Background Currently, physicians are limited in their ability to provide an accurate prognosis for COVID-19 positive patients. Existing scoring systems have been ineffective for identifying patient decompensation. Machine learning (ML) may offer an alternative strategy. A prospectively validated method to predict the need for ventilation in COVID-19 patients is essential to help triage patients, allocate resources, and prevent emergency intubations and their associated risks. Methods In a multicenter clinical trial, we evaluated the performance of a machine learning algorithm for prediction of invasive mechanical ventilation of COVID-19 patients within 24 h of an initial encounter. We enrolled patients with a COVID-19 diagnosis who were admitted to five United States health systems between March 24 and May 4, 2020. Results 197 patients were enrolled in the REspirAtory Decompensation and model for the triage of covid-19 patients: a prospective studY (READY) clinical trial. The algorithm had a higher diagnostic odds ratio (DOR, 12.58) for predicting ventilation than a comparator early warning system, the Modified Early Warning Score (MEWS). The algorithm also achieved significantly higher sensitivity (0.90) than MEWS, which achieved a sensitivity of 0.78, while maintaining a higher specificity (p < 0.05). Conclusions In the first clinical trial of a machine learning algorithm for ventilation needs among COVID-19 patients, the algorithm demonstrated accurate prediction of the need for mechanical ventilation within 24 h. This algorithm may help care teams effectively triage patients and allocate resources. Further, the algorithm is capable of accurately identifying 16% more patients than a widely used scoring system while minimizing false positive results.

Background Racial disparities in health care are well documented in the United States. As machine learning methods become more common in health care settings, it is important to ensure that these methods do not contribute to racial disparities through biased predictions or differential accuracy across racial groups. Objective The goal of the research was to assess a machine learning algorithm intentionally developed to minimize bias in in-hospital mortality predictions between white and nonwhite patient groups. Methods Bias was minimized through preprocessing of algorithm training data. We performed a retrospective analysis of electronic health record data from patients admitted to the intensive care unit (ICU) at a large academic health center between 2001 and 2012, drawing data from the Medical Information Mart for Intensive Care–III database. Patients were included if they had at least 10 hours of available measurements after ICU admission, had at least one of every measurement used for model prediction, and had recorded race/ethnicity data. Bias was assessed through the equal opportunity difference. Model performance in terms of bias and accuracy was compared with the Modified Early Warning Score (MEWS), the Simplified Acute Physiology Score II (SAPS II), and the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE). Results The machine learning algorithm was found to be more accurate than all comparators, with a higher sensitivity, specificity, and area under the receiver operating characteristic. The machine learning algorithm was found to be unbiased (equal opportunity difference 0.016, P=.20). APACHE was also found to be unbiased (equal opportunity difference 0.019, P=.11), while SAPS II and MEWS were found to have significant bias (equal opportunity difference 0.038, P=.006 and equal opportunity difference 0.074, P<.001, respectively). Conclusions This study indicates there may be significant racial bias in commonly used severity scoring systems and that machine learning algorithms may reduce bias while improving on the accuracy of these methods.

Therapeutic agents for the novel coronavirus disease 2019 (COVID-19) have been proposed, but evidence supporting their use is limited. A machine learning algorithm was developed in order to identify a subpopulation of COVID-19 patients for whom hydroxychloroquine was associated with improved survival; this population might be relevant for study in a clinical trial. A pragmatic trial was conducted at six United States hospitals. We enrolled COVID-19 patients that were admitted between 10 March and 4 June 2020. Treatment was not randomized. The study endpoint was mortality; discharge was a competing event. Hazard ratios were obtained on the entire population, and on the subpopulation indicated by the algorithm as suitable for treatment. A total of 290 patients were enrolled. In the subpopulation that was identified by the algorithm, hydroxychloroquine was associated with a statistically significant (p = 0.011) increase in survival (adjusted hazard ratio 0.29, 95% confidence interval (CI) 0.11–0.75). Adjusted survival among the algorithm indicated patients was 82.6% in the treated arm and 51.2% in the arm not treated. No association between treatment and mortality was observed in the general population. A 31% increase in survival at the end of the study was observed in a population of COVID-19 patients that were identified by a machine learning algorithm as having a better outcome with hydroxychloroquine treatment. Precision medicine approaches may be useful in identifying a subpopulation of COVID-19 patients more likely to be proven to benefit from hydroxychloroquine treatment in a clinical trial.

