Search

Background: Clinical uncertainty in primary care regarding the prognosis of children with respiratory tract infections contributes to the unnecessary use of antibiotics. Improved identification of children at low risk of future hospitalisation might reduce clinical uncertainty. A National Institute for Health and Care Research-funded 5-year programme (RP-PG-0608-10018) was used to develop and feasibility test an intervention., Objectives: The aim of the children with acute cough randomised controlled trial was to reduce antibiotic prescribing among children presenting with acute cough and respiratory tract infection without increasing hospital admission., Design: An efficient, pragmatic open-label, two-arm trial (with embedded qualitative and health economic analyses) using practice-level randomisation using routinely collected data as the primary outcome., Setting: General practitioner practices in England., Participants: General practitioner practices using the Egton Medical Information Systems ® patient-record system for children aged 0-9 years presenting with a cough or upper respiratory tract infection. Recruited by Clinical Research Networks and Clinical Commissioning Groups., Intervention: Comprised: (1) elicitation of parental concerns during consultation; (2) a clinician-focused prognostic algorithm to identify children with acute cough and respiratory tract infection at low, average or elevated risk of hospitalisation in the next 30 days accompanied by prescribing guidance, (3) provision of a printout for carers including safety-netting advice., Main Outcome Measures: Co-primaries using the practice list-size for children aged 0-9 years as the denominator: rate of dispensed amoxicillin and macrolide items at each practice (superiority comparison) from NHS Business Services Authority ePACT2 and rate of hospital admission for respiratory tract infection (non-inferiority comparison) from Clinical Commissioning Groups, both routinely collected over 12 months., Results: Of the 310 practices required, 294 (95%) were recruited (144 intervention and 150 controls) with 336,496 registered 0-9-year-olds (5% of all 0-9-year-old children in England) from 47 Clinical Commissioning Groups. Included practices were slightly larger than those not included, had slightly lower baseline dispensing rates and were located in more deprived areas (reflecting the distribution for practice postcodes nationally). Twelve practices (4%) subsequently withdrew (six related to the pandemic). The median number of times the intervention was used was 70 per practice (by a median of 9 clinicians) over 12 months. There was no evidence that the antibiotic dispensing rate in the intervention practices [0.155 (95% confidence interval 0.135 to 0.179)] differed to controls [0.154 (95% confidence interval 0.130 to 0.182), relative risk= 1.011 (95% confidence interval 0.992 to 1.029); p = 0.253]. There was, overall, a reduction in dispensing levels and intervention usage during the pandemic. The rate of hospitalisation for respiratory tract infection in the intervention practices [0.019 (95% confidence interval 0.014 to 0.026)] compared to the controls [0.021 (95% confidence interval 0.014 to 0.029)] was non-inferior [relative risk = 0.952 (95% confidence interval 0.905 to 1.003)]. The qualitative evaluation found the clinicians liked the intervention, used it as a supportive aid, especially with borderline cases but that it, did not always integrate well within the consultation flow and was used less over time. The economic evaluation found no evidence of a difference in mean National Health Service costs between arms; mean difference -£1999 (95% confidence interval -£6627 to 2630)., Conclusions: The intervention was feasible and subjectively useful to practitioners, with no evidence of harm in terms of hospitalisations, but did not impact on antibiotic prescribing rates., Future Work and Limitations: Although the intervention does not appear to change prescribing behaviour, elements of the approach may be used in the design of future interventions., Trial Registration: This trial is registered as ISRCTN11405239 (date assigned 20 April 2018) at www.controlled-trials.com (accessed 5 September 2022). Version 4.0 of the protocol is available at: https://www.journalslibrary.nihr.ac.uk/ (accessed 5 September 2022)., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (NIHR award ref: 16/31/98) programme and is published in full in Health Technology Assessment ; Vol. 27, No. 32. See the NIHR Funding and Awards website for further award information.

