Diagnostic accuracy of point-of-care tests for acute respiratory infection: a systematic review of reviews.

Background: Acute respiratory infections are a common reason for consultation with primary and emergency healthcare services. Identifying individuals with a bacterial infection is crucial to ensure appropriate treatment. However, it is also important to avoid overprescription of antibiotics, to prevent unnecessary side effects and antimicrobial resistance. We conducted a systematic review to summarise evidence on the diagnostic accuracy of symptoms, signs and point-of-care tests to diagnose bacterial respiratory tract infection in adults, and to diagnose two common respiratory viruses, influenza and respiratory syncytial virus. Methods: The primary approach was an overview of existing systematic reviews. We conducted literature searches (22 May 2023) to identify systematic reviews of the diagnostic accuracy of point-of-care tests. Where multiple reviews were identified, we selected the most recent and comprehensive review, with the greatest overlap in scope with our review question. Methodological quality was assessed using the Risk of Bias in Systematic Reviews tool. Summary estimates of diagnostic accuracy (sensitivity, specificity or area under the curve) were extracted. Where no systematic review was identified, we searched for primary studies. We extracted sufficient data to construct a 2 × 2 table of diagnostic accuracy, to calculate sensitivity and specificity. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Where possible, meta-analyses were conducted. We used GRADE to assess the certainty of the evidence from existing reviews and new analyses. Results: We identified 23 reviews which addressed our review question; 6 were selected as the most comprehensive and similar in scope to our review protocol. These systematic reviews considered the following tests for bacterial respiratory infection: individual symptoms and signs; combinations of symptoms and signs (in clinical prediction models); clinical prediction models incorporating C-reactive protein; and biological markers related to infection (including C-reactive protein, procalcitonin and others). We also identified systematic reviews that reported the accuracy of specific tests for influenza and respiratory syncytial virus. No reviews were found that assessed the diagnostic accuracy of white cell count for bacterial respiratory infection, or multiplex tests for influenza and respiratory syncytial virus. We therefore conducted searches for primary studies, and carried out meta-analyses for these index tests. Overall, we found that symptoms and signs have poor diagnostic accuracy for bacterial respiratory infection (sensitivity ranging from 9.6% to 89.1%; specificity ranging from 13.4% to 95%). Accuracy of biomarkers was slightly better, particularly when combinations of biomarkers were used (sensitivity 80-90%, specificity 82-93%). The sensitivity and specificity for influenza or respiratory syncytial virus varied considerably across the different types of tests. Tests involving nucleic acid amplification techniques (either single pathogen or multiplex tests) had the highest diagnostic accuracy for influenza (sensitivity 91-99.8%, specificity 96.8-99.4%). Limitations: Most of the evidence was considered low or very low certainty when assessed with GRADE, due to imprecision in effect estimates, the potential for bias and the inclusion of participants outside the scope of this review (children, or people in hospital). Future work: Currently evidence is insufficient to support routine use of point-of-care tests in primary and emergency care. Further work must establish whether the introduction of point-of-care tests adds value, or simply increases healthcare costs. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159948.

Respiratory infections are a common cause of illness. Currently, healthcare professionals use clinical experience to decide whether an infection is caused by a virus or bacteria, and whether antibiotics are needed. However, this is not always easy to establish. We tried to identify the effectiveness of rapid tests (with results in under 45 minutes) at distinguishing between viral and bacterial respiratory infections. We identified and summarised all the existing reviews and studies in this area. We looked at many different tests which aim to distinguish between bacterial and viral causes of respiratory infections. In particular, we assessed: individual symptoms and signs (such as the presence of cough, or a fever) combinations of symptoms and signs (the presence or absence of multiple symptoms) various 'biomarker' tests (blood tests for evidence that the body has used its defence mechanisms) We also looked at specific tests for flu and respiratory syncytial virus, which are common causes of viral infection. The reviews we found showed symptoms and signs were not able to identify bacterial infections in people accurately. The accuracy of biomarker tests was slightly better, particularly when multiple markers were used. The accuracy of rapid tests for flu and respiratory syncytial virus varied; the most accurate tests were those that detect viral genetic material. We also found studies showing that genetic tests that identify many viruses at once (multiplex tests) were very accurate. However, most of the evidence we identified was not robust. There were concerns about the conduct of some of the studies. In some cases there was uncertainty whether a test was really accurate enough to be useful. Therefore there is still doubt about whether any of these tests will be useful additions to current clinical care.

