Modeling event count data in the presence of informative dropout with application to bleeding and transfusion events in myelodysplastic syndrome

In many biomedical studies, it is often of interest to model event count data over the study period. For some patients, we may not follow up them for the entire study period owing to informative dropout. The dropout time can potentially provide valuable insight on the rate of the events. We propose a joint semiparametric model for event count data and informative dropout time that allows for correlation through a Gamma frailty. We develop efficient likelihood-based estimation and inference procedures. The proposed nonparametric maximum likelihood estimators are shown to be consistent and asymptotically normal. Furthermore, the asymptotic covariances of the finite-dimensional parameter estimates attain the semiparametric efficiency bound. Extensive simulation studies demonstrate that the proposed methods perform well in practice. We illustrate the proposed methods through an application to a clinical trial for bleeding and transfusion events in myelodysplastic syndrome

Bayesian Semiparametric Methods for Analyzing Panel Count Data

Panel count data commonly arise in epidemiological, social science, medical studies, in which subjects have repeated measurements on the recurrent events of interest at different observation times. Since the subjects are not under continuous monitoring, the exact times of those recurrent events are not observed but the counts of such events within the adjacent observation times are known. Panel count data can be considered as a special type of longitudinal data with a count response variable in the literature. Compared to the frequentist literature, very limited Bayesian approaches have been developed to analyze panel count data. In this dissertation, several Bayesian estimation approaches are proposed for analyzing panel count data under different semiparametric regression models. Chapter 1 of this dissertation provides some description of panel count data, literature review on existing methods, and background knowledge of related tools used in the proposed methods. Chapter 2 proposes a Bayesian estimation approach under the Poisson proportional mean model, in which we model the baseline mean function with the monotone splines of Ramsay (1988) [1]. An efficient Gibbs sampler is proposed, all parameters can be either sampled directly from their full conditional distributions in standard forms or updated through automatic adaptive rejection sampling. Our proposed method is evaluated through extensive simulations and compared with two exiting methods. Our method is applied to a bladder cancer data set for illustration. Chapter 3 proposes a new Bayesian estimation approach for analyzing panel count data when there is heterogeneity in the population (that cannot be described by the available covariates). A frailty Poisson proportional mean model is proposed with the unobserved gamma frailties representing the heterogeneity among the subjects. Simulation studies suggest that our method not only has a good performance when such frailty exists but also provides robust estimation when there is no frailty. The bladder cancer tumor data is analyzed for illustration. Chapter 4 investigates the robustness of our proposed Bayesian approaches in Chapter 2 and Chapter 3 through simulations. We draw the conclusion that our proposed Bayesian methods still have a good performance in most cases when the assumptions are invalid

Cardiovascular data analytics for real time patient monitoring

Improvements in wearable sensor devices make it possible to constantly monitor physiological parameters such as electrocardiograph (ECG) signals for long periods. Remote patient monitoring with wearable sensors has an important role to play in health care, particularly given the prevalence of chronic conditions such as cardiovascular disease (CVD)—one of the prominent causes of morbidity and mortality worldwide. Approximately 4.2 million Australians suffer from long-term CVD with approximately one death every 12 minutes. The assessment of ECG features, especially heart rate variability (HRV), represents a non-invasive technique which provides an indication of the autonomic nervous system (ANS) function. Conditions such as sudden cardiac death, hypertension, heart failure, myocardial infarction, ischaemia, and coronary heart disease can be detected from HRV analysis. In addition, the analysis of ECG features can also be used to diagnose many types of life-threatening arrhythmias, including ventricular fibrillation and ventricular tachycardia. Non-cardiac conditions, such as diabetes, obesity, metabolic syndrome, insulin resistance, irritable bowel syndrome, dyspepsia, anorexia nervosa, anxiety, and major depressive disorder have also been shown to be associated with HRV. The analysis of ECG features from real time ECG signals generated from wearable sensors provides distinctive challenges. The sensors that receive and process the signals have limited power, storage and processing capacity. Consequently, algorithms that process ECG signals need to be lightweight, use minimal storage resources and accurately detect abnormalities so that alarms can be raised. The existing literature details only a few algorithms which operate within the constraints of wearable sensor networks. This research presents four novel techniques that enable ECG signals to be processed within the limitations of resource constraints on devices to detect some key abnormalities in heart function. - The first technique is a novel real-time ECG data reduction algorithm, which detects and transmits only those key points that are critical for the generation of ECG features for diagnoses. - The second technique accurately predicts the five-minute HRV measure using only three minutes of data with an algorithm that executes in real-time using minimal computational resources. - The third technique introduces a real-time ECG feature recognition system that can be applied to diagnose life threatening conditions such as premature ventricular contractions (PVCs). - The fourth technique advances a classification algorithm to enhance the performance of automated ECG classification to determine arrhythmic heart beats based on noisy ECG signals. The four novel techniques are evaluated in comparison with benchmark algorithms for each task on the standard MIT-BIH Arrhythmia Database and with data generated from patients in a major hospital using Shimmer3 wearable ECG sensors. The four techniques are integrated to demonstrate that remote patient monitoring of ECG using HRV and ECG features is feasible in real time using minimal computational resources. The evaluation show that the ECG reduction algorithm is significantly better than existing algorithms that can be applied within sensor nodes, such as time-domain methods, transformation methods and compressed sensing methods. Furthermore, the proposed ECG reduction is found to be computationally less complex for resource constrained sensors and achieves higher compression ratios than existing algorithms. The prediction of a common HRV measure, the five-minute standard deviation of inter-beat variations (SDNN) and the accurate detection of PVC beats was achieved using a Count Data Model, combined with a Poisson-generated function from three-minute ECG recordings. This was achieved with minimal computational resources and was well suited to remote patient monitoring with wearable sensors. The PVC beats detection was implemented using the same count data model together with knowledge-based rules derived from clinical knowledge. A real-time cardiac patient monitoring system was implemented using an ECG sensor and smartphone to detect PVC beats within a few seconds using artificial neural networks (ANN), and it was proven to provide highly accurate results. The automated detection and classification were implemented using a new wrapper-based hybrid approach that utilized t-distributed stochastic neighbour embedding (t-SNE) in combination with self-organizing maps (SOM) to improve classification performance. The t-SNE-SOM hybrid resulted in improved sensitivity, specificity and accuracy compared to most common hybrid methods in the presence of noise. It also provided a better, more accurate identification for the presence of many types of arrhythmias from the ECG recordings, leading to a more timely diagnosis and treatment outcome.Doctor of Philosoph