PEDIATRICS Vol. 120 No. 6 December 2007, pp. 1334-1343 (doi:10.1542/peds.2006-3381)
STATE-OF-THE-ART REVIEW ARTICLE |
State of the Evidence on Acute Asthma Management in Children: A Critical Appraisal of Systematic Reviews
a Department of Pediatric Clinical Epidemiology, Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands
b Academic General Pediatrics, Baylor College of Medicine, Houston, Texas
c Princess Amalia Children's Clinic, Isala Klinieken, Zwolle, Netherlands
ABSTRACT
OBJECTIVE. Our goal was to evaluate clinical, methodologic, and reporting aspects of systematic reviews on the management of acute asthma in children.
METHODS. We undertook a systematic review of systematic reviews on acute asthma management in children. We identified eligible reviews by searching the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Medline, and Embase 1990 to March 2006. Data were extracted on clinical issues, methodologic characteristics, and results of the reviews. Methodologic quality was assessed with the Overview Quality Assessment Questionnaire and with additional questions on heterogeneity. Separate reporting on children in mixed adult-pediatric population reviews was assessed. Methodologic quality of systematic reviews published in peer-reviewed journals was compared with Cochrane reviews.
RESULTS. A total of 23 systematic reviews were included: 14 were published in the Cochrane Library, and 9 were published in peer-reviewed journals. Eight reviews included children only, and 15 were mixed-population reviews. The majority of reviews defined the study population as having "acute asthma" without a more precise definition, and 16 different health outcomes were reported. The overall quality according to the Overview Quality Assessment Questionnaire was good, with Cochrane reviews showing minimal flaws and journal reviews showing minor flaws (median scores: 7 vs 5). Results on children were reported separately in 8 of 15 mixed-population reviews. Clinical heterogeneity was explored in only 2 of 23 reviews, and the methods used to identify and address heterogeneity were diverse.
CONCLUSIONS. The methodologic quality of both the Cochrane and journal reviews on the management of acute asthma in children seems good, with Cochrane reviews being more rigorous. However, their usefulness for clinical practice is hampered by a lack of clear definitions of included populations, clinically important health outcomes, and separate reporting on children in mixed reviews. A major threat to these reviews’ validity is the insufficient identification and handling of heterogeneity.
Key Words: acute asthma • review literature • child • evaluation studies • quality assurance/health care
Abbreviations: ED—emergency department • OQAQ—Overview Quality Assessment Questionnaire • FEV1—forced expiratory volume in 1 second • PEF—peak expiratory flow
Acute asthma is a common reason for coming to emergency departments (EDs). In the United States alone, acute asthma accounts for almost 2 million ED visits per year.1 Approximately 10% to 20% of these patients require hospital admission, and another 10% to 20% will relapse within the subsequent 2 weeks.2,3 These outcomes depend on the treatment prescribed in the ED and at discharge, which consists mainly of inhaled β2 agonists and systemic corticosteroids.
Our aim was to develop a research agenda on acute asthma management in children. A research agenda should ideally be informed by all the available evidence, pediatricians’ priorities for future research in the field, and patients’ preferences. In this article we address the first step, that is, the available evidence summarized in systematic reviews.
Systematic reviews have gained popularity as a way of coping with increasing amounts of research information. Systematic reviews appraise and synthesize this information to help bridge the gap between evidence from single studies and clinical practice. In addition, they guide future research into the information gaps that are identified through the review process. Systematic reviews may include meta-analysis (ie, the statistical combination of results of several independent studies to produce a single estimate of the effect of a particular health care intervention).4,5
Properly performed, systematic reviews represent the highest level of evidence available to clinicians. Yet, if clinicians are to have confidence that the results of systematic reviews can be used to guide clinical practice and the research agenda, then these reviews need to be of high quality. Unfortunately, most systematic reviews on health care interventions in adult patients published in peer-reviewed journals have been shown to have methodologic deficiencies that limit their validity.6–12
In the field of pediatrics, 2 additional challenges need to be addressed. First, the volume of trials and the number of children included is often small, which makes definite conclusions difficult to draw. Second, many reviews include both adults and children (mixed-populations reviews). Given the differences in response to treatments between adults and children, pooling of data from mixed populations could lead to the incorporation of invalid findings for pediatric clinical practice. On the other hand, if mixed reviews are disregarded altogether, important information could be missed.13
We undertook a comprehensive search for systematic reviews on pediatric acute asthma management issues with the following goals:
- to provide an overview of the currently available evidence syntheses on acute asthma treatment in children by examining the subject content, clinical aspects, methodologic aspects, and the results of these systematic reviews;
- to evaluate the quality of these systematic reviews, compare the methodologic quality of Cochrane reviews with reviews published in peer-reviewed journals, and assess if outcomes for children are reported separately in mixed reviews; and
- to identify areas for improvement in the methods and reporting of these reviews.
