Analysis of guideline recommendations for treatment of asthma exacerbations in children: a Pediatric Emergency Research Networks (PERN) study.

RATIONALE: There is significant practice variation in acute paediatric asthma, particularly severe exacerbations. It is unknown whether this is due to differences in clinical guidelines. OBJECTIVES: To describe and compare the content and quality of clinical guidelines for the management of acute exacerbations of asthma in children between geographic regions. METHODS: Observational study of guidelines for the management of acute paediatric asthma from institutions across a global collaboration of six regional paediatric emergency research networks. MEASUREMENTS AND MAIN RESULTS: 158 guidelines were identified. Half provided recommendations for at least two age groups, and most guidelines provided treatment recommendations according to asthma severity.There were consistent recommendations for the use of inhaled short-acting beta-agonists and systemic corticosteroids. Inhaled anticholinergic therapy was recommended in most guidelines for severe and critical asthma, but there were inconsistent recommendations for its use in mild and moderate exacerbations. Other inhaled therapies such as helium-oxygen mixture (Heliox) and nebulised magnesium were inconsistently recommended for severe and critical illness.Parenteral bronchodilator therapy and epinephrine were mostly reserved for severe and critical asthma, with intravenous magnesium most recommended. There were regional differences in the use of other parenteral bronchodilators, particularly aminophylline.Guideline quality assessment identified high ratings for clarity of presentation, scope and purpose, but low ratings for stakeholder involvement, rigour of development, applicability and editorial independence. CONCLUSIONS: Current guidelines for the management of acute paediatric asthma exacerbations have substantial deficits in important quality domains and provide limited and inconsistent guidance for severe exacerbations.

Procedural sedation programme minimising adverse events: a 3-year experience from a tertiary paediatric emergency department.

INTRODUCTION: A well-developed procedural sedation programme in the paediatric emergency department can minimise adverse events. We examined how adherence to current best evidence ensures safe delivery of paediatric sedation in a newly established tertiary paediatric hospital. METHODS: Our sedation service uses a robust provider training and privileging system, standardised policy and procedures and rigorous data collection all within an evidence-based clinical governance process. We examined sedation data from the first 3 years of operation. RESULTS: From July 2018 to May 2022, ketamine was used in 3388 of the 3405 sedations. The mean age of sedated children was 5.5 years (range 6 months to 17.8 years) and common indications were closed reduction of fractures and laceration repairs. A total of 148 (4.37%, 95% CI 3.68% to 5.06%) adverse events were documented, including 88 (2.59%, 95% CI 2.06% to 3.13%) cases of vomiting, 50 (1.48%, 95% CI 1.07% to 1.88%) cases related to airway and breathing with 40 (1.18%, 95% CI 0.82% to 1.54%) cases of oxygen desaturation, 6 (0.18%, 95% CI 0.04% to 0.32%) cases of laryngospasm, 4 (0.12%, 95% CI 0% to 0.23%) cases of apnoea. CONCLUSION: This study presents a large single-centre dataset on the use of intravenous ketamine in paediatric procedural sedation. Adhering to international standards and benchmarks for provider skills and training, drug administration and monitoring facilities, with a strict clinical governance process, optimizes patient safety.

Core outcomes and factors influencing the experience of care for children with severe acute exacerbations of asthma: a qualitative study.

OBJECTIVE: To identify the outcomes considered important, and factors influencing the patient experience, for parents and caregivers of children presenting to hospital with a severe acute exacerbation of asthma. This work contributes to the outcome-identification process in developing a core outcome set (COS) for future clinical trials in children with severe acute asthma. DESIGN: A qualitative study involving semistructured interviews with parents and caregivers of children who presented to hospital with a severe acute exacerbation of asthma. SETTING: Hospitals in 12 countries associated with the global Pediatric Emergency Research Networks, including high-income and middle-income countries. Interviews were conducted face-to-face, by teleconference/video-call, or by phone. FINDINGS: Overall, there were 54 interviews with parents and caregivers; 2 interviews also involved the child. Hospital length of stay, intensive care unit or high-dependency unit (HDU) admission, and treatment costs were highlighted as important outcomes influencing the patient and family experience. Other potential clinical trial outcomes included work of breathing, speed of recovery and side effects. In addition, the patient and family experience was impacted by decision-making leading up to seeking hospital care, transit to hospital, waiting times and the use of intravenous treatment. Satisfaction of care was related to communication with clinicians and frequent reassessment. CONCLUSIONS: This study provides insight into the outcomes that parents and caregivers believe to be the most important to be considered in the process of developing a COS for the treatment of acute severe exacerbations of asthma.

