Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial.

OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.

Post-consultation acute respiratory tract infection recovery: a latent class-informed analysis of individual patient data.

BACKGROUND: There is a lack of evidence regarding post-consultation symptom trajectories for patients with respiratory tract infections (RTIs) and whether patient characteristics can be used to predict illness duration. AIM: To describe symptom trajectories in patients with RTIs, and assess baseline characteristics and adverse events associated with trajectories. DESIGN AND SETTING: The study included data about 9103 adults and children from 12 primary care studies. METHOD: A latent class-informed regression analysis of individual patient data from randomised controlled trials and observational cohort studies was undertaken. Post-consultation symptom trajectory (severity and duration), re-consultation with same or worsening illness, and admission to hospital were assessed. RESULTS: In total, 90% of participants recovered from all symptoms by 28 days, regardless of antibiotic prescribing strategy (none, immediate, and delayed antibiotics). For studies of RTI with cough as a dominant symptom (n = 5314), four trajectories were identified: 'rapid (6 days)' (90% of participants recovered within 6 days) in 52.0%; 'intermediate (10 days)' (28.9%); 'slow progressive improvement (27 days)' (12.5%); and 'slow improvement with initial high symptom burden (27 days)' (6.6%). For cough, being aged 16-64 years (odds ratio [OR] 2.57, 95% confidence interval [CI] = 1.72 to 3.85 compared with <16 years), higher presenting illness baseline severity (OR 1.51, 95% CI = 1.12 to 2.03), presence of lung disease (OR 1.78, 95% CI = 1.44 to 2.21), and median and above illness duration before consultation (≥7 days) (OR 1.99, 95% CI = 1.68 to 2.37) were associated with slower recovery (>10 days) compared with faster recovery (≤10 days). Re-consultations and admissions to hospital for cough were higher in those with slower recovery (ORs: 2.15, 95% CI = 1.78 to 2.60 and 7.42, 95% CI = 3.49 to 15.78, respectively). CONCLUSION: Older patients presenting with more severe, longer pre-consultation symptoms and chronic lung disease should be advised they are more likely to experience longer post-consultation illness durations, and that recovery rates are similar with and without antibiotics.

Non-pharmaceutical interventions and risk of COVID-19 infection: survey of U.K. public from November 2020 - May 2021.

INTRODUCTION: Non-pharmaceutical interventions (NPIs), such as handwashing, social distancing and face mask wearing, have been widely promoted to reduce the spread of COVID-19. This study aimed to explore the relationship between self-reported use of NPIs and COVID-19 infection. METHODS: We conducted an online questionnaire study recruiting members of the UK public from November 2020 to May 2021. The association between self-reported COVID-19 illness and reported use of NPIs was explored using logistic regression and controlling for participant characteristics, month of questionnaire completion, and vaccine status. Participants who had been exposed to COVID-19 in their household in the previous 2 weeks were excluded. RESULTS: Twenty-seven thousand seven hundred fifty-eight participants were included and 2,814 (10.1%) reported having a COVID-19 infection. The odds of COVID-19 infection were reduced with use of a face covering in unadjusted (OR 0.17 (95% CI: 0.15 to 0.20) and adjusted (aOR 0.19, 95% CI 0.16 to 0.23) analyses. Social distancing (OR 0.27, 95% CI: 0.22 to 0.31; aOR 0.35, 95% CI 0.28 to 0.43) and handwashing when arriving home (OR 0.57, 95% CI 0.46 to 0.73; aOR 0.63, 95% CI: 0.48 to 0.83) also reduced the odds of COVID-19. Being in crowded places of 10-100 people (OR 1.89, 95% CI: 1.70 to 2.11; aOR 1.62, 95% CI: 1.42 to 1.85) and > 100 people (OR 2.33, 95% CI: 2.11 to 2.58; aOR 1.73, 95% CI: 1.53 to 1.97) were both associated with increased odds of COVID-19 infection. Handwashing before eating, avoiding touching the face, and cleaning things with virus on were all associated with increased odds of COVID-19 infections. CONCLUSIONS: This large observational study found evidence for strong protective effects for individuals from use of face coverings, social distancing (including avoiding crowded places) and handwashing on arriving home on developing COVID-19 infection. We also found evidence for an increased risk associated with other behaviours, possibly from recall bias.

