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Background: Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in intensive care units (ICUs). Early identification of patients at risk of VAP enables early intervention, which in turn improves patient outcomes. We developed a predictive model for individualized risk assessment utilizing machine learning to identify patients at risk of developing VAP.Methods: The Philips eRI database, a multi-institution electronic medical record (EMR), was used for model development. For adult (≥18y) patients, we propose a set of criteria using indications of the start of a new antibiotic treatment temporally contiguous to a microbiological test to mark suspected infection events, of which those with a positive culture are labeled as presumed VAP if 1) the event occurs at least 48 hours after intubation, and 2) there are no indications of community-acquired pneumonia (CAP) or other hospital-acquired infections (HAI) in the patient charts. The resulting VAP and no-VAP (control) cases were then used to build an ensemble of decision trees to predict the risk of VAP in the next 24hrs using data on patient’s demographics, vitals, labs, and ventilator settings. Results: The resulting model predicts the development of VAP with an AUC of 76% and AUPRC of 75% at a lead time of 24h in advance. Additionally, we group hospitals that are similar in healthcare processes into distinct clusters and characterize VAP prediction for the identified hospital clusters. We show inter-hospital (teaching status and healthcare processes) and cohort-specific (age groups, gender, early vs late VAP, ICU mortality status) differences in VAP prediction and associated symptomologies. Conclusions: Our proposed VAP criteria provide a temporal context for the infection event and enable studying the disease course. Using the proposed criteria, we curated a patient cohort and used it to build a model to predict an impending VAP event before any clinical suspicions. We present a clustering approach to tailor the VAP prediction model for different hospital types based on their EMR data characteristics. The developed VAP prediction model provides instantaneous risk score that allows early interventions and confirmatory diagnostic actions.

Given an array of phenotypes (e.g., yield across strains and conditions), one can ask how to best choose subsets of conditions that are informative about the whole dataset, enabling efficient system identification and providing a basis vector in phenotype space. Here we introduce a mixed integer linear programming approach to choose explanatory and response variables for a phenotypic matrix. We applied the algorithm to a set of fitness measurements for 462 yeast strains under 38 carbon sources, and to the growth phenotypes of 65 marine bacteria on 11 media. The algorithm identifies environments that can be used as features to predict growth under other conditions, providing biologically interpretable metabolic axes for strain discrimination. Our approach could be used to reduce the number of experiments needed to identify a strain or to map its metabolic capabilities. The generality of the algorithm makes it appropriate for addressing subset selection problems in areas beyond biology.

STUDY QUESTION Can we derive adequate models to predict the probability of conception among couples actively trying to conceive? SUMMARY ANSWER Leveraging data collected from female participants in a North American preconception cohort study, we developed models to predict pregnancy with performance of ∼70% in the area under the receiver operating characteristic curve (AUC). WHAT IS KNOWN ALREADY Earlier work has focused primarily on identifying individual risk factors for infertility. Several predictive models have been developed in subfertile populations, with relatively low discrimination (AUC: 59–64%). STUDY DESIGN, SIZE, DURATION Study participants were female, aged 21–45 years, residents of the USA or Canada, not using fertility treatment, and actively trying to conceive at enrollment (2013–2019). Participants completed a baseline questionnaire at enrollment and follow-up questionnaires every 2 months for up to 12 months or until conception. We used data from 4133 participants with no more than one menstrual cycle of pregnancy attempt at study entry. PARTICIPANTS/MATERIALS, SETTING, METHODS On the baseline questionnaire, participants reported data on sociodemographic factors, lifestyle and behavioral factors, diet quality, medical history and selected male partner characteristics. A total of 163 predictors were considered in this study. We implemented regularized logistic regression, support vector machines, neural networks and gradient boosted decision trees to derive models predicting the probability of pregnancy: (i) within fewer than 12 menstrual cycles of pregnancy attempt time (Model I), and (ii) within 6 menstrual cycles of pregnancy attempt time (Model II). Cox models were used to predict the probability of pregnancy within each menstrual cycle for up to 12 cycles of follow-up (Model III). We assessed model performance using the AUC and the weighted-F1 score for Models I and II, and the concordance index for Model III. MAIN RESULTS AND THE ROLE OF CHANCE Model I and II AUCs were 70% and 66%, respectively, in parsimonious models, and the concordance index for Model III was 63%. The predictors that were positively associated with pregnancy in all models were: having previously breastfed an infant and using multivitamins or folic acid supplements. The predictors that were inversely associated with pregnancy in all models were: female age, female BMI and history of infertility. Among nulligravid women with no history of infertility, the most important predictors were: female age, female BMI, male BMI, use of a fertility app, attempt time at study entry and perceived stress. LIMITATIONS, REASONS FOR CAUTION Reliance on self-reported predictor data could have introduced misclassification, which would likely be non-differential with respect to the pregnancy outcome given the prospective design. In addition, we cannot be certain that all relevant predictor variables were considered. Finally, though we validated the models using split-sample replication techniques, we did not conduct an external validation study. WIDER IMPLICATIONS OF THE FINDINGS Given a wide range of predictor data, machine learning algorithms can be leveraged to analyze epidemiologic data and predict the probability of conception with discrimination that exceeds earlier work. STUDY FUNDING/COMPETING INTEREST(S) The research was partially supported by the U.S. National Science Foundation (under grants DMS-1664644, CNS-1645681 and IIS-1914792) and the National Institutes for Health (under grants R01 GM135930 and UL54 TR004130). In the last 3 years, L.A.W. has received in-kind donations for primary data collection in PRESTO from FertilityFriend.com, Kindara.com, Sandstone Diagnostics and Swiss Precision Diagnostics. L.A.W. also serves as a fibroid consultant to AbbVie, Inc. The other authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.

