This study focuses on the way in which rapid structural changes (such as economic development, urbanisation and other demographic factors, and the economic crisis of 1997) have raised issues that are seen to require a social policy response in the mental health care arena under Confucian governance in South Korea. These structural changes happened over a couple of hundred years in Western Europe but have taken place over only the past 40 years in Korea. The main thrust of the study is on the extent to which the decisions about policy responses to perceived social problems, especially the increasing number of people with mental health problems, are structurally driven or the extent to which they are informed and shaped by Korean politics and culture. The industrial and economic base of Korea grew dramatically until the late 1990s. This facilitated the development of social policies - particularly in areas such as education, health and housing, which support economic growth. However, although the structure of the family changed to be closer to its structure in the West, it could be argued that evidence pointing to a broader ‘Westernisation’ of Korean society was premature. Confucianism may have been a factor in Korea's development, but it may yet prove a hindrance to any further moves to modernity and equalisation of life chances amongst its citizens. Since the economic crisis of 1997, Korea has experienced a rapid expansion of social welfare provision following a series of reforms. These reforms have gone beyond the functional minima necessary to deal with social problems caused by the economic crisis. However, the government has tended to stress the greater role played by family members, particularly women, in providing care to their elderly relatives, and the desirability of multigenerational households over nuclear families. A similar emphasis on the caring roles of the family and community is also seen in the Korean state's renewed public emphasis on the country's Confucian cultural tradition. As a result of this, there has been a tension between the increased emphasis given to the role of the informal carer within mental health policy as the Korean government has introduced a community-based scheme which assumes that families want to care and those with mental health problems want to be cared for by their families. Accordingly, the main burden of care falls upon women. This still tends to be ignored by policy makers. Despite the country's rapid demographic, economic and social changes, there has been a widening gap between the population's expectations and needs and health and social service provision in the mental health arena. Neither long-term care services nor personal social services are well developed for those with long-term mental health problems. In addition there is a marked disparity between the acute services, which are predominantly provided by private sector organisations in a highly competitive market and broadly achieve high standards, and public primary care and rudimentary residential services in the mental health arena. In this context, it could be argued that Korean mental health policy is concerned with maintaining social order rather than care and treatment of those with mental health problems.

There are various views towards Attention Deficit Hyperactivity Disorder (ADHD) and the recent introduction of the disorder for adults has added to the controversies. I intend to explore variation in clinicians’ perception and approach towards adults with ADHD. I produced a vignette describing an adult with a diagnosis of ADHD and sent it to 150 clinicians. I received 44 replies, and performed 16 semi-structured interviews. I found participants suggested various diagnoses, causes of the problem, treatments, and the appropriate professional group for the vignette. Participants confirmed the existence of variation in the clinicians’ perception and approach. Their views also suggested that the different characteristics of clinicians, diagnostic methods, psychiatric disorders, the possibility of access to different information and social factors were contributing to the variation. In addition, my analysis indicated that participants might have different perceptions according to their experience, awareness and work-settings. I found that the variation might be also related to the inclination of participants towards particular disorders or styles of practice, and hermeneutical factors. Finally, I produced a model that illustrates a relationship between different factors with the variations in clinicians’ perception and approach. In conclusion, I suggested the dependency of diagnosis on clinicians, the possibility of a variation in their knowledge, and gaps between research and practice. I described different types of competition that exist in the process of the medicalization of ADHD. Finally, I discussed directions for future investigations.

