Use of the FebriDx® host-response point-of-care test may reduce antibiotic use for respiratory tract infections in primary care: a mixed-methods feasibility study.

INTRODUCTION: FebriDx® is a CE-marked, single-use point-of-care test with markers for bacterial [C-reactive protein (CRP)] and viral [myxovirus resistance protein A (MxA)] infection, using finger-prick blood samples. Results are available after 10-12 min. We explored the usability and potential impact of FebriDx® in reducing antibiotic prescriptions for lower respiratory tract infection (LRTI) in primary care, and the feasibility of conducting a randomized controlled trial (RCT). METHODS: Patients (aged ≥1 year) with LRTI deemed likely to receive antibiotic prescription were recruited at nine general practices and underwent FebriDx® testing. Data collection included FebriDx® results, antibiotic prescribing plan (before and after testing) and re-consultation rates. Staff completed System Usability Scale questionnaires. RESULTS: From 31 January 2023 to 9 June 2023, 162 participants participated (median age 57 years), with a median symptom duration of 7 days (IQR 5-14). A valid FebriDx® result was obtained in 97% (157/162). Of 155 patients with available results, 103 (66%) had no detectable CRP or MxA, 28 (18%) had CRP only, 5 (3%) had MxA only, and 19 (12%) had both CRP and MxA. The clinicians' stated management plan was to prescribe antibiotics for 86% (134/155) before testing and 45% (69/155) after testing, meaning a 41% (95% CI: 31%, 51%) difference after testing, without evidence of increased re-consultation rates. Ease-of-use questionnaires showed 'good' user-friendliness. CONCLUSIONS: Use of FebriDx® to guide antibiotic prescribing for LRTI in primary care was associated with a substantial reduction in prescribing intentions. These results support a fully powered RCT to confirm its impact and safety.

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.].

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

BACKGROUND: Sore throat is a common problem and a common reason for the overuse of antibiotics. A web-based tool that helps people assess their sore throat, through the use of clinical prediction rules, taking throat swabs or saliva samples, and taking throat photographs, has the potential to improve self-management and help identify those who are the most and least likely to benefit from antibiotics. OBJECTIVE: We aimed to develop a web-based tool to help patients and parents or carers self-assess sore throat symptoms and take throat photographs, swabs, and saliva samples for diagnostic testing. We then explored the acceptability and feasibility of using the tool in adults and children with sore throats. METHODS: We used the Person-Based Approach to develop a web-based tool and then recruited adults and children with sore throats who participated in this study by attending general practices or through social media advertising. Participants self-assessed the presence of FeverPAIN and Centor score criteria and attempted to photograph their throat and take throat swabs and saliva tests. Study processes were observed via video call, and participants were interviewed about their views on using the web-based tool. Self-assessed throat inflammation and pus were compared to clinician evaluation of patients' throat photographs. RESULTS: A total of 45 participants (33 adults and 12 children) were recruited. Of these, 35 (78%) and 32 (71%) participants completed all scoring elements for FeverPAIN and Centor scores, respectively, and most (30/45, 67%) of them reported finding self-assessment relatively easy. No valid response was provided for swollen lymph nodes, throat inflammation, and pus on the throat by 11 (24%), 9 (20%), and 13 (29%) participants respectively. A total of 18 (40%) participants provided a throat photograph of adequate quality for clinical assessment. Patient assessment of inflammation had a sensitivity of 100% (3/3) and specificity of 47% (7/15) compared with the clinician-assessed photographs. For pus on the throat, the sensitivity was 100% (3/3) and the specificity was 71% (10/14). A total of 89% (40/45), 93% (42/45), 89% (40/45), and 80% (30/45) of participants provided analyzable bacterial swabs, viral swabs, saliva sponges, and saliva drool samples, respectively. Participants were generally happy and confident in providing samples, with saliva samples rated as slightly more acceptable than swab samples. CONCLUSIONS: Most adult and parent participants were able to use a web-based intervention to assess the clinical features of throat infections and generate scores using clinical prediction rules. However, some had difficulties assessing clinical signs, such as lymph nodes, throat pus, and inflammation, and scores were assessed as sensitive but not specific. Many participants had problems taking photographs of adequate quality, but most were able to take throat swabs and saliva samples.

Feasibility of a placebo-controlled trial of antibiotics for possible urinary tract infection in care homes: a qualitative interview study.

