Sepsis is the leading cause of mortality in the ICU. It is challenging to manage because individual patients respond differently to treatment. Thus, tailoring treatment to the individual patient is essential for the best outcomes. In this paper, we take steps toward this goal by applying a mixture-of-experts framework to personalize sepsis treatment. The mixture model selectively alternates between neighbor-based (kernel) and deep reinforcement learning (DRL) experts depending on patient's current history. On a large retrospective cohort, this mixture-based approach outperforms physician, kernel only, and DRL-only experts.
Sepsis is a dangerous condition that is a leading cause of patient mortality. Treating sepsis is highly challenging, because individual patients respond very differently to medical interventions and there is no universally agreed-upon treatment for sepsis. In this work, we explore the use of continuous state-space model-based reinforcement learning (RL) to discover high-quality treatment policies for sepsis patients. Our quantitative evaluation reveals that by blending the treatment strategy discovered with RL with what clinicians follow, we can obtain improved policies, potentially allowing f…
Guideline-based treatment for sepsis and septic shock is difficult because sepsis is a disparate range of life-threatening organ dysfunctions whose pathophysiology is not fully understood. Early intervention in sepsis is crucial for patient outcome, yet those interventions have adverse effects and are frequently overadministered. Greater personalization is necessary, as no single action is suitable for all patients. We present a novel application of reinforcement learning in which we identify optimal recommendations for sepsis treatment from data, estimate their confidence level, and identify …
Cambridge University（剑桥大学）；Imperial College London（伦敦帝国学院）；MIT（麻省理工学院）
Sepsis is a leading cause of mortality in intensive care units and costs hospitals billions annually. Treating a septic patient is highly challenging, because individual patients respond very differently to medical interventions and there is no universally agreed-upon treatment for sepsis. In this work, we propose an approach to deduce treatment policies for septic patients by using continuous state-space models and deep reinforcement learning. Our model learns clinically interpretable treatment policies, similar in important aspects to the treatment policies of physicians. The learned policie…
Sepsis is a life-threatening condition caused by the body's response to an infection. In order to treat patients with sepsis, physicians must control varying dosages of various antibiotics, fluids, and vasopressors based on a large number of variables in an emergency setting. In this project we employ a "world model" methodology to create a simulator that aims to predict the next state of a patient given a current state and treatment action. In doing so, we hope our simulator learns from a latent and less noisy representation of the EHR data. Using historical sepsis patient records from the MI…
Beijing Institute of Technology（北京理工大学）；Tsinghua University（清华大学）
Sepsis is a leading cause of death in the ICU. It is a disease requiring complex interventions in a short period of time, but its optimal treatment strategy remains uncertain. Evidence suggests that the practices of currently used treatment strategies are problematic and may cause harm to patients. To address this decision problem, we propose a new medical decision model based on historical data to help clinicians recommend the best reference option for real-time treatment. Our model combines offline reinforcement learning and deep reinforcement learning to solve the problem of traditional rei…
EHR-MPC: Inference-Time Control for Sepsis Treatment with Generative Patient Digital Twins
Broad Institute of MIT and Harvard（MIT和哈佛大学Broad研究所）；Harvard University（哈佛大学）；Brigham and Women’s Hospital（布莱根妇女医院）；Technion–Israel Institute of Technology（技术学院-以色列理工学院）
Sepsis is a leading cause of mortality and its treatment is very expensive. Sepsis treatment is also very challenging because there is no consensus on what interventions work best and different patients respond very differently to the same treatment. Deep Reinforcement Learning methods can be used to come up with optimal policies for treatment strategies mirroring physician actions. In the healthcare scenario, the available data is mostly collected offline with no interaction with the environment, which necessitates the use of offline RL techniques. The Offline RL paradigm suffers from action …
University of Pittsburgh（匹兹堡大学）；University of Pittsburgh School of Medicine（匹兹堡大学医学院）；Carnegie Mellon University（卡内基梅隆大学）；McGowan Institute for Regenerative Medicine（麦高恩再生医学研究所）
