Voice-Enabled Response Analysis Agent (VERAA): Leveraging Large Language Models to Map Voice Responses in SDoH Survey.

Social Determinants of Health (SDoH) have been shown to have profound impacts on health-related outcomes, yet this data suffers from high rates of missingness in electronic health records (EHR). Moreover, limited English proficiency in the United States can be a barrier to communication with health care providers. In this study, we have designed a multilingual conversational agent capable of conducting SDoH surveys for use in healthcare environments. The agent asks questions in the patient's native language, translates responses into English, and subsequently maps these responses via a large language model (LLM) to structured options in a SDoH survey. This tool can be extended to a variety of survey instruments in either hospital or home settings, enabling the extraction of structured insights from free-text answers. The proposed approach heralds a shift towards more inclusive and insightful data collection, marking a significant stride in SDoH data enrichment for optimizing health outcome predictions and interventions.

Impact of a deep learning sepsis prediction model on quality of care and survival.

Sepsis remains a major cause of mortality and morbidity worldwide. Algorithms that assist with the early recognition of sepsis may improve outcomes, but relatively few studies have examined their impact on real-world patient outcomes. Our objective was to assess the impact of a deep-learning model (COMPOSER) for the early prediction of sepsis on patient outcomes. We completed a before-and-after quasi-experimental study at two distinct Emergency Departments (EDs) within the UC San Diego Health System. We included 6217 adult septic patients from 1/1/2021 through 4/30/2023. The exposure tested was a nurse-facing Best Practice Advisory (BPA) triggered by COMPOSER. In-hospital mortality, sepsis bundle compliance, 72-h change in sequential organ failure assessment (SOFA) score following sepsis onset, ICU-free days, and the number of ICU encounters were evaluated in the pre-intervention period (705 days) and the post-intervention period (145 days). The causal impact analysis was performed using a Bayesian structural time-series approach with confounder adjustments to assess the significance of the exposure at the 95% confidence level. The deployment of COMPOSER was significantly associated with a 1.9% absolute reduction (17% relative decrease) in in-hospital sepsis mortality (95% CI, 0.3%-3.5%), a 5.0% absolute increase (10% relative increase) in sepsis bundle compliance (95% CI, 2.4%-8.0%), and a 4% (95% CI, 1.1%-7.1%) reduction in 72-h SOFA change after sepsis onset in causal inference analysis. This study suggests that the deployment of COMPOSER for early prediction of sepsis was associated with a significant reduction in mortality and a significant increase in sepsis bundle compliance.

Unsupervised Detection and Correction of Model Calibration Shift at Test-Time.

The wide adoption of predictive models into clinical practice require generalizability across hospitals and maintenance of consistent performance across time. Model calibration shift, caused by factors such as changes in prevalence rates or data distribution shift, can affect the generalizability of such models. In this work, we propose a model calibration detection and correction (CaDC) method, specifically designed to utilize only unlabeled data at a target hospital. The proposed method is very flexible and can be used alongside any deep learning-based clinical predictive model. As a case study, we focus on the problem of detecting and correcting model calibration shift in the context of early prediction of sepsis. Three patient cohorts consisting of 545,089 adult patients admitted to the emergency departments at three geographically diverse healthcare systems in the United States were used to train and externally validate the proposed method. We successfully show that utilizing the CaDC model can help assist the sepsis prediction model in achieving a predefined positive predictive value (PPV). For instance, when trained to achieve a PPV of 20%, the performance of the sepsis prediction model with and without the calibration shift estimation model was 18.0% vs 12.9% and 23.1% vs 13.4% at the two external validation cohorts, respectively. As such, the proposed CaDC method has potential applications in maintaining performance claims of predictive models deployed across hospital systems.Clinical relevance- Model generalizability is a requirement of wider adoption of clinical predictive models.

Voice-Enabled Response Analysis Agent (VERAA): Leveraging Large Language Models to Map Voice Responses in SDoH Survey.