Background: Antibiotics are commonly prescribed for children with lower respiratory tract infections (LRTIs), fuelling antibiotic resistance, and there are few prognostic tools available to inform management., Aim: To externally validate an existing prognostic model (STARWAVe) to identify children at low risk of illness progression, and if model performance was limited to develop a new internally validated prognostic model., Design and Setting: Prospective cohort study with a nested trial in a primary care setting., Method: Children aged 6 months to 12 years presenting with uncomplicated LRTI were included in the cohort. Children were randomised to receive amoxicillin 50 mg/kg per day for 7 days or placebo, or if not randomised they participated in a parallel observational study to maximise generalisability. Baseline clinical data were used to predict adverse outcome (illness progression requiring hospital assessment)., Results: A total of 758 children participated ( n = 432 trial, n = 326 observational). For predicting illness progression the STARWAVe prognostic model had moderate performance (area under the receiver operating characteristic [AUROC] 0.66, 95% confidence interval [CI] = 0.50 to 0.77), but a new, internally validated model (seven items: baseline severity; respiratory rate; duration of prior illness; oxygen saturation; sputum or a rattly chest; passing urine less often; and diarrhoea) had good discrimination (bootstrapped AUROC 0.83, 95% CI = 0.74 to 0.92) and calibration. A three-item model (respiratory rate; oxygen saturation; and sputum or a rattly chest) also performed well (AUROC 0.81, 95% CI = 0.70 to 0.91), as did a score (ranging from 19 to 102) derived from coefficients of the model (AUROC 0.78, 95% CI = 0.67 to 0.88): a score of <70 classified 89% ( n = 600/674) of children having a low risk (<5%) of progression of illness., Conclusion: A simple three-item prognostic score could be useful as a tool to identify children with LRTI who are at low risk of an adverse outcome and to guide clinical management., (© The Authors.)

Objective: To assess whether an easy-to-use multifaceted intervention for children presenting to primary care with respiratory tract infections would reduce antibiotic dispensing, without increasing hospital admissions for respiratory tract infection., Design: Two arm randomised controlled trial clustered by general practice, using routine outcome data, with qualitative and economic evaluations., Setting: English primary care practices using the EMIS electronic medical record system., Participants: Children aged 0-9 years presenting with respiratory tract infection at 294 general practices, before and during the covid-19 pandemic., Intervention: Elicitation of parental concerns during consultation; a clinician focused prognostic algorithm to identify children at very low, normal, or elevated 30 day risk of hospital admission accompanied by antibiotic prescribing guidance; and a leaflet for carers including safety netting advice., Main Outcome Measures: Rate of dispensed amoxicillin and macrolide antibiotics (superiority comparison) and hospital admissions for respiratory tract infection (non-inferiority comparison) for children aged 0-9 years over 12 months (same age practice list size as denominator)., Results: Of 310 practices needed, 294 (95%) were randomised (144 intervention and 150 controls) representing 5% of all registered 0-9 year olds in England. Of these, 12 (4%) subsequently withdrew (six owing to the pandemic). Median intervention use per practice was 70 (by a median of 9 clinicians). No evidence was found that antibiotic dispensing differed between intervention practices (155 (95% confidence interval 138 to 174) items/year/1000 children) and control practices (157 (140 to 176) items/year/1000 children) (rate ratio 1.011, 95% confidence interval 0.992 to 1.029; P=0.25). Pre-specified subgroup analyses suggested reduced dispensing in intervention practices with fewer prescribing nurses, in single site (compared with multisite) practices, and in practices located in areas of lower socioeconomic deprivation, which may warrant future investigation. Pre-specified sensitivity analysis suggested reduced dispensing among older children in the intervention arm (P=0.03). A post hoc sensitivity analysis suggested less dispensing in intervention practices before the pandemic (rate ratio 0.967, 0.946 to 0.989; P=0.003). The rate of hospital admission for respiratory tract infections in the intervention practices (13 (95% confidence interval 10 to 18) admissions/1000 children) was non-inferior compared with control practices (15 (12 to 20) admissions/1000 children) (rate ratio 0.952, 0.905 to 1.003)., Conclusions: This multifaceted antibiotic stewardship intervention for children with respiratory tract infections did not reduce overall antibiotic dispensing or increase respiratory tract infection related hospital admissions. Evidence suggested that in some subgroups and situations (for example, under non-pandemic conditions) the intervention slightly reduced prescribing rates but not in a clinically relevant way., Trial Registration: ISRCTN11405239ISRCTN registry ISRCTN11405239., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the NIHR Health Technology Assessment programme; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; AH is a member of the NIHR Efficacy and Mechanism Evaluation Committee; JAL is a member of a clinical trials unit in receipt of NIHR support funding; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is a lack of evidence regarding post-consultation symptom trajectories for patients with respiratory tract infections (RTIs) and whether patient characteristics can be used to predict illness duration., Aim: To describe symptom trajectories in patients with RTIs, and assess baseline characteristics and adverse events associated with trajectories., Design and Setting: The study included data about 9103 adults and children from 12 primary care studies., Method: A latent class-informed regression analysis of individual patient data from randomised controlled trials and observational cohort studies was undertaken. Post-consultation symptom trajectory (severity and duration), re-consultation with same or worsening illness, and admission to hospital were assessed., Results: In total, 90% of participants recovered from all symptoms by 28 days, regardless of antibiotic prescribing strategy (none, immediate, and delayed antibiotics). For studies of RTI with cough as a dominant symptom ( n = 5314), four trajectories were identified: 'rapid (6 days)' (90% of participants recovered within 6 days) in 52.0%; 'intermediate (10 days)' (28.9%); 'slow progressive improvement (27 days)' (12.5%); and 'slow improvement with initial high symptom burden (27 days)' (6.6%). For cough, being aged 16-64 years (odds ratio [OR] 2.57, 95% confidence interval [CI] = 1.72 to 3.85 compared with <16 years), higher presenting illness baseline severity (OR 1.51, 95% CI = 1.12 to 2.03), presence of lung disease (OR 1.78, 95% CI = 1.44 to 2.21), and median and above illness duration before consultation (≥7 days) (OR 1.99, 95% CI = 1.68 to 2.37) were associated with slower recovery (>10 days) compared with faster recovery (≤10 days). Re-consultations and admissions to hospital for cough were higher in those with slower recovery (ORs: 2.15, 95% CI = 1.78 to 2.60 and 7.42, 95% CI = 3.49 to 15.78, respectively)., Conclusion: Older patients presenting with more severe, longer pre-consultation symptoms and chronic lung disease should be advised they are more likely to experience longer post-consultation illness durations, and that recovery rates are similar with and without antibiotics., (© The Authors.)

