Statistical methods for NHS incident reporting data

The National Reporting and Learning System (NRLS) is the English and Welsh NHS’ national repository of incident reports from healthcare. It aims to capture details of incident reports, at national level, and facilitate clinical review and learning to improve patient safety. These incident reports range from minor ‘near-misses’ to critical incidents that may lead to severe harm or death. NRLS data are currently reported as crude counts and proportions, but their major use is clinical review of the free-text descriptions of incidents. There are few well-developed quantitative analysis approaches for NRLS, and this thesis investigates these methods. A literature review revealed a wealth of clinical detail, but also systematic constraints of NRLS’ structure, including non-mandatory reporting, missing data and misclassification. Summary statistics for reports from 2010/11 – 2016/17 supported this and suggest NRLS was not suitable for statistical modelling in isolation. Modelling methods were advanced by creating a hybrid dataset using other sources of hospital casemix data from Hospital Episode Statistics (HES). A theoretical model was established, based on ‘exposure’ variables (using casemix proxies), and ‘culture’ as a random-effect. The initial modelling approach examined Poisson regression, mixture and multilevel models. Overdispersion was significant, generated mainly by clustering and aggregation in the hybrid dataset, but models were chosen to reflect these structures. Further modelling approaches were examined, using Generalized Additive Models to smooth predictor variables, regression tree-based models including Random Forests, and Artificial Neural Networks. Models were also extended to examine a subset of death and severe harm incidents, exploring how sparse counts affect models. Text mining techniques were examined for analysis of incident descriptions and showed how term frequency might be used. Terms were used to generate latent topics models used, in-turn, to predict the harm level of incidents. Model outputs were used to create a ‘Standardised Incident Reporting Ratio’ (SIRR) and cast this in the mould of current regulatory frameworks, using process control techniques such as funnel plots and cusum charts. A prototype online reporting tool was developed to allow NHS organisations to examine their SIRRs, provide supporting analyses, and link data points back to individual incident reports

Quantitative Magnetic Resonance Imaging Techniques for the Measurement of Organ Fat and Body Composition - Validation and Initial Clinical Utility

Ectopic fat is defined by excess deposition of triglycerides in non-adipose tissues that normally contain only small amounts of fat. Measuring the distribution of ectopic fat is important for understanding the pathogenesis of diseases such as obesity and type 2 diabetes mellitus (T2DM) and understanding variation in treatment response amongst patients. Body composition (the proportion of fat and lean mass in the body) is thought to influence both the development of T2DM and outcomes for treatments such as weight-loss surgery. It can also affect clinical outcomes in chronic diseases and malignancy. Quantitative magnetic resonance imaging (qMRI) enables objective measurements of tissue characteristics to be made directly from acquired data. In this thesis, a qMRI protocol based on chemical shift-encoded (CSE)-MRI, specifically the derived proton density fat fraction (PDFF) measurements, was validated against phantoms, and in volunteers and patients with obesity. A new, semi-automated tool for measurement of body composition from CSE-MRI images was developed and validated. CSE-MRI was used to quantify ectopic organ fat depots and body composition in diseases including obesity, T2DM and cancer. Specifically, differences in organ fat between patients with and without remission of T2DM after bariatric surgery was explored. Body composition was investigated in T2DM remission and it was also compared between patients with colorectal and lung cancer undergoing whole body MRI staging. Data from the pilot phase of a study investigating a new duodenal surfacing procedural treatment for T2DM (Revita-2) is presented, demonstrating the utility of hepatic fat content measured using PDFF as an endpoint in an international, multi-centre clinical trial. Finally, I describe the development of a novel technique for quantification of bone mineral density (BMD) using CSE-MRI techniques. The methodology and tools described in this thesis could be used to measure ectopic fat and body composition in future studies and have the potential for integration into clinical care pathways

Statistical Modelling

The book collects the proceedings of the 19th International Workshop on Statistical Modelling held in Florence on July 2004. Statistical modelling is an important cornerstone in many scientific disciplines, and the workshop has provided a rich environment for cross-fertilization of ideas from different disciplines. It consists in four invited lectures, 48 contributed papers and 47 posters. The contributions are arranged in sessions: Statistical Modelling; Statistical Modelling in Genomics; Semi-parametric Regression Models; Generalized Linear Mixed Models; Correlated Data Modelling; Missing Data, Measurement of Error and Survival Analysis; Spatial Data Modelling and Time Series and Econometrics

