Acceptability of interventional materials: public participation in public health interventional research / Acceptabilité d'une intervention : exemple de participation des publics en recherche interventionnelle en santé publique

Introduction: The uptake rate of colorectal cancer screening remains insufficient in France and decreases as the level of deprivation increases. Participants' health literacy appears to be an important determinant of screening uptake. Aim of the study: The aim of this study, nested in our multicenter-randomized controlled trial, was to present the development and acceptability of interventional material (training and a pictorial brochure) for general practitioners and healthcare users in disadvantaged geographical areas using a participatory involvement approach. Methods: The development of the brochure and the training was carried out in three stages, two for the development, usability, and acceptability testing and a third for its evaluation with the target audience. We used a qualitative approach based on focus groups and cognitive interviews. The qualitative analysis was based on Morville's "Honeycomb" conceptual model and the COREQ checklist. Results: The development and test of the acceptability of the material enabled us to adjust the content of the training by proposing examples that were more rooted in professional reality, and to produce a brochure that was easy to read, understand, acceptable and adapted to the intervention's targeted audience. Conclusions: This experience illustrates in a concrete way the feasibility of public participation and its value in the context of interventional research, and more generally in the creation of interventional material.

Introduction: Le taux de participation au dépistage du cancer colorectal reste insuffisant en France et diminue à mesure que le niveau de précarité augmente. La littératie en santé est un déterminant important du recours au dépistage. But de l'étude: Cette étude, nichée dans notre essai randomisé multicentrique, a pour but de présenter la procédure d'élaboration (procédé itératif de test d'utilisabilité et d'acceptabilité) et de vérification de l'acceptabilité de l'intervention (formation et brochure imagée) ciblant les médecins généralistes et usagers du soin dans des zones géographiques défavorisées, selon une approche participative. Méthodes: Le développement de la brochure et de la formation a été réalisé en trois étapes : deux pour l'élaboration et tests itératifs d'utilisabilité et acceptabilité et une troisième pour vérifier l'acceptabilité auprès des publics cibles. Nous avons utilisé une approche qualitative par focus group et entretiens individuels cognitifs dont l'analyse repose sur le « nid d'abeille ¼ de Morville et la grille COREQ. Résultats: Le développement itératif et la vérification de l'acceptabilité du matériel nous ont permis, d'une part, de réaliser des ajustements quant au contenu de la formation, en proposant des exemples plus ancrés dans la réalité professionnelle et, d'autre part, de produire une brochure imagée facile à lire et à comprendre, acceptable et adaptée au public ciblé par l'intervention. Conclusions: Cette expérience illustre, de manière concrète, la faisabilité de cette modalité de participation des publics concernés et son intérêt dans le cadre de la recherche interventionnelle et, plus généralement, dans le matériel interventionnel.

The level of education is associated with an anxiety-depressive state among men and women - findings from France during the first quarter of the COVID-19 pandemic.

CONTEXT: It is widely recognised that the COVID-19 pandemic has negatively impacted individuals' mental health. However, little emphasis has been put on the possible influence of socio-economic factors in the relationship. In the context of the COVID-19 pandemic, our objectives were (i) to assess the relationship between education level and mental health in French adults, and (ii) to study the influence of the economic, social, health and the COVID-19-related factors in men and women respectively. METHOD: Data are from 32,581 individuals representative of the French population who responded to the weekly survey "Baromètre COVID-19" between April 7th and May 31st 2020. Education level was self-reported (university degree, high school qualification, vocational certificate/qualification, no diploma). Anxiety-depressive state was derived from four items related to the frequency of occurrence of depressive and anxiety symptoms, and summarized in an overall validated anxiety-depressive score. Multivariate linear regression analyses were carried out with nested adjustments of variables related to economic, social, health and COVID-19 contexts to assess the relationship between education and anxiety-depressive state. RESULTS: In total, 45% of individuals reported symptoms of anxiety-depressive state (53% in women versus 36% in men). Among men, those with a vocational certificate/qualification and those with no diploma had a greater risk of having a higher anxiety-depressive state compared to those with a university degree (ßVocational certificate/qualification = 0.16 [0.04; 0.27]; ßNo diploma = 0.75 [0.43; 1.07]) while among women, the risk of anxiety-depressive state increased as education level decreased (ßBaccalaureate = 0.37 [0.25; 0.49]; ßVocational certificate/qualification = 0.41 [0.28; 0.54]; ßNo diploma = 0.8 [0.49; 1.12]). For both men and women, economic, health, and COVID-19 factors partly attenuate these associations while social factors marginally modified the relationship. After accounting for confounders and intermediate variables, the absence of a diploma remained associated with anxiety-depressive state among men, while the whole educational gradient of anxiety-depressive state persisted among women. CONCLUSION: In France, at the end of the first wave of COVID-19, individuals with a lower level of education had a higher risk of anxiety-depressive state. This association was more pronounced for women, highlighting a process of social inequality in health possibly related to gender. This should be considered in future prevention and public health interventions.

