Remote Short Sessions of Heart Rate Variability Biofeedback Monitored With Wearable Technology: Open-Label Prospective Feasibility Study.

BACKGROUND: Heart rate variability (HRV) biofeedback is often performed with structured education, laboratory-based assessments, and practice sessions. It has been shown to improve psychological and physiological function across populations. However, a means to remotely use and monitor this approach would allow for wider use of this technique. Advancements in wearable and digital technology present an opportunity for the widespread application of this approach. OBJECTIVE: The primary aim of the study was to determine the feasibility of fully remote, self-administered short sessions of HRV-directed biofeedback in a diverse population of health care workers (HCWs). The secondary aim was to determine whether a fully remote, HRV-directed biofeedback intervention significantly alters longitudinal HRV over the intervention period, as monitored by wearable devices. The tertiary aim was to estimate the impact of this intervention on metrics of psychological well-being. METHODS: To determine whether remotely implemented short sessions of HRV biofeedback can improve autonomic metrics and psychological well-being, we enrolled HCWs across 7 hospitals in New York City in the United States. They downloaded our study app, watched brief educational videos about HRV biofeedback, and used a well-studied HRV biofeedback program remotely through their smartphone. HRV biofeedback sessions were used for 5 minutes per day for 5 weeks. HCWs were then followed for 12 weeks after the intervention period. Psychological measures were obtained over the study period, and they wore an Apple Watch for at least 7 weeks to monitor the circadian features of HRV. RESULTS: In total, 127 HCWs were enrolled in the study. Overall, only 21 (16.5%) were at least 50% compliant with the HRV biofeedback intervention, representing a small portion of the total sample. This demonstrates that this study design does not feasibly result in adequate rates of compliance with the intervention. Numerical improvement in psychological metrics was observed over the 17-week study period, although it did not reach statistical significance (all P>.05). Using a mixed effect cosinor model, the mean midline-estimating statistic of rhythm (MESOR) of the circadian pattern of the SD of the interbeat interval of normal sinus beats (SDNN), an HRV metric, was observed to increase over the first 4 weeks of the biofeedback intervention in HCWs who were at least 50% compliant. CONCLUSIONS: In conclusion, we found that using brief remote HRV biofeedback sessions and monitoring its physiological effect using wearable devices, in the manner that the study was conducted, was not feasible. This is considering the low compliance rates with the study intervention. We found that remote short sessions of HRV biofeedback demonstrate potential promise in improving autonomic nervous function and warrant further study. Wearable devices can monitor the physiological effects of psychological interventions.

Development of the ehive Digital Health App: Protocol for a Centralized Research Platform.

BACKGROUND: The increasing use of smartphones, wearables, and connected devices has enabled the increasing application of digital technologies for research. Remote digital study platforms comprise a patient-interfacing digital application that enables multimodal data collection from a mobile app and connected sources. They offer an opportunity to recruit at scale, acquire data longitudinally at a high frequency, and engage study participants at any time of the day in any place. Few published descriptions of centralized digital research platforms provide a framework for their development. OBJECTIVE: This study aims to serve as a road map for those seeking to develop a centralized digital research platform. We describe the technical and functional aspects of the ehive app, the centralized digital research platform of the Hasso Plattner Institute for Digital Health at Mount Sinai Hospital, New York, New York. We then provide information about ongoing studies hosted on ehive, including usership statistics and data infrastructure. Finally, we discuss our experience with ehive in the broader context of the current landscape of digital health research platforms. METHODS: The ehive app is a multifaceted and patient-facing central digital research platform that permits the collection of e-consent for digital health studies. An overview of its development, its e-consent process, and the tools it uses for participant recruitment and retention are provided. Data integration with the platform and the infrastructure supporting its operations are discussed; furthermore, a description of its participant- and researcher-facing dashboard interfaces and the e-consent architecture is provided. RESULTS: The ehive platform was launched in 2020 and has successfully hosted 8 studies, namely 6 observational studies and 2 clinical trials. Approximately 1484 participants downloaded the app across 36 states in the United States. The use of recruitment methods such as bulk messaging through the EPIC electronic health records and standard email portals enables broad recruitment. Light-touch engagement methods, used in an automated fashion through the platform, maintain high degrees of engagement and retention. The ehive platform demonstrates the successful deployment of a central digital research platform that can be modified across study designs. CONCLUSIONS: Centralized digital research platforms such as ehive provide a novel tool that allows investigators to expand their research beyond their institution, engage in large-scale longitudinal studies, and combine multimodal data streams. The ehive platform serves as a model for groups seeking to develop similar digital health research programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49204.

