The research investigated: (i) potential missed opportunities for primary prevention of stroke and transient ischaemic attack (TIA) with pharmacotherapy through a retrospective case series analysis and (ii) fatigue, psychological and cognitive impairment following TIA through a systematic review and retrospective cohort study. The case series and cohort studies used electronic primary care medical records from The Health Improvement Network (THIN). The case series analysis found preventative drugs were under prescribed to people with clinical indications for these drugs prior to stroke or TIA. There were potential missed opportunities for prevention in 49% (7,836/16,028) of people with stroke or TIA who were eligible for lipid lowering drugs, 52% (1,647/3,194) for anticoagulant drugs and 25% (1,740/7,008) for antihypertensive drugs. Improving prescription of these drugs has the potential to reduce the incidence and subsequent burden of stroke and TIA. The systematic review revealed there were few high quality studies investigating residual impairments in people with TIA and minor stroke; however, there was limited evidence to suggest a relatively high prevalence of cognitive impairment and depression post-TIA and minor stroke. The retrospective cohort study found that TIA patients were significantly more likely to consult in primary care for fatigue, psychological and cognitive impairment compared to matched controls. This association remained when adjusted for the potential confounding variables and the presence of the impairment prior to TIA. These findings suggest that impairments exist after initial symptoms of TIA have resolved and challenge the ‘transient’ characterisation of TIA. Residual impairments should be considered by primary care clinicians when treating patients following TIA.

The inappropriate use of antibiotics is a key factor in the development of antimicrobial resistance (AMR). UK national guidance has been ineffective in standardising the management of infections in the community. Many prescribers in the community are sceptical that their actions have an effect on AMR in their locality. As part of this study, routine surveillance of AMR in a large regional population was established. To help interpret surveillance data, two surveys were undertaken: a survey of laboratory methods, and a survey of GP sampling and prescribing protocols. Using these survey results, surveillance tools were developed to provide hospital and community prescribers with data on antibiotic resistance in bacteria within their locality; and enable laboratories to compare methods for determining antibiotic susceptibility. This thesis demonstrated that routine AMR surveillance can be used to monitor key antibiotic resistance, detect emergence of new or unusual resistance mechanisms, and enable the bench-marking of laboratory methods. This study was also able to demonstrate that small increases in antibiotic prescribing by individual GPs increases the number of non-susceptible bacteria isolated from specimens taken from their practice population. The results of this thesis provides supporting evidence to those developing strategies to combat AMR in the community.

Background: Stratified medicine was defined as the use of biomarkers to select patients more likely to respond to a treatment or experience an adverse event. Alms: To investigate the hypothesis that there is a mismatch between the theoretical proposals and practice of predictive biomarker research, focusing on the clinical utility stage. Methods: Methodological research was identified in a systematic review of frameworks for staged evaluation of predictive biomarkers. Actual research supporting 50 real cases identified in European Medicines Agency licensing was analysed. A case study of recent research into ERCC l in non-small cell lung cancer was undertaken. Existing discrepancies between the theory and practice were identified and possible reasons and consequences of these were discussed. Findings: A mismatch between theory and practice was identified. It appeared to be a result of both the practice not following some theoretical requirements, and the underdevelopment of methodology for certain situations. Areas of clinical research with insufficient relevant methodology were identified. Conclusions: The major research priorities identified in this thesis were development of a clear hierarchy of biomarker research designs and development of methodology related to the biomarker threshold.

Occupational asthma (OA) is associated with an estimated annual societal cost in the UK of £100 million, which is avoidable if workers are identified quickly and removed from exposure to a sensitizing agent. The aim of this work was to identify barriers to diagnosing OA on the part of workers and healthcare professionals. The first study evaluated current practice in assessing working-age asthmatics for OA in a West Midlands primary care population. There was poor enquiry regarding occupation (14% of cases) and the effect of work on asthma symptoms (2%). The second study used qualitative methodology to explore beliefs and behaviours in symptomatic workers. Major influences on workers’ health seeking behavior were (1) understanding of their symptoms, (2) working relationships, (3) course of action with symptoms and (4) negotiation with healthcare professionals. The third study defined the important barriers from the point of view of healthcare professionals. Low awareness and adherence to OA guidelines was evident in all non-specialist groups. The fourth study evaluated the feasibility of introducing an electronic OA screening-tool for primary care. Healthcare professionals who used the tool found it to be quick and easy to implement and user-friendly, without impacting on the length of a consultation.

