Recurrent urinary tract infections and prophylactic antibiotic use in women: cross-sectional study.

BACKGROUND: Despite the considerable morbidity caused by recurrent UTIs (rUTIs), and the wider personal and public health implications from frequent antibiotic use, few studies adequately describe the prevalence and characteristics of women with rUTIs or those who use prophylactic antibiotics. AIM: To describe the prevalence, characteristics, and urine profiles of women with rUTIs with and without prophylactic antibiotic use in Welsh primary care. DESIGN AND SETTING: Retrospective cross-sectional study in Welsh General Practice using the SAIL Databank. METHOD: We describe the characteristics of women aged ≥18 years with rUTIs or using prophylactic antibiotics from 2010-2020, and associated urine culture results from 2015 - 2020. RESULTS: 6.0% of women (n=92,213) had rUTIs, and 1.7% (n=26,862) were prescribed prophylactic antibiotics. Only 49% of prophylactic antibiotic users met the definition of rUTIs before initiation. 81% of women with rUTIs had a urine culture result in the preceding 12 months with high rates of resistance to trimethoprim and amoxicillin. 64% of women taking prophylactic antibiotics had a urine culture result before initiation, and 18% (n=320) of women prescribed trimethoprim had resistance to it on the antecedent sample. CONCLUSION: A substantial proportion of women had rUTIs or incident prophylactic antibiotic use. However, 64% of women had urine cultured before starting prophylaxis. There was a high proportion of cultured bacteria resistant to two antibiotics used for rUTI prevention and evidence of resistance to the prescribed antibiotic. More frequent urine cultures for rUTI diagnosis and before prophylactic antibiotic initiation could better inform antibiotic choices.

Assessing the heterogeneity of ethnic categories for patient records in primary care.

BACKGROUND: UK general practice surgeries collect data regarding patient ethnicities, typically at registration. These data are subsequently used in both clinical care and research, for example, when embedded in risk modelling tools. The published standard list of ethnic categories exists, but little is known about what happens in frontline practice. AIM: To document the variation in ethnic categories available on online patient registration forms across GP surgeries in Oxfordshire. METHOD: Of all 67 GP surgeries in Oxfordshire, 56 had online registration forms that included an option list for ethnicity reporting. The authors compared these against the 2001, 2011, and 2021 UK census ethnic group categorisation. RESULTS: Significant heterogeneity was identified across practices. The number of options for ethnicity group ranged from 5 to 84, with a median of 14, compared to the census lists that comprise of 19 (2021), 18 (2011), and 16 (2001) groups. Of the 56 practices, six used the 2001 census list, five used the 2011 census list, and none used the 2021 census list. Overall, 45 practices used lists that differed from any census list, including categories not typically considered to be ethnic, for example 'Muslim' or 'Buddhist', meaning individuals could potentially identify with multiple options. CONCLUSION: High-quality research and healthcare data that includes patient ethnicity is essential to understand, document, and mitigate against health inequalities. However, this may be compromised by poorly conceived ethnic categorisations and a lack of standardisation. This pilot/exploratory study suggests that the ethnicity records in primary health care may be neither standardised nor meaningful.

Trends in C reactive protein testing: a retrospective cohort study in paediatric ambulatory care settings.

OBJECTIVES: This study aims to investigate C reactive protein (CRP) testing practices in paediatric ambulatory care across British primary care and accident and emergency (A&E) departments. DESIGN, SETTING, PARTICIPANTS: This retrospective cohort study included children <18 years old having ≥1 CRP test at primary care or A&E departments in Oxfordshire between 2007 and 2021. OUTCOMES: We estimated the frequency and annual changes in CRP testing in both settings and evaluated referral and admission patterns based on CRP levels: low (<20 mg/L), intermediate or high (≥80 mg/L). RESULTS: Over 15 years, 91 540 CRP tests were requested in 63 226 children, with 33 882 (53.6%) in primary care and 29 344 (46.4%) in A&E. Both settings showed rising trends in test requests, with average annual percentage change of 3.0% (95% CI 1.2% to 4.7%) in primary care and 11.5% (95% CI 8.6% to 14.6%) in A&E. The proportion of intermediate/high-test results remained stable. In primary care, 50 709 (95.8%) of CRP tests were <20 mg/L, with 99.0% of these children managed at home. High and intermediate CRP values increased odds of referral versus low CRP (OR adjusted for age=21.80; 95% CI 16.49 to 28.81 and 4.77; 3.78 to 6.02, respectively). At A&E, 27 610 (71.5%) children had CRP<20 mg/L, of whom 42.5% were admitted while 3776 (9.8%) had CRP≥80 mg/L with 57.9% admission rate. High and intermediate CRP values increased odds of admission versus low CRP (OR adjusted for age=1.90; 95% CI 1.78 to 2.04 and 1.39; 1.32 to 1.46, respectively). CONCLUSION: There are rising trends of CRP test requests in paediatric ambulatory care settings, with no evidence of increases in proportion of intermediate/high-test results in primary care. Low CRP values at primary care were linked to children managed at home, while almost half of children with low CRP values at A&E were admitted to the hospital.