Trans-synaptic degeneration in the optic pathway: Exploring the role of lateral geniculate nucleus in early stages of relapsing-remitting multiple sclerosis.

BACKGROUND: Optic pathway is considered an ideal model to study the interaction between inflammation and neurodegeneration in multiple sclerosis (MS). METHODS: Optical Coherence Tomography (OCT) and 3.0 T magnetic resonance imaging (MRI) were acquired in 92 relapsing remitting (RR) MS at clinical onset. Peripapillary RNFL (pRNFL) and macular layers were measured. White matter (WM) and gray matter (GM) lesion volumes (LV), lateral geniculate nucleus (LGN) volume, optic radiations (OR) WM LV, thickness of pericalcarine cortex were evaluated. OCT and MRI control groups (healthy controls [HC]-OCT and HC-MRI) were included. RESULTS: A significant thinning of temporal pRNFL and papillo-macular bundle (PMB) was observed (p<0.001) in 16 (17%) patients presented with monocular optic neuritis (MSON+), compared to 76 MSON- and 30 HC (-15 µm). In MSON-, PMB was reduced (-3 µm) compared to HC OCT (p<0.05). INL total volume was increased both in MSON+ (p<0.001) and MSON- (p = 0.033). Inner retinal layers volumes (macular RNFL, GCL and IPL) were significantly decreased in MSON+ compared to HC (p<0.001) and MSON- (p<0.001). Reduced GCL volume in the parafoveal ring was observed in MSON- compared to HCOCT (p < 0.05). LGN volume was significantly reduced only in MSON+ patients compared to HC-MRI (p<0.001) and MSON- (p<0.007). GCL, IPL and GCIP volumes associated with ipsilateral LGN volume in MSON+ and MSON-. Finally, LGN volume associated with visual cortex thickness with no significant difference between MSON+ and MSON-. CONCLUSIONS: Anterograde trans-synaptic degeneration is early detectable in RRMS presenting with optic neuritis but does not involve LGN.

A machine learning approach to determine resilience utilizing wearable device data: analysis of an observational cohort.

Objective: To assess whether an individual's degree of psychological resilience can be determined from physiological metrics passively collected from a wearable device. Materials and Methods: Data were analyzed in this secondary analysis of the Warrior Watch Study dataset, a prospective cohort of healthcare workers enrolled across 7 hospitals in New York City. Subjects wore an Apple Watch for the duration of their participation. Surveys were collected measuring resilience, optimism, and emotional support at baseline. Results: We evaluated data from 329 subjects (mean age 37.4 years, 37.1% male). Across all testing sets, gradient-boosting machines (GBM) and extreme gradient-boosting models performed best for high- versus low-resilience prediction, stratified on a median Connor-Davidson Resilience Scale-2 score of 6 (interquartile range = 5-7), with an AUC of 0.60. When predicting resilience as a continuous variable, multivariate linear models had a correlation of 0.24 (P = .029) and RMSE of 1.37 in the testing data. A positive psychological construct, comprised of resilience, optimism, and emotional support was also evaluated. The oblique random forest method performed best in estimating high- versus low-composite scores stratified on a median of 32.5, with an AUC of 0.65, a sensitivity of 0.60, and a specificity of 0.70. Discussion: In a post hoc analysis, machine learning models applied to physiological metrics collected from wearable devices had some predictive ability in identifying resilience states and a positive psychological construct. Conclusions: These findings support the further assessment of psychological characteristics from passively collected wearable data in dedicated studies.

StudyU: A Platform for Designing and Conducting Innovative Digital N-of-1 Trials.

N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available. Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app. With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health. Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.

