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Register a new userMachine learning approach to dynamic risk modeling of mortality in COVID-19: a UK Biobank study
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The COVID-19 pandemic has created an urgent need for robust, scalable monitoring tools supporting stratification of high-risk patients. This research aims to develop and validate prediction models, using the UK Biobank, to estimate COVID-19 mortality risk in confirmed cases. From the 11,245 participants testing positive for COVID-19, we develop a data-driven random forest classification model with excellent performance (AUC: 0.91), using baseline characteristics, pre-existing conditions, symptoms, and vital signs, such that the score could dynamically assess mortality risk with disease deterioration. We also identify several significant novel predictors of COVID-19 mortality with equivalent or greater predictive value than established high-risk comorbidities, such as detailed anthropometrics and prior acute kidney failure, urinary tract infection, and pneumonias. The model design and feature selection enables utility in outpatient settings. Possible applications include supporting individual-level risk profiling and monitoring disease progression across patients with COVID-19 at-scale, especially in hospital-at-home settings.
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Diabetes affects over 400 million people and is among the leading causes of morbidity worldwide. Identification of high-risk individuals can support early diagnosis and prevention of disease development through lifestyle changes. However, the majority of existing risk scores require information about blood-based factors which are not obtainable outside of the clinic. Here, we aimed to develop an accessible solution that could be deployed digitally and at scale. We developed a predictive 10-year type 2 diabetes risk score using 301 features derived from 472,830 participants in the UK Biobank dataset while excluding any features which are not easily obtainable by a smartphone. Using a data-driven feature selection process, 19 features were included in the final reduced model. A Cox proportional hazards model slightly overperformed a DeepSurv model trained using the same features, achieving a concordance index of 0.818 (95% CI: 0.812-0.823), compared to 0.811 (95% CI: 0.806-0.815). The final model showed good calibration. This tool can be used for clinical screening of individuals at risk of developing type 2 diabetes and to foster patient empowerment by broadening their knowledge of the factors affecting their personal risk.
Background: Providing appropriate care for people suffering from COVID-19, the disease caused by the pandemic SARS-CoV-2 virus is a significant global challenge. Many individuals who become infected have pre-existing conditions that may interact with COVID-19 to increase symptom severity and mortality risk. COVID-19 patient comorbidities are likely to be informative about individual risk of severe illness and mortality. Accurately determining how comorbidities are associated with severe symptoms and mortality would thus greatly assist in COVID-19 care planning and provision. Methods: To assess the interaction of patient comorbidities with COVID-19 severity and mortality we performed a meta-analysis of the published global literature, and machine learning predictive analysis using an aggregated COVID-19 global dataset. Results: Our meta-analysis identified chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CEVD), cardiovascular disease (CVD), type 2 diabetes, malignancy, and hypertension as most significantly associated with COVID-19 severity in the current published literature. Machine learning classification using novel aggregated cohort data similarly found COPD, CVD, CKD, type 2 diabetes, malignancy and hypertension, as well as asthma, as the most significant features for classifying those deceased versus those who survived COVID-19. While age and gender were the most significant predictor of mortality, in terms of symptom-comorbidity combinations, it was observed that Pneumonia-Hypertension, Pneumonia-Diabetes and Acute Respiratory Distress Syndrome (ARDS)-Hypertension showed the most significant effects on COVID-19 mortality. Conclusions: These results highlight patient cohorts most at risk of COVID-19 related severe morbidity and mortality which have implications for prioritization of hospital resources.
Background: Cardiovascular diseases (CVDs) are among the leading causes of death worldwide. Predictive scores providing personalised risk of developing CVD are increasingly used in clinical practice. Most scores, however, utilise a homogenous set of features and require the presence of a physician. Objective: The aim was to develop a new risk model (DiCAVA) using statistical and machine learning techniques that could be applied in a remote setting. A secondary goal was to identify new patient-centric variables that could be incorporated into CVD risk assessments. Methods: Across 466,052 participants, Cox proportional hazards (CPH) and DeepSurv models were trained using 608 variables derived from the UK Biobank to investigate the 10-year risk of developing a CVD. Data-driven feature selection reduced the number of features to 47, after which reduced models were trained. Both models were compared to the Framingham score. Results: The reduced CPH model achieved a c-index of 0.7443, whereas DeepSurv achieved a c-index of 0.7446. Both CPH and DeepSurv were superior in determining the CVD risk compared to Framingham score. Minimal difference was observed when cholesterol and blood pressure were excluded from the models (CPH: 0.741, DeepSurv: 0.739). The models show very good calibration and discrimination on the test data. Conclusion: We developed a cardiovascular risk model that has very good predictive capacity and encompasses new variables. The score could be incorporated into clinical practice and utilised in a remote setting, without the need of including cholesterol. Future studies will focus on external validation across heterogeneous samples.
Predictive models with a focus on different spatial-temporal scales benefit governments and healthcare systems to combat the COVID-19 pandemic. Here we present the conditional Long Short-Term Memory networks with Quantile output (condLSTM-Q), a well-performing model for making quantile predictions on COVID-19 death tolls at the county level with a two-week forecast window. This fine geographical scale is a rare but useful feature in publicly available predictive models, which would especially benefit state-level officials to coordinate resources within the state. The quantile predictions from condLSTM-Q inform people about the distribution of the predicted death tolls, allowing better evaluation of possible trajectories of the severity. Given the scalability and generalizability of neural network models, this model could incorporate additional data sources with ease, and could be further developed to generate other useful predictions such as new cases or hospitalizations intuitively.
The black-box nature of machine learning models hinders the deployment of some high-accuracy models in medical diagnosis. It is risky to put ones life in the hands of models that medical researchers do not fully understand. However, through model interpretation, black-box models can promptly reveal significant biomarkers that medical practitioners may have overlooked due to the surge of infected patients in the COVID-19 pandemic. This research leverages a database of 92 patients with confirmed SARS-CoV-2 laboratory tests between 18th Jan. 2020 and 5th Mar. 2020, in Zhuhai, China, to identify biomarkers indicative of severity prediction. Through the interpretation of four machine learning models, decision tree, random forests, gradient boosted trees, and neural networks using permutation feature importance, Partial Dependence Plot (PDP), Individual Conditional Expectation (ICE), Accumulated Local Effects (ALE), Local Interpretable Model-agnostic Explanations (LIME), and Shapley Additive Explanation (SHAP), we identify an increase in N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), C-Reaction Protein (CRP), and lactic dehydrogenase (LDH), a decrease in lymphocyte (LYM) is associated with severe infection and an increased risk of death, which is consistent with recent medical research on COVID-19 and other research using dedicated models. We further validate our methods on a large open dataset with 5644 confirmed patients from the Hospital Israelita Albert Einstein, at S~ao Paulo, Brazil from Kaggle, and unveil leukocytes, eosinophils, and platelets as three indicative biomarkers for COVID-19.
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