Patients in the intensive care unit (ICU) require constant and close supervision. To assist clinical staff in this task, hospitals use monitoring systems that trigger audiovisual alarms if their algorithms indicate that a patient's condition may be worsening. However, current monitoring systems are extremely sensitive to movement artefacts and technical errors. As a result, they typically trigger hundreds to thousands of false alarms per patient per day - drowning the important alarms in noise and adding to the exhaustion of clinical staff. In this setting, data is abundantly available, but obtaining trustworthy annotations by experts is laborious and expensive. We frame the problem of false alarm reduction from multivariate time series as a machine-learning task and address it with a novel multitask network architecture that utilises distant supervision through multiple related auxiliary tasks in order to reduce the number of expensive labels required for training. We show that our approach leads to significant improvements over several state-of-the-art baselines on real-world ICU data and provide new insights on the importance of task selection and architectural choices in distantly supervised multitask learning.
@cite_37: In the scenario of real-time monitoring of hospital patients, high-quality inference of patients' health status using all information available from clinical covariates and lab tests is essential to enable successful medical interventions and improve patient outcomes. Developing a computational framework that can learn from observational large-scale electronic health records (EHRs) and make accurate real-time predictions is a critical step. In this work, we develop and explore a Bayesian nonparametric model based on Gaussian process (GP) regression for hospital patient monitoring. We propose MedGP, a statistical framework that incorporates 24 clinical and lab covariates and supports a rich reference data set from which relationships between observed covariates may be inferred and exploited for high-quality inference of patient state over time. To do this, we develop a highly structured sparse GP kernel to enable tractable computation over tens of thousands of time points while estimating correlations among clinical covariates, patients, and periodicity in patient observations. MedGP has a number of benefits over current methods, including (i) not requiring an alignment of the time series data, (ii) quantifying confidence regions in the predictions, (iii) exploiting a vast and rich database of patients, and (iv) inferring interpretable relationships among clinical covariates. We evaluate and compare results from MedGP on the task of online prediction for three patient subgroups from two medical data sets across 8,043 patients. We found MedGP improves online prediction over baseline methods for nearly all covariates across different disease subgroups and studies. The publicly available code is at this https URL.
@cite_18: Clinical medical data, especially in the intensive care unit (ICU), consist of multivariate time series of observations. For each patient visit (or episode), sensor data and lab test results are recorded in the patient's Electronic Health Record (EHR). While potentially containing a wealth of insights, the data is difficult to mine effectively, owing to varying length, irregular sampling and missing data. Recurrent Neural Networks (RNNs), particularly those using Long Short-Term Memory (LSTM) hidden units, are powerful and increasingly popular models for learning from sequence data. They effectively model varying length sequences and capture long range dependencies. We present the first study to empirically evaluate the ability of LSTMs to recognize patterns in multivariate time series of clinical measurements. Specifically, we consider multilabel classification of diagnoses, training a model to classify 128 diagnoses given 13 frequently but irregularly sampled clinical measurements. First, we establish the effectiveness of a simple LSTM network for modeling clinical data. Then we demonstrate a straightforward and effective training strategy in which we replicate targets at each sequence step. Trained only on raw time series, our models outperform several strong baselines, including a multilayer perceptron trained on hand-engineered features.
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@cite_8: Leveraging large historical data in electronic health record (EHR), we developed Doctor AI, a generic predictive model that covers observed medical conditions and medication uses. Doctor AI is a temporal model using recurrent neural networks (RNN) and was developed and applied to longitudinal time stamped EHR data from 260K patients over 8 years. Encounter records (e.g. diagnosis codes, medication codes or procedure codes) were input to RNN to predict (all) the diagnosis and medication categories for a subsequent visit. Doctor AI assesses the history of patients to make multilabel predictions (one label for each diagnosis or medication category). Based on separate blind test set evaluation, Doctor AI can perform differential diagnosis with up to 79 recall@30, significantly higher than several baselines. Moreover, we demonstrate great generalizability of Doctor AI by adapting the resulting models from one institution to another without losing substantial accuracy.