This thesis examines the health-seeking behaviours of Korean migrant women living in the UK. Theoretically, it argues for treating migration as a process of 'subjectivisation', in the specific sense in which this concept is employed in the work of Michel Foucault, and cliams that migrants' health-seeking behaviours always presuppose and refer back to a fundamental process of assuming, appropriating and manifesting the dominant form(s) of subjectivity within the domain of medicine of the host country-in the case of the UK, the medical subjective form of the 'active patient' and/or 'healthy citizen'. In the present work I show that Korean migrant women tend to resist this process of becoming subject to the ideal active patient model until they happen to undergo some profound and life-altering experience that forces them to come to terms with the British system and its ideal forms of knowledge and behaviour. For (but not all) Korean migrant women, this life-altering experience is that of pregnancy, delivery and childbearing. Pregnancy and childbirth constitute the turning point in a process of subjectivisation and culminates in the institution of a dual medical citizenship. In other words, while they never totally reject their former autochthonous mode of medical subjectivity ('good patient'), they nevertheless come more and more to appoximate the British model subjective form. On the other hand, when it comes to their children, who are ethnically Korean but born and raised in the UK, they tend almost fully to surrender to the British ideal, recognising that their childrn, while Korean, nevertheless possess originally British bodies that demand British treatment. This causes them to become extra vigilant and resourceful regarding their health-seeking behaviours, bringing them more fully in line with the ideal form of medical subjectivity of the active/healthy citizen.

The toxicological investigations demonstrated quite clearly the different toxicological properties of the MA, CRS and ANR. The CRS proved to be fibrogenic in rat lung with a 5.0mg single instillation dose after long-term (1 year) exposure whereas ANR was minimally bioreactive. The MA did not cause inflammation in the lung until 49 weeks post-instillation even though size augmentation with granuloma formation in thoracic lymph nodes were recognised at 13 weeks. These findings suggested that the size and granuloma formation of thoracic lymph nodes were good early markers to assess the toxicity of crystalline silica containing volcanic ash. Histopathological and physicochemical investigations confirmed that the particles drained from the lung were deposited in mainly the granulomatous areas in the nodes. Furthermore, the crystalline silica content of the MA in the nodes was greater than that noted in the MA in the lung tissue and the original instillate. The macroarray technology has provided additional information on MA and CRS induced inflammation. A number of candidate inflammatory markers were identified

Background and Importance: comparative evidence generated using systematic reviews and meta-analyses can form the basis of high quality prescribing decisions in clinical practice. Such evidence is imperative when choosing a first-line treatment among multiple alternatives, particularly in the United States where there is no single national authority responsible for providing practice guidelines for prescribers. Objective: Using cholesterol-lowering statins as a case study, this thesis set out to evaluate the comparative clinical benefits and harms of statins for the prevention of coronary heart disease. Novelty and Empirical Contribution: The empirical work presented in this thesis was based on a systematic review and network meta-analysis, for the first time combining the placebo-controlled and active-comparator trials of statins. Using 184 randomized trials including 260,630 individuals with or without cardiovascular disease, this thesis makes four major contributions to the literature on the comparative effectiveness and safety of statins, showing the following:(1) cholesterol-lowering effects of statins are less pronounced than suggested by the previous reviews; (2) statins potentially differ in terms of their comparative effects on clinically meaningful benefit outcomes, which are not fully explained by their cholesterol-lowering effects;(3) harms associated with statins are rare; still, some statins are safer than others; and (4) unlike previous findings in the literature, there is no evidence of industry sponsorship bias affecting the trials of statins. Implications for Clinical Practice: Although there are statistically detectable and clinically relevant differences among individual statins, the empirical work presented in this thesis does not conclusively identify a clear winner among statins that should be favored in clinical practice. Future&Research Directions: The potential mechanisms underlying the observed differences between individual statins should be investigated in future studies. Policy Relevance: The findings presented in this thesis suggest that statin prescribing patterns over the past decade – and in particular atorvastatin’s exceptional sales performance despite its equivalence to simvastatin – are not supported by the current best evidence. A proposed policy option is to raise the bar for market entry of new drugs by requiring comparative evidence at the time of approval decisions. Network meta-analysis methods can be used at the United States Food and Drug Administration setting, thereby making comparative evidence available before prescribing patterns are established.

