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Challenges in the application of a mortality prediction model for COVID-19 patients on an Indian cohort

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 Added by Samarth Bhatia
 Publication date 2021
and research's language is English
 Authors Yukti Makhija




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Many countries are now experiencing the third wave of the COVID-19 pandemic straining the healthcare resources with an acute shortage of hospital beds and ventilators for the critically ill patients. This situation is especially worse in India with the second largest load of COVID-19 cases and a relatively resource-scarce medical infrastructure. Therefore, it becomes essential to triage the patients based on the severity of their disease and devote resources towards critically ill patients. Yan et al. 1 have published a very pertinent research that uses Machine learning (ML) methods to predict the outcome of COVID-19 patients based on their clinical parameters at the day of admission. They used the XGBoost algorithm, a type of ensemble model, to build the mortality prediction model. The final classifier is built through the sequential addition of multiple weak classifiers. The clinically operable decision rule was obtained from a single-tree XGBoost and used lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP) values. This decision tree achieved a 100% survival prediction and 81% mortality prediction. However, these models have several technical challenges and do not provide an out of the box solution that can be deployed for other populations as has been reported in the Matters Arising section of Yan et al. Here, we show the limitations of this model by deploying it on one of the largest datasets of COVID-19 patients containing detailed clinical parameters collected from India.



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119 - Samarth Bhatia 2021
As the second wave in India mitigates, COVID-19 has now infected about 29 million patients countrywide, leading to more than 350 thousand people dead. As the infections surged, the strain on the medical infrastructure in the country became apparent. While the country vaccinates its population, opening up the economy may lead to an increase in infection rates. In this scenario, it is essential to effectively utilize the limited hospital resources by an informed patient triaging system based on clinical parameters. Here, we present two interpretable machine learning models predicting the clinical outcomes, severity, and mortality, of the patients based on routine non-invasive surveillance of blood parameters from one of the largest cohorts of Indian patients at the day of admission. Patient severity and mortality prediction models achieved 86.3% and 88.06% accuracy, respectively, with an AUC-ROC of 0.91 and 0.92. We have integrated both the models in a user-friendly web app calculator, https://triage-COVID-19.herokuapp.com/, to showcase the potential deployment of such efforts at scale.
The unprecedented global crisis brought about by the COVID-19 pandemic has sparked numerous efforts to create predictive models for the detection and prognostication of SARS-CoV-2 infections with the goal of helping health systems allocate resources. Machine learning models, in particular, hold promise for their ability to leverage patient clinical information and medical images for prediction. However, most of the published COVID-19 prediction models thus far have little clinical utility due to methodological flaws and lack of appropriate validation. In this paper, we describe our methodology to develop and validate multi-modal models for COVID-19 mortality prediction using multi-center patient data. The models for COVID-19 mortality prediction were developed using retrospective data from Madrid, Spain (N=2547) and were externally validated in patient cohorts from a community hospital in New Jersey, USA (N=242) and an academic center in Seoul, Republic of Korea (N=336). The models we developed performed differently across various clinical settings, underscoring the need for a guided strategy when employing machine learning for clinical decision-making. We demonstrated that using features from both the structured electronic health records and chest X-ray imaging data resulted in better 30-day-mortality prediction performance across all three datasets (areas under the receiver operating characteristic curves: 0.85 (95% confidence interval: 0.83-0.87), 0.76 (0.70-0.82), and 0.95 (0.92-0.98)). We discuss the rationale for the decisions made at every step in developing the models and have made our code available to the research community. We employed the best machine learning practices for clinical model development. Our goal is to create a toolkit that would assist investigators and organizations in building multi-modal models for prediction, classification and/or optimization.
Machine Learning (ML) models typically require large-scale, balanced training data to be robust, generalizable, and effective in the context of healthcare. This has been a major issue for developing ML models for the coronavirus-disease 2019 (COVID-19) pandemic where data is highly imbalanced, particularly within electronic health records (EHR) research. Conventional approaches in ML use cross-entropy loss (CEL) that often suffers from poor margin classification. For the first time, we show that contrastive loss (CL) improves the performance of CEL especially for imbalanced EHR data and the related COVID-19 analyses. This study has been approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai. We use EHR data from five hospitals within the Mount Sinai Health System (MSHS) to predict mortality, intubation, and intensive care unit (ICU) transfer in hospitalized COVID-19 patients over 24 and 48 hour time windows. We train two sequential architectures (RNN and RETAIN) using two loss functions (CEL and CL). Models are tested on full sample data set which contain all available data and restricted data set to emulate higher class imbalance.CL models consistently outperform CEL models with the restricted data set on these tasks with differences ranging from 0.04 to 0.15 for AUPRC and 0.05 to 0.1 for AUROC. For the restricted sample, only the CL model maintains proper clustering and is able to identify important features, such as pulse oximetry. CL outperforms CEL in instances of severe class imbalance, on three EHR outcomes with respect to three performance metrics: predictive power, clustering, and feature importance. We believe that the developed CL framework can be expanded and used for EHR ML work in general.
COVID-19 pandemic has created an extreme pressure on the global healthcare services. Fast, reliable and early clinical assessment of the severity of the disease can help in allocating and prioritizing resources to reduce mortality. In order to study the important blood biomarkers for predicting disease mortality, a retrospective study was conducted on 375 COVID-19 positive patients admitted to Tongji Hospital (China) from January 10 to February 18, 2020. Demographic and clinical characteristics, and patient outcomes were investigated using machine learning tools to identify key biomarkers to predict the mortality of individual patient. A nomogram was developed for predicting the mortality risk among COVID-19 patients. Lactate dehydrogenase, neutrophils (%), lymphocyte (%), high sensitive C-reactive protein, and age - acquired at hospital admission were identified as key predictors of death by multi-tree XGBoost model. The area under curve (AUC) of the nomogram for the derivation and validation cohort were 0.961 and 0.991, respectively. An integrated score (LNLCA) was calculated with the corresponding death probability. COVID-19 patients were divided into three subgroups: low-, moderate- and high-risk groups using LNLCA cut-off values of 10.4 and 12.65 with the death probability less than 5%, 5% to 50%, and above 50%, respectively. The prognostic model, nomogram and LNLCA score can help in early detection of high mortality risk of COVID-19 patients, which will help doctors to improve the management of patient stratification.
The COVID-19 pandemic continues to have a devastating global impact, and has placed a tremendous burden on struggling healthcare systems around the world. Given the limited resources, accurate patient triaging and care planning is critical in the fight against COVID-19, and one crucial task within care planning is determining if a patient should be admitted to a hospitals intensive care unit (ICU). Motivated by the need for transparent and trustworthy ICU admission clinical decision support, we introduce COVID-Net Clinical ICU, a neural network for ICU admission prediction based on patient clinical data. Driven by a transparent, trust-centric methodology, the proposed COVID-Net Clinical ICU was built using a clinical dataset from Hospital Sirio-Libanes comprising of 1,925 COVID-19 patients, and is able to predict when a COVID-19 positive patient would require ICU admission with an accuracy of 96.9% to facilitate better care planning for hospitals amidst the on-going pandemic. We conducted system-level insight discovery using a quantitative explainability strategy to study the decision-making impact of different clinical features and gain actionable insights for enhancing predictive performance. We further leveraged a suite of trust quantification metrics to gain deeper insights into the trustworthiness of COVID-Net Clinical ICU. By digging deeper into when and why clinical predictive models makes certain decisions, we can uncover key factors in decision making for critical clinical decision support tasks such as ICU admission prediction and identify the situations under which clinical predictive models can be trusted for greater accountability.

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