Liza Bialy

Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysis.

Objective To evaluate and compare the efficacy and safety of bronchodilators and steroids, alone or combined, for the acute management of bronchiolitis in children aged less than 2 years. Design Systematic review and meta-analysis. Data sources Medline, Embase, Central, Scopus, PubMed, LILACS, IranMedEx, conference proceedings, and trial registers. Inclusion criteria Randomised controlled trials of children aged 24 months or less with a first episode of bronchiolitis with wheezing comparing any bronchodilator or steroid, alone or combined, with placebo or another intervention (other bronchodilator, other steroid, standard care). Review methods Two reviewers assessed studies for inclusion and risk of bias and extracted data. Primary outcomes were selected by clinicians a priori based on clinical relevance: rate of admission for outpatients (day 1 and up to day 7) and length of stay for inpatients. Direct meta-analyses were carried out using random effects models. A mixed treatment comparison using a Bayesian network model was used to compare all interventions simultaneously. Results 48 trials (4897 patients, 13 comparisons) were included. Risk of bias was low in 17% (n=8), unclear in 52% (n=25), and high in 31% (n=15). Only adrenaline (epinephrine) reduced admissions on day 1 (compared with placebo: pooled risk ratio 0.67, 95% confidence interval 0.50 to 0.89; number needed to treat 15, 95% confidence interval 10 to 45 for a baseline risk of 20%; 920 patients). Unadjusted results from a single large trial with low risk of bias showed that combined dexamethasone and adrenaline reduced admissions on day 7 (risk ratio 0.65, 0.44 to 0.95; number needed to treat 11, 7 to 76 for a baseline risk of 26%; 400 patients). A mixed treatment comparison supported adrenaline alone or combined with steroids as the preferred treatments for outpatients (probability of being the best treatment based on admissions at day 1 were 45% and 39%, respectively). The incidence of reported harms did not differ. None of the interventions examined showed clear efficacy for length of stay among inpatients. Conclusions Evidence shows the effectiveness and superiority of adrenaline for outcomes of most clinical relevance among outpatients with acute bronchiolitis, and evidence from a single precise trial for combined adrenaline and dexamethasone.

A systematic review on the diagnosis of pediatric bacterial pneumonia: when gold is bronze.

Background In developing countries, pneumonia is one of the leading causes of death in children under five years of age and hence timely and accurate diagnosis is critical. In North America, pneumonia is also a common source of childhood morbidity and occasionally mortality. Clinicians traditionally have used the chest radiograph as the gold standard in the diagnosis of pneumonia, but they are becoming increasingly aware that it is not ideal. Numerous studies have shown that chest radiography findings lack precision in defining the etiology of childhood pneumonia. There is no single test that reliably distinguishes bacterial from non-bacterial causes. These factors have resulted in clinicians historically using a combination of physical signs and chest radiographs as a ‘gold standard’, though this combination of tests has been shown to be imperfect for diagnosis and assigning treatment. The objectives of this systematic review are to: 1) identify and categorize studies that have used single or multiple tests as a gold standard for assessing accuracy of other tests, and 2) given the ‘gold standard’ used, determine the accuracy of these other tests for diagnosing childhood bacterial pneumonia. Methods and Findings Search strategies were developed using a combination of subject headings and keywords adapted for 18 electronic bibliographic databases from inception to May 2008. Published studies were included if they: 1) included children one month to 18 years of age, 2) provided sufficient data regarding diagnostic accuracy to construct a 2×2 table, and 3) assessed the accuracy of one or more index tests as compared with other test(s) used as a ‘gold standard’. The literature search revealed 5,989 references of which 256 were screened for inclusion, resulting in 25 studies that satisfied all inclusion criteria. The studies examined a range of bacterium types and assessed the accuracy of several combinations of diagnostic tests. Eleven different gold standards were studied in the 25 included studies. Criterion validity was calculated for fourteen different index tests using eleven different gold standards. The most common gold standard utilized was blood culture tests used in six studies. Fourteen different tests were measured as index tests. PCT was the most common measured in five studies each with a different gold standard. Conclusions We have found that studies assessing the diagnostic accuracy of clinical, radiological, and laboratory tests for bacterial childhood pneumonia have used a heterogeneous group of gold standards, and found, at least in part because of this, that index tests have widely different accuracies. These findings highlight the need for identifying a widely accepted gold standard for diagnosis of bacterial pneumonia in children.

