Multivariate sequential contrast pattern mining and prediction models for critical care clinical informatics

University of Technology Sydney. Faculty of Engineering and Information Technology.Data mining and knowledge discovery involves efficient search and discovery of patterns in data that are able to describe the underlying complex structure and properties of the corresponding system. To be of practical use, the discovered patterns need to be novel, informative and interpretable. Large-scale unstructured biomedical databases such as electronic health records (EHRs) tend to exacerbate the problem of discovering interesting and useful patterns. Typically, patients in intensive care units (ICUs) require constant monitoring of vital signs. To this purpose, significant quantities of patient data, coupled with waveform signals are gathered from biosensors and clinical information systems. Subsequently, clinicians face an enormous challenge in the assimilation and interpretation of large volumes of unstructured, multidimensional, noisy and dynamically fluctuating patient data. The availability of de-identified ICU datasets like the MIMIC-II (Multiparameter Intelligent Monitoring in Intensive Care) databases provide an opportunity to advance medical care, by benchmarking algorithms that capture subtle patterns associated with specific medical conditions. Such patterns are able to provide fresh insights into disease dynamics over long time scales. In this research, we focus on the extraction of computational physiological markers, in the form of relevant medical episodes, event sequences and distinguishing sequential patterns. These interesting patterns known as sequential contrast patterns are combined with patient clinical features to develop powerful clinical prediction models. Later, the clinical models are used to predict critical ICU events, pertaining to numerous forms of hemodynamic instabilities causing acute hypotension, multiple organ failures, and septic shock events. In the process, we employ novel sequential pattern mining methodologies for the structured analysis of large-scale ICU datasets. The reported algorithms use a discretised representation such as symbolic aggregate approximation for the analysis of physiological time series data. Thus, symbolic sequences are used to abstract physiological signals, facilitating the development of efficient sequential contrast mining algorithms to extract high risk patterns and then risk stratify patient populations, based on specific clinical inclusion criteria. Chapter 2 thoroughly reviews the pattern mining research literature relating to frequent sequential patterns, emerging and contrast patterns, and temporal patterns along with their applications in clinical informatics. In Chapter 3, we incorporate a contrast pattern mining algorithm to extract informative sequential contrast patterns from hemodynamic data, for the prediction of critical care events like Acute Hypotension Episodes (AHEs). The proposed technique extracts a set of distinguishing sequential patterns to predict the occurrence of an AHE in a future time window, following the passage of a user-defined gap interval. The method demonstrates that sequential contrast patterns are useful as potential physiological biomarkers for building optimal patient risk stratification systems and for further clinical investigation of interesting patterns in critical care patients. Chapter 4 reports a generic two stage sequential patterns based classification framework, which is used to classify critical patient events including hypotension and patient mortality, using contrast patterns. Here, extracted sequential patterns undergo transformation to construct binary valued and frequency based feature vectors for developing critical care classification models. Chapter 5 proposes a novel machine learning approach using sequential contrast patterns for the early prediction of septic shock. The approach combines highly informative sequential patterns extracted from multiple physiological variables and captures the interactions among these patterns via Coupled Hidden Markov Models (CHMM). Our results demonstrate a strong competitive accuracy in the predictions, especially when the interactions between the multiple physiological variables are accounted for using multivariate coupled sequential models. The novelty of the approach stems from the integration of sequence-based physiological pattern markers with the sequential CHMM to learn dynamic physiological behavior as well as from the coupling of such patterns to build powerful risk stratification models for septic shock patients. All of the described methods have been tested and bench-marked using numerous real world critical care datasets from the MIMIC-II database. The results from these experiments show that multivariate sequential contrast patterns based coupled models are highly effective and are able to improve the state-of-the-art in the design of patient risk prediction systems in critical care settings

Learning Better Clinical Risk Models.

Risk models are used to estimate a patient’s risk of suffering particular outcomes throughout clinical practice. These models are important for matching patients to the appropriate level of treatment, for effective allocation of resources, and for fairly evaluating the performance of healthcare providers. The application and development of methods from the field of machine learning has the potential to improve patient outcomes and reduce healthcare spending with more accurate estimates of patient risk. This dissertation addresses several limitations of currently used clinical risk models, through the identification of novel risk factors and through the training of more effective models. As wearable monitors become more effective and less costly, the previously untapped predictive information in a patient’s physiology over time has the potential to greatly improve clinical practice. However translating these technological advances into real-world clinical impacts will require computational methods to identify high-risk structure in the data. This dissertation presents several approaches to learning risk factors from physiological recordings, through the discovery of latent states using topic models, and through the identification of predictive features using convolutional neural networks. We evaluate these approaches on patients from a large clinical trial and find that these methods not only outperform prior approaches to leveraging heart rate for cardiac risk stratification, but that they improve overall prediction of cardiac death when considered alongside standard clinical risk factors. We also demonstrate the utility of this work for learning a richer description of sleep recordings. Additionally, we consider the development of risk models in the presence of missing data, which is ubiquitous in real-world medical settings. We present a novel method for jointly learning risk and imputation models in the presence of missing data, and find significant improvements relative to standard approaches when evaluated on a large national registry of trauma patients.PhDComputer Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113326/1/alexve_1.pd