How do primary care clinicians approach the management of frailty? A qualitative interview study.

BACKGROUND: Around 15% of adults aged over 65 live with moderate or severe frailty. Contractual requirements for management of frailty are minimal and neither incentivised nor reinforced. Previous research has shown frailty identification in primary care is ad hoc and opportunistic, but there has been little focus on the challenges of frailty management, particularly within the context of recent introduction of primary care networks and an expanding allied health professional workforce. AIM: Explore the views of primary care clinicians in England on the management of frailty. DESIGN AND SETTING: Semi-structured interviews were conducted with clinicians across England, including general practitioners (GPs), physician associates, nurse practitioners, paramedics and clinical pharmacists. Thematic analysis was facilitated through NVivo (Version 12). RESULTS: A total of 31 clinicians participated. Frailty management was viewed as complex and outside of clinical guidelines with medication optimisation highlighted as a key example. Senior clinicians, particularly experienced GPs, were more comfortable with managing risk. Relational care was important in prioritising patient wishes and autonomy, for instance to remain at home despite deteriorations in health. In settings where more formalised multidisciplinary frailty services had been established this was viewed as successful by clinicians involved. CONCLUSION: Primary care clinicians perceive frailty as best managed through trusted relationships with patients, and with support from experienced clinicians. New multidisciplinary working in primary care could enhance frailty services, but must keep continuity in mind. There is a lack of evidence or guidance for specific interventions or management approaches.

Diagnosis and Severity Assessment of COPD Using a Novel Fast-Response Capnometer and Interpretable Machine Learning.

INTRODUCTION: Spirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, nonspecific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study's aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide (CO2) breath records captured with TidalSense's N-TidalTM capnometer. METHOD: For COPD diagnosis, machine learning algorithms were trained and evaluated on 294 COPD (including GOLD stages 1-4) and 705 non-COPD participants. A logistic regression model was also trained to distinguish GOLD 1 from GOLD 4 COPD with the output probability used as an index of severity. RESULTS: The best diagnostic model achieved an AUROC of 0.890, sensitivity of 0.771, specificity of 0.850 and positive predictive value (PPV) of 0.834. Evaluating performance on all test capnograms that were confidently ruled in or out yielded PPV of 0.930 and NPV of 0.890. The severity determination model yielded an AUROC of 0.980, sensitivity of 0.958, specificity of 0.961 and PPV of 0.958 in distinguishing GOLD 1 from GOLD 4. Output probabilities from the severity determination model produced a correlation of 0.71 with percentage predicted FEV1. CONCLUSION: The N-TidalTM device could be used alongside interpretable machine learning as an accurate, point-of-care diagnostic test for COPD, particularly in primary care as a rapid rule-in or rule-out test. N-TidalTM also could be effective in monitoring disease progression, providing a possible alternative to spirometry for disease monitoring.

Clinician and parent views on urine collection in precontinent children in the UK: a qualitative interview study.

OBJECTIVE: To explore the experiences of healthcare professionals (HCPs) and parents of urine collection methods, to identify barriers to successful sampling and what could improve the process. DESIGN: Qualitative research, using individual semistructured interviews with HCPs and parents. The interviews were audiorecorded, transcribed and thematically analysed. SETTING: UK-based HCPs from primary and secondary care settings and parents with experience with urine collection in primary and/or secondary care settings. PARTICIPANTS: HCPs who were involved in aiding, supervising or ordering urine samples. Parents who had experience with urine collection in at least one precontinent child. RESULTS: 13 HCPs and 16 parents were interviewed. 2 participating HCPs were general practitioners (GPs), 11 worked in paediatric secondary care settings (8 were nurses and 3 were doctors). Two parents had children with underlying conditions where frequent urine collection was required to rule out infections.HCPs and parents reported that there were no straightforward methods of urine collection for precontinent children. Each method-'clean catch', urine bag and urine pad-had limitations and problems with usage. 'Clean catch', regarded as the gold standard by HCPs with a lower risk of contamination, often proved difficult for parents to achieve. Other methods had elevated risk of contamination but were more acceptable to parents because they were less challenging. Many of the parents expressed the need for more information about urine collection. CONCLUSIONS: Current methods of urine collection are challenging to use and may be prone to contamination. A new device is required to assist with urine collection in precontinent children, to simplify and reduce the stress of the situation for those involved. Parents are key partners in the process of urine collection with young children. Meeting their expressed need for more information could be an important way to achieve better-quality samples while awaiting a new device.