Mortality from angiotensin-converting enzyme-inhibitors and angiotensin receptor blockers in people infected with COVID-19: a cohort study of 3.7 million people.

BACKGROUND: Concerns have been raised that angiotensin-converting enzyme-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) might facilitate transmission of severe acute respiratory syndrome coronavirus 2 leading to more severe coronavirus disease (COVID-19) disease and an increased risk of mortality. We aimed to investigate the association between ACE-I/ARB treatment and risk of death amongst people with COVID-19 in the first 6 months of the pandemic. METHODS: We identified a cohort of adults diagnosed with either confirmed or probable COVID-19 (from 1 January to 21 June 2020) using computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. This comprised 465 general practices in England, United Kingdom with a nationally representative population of 3.7 million people. We constructed mixed-effects logistic regression models to quantify the association between ACE-I/ARBs and all-cause mortality among people with COVID-19, adjusted for sociodemographic factors, comorbidities, concurrent medication, smoking status, practice clustering, and household number. RESULTS: There were 9,586 COVID-19 cases in the sample and 1,463 (15.3%) died during the study period between 1 January 2020 and 21 June 2020. In adjusted analysis ACE-I and ARBs were not associated with all-cause mortality (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.85-1.21 and OR 0.84, 95% CI 0.67-1.07, respectively). CONCLUSION: Use of ACE-I/ARB, which are commonly used drugs, did not alter the odds of all-cause mortality amongst people diagnosed with COVID-19. Our findings should inform patient and prescriber decisions concerning continued use of these medications during the pandemic.

Postal methods for monitoring HbA1c in diabetes mellitus: A protocol for systematic review.

BACKGROUND: Worldwide there are an estimated 463 million people with diabetes. In the UK people with diabetes are offered annual review which includes monitoring of Haemoglobin A1c (HbA1c). This can identify people with diabetes who are not meeting their glycaemic targets, enabling early intervention. Those who do not attend these reviews often have poorer health outcomes. During the Coronavirus disease 2019 (COVID-19) pandemic, there was a 77% reduction in monitoring of HbA1c in the UK. AIM: We hypothesise that people with diabetes could take finger-prick samples at home for measurement of HbA1c. We will examine the agreement and correlation of capillary HbA1c values compared to a venous reference standard. We will explore reliability and repeatability of capillary HbA1c testing methods. We will explore the direction of effect of storage variables. We will also explore patient acceptability and safety. We will look at capillary blood methods which would be suitable for posting. METHOD: Using core terms of 'Diabetes', 'HbA1c' and 'Capillary sampling' we will search MEDLINE, Embase, CINAHL, Web of Science Core Collection, Google Scholar, Open Grey, and other grey literature from database inception until 2021. Risk of bias will be assessed using the 'COSMIN risk of bias tool to assess the quality of studies on reliability and measurement error'. CONCLUSION: We will produce a narrative synthesis to explore whether there are viable postal alternatives to venous sampling as well as exploring acceptability and safety of patient self-collection. PROSPERO REGISTRATION NUMBER: CRD42021225606.

Risk factors for community-acquired respiratory infections in a non-pandemic context: Secondary analysis of the PRIMIT study.