Estimating the burden of vaccine preventable lower respiratory tract disease in primary care, UK: protocol for a prospective surveillance study (AvonCAP GP2).

BACKGROUND: The true burden of acute lower respiratory tract diseases (aLRTD; includes acute lower respiratory tract infection, acute exacerbation of pre-existing heart failure and chronic lung disease) among adults presenting to primary care, and the proportion that are potentially vaccine preventable, is unknown. AIMS: To describe aLRTD incidence in adults presenting to primary care; estimate proportions caused by RSV, SARS-CoV-2 and pneumococcus; and investigate disease burden from patient and NHS perspectives. DESIGN & SETTING: Primary care prospective cohort study conducted in six representative General Practices (total Ì´83 000 registered adults) in Bristol, UK. METHOD: Adults (aged≥18 years) registered at participating General Practices and presenting to primary care (in-hours or out-of-hours) or emergency department (if not admitted) with aLRTD will be eligible and identified by real-time primary care record searches. Researchers will screen electronic GP records, including free text, contact patients to assess eligibility, and offer enrolment in a surveillance study and an enhanced diagnostic study (urine, saliva and respiratory samples; physical examination; and symptom diaries). Data will be collected for all aLRTD episodes, with patients assigned to one of three arms: surveillance, embedded diagnostic, and descriptive dataset. Outcome measures will include clinical and pathogen defined aLRTD incidence rates, symptom severity and duration, NHS contacts and costs, health-related quality of life changes, and mortality (≤30 days post identification). CONCLUSION: This comprehensive surveillance study of adults presenting to primary care with aLRTD, with embedded detailed data and sample collection, will provide an accurate assessment of aLRTD burden due to vaccine preventable infections.

AI-guided deep vein thrombosis diagnosis in primary care: protocol for cohort with qualitative assessment.

BACKGROUND: Deep vein thrombosis (DVT), a formation of blood clots within deep veins, mostly of the proximal lower limb, has an annual incidence of 1-2 per 1,000. Patients who are affected by multiple chronic health conditions and who experience limited mobility are at high risk of developing DVT.Traditional DVT diagnosis involves probabilistic assessment in primary care, followed by specialised ultrasound scans (USS), mainly conducted in hospitals. The emergence of point-of-care ultrasound (POCUS), coupled with artificial intelligence (AI)-applications has the potential to expand primary care diagnostic capabilities. AIM: To assess the accuracy and acceptability of AI-guided POCUS for DVT diagnosis when performed by non-specialists in primary care. DESIGN & SETTING: Diagnostic cross-sectional study coupled with a qualitative evaluation conducted at primary care DVT clinics. METHOD: First, a diagnostic test accuracy (DTA) study will investigate the accuracy of AI-guided POCUS in 500 individuals with suspected DVT, performed by healthcare assistants (HCAs). The reference standard is the standard of care USS conducted by sonographers. Second, after receiving both scans, participants will be invited to complete a patient satisfaction survey (PSS). Finally, semi-structured interviews with 20 participants and 5 HCAs will explore the acceptability of AI-guided POCUS DVT diagnosis. CONCLUSION: This study will rigorously evaluate the accuracy and acceptability of AI-guided POCUS DVT diagnosis conducted by non-specialists in primary care.

Incidence, antimicrobial prescribing practice and associated healthcare costs of paediatric otorrhoea in primary care in the UK: A longitudinal population study.

