Infection after trauma complicates the patients clinical course. Infection leads to longer critical care and hospital stays, has been associated with increased mortality rates and places considerable cost pressures on health economies. The predictors of infection after severe injury are not known, and the effects on outcomes other than mortality are under-reported. The overall objective of this research was to characterise factors predictive of infection in severely injured patients admitted to critical care. A prospective cohort study of 271 patients investigated admission factors predictive of the development of infection. A second study of 280 patients evaluated post-injury immune cell changes and the association with infection. Thirdly the relationship between early coagulopathy and infections was investigated in 158 patients. Finally a study of 385 patients examined the use of Tranexamic Acid (TXA) and its association with infection and other outcomes. Infection was a significant burden for severely injured patients. Admission hypoperfusion was the only early characteristic associated with the development of infection, and a dose dependent relationship was observed between severity of shock and increased percentage of infection (p<0.01). Lymphopenia prolonged to day four post injury was strongly predictive infection (OR 0.10, CI 0.02-0.48, p<0.01). At 24 hours, the anticoagulant Protein C was lower in those with infection (Infection: 70.2 iu/dL vs. No infection: 83.3 iu/dL p=0.02), and increased fibrinolysis was also associated with infectious complications (Infection: 6156 μg/L vs. No infection: 3324 μg/L p=0.03). There was a trend to a beneficial relationship between TXA and infection, and it was independently associated with reduced organ failure (OR 0.27, CI: 0.10 – 0.73, p=0.01) and mortality (OR 0.16 CI 0.03 - 0.86, p=0.03). In severely injured patients, admission shock, prolonged lymphopenia and early coagulation dysfunction post severe injury were independent predictors of infection. Timely modulation of these responses after trauma may help to reduce the burden of infection.

Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the relative uptake of new medicines recommended by the National Institute for Health and Care Excellence often lags behind other comparative countries’ health systems. One example is the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation, which was slow and had a high level of unexplained variation across different health economies in England. This research aimed to explore barriers and enablers to the uptake of DOACs from the perspectives of patients, healthcare professionals, and key stakeholders by conducting systematic and narrative reviews and semi-structured interviews. Data collected from 21 patients, 23 healthcare professionals, and 23 key stakeholders recruited from three different health economies was analysed using the Framework method. The findings identified a range of intersecting factors acting as barriers and/or enablers to the uptake DOACs. While there were a wide range of experiences and views, an agreement between patients and healthcare professionals/key stakeholders on several identified factors was observed. Attributes of the innovation, characteristics of patients and prescribers, local health economy readiness for change, implementation process, and external health system context were suggested as influences. Mapping of the findings to the Diffusion of Innovations in Service Organisations model identified 11 components for a future toolkit development to facilitate uptake of nationally recommended new medicines. This thesis highlighted the role of patients, consideration of all costs associated with new medicines, and compatibility with the health economy’s care model impact on the uptake.