Enhancing DNA barcode reference libraries by harvesting terrestrial arthropods at the Smithsonian's National Museum of Natural History.

The use of DNA barcoding has revolutionised biodiversity science, but its application depends on the existence of comprehensive and reliable reference libraries. For many poorly known taxa, such reference sequences are missing even at higher-level taxonomic scales. We harvested the collections of the Smithsonian's National Museum of Natural History (USNM) to generate DNA barcoding sequences for genera of terrestrial arthropods previously not recorded in one or more major public sequence databases. Our workflow used a mix of Sanger and Next-Generation Sequencing (NGS) approaches to maximise sequence recovery while ensuring affordable cost. In total, COI sequences were obtained for 5,686 specimens belonging to 3,737 determined species in 3,886 genera and 205 families distributed in 137 countries. Success rates varied widely according to collection data and focal taxon. NGS helped recover sequences of specimens that failed a previous run of Sanger sequencing. Success rates and the optimal balance between Sanger and NGS are the most important drivers to maximise output and minimise cost in future projects. The corresponding sequence and taxonomic data can be accessed through the Barcode of Life Data System, GenBank, the Global Biodiversity Information Facility, the Global Genome Biodiversity Network Data Portal and the NMNH data portal.

A workflow for expanding DNA barcode reference libraries through 'museum harvesting' of natural history collections.

Natural history collections are the physical repositories of our knowledge on species, the entities of biodiversity. Making this knowledge accessible to society - through, for example, digitisation or the construction of a validated, global DNA barcode library - is of crucial importance. To this end, we developed and streamlined a workflow for 'museum harvesting' of authoritatively identified Diptera specimens from the Smithsonian Institution's National Museum of Natural History. Our detailed workflow includes both on-site and off-site processing through specimen selection, labelling, imaging, tissue sampling, databasing and DNA barcoding. This approach was tested by harvesting and DNA barcoding 941 voucher specimens, representing 32 families, 819 genera and 695 identified species collected from 100 countries. We recovered 867 sequences (> 0 base pairs) with a sequencing success of 88.8% (727 of 819 sequenced genera gained a barcode > 300 base pairs). While Sanger-based methods were more effective for recently-collected specimens, the methods employing next-generation sequencing recovered barcodes for specimens over a century old. The utility of the newly-generated reference barcodes is demonstrated by the subsequent taxonomic assignment of nearly 5000 specimen records in the Barcode of Life Data Systems.

Prognostic value of upper respiratory tract microbes in children presenting to primary care with respiratory infections: A prospective cohort study.

