This thesis identifies and demonstrates the methodological challenges of meta-analysing risk prediction models using either aggregate data or individual patient data (IPD). Firstly, a systematic review of published breast cancer models is performed, to summarise their content and performance using aggregate data. It is found that models were not available for comparison. To address this issue, a systematic review is performed to examine articles that develop and/or validate a risk prediction model using IPD from multiple studies. This identifies that most articles only use the IPD for model development, and thus ignore external validation, and also ignore clustering of patients within studies. In response to these issues, IPD is obtained from an article which uses parathyroid hormone (PTH) assay (a continuous variable) to predict postoperative hypocalcaemia after thyroidectomy. It is shown that ignoring clustering is inappropriate, as it ignores potential between-study heterogeneity in discrimination and calibration performance. This dataset was also used to evaluate an imputation method for dealing with missing thresholds when IPD are unavailable, and the simulation results indicate the approach performs well, though further research is required. This thesis therefore makes a positive contribution towards meta-analysis of risk prediction models to improve clinical practice.

Pancreatic cancer is a common cause of cancer death and is difficult to diagnose and treat. A prognostic index can be used in clinical practice to predict survival. Thirty six prognostic factor studies were identified but size and statistical methods were inappropriate. Continuous variables are often simplified incorrectly i) assuming linear relationships between predictors and log-hazard or ii) using dichotomisation. Non-linearity is addressed for the first time in this disease site using restricted cubic spline and fractional polynomial functions. Multivariable models containing non-linear transformations gave a substantially better fit. Important effects of some covariates were unrecognised under simplistic assumptions. The fitted functions generated by the two methods were similar. A direct comparison of these strategies was based on assessing the difference in the AIC values by calculating a sampling distribution in multiple bootstrap resamples. Model validation is also addressed for the first time in this disease and suggested minimal over-fitting with reproducible prognostic information when fitted to external data. This thesis provides the first validated prognostic tool in advanced pancreatic cancer developed using appropriate statistical methodology. Risk-sets identified by the model could help clinicians target treatments to patients more appropriately and have an impact on future trial design and analysis.

This thesis focuses on a nurse-led trial assessing the thromboprophylactic utility of warfarin in cancer patients (n=1590) with central venous catheters and designed following a UK survey of practice. Clinicians who were ‘uncertain’ of the benefits of warfarin, randomised patients to no warfarin vs fixed dose warfarin of 1mg (FDW) vs dose adjusted warfarin (DAW) to maintain the international normalised ratio (INR) between 1.5 and 2.0. Clinicians, who were ‘certain’, randomised patients between FDW and DAW. The primary endpoint was the number of symptomatic catheter-related thrombotic events (CRT). Compared to no warfarin, warfarin (79% FDW; 21% DAW) did not reduce CRT [5.9% vs 5.9%; relative risk (RR) 0.99, (95% Confidence Interval (CI) 0.57-1.72), p=0.98]. However, compared to FDW, DAW was superior in preventing CRT [2.8% vs 7.2%; RR 0.38, (95%CI 0.20-0.71), p=0.002]. Major bleeding events were rare; an excess was observed with warfarin compared to no warfarin (7 vs 1, p=0.07) and with DAW compared to FDW (16 vs 7, p=0.09). There is no benefit in using low dose warfarin in CRT prophylaxis. DAW shows benefit over FDW but at a cost of major bleeding events. Subsequent meta-analysis confirmed the primary finding. This research has changed clinical practice internationally.

South Asians, specifically Pakistanis, living in areas of socio-economic deprivation across the UK, have an elevated risk of cardiovascular disease (CVD). The purpose of this research was to explore how social networks function as a source of support and information (social capital) in creating lifestyles associated with CVD prevention in a migrant, minority-ethnic Pakistani population. Semi-structured qualitative interviews were carried out using an interview guide and the convoy model diagram to elicit participant’s responses on social networks, community interactions and lifestyle choices (diet and exercise). A total of 42 participants across three migrant generations, diverse educational and occupational backgrounds, men and women aged 18 years and above participated. Framework analysis was used to analyse transcripts and organise codes, themes and categories. Findings distinguished a diverse narrative amongst men and women with regards to making lifestyle choices and gaining access to social support within or outside of the Pakistani community. Conclusively, engagement beyond familiar community contexts could provide greater or novel sources of support and information for pursuing (at times) non-traditional, healthier lifestyles. Understanding shifting perceptions of health in relation to religion, culture and ethnic-identity could provide primary care practitioners with a better understanding of how to treat high-risk patients.

Concentrations of selected PFRs were determined in indoor dust from cars, couches, living rooms, offices, and school classrooms in Australia, Canada, Germany, Kazakhstan, and the UK. Significant differences were found between concentrations of PFRs in dust from different microenvironment categories in the same country. Assessment of human exposure via dust ingestion, revealed the majority of exposure to most PFRs occurs in the domestic environment. However, exposure to TDCIPP occurs primarily in cars, and a substantial proportion of the exposure of young children to EHDPP occurs in classrooms. Reassuringly, the exposure estimates in this study are at least 2 orders of magnitude below health based limit values reported in the literature. However, improved characterisation of exposure to TCIPP via inhalation is identified as a research priority. To address the substantial uncertainty in existing values reported for PFR vapour pressures, they were determined experimentally via the GC-RT method. For most target PFRs, results showed good overall agreement with the mean of experimental and \(in\) \(silico\) literature values. However, values for the chlorinated PFRs exceeded the average of literature values.

