The six studies presented in this thesis investigated the extent to which people compare to others when making a range of health-related judgements and decisions and aimed to identify the cognitive mechanisms used in this comparison process. A key question was whether biases found in specific judgements and decisions, such as deciding to seek help when it is not needed or not seeking help when it is needed, could be explained by social comparison effects. It was found that participants compared to others using rank-based strategies when making judgements and decisions about mental and physical health symptoms and when judging their health in general (Study 1, 2 and 4). Social comparison effects were generally small to medium in size (average Cohen's f2 = 0.09, range = 0.01-0.39). Health-related help-seeking accuracy was associated with how participants believed their experience of symptoms compared to that of others. Participants were four times more likely to seek help when it was not needed if they believed that they experienced symptoms more frequently than others, and two to three times more likely not to seek help when it was needed if they believed that they experienced symptoms less frequently than others (Study 1). However, participants' beliefs about how their sleep compared to that of others had little influence on their sleep-related judgement and decision-making (Study 3). There was no evidence that participants' beliefs about how much support they received relative to others was associated with perceptions of this support (Study 5 and 6). The findings have implications for the development of both interventions that may improve accuracy in health help-seeking decisions and social norms-based interventions, the measurement of comparison effects, self-rated health and social support, social comparison theory, and models of symptom appraisal and health-related help-seeking.

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. Due to ageing of the general population and improved survival from cardiac disease the prevalence of heart failure is rising. Despite the fact that the majority of patients with heart failure are aged over 65 years old, many with multiple co-morbidities, the association between cognitive impairment and heart failure has received relatively little research interest compared to other aspects of cardiac disease. The presence of concomitant cognitive impairment has implications for the management of patients with heart failure in the community. There are many evidence based pharmacological therapies used in heart failure management which obviously rely on patient education regarding compliance. Also central to the treatment of heart failure is patient self-monitoring for signs indicative of clinical deterioration which may prompt them to seek medical assistance or initiate a therapeutic intervention e.g. taking additional diuretic. Adherence and self-management may be jeopardised by cognitive impairment. Formal diagnosis of cognitive impairment requires evidence of abnormalities on neuropsychological testing (typically a result ≥1.5 standard deviation below the age-standardised mean) in at least one cognitive domain. Cognitive impairment is associated with an increased risk of dementia and people with mild cognitive impairment develop dementia at a rate of 10-15% per year, compared with a rate of 1-2% per year in healthy controls. Cognitive impairment has been reported in a variety of cardiovascular disorders. It is well documented among patients with hypertension, atrial fibrillation and coronary artery disease, especially after coronary artery bypass grafting. This background is relevant to the study of patients with heart failure as many, if not most, have a history of one or more of these co-morbidities. A systematic review of the literature to date has shown a wide variation in the reported prevalence of cognitive impairment in heart failure. This range in variation probably reflects small study sample sizes, differences in the heart failure populations studied (inpatients versus outpatients), neuropsychological tests employed and threshold values used to define cognitive impairment. The main aim of this study was to identify the prevalence of cognitive impairment in a representative sample of heart failure patients and to examine whether this association was due to heart failure per se rather than the common cardiovascular co-morbidities that often accompany it such as atherosclerosis and atrial fibrillation. Of the 817 potential participants screened, 344 were included in this study. The study cohort included 196 patients with HF, 61 patients with ischaemic heart disease and no HF and 87 healthy control participants. The HF cohort consisted of 70 patients with HF and coronary artery disease in sinus rhythm, 51 patients with no coronary artery disease in sinus rhythm and 75 patients with HF and atrial fibrillation. All patients with HF had evidence of HF-REF with a LVEF < 45% on transthoracic echocardiography. The majority of the cohort was male and elderly. HF patients with AF were more likely to have multiple co-morbidities. Patients recruited from cardiac rehabilitation clinics had proven coronary artery disease, no clinical HF and a LVEF >55%. The ischaemic heart disease group were relatively well matched to healthy controls who had no previous diagnosis of any chronic illness, prescribed no regular medication and also had a LVEF >55%. All participants underwent the same baseline investigations and there were no obvious differences in baseline demographics between each of the cohorts. All 344 participants attended for 2 study visits. Baseline investigations including physiological measurements, electrocardiography, echocardiography and laboratory testing were all completed at the initial screening visit. Participants were then invited to attend their second study visit within 10 days of the screening visit. 342 participants completed all neuropsychological assessments (2 participants failed to complete 1 questionnaire). A full comprehensive battery of neuropsychological assessment tools were administered in the 90 minute study visit. These included three global cognitive screening assessment tools (mini mental state examination, Montreal cognitive assessment tool and the repeatable battery for the assessment of neuropsychological status) and additional measures of executive function (an area we believe has been understudied to date). In total there were 9 cognitive tests performed. These were generally well tolerated. Data were also collected using quality of life questionnaires and health status measures. In addition to this, carers of the study participant were asked to complete a measure of caregiver strain and an informant questionnaire on cognitive decline. The prevalence of cognitive impairment varied significantly depending on the neuropsychological assessment tool used and cut-off value used to define cognitive impairment. Despite this, all assessment tools showed the same pattern of results with those patients with heart failure and atrial fibrillation having poorer cognitive performance than those with heart failure in sinus rhythm. Cognitive impairment was also more common in patients with cardiac disease (either coronary artery disease or heart failure) than age-, sex- and education-matched healthy controls, even after adjustment for common vascular risk factors.

The experiences of stroke survivors have been researched quite extensively, in particular the effect that stroke can have on a person’s life and sense of self, but how much upper limb dysfunction contributes to these experiences is not fully known. This study explores the impact that upper limb dysfunction, specifically, could have on people’s lives after stroke, and their hopes and expectations for recovery of the upper limb. Method: a longitudinal phenomenological study with a series of four semi-structured interviews at two-, six-, twelve-, and eighteen months post stroke with 13 participants recruited from a stroke rehabilitation unit. Data were analysed using thematic analysis and a modified form of framework analysis. Results: Three main themes were identified in the data: The Altered Life; The Disrupted Self; The Experience of Recovery. Findings indicated that upper limb dysfunction after stroke, and the loss of two-handedness, can adversely affect the lives of stroke survivors, and this, in turn, can affect a person’s self-esteem, self-image and identity. Stroke survivors initially viewed recovery of the lower limb as more important than the upper limb, but on returning home they recognised that the upper limb recovery was crucial in managing self-care and returning to meaningful activities and life roles. Therapy services, after hospital discharge, were short term and focused on mobility, not the upper limb, and stroke survivors were frustrated with the lack of information and advice. Participants wanted to be active partners with therapists, to self-manage recovery in their upper limb. Conclusion: Therapists should be more aware of the impact that upper limb dysfunction can have on stroke survivors’ lives and sense of self. Therapy, information and advice for the upper limb should be considered vital in rehabilitation, and models of services that capitalise on stroke survivors’ desire to self-manage their recovery should be explored.

Current orthopaedics treatments of bone defects often involve the use of implanted fixatives and/or autograft procedures to restore function to the afflicted area following injury. Fixatives and implants are usually temporary solutions, since they are intrinsically prone to failure. In addition to this, replacing implants involve expensive and invasive procedures that cause great hardship to patients. Whilst autografts can provide an excellent outcome in healing of the initial injury site, donor site morbidity from the autologous bone graft can lead to complications such as infection, chronic pain and an abnormal walking gait. Bone tissue engineering is a field of science aiming to address these limitations by providing in vitro manufactured bone to replace autografts, and also limit the use of temporary fixatives. Hydrostatic force bioreactors are currently being developed within this field to attempt improve the outcome of the tissue engineered bone by mimicking the forces typically experienced by cells in the native bone niche. Based on this principle, it is hoped that such systems will aid the translation of research in bone tissue engineering from the lab to the clinic. This research aims to investigate and validate the use of a hydrostatic force bioreactor for improving the outcome of in vitro manufactured bone using a clinically relative strategy employing human mesenchymal stem cells seeded in 3D scaffolds. The research first describes a validation process to determine the initial response of cells to hydrostatic pressure in monolayer cultures. The outcome of this study indicated that mechanical responsiveness in cells can vary according to cell phenotype and the integrity of the f-actin cytoskeleton. Next it was demonstrated that hydrostatic pressure can improve the outcome of in vitro bone formation by MG-63 human osteoblast like cells, validating the bioreactor as a potential preconditioning platform. Following this, a model of bone formation in hMSCs/collagen scaffolds was described, whereby a predictable rate of bone formation was determined by adjusting cellular distribution and protein concentration in collagen type-1 scaffolds. Finally, an organotypic fracture repair model was established using explanted embryonic chick femurs to test the hypothesis that hydrostatic preconditioning of hMSC/collagen hydrogels can improve the outcome of fracture repair. The results of this study showed that bioreactor stimulation could enhance the outcome of repair using a combination of undifferentiated hMSC/collagen type-1 scaffolds, and global mechanical signalling (stimulation of entire femur constructs). It was then shown that hydrostatic preconditioning of hMSC seeded hydrogels prior to implantation did not increase the rate of in vitro bone formation. Following implantation of the hydrogels into the fracture repair model, it was demonstrated that highly mineralised preconditioned implants actually inhibited the fracture repair process. In addition to this, it was shown that preconditioned implants with a lower level of mineralisation allowed invasion and bone formation by native cells from the host tissue. Collectively, the results implied that the outcome of repair using this model relied on three main factors: the presence of global hydrostatic stimulation; the lineage commitment of hMSCs in collagen scaffolds at the time of implantation; and the permeability and cell invasion capacity of the implant.