OBJECTIVES: Respiratory tract infection (RTI) incidence varies between people, but little is known about why. The aim of this study is therefore to identify risk factors for acquiring RTIs. METHODS: We conducted a secondary analysis of 16,908 participants in the PRIMIT study, a pre-pandemic randomised trial showing handwashing reduced incidence of RTIs in the community. Data was analysed using multivariable logistic regression analyses of self-reported RTI acquisition. RESULTS: After controlling for handwashing, RTI in the previous year (1 to 2 RTIs: adjusted OR 1.96, 95% CI 1.79 to 2.13, p<0.001; 3 to 5 RTIs: aOR 3.89, 95% CI 3.49 to 4.33, p<0.001; ≥6 RTIs: OR 5.52, 95% CI 4.37 to 6.97, p<0.001); skin conditions that prevent handwashing (aOR 1.39, 95% CI 1.24 to 1.55, p<0.001); children under 16 years in the household (aOR 1.27, 95% CI 1.12, 1.43, p<0.001); chronic lung condition (aOR 1.16, 95% CI 1.02 to 1.32, p = 0.026); female sex (aOR 1.10, 95% CI 1.03 to 1.18, p = 0.005), and post-secondary education (aOR 1.09, 95% CI 1.02 to 1.17, p = 0.01) increased the likelihood of RTI. Those over the age of 65 years were less likely to develop an infection (aOR 0.89, 95% CI 0.82 to 0.97, p = 0.009). Household crowding and influenza vaccination do not influence RTI acquisition. A post-hoc exploratory analysis found no evidence these subgroups differentially benefited from handwashing. CONCLUSIONS: Previous RTIs, chronic lung conditions, skin conditions that prevent handwashing, and the presence of household children predispose to RTI acquisition. Further research is needed to understand how host and microbial factors explain the relationship between previous and future RTIs.

Self-sampling to identify pathogens and inflammatory markers in patients with acute sore throat: Feasibility study.

Introduction: Sore throat is a common reason for overuse of antibiotics. The value of inflammatory or biomarkers in throat swab or saliva samples in predicting benefit from antibiotics is unknown. Methods: We used the 'person-based approach' to develop an online tool to support self-swabbing and recruited adults and children with sore throats through participating general practices and social media. Participants took bacterial and viral swabs and a saliva sponge swab and passive drool sample. Bacterial swabs were cultured for streptococcus (Group A, B, C, F and G). The viral swab and saliva samples were tested using a routine respiratory panel PCR and Covid-19 PCR testing. We used remaining viral swab and saliva sample volume for biomarker analysis using a panel of 13 biomarkers. Results: We recruited 11 asymptomatic participants and 45 symptomatic participants. From 45 symptomatic participants, bacterial throat swab, viral throat swab, saliva sponge and saliva drool samples were returned by 41/45 (91.1%), 43/45 (95.6%), 43/45 (95.6%) and 43/45 (95.6%) participants respectively. Three saliva sponge and 6 saliva drool samples were of insufficient quantity. Two adult participants had positive bacterial swabs. Six participants had a virus detected from at least one sample (swab or saliva). All of the biomarkers assessed were detectable from all samples where there was sufficient volume for testing. For most biomarkers we found higher concentrations in the saliva samples. Due to low numbers, we were not able to compare biomarker concentrations in those who did and did not have a bacterial pathogen detected. We found no evidence of a difference between biomarker concentrations between the symptomatic and asymptomatic participants but the distributions were wide. Conclusions: We have demonstrated that it is feasible for patients with sore throat to self-swab and provide saliva samples for pathogen and biomarker analysis. Typical bacterial and viral pathogens were detected but at low prevalence rates. Further work is needed to determine if measuring biomarkers using oropharyngeal samples can help to differentiate between viral and bacterial pathogens in patients classified as medium or high risk using clinical scores, in order to better guide antibiotic prescribing and reduce inappropriate prescriptions.

Antibiotic Use and Bacterial Infection in COVID-19 Patients in the Second Phase of the SARS-CoV-2 Pandemic: A Scoping Review.