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@cite_49: The management of invasive mechanical ventilation, and the regulation of sedation and analgesia during ventilation, constitutes a major part of the care of patients admitted to intensive care units. Both prolonged dependence on mechanical ventilation and premature extubation are associated with increased risk of complications and higher hospital costs, but clinical opinion on the best protocol for weaning patients off of a ventilator varies. This work aims to develop a decision support tool that uses available patient information to predict time-to-extubation readiness and to recommend a personalized regime of sedation dosage and ventilator support. To this end, we use off-policy reinforcement learning algorithms to determine the best action at a given patient state from sub-optimal historical ICU data. We compare treatment policies from fitted Q-iteration with extremely randomized trees and with feedforward neural networks, and demonstrate that the policies learnt show promise in recommending weaning protocols with improved outcomes, in terms of minimizing rates of reintubation and regulating physiological stability.
@cite_50: Inferring precise phenotypic patterns from population-scale clinical data is a core computational task in the development of precision, personalized medicine. The traditional approach uses supervised learning, in which an expert designates which patterns to look for (by specifying the learning task and the class labels), and where to look for them (by specifying the input variables). While appropriate for individual tasks, this approach scales poorly and misses the patterns that we don’t think to look for. Unsupervised feature learning overcomes these limitations by identifying patterns (or features) that collectively form a compact and expressive representation of the source data, with no need for expert input or labeled examples. Its rising popularity is driven by new deep learning methods, which have produced high-profile successes on difficult standardized problems of object recognition in images. Here we introduce its use for phenotype discovery in clinical data. This use is challenging because the largest source of clinical data – Electronic Medical Records – typically contains noisy, sparse, and irregularly timed observations, rendering them poor substrates for deep learning methods. Our approach couples dirty clinical data to deep learning architecture via longitudinal probability densities inferred using Gaussian process regression. From episodic, longitudinal sequences of serum uric acid measurements in 4368 individuals we produced continuous phenotypic features that suggest multiple population subtypes, and that accurately distinguished (0.97 AUC) the uric-acid signatures of gout vs. acute leukemia despite not being optimized for the task. The unsupervised features were as accurate as gold-standard features engineered by an expert with complete knowledge of the domain, the classification task, and the class labels. Our findings demonstrate the potential for achieving computational phenotype discovery at population scale. We expect such data-driven phenotypes to expose unknown disease variants and subtypes and to provide rich targets for genetic association studies.
@cite_46: The ability to determine patient acuity (or severity of illness) has immediate practical use for clinicians. We evaluate the use of multivariate timeseries modeling with the multi-task Gaussian process (GP) models using noisy, incomplete, sparse, heterogeneous and unevenly-sampled clinical data, including both physiological signals and clinical notes. The learned multi-task GP (MTGP) hyperparameters are then used to assess and forecast patient acuity. Experiments were conducted with two real clinical data sets acquired from ICU patients: firstly, estimating cerebrovascular pressure reactivity, an important indicator of secondary damage for traumatic brain injury patients, by learning the interactions between intracranial pressure and mean arterial blood pressure signals, and secondly, mortality prediction using clinical progress notes. In both cases, MTGPs provided improved results: an MTGP model provided better results than single-task GP models for signal interpolation and forecasting (0.91 vs 0.69 RMSE), and the use of MTGP hyperparameters obtained improved results when used as additional classification features (0.812 vs 0.788 AUC).