This study examined records of 2566 consecutive COVID-19 patients at five Massachusetts hospitals and sought to predict level-of-care requirements based on clinical and laboratory data. Several classification methods were applied and compared against standard pneumonia severity scores. The need for hospitalization, ICU care, and mechanical ventilation were predicted with a validation accuracy of 88%, 87%, and 86%, respectively. Pneumonia severity scores achieve respective accuracies of 73% and 74% for ICU care and ventilation. When predictions are limited to patients with more complex disease, the accuracy of the ICU and ventilation prediction models achieved accuracy of 83% and 82%, respectively. Vital signs, age, BMI, dyspnea, and comorbidities were the most important predictors of hospitalization. Opacities on chest imaging, age, admission vital signs and symptoms, male gender, admission laboratory results, and diabetes were the most important risk factors for ICU admission and mechanical ventilation. The factors identified collectively form a signature of the novel COVID-19 disease., eLife digest The new coronavirus (now named SARS-CoV-2) causing the disease pandemic in 2019 (COVID-19), has so far infected over 35 million people worldwide and killed more than 1 million. Most people with COVID-19 have no symptoms or only mild symptoms. But some become seriously ill and need hospitalization. The sickest are admitted to an Intensive Care Unit (ICU) and may need mechanical ventilation to help them breath. Being able to predict which patients with COVID-19 will become severely ill could help hospitals around the world manage the huge influx of patients caused by the pandemic and save lives. Now, Hao, Sotudian, Wang, Xu et al. show that computer models using artificial intelligence technology can help predict which COVID-19 patients will be hospitalized, admitted to the ICU, or need mechanical ventilation. Using data of 2,566 COVID-19 patients from five Massachusetts hospitals, Hao et al. created three separate models that can predict hospitalization, ICU admission, and the need for mechanical ventilation with more than 86% accuracy, based on patient characteristics, clinical symptoms, laboratory results and chest x-rays. Hao et al. found that the patients’ vital signs, age, obesity, difficulty breathing, and underlying diseases like diabetes, were the strongest predictors of the need for hospitalization. Being male, having diabetes, cloudy chest x-rays, and certain laboratory results were the most important risk factors for intensive care treatment and mechanical ventilation. Laboratory results suggesting tissue damage, severe inflammation or oxygen deprivation in the body's tissues were important warning signs of severe disease. The results provide a more detailed picture of the patients who are likely to suffer from severe forms of COVID-19. Using the predictive models may help physicians identify patients who appear okay but need closer monitoring and more aggressive treatment. The models may also help policy makers decide who needs workplace accommodations such as being allowed to work from home, which individuals may benefit from more frequent testing, and who should be prioritized for vaccination when a vaccine becomes available.