This scoping review aimed to explore the prevalence and patterns of global antibiotic use and bacterial infection in COVID-19 patients from studies published between June 2020 and March 2021. This review was reported in line with the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews, and the protocol is registered with the Open Science Framework. Compared with our previously-published review of the period (December 2019-June 2020), the antibiotic prescribing rate for COVID-19 patients (June 2020-March 2021) was found to have declined overall (82.3% vs. 39.7%), for mild and moderate patients (75.1% vs. 15.5%), and for severe and critical patients (75.3% vs. 48.3%). The seven most frequently prescribed antibiotics in COVID-19 patients were all on the "Watch" list of the WHO AWaRe antibiotics classification. The overall reported bacterial infection rate in COVID-19 patients was 10.5%, and the most frequently reported resistant pathogen in COVID-19 patients was Staphylococcus aureus, followed by Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. There is an urgent need to establish comprehensive and consistent guidelines to assist clinicians in selecting appropriate antibiotics for COVID-19 patients when needed. The resistance data on the most frequently used antibiotics for COVID-19 patients for certain resistant pathogens should be closely monitored.

Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study.

Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.

Physical Activity, Mental Health and Wellbeing of Adults within and during the Easing of COVID-19 Restrictions, in the United Kingdom and New Zealand.

Physical activity (PA) participation was substantially reduced at the start of the COVID-19 pandemic. The purpose of this study was to assess the association between PA, mental health, and wellbeing during and following the easing of COVID-19 restrictions in the United Kingdom (UK) and New Zealand (NZ). In this study, 3363 adults completed online surveys within 2-6 weeks of initial COVID-19 restrictions (April/May 2020) and once restrictions to human movement had been eased. Outcome measures included the International Physical Activity Questionnaire Short-Form, Depression Anxiety and Stress Scale-9 (mental health) and World Health Organisation-5 Wellbeing Index. There were no differences in PA, mental health or wellbeing between timepoints (p > 0.05). Individuals engaging in moderate or high volume of PA had significantly better mental health (-1.1 and -1.7 units, respectively) and wellbeing (11.4 and 18.6 units, respectively) than individuals who engaged in low PA (p < 0.001). Mental health was better once COVID-19 restrictions were eased (p < 0.001). NZ had better mental health and wellbeing than the UK (p < 0.001). Participation in moderate-to-high volumes of PA was associated with better mental health and wellbeing, both during and following periods of COVID-19 containment, compared to participation in low volumes of PA. Where applicable, during the current or future pandemic(s), moderate-to-high volumes of PA should be encouraged.

Cluster randomised controlled trial to assess a tailored intervention to reduce antibiotic prescribing in rural China: study protocol.

INTRODUCTION: Up to 80% of patients with respiratory tract infections (RTI) attending healthcare facilities in rural areas of China are prescribed antibiotics, many of which are unnecessary. Since 2009, China has implemented several policies to try to reduce inappropriate antibiotic use; however, antibiotic prescribing remains high in rural health facilities. METHODS AND ANALYSIS: A cluster randomised controlled trial will be carried out to estimate the effectiveness and cost effectiveness of a complex intervention in reducing antibiotic prescribing at township health centres in Anhui Province, China. 40 Township health centres will be randomised at a 1:1 ratio to the intervention or usual care arms. In the intervention group, practitioners will receive an intervention comprising: (1) training to support appropriate antibiotic prescribing for RTI, (2) a computer-based treatment decision support system, (3) virtual peer support, (4) a leaflet for patients and (5) a letter of commitment to optimise antibiotic use to display in their clinic. The primary outcome is the percentage of antibiotics (intravenous and oral) prescribed for RTI patients. Secondary outcomes include patient symptom severity and duration, recovery status, satisfaction, antibiotic consumption. A full economic evaluation will be conducted within the trial period. Costs and savings for both clinics and patients will be considered and quality of life will be measured by EuroQoL (EQ-5D-5L). A qualitative process evaluation will explore practitioner and patient views and experiences of trial processes, intervention fidelity and acceptability, and barriers and facilitators to implementation. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Biomedical Research Ethics Committee of Anhui Medical University (Ref: 20180259); the study has undergone due diligence checks and is registered at the University of Bristol (Ref: 2020-3137). Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals in China, the UK and internationally. TRIAL REGISTRATION NUMBER: ISRCTN30652037.