A pivotal component of prognosis research is the prediction of future outcome risk. This thesis applies, develops and evaluates novel statistical methods for development and validation of risk prediction (prognostic) models. In the first part, a literature review of published prediction models shows that the Cox model remains the most common approach for developing a model using survival data; however, this avoids modelling the baseline hazard and therefore restricts individualised predictions. Flexible parametric survival models are shown to address this by flexibly modelling the baseline hazard, thereby enabling individualised risk predictions over time. Clinical application reveals discrepant mortality rates for different hip replacement procedures, and identifies common issues when developing models using clinical trial data. In the second part, univariate and multivariate random-effects meta-analyses are proposed to summarise a model’s performance across multiple validation studies. The multivariate approach accounts for correlation in multiple statistics (e.g. C-statistic and calibration slope), and allows joint predictions about expected model performance in applied settings. This allows competing implementation strategies (e.g. regarding baseline hazard choice) to be compared and ranked. A simulation study also provides recommendations for the scales on which to combine performance statistics to best satisfy the between-study normality assumption in random-effects meta-analysis.

Background: The burden of mental disorders in post-conflict areas is higher than in countries where there is no conflict. Post-conflict areas lack the resources to respond to such high burden, resulting in a treatment gap. This study explored the potential for mental health reform in Gaza. Design: Mixed methods study. Methods: The WHO-AIMS questionnaire was used to assess mental health services in Gaza and documentary analysis was conducted to evaluate the Mental Health Policy and Plan. Healthcare professionals‟ mental health training needs were identified and policy makers, healthcare professionals, service users and carers took part in focus groups to elicit their perspectives on mental health reform. Framework analysis was used to identify recurrent themes. Results: Psychotherapy, recovery, family intervention and crisis management were rated priority training areas. Poor coordination between governmental and non-governmental organisations and short-term funding were identified as main barriers to mental health reform. Service users and carers felt excluded from service delivery and development and suggested possible models of partnership working with service providers to address exclusion. Conclusion: Meaningful mental health reform in post-conflict areas requires inclusive policy development, targeted staff training, improved coordination between different service providers, and partnership working between service providers and service users and carers.

Background: Obesity remains a significant public health priority despite ongoing efforts, with few notable advances made in recent years. Individual behaviour change mechanisms, or 'active ingredients', can only partially explain and predict successful weight loss. In addition, maintenance following a period of initial weight loss is rare and relies upon unique combinations of interrelated and overlapping factors. Whilst the outcome of weight loss and its maintenance has been the focus of much research, the individual weight loss journey as a process has been largely overlooked. By looking through the lens of the lived experience, there lies an opportunity to sequence the temporal and contextual dimensions of the weight journey and gain greater insight into this process. Aims: The current study aimed to examine the temporal and contextual dynamics of the weight loss journey by listening to the personal narratives of people who had attended a psychologically-led weight loss intervention, in this way revealing the barriers and enablers to their initial weight loss and maintenance over time. Methods: The study adopted a qualitative approach, using a combination of focus groups and 1-1 interviews with participants who had previously attended a psychologically-based weight management intervention. Results: The study recruited a total of 46 individuals who took part in either a focus group (n=40) or 1-1 interview (n=6). A conceptual linear framework was devised which highlighted three core superordinate themes; Alienation, Connectedness and The Future (Abandonment or Autonomy), representing distinct stages of the weight journey. In exploring the conditions under which individuals migrate across stages results indicated a role for the development of a self-identity which assumes personal responsibility for meeting psychological and emotional needs beyond the physical realm of weight loss. Although most personal narratives reflected a sense of abandonment post intervention and associated weight relapse, a small minority engendered a sense of autonomy and a focus upon psychological and emotional capacities as a metric for their weight loss journey. Conclusions: Bringing into view temporal and contextual dimensions involved in managing weight over time, the findings have implications for addressing the issue of weight as a symptom rather than as a cause and centralise the importance of meeting psychological and emotional needs over and above a unilateral focus on weight loss.