The global incidence of Type 2 Diabetes Mellitus (T2DM) is increasing rapidly. Many people with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) will however not progress to T2DM but appear to spontaneous revert to normal glucose homeostasis, others however will progress slowly and in some cases rapidly progress towards diabetes. Therapeutic interventions will reduce the risk, or at least the pace, of deterioration from IFG and IGT to T2DM. However, in order to target interventions appropriately, to prevent progression in those at greatest risk further information as to which individuals are most likely to progress is needed. There is a variable rate of progression from either IFG, IGT or combined IFG and IGT to T2DM and in general, progression rates are lowest in the general population and highest in target “at-risk” group. Age, body mass index (BMI), fasting and 2 hour plasma glucose concentrations, elevated fasting pro-insulin, low 2-hour insulin and fasting triglyceride levels are known to be associated with a greater risk of progression and in order to maintain normoglycemia, adequate quantitative and qualitative moment-by-moment pancreatic beta-cell secretion and action is essential. A marker of deteriorating carbohydrate homeostasis would be increased fluctuations in blood glucose levels and continuous glucose monitoring (CGM) is an ideal method to look at just this. The use of CGM to quantify the fluctuations was proposed to assess whether CGM can help identify people with abnormal glucose tolerance that progress to T2DM. In this study, CGM profiles inspected by eye for variability appeared to correlate well with mathematically devised CGM parameters based on CGM data, both at baseline and at Year 1. However, neither the subject CGM profiles nor the CGM parameters at baseline were significant in predicting progression to diabetes (T2DM) at Year 1 or Year 3 from a pre diabetic state at baseline. However, when one looked at progression from pre diabetes to diabetes, with regard to CGM profiles and CGM parameters, the interval period between study baseline and Year 1 appeared to be when most variation in glucose levels occurred; this was especially the case for those subjects with IFG, compared to subjects with IGT or IFG+IGT mix, respectively. This effect was diluted at Year 3 and not observed. In conclusion, this study demonstrated that CGM did not predict progression from pre diabetes to diabetes (T2DM), but did however, correlate well by eye with mathematical assessments models of the same CGM data and identify an at risk IFG group that could be targeted at baseline with more intensive therapy.

