This thesis focuses on the challenges of evidence synthesis to inform healthcare decision making within public health. It encompasses both methodological advancement and practical application of existing synthesis methodology, using as an example - accidents prevention in children to illustrate application of the methods within a public health context. The thesis commences with a systematic review of NICE public health appraisals to identify the barriers to quantitative synthesis of evidence in public health. Then focusing on the prevention of unintentional poisonings in pre-school children, a series of network metaanalyses of the effectiveness evidence are conducted, demonstrating how complex synthesis methodology can be employed to help overcome some challenges of evidence synthesis in a identified in the review of the NICE public health appraisals. New synthesis methodology is then developed in which the standard network meta-analysis model is first extended to include a covariate for the baseline risk and then to a multiple outcome settings. Baseline risk is a proxy for unmeasured but important patient-level characteristics, which may be modifiers of the treatment effect in a meta-analysis. Thus adjusting for it can account for heterogeneity across different study populations and identify those more likely to benefit from the intervention. The multiple outcome models account for the dependency structure within the data which is important in a decision modelling context, as correlations between effect estimates on different outcomes may have implications for estimating the net benefit associated with treatment. Finally, a substantive decision analytic model is presented incorporating results from the network meta-analysis and application of the methodology developed to the poison prevention data. The analyses suggest that compared to usual care, more intensive home safety interventions are more effective in preventing medicinal poisonings in pre-school children but are unlikely to be cost-effective for the UK NHS unless policy makers are willing to pay upwards of £75,000 for every QALY gained.

Background: Approximately one in three older adults (aged 65 and over) fall each year. Such falls commonly present at EDs (Help the Aged, 2005; Close, Ellis, Hooper, Glucksman, Jackson and Swift, 1999). The National Institute for Health and Care Excellence (NICE) 'Falls' guidelines (2004) were developed to improve management of falls, including their assessment and ways to prevent future falls. However, there is evidence of poor adherence to the guidelines (Sheldon et al., 2004). This research explores how falls are managed in EDs and the reasons why guidelines are not always followed. Methods: I undertook a detailed review of relevant research on the management of falls in EDs. Research also took place at two sites. Two particular research methods were employed; 1) observation research of healthcare professional and patient interaction, and 2) interviews with healthcare professionals. I observed the care of 27 patients and interviewed 30 health professionals. These methods were chosen in order to investigate factors influencing adherence. Results: Adherence to the guidelines was poor at both EDs. Various barriers and enablers (determinants of practice) influenced adherence, including: communication, complexity of patient care, services offered outside the ED, ED care processes (including education and busyness), variation in staff and cross-boundary care. Conclusions: A variety of factors influence adherence to the Falls guidelines within an ED, but it may be difficult to address all of them simultaneously and in the context of busy EDs. Simple interventions such as education and pro-formas are unlikely to have substantial effect on their own, although taking advantage of the influence of senior staff could enhance their effectiveness. In addition to such interventions, collaborative care with other NHS services offers a potential approach.

Relationship and relatedness estimation from genetic markers is relevant to many areas, including genealogical research, genetic counselling, forensics, linkage analysis and association analyses in genetic epidemiology. Traditionally unlinked genetic markers (microsatellites) are used. But the problems which can be solved by such markers are limited. Linked genetic markers are not only available in much larger numbers, but also provide extra information which is not available from unlinked markers. It is desirable to exploit the increasing availability of dense genome-wide single nucleotide polymorphisms (SNP) data for estimating relationships and relatedness. While Method of Moments (MoM) methods and other non-pedigree approaches only give a degree of pairwise relatedness, a pedigree likelihood approach can distinguish exact relationships. The pedigree likelihood approach also has advantages in that extra individuals can be considered jointly and extra data such as Y-chromosomal and mitochondrial SNPs can be incorporated with autosomal SNPs easily. In this thesis I firstly confirm that the increase in information obtained from large sets of linked markers substantially increases the number of problems that can be solved with pedigree approach. Furthermore, when two distant relatives do share genome segments through identity by descent (IBD), we usually have greater power to distinguish more distant relatives from unrelated pairs than was previously believed. Data on extra individuals always improve discriminatory power, but the position of the extra individuals in the pedigree dictates the extent of this increase of power. Linkage Disequilibrium (LD) is an issue for pedigree likelihood approach and it needs to be dealt with. MoM methods are easy to use and are generally robust to the effect of LD, but they are only accurate for relatives up to second cousins. I propose using pedigree likelihood approach to estimate pairwise relatedness and find we can greatly improve the accuracy in detecting distant relatives.