Social Determinants of Health (SDoH) have been shown to have profound impacts on health-related outcomes, yet this data suffers from high rates of missingness in electronic health records (EHR). Moreover, limited English proficiency in the United States can be a barrier to communication with health care providers. In this study, we have designed a multilingual conversational agent capable of conducting SDoH surveys for use in healthcare environments. The agent asks questions in the patient's native language, translates responses into English, and subsequently maps these responses via a large language model (LLM) to structured options in a SDoH survey. This tool can be extended to a variety of survey instruments in either hospital or home settings, enabling the extraction of structured insights from free-text answers. The proposed approach heralds a shift towards more inclusive and insightful data collection, marking a significant stride in SDoH data enrichment for optimizing health outcome predictions and interventions.

Optimizing the Implementation of Clinical Predictive Models to Minimize National Costs: Sepsis Case Study.

BACKGROUND: Sepsis costs and incidence vary dramatically across diagnostic categories, warranting a customized approach for implementing predictive models. OBJECTIVE: The aim of this study was to optimize the parameters of a sepsis prediction model within distinct patient groups to minimize the excess cost of sepsis care and analyze the potential effect of factors contributing to end-user response to sepsis alerts on overall model utility. METHODS: We calculated the excess costs of sepsis to the Centers for Medicare and Medicaid Services (CMS) by comparing patients with and without a secondary sepsis diagnosis but with the same primary diagnosis and baseline comorbidities. We optimized the parameters of a sepsis prediction algorithm across different diagnostic categories to minimize these excess costs. At the optima, we evaluated diagnostic odds ratios and analyzed the impact of compliance factors such as noncompliance, treatment efficacy, and tolerance for false alarms on the net benefit of triggering sepsis alerts. RESULTS: Compliance factors significantly contributed to the net benefit of triggering a sepsis alert. However, a customized deployment policy can achieve a significantly higher diagnostic odds ratio and reduced costs of sepsis care. Implementing our optimization routine with powerful predictive models could result in US $4.6 billion in excess cost savings for CMS. CONCLUSIONS: We designed a framework for customizing sepsis alert protocols within different diagnostic categories to minimize excess costs and analyzed model performance as a function of false alarm tolerance and compliance with model recommendations. We provide a framework that CMS policymakers could use to recommend minimum adherence rates to the early recognition and appropriate care of sepsis that is sensitive to hospital department-level incidence rates and national excess costs. Customizing the implementation of clinical predictive models by accounting for various behavioral and economic factors may improve the practical benefit of predictive models.

Inclusion of social determinants of health improves sepsis readmission prediction models.

OBJECTIVE: Sepsis has a high rate of 30-day unplanned readmissions. Predictive modeling has been suggested as a tool to identify high-risk patients. However, existing sepsis readmission models have low predictive value and most predictive factors in such models are not actionable. MATERIALS AND METHODS: Data from patients enrolled in the AllofUs Research Program cohort from 35 hospitals were used to develop a multicenter validated sepsis-related unplanned readmission model that incorporates clinical and social determinants of health (SDH) to predict 30-day unplanned readmissions. Sepsis cases were identified using concepts represented in the Observational Medical Outcomes Partnership. The dataset included over 60 clinical/laboratory features and over 100 SDH features. RESULTS: Incorporation of SDH factors into our model of clinical and demographic features improves model area under the receiver operating characteristic curve (AUC) significantly (from 0.75 to 0.80; P < .001). Model-agnostic interpretability techniques revealed demographics, economic stability, and delay in getting medical care as important SDH predictive features of unplanned hospital readmissions. DISCUSSION: This work represents one of the largest studies of sepsis readmissions using objective clinical data to date (8935 septic index encounters). SDH are important to determine which sepsis patients are more likely to have an unplanned 30-day readmission. The AllofUS dataset provides granular data from a diverse set of individuals, making this model potentially more generalizable than prior models. CONCLUSION: Use of SDH improves predictive performance of a model to identify which sepsis patients are at high risk of an unplanned 30-day readmission.

Leveraging clinical data across healthcare institutions for continual learning of predictive risk models.