Continued pressure to reduce costs and manage healthcare delivery in risk-based reimbursement environments, has, internationally, resulted in hospitals adopting different methods to manage pharmaceutical and surgical consumable products. An initial review of systems of management of these products showed that the trend is to manage them separately. Pharmaceutical products are managed using dedicated resources and structures in each hospital, which may be difficult to establish and sustain in smaller, non-academic hospitals. Amongst other factors, the absence of a classification system and a lack of utilisation information hindered the development of management systems for surgical consumable products. In addition, traditional materials management processes applied to these products, often do not adequately address the impact that these products have on clinical care. In this study, the decision was made to develop an integrated system for both pharmaceutical and surgical consumable products and to adopt a systems approach in which all hospitals in the group were included as a single system. The study was multi-methodological with the design being contextual and qualitative and the research strategy, exploratory and descriptive. A multi-phased, action research approach was used, comprising of three (3) cycles, two (2) in which the integrated system was developed and enhanced and a third in which it was independently tested in 19 newly acquired hospitals. The result of the three (3) cycles was an implemented integrated system across 43 acute-care hospitals in the group comprising six (6) processes namely: a product selection process, information technology (IT) support system, a hospital implementation process, measurement and management tools, pharmacy capability and a supplier strategy and interface process. These processes included several key unique features, such as one (1) product selection team for all hospitals, a surgical classification system based on functional therapeutic uses, a single IT system and utilisation review capability for all products, extending the role of pharmacy departments in hospitals to include the management of surgical consumable products and an integrated quality assessment process for both types of products. By the end of the three (3) cycles (September 1999), the product selection process covered 66,5% of value of product spend, the percentage reduction in the number of products used was 68% and the value of products purchased that complied with specified products and suppliers was 90%. Ongoing and further application showed that the integrated system could be sustained in existing hospitals, applied to a further four (4) newly acquired hospitals and expanded to include specialised pharmaceutical and surgical consumable products in cardiac catheterisation laboratories. By September 2003, the total spend on pharmaceutical and surgical consumable products had reached R1,7 billion. The product selection process covered 67,6% of total spend, the compliance value reached 95% and there were additional financial improvements realised. Following a further literature review, limitations and improvements to the approach were identified and further adaptations were added as concepts in the graphic representation of system. One (1) of these was to show the integrated system as an open system. The second adaptation highlighted the systems-based input-process-outcomes feedback concept that is critical to continuous improvement of the system. In the final progression, a systems approach to strategic planning and management was incorporated in order to provide a structured approach for adapting to the rapid and ongoing changes in healthcare and aligning the system of management of pharmaceutical and surgical consumables to the overall business strategy. Overall, this research study succeeded in bringing new perspectives and an innovative approach to the management of pharmaceutical and surgical consumable products by developing and implementing an integrated system for both products, establishing essential processes with key unique features and tools, and the application of a systems thinking approach. Four (4) areas of further research are suggested, namely testing the integrated system in other contexts, improved methods of measurement of quality of care, extension to other areas of healthcare and use of the systems approach in other areas of the business.

Background and Aims: To explore outcomes following gastrointestinal endoscopy using a clinical dataset and then routinely collected administrative data linked to death registry data. Predictors of outcome were studied and variations in crude mortality were analysed. Methods: Endoscopy cases from a single tertiary centre were identified retrospectively using a clinical endoscopy database. Sedation levels, type of procedure and demographic data were analysed. Adverse events following the procedures, including mortality were assessed before and after changes in sedation practice were introduced. For subsequent chapters national administrative data in the form of Hospital Episode Statistics (HES) were linked to the Office of National Statistics Death Registry. Data from 2006 – 2008 were analysed. Episodes of care containing codes for therapeutic endoscopic procedures were extracted (Endoscopic retrograde cholangio-pancreatography (ERCP) and percutaneous endoscopic gastrostomy (PEG)). Finally, episodes of care containing new stroke diagnoses were extracted to analyse the use of percutaneous gastrostomies in the stroke population in England. Factors associated with death following endoscopy were identified. Crude and case-mix adjusted mortality were analysed at institutional level. Results: 7,234 endoscopy cases were identified from the endoscopy clinical database. Following changes in sedation practice 7,071 cases were assessed. Significant reductions in sedation doses were achieved but mortality rates did not fall (0.7% in 2004 and 0.8% in 2006 (p=0.5)). 