Types of studies
All systemic reviews of Randomized Controlled Trials and Cohort study designs comparing the effects of glucocorticoids on acute respiratory syndrome without language and date restriction were included. This umbrella review was registered in Prospero international prospective register of systemic reviews (CRD42019130539).
Types of participants
All Systemic reviews incorporating adult ICU patient with ARDS receiving glucocorticoid and placebo were considered
Intervention
The intervention was any type of glucocorticoids administered to patients with acute respiratory distress syndrome.
Comparator
The control was patients who took a placebo or other form of treatment with the purpose of comparing it with glucocorticoids.
Types of outcomes
The primary outcomes were hospital mortality and the number of mechanical ventilator-free days. The secondary outcomes were duration of ICU stay and glucocorticoid related adverse effects including the incidence of infection, hyperglycemia, and neuromuscular dysfunction.
Eligibility criteria
Inclusion criteria
The umbrella review included all systemic reviews with or without meta-analysis comparing the effectiveness of glucocorticoids on acute respiratory disease syndrome either for treatment or prevention strategies.
Exclusion criteria
The overview view excluded systemic reviews assessing the effectiveness of glucocorticoid on pediatrics acute respiratory syndrome, a systemic review of cross-sectional studies and clinical reviews.
Search strategy
The search strategy was intended to explore all available published and unpublished systemic reviews on the effectiveness of glucocorticoids for treatment or prevention of acute respiratory distress syndrome. A three-phase search strategy was employed in this umbrella review. An initial search on PubMed/Medline, Cochrane Library, Science direct, LILACS, and African Online Journal was carried out followed by an analysis of the text words contained in Title/Abstract and indexed terms. A second search was undertaken by combining free text words and indexed terms with Boolean operators. The third search was conducted with the reference lists of all identified reports and articles for additional studies. Finally, an additional and grey literature search was conducted on Google scholars up to ten pages. The result of the search strategy was presented with the Prisma flow chart (figure-1). The search strategy conducted in PubMed was presented in appendix 1.
Methodological Quality Assessment
The methodological quality of each included systemic review was evaluated with the AMSTAR tool (Assessing the Methodological quality of systemic reviews) by two independent authors25. A score was given for each included systemic review from the sum of all positive points to the checklist items and the inconvenience between the two authors was resolved by the third author. The included systemic reviews were classified based on the AMSTAR scores as high quality 8-11, moderate quality 4-7 and low quality 0-3 score values (Table 1).
Table 1 Assessment of Methodological quality
Author/year
|
Q1
|
Q2
|
Q3
|
Q4
|
Q5
|
Q6
|
Q7
|
Q8
|
Q9
|
Q10
|
Q11
|
Score
|
Menduri et al 16 2018
|
√
|
X
|
√
|
X
|
√
|
√
|
X
|
√
|
√
|
X
|
√
|
7
|
Yang et al21 2017
|
√
|
√
|
√
|
√
|
√
|
√
|
√
|
X
|
X
|
√
|
X
|
8
|
Menduri et al18 2016
|
√
|
X
|
X
|
X
|
X
|
√
|
X
|
X
|
√
|
√
|
√
|
5
|
Horita et al23 2015
|
√
|
√
|
√
|
X
|
√
|
√
|
√
|
X
|
√
|
√
|
√
|
9
|
Ruan et al 19 2014
|
√
|
√
|
√
|
√
|
√
|
√
|
√
|
X
|
X
|
X
|
√
|
9
|
Khilnani and colleague 22 2011
|
√
|
√
|
√
|
√
|
X
|
X
|
X
|
√
|
X
|
X
|
X
|
5
|
Curtis and colleague26 2010
|
√
|
X
|
X
|
X
|
X
|
X
|
√
|
√
|
X
|
X
|
X
|
3
|
Benjamin et al17 2009
|
√
|
√
|
√
|
√
|
X
|
√
|
X
|
X
|
√
|
X
|
X
|
6
|
Peter et al20 2008
|
√
|
√
|
√
|
√
|
X
|
X
|
√
|
√
|
√
|
X
|
√
|
8
|
Marik et al
|
x
|
√
|
x
|
X
|
x
|
√
|
x
|
√
|
x
|
x
|
x
|
3
|
The AMSTAR tool (Assessing the Methodological quality of systemic reviews)
Q1: Was an 'a priori' design provided?
Q2: Was there duplicate study selection and data extraction?
Q3: Was a comprehensive literature search performed?
Q4: Was the status of publication (i.e. grey literature) used as an inclusion criterion?
Q5: Was a list of studies (included and excluded) provided?
Q6: Were the characteristics of the included studies provided?
Q7: Was the scientific quality of the included studies assessed and documented?
Q8: Was the scientific quality of the included studies used appropriately in formulating conclusions?
Q9: Were the methods used to combine the findings of studies appropriate?
Q10: Was the likelihood of publication bias assessed?
Q11: Was the conflict of interest included?
Data extraction
The data from each systemic review and meta-analysis was extracted with two independent authors for description of included studies and grading the overall quality of evidence of each systemic reviews and meta-analysis. The data extracted included author, year of publication, number of RCTs included, number of participants, methodological quality, outcome of interest, total events in treatment and control and effect sizes (Odds Ratio, Relative Risk, Mean difference and 95% confidence interval). The overall quality of evidence was graded with online GRADEpro GDT software. The umbrella review was presented based on the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA)27 (additional File).
Grading the quality of evidence
The overall qualities of evidence for the studied outcome were evaluated using the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation)28,29. The system incorporates study quality (risk of bias), inconsistency (comparison of effect estimates across studies), indirectness (applicability of the population, intervention, comparator and outcomes to the clinical decision), imprecision (certainty of confidence interval) and high probability of publication bias. The overall quality of evidence was categorized as follows by evaluating and combing the above five parameters for mortality, mechanical ventilator free days and incidence of infection.
- Effective interventions: indicated that the review found high-quality evidence of effectiveness for an intervention.
- Possibly effective interventions: indicated that the review found moderate-quality evidence of effectiveness for an intervention, but more evidence is needed.
- Ineffective interventions: indicated that the review found high-quality evidence of lack of effectiveness (or harm) for an intervention.
- Probably ineffective interventions: indicated that the review found moderate-quality evidence suggesting a lack of effectiveness (or harm) for an intervention, but more evidence is needed.
- No conclusions possible: indicated that the review found low or very low-quality evidence, or insufficient evidence to comment on the effectiveness or safety of an intervention.