The inherent flexibility of machine learning-based clinical predictive models to learn from episodes of patient care at a new institution (site-specific training) comes at the cost of performance degradation when applied to external patient cohorts. To exploit the full potential of cross-institutional clinical big data, machine learning systems must gain the ability to transfer their knowledge across institutional boundaries and learn from new episodes of patient care without forgetting previously learned patterns. In this work, we developed a privacy-preserving learning algorithm named WUPERR (Weight Uncertainty Propagation and Episodic Representation Replay) and validated the algorithm in the context of early prediction of sepsis using data from over 104,000 patients across four distinct healthcare systems. We tested the hypothesis, that the proposed continual learning algorithm can maintain higher predictive performance than competing methods on previous cohorts once it has been trained on a new patient cohort. In the sepsis prediction task, after incremental training of a deep learning model across four hospital systems (namely hospitals H-A, H-B, H-C, and H-D), WUPERR maintained the highest positive predictive value across the first three hospitals compared to a baseline transfer learning approach (H-A: 39.27% vs. 31.27%, H-B: 25.34% vs. 22.34%, H-C: 30.33% vs. 28.33%). The proposed approach has the potential to construct more generalizable models that can learn from cross-institutional clinical big data in a privacy-preserving manner.

Artificial intelligence sepsis prediction algorithm learns to say "I don't know".

Sepsis is a leading cause of morbidity and mortality worldwide. Early identification of sepsis is important as it allows timely administration of potentially life-saving resuscitation and antimicrobial therapy. We present COMPOSER (COnformal Multidimensional Prediction Of SEpsis Risk), a deep learning model for the early prediction of sepsis, specifically designed to reduce false alarms by detecting unfamiliar patients/situations arising from erroneous data, missingness, distributional shift and data drifts. COMPOSER flags these unfamiliar cases as indeterminate rather than making spurious predictions. Six patient cohorts (515,720 patients) curated from two healthcare systems in the United States across intensive care units (ICU) and emergency departments (ED) were used to train and externally and temporally validate this model. In a sequential prediction setting, COMPOSER achieved a consistently high area under the curve (AUC) (ICU: 0.925-0.953; ED: 0.938-0.945). Out of over 6 million prediction windows roughly 20% and 8% were identified as indeterminate amongst non-septic and septic patients, respectively. COMPOSER provided early warning within a clinically actionable timeframe (ICU: 12.2 [3.2 22.8] and ED: 2.1 [0.8 4.5] hours prior to first antibiotics order) across all six cohorts, thus allowing for identification and prioritization of patients at high risk for sepsis.

A Locally Optimized Data-Driven Tool to Predict Sepsis-Associated Vasopressor Use in the ICU.

OBJECTIVES: To train a model to predict vasopressor use in ICU patients with sepsis and optimize external performance across hospital systems using domain adaptation, a transfer learning approach. DESIGN: Observational cohort study. SETTING: Two academic medical centers from January 2014 to June 2017. PATIENTS: Data were analyzed from 14,512 patients (9,423 at the development site and 5,089 at the validation site) who were admitted to an ICU and met Center for Medicare and Medicaid Services definition of severe sepsis either before or during the ICU stay. Patients were excluded if they never developed sepsis, if the ICU length of stay was less than 8 hours or more than 20 days or if they developed shock up to the first 4 hours of ICU admission. MEASUREMENTS AND MAIN RESULTS: Forty retrospectively collected features from the electronic medical records of adult ICU patients at the development site (four hospitals) were used as inputs for a neural network Weibull-Cox survival model to derive a prediction tool for future need of vasopressors. Domain adaptation updated parameters to optimize model performance in the validation site (two hospitals), a different healthcare system over 2,000 miles away. The cohorts at both sites were randomly split into training and testing sets (80% and 20%, respectively). When applied to the test set in the development site, the model predicted vasopressor use 4-24 hours in advance with an area under the receiver operator characteristic curve, specificity, and positive predictive value ranging from 0.80 to 0.81, 56.2% to 61.8%, and 5.6% to 12.1%, respectively. Domain adaptation improved performance of the model to predict vasopressor use within 4 hours at the validation site (area under the receiver operator characteristic curve 0.81 [CI, 0.80-0.81] from 0.77 [CI, 0.76-0.77], p < 0.01; specificity 59.7% [CI, 58.9-62.5%] from 49.9% [CI, 49.5-50.7%], p < 0.01; positive predictive value 8.9% [CI, 8.5-9.4%] from 7.3 [7.1-7.4%], p < 0.01). CONCLUSIONS: Domain adaptation improved performance of a model predicting sepsis-associated vasopressor use during external validation.