METHODS
Literature Search and Study Selection
We identified eligible studies by searching the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE) (Cochrane Library; issue 1, 2006), Medline, and Embase 1990 to March 2006 using the search term "asthma" with limits "all child: 0–18 years." In Medline and Embase we added a comprehensive search strategy for systematic reviews and meta-analyses. In addition, the National Guideline Clearinghouse (www.guideline.gov) was searched for evidence-based practice guidelines, and reference lists of the guidelines were checked for systematic reviews. Abstracts of potentially eligible reviews were assessed independently by 2 reviewers for inclusion. The final decision on inclusion in the review was made by consensus.
Inclusion Criteria
To be included, a report had to explicitly indicate the use of a strategy for locating evidence or had to be described as a systematic review or a meta-analysis on the treatment of acute asthma in children, which we defined as individuals 
18 years of age. We also included systematic reviews and meta-analyses on mixed populations.
Data Extraction
Two reviewers extracted data independently by using a data-collection form specifically designed for this study and piloted on 5 systematic reviews not included in this sample. Data were extracted on general characteristics of the reviews (publication year, source, source of funding); clinical issues (population, definition of acute asthma, intervention, and outcomes reviewed); methodologic characteristics (design, methodologic quality and funding of the included trials, heterogeneity testing, updating); and results. Differences were resolved by consensus.
Methodologic quality was assessed with the Overview Quality Assessment Questionnaire (OQAQ), the only validated instrument available for the critical appraisal of review articles.14,15 The OQAQ checklist addresses 5 different aspects of scientific quality of a systematic review (search strategy, selection, quality assessment, pooling, and results) and evaluates the overall scientific quality of the review on a 7-point scale, with 1 and 2 indicating extensive flaws, 3 and 4 indicating major flaws, 5 and 6 indicating minor flaws, and 7 indicating minimal flaws. We added questions that were not fully covered by the OQAQ on the presence of heterogeneity: (1) Was the presence or absence of heterogeneity identified? (2) Was clinical heterogeneity explored? (3) Were a priori subgroup analyses by age and/or asthma severity planned? (4) Were the reasons for statistical heterogeneity, if present, explored? (5) Was heterogeneity, if present, correctly accounted for either by using alternative data-pooling techniques or refraining from pooling?
Analysis
The main analysis of the data was descriptive. To test the difference in OQAQ total scores between Cochrane and journal systematic reviews, a Mann-Whitney test was performed, because data were not normally distributed.
RESULTS
Search and General Characteristics
Twenty-three citations met our inclusion criteria,16–38 the earliest of which was published in 1992.33 Fourteen of them were Cochrane reviews,* and 9 were published in peer-reviewed journals ("journal reviews").
Patients, Interventions, and Outcomes
Table 1 shows clinical characteristics and main results of the reviews according to intervention.
|
Eight reviews included children only, and 15 were mixed-population reviews.
In all the reviews the study population was defined as having "acute asthma." Four reviews (17%) described the definition of acute asthma and severity; it was based on a clinical score,19 a combination of a clinical score and forced expiratory volume in 1 second (FEV1),30 or FEV1 or peak expiratory flow (PEF).18,32 Nineteen reviews (83%) did not report a definition of acute asthma or the inclusion criteria for eligible patients.
Sixteen different outcomes were reported; 22 reviews reported pulmonary-function test results, 18 the hospitalization rate, 12 adverse effects, 10 asthma symptoms, 7 length of hospitalization, 5 vital signs, 4 ED treatment duration, 4 relapse to additional care, 4 β2 agonist use, 4 heart rate, 4 mechanical ventilation, 3 costs, 2 corticosteroid use, 2 quality of life, 2 ICU admissions, and 1 arterial blood gas values.
