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Background: Frailty is a syndrome associated with poor health outcomes and, with an ageing population, it has become a focus for research and intervention. Pre-frailty, as a distinct stage of emerging age-related changes, is less well considered in the literature. Interventions to prevent progression from pre-frailty to frailty are being introduced, but lack supporting evidence on the needs and outcomes of this group. There is a need for improved understanding of patient outcomes, including experiential accounts of the application of such outcomes to daily lives. Methods: The research used a mixed methods realistic evaluation of the experience and outcomes of people identified as being at risk of developing frailty and engaged in a frailty-prevention course. Pre/post-test data, relating to physical and functional health outcomes generated at three time points, were analysed for 212 participants. A mixed methods exploration, using framework analysis, of experiences and perceptions of participants occurred based on nineteen semi-structured interviews with eight participants. This considered the way physical health, functional status, well-being and activity participation are understood and interact. Results and Findings: Classification of frailty highlighted that 64.7% of the sample were living with frailty and a further 29.4% with pre-frailty. At baseline there were weak, but significant associations, between increased lower frailty classification and more favourable functional outcomes for all measures, except for the Falls Efficacy Scale. Functional and frailty measures showed improvement after the twelve-week intervention, which was maintained for functional measures only at six-month follow-up. The mixed methods analysis developed knowledge from these outcomes, highlighting that the experience of participants did not closely align with measured outcomes. Participants rejected the term frailty, yet engaged with the need to mitigate for, and adapt to, age-related deterioration that threatened independence and well-being. This was achieved through occupational adaptation to preserve function and well-being. Conclusion: Considering frailty in terms of physical and functional status, mental well-being and occupational performance aligns with the experiences of those living with pre-frailty and frailty. The frailty-prevention intervention was highly acceptable to participants as it adopted a function and assets-based approach to health, which aligned with their conceptualisation of health and self-management. Additionally, improvement, or at least maintenance, of function, was of greatest importance to participants.

Background: Despite the extremely low mortality and morbidity rates of coronary artery bypass graft (CABG) surgery involving cardiopulmonary bypass (CPB), there are a number of pathological injuries believed to be due to the CPB circuit. Lipid Microemboli (LME) are produced when fats are released from bone marrow during a sternotomy, which then mix with blood in the pericardium during surgery. This blood is passed into the CPB circuit and reintroduced into the systemic circulation and is thought to promote an increased inflammatory response and ischaemia-inducing blockages. There are at present no adequate methods of dealing with this problem. Methods: A randomised controlled trial was undertaken to determine if a new Oxygenator, the RemoweLL, which contains a lipid and leucocyte filter, can effectively remove LME from the patient’s circulation compared with current gold standard CPB technologies and examine the effects on markers of cerebral, renal injury; neuron specific enolase, Cystatin C and pulmonary function. The Null hypothesis was that there would be no difference in peak neuron specific enolase concentrations. Results: The data presented in this Thesis provide the first biochemical evidence for a direct effect of LME upon neuron specific enolase release, which correlates in a linear fashion with increasing numbers of LME. The filtration of LME does not appear to significantly reduce systemic levels of activated leucocytes, which is reflected in similar pulmonary functions of those patients with and without LME filtration. However, there is evidence of a weak association towards renal protection with LME, with peak Cystatin C clearance lower than non-filtered patients. This met statistical trial stopping criteria. Conclusions: The RemoweLL CPB system removes significant numbers of LME compared to current CPB technology. Significant differences in the release of neuron specific enolase in the immediate postoperative period have been demonstrated. Furthermore, there is weak evidence towards improved clearance of Cystatin C. Further work is now planned to determine if LME filtration translates into longer-term neurocognitive and renal protection. The statistical differences between groups were so great from neuron specific enolase that the Ethics Committee advised early termination of the trial.

Community case management services provide targeted care to patients with long term health conditions (LTCs) and complex needs, at high risk of adverse events such as emergency hospital admissions. However, there is no standardised evidence informed programme for providing such care, including for patient monitoring. The complexity of older patients, those most likely to have multiple LTCs, and who often present with frailty and atypical symptoms, enhance the difficulty of on-going monitoring and targeting of care. There is an established relationship between ageing and LTCs, frailty and muscle strength, and function and service use, suggesting that muscle strength may be a useful aid to monitoring. Whilst muscle strength is a known indicator for future health, it is not known whether monitoring it is feasible or useful as a short term indicator in older people, especially those at high risk of adverse events. Patients are initially identified for case management by predictive modelling and/or clinical judgement, but little is known about the patients who go on to receive such care. The feasibility and usefulness of routine measures of muscle strength to help clinicians provide timely interventions were investigated alongside case management patients’ health, functional and physical status. An initial pilot study in healthy older adults (n=21) investigated four portable measures of strength, grip strength, sniff nasal inspiratory pressure (SNIP), peak inspiratory flow (PIF) and peak expiratory flow (PEF), and confirmed, via the collection of repeated measures at two time points one week apart, the reliability and acceptability of all but SNIP. A follow on feasibility study explored the acceptability and stability of the three successfully piloted measures in case management patients (n=8) and clinicians (n=5) via researcher administered questionnaire, with the reliability and stability of the measures assessed using a variety of statistical tests including intra-class correlation coefficients and Bland-Altman plots, on data collected over a maximum 7 week period. Concurrently measures of physical and functional ability and health were conducted. A third study analysed routine primary and secondary care case management patient data (n=101), allowing the development of a health and demographic profile of patients, including an assessment of frailty. The pilot and feasibility studies confirmed the reliability and acceptability of three portable measures of strength, PIF, PEF and grip strength. The high level of muscle strength stability observed in patients over the short-medium term, despite adverse events, suggested that whilst monitoring muscle strength may be feasible it would not be useful over this time period. Analysis of routine primary and secondary care data, identified case management patients as predominately female, with age skewed towards the older old and experiencing high levels of deprivation. Multiple LTCs were commonly recorded, and a wide variety of conditions noted. Health service use varied greatly, with few patients recording frequent usage. A frailty index suggested that frailty was common, and highlighted the potential for the development of a useful frailty index using routine data to improve the targeting of case management services towards those who are most at risk.