DeepAISE - An interpretable and recurrent neural survival model for early prediction of sepsis.

Sepsis, a dysregulated immune system response to infection, is among the leading causes of morbidity, mortality, and cost overruns in the Intensive Care Unit (ICU). Early prediction of sepsis can improve situational awareness among clinicians and facilitate timely, protective interventions. While the application of predictive analytics in ICU patients has shown early promising results, much of the work has been encumbered by high false-alarm rates and lack of trust by the end-users due to the 'black box' nature of these models. Here, we present DeepAISE (Deep Artificial Intelligence Sepsis Expert), a recurrent neural survival model for the early prediction of sepsis. DeepAISE automatically learns predictive features related to higher-order interactions and temporal patterns among clinical risk factors that maximize the data likelihood of observed time to septic events. A comparative study of four baseline models on data from hospitalized patients at three different healthcare systems indicates that DeepAISE produces the most accurate predictions (AUCs between 0.87 and 0.90) at the lowest false alarm rates (FARs between 0.20 and 0.25) while simultaneously producing interpretable representations of the clinical time series and risk factors.

Development and Prospective Validation of a Deep Learning Algorithm for Predicting Need for Mechanical Ventilation.

BACKGROUND: Objective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation (MV) may aid in delivering timely treatment. RESEARCH QUESTION: Can a transparent deep learning (DL) model predict the need for MV in hospitalized patients and those with COVID-19 up to 24 h in advance? STUDY DESIGN AND METHODS: We trained and externally validated a transparent DL algorithm to predict the future need for MV in hospitalized patients, including those with COVID-19, using commonly available data in electronic health records. Additionally, commonly used clinical criteria (heart rate, oxygen saturation, respiratory rate, Fio2, and pH) were used to assess future need for MV. Performance of the algorithm was evaluated using the area under receiver operating characteristic curve (AUC), sensitivity, specificity, and positive predictive value. RESULTS: We obtained data from more than 30,000 ICU patients (including more than 700 patients with COVID-19) from two academic medical centers. The performance of the model with a 24-h prediction horizon at the development and validation sites was comparable (AUC, 0.895 vs 0.882, respectively), providing significant improvement over traditional clinical criteria (P < .001). Prospective validation of the algorithm among patients with COVID-19 yielded AUCs in the range of 0.918 to 0.943. INTERPRETATION: A transparent deep learning algorithm improves on traditional clinical criteria to predict the need for MV in hospitalized patients, including in those with COVID-19. Such an algorithm may help clinicians to optimize timing of tracheal intubation, to allocate resources and staff better, and to improve patient care.

Development and Prospective Validation of a Transparent Deep Learning Algorithm for Predicting Need for Mechanical Ventilation.