Background: Antibiotics are commonly prescribed for children with chest infections but there is little randomised evidence and trials commonly recruit selected populations, which undermines their applicability., Aim: To document the effectiveness of antibiotics for chest infections in children., Design and Setting: This was a prospective cohort study with nested trial in primary care., Method: Children aged 1-12 years presenting with uncomplicated lower respiratory tract infections were included in the cohort. Children were either randomised to receive amoxicillin 50 mg/kg per day for 7 days or placebo, or participated in a parallel observational study, where propensity scores controlled for confounding by indication. The outcomes were duration of symptoms rated moderately bad or worse (primary outcome) and illness progression requiring hospital assessment., Results: A total of 764 children participated (438 trial, 326 observational), and children were more unwell than in previous cohorts (more sputum, fever, shortness of breath). Children had been unwell for a median of 5-6 days, and symptoms rated moderately bad or worse lasted another 6 days when no antibiotics were given.With antibiotics there was a non-significant reduction of approximately 1 day in duration of symptoms rated moderately bad or worse for the whole cohort (hazard ratio [HR] 1.16, 95% confidence interval [CI] = 0.95 to 1.41), similar to the trial alone (HR 1.13, 95% CI = 0.90 to 1.43). The effect of antibiotic treatment on secondary outcomes was also non-significant., Conclusion: Antibiotics for uncomplicated chest infections, even in a sample of more unwell children, are unlikely to be clinically very effective., (© The Authors.)

Objectives: This study aimed to assess whether the presence of bacteria or viruses in the upper airway of children presenting with uncomplicated lower respiratory tract infection (LRTI) predicts the benefit of antibiotics., Methods: Children between 6 months and 12 years presenting to UK general practices with an acute LRTI were randomized to receive amoxicillin 50 mg/kg/d for 7 days or placebo. Children not randomized (ineligible or clinician/parental choice) could participate in a parallel observational study. The primary outcome was the duration of symptoms rated moderately bad or worse. Throat swabs were taken and analyzed for the presence of bacteria and viruses by multiplex PCR., Results: Swab results were available for most participants in the trial (306 of 432; 71%) and in the observational (182 of 326; 59%) studies. Bacterial pathogens potentially sensitive to amoxicillin (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae) were detected among 51% of the trial placebo group and 49% of the trial antibiotic group. The median difference in the duration of symptoms rated moderately bad or worse between antibiotic and placebo was similar when potentially antibiotic-susceptible bacteria were present (median: -1 day; 99% CI, -12.3 to 10.3) or not present (median: -1 day; 99% CI, -4.5 to 2.5). Furthermore, bacterial genome copy number did not predict benefit. There were similar findings for all secondary outcomes and when including the data from the observational study., Discussion: There was no clear evidence that antibiotics improved clinical outcomes conditional on the presence or concentration of bacteria or viruses in the upper airway. Before deploying microbiologic point-of-care tests for children with uncomplicated LRTI in primary care, rigorous validating trials are needed., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections., Aim: To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found., Design and Setting: Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care ( n = 3266) in 15 European countries., Method: Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications., Results: Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology., Conclusion: Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-and-see policy in most of these patients with flu-like illness seems the best option., (© The Authors.)

Background: Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups., Methods: ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298)., Findings: Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4-11] in the antibiotics group vs 6 days [4-15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90-1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis., Interpretation: Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections., Funding: National Institute for Health Research., Competing Interests: Declaration of interests SNF is part funded by the Southampton NIHR Biomedical Research Centre. TV reports grants from the EU and the Netherlands Organisation for Health Research and Development, during the conduct of the study; and grants from Abbott, Becton Dickinson, bioMérieux, and Janssen Pharmaceuticals, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible., Aim: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care., Design and Setting: Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial)., Method: Clinicians collected participants' demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP <20 mg/l, or CRP ≥20 mg/l)., Results: A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85)., Conclusion: Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions., (© The Authors.)