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.

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.].

Ivermectin for COVID-19 in adults in the community (PRINCIPLE): An open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes.

BACKGROUND: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials. METHODS: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 µg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome. TRIAL REGISTRATION: ISRCTN86534580. FINDINGS: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n = 2157), usual care (n = 3256), and other treatments (n = 3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months. INTERPRETATION: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted. FUNDING: UKRI/National Institute of Health Research (MC_PC_19079).

GPs' perspectives on diagnostic tests for children: a qualitative interview study.

BACKGROUND: Most healthcare contacts for children in the UK occur in general practice. Diagnostic tests can be beneficial in narrowing differential diagnoses; however, there is substantial variation in the use of tests for children in general practice. Unwarranted variation in testing can lead to variation in quality of care and may exacerbate health inequities. To our knowledge, no previous study has tried to understand why variation in testing exists for children in general practice. AIM: To explore GPs' perspectives on using diagnostic tests for children in primary care and the underlying drivers of variation. DESIGN AND SETTING: Qualitative study in which semi-structured interviews were conducted with GPs and trainee GPs in England. METHOD: Interviews were conducted with 18 GPs and two trainee GPs between April and June 2023. The interviews were transcribed and analysed using reflexive thematic analysis. RESULTS: GPs reflected that their approach to testing in children differed from their approach to testing in adults: their threshold to test was higher, and their threshold to refer to specialists was lower. GPs' perceptions of test utility varied, including objective testing for asthma. Perceived drivers of variation in testing were intrinsic (clinician-specific) factors relating to their risk tolerance and experience; and extrinsic factors, including disease prevalence, parental concern and expectations of health care, workforce changes leading to fragmentation in care, time constraints, and differences in guidelines. CONCLUSION: The findings of this study identify actionable issues for clinicians, researchers, and policymakers to address gaps in education, evidence, and guidance, reduce unwarranted differences in test use, and improve the quality of health care delivered to children in general practice.

Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients.

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031.

Epidemiology and microbiology of recurrent UTI in women in the community in Oxfordshire, UK.

Background: Recurrent urinary tract infection (rUTI) contributes to significant morbidity and antibiotic usage. Objectives: To characterize the age of women experiencing rUTI, the microbiology of rUTIs, and the risk of further rUTIs in Oxfordshire, UK. Patients and methods: We retrospectively analysed de-identified linked microbiology and hospital admissions data (Infections in Oxfordshire Research Database), between 2008 and 2019, including positive urine cultures from women aged ≥16 years in community settings. We defined rUTI as ≥2 positive urine cultures within 6 months or ≥3 within 12 months. Results: Of 201 927 women with urine culture performed, 84 809 (42%) had ≥1 positive culture, and 15 617 (18%) of these experienced ≥1 rUTI over a median (IQR) follow-up of 6 (3-9) years. Women with rUTI were 17.0 (95% CI: 16.3-17.7) years older on average. rUTI was commonest (6204; 40%) in those aged 70-89 years. Post-rUTI, the risk of further UTI within 6 months was 29.4% (95% CI: 28.7-30.2). Escherichia coli was detected in 65% of positive cultures. Among rUTIs where the index UTI was E. coli associated, the second UTI was also E. coli associated in 81% of cases. Conclusions: rUTIs represent a substantial healthcare burden, particularly in women >60 years. One-third of women experiencing rUTI have a further microbiologically confirmed UTI within 6 months.

Infections diagnosed in children and young people screened for malaria in UK emergency departments: a retrospective multi-centre study.

