Objectives: To evaluate the accuracy of the four main Intensive Care severity of illness scoring models using a large Scottish database, and to investigate different strategies for improving their accuracy in a Scottish setting. Method: Twenty two out of 25 general adult Intensive Care Units in Scotland collected data for two and half years to allow calculation of Acute Physiology and Chronic Health Evaluation (APACHE) version II and III, Simplified Acute Physiology Score (SAPS) version II, Mortality Probability Model (MPM) version II (calculated on admission and at 24 hours). The models' Goodness of Fit (discrimination and calibration) and performances in subgroups (Uniformity of Fit) were evaluated using Receiver Operating Characteristic Curves, Hosmer-Lemeshow Goodness of Fit test, Chi Squared test and Confidence Intervals. Three of the Models (APACHE II, SAPS II, and MPM II) were customised with Scottish data using logistic regression techniques. Results: All models had good discrimination but poor calibration. However, the SAPS II and APACHE II models appeared to have better calibration than other models. All models, except the new APACHE II model, showed significant differences in important subgroups. Conclusions: Questions remain about the accuracy of these models even after customisation. Further research is needed to investigate variations in Intensive Care Units and the relationship to clinical effectiveness. However, where case mix adjustment is needed the new customised models remain the most accurate means of doing this in Scottish data.

The role of intestinal nematode infections in the aetiology of iron deficiency and anaemia in pregnant women was investigated in peri-urban and rural areas of Western Sierra Leone. A randomised placebo-controlled field trial was carried out to evaluate the efficacy of a single course of albendazole (400 mg) and daily iron-folate supplements (36 g iron and 5 mg folate), administered after the first trimester, as control interventions for intestinal nematode infections and anaemia during pregnancy. At baseline, in the first trimester of pregnancy, the prevalence (and geometric mean intensity) of intestinal nematodes was as follows: <I>Ascaris lumbricoides </I>21.1% (267 eggs per gram); <I>Necator americanus </I>66.5% (191 epg); and <I>Trichuris trichiura </I>71.9% (93 epg). Chronic undernutrition (height < 150 cm) and chronic energy deficiency (body mass index < 18.5 kg/m<SUP>2</SUP>) was found in 5.4% and 8.2% of women respectively. Anaemia (Hb < 110 g/l) was diagnosed in 58.7% of women and associated with iron deficiency (serum ferritin < 20 μg/l) in 21.2% of women. Iron deficiency is likely to have a dietary basis in these women. The dietary iron intake was predominantly non-haem, and was estimated to supply less than 1 g of absorbable iron daily. High fertility and closely spaced pregnancies placed additional stress on iron stores. The findings of this study indicate that anthelminthic treatment should be included in strategies to control maternal anaemia in Western Sierra Leone. It is recommended that pregnant women routinely receive a single course of anthelminthics after the first trimester, alongside daily iron-folate supplements, to minimise the decline in maternal Hb concentration during pregnancy. These interventions could be implemented through the existing primary health care system, although the use of traditional birth attendants should be investigated as a means of improving compliance and coverage. The implications of these findings for public health policy in other antenatal populations will depend on the local epidemiology of intestinal nematode infections and on the extent of underlying maternal iron deficiency and anaemia.

No description available.

This study was conceived against the backdrop of academic and medically based discussions about inappropriate use of General Practice, in the context of an overburdened and under resourced National Health Service. Both frequent and less frequent consulters prioritised dilemmas around functional ability, reporting attempts to control illness, and resist loss of normal life and familiar selves. Despite our attempts to sample frequent and less frequent users with similar levels of morbidity in the more detailed qualitative interviews the frequent consulters conveyed more severe illness, which limited their lives and challenged their coherent and moral identities. Cultural, structural and social factors combined to influence health actions; personal troubles were linked to public matters. The accounts revealed how the severity of condition combined with social position influenced the place of the GP consultation in overall management strategies. Women and men communicated common problems, but also discussed experiences which were related to their traditional family roles. Housing status was not revealed as significant, in the context of a complex combination of micro and macro influences on experience. In the frequent consulters’ accounts the role of the GP was magnified in lives diminished and disrupted by chronic illness, whereas the less frequent consulters’ accounts presented a more peripheral role for their GP. Using Bourdieu’s central concepts, the GP was conceptualised as a ‘dispenser of capital’. Throughout, all of the participants described the hard work of illness management, and they used the accounts to display their moral competence. The medical encounter was conveyed against a moral backdrop, and this may have had implications for frequency of consulting. Overall, the symbolic and physical burden of chronic illness was highlighted.

