Causal Bayesian machine learning to assess treatment effect heterogeneity by dexamethasone dose for patients with COVID-19 and severe hypoxemia.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
21 04 2023
Historique:
received: 03 01 2023
accepted: 12 04 2023
medline: 25 4 2023
pubmed: 22 4 2023
entrez: 21 04 2023
Statut: epublish

Résumé

The currently recommended dose of dexamethasone for patients with severe or critical COVID-19 is 6 mg per day (mg/d) regardless of patient features and variation. However, patients with severe or critical COVID-19 are heterogenous in many ways (e.g., age, weight, comorbidities, disease severity, and immune features). Thus, it is conceivable that a standardized dosing protocol may not be optimal. We assessed treatment effect heterogeneity in the COVID STEROID 2 trial, which compared 6 mg/d to 12 mg/d, using a causal inference framework with Bayesian Additive Regression Trees, a flexible modeling method that detects interactive effects and nonlinear relationships among multiple patient characteristics simultaneously. We found that 12 mg/d of dexamethasone, relative to 6 mg/d, was probably associated with better long-term outcomes (days alive without life support and mortality after 90 days) among the entire trial population (i.e., no signals of harm), and probably more beneficial among those without diabetes mellitus, that were older, were not using IL-6 inhibitors at baseline, weighed less, or had higher level respiratory support at baseline. This adds more evidence supporting the use of 12 mg/d in practice for most patients not receiving other immunosuppressants and that additional study of dosing could potentially optimize clinical outcomes.

Identifiants

pubmed: 37085591
doi: 10.1038/s41598-023-33425-3
pii: 10.1038/s41598-023-33425-3
pmc: PMC10120498
doi:

Substances chimiques

Dexamethasone 7S5I7G3JQL

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6570

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL126802
Pays : United States
Organisme : Department of Health
ID : CS-2016-16-011
Pays : United Kingdom

Informations de copyright

© 2023. The Author(s).

Références

Stat Med. 2018 Oct 15;37(23):3309-3324
pubmed: 29862536
J Clin Epidemiol. 2005 Mar;58(3):261-8
pubmed: 15718115
Intensive Care Med. 2022 Jan;48(1):45-55
pubmed: 34757439
Acta Anaesthesiol Scand. 2022 Sep;66(8):987-995
pubmed: 35781689
Ann Intern Med. 2007 Oct 16;147(8):573-7
pubmed: 17938396
Intensive Care Med. 2022 Nov;48(11):1525-1538
pubmed: 36102943
Science. 2020 Sep 4;369(6508):
pubmed: 32669297
JAMA. 2021 Nov 9;326(18):1807-1817
pubmed: 34673895
JAMA. 2022 Feb 15;327(7):683
pubmed: 35166802
Nat Med. 2020 Oct;26(10):1623-1635
pubmed: 32807934
Stat Med. 2021 Sep 20;40(21):4691-4713
pubmed: 34114252
Nature. 2020 Aug;584(7821):463-469
pubmed: 32717743
Nature. 2021 Feb;590(7847):635-641
pubmed: 33429418
Stat Methods Med Res. 2019 Apr;28(4):1079-1093
pubmed: 29254443
Acta Anaesthesiol Scand. 2021 Jul;65(6):834-845
pubmed: 33583034
JAMA. 2021 Aug 10;326(6):499-518
pubmed: 34228774
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
Stat Med. 2021 May 20;40(11):2665-2691
pubmed: 33751659
BMJ. 2020 Sep 4;370:m3379
pubmed: 32887691
Nat Med. 2022 Jan;28(1):39-50
pubmed: 35064248
Crit Care. 2006 Feb;10(1):103
pubmed: 16420653
J Comput Graph Stat. 2018;27(1):209-219
pubmed: 29706752
Acta Anaesthesiol Scand. 2021 Nov;65(10):1421-1430
pubmed: 34138478
Health Technol Assess. 2001;5(33):1-56
pubmed: 11701102
JAMA. 2020 Oct 6;324(13):1330-1341
pubmed: 32876694
Trends Pharmacol Sci. 2019 Jan;40(1):38-49
pubmed: 30497693
Acta Anaesthesiol Scand. 2023 Feb;67(2):195-205
pubmed: 36314057
BMJ. 2015 Nov 04;351:h5651
pubmed: 26537915

Auteurs

Bryan S Blette (BS)

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Clinical Trials Methods and Outcomes Lab, Palliative and Advanced Illness Research (PAIR) Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Anders Granholm (A)

Department of Intensive Care, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark.
Collaboration for Research in Intensive Care, Copenhagen, Denmark.

Fan Li (F)

Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.
Center for Methods in Implementation and Prevention Science, Yale University School of Public Health, New Haven, CT, USA.

Manu Shankar-Hari (M)

Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.

Theis Lange (T)

Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Marie Warrer Munch (MW)

Department of Intensive Care, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark.
Collaboration for Research in Intensive Care, Copenhagen, Denmark.

Morten Hylander Møller (MH)

Department of Intensive Care, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark.
Collaboration for Research in Intensive Care, Copenhagen, Denmark.

Anders Perner (A)

Department of Intensive Care, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark.
Collaboration for Research in Intensive Care, Copenhagen, Denmark.

Michael O Harhay (MO)

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mharhay@pennmedicine.upenn.edu.
Clinical Trials Methods and Outcomes Lab, Palliative and Advanced Illness Research (PAIR) Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mharhay@pennmedicine.upenn.edu.
Division of Pulmonary and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 304 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-6021, USA. mharhay@pennmedicine.upenn.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH