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.

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.

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.

Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial.

BACKGROUND: Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. We tested whether a community-based screening intervention could reduce fractures in older women. METHODS: We did a two-arm randomised controlled trial in women aged 70-85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management. Women were recruited from 100 general practitioner (GP) practices in seven regions of the UK: Birmingham, Bristol, Manchester, Norwich, Sheffield, Southampton, and York. We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study (eg, known dementia, terminally ill, or recently bereaved). The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period. In the screening group, treatment was recommended in women identified to be at high risk of hip fracture, according to the FRAX 10-year hip fracture probability. Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture, any clinical fracture, or mortality; and the effect of screening on anxiety and health-related quality of life. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN 55814835. FINDINGS: 12 483 eligible women were identified and participated in the trial, and 6233 women randomly assigned to the screening group between April 15, 2008, and July 2, 2009. Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio [HR] 0·94, 95% CI 0·85-1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86-1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59-0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life. INTERPRETATION: Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures. FUNDING: Arthritis Research UK and Medical Research Council.

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.

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.

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.

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.

Increased platelet reactivity as measured by plasma glycoprotein VI in gout.

Patients with gout have an increased risk of cardiovascular events. The glycoprotein VI (GPVI) receptor is found exclusively on platelets and megakaryocytes, is proteolytically cleaved upon platelet activation, and detectable in plasma as soluble GPVI (sGPVI). Therefore, elevated sGPVI is a marker of platelet activation and a risk marker for cardiovascular events. The aim of this study was to assess platelet activation, as measured by plasma sGPVI level in gout. Blood samples were taken from patients with gout or osteoarthritis, and from healthy volunteers. Demographic and clinical data were collected for all participants. Blood samples were processed as double-spun platelet-poor plasma. Plasma sGPVI levels were measured using enzyme-linked immunosorbent assay. Mann-Whitney U test was used to compare groups. In total, 91 patients were included, 27 during gout flare, 41 with intercritical gout, 23 with osteoarthritis, and 53 healthy controls. Median (interquartile range) sGPVI levels were 6.51 ng/mL (4.52, 8.41) in gout flare, 3.58 ng/mL (2.11, 5.55) in intercritical gout, 2.73 ng/mL (2.17, 3.72) in osteoarthritis, and 2.19 ng/mL (1.72, 3.31) in healthy controls. Plasma sGPVI levels in both gout groups were significantly increased compared to healthy controls (p < 0.005 for each), in gout flare compared to osteoarthritis (p < 0.005), and in gout flare compared to intercritical gout (p = 0.001). There was no significant difference in sGPVI levels in gout patients with and without tophi or in those prescribed colchicine. We conclude that patients with gout exhibit platelet hyperactivity as demonstrated by elevated sGPVI levels. Platelet activation is exacerbated in gout, especially during gout flares.

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.

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.

Development of an intervention to reduce antibiotic use for childhood coughs in UK primary care using critical synthesis of multi-method research.

BACKGROUND: Overuse of antibiotics contributes to the global threat of antimicrobial resistance. Antibiotic stewardship interventions address this threat by reducing the use of antibiotics in occasions or doses unlikely to be effective. We aimed to develop an evidence-based, theory-informed, intervention to reduce antibiotic prescriptions in primary care for childhood respiratory tract infections (RTI). This paper describes our methods for doing so. METHODS: Green and Krueter's Precede/Proceed logic model was used as a framework to integrate findings from a programme of research including 5 systematic reviews, 3 qualitative studies, and 1 cohort study. The model was populated using a strength of evidence approach, and developed with input from stakeholders including clinicians and parents. RESULTS: The synthesis produced a series of evidence-based statements summarizing the quantitative and qualitative evidence for intervention elements most likely to result in changes in clinician behaviour. Current evidence suggests that interventions which reduce clinical uncertainty, reduce clinician/parent miscommunication, elicit parent concerns, make clear delayed or no-antibiotic recommendations, and provide clinicians with alternate treatment actions have the best chance of success. We designed a web-based within-consultation intervention to reduce clinician uncertainty and pressure to prescribe, designed to be used when children with RTI present to a prescribing clinician in primary care. CONCLUSIONS: We provide a worked example of methods for the development of future complex interventions in primary care, where multiple factors act on multiple actors within a complex system. Our synthesis provided intervention guidance, recommendations for practice, and highlighted evidence gaps, but questions remain about how best to implement these recommendations. The funding structure which enabled a single team of researchers to work on a multi-method programme of related studies (NIHR Programme Grant scheme) was key in our success. TRIAL REGISTRATION: The feasibility study accompanying this intervention was prospectively registered with the ISRCTN registry ( ISRCTN23547970 ), on 27 June 2014.

Throat swabs in children with respiratory tract infection: associations with clinical presentation and potential targets for point-of-care testing.