IMPORTANCE: Objective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation is of great importance and may aid in delivering timely treatment. OBJECTIVE: To develop, externally validate and prospectively test a transparent deep learning algorithm for predicting 24 hours in advance the need for mechanical ventilation in hospitalized patients and those with COVID-19. DESIGN: Observational cohort study SETTING: Two academic medical centers from January 01, 2016 to December 31, 2019 (Retrospective cohorts) and February 10, 2020 to May 4, 2020 (Prospective cohorts). PARTICIPANTS: Over 31,000 admissions to the intensive care units (ICUs) at two hospitals. Additionally, 777 patients with COVID-19 patients were used for prospective validation. Patients who were placed on mechanical ventilation within four hours of their admission were excluded. MAIN OUTCOME(S) and MEASURE(S): Electronic health record (EHR) data were extracted on an hourly basis, and a set of 40 features were calculated and passed to an interpretable deep-learning algorithm to predict the future need for mechanical ventilation 24 hours in advance. Additionally, commonly used clinical criteria (based on heart rate, oxygen saturation, respiratory rate, FiO2 and pH) was used to assess future need for mechanical ventilation. Performance of the algorithms were evaluated using the area under receiver-operating characteristic curve (AUC), sensitivity, specificity and positive predictive value. RESULTS: After applying exclusion criteria, the external validation cohort included 3,888 general ICU and 402 COVID-19 patients. The performance of the model (AUC) with a 24-hour prediction horizon at the validation site was 0.882 for the general ICU population and 0.918 for patients with COVID-19. In comparison, commonly used clinical criteria and the ROX score achieved AUCs in the range of 0.773 - 0.782 and 0.768 - 0.810 for the general ICU population and patients with COVID-19, respectively. CONCLUSIONS AND RELEVANCE: A generalizable and transparent deep-learning algorithm improves on traditional clinical criteria to predict the need for mechanical ventilation in hospitalized patients, including those with COVID-19. Such an algorithm may help clinicians with optimizing timing of tracheal intubation, better allocation of mechanical ventilation resources and staff, and improve patient care.

Early Prediction of Sepsis From Clinical Data: The PhysioNet/Computing in Cardiology Challenge 2019.

OBJECTIVES: Sepsis is a major public health concern with significant morbidity, mortality, and healthcare expenses. Early detection and antibiotic treatment of sepsis improve outcomes. However, although professional critical care societies have proposed new clinical criteria that aid sepsis recognition, the fundamental need for early detection and treatment remains unmet. In response, researchers have proposed algorithms for early sepsis detection, but directly comparing such methods has not been possible because of different patient cohorts, clinical variables and sepsis criteria, prediction tasks, evaluation metrics, and other differences. To address these issues, the PhysioNet/Computing in Cardiology Challenge 2019 facilitated the development of automated, open-source algorithms for the early detection of sepsis from clinical data. DESIGN: Participants submitted containerized algorithms to a cloud-based testing environment, where we graded entries for their binary classification performance using a novel clinical utility-based evaluation metric. We designed this scoring function specifically for the Challenge to reward algorithms for early predictions and penalize them for late or missed predictions and for false alarms. SETTING: ICUs in three separate hospital systems. We shared data from two systems publicly and sequestered data from all three systems for scoring. PATIENTS: We sourced over 60,000 ICU patients with up to 40 clinical variables for each hour of a patient's ICU stay. We applied Sepsis-3 clinical criteria for sepsis onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 104 groups from academia and industry participated, contributing 853 submissions. Furthermore, 90 abstracts based on Challenge entries were accepted for presentation at Computing in Cardiology. CONCLUSIONS: Diverse computational approaches predict the onset of sepsis several hours before clinical recognition, but generalizability to different hospital systems remains a challenge.

Contextual Embeddings from Clinical Notes Improves Prediction of Sepsis.

Sepsis, a life-threatening organ dysfunction, is a clinical syndrome triggered by acute infection and affects over 1 million Americans every year. Untreated sepsis can progress to septic shock and organ failure, making sepsis one of the leading causes of morbidity and mortality in hospitals. Early detection of sepsis and timely antibiotics administration is known to save lives. In this work, we design a sepsis prediction algorithm based on data from electronic health records (EHR) using a deep learning approach. While most existing EHR-based sepsis prediction models utilize structured data including vitals, labs, and clinical information, we show that incorporation of features based on clinical texts, using a pre-trained neural language representation model, allows for incorporation of unstructured data without an explicit need for ontology-based named-entity recognition and classification. The proposed model is trained on a large critical care database of over 40,000 patients, including 2805 septic patients, and is compared against competing baseline models. In comparison to a baseline model based on structured data alone, incorporation of clinical texts improved AUC from 0.81 to 0.84. Our findings indicate that incorporation of clinical text features via a pre-trained language representation model can improve early prediction of sepsis and reduce false alarms.

