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Rationale Prediction of patients at risk for mortality can help triage patients and assist in resource allocation. Objectives Develop and evaluate a machine learning-based algorithm which accurately predicts mortality in COVID-19, pneumonia, and mechanically ventilated patients. Methods Retrospective study of 53,001 total ICU patients, including 9166 patients with pneumonia and 25,895 mechanically ventilated patients, performed on the MIMIC dataset. An additional retrospective analysis was performed on a community hospital dataset containing 114 patients positive for SARS-COV-2 by PCR test. The outcome of interest was in-hospital patient mortality. Results When trained and tested on the MIMIC dataset, the XGBoost predictor obtained area under the receiver operating characteristic (AUROC) values of 0.82, 0.81, 0.77, and 0.75 for mortality prediction on mechanically ventilated patients at 12-, 24-, 48-, and 72- hour windows, respectively, and AUROCs of 0.87, 0.78, 0.77, and 0.734 for mortality prediction on pneumonia patients at 12-, 24-, 48-, and 72- hour windows, respectively. The predictor outperformed the qSOFA, MEWS and CURB-65 risk scores at all prediction windows. When tested on the community hospital dataset, the predictor obtained AUROCs of 0.91, 0.90, 0.86, and 0.87 for mortality prediction on COVID-19 patients at 12-, 24-, 48-, and 72- hour windows, respectively, outperforming the qSOFA, MEWS and CURB-65 risk scores at all prediction windows. Conclusions This machine learning-based algorithm is a useful predictive tool for anticipating patient mortality at clinically useful timepoints, and is capable of accurate mortality prediction for mechanically ventilated patients as well as those diagnosed with pneumonia and COVID-19., Highlights • Mortality predictions have not previously been evaluated for COVID-19 patients. • Machine learning may be a useful predictive tool for anticipating patient mortality. • Prediction can be estimated at clinically useful windows up to 72 h in advance.

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.

Introduction: Acute heart failure (AHF) syndromes are associated with significant morbidity, mortality, and hemodynamic complications. Patients at risk of AHF are likely to experience rehospitalization or death post-discharge. AHF patient risk stratification remains an unmet need. Hypothesis: Gradient boosted machine learning can be used to predict likelihood of AHF diagnosis, enabling identification of at-risk patients. Methods: A gradient boosted machine learning algorithm was developed on retrospective data from 236,275 total emergency department patients, 807 of whom experienced AHF and were prescribed a vasodilator during their stay. A model was developed using age, sex, and six vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, peripheral oxygen saturation, and temperature). A second model used these demographics, vitals, and laboratory data (troponin, bicarbonate, and O2 saturation) as available to predict AHF diagnosis, as defined by ICD code and prescription of beta-blocker and angiotensin converting enzyme (ACE) inhibitor vasodilators. Model performance was assessed with regard to area under the receiver operating characteristic (AUROC). Results: The algorithm obtained AUROCs of 0.860 and 0.767 for prediction of AHF diagnosis and prescription of vasodilator at discharge with and without laboratory data, respectively (Figure 1). Predictions from the vitals only model were made an average of 38.5 hours prior to AHF diagnosis. Predictions from the model which included labs were made an average of 34 hours prior to AHF diagnosis. Conclusion: Machine learning is a useful method for predicting AHF diagnosis. Patient risk stratification enabled by the tool may serve to reduce duration of hospital stay for patients at low risk of developing AHF. Identification of high risk patient populations may also allow for earlier diagnosis and treatment, preventing development of chronic heart failure and other sequelae of AHF.

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&ndash, 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.