Background Paediatric otorrhoea (PO) is a symptom-based diagnosis encompassing acute and chronic ear infections which cause otorrhoea in children and young people (CYP). Aim To understand the burden of PO on primary care services. Design and Setting A longitudinal population study in UK primary care. Methods Data from the Clinical Practice Research Datalink (CPRD Aurum), January 2005 to December 2019, was analysed. CYP under 17 years of age with otorrhoea were included. Standardised annual incidence and presentation rates were estimated. Poisson regression modelling was used to determine risk ratios comparing sex, age and IMD. A probabilistic simulation scaled-up estimates for the UK population. Results The cohort included 6,605,193 CYP, observed over 32,942,594 person-years. There were 80,454 incident cases and 106,318 presentations of PO during the 15-year period, equating to standardised annual incidence and presentation rates per 1000 patient-years of 2.42 (95% CI: 2.40-2.44) and 3.15 (3.13-3.17) respectively. In the UK this equates to 41,141 primary care appointments per year. Incidence was higher in males, those aged 0-2 years, and those living in the least deprived quintile. Treatment involved oral antibiotics (57.1%), no prescription (28.1%), topical antibiotics (9.7%), or combination (4.9%). The cost to NHS primary care is estimated at £1.97 million per year. Conclusions This is the first longitudinal population-based study investigating PO which demonstrates the burden on primary care. Antimicrobial prescribing predominantly follows NICE guidelines using oral amoxicillin. Aminoglycosides are the most frequently prescribed topical antibiotic despite the concern of ototoxicity.

Nasal sprays and behavioural interventions compared with usual care for acute respiratory illness in primary care: a randomised, controlled, open-label, parallel-group trial.

BACKGROUND: A small amount of evidence suggests that nasal sprays, or physical activity and stress management, could shorten the duration of respiratory infections. This study aimed to assess the effect of nasal sprays or a behavioural intervention promoting physical activity and stress management on respiratory illnesses, compared with usual care. METHODS: This randomised, controlled, open-label, parallel-group trial was done at 332 general practitioner practices in the UK. Eligible adults (aged ≥18 years) had at least one comorbidity or risk factor increasing their risk of adverse outcomes due to respiratory illness (eg, immune compromise due to serious illness or medication; heart disease; asthma or lung disease; diabetes; mild hepatic impairment; stroke or severe neurological problem; obesity [BMI ≥30 kg/m2]; or age ≥65 years) or at least three self-reported respiratory tract infections in a normal year (ie, any year before the COVID-19 pandemic). Participants were randomly assigned (1:1:1:1) using a computerised system to: usual care (brief advice about managing illness); gel-based spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); saline spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); or a brief behavioural intervention in which participants were given access to a website promoting physical activity and stress management. The study was partially masked: neither investigators nor medical staff were aware of treatment allocation, and investigators who did the statistical analysis were unaware of treatment allocation. The sprays were relabelled to maintain participant masking. Outcomes were assessed using data from participants' completed monthly surveys and a survey at 6 months. The primary outcome was total number of days of illness due to self-reported respiratory tract illnesses (coughs, colds, sore throat, sinus or ear infections, influenza, or COVID-19) in the previous 6 months, assessed in the modified intention-to-treat population, which included all randomly assigned participants who had primary outcome data available. Key secondary outcomes were possible harms, including headache or facial pain, and antibiotic use, assessed in all randomly assigned participants. This trial was registered with ISRCTN, 17936080, and is closed to recruitment. FINDINGS: Between Dec 12, 2020, and April 7, 2023, of 19 475 individuals screened for eligibility, 13 799 participants were randomly assigned to usual care (n=3451), gel-based nasal spray (n=3448), saline nasal spray (n=3450), or the digital intervention promoting physical activity and stress management (n=3450). 11 612 participants had complete data for the primary outcome and were included in the primary outcome analysis (usual care group, n=2983; gel-based spray group, n=2935; saline spray group, n=2967; behavioural website group, n=2727). Compared with participants in the usual care group, who had a mean of 8·2 (SD 16·1) days of illness, the number of days of illness was significantly lower in the gel-based spray group (mean 6·5 days [SD 12·8]; adjusted incidence rate ratio [IRR] 0·82 [99% CI 0·76-0·90]; p<0·0001) and the saline spray group (6·4 days [12·4]; 0·81 [0·74-0·88]; p<0·0001), but not in the group allocated to the behavioural website (7·4 days [14·7]; 0·97 [0·89-1·06]; p=0·46). The most common adverse event was headache or sinus pain in the gel-based group: 123 (4·8%) of 2556 participants in the usual care group; 199 (7·8%) of 2498 participants in the gel-based group (risk ratio 1·61 [95% CI 1·30-1·99]; p<0·0001); 101 (4·5%) of 2377 participants in the saline group (0·81 [0·63-1·05]; p=0·11); and 101 (4·5%) of 2091 participants in the behavioural intervention group (0·95 [0·74-1·22]; p=0·69). Compared with usual care, antibiotic use was lower for all interventions: IRR 0·65 (95% CI 0·50-0·84; p=0·001) for the gel-based spray group; 0·69 (0·45-0·88; p=0·003) for the saline spray group; and 0·74 (0·57-0·94; p=0·02) for the behavioural website group. INTERPRETATION: Advice to use either nasal spray reduced illness duration and both sprays and the behavioural website reduced antibiotic use. Future research should aim to address the impact of the widespread implementation of these simple interventions. FUNDING: National Institute for Health and Care Research.

