Statistical Note: Confounding and Causality in Observational Studies

Horvat, Christopher M.

doi:10.1097/pcc.0000000000002702

Cited by 12 publications

(12 citation statements)

References 18 publications

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“…Parameter estimates and 95% confidence intervals (CI) were exponentiated. Other than the primary independent variable (steroid and IVIG and their combination versus none), other variables were selected based on prior evidence, expert knowledge, 29 or the potential impact on LOS (and illness severity) of patients admitted to the pediatric ICU and more specifically for COVID‐19 related illness. 28 , 30 The variables included age (in years), the number of abnormal inflammatory mediators on admission, race (dichotomized as non‐Hispanic white versus not), a composite variable of obesity and any comorbidity, a composite variable of bacterial or viral coinfection at admission, and a composite variable of WHO ordinal scale ≥ 4 on admission or ICU admission within ≤ 2 days.…”

Section: Methodsmentioning

confidence: 99%

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS‐C) associated with COVID‐19: A retrospective cohort analysis from 28 U.S. Hospitals

et al. 2022

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Objectives: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19).

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Section: Methodsmentioning

confidence: 99%

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS‐C) associated with COVID‐19: A retrospective cohort analysis from 28 U.S. Hospitals

et al. 2022

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“… 53 , 54 Although there seems to be a sound pathophysiological explanation for the observed association in this review, 55 further insight of the complex association between oxygen supplementation and outcome from additional prospective pediatric studies is needed. 10 , 56 In addition, the clinical implications need to be addressed in clinical trials. On this note, there have been several trials comparing liberal vs restrictive oxygen targets over the past years in critically ill adults.…”

Section: Discussionmentioning

confidence: 99%

“…Another hypothesis could be that children's susceptibility to oxygen toxic effects differs from that of adults owing to age-related differences in vulnerability, which, for example, appears to be true for ventilator-induced lung injury . Although there seems to be a sound pathophysiological explanation for the observed association in this review, further insight of the complex association between oxygen supplementation and outcome from additional prospective pediatric studies is needed . In addition, the clinical implications need to be addressed in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Association of Arterial Hyperoxia With Outcomes in Critically Ill Children

et al. 2022

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IMPORTANCEOxygen supplementation is a cornerstone treatment in pediatric critical care.Accumulating evidence suggests that overzealous use of oxygen, leading to hyperoxia, is associated with worse outcomes compared with patients with normoxia.OBJECTIVES To evaluate the association of arterial hyperoxia with clinical outcome in critically ill children among studies using varied definitions of hyperoxia.DATA SOURCES A systematic search of EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception to February 1, 2021, was conducted.STUDY SELECTION Clinical trials or observational studies of children admitted to the pediatric intensive care unit that examined hyperoxia, by any definition, and described at least 1 outcome of interest. No language restrictions were applied. DATA EXTRACTION AND SYNTHESISThe Meta-analysis of Observational Studies in Epidemiology guideline and Newcastle-Ottawa Scale for study quality assessment were used. The review process was performed independently by 2 reviewers. Data were pooled with a random-effects model. MAIN OUTCOMES AND MEASURESThe primary outcome was 28-day mortality; this time was converted to mortality at the longest follow-up owing to insufficient studies reporting the initial primary outcome. Secondary outcomes included length of stay, ventilator-related outcomes, extracorporeal organ support, and functional performance. RESULTSIn this systematic review, 16 studies (27 555 patients) were included. All, except 1 randomized clinical pilot trial, were observational cohort studies. Study populations included were post-cardiac arrest (n = 6), traumatic brain injury (n = 1), extracorporeal membrane oxygenation (n = 2), and general critical care (n = 7). Definitions and assessment of hyperoxia differed among included studies. Partial pressure of arterial oxygen was most frequently used to define hyperoxia and mainly by categorical cutoff. In total, 11 studies (23 204 patients) were pooled for meta-analysis.Hyperoxia, by any definition, showed an odds ratio of 1.59 (95% CI, 1.00-2.51; after Hartung-Knapp adjustment, 95% CI, 1.05-2.38) for mortality with substantial between-study heterogeneity (I 2 = 92%). This association was also found in less heterogeneous subsets. A signal of harm was observed at higher thresholds of arterial oxygen levels when grouped by definition of hyperoxia.Secondary outcomes were inadequate for meta-analysis. CONCLUSIONS AND RELEVANCEThese results suggest that, despite methodologic limitations of the studies, hyperoxia is associated with mortality in critically ill children. This finding identifies the (continued) Key Points Question What is the association between arterial hyperoxia and outcomes in critically ill children admitted to the pediatric intensive care unit? Findings This systematic review of 16 studies and meta-analysis of 11 studies comprising a total of 23 204 patients found an association between hyperoxia and mortality in children admitted to the pediatric intensive care unit. Meaning These findings suggest that hyperoxia is a...

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“…For example, the strategy of hyperoxemic therapy is used for preconditioning of the myocardium when the disadvantages of the technique do not outweigh the potential advantages (5). However, in both critically ill adults and children, there is an increasing body of evidence of an association between hyperoxia and mortality (6)(7)(8).…”

mentioning

confidence: 99%