@cite_16: Objective: We sought to develop an intensive care unit research database applying automated techniques to aggregate high-resolution diagnostic and therapeutic data from a large, diverse population of adult intensive care unit patients. This freely available database is intended to support epidemiologic research in critical care medicine and serve as a resource to evaluate new clinical decision support and monitoring algorithms. Design: Data collection and retrospective analysis. Setting: All adult intensive care units (medical intensive care unit, surgical intensive care unit, cardiac care unit, cardiac surgery recovery unit) at a tertiary care hospital. Patients: Adult patients admitted to intensive care units between 2001 and 2007. Interventions: None. Measurements and Main Results: The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database consists of 25,328 intensive care unit stays. The investigators collected detailed information about intensive care unit patient stays, including laboratory data, therapeutic intervention profiles such as vasoactive medication drip rates and ventilator settings, nursing progress notes, discharge summaries, radiology reports, provider order entry data, International Classification of Diseases, 9th Revision codes, and, for a subset of patients, high-resolution vital sign trends and waveforms. Data were automatically deidentified to comply with Health Insurance Portability and Accountability Act standards and integrated with relational database software to create electronic intensive care unit records for each patient stay. The data were made freely available in February 2010 through the Internet along with a detailed user’s guide and an assortment of data processing tools. The overall hospital mortality rate was 11.7 , which varied by critical care unit. The median intensive care unit length of stay was 2.2 days (interquartile range, 1.1‐4.4 days). According to the primary International Classification of Diseases, 9th Revision codes, the following disease categories each comprised at least 5 of the case records: diseases of the circulatory system (39.1 ); trauma (10.2 ); diseases of the digestive system (9.7 ); pulmonary diseases (9.0 ); infectious diseases (7.0 ); and neoplasms (6.8 ). Conclusions: MIMIC-II documents a diverse and very large population of intensive care unit patient stays and contains comprehensive and detailed clinical data, including physiological waveforms and minute-by-minute trends for a subset of records. It establishes a new public-access resource for critical care research, supporting a diverse range of analytic studies spanning epidemiology, clinical decision-rule development, and electronic tool development. (Crit Care Med 2011; 39:952‐960)
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@cite_12: Multivariate time series data in practical applications, such as health care, geoscience, and biology, are characterized by a variety of missing values. In time series prediction and other related tasks, it has been noted that missing values and their missing patterns are often correlated with the target labels, a.k.a., informative missingness. There is very limited work on exploiting the missing patterns for effective imputation and improving prediction performance. In this paper, we develop novel deep learning models, namely GRU-D, as one of the early attempts. GRU-D is based on Gated Recurrent Unit (GRU), a state-of-the-art recurrent neural network. It takes two representations of missing patterns, i.e., masking and time interval, and effectively incorporates them into a deep model architecture so that it not only captures the long-term temporal dependencies in time series, but also utilizes the missing patterns to achieve better prediction results. Experiments of time series classification tasks on real-world clinical datasets (MIMIC-III, PhysioNet) and synthetic datasets demonstrate that our models achieve state-of-the-art performance and provides useful insights for better understanding and utilization of missing values in time series analysis.
Driven by widespread efforts to automate patient monitoring, there has been a recent surge in works applying machine learning to the vast amounts of data generated in ICUs. One notable driver is the MIMIC @cite_16 dataset that has made ICU data accessible to a large number of researchers. Related works have, for example, explored the use of ICU data for tasks such as mortality modelling @cite_13 , illness assessment and forecasting @cite_46 , diagnostic support @cite_18 , patient state prediction @cite_37 and learning weaning policies for mechanical ventilation @cite_49 . Applying machine-learning approaches to clinical and physiological data is challenging, because it is heterogenous, noisy, confounded, sparse and of high temporal resolution over long periods of time. These properties are in stark contrast to many of the benchmark datasets that machine-learning approaches are typically developed and evaluated on. Several works therefore deal with adapting existing machine-learning approaches to the idiosyncrasies of clinical and physiological data, such as missingness @cite_14 @cite_12 , long-term temporal dependencies @cite_8 , noise @cite_3 , heterogeneity @cite_26 and sparsity @cite_50 . We build on several of these innovations in this work.