The purpose of this phenomenological enquiry was to gain a deeper understanding of what it means to be an adolescent living with a sibling who has a chronic illness. Children’s chronic illness has an impact on well siblings and research findings have been inconsistent as to what effect this has on them. Semi-structured interviews using photo-elicitation were conducted with eight adolescents who had siblings with a chronic illness. Through the use of interpretive phenomenology, three themes emerged: Making Sense over Time, Getting Away from It All, and Creating Common Ground with Siblings and Family. The adolescents were able to make sense of chronic illness over time by asking parents questions about the illness and attending support groups. Siblings found normalcy in their lives by getting away to spend time alone or connecting with friends.

The study of the immune system has provided insight in the mechanism of protection induced by vaccination; primarily that most clinically protective vaccines are potent in generating neutralizing antibody responses. However, vaccination fails to protect against a wide range of acquired chronic infections caused by viruses, such as HIV, HBV and HCV. One of the major reasons for weak responses to therapeutic vaccine is the impaired function of effector T cells resulting from viral persistence. Although IL-2 can potently increase effect function of viral specific T cells, systemic administration of IL-2 induces organ pathology and expansion of Treg cells. In this study, we have now developed a novel vaccine delivery system IL-2-nanoAPC delivering antigen-MHC complexes (pMHC), co-stimulatory molecules and IL-2 to antigen specific T cells. NanoAPC are derived from the endoplasmic reticulum (ER) membranes of human B cell line 721.221 engineered with selected HLA allele and IL-2 as the ER retention proteins. The IL-2-nanoAPC interacted with antigen specific T cells, induced immune synapses and expression of high affinity IL-2 receptor and enhanced effector function of antigen specific T cells, but did not affect bystander T cells and Foxp3+ Treg cells. Together with pMHC, co-stimulatory molecules, the selective delivery of IL-2 not only increased the CD4 and CD8 T cell responses to viral antigens but also enhanced TCR proximal signalling and suppressed expression of PD1 molecules on IFNγ producing effector CD8 T cells. We also found that the co-induction of T helper responses by IL-2-nanoAPC in a mixed culture could increase CD8 T cell responses to viral antigen. The IL-2-nanoAPC effectively induced responses of CD4 and CD8 T cells from chronic HBV patients. The results demonstrate that selective delivery of IL-2, together with pMHC and co-stimulatory molecules, by nanoAPC to antigen specific T cells has potential to recover anti-viral immune responses in chronic HBV patients.

Heart failure is a common and serious chronic condition, which can be as ‘malignant’ as most forms of cancer (Stewart, MacIntyre, Hole, Capewell, & McMurray, 2001). Recent estimates are that around 40,000 men and 45,000 women are living with heart failure in Scotland (Stewart, MacIntyre, Capewell, & McMurray, 2003). Heart failure is significantly influenced by socioeconomic factors, with people on lower incomes being more likely to develop, and die faster from, heart failure (McAlister et al, 2004). There is a growing body of research on the experience of living with heart failure, however, none provides serious consideration of the role of socioeconomic factors in impacting the experience of heart failure, and some qualitative research may actually obscure such factors. There were two main aims in this thesis. One was to explore how qualitative research methods can better consider the relationship between experience and broader context, such as the influence of socio-economic factors on health. The other aim was to examine the experiences of people as they live with and die from heart failure in ways that situate their accounts in the broader context of their lives. An initial research study, on which I was the main researcher, focused on the experiences of 30 people living with advanced heart failure. These people, their carers and key health professionals were interviewed, where possible, three times over a six months period. This thesis re-examines that study, focusing on 20 of those participants, for which a total of 122 interviews were conducted. I used a dialogical approach to see whether the socioeconomic context of heart failure for these respondents, could be captured through exploring experiences, performance, relationships, discourses and institutional practices, the social processes that mediate the relationship between socioeconomic disadvantage and chronic diseases were explored. This offers important learning in relation to the experience of living with heart failure, along with the experience of providing care. The findings highlight the need to broaden our view of chronic illness beyond biomedical approaches, and grow our methodological approaches along with that, in order to develop knowledge and practice that has relevance for people who live with and die from heart failure.

UK Health policy over the past decade has sought to accelerate established trends of moving services for type 2 diabetes into primary care. This has aimed to make services more accessible and to enable patients to benefit from having their diabetes care incorporated into the “generic and holistic” approach of primary care. However, in 2004 the introduction of a new General Medical Services (nGMS) contract signalled a change in primary care by linking clinical targets to financial rewards on a larger scale than ever before. Diabetes is one of nineteen financially incentivised clinical areas under the nGMS contract (2006). This thesis considers how these health policies may have influenced the organisation and experience of providing and receiving care for type 2 diabetes in Scottish primary care settings. It also aims to bridge two usually separate areas of sociological interest: how health professionals interpret and implement policy, and how patients experience and perceive chronic illness and their health care. A multiple case study approach was employed in order to compare and explore the organisation and experience of type 2 diabetes care associated with three general practices of differing size and location. In each case study a period of non participant observation was undertaken and in-depth interviews conducted with health professionals and their type 2 diabetes patients. Analysis of these data shows that multiple factors influence the way diabetes care is organised and experienced in primary care. I argue that the local context of interpersonal relationships of trust, professional identities and role expectations influence both the organisation of care and the way patients interpret that organisation. Moreover, the meanings patients attribute to the local organisation of diabetes care can inform their perceptions of their condition and influence their desire to be involved in diabetes management.

