Dex single dose Pred- 5 day course Mean Difference Mean Difference Mean 3.5. Weight 100.0% IV, Fixed, 95% CI [-1.97, 0.37] 100.

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1 Question : In the child with asthma exacerbation in the ED should prednisolone/prednisone vs. dexamethasone be used to prevent hospitalization, decrease time in the ED or improve pulmonary function? Forest Plots of Single Studies Oral dexamethasone vs. 5 day oral prednisone, Outcome: Length of Stay in ED (hrs). (5% CI) Heterogeneity: Not applicable Test for overall effect: Z = 1.34 (P = 0.18) Dex single dose Pred- 5 day course Difference Difference IV, Fixed, 5% CI [-1.7, 0.37] IV, Fixed, 5% CI Oral dexamethasone vs. 5 day oral prednisone, outcome: Hospital admission. (5% CI) events 6 Heterogeneity: Not applicable Test for overall effect: Z = 0.0 (P = 0.37) Oral dexamethasone vs. 5 day oral prednisone, outcome: PEF at discharge [-1.7, 0.37] Favours experimental Favours control Dex single dose Pred- 5 day course Odds Ratio Odds Ratio 6 M-H, Fixed, 5% CI 0.60 [0.20, 1.82] M-H, Fixed, 5% CI 0.60 [0.20, 1.82] Favours experimental Favours control Dex single dose Pred- 5 day course Difference Difference IV, Fixed, 5% CI [-.32, ] IV, Fixed, 5% CI (5% CI) Heterogeneity: Not applicable Test for overall effect: Z = 0.75 (P = 0.45) [-.32, ] Favours control Favours experimental 42

2 Oral Dexamethasone vs. Oral Prednisone, outcome: Unscheduled follow up appointment(s). Greenberg 2008 (5% CI) 82 events 12 4 Heterogeneity: Chi² = 0.06, df = 1 (P = 0.81); I² = 0% Test for overall effect: Z = 1.1 (P = 0.06) Synthesis Authors: EBP Scholars (Allen, N. H., Carlson, E., Dusin, J., Gutierrez, C., Hodges, K., & Pirvu, D.) Date: 10/21/2101 Risk of bias summary figure: Dexamethasone Prednisone Odds Ratio Odds Ratio % 70.0% M-H, Fixed, 5% CI 4.08 [0.44, 37.70] 2.6 [0.68, 12.1] M-H, Fixed, 5% CI [0.7, 11.22] Favours experimental Favours control Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding (performance bias and detection bias) Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Other bias Greenberg 2008? 43

3 Included Single Study Characteristics and Risk of Bias Tables: Characteristics of included study: Methods Randomization: prepared sealed randomization cards, prepared the cards, as well as the study drugs. Blinding: medications were made to look and taste the same. Excluded: Withdrawals: 2 patients vomited in the ED; for the five day follow up in the dexamethasone group and 13 in the prednisone group were admitted or lost to follow up. Baseline characteristics:110 subjects enrolled, in dexamethasone group and in the prednisone group. Similar base line characteristics. Per protocol analysis Power calculation: non-inferiority was accepted if single dose oral dexamethasone was no worse that 1 extra day. Chose a small beta of 0.05 d/t non-inferiority. Power calc= 134 or 67 in each group. Participants Setting: British Columbia CANADA urban ED. Inclusion Criteria: children 2-16 in the ED with mild to moderate asthma, with at least one episode of "asthma like" symptoms. Defined mild to moderate with a Pulmonary Index Score (PIS) of < and a PEF of 60% or more of predicted value for height Exclusion Criteria: signs and symptoms of severe asthma ( PEF less than 60% predicted for height. PIS > 10, compete recovery after first salbutamol treatment, use of oral steroids over the the last 2 weeks Interventions Group A: ED medication-0.6 mg/kg of dexamethasone in 1 ml/kg, Discharge medication: Placebo Group B: ED medication: 1 mg/kg prednisone in 1 ml/kg Discharge medication: 1 mg/kg prednisone per dose Outcomes Primary outcome: number of days needed for asthma score to return to baseline or PEF to return to 80% predicted for height Secondary: short term improvement in PEF asthma score at the time of discharge from the ED, actual time to discharge, number of salbutamol therapies needed in the ED, initial admission rate, number of salbutamol therapies given at home, return to the ED, need for admission after initial discharge and improvement in asthma score on day 5. Risk of bias: Bias Authors' judgment Support for judgment Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding (performance bias and detection bias) 44

4 Incomplete outcome data (attrition bias) High risk They powered the study for 67 enrolled in each group, but had inherent drop out points. Did not meet power at time of analysis Selective reporting (reporting bias) Other bias High risk competing nurse project initiated nursing guideline implemented at the same time as the study started, patients were quickly treated with beta agonists and oral steroids prior to study enrollment Greenberg 2008 Characteristic of included study: Methods Randomization: Block randomization < 7 years and > 7 years, Blinding: pharmacy prepared drugs to look identical as a white powder capsule. Excluded: children who were admitted, lost to follow-up, or vomited study drug twice. subjects were excluded for unknown reasons. Excluded patients had higher PAS, but admission was a criterion for exclusion. Withdrawals: Baseline characteristics: There were more Caucasians in the Dexamethosone group and more "others" in the prednisone group Intention to treat: Power calculation: Participants Children 2-18 years of age with a history of asthma ( 2 or more episodes of wheezing treated with Beta agonists. Urban tertiary ED Inclusion Criteria Exclusion Criteria the use of oral steroids in the past month; history of intubation for a previous asthma exacerbation; varicella exposure in the past 3 weeks; possible foreign body aspiration; any chronic lung disease (e.g., cystic fibrosis) that would affect the patient s management; chronic heart, liver, or kidney disease; significant respiratory distress necessitating airway intervention (e.g., intubation); previous enrollment in this study; no telephone for follow-up; and 2 episodes of emesis after steroid administration in the ED. Interventions Experimental: 2 doses of oral dexamethasone 0.6 mg/kg, maximum dose 16 mg- rounded to nearest 2 mg. Control: 5 day course of oral prednisone 2 mg/kg, maximum dose 80 mg. rounded to the nearest 5 mg. Outcomes Primary: relapse in 10 days Secondary: vomiting in the ED 45

5 Risk of bias: Bias Authors' judgment Support for judgment Random sequence generation (selection bias) Unclear risk They used block randomization, but do say how. Allocation concealment (selection bias) Blinding (performance bias and detection bias) All received 5 pills to take one per day. In the dexamethasone group, only one pill had study drug. In the prednisone group, all pills had study drug. Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Unclear risk Other bias Search Strategies: PubMed search Sept 23, 2010 (("Asthma"[Mesh] AND ("Emergency Service, Hospital"[Mesh] OR "Emergency Nursing"[Mesh] OR "Emergency Medical Services"[Mesh] OR "Emergency Medicine"[Mesh] OR "Acute Disease"[Mesh] OR exacerbation[all Fields] OR attack[all Fields])) AND (("Dexamethasone"[Mesh] OR "Dexamethasone Isonicotinate"[Mesh] OR "Methylprednisolone"[Mesh] OR "Methylprednisolone Hemisuccinate"[Mesh] OR "Prednisolone"[Mesh] OR "Prednisone"[Mesh] OR "Hydrocortisone"[Mesh]) AND ("Injections, Intramuscular"[Mesh] OR "Administration, Oral"[Mesh] OR "Infusions, Intravenous"[Mesh] OR "Injections, Intravenous"[Mesh] OR "administration and dosage "[Subheading]))) AND (((Meta-Analysis[ptyp] OR Practice Guideline[ptyp] OR Randomized Controlled Trial[ptyp] OR Guideline[ptyp] OR Comparative Study[ptyp]) OR ("Cohort Studies"[Mesh] OR systematic[sb])) AND English[lang] AND ("infant"[mesh Terms] OR "child"[mesh Terms] OR "adolescent"[mesh Terms]) AND ("2006/03"[PDAT] : "2010"[PDAT])) 16 results CINAHL search Sept 23, 2010 S1 (MH "Acute Disease") Limiters - Exclude MEDLINE records Search modes - Boolean/Phrase S2 (MH "Emergency Medical Services") OR (MH "Emergency Service") OR (MH "Emergency Nursing") OR (MH "Emergency Medicine") Limiters - Exclude MEDLINE records Search modes - Boolean/Phrase S3 (MH "Asthma") Limiters - Exclude MEDLINE records Search modes - Boolean/Phrase S4 (MH "Disease Exacerbation") Search modes - Boolean/Phrase S5 S1 or S2 or S4 Search modes - Boolean/Phrase S6 S3 and S5 Search modes - Boolean/Phrase 46

6 S7 (MH "Dexamethasone") OR (MH "Methylprednisolone") OR (MH "Prednisolone") OR (MH "Prednisone") OR (MH "Hydrocortisone") Limiters - Exclude MEDLINE records Search modes - Boolean/Phrase S8 dexamethasone isonicotinate OR Methylprednisolone hemisuccinate Limiters - Exclude MEDLINE records Search modes - Boolean/Phrase S (MH "Injections, Intramuscular") OR (MH "Administration, Oral") OR (MH "Infusions, Intravenous") OR (MH "Injections, Intravenous") Limiters - Exclude MEDLINE records Search modes - Boolean/Phrase S10 S7 or S8 Search modes - Boolean/Phrase S11 S6 and S and S10 Search modes - Boolean/Phrase S12 S6 and S and S10 Limiters - Published Date from: ; English Language; Age Groups: All Child Search modes - Boolean/Phrase 0 results 47