Evaluation of a machine learning approach utilizing wearable data for prediction of SARS-CoV-2 infection in healthcare workers.

Objective: To determine whether a machine learning model can detect SARS-CoV-2 infection from physiological metrics collected from wearable devices. Materials and Methods: Health care workers from 7 hospitals were enrolled and prospectively followed in a multicenter observational study. Subjects downloaded a custom smart phone app and wore Apple Watches for the duration of the study period. Daily surveys related to symptoms and the diagnosis of Coronavirus Disease 2019 were answered in the app. Results: We enrolled 407 participants with 49 (12%) having a positive nasal SARS-CoV-2 polymerase chain reaction test during follow-up. We examined 5 machine-learning approaches and found that gradient-boosting machines (GBM) had the most favorable validation performance. Across all testing sets, our GBM model predicted SARS-CoV-2 infection with an average area under the receiver operating characteristic (auROC) = 86.4% (confidence interval [CI] 84-89%). The model was calibrated to value sensitivity over specificity, achieving an average sensitivity of 82% (CI ±âˆ¼4%) and specificity of 77% (CI ±âˆ¼1%). The most important predictors included parameters describing the circadian heart rate variability mean (MESOR) and peak-timing (acrophase), and age. Discussion: We show that a tree-based ML algorithm applied to physiological metrics passively collected from a wearable device can identify and predict SARS-CoV-2 infection. Conclusion: Applying machine learning models to the passively collected physiological metrics from wearable devices may improve SARS-CoV-2 screening methods and infection tracking.

Factors Associated With Longitudinal Psychological and Physiological Stress in Health Care Workers During the COVID-19 Pandemic: Observational Study Using Apple Watch Data.

BACKGROUND: The COVID-19 pandemic has resulted in a high degree of psychological distress among health care workers (HCWs). There is a need to characterize which HCWs are at an increased risk of developing psychological effects from the pandemic. Given the differences in the response of individuals to stress, an analysis of both the perceived and physiological consequences of stressors can provide a comprehensive evaluation of its impact. OBJECTIVE: This study aimed to determine characteristics associated with longitudinal perceived stress in HCWs and to assess whether changes in heart rate variability (HRV), a marker of autonomic nervous system function, are associated with features protective against longitudinal stress. METHODS: HCWs across 7 hospitals in New York City, NY, were prospectively followed in an ongoing observational digital study using the custom Warrior Watch Study app. Participants wore an Apple Watch for the duration of the study to measure HRV throughout the follow-up period. Surveys measuring perceived stress, resilience, emotional support, quality of life, and optimism were collected at baseline and longitudinally. RESULTS: A total of 361 participants (mean age 36.8, SD 10.1 years; female: n=246, 69.3%) were enrolled. Multivariate analysis found New York City's COVID-19 case count to be associated with increased longitudinal stress (P=.008). Baseline emotional support, quality of life, and resilience were associated with decreased longitudinal stress (P<.001). A significant reduction in stress during the 4-week period after COVID-19 diagnosis was observed in the highest tertial of emotional support (P=.03) and resilience (P=.006). Participants in the highest tertial of baseline emotional support and resilience had a significantly different circadian pattern of longitudinally collected HRV compared to subjects in the low or medium tertial. CONCLUSIONS: High resilience, emotional support, and quality of life place HCWs at reduced risk of longitudinal perceived stress and have a distinct physiological stress profile. Our findings support the use of these characteristics to identify HCWs at risk of the psychological and physiological stress effects of the pandemic.

A Resilience-Building App to Support the Mental Health of Health Care Workers in the COVID-19 Era: Design Process, Distribution, and Evaluation.