Background Research has shown that healthcare organisations can cause harm to patients, much of which is avoidable, and there is reliable evidence to suggest that this harm is a widespread and recurring phenomena (Institute of Medicine 1999; Department of Health 2000; Leape et al 2002; de Vries et al 2008; Longtin et al 2009; Jha et al 2010). Encouraging patients to take an active role in their own healthcare was identified in the landmark patient safety publication ‘To Err is Human’ (Institute of Medicine 2000) as a vital factor in the quest to improve patient safety. It has since been contended that if patients were involved in their healthcare they could help to further reduce opportunities for accidents and errors during the course of their care (Vincent and Coulter 2002; Koutantji et al 2005; Weingart et al 2005; Unruh and Pratt 2006; Davis et al 2007). More recently, there has been growing interest in the development and use of interventions to promote and support patients’ roles in securing their own safety in healthcare contexts (Hall et al 2010; Longtin et al 2010; Peat et al 2010; Doherty and Stavropoulou 2012; Vaismoradi et al 2014). Aims The broad aim of this study is to explore the extent to which patients are involved in attempts to improve their own healthcare safety through enrolment in an enhanced recovery after surgery (ERAS) programme. Recognising that patient safety is just one aspect of the ERAS programme theory, this research evaluates those elements of the programme that see patients taking a role in their own healthcare safety. This is achieved by considering in realist terms the mechanisms of effect by which patients might contribute to their healthcare safety and investigating the conditions and circumstances (contexts) that are required to enable this involvement. The overall aim of this research is to seek out regularities in the patterns of these contexts and mechanisms which result in patient involvement in patient safety. The emerging theory will explain implementation variations, and the experiences of the programme participants in the different cases will provide an opportunity to make comparisons with initial programme theories, the objective being to better understand when and why patient involvement in patient safety works in an ERAS programme. Methods The underpinning methodological framework for this research is realist evaluation (Pawson and Tilley 1997), which is a technique concerned with exploring the interaction among context, mechanism and outcome, based on the realist principle of generative causation. This study uses an in-depth multiple case study approach, with each of the three surgical units under study purposively selected to represent involvement in the ERAS programme. To capture the complex and dynamic nature of the programme under investigation, the study draws on a wide range of empirical data sources, methods and materials, including ethnographic observations, semi-structured interviews and document analysis. Taking ‘early mobilisation’ as a tracer outcome, the study examines the mechanisms and contexts involved in programme outcomes in relation to patient involvement in patient safety. The first stage of the enquiry involves eliciting and formalising the programme theories relating to patient involvement in patient safety in an ERAS programme which are then articulated in conjectured context-mechanism-outcome configurations (CMO) terms. The next stage involves collecting data that will allow interrogation of these hypotheses, comparing the programme’s intentions with case study data of actual practice that occurred and the views and experiences of key stakeholders, including patients and nursing staff. This is followed by cross case comparisons which attempt to determine how the same mechanisms played out in different contexts. Key findings Overall, the findings show that there are many contextual factors relating to the successful outcomes of the programme theories postulated. The key findings of this study demonstrate that successful patient involvement in patient safety related elements of an ERAS programme requires that: ward staffs are aligned with the programme objectives; that patients’ expectations for their post-operative recovery are managed prior to surgery and the underlying rationale for their care is understood and; in the post-operative period patients’ enrolment in the programme is sustained and reinforced by ward based staff. The study also demonstrates how differences in the implementation of ERAS across the study sites, support for early mobilisation and individual patient differences (for example emotional status and operation type) were consequential for the outcomes of the programme theory. Conclusion This thesis sits at the interface of a number of health policy and quality improvement trends including patient involvement, patient safety, standardisation, patient centred care, co-production and the growing interest in healthcare with the implementation and embedding of interventions. The aspirations of policy and programme documentation to ‘empower’ patients to take a more active role in their care also proved more complex in reality. The study highlights the tensions between achieving a quality standard and patient centred care and how the approach to postoperative care in the three different case study sites shaped nurses’ willingness to adapt the programme and support patient involvement. The main areas for consideration from this study include the importance of the role of healthcare staff in attempts to involve patients in patient safety, along with the tensions between standardisation of care versus the aspirations of providing person-centred, individual care for patients. This is considered in relation to the ongoing standardisation of healthcare through an increasing reliance on protocols and pathways, such as the ERAS programme.

Introduction: Synovial fibroblasts (SF) display a ‘hyperactive’ phenotype in patients with rheumatoid arthritis (RA). Nicotinamide adenine dinucleotide (NAD+) plays a role in cell metabolism, but may also be a key molecule in maintaining this ‘activated’ phenotype. NAD+ can be synthesised from precursor vitamin molecules, nicotinamide (Nam), nicotinic acid (NA) and Tryptophan (TRP); with their respective phosphoribosyl transferases (NAMPT, NAPRT, QAPRT) and Indoleamine (IDO) being the rate limiting enzymes involved in these pathways. NAMPT and IDO are known to be elevated in RA synovial tissue (ST). However, the expression and regulation of other NAD+ biosynthesis enzymes are unknown. Methods: RA, OA and normal ST were obtained from joints of patients undergoing surgery and expression of NAD+ biosynthesis enzymes were quantified using qPCR. Synovial fibroblasts were cultured and stimulated with 10ng/ml of TNF-α, IL-1β, OSM & IFN- and the expression of NAD+ biosynthesis enzymes were quantified using qPCR. Results: qPCR analyses showed that all NAD+ biosynthesis enzymes tested were constitutively expressed in synovial tissue ex vivo and in vitro, with the exception of NMN adenyltransferase (NMNAT)-3. NAMPT, IDO, QAPRT, NADSYN and NMNAT-2 were all upregulated in RA ST compared to normal tissue, however only NAMPT was significantly upregulated in RA compared to OA and normal, (NAMPT reached statistical significance when patients on anti-TNF therapy were excluded). Moreover, NAMPT was found to be upregulated in ST of young actively developing individuals, decreasing with age. Expression of NAD salvage enzymes, NAMPT and NMNAT-2 in ST correlated with each other and de novo NAD enzymes, IDO, QAPRT, NADSYN and NMNAT-2 were also correlated with each other in ST. NAMPT and IDO were both significantly upregulated in vitro following stimulation with OSM & IFN- but only NAMPT and NMNAT-2 were upregulated following stimulation with TNF-α & IL-1β. NAPRT expression was found to be low in RA ST and there was no upregulation following stimulation by OSM, IFN-, TNF-α & IL-1β. Conclusion: The data presented in this thesis emphasises NAMPT and IDO as a potential therapeutic target in rheumatoid arthritis.

