Poor sleep and pain conditions present a major public health challenge due to their pervasive impact on well-being. Using a mix of experimental and observational methodologies, this thesis assesses sleep disruptions and its potential associations with the experience of pain. Chapter 4 comprises two experimental studies in healthy young adults (n = 57; n = 118) revealing that impairment in central pain inhibitory processes (conditioned pain modulation response) may be associated with self- reported sleep disruptions. The studies also support the validity of the conditioned pain modulation response as a physiological marker of pain inhibition. Chapter 5 presented a quasi-experimental study comparing chronic pain groups (Fibromyalgia n = 9; Chronic Back Pain n = 8) with healthy controls (n = 9) across range of self-reported and objective sleep and pain-related parameters. Findings revealed differences in patterns of self-reported sleep but not objective sleep between the two chronic pain conditions compared with healthy controls. The study also provided some extension of the findings from Chapter 4 by exploring the associations of objective sleep disturbance with less efficient pain inhibitory processes. To expand on these findings, the thesis adopted an epidemiological approach to explore the long-term interrelationship between sleep and pain-related outcomes in the general population. A systematic literature review (Chapter 6) of 16 longitudinal studies involving 61,000 participants consolidated evidence that changes in sleep are associated with several dimensions of the pain experience (risk of developing a pain condition, elevations in levels of inflammatory markers, and a decline in self-reported physical health status). Finally, Chapter 7 presents an analysis of a sample of the UK population and revealed the association between four-year changes in different insomnia symptom (sleep onset latency, awakenings, and daytime sleepiness) and perceived physical and psychological well-being in the general population (n = 30,594) and a subgroup with arthritis (n = 4,300). Overall, the findings from this thesis provide support for the associations of sleep disturbances with the processes underlying and shaping the experience of pain. The thesis highlights future research and beneficial interventions aimed at improving sleep and addressing associated pain-related health outcomes.

Gastroenteritis, causing vomiting and diarrhoea, is very common all over the world. Viral causes, such as norovirus and rotavirus, are the most frequent, although some bacteria, parasites and fungi can also lead to gastroenteritis. Many countries operate surveillance systems of diseases, including gastroenteritis or specific gastroenteritis causing pathogens. Typically, statistical methods are used to analyse surveillance data and alert public health authorities of unexpectedly high levels of illness. These methods use historical data to predict the expected value of current data. In this thesis, we address some of the challenges that remain when analysing gastroenteritis surveillance data, with a particular focus on syndromic surveillance data. We work with both mechanistic and statistical modelling approaches in an attempt to bridge the gap between the statistical methods that are used in practice for syndromic surveillance and mechanistic models that are used to model infectious diseases. In particular, we address three challenges. In chapter 2 we present a flexible framework for deriving approximations of stochastic mechanistic models of epidemics for fast inference. In chapter 3 we investigate day of the week and public holiday effects in syndromic indicators of gastroenteritis from syndromic surveillance systems operated by Public Health England in order to improve existing surveillance methodologies. In chapter 4 we identify and analyse additional online datasets for gastroenteritis, and in particular norovirus, surveillance.

Evidence of inadvertent patient harm due to healthcare staff errors - both within the NHS and in other healthcare providers worldwide - prompted regulator-led changes to eliminate such distressing incidents to patients and medical staff alike. Surgical disciplines, including orthopaedic surgery, became a focus of attention given the scale of the problem within operating theatres. Orthopaedic theatres are an example of a complex working environment that has been likened to an airplane cockpit whereby the delivery of unsafe and low quality service can lead to highly significant consequences. Around 32.6% of all surgical patient safety incidents reported by the NPSA are related to orthopaedics. Evidence suggests that harm incidents are influenced by the surgical team’s non-­‐technical skills, and can occur through an unpredicted combination of small, seemingly innocuous everyday events. It is also suggested that non-technical factors including the non-technical skills of the operating team can influence the technical tasks during surgery. In elective orthopaedic surgery, one important technical task during TKA surgery is achieving a neutral limb alignment making it a suitable surrogate for technical success and quality indicator for intra-operative performance. The impact of malalignment on patient outcomes is not fully understood. A systematic review of the literature demonstrated that although malalignment appears to associate with poor procedure outcomes however, the evidence in the literature to support this conclusion is subject to several limitations. There is also variability in the assessment methods qualities and a checklist to assess the radiological assessment methods is presented. Malalignment on the coronal plane is regarded as the most significant in determining long term implant survival. A novel X-­‐ray method using custom made jig and trigonometry principles designed during this thesis has demonstrated higher agreement with CT scan than the commonly used conventional short leg X-­‐rays in assessing coronal malalignment; (95% Limits of agreement = -­‐3.616867 to 3.616867 for novel technique versus -­‐6.333201 to 5.754254 for conventional short leg X-­‐rays). In order to explore the relationship between non-­‐technical factors and technical success, successive TKAs were observed to collect data on surgical team’s non-­‐ technical performance and the number of unwanted events. 3D malalignment was assessed using a low dose CT. Parson’s correlation and regression analysis showed that better overall limb alignment following TKA correlates significantly with better intra-­‐operative non-­‐technical skills measured using the Oxford NOTECHS II score (r=-­‐ 0.407, p=0.01), and not with eventless procedures (measured by the glitch count). The surgical teams’ non-­‐technical skills play a significant role in the team’s ability to carry out technical tasks. If we are to provide optimal patient care we need to invest in improving non-­‐technical skills in the theatre.