40,938 episodes of care containing ERCP procedures were identified within the HES data. Logistic regression analysis confirmed age, sex, cancer, emergency admission, and non-cancer co-morbidity as independent predictors of 30-day death after ERCP. Adjusted odds ratios for age were 6.2 for ≥85 yrs vs. <55 yrs; male sex 1.2 vs. female; emergency admission 2.0 vs. elective; cancer 8.6 vs. no cancer and non-cancer co-morbidity 1.5 vs. none. Trust volume of ERCP was not found to be a significant factor in post procedure mortality. Funnel plots of trust level mortality rates, both unadjusted and adjusted, showed all trusts lying within 3 standard deviations of the national mean. 10,952 PEG cases were identified. All-cause mortality was 4.2% at 7 days and 14.6% at 30 days. Logistic regression identified age over 85 years, male sex, emergency admission, motor neurone disease and dementia as predictors of death within 30 days of PEG procedure (p<0.03 for all). No correlation for 30-day death versus PEG volume was identified at NHS Trust level (Pearson r=0.04). 1560 emergency stroke admissions that had a new PEG procedure were identified. Admission to Trusts with a high PEG procedure volume was associated with lower 7-day mortality after PEG procedure of 4.3%, compared to 7.8% and 6.8% in low and medium volume Trusts respectively (p=0.045). Although suggestive of a lower threshold for PEG insertion, the 5 Trusts with the highest rate of PEG insertions in stroke patients had a higher mortality at 30 days (3% compared to 0.9% in the other Trusts). Conclusions: Patient factors are the main determinants of outcome following endoscopy. Analyses of clinical and administrative datasets both require significant man-hours to produce results. Assessing disease severity within HES data is unsatisfactory, limiting case-mix adjustment. However, the data have the advantage of allowing consistent methods of analysis across institutions at a national level providing a more real world analysis than smaller or single centre studies.

Antivenom is the only effective treatment against the systemic effects of snakebite and is currently developed by a century-old immunisation protocol that aims to generate IgGs capable of binding and neutralizing most (if not all) of the venom toxins. However, snake venoms comprise more than a hundred proteins and peptides that exhibit a significant diversity in terms of isoform complexity, toxicity and immunogenicity. Therefore, antivenom doesn’t take into account the representation of venom toxins and contains therapeutically redundant IgGs to non-toxic venom components, and a lack of high titre IgGs to highly toxic, but weakly immunogenic components. The usual consequence of the century old immunisation protocol is the need to administer large volumes to achieve venom-neutralisation in an envenomed patient, which greatly increases the risk of antivenom-induced adverse effects and reduces its affordability. The Alistair Reid Venom Research Unit has pioneered a new approach using the rationale of generating venom toxin‐specific antibodies on the basis that an antivenom that only targets the most pathogenic toxin groups would be predicted to overcome these issues by improving the clinical efficacy of the treatment. Based upon preliminary work illustrating extensive cross‐specific and cross‐generic reactivity of a toxin‐specific antibodies generated against some of the most pathogenic toxin groups of venoms from medically-important species, the overarching aim of the work described in this thesis was to extended this toxin-specific antivenom approach with a view to ultimately generating a therapy against all the African species of the Echis genus. In order to overcome the high isoform diversity known for most of the pathologically-important venom toxin groups, we conducted a bioinformatic interrogation of the venom gland transcriptomes of Echis ocellatus, Echis pyramidum leakeyi and Echis coloratus for five major target toxin groups: Phospholipases A2 (PLA2), Serine proteases (SP) C-type lectins (CTLs), Metalloproteinases (SVMPs) and Disintegrins that identified epitopes on the basis of i) sequence conservation, ii) antigenicity, (iii) surface exposure and (iv) coverage across the EST data. Resultant sequences were synthesised as epitope-strings and subsequently delivered as DNA and recombinant proteins immunogens that in a proteic form successfully generated antibodies capable of binding to a number of reduced venom proteins in a cross-reactive manner, suggesting the presence of specific and generic shared epitopes of importance. The results obtained in this study helped identifying key elements of the toxin-specific approach for the design of antivenoms and highlighted the need to elucidate several aspects of the molecular interaction of the raised antibodies against the target venom proteins, in order to have an accurate approach to their binding in a native state. In addition, the study successfully approached venom glycosylation, and aspect that hasn’t been studied in detail and came apparent during the progress of the toxin specific antivenom gave light in the future stages of its development.