BACKGROUND The novel coronavirus SARS-CoV-2 and its associated disease, COVID-19, have caused worldwide disruption, leading countries to take drastic measures to address the progression of the disease. As SARS-CoV-2 continues to spread, hospitals are struggling to allocate resources to patients who are most at risk. In this context, it has become important to develop models that can accurately predict the severity of infection of hospitalized patients to help guide triage, planning, and resource allocation. OBJECTIVE The aim of this study was to develop accurate models to predict the mortality of hospitalized patients with COVID-19 using basic demographics and easily obtainable laboratory data. METHODS We performed a retrospective study of 375 hospitalized patients with COVID-19 in Wuhan, China. The patients were randomly split into derivation and validation cohorts. Regularized logistic regression and support vector machine classifiers were trained on the derivation cohort, and accuracy metrics (F1 scores) were computed on the validation cohort. Two types of models were developed: the first type used laboratory findings from the entire length of the patient’s hospital stay, and the second type used laboratory findings that were obtained no later than 12 hours after admission. The models were further validated on a multicenter external cohort of 542 patients. RESULTS Of the 375 patients with COVID-19, 174 (46.4%) died of the infection. The study cohort was composed of 224/375 men (59.7%) and 151/375 women (40.3%), with a mean age of 58.83 years (SD 16.46). The models developed using data from throughout the patients’ length of stay demonstrated accuracies as high as 97%, whereas the models with admission laboratory variables possessed accuracies of up to 93%. The latter models predicted patient outcomes an average of 11.5 days in advance. Key variables such as lactate dehydrogenase, high-sensitivity C-reactive protein, and percentage of lymphocytes in the blood were indicated by the models. In line with previous studies, age was also found to be an important variable in predicting mortality. In particular, the mean age of patients who survived COVID-19 infection (50.23 years, SD 15.02) was significantly lower than the mean age of patients who died of the infection (68.75 years, SD 11.83; P CONCLUSIONS Machine learning models can be successfully employed to accurately predict outcomes of patients with COVID-19. Our models achieved high accuracies and could predict outcomes more than one week in advance; this promising result suggests that these models can be highly useful for resource allocation in hospitals.

IntroductionNew financial incentives, such as reduced Medicare reimbursements, have led hospitals to closely monitor their readmission rates and initiate efforts aimed at reducing them. In this context, many surgical departments participate in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which collects detailed demographic, laboratory, clinical, procedure and perioperative occurrence data. The availability of such data enables the development of data science methods which predict readmissions and, as done in this paper, offer specific recommendations aimed at preventing readmissions.Materials and methodsThis study leverages NSQIP data for 722,101 surgeries to develop predictive and prescriptive models, predicting readmissions and offering real-time, personalized treatment recommendations for surgical patients during their hospital stay, aimed at reducing the risk of a 30-day readmission. We applied a variety of classification methods to predict 30-day readmissions and developed two prescriptive methods to recommend pre-operative blood transfusions to increase the patient's hematocrit with the objective of preventing readmissions. The effect of these interventions was evaluated using several predictive models.ResultsPredictions of 30-day readmissions based on the entire collection of NSQIP variables achieve an out-of-sample accuracy of 87% (Area Under the Curve-AUC). Predictions based only on pre-operative variables have an accuracy of 74% AUC, out-of-sample. Personalized interventions, in the form of pre-operative blood transfusions identified by the prescriptive methods, reduce readmissions by 12%, on average, for patients considered as candidates for pre-operative transfusion (pre-operative hematoctic ConclusionsThis study is among the first to develop a methodology for making specific, data-driven, personalized treatment recommendations to reduce the 30-day readmission rate. The reported predicted reduction in readmissions can lead to more than $20 million in savings in the U.S. annually.