BACKGROUND: Diagnosis of suspected urinary tract infection (UTI) in care and nursing home residents is commonly based on vague non-localising symptoms (for example, confusion), potentially leading to inappropriate antibiotic prescription. The safety of withholding antibiotics in such cases could be addressed by a randomised controlled trial (RCT); however, this would require close monitoring of residents, and support from care home staff, clinicians, residents, and families. AIM: To explore the views of residential care and nursing home staff (herein referred to as care home staff) and primary care clinicians on the feasibility and design of a potential RCT of antibiotics for suspected UTI in care home residents, with no localising urinary symptoms. DESIGN & SETTING: A qualitative interview study with primary care clinicians and care home staff in the UK. METHOD: Semi-structured interviews with 16 care home staff and 11 primary care clinicians were thematically analysed. RESULTS: Participants were broadly supportive of the proposed RCT. The safety of residents was a priority and there was strong support for using the RESTORE2 (Recognise Early Soft Signs, Take Observations, Respond, Escalate) assessment tool to monitor residents; however, there were concerns about associated training requirements, especially for night and temporary staff. Effective communication (with residents, families, and staff) was deemed essential, and carers were confident that residents and families would be supportive of the RCT if the rationale was clearly explained and safety systems were robust. There were mixed views on a placebo-controlled design. The perceived additional burden was seen as a potential barrier, and the use of temporary staff and the out-of-hours period were highlighted as potential risk areas. CONCLUSION: The support for this potential trial was encouraging. Future development will need to prioritise resident safety (especially in the out-of-hours period), effective communication, and minimising additional burden on staff to optimise recruitment.

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.

Mortality in COVID-19 among women on hormone replacement therapy: a retrospective cohort study.

BACKGROUND: Limited recent observational data have suggested that there may be a protective effect of oestrogen on the severity of COVID-19 disease. Our aim was to investigate the association between hormone replacement therapy (HRT) or combined oral contraceptive pill (COCP) use and the likelihood of death in women with COVID-19. METHODS: We undertook a retrospective cohort study using routinely collected computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. We identified a cohort of 1,863,478 women over 18 years of age from 465 general practices in England. Mixed-effects logistic regression models were used to quantify the association between HRT or COCP use and all-cause mortality among women diagnosed with confirmed or suspected COVID-19 in unadjusted and adjusted models. RESULTS: There were 5,451 COVID-19 cases within the cohort. HRT was associated with a reduction in all-cause mortality in COVID-19 (adjusted OR 0.22, 95% CI 0.05 to 0.94). There were no reported events for all-cause mortality in women prescribed COCPs. This prevented further examination of the impact of COCP. CONCLUSIONS: We found that HRT prescription within 6 months of a recorded diagnosis of COVID-19 infection was associated with a reduction in all-cause mortality. Further work is needed in larger cohorts to examine the association of COCP in COVID-19, and to further investigate the hypothesis that oestrogens may contribute a protective effect against COVID-19 severity.

Applicability of the GAIA Maternal and Neonatal Outcome Case Definitions for the Evaluation of Adverse Events Following Vaccination in Pregnancy in High-income Countries.

BACKGROUND: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. METHODS: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. RESULTS: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. CONCLUSIONS: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.

Association between influenza vaccination and hospitalisation or all-cause mortality in people with COVID-19: a retrospective cohort study.

INTRODUCTION: Recent evidence suggests that influenza vaccination may offer protection against COVID-19 severity. Our aim was to quantify the association between influenza vaccination status and risk of hospitalisation or all-cause mortality in people diagnosed with COVID-19. METHODS: A retrospective cohort study using routinely collected health records from patients registered to a General Practitioner (GP) practice in South West England within the Electronic Care and Health Information Analytics database. The cohort included 6921 people with COVID-19 during the first wave of the pandemic (1 January-31 July 2020). Data on influenza vaccination, hospitalisation and all-cause mortality were ascertained through linked clinical and demographic records. We applied propensity score methods (stabilised inverse probability of treatment weight) to quantify the association between influenza vaccination status and COVID-19 outcomes (hospitalisation or all-cause mortality). RESULTS: 2613 (38%) participants received an influenza vaccination between 1 January 2019 and COVID-19 diagnosis. Receipt of influenza vaccination was associated with a significantly lower odds of hospitalisation or all-cause mortality (adjusted OR: 0.85, 95% CI 0.75 to 0.97, p=0.02), and 24% reduced odds of all-cause mortality (adjusted OR: 0.76, 95% CI 0.64 to 0.90). DISCUSSION: Influenza vaccination was associated with a 15%-24% lower odds of severe COVID-19 outcomes. The current UK influenza vaccination programme needs urgent expansion as an integral component of the ongoing response plans to the COVID-19 pandemic.

Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review.

OBJECTIVE: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease. DESIGN: Systematic review. DATA SOURCE: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science. STUDY SELECTION: Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. DATA EXTRACTION AND SYNTHESIS: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies. RESULTS: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2). CONCLUSIONS: There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.

Patients' views about screening for atrial fibrillation (AF): a qualitative study in primary care.

