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Objectives: Limited evidence exists for the diagnostic performance of point-of-care tests for SARS-CoV-2 and influenza in community healthcare. We carried out a prospective diagnostic accuracy study of the LumiraDx™ SARS-CoV-2 and influenza A or B assay in primary care., Methods: Total of 913 adults and children with symptoms of current SARS-CoV-2 infection were recruited from 18 UK primary care practices during a period when Omicron was the predominant COVID variant of concern (June 2022 to December 2022). Trained health care staff performed the index test, with diagnostic accuracy parameters estimated for SARS-CoV-2 and influenza against real-time reverse-transcription PCR (rtRT-PCR)., Results: 151/887 participants were SARS-CoV-2 rtRT-PCR positive, 109 positive for Influenza A, 6 for Influenza B. Index test sensitivity for SARS-CoV-2 was 80.8% (122 of the 151, 95% CI, 73.6-86.7%) and specificity 98.9% (728 of the 736, 95% CI, 97.9-99.5%). For influenza A, sensitivity was 61.5% (67 of the 109, 95% CI, 51.7-70.6%) and specificity 99.4% (771 of the 776, 95% CI, 98.5-99.8%). Sensitivity to detect SARS-CoV-2 and influenza dropped sharply at rtRT-PCR cycle thresholds (Ct) > 30., Discussions: The LumiraDx™ SARS-CoV-2 and influenza A/B assay had moderate sensitivity for SARS-CoV-2 in symptomatic patients in primary care, with lower performance with high rtRT-PCR Ct. Negative results in this patient group cannot definitively rule out SARS-CoV-2 or influenza., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To characterise the quality of life, healthcare use and costs associated with early antibiotic treatment of influenza-like illness (ILI) in 'at-risk' children., Design: Economic analysis of a two-arm double-blind parallel group pragmatic randomised controlled trial., Setting: Children were recruited from community-based healthcare settings, including general practices, walk-in centres and hospital ambulatory care., Participants: Children with risk factors for influenza-related complications, including respiratory, cardiac and neurological conditions, who presented within the first 5 days of an ILI., Interventions: Co-amoxiclav 400/57 suspension or placebo., Outcome Measures: This economic analysis focused on quality of life measured by the EQ-5D-Y, symptoms assessed by the Canadian Acute Respiratory Infection and Flu Scale (CARIFS), healthcare use and costs including medication, hospital visits and admissions, general practitioner and nurse contacts. Outcomes were assessed for up to 28 days post randomisation., Results: Information on resource use, EQ-5D-Y (day 28) and CARIFS (day 7) was available for 265 (98%), 72 (27%) and 123 (45%) out of 271 participants, respectively. Average costs in the co-amoxiclav group were £25 lower (95% CI -£113 to £65), but this difference was not statistically significant (p=0.566). The difference in EQ-5D-Y scores between groups was also not statistically significant (-0.014 (95% CI -0.124 to 0.096), p=0.798). However, day 7 CARIFS scores were 3.5 points lower in the co-amoxiclav arm (95% CI -6.9 to -0.1, p=0.044)., Conclusions: Our findings did not show evidence that early co-amoxiclav treatment improves quality of life or reduces healthcare use and costs in 'at-risk' children with ILI, but may reduce symptom severity though confirmation from further research would be important. Reliable data collection from children's parents/carers was challenging, and resulted in high levels of missing data, which is common in pragmatic trials involving children with acute respiratory tract infections., Trial Registration Number: ISRCTN70714783; EudraCT 2013-002822-21., Competing Interests: Competing interests: KW held a National Institute for Health Research (NIHR) Academic Clinical Lectureship during the conduct of the study and currently holds an NIHR Postdoctoral Fellowship., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces reconsultation due to clinical deterioration in "at risk" children presenting with influenza-like illness (ILI) in primary or ambulatory care., Methods: "At risk" children aged from 6 months to 12 years presenting within 5 days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or a placebo twice daily for 5 days (dosing based on age±weight). "At risk" groups included children with respiratory, cardiac and neurological conditions. Randomisation was stratified by region and used a non-deterministic minimisation algorithm to balance age and current seasonal influenza vaccination status. Our target sample size was 650 children which would have allowed us to detect a reduction in the proportion of children reconsulting due to clinical deterioration from 40% to 26%, with 90% power and 5% two-tailed alpha error (including allowance for 25% loss to follow-up and an inflation factor of 1.041). Participants, caregivers and investigators were blinded to treatment allocation. Intention-to-treat analysis included all randomised participants with primary outcome data on reconsultation due to clinical deterioration within 28 days. Safety analysis included all randomised participants., Trial Registration: ISRCTN 70714783. EudraCT 2013-002822-21., Results: We recruited 271 children between February 11, 2015 and April 20, 2018. Primary outcome data were available for 265 children. Only 61 out of 265 children (23.0%) reconsulted due to clinical deterioration. No evidence of a treatment effect was observed for reconsultation due to clinical deterioration (33 out of 133 for co-amoxiclav (24.8%) and 28 out of 132 (21.2%) for placebo; adjusted risk ratio (RR) 1.16, 95% confidence interval (CI) 0.75-1.80). There was also no evidence of a difference between groups in the proportion of children for whom one or more adverse events (AEs) were reported (32 out of 136 (23.5%) for co-amoxiclav and 22 out of 135 (16.3%) for placebo; adjusted RR 1.45, 