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Reinforcement learning (RL) has garnered increasing recognition for its potential to optimise dynamic treatment regimes (DTRs) in personalised medicine, particularly for drug dosage prescriptions and medication recommendations. However, a significant challenge persists: the absence of a unified framework for simulating diverse healthcare scenarios and a comprehensive analysis to benchmark the effectiveness of RL algorithms within these contexts. To address this gap, we introduce \textit{DTR-Bench}, a benchmarking platform comprising four distinct simulation environments tailored to common DTR applications, including cancer chemotherapy, radiotherapy, glucose management in diabetes, and sepsis treatment. We evaluate various state-of-the-art RL algorithms across these settings, particularly highlighting their performance amidst real-world challenges such as pharmacokinetic/pharmacodynamic (PK/PD) variability, noise, and missing data. Our experiments reveal varying degrees of performance degradation among RL algorithms in the presence of noise and patient variability, with some algorithms failing to converge. Additionally, we observe that using temporal observation representations does not consistently lead to improved performance in DTR settings. Our findings underscore the necessity of developing robust, adaptive RL algorithms capable of effectively managing these complexities to enhance patient-specific healthcare. We have open-sourced our benchmark and code at https://github.com/GilesLuo/DTR-Bench., Comment: 13 pages for main content

In the rapidly changing healthcare landscape, the implementation of offline reinforcement learning (RL) in dynamic treatment regimes (DTRs) presents a mix of unprecedented opportunities and challenges. This position paper offers a critical examination of the current status of offline RL in the context of DTRs. We argue for a reassessment of applying RL in DTRs, citing concerns such as inconsistent and potentially inconclusive evaluation metrics, the absence of naive and supervised learning baselines, and the diverse choice of RL formulation in existing research. Through a case study with more than 17,000 evaluation experiments using a publicly available Sepsis dataset, we demonstrate that the performance of RL algorithms can significantly vary with changes in evaluation metrics and Markov Decision Process (MDP) formulations. Surprisingly, it is observed that in some instances, RL algorithms can be surpassed by random baselines subjected to policy evaluation methods and reward design. This calls for more careful policy evaluation and algorithm development in future DTR works. Additionally, we discussed potential enhancements toward more reliable development of RL-based dynamic treatment regimes and invited further discussion within the community. Code is available at https://github.com/GilesLuo/ReassessDTR., Comment: Accepted at ICML 2024. 9 pages for main content, 34 pages in total

Advancements in wearable sensor technologies and the digitization of medical records have contributed to the unprecedented ubiquity of biomedical time series data. Data-driven models have tremendous potential to assist clinical diagnosis and improve patient care by improving long-term monitoring capabilities, facilitating early disease detection and intervention, as well as promoting personalized healthcare delivery. However, accessing extensively labeled datasets to train data-hungry deep learning models encounters many barriers, such as long-tail distribution of rare diseases, cost of annotation, privacy and security concerns, data-sharing regulations, and ethical considerations. An emerging approach to overcome the scarcity of labeled data is to augment AI methods with human-like capabilities to leverage past experiences to learn new tasks with limited examples, called few-shot learning. This survey provides a comprehensive review and comparison of few-shot learning methods for biomedical time series applications. The clinical benefits and limitations of such methods are discussed in relation to traditional data-driven approaches. This paper aims to provide insights into the current landscape of few-shot learning for biomedical time series and its implications for future research and applications., Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible

We study the synchronized behavior of the inertial Kuramoto oscillators with frustration effect under a symmetric and connected network. Due to the lack of second-order gradient flow structure and singularity of second-order derivative of diameter, we shift to construct convex combinations of oscillators and related new energy functions that can control the phase and frequency diameters. Under sufficient frameworks on initial data and system parameters, we derive first-order dissipative differential inequalities of constructed energy functions. This eventually gives rise to the emergence of frequency synchronization exponentially fast.

We study the collective synchronized behavior of the Kuramoto model with inertia and frustration effects on a connected and symmetric network. We aim to establish sufficient frameworks for achieving complete frequency synchronization, taking into account initial configuration, small inertia and frustration, and large coupling strength. More precisely, we first demonstrate that the phase diameter will be uniformly bounded by a small value after a finite time. Then we prove that the frequency diameter exhibits exponential decay to zero. Our approach relies on a careful construction of energy functionals, which effectively control the dissipation of phase and frequency diameters.