Background and introduction: Maternal deaths are highest in low resource countries. Skilled attendance at birth (SBA) and the availability of emergency obstetric care (EmOC) are key strategies to improve maternal health and achieve the millennium development goal number 5. In-service emergency obstetric and newborn care (EmONC) training has been used for many years to improve the quality of skilled attendance at birth and availability of EmOC, however few packages have been properly described and evaluated. There is no published comprehensive evaluation of EmONC in-service training packages in low resourced countries. An evaluation of the effectiveness of an EmONC training intervention in 10 comprehensive EmOC Kenya hospitals was carried out from 2010-2011. Methods: A systematic review was performed based on grading of recommendations assessments development and evaluation (GRADE) guidelines to identify the various EmONC training packages in low and middle income countries, identify literature on the effectiveness of these packages or effectiveness of various components of EmONC training globally. The components of the intervention were training in EmONC, provision of EmOC equipment and supportive supervision. The objective of the intervention was to improve the recognition and treatment of emergency obstetric and newborn complications at all study sites by trained maternity care providers (MCP). A before/after study design and an adapted four level Kirkpatrick framework (level 1: reaction to training, level 2: learning, level 3: behaviour/practice, level 4: EmOC availability, health outcomes and ‘up-skilling’) was used to evaluate the effectiveness of the training package. Mixed research methods (quantitative and qualitative approaches) were used to collect data 3 months before the intervention and at 3 monthly intervals after up to 12 months after the intervention. Quantitative data were analysed using SPSS version 20 and qualitative data was analysed using Nvivo 9. Descriptive statistics and analysis using t-tests were performed for quantitative data (significance in mean difference at 95% confidence) while framework analysis was used for qualitative data. Results: 20 EmONC in-service training programmes implemented in low and middle-income countries were identified. The content of 85% (17) of the programmes identified included EmOC signal functions and 7 programmes were 7 days or more in duration. 50% (10) of the EmONC training packages identified had training reports of which only two studies were evaluated at Kirkpatrick level 3 (behaviour) and there was no evaluation at level 4 (health outcomes) identified. Over 70% of all identified maternity care providers from all 10 hospitals were trained. 83% (328) of the 400 health care workers trained were midwives, 6% (26) were medical doctors, 2% (8) were clinical officers and 3% (11) were obstetricians. At 12 months post training the proportion of MCP trained in each hospital was at least 83% except for Nakuru PGH (23%) and Mbagathi GH (50%). Kirkpatrick level 1: About 95% (380) participants responded to level 1 assessment questionnaire. Trainees reacted positively to all lectures (n=11, mean score was 9.38/100, SD: 0.12) and breakout sessions (n=25, mean score was 9.33/10, SD: 0.14). Kirkpatrick level 2: There was a statistically significant difference between the pre and post training knowledge scores in all modules except preventing obstructed labour 0.10 CI (0.06-0.26) p=0.201. The mean difference between pre and post-test skill scores was statistically significant 3.5 CI (3.3-3.8) P<0.001, n=284. Kirkpatrick level 3: 153 data sources (FGDs, paired interviews, KIIs) were collected over 12 months and analysed. 49% (184) and 129 (34.5%) of health care workers and managers participated. They reported a positive impact of the intervention on communication and teamwork, pre-service midwifery education, reduced treatment time, improved knowledge, skills, improved confidence to perform EmOC, organisation of care and supportive supervision. Availability of EmOC equipment post training and supportive supervisors were factors that facilitated change in practice post training. Barriers to availability of EmOC identified were poor staff deployment and retention policy post training, lack of equipment to perform EmONC, lack of support from obstetricians, senior midwives and nurse/midwifery administrators, lack of training for all MCP (including medical interns, medical officers and staff from lower level health care facilities) and lack of clarity on the