Ventricular ectopic beat detection using a wavelet transform and a convolutional neural network.

OBJECTIVE: Ventricular contractions in healthy individuals normally follow the contractions of atria to facilitate more efficient pump action and cardiac output. With a ventricular ectopic beat (VEB), volume within the ventricles are pumped to the body's vessels before receiving blood from atria, thus causing inefficient blood circulation. VEBs tend to cause perturbations in the instantaneous heart rate time series, making the analysis of heart rate variability inappropriate around such events, or requiring special treatment (such as signal averaging). Moreover, VEB frequency can be indicative of life-threatening problems. However, VEBs can often mimic artifacts both in morphology and timing. Identification of VEBs is therefore an important unsolved problem. The aim of this study is to introduce a method of wavelet transform in combination with deep learning network for the classification of VEBs. APPROACH: We proposed a method to automatically discriminate VEB beats from other beats and artifacts with the use of wavelet transform of the electrocardiogram (ECG) and a convolutional neural network (CNN). Three types of wavelets (Morlet wavelet, Paul wavelet and Gaussian derivative) were used to transform segments of single-channel (1D) ECG waveforms to two-dimensional (2D) time-frequency 'images'. The 2D time-frequency images were then passed into a CNN to optimize the convolutional filters and classification. Ten-fold cross validation was used to evaluate the approach on the MIT-BIH arrhythmia database (MIT-BIH). The American Heart Association (AHA) database was then used as an independent dataset to evaluate the trained network. MAIN RESULTS: Ten-fold cross validation results on MIT-BIH showed that the proposed algorithm with Paul wavelet achieved an overall F1 score of 84.94% and accuracy of 97.96% on out of sample validation. Independent test on AHA resulted in an F1 score of 84.96% and accuracy of 97.36%. SIGNIFICANCE: The trained network possessed exceptional transferability across databases and generalization to unseen data.

Deep learning in the cross-time frequency domain for sleep staging from a single-lead electrocardiogram.

OBJECTIVE: This study classifies sleep stages from a single lead electrocardiogram (ECG) using beat detection, cardiorespiratory coupling in the time-frequency domain and a deep convolutional neural network (CNN). APPROACH: An ECG-derived respiration (EDR) signal and synchronous beat-to-beat heart rate variability (HRV) time series were derived from the ECG using previously described robust algorithms. A measure of cardiorespiratory coupling (CRC) was extracted by calculating the coherence and cross-spectrogram of the EDR and HRV signal in 5 min windows. A CNN was then trained to classify the sleep stages (wake, rapid-eye-movement (REM) sleep, non-REM (NREM) light sleep and NREM deep sleep) from the corresponding CRC spectrograms. A support vector machine was then used to combine the output of CNN with the other features derived from the ECG, including phase-rectified signal averaging (PRSA), sample entropy, as well as standard spectral and temporal HRV measures. The MIT-BIH Polysomnographic Database (SLPDB), the PhysioNet/Computing in Cardiology Challenge 2018 database (CinC2018) and the Sleep Heart Health Study (SHHS) database, all expert-annotated for sleep stages, were used to train and validate the algorithm. MAIN RESULTS: Ten-fold cross validation results showed that the proposed algorithm achieved an accuracy (Acc) of 75.4% and a Cohen's kappa coefficient of [Formula: see text] = 0.54 on the out of sample validation data in the classification of Wake, REM, NREM light and deep sleep in SLPDB. This rose to Acc = 81.6% and [Formula: see text] = 0.63 for the classification of Wake, REM sleep and NREM sleep and Acc = 85.1% and [Formula: see text] = 0.68 for the classification of NREM sleep versus REM/wakefulness in SLPDB. SIGNIFICANCE: The proposed ECG-based sleep stage classification approach that represents the highest reported results on non-electroencephalographic data and uses datasets over ten times larger than those in previous studies. By using a state-of-the-art QRS detector and deep learning model, the system does not require human annotation and can therefore be scaled for mass analysis.

