Bobak J. Mortazavi

Gregory Holste, Evangelos K. Oikonomou, Bobak J. Mortazavi et al.

Advances in self-supervised learning (SSL) have shown that self-supervised pretraining on medical imaging data can provide a strong initialization for downstream supervised classification and segmentation. Given the difficulty of obtaining expert labels for medical image recognition tasks, such an "in-domain" SSL initialization is often desirable due to its improved label efficiency over standard transfer learning. However, most efforts toward SSL of medical imaging data are not adapted to video-based medical imaging modalities. With this progress in mind, we developed a self-supervised contrastive learning approach, EchoCLR, catered to echocardiogram videos with the goal of learning strong representations for efficient fine-tuning on downstream cardiac disease diagnosis. EchoCLR leverages (i) distinct videos of the same patient as positive pairs for contrastive learning and (ii) a frame re-ordering pretext task to enforce temporal coherence. When fine-tuned on small portions of labeled data (as few as 51 exams), EchoCLR pretraining significantly improved classification performance for left ventricular hypertrophy (LVH) and aortic stenosis (AS) over other transfer learning and SSL approaches across internal and external test sets. For example, when fine-tuning on 10% of available training data (519 studies), an EchoCLR-pretrained model achieved 0.72 AUROC (95% CI: [0.69, 0.75]) on LVH classification, compared to 0.61 AUROC (95% CI: [0.57, 0.64]) with a standard transfer learning approach. Similarly, using 1% of available training data (53 studies), EchoCLR pretraining achieved 0.82 AUROC (95% CI: [0.79, 0.84]) on severe AS classification, compared to 0.61 AUROC (95% CI: [0.58, 0.65]) with transfer learning. EchoCLR is unique in its ability to learn representations of medical videos and demonstrates that SSL can enable label-efficient disease classification from small, labeled datasets.

Zepeng Huo, Xiaoning Qian, Shuai Huang et al.

Medical events of interest, such as mortality, often happen at a low rate in electronic medical records, as most admitted patients survive. Training models with this imbalance rate (class density discrepancy) may lead to suboptimal prediction. Traditionally this problem is addressed through ad-hoc methods such as resampling or reweighting but performance in many cases is still limited. We propose a framework for training models for this imbalance issue: 1) we first decouple the feature extraction and classification process, adjusting training batches separately for each component to mitigate bias caused by class density discrepancy; 2) we train the network with both a density-aware loss and a learnable cost matrix for misclassifications. We demonstrate our model's improved performance in real-world medical datasets (TOPCAT and MIMIC-III) to show improved AUC-ROC, AUC-PRC, Brier Skill Score compared with the baselines in the domain.

Zepeng Huo, Bobak J. Mortazavi, Theodora Chaspari et al.

Sustained high levels of blood glucose in type 2 diabetes (T2DM) can have disastrous long-term health consequences. An essential component of clinical interventions for T2DM is monitoring dietary intake to keep plasma glucose levels within an acceptable range. Yet, current techniques to monitor food intake are time intensive and error prone. To address this issue, we are developing techniques to automatically monitor food intake and the composition of those foods using continuous glucose monitors (CGMs). This article presents the results of a clinical study in which participants consumed nine standardized meals with known macronutrients amounts (carbohydrate, protein, and fat) while wearing a CGM. We built a multitask neural network to estimate the macronutrient composition from the CGM signal, and compared it against a baseline linear regression. The best prediction result comes from our proposed neural network, trained with subject-dependent data, as measured by root mean squared relative error and correlation coefficient. These findings suggest that it is possible to estimate macronutrient composition from CGM signals, opening the possibility to develop automatic techniques to track food intake.

Arash Pakbin, Aaron Su, Donald K. K. Lee et al.

Objective: realtime monitoring of invasive ventilation (iV) in intensive care units (ICUs) plays a crucial role in ensuring prompt interventions and better patient outcomes. However, conventional methods often overlook valuable insights embedded within clinical notes, relying solely on tabular data. In this study, we propose an innovative approach to enhance iV risk monitoring by incorporating clinical notes into the monitoring pipeline through using language models for text summarization. Results: We achieve superior performance in all metrics reported by the state-of-the-art in iV risk monitoring, namely: an AUROC of 0.86, an AUC-PR of 0.35, and an AUCt of up to 0.86. We also demonstrate that our methodology allows for more lead time in flagging iV for certain time buckets. Conclusion: Our study underscores the potential of integrating clinical notes and language models into realtime iV risk monitoring, paving the way for improved patient care and informed clinical decision-making in ICU settings.

