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.

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.

Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews.

BACKGROUND: Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management. OBJECTIVES: Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta2-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'. MAIN RESULTS: We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high. AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta2-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.

Review article: A primer for clinical researchers in the emergency department: Part VI. Measuring what matters: Core outcome sets in emergency medicine research.

In this series we address important topics for clinicians who participate in research as part of their work in the ED. The overarching goal of clinical research is to improve care and determine which treatment is best. Yet, defining and measuring outcomes - what is 'best' - can be one of the most difficult steps in the design of a study, in particular when answers to research questions cannot be captured in simple binary results. This article addresses how to choose outcome measures and highlights the increasingly important concept of core outcome sets.

Oral steroids for hearing loss associated with otitis media with effusion in children aged 2-8 years: the OSTRICH RCT.

BACKGROUND: Children with hearing loss associated with otitis media with effusion (OME) are commonly managed through surgical intervention, hearing aids or watchful waiting. A safe, inexpensive, effective medical treatment would enhance treatment options. Small, poorly conducted trials have found a short-term benefit from oral steroids. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of a 7-day course of oral steroids in improving hearing at 5 weeks in children with persistent OME symptoms and current bilateral OME and hearing loss demonstrated by audiometry. DESIGN: Double-blind, individually randomised, placebo-controlled trial. SETTING: Ear, nose and throat outpatient or paediatric audiology and audiovestibular medicine clinics in Wales and England. PARTICIPANTS: Children aged 2-8 years, with symptoms of hearing loss attributable to OME for at least 3 months, a diagnosis of bilateral OME made on the day of recruitment and audiometry-confirmed hearing loss. INTERVENTIONS: A 7-day course of oral soluble prednisolone, as a single daily dose of 20 mg for children aged 2-5 years or 30 mg for 6- to 8-year-olds, or matched placebo. MAIN OUTCOME MEASURES: Acceptable hearing at 5 weeks from randomisation. Secondary outcomes comprised acceptable hearing at 6 and 12 months, tympanometry, otoscopic findings, health-care consultations related to OME and other resource use, proportion of children who had ventilation tube (grommet) surgery at 6 and 12 months, adverse effects, symptoms, functional health status, health-related quality of life, short- and longer-term cost-effectiveness. RESULTS: A total of 389 children were randomised. Satisfactory hearing at 5 weeks was achieved by 39.9% and 32.8% in the oral steroid and placebo groups, respectively (absolute difference of 7.1%, 95% confidence interval -2.8% to 16.8%; number needed to treat = 14). This difference was not statistically significant. The secondary outcomes were consistent with the picture of a small or no benefit, and we found no subgroups that achieved a meaningful benefit from oral steroids. The economic analysis showed that treatment with oral steroids was more expensive and accrued fewer quality-adjusted life-years than treatment as usual. However, the differences were small and not statistically significant, and the sensitivity analyses demonstrated large variation in the results. CONCLUSIONS: OME in children with documented hearing loss and attributable symptoms for at least 3 months has a high rate of spontaneous resolution. Discussions about watchful waiting and other interventions will be enhanced by this evidence. The findings of this study suggest that any benefit from a short course of oral steroids for OME is likely to be small and of questionable clinical significance, and that the treatment is unlikely to be cost-effective and, therefore, their use cannot be recommended. FUTURE WORK: Studies exploring optimal approaches to sharing natural history data and enhancing shared decision-making are needed for this condition. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49798431 and EudraCT 2012-005123-32. 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. 22, No. 61. See the NIHR Journals Library website for further project information.

Defining significant childhood illness and injury in the Emergency Department: a consensus of UK and Ireland expert opinion.

BACKGROUND: Clarifying whether paediatric early warning scores (PEWS) accurately predict significant illness is a research priority for UK and Ireland paediatric emergency medicine (EM). However, a standardised list of significant conditions to benchmark these scores does not exist. OBJECTIVES: To establish standardised significant illness endpoints for use in determining the performance accuracy of PEWS and safety systems in emergency departments (ED), using a consensus of expert opinion in the UK and Ireland. DESIGN: Between July 2017 and February 2018, three online Delphi rounds established a consensus on 'significant' clinical conditions, derived from a list of common childhood illness/injury ED presentations. Conditions warranting acute hospital admission in the opinion of the respondent were defined as 'significant', using a 5-point Likert scale. The consensus was a priori ≥80% (positive or negative). 258 clinical conditions were tested. PARTICIPANTS AND SETTINGS: Eligible participants were consultants in acute or EM paediatrics, or adult EM, accessed via 53 PERUKI (Paediatric Emergency Research in the UK and Ireland)'s research collaborative sites, and 27 GAPRUKI (General and Adolescent Paediatric Research in the UK and Ireland)'s sites, 17 of which overlap with PERUKI. MAIN OUTCOME MEASURES: To create a list of conditions regarded as 'significant'with ≥80% expert consensus. RESULTS: 43 (68%) of 63 PERUKI and GAPRUKI sites responded; 295 experts were invited to participate. Participants in rounds 1, 2 and 3 were 223 (76%), 177 (60%) and 148 (50%), respectively; 154 conditions reached positive consensus as 'significant'; 1 condition reached a negative consensus (uncomplicated Henoch-Schönlein purpura); and 37 conditions achieved non-consensus. CONCLUSIONS: A list of significant childhood conditions has been created using UK and Irish expert consensus, for research purposes, for the first time. This will be used as the benchmark endpoint list for future research into PEWS/safety systems performance in EDs.

Acute severe asthma.

Acute exacerbations of asthma are very common reasons for a presentation to emergency departments. This paper focuses on defining the high-risk group, consideration of the concept of phenotypes of acute asthma, the assessment of severe and life-threatening exacerbations and an emphasis on the management of the more severe end of the exacerbation severity. A number of evidence-based guidelines exist throughout the world and are all slightly different. This reflects the poor evidence base for some of those recommendations. Thus, a large variation of treatment drugs, doses and regimen are used and clearly not standardised. This paper aims to present a summary of the best evidence and discuss some of these controversies. The most important aspect of treating an exacerbation of acute asthma is to review regularly and assess response to treatment. Severe and life-threatening episodes should be treated with early use of intravenous treatment in a stepwise manner following the local guidelines. Non-invasive ventilation and high flow nasal cannulae delivery of oxygen in the emergency department are evolving modalities, but evidence for their use is currently limited.

Teaching pediatric communication skills to medical students.

BACKGROUND: Delivering effective clinical pediatric communication skills training to undergraduate medical students is a distinct and important challenge. Pediatric-specific communication skills teaching is complex and under-researched. We report on the development of a scenario-based pediatric clinical communication skills program as well as students' assessment of this module. METHODS: We designed a pediatric clinical communication skills program and delivered it five times during one academic year via small-group teaching. Students were asked to score the workshop in eight domains (learning objectives, complexity, interest, competencies, confidence, tutors, feedback, and discussion) using 5-point Likert scales, along with free text comments that were grouped and analyzed thematically, identifying both the strengths of the workshop and changes suggested to improve future delivery. RESULTS: Two hundred and twenty-one of 275 (80%) student feedback forms were returned. Ninety-six percent of students' comments were positive or very positive, highlighting themes such as the timing of teaching, relevance, group sizes, and the use of actors, tutors, and clinical scenarios. CONCLUSION: Scenario-based teaching of clinical communication skills is positively received by students. Studies need to demonstrate an impact on practice, performance, development, and sustainability of communications training.