Developing Clinical Decision Support Systems for Sepsis Prediction Using Temporal and Non-Temporal Machine Learning Methods

In healthcare, diagnostic errors represent the biggest challenge to synthesize accurate treatments. In the United States, patient deaths due to misdiagnoses are estimated at 40,000 to 80,000 per year. It was also found that 30% of the annual healthcare spending was consumed on unnecessary services and other inefficiencies. The diagnostic errors could be reduced, and public health can be improved by applying machine learning and artificial intelligence in healthcare problems. This dissertation is an attempt to formulate clinical decision support systems and to develop new algorithms to reduce clinical errors.This dissertation aims at developing clinical decision support systems to diagnose sepsis in the early stages. The key feature of our work is that we captured the dynamics among body organs using Bayesian networks. The richness of the proposed model is measured not only by achieving high accuracy but also by utilizing fewer lab results.To further improve the accuracy of the clinical decision support system, we utilize longitudinal data to develop a mortality progression model. This part of the dissertation proposes a hidden Markov model (HMM) framework to model the mortality progression. In comparison to existing approaches, the proposed framework leverages the longitudinal data available in the electronic health records (EHR).In addition, this dissertation proposes an initialization procedure to train the parameters of HMM efficiently. The current HMM learning algorithms are sensitive to initialization. The proposed method computes an initial set of parameters by relaxing the time dependency in sequential time series data and incorporating the multinomial logistic regression.Finally, this dissertation compares the prognostic accuracy of two popularly used early sepsis diagnostic criteria: Systemic Inflammatory Response Syndrome (SIRS) and quick Sepsis-related Organ Failure Assessment (qSOFA). Using statistical and machine learning methods, we found that qSOFA is a better diagnostic criteria than SIRS. These findings will guide healthcare providers in selecting the best bedside diagnostic criteria

Methods for Estimating Kidney Disease Stage Transition Probabilities Using Electronic Medical Records

Chronic diseases are often described by stages of severity. Clinical decisions about what to do are influenced by the stage, whether a patient is progressing, and the rate of progression. For chronic kidney disease (CKD), relatively little is known about the transition rates between stages. To address this, we used electronic health records (EHR) data on a large primary care population, which should have the advantage of having both sufficient follow-up time and sample size to reliably estimate transition rates for CKD. However, EHR data have some features that threaten the validity of any analysis. In particular, the timing and frequency of labratory values and clinical measurements are not determined a priori by research investigators, but rather, depend on many factors, including the current health of the patient. We developed an approach for estimatating CKD stage transition rates using hidden Markov models (HMMs), when the level of information and observation time vary among individuals. To estimate the HMMs in a computationally manageable way, we used a “discretization” method to transform daily data into intervals of 30 days, 90 days, or 180 days. We assessed the accuracy and computation time of this method via simulation studies. We also used simulations to study the effect of informative observation times on the estimated transition rates. Our simulation results showed good performance of the method, even when missing data are non-ignorable. We applied the methods to EHR data from over 60,000 primary care patients who have chronic kidney disease (stage 2 and above). We estimated transition rates between six underlying disease states. The results were similar for men and women

Markov-modulated marked Poisson processes for modelling disease dynamics based on medical claims data

We explore Markov-modulated marked Poisson processes (MMMPPs) as a natural framework for modelling patients' disease dynamics over time based on medical claims data. In claims data, observations do not only occur at random points in time but are also informative, i.e. driven by unobserved disease levels, as poor health conditions usually lead to more frequent interactions with the healthcare system. Therefore, we model the observation process as a Markov-modulated Poisson process, where the rate of healthcare interactions is governed by a continuous-time Markov chain. Its states serve as proxies for the patients' latent disease levels and further determine the distribution of additional data collected at each observation time, the so-called marks. Overall, MMMPPs jointly model observations and their informative time points by comprising two state-dependent processes: the observation process (corresponding to the event times) and the mark process (corresponding to event-specific information), which both depend on the underlying states. The approach is illustrated using claims data from patients diagnosed with chronic obstructive pulmonary disease (COPD) by modelling their drug use and the interval lengths between consecutive physician consultations. The results indicate that MMMPPs are able to detect distinct patterns of healthcare utilisation related to disease processes and reveal inter-individual differences in the state-switching dynamics

Progression Modeling of Cognitive Disease Using Temporal Data Mining: Research Landscape, Gaps and Solution Design

Dementia is a cognitive disorder whose diagnosis and progression monitoring is very difficult due to a very slow onset and progression. It is difficult to detect whether cognitive decline is due to ageing process or due to some form of dementia as MRI scans of the brain cannot reliably differentiate between ageing related volume loss and pathological changes. Laboratory tests on blood or CSF samples have also not proved very useful. Alzheimer�s disease (AD) is recognized as the most common cause of dementia. Development of sensitive and reliable tool for evaluation in terms of early diagnosis and progression monitoring of AD is required. Since there is an absence of specific markers for predicting AD progression, there is a need to learn more about specific attributes and their temporal relationships that lead to this disease and determine progression from mild cognitive impairment to full blown AD. Various stages of disease and transitions from one stage to the have be modelled based on longitudinal patient data. This paper provides a critical review of the methods to understand disease progression modelling and determine factors leading to progression of AD from initial to final stages. Then the design of a machine learning based solution is proposed to handle the gaps in current research