Dexamethasone use and mortality in hospitalized patients with coronavirus disease 2019: A multicentre retrospective observational study

  1. Nicolas Hoertel
  2. Marina Sánchez‐Rico
  3. Raphaël Vernet
  4. Nathanaël Beeker
  5. Antoine Neuraz
  6. Jesús M. Alvarado
  7. Christel Daniel
  8. Nicolas Paris
  9. Alexandre Gramfort
  10. Guillaume Lemaitre
  11. Elisa Salamanca
  12. Mélodie Bernaux
  13. Ali Bellamine
  14. Anita Burgun
  15. Frédéric Limosin
  16. AP‐HP/Université de Paris/INSERM Covid‐19 research collaboration and AP‐HP Covid CDR Initiative

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Abstract

To examine the association between dexamethasone use and mortality among patients hospitalized for COVID‐19.

Methods

We examined the association between dexamethasone use and mortality at AP‐HP Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was time to death. We compared this endpoint between patients who received dexamethasone and those who did not in time‐to‐event analyses adjusted for patient characteristics (such as age, sex and comorbidity) and clinical and biological markers of clinical severity of COVID‐19, and stratified by the need for respiratory support, i.e. mechanical ventilation or oxygen. The primary analysis was a multivariable Cox regression model.

Results

Of 12 217 adult patients hospitalized with a positive COVID‐19 reverse transcriptase–polymerase chain reaction test, 171 (1.4%) received dexamethasone orally or by intravenous perfusion during the visit. Among patients who required respiratory support, the end‐point occurred in 10/63 (15.9%) patients who received dexamethasone and 298/1129 (26.4%) patients who did not. In this group, there was a significant association between dexamethasone use and reduced mortality in the primary analysis (hazard ratio, 0.46; 95% confidence interval 0.22–0.96, P  = .039). Among patients who did not require respiratory support, there was no significant association between dexamethasone use and the endpoint.

Conclusions

In this multicentre observational study, dexamethasone use administered either orally or by intravenous injection at a cumulative dose between 60 mg and 150 mg was associated with reduced mortality among patients with COVID‐19 requiring respiratory support.

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  1. Version published to 10.1111/bcp.14784
  2. ScreenIT

    SciScore for 10.1101/2020.10.23.20218172: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: This observational study using routinely collected data received approval from the Institutional Review Board of the AP-HP clinical data warehouse (decision CSE-20-20_COVID19, IRB00011591).
    Consent: AP-HP clinical Data Warehouse initiative ensures patients’ information and consent regarding the different approved studies through a transparency portal in accordance with European Regulation on data protection and authorization n°1980120 from National Commission for Information Technology and Civil Liberties (CNIL). 2.2.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    Variables assessed: We obtained the following data for each patient at the time of the hospitalization: sex; age, which was categorized based on the OpenSAFELY study results2 (i.e. 18-50, 51-70, 71+); obesity, defined as having a body-mass index higher than 30 kg/m2 or an International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnosis code for obesity (E66.0, E66.1, E66.2, E66.8, E66.9); self-reported current smoking status; any medical condition associated with increased COVID-19-related mortality2,3 based on ICD-10 diagnosis codes, including diabetes mellitus (E11), diseases of the circulatory system (I00-I99), diseases of the respiratory system (J00-J99), neoplasms (C00-D49), and diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism (D5-D8); clinical severity of COVID-19 at admission, defined as having at least one of the following criteria:4 (i) respiratory rate > 24 breaths/min or < 12 breaths/min, (ii) resting peripheral capillary oxygen saturation in ambient air < 90%, (iii) temperature > 40°C, or (iv) systolic blood pressure < 100 mm Hg; and biological severity of COVID-19 at admission, defined as having at least one of the following criteria:4,5 (i) high neutrophil-to-lymphocyte ratio or (ii) low lymphocyte-to-C-reactive protein ratio (both variables were dichotomized at the median of the values observed in the full sample), or (iii) plasma lactate levels higher than 2 mmol/L.
    results2
    suggested: None
    Software and Algorithms
    SentencesResources
    Medications and their mode of administration (i.e., dosage, frequency, date, condition of intake) were identified from medication administration data or scanned hand-written medical prescriptions, through two deep learning models based on BERT contextual embeddings,6 one for the medications and another for their mode of administration.
    BERT
    suggested: (BERT, RRID:SCR_018008)
    3 (R Project for Statistical Computing).
    R Project for Statistical
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has several limitations. First, some amount of unmeasured confounding may remain. However, our analyses adjusted for numerous potential confounders, including sex, age, obesity, current smoking status, any medical condition associated with increased COVID-19-related mortality, and clinical and biological severity of COVID-19 at admission. Second, there are missing data for some variables and potential for inaccuracies in the electronic health records, such as the possible lack of documentation of illnesses or medications, or the misidentification of treatment mode of administration (e.g., dose, frequency), especially for hand-written medical prescriptions. Finally, despite the multicenter design, our results may not be generalizable to other settings or regions. In this observational study involving patients with Covid-19 who had been admitted to the hospital, dexamethasone use administered either orally or by intravenous injection at a cumulative dose between 60 mg and 150 mg was associated with decreased mortality among patients requiring respiratory support.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.10.23.20218172v1 on medRxiv