OBJECTIVE: The objective of this systematic review was to explore the effectiveness of various systemic corticosteroid (SCS) regimens to mitigate relapse in children with asthma discharged from an acute care setting.
DATA SOURCES: Medline, EMBASE, Global Health, International Pharmaceutical Abstracts, EMB ALL, CINAHL, SCOPUS, Proquest Dissertations and Theses Global, and LILACS were searched using controlled vocabulary and key words. Additional citations were searched via clinical trial registries, Google Scholar, bibliographies, a SCOPUS forward search of a sentinel paper, and hand searching conference abstracts.
STUDY SELECTION: No limitations based on language, publication status, or year of publication were applied. Two independent reviewers searched to identify randomized controlled trials comparing the effectiveness of SCS regimens to prevent relapse in children following treatment for acute asthma.
RESULTS: Fifteen studies were included. In three studies comparing SCS to placebo, asthma relapse was significantly reduced (RR = 0.10; 95% CI: 0.01, 0.77; I
CONCLUSION: This review found evidence that SCS corticosteroids reduce relapse in children following treatment for acute asthma, albeit based on a limited number of studies. Additional studies are required to assess the differential effect of SCS doses and treatment duration to prevent relapse in children following discharge for acute asthma.
OBJECTIVES: While systemic corticosteroids (SCS) are widely used to prevent relapse in adults with acute asthma discharged from the emergency department, the most effective route of administration is unclear. The objective of this review was to examine the effectiveness of SCS in adults and to identify the most effective route of SCS to preventing relapse.
METHODS: A search was conducted to identify randomized controlled trials comparing the effectiveness of intramuscular, oral short-course or long-course corticosteroids to prevent relapse in adults with acute asthma. Two independent reviewers judged study relevance, inclusion, and risk of bias. Pooled statistics were calculated as risk ratios (RR) and odds ratios (OR) with 95% confidence intervals (CI) and credibility intervals (CrI) using a random effects model. A Bayesian network meta-analysis was performed for indirect comparisons of SCS to placebo. Probability of best analysis was reported for comparisons between the routes of administration.
RESULTS: Thirteen studies of moderate quality were included. Four studies compared SCS to placebo, in which SCS significantly reduced relapse (RR = 0.43; 95% CI: 0.25, 0.74). In the network meta-analysis, a significant reduction in relapse within 10 days of discharge was found in adults receiving intramuscular (OR 0.21; 95% CrI: 0.05, 0.73) and oral long-course (OR 0.31; 95% CrI: 0.09, 0.95) corticosteroids. Relapse rates between oral short-course corticosteroids and placebo were not statistically significantly different (OR 0.37; 95% CrI: 0.04, 3.38). Probability of best analysis favored intramuscular corticosteroids (62%) followed by oral short-course (20.3%) and oral long-course (14.1%) corticosteroids.
CONCLUSIONS: The network analysis identified IM corticosteroids and oral long-course corticosteroids as the most effective strategies to prevent relapse among adults with acute asthma, compared to oral short-course corticosteroids. The lack of significant findings with oral short-course corticosteroids is likely due to the paucity of research. Further comparative studies are required to determine the safety and effectiveness of briefer oral SCS treatment options in adults. This article is protected by copyright. All rights reserved.
OBJECTIVES: The aim of this systematic literature review was to summarize the current knowledge regarding the prevalence of, time to recovery from, and influence of glucocorticoid dose and duration on glucocorticoid-induced adrenal insufficiency (AI).
METHODS: Eligible studies were original research articles, which included adult patients with an indication for glucocorticoids and measured adrenal function following exposure to systemic glucocorticoids. Searches were performed in Web of Science and MEDLINE, with further articles identified from reference lists. Screening was performed in duplicate. Data were extracted for each group of glucocorticoid-exposed patients within eligible studies. The reported proportion of patients with AI was summarized as median and inter-quartile range. Results were then stratified by daily dose, cumulative dose, duration of exposure and time since last glucocorticoid use. The risk of bias within and across studies was considered: for randomised controlled trials risk of bias was assessed using the tool developed by the Cochrane Collaboration.
RESULTS: Overall, 73 eligible studies were identified out of 673 screened. The percentage of patients with AI ranged from 0% to 100% with a median (IQR) = 37.4% (13-63%). Studies were small-median (IQR) group size 16 (9-38)-and heterogeneous in methodology. AI persisted in 15% of patients retested 3 years after glucocorticoid withdrawal. Results remained widely distributed following stratification. AI was demonstrated at <5mg prednisolone equivalent dose/day, <4 weeks of exposure, cumulative dose <0.5g, and following tapered withdrawal.