Psychological adjustment to chronic pain has been recently explored within three separate frameworks: a behaviour-focused account of chronic pain acceptance within the broader remit of Acceptance and Commitment Therapy; an emotion-focused approach with various research programs investigating the role of anger, fear, depression and also shame and positive emotions in chronic pain; and a cognitionfocused perspective more recently reframed in terms of illness perceptions as part of a wider model of response to health threats, the Self-Regulatory Model. Although these frameworks have broad areas of overlap, limited research has been directed at integrating acceptance, emotions and illness perceptions into a common, comprehensive account of psychological adjustment to chronic pain. Such an account would be beneficial both for providing a parsimonious approach that would guide further research and for developing pain management interventions that would take advantage of existing research from all three domains. The aim of the present thesis was to explore the possibility of integrating these separate areas by studying the relationships between the main concepts (acceptance, emotions, and illness perceptions) in the context of chronic pain. Based on a review of the relevant conceptual and methodological issues of each domain, a theoretical analysis of the similarities and differences between them was developed, with particular emphasis on the potential of existing models to support an integrative account. This analysis provided specific hypotheses regarding each domain and the interrelationships between them, which were investigated in a longitudinal study on a heterogeneous sample of 265 chronic pain patients using the services of the NHS Lothian Pain Clinic and several patient support organisations. Data were collected via postal and online questionnaires at 3 time points, at 41/2-month intervals (21% attrition rate). Validated questionnaires were used to measure the relevant constructs, with additional questions obtaining information regarding health status, medical history and demographics. The confirmatory analysis (employing a variety of statistical procedures, from correlation to multiple regression, factor analysis, cluster analysis and structural equation modeling) largely confirmed the expected relations within and between domains and was also informative regarding the most suitable data reduction methods. A detailed psychometric analysis of the questionnaires used offered a complementary view on the theoretical and methodological issues involved. An additional exploratory analysis focused on identifying the comparative characteristics of acceptance, emotions, and illness perceptions in predicting health status indicators, controlling for contextual factors such as medical history and demographics. Although no significant longitudinal changes were identified in most parameters (confirming the clinical observation of chronic pain as a stable condition), the longitudinal data allowed an analysis of the stability of the concepts and of the magnitude of their relationships in this patient sample. The analysis of intra- and interpersonal variation via hierarchical longitudinal modeling confirmed the stability of the data, highlighted the necessity of studying variation at both levels, and revealed interesting moderation effects, explained via the proposed concept of ‘discrimination ability’ and several alternative mechanisms. These results can be considered as first steps towards an integrative model of psychological adjustment to chronic pain. It is proposed that the behavioural, cognitive and emotional aspects need further conceptual clarification and these future efforts can be supported by the Cognitive-Affective Model of the Interruptive Function of Pain, within the wider framework of the Self-Regulatory Model.

Methods: All patients (5606) with at least one serum creatinine ≥130μmol/L in females and ≥150μmol/L (Index creatinine) in males during a 6 month period in 2003 were grouped according to whether they had Acute Kidney Injury (AKI), Acute on chronic renal failure (ACRF) and chronic kidney disease (CKD). 1903 patients could  not be classified. After using all available creatinine data and identifying markers of kidney damage a further group of patients with CKD were identified. Case records were examined for the presence of co-morbidity, date of death, cause of death and whether they were known to a renal physician. Results: 1225 patients were identified as having CKD out of the 1903 “Unclassified” cohort (65%). The majority of CKD patients were elderly females with Stage 3 CKD. Hypertension and ischaemic heart disease were the two most common co-morbid conditions. Only 12% of CKD patients were referred to a nephrologists. 43% of CKD patients were dead at follow-up mostly from cardiovascular causes (31^st December 2005). The presence of proteinuria was independently associated with death. The age adjusted standardised prevalence of CKD, excluding those on RRT, was 20929 per million adult population. 3.6% went on to start RRT by the end of follow-up. Conclusions: CKD is predominantly a condition of elderly females, associated with considerable morbidity and mortality. However the majority of patients die from cardiovascular disease before progressing to ESRD. Therefore these patients may be appropriately managed in primary care without the need for specialist renal input allowing targeting of the specialist renal resources to the fewer patients who require them.