Persuasive arguments exist as to why the harmonisation of tissue banks is important. Yet harmonisation has not happened on a large scale and empirical research has not investigated the reasons for this in detail. This thesis presents the results of ethnographic research using the case study of cancer tissue banks to identify influences on harmonisation. The research involved 40 interviews and over 117 hours of observations with professionals working across 15 organisations. Data analysis was based on the constant comparative method with use of sensitising constructs from literatures on standards and diffusion of innovation. A new model of the tissue supply chain was developed and refined against the findings. Harmonisation depends on the creation, implementation and outcome of standards. The empirical work showed that a complex picture of harmonisation emerges when the creation, implementation and outcome of standards are considered separately. Different factors act as barriers or facilitators, or as both, at each stage. Standard creation in cancer tissue banks is obstructed by a lack of agreement between organisations and professionals, who may have differing interests and views on the appropriate type and scope of standards, who should create them and how. Standard implementation can be enabled or hindered by standard design, the actions and features of organisations, and individual and professional factors. Critically, the outcome of implementing standards has not always increased harmonisation; in some cases the result is fragmentation, duplication or exclusion. The thesis describes cross-cutting political, social and technical issues that arise during the tissue supply chain and throughout the stages of standard creation and implementation, making harmonisation complicated and difficult to achieve. Eight recommendations are offered for how harmonisation can be facilitated in practice.

The reproductive health problems of migrant women are a growing concern, especially in developing countries. The empirical literature indicates that migration characteristics (e.g., selection, adaptation and disruption) and migrant’s socio-demographic backgrounds are the potential pathway through which migration can affect reproductive health care services utilization. This study aimed to examine the effect of migration on women’s reproductive health care service utilization and to identify the major barriers that affect migrant women’s access to quality reproductive health care services. The study aim and objectives were achieved using two studies. Study one comprises a secondary analysis of the 2005 Ethiopian Demographic and Health Survey (EDHS). The EDHS was administered to women aged 15-49 years and a total of 14,070 women were interviewed and study two was a primary survey conducted in Dabat rural areas and Gondar town. A total of 1800 women were interviewed: 500 women from Dabat rural areas and 1300 women from Gondar town. Both surveys were employed a cross-sectional survey design. The two studies found that rural to urban migrants were relatively lower in knowledge and use of reproductive health care services compared to urban natives, but more likely to know and use of services than rural natives. The primary study also found that among migrant women, those who registered as kebele residents were more likely to know of, or utilize contraceptives and maternal health care services compared with non-registered migrants. To ensure the reproductive health care access of migrants, the urban kebele administrative offices should revise the policies that demand migrants to be registered as a kebele residents and having a kebele identification card to be eligible for social, economic and health care benefits. Therefore, the policy makers should target the disadvantaged groups of migrants to provide equal opportunities to access health care services.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Lung function measures obtained through spirometry play a key role in the diagnosis of COPD. Both COPD and lung function are affected by genetic factors, and identifying genetic variants that have an effect on lung function or COPD risk has the potential to lead to improved treatment and prevention of COPD. This thesis is structured in five chapters, an introductory, a concluding chapter and three main chapters which present different approaches that aim to bring insights into the genetics of COPD and lung function. Chapter 2 tests the association with COPD risk of genetic variants previously associated with lung function, and tests their combined effect on lung function and COPD risk, in order to explore the role of risk prediction. Chapter 3 aims to identify new genetic variants associated with lung function and tests the association of genetic variants genome-wide. Chapter 4 focuses on the analysis of low frequency variants using different approaches and methodologies, and includes two studies. One study assesses associations of low frequency variants genome-wide, and the other focuses on genetic regions associated with lung function, in order to improve the localization of association signals that often comprise broad regions and several genes. These studies overall have identified 16 new genetic variants associated with lung function, have shown the association with COPD of 4 genetic variants previously associated with lung function, and present suggestive evidence of association with COPD for low frequency variants within regions associated with lung function.

Traumatic osteoarthritis of the wrist is a disabling disease that affects middleaged active adults in the prime of their working life. I set out to assess wrist function and disability in patients with traumatic wrist osteoarthritis before and after surgery. I measured wrist range of motion with flexible electrogoniometer, grip strength with force-time curves using dynamometer, hand function with timed Sollerman hand function test and patient-reported outcome. I first developed these techniques in normal volunteers and then extended them to patients with wrist osteoarthritis before surgery and after four-corner fusion, three-corner fusion, total wrist fusion, and proximal row carpectomy. I used flexible electrogoniometry to generate circumduction curves to measure range, rate and rhythm of circumduction of the wrist. It showed that there was no difference in range of motion parameters in patients with wrist osteoarthritis before surgery and after four-corner fusion and three-corner fusion. Proximal row carpectomy provides better flexion-extension and poorer radio-ulnar deviation than four-corner fusion. Three-corner fusion allows better rate and rhythm of movements in flexion and ulnar deviation compared to four-corner fusion. Grip strength was measured with dynamometer to generate force time curves to measure sustainability of grip. There was no difference between our groups with wrist osteoarthritis before surgery and after wrist fusion, four-corner fusion or three-corner fusion. I developed the Timed Sollerman hand function test by measuring the time taken to complete each of the tasks without summarisation into a 5-point scale. It showed that volunteers completed the tasks quicker with the dominant hand than with the nondominant hand. Women took less time to complete the tasks in the 30-40 years age group than women in the 20-30 years age group and beyond 40 years. The patients with PRC completed the different activities of daily living quicker than the 4CF patients, except for activities requiring wrist torque strength.

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