95% CI 0.90-2.34). In total, 66 AEs were reported (co-amoxiclav, n=37; placebo, n=29). Nine serious AEs were reported per group, although none were considered related to study medication., Conclusion: Our trial did not find evidence that treatment with co-amoxiclav reduces risk of reconsultation due to clinical deterioration in "at risk" children who present early with ILI during influenza season. Our findings therefore do not support early co-amoxiclav use in children with seasonal ILI., Competing Interests: Conflict of interest: K. Wang held a National Institute for Health Research (NIHR) Academic Clinical Lectureship during the conduct of the study and currently holds a NIHR Postdoctoral Fellowship. Conflict of interest: M.G. Semple reports grants from the UK NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool and the Wellcome Trust Enhancing Research Activity in Epidemic Situations (ERAES) Programme during the conduct of the study, and grants from the Wellcome Trust and the Bill & Melinda Gates Foundation, as well as grants from UK NIHR Efficacy and Mechanism Evaluation, outside the submitted work; and is a minority owner of Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work. Conflict of interest: M. Moore has nothing to disclose. Conflict of interest: A.D. Hay has nothing to disclose. Conflict of interest: S. Tonner has nothing to disclose. Conflict of interest: U. Galal has nothing to disclose. Conflict of interest: J. Grabey has nothing to disclose. Conflict of interest: T. Carver has nothing to disclose. Conflict of interest: R. Perera receives funding from the NIHR Oxford Biomedical Research Centre (BRC), the NIHR Oxford Medtech and In-Vitro Diagnostics Cooperative (MIC), the NIHR Applied Research Collaboration (ARC) Oxford and Thames Valley, and the Oxford Martin School. Conflict of interest: L-M. Yu has nothing to disclose. Conflict of interest: J. Mollison has nothing to disclose. Conflict of interest: P. Little has nothing to disclose. Conflict of interest: A. Farmer receives funding from the NIHR Oxford BRC and is a NIHR Senior Investigator. Conflict of interest: C.C. Butler reports grants from the NIHR as an NIHR Senior Investigator and the NIHR Health Technology Assessment Programme to support the study, as well as grants from the NIHR Health Protection Research Unit on Health Care Associated Infections and Antimicrobial Resistance and grants from NIHR Health for the MIC for innovative diagnostics and monitoring technology to enhance community healthcare, during the conduct of the study; personal fees for advisory board work from Roche Molecular Systems and Pfizer, and grants from Roche Molecular Diagnostics, outside the submitted work. Afinion CRP devices and associated training to participating general practices were provided at no cost to the study by Alere and was part of a publicly funded research consortia that include industrial partners. Conflict of interest: A. Harnden has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Influenza and influenza-like illness (ILI) create considerable burden on healthcare resources each winter. Children with pre-existing conditions such as asthma, diabetes mellitus and cerebral palsy are among those at greatest risk of clinical deterioration from influenza/ILI. The Antibiotics for at Risk CHildren with InfluEnza (ARCHIE) trial aims to determine whether early oral treatment with the antibiotic co-amoxiclav reduces the likelihood of reconsultation due to clinical deterioration in these 'at risk' children., Methods and Analysis: The ARCHIE trial is a double-blind, parallel, randomised, placebo-controlled trial. 'At risk' children aged 6 months to 12 years inclusive who present within the first 5 days of an ILI episode will be randomised to receive a 5-day course of oral co-amoxiclav 400/57 twice daily or placebo. Randomisation will use a non-deterministic minimisation algorithm to balance age and seasonal influenza vaccination status.To detect respiratory virus infections, a nasal swab will be obtained from each participant before commencing study medication. To identify carriage of potential bacterial respiratory pathogens, we will also obtain a throat swab where possible.The primary outcome is reconsultation in any healthcare setting due to clinical deterioration within 28 days of randomisation. We will analyse this outcome using log-binomial regression model adjusted for region, age and seasonal influenza vaccination status.Secondary outcomes include duration of fever, duration of symptoms and adverse events. Continuous outcomes will be compared using regression analysis (or equivalent non-parametric method for non-normal data) adjusting for minimisation variables. Binary outcomes will be compared using χ 2 /Fisher's exact test and log-binomial regression., Ethics: The ARCHIE trial has been reviewed and approved by the North West-Liverpool East Research Ethics Committee, Health Research Authority and Medicines and Healthcare Products Regulatory Agency. Our findings will be published in peer-reviewed journals and disseminated via our study website (www.archiestudy.com) and links with relevant charities., Trial Registration Numbers: ISRCTN 70714783; Pre-results. EudraCT 2013-002822-21; Pre-results., Competing Interests: Competing interests: KW is a National Institute for Health Research (NIHR) Postdoctoral Fellow. AF is a NIHR Senior Investigator and is supported by the Oxford NIHR Biomedical Research Centre. AH is Deputy Chairman of the Joint Committee on Vaccination and Immunisation, which advises the UK government on vaccine policy. MGS is an NIHR Investigator, is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections and is a member of the New and Emerging Respiratory Viral Threats Advisory Group, whose remit includes advice to the UK government on antibiotic and antiviral stockpile policy., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)