Omental infarction in an overweight child: conservative treatment is a safe approach.

A previously healthy but overweight (body mass index (BMI) of 24.4) adolescent boy presented with fever and significant right-sided abdominal pain. An abdominal ultrasound scan revealed an omental infarction (OI), which was treated conservatively. OI has been described in overweight teenage children with abdominal trauma but can be missed if not considered. A missed diagnosis could result in an unnecessary laparotomy or laparoscopic surgery. Although CT is the gold standard for diagnosis, ultrasonography is an effective approach to identifying OI in children. The benefits of early diagnosis of OI by abdominal ultrasound include a shorter hospital stay and a reduction in unnecessary investigations and surgery.

Acute paediatric asthma treatment in the prehospital setting: a retrospective observational study.

OBJECTIVES: To describe the incidence of and patterns of 'escalated care' (care in addition to standard treatment with systemic corticosteroids and inhaled bronchodilators) for children receiving prehospital treatment for asthma. DESIGN: Retrospective observational study. SETTING: State-wide ambulance service data (Ambulance Victoria in Victoria, Australia, population 6.5 million) PARTICIPANTS: Children aged 1-17 years and given a final diagnosis of asthma by the treating paramedics and/or treated with inhaled bronchodilators from 1 July 2019 to 30 June 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: We classified 'escalation of care' as parenteral administration of epinephrine, or provision of respiratory support. We compared clinical, demographic and treatments administered between those receiving and not receiving escalation of care. RESULTS: Paramedics attended 1572 children with acute exacerbations of asthma during the 1 year study period. Of these, 22 (1.4%) had escalated care, all receiving parenteral epinephrine. Patients with escalated care were more likely to be older, had previously required hospital admission for asthma and had severe respiratory distress at initial assessment.Of 1307 children with respiratory status data available, at arrival to hospital, the respiratory status of children had improved overall (normal/mild respiratory distress at initial assessment 847 (64.8%), normal/mild respiratory distress at hospital arrival 1142 (87.4%), p<0.0001). CONCLUSIONS: Most children with acute exacerbations of asthma did not receive escalated therapy during their pre-hospital treatment from ambulance paramedics. Most patients were treated with inhaled bronchodilators only and clinically improved by the time they arrived in hospital.

International perspective on research priorities and outcome measures of importance in the care of children with acute exacerbations of asthma: a qualitative interview study.

BACKGROUND: Acute exacerbations of asthma are common in children, however, treatment decisions for severe exacerbations are challenging due to a lack of robust evidence. In order to create more robust research, a core set of outcome measures needs to be developed. In developing these outcomes, it is important to understand the views of clinicians who care for these children in particular, views that relate to outcome measures and research priorities. METHODS: To determine the views of clinicians, a total of 26 semistructured interviews based on the theoretical domains framework were conducted. These included experienced clinicians from emergency, intensive care and inpatient paediatrics across 17 countries. The interviews were recorded, and later transcribed. All data analyses were conducted in Nvivo by using thematic analysis. RESULTS: The length of stay in hospital and patient-focused parameters, such as timing to return to school and normal activity, were the most frequently highlighted outcome measures, with clinicians identifying the need to achieve a consensus on key core outcome measure sets. Most research questions focused on understanding the best treatment options, including the role of novel therapies and respiratory support. CONCLUSION: Our study provides an insight into what research questions and outcome measures clinicians view as important. In addition, information on how clinicians define asthma severity and measure treatment success will assist with methodological design in future trials. The current findings will be used in parallel with a further Paediatric Emergency Research Network study focusing on the child and family perspectives and will contribute to develop a core outcome set for future research.

Positional and between quarter differences in physical demands of elite female field hockey players during international matches.

Objectives: The main aims of this study were to examine whether there are positional- and between-quarter differences in the physical load of elite female field hockey players during international matches. Methods: Twenty-three international female field hockey players were equipped with Global Positioning Systems devices, while competing over nine international matches. Results: Players covered a mean relative distance, relative player load, and distance covered in the form of low-, moderate-, and high intensity activities of 107.5 m/min, 10.3 AU/min, 41.6%, 47.9%, and 9.9%, respectively. Defenders achieved the lowest relative Player load (ES: 0.8-1.1) and greatest distance covered in the form of low intensity activities compared to Midfielders and Forwards (ES: 0.8-0.9). Forwards and Midfielders covered significantly greater distance in the form of high intensity activity compared to Defenders (ES: 1.6-2.2). Significant reductions in relative distance, relative Player load, and moderate intensity activity are observed for all positions between Quarters 1-4 despite the availability of unlimited substitutions. However, players were able to maintain their high intensity activity throughout the match with no significant differences between Quarters 1-4. The majority of variables were higher (ES > 0.2) during Quarter 2 compared to Quarter 3, especially for Midfielders and Defenders. Conclusions: Current findings provide further evidence on the positional- and between-quarter external match load of international female field hockey players that coaches should consider when designing training programs and drills to better prepare players for match demands. The results also provide some insight into the fatigue experienced by players and the possible pacing strategies they employ during matches. These findings support the need for re-warm-ups and may further influence how coaches time their substitutions to enhance running performance in future.

