Therapeutic Efficacies of Normobaric Oxygen Therapy in Healthcare: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundNormobaric oxygen therapy is one of the most commonly used treatments in healthcare; however, oxygen is not a panacea. There is currently a lack of a comprehensive review summarizing different normobaric oxygen therapies and their therapeutic efficacies based on randomized controlled trials across healthcare. MethodsWe systematically searched Ovid MEDLINE, Ovid Embase, Web of Science, and the Cochrane database from inception to April 4, 2019, for randomized controlled trials investigating the therapeutic efficacy of normobaric oxygen therapy compared to usual care. Two investigators independently extracted study data and assessed study quality.ResultsA total of 173 studies involving 81,792 patients were included in qualitative analysis, and 95 of these studies, segregated in 49 bodies of evidence according to methods of oxygen therapy used, patient populations treated, and outcomes measured, were included in meta-analyses. Normobaric oxygen therapy was guided by oxygen flow, inspired oxygen fraction (FiO2), or an oxygenation monitor. Each method had multiple different protocols. Eighteen different outcome measures were commonly used to assess the therapeutic efficacy. Ten (20%), 2 (4%) and 37 (76%) bodies of evidence suggested a beneficial, harmful, and futile effect, respectively. The quality of only two bodies of evidence (4%) was high, i.e., the significant reduction of prematurity-related mortality and necrotizing enterocolitis by 91-95% pulse oxygen saturation-guided therapy. The quality of the remaining 47 bodies of evidence was moderate (39%), low (43%), or very low (14%). Contrary to the World Health Organization recommendation, 80% FiO2-guided oxygen therapy did not affect surgical site infection in intubated surgical patients (risk ratio, 0.84; 95% confidence interval, 0.69 to 1.01; p=0.07; moderate quality).ConclusionsNormobaric oxygen therapy is widely used across healthcare; however, more than 70% of bodies of evidence suggested a futile effect and the quality of more than 50% of bodies of evidence was low or very low. How to best use normobaric oxygen therapy deserves further research.

An optimal Wilcoxon–Mann–Whitney test of mortality and a continuous outcome

We consider a two-group randomized clinical trial, where mortality affects the assessment of a follow-up continuous outcome. Using the worst-rank composite endpoint, we develop a weighted Wilcoxon–Mann–Whitney test statistic to analyze the data. We determine the optimal weights for the Wilcoxon–Mann–Whitney test statistic that maximize its power. We derive a formula for its power and demonstrate its accuracy in simulations. Finally, we apply the method to data from an acute ischemic stroke clinical trial of normobaric oxygen therapy.