Variability of outcome measures in trials of intravenous therapy in acute severe paediatric asthma: a systematic review.

OBJECTIVE: To determine the variability of primary and secondary outcomes used in trials of intravenous bronchodilators in children with acute severe paediatric asthma. METHODS: Systematic search of MEDLINE, EMBASE, Cochrane CENTRAL and the WHO International Clinical Trials Registry Platform for randomised trials in children (less than18 years) with acute severe paediatric asthma comparing intravenous bronchodilator therapy to another treatment. Initial search was performed on 7 January 2016 with an updated search performed on 6 September 2018. Primary and secondary outcomes were collated. RESULTS: We identified 35 published papers and four registered study protocols. 56 primary outcomes were found, the most common being a clinical asthma score (23/56; 41%). Other identified primary outcomes included bedside tests of respiratory function (11/56; 20%) and measures of length of stay (9/56; 16%). There were a total of 60 different secondary outcomes, the most common were various length of stay measures (24/60; 40%) and adverse events (11/60; 18%). CONCLUSION: Studies comparing intravenous treatment modalities for children with acute severe paediatric asthma exhibit great variation in the type, number and timing of outcome measures used. There are no patient or family-specific outcomes reported. There is a need to develop international consensus. TRIAL REGISTRATION NUMBER: CRD42017055331.

The role of magnesium sulfate in acute asthma: does route of administration make a difference?

PURPOSE OF REVIEW: The role of magnesium sulfate (MgSO4) in the treatment of acute asthma is not clear. Four recent systematic reviews suggest a limited role of intravenous (i.v.) and inhaled nebulized treatment. The purpose of this review is to summarize the current literature, focus on two recent large multicenter randomized controlled trials, and discuss future research directions. RECENT FINDINGS: The Magnesium Nebulized Trial In Children (MAGNETIC) trial has shown little benefit to routine use of nebulized MgSO4 in children with acute asthma, but there may be a benefit in those with severe exacerbations and a shorter duration of symptoms. The 3Mg trial has shown no role for nebulized MgSO4 in adults and, at best a limited role for i.v. MgSO4 in only the most severe exacerbations. This is the only study with direct comparison of nebulized and i.v. MgSO4. SUMMARY: MgSO4 has a role in severe exacerbations of acute asthma and there is no evidence of benefit outside this clinical situation. Both nebulized and i.v. treatments are well tolerated and inexpensive. In adults, the most effective route of administration is i.v. There are no direct comparison studies in children. Further research should focus on more severe exacerbations.

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.

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.

Paediatric pneumonia or empyema and prior antibiotic use in primary care: a case-control study.

OBJECTIVES: To investigate the association between hospital presentation for paediatric pneumonia or empyema and prior antibiotic use for respiratory tract infection (RTI). METHODS: Case-control study of children aged 6 months to 16 years presenting to hospital with radiographic evidence of pneumonia or empyema and a history of general practitioner (GP) consultation for the index illness. Cases were recruited from seven hospitals in South Wales between October 2008 and December 2009. Controls were children from the same age group who were diagnosed with an uncomplicated RTI in general practice in the same area and at a similar time of year. Primary data were collected from carers by a self-complete questionnaire, with a subsample compared against general practice records. RESULTS: We recruited 89 eligible cases and 166 eligible controls. Cases were less likely than controls to have been prescribed antibiotics at the first GP consultation for the index illness [odds ratio (OR) 0.53; 95% confidence interval (95% CI) 0.31-0.90]. Stratified analyses revealed that this association was limited to children who consulted a GP <3 days after illness onset (OR 0.23; 95% CI 0.10-0.50). Cases were also less likely to have taken antibiotics before the date of index hospital presentation, but this finding was not statistically significant after adjustment for confounding factors (adjusted OR 0.84; 95% CI 0.47-1.49). CONCLUSIONS: Antibiotics prescribed at the first GP consultation for an RTI may protect against subsequent hospital presentation for pneumonia or empyema in some children. Given the strong rationale against unnecessary antibiotic prescribing, further research is needed to identify which children are most likely to benefit from early antibiotic treatment.

