Personalised antimicrobial management in secondary care

Background: The growing threat of Antimicrobial Resistance (AMR) requires innovative methods to promote the sustainable effectiveness of antimicrobial agents. Hypothesis: This thesis aimed to explore the hypothesis that personalised decision support interventions have the utility to enhance antimicrobial management across secondary care. Methods: Different research methods were used to investigate this hypothesis. Individual physician decision making was mapped and patient experiences of engagement with decision making explored using semi-structured interviews. Cross-specialty engagement with antimicrobial management was investigated through cross-sectional analysis of conference abstracts and educational training curricula. Artificial intelligence tools were developed to explore their ability to predict the likelihood of infection and provide individualised prescribing recommendations using routine patient data. Dynamic, individualised dose optimisation was explored through: (i) development of a microneedle based, electrochemical biosensor for minimally invasive monitoring of beta-lactams; and (ii) pharmacokinetic (PK)-pharmacodynamic (PD) modelling of a new PK-PD index using C-Reactive protein (CRP) to predict the pharmacodynamics of vancomycin. Ethics approval was granted for all aspects of work explored within this thesis. Results: Mapping of individual physician decision making during infection management demonstrated several areas where personalised, technological interventions could enhance antimicrobial management. At specialty level, non-infection specialties have little engagement with antimicrobial management. The importance of engaging surgical specialties, who have relatively high rates of antimicrobial usage and healthcare associated infections, was observed. An individualised information leaflet, co-designed with patients, to provide personalised infection information to in-patients receiving antibiotics significantly improved knowledge and reported engagement with decision making. Artificial intelligence was able to enhance the prediction of infection and the prescribing of antimicrobials using routinely available clinical data. Real-time, continuous penicillin monitoring was demonstrated using a microneedle based electrochemical sensor in-vivo. A new PK-PD index, using C-Reactive Protein, was able to predict individual patient response to vancomycin therapy at 96-120 hours of therapy. Conclusion: Through co-design and the application of specific technologies it is possible to provide personalised antimicrobial management within secondary care.Open Acces

Modelling mobile health systems: an application of augmented MDA for the extended healthcare enterprise

Mobile health systems can extend the enterprise computing system of the healthcare provider by bringing services to the patient any time and anywhere. We propose a model-driven design and development methodology for the development of the m-health components in such extended enterprise computing systems. The methodology applies a model-driven design and development approach augmented with formal validation and verification to address quality and correctness and to support model transformation. Recent work on modelling applications from the healthcare domain is reported. One objective of this work is to explore and elaborate the proposed methodology. At the University of Twente we are developing m-health systems based on Body Area Networks (BANs). One specialization of the generic BAN is the health BAN, which incorporates a set of devices and associated software components to provide some set of health-related services. A patient will have a personalized instance of the health BAN customized to their current set of needs. A health professional interacts with their\ud patients¿ BANs via a BAN Professional System. The set of deployed BANs are supported by a server. We refer to this distributed system as the BAN System. The BAN system extends the enterprise computing system of the healthcare provider. Development of such systems requires a sound software engineering approach and this is what we explore with the new methodology. The methodology is illustrated with reference to recent modelling activities targeted at real implementations. In the context of the Awareness project BAN implementations will be trialled in a number of clinical settings including epilepsy management and management of chronic pain

Monitoring and detection of agitation in dementia: towards real-time and big-data solutions

The changing demographic profile of the population has potentially challenging social, geopolitical, and financial consequences for individuals, families, the wider society, and governments globally. The demographic change will result in a rapidly growing elderly population with healthcare implications which importantly include Alzheimer type conditions (a leading cause of dementia). Dementia requires long term care to manage the negative behavioral symptoms which are primarily exhibited in terms of agitation and aggression as the condition develops. This paper considers the nature of dementia along with the issues and challenges implicit in its management. The Behavioral and Psychological Symptoms of Dementia (BPSD) are introduced with factors (precursors) to the onset of agitation and aggression. Independent living is considered, health monitoring and implementation in context-aware decision-support systems is discussed with consideration of data analytics. Implicit in health monitoring are technical and ethical constraints, we briefly consider these constraints with the ability to generalize to a range of medical conditions. We postulate that health monitoring offers exciting potential opportunities however the challenges lie in the effective realization of independent assisted living while meeting the ethical challenges, achieving this remains an open research question remains.Peer ReviewedPostprint (author's final draft

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Smartphone-based safety planning and self-monitoring for suicidal patients: Rationale and study protocol of the CASPAR (Continuous Assessment for Suicide Prevention And Research) study

Background: It remains difficult to predict and prevent suicidal behaviour, despite growing understanding of the aetiology of suicidality. Clinical guidelines recommend that health care professionals develop a safety plan in collaboration with their high-risk patients, to lower the imminent risk of suicidal behaviour. Mobile health applications provide new opportunities for safety planning, and enable daily self-monitoring of suicide-related symptoms that may enhance safety planning. This paper presents the rationale and protocol of the Continuous Assessment for Suicide Prevention And Research (CASPAR) study. The aim of the study is two-fold: to evaluate the feasibility of mobile safety planning and daily mobile self-monitoring in routine care treatment for suicidal patients, and to conduct fundamental research on suicidal processes. Methods: The study is an adaptive single cohort design among 80 adult outpatients or day-care patients, with the main diagnosis of major depressive disorder or dysthymia, who have an increased risk for suicidal behaviours. There are three measurement points, at baseline, at 1 and 3 months after baseline. Patients are instructed to use their mobile safety plan when necessary and monitor their suicidal symptoms daily. Both these apps will be used in treatment with their clinician. Conclusion: The results from this study will provide insight into the feasibility of mobile safety planning and self-monitoring in treatment of suicidal patients. Furthermore, knowledge of the suicidal process will be enhanced, especially regarding the transition from suicidal ideation to behaviour