Background: Integrated care is a policy imperative in health and social care services globally, and yet there are reported difficulties in defining, developing and sustaining this way of working. Research Question: This research explores staff views and experiences of the presence, nature and development of integrated care in two programmes of community services. Method: A case study approach was adopted using secondary analysis of qualitative data from staff questionnaires using themed content analysis and pattern matching, with findings triangulated with documentary sources. The study considers the presence and nature of integrated care using the conceptual framework “to what extent integrated care is for everyone (inclusive) and not just for some (exclusive)” as interpreted from the literature. The development of integrated care was explored using systems theory for the management of change in a complex environment. Findings: A meta-analysis of the two case studies demonstrated that integration was present in all 66 services within the two programmes. The nature of integrated care varied and was demonstrated as multiple types (in community hospitals) and processes (in community services). The most frequently reported type was multidisciplinary working. The processes most teams chose to develop were information sharing systems. The development of integration within the case studies was affected by a number of factors, such as commitment and staffing. Conclusion: This study provides new evidence of the presence, nature and development of integration within a wide range of established services spanning all ages. From this and other measures, the extent to which integrated care is presented as “exclusive” can be questioned. These findings have informed the development of a framework of five principles, reflecting whether integrated care is: for everyone, extensive, enduring, can be enabled and essential. The implications and application of this research for policy, service development and training are discussed, and proposals for further research include testing the applicability of this framework and widening this study.

Aim: I describe the original contribution my work has made to understanding individual, social and environmental influences on physical activity among young people in Scotland. The work I present is based on six publications from five studies. Design/Methodology/Approach: Two studies used quantitative methods and include a 5-year longitudinal study and a cross-sectional pupil and school-level study. Data were collected through self-administered questionnaires. Three studies used qualitative methods including focus group discussions, photography and descriptive writing. All studies involved adolescents (10-15 years) attending schools in Scotland. Key Findings: My longitudinal evidence showed significant gender and developmental effects through early-mid adolescence, particularly at the primary-secondary school transition. While boys reported higher levels of physical activity than girls at all ages, baseline physical activity was a significant predictor of later activity levels for both genders. The importance of social influences was evident across my research. Survey data showed boys to report higher peer support, parental support and independent play than girls. Among both genders, peer, paternal and maternal support decreased with age, whereas independent play increased. Time spent with friends was particularly important and was further highlighted in qualitative findings. Being with friends was a benefit of active travel to school, walking, and general physical activity. Other factors influencing physical activity included proximity and access to local facilities, and the school environment. Most notable was the importance of cost and value for money. In general, pupils were satisfied with school facilities, but felt time for physical education (PE) could be increased. Among adolescent girls, survey data showed the best predictor of physical activity to be hours allocated to PE in fourth year of secondary school. Provision of PE and extra-curricular clubs are likely to be of greater importance to girls’ participation than schools facilities. Longitudinal data showed girls reporting lower levels of perceived competence, self-esteem and physical self-worth than boys at each age. Furthermore, girls’ physical perceptions decreased markedly over time, whereas among boys, only perceived competence decreased, while global esteem increased. Influences on physical activity participation were shown to be context specific, e.g. pupils reported not having bicycle storage as a barrier to cycling to school. Walking was a popular activity among girls, although areas in which walking took place, and reasons for walking could differ between geographical locations. Conclusions: In line with the socio-ecological model, my findings demonstrate the complex interaction of individual, social and environmental factors on physical activity participation among young people. They highlight the need for all sectors to work together in developing the most suitable interventions, considering the activity, its context and the population being targeted.

BACKGROUND Oral epithelial dysplasia has a malignant potential. Three inter-related challenges currently exist for this condition. Prediction of which lesions will progress to cancer is not possible, requiring most patients to undergo unnecessary treatment. Attempts to identify prognostic biomarkers are hampered by limited tissue availability. Surgery remains the mainstay of treatment, with significant functional consequences and poor efficacy in preventing malignant transformation. All three are addressed here, through improved identification of dysplastic lesions likely to become cancerous, validating high-throughput laboratory techniques in oral dysplasia, and assessing the feasibility of a novel chemoprevention trial in the UK. IMPROVING PATIENT SELECTION Improvements to the current best predictive method of histological grading were explored. The performance of the binary grading system was validated before improvements in its predictive ability made by altering its diagnostic threshold. Current prognostic biomarkers were then identified by systematic literature review. The hypothesis generated was that the Epidermal Growth Factor Receptor and related pathway biomarkers are prognostically significant. By examining the largest published oral dysplasia cohort, it was demonstrated that EGFR, COX-2 and tetraspanins CD9 and 151 possess a significant prognostic ability in oral dysplasia. VALIDATION OF TISSUE MICROARRAYS IN ORAL DYSPLASIA Tissue microarrays can maximise the utilisation of finite pathological archives. Their use in dysplasia was validated for the first time through the development of a novel tissue-sparing virtual-array technique. ALTERNATIVES TO SURGICAL TREATMENT A feasibility chemoprevention trial was designed and initiated. The main finding was that national multicentre participation would be required for adequate recruitment. The significant resources required mean it is not currently feasible to execute such a trial in a population with a low incidence of oral dysplasia like the United Kingdom. DISCUSSION In summarising the current literature, this thesis highlights the key challenges in managing oral dysplasia. Improvements in identifying cases at highest risk of transformation have been made and will direct future work in a prospective cohort. Difficulties highlighted during the feasibility trial are already guiding the design of future trials.