OBJECTIVES: There has been increased interest in screening for atrial fibrillation (AF) with commissioned pilot schemes, ongoing large clinical trials and the emergence of inexpensive consumer single-lead ECG devices that can be used to detect AF. This qualitative study aimed to explore patients' views and understanding of AF and AF screening to determine acceptability and inform future recommendations. SETTING: A single primary care practice in Hampshire, UK. PARTICIPANTS: 15 participants (11 female) were interviewed from primary care who had taken part in an AF screening trial. A semistructured interview guide was used flexibly to enable the interviewer to explore any relevant topics raised by the participants. Interviews were recorded, transcribed verbatim and analysed using inductive thematic analysis. RESULTS: Participants generally had an incomplete understanding of AF and conflated it with other heart problems or with raised blood pressure. With regards to potential drawbacks from screening, some participants considered anxiety and the cost of implementation, but none acknowledged potential harms associated with screening such as side effects of anticoagulation treatment or the risk of further investigations. The screening was generally well accepted, and participants were generally in favour of engaging with prolonged screening. CONCLUSIONS: Our study highlights that there may be poor understanding (of both the nature of AF and potential negatives of screening) among patients who have been screened for AF. Further work is required to determine if resources including decision aids can address this important knowledge gap and improve clinical informed consent for AF screening. TRIAL REGISTRATION NUMBER: ISRCTN 17495003.

Digital interventions for parents of acutely ill children and their treatment-seeking behaviour: a systematic review.

BACKGROUND: Consultations for self-limiting infections in children are increasing. It has been proposed that digital technology could be used to enable parents' decision making in terms of self-care and treatment seeking. AIM: To evaluate the evidence that digital interventions facilitate parents deciding whether to self-care or seek treatment for acute illnesses in children. DESIGN AND SETTING: Systematic review of studies undertaken worldwide. METHOD: Searches of MEDLINE and EMBASE were made to identify studies (of any design) published between database inception and January 2019 that assessed digital interventions for parents of children (from any healthcare setting) with acute illnesses. The primary outcome of interest was whether the use of digital interventions reduced the use of urgent care services. RESULTS: Three studies were included in the review. They assessed two apps and one website: Children's On-Call - a US advice-only app; Should I See a Doctor? - a Dutch self-triage app for any acute illness; and Strategy for Off-Site Rapid Triage (SORT) for Kids - a US self-triage website for influenza-like illness. None of the studies involved parents during intervention development and it was shown that many parents did not find the two apps easy to use. The sensitivity of self-triage interventions was 84% for Should I See a Doctor? compared with nurse triage, and 93.3% for SORT for Kids compared with the need for emergency-department intervention; however, both had lower specificity (74% and 13%, respectively). None of the interventions demonstrated reduced use of urgent-care services. CONCLUSION: There is little evidence to support the use of digital interventions to help parent and/or carers looking after children with acute illness. Future research should involve parents during intervention development, and adequately powered trials are needed to assess the impact of such interventions on health services and the identification of children who are seriously ill.

Embedding the delivery of antenatal vaccination within routine antenatal care: a key opportunity to improve uptake.

Improving the uptake of vaccination in pregnancy has been highlighted as a priority by the World Health Organisation, yet establishing the optimal location for delivery of the antenatal vaccination program remains a topic of debate internationally. In many countries, antenatal vaccines are usually delivered within Primary Care (under the lead of general practitioners [GPs] or family physicians), yet this often presents a logistic barrier to accessing vaccination, and increasing evidence demonstrates that embedding vaccination within routine antenatal care visits may significantly improve uptake. In this commentary, we discuss recent evidence to support this approach, including anonymous feedback from patients and staff at our own institution, in which a dedicated midwife-led vaccine clinic has recently been set up. Furthermore, we highlight a number of individual and institution-level barriers which would need addressing before this approach can be routinely adopted, and suggest targets for future education and research.

Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vaccination Against Respiratory Syncytial Virus: A Multicenter Questionnaire Study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a common cause of infant hospitalization and mortality. With multiple vaccines in development, we aimed to determine: (1) the awareness of RSV among pregnant women and healthcare professionals (HCPs), and (2) attitudes toward clinical trials and routine implementation of antenatal RSV vaccination. METHODS: Separate questionnaires for pregnant women and HCPs were distributed within 4 hospitals in South England (July 2017-January 2018). RESULTS: Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unknown) were analyzed. Most pregnant women (88%) and midwives (66%) had no/very little awareness of RSV, unlike obstetricians (14%). Among pregnant women, 29% and 75% would likely accept RSV vaccination as part of a trial, or if routinely recommended, respectively. Younger women (16-24 years), those of 21-30 weeks' gestation, and with experience of RSV were significantly more likely to participate in trials [odds ratio (OR): 1.42 (1.72-9.86); OR: 2.29 (1.22-4.31); OR: 9.07 (1.62-50.86), respectively]. White-British women and those of 21-30 weeks' gestation were more likely to accept routinely recommended vaccination [OR: 2.16 (1.07-4.13); OR: 2.10 (1.07-4.13)]. Obstetricians were more likely than midwives to support clinical trials [92% vs. 68%, OR: 2.50 (1.01-6.16)] and routine RSV vaccination [89% vs. 79%, OR: 4.08 (1.53-9.81)], as were those with prior knowledge of RSV, and who deemed it serious. CONCLUSIONS: RSV awareness is low among pregnant women and midwives. Education will be required to support successful implementation of routine antenatal vaccination. Research is needed to understand reasons for vaccine hesitancy among pregnant women and HCPs, particularly midwives.

Determinants of Influenza and Pertussis Vaccination Uptake in Pregnancy: A Multicenter Questionnaire Study of Pregnant Women and Healthcare Professionals.

INTRODUCTION: Uptake rates of antenatal vaccination remain suboptimal. Our aims were to determine (1) the acceptability of routine vaccination among pregnant women, (2) the confidence of maternity healthcare professionals (HCPs) discussing vaccination and (3) HCP opinion regarding the optimum healthcare site for vaccine administration. METHODS: Separate questionnaires for pregnant women and HCPs were distributed within 4 national health service (NHS) trusts in South England (July 2017 to January 2018). RESULTS: Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unidentified) were analyzed. Previous/intended uptake of influenza and pertussis vaccination was 78% and 92%, respectively. The commonest reason for declining vaccination was feared side effects for their child. White British women (79%) were significantly more accepting of influenza [85% vs. 61%; odds ratio (OR) 3.25; 95% confidence interval [CI], 1.67-6.32] and pertussis vaccination (96% vs. 83%; OR 4.83; 95% CI: 1.77-13.19) compared with nonwhite British women. Among HCPs, 25% were slightly or not at all confident discussing vaccination. Obstetricians felt significantly more confident discussing pertussis vaccination than midwives (68% vs. 55% were very/moderately confident; OR 2.05; 95% CI: 1.02-4.12). Among HCPs, 53%, 25% and 16% thought vaccines should be administered in primary care (general practice), community midwifery and in hospital, respectively. CONCLUSION: Misconceptions exist regarding safety/efficacy of antenatal vaccination, and framing information towards the child's safety may increase uptake. Education of HCPs is essential, and vaccine promotion should be incorporated into routine antenatal care, with an emphasis on women from ethnic minorities. Administration of vaccines in primary care presents logistical barriers; however, support for alternative sites appears low among HCPs.

Influenza and pertussis vaccination in pregnancy: Portrayal in online media articles and perceptions of pregnant women and healthcare professionals.

INTRODUCTION: Online media may influence women's decision to undergo vaccination during pregnancy. The aims of this mixed-methods study were to: (1) examine the portrayal of maternal vaccination in online media and (2) establish the perceived target of vaccine protection as viewed by pregnant women and maternity healthcare professionals (HCPs). METHODS: Online media articles on maternal vaccination (published July-December 2012 or November 2015-April 2016) were identified through the London School of Hygiene & Tropical Medicine's Vaccine Confidence Database and thematically analysed. Questionnaires for pregnant women and HCPs were distributed within four English hospitals (July 2017-January 2018). RESULTS: Of 203 articles identified, 60% related to pertussis vaccination, 33% to influenza and 6% both. The majority positively portrayed vaccination in pregnancy (97%), but inaccurate, negative articles persist which criticize pertussis vaccination's safety and efficacy. Positively-worded articles about pertussis tended to focus on infant protection and highlight examples of recent cases, whereas positively-worded articles about influenza focused on maternal protection. These themes were reflected in questionnaire responses from 314 pregnant women and 204 HCPs, who perceived pertussis vaccination as protecting the baby, and influenza vaccination as protecting the mother, or mother and baby equally. A minority of the pregnant women surveyed intended to decline influenza (22%) or pertussis (8%) vaccination. CONCLUSIONS: The majority of online articles support pertussis and influenza vaccination during pregnancy. The portrayal of pertussis vaccination as primarily benefiting the child, using real-examples, may influence its higher uptake compared with influenza. This approach should be considered by HCPs when recommending vaccination. HCPs should be prepared to provide advice to women hesitant about vaccination, including addressing any negative media, and consider educational strategies to counteract inaccurate information. Future studies should directly assess the influence of media on vaccine decision-making and establish which media platforms are typically used by pregnant women to gather information.