BACKGROUND: The COVID-19 pandemic has resulted in increased strain on health care systems and negative psychological effects on health care workers (HCWs). This is anticipated to result in long-term negative mental health effects on the population, with HCWs representing a particularly vulnerable group. The scope of the COVID-19 pandemic necessitates the development of a scalable mental health platform to provide services to large numbers of at-risk or affected individuals. The Mount Sinai Health System in New York City was at the epicenter of the pandemic in the United States. OBJECTIVE: The Center for Stress, Resilience, and Personal Growth (CSRPG) was created to address the current and anticipated psychological impact of the pandemic on the HCWs in the health system. The mission of the Center is to support the resilience and mental health of employees through educational offerings, outreach, and clinical care. Our aim was to build a mobile app to support the newly founded Center in its mission. METHODS: We built the app as a standalone digital platform that hosts a suite of tools that users can interact with on a daily basis. With consideration for the Center's aims, we determined the overall vision, initiatives, and goals for the Wellness Hub app, followed by specific milestone tasks and deliverables for development. We defined the app's primary features based on the mental health assessment and needs of HCWs. Feature definition was informed by the results of a resilience survey widely distributed to Mount Sinai HCWs and by the resources offered at CSRPG, including workshop content. RESULTS: We launched our app over the course of two phases, the first phase being a "soft" launch and the second being a broader launch to all of Mount Sinai. Of the 231 HCWs who downloaded the app, 173 (74.9%) completed our baseline assessment of all mental health screeners in the app. Results from the baseline assessment show that more than half of the users demonstrate a need for support in at least one psychological area. As of 3 months after the Phase 2 launch, approximately 55% of users re-entered the app after their first opening to explore additional features, with an average of 4 app openings per person. CONCLUSIONS: To address the mental health needs of HCWs during the COVID-19 pandemic, the Wellness Hub app was built and deployed throughout the Mount Sinai Health System. To our knowledge, this is the first resilience app of its kind. The Wellness Hub app is a promising proof of concept, with room to grow, for those who wish to build a secure mobile health app to support their employees, communities, or others in managing and improving mental and physical well-being. It is a novel tool offering mental health support broadly.

Predicting Lyme Disease From Patients' Peripheral Blood Mononuclear Cells Profiled With RNA-Sequencing.

Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. Based on the projection of the RNA-seq data into lower dimensions, we observe that the cases are separated from controls, and almost all cases never return to cluster with the controls over time. Enrichment analysis of the differentially expressed genes between clusters identifies up-regulation of immune response genes. This observation is also supported by deconvolution analysis to identify the changes in cell type composition due to Lyme disease infection. Importantly, we developed several machine learning classifiers that attempt to perform various Lyme disease classifications. We show that Lyme patients can be distinguished from the controls as well as from COVID-19 patients, but classification was not successful in distinguishing those patients with early Lyme disease cases that would advance to develop post-treatment persistent symptoms.

Use of Physiological Data From a Wearable Device to Identify SARS-CoV-2 Infection and Symptoms and Predict COVID-19 Diagnosis: Observational Study.

BACKGROUND: Changes in autonomic nervous system function, characterized by heart rate variability (HRV), have been associated with infection and observed prior to its clinical identification. OBJECTIVE: We performed an evaluation of HRV collected by a wearable device to identify and predict COVID-19 and its related symptoms. METHODS: Health care workers in the Mount Sinai Health System were prospectively followed in an ongoing observational study using the custom Warrior Watch Study app, which was downloaded to their smartphones. Participants wore an Apple Watch for the duration of the study, measuring HRV throughout the follow-up period. Surveys assessing infection and symptom-related questions were obtained daily. RESULTS: Using a mixed-effect cosinor model, the mean amplitude of the circadian pattern of the standard deviation of the interbeat interval of normal sinus beats (SDNN), an HRV metric, differed between subjects with and without COVID-19 (P=.006). The mean amplitude of this circadian pattern differed between individuals during the 7 days before and the 7 days after a COVID-19 diagnosis compared to this metric during uninfected time periods (P=.01). Significant changes in the mean and amplitude of the circadian pattern of the SDNN was observed between the first day of reporting a COVID-19-related symptom compared to all other symptom-free days (P=.01). CONCLUSIONS: Longitudinally collected HRV metrics from a commonly worn commercial wearable device (Apple Watch) can predict the diagnosis of COVID-19 and identify COVID-19-related symptoms. Prior to the diagnosis of COVID-19 by nasal swab polymerase chain reaction testing, significant changes in HRV were observed, demonstrating the predictive ability of this metric to identify COVID-19 infection.