Ryan King, Conrad Krueger, Ethan Veselka et al.

In recent years, machine learning has made significant progress in clinical outcome prediction, demonstrating increasingly accurate results. However, the substantial resources required for hospitals to train these models, such as data collection, labeling, and computational power, limit the feasibility for smaller hospitals to develop their own models. An alternative approach involves transferring a machine learning model trained by a large hospital to smaller hospitals, allowing them to fine-tune the model on their specific patient data. However, these models are often trained and validated on data from a single hospital, raising concerns about their generalizability to new data. Our research shows that there are notable differences in measurement distributions and frequencies across various regions in the United States. To address this, we propose a benchmark that tests a machine learning model's ability to transfer from a source domain to different regions across the country. This benchmark assesses a model's capacity to learn meaningful information about each new domain while retaining key features from the original domain. Using this benchmark, we frame the transfer of a machine learning model from one region to another as a domain incremental learning problem. While the task of patient outcome prediction remains the same, the input data distribution varies, necessitating a model that can effectively manage these shifts. We evaluate two popular domain incremental learning methods: data replay, which stores examples from previous data sources for fine-tuning on the current source, and Elastic Weight Consolidation (EWC), a model parameter regularization method that maintains features important for both data sources.

Sicong Huang, Roozbeh Jafari, Bobak J. Mortazavi

Continuous arterial blood pressure (ABP) monitoring is invasive but essential for hemodynamic monitoring. Recent techniques have reconstructed ABP non-invasively using pulsatile signals but produced inaccurate systolic and diastolic blood pressure (SBP and DBP) values and were sensitive to individual variability. ArterialNet integrates generalized pulsatile-to-ABP signal translation and personalized feature extraction using hybrid loss functions and regularization. We validated ArterialNet using the MIMIC-III dataset and achieved a root mean square error (RMSE) of 5.41 mmHg, with at least a 58% lower standard deviation. ArterialNet reconstructed ABP with an RMSE of 7.99 mmHg in remote health scenarios. ArterialNet achieved superior performance in ABP reconstruction and SBP and DBP estimations, with significantly reduced subject variance, demonstrating its potential in remote health settings. We also ablated ArterialNet architecture to investigate the contributions of each component and evaluated its translational impact and robustness by conducting a series of ablations on data quality and availability.

Ryan King, Shivesh Kodali, Conrad Krueger et al.

Machine learning has revolutionized the modeling of clinical timeseries data. Using machine learning, a Deep Neural Network (DNN) can be automatically trained to learn a complex mapping of its input features for a desired task. This is particularly valuable in Electronic Health Record (EHR) databases, where patients often spend extended periods in intensive care units (ICUs). Machine learning serves as an efficient method for extract meaningful information. However, many state-of-the-art (SOTA) methods for training DNNs demand substantial volumes of labeled data, posing significant challenges for clinics in terms of cost and time. Self-supervised learning offers an alternative by allowing practitioners to extract valuable insights from data without the need for costly labels. Yet, current SOTA methods often necessitate large data batches to achieve optimal performance, increasing computational demands. This presents a challenge when working with long clinical timeseries data. To address this, we propose an efficient method of contrastive pretraining tailored for long clinical timeseries data. Our approach utilizes an estimator for negative pair comparison, enabling effective feature extraction. We assess the efficacy of our pretraining using standard self-supervised tasks such as linear evaluation and semi-supervised learning. Additionally, our model demonstrates the ability to impute missing measurements, providing clinicians with deeper insights into patient conditions. We demonstrate that our pretraining is capable of achieving better performance as both the size of the model and the size of the measurement vocabulary scale. Finally, we externally validate our model, trained on the MIMIC-III dataset, using the eICU dataset. We demonstrate that our model is capable of learning robust clinical information that is transferable to other clinics.

Zhale Nowroozilarki, Arash Pakbin, James Royalty et al.