Ventilator-associated pneumonia (VAP) is the most common and fatal nosocomial infection in intensive care units (ICUs). Existing methods for identifying VAP display low accuracy, and their use may delay antimicrobial therapy. VAP diagnostics derived from machine learning (ML) methods that utilize electronic health record (EHR) data have not yet been explored. The objective of this study is to compare the performance of a variety of ML models trained to predict whether VAP will be diagnosed during the patient stay. A retrospective study examined data from 6126 adult ICU encounters lasting at least 48 hours following the initiation of mechanical ventilation. The gold standard was the presence of a diagnostic code for VAP. Five different ML models were trained to predict VAP 48 hours after initiation of mechanical ventilation. Model performance was evaluated with regard to the area under the receiver operating characteristic (AUROC) curve on a 20% hold-out test set. Feature importance was measured in terms of Shapley values. The highest performing model achieved an AUROC value of 0.854. The most important features for the best-performing model were the length of time on mechanical ventilation, the presence of antibiotics, sputum test frequency, and the most recent Glasgow Coma Scale assessment. Supervised ML using patient EHR data is promising for VAP diagnosis and warrants further validation. This tool has the potential to aid the timely diagnosis of VAP.

Deep venous thrombosis (DVT) is associated with significant morbidity, mortality, and increased healthcare costs. Standard scoring systems for DVT risk stratification often provide insufficient stratification of hospitalized patients and are unable to accurately predict which inpatients are most likely to present with DVT. There is a continued need for tools which can predict DVT in hospitalized patients. We performed a retrospective study on a database collected from a large academic hospital, comprised of 99,237 total general ward or ICU patients, 2,378 of whom experienced a DVT during their hospital stay. Gradient boosted machine learning algorithms were developed to predict a patient’s risk of developing DVT at 12- and 24-hour windows prior to onset. The primary outcome of interest was diagnosis of in-hospital DVT. The machine learning predictors obtained AUROCs of 0.83 and 0.85 for DVT risk prediction on hospitalized patients at 12- and 24-hour windows, respectively. At both 12 and 24 hours before DVT onset, the most important features for prediction of DVT were cancer history, VTE history, and internal normalized ratio (INR). Improved risk stratification may prevent unnecessary invasive testing in patients for whom DVT cannot be ruled out using existing methods. Improved risk stratification may also allow for more targeted use of prophylactic anticoagulants, as well as earlier diagnosis and treatment, preventing the development of pulmonary emboli and other sequelae of DVT.

Purpose : Coronavirus Disease 2019 ( COVID-19) continues to be a global threat and remains a significant cause of hospitalizations. Recent clinical guidelines have supported the use of corticosteroids and remdesivir in the treatment of COVID-19. However, uncertainty remains about which patients are most likely to benefit from treatment with either drug; such knowledge is crucial for avoiding preventable side effects, minimizing costs, and effectively allocating resources. This study presents a machine learning system capable of identifying patients for whom treatment with corticosteroids or remdesivir is associated with improved survival time. Methods : Gradient boosted decision tree models to predict treatment benefit were trained and tested on data from patients hospitalized at 10 hospitals in the United States between December 18, 2019 and October 18, 2020. 893 patients were treated with remdesivir, and 1,471 were treated with corticosteroids. Models were evaluated for their ability to identify patients that exhibited longer survival times when treated with corticosteroids or remdesivir. Fine and Gray models for the proportional hazard were evaluated comparing treated and untreated patients in the full COVID-19 population, in patients receiving supplemental oxygen, and in patients identified by the algorithm. Inverse probability of treatment weights were used to adjust for confounding. Models for each treatment were trained and tested separately. Findings : .Adult patients (age ≥ 18) were included in this study, with men comprising slightly more than 50% of the sample. After adjusting for confounding, neither corticosteroids nor remdesivir were associated with increased survival time in the full hospitalized COVID-19 population or in the population receiving supplemental oxygen. However, in the populations identified by the algorithms, both corticosteroids and remdesivir were significantly associated with an increase in survival time, with hazard ratios of 0.56 (p = 0.04) and 0.40 (p = 0.04), respectively Implications : Machine learning methods are capable of identifying hospitalized COVID-19 patients for whom treatment with corticosteroids or remdesivir is associated with an increase in survival time. These methods may help improve patient outcomes and allocate resources during the COVID-19 crisis.

Background The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. Methods Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. Results Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. Conclusion Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

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