Introduction: Delayed prescribing can be a useful strategy to reduce antibiotic prescribing, but it is not clear for whom delayed prescribing might be effective. This protocol outlines an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) and observational cohort studies to explore the overall effect of delayed prescribing and identify key patient characteristics that are associated with efficacy of delayed prescribing., Methods and Analysis: A systematic search of the databases Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL Plus and Web of Science was conducted to identify relevant studies from inception to October 2017. Outcomes of interest include duration of illness, severity of illness, complication, reconsultation and patient satisfaction. Study authors of eligible papers will be contacted and invited to contribute raw IPD data. IPD data will be checked against published data, harmonised and aggregated to create one large IPD database. Multilevel regression will be performed to explore interaction effects between treatment allocation and patient characteristics. The economic evaluation will be conducted based on IPD from the combined trial and observational studies to estimate the differences in costs and effectiveness for delayed prescribing compared with normal practice. A decision model will be developed to assess potential savings and cost-effectiveness in terms of reduced antibiotic usage of delayed prescribing and quality-adjusted life years., Ethics and Dissemination: Ethical approval was obtained from the University of Southampton Faculty of Medicine Research Ethics Committee (Reference number: 30068). Findings of this study will be published in peer-reviewed academic journals as well as General Practice trade journals and will be presented at national and international conferences. The results will have important public health implications, shaping the way in which antibiotics are prescribed in the future and to whom delayed prescriptions are issued., Prospero Registration Number: CRD42018079400., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Point of care tests (POCTs) are increasingly being promoted for guiding the primary medical care of community acquired lower respiratory tract infections (CA-LRTI). POCT development has seldom been guided by explicitly identified clinical need and requirements of the intended users. Approaches for identifying POCT priorities and developing target product profiles (TPPs) for POCTs in primary medical care are not well developed, and there is no published TPP for a CA-LRTI POCT aimed at developed countries., Methods: We conducted workshops with expert stakeholders and a survey with primary care clinicians to produce a target product profile (TPP) to guide the development of a clinically relevant and technologically feasible POCT for CA-LRTI., Results: Participants with clinical, academic, industrial, technological and basic scientific backgrounds contributed to four expert workshops, and 45 practicing primary care clinicians responded to an online survey and prioritised community-acquired pneumonia (CAP) as the CA-LRTI where a new POCT was most urgently needed. Consensus was reached on a TPP document that included information on the intended niche in the clinical pathway in primary medical care; diagnostic product specification (intended use statement and test concept), and minimum and ideal user specifications. Clinicians minimum requirements of a CA-LRTI POCT included the use of minimally invasive samples, a result in less than 30 minutes, no more than a single preparation step, minimum operational requirements, and detection of common respiratory pathogens and their resistance to commonly prescribed antibiotics., Conclusions: This multidisciplinary, multistage partnership approach generated a clinically-driven TPP for guiding the development of a new POCT, and this approach as well as the TPP itself may be useful to others developing a new POCT., Competing Interests: Author JV was employed by the commercial company, "Janssen Diagnostics BVBA", which is one of the European Federation of Pharamaceutical Industries and Associations (EFPIA) member companies of the IMI RAPP-ID Consortium. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Antibiotics are too often prescribed in childhood respiratory tract infection (RTI), despite limited effectiveness, potential side effects and bacterial resistance. We aimed to reduce antibiotic prescribing for children with RTI by online training for general practitioners (GPs) and information for parents., Methods: A pragmatic cluster randomized controlled trial in primary care. The intervention consisted of online training for GPs and an information booklet for parents. The primary outcome was the antibiotic prescription rate for children presenting with RTI symptoms, as registered by GPs. Secondary outcomes were number of reconsultations within the same disease episode, consultations for new episodes, hospital referrals and pharmacy-dispensed antibiotic courses for children. This trial was registered at the Dutch Trial Register (NTR), registration number: NTR4240., Results: After randomization, GPs from a total of 32 general practices registered 1009 consultations. An antibiotic was prescribed in 21% of consultations in the intervention group, compared with 33% in the usual care group, controlled for baseline prescribing (rate ratio 0.65, 95% CI 0.46-0.91). The probability of reconsulting during the same RTI episode did not differ significantly between the intervention and control groups, and nor did the numbers of consultations for new episodes and hospital referrals. In the intervention group antibiotic dispensing was 32 courses per 1000 children/year lower than the control group, adjusted for baseline prescribing (rate ratio 0.78, 95% CI 0.66-0.92). The numbers and proportion of second-choice antibiotics did not differ significantly., Conclusions: Concise, feasible, online GP training, with an information booklet for parents, showed a relevant reduction in antibiotic prescribing for children with RTI.