Infection Control Behavior at Home During the COVID-19 Pandemic: Observational Study of a Web-Based Behavioral Intervention (Germ Defence).

BACKGROUND: To control the COVID-19 pandemic, people should adopt protective behaviors at home (self-isolation, social distancing, putting shopping and packages aside, wearing face coverings, cleaning and disinfecting, and handwashing). There is currently limited support to help individuals conduct these behaviors. OBJECTIVE: This study aims to report current household infection control behaviors in the United Kingdom and examine how they might be improved. METHODS: This was a pragmatic cross-sectional observational study of anonymous participant data from Germ Defence between May 6-24, 2020. Germ Defence is an open-access fully automated website providing behavioral advice for infection control within households. A total of 28,285 users sought advice from four website pathways based on household status (advice to protect themselves generally, to protect others if the user was showing symptoms, to protect themselves if household members were showing symptoms, and to protect a household member who is at high risk). Users reported current infection control behaviors within the home and intentions to change these behaviors. RESULTS: Current behaviors varied across all infection control measures but were between sometimes (face covering: mean 1.61, SD 1.19; social distancing: mean 2.40, SD 1.22; isolating: mean 2.78, SD 1.29; putting packages and shopping aside: mean 2.75, SD 1.55) and quite often (cleaning and disinfecting: mean 3.17, SD 1.18), except for handwashing (very often: mean 4.00, SD 1.03). Behaviors were similar regardless of the website pathway used. After using Germ Defence, users recorded intentions to improve infection control behavior across all website pathways and for all behaviors (overall average infection control score mean difference 0.30, 95% CI 0.29-0.31). CONCLUSIONS: Self-reported infection control behaviors other than handwashing are lower than is optimal for infection prevention, although handwashing is much higher. Advice using behavior change techniques in Germ Defence led to intentions to improve these behaviors. Promoting Germ Defence within national and local public health and primary care guidance could reduce COVID-19 transmission.

Primary care consultations for respiratory tract symptoms during the COVID-19 pandemic: a cohort study including 70,000 people in South West England.

BACKGROUND: Primary care consultations for respiratory tract symptoms including identifying and managing COVID-19 during the pandemic have not been characterized. METHODS: A retrospective cohort analysis using routinely collected records from 70,431 adults aged 18+ in South England within the Electronic Care and Health Information Analytics (CHIA) database. Total volume and type of consultations (face-to-face, home visits, telephone, email/video, or out of hours) for respiratory tract symptoms between 1 January and 31 July 2020 (during the first wave of the pandemic) were compared with the equivalent period in 2019 for the same cohort. Descriptive statistics were used to summarize consultations by sociodemographic and clinical characteristics, and by COVID-19 diagnosis and outcomes (death, hospitalization, and pneumonia). RESULTS: Overall consultations for respiratory tract symptoms increased by 229% during the pandemic compared with the preceding year. This included significant increases in telephone consultations by 250%, a 1,574% increase in video/email consultations, 105% increase in home visits, and 92% increase in face-to-face consultations. Nearly 60% of people who presented with respiratory symptoms were tested for COVID-19 and 16% confirmed or clinically suspected to have the virus. Those with complications including pneumonia, requiring hospitalization, and who died were more likely to be seen in-person. CONCLUSION: During the pandemic, primary care substantially increased consultations for respiratory tract symptoms to identify and manage people with COVID-19. These findings should be balanced against national reports of reduced GP workload for non-COVID care.

Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups. METHODS: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298). FINDINGS: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis. INTERPRETATION: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections. FUNDING: National Institute for Health Research.

Spironolactone for adult female acne (SAFA): protocol for a double-blind, placebo-controlled, phase III randomised study of spironolactone as systemic therapy for acne in adult women.