BACKGROUND: The association between upper respiratory tract microbial positivity and illness prognosis in children is unclear. This impedes clinical decision-making and means the utility of upper respiratory tract microbial point-of-care tests remains unknown. We investigated for relationships between pharyngeal microbes and symptom severity in children with suspected respiratory tract infection (RTI). METHODS: Baseline characteristics and pharyngeal swabs were collected from 2,296 children presenting to 58 general practices in Bristol, UK with acute cough and suspected RTI between 2011-2013. Post-consultation, parents recorded the severity of six RTI symptoms on a 0-6 scale daily for ≤28 days. We used multivariable hurdle regression, adjusting for clinical characteristics, antibiotics and other microbes, to investigate associations between respiratory microbes and mean symptom severity on days 2-4 post-presentation. RESULTS: Overall, 1,317 (57%) children with complete baseline, microbiological and symptom data were included. Baseline characteristics were similar in included participants and those lacking microbiological data. At least one virus was detected in 869 (66%) children, and at least one bacterium in 783 (60%). Compared to children with no virus detected (mean symptom severity score 1.52), adjusted mean symptom severity was 0.26 points higher in those testing positive for at least one virus (95% CI 0.15 to 0.38, p<0.001); and was also higher in those with detected Influenza B (0.44, 0.15 to 0.72, p = 0.003); RSV (0.41, 0.20 to 0.60, p<0.001); and Influenza A (0.25, -0.01 to 0.51, p = 0.059). Children positive for Enterovirus had a lower adjusted mean symptom severity (-0.24, -0.43 to -0.05, p = 0.013). Children with detected Bordetella pertussis (0.40, 0.00 to 0.79, p = 0.049) and those with detected Moraxella catarrhalis (-0.76, -1.06 to -0.45, p<0.001) respectively had higher and lower mean symptom severity compared to children without these bacteria. CONCLUSIONS: There is a potential role for upper respiratory tract microbiological point-of-care tests in determining the prognosis of childhood RTIs.

Impact of a health literacy intervention combining general practitioner training and a consumer facing intervention to improve colorectal cancer screening in underserved areas: protocol for a multicentric cluster randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer burden worldwide. In France, it is the second most common cause of cancer death after lung cancer. Systematic uptake of CRC screening can improve survival rates. However, people with limited health literacy (HL) and lower socioeconomic position rarely participate. Our aim is to assess the impact of an intervention combining HL and CRC screening training for general practitioners (GPs) with a pictorial brochure and video targeting eligible patients, to increase CRC screening and other secondary outcomes, after 1 year, in several underserved geographic areas in France. METHODS: We will use a two-arm multicentric randomized controlled cluster trial with 32 GPs primarily serving underserved populations across four regions in France with 1024 patients recruited. GPs practicing in underserved areas (identified using the European Deprivation Index) will be block-randomized to: 1) a combined intervention (HL and CRC training + brochure and video for eligible patients), or 2) usual care. Patients will be included if they are between 50 and 74 years old, eligible for CRC screening, and present to recruited GPs. The primary outcome is CRC screening uptake after 1 year. Secondary outcomes include increasing knowledge and patient activation. After trial recruitment, we will conduct semi-structured interviews with up to 24 GPs (up to 8 in each region) and up to 48 patients (6 to 12 per region) based on data saturation. We will explore strategies that promote the intervention's sustained use and rapid implementation using Normalization Process Theory. We will follow a community-based participatory research approach throughout the trial. For the analyses, we will adopt a regression framework for all quantitative data. We will also use exploratory mediation analyses. We will analyze all qualitative data using a framework analysis guided by Normalization Process Theory. DISCUSSION: Limited HL and its impact on the general population is a growing public health and policy challenge worldwide. It has received limited attention in France. A combined HL intervention could reduce disparities in CRC screening, increase screening rates among the most vulnerable populations, and increase knowledge and activation (beneficial in the context of repeated screening). TRIAL REGISTRATION: Registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: 2020-A01687-32 . Date of registration: 17th November 2020.

Drug Use in Street Sex worKers (DUSSK) study: results of a mixed methods feasibility study of a complex intervention to reduce illicit drug use in drug dependent female sex workers.