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.

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.

Rebound stridor in children with croup after nebulised adrenaline: does it really exist?

Rebound stridor after the use of nebulised adrenaline does not exist http://ow.ly/aoOd30o5lEo.

Gastro-oesophageal reflux is not a major cause of brief resolved unexplained events in infants.

Although it is often stated that gastro-oesophageal reflux is the most common cause of a brief resolved unexplained event or apparent life-threatening event, there are very few data to support the hypothesis of cause and effect http://bit.ly/2FjknUy.

Efficacy, safety and impact on antimicrobial resistance of duration and dose of amoxicillin treatment for young children with Community-Acquired Pneumonia: a protocol for a randomIsed controlled Trial (CAP-IT).

INTRODUCTION: Community-acquired pneumonia (CAP) is a common indication for antibiotic treatment in young children. Data are limited regarding the ideal dose and duration of amoxicillin, leading to practice variation which may impact on treatment failure and antimicrobial resistance (AMR). Community-Acquired Pneumonia: a randomIsed controlled Trial (CAP-IT) aims to determine the optimal amoxicillin treatment strategies for CAP in young children in relation to efficacy and AMR. METHODS AND ANALYSIS: The CAP-IT trial is a multicentre, randomised, double-blind, placebo-controlled 2×2 factorial non-inferiority trial of amoxicillin dose and duration. Children are enrolled in paediatric emergency and inpatient environments, and randomised to receive amoxicillin 70-90 or 35-50 mg/kg/day for 3 or 7 days following hospital discharge. The primary outcome is systemic antibacterial treatment for respiratory tract infection (including CAP) other than trial medication up to 4 weeks after randomisation. Secondary outcomes include adverse events, severity and duration of parent-reported CAP symptoms, adherence and antibiotic resistance. The primary analysis will be by intention to treat. Assuming a 15% primary outcome event rate, 8% non-inferiority margin assessed against an upper one-sided 95% CI, 90% power and 15% loss to follow-up, 800 children will be enrolled to demonstrate non-inferiority for the primary outcome for each of duration and dose. ETHICS AND DISSEMINATION: The CAP-IT trial and relevant materials were approved by the National Research Ethics Service (reference: 16/LO/0831; 30 June 2016). The CAP-IT trial results will be published in peer-reviewed journals, and in a report published by the National Institute for Health Research Health Technology Assessment programme. Oral and poster presentations will be given to national and international conferences, and participating families will be notified of the results if they so wish. Key messages will be constructed in partnership with families, and social media will be used in their dissemination. TRIAL REGISTRATION NUMBER: ISRCTN76888927, EudraCT2016-000809-36.

A cross-sectional survey of complementary and alternative medicine use by children and adolescents attending the University Hospital of Wales.

