Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

Highlighted lines and questions below provide links to the pertinent description of criteria in The EBM User's Guide, now available at the Canadian Centres for Health Evidence

Article Reviewed:

Please visit the new Evidence Based Journal Club Reviews

Systemic Corticosteroids in Infant Bronchiolitis: A Meta-analysis.

Garrison MM, Christakis DA, Harvey E, Cummings P, Davis RL.

Pediatrics 2000;105:e44. [abstract] [full-text]

Reviewed by M. Bonnie Dutta, Medical College of Ohio, Toledo, Ohio

Review posted September 25, 2000

---

I. Are the results of the study valid?

A. Primary questions:

1. Did the overview address a focused clinical question?

Yes: To determine whether treatment with systemic corticosteroids decreases length of hospital stay or provides symptomatic relief in hospitalized infants with bronchiolitis.

2. Were the criteria used to select articles for inclusion appropriate?

Yes. Selection criteria used to identify studies were clearly stated as follows:

1. Study design: Prospective, randomized, double blind, placebo-controlled clinical trial
2. Population: All study subjects were hospitalized and younger than 24 months old, and 2 of the 6 studies were limited to infants younger than 12 months old. The most common exclusion criteria used were previous wheezing and chronic cardiorespiratory distress. Two of the 6 studies included only infants with positive laboratory test results for RSV. To increase homogeneity of the sample, only data concerning hospitalized patients who did not require mechanical ventilation were included.
3. Intervention: Treatment with intravenous, intramuscular or oral corticosteroids. To allow comparability of dosage and types of corticosteroids, doses were converted to mg/kg prednisone equivalents.
4. Outcome: Length of hospital stay (LOS), duration of symptoms (DOS), clinical scores and oxygen saturation (oximetry) were chosen as the outcome measures. Because all patients were hospitalized in the studies, LOS and DOS were considered to be proxies of one another, and these two measures were combined into one measure (LOS-DOS). The 2 measures were also analyzed independently in a subanalysis. Clinical score and oxygen saturation were analyzed for 24-72 hours after initial treatment.

B. Secondary questions:

3. Is it unlikely that important, relevant studies were missed?

Yes. The authors searched MEDLINE 1966-Jan 1999, the Cochrane Clinical Trials Registry (as of January 1999), and EMBASE Jan 1990 Ð Jan 1999. The bibliographies of review articles and all selected articles were examined. The authors do not mention contacting experts in the area of bronchiolitis. These limitations could contribute to relevant studies being missed. Attempts were made to contact authors to provide more information when data was missing or unclear. There is no mention if they included literature from all languages.

4. Was the validity of the included studies appraised?

Yes. A methodologic quality scoring system was used to critically appraise each of the primary studies. The methodologic assessment included an evaluation of patient selection, baseline characteristics, randomization, blinding, interventions, complications and adherence to protocol. Five studies were deemed to be of high methodologic quality (score 8) and 4 of lower quality (score < 8).

5. Were assessments of studies reproducible?

Yes. The articles were independently reviewed by two of the authors to decide on inclusion/exclusion. The investigators were blinded to the results of the studies, as well as to the journal and author names. Disagreements were resolved through discussion, and consensus was achieved in the selection of articles for analysis. Data were then independently abstracted by three authors (EAC, DH and MMG) using a standardized reporting form.

Two of the authors independently assessed the validity of the 9 studies selected. To avoid bias in the assessments, one reviewer was again blinded. Authors of the primary study were also asked to ensure the accuracy of the methodological scores and to provide important additional information when it was not reported in their publication. The weighted kappa for agreement between reviewers on each quality assessment item was 0.71 to 1.0. Disagreements were resolved by discussion and consensus.

6. Were the results similar from study to study?

Yes. No heterogeneity was found using the Q-statistic for pooled effect sizes for LOS or DOS. Combining LOS and DOS increased the homogeneity of the data. The 24-hour clinical scores and oximetry were the only time points where data could be pooled. The measurements at 72 hours were too heterogeneous for pooling.

II. What are the results?

1. What are the overall results of the review?

Of 238 articles retrieved in the search, 12 clinical trials of corticosteroid therapy in infant bronchiolitis were found. Six trials were included in the final analysis. Three trials were excluded because they were not randomized. One study was excluded because the subjects were randomized before hospital admission and not all patients were subsequently hospitalized, leading to a nonrandom distribution of hospitalized patients. One additional trial, now 30 years old, was later excluded because of inconsistencies in the data that could not be resolved despite attempts at contacting the authors. One study included patients on mechanical ventilation - this was excluded from the study but was discussed in the Discussion section. Only three of the six included studies had extractable data for the analysis of clinical symptoms and oximetry.

Publication bias is the possibility that only positive studies were published and negative studies filed away and forgotten. The fact that the majority of published studies were negative decreases the possibility that publication bias could explain the results. There was also no statistical evidence of publication bias (p = 1.0) among the six trials included in the analysis.

Corticosteroid therapy was associated with a statistically significant reduction in length of hospital stay of 0.43 days in the pooled set of 347 patients. Clinical scores were significantly lower at 24 hours in the corticosteroid group at a standardized mean difference of 1.6 in the subset of 197 patients.

2. How precise were the results?

The 95% confidence interval for the reduction in length of hospital stay was 0.81 days to 0.05 days. Although this did not cross zero days, the lower limit of the confidence interval is close to zero. For the clinical scores difference estimate, the 95% confidence interval was 1.92 to 1.28.

III. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

Somewhat. The study excluded patients who required mechanical ventilation. The authors do mention in the one study that included patients on mechanical ventilation (excluded from the meta-analysis), this group of patients had a length of stay 6 days shorter than the placebo group on mechanical ventilation. There was only a difference of one day in nonventilated patients in this study. The benefits of systemic steroids could be substantial in the hospital setting. With a mean reduction in length of stay of 0.43 days per patient, the authors estimate that approximately 51,600 hospital days could potentially saved through the use of steroid treatment.

2. Were all clinically important outcomes considered?

No. Complications of steroids were not evaluated such as gastrointestinal bleeding and infections.

3. Are the benefits worth the harms and costs?

Probably. Steroids are relatively inexpensive. If they do shorten hospital length of stay, they would be cost-effective.

References

1. Bulow SM, Marta N, Levin E. et al . Prednisolone treatment of respiratory syncytial virus infection: a randomized controlled trial of 147 infants. Pediatrics 1999; 104(6).

Comment

A study by Bulow et al. (1) not included in the review was published four months before the meta-analysis. This study found no significant difference using prednisolone 2 mg/kg daily for 5 days (73 infants) versus placebo (74 infants). The median length of stay was 3.6 days in the prednisolone group and 4 days in the placebo group (NS). Patients were followed up at 1 month and one year after discharge. The frequency of patients admitted for respiratory infections, those being treated for asthma and the number coughing at night was not statistically different between the two groups.

Comments

Back to the EB Journal Club Index