With the widespread of machine learning models for healthcare applications, there is increased interest in building applications for personalized medicine. Despite the plethora of proposed research for personalized medicine, very few focus on representing missingness and learning from the missingness patterns in time-series Electronic Health Records (EHR) data. The lack of focus on missingness representation in an individualized way limits the full utilization of machine learning applications towards true personalization. In this brief communication, we highlight new insights into patterns of missingness with real-world examples and implications of missingness in EHRs. The insights in this work aim to bridge the gap between theoretical assumptions and practical observations in real-world EHRs. We hope this work will open new doors for exploring directions for better representation in predictive modelling for true personalization.

The burden of diseases is rising worldwide, with unequal treatment efficacy for patient populations that are underrepresented in clinical trials. Healthcare, however, is driven by the average population effect of medical treatments and, therefore, operates in a "one-size-fits-all" approach, not necessarily what best fits each patient. These facts suggest a pressing need for methodologies to study individualized treatment effects (ITE) to drive personalized treatment. Despite the increased interest in machine-learning-driven ITE estimation models, the vast majority focus on tabular data with limited review and understanding of methodologies proposed for time-series electronic health records (EHRs). To this end, this work provides an overview of ITE works for time-series data and insights into future research. The work summarizes the latest work in the literature and reviews it in light of theoretical assumptions, types of treatment settings, and computational frameworks. Furthermore, this work discusses challenges and future research directions for ITEs in a time-series setting. We hope this work opens new directions and serves as a resource for understanding one of the exciting yet under-studied research areas.

Electronic Health Records present a valuable modality for driving personalized medicine, where treatment is tailored to fit individual-level differences. For this purpose, many data-driven machine learning and statistical models rely on the wealth of longitudinal EHRs to study patients' physiological and treatment effects. However, longitudinal EHRs tend to be sparse and highly missing, where missingness could also be informative and reflect the underlying patient's health status. Therefore, the success of data-driven models for personalized medicine highly depends on how the EHR data is represented from physiological data, treatments, and the missing values in the data. To this end, we propose a novel deep-learning model that learns the underlying patient dynamics over time across multivariate data to generate personalized realistic values conditioning on an individual's demographic characteristics and treatments. Our proposed model, IGNITE (Individualized GeNeration of Imputations in Time-series Electronic health records), utilises a conditional dual-variational autoencoder augmented with dual-stage attention to generate missing values for an individual. In IGNITE, we further propose a novel individualized missingness mask (IMM), which helps our model generate values based on the individual's observed data and missingness patterns. We further extend the use of IGNITE from imputing missingness to a personalized data synthesizer, where it generates missing EHRs that were never observed prior or even generates new patients for various applications. We validate our model on three large publicly available datasets and show that IGNITE outperforms state-of-the-art approaches in missing data reconstruction and task prediction.

Survival analysis focuses on estimating time-to-event distributions which can help in dynamic risk prediction in healthcare. Extending beyond the classical Cox model, deep learning techniques have been developed which moved away from the constraining assumptions of proportional hazards. Traditional statistical models often only include static information where, in this work, we propose a novel conditional variational autoencoder-based method called DySurv, which uses a combination of static and time-series measurements from patient electronic health records to estimate the risk of death dynamically. DySurv has been tested on several time-to-event benchmarks where it outperforms existing methods, including deep learning methods, and we evaluate it on real-world intensive care unit data from MIMIC-IV and eICU. The predictive capacity of DySurv is consistent and the survival estimates remain disentangled across different datasets supporting the idea that dynamic deep learning models based on conditional variational inference in multi-task cases can be robust models for survival analysis.

Semantic communications (SC) have been expected to be a new paradigm shifting to catalyze the next generation communication, whose main concerns shift from accurate bit transmission to effective semantic information exchange in communications. However, the previous and widely-used metrics for images are not applicable to evaluate the image semantic similarity in SC. Classical metrics to measure the similarity between two images usually rely on the pixel level or the structural level, such as the PSNR and the MS-SSIM. Straightforwardly using some tailored metrics based on deep-learning methods in CV community, such as the LPIPS, is infeasible for SC. To tackle this, inspired by BERTScore in NLP community, we propose a novel metric for evaluating image semantic similarity, named Vision Transformer Score (ViTScore). We prove theoretically that ViTScore has 3 important properties, including symmetry, boundedness, and normalization, which make ViTScore convenient and intuitive for image measurement. To evaluate the performance of ViTScore, we compare ViTScore with 3 typical metrics (PSNR, MS-SSIM, and LPIPS) through 4 classes of experiments: (i) correlation with BERTScore through evaluation of image caption downstream CV task, (ii) evaluation in classical image communications, (iii) evaluation in image semantic communication systems, and (iv) evaluation in image semantic communication systems with semantic attack. Experimental results demonstrate that ViTScore is robust and efficient in evaluating the semantic similarity of images. Particularly, ViTScore outperforms the other 3 typical metrics in evaluating the image semantic changes by semantic attack, such as image inverse with Generative Adversarial Networks (GANs). This indicates that ViTScore is an effective performance metric when deployed in SC scenarios.