Meta-analyses of safety data: a comparison of exact versus asymptotic methods

The objectives of this study were to establish and describe a database of Cochrane and non-Cochrane meta-analyses of safety data and to determine under what conditions exact methods differ from asymptotic methods in meta-analyses of safety data. A sample of Cochrane (n = 500) and non-Cochrane (n = 200) systematic reviews was randomly selected and a database of safety meta-analyses established. Point estimates and confidence intervals for each meta-analysis were recalculated using exact methods and compared to the results of asymptotic methods. Cochrane reviews were nearly four times as likely as non-Cochrane reviews to contain meta-analyses of safety data (35% compared to 9%). More than 50% of safety meta-analyses contained an outcome with a rare event rate (<5%) and 30% contained at least one study with no events in one arm of the study. For rare event meta-analyses, exact point estimates differed substantially from asymptotic estimates 46% of the time, compared to 17% for those without rare events. Exact confidence intervals differed substantially from asymptotic ones 67% of the time compared to only 19% for those without rare events. The magnitude of differences was also correlated with the number of studies and the summary statistic used to combine the data. Asymptotic methods will not always be a good approximation for exact methods in safety meta-analyses. Event rates and number of studies should be closely examined when choosing the statistical method for combining rare event data.

Improving Outcomes for Ill and Injured Children in Emergency Departments: Protocol for a Program in Pediatric Emergency Medicine and Knowledge Translation Science

Approximately one-quarter of all Canadian children will seek emergency care in any given year, with the two most common medical problems affecting children in the emergency department (ED) being acute respiratory illness and injury. Treatment for some medical conditions in the ED remains controversial due to a lack of strong supporting evidence.The purpose of this paper is to describe a multi-centre team grant in pediatric emergency medicine (PEM) that has been recently funded by the Canadian Institutes of Health Research (CIHR). This program of research integrates clinical research (in the areas of acute respiratory illness and injury) and knowledge translation (KT). This initiative includes seven distinct projects that address the objective to generate new evidence for clinical care and KT in the pediatric ED. Five of the seven research projects in this team grant make significant contributions to knowledge development in KT science, and these contributions are the focus of this paper.The research designs employed in this program include: cross-sectional surveys, randomized controlled trials (RCTs), quasi-experimental designs with interrupted time-series analysis and staggered implementation strategies, and qualitative designs.This team grant provides unique opportunities for making important KT methodological developments, with a particular focus on developing a better theoretical understanding of the causal mechanisms and effect modifiers of different KT interventions.

Pediatric Emergency Research Networks: a global initiative in pediatric emergency medicine.

Objectives The objectives of the Pediatric Emergency Research Networks (PERN) meeting were to (i) learn about each of the participating networks missions, goals, and infrastructure; (ii) share important contributions that each network has made to the creation of new knowledge; (iii) discuss ‘best practices’ to improve each networks effectiveness and (iv) explore the potential for a collaborative research project as proof-of-concept that would help promote quality of care of the acutely ill and injured child/youth globally. Methods In October 2009 a multiday meeting was attended by 18 delegates representing the following pediatric emergency medicine research networks: Pediatric Emergency Medicine Collaborative Research Committee (USA); Pediatric Emergency Care Applied Research Network (USA); Pediatric Emergency Research of Canada (Canada); Pediatric Research in Emergency Departments International Collaborative (Australia and New Zealand); and Research in European Pediatric Emergency Medicine (15 countries in Europe and the Middle East). Results The inaugural meeting of PERN showed that there is a common desire for high-quality research and the dissemination of this research to improve health and outcomes of acutely ill and injured children and youths throughout the world. At present, the PERN group is in the final stages of developing a protocol to assess H1N1 risk factors with the collection of retrospective data. Conclusion Several members of PERN will be gathering at the International Conference on Emergency Medicine in Singapore, where the group will be presenting information about the H1N1 initiative. The PERN group is planning to bring together all five networks later in 2010 to discuss future global collaborations.

Pediatric Emergency Research Canada (PERC): Patient/Family-Informed Research Priorities for Pediatric Emergency Medicine.

BACKGROUND A growing body of literature supports patient and public involvement in the design, prioritization, and dissemination of research and evidence-based medicine. The objectives of this project were to engage patients and families in developing a prioritized list of research topics for pediatric emergency medicine (PEM) and to compare results with prior research prioritization initiatives in the emergency department (ED) setting. METHODS We utilized a systematic process to combine administrative data on frequency of patient presentations to the ED with multiple stakeholder input including an initial stakeholder survey followed by a modified Delphi consensus methodology consisting of two Web-based surveys and a face-to-face meeting. RESULTS The prioritization process resulted in a ranked list of 15 research priorities. The top five priorities were mental health presentations, pain and sedation, practice tools, quality of care delivery, and resource utilization. Mental health, pain and sedation, clinical prediction rules, respiratory illnesses/wheeze, patient safety/medication error, and sepsis were identified as shared priorities with prior initiatives. Topics identified in our process that were not identified in prior work included resource utilization, ED communication, antibiotic stewardship, and patient/family adherence with recommendations. CONCLUSIONS This work identifies key priorities for research in PEM. Comparing our results with prior initiatives in the ED setting identified shared research priorities and opportunities for collaboration among PEM research networks. This work in particular makes an important contribution to the existing literature by including the patient/family perspective missing from prior work.