Post-COVID mRNA vaccine myocarditis in children: report of two cases.

The SARS-COV-2 pandemic led to the development of several vaccinations to contain the disease. The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine was recommended on May 2021 for use in children above 12 years and older. The vaccine is safe, well tolerated and highly effective. Initial reports showed no serious adverse events; however, cases of myocarditis in young healthy male adolescents have been reported. We report two cases of myocarditis/perimyocarditis who presented with short history of chest pain following administration of the second dose of the MRN COVID-19 vaccine.

Reply to: Magnesium sulphate intravenously reduces tachycardia side-effects of ß2-agonists.

Intravenous magnesium sulphate reduces ß2-agonist induced tachycardia https://bit.ly/3pPnGKl.

Anti-IL-5 therapies for asthma.

BACKGROUND: This is the second update of previously published reviews in the Cochrane Library (2015, first update 2017). Interleukin-5 (IL-5) is the main cytokine involved in the proliferation, maturation, activation and survival of eosinophils, which cause airway inflammation and are a classic feature of asthma. Studies of monoclonal antibodies targeting IL-5 or its receptor (IL-5R) suggest they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function in appropriately selected patients, justifying their inclusion in the latest guidelines. OBJECTIVES: To compare the effects of therapies targeting IL-5 signalling (anti-IL-5 or anti-IL-5Rα) with placebo on exacerbations, health-related quality-of-life (HRQoL) measures and lung function in adults and children with chronic asthma, and specifically in those with eosinophilic asthma refractory to existing treatments. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers, manufacturers' websites, and reference lists of included studies. The most recent search was 7 February 2022. SELECTION CRITERIA: We included randomised controlled trials comparing mepolizumab, reslizumab and benralizumab versus placebo in adults and children with asthma. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by Cochrane. MAIN RESULTS: Seventeen studies on about 7600 participants met the inclusion criteria. Six used mepolizumab, five used reslizumab, and six used benralizumab. One study using benralizumab was terminated early due to sponsor decision and contributed no data. The studies were predominantly on people with severe eosinophilic asthma, which was similarly but variably defined. One was in children aged 6 to 17 years; nine others included children over 12 years but did not report results by age group separately. We deemed the overall risk of bias to be low, with all studies contributing data of robust methodology. We considered the certainty of the evidence for all comparisons to be high overall using the GRADE scheme, except for intravenous (IV) mepolizumab and subcutaneous (SC) reslizumab because these are not currently licensed delivery routes. The anti-IL-5 treatments assessed reduced rates of 'clinically significant' asthma exacerbation (defined by treatment with systemic corticosteroids for three days or more) by approximately half in participants with severe eosinophilic asthma on standard care (at least medium-dose inhaled corticosteroids (ICS)) with poorly controlled disease (either two or more exacerbations in the preceding year or Asthma Control Questionnaire (ACQ) score of 1.5 or more), except for reslizumab SC. The rate ratios for these effects were 0.45 (95% confidence interval (CI) 0.36 to 0.55; high-certainty evidence) for mepolizumab SC, 0.53 (95% CI 0.44 to 0.64; moderate-certainty evidence) for mepolizumab IV, 0.43 (95% CI 0.33 to 0.55; high-certainty evidence) for reslizumab IV, and 0.59 (95% CI 0.52 to 0.66; high-certainty evidence) for benralizumab SC. Non-eosinophilic participants treated with benralizumab also showed a significant reduction in exacerbation rates, an effect not seen with reslizumab IV, albeit in only one study. No data were available for non-eosinophilic participants treated with mepolizumab. There were improvements in validated HRQoL scores with all anti-IL-5 agents in severe eosinophilic asthma. This met the minimum clinically important difference (MCID) for the broader St. George's Respiratory Questionnaire (SGRQ; 4-point change) for benralizumab only, but the improvement in the ACQ and Asthma Quality of Life Questionnaire (AQLQ), which focus on asthma symptoms, fell short of the MCID (0.5 point change for both ACQ and AQLQ) for all of the interventions. The evidence for an improvement in HRQoL scores in non-eosinophilic participants treated with benralizumab and reslizumab was weak, but the tests for subgroup difference were negative. All anti-IL-5 treatments produced small improvements in mean pre-bronchodilator forced expiratory flow in one second (FEV1) of between 0.08 L and 0.15 L in eosinophilic participants, which may not be sufficient to be detected by patients. There were no excess serious adverse events with any anti-IL-5 treatment; in fact, there was a reduction in such events with benralizumab, likely arising from fewer asthma-related hospital admissions. There was no difference compared to placebo in adverse events leading to discontinuation with mepolizumab or reslizumab, but significantly more discontinued benralizumab than placebo, although the absolute numbers were small (42/2026 (2.1%) benralizumab versus 11/1227 (0.9%) placebo). The implications for efficacy or adverse events are unclear. AUTHORS' CONCLUSIONS: Overall this analysis supports the use of anti-IL-5 treatments as an adjunct to standard care in people with severe eosinophilic asthma and poor symptom control. These treatments roughly halve the rate of asthma exacerbations in this population. There is limited evidence for improved HRQoL scores and lung function, which may not meet clinically detectable levels. The studies did not report safety concerns for mepolizumab or reslizumab, or any excess serious adverse events with benralizumab, although there remains a question over adverse events significant enough to prompt discontinuation. Further research is needed on biomarkers for assessing treatment response, optimal duration and long-term effects of treatment, risk of relapse on withdrawal, non-eosinophilic patients, children (particularly under 12 years), comparing anti-IL-5 treatments to each other and, in patients meeting relevant eligibility criteria, to other biological (monoclonal antibody) therapies. For benralizumab, future studies should closely monitor rates of adverse events prompting discontinuation.