A FHIR-Enabled Streaming Sepsis Prediction System for ICUs.

Sepsis is a common disease with very costly, potentially deadly implications. Early prediction of Sepsis and initiation of antibiotic is widely considered as an important determinant of patient survival. Cross-institutional validation and implementation of algorithms for early prediction of Sepsis at a minimum require common data formats, streaming analytic platforms for timely risk assessment, and interoperable and standardized interfaces. In this work we present an open-source cloud-based analytic pipeline, which receives de-identified patient data from an interoperable server and produces real-time Sepsis risk scores for Intensive Care Unit (ICU) patients.

Multiscale network dynamics between heart rate and locomotor activity are altered in schizophrenia.

OBJECTIVE: Changes in heart rate (HR) and locomotor activity reflect changes in autonomic physiology, behavior, and mood. These systems may involve interrelated neural circuits that are altered in psychiatric illness, yet their interactions are poorly understood. We hypothesized interactions between HR and locomotor activity could be used to discriminate patients with schizophrenia from controls, and would be less able to discriminate non-psychiatric patients from controls. APPROACH: HR and locomotor activity were recorded via wearable patches in 16 patients with schizophrenia and 19 healthy controls. Measures of signal complexity and interactions were calculated over multiple time scales, including sample entropy, mutual information, and transfer entropy. A support vector machine was trained on these features to discriminate patients from controls. Additionally, time series were converted into a network with nodes comprised of HR and locomotor activity states, and edges representing state transitions. Graph properties were used as features. Leave-one-out cross validation was performed. To compare against non-psychiatric illness, the same approach was repeated in 41 patients with atrial fibrillation (AFib) and 53 controls. MAIN RESULTS: Network features enabled perfect discrimination of schizophrenia patients from controls with an areas under the receiver operating characteristic curve (AUC) of 1.00 for training and test data. Other bivariate measures of interaction achieved lower AUCs (train 0.98, test 0.96), and univariate measures of complexity achieved the lowest performance. Conversely, interaction features did not improve discrimination of AFib patients from controls beyond univariate approaches. SIGNIFICANCE: Interactions between HR and locomotor activity enabled perfect discrimination of subjects with schizophrenia from controls, but these features were less performant in a non-psychiatric illness. This is the first quantitative evaluation of interactions between physiology and behavior in patients with psychiatric illness.

Multiscale network representation of physiological time series for early prediction of sepsis.

Objective and Approach: Sepsis, a dysregulated immune-mediated host response to infection, is the leading cause of morbidity and mortality in critically ill patients. Indices of heart rate variability and complexity (such as entropy) have been proposed as surrogate markers of neuro-immune system dysregulation with diseases such as sepsis. However, these indices only provide an average, one dimensional description of complex neuro-physiological interactions. We propose a novel multiscale network construction and analysis method for multivariate physiological time series, and demonstrate its utility for early prediction of sepsis. MAIN RESULTS: We show that features derived from a multiscale heart rate and blood pressure time series network provide approximately 20% improvement in the area under the receiver operating characteristic (AUROC) for four-hour advance prediction of sepsis over traditional indices of heart rate entropy ([Formula: see text] versus [Formula: see text]). Our results indicate that this improvement is attributable to both the improved network construction method proposed here, as well as the information embedded in the higher order interaction of heart rate and blood pressure time series dynamics. Our final model, which included the most commonly available clinical measurements in patients' electronic medical records and multiscale entropy features, as well as the proposed network-based features, achieved an AUROC of [Formula: see text]. SIGNIFICANCE: Prediction of the onset of sepsis prior to clinical recognition will allow for meaningful earlier interventions (e.g. antibiotic and fluid administration), which have the potential to decrease sepsis-related morbidity, mortality and healthcare costs.