Tokenization strategies shape how models process electronic health records, yet fair comparisons of their effectiveness remain limited. We present a systematic evaluation of tokenization approaches for clinical time series modeling using transformer-based architectures, revealing task-dependent and sometimes counterintuitive findings about temporal and value feature importance. Through controlled ablations across four clinical prediction tasks on MIMIC-IV, we demonstrate that explicit time encodings provide no consistent statistically significant benefit for the evaluated downstream tasks. Value features show task-dependent importance, affecting mortality prediction but not readmission, suggesting code sequences alone can carry sufficient predictive signal. We further show that frozen pretrained code encoders dramatically outperform their trainable counterparts while requiring dramatically fewer parameters. Larger clinical encoders provide consistent improvements across tasks, benefiting from frozen embeddings that eliminate computational overhead. Our controlled evaluation enables fairer tokenization comparisons and demonstrates that simpler, parameter-efficient approaches can, in many cases, achieve strong performance, though the optimal tokenization strategy remains task-dependent.

Clinical time series data are critical for patient monitoring and predictive modeling. These time series are typically multivariate and often comprise hundreds of heterogeneous features from different data sources. The grouping of features based on similarity and relevance to the prediction task has been shown to enhance the performance of deep learning architectures. However, defining these groups a priori using only semantic knowledge is challenging, even for domain experts. To address this, we propose a novel method that learns feature groups by clustering weights of feature-wise embedding layers. This approach seamlessly integrates into standard supervised training and discovers the groups that directly improve downstream performance on clinically relevant tasks. We demonstrate that our method outperforms static clustering approaches on synthetic data and achieves performance comparable to expert-defined groups on real-world medical data. Moreover, the learned feature groups are clinically interpretable, enabling data-driven discovery of task-relevant relationships between variables.

We present a compact, strictly causal benchmark for streaming clinical time series on the MIT--BIH Arrhythmia Database using per-second heart rate. Two tasks are studied under record-level, non-overlapping splits: near-term tachycardia risk (next ten seconds) and one-step heart rate forecasting. We compare a GRU-D (RNN) and a Transformer under matched training budgets against strong non-learned baselines. Evaluation is calibration-aware for classification and proper for forecasting, with temperature scaling and grouped bootstrap confidence intervals. On MIT-BIH, GRU-D slightly surpasses the Transformer for tachycardia risk, while the Transformer clearly lowers forecasting error relative to GRU-D and persistence. Our results show that, in longitudinal monitoring, model choice is task-dependent: compact RNNs remain competitive for short-horizon risk scoring, whereas compact Transformers deliver clearer gains for point forecasting.

We develop and evaluate a structure learning algorithm for clinical time series. Clinical time series are multivariate time series observed in multiple patients and irregularly sampled, challenging existing structure learning algorithms. We assume that our times series are realizations of StructGP, a k-dimensional multi-output or multi-task stationary Gaussian process (GP), with independent patients sharing the same covariance function. StructGP encodes ordered conditional relations between time series, represented in a directed acyclic graph. We implement an adapted NOTEARS algorithm, which based on a differentiable definition of acyclicity, recovers the graph by solving a series of continuous optimization problems. Simulation results show that up to mean degree 3 and 20 tasks, we reach a median recall of 0.93% [IQR, 0.86, 0.97] while keeping a median precision of 0.71% [0.57-0.84], for recovering directed edges. We further show that the regularization path is key to identifying the graph. With StructGP, we proposed a model of time series dependencies, that flexibly adapt to different time series regularity, while enabling us to learn these dependencies from observations.

The breadth, scale, and temporal granularity of modern electronic health records (EHR) systems offers great potential for estimating personalized and contextual patient health trajectories using sequential deep learning. However, learning useful representations of EHR data is challenging due to its high dimensionality, sparsity, multimodality, irregular and variable-specific recording frequency, and timestamp duplication when multiple measurements are recorded simultaneously. Although recent efforts to fuse structured EHR and unstructured clinical notes suggest the potential for more accurate prediction of clinical outcomes, less focus has been placed on EHR embedding approaches that directly address temporal EHR challenges by learning time-aware representations from multimodal patient time series. In this paper, we introduce a dynamic embedding and tokenization framework for precise representation of multimodal clinical time series that combines novel methods for encoding time and sequential position with temporal cross-attention. Our embedding and tokenization framework, when integrated into a multitask transformer classifier with sliding window attention, outperformed baseline approaches on the exemplar task of predicting the occurrence of nine postoperative complications of more than 120,000 major inpatient surgeries using multimodal data from three hospitals and two academic health centers in the United States.