Wearable Devices Are Well Accepted by Patients in the Study and Management of Inflammatory Bowel Disease: A Survey Study.

BACKGROUND: Wearable devices are designed to capture health-related and physiological data. They may be able to improve inflammatory bowel disease management and address evolving research needs. Little is known about patient perceptions for their use in the study and management of inflammatory bowel disease. AIMS: The aim of this survey study is to understand patient preferences and interest in wearable technology. METHODS: Consecutive adult patients who self-reported having inflammatory bowel disease were approached at the Susan and Leonard Feinstein Inflammatory Bowel Disease Center at the Mount Sinai Hospital to complete a 28-question survey. Reponses were analyzed with descriptive statistics. The Pearson Chi-square test and Fischer's exact test were used to determine the association between demographic and disease-related features and survey responses. RESULTS: Four hundred subjects completed the survey. 42.7% of subjects reported prior or current use of wearable devices. 89.0% of subjects believed that wearable devices can provide important information about their health, while 93.8% reported that they would use a wearable device if it could help their doctor manage their IBD. Subjects identified wrist-worn devices as the preferred device type and a willingness to wear these devices at least daily. CONCLUSIONS: Patients with inflammatory bowel disease believe that wearable devices can provide important information about their health and report a willingness to wear them frequently in research studies and as part the routine management of inflammatory bowel disease.

Longitudinal Autonomic Nervous System Measures Correlate With Stress and Ulcerative Colitis Disease Activity and Predict Flare.

BACKGROUND: Differences in autonomic nervous system function, measured by heart rate variability (HRV), have been observed between patients with inflammatory bowel disease and healthy control patients and have been associated in cross-sectional studies with systemic inflammation. High HRV has been associated with low stress. METHODS: Patients with ulcerative colitis (UC) were followed for 9 months. Their HRV was measured every 4 weeks using the VitalPatch, and blood was collected at baseline and every 12 weeks assessing cortisol, adrenocorticotropin hormone, interleukin-1ß, interleukin-6, tumor necrosis factor-α, and C-reactive protein (CRP). Stool was collected at enrollment and every 6 weeks for fecal calprotectin. Surveys assessing symptoms, stress, resilience, quality of life, anxiety, and depression were longitudinally collected. RESULTS: Longitudinally evaluated perceived stress was significantly associated with systemic inflammation (CRP, P = 0.03) and UC symptoms (P = 0.02). There was a significant association between HRV and stress (low-frequency to high-frequency power [LFHF], P = 0.04; root mean square of successive differences [RMSSD], P = 0.04). The HRV was associated with UC symptoms (LFHF, P = 0.03), CRP (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001), and fecal calprotectin (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001; LFHF, P < 0.001). Significant changes in HRV indices from baseline developed before the identification of a symptomatic or inflammatory flare (P < 0.001). CONCLUSIONS: Longitudinally evaluated HRV was associated with UC symptoms, inflammation, and perceived and physiological measures of stress. Significant changes in HRV were observed before the development of symptomatic or inflammatory flare.

Retrospective cohort study of clinical characteristics of 2199 hospitalised patients with COVID-19 in New York City.

OBJECTIVE: The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive. DESIGN: Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive. SETTING: All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system. PARTICIPANTS: Participants over the age of 18 years were included. PRIMARY OUTCOMES: We investigated in-hospital mortality during the study period. RESULTS: A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 µg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 µg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL. CONCLUSIONS: In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged.

Machine Learning to Predict Mortality and Critical Events in a Cohort of Patients With COVID-19 in New York City: Model Development and Validation.

BACKGROUND: COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking. OBJECTIVE: The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points. METHODS: We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions. RESULTS: Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction. CONCLUSIONS: We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes.

Deep representation learning of electronic health records to unlock patient stratification at scale.