INTRODUCTION: Acne is one of the most common inflammatory skin diseases worldwide and can have significant psychosocial impact and cause permanent scarring. Spironolactone, a potassium-sparing diuretic, has antiandrogenic properties, potentially reducing sebum production and hyperkeratinisation in acne-prone follicles. Dermatologists have prescribed spironolactone for acne in women for over 30 years, but robust clinical study data are lacking. This study seeks to evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. METHODS AND ANALYSIS: Women (≥18 years) with persistent facial acne requiring systemic therapy are randomised to receive one tablet per day of 50 mg spironolactone or a matched placebo until week 6, increasing to up to two tablets per day (total of 100 mg spironolactone or matched placebo) until week 24, along with usual topical therapy if desired. Study treatment stops at week 24; participants are informed of their treatment allocation and enter an unblinded observational follow-up period for up to 6 months (up to week 52 after baseline). Primary outcome is the Acne-specific Quality of Life (Acne-QoL) symptom subscale score at week 12. Secondary outcomes include Acne-QoL total and subscales; participant acne self-assessment recorded on a 6-point Likert scale at 6, 12, 24 weeks and up to 52 weeks; Investigator's Global Assessment at weeks 6 and 12; cost and cost effectiveness are assessed over 24 weeks. Aiming to detect a group difference of 2 points on the Acne-QoL symptom subscale (SD 5.8, effect size 0.35), allowing for 20% loss to follow-up, gives a sample size of 398 participants. ETHICS AND DISSEMINATION: This protocol was approved by Wales Research Ethics Committee (18/WA/0420). Follow-up to be completed in early 2022. Findings will be disseminated to participants, peer-reviewed journals, networks and patient groups, on social media, on the study website and the Southampton Clinical Trials Unit website to maximise impact. TRIAL REGISTRATION NUMBER: ISRCTN12892056;Pre-results.

Understanding GPs' views and experiences of using clinical prediction rules in the management of respiratory infections: a qualitative study.

BACKGROUND: Respiratory tract infections (RTIs) account for 60% of antibiotic prescribing in primary care. Several clinical prediction rules (CPRs) have been developed to help reduce unnecessary prescribing for RTIs, but there is a lack of studies exploring whether or how these CPRs are being used in UK general practice. AIM: To explore UK GPs' views and experiences with regards to RTI CPRs, and to identify barriers and facilitators to their use in practice. DESIGN & SETTING: A qualitative analysis of interviews with in-hours GPs working in the South and South West of England. METHOD: Semi-structured qualitative telephone interviews were conducted, digitally recorded, transcribed verbatim, and analysed using an inductive thematic approach. Patient and public involvement representatives contributed to study design and interpretation of findings. RESULTS: Thirty-two GPs were interviewed. Some CPRs were more commonly used than others. Participants used CPRs to facilitate patient-clinician discussion, confirm and support their decision, and document the consultation. GPs also highlighted concerns including lack of time, inability of CPRs to incorporate patient complexity, a shift in focus from the patient during consultations, and limited use in remote consultation (during the COVID-19 pandemic). CONCLUSION: This study highlights the need for user-friendly CPRs that are readily integrated into computer systems, and easily embedded into routine practice to complement clinical decision-making. Existing CPRs need to be validated for other populations where demographics and clinical characteristics may differ, as well different settings including remote consultations and self-assessment.