The lack of labeled data is a key challenge for learning useful representation from time series data. However, an unsupervised representation framework that is capable of producing high quality representations could be of great value. It is key to enabling transfer learning, which is especially beneficial for medical applications, where there is an abundance of data but labeling is costly and time consuming. We propose an unsupervised contrastive learning framework that is motivated from the perspective of label smoothing. The proposed approach uses a novel contrastive loss that naturally exploits a data augmentation scheme in which new samples are generated by mixing two data samples with a mixing component. The task in the proposed framework is to predict the mixing component, which is utilized as soft targets in the loss function. Experiments demonstrate the framework's superior performance compared to other representation learning approaches on both univariate and multivariate time series and illustrate its benefits for transfer learning for clinical time series.

Healthcare data continues to flourish yet a relatively small portion, mostly structured, is being utilized effectively for predicting clinical outcomes. The rich subjective information available in unstructured clinical notes can possibly facilitate higher discrimination but tends to be under-utilized in mortality prediction. This work attempts to assess the gain in performance when multiple notes that have been minimally preprocessed are used as an input for prediction. A hierarchical architecture consisting of both convolutional and recurrent layers is used to concurrently model the different notes compiled in an individual hospital stay. This approach is evaluated on predicting in-hospital mortality on the MIMIC-III dataset. On comparison to approaches utilizing structured data, it achieved higher metrics despite requiring less cleaning and preprocessing. This demonstrates the potential of unstructured data in enhancing mortality prediction and signifies the need to incorporate more raw unstructured data into current clinical prediction methods.

Real-world clinical time series data sets exhibit a high prevalence of missing values. Hence, there is an increasing interest in missing data imputation. Traditional statistical approaches impose constraints on the data-generating process and decouple imputation from prediction. Recent works propose recurrent neural network based approaches for missing data imputation and prediction with time series data. However, they generate deterministic outputs and neglect the inherent uncertainty. In this work, we introduce a unified Bayesian recurrent framework for simultaneous imputation and prediction on time series data sets. We evaluate our approach on two real-world mortality prediction tasks using the MIMIC-III and PhysioNet benchmark datasets. We demonstrate significant performance gains over state-of-the-art methods, and provide strategies to use the resulting probability distributions to better assess reliability of the imputations and predictions.

Effective modeling of electronic health records presents many challenges as they contain large amounts of irregularity most of which are due to the varying procedures and diagnosis a patient may have. Despite the recent progress in machine learning, unsupervised learning remains largely at open, especially in the healthcare domain. In this work, we present a two-step unsupervised representation learning scheme to summarize the multi-modal clinical time series consisting of signals and medical codes into a patient status vector. First, an auto-encoder step is used to reduce sparse medical codes and clinical time series into a distributed representation. Subsequently, the concatenation of the distributed representations is further fine-tuned using a forecasting task. We evaluate the usefulness of the representation on two downstream tasks: mortality and readmission. Our proposed method shows improved generalization performance for both short duration ICU visits and long duration ICU visits.

Sepsis is a poorly understood and potentially life-threatening complication that can occur as a result of infection. Early detection and treatment improves patient outcomes, and as such it poses an important challenge in medicine. In this work, we develop a flexible classifier that leverages streaming lab results, vitals, and medications to predict sepsis before it occurs. We model patient clinical time series with multi-output Gaussian processes, maintaining uncertainty about the physiological state of a patient while also imputing missing values. The mean function takes into account the effects of medications administered on the trajectories of the physiological variables. Latent function values from the Gaussian process are then fed into a deep recurrent neural network to classify patient encounters as septic or not, and the overall model is trained end-to-end using back-propagation. We train and validate our model on a large dataset of 18 months of heterogeneous inpatient stays from the Duke University Health System, and develop a new "real-time" validation scheme for simulating the performance of our model as it will actually be used. Our proposed method substantially outperforms clinical baselines, and improves on a previous related model for detecting sepsis. Our model's predictions will be displayed in a real-time analytics dashboard to be used by a sepsis rapid response team to help detect and improve treatment of sepsis.