Objective: To investigate recruitment and retention, data collection methods and the acceptability of a 'within-consultation' complex intervention designed to reduce antibiotic prescribing., Design: Primary care feasibility cluster randomised controlled trial., Setting: 32 general practices in South West England recruiting children from October 2014 to April 2015., Participants: Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI)., Intervention: A web-based clinician-focussed clinical rule to predict risk of future hospitalisation and a printed leaflet with individualised child health information for carers, safety-netting advice and a treatment decision record., Controls: Usual practice, with clinicians recording data on symptoms, signs and treatment decisions., Results: Of 542 children invited, 501 (92.4%) consented to participate, a month ahead of schedule. Antibiotic prescribing data were collected for all children, follow-up data for 495 (98.8%) and the National Health Service resource use data for 494 (98.6%). The overall antibiotic prescribing rates for children's RTIs were 25% and 15.8% (p=0.018) in intervention and control groups, respectively. We found evidence of postrandomisation differential recruitment: the number of children recruited to the intervention arm was higher (292 vs 209); over half were recruited by prescribing nurses compared with less than a third in the control arm; children in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03) and appeared to be more unwell than those in the control arm with higher respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews with clinicians confirmed preferential recruitment of less unwell children to the trial, more so in the control arm., Conclusion: Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records., Trial Registration Number: ISRCTN 23547970 UKCRN STUDY ID: 16891., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Evidence shows a high rate of unnecessary antibiotic prescriptions in primary care in Europe and the United States. Given the costs of widespread use and associated antibiotic resistance, reducing inappropriate use is a public health priority., Objective: We aimed to explore clinicians' experiences of training in communication skills and use of a patient booklet and/or a C-reactive protein (CRP) point-of-care test to reduce antibiotic prescribing for acute respiratory tract infections (RTIs)., Design: We used a qualitative research approach, interviewing clinicians who participated in a randomised controlled trial (RCT) testing two contrasting interventions., Participants: General practice clinicians in Belgium, England, The Netherlands, Poland, Spain and Wales participated in the study., Approach: Sixty-six semi-structured interviews were transcribed verbatim, translated into English where necessary, and analysed using thematic and framework analysis., Key Results: Clinicians from all countries attributed benefits for themselves and their patients to using both interventions. Clinicians reported that the communication skills training and use of the patient booklet gave them greater confidence in addressing patient expectations for an antibiotic by providing answers to common questions and supporting the clinician's own explanations. Clinicians felt the booklet could be used for a variety of patients and for different types of infections. The CRP test was viewed as a tool to decrease diagnostic uncertainty, to support non-prescription decisions, and to reassure patients, but was only necessary when clinicians were uncertain about the need for antibiotics., Conclusion: Providing clinicians with training and support tools for use in practice was received positively and was valued by clinicians across countries. Interventions seemed to have influenced behaviour by increasing clinician knowledge about illness severity and prescribing, increasing confidence in making non-prescribing decisions when antibiotics were unnecessary, and enabling clinicians to anticipate positive outcomes when making such decisions. Addressing such determinants of behaviour change enabled interventions to be relevant for clinicians working across different contexts.

BACKGROUND It is largely unknown what medication is used by patients with lower respiratory tract infection (LRTI). AIM To describe the use of self-medication and prescribed medication in adults presenting with LRTI in different European countries, and to relate self-medication to patient characteristics. DESIGN AND SETTING An observational study in 16 primary care networks in 12 European countries. METHOD A total of 2530 adult patients presenting with LRTI in 12 European countries filled in a diary on any medication used before and after a primary care consultation. Patient characteristics related to self-medication were determined by univariable and multivariable logistic regression analysis. RESULTS The frequency and types of medication used differed greatly between European countries. Overall, 55.4% self-medicated before consultation, and 21.5% after consultation, most frequently with paracetamol, antitussives, and mucolytics. Females, non-smokers, and patients with more severe symptoms used more self-medication. Patients who were not prescribed medication during the consultation self-medicated more often afterwards. Self-medication with antibiotics was relatively rare. CONCLUSION A considerable amount of medication, often with no proven efficacy, was used by adults presenting with LRTI in primary care. There were large differences between European countries. These findings should help develop patient information resources, international guidelines, and international legislation concerning the availability of over-the-counter medication, and can also support interventions against unwarranted variations in care. In addition, further research on the effects of symptomatic medication is needed.