Sepsis is a potentially life threatening inflammatory response to infection or severe tissue damage. It has a highly variable clinical course, requiring constant monitoring of the patient's state to guide the management of intravenous fluids and vasopressors, among other interventions. Despite decades of research, there's still debate among experts on optimal treatment. Here, we combine for the first time, distributional deep reinforcement learning with mechanistic physiological models to find personalized sepsis treatment strategies. Our method handles partial observability by leveraging know…
Our aim is to establish a framework where reinforcement learning (RL) of optimizing interventions retrospectively allows us a regulatory compliant pathway to prospective clinical testing of the learned policies in a clinical deployment. We focus on infections in intensive care units which are one of the major causes of death and difficult to treat because of the complex and opaque patient dynamics, and the clinically debated, highly-divergent set of intervention policies required by each individual patient, yet intensive care units are naturally data rich. In our work, we build on RL approache…
TECM*: A Data-Driven Assessment to Reinforcement Learning Methods and Application to Heparin Treatment Strategy for Surgical Sepsis
Chongqing Institute of Green and Intelligent Technology, CAS（中国科学院重庆绿色智能技术研究院）；Institute of Software, CAS（中国科学院软件研究所）；First Affiliated Hospital of Chongqing Medical University（重庆医科大学第一附属医院）
Learning Preference-Based Objectives from Clinical Narratives for Dynamic Sepsis Treatment
Institute of Data Science, National University of Singapore, Singapore（新加坡国立大学数据科学研究所）；National University Hospital, Singapore（新加坡国立大学医院）；Saw Swee Hock School of Public Health, National University of Singapore, Singapore（新加坡国立大学 Saw Swee Hock 公共卫生学院）
Lawrence Livermore National Laboratory（劳伦斯利弗莫尔国家实验室）；University of Chicago（芝加哥大学）；LLNL（劳伦斯利弗莫尔国家实验室）
Sepsis is a life-threatening condition affecting one million people per year in the US in which dysregulation of the body's own immune system causes damage to its tissues, resulting in a 28 - 50% mortality rate. Clinical trials for sepsis treatment over the last 20 years have failed to produce a single currently FDA approved drug treatment. In this study, we attempt to discover an effective cytokine mediation treatment strategy for sepsis using a previously developed agent-based model that simulates the innate immune response to infection: the Innate Immune Response agent-based model (IIRABM).…
ETH Zurich（苏黎世联邦理工学院）；SIB Swiss Institute of Bioinformatics（瑞士生物信息学研究所）
Sepsis is a life-threatening host response to infection associated with high mortality, morbidity, and health costs. Its management is highly time-sensitive since each hour of delayed treatment increases mortality due to irreversible organ damage. Meanwhile, despite decades of clinical research, robust biomarkers for sepsis are missing. Therefore, detecting sepsis early by utilizing the affluence of high-resolution intensive care records has become a challenging machine learning problem. Recent advances in deep learning and data mining promise to deliver a powerful set of tools to efficiently …
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 effe…
The potential of Reinforcement Learning (RL) has been demonstrated through successful applications to games such as Go and Atari. However, while it is straightforward to evaluate the performance of an RL algorithm in a game setting by simply using it to play the game, evaluation is a major challenge in clinical settings where it could be unsafe to follow RL policies in practice. Thus, understanding sensitivity of RL policies to the host of decisions made during implementation is an important step toward building the type of trust in RL required for eventual clinical uptake. In this work, we pe…
Health-related data is noisy and stochastic in implying the true physiological states of patients, limiting information contained in single-moment observations for sequential clinical decision making. We model patient-clinician interactions as partially observable Markov decision processes (POMDPs) and optimize sequential treatment based on belief states inferred from history sequence. To facilitate inference, we build a variational generative model and boost state representation with a recurrent neural network (RNN), incorporating an auxiliary loss from sequence auto-encoding. Meanwhile, we o…
Computer Science and Artificial Intelligence Lab, MIT（麻省理工学院计算机科学与人工智能实验室）
Sepsis is a leading cause of mortality in intensive care units (ICUs) and costs hospitals billions annually. Treating a septic patient is highly challenging, because individual patients respond very differently to medical interventions and there is no universally agreed-upon treatment for sepsis. Understanding more about a patient's physiological state at a given time could hold the key to effective treatment policies. In this work, we propose a new approach to deduce optimal treatment policies for septic patients by using continuous state-space models and deep reinforcement learning. Learning…