OBJECTIVES: The majority of female street-based sex workers (SSWs) are dependent on illicit drugs and sell sex to fund their drug use. They typically face multiple traumatic experiences, starting at a young age, which continue through sex work involvement. Their trauma-related symptoms tend to increase when drug use is reduced, hindering sustained reduction. Providing specialist trauma care to address post-traumatic stress disorder (PTSD) alongside drug treatment may therefore improve treatment outcomes. Aims to (1) evaluate recruitment and retention of participants; (2) examine intervention experiences and acceptability; and (3) explore intervention costs using a mixed methods feasibility study. SETTING: Female SSW charity premises in a large UK inner city. PARTICIPANTS: Females aged 18 years or older, who have sold sex on the street and used heroin and/or crack cocaine at least once a week in the last calendar month. INTERVENTION: Female SSW-only drug treatment groups in a female SSW-only setting delivered by female staff. Targeted PTSD screening then treatment of positive diagnoses with eye movement desensitisation and reprocessing (EMDR) therapy by female staff from a specialist National Health Service trauma service. RESULTS: (1) Of 125 contacts, 11 met inclusion criteria and provided informed consent, 4 reached the intervention final stage, (2) service providers said working in collaboration with other services was valuable, the intervention was worthwhile and had a positive influence on participants. Participants viewed recruitment as acceptable and experienced the intervention positively. The unsettled nature of participant's lives was a key attendance barrier. (3) The total cost of the intervention was £11 710, with staff costs dominating. CONCLUSIONS: Recruitment and retention rates reflected study inclusion criteria targeting women with the most complex needs. Two participants received EMDR demonstrating that the three agencies working together was feasible. Staff heavy costs highlight the importance of supporting participant attendance to minimise per participant costs in a future trial.

Association between National Early Warning Scores in primary care and clinical outcomes: an observational study in UK primary and secondary care.

BACKGROUND: NHS England has mandated use of the National Early Warning Score (NEWS), more recently NEWS2, in acute settings, and suggested its use in primary care. However, there is reluctance from GPs to adopt NEWS/NEWS2. AIM: To assess whether NEWS calculated at the point of GP referral into hospital is associated with outcomes in secondary care. DESIGN AND SETTING: An observational study using routinely collected data from primary and secondary care. METHOD: NEWS values were prospectively collected for 13 047 GP referrals into acute care between July 2017 and December 2018. NEWS values were examined and multivariate linear and logistic regression used to assess associations with process measures and clinical outcomes. RESULTS: Higher NEWS values were associated with faster conveyance for patients travelling by ambulance, for example, median 94 minutes (interquartile range [IQR] 69-139) for NEWS ≥7; median 132 minutes, (IQR 84-236) for NEWS = 0 to 2); faster time from hospital arrival to medical review (54 minutes [IQR 25-114] for NEWS ≥7; 78 minutes [IQR 34-158] for NEWS = 0 to 2); as well as increased length of stay (5 days [IQR 2-11] versus 1 day [IQR 0-5]); intensive care unit admissions (2.0% versus 0.5%); sepsis diagnosis (11.7% versus 2.5%); and mortality, for example, 30-day mortality 12.0% versus 4.1% for NEWS ≥7 versus NEWS = 0 to 2, respectively. On average, for patients referred without a NEWS value (NEWS = NR), most clinical outcomes were comparable with patients with NEWS = 3 to 4, but ambulance conveyance time and time to medical review were comparable with patients with NEWS = 0 to 2. CONCLUSION: This study has demonstrated that higher NEWS values calculated at GP referral into hospital are associated with a faster medical review and poorer clinical outcomes.

Correction to: Rapid development of HIV elite control in a patient with acute infection.

After publication of the original article [1], we were notified in Table 1 a column should be removed.

Rapid development of HIV elite control in a patient with acute infection.

BACKGROUND: Elite controllers (EC), a small subset of the HIV-positive population (< 1%), suppress HIV viremia below the limit of quantification of clinical viral load assays in the absence of antiretroviral therapy (ART). However, there is a paucity of longitudinal data detailing the viral and immune dynamics or HIV reservoir seeding during acute infection in individuals that go on to become Elite Controllers. CASE PRESENTATION: In this report, we describe a case of a 42 year old woman diagnosed during acute infection who rapidly and permanently suppressed her viremia in the absence of antiretroviral therapy (ART). Rapid antibody/antigen testing was either negative or equivocal during acute infection, despite subsequent viral load testing at that time point with 71,550 plasma HIV RNA copies/mL, making initial diagnosis challenging. The patient subsequently developed detectable anti-HIV antibodies and an increase in HIV-specific CD8+ T cell responses to overlapping subtype C HIV gag peptide; very low-level plasma viremia (0.84 RNA copies/mL) was detected by an ultrasensitive assay 2 years following infection. Subsequently, she was started on ART for multifocal furunculosis despite continued suppression of virus and stable CD4+ T cell counts. Following ART initiation, HIV specific antibody levels and CD8+ T cell responses increased, but no HIV DNA or RNA was able to be isolated from large numbers of peripheral blood CD4+ T cells. CONCLUSION: This case provides important information regarding the establishment of elite HIV control during acute infection and also demonstrates an increase in HIV-specific immune responses following ART despite undetectable peripheral blood cellular measures of HIV persistence. This case also highlights the challenges in diagnosing acute HIV infection without the use of viral load testing in this rare elite controller phenotype.