Background and objectives: Diagnostic uncertainty over respiratory tract infections (RTIs) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. If symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. This study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs. Methods: Cross-sectional study of children ≥3 months to <16 years presenting with acute cough and RTI, with subset follow-up. Associations and area under receiver operating curve (AUROC) statistics sought between clinical presentation and baseline microbe detection. Microbe prevalence compared between baseline (symptomatic) and follow-up (asymptomatic) visits. Results: At baseline, ≥1 bacteria was detected in 1257/2113 (59.5%) children and ≥1 virus in 894/2127 (42%) children. Clinical presentation was not associated with detection of ≥1 bacteria [AUROC 0.54 (95% CI 0.52-0.56)] or ≥1 virus [0.64 (95% CI 0.61-0.66)]. Individually, only respiratory syncytial virus (RSV) was associated with clinical presentation [AUROC 0.80 (0.77-0.84)]. Prevalence fell between baseline and follow-up; more so in viruses (68% versus 26%, P < 0.001) than bacteria (56% versus 40%, P = 0.01); greatest reductions seen in RSV, influenza B and Haemophilus influenzae. Conclusion: Findings demonstrate that clinical presentation cannot distinguish the presence of bacteria or viruses in the upper respiratory tract. However, individual and overall microbe prevalence was greater when children were unwell than when well, providing some evidence that upper respiratory tract microbes may be the cause or consequence of the illness. If causal, selective microbial point-of-care testing could be beneficial.

Influence of Clinical Communication on Parents' Antibiotic Expectations for Children With Respiratory Tract Infections.

PURPOSE: The purpose of this study was to understand clinicians' and parents' perceptions of communication within consultations for respiratory tract infections (RTI) in children and what influence clinician communication had on parents' understanding of antibiotic treatment. METHODS: We video recorded 60 primary care consultations for children aged 3 months to 12 years who presented with RTI and cough in 6 primary care practices in England. We then used purposive sampling to select 27 parents and 13 clinicians for semistructured video-elicitation interviews. The videos were used as prompts to investigate participants' understanding and views of communication within the consultations. We analyzed the interview data thematically. RESULTS: While clinicians commonly told parents that antibiotics are not effective against viruses, this did not have much impact on parents' beliefs about the need to consult or on their expectations concerning antibiotics. Parents believed that antibiotics were needed to treat more severe illnesses, a belief that was supported by the way clinicians accompanied viral diagnoses with problem-minimizing language and antibiotic prescriptions with more problem-oriented language. Antibiotic prescriptions tended to confirm parents' beliefs about what indicated illness severity, which often took into account the wider impact on a child's life. While parents understood antimicrobial resistance poorly, most held beliefs that supported reduced antibiotic prescribing. A minority attributed it to resource rationing, however. CONCLUSIONS: Clinician communication and prescribing behavior confirm parents' beliefs that antibiotics are needed to treat more severe illnesses. Interventions to reduce antibiotic expectations need to address communication within the consultation, prescribing behavior, and lay beliefs.

An evaluation of the impact and costs of three strategies used to recruit acutely unwell young children to a randomised controlled trial in primary care.

BACKGROUND: Recruitment to primary care trials, particularly those involving young children, is known to be difficult. There are limited data available to inform researchers about the effectiveness of different trial recruitment strategies and their associated costs. PURPOSE: To describe, evaluate, and investigate the costs of three strategies for recruiting febrile children to a community-based randomised trial of antipyretics. METHODS: The three recruitment strategies used in the trial were termed as follows: (1) 'local', where paediatric research nurses stationed in primary care sites invited parents of children to participate; (2) 'remote', where clinicians at primary care sites faxed details of potentially eligible children to the trial office; and (3) 'community', where parents, responding to trial publicity, directly contacted the trial office when their child was unwell. RESULTS: Recruitment rates increased in response to the sequential introduction of three recruitment strategies, which were supplemented by additional recruiting staff, flexible staff work patterns, and improved clinician reimbursement schemes. The three strategies yielded different randomisation rates. They also appeared to be interdependent and highly effective together. Strategy-specific costs varied from £297 to £857 per randomised participant and represented approximately 10% of the total trial budget. LIMITATIONS: Because the recruitment strategies were implemented sequentially, it was difficult to measure their independent effects. The cost analysis was performed retrospectively. CONCLUSIONS: Trial recruiter expertise and deployment of several interdependent, illness-specific strategies were key factors in achieving rapid recruitment of young children to a community-based randomised controlled trial (RCT). The 'remote' recruitment strategy was shown to be more cost-effective compared to 'community' and 'local' strategies in the context of this trial. Future trialists should report recruitment costs to facilitate a transparent evaluation of recruitment strategy cost-effectiveness.

The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses.

BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.

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.

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.

Acceptability of screening to prevent osteoporotic fractures: a qualitative study with older women.

BACKGROUND: Osteoporotic fractures have a detrimental impact on health and quality of life, are more common in older women and are costly to treat. Screening to identify older women at high risk of fracture has the potential to offer substantial benefits. Understanding women's and professionals' experiences of screening will inform the implementation of screening in routine care. OBJECTIVE: To explore the views of older women and GPs about the acceptability of screening to prevent fractures. METHODS: A qualitative study conducted within a multi-centre randomized controlled trial of the effectiveness and cost-effectiveness of screening women aged 70-85 years for the prevention of fractures; 30 women randomized to the trial screening group and 15 GPs were recruited from general practices in North Somerset and Norfolk, UK. All 30 women and 11 of the GPs participated in face-to-face semi-structured interviews. Four GPs participated in a focus group. Data were analysed thematically, using the Framework Approach. RESULTS: Women and GPs viewed screening positively, recognizing its potential to improve fracture prevention and future health. Attending screening was not found to result in anxiety or excessive activity restriction. Demonstrating cost-effectiveness was key to the acceptability of screening amongst GPs. Implementing similar screening in routine care would require consideration of access to bone density scans, information provision to participants and mode of administration. CONCLUSIONS: Our findings suggest an effective and cost-effective screening programme to reduce osteoporotic fractures could be implemented in routine care and would be well received by women and GPs.