Background: 'When should I worry?' is an interactive booklet for parents of children presenting with respiratory tract infections (RTIs) in primary care and associated training for clinicians. A randomised controlled trial (the EQUIP study) demonstrated that this intervention reduced antibiotic prescribing and future consulting intentions. The aims of this qualitative process evaluation were to understand how acceptable the intervention was to clinicians and parents, how it was implemented, the mechanisms for any observed effects, and contextual factors that could have influenced its effects., Methods: Semi-structured interviews were conducted with 20 parents and 13 clinicians who participated in the trial. Interviews were audio-recorded and transcribed verbatim. Data were analysed using a framework approach, which involved five stages; familiarisation, development of a thematic framework, indexing, charting, and interpretation., Results: Most parents and clinicians reported that the 'When should I worry' interactive booklet (and online training for clinicians) was easy to use and valuable. Information on recognising signs of serious illness and the usual duration of illness were most valued. The interactive use of the booklet during consultations was considered to be important, but this did not always happen. Clinicians reported lack of time, lack of familiarity with using the booklet, and difficulty in modifying their treatment plan/style of consultation as barriers to use. Increased knowledge and confidence amongst clinicians and patients were seen as key components that contributed to the reductions in antibiotic prescribing and intention to consult seen in the trial. This was particularly pertinent in a context where decisions about the safe and appropriate management of childhood RTIs were viewed as complex and parents reported frequently receiving inconsistent messages., Conclusions: The 'When should I worry' booklet, which is effective in reducing antibiotic prescribing, has high acceptability for clinicians and parents, helps address gaps in knowledge, increases confidence, and provides a consistent message. However, it is not always implemented as intended. Plans for wider implementation of the intervention in health care settings would need to address clinician-related barriers to implementation., Trial Registration: ISRCTN46104365.

Background: To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes., Methods: GPs were cluster randomised to one of three intervention groups or a control group. The intervention groups received web-based training in either use of the C-reactive protein (CRP) test, communication skills and use of a patient booklet, or training in both. GP attitudes were measured before and after the intervention using constructs from the Theory of Planned Behaviour and a Website Satisfaction Questionnaire. Effects of the interventions on patients were assessed by a post-intervention questionnaire assessing patient enablement, satisfaction with the consultation, and beliefs about the risks and need for antibiotics., Results: GPs in all countries and intervention groups had very positive perceptions of the intervention and the web-based training, and felt that taking part had helped them to reduce prescribing. All GPs perceived reducing prescribing as more important and less risky following the intervention, and GPs in the communication groups reported increased confidence to reduce prescribing. Patients in the communication groups who received the booklet reported the highest levels of enablement and satisfaction and had greater awareness that antibiotics could be unnecessary and harmful., Conclusions: Our findings suggest that the interventions should be broadly acceptable to both GPs and patients, as well as feasible to roll out more widely across Europe. There are also some indications that they could help to engender changes in GP and patient attitudes that will be helpful in the longer-term, such as increased awareness of the potential disadvantages of antibiotics and increased confidence to manage LRTI without them. Given the positive effects of the booklet on patient beliefs and attitudes, it seems logical to extend the use of the patient booklet to all patients.

Purpose: The purpose of the study was to assess the long-term effect of family physicians' use of C-reactive protein (CRP) point-of-care testing and/or physician training in enhanced communication skills on office visit rates and antibiotic prescriptions for patients with respiratory tract infections., Methods: We conducted a 3.5-year follow-up of a pragmatic, factorial, cluster-randomized controlled trial; 379 patients (20 family practices in the Netherlands) who visited their family physician for acute cough were enrolled in the trial and had follow-up data available (88% of original trial cohort). Main outcome measures were the average number of episodes of respiratory tract infections for which patients visited their family physician per patient per year (PPPY), and the percentage of the episodes for which patients were treated with antibiotics during follow-up., Results: The mean number of episodes of respiratory tract infections during follow-up was 0.40 PPPY in the CRP test group and 0.56 PPPY in the no CRP test group (P = .12). In the communication skills training group, there was a mean of 0.36 PPPY episodes of respiratory tract infections, and in the no training group the mean was 0.57 PPPY (P = .09). During follow-up 30.7% of all episodes of respiratory tract infection were treated with antibiotics in the CRP test group compared with 35.7% in the no test group (P = .36). Family physicians trained in communication skills treated 26.3% of all episodes of respiratory tract infection with antibiotics compared with 39.1% treated by family physicians without training in communication skills (P = .02), Conclusions: Family physicians' use of CRP point-of-care testing and/or training in enhanced communication skills did not significantly affect office visit rates related to respiratory tract infections. Patients who saw a family physician trained in enhanced communication skills were prescribed significantly fewer antibiotics during episodes of respiratory tract infection in the subsequent 3.5 years.