Methodologic Characteristics
Table 2 summarizes the component scores of the OQAQ and some other methodologic quality items for reviews published in the Cochrane Library and in other journals. Additional details are provided in Tables 3 and 4, which are published as supporting information on www.pediatrics.org/cgi/content/full/120/6/1334.
|
Overview Quality Assessment Questionnnaire
The median OQAQ score of all reviews was 7 (range: 2–7), indicating minimal flaws. Cochrane reviews had a median score of 7 (range: 6–7), indicating minimal flaws, and journal reviews had a median score of 5 (range: 2–7), indicating minor flaws (P < .001). Of 9 journal reviews, 7 exhibited minor to minimal flaws, and 2 had extensive flaws.
Heterogeneity
Details per review are provided in Tables 3 and 4. The presence or absence of heterogeneity was mentioned in 20 reviews, but only 2 reviews stated in their methods the intent to explore clinical heterogeneity between studies. Of the 20 reviews that considered heterogeneity, 13 prespecified subgroup or sensitivity analyses. Of 15 mixed reviews, 8 reported results on children separately. Ten of the 15 mixed reviews prespecified a subgroup analysis for age, and 5 of them did not. However, 6 of 10 reviews that planned a subgroup analysis for age did not actually report children separately because either no heterogeneity was found or the number of studies in children was considered insufficient. A subgroup analysis based on asthma severity was prespecified in 11 of 23 reviews. Most reviews accounted for heterogeneity by sensitivity or subgroup analyses (n = 5), by using the more conservative random-effects model (n = 8), or by refraining from pooling (n = 3).
Funding
None of the systematic reviews provided information about the sources of funding of the individual studies that they included. Seven of the 14 Cochrane reviews stated no potential conflicts of interest; the 7 others stated that the authors had received grants from industry. Of 9 journal reviews, 8 did not provide any information about a potential conflict of interest.
Updating
Of the Cochrane reviews, 6 of 14 were >3 years old (range: 3–6 years). Publication dates of the journal reviews ranged from 1992 to 2005, with 5 of 9 reviews being published >3 years before our search.
DISCUSSION
Our assessment of the existing volume and quality of systematic reviews on the management of acute asthma for children presenting to the ED provides useful insights with regard to the current scientific basis for clinical decision-making and the research agenda. In the following we discuss our findings on the clinical and methodologic characteristics of the reviews and give recommendations for future trials and systematic reviews in this field.
Clinical Characteristics of Included Systematic Reviews
The majority (83%) of the reviews did not state a clear definition of acute asthma but instead used whatever definition was used by the included primary studies. This holds 2 potential problems. Because treatments may have different effects sizes in patients with different clinical presentations or severity levels of acute asthma, pooling such heterogeneous studies results in an invalid overall effect size.39 The second problem is that without specifically stating population characteristics, clinicians will not be able to evaluate external validity (ie, the extent to which the results are applicable to their own population of children with acute asthma).
Many different health outcomes were reported. Reporting of pulmonary-function tests in the individual trials was heterogeneous (eg, percent predicted or percent change from baseline), which limits pooling possibilities. In addition, selective reporting of trial outcomes has to be considered.40,41 The most common reason for nonpublication of selective outcomes is lack of statistical significance. Because selective reporting is widespread and can change the conclusions of systematic reviews, it should be routinely investigated in future systematic reviews.41
Methodologic Characteristics of Included Systematic Reviews
The OQAQ scores of the systematic reviews published in peer-reviewed journals exceeded those reported in other (adult) studies.6–12 An evaluation of 50 systematic reviews on asthma treatment for adults published before 1999 showed that 80% of reviews published in peer-reviewed journals had major flaws, compared with 23% in our sample.11 The publication of QUOROM (Quality of Reporting of Meta-analysis) in 1999 probably resulted in higher-quality systematic reviews in peer-reviewed journals after that time.
Publication bias occurs in systematic reviews because smaller or negative studies are less likely to be published, which leads to an overestimation of the treatment effect.42 For that reason a comprehensive search should be performed of published and unpublished research (item 2 of the OQAQ [Table 2]). All Cochrane reviews in our sample searched the 3 major electronic databases (Medline, Embase, and the Cochrane Library), but the majority (56%) of the journal reviews only searched Medline. A method for identifying unpublished studies was stated by all Cochrane reviews and 33% of the journal reviews. The only satisfactory way to address publication bias and improve the quality of the conduct, analysis, and reporting of studies, meta-analyses, and systematic reviews is through prospective registration of trials.39 Unfortunately, these trial registers are still voluntary.
