MEWS++: Enhancing the Prediction of Clinical Deterioration in Admitted Patients through a Machine Learning Model.

Early detection of patients at risk for clinical deterioration is crucial for timely intervention. Traditional detection systems rely on a limited set of variables and are unable to predict the time of decline. We describe a machine learning model called MEWS++ that enables the identification of patients at risk of escalation of care or death six hours prior to the event. A retrospective single-center cohort study was conducted from July 2011 to July 2017 of adult (age > 18) inpatients excluding psychiatric, parturient, and hospice patients. Three machine learning models were trained and tested: random forest (RF), linear support vector machine, and logistic regression. We compared the models' performance to the traditional Modified Early Warning Score (MEWS) using sensitivity, specificity, and Area Under the Curve for Receiver Operating Characteristic (AUC-ROC) and Precision-Recall curves (AUC-PR). The primary outcome was escalation of care from a floor bed to an intensive care or step-down unit, or death, within 6 h. A total of 96,645 patients with 157,984 hospital encounters and 244,343 bed movements were included. Overall rate of escalation or death was 3.4%. The RF model had the best performance with sensitivity 81.6%, specificity 75.5%, AUC-ROC of 0.85, and AUC-PR of 0.37. Compared to traditional MEWS, sensitivity increased 37%, specificity increased 11%, and AUC-ROC increased 14%. This study found that using machine learning and readily available clinical data, clinical deterioration or death can be predicted 6 h prior to the event. The model we developed can warn of patient deterioration hours before the event, thus helping make timely clinical decisions.

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease.

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease.

Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning.

Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. As the number of drug repurposing investigations increases, a new opportunity has emerged to understand factors driving drug repositioning through systematic analyses of drugs, drug targets and associated disease indications. However, such analyses have so far been hampered by the lack of a centralized knowledgebase, benchmarking data sets and reporting standards. To address these knowledge and clinical needs, here, we present RepurposeDB, a collection of repurposed drugs, drug targets and diseases, which was assembled, indexed and annotated from public data. RepurposeDB combines information on 253 drugs [small molecules (74.30%) and protein drugs (25.29%)] and 1125 diseases. Using RepurposeDB data, we identified pharmacological (chemical descriptors, physicochemical features and absorption, distribution, metabolism, excretion and toxicity properties), biological (protein domains, functional process, molecular mechanisms and pathway cross talks) and epidemiological (shared genetic architectures, disease comorbidities and clinical phenotype similarities) factors mediating drug repositioning. Collectively, RepurposeDB is developed as the reference database for drug repositioning investigations. The pharmacological, biological and epidemiological principles of drug repositioning identified from the meta-analyses could augment therapeutic development.

EHDViz: clinical dashboard development using open-source technologies.

OBJECTIVE: To design, develop and prototype clinical dashboards to integrate high-frequency health and wellness data streams using interactive and real-time data visualisation and analytics modalities. MATERIALS AND METHODS: We developed a clinical dashboard development framework called electronic healthcare data visualization (EHDViz) toolkit for generating web-based, real-time clinical dashboards for visualising heterogeneous biomedical, healthcare and wellness data. The EHDViz is an extensible toolkit that uses R packages for data management, normalisation and producing high-quality visualisations over the web using R/Shiny web server architecture. We have developed use cases to illustrate utility of EHDViz in different scenarios of clinical and wellness setting as a visualisation aid for improving healthcare delivery. RESULTS: Using EHDViz, we prototyped clinical dashboards to demonstrate the contextual versatility of EHDViz toolkit. An outpatient cohort was used to visualise population health management tasks (n=14,221), and an inpatient cohort was used to visualise real-time acuity risk in a clinical unit (n=445), and a quantified-self example using wellness data from a fitness activity monitor worn by a single individual was also discussed (n-of-1). The back-end system retrieves relevant data from data source, populates the main panel of the application and integrates user-defined data features in real-time and renders output using modern web browsers. The visualisation elements can be customised using health features, disease names, procedure names or medical codes to populate the visualisations. The source code of EHDViz and various prototypes developed using EHDViz are available in the public domain at http://ehdviz.dudleylab.org. CONCLUSIONS: Collaborative data visualisations, wellness trend predictions, risk estimation, proactive acuity status monitoring and knowledge of complex disease indicators are essential components of implementing data-driven precision medicine. As an open-source visualisation framework capable of integrating health assessment, EHDViz aims to be a valuable toolkit for rapid design, development and implementation of scalable clinical data visualisation dashboards.