BACKGROUND: A high prevalence of CAM use has been documented worldwide in children and adolescents with chronic illnesses. Only a small number of studies, however, have been conducted in the United Kingdom. The primary aim of this study was to examine the use of CAM by children and adolescents with a wide spectrum of acute and chronic medical problems in a tertiary children's hospital in Wales. METHODS: Structured personal interviews of 100 inpatients and 400 outpatients were conducted over a 2-month period in 2004. The yearly and monthly prevalence of CAM use were assessed and divided into medicinal and non-medicinal therapies. This use was correlated with socio-demographic factors. RESULTS: There were 580 patients approached to attain 500 completed questionnaires. The use of at least one type of CAM in the past year was 41% (95% CI 37-46%) and past month 26% (95% CI 23-30%). The yearly prevalence of medicinal CAM was 38% and non-medicinal 12%. The users were more likely to have parents that were tertiary educated (mother: OR = 2.3, 95%CI 1.6-3.3) and a higher family income (Pearson chi-square for trend = 14.3, p < 0.001). The most common medicinal types of CAM were non-prescribed vitamins and minerals (23%) and herbal therapies (10%). Aromatherapy (5%) and reflexology (3%) were the most prevalent non-medicinal CAMs. None of the inpatient medical records documented CAM use in the past month. Fifty-two percent of medicinal and 38% of non-medicinal CAM users felt their doctor did not need to know about CAM use. Sixty-six percent of CAM users did not disclose the fact to their doctor. Three percent of all participants were using herbs and prescription medicines concurrently. CONCLUSION: There is a high prevalence of CAM use in our study population. Paediatricians need to ensure that they ask parents and older children about their CAM usage and advise caution with regard to potential interactions.CAM is a rapidly expanding industry that requires further evidence-based research to provide more information on the effectiveness and safety of many CAM therapies. Statutory or self-regulation of the different segments of the industry is important. Integration of CAM with allopathic western medicine through education and better communication is slowly progressing.

A survey of facilitators and barriers to recruitment to the MAGNETIC trial.

BACKGROUND: Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. METHODS: MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from -3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (-3 to -1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. RESULTS: The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. CONCLUSIONS: This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting. TRIAL REGISTRATION: ISRCTN, ISRCTN81456894 . Registered on 15 November 2007.

Variation in treatment of acute childhood wheeze in emergency departments of the United Kingdom and Ireland: an international survey of clinician practice.

OBJECTIVE: National clinical guidelines for childhood wheeze exist, yet despite being one of the most common reasons for childhood emergency department (ED) attendance, significant variation in practice occurs in other settings. We, therefore, evaluated practice variations of ED clinicians in the UK and Ireland. DESIGN: Two-stage survey undertaken in March 2013. Stage one examined department practice and stage two assessed ED consultant practice in acute childhood wheeze. Questions interrogated pharmacological and other management strategies, including inhaled and intravenous therapies. SETTING AND PARTICIPANTS: Member departments of Paediatric Emergency Research in the United Kingdom and Ireland and ED consultants treating children with acute wheeze. RESULTS: 30 EDs and 183 (81%) clinicians responded. 29 (97%) EDs had wheeze guidelines and 12 (40%) had care pathways. Variation existed between clinicians in dose, timing and frequency of inhaled bronchodilators across severities. When escalating to intravenous bronchodilators, 99 (54%) preferred salbutamol first line, 52 (28%) magnesium sulfate (MgSO4) and 27 (15%) aminophylline. 87 (48%) administered intravenous bronchodilators sequentially and 30 (16%) concurrently, with others basing approach on case severity. 146 (80%) continued inhaled therapy after commencing intravenous bronchodilators. Of 170 who used intravenous salbutamol, 146 (86%) gave rapid boluses, 21 (12%) a longer loading dose and 164 (97%) an ongoing infusion, each with a range of doses and durations. Of 173 who used intravenous MgSO4, all used a bolus only. 41 (24%) used non-invasive ventilation. CONCLUSIONS: Significant variation in ED consultant management of childhood wheeze exists despite the presence of national guidance. This reflects the lack of evidence in key areas of childhood wheeze and emphasises the need for further robust multicentre research studies.

Why some children hospitalized for pneumonia do not consult with a general practitioner before the day of hospitalization.