Understanding the influence of parent-clinician communication on antibiotic prescribing for children with respiratory tract infections in primary care: a qualitative observational study using a conversation analysis approach.

BACKGROUND: Acute respiratory tract infections (RTI) in children are a common reason for antibiotic prescribing. Clinicians' prescribing decisions are influenced by perceived parental expectations for antibiotics, however there is evidence that parents actually prefer to avoid antibiotics. This study aimed to investigate the influence of parent-clinician communication on antibiotic prescribing for RTI in children in England. METHODS: A mixed methods analysis of videoed primary care consultations for children (under 12 years) with acute cough and RTI. Consultations were video-recorded in six general practices in southern England, selected for socio-economic diversity. 56 recordings were transcribed in detail and a subset of recordings and transcripts used to develop a comprehensive interaction-based coding scheme. The scheme was used to examine communication practices between parents and clinicians and how these related to antibiotic or non-antibiotic treatment strategies. RESULTS: Parents' communication rarely implied an expectation for antibiotics, some explicitly offering a possible viral diagnosis. Clinicians mostly gave, or implied, a viral diagnosis and mainly recommended non-antibiotic treatment strategies. In the minority of cases where parents' communication behaviours implied they may be seeking antibiotic treatment, antibiotics were not usually prescribed. Where clinicians did prescribe antibiotics, they voiced concern about symptoms or signs, including chest pain, discoloured phlegm, prolonged fever, abnormal chest sounds, or pink /bulging ear drums. CONCLUSIONS: We found little evidence of a relationship between parents' communication behaviours and antibiotic prescribing. Rather, where antibiotics were prescribed, this was associated with clinicians' expressed concerns regarding symptoms and signs.

Parental and clinician agreement of illness severity in children with RTIs: secondary analysis of data from a prospective cohort study.

BACKGROUND: Severity assessments of respiratory tract infection (RTI) in children are known to differ between parents and clinicians, but determinants of perceived severity are unknown. AIM: To investigate the (dis)agreement between, and compare the determinants of, parent and clinician severity scores. DESIGN AND SETTING: Secondary analysis of data from a prospective cohort study of 8394 children presenting to primary care with acute (≤28 days) cough and RTI. METHOD: Data on sociodemographic factors, parent-reported symptoms, clinician-reported findings, and severity assessments were used. Kappa (κ)-statistics were used to investigate (dis) agreement, whereas multivariable logistic regression was used to identify the factors associated with illness severity. RESULTS: Parents reported higher illness severity (mean 5.2 [standard deviation (SD) 1.8], median 5 [interquartile range (IQR) 4-7]), than clinicians (mean 3.1 [SD 1.7], median 3 [IQR 2-4], P<0.0001). There was low positive correlation between these scores (+0.43) and poor inter-rater agreement between parents and clinicians (κ 0.049). The number of clinical signs was highly correlated with clinician scores (+0.71). Parent-reported symptoms (in the previous 24 hours) that were independently associated with higher illness severity scores, in order of importance, were: severe fever, severe cough, rapid breathing, severe reduced eating, moderate-to-severe reduced fluid intake, severe disturbed sleep, and change in cry. Three of these symptoms (severe fever, rapid breathing, and change in cry) along with inter/subcostal recession, crackles/crepitations, nasal flaring, wheeze, and drowsiness/irritability were associated with higher clinician scores. CONCLUSION: Clinicians and parents use different factors and make different judgements about the severity of children's RTI. Improved understanding of the factors that concern parents could improve parent-clinician communication and consultation outcomes.