The confidence in results generated by systematic reviews depends, to a large extent, on the quality of the primary studies included. Including studies of low quality in systematic reviews has been shown to exaggerate treatment effectiveness by 30% to 50%.43 The 2 most important items that may lead to overestimation of treatment effect are lack of allocation concealment and lack of blinding of outcome assessors.43,44 Almost all reviews (91%) included randomized, controlled trials, but 33% also included quasi-randomized, controlled trials that, by definition, lack allocation concealment. All Cochrane reviews and 33% of the journal reviews assessed allocation concealment and blinding in the individual studies (item 6 of the OQAQ).
Heterogeneity
Statistical pooling of study results can produce serious errors in the estimation of effect sizes, especially when combining heterogeneous results of individual studies.39,45 Various types of heterogeneity can be distinguished; variability in the participants, interventions, and outcomes in studies is described as "clinical heterogeneity," and variability in trial design and quality is described as "methodologic heterogeneity." The pooling of data from heterogeneous primary studies can lead to the occurrence of statistical heterogeneity, which is variability in estimates of effect sizes across individual studies.39 Meta-analysis should only be considered when a group of trials is sufficiently homogeneous in terms of participants, interventions, health outcomes, and methodology.
The majority of the reviews in our study (87%) tried to identify the presence of heterogeneity, but only 2 of them considered clinical heterogeneity. The statistical tests to detect heterogeneity that were used by 17 of 20 reviews that considered heterogeneity are known to have limited power when a small number of studies is included, which is often the case in pediatric systematic reviews.45 Thus, the presence of heterogeneity is probably underestimated. The more recently developed measure I2 is used to assess the impact of heterogeneity on a meta-analysis independent of the number of studies.46 Three of the most recent reviews used this measure.20,28,32 The majority (87%) of reviews pooled individual study results despite possible heterogeneity in the study populations caused by lack of clear definitions for acute asthma. Additional subgroup analyses, such as for asthma severity and age (for mixed reviews), should be specified a priori.45 Only half of the reviews prespecified subgroups on the basis of these characteristics. The presentation and etiology of acute asthma exacerbations differ among different age groups of children. None of the reviews presented subgroup analyses for different age groups of children. Thus, despite a good overall score on the OQAQ, we think that the main current threat to the validity of pediatric systematic reviews (both Cochrane and journal reviews) is how they deal with clinical and statistical heterogeneity.
Funding of Primary Trials and Reviews
Published trials sponsored by industry have been shown to exaggerate treatment effects and come to a positive conclusion in favor of the sponsor's drug 5 times more often than do not-for-profit–sponsored trials.47 None of the systematic reviews in this field stated the source of funding of the individual studies. Like individual studies, reviews performed with industry sponsorship have been shown to have an increased risk of producing favorable results.48,49 In this series, all Cochrane reviews addressed potential conflicts of interest. In contrast, 88% of the journal reviews did not give any information regarding a potential conflict of interest.
Updating of Reviews
Reviews should be updated regularly, because new trials may change the conclusion of a systematic review. Cochrane reviews are supposed to be updated every 2 years.39 In the Cochrane reviews identified, 43% had not been updated for 3 years. The reason for this could be that no new studies have been published. However, to keep readers informed, this should be stated in a biannually updated review. Hard-copy journal reviews cannot be updated and should be appraised critically for their freshness; 56% were published >3 years ago (as of July 2006).
Mixed Populations
Only 8 of the 15 reviews that included both adults and children reported results for children separately. The reasons stated were that either there were not enough data on children or "no heterogeneity was found." As pointed out earlier, in most cases the number of included studies was small, in which case the power of the traditional statistical test to detect heterogeneity is low.
Mixed reviews limit generalizability of study results, and pediatricians may not be comfortable relying on mixed-data results. A recent study that investigated differences in effect sizes between adults and children in mixed-population systematic reviews could not exclude clinically important differences because of a lack of power.50 Yet, there is evidence that in children with asthma the mechanisms of drug action may be different than that in adults.51 Likewise, the optimal management may differ among different age groups of children, particularly between preschool-aged children and older children.