scope of practice for nurses/midwives. Kirkpatrick level 4: 16, 764 and 17, 404 deliveries were conducted at baseline and at 12 months post intervention respectively. There was 66.8% increase in obstetric complications recorded and managed at 12 months post training compared to baseline. Health outcome indicators: There was an expected increasing trend for number of complications recorded and treated, availability of SBA and EmOC. There was also an expected decreasing trend in the proportion of newborns admitted to NBU for birth asphyxia, direct obstetric case fatality rate (DOCFR) and stillbirth rate (SBR). There was no change in caesarean section (C/S) rate or Fresh stillbirth rate (FSBR). For the health outcome indicators (DOCFR, SBR, FSBR), when PGH Nakuru was excluded from the analysis, a non-statistically significant reduction but greater effect at 12 months compared to baseline was observed for complications recorded and treated (87.9% vs. 66.8%), DOCFR (47% vs. 35%), SBR (66% vs. 34%) and FSBR (14 vs. 10%). There was 34%, 48%, and 35% mean reduction in the SBR, proportion of newborns admitted to newborn care unit and DOCFR at 12 months post intervention compared to baseline respectively. “Up-skilling” indicators: There was a 53.8%, 80%, 100% mean increase in the proportion of all breech vaginal deliveries, proportion of all vacuum extractions performed and proportion of vacuum extractions performed by non-physician clinicians, at 12 months post intervention compared to baseline. Assisted vaginal delivery by vacuum extraction was the least available EmOC signal function (SF) and medical doctors only performed this SF at baseline. At 12 months post intervention, non-physician clinicians performed this as well, in all study sites. Overall the EmONC training intervention resulted in improved ‘up-skilling’ of maternity care providers, a trend towards improved availability of SBA and EmOC and improved health outcomes. Implications for policy and practice The results of this study are important for designing and implementing evidence based EmONC programmes in resource poor countries. None medical doctors can be ‘up-skilled’, the recognition and management of obstetric and newborn emergencies and the availability of quality EmOC can be improved using similar packages and implementation methods in other resource poor settings. Future research: Evaluation designs that include control groups are needed. Studies to assess the relative importance of supportive supervision for behaviour change after training, the knowledge and skills retention with time post training in resource limited settings should be undertaken.

During rehabilitation from Stroke, patients require assessment of their upper-limb motor control. Outcome measures can often be subjective and objective data is required to supplement therapist/patient opinion on progress. This can be performed through goniometry; however, goniometry can be time-consuming, have inaccuracies of ±23º, and is therefore, often not used. Motion tracking technology is a possible answer to this problem, but can also be costly, time-consuming and not suitable for the clinical environment. This thesis aims to provide an objective, digital intervention method for assessing range of motion to supplement current outcome measures which is suitable for the clinical environment. This was performed by creating a low-cost technology through a user-centred design approach. Requirements elicitation demonstrated that a motivational, portable, cost-effective, non-invasive, time saving system for assessing functional activities was needed. Therefore, a system which utilised a Microsoft Kinect and EZ430 chronos wrist watch to track patient’s movements during and/or outside of therapy sessions was created. Measurements can be taken in a matter of minutes and provide a high quantity of objective data regarding patient movement. The system was verified, using healthy volunteers, by showing similar error rates in the system across 3 weeks in 10 able-bodied individuals, with error rates produced by a physiotherapist using goniometry. The system was also validated in the clinical setting with 6 stroke patients, over 15 weeks, as selected by 6 occupational therapists and 3 physiotherapists in 2 NHS stroke wards. The approach which has been created in this thesis is objective, repeatable, low-cost, portable, and non-invasive; allowing it to be the first tool for the objective assessment of upper-limb ROM which is efficiently designed and suitable for everyday use in stroke rehabilitation.