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IP Pragmatics

3 Projects, page 1 of 1
  • Funder: UK Research and Innovation Project Code: EP/N014391/2
    Funder Contribution: 242,649 GBP

    Our Centre brings together a world leading team of mathematicians, statisticians and clinicians with a range of industrial partners, patients and other stakeholders to focus on the development of new methods for managing and treating chronic health conditions using predictive mathematical models. This unique approach is underpinned by the expertise and breadth of experience of the Centre's team and innovative approaches to both the research and translational aspects. At present, many chronic disorders are diagnosed and managed based upon easily identifiable phenomena in clinically collected data. For example, features of the electrical activity of the heart of brain are used to diagnose arrhythmias and epilepsy. Sampling hormone levels in the blood is used for a range of endocrine conditions, and psychological testing is used in dementia and schizophrenia. However, it is becoming increasingly understood that these clinical observables are not static, but rather a reflection of a highly dynamic and evolving system at a single snapshot in time. The qualitative nature of these criteria, combined with observational data which is incomplete and changes over time, results in the potential for non-optimal decision-making. As our population ages, the number of people living with a chronic disorder is forecast to rise dramatically, increasing an already unsustainable financial burden of healthcare costs on society and potentially a substantial reduction in quality of life for the many affected individuals. Critical to averting this are early and accurate diagnoses, optimal use of available medications, as well as new methods of surgery. Our Centre will facilitate these through developing mathematical and statistical tools necessary to inform clinical decision making on a patient-by-patient basis. The basis of this approach is patient-specific mathematical models, the parameters of which are determined directly from clinical data obtained from the patient. As an example of this, our recent research in the field of epilepsy has revealed that seizures may emerge from the interplay between the activity in specific regions of the brain, and the network structures formed between those regions. This hypothesis has been tested in a cohort of people with epilepsy and we identified differences in their brain networks, compared to healthy volunteers. Mathematical analysis of these networks demonstrated that they had a significantly increased propensity to generate seizures, in silico, which we proposed as a novel biomarker of epilepsy. To validate this, an early phase clinical trial at King's Health Partners in London has recently commenced, the success of which could ultimately lead to a revolution in diagnosis of epilepsy by enabling diagnosis from markers that are present even in the absence of seizures; reducing time spent in clinic and increasing accuracy of diagnosis. Indeed it may even make diagnosis in the GP clinic a reality. However, epilepsy is just the tip of the iceberg! Patient-specific mathematical models have the potential to revolutionise a wide range of clinical conditions. For example, early diagnosis of dementia could enable much more effective use of existing medication and result in enhanced quality and quantity of life for millions of people. For other conditions, such as cortisolism and diabetes where a range of treatment options exist, identifying the optimal medication, and the pattern of its delivery, based upon the profile of the individual will enable us to maximise efficacy, whilst minimising unwanted side effects.

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  • Funder: UK Research and Innovation Project Code: EP/N014391/1
    Funder Contribution: 2,008,950 GBP