BACKGROUND: Early consultation in primary care may provide an opportunity for early intervention in children developing pneumonia, but little is known about why some children do not consult a general practitioner (GP) before hospitalization. OBJECTIVES: To identify differences between children who consulted a GP and children who did not consult a GP before the day of hospital presentation with pneumonia or empyema. METHODS: Carers of children aged six months to 16 years presenting to hospital with pneumonia or empyema completed a questionnaire, with a subset participating in an interview to identify physical, organizational and psychological barriers to consultation. Responses from those who had consulted a GP before the day of hospital presentation were compared with those who had not on a range of medical, social and environmental variables. RESULTS: Fifty seven (38%) of 151 participants had not consulted a GP before the day of hospital presentation. On multivariate analysis, illness duration ≥ 3 days (odds ratio [OR] 4.36, 95% confidence interval [CI]: 1.67-11.39), prior antibiotic use (OR: 10.35, 95% CI: 2.16-49.55) and home ownership (OR: 3.17, 95% CI: 1.07-9.37) were significantly associated with early GP consultation (P < 0.05). Interviews with 28 carers whose children had not seen a GP before the day of presentation revealed that most had not considered it and/or did not think their child's initial symptoms were serious or unusual; 11 (39.3%) had considered consulting a GP but reported barriers to access. CONCLUSION: Lack of early GP consultation was strongly associated with rapid evolution of pneumonia.

Carers' perspectives on the presentation of community-acquired pneumonia and empyema in children: a case series.

OBJECTIVE: To describe carers' perceptions of the development and presentation of community-acquired pneumonia or empyema in their children. DESIGN: Case series. SETTING: Seven hospitals with paediatric inpatient units in South Wales, UK. PARTICIPANTS: Carers of 79 children aged 6 months to 16 years assessed in hospital between October 2008 and September 2009 with radiographic, community-acquired pneumonia or empyema. METHODS: Carers were recruited in hospital and participated in a structured face-to-face or telephone interview about the history and presenting features of their children's illnesses. Responses to open questions were initially coded very finely and then grouped into common themes. Cases were classified into two age groups: 3 or more years and under 3 years. RESULTS: The reported median duration of illness from onset until the index hospital presentation was 4 days (IQR 2-9 days). Pain in the torso was reported in 84% of cases aged 3 or more years and was the most common cause for carer concern in this age group. According to carer accounts, clinicians sometimes misjudged the origin of this pain. Almost all carers reported something unusual about the index illness that had particularly concerned them-mostly non-specific physical symptoms and behavioural changes. CONCLUSIONS: Pain in the torso and carer concerns about unusual symptoms in their child may provide valuable additional information in a clinician's assessment of the risk of pneumonia in primary care. Further research is needed to confirm the diagnostic value of these features.

Randomized clinical trial of rapid versus 24-hour rehydration for children with acute gastroenteritis.

OBJECTIVE: To compare the efficacy of 2 nasogastric rehydration regimens for children with acute viral gastroenteritis. METHODS: Children 6 to 72 months of age with acute viral gastroenteritis and moderate dehydration were recruited from emergency departments (EDs) at 2 metropolitan, pediatric, teaching hospitals. After clinical assessment of the degree of dehydration, patients were assigned randomly to receive either standard nasogastric rehydration (SNR) over 24 hours in the hospital ward or rapid nasogastric rehydration (RNR) over 4 hours in the ED. Primary (>2% weight loss, compared with the admission weight) and secondary treatment failures were assessed. RESULTS: Of 9331 children with acute gastroenteritis who were screened, 254 children were assigned randomly to receive either RNR (n = 132 [52.0%]) or SNR (n = 122 [48.0%]). Baseline characteristics for the 2 groups were similar. All patients made a full recovery without severe adverse events. The primary failure rates were similar for RNR (11.8% [95% confidence interval [CI]: 6.0%-17.6%]) and SNR (9.2% [95% CI: 3.7%-14.7%]; P = .52). Secondary treatment failure was more common in the SNR group (44% [95% CI: 34.6%-53.4%]) than in the RNR group (30.3% [95% CI: 22.5%-38.8%]; P = .03). Discharge from the ED after RNR failed for 27 patients (22.7%), and another 9 (7.6%) were readmitted to the hospital within 24 hours. CONCLUSIONS: Primary treatment failure and clinical outcomes were similar for RNR and SNR. Although RNR generally reduced the need for hospitalization, discharge home from the ED failed for approximately one-fourth of the patients.