Distributions of the National Early Warning Score (NEWS) across a healthcare system following a large-scale roll-out.

BACKGROUND: Early warning scores (EWS) were developed in acute hospital settings to improve recognition and response to patient deterioration. In 2012, the UK Royal College of Physicians developed the National Early Warning Score (NEWS) to standardise EWS across the NHS. Its use was also recommended outside acute hospital settings; however, there is limited information about NEWS in these settings. From March 2015, NEWS was implemented across the healthcare system in the West of England, with the aim that NEWS would be calculated for all patients prior to referral into acute care. AIM: To describe the distribution and use of NEWS in out-of-hospital settings for patients with acute illness or long-term conditions, following system wide implementation. METHOD: Anonymised data were obtained from 115 030 emergency department (ED) attendances, 1 137 734 ambulance electronic records, 31 063 community attendances and 15 160 general practitioner (GP) referrals into secondary care, in the West of England. Descriptive statistics are presented. RESULTS: Most attendance records had NEWS=0-2: 80% in ED, 67% of ambulance attendances and 72% in the community. In contrast, only 8%, 18% and 11% of attendances had NEWS ≥5 (the trigger for escalation of care in-hospital), respectively. Referrals by a GP had higher NEWS on average (46% NEWS=0-2 and 30% NEWS ≥5). By April 2016, the use of NEWS was reasonably stable in ED, ambulance and community populations, and still increasing for GP referrals. CONCLUSIONS: NEWS ≥5 occurred in less than 20% of ED, ambulance and community populations studied and 30% of GP referrals. This suggests that in most out-of-hospital settings studied, high scores are reasonably uncommon.

Therapeutic drug monitoring of darunavir/ritonavir in pregnancy.

BACKGROUND: Physiological changes during pregnancy can have a significant impact on antiretroviral pharmacokinetics (PK), which may result in reduced drug efficacy. Here we describe the PK of darunavir/ritonavir (DRV/r) 800/100 once daily in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM) as well as transplacental passage of DRV by measuring and comparing cord blood and maternal blood samples at delivery. METHODS: Pregnant HIV-positive women received DRV/r as part of routine pre-natal care. Demographic and clinical data were collected. DRV plasma concentrations [DRV] were determined in the first (T1), second (T2) and third (T3) trimester and at postpartum (PP). The target concentration was 550 ng/ml. Where possible, paired maternal and cord blood samples were taken at delivery. RESULTS: A total of 33 women were enrolled. Samples were taken 14-20 h post-dose and measured concentrations were extrapolated to 24 h post-dose. At the time nearest to delivery, all but four had undetectable plasma viral loads (pVL). [DRV] were determined in 1 (T1); 14 (T2); 32 (T3) and 29 (PP). 1 sample was <550 ng/ml at T2, 6 at T3 and 3 at PP. [DRV] were significantly lower at T2/T3 relative to PP. CONCLUSIONS: [DRV] in T2 and T3 were 36-55% when compared with PP. However, DRV PK in pregnancy were not associated with a lack of virological suppression at delivery as of the 33 patients enrolled in this study, 31 had no HIV transmission from mother to child. Data regarding two candidates were not available as they delivered in a separate health-care facility.

Drug use in street sex workers (DUSSK) study protocol: a feasibility and acceptability study of a complex intervention to reduce illicit drug use in drug-dependent female street sex workers.