Introduction/Background: Chronic widespread pain (CWP) affects around 11% of the population and while aetiology is well documented it has been difficult to translate this into effective management strategies. Patients in clinical trials are known to be different from the patient populations that they represent and treatment preference is one area where they may differ. Treatment preference may also influence outcome, particularly when participants cannot be blinded to treatment allocation. Aims: To assess whether patient treatment preference has an influence on 1. Recruitment, 2. Outcome, and 3. Adherence In a clinical trial of interventions for CWP. Methods: In the MUSICIAN trial, a 2x2 factorial trial of exercise and telephone cognitive behavioural therapy (T-CBT) for CWP, treatment preferences were recorded when eligibility was assessed using a population postal survey. Eligible individuals who did and did not go on to enter the trial were compared to address aim 1. Trial participants were followed up after 6 months of treatment and outcomes were compared according to whether they received their preferred treatment to address aim 2 and T-CBT and exercise logs were used to assess adherence to examine aim 3. Results: Eligible individuals were more likely to be randomised into the MUSICIAN trial if they expressed a treatment preference in the screening questionnaire (Relative Risk 1.46, 95% confidence interval 1.19-1.79). Treatment preferences were also associated with prognostic factors (anxiety and fear of movement). At follow-up participants were more likely to achieve a good outcome (global assessment of change) if they had received their preferred treatment (Relative Risk 2.50, 95% confidence interval 1.54-4.03)and this may be due to those individuals being more likely to adhere to treatment programmes. Conclusions: Wherever possible participant treatment preferences should be recorded prior to randomisation in clinical trials. Additional benefit may be gained in clinical practice by tailoring treatment to patients’ preferences.

This mini-dissertation was submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban Institute of Technology, 2005. xxvii, 153 p. / Chronic fatigue syndrome (CFS) remains a medically unexplained syndrome, with differing aetiological models, case definitions and treatment recommendations (Ranjith, 2005:13). Sharpe & Wessely (1997:179) state that the current case definition for CFS has assumed acceptance as representing nothing more than a working definition of a clinical problem, pending further understanding. CFS has subsequently become the focus of much research and debate (Wessely, Hotopf & Sharpe, 1999:13). Notwithstanding, the definition in terms of diagnostic criteria is adequate in meeting the needs of research studies (Rutherford, 2003). Anecdotal reports, espousing the effectiveness of homoeopathic treatment of CFS, points to the use of the similimum. (Bailey, 1995:189; De Schepper, 2001:6-7; Hardy, 2005:8-10). However, the limited research available on the subject suggests that more research needs to be conducted in this regard (Wessely, Hotopf & Sharpe, 1999:371; Walach, 2004:210-211). This double-blind placebo-controlled study was conducted to determine the effectiveness of homoeopathic similimum treatment in chronic fatigue syndrome (CFS). / M

Background: Diabetes is one of the most common and pernicious chronic illnesses. Guidelines recommend visiting a physician for the secondary prevention of complications. Many risk factors and barriers exist, which hinder healthcare usage. Males are at higher risk for many health issues, including diabetes, yet research shows that women are more likely to receive preventive services. The purpose of this study is to examine whether putative risk factors and barriers to care are diabetes-specific and whether their impact varies by gender. Methods: The Behavioral Risk Factor Surveillance System was used to assess disparities between genders related to diabetes-specific care. In addition, logistic regression was used to determine whether barriers to healthcare, such as education, lack of health insurance, and out-of-pocket-costs, were also diabetes-specific; and did they significantly vary by gender. Results: Analyses demonstrated that males were less likely to visit the physician for their diabetes care. Results indicated that while there were main effects for the additional barriers, they did not vary by gender. Within-groups analyses showed that the odds of not receiving adequate care for those with a lack of insurance were greater for males. Conclusion: Results demonstrated that in many instances, both gender and the chosen barriers increased the odds that individuals would not receive the optimum level of care, although not varying by gender. The lack of an insurance plan was shown to reduce the likelihood that males would receive the appropriate care. These findings potentially aid in the development of more gender-specific interventions and policies.

This study investigated the expression and activity of tissue transglutaminase (tTG) in human umbilical vein endothelial cells (HUVEC) and vessel wall. tTG was located in the SMC and sub-endothelium of normal vessels. Cross-linking activity was also in this area. Vessels with atherosclerotic plaque showed increased staining for tTG and cross-links. Positive staining for tTG was located in the SMC, neointima, macrophages and the fibrous cap. Most cross-linking activity was observed in the fibrous cap, and cross-linking was observed around macrophages and smooth muscle cells. Cross-linking activity was also observed with incorporation of a labelled cross-linking substrate into vessel sections. Free tTG could be extracted from the vessel wall. HUVEC expressed 10 g tTG/mg total protein. tTG was detected in cell lysate and extracellular matrix, but not in the culture supernatant. Thrombin up-regulated tTG expression at both the mRNA and protein level. Optimal up-regulation was at a thrombin concentration of 1 U/ml The up-regulation by thrombin was dependent on thrombin activity, and was mediated through the thrombin receptor, protease-activated receptor 1 (PAR-1). Cross-linking activity was also increased after thrombin treatment, measured with a microtitre plate assay and an in situ assay. The specific activity of tTG increased after thrombin treatment. Thrombin treatment increased the level of tTG in the HUVEC ECM. Treatment of HUVEC with PMA reduced the expression of tTG mRNA, reduced the level of tTG protein, but increased the tTG cross-linking activity compared to untreated cells.