Improving outcomes of sepsis, using precision antimicrobial prescribing

This project intends to identify patients at risk of sepsis earlier, predicting their severity and clinical outcome; and provide informed and timely decisions on interventions such as antimicrobials and supporting care. It will answer the question of "what antibiotic, when, and in whom?". It will evaluate and potentially integrate scoring systems such as Sepsis-related Organ Failure Assessment score (SOFA). By linking data on patients presenting to acute care with sepsis with their primary care data, predictive values of different sepsis indicators / prognostic markers will be studied based on their comorbidities and pathway to care.

One in five deaths worldwide is caused by sepsis. Early identification and timely intervention are key to increased survival, but diagnosis can be difficult in the early stages, especially at extremes of age, and clinical manifestations can be non-specific, depending on the pathogen type, portal of entry, and progression of the condition. Potential benefits would reduce mortality and reduce length of hospital stay due to timely interventions, including the administration of working antibiotics as well as the effect of reducing population antimicrobial resistance. In the study region, 5,000 patients will benefit per year, with an estimated 200,000 cases and 50,000 sepsis deaths in the whole of the UK.

Clinical decision support system (CDSS) support for antimicrobial prescribing has previously been based on static models built with expert guidance from published evidence. Now for the first time, underpinned by Bristol's new Health Data Research UK South-West Partnership, antimicrobial use and resistance histories of each patient across primary and secondary care can be integrated with local susceptibility testing and genomic analysis of resistance mechanisms. Hence this will lead to more in-patient precision through a step-change in breadth and depth of data available to train novel models - namely, all individuals in the Bristol, North Somerset and South Gloucester (BNSSG) clinical commissioning area. The methodology is also novel, using cutting-edge Gaussian Process classification models.

For the first year, focus will be on patient data at presentation, integrated with population-level predictive modelling. There will be "sandpit" events to consider user-requirements for the clinical decision support tool.

In the second year, identifiable data and predictions back to individual providers will enable patient-specific AM use and AMR histories from primary and secondary care to be integrated into the clinical decision support model.

In the third year, there will be co-design of dashboards for the CDSS with clinicians, and the CDSS will be evaluated in a clinical setting.

The project will be based on an underpinning platform of Bayesian learning and prediction. This is now possible because of the HDR-UK partnership and BNSSG Systemwide dataset, which has integrated routine primary and secondary care electronic healthcare records with the Severn Pathology laboratory database (the diagnostic test provider for BNSSG). There will be statistical analysis and machine learning applied to assess relation between National Early Warning Score (NEWS) and SOFA score at baseline and on presentation during a sepsis episode, as well as dynamics of NEWS and SOFA score in relation to interventions.

Impact on Health and Care
The CDT primarily addresses the most pressing needs of nations such as the UK - namely the growth of expenditure on long term health conditions. These conditions (e.g. diabetes, depression, arthritis) cost the NHS over £70Bn a year (~70% of its budget). As our populations continue to age these illnesses threaten the nation's health and its finances.

Digital technologies transforming our world - from transport to relationships, from entertainment to finance - and there is consensus that digital solutions will have a huge role to play in health and care. Through the CDT's emphasis on multidisciplinarity, teamwork, design and responsible innovation, it will produce future leaders positioned to seize that opportunity.

Impact on the Economy
The UK has Europe's 2nd largest medical technology industry and a hugely strong track record in health, technology and societal research. It is very well-placed to develop digital health and care solutions that meet the needs of society through the creation of new businesses.

Achieving economic impact is more than a matter of technology. The CDT has therefore been designed to ensure that its graduates are team players with deep understanding of health and social care systems, good design and the social context within which a new technology is introduced.

Many multinationals have been keen to engage the CDT (e.g. Microsoft, AstraZeneca, Lilly, Biogen, Arm, Huawei ) and part of the Director's role will be to position the UK as a destination for inwards investment in Digital Health. CDT partners collectively employ nearly 1,000,000 people worldwide and are easily in a position to create thousands of jobs in the UK.

The connection to CDT research will strongly benefit UK enterprises such as System C and Babylon, along with smaller companies such as Ayuda Heuristics and Evolyst.

Impact on the Public
When new technologies are proposed to collect and analyse highly personal health data, and are potentially involved in life or death decisions, it is vital that the public are given a voice. The team's experience is that listening to the public makes research better, however involving a full spectrum of the community in research also has benefits to those communities; it can be empowering, it can support the personal development of individuals within communities who may have little awareness of higher education and it can catalyse community groups to come together around key health and care issues.

Policy Makers
From the team's conversations with the senior leadership of the NHS, local leaders of health and social care transformation (see letters from NHS and Bristol City Council) and national reports, it is very apparent that digital solutions are seen as vital to the delivery of health and care. The research of the CDT can inform policy makers about the likely impact of new technology on future services.

Partner organisation Care & Repair will disseminate research findings around independent living and have a track record of translating academic research into changes in practice and policy.

Carers UK represent the role of informal carers, such as family members, in health and social care. They have a strong voice in policy development in the UK and are well-placed to disseminate the CDTs research to policy makers.

STEM Education
It has been shown that outreach for school age children around STEM topics can improve engagement in STEM topics at school. However female entry into STEM at University level remains dramatically lower than males; the reverse being true for health and life sciences. The CDT outreach leverages this fact to focus STEM outreach activities on digital health and care, which can encourage young women into computer science and impact on the next generation of women in higher education.

For academic impact see "Academic Beneficiaries" section.