A pragmatic cluster randomised controlled trial of air filtration to prevent symptomatic winter respiratory infections (including COVID-19) in care homes (AFRI-c) in England: Trial protocol.

BACKGROUND: Respiratory tract infections are readily transmitted in care homes. Airborne transmission of pathogens causing respiratory tract illness is largely unmitigated. Portable high-efficiency-particulate-air (HEPA) filtration units capture microbial particles from the air, but it is unclear whether this is sufficient to reduce infections in care home residents. The Air Filtration to prevent symptomatic winter Respiratory Infections (including COVID-19) in care homes (AFRI-c) randomized controlled trial will determine whether using HEPA filtration units reduces respiratory infection episodes in care home residents. METHODS: AFRI-c is a cluster randomized controlled trial that will be delivered in residential care homes for older people in England. Ninety-one care homes will be randomised to take part for one winter period. The intervention care homes will receive HEPA filtration units for use in communal areas and private bedrooms. Normal infection control measures will continue in all care homes. Anonymised daily data on symptoms will be collected for up to 30 residents. Ten to 12 of these residents will be invited to consent to a primary care medical notes review and (in intervention homes) to having an air filter switched on in their private room. The primary outcome will be number of symptomatic winter respiratory infection episodes. Secondary outcomes include specific clinical measures of infection, number of falls / near falls, number of laboratory confirmed infections, hospitalisations, staff sickness and cost-effectiveness. A mixed methods process evaluation will assess intervention acceptability and implementation. DISCUSSION: The results of AFRI-c will provide vital information about whether portable HEPA filtration units reduce symptomatic winter respiratory infections in older care home residents. Findings about effectiveness, fidelity, acceptability and cost-effectiveness will support stakeholders to determine the use of HEPA filtration units as part of infection control policies.

Assessing acutely ill children in general practice using the National PEWS and LqSOFA clinical scores: a retrospective cohort study.

BACKGROUND: Clinical tools are needed in general practice to help identify seriously ill children. The Liverpool quick Sequential Organ Failure Assessment (LqSOFA) was validated in an Emergency Department and performed well. The National Paediatric Early Warning score (PEWS) has been introduced in hospitals throughout England with hopes for implementation in general practice. AIM: To validate the LqSOFA and National PEWS in general practice. DESIGN/SETTING: Secondary analysis of 6,703 children <5 years presenting to 225 general practices in England and Wales with acute illnesses, linked to hospital data. METHOD: Variables from the LqSOFA and National PEWS were mapped onto study data to calculate score totals. A primary outcome of admission within two days of GP consultation was used to calculate sensitivity, specificity, negative predictive values (NPV), positive predictive values (PPV) and area-under-the-curve (AUC). RESULTS: 104/6,703 children were hospitalised within two days (pre-test probability 1.6%). The sensitivity of the LqSOFA was 30.6% (95% confidence interval 21.8% - 41.0%), with a specificity of 84.7% (83.7% - 85.6%), PPV of 3.0% (2.1% - 4.4%), NPV of 98.7% (98.4% - 99.0%), and AUC of 0.58 (0.53 - 0.63). The sensitivity of the National PEWS was 81.0% (71.0% - 88.1%), with a specificity of 32.5% (31.2% - 33.8%); PPV of 1.9% (1.5% - 2.5%); NPV of 99.1% (98.4% - 99.4%) and AUC of 0.66 (0.59 - 0.72). CONCLUSION: Although the NPVs appear useful, due to low pre-test probabilities rather than discriminative ability, neither tool accurately identified hospitalisations. Unconsidered use by GPs could result in unsustainable referrals.