BACKGROUND: Data on imported infections in children and young people (CYP) are sparse. AIMS: To describe imported infections in CYP arriving from malaria-endemic areas and presenting to UK emergency departments (ED) who were screened for malaria. METHODS: This is a retrospective, multi-centre, observational study nested in a diagnostic accuracy study for malaria rapid diagnostic tests. Any CYP < 16 years presenting to a participating ED with a history of fever and travel to a malaria-endemic area between 1 January 2016 and 31 December 2017 and who had a malaria screen as a part of standard care were included. Geographical risk was calculated for the most common tropical infections. RESULTS: Of the 1414 CYP screened for malaria, 44.0% (n = 622) arrived from South Asia and 33.3% (n = 471) from sub-Saharan Africa. Half (50.0%) had infections common in both tropical and non-tropical settings such as viral upper respiratory tract infection (URTI); 21.0% of infections were coded as tropical if gastro-enteritis is included, with a total of 4.2% (60) cases of malaria. CYP diagnosed with malaria were 7.44 times more likely to have arrived from sub-Saharan Africa than from South Asia (OR 7.44, 3.78-16.41). CONCLUSION: A fifth of CYP presenting to participating UK EDs with fever and a history of travel to a malaria-endemic area and who were screened for malaria had a tropical infection if diarrhoea is included. A third of CYP had no diagnosis. CYP arriving from sub-Saharan Africa had the greatest risk of malaria.Abbreviations: CYP: children and young people; ED: emergency department; PERUKI: Paediatric Emergency Research in the UK and Ireland; RDT: rapid diagnostic test; VFR: visiting friends and relatives.

Cost-utility analysis of molnupiravir for high-risk, community-based adults with COVID-19: an economic evaluation of the PANORAMIC trial.

BACKGROUND: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations. AIM: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over 6 months. DESIGN AND SETTING: An economic evaluation of the PANORAMIC trial in the UK. METHOD: A cost-utility analysis that adopted a UK NHS and personal social services perspective and a 6-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement. RESULTS: In the base-case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] = 445 to 453) and higher mean QALYs of 0.0055 (95% CI = 0.0044 to 0.0067) than usual care (mean incremental cost per QALY of £81 190). Sensitivity and subgroup analyses showed similar results, except for those aged ≥75 years, with a 55% probability of being cost-effective at a £30 000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15 000 per QALY threshold. CONCLUSION: At the current cost of £513 per course, molnupiravir is unlikely to be cost-effective relative to usual care over a 6-month time horizon among mainly vaccinated patients with COVID-19 at increased risk of adverse outcomes, except those aged ≥75 years.

Identifying infection in chronic wounds in a community setting: A systematic review of diagnostic test accuracy studies.

AIM: To determine the diagnostic accuracy of different methods currently available to identify infection in chronic wounds applicable to adult patients in a community setting. DESIGN: Systematic review of diagnostic test accuracy studies. REVIEW METHODS: Two authors independently completed screening, data extraction and quality and bias assessments (QUADAS2). Eligible studies compared a method (index test) for detecting infection (diagnosis of interest) with microscopy and culture of either deep tissue biopsy or wound swab (reference test) in adult patients with wounds of >4 weeks duration (participants). The results were synthesized narratively. DATA SOURCES: We systematically searched CINAHL, Embase and Medline from 2011 to April 2022. RESULTS: Four studies were included, all recruiting from secondary care wound clinics. Two studies assessed the diagnostic accuracy of Moleculight i:X, a bacterial fluorescence imaging device against deep tissue biopsy culture. One study assessed the diagnostic accuracy of the elevation of various enzymes detected in wound fluid against wound swab microscopy of culture. One study assessed the diagnostic accuracy of bacterial protease activity against wound swab microscopy and culture. Sensitivities of these methods ranged from 50 to 75% and specificities from 47 to 100%. CONCLUSION: Only a small number of studies were included in this systematic review due to our strict inclusion criteria. We have not identified any methods for diagnosing infection in chronic wounds with either a sufficient quality of evidence to recommend their use in community settings at present. Further research is needed to develop and evaluate appropriate diagnostics for this purpose. IMPACT: This study highlights the paucity of research into wound diagnostics in a community setting and should prompt further research in this area. Accurate diagnostic tests have the potential to improve community-based wound care by optimizing antibiotic use and potentially improving healing time. REPORTING METHOD: PRISMA-DTA checklist. PATIENT OR PUBLIC CONTRIBUTION: The PPI group for the NIHR Community Healthcare MIC were supportive of this topic of work.

Diagnostic accuracy of a point-of-care antigen test for SARS-CoV-2 and influenza in a primary care population (RAPTOR-C19).

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.

Development and validation of the Baseline Recurrence Risk in Cellulitis (BRRISC) score.