ANTECEDENTES: Esta la segunda actualización de una revisión publicada anteriormente en la Biblioteca Cochrane (2015, primera actualización en 2017). La interleucina 5 (IL­5) es la principal citoquina implicada en la proliferación, maduración, activación y supervivencia de los eosinófilos, que provocan la inflamación de las vías respiratorias y son una característica típica del asma. Los estudios sobre los anticuerpos monoclonales dirigidos a la IL­5 o a su receptor (IL­5R) indican que estos reducen las exacerbaciones del asma, mejoran la calidad de vida relacionada con la salud (CdVRS) y la función pulmonar en pacientes adecuadamente seleccionados, lo cual justifica su inclusión en las últimas guías. OBJETIVOS: Comparar los efectos de los tratamientos dirigidos a la señalización de la IL­5 (anti­IL­5 o anti­IL­5Rα) con placebo, con respecto a las exacerbaciones, las medidas de calidad de vida relacionada con la salud (CdVRS) y la función pulmonar en adultos y niños con asma crónica, y específicamente en los que presentan asma eosinofílica resistente a los tratamientos existentes. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en CENTRAL, MEDLINE, Embase, y en dos registros de ensayos clínicos, sitios web de fabricantes y listas de referencias de los estudios incluidos. La búsqueda más reciente se realizó el 7 de febrero de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados aleatorizados que compararon mepolizumab, reslizumab y benralizumab versus placebo en adultos y niños con asma. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión de forma independiente extrajeron los datos y analizaron los desenlaces mediante un modelo de efectos aleatorios. Se utilizaron los métodos estándar previstos por Cochrane. RESULTADOS PRINCIPALES: Diecisiete estudios con unos 7600 participantes cumplieron los criterios de inclusión. Seis administraron mepolizumab, cinco proporcionaron reslizumab y seis benralizumab. Un estudio que utilizó benralizumab finalizó antes de tiempo por decisión de los patrocinadores y no proporcionó datos. Los estudios se realizaron principalmente en personas con asma eosinofílica grave, que se definió de forma parecida aunque variable. Uno de ellos se realizó en niños de seis a 17 años; otros nueve incluyeron a niños mayores de 12 años, pero no informaron de los resultados por grupos de edad por separado. Se consideró que el riesgo general de sesgo fue bajo, ya que todos los estudios que aportaron datos tuvieron una metodología sólida. La certeza de la evidencia para todas las comparaciones fue en general alta al utilizar el método GRADE, con la excepción del mepolizumab intravenoso (IV) y subcutáneo (SC) porque se trata de vías de administración no autorizadas en la actualidad. Los tratamientos con inhibidores de la IL­5 evaluados redujeron las tasas de exacerbación del asma "clínicamente significativa" (definida por el tratamiento con corticosteroides sistémicos durante tres días o más) en aproximadamente la mitad de los participantes con asma eosinofílica grave que recibían atención estándar (al menos una dosis media de corticosteroides inhalados [CSI]) con un control deficiente de la enfermedad (dos o más exacerbaciones en el año anterior o una puntuación de 1,5 o más según el Asthma Control Questionnaire [ACQ]). Los cocientes de tasas para estos efectos fueron de 0,45 (intervalo de confianza [IC] del 95%: 0,36 a 0,55; evidencia de certeza alta) para mepolizumab SC, 0,53 (IC del 95%: 0,44 a 0,64; evidencia de certeza moderada) para mepolizumab IV, 0,43 (IC del 95%: 0,33 a 0,55; evidencia de certeza alta) para