Stanford University（斯坦福大学）；University of Pennsylvania（宾夕法尼亚大学）
A key challenge to deploying reinforcement learning in practice is avoiding excessive (harmful) exploration in individual episodes. We propose a natural constraint on exploration -- \textit{uniformly} outperforming a conservative policy (adaptively estimated from all data observed thus far), up to a per-episode exploration budget. We design a novel algorithm that uses a UCB reinforcement learning policy for exploration, but overrides it as needed to satisfy our exploration constraint with high probability. Importantly, to ensure unbiased exploration across the state space, our algorithm adapti…
Much attention has been devoted recently to the development of machine learning algorithms with the goal of improving treatment policies in healthcare. Reinforcement learning (RL) is a sub-field within machine learning that is concerned with learning how to make sequences of decisions so as to optimize long-term effects. Already, RL algorithms have been proposed to identify decision-making strategies for mechanical ventilation, sepsis management and treatment of schizophrenia. However, before implementing treatment policies learned by black-box algorithms in high-stakes clinical decision probl…
MIT（麻省理工学院）；Harvard Medical School（哈佛医学院）；Harvard Pilgrim Healthcare Institute（哈佛朝圣者医疗保健研究所）
Reinforcement learning (RL) has the potential to significantly improve clinical decision making. However, treatment policies learned via RL from observational data are sensitive to subtle choices in study design. We highlight a simple approach, trajectory inspection, to bring clinicians into an iterative design process for model-based RL studies. We identify where the model recommends unexpectedly aggressive treatments or expects surprisingly positive outcomes from its recommendations. Then, we examine clinical trajectories simulated with the learned model and policy alongside the actual hospi…
There has been considerable interest in leveraging RL and stochastic control methods to learn optimal treatment strategies for critically ill patients, directly from observational data. However, there is significant ambiguity on the control objective and on the best reward choice for the standard RL objective. In this work, we propose a clinically motivated control objective for critically ill patients, for which the value functions have a simple medical interpretation. Further, we present theoretical results and adapt our method to a practical Deep RL algorithm, which can be used alongside an…
King's College London（伦敦国王学院）；University College London（伦敦大学学院）；University of Edinburgh（爱丁堡大学）；East and North Hertfordshire NHS Trust（东赫特福德郡和北赫特福德郡国民保健信托基金会）；University of Augsburg（奥格斯堡大学）；Luigi Sacco Hospital（路易吉·萨科医院）
Current machine learning models aiming to predict sepsis from Electronic Health Records (EHR) do not account for the heterogeneity of the condition, despite its emerging importance in prognosis and treatment. This work demonstrates the added value of stratifying the types of organ dysfunction observed in patients who develop sepsis in the ICU in improving the ability to recognise patients at risk of sepsis from their EHR data. Using an ICU dataset of 13,728 records, we identify clinically significant sepsis subpopulations with distinct organ dysfunction patterns. Classification experiments usi…
Heidelberg University（海德堡大学）；University of Manitoba（曼尼托巴大学）
Sepsis is the leading cause of death in non-coronary intensive care units. Moreover, a delay of antibiotic treatment of patients with severe sepsis by only few hours is associated with increased mortality. This insight makes accurate models for early prediction of sepsis a key task in machine learning for healthcare. Previous approaches have achieved high AUROC by learning from electronic health records where sepsis labels were defined automatically following established clinical criteria. We argue that the practice of incorporating the clinical criteria that are used to automatically define g…
We consider the task of Inverse Reinforcement Learning in Contextual Markov Decision Processes (MDPs). In this setting, contexts, which define the reward and transition kernel, are sampled from a distribution. In addition, although the reward is a function of the context, it is not provided to the agent. Instead, the agent observes demonstrations from an optimal policy. The goal is to learn the reward mapping, such that the agent will act optimally even when encountering previously unseen contexts, also known as zero-shot transfer. We formulate this problem as a non-differential convex optimiz…
Helsinki Institute for Information Technology HIIT（赫尔辛基信息技术研究所 HIIT）；Aalto University（阿尔托大学）
