Katrina Cathie

OBJECTIVES: The Breathing Assistance in Children with bronchiolitis (BACHb) trial aims to evaluate the clinical and cost-effectiveness of high-flow nasal cannula (HFNC) therapy compared with humidified standard oxygen (HSO) in infants with moderate bronchiolitis, and HFNC with continuous positive airway pressure (CPAP) in severe bronchiolitis. DESIGN: Pragmatic, group-sequential, two-stratum, multicenter, open-label randomized clinical trial. SETTING: Fifty hospitals across England, Scotland, and Wales. PATIENTS: Hospitalized infants younger than 12 months old with a clinical diagnosis of bronchiolitis, assessed at least twice 15 minutes apart to fulfill criteria for either severe bronchiolitis (one or more of: respiratory rate > 70 breaths/min, grunting, marked chest recession, recurrent short apneas) or moderate bronchiolitis (lack of response to low-flow oxygen, indicated by persistent hypoxemia and/or moderate respiratory distress). INTERVENTIONS: “Moderate bronchiolitis stratum”: HFNC at a flow rate of 2 L/kg/min vs. HSO through a facemask or headbox at a flow rate up to 15 L/min. “Severe bronchiolitis stratum”: HFNC at a flow rate of 2 L/kg/min vs. CPAP pressure set at 6–8 cm H₂O. MEASUREMENTS AND MAIN RESULTS: In each stratum, eligible infants will be randomly allocated on a 1:1 basis to the trial treatments using a web-based system by permuted block randomization, stratified by site of recruitment and age (< 6 wk and ≥ 6 wk). Due to the emergency nature of the treatments, written informed consent will be deferred. The primary outcome is time from randomization to hospital discharge within 30 days. Baseline clinical characteristics and hospital course, including details of respiratory support, and discharge and cost-effectiveness outcomes will be collected. The trial received Health Research Authority and Research Ethics Committee approval from the Yorkshire and The Humber—South Yorkshire Research Ethics Committee on August 3, 2023 (reference: 23/YH/0166). The trial registration is ISRCTN52937119. CONCLUSIONS: Trial findings will be disseminated in national and international conferences, in peer-reviewed journals and through social media.

Background: Procalcitonin is a biomarker specific for bacterial infection, with a more rapid response than other commonly used biomarkers, such as C-reactive protein, but it is not routinely used in the National Health Service. Objective: To determine if using a procalcitonin-guided algorithm may safely reduce duration of antibiotic therapy compared to standard of care in hospitalised children with suspected or confirmed infection. Design: A pragmatic, multicentre, open-label, parallel two-arm, individually randomised controlled trial with internal pilot phase, qualitative study and health economic evaluations. Setting: Paediatric wards or paediatric intensive care units within children’s hospitals (n = 6) and district general hospitals (n = 9) in the United Kingdom. Participants: Children aged between 72 hours and 18 years admitted to hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Interventions: Procalcitonin-guided algorithm versus usual standard care alone. Main outcome measures: Coprimary outcomes were duration of intravenous antibiotic use and a composite safety measure. Results: Between 11 June 2018 and 12 October 2022, 1949 children were recruited: 977 to the procalcitonin group [427 female (43.7%), 550 male (56.3%)], and 972 to the usual care group [478 female (49.2%), 494 male (50.8%)]. Duration of intravenous antibiotics was not significantly different between the procalcitonin group (median 96.0 hours) and the usual care group (median 99.7 hours) [hazard ratio = 0.96 (0.87, 1.05)], and the procalcitonin-guided algorithm was non-inferior to usual care [risk difference = −0.81% (95% confidence interval upper bound 1.11%)]. At clinical review, a procalcitonin result was available for 81.8% of the time, which was considered as part of clinical decision-making 66.6% of the time, and the algorithm was adhered to 57.2% of the time. Incremental cost-effectiveness ratio per duration of intravenous antibiotics hour avoided from bootstrapped samples was £467.62 per intravenous antibiotic hour avoided. Cost analysis of complete cases was also higher in the procalcitonin arm for all age groups, and for children aged 5 years and over. The intervention is not cost-effective as it is more expensive with no significant improvement in intravenous antibiotic duration. Limitations: Robust antimicrobial stewardship programmes were already implemented in the lead recruiting sites, and adherence to the algorithm was poor. Clinicians may be reluctant to adhere to biomarker-guided algorithms, due to unfamiliarity with interpreting the test result. Conclusions: In children hospitalised with confirmed or suspected bacterial infection, the addition of a procalcitonin-guided algorithm to usual care is non-inferior in terms of safety, but does not reduce duration of intravenous antibiotics, and is not cost-effective. In the presence of robust antimicrobial stewardship programmes to reduce antibiotic use, a procalcitonin-guided algorithm may offer little added value. Future work: Future trials must include an implementation framework to improve trial intervention fidelity, and repeated cycles of education and training to facilitate implementation of biomarker-guided algorithms into routine clinical care. Trial registration: This trial is registered as ISRCTN11369832. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/188/42) and is published in full in Health Technology Assessment; Vol. 29, No. 16. See the NIHR Funding and Awards website for further award information.