reslizumab IV y 0,59 (IC del 95%: 0,52 a 0,66; evidencia de certeza alta) para benralizumab SC. Los participantes que no presentaban asma eosinofílica tratados con benralizumab también mostraron una reducción significativa de las tasas de exacerbaciones, un efecto que no se observó con reslizumab IV, aunque solo en un estudio. No hubo datos sobre los participantes que no presentaban asma eosinofílica tratados con mepolizumab. Hubo mejorías moderadas en las puntuaciones validadas de la CdVRS con todos los inhibidores de la IL­5 en el asma eosinofílica grave. Se alcanzó la diferencia mínima clínicamente importante (DMCI) del George's Respiratory Questionnaire (SGRQ; cambio de 4 puntos) para benralizumab, pero la mejoría en el ACQ y el Asthma Quality of Life Questionnaire (AQLQ), que se centran en los síntomas del asma, no alcanzó la DMCI (cambio de 0,5 puntos tanto en el ACQ como en el AQLQ) para todas las intervenciones. La evidencia fue débil en cuanto a la mejoría en las puntuaciones de la CdVRS en los participantes que no presentaban asma eosinofílica tratados con benralizumab y reslizumab, pero los análisis de las diferencias de subgrupos obtuvieron resultados negativos. Todos los tratamientos con inhibidores de la IL­5 produjeron pequeñas mejorías en el flujo espiratorio forzado prebroncodilatador en un segundo (VEF1) de entre 0,08 y 0,15 l en los participantes con asma eosinofílica, las cuales podrían no ser suficientes para que los pacientes las detecten. No hubo un exceso de eventos adversos graves con ningún tratamiento inhibidor de la IL­5; de hecho, hubo una reducción de tales eventos con benralizumab, probablemente derivada de un menor número de ingresos hospitalarios relacionados con el asma. No hubo diferencias en comparación con placebo en los eventos adversos que provocaran la suspensión del tratamiento con mepolizumab o reslizumab, pero hubo significativamente más interrupciones con el benralizumab que con placebo, aunque los números absolutos fueron pequeños (42/2026 [2,1%] benralizumab versus 11/1227 [0,9%] placebo). No están claras las implicaciones con respecto a la eficacia o los eventos adversos. CONCLUSIONES DE LOS AUTORES: En general este análisis apoya la administración de los tratamientos inhibidores de la IL­5 como complemento a la atención estándar en las personas con asma eosinofílica grave y un control deficiente de los síntomas. Estos tratamientos reducen a cerca de la mitad la tasa de exacerbaciones del asma en esta población. Hay evidencia limitada de mejorías en las puntuaciones de la CdVRS y en la función pulmonar, aunque es posible que no alcancen niveles clínicamente detectables. Los estudios no informaron de problemas de seguridad con el mepolizumab ni el reslizumab, ni eventos adversos graves excesivos con benralizumab, aunque se mantiene la duda sobre qué eventos adversos son lo suficientemente significativos para la suspensión inmediata. Se necesitan estudios de investigación adicionales sobre los marcadores biológicos para evaluar la respuesta al tratamiento, la duración óptima y los efectos a largo plazo del tratamiento, el riesgo de recurrencia al retirarlo, los pacientes que no presentan asma eosinofílica, los niños (especialmente menores de 12 años), que comparen los tratamientos inhibidores de la IL­5 entre sí y, en pacientes que cumplan criterios de elegibilidad relevantes, con otros tratamientos biológicos (anticuerpos monoclonales). En el caso del benralizumab, los estudios futuros deben vigilar atentamente las tasas de eventos adversos que provocan la interrupción inmediata.

