TY - JOUR
T1 - Early identification of patients admitted to hospital for covid-19 at risk of clinical deterioration
T2 - Model development and multisite external validation study
AU - Kamran, Fahad
AU - Tang, Shengpu
AU - Otles, Erkin
AU - McEvoy, Dustin S.
AU - Saleh, Sameh N.
AU - Gong, Jen
AU - Li, Benjamin Y.
AU - Dutta, Sayon
AU - Liu, Xinran
AU - Medford, Richard J.
AU - Valley, Thomas S.
AU - West, Lauren R.
AU - Singh, Karandeep
AU - Blumberg, Seth
AU - Donnelly, John P.
AU - Shenoy, Erica S.
AU - Ayanian, John Z.
AU - Nallamothu, Brahmajee K.
AU - Sjoding, Michael W.
AU - Wiens, Jenna
N1 - Funding Information:
disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from National Science Foundation (NSF), National Institutes of Health (NIH) -National Library of Medicine (NLM) and -National Heart, Lung, and Blood Institute (NHLBI), Agency for Healthcare Research and Quality (AHRQ), Centers for Disease Control and Prevention (CDC) -National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Precision Health at the University of Michigan, and the Institute for Healthcare Policy and Innovation at the University of Michigan. JZA received grant funding from National Institute on Aging, Michigan Department of Health and Human Services, and Merck Foundation, outside of the submitted work; JZA also received personal fees for consulting at JAMA Network and New England Journal of Medicine, honorariums from Harvard University, University of Chicago, and University of California San Diego, and monetary support for travel reimbursements from NIH, National Academy of Medicine, and AcademyHealth, during the conduct of the study; JZA also served as a board member of AcademyHealth, Physicians Health Plan, and Center for Health Research and Transformation, with no compensation, during the conduct of the study. SB reports receiving grant funding from NIH, outside of the submitted work. JPD reports receiving personal fees from the Annals of Emergency Medicine, during the conduct of the study. RJM reports receiving grant funding from Verily Life Sciences, Sergey Brin Family Foundation, and Texas Health Resources Clinical Scholar, outside of the submitted work; RJM also served on the advisory committee of Infectious Diseases Society of America - Digital Strategy Advisory Group, during the conduct of the study. BKN reports receiving grant funding from NIH, Veterans Affairs -Health Services Research and Development Service, the American Heart Association (AHA), Janssen, and Apple, outside of the submitted work; BKN also received compensation as editor in chief of Circulation: Cardiovascular Quality and Outcomes, a journal of AHA, during the conduct of the study; BKN is also a co-inventor on US Utility Patent No US15/356012 (US20170148158A1) entitled “Automated Analysis of Vasculature in Coronary Angiograms,” that uses software technology with signal processing and machine learning to automate the reading of coronary angiograms, held by the University of Michigan; the patent is licensed to AngioInsight, in which BKN holds ownership shares and receives consultancy fees. EO reports having a patent pending for the University of Michigan for an artificial intelligence based approach for the dynamic prediction of health states for patients with occupational injuries. SNS reports serving on the editorial board for the Journal of the American Medical Informatics Association, and on the student editorial board for Applied Informatics Journal, during the conduct of the study. KS reports receiving grant funding from Blue Cross Blue Shield of Michigan, and Teva Pharmaceuticals, outside of the submitted work; KS also serves on a scientific advisory board for Flatiron Health, where he receives consulting fees and honorariums for invited lectures, during the conduct of the study. MWS reports serving on the planning committee for the Machine Learning for Healthcare Conference (MLHC), a non-profit organization that hosts a yearly academic meeting. JW reports receiving grant funding from Cisco Systems, D Dan and Betty Kahn Foundation, and Alfred P Sloan Foundation, during the conduct of the study outside of the submitted work; JW also served on the international advisory board for Lancet Digital Health, and on the advisory board for MLHC, during the conduct of the study. No other disclosures were reported that could appear to have influenced the submitted work. SD, JG, FK, BYL, XL, DSM, ESS, ST, TSV, and LRW all declare: no additional support from any organization for the submitted work; no additional financial relationships with any organizations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: This study was approved by the institutional review boards of all participating sites (University of Michigan, Michigan Medicine HUM00179831, Mass General Brigham 2012P002359, University of Texas Southwestern Medical Center STU-2020-0922, University of California San Francisco 20-31825), with a waiver of informed consent. Data sharing: To guarantee the confidentiality of personal and health information, only the authors have had access to the data during the study in accordance with the relevant license agreements. The full model (including model coefficients and supporting code) are available online at https://github.com/MLD3/M-CURES. FK, ST, MWS, and JW affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.
