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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.

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.

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.

Background Efforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed. Methods and findings We conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57–82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0–4 years old, the NNT was 29,773 (95% UI 18,458–71,091) in boys and 27,014 (16,739–65,709) in girls; over 85 years old, NNT was 262 (236–293) in men and 385 (352–421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55–64 years, the NNT was 247 (156–459) in men and 343 (234–556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65–74 years, the NNT following RTI was 1,257 (1,112–1,434) in men and 2,278 (1,966–2,686) in women; the NNT following skin infection was 503 (398–646) in men and 784 (602–1,051) in women; following UTI, the NNT was 121 (102–145) in men and 284 (241–342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period. Conclusions These stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs., In this cohort study, Martin Gulliford and colleagues investigate probability of sepsis in primary care patients with or without prescribed antibiotics., Author summary Why was this study done? Sepsis is a severe reaction to an infection that may lead to life threatening damage to organ systems. Sepsis is an increasingly recognised concern for health professionals and patients in primary care. Inappropriate and unnecessary antibiotic prescribing is a widespread problem in primary care that may be contributing to antimicrobial resistance. This study aimed to estimate the probability of a patient developing sepsis after an infection consultation in primary care if antibiotics are or are not prescribed. What did the researchers do and find? We analysed the electronic health records of all registered patients at 706 general practices, with 66.2 million person-years of follow-up from 2002 to 2017 and 35,244 first episodes of sepsis. We found that the probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. Frailty was associated with greater risk of sepsis and lower NNT. At all ages, the probability of sepsis was greatest for urinary tract infection, followed by skin infection, followed by respiratory tract infection. What do these findings mean? These results show that risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following urinary tract infections. Antibiotic use may be more safely reduced in groups with lower probability of sepsis. We caution that our results represent averages over diverse localities and years of study, and lack of random allocation to antibiotic therapy might have caused bias.

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.

Background Sepsis 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 findings Cohort study including 378 general practices in England from Clinical Practice Research Datalink (CPRD) GOLD database from 2002–2017 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. Those diagnosed during 2007:2011 were less likely to have a concurrent HES record given CPRD compared to those diagnosed during 2012–2017 (odd ratio 0.65, 95% confidence interval 0.60–0.70). At age 85 and older, primary care incidence was 5.22 per 1,000 patient years (95% CI 1.75–11.97) in men and 3.55 (0.87–9.58) in women which increased to 10.09 (4.86–18.51) for men and 7.22 (2.96–14.72) for women after inclusion of all three sources. Conclusion Explicit 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.

Background We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). Methods We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990–Jan 2016). Two authors extracted data. Findings 71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80–2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06–2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heteroge-nous (I2 59–90%). The effects of alcohol reduction interventions were inconclusive. Conclusions Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes 3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs.

Background Internet-accessed sexually transmitted infection testing (e-STI testing) is increasingly available as an alternative to testing in clinics. Typically this testing modality enables users to order a test kit from a virtual service (via a website or app), collect their own samples, return test samples to a laboratory, and be notified of their results by short message service (SMS) or telephone. e-STI testing is assumed to increase access to testing in comparison with face-to-face services, but the evidence is unclear. We conducted a randomised controlled trial to assess the effectiveness of an e-STI testing and results service (chlamydia, gonorrhoea, HIV, and syphilis) on STI testing uptake and STI cases diagnosed. Methods and findings The study took place in the London boroughs of Lambeth and Southwark. Between 24 November 2014 and 31 August 2015, we recruited 2,072 participants, aged 16–30 years, who were resident in these boroughs, had at least 1 sexual partner in the last 12 months, stated willingness to take an STI test, and had access to the internet. Those unable to provide consent and unable to read English were excluded. Participants were randomly allocated to receive 1 text message with the web link of an e-STI testing and results service (intervention group) or to receive 1 text message with the web link of a bespoke website listing the locations, contact details, and websites of 7 local sexual health clinics (control group). Participants were free to use any other services or interventions during the study period. The primary outcomes were self-reported STI testing at 6 weeks, verified by patient record checks, and self-reported STI diagnosis at 6 weeks, verified by patient record checks. Secondary outcomes were the proportion of participants prescribed treatment for an STI, time from randomisation to completion of an STI test, and time from randomisation to treatment of an STI. Participants were sent a £10 cash incentive on submission of self-reported data. We completed all follow-up, including patient record checks, by 17 June 2016. Uptake of STI testing was increased in the intervention group at 6 weeks (50.0% versus 26.6%, relative risk [RR] 1.87, 95% CI 1.63 to 2.15, P < 0.001). The proportion of participants diagnosed was 2.8% in the intervention group versus 1.4% in the control group (RR 2.10, 95% CI 0.94 to 4.70, P = 0.079). No evidence of heterogeneity was observed for any of the pre-specified subgroup analyses. The proportion of participants treated was 1.1% in the intervention group versus 0.7% in the control group (RR 1.72, 95% CI 0.71 to 4.16, P = 0.231). Time to test, was shorter in the intervention group compared to the control group (28.8 days versus 36.5 days, P < 0.001, test for difference in restricted mean survival time [RMST]), but no differences were observed for time to treatment (83.2 days versus 83.5 days, P = 0.51, test for difference in RMST). We were unable to recruit the planned 3,000 participants and therefore lacked power for the analyses of STI diagnoses and STI cases treated. Conclusions The e-STI testing service increased uptake of STI testing for all groups including high-risk groups. The intervention required people to attend clinic for treatment and did not reduce time to treatment. Service innovations to improve treatment rates for those diagnosed online are required and could include e-treatment and postal treatment services. e-STI testing services require long-term monitoring and evaluation. Trial registration ISRCTN Registry ISRCTN13354298., In a single-blind randomised trial, Emma Wilson and colleagues assess the impact of an e-STI service on testing uptake and cases diagnosed., Author summary Why was this study done? Internet-accessed sexually transmitted infection testing (e-STI testing) is increasingly available. Yet the effectiveness of e-STI testing compared to face-to-face services is unclear. What did the researchers do and find? We conducted a large randomised controlled trial in London, United Kingdom, to assess the effects of an e-STI testing and results service (SH:24) on uptake of STI testing and STI cases diagnosed and treated, when delivered alongside usual care. The intervention offered postal self-sampling test kits for chlamydia, gonorrhoea, HIV, and syphilis, results delivered via text message or telephone, and web-based safer sex health information. We found that e-STI testing almost doubled uptake of testing among all groups, including groups at high risk for STIs. A larger study is required to understand the effects of e-STI testing on STI diagnosis and STI cases treated. Further research is required to evaluate the proportion of those diagnosed who are treated. Our findings suggest that additional inputs may be required to strengthen linkages to treatment (e.g., postal treatment). What do these findings mean? e-STI testing should be considered as a complement to existing services and as an effective measure to increase uptake of STI testing. The effect of e-STI testing on cases diagnosed and treated requires further evaluation.

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.