Cochrane Versus Peer-Reviewed Journal Reviews
Our study confirms that Cochrane reviews tend to be more rigorous in their methods and reporting than reviews published in peer-reviewed journals.11,52 The reason is probably that Cochrane reviews are developed following standardized instructions, have a peer-reviewed protocol, and receive input from different reviewers at different stages of development. The 2 systematic reviews with highest quality published in peer-reviewed journals were both written by authors who were also involved in Cochrane reviews.
Limitations
We used the OQAQ to assess the quality of systematic reviews. One limitation of this checklist is that it does not distinguish between flaws in methodology (leading to bias) and reporting. Reviews published in peer-reviewed journals especially have limited space, and methodologic details are often not reported. Therefore, we do not recommend that the reader dismiss reviews that received OQAQ scores of <5; however, caution is advised when interpreting their conclusions. Although the quality of a review can be high according to a checklist, its validity can be compromised by overlooking important details in the included trials.53 This information on individual trial quality, clinical heterogeneity, definition of included population, outcomes used, and whether children were reported separately in mixed reviews should be assessed next to the use of any quality score for systematic reviews.
Recommendations
For Clinicians
To be able to combine the results of future trials appropriately, an internationally accepted definition of acute asthma and its severity is needed. This definition may be different for different age groups of children; therefore, it is unlikely that there will be one rigorous, reproducible, all-purpose definition any time soon. Furthermore, efforts to quantify severity have relied heavily on FEV1 or PEF, which are parameters that are not available for young children. A standard set of well-defined clinically important outcomes, for different age groups, should be used in future trials on the management of acute asthma.
For Future Pediatric Systematic Reviews
Journals could improve the quality of systematic reviews they publish by providing authors and peer reviewers with clear reporting criteria and encouraging authors to have the protocol checked by peer reviewers before the actual systematic review is performed, as the major general medical journals already do for clinical trials.11 Sources of funding of the included trials and of the review itself should be clearly stated. Until there is clear evidence that there are no differences between adults and children in their response to acute asthma interventions, separate analyses need to be conducted. Clinical heterogeneity should always be discussed. Because pediatric reviews often include small numbers of studies, the currently used statistical test to detect heterogeneity is inappropriate. Future reviews should use I2 to measure statistical heterogeneity.54 Reviewers need guidance on how to cope with the various forms of heterogeneity in reviews. Because the validity and usefulness of systematic reviews cannot solely be based on scoring lists such as the OQAQ, pediatricians with both clinical and methodologic experience will be needed to write systematic reviews.
ACKNOWLEDGMENTS
We thank Helena Buitelaar, medical student, for help with the searches of the systematic reviews.
FOOTNOTES
Accepted Jun 18, 2007.
Address correspondence to Nicole Boluyt, MD, PhD, Emma Children's Hospital/Department of Pediatric Clinical Epidemiology, Room H3-145, Academic Medical Center, PO Box 22700, 1100 DD Amsterdam, Netherlands. E-mail:n.boluyt{at}amc.uva.nl
The authors have indicated they have no financial relationships relevant to this article to disclose.
* Refs 18, 19, 21, 23, 24, 26, 28, 31, and 34–39. 
Refs 16, 17, 20, 22, 25, 27, 29, 32, and 33.
REFERENCES
- Mannino DM, Homa DM, Pertowski CA, Ashizawa A, Nixon LL, Johnson CA. Surveillance for asthma: United States, 1960–1995. MMWR CDC Surveill Summ. 1998;47(1) :1 –27
- Camargo CA Jr; MARC investigators. Acute asthma among children presenting to the emergency department: the Multicenter Asthma Research Collaboration [abstract]. Acad Emerg Med. 1998;5 :380
- Camargo CA Jr; MARC investigators. Management of acute asthma in US emergency departments: the Multicenter Asthma Research Collaboration [abstract]. Am J Respir Crit Care Med. 1998:157
- Chalmers I, Egger M, Davey-Smith G, Altman DG. Systematic Reviews in Health Care: Meta-analysis in Context. London, United Kingdom: BMJ Publishing Group; 2001
- Greenhalgh T. Papers that summarise other papers (systematic reviews and meta-analyses).
BMJ. 1997;315
:672
–675
[Free Full Text] - Assendelft WJ, Koes BW, Knipschild PG, Bouter LM. The relationship between methodological quality and conclusions in reviews of spinal manipulation.