Topical or oral antibiotics in childhood acute otitis media and ear discharge: a randomized controlled non-inferiority trial.

BACKGROUND: Current guidance suggests oral antibiotics can be considered for children with acute otitis media (AOM) and ear discharge, but there is an absence of evidence regarding the relative effectiveness of antibiotic-corticosteroid eardrops. AIM: To establish whether antibiotic-corticosteroid eardrops are non-inferior to oral antibiotics in children with AOM and ear discharge. DESIGN AND SETTING: Open randomized controlled non-inferiority trial set in Dutch primary care. METHODS: Children were randomized to hydrocortisone-bacitracin-colistin eardrops (five drops, three times per day in the discharging ear(s)) or amoxicillin suspension (50 mg per kilogram of body weight per day, divided over three doses administered orally) for 7 days. The primary outcome was the proportion of children with resolution of ear pain and fever at day 3. RESULTS: Between December 2017 and March 2023, 58 of the planned 350 children were recruited due to slow accrual for various reasons. Children assigned to eardrops (n = 26) had lower resolution rates of ear pain and fever at 3 days compared to those receiving oral antibiotics (n = 31): 42% vs 65%; adjusted risk difference 20.3%, 95% confidence interval -5.3% to 41.9%), longer parent-reported ear discharge (6 vs 3 days; P = .04), and slightly higher mean ear pain scores (Likert scale 0-6) over days 1-3 (2.1 vs 1.4, P = .02), but received fewer oral antibiotic courses in 3months (11 for 25 children vs 33 for 30 children), and had less GI upset and rash (12% vs 32% and 8% vs 16%, respectively). CONCLUSION: Early termination stopped us from determining non-inferiority of antibiotic-corticosteroid eardrops. Our limited data, requiring confirmation, suggest that oral antibiotics may be more effective than antibiotic-corticosteroid eardrops in resolving symptoms and shortening the duration of ear discharge.

A call from 40 public health scientists for an end to the continuing humanitarian and environmental catastrophe in Gaza.

An under-recognised aspect of the current humanitarian catastrophe in Gaza is the impact of the war on the environment and the associated risks for human health. This commentary contextualises these impacts against the background of human suffering produced by the overwhelming violence associated with the use of military force against the general population of Gaza. In calling for an immediate cessation to the violence, the authors draw attention to the urgent need to rebuild the health care system and restore the physical and human infrastructure that makes a liveable environment possible and promotes human health and well-being, especially for the most vulnerable in the population. Environmental remediation should therefore form one of the most important parts of international efforts to assist reconstruction, through which we hope Palestinians and Israelis will achieve lasting peace, health, and sustainable development, all as part of accepted international human rights obligations.

Long-term consequences of urinary tract infection in childhood: an electronic population-based cohort study in Welsh primary and secondary care.

BACKGROUND: Childhood urinary tract infection (UTI) can cause renal scarring, and possibly hypertension, chronic kidney disease (CKD), and end-stage renal failure (ESRF). Previous studies have focused on selected populations, with severe illness or underlying risk factors. The risk for most children with UTI is unclear. AIM: To examine the association between childhood UTI and outcomes in an unselected population of children. DESIGN AND SETTING: A retrospective population-based cohort study using linked GP, hospital, and microbiology records in Wales, UK. METHOD: Participants were all children born in 2005-2009, with follow-up until 31 December 2017. The exposure was microbiologically confirmed UTI before the age of 5 years. The key outcome measures were renal scarring, hypertension, CKD, and ESRF. RESULTS: In total, 159 201 children were included; 77 524 (48.7%) were female and 7% (n = 11 099) had UTI before the age of 5 years. A total of 0.16% (n = 245) were diagnosed with renal scarring by the age of 7 years. Odds of renal scarring were higher in children by age 7 years with UTI (1.24%; adjusted odds ratio 4.60 [95% confidence interval [CI] = 3.33 to 6.35]). Mean follow-up was 9.53 years. Adjusted hazard ratios were: 1.44 (95% CI = 0.84 to 2.46) for hypertension; 1.67 (95% CI = 0.85 to 3.31) for CKD; and 1.16 (95% CI = 0.56 to 2.37) for ESRF. CONCLUSION: The prevalence of renal scarring in an unselected population of children with UTI is low. Without underlying risk factors, UTI is not associated with CKD, hypertension, or ESRF by the age of 10 years. Further research with systematic scanning of children's kidneys, including those with less severe UTI and without UTI, is needed to increase the certainty of these results, as most children are not scanned. Longer follow-up is needed to establish if UTI, without additional risk factors, is associated with hypertension, CKD, or ESRF later in life.