Urban living in modern large cities has significant adverse effects on health, increasing the risk of several chronic diseases. We focus on the two leading clusters of chronic diseases, heart disease and diabetes, and develop data-driven methods to predict hospitalizations due to these conditions. We base these predictions on the patients’ medical history, recent and more distant, as described in their Electronic Health Records (EHRs). We formulate the prediction problem as a binary classification problem and consider a variety of machine learning methods, including kernelized and sparse Support Vector Machines (SVMs), sparse logistic regression, and random forests. To strike a balance between accuracy and interpretability of the prediction, which is important in a medical setting, we propose two novel methods: $K$ -LRT, a likelihood ratio test-based method, and a Joint Clustering and Classification (JCC) method which identifies hidden patient clusters and adapts classifiers to each cluster. We develop theoretical out-of-sample guarantees for the latter method. We validate our algorithms on large data sets from the Boston Medical Center, the largest safety-net hospital system in New England.

Understanding how microbes assemble into communities is a fundamental open issue in biology, relevant to human health, metabolic engineering, and environmental sustainability. A possible mechanism for interactions of microbes is through cross-feeding, i.e., the exchange of small molecules. These metabolic exchanges may allow different microbes to specialize in distinct tasks and evolve division of labor. To systematically explore the space of possible strategies for division of labor, we applied advanced optimization algorithms to computational models of cellular metabolism. Specifically, we searched for communities able to survive under constraints (such as a limited number of reactions) that would not be sustainable by individual species. We found that predicted consortia partition metabolic pathways in ways that would be difficult to identify manually, possibly providing a competitive advantage over individual organisms. In addition to helping understand diversity in natural microbial communities, our approach could assist in the design of synthetic consortia., Microbes face a trade-off between being metabolically independent and relying on neighboring organisms for the supply of some essential metabolites. This balance of conflicting strategies affects microbial community structure and dynamics, with important implications for microbiome research and synthetic ecology. A “gedanken” (thought) experiment to investigate this trade-off would involve monitoring the rise of mutual dependence as the number of metabolic reactions allowed in an organism is increasingly constrained. The expectation is that below a certain number of reactions, no individual organism would be able to grow in isolation and cross-feeding partnerships and division of labor would emerge. We implemented this idealized experiment using in silico genome-scale models. In particular, we used mixed-integer linear programming to identify trade-off solutions in communities of Escherichia coli strains. The strategies that we found revealed a large space of opportunities in nuanced and nonintuitive metabolic division of labor, including, for example, splitting the tricarboxylic acid (TCA) cycle into two separate halves. The systematic computation of possible solutions in division of labor for 1-, 2-, and 3-strain consortia resulted in a rich and complex landscape. This landscape displayed a nonlinear boundary, indicating that the loss of an intracellular reaction was not necessarily compensated for by a single imported metabolite. Different regions in this landscape were associated with specific solutions and patterns of exchanged metabolites. Our approach also predicts the existence of regions in this landscape where independent bacteria are viable but are outcompeted by cross-feeding pairs, providing a possible incentive for the rise of division of labor. IMPORTANCE Understanding how microbes assemble into communities is a fundamental open issue in biology, relevant to human health, metabolic engineering, and environmental sustainability. A possible mechanism for interactions of microbes is through cross-feeding, i.e., the exchange of small molecules. These metabolic exchanges may allow different microbes to specialize in distinct tasks and evolve division of labor. To systematically explore the space of possible strategies for division of labor, we applied advanced optimization algorithms to computational models of cellular metabolism. Specifically, we searched for communities able to survive under constraints (such as a limited number of reactions) that would not be sustainable by individual species. We found that predicted consortia partition metabolic pathways in ways that would be difficult to identify manually, possibly providing a competitive advantage over individual organisms. In addition to helping understand diversity in natural microbial communities, our approach could assist in the design of synthetic consortia.

We consider {\em Mixed Linear Regression (MLR)}, where training data have been generated from a mixture of distinct linear models (or clusters) and we seek to identify the corresponding coefficient vectors. We introduce a {\em Mixed Integer Programming (MIP)} formulation for MLR subject to regularization constraints on the coefficient vectors. We establish that as the number of training samples grows large, the MIP solution converges to the true coefficient vectors in the absence of noise. Subject to slightly stronger assumptions, we also establish that the MIP identifies the clusters from which the training samples were generated. In the special case where training data come from a single cluster, we establish that the corresponding MIP yields a solution that converges to the true coefficient vector even when training data are perturbed by (martingale difference) noise. We provide a counterexample indicating that in the presence of noise, the MIP may fail to produce the true coefficient vectors for more than one clusters. We also provide numerical results testing the MIP solutions in synthetic examples with noise.

