EDMON - Electronic Disease Surveillance and Monitoring Network: A Personalized Health Model-based Digital Infectious Disease Detection Mechanism using Self-Recorded Data from People with Type 1 Diabetes

Through time, we as a society have been tested with infectious disease outbreaks of different magnitude, which often pose major public health challenges. To mitigate the challenges, research endeavors have been focused on early detection mechanisms through identifying potential data sources, mode of data collection and transmission, case and outbreak detection methods. Driven by the ubiquitous nature of smartphones and wearables, the current endeavor is targeted towards individualizing the surveillance effort through a personalized health model, where the case detection is realized by exploiting self-collected physiological data from wearables and smartphones. This dissertation aims to demonstrate the concept of a personalized health model as a case detector for outbreak detection by utilizing self-recorded data from people with type 1 diabetes. The results have shown that infection onset triggers substantial deviations, i.e. prolonged hyperglycemia regardless of higher insulin injections and fewer carbohydrate consumptions. Per the findings, key parameters such as blood glucose level, insulin, carbohydrate, and insulin-to-carbohydrate ratio are found to carry high discriminative power. A personalized health model devised based on a one-class classifier and unsupervised method using selected parameters achieved promising detection performance. Experimental results show the superior performance of the one-class classifier and, models such as one-class support vector machine, k-nearest neighbor and, k-means achieved better performance. Further, the result also revealed the effect of input parameters, data granularity, and sample sizes on model performances. The presented results have practical significance for understanding the effect of infection episodes amongst people with type 1 diabetes, and the potential of a personalized health model in outbreak detection settings. The added benefit of the personalized health model concept introduced in this dissertation lies in its usefulness beyond the surveillance purpose, i.e. to devise decision support tools and learning platforms for the patient to manage infection-induced crises

Detecting Chronic Diseases from Sleep-Wake Behaviour and Clinical Features

The file attached to this record is the author's final peer reviewed version.Many chronic diseases show evidence of correlations with sleep-wake behaviour, and there is an increasing interest in making use of such correlations for early warning systems. This research presents an approach towards early chronic disease detection by mining sleep-wake measurements using deep learning. Specifically, a Long-Short-Term-Memory network is applied on actigraph data enriched with clinical history of patients. Experiments and analysis are performed targeting detection at an early and advanced disease stage based on different clinical data features. The results show for disease detection an averaged accuracy of 0:62, 0:73, 0:81, 0:77 for hypertension, diabetes, sleep apnea and chronic kidney disease, respectively. Early detection performs with an averaged accuracy of 0:49 for sleep apnea and 0:56 for diabetes. Nevertheless, compared to existing work, our approach shows an improvement in performance and demonstrates that predicting chronic diseases from sleep-wake behavior is feasible, though further investigation will be needed for early prediction

State of the art of audio- and video based solutions for AAL

Working Group 3. Audio- and Video-based AAL ApplicationsIt is a matter of fact that Europe is facing more and more crucial challenges regarding health and social care due to the demographic change and the current economic context. The recent COVID-19 pandemic has stressed this situation even further, thus highlighting the need for taking action. Active and Assisted Living (AAL) technologies come as a viable approach to help facing these challenges, thanks to the high potential they have in enabling remote care and support. Broadly speaking, AAL can be referred to as the use of innovative and advanced Information and Communication Technologies to create supportive, inclusive and empowering applications and environments that enable older, impaired or frail people to live independently and stay active longer in society. AAL capitalizes on the growing pervasiveness and effectiveness of sensing and computing facilities to supply the persons in need with smart assistance, by responding to their necessities of autonomy, independence, comfort, security and safety. The application scenarios addressed by AAL are complex, due to the inherent heterogeneity of the end-user population, their living arrangements, and their physical conditions or impairment. Despite aiming at diverse goals, AAL systems should share some common characteristics. They are designed to provide support in daily life in an invisible, unobtrusive and user-friendly manner. Moreover, they are conceived to be intelligent, to be able to learn and adapt to the requirements and requests of the assisted people, and to synchronise with their specific needs. Nevertheless, to ensure the uptake of AAL in society, potential users must be willing to use AAL applications and to integrate them in their daily environments and lives. In this respect, video- and audio-based AAL applications have several advantages, in terms of unobtrusiveness and information richness. Indeed, cameras and microphones are far less obtrusive with respect to the hindrance other wearable sensors may cause to one’s activities. In addition, a single camera placed in a room can record most of the activities performed in the room, thus replacing many other non-visual sensors. Currently, video-based applications are effective in recognising and monitoring the activities, the movements, and the overall conditions of the assisted individuals as well as to assess their vital parameters (e.g., heart rate, respiratory rate). Similarly, audio sensors have the potential to become one of the most important modalities for interaction with AAL systems, as they can have a large range of sensing, do not require physical presence at a particular location and are physically intangible. Moreover, relevant information about individuals’ activities and health status can derive from processing audio signals (e.g., speech recordings). Nevertheless, as the other side of the coin, cameras and microphones are often perceived as the most intrusive technologies from the viewpoint of the privacy of the monitored individuals. This is due to the richness of the information these technologies convey and the intimate setting where they may be deployed. Solutions able to ensure privacy preservation by context and by design, as well as to ensure high legal and ethical standards are in high demand. After the review of the current state of play and the discussion in GoodBrother, we may claim that the first solutions in this direction are starting to appear in the literature. A multidisciplinary 4 debate among experts and stakeholders is paving the way towards AAL ensuring ergonomics, usability, acceptance and privacy preservation. The DIANA, PAAL, and VisuAAL projects are examples of this fresh approach. This report provides the reader with a review of the most recent advances in audio- and video-based monitoring technologies for AAL. It has been drafted as a collective effort of WG3 to supply an introduction to AAL, its evolution over time and its main functional and technological underpinnings. In this respect, the report contributes to the field with the outline of a new generation of ethical-aware AAL technologies and a proposal for a novel comprehensive taxonomy of AAL systems and applications. Moreover, the report allows non-technical readers to gather an overview of the main components of an AAL system and how these function and interact with the end-users. The report illustrates the state of the art of the most successful AAL applications and functions based on audio and video data, namely (i) lifelogging and self-monitoring, (ii) remote monitoring of vital signs, (iii) emotional state recognition, (iv) food intake monitoring, activity and behaviour recognition, (v) activity and personal assistance, (vi) gesture recognition, (vii) fall detection and prevention, (viii) mobility assessment and frailty recognition, and (ix) cognitive and motor rehabilitation. For these application scenarios, the report illustrates the state of play in terms of scientific advances, available products and research project. The open challenges are also highlighted. The report ends with an overview of the challenges, the hindrances and the opportunities posed by the uptake in real world settings of AAL technologies. In this respect, the report illustrates the current procedural and technological approaches to cope with acceptability, usability and trust in the AAL technology, by surveying strategies and approaches to co-design, to privacy preservation in video and audio data, to transparency and explainability in data processing, and to data transmission and communication. User acceptance and ethical considerations are also debated. Finally, the potentials coming from the silver economy are overviewed.publishedVersio

Deep Risk Prediction and Embedding of Patient Data: Application to Acute Gastrointestinal Bleeding

Acute gastrointestinal bleeding is a common and costly condition, accounting for over 2.2 million hospital days and 19.2 billion dollars of medical charges annually. Risk stratification is a critical part of initial assessment of patients with acute gastrointestinal bleeding. Although all national and international guidelines recommend the use of risk-assessment scoring systems, they are not commonly used in practice, have sub-optimal performance, may be applied incorrectly, and are not easily updated. With the advent of widespread electronic health record adoption, longitudinal clinical data captured during the clinical encounter is now available. However, this data is often noisy, sparse, and heterogeneous. Unsupervised machine learning algorithms may be able to identify structure within electronic health record data while accounting for key issues with the data generation process: measurements missing-not-at-random and information captured in unstructured clinical note text. Deep learning tools can create electronic health record-based models that perform better than clinical risk scores for gastrointestinal bleeding and are well-suited for learning from new data. Furthermore, these models can be used to predict risk trajectories over time, leveraging the longitudinal nature of the electronic health record. The foundation of creating relevant tools is the definition of a relevant outcome measure; in acute gastrointestinal bleeding, a composite outcome of red blood cell transfusion, hemostatic intervention, and all-cause 30-day mortality is a relevant, actionable outcome that reflects the need for hospital-based intervention. However, epidemiological trends may affect the relevance and effectiveness of the outcome measure when applied across multiple settings and patient populations. Understanding the trends in practice, potential areas of disparities, and value proposition for using risk stratification in patients presenting to the Emergency Department with acute gastrointestinal bleeding is important in understanding how to best implement a robust, generalizable risk stratification tool. Key findings include a decrease in the rate of red blood cell transfusion since 2014 and disparities in access to upper endoscopy for patients with upper gastrointestinal bleeding by race/ethnicity across urban and rural hospitals. Projected accumulated savings of consistent implementation of risk stratification tools for upper gastrointestinal bleeding total approximately $1 billion 5 years after implementation. Most current risk scores were designed for use based on the location of the bleeding source: upper or lower gastrointestinal tract. However, the location of the bleeding source is not always clear at presentation. I develop and validate electronic health record based deep learning and machine learning tools for patients presenting with symptoms of acute gastrointestinal bleeding (e.g., hematemesis, melena, hematochezia), which is more relevant and useful in clinical practice. I show that they outperform leading clinical risk scores for upper and lower gastrointestinal bleeding, the Glasgow Blatchford Score and the Oakland score. While the best performing gradient boosted decision tree model has equivalent overall performance to the fully connected feedforward neural network model, at the very low risk threshold of 99% sensitivity the deep learning model identifies more very low risk patients. Using another deep learning model that can model longitudinal risk, the long-short-term memory recurrent neural network, need for transfusion of red blood cells can be predicted at every 4-hour interval in the first 24 hours of intensive care unit stay for high risk patients with acute gastrointestinal bleeding. Finally, for implementation it is important to find patients with symptoms of acute gastrointestinal bleeding in real time and characterize patients by risk using available data in the electronic health record. A decision rule-based electronic health record phenotype has equivalent performance as measured by positive predictive value compared to deep learning and natural language processing-based models, and after live implementation appears to have increased the use of the Acute Gastrointestinal Bleeding Clinical Care pathway. Patients with acute gastrointestinal bleeding but with other groups of disease concepts can be differentiated by directly mapping unstructured clinical text to a common ontology and treating the vector of concepts as signals on a knowledge graph; these patients can be differentiated using unbalanced diffusion earth mover’s distances on the graph. For electronic health record data with data missing not at random, MURAL, an unsupervised random forest-based method, handles data with missing values and generates visualizations that characterize patients with gastrointestinal bleeding. This thesis forms a basis for understanding the potential for machine learning and deep learning tools to characterize risk for patients with acute gastrointestinal bleeding. In the future, these tools may be critical in implementing integrated risk assessment to keep low risk patients out of the hospital and guide resuscitation and timely endoscopic procedures for patients at higher risk for clinical decompensation