Electronic Health Record (EHR) systems provide critical, rich and valuable information at high frequency. One of the most exciting applications of EHR data is in developing a real-time mortality warning system with tools from survival analysis. However, most of the survival analysis methods used recently are based on (semi)parametric models using static covariates. These models do not take advantage of the information conveyed by the time-varying EHR data. In this work, we present an application of a highly scalable survival analysis method, BoXHED 2.0 to develop a real-time in-ICU mortality warning indicator based on the MIMIC IV data set. Importantly, BoXHED can incorporate time-dependent covariates in a fully nonparametric manner and is backed by theory. Our in-ICU mortality model achieves an AUC-PRC of 0.41 and AUC-ROC of 0.83 out of sample, demonstrating the benefit of real-time monitoring.

Arash Pakbin, Xiaochen Wang, Bobak J. Mortazavi et al.

Modern applications of survival analysis increasingly involve time-dependent covariates. The Python package BoXHED2.0 is a tree-boosted hazard estimator that is fully nonparametric, and is applicable to survival settings far more general than right-censoring, including recurring events and competing risks. BoXHED2.0 is also scalable to the point of being on the same order of speed as parametric boosted survival models, in part because its core is written in C++ and it also supports the use of GPUs and multicore CPUs. BoXHED2.0 is available from PyPI and also from www.github.com/BoXHED.

Justin Lovelace, Nathan C. Hurley, Adrian D. Haimovich et al.

Problem lists are intended to provide clinicians with a relevant summary of patient medical issues and are embedded in many electronic health record systems. Despite their importance, problem lists are often cluttered with resolved or currently irrelevant conditions. In this work, we develop a novel end-to-end framework that first extracts diagnosis and procedure information from clinical notes and subsequently uses the extracted medical problems to predict patient outcomes. This framework is both more performant and more interpretable than existing models used within the domain, achieving an AU-ROC of 0.710 for bounceback readmission and 0.869 for in-hospital mortality occurring after ICU discharge. We identify risk factors for both readmission and mortality outcomes and demonstrate that our framework can be used to develop dynamic problem lists that present clinical problems along with their quantitative importance. We conduct a qualitative user study with medical experts and demonstrate that they view the lists produced by our framework favorably and find them to be a more effective clinical decision support tool than a strong baseline.

Lida Zhang, Nathan C. Hurley, Bassem Ibrahim et al.

Blood pressure monitoring is an essential component of hypertension management and in the prediction of associated comorbidities. Blood pressure is a dynamic vital sign with frequent changes throughout a given day. Capturing blood pressure remotely and frequently (also known as ambulatory blood pressure monitoring) has traditionally been achieved by measuring blood pressure at discrete intervals using an inflatable cuff. However, there is growing interest in developing a cuffless ambulatory blood pressure monitoring system to measure blood pressure continuously. One such approach is by utilizing bioimpedance sensors to build regression models. A practical problem with this approach is that the amount of data required to confidently train such a regression model can be prohibitive. In this paper, we propose the application of the domain-adversarial training neural network (DANN) method on our multitask learning (MTL) blood pressure estimation model, allowing for knowledge transfer between subjects. Our proposed model obtains average root mean square error (RMSE) of $4.80 \pm 0.74$ mmHg for diastolic blood pressure and $7.34 \pm 1.88$ mmHg for systolic blood pressure when using three minutes of training data, $4.64 \pm 0.60$ mmHg and $7.10 \pm 1.79$ respectively when using four minutes of training data, and $4.48 \pm 0.57$ mmHg and $6.79 \pm 1.70$ respectively when using five minutes of training data. DANN improves training with minimal data in comparison to both directly training and to training with a pretrained model from another subject, decreasing RMSE by $0.19$ to $0.26$ mmHg (diastolic) and by $0.46$ to $0.67$ mmHg (systolic) in comparison to the best baseline models. We observe that four minutes of training data is the minimum requirement for our framework to exceed ISO standards within this cohort of patients.

Xiaochen Wang, Arash Pakbin, Bobak J. Mortazavi et al.