We augment linear Support Vector Machine (SVM) classifiers by adding three important features: (i) we introduce a regularization constraint to induce a sparse classifier; (ii) we devise a method that partitions the positive class into clusters and selects a sparse SVM classifier for each cluster; and (iii) we develop a method to optimize the values of controllable variables in order to reduce the number of data points which are predicted to have an undesirable outcome, which, in our setting, coincides with being in the positive class. The latter feature leads to personalized prescriptions/recommendations. We apply our methods to the problem of predicting and preventing hospital readmissions within 30-days from discharge for patients that underwent a general surgical procedure. To that end, we leverage a large dataset containing over 2.28 million patients who had surgeries in the period 2011--2014 in the U.S. The dataset has been collected as part of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP).

Background The novel coronavirus SARS-CoV-2 and its associated disease, COVID-19, have caused worldwide disruption, leading countries to take drastic measures to address the progression of the disease. As SARS-CoV-2 continues to spread, hospitals are struggling to allocate resources to patients who are most at risk. In this context, it has become important to develop models that can accurately predict the severity of infection of hospitalized patients to help guide triage, planning, and resource allocation. Objective The aim of this study was to develop accurate models to predict the mortality of hospitalized patients with COVID-19 using basic demographics and easily obtainable laboratory data. Methods We performed a retrospective study of 375 hospitalized patients with COVID-19 in Wuhan, China. The patients were randomly split into derivation and validation cohorts. Regularized logistic regression and support vector machine classifiers were trained on the derivation cohort, and accuracy metrics (F1 scores) were computed on the validation cohort. Two types of models were developed: the first type used laboratory findings from the entire length of the patient’s hospital stay, and the second type used laboratory findings that were obtained no later than 12 hours after admission. The models were further validated on a multicenter external cohort of 542 patients. Results Of the 375 patients with COVID-19, 174 (46.4%) died of the infection. The study cohort was composed of 224/375 men (59.7%) and 151/375 women (40.3%), with a mean age of 58.83 years (SD 16.46). The models developed using data from throughout the patients’ length of stay demonstrated accuracies as high as 97%, whereas the models with admission laboratory variables possessed accuracies of up to 93%. The latter models predicted patient outcomes an average of 11.5 days in advance. Key variables such as lactate dehydrogenase, high-sensitivity C-reactive protein, and percentage of lymphocytes in the blood were indicated by the models. In line with previous studies, age was also found to be an important variable in predicting mortality. In particular, the mean age of patients who survived COVID-19 infection (50.23 years, SD 15.02) was significantly lower than the mean age of patients who died of the infection (68.75 years, SD 11.83; P Conclusions Machine learning models can be successfully employed to accurately predict outcomes of patients with COVID-19. Our models achieved high accuracies and could predict outcomes more than one week in advance; this promising result suggests that these models can be highly useful for resource allocation in hospitals.

Objective: To derive a predictive model to identify patients likely to be hospitalized during the following year due to complications attributed to Type II diabetes. Methods: A variety of supervised machine learning classification methods were tested and a new method that discovers hidden patient clusters in the positive class (hospitalized) was developed while, at the same time, sparse linear support vector machine classifiers were derived to separate positive samples from the negative ones (non-hospitalized). The convergence of the new method was established and theoretical guarantees were proved on how the classifiers it produces generalize to a test set not seen during training. Results: The methods were tested on a large set of patients from the Boston Medical Center – the largest safety net hospital in New England. It is found that our new joint clustering/classification method achieves an accuracy of 89% (measured in terms of area under the ROC Curve) and yields informative clusters which can help interpret the classification results, thus increasing the trust of physicians to the algorithmic output and providing some guidance towards preventive measures. While it is possible to increase accuracy to 92% with other methods, this comes with increased computational cost and lack of interpretability. The analysis shows that even a modest probability of preventive actions being effective (more than 19%) suffices to generate significant hospital care savings. Conclusions: Predictive models are proposed that can help avert hospitalizations, improve health outcomes and drastically reduce hospital expenditures. The scope for savings is significant as it has been estimated that in the USA alone, about $5.8 billion are spent each year on diabetes-related hospitalizations that could be prevented.