CONCLUSIONS: The heterogeneity of studies and variability in results make it difficult to answer the research questions with confidence based on the current literature. There is evidence of AI following low doses and short durations of glucocorticoids. Hence, clinicians should be vigilant for adrenal insufficiency at all degrees of glucocorticoid exposure.
BACKGROUND: Short-course oral corticosteroids are commonly used in children but are known to be associated with adverse drug reactions (ADRs). This review aimed to identify the most common and serious ADRs and to determine their relative risk levels.
METHODS: A literature search of EMBASE, MEDLINE, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions to identify studies in which oral corticosteroids were administered to patients aged 28 days to 18 years of age for up to and including 14 days of treatment. Each database was searched from their earliest dates to December 2013. All studies providing clear information on ADRs were included.
RESULTS: Thirty-eight studies including 22 randomised controlled trials (RCTs) met the inclusion criteria. The studies involved a total of 3200 children in whom 850 ADRs were reported. The three most frequent ADRs were vomiting, behavioural changes and sleep disturbance, with respective incidence rates of 5.4%, 4.7% and 4.3% of patients assessed for these ADRs. Infection was one of the most serious ADRs; one child died after contracting varicella zoster. When measured, 144 of 369 patients showed increased blood pressure; 21 of 75 patients showed weight gain; and biochemical hypothalamic-pituitary-adrenal axis suppression was detected in 43 of 53 patients.
CONCLUSIONS: Vomiting, behavioural changes and sleep disturbance were the most frequent ADRs seen when short-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.
TRIAL REGISTRATION NUMBER: CRD42014008774. By PROSPERO International prospective register of systematic reviews.
BACKGROUND: Asthma is a common long-term breathing condition that affects approximately 300 million people worldwide. People with asthma may experience short-term worsening of their asthma symptoms; these episodes are often known as ‘exacerbations’, ‘flare-ups’, ‘attacks’ or 'acute asthma'. Oral steroids, which have a potent anti-inflammatory effect, are recommended for all but the most mild asthma exacerbations; they should be initiated promptly. The most often prescribed oral steroids are prednisolone and dexamethasone, but current guidelines on dosing vary between countries, and often among different guideline producers within the same country. Despite their proven efficacy, use of steroids needs to be balanced against their potential to cause important adverse events. Evidence is somewhat limited regarding optimal dosing of oral steroids for asthma exacerbations to maximise recovery while minimising potential side effects, which is the topic of this review.
OBJECTIVES: To assess the efficacy and safety of any dose or duration of oral steroids versus any other dose or duration of oral steroids for adults and children with an asthma exacerbation.
SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/) and reference lists of all primary studies and review articles. This search was up to date as of April 2016.
SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs), irrespective of blinding or duration, that evaluated one dose or duration of oral steroid versus any other dose or duration, for management of asthma exacerbations. We included studies involving both adults and children with asthma of any severity, in which investigators analysed adults and children separately. We allowed any other co-intervention in the management of an asthma exacerbation, provided it was not part of the randomised treatment. We included studies reported as full text, those published as abstract only and unpublished data.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results for included trials, extracted numerical data and assessed risk of bias; all data were cross-checked for accuracy. We resolved disagreements by discussion with the third review author or with an external advisor.We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs) using study participants as the unit of analysis; we analysed continuous data as mean differences (MDs). We used a random-effects model, and we carried out a fixed-effect analysis if we detected statistical heterogeneity. We rated all outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system and presented results in 'Summary of findings' tables.
MAIN RESULTS: We included 18 studies that randomised a total of 2438 participants - both adults and children - and performed comparisons of interest. Included studies assessed higher versus lower doses of prednisolone (n = 4); longer versus shorter courses of prednisolone (n = 3) or dexamethasone (n = 1); tapered versus non-tapered courses of prednisolone (n = 4); and prednisolone versus dexamethasone (n = 6). Follow-up duration ranged from seven days to six months. The smallest study randomised just 15 participants, and the largest 638 (median 93). The varied interventions and outcomes reported limited the number of meaningful meta-analyses that we could perform.For two of our primary outcomes - hospital admission and serious adverse events - events were too infrequent to permit conclusions about the superiority of one treatment over the other, or their equivalence. Researchers in the included studies reported asthma symptoms in different ways and rarely used validated scales, again limiting our conclusions. Secondary outcome meta-analysis was similarly hampered by heterogeneity among interventions and outcome measures used. Overall, we found no convincing evidence of differences in outcomes between a higher dose or longer course and a lower dose or shorter course of prednisolone or dexamethasone, or between prednisolone and dexamethasone.Included studies were generally of reasonable methodological quality. Review authors assessed most outcomes in the review as having low or very low quality, meaning we are not confident in the effect estimates. The predominant reason for downgrading was imprecision, but indirectness and risk of bias also reduced our confidence in some estimates.