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

The 2023 wearable photoplethysmography roadmap

Photoplethysmography is a key sensing technology which is used in wearable devices such as smartwatches and fitness trackers. Currently, photoplethysmography sensors are used to monitor physiological parameters including heart rate and heart rhythm, and to track activities like sleep and exercise. Yet, wearable photoplethysmography has potential to provide much more information on health and wellbeing, which could inform clinical decision making. This Roadmap outlines directions for research and development to realise the full potential of wearable photoplethysmography. Experts discuss key topics within the areas of sensor design, signal processing, clinical applications, and research directions. Their perspectives provide valuable guidance to researchers developing wearable photoplethysmography technology

Unsupervised machine learning of high dimensional data for patient stratification

The development mechanisms of numerous complex, rare diseases are largely unknown to scientists partly due to their multifaceted heterogeneity. Stratifying patients is becoming a very important objective as we further research that inherent heterogeneity which can be utilised towards personalised medicine. However, considerable difficulties slow down accurate patient stratification mainly represented by outdated clinical criteria, weak associations or simple symptom categories. Fortunately, immense steps have been taken towards multiple omic data generation and utilisation aiming to produce new insights as in exploratory machine learning which showed the potential to identify the source of disease mechanisms from patient subgroups. This work describes the development of a modular clustering toolkit, named Omada, designed to assist researchers in exploring disease heterogeneity without extensive expertise in the machine learning field. Subsequently, it assesses Omada’s capabilities and validity by testing the toolkit on multiple data modalities from pulmonary hypertension (PH) patients. I first demonstrate the toolkit’s ability to create biologically meaningful subgroups based on whole blood RNA-seq data from H/IPAH patients in the manuscript “Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood”. Our work on the manuscript titled “Diagnostic miRNA signatures for treatable forms of pulmonary hypertension highlight challenges with clinical classification” aimed to apply the same clustering approach on a PH microRNA dataset as a first step in forming microRNA diagnostic signatures by recognising the potential of microRNA expression in identifying diverse disease sub-populations irrespectively of pre-existing PH classes. The toolkit’s effectiveness on metabolite data was also tested. Lastly, a longitudinal clustering approach was explored on activity readouts from wearables on COVID-19 patients as part of our manuscript “Unsupervised machine learning identifies and associates trajectory patterns of COVID-19 symptoms and physical activity measured via a smart watch”. Two clusters of high and low activity trajectories were generated and associated with symptom classes showing a weak but interesting relationship between the two. In summary, this thesis is examining the potential of patient stratification based on several data types from patients that represent a new, unseen picture of disease mechanisms. The tools presented provide important indications of distinct patient groups and could generate the insights needed for further targeted research and clinical associations that can help towards understanding rare, complex diseases