Introduction: Moral complexities exist in every day health care practice creating conflicting responsibilities in providing care. Health care ethics (HCE) enable an applied practical linkage of theory and practice to create professional behaviour that focuses on service user benefit. This thesis explored how physiotherapists and podiatrists embodied health care ethics in their practice. Methods: Interpretative Phenomenological Analysis (IPA) as a hermeneutical approach was utilised in order to explore how HCE informs physiotherapy and podiatry practice. Whilst always involving interpretation, this method has the ability to describe the human experience as it is lived. Using a framework embedded in hermeneutic IPA facilitated an inquiry that promotes the participant’s own reflections of experiential practice (phenomenology) and then interpreting them (hermeneutical) in the relevant and wider context. Purposively sampled individual interviews were carried out (n=21) in an attempt to interpret the participants’ lifeworld of embodied HCE. The preliminary findings were taken to one purposively sampled group interview for discussion which contributed to further interpretation. Findings: Five themes emerged from the data. The themes indicated that there is a desire by participants to extol ethical practice, but acknowledged various limitations in the reality of achieving this. The place of empathy has a key role in HCE for clinical reasoning and decision making which may prevent HCPs from passively following performance guidelines and checklists. If empathy and virtue ethics can be taught and utilised by HCPs then guidelines may be considered for individual implementation as an outcome, rather than a prerequisite, of ethical decision making. Conclusion: Ethical decision making may be enhanced by reconsidering the education of character virtues including empathy. Empathy is a basic condition and source of morality. As a central component of phronesis, empathy may enable understanding of a service user’s needs and increase motivation for HCPs to act in a caring way, thus making the service user the bearer of an ethical interaction.

In low-income countries, lack of respectful maternity care (RMC) is a key deterrent in women’s access to, and satisfaction with, facility-based birth, undermining global efforts to tackle maternal mortality. Much of what we know about RMC and disrespect in the labour ward has been informed by women’s perspectives. Midwives’ voices are largely missing from the discourse. This thesis poses two overarching questions: How do Malawian midwives conceptualise, practice and value RMC? What constraints and enablers do they face in providing RMC? I used a qualitative, critical realist approach to foreground midwives’ voices. Narrative (n=21) and critical incident technique (n=23) interviews with midwives were supplemented by 26 key informant interviews. The theoretical frame of postcolonialism provided the key anchor point for interpreting the data. Many midwives aspire to RMC but face significant challenges. A clash between traditional values and democracy manifests in poor attitudes to the public sector, inadequate leadership and lack of accountability, while student recruitment processes allow entry of ‘just a job’ midwives - both factors allow poor behaviour and attitudes to become normalised. Midwifery’s low status and professional invisibility under a dual-qualification nurse-midwife model, plus lack of a united vision for the future of midwifery, leave midwives feeling unvalued and demotivated. Unconducive work environments, low staff numbers, lack of support and horizontal violence block professionalism and good practice at facility level. Policies to strengthen health systems and strategic consideration of the midwifery profession’s future are needed, as well as explicit attention to fostering teamwork and positive organisational cultures. Malawi’s labour ward dynamics are contingent upon the historical, cultural and health systems factors prevailing in this postcolonial context. An inter-disciplinary perspective to research in this area has been lacking but is crucial to frame and devise more appropriate interventions to improve the intrapartum experience for both women and midwives.

Boredom or ennui is a subjective feeling that embodies a number of symptoms similar to those implied by the term "depression," and varies in degree of depth from what might be described as normal to several levels or pathology. When met with as a "normal" phenomenon, it is usually of transient duration and of little consequence, although Schopenhauer takes another view of the matter.