Recent advancements in AI applications to healthcare have shown incredible promise in surpassing human performance in diagnosis and disease prognosis. With the increasing complexity of AI models, however, concerns regarding their opacity, potential biases, and the need for interpretability. To ensure trust and reliability in AI systems, especially in clinical risk prediction models, explainability becomes crucial. Explainability is usually referred to as an AI system's ability to provide a robust interpretation of its decision-making logic or the decisions themselves to human stakeholders. In clinical risk prediction, other aspects of explainability like fairness, bias, trust, and transparency also represent important concepts beyond just interpretability. In this review, we address the relationship between these concepts as they are often used together or interchangeably. This review also discusses recent progress in developing explainable models for clinical risk prediction, highlighting the importance of quantitative and clinical evaluation and validation across multiple common modalities in clinical practice. It emphasizes the need for external validation and the combination of diverse interpretability methods to enhance trust and fairness. Adopting rigorous testing, such as using synthetic datasets with known generative factors, can further improve the reliability of explainability methods. Open access and code-sharing resources are essential for transparency and reproducibility, enabling the growth and trustworthiness of explainable research. While challenges exist, an end-to-end approach to explainability in clinical risk prediction, incorporating stakeholders from clinicians to developers, is essential for success.

Heart attack remain one of the greatest contributors to mortality in the United States and globally. Patients admitted to the intensive care unit (ICU) with diagnosed heart attack (myocardial infarction or MI) are at higher risk of death. In this study, we use two retrospective cohorts extracted from the eICU and MIMIC-IV databases, to develop a novel pseudo-dynamic machine learning framework for mortality prediction in the ICU with interpretability and clinical risk analysis. The method provides accurate prediction for ICU patients up to 24 hours before the event and provide time-resolved interpretability results. The performance of the framework relying on extreme gradient boosting was evaluated on a held-out test set from eICU, and externally validated on the MIMIC-IV cohort using the most important features identified by time-resolved Shapley values achieving AUCs of 91.0 (balanced accuracy of 82.3) for 6-hour prediction of mortality respectively. We show that our framework successfully leverages time-series physiological measurements by translating them into stacked static prediction problems to be robustly predictive through time in the ICU stay and can offer clinical insight from time-resolved interpretability

The lack of data democratization and information leakage from trained models hinder the development and acceptance of robust deep learning-based healthcare solutions. This paper argues that irreversible data encoding can provide an effective solution to achieve data democratization without violating the privacy constraints imposed on healthcare data and clinical models. An ideal encoding framework transforms the data into a new space where it is imperceptible to a manual or computational inspection. However, encoded data should preserve the semantics of the original data such that deep learning models can be trained effectively. This paper hypothesizes the characteristics of the desired encoding framework and then exploits random projections and random quantum encoding to realize this framework for dense and longitudinal or time-series data. Experimental evaluation highlights that models trained on encoded time-series data effectively uphold the information bottleneck principle and hence, exhibit lesser information leakage from trained models.

The prevalence of artificial intelligence (AI) has envisioned an era of healthcare democratisation that promises every stakeholder a new and better way of life. However, the advancement of clinical AI research is significantly hurdled by the dearth of data democratisation in healthcare. To truly democratise data for AI studies, challenges are two-fold: 1. the sensitive information in clinical data should be anonymised appropriately, and 2. AI-oriented clinical knowledge should flow freely across organisations. This paper considers a recent deep-learning advent, dataset condensation (DC), as a stone that kills two birds in democratising healthcare data. The condensed data after DC, which can be viewed as statistical metadata, abstracts original clinical records and irreversibly conceals sensitive information at individual levels; nevertheless, it still preserves adequate knowledge for learning deep neural networks (DNNs). More favourably, the compressed volumes and the accelerated model learnings of condensed data portray a more efficient clinical knowledge sharing and flowing system, as necessitated by data democratisation. We underline DC's prospects for democratising clinical data, specifically electrical healthcare records (EHRs), for AI research through experimental results and analysis across three healthcare datasets of varying data types.

