Patient Record Summarization Through Joint Phenotype Learning and Interactive Visualization

Complex patient are becoming more and more of a challenge to the health care system given the amount of care they require and the amount of documentation needed to keep track of their state of health and treatment. Record keeping using the EHR makes this easier but mounting amounts of patient data also means that clinicians are faced with information overload. Information overload has been shown to have deleterious effects on care, with increased safety concerns due to missed information. Patient record summarization has been a promising mitigator for information overload. Subsequently, a lot of research has been dedicated to record summarization since the introduction of EHRs. In this dissertation we examine whether unsupervised inference methods can derive patient problem-oriented summaries, that are robust to different patients. By grounding our experiments with HIV patients we leverage the data of a group of patients that are similar in that they share one common disease (HIV) but also exhibit complex histories of diverse comorbidities. Using a user-centered, iterative design process, we design an interactive, longitudinal patient record summarization tool, that leverages automated inferences about the patient's problems. We find that unsupervised, joint learning of problems using correlated topic models, adapted to handle the multiple data types (structured and unstructured) of the EHR, is successful in identifying the salient problems of complex patients. Utilizing interactive visualization that exposes inference results to users enables them to make sense of a patient's problems over time and to answer questions about a patient more accurately and faster than using the EHR alone

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Digital phenotyping through multimodal, unobtrusive sensing

The growing adoption of multimodal wearable and mobile devices, such as smartphones and wrist-worn watches has generated an increase in the collection of physiological and behavioural data at scale. This digital phenotyping data enables researchers to make inferences regarding users’ physical and mental health at scale, for the first time. However, translating this data into actionable insights requires computational approaches that turn unlabelled, multimodal time-series sensor data into validated measures that can be interpreted at scale. This thesis describes the derivation of novel computational methods that leverage digital phenotyping data from wearable devices in large-scale populations to infer physical behaviours. These methods combine insights from signal processing, data mining and machine learning alongside domain knowledge in physical activity and sleep epidemiology. First, the inference of sleeping windows in free-living conditions through a heart rate sensing approach is explored. This algorithm is particularly valuable in the absence of ground truth or sleep diaries given its simplicity, adaptability and capacity for personalization. I then explore multistage sleep classification through combined movement and cardiac wearable sensing and machine learning. Further, I demonstrate that postural changes detected through wrist accelerometers can inform habitual behaviours and are valuable complements to traditional, intensity-based physical activity metrics. I then leverage the concomitant responses of heart rate to physical activity that can be captured through multimodal wearable sensors through a self-supervised training task. The resulting embeddings from this task are shown to be useful for the downstream classification of demographic factors, BMI, energy expenditure and cardiorespiratory fitness. Finally, I describe a deep learning model for the adaptive inference of cardiorespiratory fitness (VO2max) using wearable data in free living conditions. I demonstrate the robustness of the model in a large UK population and show the models’ adaptability by evaluating its performance in a subset of the population with repeated measures ~6 years after the original recordings. Together, this work increases the potential of multimodal wearable and mobile sensors for physical activity and behavioural inferences in population studies. In particular, this thesis showcases the potential of using wearable devices to make valuable physical activity, sleep and fitness inferences in large cohort studies. Given the nature of the data collected and the fact that most of this data is currently generated by commercial providers and not research institutes, laying the foundations for responsible data governance and ethical use of these technologies will be critical to building trust and enabling the development of the field of digital phenotyping.I was funded by GlaxoSmithKline and the Engineering and Physical Sciences Research Council. I was also supported by the Alan Turing Institute through their Enrichment Scheme

Digital Traces of the Mind::Using Smartphones to Capture Signals of Well-Being in Individuals