The expressive power of Gaussian processes depends heavily on the choice of kernel. In this work we propose the novel harmonizable mixture kernel (HMK), a family of expressive, interpretable, non-stationary kernels derived from mixture models on the generalized spectral representation. As a theoretically sound treatment of non-stationary kernels, HMK supports harmonizable covariances, a wide subset of kernels including all stationary and many non-stationary covariances. We also propose variational Fourier features, an inter-domain sparse GP inference framework that offers a representative set …
Detection of sepsis during emergency department triage using machine learning
Mednition Inc.（麦迪逊公司）；Sutter Mills-Peninsula Medical Center（萨特米尔半岛医疗中心）；Ascension Health（阿森松医疗）；Adventist Health White Memorial（基督复临安息日会怀特纪念医疗中心）；San Mateo Medical Center（圣马特奥医疗中心）；El Camino Hospital（埃尔卡米诺医院）；Emergency Nurses Association（急诊护士协会）；Duke University（杜克大学）
The Gibbs reference posterior distribution provides an objective full-Bayesian solution to the problem of prediction of a stationary Gaussian process with Matérn anisotropic kernel. A full-Bayesian approach is possible, because the posterior distribution is expressed as the invariant distribution of a uniformly ergodic Markovian kernel for which we give an explicit expression. In this paper, we show that it is appropriate for the Universal Kriging framework, that is when an unknown function is added to the stationary Gaussian process. We give sufficient conditions for the existence and proprie…
ETH Zurich（苏黎世联邦理工学院）；SIB Swiss Institute of Bioinformatics（SIB瑞士生物信息学研究所）
Despite decades of clinical research, sepsis remains a global public health crisis with high mortality, and morbidity. Currently, when sepsis is detected and the underlying pathogen is identified, organ damage may have already progressed to irreversible stages. Effective sepsis management is therefore highly time-sensitive. By systematically analysing trends in the plethora of clinical data available in the intensive care unit (ICU), an early prediction of sepsis could lead to earlier pathogen identification, resistance testing, and effective antibiotic and supportive treatment, and thereby be…
NPCNet: Navigator-Driven Pseudo Text for Deep Clustering of Early Sepsis Phenotyping
Institute of Data Science and Engineering（数据科学与工程研究所）；National Yang Ming Chiao Tung University（阳明交通大学）；EECS International Graduate Program（电子工程国际研究生项目）；College of Intelligent Computing and Medical Statistics Research Center（智能计算与医学统计研究室）；Chang Gung University（长庚大学）；Department of Emergency Medicine（急诊医学科）；Department of Computer Science（计算机科学系）；Computational Health Informatics Program（计算健康信息学项目）
We extend kernelized matrix factorization with a fully Bayesian treatment and with an ability to work with multiple side information sources expressed as different kernels. Kernel functions have been introduced to matrix factorization to integrate side information about the rows and columns (e.g., objects and users in recommender systems), which is necessary for making out-of-matrix (i.e., cold start) predictions. We discuss specifically bipartite graph inference, where the output matrix is binary, but extensions to more general matrices are straightforward. We extend the state of the art in t…
AI-powered skin spectral imaging enables instant sepsis diagnosis and outcome prediction in critically ill patients
German Cancer Research Center (DKFZ)（德国癌症研究中心）；Helmholtz Information and Data Science School for Health（亥姆霍兹健康信息与数据科学学院）；Heidelberg University（海德堡大学）；National Center for Tumor Diseases (NCT)（国家肿瘤疾病中心）；Heidelberg University Hospital（海德堡大学医院）；University Medical Center Mannheim（曼海姆大学医学中心）；DKFZ Hector Cancer Institute（DKFZ赫克托癌症研究所）
Sepsis is a deadly condition affecting many patients in the hospital. Recent studies have shown that patients diagnosed with sepsis have significant mortality and morbidity, resulting from the body's dysfunctional host response to infection. Clinicians often rely on the use of Sequential Organ Failure Assessment (SOFA), Systemic Inflammatory Response Syndrome (SIRS), and the Modified Early Warning Score (MEWS) to identify early signs of clinical deterioration requiring further work-up and treatment. However, many of these tools are manually computed and were not designed for automated computat…
The temporal Credit Assignment Problem (CAP) is a well-known and challenging task in AI. While Reinforcement Learning (RL), especially Deep RL, works well when immediate rewards are available, it can fail when only delayed rewards are available or when the reward function is noisy. In this work, we propose delegating the CAP to a Neural Network-based algorithm named InferNet that explicitly learns to infer the immediate rewards from the delayed rewards. The effectiveness of InferNet was evaluated on two online RL tasks: a simple GridWorld and 40 Atari games; and two offline RL tasks: GridWorld…
Data-Driven Machine Learning Approaches for Predicting In-Hospital Sepsis Mortality
University of Southern California（南加州大学）；California State Polytechnic University, Pomona（加州州立理工大学波莫纳分校）；California State University, Long Beach（加州州立大学长滩分校）