JAMA. 1995;274
:1942
–1948
[Abstract/Free Full Text] - Choi PT, Halpern SH, Malik N, Jadad AR, Tramer MR, Walder B. Examining the evidence in anesthesia literature: a critical appraisal of systematic reviews.
Anesth Analg. 2001;92
:700
–709
[Abstract/Free Full Text] - Delaney A, Bagshaw SM, Ferland A, Manns B, Laupland KB, Doig CJ. A systematic evaluation of the quality of meta-analyses in the critical care literature. Crit Care. 2005;9 :R575 –R582[CrossRef][Web of Science][Medline]
- Dixon E, Hameed M, Sutherland F, Cook DJ, Doig C. Evaluating meta-analyses in the general surgical literature: a critical appraisal. Ann Surg. 2005;241 :450 –459[CrossRef][Web of Science][Medline]
- Jadad AR, McQuay HJ. Meta-analyses to evaluate analgesic interventions: a systematic qualitative review of their methodology. J Clin Epidemiol. 1996;49 :235 –243[CrossRef][Web of Science][Medline]
- Jadad AR, Moher M, Browman GP, et al. Systematic reviews and meta-analyses on treatment of asthma: critical evaluation [published corrections appear in BMJ. 2000;320(7240):984 and BMJ. 2000;321(7256):275].
BMJ. 2000;320
:537
–540
[Abstract/Free Full Text] - Kelly KD, Travers A, Dorgan M, Slater L, Rowe BH. Evaluating the quality of systematic reviews in the emergency medicine literature. Ann Emerg Med. 2001;38 :518 –526[CrossRef][Web of Science][Medline]
- Smyth RL, O'Byrne PM. The promise of and problems with evidence-based medicine for paediatric asthma management. Allergy. 2002;57(suppl 74) :5 –14
- Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol. 1991;44 :1271 –1278[CrossRef][Web of Science][Medline]
- Oxman AD, Guyatt GH, Singer J, et al. Agreement among reviewers of review articles. J Clin Epidemiol. 1991;44 :91 –98[Web of Science][Medline]
- Aaron SD. The use of ipratropium bromide for the management of acute asthma exacerbation in adults and children: a systematic review. J Asthma. 2001;38 :521 –530[CrossRef][Web of Science][Medline]
- Amirav I, Newhouse MT. Metered-dose inhaler accessory devices in acute asthma: efficacy and comparison with nebulizers: a literature review.
Arch Pediatr Adolesc Med. 1997;151
:876
–882
[Abstract/Free Full Text] - Blitz M, Blitz S, Beasely R, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2005;(4) :CD003898[Medline]
- Camargo CA Jr, Spooner CH, Rowe BH. Continuous versus intermittent beta-agonists in the treatment of acute asthma. Cochrane Database Syst Rev. 2003;(4) :CD001115[Medline]
- Castro-Rodriguez JA, Rodrigo GJ. beta-agonists through metered-dose inhaler with valved holding chamber versus nebulizer for acute exacerbation of wheezing or asthma in children under 5 years of age: a systematic review with meta-analysis. J Pediatr. 2004;145 :172 –177[CrossRef][Web of Science][Medline]
- Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006;(2) :CD000052[Medline]
- Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium sulphate for treating acute asthma.
Arch Dis Child. 2005;90
:74
–77
[Abstract/Free Full Text] - Edmonds ML, Camargo CA, Saunders LD, Brenner BE, Rowe BH. Inhaled steroids in acute asthma following emergency department discharge. Cochrane Database Syst Rev. 2000;(3) :CD002316[Medline]
- Edmonds ML, Camargo CA Jr, Pollack CV Jr, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev. 2003;(3) :CD002308[Medline]
- Goodman DC, Littenberg B, O'Connor GT, Brooks JG. Theophylline in acute childhood asthma: a meta-analysis of its efficacy. Pediatr Pulmonol. 1996;21 :211 –218[CrossRef][Web of Science][Medline]
- Graham V, Lasserson T, Rowe BH. Antibiotics for acute asthma. Cochrane Database Syst Rev. 2001;(3) :CD002741[Medline]
- Ho AM, Lee A, Karmakar MK, Dion PW, Chung DC, Contardi LH. Heliox vs air-oxygen mixtures for the treatment of patients with acute asthma: a systematic overview. Chest. 2003;123 :882 –890[CrossRef][Web of Science][Medline]
- Mitra A, Bassler D, Goodman K, Lasserson TJ, Ducharme FM. Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators. Cochrane Database Syst Rev. 2005;(2) :CD001276[Medline]
- Osmond MH, Klassen TP. Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis. Acad Emerg Med. 1995;2 :651 –656[Web of Science][Medline]
- Plotnick LH, Ducharme FM. Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children. Cochrane Database Syst Rev. 2000;(4) :CD000060[Medline]
- Rodrigo G, Pollack C, Rodrigo C, Rowe BH. Heliox for nonintubated acute asthma patients. Cochrane Database Syst Rev. 2003;(4) :CD002884[Medline]
- Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis.