Paediatric early warning systems: not a simple answer to a complex question.

Paediatric early warning systems (PEWS) to reduce in-hospital mortality have been a laudable endeavour. Evaluation of their impact has rarely examined the internal validity of the components of PEWS in achieving desired outcomes. We highlight the assumptions made regarding the mode of action of PEWS and, as PEWS become more commonplace, this paper asks whether we really understand their function, process and outcome.

Diabetic ketoacidosis fluid management in children: systematic review and meta-analyses.

IMPORTANCE: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus, which may lead to significant morbidity and mortality. OBJECTIVES: To compare the safety and efficacy of liberalised versus conservative intravenous fluid regimens in the management of DKA in children. DATA SOURCE AND STUDY SELECTION: Databases from inception to January 2022: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials were included. Only randomised controlled trials (RCTs) that included children aged under 18 years were assessed. Two reviewers performed data assessment and extraction. DATA EXTRACTION AND SYNTHESIS: Three studies out of 1536 citations were included. MAIN OUTCOMES: The time to the recovery from the DKA; the frequency of paeditric intensive care unit (PICU) admissions; development of brain oedema; reduction in Glasgow Coma Scale (GCS); development of acute kidney injury and all-cause mortality. RESULTS: We included three RCTs (n=1457). No evidence of difference was noted in the GCS reduction (risk ratio (RR)=0.77, 95% CI 0.44 to 1.36) or development of brain oedema (RR=0.50, 95% CI 0.15 to 1.68). The time to recovery from DKA was longer in the conservative group (mean difference=1.42, 95% CI 0.28 to 2.56). Time to hospital discharge, adverse or serious adverse events were comparable in the two studied groups. CONCLUSION: There is no evidence from this meta-analysis that rate of fluid administration has any effect on adverse neurological and other outcomes or length of hospital stay.

Treatment patterns and frequency of key outcomes in acute severe asthma in children: a Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study.

RATIONALE: Severe acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only. OBJECTIVES: To identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma. METHODS: Retrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS). MEASUREMENTS AND MAIN RESULTS: Of 14 029 children (median age 3 (IQR 1-3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3-63.2 hours) than children without escalation 6.7 hours, IQR 3.5-16.3 hours; p<0.001). The most common treatment escalations were respiratory support alone (400; 2.9%, 95% CI 2.6% to 3.1%), parenteral bronchodilator treatment alone (380; 2.7%, 95% CI 2.5% to 3.0%) and both respiratory support and parenteral bronchodilator treatment (209; 1.5%, 95% CI 1.3% to 1.7%). Respiratory support was predominantly nasal high-flow therapy (99.0%). The most common intravenous medication regimens were: magnesium alone (50.4%), magnesium and aminophylline (24.6%) and magnesium and salbutamol (10.0%). CONCLUSIONS: Overall, 7.3% children with acute severe asthma received some form of escalated treatment, with 4.2% receiving parenteral bronchodilators and 4.3% respiratory support. There is wide variation treatment escalation.

Development, implementation and evaluation of an evidence-based paediatric early warning system improvement programme: the PUMA mixed methods study.

BACKGROUND: Paediatric mortality rates in the United Kingdom are amongst the highest in Europe. Clinically missed deterioration is a contributory factor. Evidence to support any single intervention to address this problem is limited, but a cumulative body of research highlights the need for a systems approach. METHODS: An evidence-based, theoretically informed, paediatric early warning system improvement programme (PUMA Programme) was developed and implemented in two general hospitals (no onsite Paediatric Intensive Care Unit) and two tertiary hospitals (with onsite Paediatric Intensive Care Unit) in the United Kingdom. Designed to harness local expertise to implement contextually appropriate improvement initiatives, the PUMA Programme includes a propositional model of a paediatric early warning system, system assessment tools, guidance to support improvement initiatives and structured facilitation and support. Each hospital was evaluated using interrupted time series and qualitative case studies. The primary quantitative outcome was a composite metric (adverse events), representing the number of children monthly that experienced one of the following: mortality, cardiac arrest, respiratory arrest, unplanned admission to Paediatric Intensive Care Unit, or unplanned admission to Higher Dependency Unit. System changes were assessed qualitatively through observations of clinical practice and interviews with staff and parents. A qualitative evaluation of implementation processes was undertaken. RESULTS: All sites assessed their paediatric early warning systems and identified areas for improvement. All made contextually appropriate system changes, despite implementation challenges. There was a decline in the adverse event rate trend in three sites; in one site where system wide changes were organisationally supported, the decline was significant (ß = -0.09 (95% CI: - 0.15, - 0.05); p = < 0.001). Changes in trends coincided with implementation of site-specific changes. CONCLUSIONS: System level change to improve paediatric early warning systems can bring about positive impacts on clinical outcomes, but in paediatric practice, where the patient population is smaller and clinical outcomes event rates are low, alternative outcome measures are required to support research and quality improvement beyond large specialist centres, and methodological work on rare events is indicated. With investment in the development of alternative outcome measures and methodologies, programmes like PUMA could improve mortality and morbidity in paediatrics and other patient populations.

Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection (BATCH): protocol for a randomised controlled trial.

INTRODUCTION: Procalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in the National Health Service (NHS). Studies mainly in adults show that using PCT to guide clinicians may reduce antibiotic use, reduce hospital stay, with no associated adverse effects such as increased rates of hospital re-admission, incomplete treatment of infections, relapse or death. A review conducted for National Institute for Health and Care Excellence recommends further research on PCT testing to guide antibiotic use in children. METHODS AND ANALYSIS: Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection is a multi-centre, prospective, two-arm, individually Randomised Controlled Trial (RCT) with a 28-day follow-up and internal pilot. The intervention is a PCT-guided algorithm used in conjunction with best practice. The control arm is best practice alone. We plan to recruit 1942 children, aged between 72 hours and up to 18 years old, who are admitted to the hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection. Coprimary outcomes are duration of antibiotic use and a composite safety measure. Secondary outcomes include time to switch from broad to narrow spectrum antibiotics, time to discharge, adverse drug reactions, health utility and cost-effectiveness. We will also perform a qualitative process evaluation. Recruitment commenced in June 2018 and paused briefly between March and May 2020 due to the COVID-19 pandemic. ETHICS AND DISSEMINATION: The trial protocol was approved by the HRA and NHS REC (North West Liverpool East REC reference 18/NW/0100). We will publish the results in international peer-reviewed journals and present at scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN11369832.

Priorities for child health research across the UK and Ireland.

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.

Estimating insertion length of umbilical arterial and venous catheters in newborn infants: time for change.

BACKGROUND: Umbilical catheters are inserted through the umbilical artery or vein at birth and are crucial in neonatal care. There are several different methods of estimating adequate insertion length of umbilical catheters based on one of two hypotheses; that the insertion length of the UC is correlated to either the infant's birth weight or an external length measurement. AIM: To review the published literature on methods of estimating insertion lengths of umbilical arterial catheters (UACs) and umbilical venous catheters (UVCs) in newborn infants. METHODS: Systematic search on Medline was undertaken using keywords for relevant papers up to March 2019. Papers were selected by manual search of titles and abstracts. RESULTS: Formulae for predicting umbilical catheter insertion length are unreliable, particularly for UVCs. There is also conflicting evidence around whether birth weight-based formulae are more reliable than external length-based formulae. Studies comparing various methods to determine their efficacy to show that current formulae have a low accuracy for determining both UVC and UAC positioning. CONCLUSIONS: Current formulae for estimating insertion length of umbilical catheters are not fit for purpose. We propose a new observational study which uses a new external length measurement, the sternal notch to umbilicus length, to develop a more reliable formula for the insertion of UVC and UAC to an adequate length.

Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial.

Importance: The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear. Objective: To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days. Design, Setting, and Participants: Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019. Interventions: Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401). Main Outcomes and Measures: The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates. Results: Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -∞ to 7.4%]; P value for interaction = .73). Conclusions and Relevance: Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings. Trial Registration: ISRCTN Identifier: ISRCTN76888927.

Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT.

