Temporal Changes in Clinical Practice with COVID-19 Hospitalized Patients: Potential Explanations for Better In-Hospital Outcomes

  1. Kevin E. Kip
  2. Graham Snyder
  3. Donald M. Yealy
  4. John W. Mellors
  5. Tami Minnier
  6. Michael P. Donahoe
  7. Jeffrey McKibben
  8. Kevin Collins
  9. Oscar C. Marroquin

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Abstract

Background/Aims

We reviewed demographic and clinical profiles, along with measures of hospital-based clinical practice to identify temporal changes in clinical practice that may have affected in-hospital outcomes of patients with COVID-19.

Methods

Data consisted of sociodemographic and clinical data captured in University of Pittsburgh Medical Center (UPMC) electronic medical record (EMR) systems, linked by common variables (deidentified). The analysis population included hospitalized patients (across 21 hospitals) with a primary diagnosis of COVID-19 infection during the period March 14-August 31, 2020. The primary outcome was a composite of in-hospital mechanical ventilation/mortality. We compared temporal trends in patient characteristics, clinical practice, and hospital outcomes using 4 time-defined epochs for calendar year 2020: March 14-March 31 (epoch 1); April 1-May 15, (epoch 2), May 16-June 28 (epoch 3); and June 29-August 31 (epoch 4). We report unadjusted survival estimates, followed by propensity score analyses to adjust for differences in patient characteristics, to compare in-hospital outcomes of epoch 4 patients (recently treated) to epoch 1-3 patients (earlier treated).

Results

Mean number of hospital admissions was 9.9 per day during epoch 4, which was ∼2-to 3-fold higher than the earlier epochs. Presenting characteristics of the 1,076 COVID-19 hospitalized patients were similar across the 4 epochs, including mean age. The crude rate of mechanical ventilation/mortality was lower in epoch 4 patients (17%) than in epoch 1-3 patients (23% to 35%). When censoring for incomplete patient follow-up, the rate of mechanical ventilation/mortality was lower in epoch 4 patients ( p <0.0001), as was the individual component of mechanical ventilation ( p =0.0002) and mortality ( p =0.02). In propensity score adjusted analyses, the in-hospital relative risk (RR) of mechanical ventilation/mortality was lower in epoch 4 patients (RR=0.67, 95% CI: 0.48, 0.93). For the outcome being discharged alive within 3, 5, or 7 days of admission, adjusted odds ranged from 1.6-to 1.7-fold higher among epoch 4 patients compared to earlier treated patients. The better outcomes in epoch 4 patients were principally observed in patients under the age of 75 years. Patient level dexamethasone use was 55.6% in epoch 4 compared to 15% or less of patients in the earlier epochs. Most patients across epochs received anticoagulation drugs (principally heparin). Overall steroid (81.7% vs. 54.3%, p <0.0001) and anticoagulation use (90.4% vs. 80.7%, p =0.0001) was more frequent on the day or day after hospitalization in epoch 4 patients compared to earlier treated patients.

Conclusions

In our large system, recently treated hospitalized COVID-19 patients had lower rates of in-hospital mechanical ventilation/mortality and shorter length of hospital stay. Alongside of this was a change to early initiation of glucocorticoid therapy and anticoagulation. The extent to which the improvement in patient outcomes was related to changes in clinical practice remains to be established.

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    SciScore for 10.1101/2020.09.29.20203802: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Our study received formal ethics approval by the UPMC Ethics and Quality Improvement Review Committee (Project ID 2882), the ethics/oversight body for ensuring patient confidentiality and consent (including waiver of consent) for analysis and dissemination of deidentified data within the UPMC system.
    Consent: Our study received formal ethics approval by the UPMC Ethics and Quality Improvement Review Committee (Project ID 2882), the ethics/oversight body for ensuring patient confidentiality and consent (including waiver of consent) for analysis and dissemination of deidentified data within the UPMC system.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableIn calendar year 2019 among discharged UPMC hospital patients, there were 306,456 visits among 201,829 unique patients, with mean (median) age of 54 (60) years, 54% female, and median length of stay of 2.6 days.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Methods and results are reported in accordance with The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement24 (see Supplemental Table 2).
    RECORD
    suggested: (RECORD, RRID:SCR_009097)

    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:
    Strengths and Limitations: Strengths of this study include analysis of a large, heterogenous patient population (e.g. enhances generalizability), standardized collection of real-world data and algorithmic coding of variables harmonized in a clinical data warehouse collected for non-research purposes (e.g. reduces potential reporting and ascertainment bias), and access to a very large battery of sociodemographic, medical history, medication use, and clinical practice and outcome variables available for analysis. A limitation is that we extracted all variables from the EHR of a multisite health care system, making fidelity concerns persist. All current data are observational and cannot determine causality. We also did not collect data to inform changes in host biology or viral pathogenesis over time, and we did not attempt to assess other external factors, such as seasonal effects of temperature and humidity variation, and possible patient-specific directives against the use of mechanical ventilation. Lastly, the present analysis includes a small percentage of hospitalized patients (<13%) enrolled in clinical trials, including potential randomization to either hydroxychloroquine, steroids, immunomodulators, convalescent plasma, or placebo. While a potential impact, we think that effect is modest if at all present.

    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.
    • Thank you for including a protocol registration statement.

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  2. Version published to 10.1101/2020.09.29.20203802 on medRxiv