Thorax. 2005;60
:740
–746
[Abstract/Free Full Text] - Rowe BH, Keller JL, Oxman AD. Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Am J Emerg Med. 1992;10 :301 –310[CrossRef][Web of Science][Medline]
- Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA Jr. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev. 2000;(2) :CD001490[Medline]
- Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1) :CD002178[Medline]
- Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev. 2001;(1) :CD000195[Medline]
- Smith M, Iqbal S, Elliott TM, Everard M, Rowe BH. Corticosteroids for hospitalised children with acute asthma. Cochrane Database Syst Rev. 2003;(2) :CD002886[Medline]
- Travers A, Jones AP, Kelly K, Barker SJ, Camargo CA, Rowe BH. Intravenous beta2-agonists for acute asthma in the emergency department. Cochrane Database Syst Rev. 2001;(2) :CD002988[Medline]
- Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 4.2.5. Available at: www.cochrane.org/resources/handbook/hbook.htm. Accessed March 15, 2006
- Chan AW, Hrobjartsson A, Haahr MT, Gotzsche PC, Altman DG. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.
JAMA. 2004;291
:2457
–2465
[Abstract/Free Full Text] - Williamson PR, Gamble C, Altman DG, Hutton JL. Outcome selection bias in meta-analysis.
Stat Methods Med Res. 2005;14
:515
–524
[Abstract/Free Full Text] - Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses.
BMJ. 2000;320
:1574
–1577
[Abstract/Free Full Text] - Moher D, Pham B, Jones A, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet. 1998;352 :609 –613[CrossRef][Web of Science][Medline]
- Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials.
JAMA. 1995;273
:408
–412
[Abstract/Free Full Text] - Higgins J, Thompson S, Deeks J, Altman D. Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice.
J Health Serv Res Policy. 2002;7
:51
–61
[Abstract/Free Full Text] - Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21 :1539 –1558[CrossRef][Web of Science][Medline]
- Als-Nielsen B, Chen W, Gluud C, Kjaergard LL. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?
JAMA. 2003;290
:921
–928
[Abstract/Free Full Text] - Jorgensen AW, Hilden J, Gotzsche PC. Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review.
BMJ. 2006;333
:782
[Abstract/Free Full Text] - Barnes DE, Bero LA. Why review articles on the health effects of passive smoking reach different conclusions.
JAMA. 1998;279
:1566
–1570
[Abstract/Free Full Text] - Cramer K, Wiebe N, Moyer V, et al. Children in reviews: methodological issues in child-relevant evidence syntheses. BMC Pediatr. 2005;5 :38[CrossRef][Medline]
- Bisgaard H. Long-acting beta(2)-agonists in management of childhood asthma: a critical review of the literature. Pediatr Pulmonol. 2000;29 :221 –234[CrossRef][Web of Science][Medline]
- Jadad AR, Cook DJ, Jones A, et al. Methodology and reports of systematic reviews and meta-analyses: a comparison of Cochrane reviews with articles published in paper-based journals.
JAMA. 1998;280
:278
–280
[Abstract/Free Full Text] - Hopayian K. The need for caution in interpreting high quality systematic reviews.
BMJ. 2001;323
:681
–684
[Free Full Text] - Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses.
BMJ. 2003;327
:557
–560
[Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Minelli, J. R. Thompson, K. R. Abrams, A. Thakkinstian, and J. Attia The Quality of Meta-Analyses of Genetic Association Studies: A Review With Recommendations Am. J. Epidemiol., December 1, 2009; 170(11): 1333 - 1343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. DeMaria Meta-analysis. J. Am. Coll. Cardiol., July 15, 2008; 52(3): 237 - 238. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