Acute and long-term outcomes of SARS-CoV-2 infection in school-aged children in England: Study protocol for the joint analysis of the COVID-19 schools infection survey (SIS) and the COVID-19 mapping and mitigation in schools (CoMMinS) study.

BACKGROUND: The symptom profiles of acute SARS-CoV-2 infection and long-COVID in children and young people (CYP), risk factors, and associated healthcare needs, are poorly defined. The Schools Infection Survey 1 (SIS-1) was a nationwide study of SARS-CoV-2 infection in primary and secondary schools in England during the 2020/21 school year. The Covid-19 Mapping and Mitigation in Schools (CoMMinS) study was conducted in schools in the Bristol area over a similar period. Both studies conducted testing to identify current and previous SARS-CoV-2 infection, and recorded symptoms and school attendance. These research data have been linked to routine electronic health record (EHR) data. AIMS: To better understand the short- and long-term consequences of SARS-CoV-2 infection, and their risk factors, in CYP. METHODS: Retrospective cohort and nested case-control analyses will be conducted for SIS-1 and CoMMinS data linked to EHR data for the association between (1) acute symptomatic SARS-CoV-2 infection and risk factors; (2) SARS-CoV-2 infection and long-term effects on health: (a) persistent symptoms; (b) any new diagnosis; (c) a new prescription in primary care; (d) health service attendance; (e) a high rate of school absence. RESULTS: Our study will improve understanding of long-COVID in CYP by characterising the trajectory of long-COVID in CYP in terms of things like symptoms and diagnoses of conditions. The research will inform which groups of CYP are more likely to get acute- and long-term outcomes of SARS-CoV-2 infection, and patterns of related healthcare-seeking behaviour, relevant for healthcare service planning. Digested information will be produced for affected families, doctors, schools, and the public, as appropriate. CONCLUSION: Linked SIS-1 and CoMMinS data represent a unique and rich resource for understanding the impact of SARS-CoV-2 infection on children's health, benefiting from enhanced SARS-CoV-2 testing and ability to assess a wide range of outcomes.

Rapid respiratory microbiological point-of-care-testing and antibiotic prescribing in primary care: Protocol for the RAPID-TEST randomised controlled trial.

BACKGROUND: Antibiotics are prescribed for over 50% of respiratory tract infections in primary care, despite good evidence of there being no benefit to the patient, and evidence of over prescribing driving microbial resistance. The high treatment rates are attributed to uncertainty regarding microbiological cause and clinical prognosis. Point-of-care-tests have been proposed as potential antibiotic stewardship tools, with some providing microbiological results in 15 minutes. However, there is little research on their impact on antibiotic use and clinical outcomes in primary care. METHODS: This is a multi-centre, individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms on outcomes in patients aged 12 months and over presenting to primary care in the UK with a suspected respiratory tract infection, where the clinician and/or patient thinks antibiotic treatment may be, or is, necessary. Once consented, all participants are asked to provide a combined nose and throat swab sample and randomised to have a rapid microbiological point-of-care-test or no point-of-care-test. For intervention patients, clinicians review the result of the test, before contacting the patient to finalise treatment. Treatment decisions are made as per usual care in control group patients. The primary outcome is whether an antibiotic is prescribed at this point. All swab samples are sent to the central laboratory for further testing. Patients are asked to complete a diary to record the severity and duration of symptoms until resolution or day 28, and questionnaires at 2 months about their beliefs and intention to consult for similar future illnesses. Primary care medical records are also reviewed at 6-months to collect further infection consultations, antibiotic prescribing and hospital admissions. The trial aims to recruit 514 patients to achieve 90% power with 5% significance to detect a 15% absolute reduction in antibiotic prescribing. Qualitative interviews are being conducted with approximately 20 clinicians and 30 participants to understand any changes in beliefs and behaviour resulting from the point-of-care-test and generate attributes for clinician and patient discrete choice experiments. DISCUSSION: This trial will provide evidence of efficacy, acceptability and mechanisms of action of a rapid microbiological point-of-care test on antibiotic prescribing and patient symptoms in primary care. TRIAL REGISTRATION: ISRCTN16039192, prospectively registered on 08/11/2022.