External validation is often recommended to ensure the generalizability of ML models. However, it neither guarantees generalizability nor equates to a model's clinical usefulness (the ultimate goal of any clinical decision-support tool). External validation is misaligned with current healthcare ML needs. First, patient data changes across time, geography, and facilities. These changes create significant volatility in the performance of a single fixed model (especially for deep learning models, which dominate clinical ML). Second, newer ML techniques, current market forces, and updated regulatory frameworks are enabling frequent updating and monitoring of individual deployed model instances. We submit that external validation is insufficient to establish ML models' safety or utility. Proposals to fix the external validation paradigm do not go far enough. Continued reliance on it as the ultimate test is likely to lead us astray. We propose the MLOps-inspired paradigm of recurring local validation as an alternative that ensures the validity of models while protecting against performance-disruptive data variability. This paradigm relies on site-specific reliability tests before every deployment, followed by regular and recurrent checks throughout the life cycle of the deployed algorithm. Initial and recurrent reliability tests protect against performance-disruptive distribution shifts, and concept drifts that jeopardize patient safety.

Electronic Health Records (EHRs) contain sensitive patient information, which presents privacy concerns when sharing such data. Synthetic data generation is a promising solution to mitigate these risks, often relying on deep generative models such as Generative Adversarial Networks (GANs). However, recent studies have shown that diffusion models offer several advantages over GANs, such as generation of more realistic synthetic data and stable training in generating data modalities, including image, text, and sound. In this work, we investigate the potential of diffusion models for generating realistic mixed-type tabular EHRs, comparing TabDDPM model with existing methods on four datasets in terms of data quality, utility, privacy, and augmentation. Our experiments demonstrate that TabDDPM outperforms the state-of-the-art models across all evaluation metrics, except for privacy, which confirms the trade-off between privacy and utility., Comment: Page 2, Figure 1 is updated

Observational studies have recently received significant attention from the machine learning community due to the increasingly available non-experimental observational data and the limitations of the experimental studies, such as considerable cost, impracticality, small and less representative sample sizes, etc. In observational studies, de-confounding is a fundamental problem of individualised treatment effects (ITE) estimation. This paper proposes disentangled representations with adversarial training to selectively balance the confounders in the binary treatment setting for the ITE estimation. The adversarial training of treatment policy selectively encourages treatment-agnostic balanced representations for the confounders and helps to estimate the ITE in the observational studies via counterfactual inference. Empirical results on synthetic and real-world datasets, with varying degrees of confounding, prove that our proposed approach improves the state-of-the-art methods in achieving lower error in the ITE estimation., Comment: accepted to AISTATS 2023

We propose in this paper to exploit convolutional low density generator matrix (LDGM) codes for transmission of Bernoulli sources over binary-input output-symmetric (BIOS) channels. To this end, we present a new framework to prove the coding theorems for linear codes, which unifies the channel coding theorem, the source coding theorem and the joint source-channel coding (JSCC) theorem. In the presented framework, the systematic bits and the corresponding parity-check bits play different roles. Precisely, the noisy systematic bits are used to limit the list size of typical codewords, while the noisy parity-check bits are used to select from the list the maximum likelihood codeword. This new framework for linear codes allows that the systematic bits and the parity-check bits are transmitted in different ways and over different channels. With this framework, we prove that the Bernoulli generator matrix codes (BGMCs) are capacity-achieving over BIOS channels, entropy-achieving for Bernoulli sources, and also system-capacity-achieving for JSCC applications. A lower bound on the bit-error rate (BER) is derived for linear codes, which can be used to predict the error floors and hence serves as a simple tool to design the JSCC system. Numerical results show that the convolutional LDGM codes perform well in the waterfall region and match well with the derived error floors, which can be lowered down if required by simply increasing the encoding memory., Comment: 24 pages, 13 figures

Electronic Health Records (EHRs) are a valuable asset to facilitate clinical research and point of care applications; however, many challenges such as data privacy concerns impede its optimal utilization. Deep generative models, particularly, Generative Adversarial Networks (GANs) show great promise in generating synthetic EHR data by learning underlying data distributions while achieving excellent performance and addressing these challenges. This work aims to review the major developments in various applications of GANs for EHRs and provides an overview of the proposed methodologies. For this purpose, we combine perspectives from healthcare applications and machine learning techniques in terms of source datasets and the fidelity and privacy evaluation of the generated synthetic datasets. We also compile a list of the metrics and datasets used by the reviewed works, which can be utilized as benchmarks for future research in the field. We conclude by discussing challenges in GANs for EHRs development and proposing recommended practices. We hope that this work motivates novel research development directions in the intersection of healthcare and machine learning.