Introduction. Trace element status may be important in acutely-inflamed patients. Plasma concentrations of trace elements are known to alter during the evolution of the acute phase response, however, erythrocyte trace element concentrations do not. It is not known whether either erythrocyte or plasma concentrations reflect the status of the tissues where trace elements are utilised. Therefore trace element concentrations were examined in tissues and blood from non-inflamed patients, with plasma and erythrocyte concentration changes studied during the evolution of the acute phase response. Methods: 31 patients undergoing liver resection had liver, rectus muscle, and blood samples obtained pre-operatively, and blood sampling for 3 days post-operatively. Se, Cu and Zn concentrations were obtained by inductively coupled mass spectrometry after nitric acid digestion. Erythrocyte glutathione peroxidase (GPx) was measured by spectrophotometry. C-reactive protein and albumin concentration were measured on each day. Results: C-reactive protein increased and albumin concentration decreased over the 3 days postoperatively. Plasma Zn and Se concentration changed in the 3 days post-operatively (p<0.001); erythrocyte Cu, Zn and Se concentration, GPx activity and plasma Cu concentration did not change. Preoperatively, liver Cu concentration was associated with erythrocyte Cu concentration (r2 15.9%; p=0.036) but not plasma Cu concentration (r2 4.3%; p=0.264); plasma Zn concentration was associated with liver Zn concentration (r2 14.4%; p=0.046) but erythrocyte Zn concentration was not (r2 0.1%; p=0.896); and liver Se concentration was associated with erythrocyte Se concentration (r2 17.1%; p=0.023), erythrocyte glutathione peroxidase (r2 22.6%; 0.008) and plasma Se concentration (r2 43.1%; p<0.001). Conclusions: Erythrocyte Cu and Se concentration, and GPx activity are associated with liver Cu and Se concentration respectively, and do not change during the evolution of the acute phase response. They should be considered as potential markers of Cu and Se status. Plasma Zn is associated with liver Zn concentration but the concentration changes during the acute phase response; caution should be taken interpreting results in patients with inflammation, and further work is required to find a suitable alternative marker of Zn status.

This thesis presents men’s discussions and experiences of health and illness and its relation to, and implications for, the practices of masculinity amongst a diversity of men. Fifty five men participated in fourteen semi-structured focus group interviews. Diversity in men’s experiences of health and illness and in their constructions of masculinity was sought within the sample by age (range 15-72 years), occupational status, socio-economic background and current health status. Groups of men were recruited who had had ‘everyday’ or unremarkable experiences of masculinity and health and groups of men with health experiences that could have prompted reflection on masculinity and health. This included groups with men who had prostate cancer, coronary heart disease, mental health problems, and Myalgic Encephalomyelitis (ME). All of the men that participated in the study lived in central Scotland (Glasgow, Edinburgh, Dundee, Lanarkshire and Perthshire) and just one group was conducted with men of Asian origin, which reflects the limited ethnic diversity in this part of Britain. The first data chapter examines participants’ descriptions of their masculinity and their health-related beliefs and behaviours. The data capture both the experiences of men who felt pressured to engage in behaviours that may be harmful to their health in order to appear masculine and the accounts of those who regarded themselves as freer to embrace salutogenic health practices as they perceived there to be fewer consequences for their masculinities. These considerations are then followed by an examination of how participants re-negotiated male identity in the light of illness. The final data chapter presents participants’ discussions and experiences of help seeking and its relation to the practice of masculinity. The data suggests a widespread endorsement of a ‘hegemonic’ view that men ‘should’ be reluctant to seek help, particularly amongst younger men.

Human embryonic stem cells (hESCs) have the potential to differentiate into all cell types of the three germ layers. However, various limitations hinder their use in the clinic, including possibilities of teratoma formation, xenogenic exposure through the use of Matrigel™ and feeder layers, along with poor attachment and expansion rates and inability to transport hESCs into an in vivo site. This thesis has aimed to overcome the above limitations. Electrospun nanofibrous substrates from a purely synthetic FDA approved material have been developed and investigated for the novel use in the expansion of undifferentiated hESCs. Synergistic effects between the oxygen environment and nanofibre technology were revealed which demonstrated the expansion of pluripotent hESCs in physiological normoxia (2% O2) on these substrates, with retention of differentiation capacity. However, in hyperoxia (21% O2), hESCs cultured on these substrates dictated embryoid body formation. A range of polymers (PCL, PLLA and PLGA) were tested (aligned and random conformations) where the optimal polymer (PCL) was further investigated at 2% O2 at various fibre diameters to reveal its impact on hESC clonogenicity.

This thesis sets out to test the central hypothesis that the paradigm for clinical decision support needs to shift from a technology centred paradigm to a coherent ontological-epistemological paradigm. This was achieved by formalising a coherent ontological and epistemological framework, and then applying it practically to clinical decision support. Initially the thesis reviews the need for a coherent philosophy in clinical decision support. It then goes on to describe the systematic analysis of established fundamental principles of philosophy, and the formalism of the ontological and epistemological framework. Following this the framework is applied to an analysis of clinical decision making and clinical decision support. The models derived from the analysis are then applied practically to the modelling of the management of acute renal failure patients in the intensive care setting. The results of this modelling are then combined with the decision models as the basis for the structure of a model of the decision making which controls the patient's renal replacement therapy. Finally the models representing the clinical problem and the clinical decision making process are used in the design and development of a prototype renal replacement therapy management system. The thesis concludes that a coherent ontological and epistemological framework provides clarity and insight during the analysis for and design of clinical decision support tools. The contributions of the thesis relate to the derivation and application of the framework, and the development of the renal replacement therapy management system. Thus the thesis is a foundation for future research in these two areas.