Correction: Internet Tool to Support Self-Assessment and Self-Swabbing of Sore Throat: Development and Feasibility Study.

[This corrects the article DOI: 10.2196/39791.].

d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial.

Importance: Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established. Objective: To determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI. Design, Setting, and Participants: This 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022. Intervention: Two grams daily of d-mannose powder or matched volume of placebo powder. Main Outcomes and Measures: The primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions. Results: Of 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures. Conclusions and Relevance: In this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group. Trial Registration: isrctn.org Identifier: ISRCTN13283516.

Within-episode repeat antibiotic prescriptions in patients with respiratory tract infections: A population-based cohort study.

BACKGROUND: Antimicrobial stewardship interventions mainly focus on initial antibiotic prescriptions, with few considering within-episode repeat prescriptions. We aimed to describe the magnitude, type and determinants of within-episode repeat antibiotic prescriptions in patients presenting to primary care with respiratory tract infections (RTIs). METHODS: We conducted a population-based cohort study among 530 sampled English general practices within the Clinical Practice Research Datalink (CPRD). All individuals with a primary care RTI consultation for which an antibiotic was prescribed between March 2018 and February 2022. Main outcome measurement was repeat antibiotic prescriptions within 28 days of a RTI visit stratified by age (children vs. adults) and RTI type (lower vs. upper RTI). Multivariable logistic regression and principal components analyses were used to identify risk factors and patient clusters at risk for within-episode repeat prescriptions. FINDINGS: 905,964 RTI episodes with at least one antibiotic prescription were identified. In adults, 19.9% (95% CI 19.3-20.5%) had at least one within-episode repeat prescription for a lower RTI, compared to 10.5% (95% CI 10.3-10.8%) for an upper RTI. In children, this was around 10% irrespective of RTI type. The majority of repeat prescriptions occurred a median of 10 days after the initial prescription and was the same antibiotic class in 48.3% of cases. Frequent RTI related GP visits and prior within-RTI-episode repeat antibiotic prescriptions were main factors associated with repeat prescriptions in both adults and children irrespective of RTI type. Young (<2 years) and older (65+) age were associated with repeat prescriptions. Among those aged 2-64 years, allergic rhinitis, COPD and oral corticosteroids were associated with repeat prescriptions. INTERPRETATIONS: Repeat within-episode antibiotic use accounts for a significant proportion of all antibiotics prescribed for RTIs, with same class antibiotics unlikely to confer clinical benefit and is therefore a prime target for future antimicrobial stewardship interventions.

Dipsticks and point-of-care Microscopy to reduce antibiotic use in women with an uncomplicated Urinary Tract Infection (MicUTI): protocol of a randomised controlled pilot trial in primary care.

INTRODUCTION: Uncomplicated urinary tract infections (uUTIs) in women are common infections encountered in primary care. Evidence suggests that rapid point-of-care tests (POCTs) to detect bacteria and erythrocytes in urine at presentation may help primary care clinicians to identify women with uUTIs in whom antibiotics can be withheld without influencing clinical outcomes. This pilot study aims to provide preliminary evidence on whether a POCT informed management of uUTI in women can safely reduce antibiotic use. METHODS AND ANALYSIS: This is an open-label two-arm parallel cluster-randomised controlled pilot trial. 20 general practices affiliated with the Bavarian Practice-Based Research Network (BayFoNet) in Germany were randomly assigned to deliver patient management based on POCTs or to provide usual care. POCTs consist of phase-contrast microscopy to detect bacteria and urinary dipsticks to detect erythrocytes in urine samples. In both arms, urine samples will be obtained at presentation for POCTs (intervention arm only) and microbiological analysis. Women will be followed-up for 28 days from enrolment using self-reported symptom diaries, telephone follow-up and a review of the electronic medical record. Primary outcomes are feasibility of patient enrolment and retention rates per site, which will be summarised by means and SDs, with corresponding confidence and prediction intervals. Secondary outcomes include antibiotic use for UTI at day 28, time to symptom resolution, symptom burden, number of recurrent and upper UTIs and re-consultations and diagnostic accuracy of POCTs versus urine culture as the reference standard. These outcomes will be explored at cluster-levels and individual-levels using descriptive statistics, two-sample hypothesis tests and mixed effects models or generalised estimation equations. ETHICS AND DISSEMINATION: The University of Würzburg institutional review board approved MicUTI on 16 December 2022 (protocol n. 109/22-sc). Study findings will be disseminated through peer-reviewed publications, conferences, reports addressed to clinicians and the local citizen's forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05667207.