Background: Delayed antibiotic prescribing is promoted as a strategy to reduce antibiotic consumption, but its use and its effect on antibiotic consumption in routine care is poorly described., Aim: To quantify delayed antibiotic prescribing in adults presenting in primary care with acute cough/lower respiratory tract infection (LRTI), duration of advised delay, consumption of delayed antibiotics, and factors associated with consumption., Design and Setting: Prospective observational cohort in general practices in 14 primary care networks in 13 European countries., Method: GPs recorded clinical features and antibiotic prescribing for adults presenting with an acute infective illness with cough as the dominant symptom. Patients recorded their consumption of antibiotics from any source during the 28-day follow up., Results: Two hundred and ten (6.3%) of 3368 patients with usable consultation data were prescribed delayed antibiotics. The median recommended delay period was 3 days. Seventy-five (44.4%) of the 169 with consumption data consumed the antibiotic course and a further 18 (10.7%) took another antibiotic during the study period. 50 (29.6%) started their delayed course on the day of prescription. Clinician diagnosis of upper respiratory tract/viral infection and clinician's perception of patient's wanting antibiotics were associated with less consumption of the delayed prescription. Patient's wanting antibiotics was associated with greater consumption., Conclusion: Delayed antibiotic prescribing was used infrequently for adults presenting in general practice with acute cough/LRTI. When used, the effect on antibiotic consumption was less than found in most trials. There are opportunities for standardising the intervention and promoting wider uptake.

Aims: To explore the potential use of the CRB-65 rule (based on Confusion, Respiratory rate, Blood pressure and age >65 years) in adults with lower respiratory tract infection (LRTI) in primary care., Methods: Primary care clinicians in 13 European countries recorded antibiotic treatment and clinical features for adults with LRTI. Patients recorded daily symptoms. Multilevel regression models determined the association between an elevated CRB-65 score and prolonged moderately severe symptoms, hospitalisation, and time to recovery. Sensitivity analyses used zero imputation., Results: Respiratory rate and blood pressure were recorded in 22.7% and 31.9% of patients, respectively. A total of 2,690 patients completed symptom diaries. The CRB-65 could be calculated for 339 (12.6%). A score of >1 was not significantly associated with prolonged moderately severe symptoms (odds ratio (OR) 0.42, 95% CI 0.04 to 4.19) or hospitalisations (OR 3.12, 95% CI 0.16 to 60.24), but was associated with prolonged time to self-reported recovery when using zero imputation (hazard ratio (HR) 0.75, 95% CI 0.64 to 0.88)., Conclusions: Respiratory rate and blood pressure are infrequently measured in adults with LRTI. We found no evidence to support using the CRB-65 rule in the assessment of LRTI in primary care. However, it is unclear whether it is of value if used only in patients where the primary care clinician suspects pneumonia.

Objective: To identify potential opportunities for earlier intervention among children who develop a complicated respiratory tract infection (RTI)., Design: Qualitative, face-to-face, individual interview study, either in hospital or at home, with parents of children admitted to hospital with a complicated RTI., Setting: Participants were recruited from a large UK teaching hospital, and described events (largely) prior to hospital admission., Participants: Parents of 22 children (12 with empyema, 8 with pneumonia, 1 with peritonsillar abscess and 1 with mastoiditis)., Results: Parents' accounts revealed missed opportunities for timely treatment resulting from parental and health service associated factors. Themes relating to parental factors included problems assessing the severity of the illness (5 parents), beliefs about accessing health services (10 parents; including fear of appearing 'neurotic', belief that their concerns would not be taken seriously, and belief that their child would not be prescribed antibiotics or would be prescribed antibiotics too readily) and feeling powerless to challenge clinical authority (7 parents). Health service associated factors included perceived problems accessing healthcare services (13 parents; including inadequate primary care triage, barriers to accessing timely consultations and past experience of problems accessing healthcare leading to failure to consult) and perceived poor quality clinical encounters (11 parents; including inadequate assessment and communication)., Conclusion: Addressing, where appropriate, these parental (skills, fears and beliefs) and health service (access and consultation quality) associated factors may lead to more prompt care for seriously ill children.

Respiratory tract infections (RTIs) remain the commonest reason for acute consultations in primary care in resource-rich countries. Their spectrum and severity has changed from the time that antibiotics were discovered, largely from improvements in the socioeconomic determinants of health as well as vaccination. The benefits from antibiotic treatment for common RTIs have been shown to be largely overstated. Nevertheless, serious infections do occur. Currently, no clinical features or diagnostic test, alone or in combination, adequately determine diagnosis, aetiology, prognosis, or response to treatment. This narrative review focuses on emerging evidence aimed at helping clinicians reduce and manage uncertainty in treating RTIs. Consultation rate and prescribing rate trends are described, evidence of increasing rates of complications are discussed, and studies and the association with antibiotic prescribing are examined. Methods of improving diagnosis and identifying those patients who are at increased risk of complications from RTIs, using clinical scoring systems, biomarkers, and point of care tests are also discussed. The evidence for alternative management options for RTIs are summarised and the methods for changing public and clinicians' beliefs about antibiotics, including ways in which we can improve clinician-patient communication skills for management of RTIs, are described.

