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1.
PLoS One ; 16(3): e0248128, 2021.
Article in English | MEDLINE | ID: covidwho-1575679

ABSTRACT

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.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Data Management/methods , Drug Therapy, Combination/methods , Female , Hospitalization , Humans , Male , SARS-CoV-2/drug effects
2.
JMIR Form Res ; 5(9): e28028, 2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-1438390

ABSTRACT

BACKGROUND: A high number of patients who are hospitalized with COVID-19 develop acute respiratory distress syndrome (ARDS). OBJECTIVE: In response to the need for clinical decision support tools to help manage the next pandemic during the early stages (ie, when limited labeled data are present), we developed machine learning algorithms that use semisupervised learning (SSL) techniques to predict ARDS development in general and COVID-19 populations based on limited labeled data. METHODS: SSL techniques were applied to 29,127 encounters with patients who were admitted to 7 US hospitals from May 1, 2019, to May 1, 2021. A recurrent neural network that used a time series of electronic health record data was applied to data that were collected when a patient's peripheral oxygen saturation level fell below the normal range (<97%) to predict the subsequent development of ARDS during the remaining duration of patients' hospital stay. Model performance was assessed with the area under the receiver operating characteristic curve and area under the precision recall curve of an external hold-out test set. RESULTS: For the whole data set, the median time between the first peripheral oxygen saturation measurement of <97% and subsequent respiratory failure was 21 hours. The area under the receiver operating characteristic curve for predicting subsequent ARDS development was 0.73 when the model was trained on a labeled data set of 6930 patients, 0.78 when the model was trained on the labeled data set that had been augmented with the unlabeled data set of 16,173 patients by using SSL techniques, and 0.84 when the model was trained on the entire training set of 23,103 labeled patients. CONCLUSIONS: In the context of using time-series inpatient data and a careful model training design, unlabeled data can be used to improve the performance of machine learning models when labeled data for predicting ARDS development are scarce or expensive.

3.
Clin Imaging ; 80: 268-273, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1368616

ABSTRACT

INTRODUCTION: The objective of this study was to assess seven configurations of six convolutional deep neural network architectures for classification of chest X-rays (CXRs) as COVID-19 positive or negative. METHODS: The primary dataset consisted of 294 COVID-19 positive and 294 COVID-19 negative CXRs, the latter comprising roughly equally many pneumonia, emphysema, fibrosis, and healthy images. We used six common convolutional neural network architectures, VGG16, DenseNet121, DenseNet201, MobileNet, NasNetMobile and InceptionV3. We studied six models (one for each architecture) which were pre-trained on a vast repository of generic (non-CXR) images, as well as a seventh DenseNet121 model, which was pre-trained on a repository of CXR images. For each model, we replaced the output layers with custom fully connected layers for the task of binary classification of images as COVID-19 positive or negative. Performance metrics were calculated on a hold-out test set with CXRs from patients who were not included in the training/validation set. RESULTS: When pre-trained on generic images, the VGG16, DenseNet121, DenseNet201, MobileNet, NasNetMobile, and InceptionV3 architectures respectively produced hold-out test set areas under the receiver operating characteristic (AUROCs) of 0.98, 0.95, 0.97, 0.95, 0.99, and 0.96 for the COVID-19 classification of CXRs. The X-ray pre-trained DenseNet121 model, in comparison, had a test set AUROC of 0.87. DISCUSSION: Common convolutional neural network architectures with parameters pre-trained on generic images yield high-performance and well-calibrated COVID-19 CXR classification.


Subject(s)
COVID-19 , Deep Learning , Humans , Neural Networks, Computer , SARS-CoV-2 , X-Rays
4.
Health Policy Technol ; 10(3): 100554, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1340667

ABSTRACT

Objective: In the wake of COVID-19, the United States (U.S.) developed a three stage plan to outline the parameters to determine when states may reopen businesses and ease travel restrictions. The guidelines also identify subpopulations of Americans deemed to be at high risk for severe disease should they contract COVID-19. These guidelines were based on population level demographics, rather than individual-level risk factors. As such, they may misidentify individuals at high risk for severe illness, and may therefore be of limited use in decisions surrounding resource allocation to vulnerable populations. The objective of this study was to evaluate a machine learning algorithm for prediction of serious illness due to COVID-19 using inpatient data collected from electronic health records. Methods: The algorithm was trained to identify patients for whom a diagnosis of COVID-19 was likely to result in hospitalization, and compared against four U.S. policy-based criteria: age over 65; having a serious underlying health condition; age over 65 or having a serious underlying health condition; and age over 65 and having a serious underlying health condition. Results: This algorithm identified 80% of patients at risk for hospitalization due to COVID-19, versus 62% identified by government guidelines. The algorithm also achieved a high specificity of 95%, outperforming government guidelines. Conclusions: This algorithm may identify individuals likely to require hospitalization should they contract COVID-19. This information may be useful to guide vaccine distribution, anticipate hospital resource needs, and assist health care policymakers to make care decisions in a more principled manner.