AUTHORS' CONCLUSIONS: Evidence is not strong enough to reveal whether shorter or lower-dose regimens are generally less effective than longer or higher-dose regimens, or indeed that the latter are associated with more adverse events. Any changes recommended for current practice should be supported by data from larger, well-designed trials. Varied study design and outcome measures limited the number of meta-analyses that we could perform. Greater emphasis on palatability and on whether some regimens might be easier to adhere to than others could better inform clinical decisions for individual patients.
BACKGROUND AND OBJECTIVE: Dexamethasone has been proposed as an equivalent therapy to prednisone/prednisolone for acute asthma exacerbations in pediatric patients. Although multiple small trials exist, clear consensus data are lacking. This systematic review and meta-analysis aimed to determine whether intramuscular or oral dexamethasone is equivalent or superior to a 5-day course of oral prednisone or prednisolone. The primary outcome of interest was return visits or hospital readmissions. METHODS: A search of PubMed (Medline) through October 19, 2013, by using the keywords dexamethasone or decadron and asthma or status asthmaticus identified potential studies. Six randomized controlled trials in the emergency department of children ≤18 years of age comparing dexamethasone with prednisone/prednisolone for the treatment of acute asthma exacerbations were included. Data were abstracted by 4 authors and verified by a second author. Two reviewers evaluated study quality independently and interrater agreement was assessed. RESULTS: There was no difference in relative risk (RR) of relapse between the 2 groups at any time point (5 days RR 0.90, 95% confidence interval [CI] 0.46-1.78, Q = 1.86, df = 3, I<sup>2</sup> = 0.0%, 10-14 days RR 1.14, 95% CI 0.77-1.67, Q = 0.84, df = 2, I<sup>2</sup> = 0.0%, or 30 days RR 1.20, 95% CI 0.03-56.93). Patients who received dexamethasone were less likely to experience vomiting in either the emergency department (RR 0.29, 95% CI 0.12-0.69, 0 = 3.78, df = 3, I<sup>2</sup> = 20.7%) or at home (RR 0.32, 95% CI 0.14-0.74, Q = 2.09, df = 2, I<sup>2</sup> = 4.2%). CONCLUSIONS: Practitioners should consider single or 2-dose regimens of dexamethasone as a viable alternative to a 5-day course of prednisone/prednisolone.
OBJECTIVE: The objective of this selective evidence based medicine review is to determine whether or not a one or two dose regimen of dexamethasone (DEX) is a safe and effective treatment for asthma exacerbations in the pediatric population. STUDY DESIGN: Review of three English language, primary randomized controlled trials (RCT) published from 2001-2008. DATA SOURCES: Three RCTs examining the efficacy of DEX either in a single dose or one dose for two days, compared to a traditional five day regimen of prednisone (PRED). OUTCOMES MEASURED: The studies examined the number of relapses within 10 days of using DEX or PRED, the number of subjects with unscheduled returns to the emergency department (ED) or other health care facility within 5 days, and episodes of emesis after administration of drug in the ED and at home within 5 days. RESULTS: These studies concluded that both a single dose and two doses of DEX was no less effective than a five day regimen of PRED, specifically in regards to relapse rates and time to recovery. DEX did not lead to a higher rate of emesis than PRED either in the ED or within five days of initial treatment. CONCLUSIONS: DEX is equally effective to PRED in the treatment of acute asthma exacerbations in pediatric patients, and does not lead to a greater rate of emesis within 5 days of treatment. Because DEX can be administered in a single dose or in a two day regimen, instead of the five day regimen required of PRED, patients may be more satisfied and have a higher compliance rate by using DEX.
The objective of this systematic review was to explore the effectiveness of various systemic corticosteroid (SCS) regimens to mitigate relapse in children with asthma discharged from an acute care setting.
DATA SOURCES:
Medline, EMBASE, Global Health, International Pharmaceutical Abstracts, EMB ALL, CINAHL, SCOPUS, Proquest Dissertations and Theses Global, and LILACS were searched using controlled vocabulary and key words. Additional citations were searched via clinical trial registries, Google Scholar, bibliographies, a SCOPUS forward search of a sentinel paper, and hand searching conference abstracts.
STUDY SELECTION:
No limitations based on language, publication status, or year of publication were applied. Two independent reviewers searched to identify randomized controlled trials comparing the effectiveness of SCS regimens to prevent relapse in children following treatment for acute asthma.
RESULTS:
Fifteen studies were included. In three studies comparing SCS to placebo, asthma relapse was significantly reduced (RR = 0.10; 95% CI.: 0.01, 0.77; I
CONCLUSION:
This review found evidence that SCS corticosteroids reduce relapse in children following treatment for acute asthma, albeit based on a limited number of studies. Additional studies are required to assess the differential effect of SCS doses and treatment duration to prevent relapse in children following discharge for acute asthma.