Mathematical models are a fundamental component of many epidemiological studies. While models of infectious disease are well established, there are evident methodological gaps when attempting to provide realistic descriptions of particular biological systems. In this thesis we probe questions related to two global public health problems, zoonotic influenza and depression, requiring innovative modelling approaches to be developed, analysed and fitted to data. We give particular consideration to parameter inference schemes to gain insights into the dynamics of these illnesses, and model simulation for validation and prediction purposes, including assessing intervention impact. First, we investigate zoonotic influenza transmission at a local scale, our example being H5N1 in Bangladesh. It is vital to devise new models incorporating zoonotic transmission, and establish the factors enabling both continued transmission within poultry and spillover across the poultry-human divide. We outline a set of candidate transmission models, with a zoonotic transmission component, parameterised with a Bayesian inference scheme using data from two H5N1 outbreaks in the Dhaka region. Applied at two distinct spatial scales, we elucidate the model considerations that best capture the size and spatial distribution of reported cases. Simulations then illustrate the predicted impact of interventions designed to reduce H5N1 transmission. Second, the emergence of influenza strains with pandemic potential is considered from a global viewpoint. Using a Bayesian model selection approach we compare plausible model hypotheses regarding the mechanisms driving influenza pandemic occurrences. Analysing the time periods between putative influenza pandemics since 1700, it is shown the weight of evidence favours influenza pandemic emergence being history-dependent, rather than a memoryless process. Predictive distributions are then presented for the expected number of pandemic events from 2010 to 2110. Third, spread of behaviour-linked health problems are amenable to being represented with methodological approaches typically used to model infectious diseases. We explore this with regards to depression, using a longitudinal dataset comprising information on both the in-school friendships and mood status of US adolescents. A novel model is described that exploits the dynamical behaviour of mood over time to ascertain which mood states spread on social networks, via a contagion-like mechanism, and which do not.

Clinical practice guidelines are developed worldwide, at an ever increasing rate (Sandström et al., 2015) and accessed internationally without a full understanding as to whether they are applicable in cross cultural settings. Informed by a review of the literature which identified a range of theories, frameworks and models to guide knowledge translation, the Promoting Action on Research Implementation in Health Services (PARIHS) framework (Kitson et al., 1998b), was selected as a suitable framework to explore evidence based clinical guideline development work in a cross cultural context. This research study was an exploration of the appropriateness and utility of the PARIHS framework, in the cultural translation and adaptation of an evidence based clinical practice guideline into clinical practice in the healthcare system in Malta. It also aimed to identify challenges and barriers to successful cultural translation and implementation to inform future cross cultural knowledge translation programs. A case study using an embedded single case was used. Data collection consisted of two focus groups with multidisciplinary healthcare professionals (n=11 and n=5), eighteen semi structured interviews (n=9 pre and n=9 post) and non-participant observation of two guideline development groups. Data was analysed both inductively and deductively using Framework Analysis. Findings of the study indicate that the components of the PARIHS framework of evidence, context and facilitation are useful to guide the cultural translation and adaptation of an evidence based clinical practice guideline. In addition, a number of challenges and barriers to successful translation and potential implementation were identified; the influence of politics, culture and context, stakeholder involvement including patient involvement, and resources, both human and financial. Overall the PARIHS framework is a useful tool to guide the cultural translation and adaptation of an evidence based clinical practice guideline. The study identified important additions to the PARIHS framework to improve its utility: expanding the use of culture in the PARIHS framework to include macro, meso and micro dimensions; the need for a definition of what context means within the PARIHS framework; the inclusion of politics as a sub element of context; the importance of resources, and acknowledging the role of the patient within the framework.