BACKGROUND: Data are limited regarding the optimal dose and duration of amoxicillin treatment for community-acquired pneumonia in children. OBJECTIVES: To determine the efficacy, safety and impact on antimicrobial resistance of shorter (3-day) and longer (7-day) treatment with amoxicillin at both a lower and a higher dose at hospital discharge in children with uncomplicated community-acquired pneumonia. DESIGN: A multicentre randomised double-blind 2 × 2 factorial non-inferiority trial in secondary care in the UK and Ireland. SETTING: Paediatric emergency departments, paediatric assessment/observation units and inpatient wards. PARTICIPANTS: Children aged > 6 months, weighing 6-24 kg, with a clinical diagnosis of community-acquired pneumonia, in whom treatment with amoxicillin as the sole antibiotic was planned on discharge. INTERVENTIONS: Oral amoxicillin syrup at a dose of 35-50 mg/kg/day compared with a dose of 70-90 mg/kg/day, and 3 compared with 7 days' duration. Children were randomised simultaneously to each of the two factorial arms in a 1 : 1 ratio. MAIN OUTCOME MEASURES: The primary outcome was clinically indicated systemic antibacterial treatment prescribed for respiratory tract infection (including community-acquired pneumonia), other than trial medication, up to 28 days after randomisation. Secondary outcomes included severity and duration of parent/guardian-reported community-acquired pneumonia symptoms, drug-related adverse events (including thrush, skin rashes and diarrhoea), antimicrobial resistance and adherence to trial medication. RESULTS: A total of 824 children were recruited from 29 hospitals. Ten participants received no trial medication and were excluded. Participants [median age 2.5 (interquartile range 1.6-2.7) years; 52% male] were randomised to either 3 (n = 413) or 7 days (n = 401) of trial medication at either lower (n = 410) or higher (n = 404) doses. There were 51 (12.5%) and 49 (12.5%) primary end points in the 3- and 7-day arms, respectively (difference 0.1%, 90% confidence interval -3.8% to 3.9%) and 51 (12.6%) and 49 (12.4%) primary end points in the low- and high-dose arms, respectively (difference 0.2%, 90% confidence interval -3.7% to 4.0%), both demonstrating non-inferiority. Resolution of cough was faster in the 7-day arm than in the 3-day arm for cough (10 days vs. 12 days) (p = 0.040), with no difference in time to resolution of other symptoms. The type and frequency of adverse events and rate of colonisation by penicillin-non-susceptible pneumococci were comparable between arms. LIMITATIONS: End-of-treatment swabs were not taken, and 28-day swabs were collected in only 53% of children. We focused on phenotypic penicillin resistance testing in pneumococci in the nasopharynx, which does not describe the global impact on the microflora. Although 21% of children did not attend the final 28-day visit, we obtained data from general practitioners for the primary end point on all but 3% of children. CONCLUSIONS: Antibiotic retreatment, adverse events and nasopharyngeal colonisation by penicillin-non-susceptible pneumococci were similar with the higher and lower amoxicillin doses and the 3- and 7-day treatments. Time to resolution of cough and sleep disturbance was slightly longer in children taking 3 days' amoxicillin, but time to resolution of all other symptoms was similar in both arms. FUTURE WORK: Antimicrobial resistance genotypic studies are ongoing, including whole-genome sequencing and shotgun metagenomics, to fully characterise the effect of amoxicillin dose and duration on antimicrobial resistance. The analysis of a randomised substudy comparing parental electronic and paper diary entry is also ongoing. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76888927, EudraCT 2016-000809-36 and CTA 00316/0246/001-0006. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 60. See the NIHR Journals Library website for further project information.

Pneumonia (an acute lung infection) is a common diagnosis in young children worldwide. To cure this, some children are given antibiotics, but we do not currently know the best amount (dose) to give and the ideal number of days (duration) of treatment. Taking antibiotics causes changes in bacteria, making them more resistant to treatment. This may be affected by the dose and duration, and is important because resistant bacteria are harder to treat and could spread to other people. Amoxicillin is the most common antibiotic treatment for children with pneumonia. CAP-IT (Community-Acquired Pneumonia: a protocol for a randomIsed controlled Trial) tested if lower doses and shorter durations of amoxicillin are as good as higher doses and longer durations, and whether or not these affect the presence of resistant bacteria. In total, 824 children in the UK and Ireland with pneumonia participated. They received either high- or low-dose amoxicillin for 3 or 7 days following discharge from hospital. To ensure that neither doctors nor parents were influenced by knowing which group a child was in, we included dummy drugs (placebo). We measured how often children were given more antibiotics for respiratory infections in the 4 weeks after starting the trial medicine. To check for resistant bacteria, a nose swab was collected before starting treatment and again after 4 weeks. One in every eight participating children was given additional antibiotics. We found no important difference in this proportion between 3 days and 7 days of amoxicillin treatment, or between lower or higher doses. Although children's coughs took slightly longer to go away when they received only 3 days of antibiotics, rash was reported slightly more often in children taking 7 days of antibiotics. There was no effect of dose of amoxicillin on any of the symptom measurements. No effect of duration of treatment or dose was observed for antibiotic resistance in bacteria living in the nose and throat.

The integral role of the clinical pharmacist in drug-assisted intubation at a newly established children's major trauma center.

This commentary outlines how the clinical pharmacist can support the safe administration of emergency medications in trauma anesthesia for seriously injured children. Promoting the professional development of the clinical pharmacist provided an opportunity to strengthen a key step in our trauma care pathway. We describe the implementation of this process in a new hospital, which was to become the designated children's trauma center for an entire country. Although the literature documents the use of pharmacists in emergency intubation, ours was a unique set of circumstances, where empowering the pharmacist in frontline clinical care provided additional quality assurance for rapid sequence induction and intubation in trauma. Medical simulation was a core part of socializing the advanced clinical practice role of pharmacy within the trauma team. It was our experience that the pharmacist helps to promote confidence and decision making among other members of the trauma team.