Deriving disease subtypes from electronic health records (EHRs) can guide next-generation personalized medicine. However, challenges in summarizing and representing patient data prevent widespread practice of scalable EHR-based stratification analysis. Here we present an unsupervised framework based on deep learning to process heterogeneous EHRs and derive patient representations that can efficiently and effectively enable patient stratification at scale. We considered EHRs of 1,608,741 patients from a diverse hospital cohort comprising a total of 57,464 clinical concepts. We introduce a representation learning model based on word embeddings, convolutional neural networks, and autoencoders (i.e., ConvAE) to transform patient trajectories into low-dimensional latent vectors. We evaluated these representations as broadly enabling patient stratification by applying hierarchical clustering to different multi-disease and disease-specific patient cohorts. ConvAE significantly outperformed several baselines in a clustering task to identify patients with different complex conditions, with 2.61 entropy and 0.31 purity average scores. When applied to stratify patients within a certain condition, ConvAE led to various clinically relevant subtypes for different disorders, including type 2 diabetes, Parkinson's disease, and Alzheimer's disease, largely related to comorbidities, disease progression, and symptom severity. With these results, we demonstrate that ConvAE can generate patient representations that lead to clinically meaningful insights. This scalable framework can help better understand varying etiologies in heterogeneous sub-populations and unlock patterns for EHR-based research in the realm of personalized medicine.

Acute Kidney Injury in Hospitalized Patients with COVID-19.

IMPORTANCE: Preliminary reports indicate that acute kidney injury (AKI) is common in coronavirus disease (COVID)-19 patients and is associated with worse outcomes. AKI in hospitalized COVID-19 patients in the United States is not well-described. OBJECTIVE: To provide information about frequency, outcomes and recovery associated with AKI and dialysis in hospitalized COVID-19 patients. DESIGN: Observational, retrospective study. SETTING: Admitted to hospital between February 27 and April 15, 2020. PARTICIPANTS: Patients aged ≥18 years with laboratory confirmed COVID-19 Exposures: AKI (peak serum creatinine increase of 0.3 mg/dL or 50% above baseline). Main Outcomes and Measures: Frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aOR) with mortality. We also trained and tested a machine learning model for predicting dialysis requirement with independent validation. RESULTS: A total of 3,235 hospitalized patients were diagnosed with COVID-19. AKI occurred in 1406 (46%) patients overall and 280 (20%) with AKI required renal replacement therapy. The incidence of AKI (admission plus new cases) in patients admitted to the intensive care unit was 68% (553 of 815). In the entire cohort, the proportion with stages 1, 2, and 3 AKI were 35%, 20%, 45%, respectively. In those needing intensive care, the respective proportions were 20%, 17%, 63%, and 34% received acute renal replacement therapy. Independent predictors of severe AKI were chronic kidney disease, systolic blood pressure, and potassium at baseline. In-hospital mortality in patients with AKI was 41% overall and 52% in intensive care. The aOR for mortality associated with AKI was 9.6 (95% CI 7.4-12.3) overall and 20.9 (95% CI 11.7-37.3) in patients receiving intensive care. 56% of patients with AKI who were discharged alive recovered kidney function back to baseline. The area under the curve (AUC) for the machine learned predictive model using baseline features for dialysis requirement was 0.79 in a validation test. CONCLUSIONS AND RELEVANCE: AKI is common in patients hospitalized with COVID-19, associated with worse mortality, and the majority of patients that survive do not recover kidney function. A machine-learned model using admission features had good performance for dialysis prediction and could be used for resource allocation.

Clinical Characteristics of Hospitalized Covid-19 Patients in New York City.

BACKGROUND: The coronavirus 2019 (Covid-19) pandemic is a global public health crisis, with over 1.6 million cases and 95,000 deaths worldwide. Data are needed regarding the clinical course of hospitalized patients, particularly in the United States. METHODS: Demographic, clinical, and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed Covid-19 between February 27 and April 2, 2020 were identified through institutional electronic health records. We conducted a descriptive study of patients who had in-hospital mortality or were discharged alive. RESULTS: A total of 2,199 patients with Covid-19 were hospitalized during the study period. As of April 2 nd , 1,121 (51%) patients remained hospitalized, and 1,078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 ug/ml, C-reactive protein was 162 mg/L, and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 ug/ml, C-reactive protein was 79 mg/L, and procalcitonin was 0.09 ng/mL. CONCLUSIONS: This is the largest and most diverse case series of hospitalized patients with Covid-19 in the United States to date. Requirement of intensive care and mortality were high. Patients who died typically had pre-existing conditions and severe perturbations in inflammatory markers.