General context and questions Adolescents and young adults typically use their smartphone several hours a day. Although there are concerns about how such behaviour might affect their well-being, the popularity of these powerful devices also opens novel opportunities for monitoring well-being in daily life. If successful, monitoring well-being in daily life provides novel opportunities to develop future interventions that provide personalized support to individuals at the moment they require it (just-in-time adaptive interventions). Taking an interdisciplinary approach with insights from communication, computational, and psychological science, this dissertation investigated the relation between smartphone app use and well-being and developed machine learning models to estimate an individual’s well-being based on how they interact with their smartphone. To elucidate the relation between smartphone trace data and well-being and to contribute to the development of technologies for monitoring well-being in future clinical practice, this dissertation addressed two overarching questions:RQ1: Can we find empirical support for theoretically motivated relations between smartphone trace data and well-being in individuals? RQ2: Can we use smartphone trace data to monitor well-being in individuals?Aims The first aim of this dissertation was to quantify the relation between the collected smartphone trace data and momentary well-being at the sample level, but also for each individual, following recent conceptual insights and empirical findings in psychological, communication, and computational science. A strength of this personalized (or idiographic) approach is that it allows us to capture how individuals might differ in how smartphone app use is related to their well-being. Considering such interindividual differences is important to determine if some individuals might potentially benefit from spending more time on their smartphone apps whereas others do not or even experience adverse effects. The second aim of this dissertation was to develop models for monitoring well-being in daily life. The present work pursued this transdisciplinary aim by taking a machine learning approach and evaluating to what extent we might estimate an individual’s well-being based on their smartphone trace data. If such traces can be used for this purpose by helping to pinpoint when individuals are unwell, they might be a useful data source for developing future interventions that provide personalized support to individuals at the moment they require it (just-in-time adaptive interventions). With this aim, the dissertation follows current developments in psychoinformatics and psychiatry, where much research resources are invested in using smartphone traces and similar data (obtained with smartphone sensors and wearables) to develop technologies for detecting whether an individual is currently unwell or will be in the future. Data collection and analysis This work combined novel data collection techniques (digital phenotyping and experience sampling methodology) for measuring smartphone use and well-being in the daily lives of 247 student participants. For a period up to four months, a dedicated application installed on participants’ smartphones collected smartphone trace data. In the same time period, participants completed a brief smartphone-based well-being survey five times a day (for 30 days in the first month and 30 days in the fourth month; up to 300 assessments in total). At each measurement, this survey comprised questions about the participants’ momentary level of procrastination, stress, and fatigue, while sleep duration was measured in the morning. Taking a time-series and machine learning approach to analysing these data, I provide the following contributions: Chapter 2 investigates the person-specific relation between passively logged usage of different application types and momentary subjective procrastination, Chapter 3 develops machine learning methodology to estimate sleep duration using smartphone trace data, Chapter 4 combines machine learning and explainable artificial intelligence to discover smartphone-tracked digital markers of momentary subjective stress, Chapter 5 uses a personalized machine learning approach to evaluate if smartphone trace data contains behavioral signs of fatigue. Collectively, these empirical studies provide preliminary answers to the overarching questions of this dissertation.Summary of results With respect to the theoretically motivated relations between smartphone trace data and wellbeing (RQ1), we found that different patterns in smartphone trace data, from time spent on social network, messenger, video, and game applications to smartphone-tracked sleep proxies, are related to well-being in individuals. The strength and nature of this relation depends on the individual and app usage pattern under consideration. The relation between smartphone app use patterns and well-being is limited in most individuals, but relatively strong in a minority. Whereas some individuals might benefit from using specific app types, others might experience decreases in well-being when spending more time on these apps. With respect to the question whether we might use smartphone trace data to monitor well-being in individuals (RQ2), we found that smartphone trace data might be useful for this purpose in some individuals and to some extent. They appear most relevant in the context of sleep monitoring (Chapter 3) and have the potential to be included as one of several data sources for monitoring momentary procrastination (Chapter 2), stress (Chapter 4), and fatigue (Chapter 5) in daily life. Outlook Future interdisciplinary research is needed to investigate whether the relationship between smartphone use and well-being depends on the nature of the activities performed on these devices, the content they present, and the context in which they are used. Answering these questions is essential to unravel the complex puzzle of developing technologies for monitoring well-being in daily life.<br/

Generating Reliable and Responsive Observational Evidence: Reducing Pre-analysis Bias

A growing body of evidence generated from observational data has demonstrated the potential to influence decision-making and improve patient outcomes. For observational evidence to be actionable, however, it must be generated reliably and in a timely manner. Large distributed observational data networks enable research on diverse patient populations at scale and develop new sound methods to improve reproducibility and robustness of real-world evidence. Nevertheless, the problems of generalizability, portability and scalability persist and compound. As analytical methods only partially address bias, reliable observational research (especially in networks) must address the bias at the design stage (i.e., pre-analysis bias) including the strategies for identifying patients of interest and defining comparators. This thesis synthesizes and enumerates a set of challenges to addressing pre-analysis bias in observational studies and presents mixed-methods approaches and informatics solutions for overcoming a number of those obstacles. We develop frameworks, methods and tools for scalable and reliable phenotyping including data source granularity estimation, comprehensive concept set selection, index date specification, and structured data-based patient review for phenotype evaluation. We cover the research on potential bias in the unexposed comparator definition including systematic background rates estimation and interpretation, and definition and evaluation of the unexposed comparator. We propose that the use of standardized approaches and methods as described in this thesis not only improves reliability but also increases responsiveness of observational evidence. To test this hypothesis, we designed and piloted a Data Consult Service - a service that generates new on-demand evidence at the bedside. We demonstrate that it is feasible to generate reliable evidence to address clinicians’ information needs in a robust and timely fashion and provide our analysis of the current limitations and future steps needed to scale such a service

Artificial Intelligence in Oncology Drug Discovery and Development

There exists a profound conflict at the heart of oncology drug development. The efficiency of the drug development process is falling, leading to higher costs per approved drug, at the same time personalised medicine is limiting the target market of each new medicine. Even as the global economic burden of cancer increases, the current paradigm in drug development is unsustainable. In this book, we discuss the development of techniques in machine learning for improving the efficiency of oncology drug development and delivering cost-effective precision treatment. We consider how to structure data for drug repurposing and target identification, how to improve clinical trials and how patients may view artificial intelligence

A Survey of Multimodal Information Fusion for Smart Healthcare: Mapping the Journey from Data to Wisdom

Multimodal medical data fusion has emerged as a transformative approach in smart healthcare, enabling a comprehensive understanding of patient health and personalized treatment plans. In this paper, a journey from data to information to knowledge to wisdom (DIKW) is explored through multimodal fusion for smart healthcare. We present a comprehensive review of multimodal medical data fusion focused on the integration of various data modalities. The review explores different approaches such as feature selection, rule-based systems, machine learning, deep learning, and natural language processing, for fusing and analyzing multimodal data. This paper also highlights the challenges associated with multimodal fusion in healthcare. By synthesizing the reviewed frameworks and theories, it proposes a generic framework for multimodal medical data fusion that aligns with the DIKW model. Moreover, it discusses future directions related to the four pillars of healthcare: Predictive, Preventive, Personalized, and Participatory approaches. The components of the comprehensive survey presented in this paper form the foundation for more successful implementation of multimodal fusion in smart healthcare. Our findings can guide researchers and practitioners in leveraging the power of multimodal fusion with the state-of-the-art approaches to revolutionize healthcare and improve patient outcomes.Comment: This work has been submitted to the ELSEVIER for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl