Additional file 1 of High-flow nasal cannula oxygen versus conventional oxygen therapy for acute respiratory failure due to COVID-19: a systematic review and meta-analysis

Additional file 1: Figure S1. Risk of bias graph (ROB 2) for intubation outcome from randomized controlled trials. Figure S2. Funnel plot for intubation rate and assessment of small-study effects by Rücker’s limit meta-analysis method using Arcsine difference and Peters arcsine test. Figure S3. Funnel plot for mortality rate and assessment of small-study effects by Rücker’s limit meta-analysis method using arcsine difference and Peters arcsine test. Figure S4. Forest plot of intubation rate comparison between HFNC and COT from prospective and retrospective studies (random-effects meta-analysis by the Mantel–Haenszel method). COT, conventional oxygen therapy; HFNC, high-flow nasal cannula; M-H, Mantel–Haenszel. Figure S5. Sensitivity analysis of the risk of intubation through the leave-one-out strategy for the randomized controlled trials (fixed-effects meta-analysis by the Mantel–Haenszel method). COT, conventional oxygen therapy; HFNC, high-flow nasal cannula. Figure S6. Sensitivity analysis of the risk of intubation through the leave-one-out strategy for all studies (random-effects meta-analysis by the Mantel–Haenszel method). COT, conventional oxygen therapy; HFNC, high-flow nasal cannula. Figure S7. Forest plot of intubation rate comparison between HFNC and COT from randomized controlled trials according to the location of admission (random-effects meta-analysis by the Mantel–Haenszel method). COT, conventional oxygen therapy; HFNC, high-flow nasal cannula; ICU, intensive care unit; M-H, Mantel–Haenszel. Figure S8. Forest plot of mortality comparison between HFNC and COT from prospective and retrospective studies (random-effects meta-analysis by the Mantel–Haenszel method). COT, conventional oxygen therapy; HFNC, high-flow nasal cannula; M-H, Mantel–Haenszel. Figure S9. Forest plot of mortality rate comparison between HFNC and COT from randomized controlled trials according to the location of admission (fixed-effects meta-analysis by the Mantel–Haenszel method). COT, conventional oxygen therapy; ICU, intensive care unit; HFNC, high-flow nasal cannula; M-H, Mantel–Hanszel. Figure S10. Trial sequential analysis of mortality outcome. Studies are shown as black-filled squares on the cumulative Z curve. For the conventional boundaries, p=0.05 and z=|1.96|. The TSA software only generates Z scores from -8 to +8. The cumulative Z curve crosses the futility boundary, suggesting that HFNC is unlikely to have an effect on mortality in comparison to COT and that the addition of more trials would not modify the conclusion. COT, conventional oxygen therapy; HFNC, high-flow nasal cannula; TSA, trial sequential analysis. Figure S11. Forest plot of intensive care unit length of stay comparison between HFNC and COT from randomized controlled trials (random-effects meta-analysis by the inverse variance method). COT, conventional oxygen therapy; HFNC, high-flow nasal cannula; IV, inverse variance. Figure S12. Forest plot of hospital length of stay comparison between HFNC and COT from randomized controlled trials (fixed-effects meta-analysis by the inverse variance method). COT, conventional oxygen therapy; HFNC, high-flow nasal cannula; IV, inverse variance. Table S1. Search strategy. Table S2. Risk of bias graph (ROBINS-I) for intubation outcome from non-randomized controlled trials. Table S3. Study characteristics of the non-randomized controlled trials. Table S4. Patient characteristics of the non-randomized controlled trials. Table S5. Pre-defined intubation criteria of the randomized controlled trials. Table S6. GRADE evidence profile for the studies in the meta-analysis.