The CHICO (Children's Cough) Trial protocol: a feasibility randomised controlled trial investigating the clinical and cost-effectiveness of a complex intervention to improve the management of children presenting to primary care with acute respiratory trac

While most respiratory tract infections (RTIs) will resolve without treatment, many children will receive antibiotics and some will develop severe symptoms requiring hospitalisation. There have been calls for evidence to reduce uncertainty regarding the identification of children who will and will not benefit from antibiotics. The aim of this feasibility trial is to test recruitment and the acceptance of a complex behavioural intervention designed to reduce antibiotic prescribing, and to inform how best to conduct a larger trial. The CHICO (Children's Cough) trial is a single-centre feasibility cluster randomised controlled trial (RCT) comparing a web-based, within-consultation, behavioural intervention with usual care for children presenting to general practitioner practices with RTI and acute cough. The trial aims to recruit at least 300 children between October 2014 and April 2015, in a single area in South West England. Following informed consent, demographic information will be recorded, and symptoms and signs measured. Parents/carers of recruited children will be followed up on a weekly basis to establish symptom duration, resource use and cost of the illness to the parent until the child's cough has resolved or up to 8 weeks, whichever occurs earlier. A review of medical notes, including clinical history, primary care reconsultations and hospitalisations will be undertaken 2 months after recruitment. The trial feasibility will be assessed by: determining acceptability of the intervention to clinicians and parent/carers; quantifying differential recruitment and follow-up; determining intervention fidelity; the success in gathering the data necessary to conduct a cost-effectiveness analysis; and collecting data about antibiotic prescribing rates to inform the sample size needed for a fully powered RCT. The study was approved by the North West-Haydock Research Ethics Committee, UK (reference number: 14/NW/1034). The findings from this feasibility trial will be disseminated through research conferences and peer-reviewed journals. ISRCTN23547970.

Turnbull SL ，Redmond NM ，Lucas P ，Cabral C ，Ingram J ，Hollinghurst S ，Hay AD ，Peters TJ ，Horwood J ，Little P ，Francis N ，Blair PS ... -  《BMJ Open》

A multifaceted intervention to reduce antibiotic prescribing among CHIldren with acute COugh and respiratory tract infection: the CHICO cluster RCT.

Blair PS ，Young GJ ，Clement C ，Dixon P ，Seume P ，Ingram J ，Taylor J ，Horwood J ，Lucas PJ ，Cabral C ，Francis NA ，Beech E ，Gulliford M ，Creavin S ，Lane JA ，Bevan S ，Hay AD ... -  《-》

Feasibility cluster randomised controlled trial of a within-consultation intervention to reduce antibiotic prescribing for children presenting to primary care with acute respiratory tract infection and cough.

To investigate recruitment and retention, data collection methods and the acceptability of a 'within-consultation' complex intervention designed to reduce antibiotic prescribing. Primary care feasibility cluster randomised controlled trial. 32 general practices in South West England recruiting children from October 2014 to April 2015. Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI). 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. Usual practice, with clinicians recording data on symptoms, signs and treatment decisions. 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. 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. ISRCTN 23547970 UKCRN STUDY ID: 16891.

Blair PS ，Turnbull S ，Ingram J ，Redmond N ，Lucas PJ ，Cabral C ，Hollinghurst S ，Dixon P ，Peters T ，Horwood J ，Little P ，Francis NA ，Gilbertson A ，Jameson C ，Hay AD ... -  《BMJ Open》

Protocol for an 'efficient design' cluster randomised controlled trial to evaluate a complex intervention to improve antibiotic prescribing for CHIldren presenting to primary care with acute COugh and respiratory tract infection: the CHICO study.

Respiratory tract infections (RTIs) in children are common and present major resource implications for primary care. Unnecessary use of antibiotics is associated with the development and proliferation of antimicrobial resistance. In 2016, the National Institute for Health Research (NIHR)-funded 'TARGET' programme developed a prognostic algorithm to identify children with acute cough and RTI at very low risk of 30-day hospitalisation and unlikely to need antibiotics. The intervention includes: (1) explicit elicitation of parental concerns, (2) the results of the prognostic algorithm accompanied by prescribing guidance and (3) provision of a printout for carers including safety netting advice. The CHIldren's COugh feasibility study suggested differential recruitment of healthier patients in control practices. This phase III 'efficiently designed' trial uses routinely collected data at the practice level, thus avoiding individual patient consent. The aim is to assess whether embedding a multifaceted intervention into general practitioner (GP) practice Information Technology (IT) systems will result in reductions of antibiotic prescribing without impacting on hospital attendance for RTI. The coprimary outcomes are (1) practice rate of dispensed amoxicillin and macrolide antibiotics, (2) hospital admission rate for RTI using routinely collected data by Clinical Commissioning Groups (CCGs). Data will be collected for children aged 0-9 years registered at 310 practices (155 intervention, 155 usual care) over a 12-month period. Recruitment and randomisation of practices (using the Egton Medical Information Systems web data management system) is conducted via each CCG stratified for children registered and baseline dispensing rates of each practice. Secondary outcomes will explore intervention effect modifiers. Qualitative interviews will explore intervention usage. The economic evaluation will be limited to a between-arm comparison in a cost-consequence analysis. Research ethics approval was given by London-Camden and Kings Cross Research Ethics Committee (ref:18/LO/0345). This manuscript refers to protocol V.4.0. Results will be disseminated through peer-reviewed journals and international conferences. ISRCTN11405239.

Seume P ，Bevan S ，Young G ，Ingram J ，Clement C ，Cabral C ，Lucas PJ ，Beech E ，Taylor J ，Horwood J ，Dixon P ，Gulliford MC ，Francis N ，Creavin ST ，Lane A ，Hay AD ，Blair PS ... -  《BMJ Open》

Antibiotics for lower respiratory tract infection in children presenting in primary care: ARTIC-PC RCT.

Little P ，Francis NA ，Stuart B ，O'Reilly G ，Thompson N ，Becque T ，Hay AD ，Wang K ，Sharland M ，Harnden A ，Yao G ，Raftery J ，Zhu S ，Little J ，Hookham C ，Rowley K ，Euden J ，Harman K ，Coenen S ，Read RC ，Woods C ，Butler CC ，Faust SN ，Leydon G ，Wan M ，Hood K ，Whitehurst J ，Richards-Hall S ，Smith P ，Thomas M ，Moore M ，Verheij T ... -  《-》