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., SCOPUS: ar.j, info:eu-repo/semantics/published

To compute the financial and mortality impact of InSight, an algorithm-driven biomarker, which forecasts the onset of sepsis with minimal use of electronic health record data.This study compares InSight with existing sepsis screening tools and computes the differential life and cost savings associated with its use in the inpatient setting. To do so, mortality reduction is obtained from an increase in the number of sepsis cases correctly identified by InSight. Early sepsis detection by InSight is also associated with a reduction in length-of-stay, from which cost savings are directly computed.InSight identifies more true positive cases of severe sepsis, with fewer false alarms, than comparable methods. For an individual ICU with 50 beds, for example, it is determined that InSight annually saves 75 additional lives and reduces sepsis-related costs by $560,000.InSight performance results are derived from analysis of a single-center cohort. Mortality reduction results rely on a simplified use case, which fixes prediction times at 0, 1, and 2 h before sepsis onset, likely leading to under-estimates of lives saved. The corresponding cost reduction numbers are based on national averages for daily patient length-of-stay cost.InSight has the potential to reduce sepsis-related deaths and to lead to substantial cost savings for healthcare facilities.

Background: The objective of this study was to develop and evaluate a machine learning-based algorithm which accurately predicts mortality in COVID-19, pneumonia, and mechanically ventilated patients. Methods: A retrospective study of 53,001 total ICU patients, including 9,166 patients with pneumonia and 25,895 mechanically ventilated patients, was performed on the MIMIC dataset. An additional retrospective analysis was performed on a community hospital dataset containing 114 patients positive for SARS-COV-2 by PCR test. The outcome of interest was in-hospital patient mortality. Findings: W hen trained and tested on the MIMIC dataset, the XGBoost predictor obtained AUROCs of 0.88, 0.86, 0.81, and 0.78 for mortality prediction on mechanically ventilated patients at 12-, 24-, 48-, and 72- hour windows, respectively, and AUROCs of 0.86, 0.82, 0.79, and 0.75 for mortality prediction on pneumonia patients at 12-, 24-, 48-, and 72- hour windows, respectively. The predictor outperformed the qSOFA risk score at all prediction windows. When tested on the community hospital dataset, the predictor obtained AUROCs of 0.934, 0.927, 0.916, and 0.916 for mortality prediction on COVID-19 PCR positive patients at 12-, 24-, 48-, and 72- hour windows, respectively, outperforming the qSOFA risk score at all prediction windows. Interpretation: This machine learning-based algorithm is a useful predictive tool for anticipating patient mortality at clinically useful windows of 12, 24, 48, and 72 hours in advance, and is capable of accurate mortality prediction for mechanically ventilated patients as well as those diagnosed with pneumonia and COVID-19. Trial Registration : This study has been registered on ClinicalTrials.gov under study number NCT 04358510. Funding Statement: N/A Declaration of Interests: All authors who have affiliations listed with Dascena (Oakland, California, USA) are employees or contractors of Dascena. All other authors declare no conflicts of interest Ethics Approval Statement: Studies performed on the de-identified data constitute non-human subject studies, and therefore, our study did not require Institutional Review Board approval.

Background: Identifying patient characteristics associated with poor outcomes is vital to minimizing death due to COVID-19. Identification of features that predict mortality may improve triage and management of COVID-19 patients. Methods: A machine learning algorithm was applied to retrospective patient data to identify features correlated with mortality. Four populations were analyzed: 221 COVID-19 patients admitted to general isolated wards or ICU in Wuhan, China between January and February 2020; 230 COVID-19 inpatients admitted across four U.S. hospitals between January and April 2020; 99,224 inpatients admitted to a U.S. hospital; and 8,492 inpatients admitted to a U.S. hospital with viral infections other than SARS-CoV-2. Findings: Features associated with predicted mortality varied across populations. Among Chinese COVID-19 patients, creatinine was the top predictor of mortality, but was not among the most important features for the U.S. COVID-19 patients. Blood pressure was a more important predictor for U.S COVID-19 patients than for the U.S. viral or general hospitalized populations. Interpretation: The SARS-CoV-2 virus may affect different patient populations in different ways. This may be due to differences in treatment practice across populations, or to evolution of SARS-Cov-2 itself over time. The finding that creatinine was an important predictor only in the Chinese COVID-19 population may indicate that kidney-related complications due to SARS-CoV-2 are becoming less severe. Blood pressure was found to be an important feature in the U.S. COVID-19 population, suggesting an increased importance of cardiac and thrombotic complications of COVID-19. Funding Statement: None. Declaration of Interests: All authors who have affiliations listed with Dascena (Oakland, California, USA) are employees or contractors of Dascena. Ethics Approval Statement: All patient data was maintained in compliance with the Health Insurance Portability and Accountability Act (HIPAA). This study has been determined by the Pearl Institutional Review Board to be Exempt according to FDA 21 CFR 56.104 and 45CFR46.104(b)(4): (4) Secondary Research Uses of Data or Specimens under study number 20-DASC-119.

Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus. The cohort underwent integrative personalized omics profiling from samples collected quarterly for up to 8 years (median, 2.8 years) using clinical measures and emerging technologies including genome, immunome, transcriptome, proteome, metabolome, microbiome and wearable monitoring. We discovered more than 67 clinically actionable health discoveries and identified multiple molecular pathways associated with metabolic, cardiovascular and oncologic pathophysiology. We developed prediction models for insulin resistance by using omics measurements, illustrating their potential to replace burdensome tests. Finally, study participation led the majority of participants to implement diet and exercise changes. Altogether, we conclude that deep longitudinal profiling can lead to actionable health discoveries and provide relevant information for precision health. Personalized omics profiling can lead to actionable health discoveries and stimulate lifestyle changes.

We have developed Halyos (http://halyos.gehlenborglab.org), a visual EHR web application that complements the functionality of existing patient portals. Halyos is designed to integrate with existing EHR systems to help patients interpret their health data. The Halyos application utilizes the SMART on FHIR (Substitutable Medical Applications and Reusable Technologies on Fast Healthcare Interoperability Resources) platform to create an interoperable interface that provides interactive visualizations of clinically validated risk scores and longitudinal data derived from a patient’s clinical measurements. These visualizations allow patients to investigate the relationships between clinical measurements and risk over time. By enabling patients to set hypothetical future values for these clinical measurements, patients can see how changes in their health will impact their risks. Using Halyos, patients are provided with the opportunity to actively improve their health based on increased understanding of longitudinal information available in EHRs and to begin a dialogue with their providers.

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.

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 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.

Introduction Several methods have been developed to electronically monitor patients for severe sepsis, but few provide predictive capabilities to enable early intervention; furthermore, no severe sepsis prediction systems have been previously validated in a randomised study. We tested the use of a machine learning-based severe sepsis prediction system for reductions in average length of stay and in-hospital mortality rate. Methods We conducted a randomised controlled clinical trial at two medical-surgical intensive care units at the University of California, San Francisco Medical Center, evaluating the primary outcome of average length of stay, and secondary outcome of in-hospital mortality rate from December 2016 to February 2017. Adult patients (18+) admitted to participating units were eligible for this factorial, open-label study. Enrolled patients were assigned to a trial arm by a random allocation sequence. In the control group, only the current severe sepsis detector was used; in the experimental group, the machine learning algorithm (MLA) was also used. On receiving an alert, the care team evaluated the patient and initiated the severe sepsis bundle, if appropriate. Although participants were randomly assigned to a trial arm, group assignments were automatically revealed for any patients who received MLA alerts. Results Outcomes from 75 patients in the control and 67 patients in the experimental group were analysed. Average length of stay decreased from 13.0 days in the control to 10.3 days in the experimental group (p=0.042). In-hospital mortality decreased by 12.4 percentage points when using the MLA (p=0.018), a relative reduction of 58.0%. No adverse events were reported during this trial. Conclusion The MLA was associated with improved patient outcomes. This is the first randomised controlled trial of a sepsis surveillance system to demonstrate statistically significant differences in length of stay and in-hospital mortality. Trial registration NCT03015454.