The proliferation of medical monitoring devices makes it possible to track health vitals at high frequency, enabling the development of dynamic health risk scores that change with the underlying readings. Survival analysis, in particular hazard estimation, is well-suited to analyzing this stream of data to predict disease onset as a function of the time-varying vitals. This paper introduces the software package BoXHED (pronounced 'box-head') for nonparametrically estimating hazard functions via gradient boosting. BoXHED 1.0 is a novel tree-based implementation of the generic estimator proposed in Lee, Chen, Ishwaran (2017), which was designed for handling time-dependent covariates in a fully nonparametric manner. BoXHED is also the first publicly available software implementation for Lee, Chen, Ishwaran (2017). Applying BoXHED to cardiovascular disease onset data from the Framingham Heart Study reveals novel interaction effects among known risk factors, potentially resolving an open question in clinical literature.

Justin R. Lovelace, Nathan C. Hurley, Adrian D. Haimovich et al.

Clinical notes contain a large amount of clinically valuable information that is ignored in many clinical decision support systems due to the difficulty that comes with mining that information. Recent work has found success leveraging deep learning models for the prediction of clinical outcomes using clinical notes. However, these models fail to provide clinically relevant and interpretable information that clinicians can utilize for informed clinical care. In this work, we augment a popular convolutional model with an attention mechanism and apply it to unstructured clinical notes for the prediction of ICU readmission and mortality. We find that the addition of the attention mechanism leads to competitive performance while allowing for the straightforward interpretation of predictions. We develop clear visualizations to present important spans of text for both individual predictions and high-risk cohorts. We then conduct a qualitative analysis and demonstrate that our model is consistently attending to clinically meaningful portions of the narrative for all of the outcomes that we explore.

Nathan C. Hurley, Erica S. Spatz, Harlan M. Krumholz et al.

Cardiovascular disorders account for nearly 1 in 3 deaths in the United States. Care for these disorders are often determined during visits to acute care facilities, such as hospitals. While the length of stay in these settings represents just a small proportion of patients' lives, they account for a disproportionately large amount of decision making. To overcome this bias towards data from acute care settings, there is a need for longitudinal monitoring in patients with cardiovascular disorders. Longitudinal monitoring can provide a more comprehensive picture of patient health, allowing for more informed decision making. This work surveys the current field of sensing technologies and machine learning analytics that exist in the field of remote monitoring for cardiovascular disorders. We highlight three primary needs in the design of new smart health technologies: 1) the need for sensing technology that can track longitudinal trends in signs and symptoms of the cardiovascular disorder despite potentially infrequent, noisy, or missing data measurements; 2) the need for new analytic techniques that model data captured in a longitudinal, continual fashion to aid in the development of new risk prediction techniques and in tracking disease progression; and 3) the need for machine learning techniques that are personalized and interpretable, allowing for advancements in shared clinical decision making. We highlight these needs based upon the current state-of-the-art in smart health technologies and analytics and discuss the ample opportunities that exist in addressing all three needs in the development of smart health technologies and analytics applied to the field of cardiovascular disorders and care.

Nathan C. Hurley, Adrian D. Haimovich, R. Andrew Taylor et al.

Visual summarization of clinical data collected on patients contained within the electronic health record (EHR) may enable precise and rapid triage at the time of patient presentation to an emergency department (ED). The triage process is critical in the appropriate allocation of resources and in anticipating eventual patient disposition, typically admission to the hospital or discharge home. EHR data are high-dimensional and complex, but offer the opportunity to discover and characterize underlying data-driven patient phenotypes. These phenotypes will enable improved, personalized therapeutic decision making and prognostication. In this work, we focus on the challenge of two-dimensional patient projections. A low dimensional embedding offers visual interpretability lost in higher dimensions. While linear dimensionality reduction techniques such as principal component analysis are often used towards this aim, they are insufficient to describe the variance of patient data. In this work, we employ the newly-described non-linear embedding technique called uniform manifold approximation and projection (UMAP). UMAP seeks to capture both local and global structures in high-dimensional data. We then use Gaussian mixture models to identify clusters in the embedded data and use the adjusted Rand index (ARI) to establish stability in the discovery of these clusters. This technique is applied to five common clinical chief complaints from a real-world ED EHR dataset, describing the emergent properties of discovered clusters. We observe clinically-relevant cluster attributes, suggesting that visual embeddings of EHR data using non-linear dimensionality reduction is a promising approach to reveal data-driven patient phenotypes. In the five chief complaints, we find between 2 and 6 clusters, with the peak mean pairwise ARI between subsequent training iterations to range from 0.35 to 0.74.