INTRODUCTION: Poor health of sex workers continues to be a source of international concern. Sex work is frequently linked with problematic drug use and drug-dependent sex workers typically work on the street, experiencing the greatest risks to health compared with the general population. Street sex workers (SSWs) are much more likely to have experienced incidences of physical and sexual assault, increasing their risk of developing post-traumatic stress disorder (PTSD). We have developed a novel complex intervention designed to reduce illicit drug use in drug-dependent female SSWs which involves: female SSW drug treatment groups (provided by a specialist charity) in a female SSW setting (female sex worker charity premises) provided by female-only staff, PTSD care with eye movement desensitisation and reprocessing (EMDR) therapy provided by female staff from National Health Service (NHS) mental health services. METHODS AND ANALYSIS: A mixed methods study investigating the feasibility and acceptability of this intervention to inform the design of a future randomised controlled trial. The study aims to recruit up to 30 participants from November 2017 to March 2018 at a single site, with the intervention being delivered until December 2018. It will gather quantitative data using questionnaires and group attendance. Drug treatment group observations and in-depth interviews undertaken with up to 20 service users and 15 service providers to examine experiences and acceptability of the intervention. Study feasibility will be assessed by evaluating the recruitment and retention of participants to the intervention; the feasibility of NHS and third sector organisations working closely to coordinate care for a SSW population; the potential for specialist NHS mental health services to screen and provide EMDR therapy for drug-dependent SSWs and potential costs of implementing the intervention. ETHICS AND DISSEMINATION: This study was approved by South West-Frenchay Research Ethics Committee (REC reference: 17/SW/0033; IRAS ID: 220631) and the Health Research Authority (HRA). Findings will be disseminated through research conferences and peer-reviewed journals.

Impact of antibiotics for children presenting to general practice with cough on adverse outcomes: secondary analysis from a multicentre prospective cohort study.

BACKGROUND: Clinicians commonly prescribe antibiotics to prevent major adverse outcomes in children presenting in primary care with cough and respiratory symptoms, despite limited meaningful evidence of impact on these outcomes. AIM: To estimate the effect of children's antibiotic prescribing on adverse outcomes within 30 days of initial consultation. DESIGN AND SETTING: Secondary analysis of 8320 children in a multicentre prospective cohort study, aged 3 months to <16 years, presenting in primary care across England with acute cough and other respiratory symptoms. METHOD: Baseline clinical characteristics and antibiotic prescribing data were collected, and generalised linear models were used to estimate the effect of antibiotic prescribing on adverse outcomes within 30 days (subsequent hospitalisations and reconsultation for deterioration), controlling for clustering and clinicians' propensity to prescribe antibiotics. RESULTS: Sixty-five (0.8%) children were hospitalised and 350 (4%) reconsulted for deterioration. Clinicians prescribed immediate and delayed antibiotics to 2313 (28%) and 771 (9%), respectively. Compared with no antibiotics, there was no clear evidence that antibiotics reduced hospitalisations (immediate antibiotic risk ratio [RR] 0.83, 95% confidence interval [CI] = 0.47 to 1.45; delayed RR 0.70, 95% CI = 0.26 to 1.90, overall P = 0.44). There was evidence that delayed (rather than immediate) antibiotics reduced reconsultations for deterioration (immediate RR 0.82, 95% CI = 0.65 to 1.07; delayed RR 0.55, 95% CI = 0.34 to 0.88, overall P = 0.024). CONCLUSION: Most children presenting with acute cough and respiratory symptoms in primary care are not at risk of hospitalisation, and antibiotics may not reduce the risk. If an antibiotic is considered, a delayed antibiotic prescription may be preferable as it is likely to reduce reconsultation for deterioration.

Post-consultation illness trajectories in children with acute cough and respiratory tract infection: prospective cohort study.

Background: Little is known about respiratory tract infection (RTI) severity in children following consultation. Objectives: To investigate post-consultation symptom trajectories in children with acute cough and RTI and whether baseline characteristics predict trajectory group. Methods: Prospective cohort study of 2296 children (3 months-16 years) whose parents were invited to report cough severity and duration using a 7-point Likert scale. Longitudinal latent class analysis (LLCA) was used to identify post-consultation symptom trajectories in the first 15 days, and multinomial models to predict class membership. Results: Complete data were available for 1408 children (61%). The best LLCA model identified five post-consultation symptom trajectory groups: 'very rapid recovery' (28.5%), 'rapid recovery' (37.7%), 'intermediate recovery' (18.2%), 'persistent symptoms' (9.5%) and 'initial deterioration with persistent symptoms' (6.0%). Compared with very rapid recovery, parent-reported severe cough in the 24 hours prior to consultation increased the likelihood of rapid recovery (OR 1.79 [95% CI 1.23, 2.60]), intermediate recovery (OR 2.13 [1.38, 3.30] and initial deterioration with persistent symptoms (OR 2.29 [1.26, 4.16]). Initial deterioration was also associated with 'severe barking cough' (OR 3.64 [1.50, 8.82]), 'severely reduced energy in the 24 hours prior to consultation' (OR 3.80 [1.62, 8.87] and higher parent-assessed illness severity at consultation (OR 2.21 [1.17, 4.18]). Conclusion: We identified five distinct symptom trajectory groups showing the majority of children improved post-consultation, with only one group experiencing illness deterioration. The few characteristics associated with group membership did not fall into a pattern that seemed clinically useful.