Reconsultation for lower respiratory tract infection (LRTI) is common in general practice, but those who reconsult rarely have more significant illness warranting antibiotics. Knowledge of factors that predict patient-initiated reconsultation may allow clinicians to address specific issues during the initial consultation that could reduce reconsultations. Thirty-three per cent of a cohort of 431 LRTI patients in a randomised controlled trial reconsulted. Excluding 35 patients with GP-requested reconsultation left 28% (112/396) with a patient-initiated reconsultation during 28-day follow-up. Patient-reported dyspnoea and concerns that persisted after the initial consultation independently predicted patient-initiated reconsultation.

Objective: To establish whether an interactive booklet on respiratory tract infections in children reduces reconsultation for the same illness episode, reduces antibiotic use, and affects future consulting intentions, while maintaining parental satisfaction with care., Design: Pragmatic cluster randomised controlled trial., Setting: 61 general practices in Wales and England., Participants: 558 children (6 months to 14 years) presenting to primary care with an acute respiratory tract infection (7 days or less). Children with suspected pneumonia, asthma or a serious concomitant illness, or needing immediate hospital admission were excluded. Three withdrew and 27 were lost to follow-up, leaving 528 (94.6%) with main outcome data., Interventions: Clinicians in the intervention group were trained in the use of an interactive booklet on respiratory tract infections and asked to use the booklet during consultations with recruited patients (and provide it as a take home resource). Clinicians in the control group conducted their consultations as usual., Main Outcome Measures: The proportion of children who attended a face-to-face consultation about the same illness during the two week follow-up period. Secondary outcomes included antibiotic prescribing, antibiotic consumption, future consulting intentions, and parental satisfaction, reassurance, and enablement., Results: Reconsultation occurred in 12.9% of children in the intervention group and 16.2% in the control group (absolute risk reduction 3.3%, 95% confidence interval -2.7% to 9.3%, P=0.29). Using multilevel modelling (at the practice and individual level) to account for clustering, no significant difference in reconsulting was noted (odds ratio 0.75; 0.41 to 1.38). Antibiotics were prescribed at the index consultation to 19.5% of children in the intervention group and 40.8% of children in the control group (absolute risk reduction 21.3%, 95% confidence interval 13.7 to 28.9), P<0.001). A significant difference was still present after adjusting for clustering (odds ratio 0.29; 0.14 to 0.60). There was also a significant difference in the proportion of parents who said they would consult in the future if their child developed a similar illness (odds ratio 0.34; 0.20 to 0.57). Satisfaction, reassurance, and parental enablement scores were not significantly different between the two groups., Conclusions: Use of a booklet on respiratory tract infections in children within primary care consultations led to important reductions in antibiotic prescribing and reduced intention to consult without reducing satisfaction with care., Trial Registration: Current Controlled Trials ISRCTN46104365.

Background: Respiratory tract infections in children result in more primary care consultations than any other acute condition, and are the most common reason for prescribing antibiotics (which are largely unnecessary). About a fifth of children consult again for the same illness episode. Providing parents with written information on respiratory tract infections may result in a reduction in re-consultation rates and antibiotic prescribing for these illnesses. Asking clinicians to provide and discuss the information during the consultation may enhance effectiveness. This paper outlines the protocol for a study designed to evaluate the use of a booklet on respiratory tract infections in children within primary care consultations., Methods/design: This will be a cluster randomised controlled trial. General practices will be randomised to provide parents consulting because their child has an acute respiratory tract infection with either an interactive booklet, or usual care. The booklet provides information on the expected duration of their child's illness, the likely benefits of various treatment options, signs and symptoms that should prompt re-consultation, and symptomatic treatment advice. It has been designed for use within the consultation and aims to enhance communication through the use of specific prompts. Clinicians randomised to using the interactive booklet will receive online training in its use. Outcomes will be assessed via a telephone interview with the parent two weeks after first consulting. The primary outcome will be the proportion of children who re-consult for the same illness episode. Secondary outcomes include: antibiotic use, parental satisfaction and enablement, and illness costs. Consultation rates for respiratory tract infections for the subsequent year will be assessed by a review of practice notes., Discussion: Previous studies in adults and children have shown that educational interventions can result in reductions in re-consultation rates and use of antibiotics for respiratory tract infections. This will be the first study to determine whether providing parents with a booklet on respiratory tract infections in children, and discussing it with them during the consultation, reduces re-consultations and antibiotic use for the same illness without reducing satisfaction with care., Trial Registration: Current Controlled Trials ISRCTN46104365.