Hilbert-Huang Transform: biosignal analysis and practical implementation

Any system, however trivial, is subjected to data analysis on the signals it produces. Over the last 50 years the influx of new techniques and expansions of older ones have allowed a number of new applications, in a variety of fields, to be analysed and to some degree understood. One of the industries that is benefiting from this growth is the medical field and has been further progressed with the growth of interdisciplinary collaboration. From a signal processing perspective, the challenge comes from the complex and sometimes chaotic nature of the signals that we measure from the body, such as those from the brain and to some degree the heart. In this work we will make a contribution to dealing with such systems, in the form of a recent time-frequency data analysis method, the Hilbert-Huang Transform (HHT), and extensions to it. This thesis presents an analysis of the state of the art in seizure and heart arrhythmia detection and prediction methods. We then present a novel real-time implementation of the algorithm both in software and hardware and the motivations for doing so. First, we present our software implementation, encompassing realtime capabilities and identifying elements that need to be considered for practical use. We then translated this software into hardware to aid real-time implementation and integration. With these implementations in place we apply the HHT method to the topic of epilepsy (seizures) and additionally make contributions to heart arrhythmias and neonate brain dynamics. We use the HHT and some additional algorithms to quantify features associated with each application for detection and prediction. We also quantify significance of activity in such a way as to merge prediction and detection into one framework. Finally, we assess the real-time capabilities of our methods for practical use as a biosignal analysis tool

Artificial Intelligence for Data Analysis and Signal Processing

Artificial intelligence, or AI, currently encompasses a huge variety of fields, from areas such as logical reasoning and perception, to specific tasks such as game playing, language processing, theorem proving, and diagnosing diseases. It is clear that systems with human-level intelligence (or even better) would have a huge impact on our everyday lives and on the future course of evolution, as it is already happening in many ways. In this research AI techniques have been introduced and applied in several clinical and real world scenarios, with particular focus on deep learning methods. A human gait identification system based on the analysis of inertial signals has been developed, leading to misclassification rates smaller than 0.15%. Advanced deep learning architectures have been also investigated to tackle the problem of atrial fibrillation detection from short length and noisy electrocardiographic signals. The results show a clear improvement provided by representation learning over a knowledge-based approach. Another important clinical challenge, both for the patient and on-board automatic alarm systems, is to detect with reasonable advance the patterns leading to risky situations, allowing the patient to take therapeutic decisions on the basis of future instead of current information. This problem has been specifically addressed for the prediction of critical hypo/hyperglycemic episodes from continuous glucose monitoring devices, carrying out a comparative analysis among the most successful methods for glucose event prediction. This dissertation also shows evidence of the benefits of learning algorithms for vehicular traffic anomaly detection, through the use of a statistical Bayesian framework, and for the optimization of video streaming user experience, implementing an intelligent adaptation engine for video streaming clients. The proposed solution explores the promising field of deep learning methods integrated with reinforcement learning schema, showing its benefits against other state of the art approaches. The great knowledge transfer capability of artificial intelligence methods and the benefits of representation learning systems stand out from this research, representing the common thread among all the presented research fields

Dynamical models of the mammalian target of rapamycin network in ageing

Phd ThesisThe mammalian Target of Rapamycin (mTOR)kinase is a central regulator of cellular growth and metabolism and plays an important role in ageing and age- related diseases. The increase of invitro data collected to extend our knowledge on its regulation, and consequently improve drug intervention,has highlighted the complexity of the mTOR network. This complexity is also aggravated by the intrinsic time-dependent nature of cellular regulatory network cross-talks and feedbacks. Systems biology constitutes a powerful tool for mathematically for- malising biological networks and investigating such dynamical properties. The present work discusses the development of three dynamical models of the mTOR network. The first aimed at the analysis of the current literature-based hypotheses of mTOR Complex2(mTORC2)regulation. For each hypothesis, the model predicted specific differential dynamics which were systematically tested by invitro experiments. Surprisingly, nocurrent hypothesis could explain the data and a new hypothesis of mTORC2 activation was proposed.The second model extended the previous one with an AMPK module. In this study AMPK was reported to be activated by insulin. Using a hypothesis ranking approach based on model goodness-of-fit, AMPK activity was insilico predicted and in vitro tested to be activated by the insulin receptor substrate(IRS).Finally,the last model linked mTOR with the oxidative stress response, mitochondrial reg- ulation, DNA damage and FoxO transcription factors. This work provided the characterisation of a dynamical mechanism to explain the state transition from normal to senescent cells and their reversibility of the senescentphenotype.European Council 6FP NoE LifeSpan, School of the Faculty of Medical Sciences, Newcastle Universit