This thesis presents work from six papers written by the late Dr Carl McQueen during his time as a National Institute for Health Research Doctoral Research Fellow working at the University of Warwick. It explores how best to improve the outcomes of patients who sustain major trauma in the UK – something McQueen was passionate about. Mobile enhanced care teams can bring the specialist skills usually limited to a hospital to the patient’s side at the point of injury. One of the key specialist interventions such teams can provide is prehospital anaesthesia. In a retrospective observational study from a regional enhanced care team, McQueen showed that prehospital anaesthesia was delivered with a high success rate to patient who sustained major trauma and were unconscious, with or without airway compromise. The decision about when to send an enhanced care team to the scene of an emergency is challenging. Often insufficient information is available about the nature of the victim’s injury or illness to make an informed decision. McQueen showed that it was relatively rare for patients with medical problems or those linked to equestrian incidents to require specialist intervention. McQueen also showed the location of patients requiring enhanced care skills varies by time of day with most incidents at night occurring around cities / large towns. A systematic review of the literature found little evidence to guide decision making for primary dispatch of the enhanced care teams. Despite the paucity of evidence for triage systems to inform dispatch of enhanced care teams, reorganisation of regional trauma services in the West Midlands appears to have improved targeted dispatch of enhanced care teams. Together these papers show the potential for benefit from better co-ordination of enhanced care teams.

Introduction: Despite considerable efforts directed at developing international evidence based guidelines to improve clinical management, adoption of evidence based practices can be poor in low-income settings including Kenya. Studies in Africa rarely consider the implementation and change processes as influenced by the structural and organizational context in which clinicians are embedded nor how these can influence performance. This thesis builds on existing literature and theory on behavioural change, clinician-managers’ identity construction processes and contextualized leadership processes by examining these and their effect on guideline adoption in the complex contexts of Kenyan county hospitals. Methods: Methodologically I explored these issues through qualitative ethnographic approaches using in-depth interviews, focus group discussions and non-participant observations. I analyzed data inductively and deductively borrowing from the grounded theory approach to develop plausible explanations of collated data and observations. Results: Early work indicated limited attention to local dissemination of the new guidelines and poor leadership in implementing Evidence Based Medicine (EBM) as key barriers. However, specially introduced ‘study facilitators’ as part of an intervention study emerged as leaders of change often acting as role models, friendly supervisors and peer educators to facilitate EBM implementation. Further work reviewing literature on the roles of clinical mid-level managers (MLMs; department leaders) in improving service delivery emphasized the importance of ‘soft skills’ e.g. building interpersonal relationships, mentoring, coaching and effective communication skills. Subsequent in-depth empiric work on identity transitions of these clinical MLMs indicated that ‘identity work’, drawing on competing professional and managerial institutional logics resulted into ‘willing’, ‘ambivalent’ and ‘reluctant’ hybrids. Distributed leadership by hybrids was undermined by existing hierarchical professional autonomy and cadre delineations between nurses and doctors in the public county hospitals we studied. Discussion: The thesis describes both a set of work and a research journey. My initial work was predominantly based on applying the Theory of Planned Behaviour to explain behaviour of front-line health workers. However, it quickly became clear that this provided only a partial understanding of guideline adoption within a hospital overlooking the pivotal role of clinical team leaders / in influencing change. There emerged valuable lessons for current Kenyan leadership and management development programmes which are likely to be transferable to other African health systems. Particular recommendations from this work are the importance of a focus on the soft-skills of those stepping into clinical hybrid manager roles and considering the ‘practical norms’ of Kenyan public hospitals in understanding the gap between desired official institutional norms and health workers actual behavioural practices.

