approval was granted by The Proportionate Review Sub-Committee of the National Research Ethics Service (NRES) Committees – North of Scotland. Findings The online service was accessed by 726 individuals, 526 (72%) of whom were aged between 20 and 29 years and 427 (59%) of whom were of white ethnic group. 575 (79%) were residents of the first and second most deprived IMD quintiles. Compared with service users reported as being of white ethnic group, those of black ethnic group were significantly less likely to make repeat orders (adjusted odds ratio 0·52, 95% CI 0·31–0·89; p=0·016), as were those of Asian (0·39, 0·20–0·77; p=0·007) and mixed ethnic groups (0·37, 0·20–0·70; p=0·002). Interpretation These are the first findings on free, online contraception and suggest that early users reflect the population of the local area in terms of ethnic diversity and socioeconomic deprivation. Black and minority ethnic groups had lower odds of repeat use than did those of the white ethnic group, reflecting broader disparities in contraceptive continuation across services. Online service development should prioritise the identification and removal of barriers that might inhibit repeat online use for black and minority ethnic groups. Funding Guy's and St Thomas’ Charity.

Background Sexually transmitted infection (STI) self-sampling kits accessed via the internet (e-STI testing) is recommended despite a limited evidence base. We aimed to evaluate the effect of an e-STI testing service (chlamydia, gonorrhoea, HIV, and syphilis) on diagnoses and testing uptake, when delivered alongside usual care. Methods Individuals aged 16–30 years, resident in two London boroughs, with at least one sexual partner in the previous 12 months and willing to test, were recruited in community settings. An independent computer-based randomisation programme allocated participants to an e-STI testing service (intervention) or a website with signposting to local sexual health clinics (control). Primary outcomes at 6 weeks were diagnosis of any STI and completion of any STI test. 3000 participants were required to detect a relative risk of 3·5 for STI diagnoses, with 90% power at a 5% level of significance, allowing for 10% losses to follow up. Laboratory staff and outcome assessors were blinded to treatment allocation. All analyses were intention to treat. We used multivariate imputation by chained equations (MICE) for the primary analyses. All participants provided written informed consent. Ethics approval was granted by the National Research Ethics Service Committee London-Camberwell St Giles (ref 14/LO/1477). This trial is registered with Current Controlled Trials, number ISRCTN13354298. Findings 2072 participants were randomised (after nine exclusions, 1031 intervention, 1032 control, mean age 23 years, SD 3·6). Response rate was 84%. 1031 participants were analysed in the intervention and 1032 in the control group. At 6 weeks, 50·0% of the intervention group completed an STI test compared with 26·6% of the control group (relative risk 1·87, 95% CI 1·63–2·15; p vs 36·5 [0·4], p Interpretation The findings show that e-STI testing increased testing uptake. We were underpowered for the analyses of STI diagnoses and STI cases treated but our estimates suggested effects in the expected direction. Future service innovations may ensure that gains in testing and diagnoses translate into similar gains in cases treated. e-STI services require long-term evaluation. Funding Guy's and St Thomas' Charity.