Diabetes has been described as an epidemic with a significant global burden of illness. This burden is associated with poorer engagement with services and the cost of managing avoidable complications. One outcome measure of engagement in the national health service (NHS) in the United Kingdom (UK) is attendance at appointments. The cost implications (direct and indirect) of non-attendance are significant, with empirical evidence consistently demonstrating higher than average non-attendance rates for out-patient appointments and education sessions by minority ethnic and socio-economically deprived individuals. A gap was identified whereby a comprehensive understanding of non-attendance which moves beyond clinical and technical aspects such as capacity and demand is still required. This thesis provides a fresh approach and granular understanding of patient engagement which can influence clinical care, service delivery and policy. The main research questions in this thesis were: 1. What are the predictors of out-patient attendance? 2. What are the barriers and enablers to attendance? To answer these questions, a retrospective geo-demographic trend analysis, critical narrative literature review of Community Health Worker (CHW) and peer support interventions and a research study were conducted. The case study is based on a dataset which comprised of 35,597 appointments. Its findings highlighted that factors such as age, gender, ethnicity, local geography and deprivation were significant predictors of out-patient attendance. A critical review of CHW and peer support interventions demonstrated that despite the heterogeneity of programme designs, duration of interventions, follow up and healthcare systems in which they were used, they were assessed to be both clinically and cost effective. There was limited evidence on the sustainability of these interventions due to a lack of longitudinal studies. The research element was conducted in two stages and utilised multi methods (focus groups, semi-structured interviews and questionnaires) to evaluate the barriers and facilitators to attendance. Key findings included the need for effective and on-going education, better alignment of health and social care due to the impact of the wider determinants of health but more interestingly, the influence of family on the concept of ownership for one's health by some individuals whose self-determination is limited by language and health literacy. The relationship between patient activation (knowledge, skills and confidence) and attendance was also evaluated. This evaluation demonstrated that the more activated individuals are, they are significantly more likely to attend appointments. However, to maximise care planning and operational effectiveness, activation should not be assessed in isolation. The findings of this thesis highlighted the influence of individual, organisational and structural factors on patients' engagement with out-patient services and the need for a synergistic approach involving service users, clinicians, organisations and policy makers to minimise patient dis-engagement with healthcare services.

This study explores public attitudes towards healthcare in the Eastern Province of KSA. It employs a sequential mixed-method design. Semi-structured focus group discussions (FGDs) were conducted with fifty-four participants in the Eastern Province. The qualitative arm of the study used a framework thematic analysis. A questionnaire was constructed from evidence-based items from four sources: an international performance assessment framework, literature review, systematic review, and the FGDs. The questionnaire was administered to 813 participants using on-site and online recruitment modes. Two qualitative validity assessments and quantitative construct validity and reliability tests were then carried out for the questionnaire. The FGDs indicate a public sense of pride in the Saudi health system. However, some concerns emerged from the FDGs-most notably, access barriers to the government health sector including the referral system from primary to secondary care and the necessity of personal connections, or 'wasta', to access timely care. Access barriers also emerged in the private health sector, namely the affordability of care and health insurance companies' delays in responding to medical claims. Participants also considered their inability to discuss treatment plans and to be involved in decision-making processes with their doctors as issues in both the public and private sectors. Participants were also concerned about the Ministry of Health (MOH) monitoring and regulating both sectors. This affected participant attitudes towards health service provisions. The questionnaire demonstrated qualitative validity and good psychometric properties in construct validity and internal reliability. Participants perceived doctor-patient communication as the most positive aspect of the Saudi health system while they perceived MOH monitoring of the private sector and affordability of care as the most negative aspects. Socio-demographic characteristics were considered as strong predictors of participants' attitudes towards the health system, and nationality and insurance status were identified as the most frequent predictors of satisfaction. Recommendations include implementing policies that monitor pricing in the private sector, fairer access to government healthcare, and patient involvement in decision-making processes. Future research should investigate the relationship between public attitudes towards the Saudi health system and health-related decisions to ensure better use of healthcare services in KSA.

This thesis concerns investigations into adverse health outcomes among survivors of childhood cancer using the British Childhood Cancer Survivor Study (BCCSS). The BCCSS is a large-scale population-based cohort of 17,981 survivors of childhood cancer who were diagnosed with childhood cancer (age 0-14 years) between 1940 and 1991, in Britain, and had survived for at least five years. The specific aims were to investigate, within the BCCSS cohort; (1) the psychometric properties of the SF-36 health-status questionnaire, (2) the self-reported health-status by using the SF-36, (3) the effect of therapeutic radiation on the offspring sex ratio, (4) the risks of adverse pregnancy outcomes, and (5) the risks of second primary breast cancer. This thesis demonstrates that the SF-36 questionnaire exhibits good validity and reliability when used in long-term survivors of childhood cancer. Survivors rate their physical and mental health similarly to those in the general population, apart from bone and central nervous system tumour survivors who rate their physical health below population norms. Therapeutic irradiation does not alter the sex ratio of offspring. Female survivors exposed to abdominal irradiation are at a three-fold risk of delivering premature and two-fold risk of producing low birth-weight offspring. Lastly, the risk of breast cancer among female survivors is two-fold that of the general population, but is not sustained into ages at which the risk of breast cancer in the general population becomes substantial.