    Our Centre brings together a world leading team of mathematicians, statisticians and clinicians with a range of industrial partners, patients and other stakeholders to focus on the development of new methods for managing and treating chronic health conditions using predictive mathematical models. This unique approach is underpinned by the expertise and breadth of experience of the Centre's team and innovative approaches to both the research and translational aspects. At present, many chronic disorders are diagnosed and managed based upon easily identifiable phenomena in clinically collected data. For example, features of the electrical activity of the heart of brain are used to diagnose arrhythmias and epilepsy. Sampling hormone levels in the blood is used for a range of endocrine conditions, and psychological testing is used in dementia and schizophrenia. However, it is becoming increasingly understood that these clinical observables are not static, but rather a reflection of a highly dynamic and evolving system at a single snapshot in time. The qualitative nature of these criteria, combined with observational data which is incomplete and changes over time, results in the potential for non-optimal decision-making. As our population ages, the number of people living with a chronic disorder is forecast to rise dramatically, increasing an already unsustainable financial burden of healthcare costs on society and potentially a substantial reduction in quality of life for the many affected individuals. Critical to averting this are early and accurate diagnoses, optimal use of available medications, as well as new methods of surgery. Our Centre will facilitate these through developing mathematical and statistical tools necessary to inform clinical decision making on a patient-by-patient basis. The basis of this approach is patient-specific mathematical models, the parameters of which are determined directly from clinical data obtained from the patient. As an example of this, our recent research in the field of epilepsy has revealed that seizures may emerge from the interplay between the activity in specific regions of the brain, and the network structures formed between those regions. This hypothesis has been tested in a cohort of people with epilepsy and we identified differences in their brain networks, compared to healthy volunteers. Mathematical analysis of these networks demonstrated that they had a significantly increased propensity to generate seizures, in silico, which we proposed as a novel biomarker of epilepsy. To validate this, an early phase clinical trial at King's Health Partners in London has recently commenced, the success of which could ultimately lead to a revolution in diagnosis of epilepsy by enabling diagnosis from markers that are present even in the absence of seizures; reducing time spent in clinic and increasing accuracy of diagnosis. Indeed it may even make diagnosis in the GP clinic a reality. However, epilepsy is just the tip of the iceberg! Patient-specific mathematical models have the potential to revolutionise a wide range of clinical conditions. For example, early diagnosis of dementia could enable much more effective use of existing medication and result in enhanced quality and quantity of life for millions of people. For other conditions, such as cortisolism and diabetes where a range of treatment options exist, identifying the optimal medication, and the pattern of its delivery, based upon the profile of the individual will enable us to maximise efficacy, whilst minimising unwanted side effects.

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  • Funder: UK Research and Innovation Project Code: EP/T017856/1
    Funder Contribution: 1,231,620 GBP

    Our Hub brings together a team of mathematicians, statisticians and clinicians with a range of industrial partners, patients and other stakeholders to focus on the development of new quantitative methods for applications to diagnosing and managing long-term health conditions such as diabetes and psychosis and combating antimicrobial infections such as sepsis and bronchiectasis. This approach is underpinned by the world-leading expertise in diabetes, microbial communities, medical mycology and mental health concentrated at the University of Exeter. It uses the breadth of theoretical and methodological expertise of the Hub's team to give innovative approaches to both research and translational aspects. Although quantitative modelling is a well-established tool used in the fields of economics and finance, cutting-edge quantitative analysis has only recently become possible in health care. However, up to now it has been restricted to health economics in the context of healthcare services and systems management. Applications to develop future therapies, optimising treatments and improving community health and care are in its infancy. This is due to a number of challenges from both mathematical (methodological) as well as clinical and patients' perspectives. Our Hub approach will allow us to develop novel statistical and mathematical methodologies of relevance to our clinical and industrial partners, informed by relevant patient groups. Building this new generation of quantitative models requires that we advance our mathematical understanding of the effective network interaction and emergent patterns of health and disease. Clinical translation of mathematical and statistical advances necessitates that we further develop robust uncertainty quantification methodology for novel therapy, treatment or intervention prediction and evaluation. NHS long-term planning aspires to deliver healthcare that is more personalised and patient centred, more focused on prevention, and more likely to be delivered in the community, out of hospital. Our Hub will contribute to this through developing mathematical and statistical tools needed to inform clinical decision making on a patient-by-patient basis. The basis of this approach is quantitative patient-specific mathematical models, the parameters of which are determined directly from individual patient's data. As an example of this, our recent research in the field of mental health has revealed that movement signatures could be used to distinguish between healthy subjects and patients with schizophrenia. This hypothesis was tested in a cohort of people with schizophrenia and we developed a quantitative analysis pipe line allowing for classification of individuals as healthy or patients. The features used for classification involving data-driven models of individual movement properties as well as measures of coordination with a virtual partner were proposed as a novel biomarker of social phobias. To validate this in an NHS setting, we have recently carried out a feasibility study in collaboration with the early intervention for psychosis teams in Devon Partnership Mental Health Trust. The success of this study could significantly advance the early detection of psychosis by enabling diagnosis using novel markers that are easily measured and analysed and improve accuracy of diagnosis. Indeed, personalised quantitative models hold the promise for transforming prognosis, diagnosis and treatment of a wide range of clinical conditions. For example, in diabetes where a range of treatment options exist, identifying the optimal medication, and the pattern of its delivery, based upon the profile of the individual will enable us to maximise efficacy, whilst minimising unwanted side effects.

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