Bacterial infection is a major cause of morbidity and mortality in sub-Saharan Africa especially among young children. Despite the high burden of disease caused by bacterial infection in Africa, there remains a significant paucity of data on the molecular epidemiology of most pathogens in the sub-region. Healthcare facilities are generally underfunded in West Africa and most facilities lack the basic capacity to perform standard microbiological identification of bacterial pathogens. Understanding the biology and epidemiology of pathogens is fundamental to a successful intervention strategy. Genomics offers unprecedented insights into the epidemiology and biology of infectious diseases, which dominate the public health agenda in West Africa. Here, I introduce a case study of three important pathogens in West Africa. I describe a unique scenario associated with each pathogen and present WGS as a solution to the problem. Firstly, whole genome sequencing has provided insights into the evolutionary origin of Staphylococcus aureus in monkeys from The Gambia and established that monkeys in The Gambia do not pose a threat of serving as reservoirs of highly virulent S. aureus that can infect humans. Secondly, genomics has unravelled the evolutionary mechanisms that led to the emergence of a novel clone of serotype 1 Streptococcus pneumoniae, which caused an outbreak of meningitis in Ghana following the introduction of the 13-valent pneumococcal vaccine, PCV-13. Thirdly, through genomics we are beginning to build a deeper understanding of the epidemiology of Mycobacterium tuberculosis complex in West Africa. Genomics is unravelling the evolutionary mechanisms that are driving the emergence of multidrug resistant tuberculosis. Importantly, genomics has shown that lineages of MTBC that are endemic to West Africa are the principal proponents of multidrug resistance in this sub-region. The time has come for West Africa to embrace the genomics era and exploit the full potential of microbial genomics. I hope that my work will inspire West African scientists to embrace whole genome sequencing in the fight against infectious bacterial disease.

This PhD submission presents a case study of an academic group working as infomediaries at the interface between research and global policy, and at the interface between global policy and national decisions: advising on methodological issues, conducting systematic evidence reviews in response to information needs, and developing approaches for reinterpreting global guidance for national decision-making. The included systematic reviews were among the first to adopt innovative elements such as: summary of findings tables, standardized language reflecting the level of certainty in effect estimates, logic frameworks, and brief economic summaries; and have contributed to the further development of these methods. This work has helped to establish formal and transparent methods within global malaria guidance, and contributed to improved standards in global guidance more broadly.

Background: Rheumatoid Arthritis (RA) is associated with increased risk of cardiovascular disease (CVD). Physical inactivity is a modifiable risk factors of CVD and frequently associated with impaired functional status and health related quality of life. Objectives: This single blind randomised controlled trial investigated the impact of a pedometer-supported walking and education programme (Walk for RA-WARA) on PA, sedentary time, PA self-efficacy, disease activity, functional capacity, quality of life and cardiovascular (CV) risk in people with RA. Methods: Seventy-six individuals, aged 56 (±15) years and within 5 years from RA diagnosis were randomly assigned to either the WARA intervention group (six weekly group education sessions and two booster sessions at 3 and 6 months) or the control group (single session). Demographic data were recorded and Body Mass Index (BMI), Waist-Hip ratio (WHR), Waist-Height ratio (WHtR), and blood pressure were measured. The primary outcomes were objectively measured PA profiles, daily step counts and time spent sedentary, using an activPALTM and self-reported using international physical activity questionnaire (IPAQ). Functional status was assessed with six-minute walk test (6MWT), health assessment questionnaire (HAQ), and hand grip strength. Rheumatoid arthritis quality of life (RAQoL) and PA Self-efficacy were evaluated. Blood samples were taken and the 10-year risk of CVD scores were calculated, using the Scottish Intercollegiate Guidelines Network (ASSIGN). Data were analysed descriptively and mixed generalised linear models (GLM) were used incorporating restricted maximum likelihood (REML) and post-hoc analyses. Interviews were undertaken with 10 people from the intervention and data were analysed thematically using the framework approach and NVivo 11 software. Results: The intervention group showed a significantly greater increase than the control group in steps/day at 3 months (by 3413 (1835-4990) steps/day, mean (95%CI)) (P < 0.001), and 6 months (3599 (2135-5062) steps/day) (P < 0.001) and a significant reduction in IPAQ weekday (P=0.014) and weekend sitting time (P=0.046). There were significant improvements in 6MWT (P < 0.001), PA self-efficacy (P=0.008), systolic blood pressure (P=0.002) and ASSIGN scores (P < 0.001) in the intervention group. Participants found education sessions, booster sessions, hand-outs, pedometer, PA diaries were important factors in increasing their step counts. In addition, they stated that WARA programme was enjoyable and helpful in terms of raising their knowledge regarding their condition. They also reported they felt much healthier and their mood had improved. Conclusions: The 6-month WARA intervention was effective in promoting PA, PA self-efficacy, physical function, and reducing the 10-year risk of CVD. The WARA programme may be a useful adjunct to current clinical practice in rheumatology.