The purpose of the present thesis was driven by the limited existing evidence examining nutritional and physical activity (PA) profiles of older migrant women, and the importance of such studies for the planning and development of appropriate strategies to promote healthy ageing. This thesis adopted a mixed-methods approach to explore current dietary intake, nutrient status, and key factors influencing dietary factors (Chapter 3) of first generation migrant older women from diverse ethnic, socio-economic, and migration backgrounds (n=76). Chapter 4 sought to explore if the reported low energy and low nutrient intakes found in Chapter 3 were associated with frailty. Chapter 5 examined the association between objectively measured PA/ST and frailty, and identified key factors influencing PA amongst a sub-sample of the study sample (n=60). Given that diet and PA are potential mediators to promote healthy ageing in this population, Chapter 6 explored experiences of ageing and how these, in turn, shaped participants’ perceptions of ‘good’ old age as well as nutrition and physical activity behaviours. The present thesis provided an opportunity to better understand the dietary and PA profiles of first generation migrant older women and how they relate to frailty and ageing within the contemporary super-diverse UK context.

Medical tests are essential for patient care. Evidence-based assessment of the relative accuracy of competing diagnostic tests informs clinical and policy decision making. This thesis addresses questions centred on assessing the reliability and transparency of evidence from systematic reviews and meta-analyses of comparative test accuracy, including validity of meta-analytic methods. Case studies were used to highlight key methodological issues, and provided rationale and context for the thesis. Published systematic reviews of multiple tests were identified and used to provide a descriptive survey of recent practice. Availability of comparative accuracy studies and differences between meta-analyses of direct (head-to-head) and indirect (between-study) comparisons were assessed. Comparative meta-analysis methods were reviewed and those deemed statistically robust were empirically evaluated. Using simulation, performance of hierarchical methods for meta-analysis of a single test was investigated in challenging scenarios (e.g. few studies or sparse data) and implications for test comparisons were considered. Poor statistical methods and incomplete reporting threatens the reliability of comparative reviews. Differences exist between direct and indirect comparisons but direct comparisons were seldom feasible because comparative studies were unavailable. Furthermore, inappropriate use of meta-analytic methods generated misleading results and conclusions. Therefore, recommendations for use of valid methods and a reporting checklist were developed.

40-70% of medical devices and equipment in low- and middle-income countries (LMICs) are broken, unused or unfit for purpose: ad-hoc, undiscerning and inefficient procurement methods and processes contribute towards this problem. This thesis presents the findings of four original studies on medical device and equipment procurement within LMICs. Chapter I reports findings of a systematic literature review on procurement and prioritization methods; recommendations from reviewed literature are synthesised. Chapter II describes fieldwork conducted in The Gambia and Romania to explore the processes and dynamics behind medical device procurement in contrasting settings. Findings suggest procurement processes are strongly influenced by political/cultural power dynamics; health technology assessment evidence is rarely considered. Chapter III discusses the feasibility of conducting medical device specific economic evaluations for informing procurement planning. A case study on the costeffectiveness of alternative treatment interventions for femur-shaft fracture fixation in Sub-Saharan Africa is presented. Chapter IV consists of a critical appraisal of the medical device specific elements of the One Health Tool for health system planning. The thesis concludes with a discussion contextualizing the findings and suggestions for further research.

Ice cream is a fatty, low satiating food which may increase obesity levels. This thesis aims to understand if it is possible to develop a more satiating product by manipulating formulation and/or processing. First, the effect of two emulsifiers (mono and diglycerides, MDGs and Tween 80) on the thermal behaviour of a bulk fat matrix was investigated. MDGs were shown to possibly enhance ice cream fat destabilisation more than tween 80. This research continued on an ice cream matrix, investigating the effect of different HLB (hydrophilic-lipophilic balance) number emulsifiers (MDGs based). Low and high HLB number emulsifiers (compared with intermediate HLB numbers) led to the formation of a more structured fat network. Moreover, the investigation of different solid fat content (SFC) blends and the aging step showed that 1) the fat network became more structured as the SFC increased (unless this was too high); 2) aging step could be avoided; 3) it is feasible to considerably decrease the SFC without affecting consumers’ response; and 4) SFC had a predominant effect on palatability. Finally, an appetite study allowed answering the research question of this work, demonstrating that formulation manipulation could be a promising way to reduce food intake (i.e. obesity levels).

Advanced capitalist societies are currently experiencing a series of widespread global public health challenges. The purpose of this research has been to explore the role of ‘fitness professionals’ in this landscape and to understand whether and how they are able to make the contribution to public health that is claimed. The research was conducted over three iterative phases of research: (1) a comprehensive literature review; (2) five complex case studies of fitness professionals in practice; and (3) interviews with twenty key stakeholders/policymakers in the health, fitness and leisure sectors. The findings show that fitness professionals are an important, complex, undervalued and precarious health-related occupational group. Based on the research evidence, it is clear that there is a gap between the health- and fitness-related needs of society and the capacity of the health, fitness and leisure sectors to serve those needs effectively. Using ‘neoliberalism’ as a framework, it is argued that the occupational group of fitness professionals appears to highlight critical gaps in the neoliberal ideology concerning whether, how and under what circumstances the state should intervene in a health-related market. Recommendations are made for improving the practice and/or the development of practice for fitness professionals in the future.