A Survey on Identification of Motifs and Ontology in Medical Database

Motifs and ontology are used in medical database for identifyingand diagnose of the disease. A motif is a pattern network used for analysis of the disease. It also identifies the pattern of the signal. Based on the motifs the disease can be predicted, classified and diagnosed. Ontology is knowledge based representation, and it is used as a user interface to diagnose the disease. Ontology is also used by medical expert to diagnose and analyse the disease easily. Gene ontology is used to express the gene of the disease

Septic shock prediction for ICU patients via coupled HMM walking on sequential contrast patterns

© 2016 Background and objective Critical care patient events like sepsis or septic shock in intensive care units (ICUs) are dangerous complications which can cause multiple organ failures and eventual death. Preventive prediction of such events will allow clinicians to stage effective interventions for averting these critical complications. Methods It is widely understood that physiological conditions of patients on variables such as blood pressure and heart rate are suggestive to gradual changes over a certain period of time, prior to the occurrence of a septic shock. This work investigates the performance of a novel machine learning approach for the early prediction of septic shock. The approach combines highly informative sequential patterns extracted from multiple physiological variables and captures the interactions among these patterns via coupled hidden Markov models (CHMM). In particular, the patterns are extracted from three non-invasive waveform measurements: the mean arterial pressure levels, the heart rates and respiratory rates of septic shock patients from a large clinical ICU dataset called MIMIC-II. Evaluation and results For baseline estimations, SVM and HMM models on the continuous time series data for the given patients, using MAP (mean arterial pressure), HR (heart rate), and RR (respiratory rate) are employed. Single channel patterns based HMM (SCP-HMM) and multi-channel patterns based coupled HMM (MCP-HMM) are compared against baseline models using 5-fold cross validation accuracies over multiple rounds. Particularly, the results of MCP-HMM are statistically significant having a p-value of 0.0014, in comparison to baseline models. Our experiments demonstrate a strong competitive accuracy in the prediction of septic shock, especially when the interactions between the multiple variables are coupled by the learning model. Conclusions It can be concluded that the novelty of the approach, stems from the integration of sequence-based physiological pattern markers with the sequential CHMM model to learn dynamic physiological behavior, as well as from the coupling of such patterns to build powerful risk stratification models for septic shock patients

Machine Learning for Physiological Time Series: Representing and Controlling Blood Glucose for Diabetes Management

Type 1 diabetes is a chronic health condition affecting over one million patients in the US, where blood glucose (sugar) levels are not well regulated by the body. Researchers have sought to use physiological data (e.g., blood glucose measurements) collected from wearable devices to manage this disease, either by forecasting future blood glucose levels for predictive alarms, or by automating insulin delivery for blood glucose management. However, the application of machine learning (ML) to these data is hampered by latent context, limited supervision and complex temporal dependencies. To address these challenges, we develop and evaluate novel ML approaches in the context of i) representing physiological time series, particularly for forecasting blood glucose values and ii) decision making for when and how much insulin to deliver. When learning representations, we leverage the structure of the physiological sequence as an implicit information stream. In particular, we a) incorporate latent context when predicting adverse events by jointly modeling patterns in the data and the context those patterns occurred under, b) propose novel types of self-supervision to handle limited data and c) propose deep models that predict functions underlying trajectories to encode temporal dependencies. In the context of decision making, we use reinforcement learning (RL) for blood glucose management. Through the use of an FDA-approved simulator of the glucoregulatory system, we achieve strong performance using deep RL with and without human intervention. However, the success of RL typically depends on realistic simulators or experimental real-world deployment, neither of which are currently practical for problems in health. Thus, we propose techniques for leveraging imperfect simulators and observational data. Beyond diabetes, representing and managing physiological signals is an important problem. By adapting techniques to better leverage the structure inherent in the data we can help overcome these challenges.PHDComputer Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163134/1/ifox_1.pd

Explainable AI for clinical risk prediction: a survey of concepts, methods, and modalities

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

The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis, care pathway analysis and research prioritisation

Background: Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption. Objectives: To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy. Data sources: We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, metaRegister of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report. Review methods: The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis. Results: The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck® (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care. Limitations: The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing. Conclusions: Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value. Study registration: The systematic review within this study is registered as PROSPERO CRD42014013919. Funding: The National Institute for Health Research Health Technology Assessment programme