OBJECTIVES: Cellulitis is often treated with antibiotics for longer than recommended by guidelines. Prolonged therapy may reduce recurrence in certain patients, but it is not known which patients are at greatest risk. Our objective was to develop and temporally validate a risk prediction score to identify patients attending hospital with cellulitis at highest risk of recurrence. METHODS: We included UK adult patients with cellulitis attending hospital in an electronic health records (EHR) study to identify demographic, comorbid, physiological, and laboratory factors predicting recurrence (before death) within 90 days, using multivariable logistic regression with backwards elimination in complete cases. A points-based risk score integerised model coefficients for selected predictors. Performance was assessed using the C-index in development and temporal validation samples. RESULTS: The final model included 4938 patients treated for median 8 days (IQR 6-11); 8.8% (n = 436) experienced hospitalisation-associated recurrence. A risk score using eight variables (age, heart rate, urea, platelets, albumin, previous cellulitis, venous insufficiency, and liver disease) ranged from 0-15, with C-index = 0.65 (95%CI: 0.63-0.68). Categorising as low (score 0-1), medium (2-5) and high (6-15) risk, recurrence increased fourfold; 3.2% (95%CI: 2.3-4.4%), 9.7% (8.7-10.8%), and 16.6% (13.3-20.4%). Performance was maintained in the validation sample (C-index = 0.63 (95%CI: 0.58-0.67)). Among patients at high risk, four distinct clinical phenotypes were identified using hierarchical clustering 1) young, acutely unwell with liver disease; 2) comorbid with previous cellulitis and venous insufficiency; 3) chronic renal disease with severe renal impairment; and 4) acute severe illness, with substantial inflammatory responses. CONCLUSIONS: Risk of cellulitis recurrence varies markedly according to individual patient factors captured in the Baseline Recurrence Risk in Cellulitis (BRRISC) score. Further work is needed to optimise the score, considering baseline and treatment response variables not captured in EHR data, and establish the utility of risk-based approaches to guide optimal antibiotic duration.

Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir-based antiretroviral therapy.

OBJECTIVE: We aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia. DESIGN: Cross-sectional study among people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART). METHODS: We used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia at least 1000 copies/ml using logistic regression models. In exploratory analyses, we used receiver operating curves (ROCs) to estimate optimal urine TFV and DBS TFV-DP thresholds to predict concurrent viraemia. RESULTS: Among 124 participants, 68 (54.8%) were women, median age was 39 years [interquartile range (IQR) 34-45] and 74 (59.7%) were receiving efavirenz versus 50 (40.3%) receiving dolutegravir. Higher concentrations of urine TFV [1000 ng/ml increase, odds ratio (OR) 0.97 95% CI 0.94-0.99, P  = 0.005] and DBS TFV-DP (100 fmol/punch increase, OR 0.76, 95% CI 0.67-0.86, P  < 0.001) were associated with lower odds of viraemia. There was evidence that these associations were stronger among people receiving dolutegravir than among people receiving efavirenz (urine TFV, P  = 0.072; DBS TFV-DP, P  = 0.003). Nagelkerke pseudo- R2 for the DBS TFV-DP models was higher for the urine TFV models, demonstrating a stronger relationship between DBS TFV-DP and viraemia. Among people receiving dolutegravir, a DBS TFV-DP concentration of 483 fmol/punch had 88% sensitivity and 85% specificity to predict concurrent viraemia ≥1000 copies/ml. CONCLUSION: Among PWH receiving TDF-based ART, urine TFV concentrations, and in particular DBS TFV-DP concentrations, were strongly associated with concurrent viraemia, especially among people receiving dolutegravir.

What are important areas where better technology would support women's health? Findings from a priority setting partnership.

BACKGROUND: Women's health has historically lacked investment in research and development. Technologies that enhance women's health ('FemTech') could contribute to improving this. However, there has been little work to understand which priority unmet needs should be a focus for women's health technology development. The voices of clinicians and those who experience and utilise these technologies (including those used at home or encountered in clinical settings) are needed to ensure that device development aligns with need, without risking exacerbating or creating health inequities. METHOD: We undertook a priority setting partnership project exploring unmet needs in women's health and well-being where physical technologies or innovations could help. This comprised gathering feedback from: patients and clinicians using both qualitative surveys and discussions; collating and publishing these responses and asking for feedback; evidence checking unmet needs identified, and holding a partnership priority setting event to agree a top 10 and top 20 list of priorities. RESULTS: We generated a 'longlist' of 54 suggestions for areas where better kit, devices or equipment could support women's health. For three, we found evidence of existing technologies which mitigated against that need. We took the remaining 51 suggestions to a partnership priority setting meeting which brought together clinicians and service users. Through discussion as this group, we generated a list of the top 10 areas identified as priorities for technological development and improvement. These included better devices to manage examination, diagnosis and treatment of pelvic pain (including endometriosis), prolapse care, continence (treatment and prevention, related to pregnancy and beyond), menstruation, vaginal pain and vaginismus, point of care tests for common infections, and nipple care when breastfeeding. CONCLUSION: The top priorities suggest far-reaching areas of unmet need across women's life course and across multiple domains of health and well-being, and opportunities where innovation in the devices that people use themselves or encounter in health settings could potentially enhance health and healthcare experiences.