Background: Maternal vaccination and infant monoclonal antibodies are promising avenues to protect young infants from respiratory syncytial virus (RSV) infection. Successful inclusion into the UK immunization schedule depends on parental acceptability, among other factors. Methods: An online cross-sectional survey from August to September 2023 exploring the likelihood of accepting, and preference for, either method of RSV prophylaxis, and reasons given for these. A questionnaire was distributed via social media networks to UK participants with a child under the age of 2 years and/or pregnant. Results: A total of 1620 participants completed the survey. Participants’ median age was 33 years [interquartile range (IQR), 31–36], 92% were of White ethnicity. Acceptability was high, but higher for a maternal vaccine than an infant monoclonal antibody ( P < 0.0001). Concerns about safety, need for more information and number of vaccines given to infants already were common reasons for hesitancy. Lacking knowledge about RSV was associated with a lower likelihood of accepting either option [maternal vaccine: odds ratio (OR): 0.32, 95% confidence interval (CI): 0.16–0.68, P = 0.002; infant monoclonal antibody: OR: 0.35, 95% CI: 0.19–0.68, P = 0.002], as was identifying as Black, Black British, African or Caribbean ethnic group, or having declined the routinely recommended antenatal vaccines. Conclusions: While most parents would accept a maternal vaccine or infant monoclonal antibody to protect their infant against RSV, understanding preferences, influencing factors and concerns is essential to optimize immunization programs. This study highlights the information parents require to make an informed choice about RSV protection.

Introduction Maternal vaccination and infant monoclonal antibodies are promising avenues to protect young infants from respiratory syncytial virus (RSV) infection. Successful inclusion into the UK immunisation schedule depends on parental acceptability, among other factors. Methods An online cross-sectional survey from August to September 2023 exploring the likelihood of accepting, and preference for, either method of RSV prophylaxis, and reasons given for these. A questionnaire was distributed via social media networks to UK participants with a child under the age of 2 years and/or pregnant. Results A total of 1620 participants completed the survey. Participants’ median age was 33 years (IQR 31 −36), 92% were of White ethnicity. Acceptability was high, but higher for a maternal vaccine than an infant monoclonal antibody (pConclusions Whilst most parents would accept a maternal vaccine or infant monoclonal antibody to protect their infant against RSV, understanding preferences, influencing factors and concerns is essential to optimise immunisation programmes. This study highlights the information parents require to make an informed choice about RSV protection.

Background: Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. Methods: A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). Results: In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. Conclusion: This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT.

Background The General and Adolescent Paediatric Research Network in the UK and Ireland (GAPRUKI) was established in 2016. The aims of GAPRUKI are to unite general paediatricians around the UK and Ireland, to develop research ideas and protocols, and facilitate delivery of multicentre research. Objectives To undertake a research prioritisation exercise among UK and Ireland general paediatricians. Methods This was a four-phase study using a modified Delphi survey. The first phase asked for suggested research priorities. The second phase developed ideas and ranked them in priority. In the third phase, priorities were refined; and the final stage used the Hanlon Prioritisation Process to agree on the highest priorities. Results In phase one, there were 250 questions submitted by 61 GAPRUKI members (66% of the whole membership). For phase two, 92 priorities were scored by 62 members and the mean Likert scale (1–7) scores ranged from 3.13 to 5.77. In a face-to-face meeting (phases three and four), 17 research questions were identified and ultimately 14 priorities were identified and ranked. The four priorities with the highest ranking focused on these three respiratory conditions: asthma, bronchiolitis and acute wheeze. Other priorities were in the diagnosis or management of constipation, urinary tract infection, fever, gastro-oesophageal reflux and also new models of care for scheduled general paediatric clinics. Conclusion Research priorities for child health in the UK and Ireland have been identified using a robust methodology. The next steps are for studies to be designed and funded to address these priorities.

Background The need for research priorities for UK child health was highlighted by the RCPCH’s report ‘Turning the Tide’. The General and Adolescent Paediatric Research Network in the UK and Ireland (GAPRUKI) was set up in 2016 and aims to bring together general paediatricians around the UK and Ireland to develop research ideas and protocols and deliver multi-centre research alongside existing networks such as the NIHR Clinical Research Network (CRN). Objectives To undertake a research prioritisation exercise based on gaps in the evidence that can reliably be delivered across the UK and Ireland. Methods This study was carried out in four phases using a modified Delphi survey. The first phase asked for suggested research priorities: ‘Thinking about your practice in the field of general paediatrics, both acute and in outpatients, what are the important research questions that need addressing?’. The second phase developed and ranked these suggested priorities (combining duplicate questions). The third phase refined the priorities and the final phase agreed on which were the greatest priorities (using the Hanlon Prioritisation Process (HPP)). Results 61 out of 92 GAPRUKI members responded to the first round (66%), submitting 250 questions. Members were made up of general paediatric consultants, trainees, nurses and research personnel in the UK and Ireland. All participants worked in roles where research in children was relevant to their practice. For stage 2, GAPRUKI had grown to 103 members, of which, 61 responded (60%) ranking 92 questions in the second Delphi survey. The mean scores for these questions ranged from 3.13 to 5.77 (Likert scale of 1–7 where 7 = essential priority and 1 = not a priority). In stage three, 92 priorities were reviewed and refined by 23 members who attended a face the face meeting in September 2019. In the final stage, HPP was applied and 14 priorities were identified and ranked. The ten highest priority areas are shown in the table with the Hanlon rank as well as the Delphi rank after stage 2 for comparison. Conclusions Research priorities for child health in the UK and Ireland have been identified using a robust methodology. The next steps are for studies to be designed to address these priorities. Once studies are funded, GAPRUKI will work alongside the NIHR CRN to deliver these studies across centres in the UK and Ireland.