Systematic review and meta-analysis of the accuracy of McIsaac and Centor score in patients presenting to secondary care with pharyngitis.

BACKGROUND: Centor and McIsaac scores are clinical prediction rules for diagnosing group A streptococcus (GAS) infection in patients with pharyngitis. Their recommended thresholds vary between guidelines. OBJECTIVES: To estimate the sensitivity and specificity of the McIsaac and Centor scores to diagnose GAS pharyngitis and evaluate their impact on antibiotic prescribing at each threshold in patients presenting to secondary care. DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: Studies of patients presenting with acute pharyngitis to emergency or outpatient clinics that estimated the accuracy of McIsaac or Centor scores against throat cultures and/or rapid antigen detection tests (RADT) as reference standards. TESTS: Centor or McIsaac score. REFERENCE STANDARD: Throat cultures and/or RADT. ASSESSMENT OF RISK OF BIAS: Quality Assessment of Diagnostic Accuracy Studies. METHODS OF DATA SYNTHESIS: The sensitivities and specificities of the McIsaac and Centor scores were pooled at each threshold using bivariate random effects meta-analysis. RESULTS: Fourteen studies were included (eight McIsaac and six Centor scores). Eight studies had unclear and six had a high risk of bias. The McIsaac score had higher estimated sensitivity and lower specificity relative to Centor scores at equivalent thresholds but with wide and overlapping confidence regions. Using either score as a triage to RADT to decide antibiotic treatment would reduce antibiotic prescription to patients with non-GAS pharyngitis relative to RADT test for everyone, but also reduce antibiotic prescription to patients with GAS. DISCUSSION: Centor and McIsaac scores are equally ineffective at triaging patients who need antibiotics presenting with pharyngitis at hospitals. At high thresholds, too many true positive cases are missed, whereas at low thresholds, too many false positives are treated, leading to the over prescription of antibiotics. The former may be compensated by adequate safety netting by clinicians, ensuring that patients can seek help if symptoms worsen.

Implementation of the CHIldren with acute COugh (CHICO) intervention to improve antibiotics management: a qualitative study in primary care.

BACKGROUND: Childhood respiratory tract infections (RTIs) are common and can lead to unnecessary antibiotic use and antimicrobial resistance. The CHIldren with COugh (CHICO) intervention incorporates a clinician-focused algorithm (STARWAVe) to predict future hospitalisation risk, elicitation of carer concerns, and a carer-focused personalised leaflet recording treatment decisions and safety-netting information. AIM: To examine the implementation of the CHICO intervention by primary care clinicians. DESIGN AND SETTING: A qualitative study with primary care clinicians in England taking part in the CHICO randomised controlled trial. METHOD: Interviews explored the CHICO intervention's acceptability and use. Clinicians from a range of practices with high and low antibiotic dispensing rates were recruited. Normalisation process theory underpinned data collection and thematic analysis. RESULTS: Most clinicians liked the intervention because it was quick and easy to use, it helped elicit carer concerns, and reassured clinicians and carers of the appropriateness of treatment decisions. However, clinicians used it as a supportive aid for treatment decisions rather than as a tool for behaviour change. The accompanying advice leaflet helped explain treatment decisions and support self-care. The intervention did not always align with clinicians' usual processes, which could affect use. Increased familiarisation with the algorithm led to reduced intervention use, which was further reduced during the COVID-19 pandemic as a result of changes to practice and remote consultations. CONCLUSION: Clinicians found the CHICO intervention useful to support decision making around antibiotic prescribing and it helped discussions with carers about concerns and treatment decisions. The intervention may need to be adapted to align more with clinicians' consultation flow and remote consultations.