Primary Care implementation of Germ Defence, a digital behaviour change intervention to improve household infection control during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To examine the effectiveness of randomising dissemination of the Germ Defence behaviour change website via GP practices across England UK. TRIAL DESIGN: A two-arm (1:1 ratio) cluster randomised controlled trial implementing Germ Defence via GP practices compared with usual care. PARTICIPANTS: Setting: All Primary care GP practices in England. PARTICIPANTS: All patients aged 16 years and over who were granted access by participating GP practices. INTERVENTION AND COMPARATOR: Intervention: We will ask staff at GP practices randomised to the intervention arm to share the weblink to Germ Defence with all adult patients registered at their practice during the 4-month trial implementation period and care will otherwise follow current standard management. Germ Defence is an interactive website ( http://GermDefence.org/ ) employing behaviour change techniques and practical advice on how to reduce the spread of infection in the home. The coronavirus version of Germ Defence helps people understand what measures to take and when to take them to avoid infection. This includes hand washing, avoiding sharing rooms and surfaces, dealing with deliveries and ventilating rooms. Using behaviour change techniques, it helps users think through and adopt better home hygiene habits and find ways to solve any barriers, providing personalised goal setting and tailored advice that fits users' personal circumstances and problem solving to overcome barriers. Comparator: Patients at GP practices randomised to the usual care arm will receive current standard management for the 4-month trial period after which we will ask staff to share the link to Germ Defence with all adult patients registered at their practice. MAIN OUTCOMES: The primary outcome is the effects of implementing Germ Defence on prevalence of all respiratory tract infection diagnoses during the 4-month trial implementation period. The secondary outcomes are: 1) incidence of COVID-19 diagnoses 2) incidence of COVID-19 symptom presentation 3) incidence of gastrointestinal infections 4) number of primary care consultations 5) antibiotic usage 6) hospital admissions 7) uptake of GP practices disseminating Germ Defence to their patients 8) usage of the Germ Defence website by individuals who were granted access by their GP practice RANDOMISATION: GP practices will be randomised on a 1:1 basis by the independent Bristol Randomised Trials Collaboration (BRTC). Clinical Commission Groups (CCGs) in England will be divided into blocks according to region, and equal numbers in each block will be randomly allocated to intervention or usual care. The randomisation schedule will be generated in Stata statistical software by a statistician not otherwise involved in the enrolment of general practices into the study. BLINDING (MASKING): The principal investigators, the statistician and study collaborators will remain blinded from the identity of randomised practices until the end of the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): To detect planned effect size (based on PRIMIT trial, Little et al, 2015): 11.1 million respondents from 6822 active GP practices. Assuming 25% of these GP practices will engage, we will contact all GP practices in England spread across 135 Clinical Commissioning Groups. TRIAL STATUS: Protocol version 2.0, dated 13 January 2021. Implementation is ongoing. The implementation period started on 10 November 2020 and will end on 10 March 2021. TRIAL REGISTRATION: This trial was registered in the ISRCTN registry ( isrctn.com/ ISRCTN14602359 ) on 12 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Predictors of clinical deterioration in patients with suspected COVID-19 managed in a 'virtual hospital' setting: a cohort study.

OBJECTIVE: Identify predictors of clinical deterioration in a virtual hospital (VH) setting for COVID-19. DESIGN: Real-world prospective observational study. SETTING: VH remote assessment service in West Hertfordshire NHS Trust, UK. PARTICIPANTS: Patients with suspected COVID-19 illness enrolled directly from the community (postaccident and emergency (A&E) or medical intake assessment) or postinpatient admission. MAIN OUTCOME MEASURE: Death or (re-)admission to inpatient hospital care during VH follow-up and for 2 weeks post-VH discharge. RESULTS: 900 patients with a clinical diagnosis of COVID-19 (455 referred from A&E or medical intake and 445 postinpatient) were included in the analysis. 76 (8.4%) of these experienced clinical deterioration (15 deaths in admitted patients, 3 deaths in patients not admitted and 58 additional inpatient admissions). Predictors of clinical deterioration were increase in age (OR 1.04 (95% CI 1.02 to 1.06) per year of age), history of cancer (OR 2.87 (95% CI 1.41 to 5.82)), history of mental health problems (OR 1.76 (95% CI 1.02 to 3.04)), severely impaired renal function (OR for eGFR <30=9.09 (95% CI 2.01 to 41.09)) and having a positive SARS-CoV-2 PCR result (OR 2.0 (95% CI 1.11 to 3.60)). CONCLUSIONS: These predictors may help direct intensity of monitoring for patients with suspected or confirmed COVID-19 who are being remotely monitored by primary or secondary care services. Further research is needed to confirm our findings and identify the reasons for increased risk of clinical deterioration associated with cancer and mental health problems.