5.
JMIR Public Health Surveill ; 7(6): e28265, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1231308

ABSTRACT

BACKGROUND: Despite the limitations in the use of cycle threshold (CT) values for individual patient care, population distributions of CT values may be useful indicators of local outbreaks. OBJECTIVE: We aimed to conduct an exploratory analysis of potential correlations between the population distribution of cycle threshold (CT) values and COVID-19 dynamics, which were operationalized as percent positivity, transmission rate (Rt), and COVID-19 hospitalization count. METHODS: In total, 148,410 specimens collected between September 15, 2020, and January 11, 2021, from the greater El Paso area were processed in the Dascena COVID-19 Laboratory. The daily median CT value, daily Rt, daily count of COVID-19 hospitalizations, daily change in percent positivity, and rolling averages of these features were plotted over time. Two-way scatterplots and linear regression were used to evaluate possible associations between daily median CT values and outbreak measures. Cross-correlation plots were used to determine whether a time delay existed between changes in daily median CT values and measures of community disease dynamics. RESULTS: Daily median CT values negatively correlated with the daily Rt values (P<.001), the daily COVID-19 hospitalization counts (with a 33-day time delay; P<.001), and the daily changes in percent positivity among testing samples (P<.001). Despite visual trends suggesting time delays in the plots for median CT values and outbreak measures, a statistically significant delay was only detected between changes in median CT values and COVID-19 hospitalization counts (P<.001). CONCLUSIONS: This study adds to the literature by analyzing samples collected from an entire geographical area and contextualizing the results with other research investigating population CT values.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19/epidemiology , Hospitalization/statistics & numerical data , Adult , COVID-19/transmission , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Texas , Time Factors
6.
Clin Ther ; 43(5): 871-885, 2021 05.
Article in English | MEDLINE | ID: covidwho-1188425

ABSTRACT

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 or 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 adverse effects, minimizing costs, and effectively allocating resources. This study presents a machine-learning system with the capacity to identify patients in whom treatment with a corticosteroid or remdesivir is associated with improved survival time. METHODS: Gradient-boosted decision-tree models used for predicting treatment benefit were trained and tested on data from electronic health records dated between December 18, 2019, and October 18, 2020, from adult patients (age ≥18 years) with COVID-19 in 10 US hospitals. Models were evaluated for performance in identifying patients with longer survival times when treated with a corticosteroid versus remdesivir. Fine and Gray proportional-hazards models were used for identifying significant findings in treated and nontreated patients, in a subset of patients who received supplemental oxygen, and in patients identified by the algorithm. Inverse probability-of-treatment weights were used to adjust for confounding. Models were trained and tested separately for each treatment. FINDINGS: Data from 2364 patients were included, with men comprising slightly more than 50% of the sample; 893 patients were treated with remdesivir, and 1471 were treated with a corticosteroid. After adjustment for confounding, neither corticosteroids nor remdesivir use was associated with increased survival time in the overall population or in the subpopulation that received 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 and 0.40, respectively (both, P = 0.04). IMPLICATIONS: Machine-learning methods have the capacity to identify hospitalized patients with COVID-19 in whom treatment with a corticosteroid or remdesivir is associated with an increase in survival time. These methods may help to improve patient outcomes and allocate resources during the COVID-19 crisis.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Adrenal Cortex Hormones , Alanine/analogs & derivatives , Antiviral Agents , COVID-19 , Machine Learning , Adenosine Monophosphate/therapeutic use , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Female , Humans , Male , Middle Aged , Young Adult
7.
JMIR Public Health Surveill ; 6(4): e22400, 2020 10 22.
Article in English | MEDLINE | ID: covidwho-1172949

ABSTRACT

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.


Subject(s)
Forecasting/methods , Hospital Mortality , Machine Learning/standards , APACHE , Adult , Aged , Algorithms , Cohort Studies , Early Warning Score , Electronic Health Records/statistics & numerical data , Female , Humans , Machine Learning/statistics & numerical data , Male , Middle Aged , Retrospective Studies , Simplified Acute Physiology Score
9.
J Clin Med ; 9(12)2020 Nov 26.
Article in English | MEDLINE | ID: covidwho-945860

ABSTRACT

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.

10.
Ann Med Surg (Lond) ; 59: 207-216, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-813448

ABSTRACT

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.

11.
Preprint | SSRN | ID: ppcovidwho-1590

ABSTRACT

Background: Identifying patient characteristics associated with poor outcomes is vital to minimizing death due to COVID-19. Identification of features that pre

12.
Comput Biol Med ; 124: 103949, 2020 09.
Article in English | MEDLINE | ID: covidwho-695377

ABSTRACT

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.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Machine Learning , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/physiopathology , Adult , Aged , Aged, 80 and over , Algorithms , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/statistics & numerical data , Computational Biology , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Prognosis , Prospective Studies , Respiration, Artificial , Respiratory Insufficiency/therapy , SARS-CoV-2 , Sensitivity and Specificity , Triage/methods , Triage/statistics & numerical data , United States/epidemiology
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