Sleep in the Natural Environment: A Pilot Study.

Sleep quality has been directly linked to cognitive function, quality of life, and a variety of serious diseases across many clinical domains. Standard methods for assessing sleep involve overnight studies in hospital settings, which are uncomfortable, expensive, not representative of real sleep, and difficult to conduct on a large scale. Recently, numerous commercial digital devices have been developed that record physiological data, such as movement, heart rate, and respiratory rate, which can act as a proxy for sleep quality in lieu of standard electroencephalogram recording equipment. The sleep-related output metrics from these devices include sleep staging and total sleep duration and are derived via proprietary algorithms that utilize a variety of these physiological recordings. Each device company makes different claims of accuracy and measures different features of sleep quality, and it is still unknown how well these devices correlate with one another and perform in a research setting. In this pilot study of 21 participants, we investigated whether sleep metric outputs from self-reported sleep metrics (SRSMs) and four sensors, specifically Fitbit Surge (a smart watch), Withings Aura (a sensor pad that is placed under a mattress), Hexoskin (a smart shirt), and Oura Ring (a smart ring), were related to known cognitive and psychological metrics, including the n-back test and Pittsburgh Sleep Quality Index (PSQI). We analyzed correlation between multiple device-related sleep metrics. Furthermore, we investigated relationships between these sleep metrics and cognitive scores across different timepoints and SRSM through univariate linear regressions. We found that correlations for sleep metrics between the devices across the sleep cycle were almost uniformly low, but still significant (P < 0.05). For cognitive scores, we found the Withings latency was statistically significant for afternoon and evening timepoints at P = 0.016 and P = 0.013. We did not find any significant associations between SRSMs and PSQI or cognitive scores. Additionally, Oura Ring's total sleep duration and efficiency in relation to the PSQI measure was statistically significant at P = 0.004 and P = 0.033, respectively. These findings can hopefully be used to guide future sensor-based sleep research.

Scaling structural learning with NO-BEARS to infer causal transcriptome networks.

Constructing gene regulatory networks is a critical step in revealing disease mechanisms from transcriptomic data. In this work, we present NO-BEARS, a novel algorithm for estimating gene regulatory networks. The NO-BEARS algorithm is built on the basis of the NO-TEARS algorithm with two improvements. First, we propose a new constraint and its fast approximation to reduce the computational cost of the NO-TEARS algorithm. Next, we introduce a polynomial regression loss to handle non-linearity in gene expressions. Our implementation utilizes modern GPU computation that can decrease the time of hours-long CPU computation to seconds. Using synthetic data, we demonstrate improved performance, both in processing time and accuracy, on inferring gene regulatory networks from gene expression data.

Satellite images and machine learning can identify remote communities to facilitate access to health services.

OBJECTIVE: Community health systems operating in remote areas require accurate information about where people live to efficiently provide services across large regions. We sought to determine whether a machine learning analyses of satellite imagery can be used to map remote communities to facilitate service delivery and planning. MATERIALS AND METHODS: We developed a method for mapping communities using a deep learning approach that excels at detecting objects within images. We trained an algorithm to detect individual buildings, then examined building clusters to identify groupings suggestive of communities. The approach was validated in southeastern Liberia, by comparing algorithmically generated results with community location data collected manually by enumerators and community health workers. RESULTS: The deep learning approach achieved 86.47% positive predictive value and 79.49% sensitivity with respect to individual building detection. The approach identified 75.67% (n = 451) of communities registered through the community enumeration process, and identified an additional 167 potential communities not previously registered. Several instances of false positives and false negatives were identified. DISCUSSION: Analysis of satellite images is a promising solution for mapping remote communities rapidly, and with relatively low costs. Further research is needed to determine whether the communities identified algorithmically, but not registered in the manual enumeration process, are currently inhabited. CONCLUSIONS: To our knowledge, this study represents the first effort to apply image recognition algorithms to rural healthcare delivery. Results suggest that these methods have the potential to enhance community health worker scale-up efforts in underserved remote communities.