Aims were (1) to review the literature on clinical audit; its history, methodology and role in the current National Health Service (NHS) Clinical Effectiveness initiative; and (2) to describe and discuss one national clinical audit exercise, the Gynaecology Audit Project in Scotland (GAPS) audit of the investigation and initial management of infertility. Care by general practitioners: The review of referral letters revealed that less than half of couples have basic tests of confirmation of ovulation and semen analysis performed in primary care. Conversely, up to a fifth of women with regular menses undergo unnecessary and expensive endocrine investigations. Between the two audit periods, significant, but modest, improvements occurred in the proportion of couples where the male partner was examined and had semen analysis performed and where the women's rubella status was checked. Care by gynaecologists: Between the two audit periods, significant changes in line with nine of the agreed audit criteria were demonstrated. two significant changes contrary to the agreed criteria also occurred. Patient satisfaction and experience: The patient survey indicated that 87% of women were satisfied with their care. However, over a third (39%) had never been asked to bring their partner to the clinic; 86% felt they had not been given enough help with emotional aspects of infertility; only a third had been given any written information and 78% expressed a wish for more written information. Conclusions: Clinical audit remains a cornerstone of national strategies to promote more uniform standards of high quality, evidence-based care. The GAPS Infertility Audit demonstrated the feasibility of conducting a national audit exercise encompassing patient management in both primary and secondary care settings. Modest changes in the process of care and in patients' experience were demonstrable. The modest extent of change confirms the view that audit and feedback may not be the most effective means of promoting improvements in practice. Further research is needed to determine obstacles to change and the most effective ways of overcoming them.

Peritoneal dialysis (PD) utilisation is falling in Western Countries. Concerns regarding reduced survival on PD, impact of inadequate dialysis on patient outcomes and the serious complication of encapsulating peritoneal sclerosis (EPS) may be contributing to the decline of PD. The exact incidence of EPS has been difficult to establish because of differences in design of published studies. In Scotland there was concern that the incidence of EPS was increasing, which prompted discussions about the future role and risks of PD. The aim of the MD was to establish an accurate incidence of EPS in Scotland and to examine complications and outcomes of PD patients to try to answer the question of who and for how long PD should be used in our population. Since 1999 all adult renal units in Scotland have completed a PD Audit form 6 monthly for every PD patient which gives details of PD population, source of new patients, reasons for stopping PD, causes of technique failure, details of all peritonitis episodes, adequacy test results and basic laboratory results. This prospectively collected data was linked to further demographic and laboratory data from the Scottish Renal Registry database for analysis. The analysis focussed on all incident patients commencing PD between 1st January 2000 and 31st December 2007 (n=1324), with follow-up to 30th June 2011. Our data analysis confirmed the ongoing fall in PD population in Scotland, and greater usage of APD. Peritonitis rates have remained steady at 1 episode every 19.9 months when averaged over the study period; similar to UK and Australasian results but worse than North American centres. Several risk factors for peritonitis were identified in our population including unit, CAPD compared to APD, diabetes mellitus (DM) in females, older age, hypoalbuminaemia, and lower residual renal function (RRF) at the start of PD. We established that the overall risk of EPS is low, but if PD is continued beyond 4 years the risk is substantial at 1 in 13 patients, with an exponentially increasing incidence with longer PD exposure. Survival is poor with 46.8% mortality at 1 year after diagnosis. No clear risk factors were apparent other than PD exposure. Analysis of patient survival identified several factors associated with poorer survival including increasing age, hypoalbuminaemia and RRF at the start of PD, presence of DM and multisystem primary renal diagnoses as well as having experienced peritonitis. The main causes of technique failure in our cohort include peritonitis (42.9%) and inadequate dialysis (22.1%). Predictors of technique failure include DM, lower RRF at the start of PD and being treated in more recent PD eras. Overall analysis of the PD cohort has shown that PD is a short-term treatment in Scotland with only a quarter of patients continuing PD beyond 3 years, with the remainder stopping for a transplant, technique failure or death. It is not possible to predict how long an individual patient will continue PD, but certain patients have poorer outcomes including the elderly (>70 years), those with DM and those hypoalbuminaemic at the start of PD. Therefore the actual number of patients who will continue PD long enough to be at significant risk of EPS is very small, and we believe the potential risk of EPS should not prevent patients from being offered PD in the first instance. Although some patients fare better on PD than others, we cannot state that any specific patient group should not be offered PD on the basis of our analyses particularly as we cannot show that they would have improved outcomes on haemodialysis. For the minority of patients with ongoing technique success at 4 years we suggest discussing ongoing PD, ensuring patients are informed about the EPS risk and a risk:benefit assessment of ongoing treatment should be decided on a case by case basis. It is likely that clinician attitude are driving the decline of PD, in the absence of evidence to show inferior outcomes on PD compared to HD. There would be an argument for actively increasing PD utilisation in Scotland, particularly among the elderly by expanding the assisted PD programs. Similarly, unless efforts are made to ensure adequate PD training and experience for nephrology trainees it is likely that PD will continue to decline.