Funding Information:
Contributors: FK and ST are co-first authors of equal contribution. MWS and JW are co-senior authors of equal contribution. JZA, BKN, MWS, and JW conceptualized the study. FK, ST, EO, DSM, SNS, JG, BYL, SD, XL, RJM, TSV, LRW, KS, SB, JPD, ESS, MWS, and JW acquired, analyzed, or interpreted the data. FK, ST, DSM, SNS, JG, XL, MWS, and JW had access to study data pertaining to their respective institutions and took responsibility for the integrity of the data and the accuracy of the data analysis. FK, ST, and EO drafted the manuscript. FK, ST, EO, DSM, SNS, JG, BYL, SD, XL, RJM, TSV, LRW, KS, SB, JPD, ESS, JZA, BKN, MWS, and JW critically revised the manuscript for important intellectual content. BKN, MWS, and JW supervised the conduct of this study. FK and ST are guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding: This work was supported by the National Science Foundation (NSF; award IIS-1553146 to JW), by the National Institutes of Health (NIH) -National Library of Medicine (NLM; grant R01LM013325 to JW and MWS), -National Heart, Lung, and Blood Institute (NHLBI; grant K23HL140165 to TSV; grant K12HL138039 to JPD), by the Agency for Healthcare Research and Quality (AHRQ; grant R01HS028038 TSV), by the Centers for Disease Control and Prevention (CDC) -National Center for Emerging and Zoonotic Infectious Diseases (NCEZID; grant U01CK000590 to SB and RJM), by Precision Health at the University of Michigan (U-M), and by the Institute for Healthcare Policy and Innovation at U-M. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The views and conclusions in this document are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of NSF, NIH, AHRQ, CDC, or the US government.
Publisher Copyright:
© 2019 Author(s) (or their employer(s)).
PY - 2022/2/17
Y1 - 2022/2/17
N2 - Objective To create and validate a simple and transferable machine learning model from electronic health record data to accurately predict clinical deterioration in patients with covid-19 across institutions, through use of a novel paradigm for model development and code sharing. Design Retrospective cohort study. Setting One US hospital during 2015-21 was used for model training and internal validation. External validation was conducted on patients admitted to hospital with covid-19 at 12 other US medical centers during 2020-21. Participants 33 119 adults (≥18 years) admitted to hospital with respiratory distress or covid-19. Main outcome measures An ensemble of linear models was trained on the development cohort to predict a composite outcome of clinical deterioration within the first five days of hospital admission, defined as in-hospital mortality or any of three treatments indicating severe illness: mechanical ventilation, heated high flow nasal cannula, or intravenous vasopressors. The model was based on nine clinical and personal characteristic variables selected from 2686 variables available in the electronic health record. Internal and external validation performance was measured using the area under the receiver operating characteristic curve (AUROC) and the expected calibration error-the difference between predicted risk and actual risk. Potential bed day savings were estimated by calculating how many bed days hospitals could save per patient if low risk patients identified by the model were discharged early. Results 9291 covid-19 related hospital admissions at 13 medical centers were used for model validation, of which 1510 (16.3%) were related to the primary outcome. When the model was applied to the internal validation cohort, it achieved an AUROC of 0.80 (95% confidence interval 0.77 to 0.84) and an expected calibration error of 0.01 (95% confidence interval 0.00 to 0.02). Performance was consistent when validated in the 12 external medical centers (AUROC range 0.77-0.84), across subgroups of sex, age, race, and ethnicity (AUROC range 0.78-0.84), and across quarters (AUROC range 0.73-0.83). Using the model to triage low risk patients could potentially save up to 7.8 bed days per patient resulting from early discharge. Conclusion A model to predict clinical deterioration was developed rapidly in response to the covid-19 pandemic at a single hospital, was applied externally without the sharing of data, and performed well across multiple medical centers, patient subgroups, and time periods, showing its potential as a tool for use in optimizing healthcare resources.
AB - Objective To create and validate a simple and transferable machine learning model from electronic health record data to accurately predict clinical deterioration in patients with covid-19 across institutions, through use of a novel paradigm for model development and code sharing. Design Retrospective cohort study. Setting One US hospital during 2015-21 was used for model training and internal validation. External validation was conducted on patients admitted to hospital with covid-19 at 12 other US medical centers during 2020-21. Participants 33 119 adults (≥18 years) admitted to hospital with respiratory distress or covid-19. Main outcome measures An ensemble of linear models was trained on the development cohort to predict a composite outcome of clinical deterioration within the first five days of hospital admission, defined as in-hospital mortality or any of three treatments indicating severe illness: mechanical ventilation, heated high flow nasal cannula, or intravenous vasopressors. The model was based on nine clinical and personal characteristic variables selected from 2686 variables available in the electronic health record. Internal and external validation performance was measured using the area under the receiver operating characteristic curve (AUROC) and the expected calibration error-the difference between predicted risk and actual risk. Potential bed day savings were estimated by calculating how many bed days hospitals could save per patient if low risk patients identified by the model were discharged early. Results 9291 covid-19 related hospital admissions at 13 medical centers were used for model validation, of which 1510 (16.3%) were related to the primary outcome. When the model was applied to the internal validation cohort, it achieved an AUROC of 0.80 (95% confidence interval 0.77 to 0.84) and an expected calibration error of 0.01 (95% confidence interval 0.00 to 0.02). Performance was consistent when validated in the 12 external medical centers (AUROC range 0.77-0.84), across subgroups of sex, age, race, and ethnicity (AUROC range 0.78-0.84), and across quarters (AUROC range 0.73-0.83). Using the model to triage low risk patients could potentially save up to 7.8 bed days per patient resulting from early discharge. Conclusion A model to predict clinical deterioration was developed rapidly in response to the covid-19 pandemic at a single hospital, was applied externally without the sharing of data, and performed well across multiple medical centers, patient subgroups, and time periods, showing its potential as a tool for use in optimizing healthcare resources.
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U2 - 10.1136/bmj-2021-068576
DO - 10.1136/bmj-2021-068576
M3 - Article
C2 - 35177406
AN - SCOPUS:85124779698
SN - 0959-8146
VL - 376
JO - The BMJ
JF - The BMJ
M1 - e068576
ER -