Management of Patients With High Baseline Hip Fracture Risk by FRAX Reduces Hip Fractures-A Post Hoc Analysis of the SCOOP Study.

The Screening for Osteoporosis in Older Women for the Prevention of Fracture (SCOOP) study was a community-based screening intervention in women aged 70 to 85 years in the United Kingdom. In the screening arm, licensed osteoporosis treatments were recommended in women identified to be at high risk of hip fracture using the FRAX risk assessment tool (including bone mineral density measurement). In the control arm, standard care was provided. Screening led to a 28% reduction in hip fractures over 5 years. In this planned post hoc analysis, we wished to examine for interactions between screening effectiveness on fracture outcome (any, osteoporotic, and hip fractures) on the one hand and baseline FRAX 10-year probability of hip fracture on the other. All analyses were conducted on an intention-to-treat basis, based on the group to which women were randomized, irrespective of whether screening was completed. Of 12,483 eligible participants, 6233 women were randomized to screening, with treatment recommended in 898 (14.4%). No evidence of an effect or interaction was observed for the outcomes of any fracture or osteoporotic fracture. In the screening arm, 54 fewer hip fractures were observed than in the control arm (164 versus 218, 2.6% versus 3.5%), and commensurate with treatment being targeted to those at highest hip fracture risk, the effect on hip fracture increased with baseline FRAX hip fracture probability (p = 0.021 for interaction); for example, at the 10th percentile of baseline FRAX hip probability (2.6%), there was no evidence that hip fractures were reduced (hazard ratio [HR] = 0.93; 95% confidence interval [CI] 0.71 to 1.23), but at the 90th percentile (16.6%), there was a 33% reduction (HR = 0.67; 95% CI 0.53 to 0.84). Prior fracture and parental history of hip fracture positively influenced screening effectiveness on hip fracture risk. We conclude that women at high risk of hip fracture based on FRAX probability are responsive to appropriate osteoporosis management. © 2018 American Society for Bone and Mineral Research.

What gives rise to clinician gut feeling, its influence on management decisions and its prognostic value for children with RTI in primary care: a prospective cohort study.

BACKGROUND: The objectives were to identify 1) the clinician and child characteristics associated with; 2) clinical management decisions following from, and; 3) the prognostic value of; a clinician's 'gut feeling something is wrong' for children presenting to primary care with acute cough and respiratory tract infection (RTI). METHODS: Multicentre prospective cohort study where 518 primary care clinicians across 244 general practices in England assessed 8394 children aged ≥3 months and < 16 years for acute cough and RTI. The main outcome measures were: Self-reported clinician 'gut feeling'; clinician management decisions (antibiotic prescribing, referral for acute admission); and child's prognosis (reconsultation with evidence of illness deterioration, hospital admission in the 30 days following recruitment). RESULTS: Clinician years since qualification, parent reported symptoms (illness severity score ≥ 7/10, severe fever < 24 h, low energy, shortness of breath) and clinical examination findings (crackles/ crepitations on chest auscultation, recession, pallor, bronchial breathing, wheeze, temperature ≥ 37.8 °C, tachypnoea and inflamed pharynx) independently contributed towards a clinician 'gut feeling that something was wrong'. 'Gut feeling' was independently associated with increased antibiotic prescribing and referral for secondary care assessment. After adjustment for other associated factors, gut feeling was not associated with reconsultations or hospital admissions. CONCLUSIONS: Clinicians were more likely to report a gut feeling something is wrong, when they were more experienced or when children were more unwell. Gut feeling is independently and strongly associated with antibiotic prescribing and referral to secondary care, but not with two indicators of poor child health.