It is clear that sub-clinical inflammation is a key factor that triggers type 2 diabetes mellitus (T2DM) and is directly influenced by weight gain. Current studies highlight that obesity, particularly central obesity, heightens the pathogenesis of T2DM. Additionally, factors produced by adipose tissue (AT), referred to as adipocytokines, can influence the degree of insulin resistance as well as inflammation, due to their duality of function. A recently implicated adipocytokine, visfatin, has been identified as a potential insulin mimetic, an enzyme associated with mitochondrial biogenesis and an inflammatory factor. However, current studies lack a clear understanding as to the role and influence of visfatin in human AT and insulin resistant states. Therefore, this thesis examined visfatin expression within specific human AT depots and the influence of adiposity - with specific consideration given to insulin resistant states including T2DM, non-alcoholic fatty liver disease (NAFLD) and human immunodeficiency virus (HIV). Further, serum studies addressed how different insulin resistant states influenced circulating visfatin levels, whilst mechanistic studies explored how the role of visfatin was altered by insulin, an insulin sensitiser, inflammation and/or disease. This current thesis identified that visfatin was abundant in both abdominal depots, with highest expression in the omental (Om) AT, and isolated adipocytes, with an apparent relationship with insulin resistance. Subsequent in vivo and in vitro analysis further identified that, whilst insulin appeared to increase visfatin protein expression in isolated abdominal subcutaneous (Abd Sc) adipocytes, the use of an insulin sensitiser - either used in cultured Abd Sc adipocytes or as part of an oral therapeutic treatment in subjects with T2DM - decreased circulating visfatin levels. In addition, intracellular signalling studies highlighted that visfatin regulation within AT appeared to be dependent upon both nuclear factor (NF)-B and c-Jun N-terminal kinase (JNK) activation, influencing interleukin (IL)-6 as part of a visfatin regulatory feedback mechanism. Following the potential influence of visfatin in T2DM, this thesis explored its’ potential role in disease associated with other insulin resistant phenotypes, such as liver disease and HIV. From serum assessment of visfatin in subjects with NAFLD, it was identified that progression of liver disease was accompanied by a reduction in circulating visfatin levels – a finding that occurred independently of diabetic status. However, circulating visfatin still remained significantly higher in NAFLD with T2DM than those without. Finally, this thesis examined a potentially severe insulin resistant phenotype noted in HIV patients, due to an apparent lipodystrophy - a condition which alters fat oxidation and mitochondrial activation or regulation. In such a condition, circulating visfatin levels and visfatin mRNA AT expression remained unaltered by HIV status or drug therapy. Due to the capacity of visfatin to act as an enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis, essential for mitochondrial function and oxidative phosphorylation (OXPHOS), its role in AT remained unchanged by disease status, whilst other mitochondrial and fat metabolism factors were altered by both disease state and drug treatment. Taken together, these current data suggest a duality of function of which visfatin appears to be regulated by insulin, in addition to inflammation, in different disease states and therefore expands our current understanding of this multi-functional adipocytokine.

The rise in population together with industrialisation in the first half of the nineteenth century presented central government and local authorities with new challenges. Large numbers of people crowded together in poorly constructed homes with very limited sanitation facilities and created the perfect breeding ground for infectious diseases. The endemic nature of many of these diseases affected the most vulnerable members of society and the reduction in the high death-rates was an important consideration for the authorities. The Public Health Act 1848 was the first serious attempt by Westminster to tackle the problems of urban health which had been identified in several reports published in the 1840s. During the second half of the century public health policy was hesitantly developed and concentrated on cleaning up the environment in the expectation of bringing about a reduction in deaths. At the same time, rising living standards and improved food supplies to the towns brought about slight improvements in the dietary levels of the urban poor. A combination of factors brought about a rapid decline in death-rates by the end of the nineteenth century, and a further fall mainly attributable to changes in the pattern of infant mortality in the early period of the twentieth century. This thesis tests the general pattern of change in the context of Nottingham, one of Britain's largest provincial cities. It assesses the relative roles played by improvements in the areas of public health and housing and their contribution to the reduction in deaths. It then examines the issue of the improvements in food and nutrition, particularly at the beginning of the twentieth century, by assessing how accessible a more balanced and nutritional diet was available to the working-classes. It then assesses the changes in health during the period 1850-1939 and concludes that the improvements in the environment were minimal until 1920 and had little to do with the reduction in the death rate. The suggestion is that a better diet together with gradual improvements in the environment brought about the decline in deaths from certain diseases.

This thesis explores aspects of Streptococcus pneumoniae (pneumococcus) epidemiology and control, in view of the possible widespread introduction of conjugate vaccines in England and Wales. A review and analysis of a range of different epidemiological data sources showed that the burden of pneumococcal disease in England and Wales is high and remains mostly a condition of the very young and the elderly. A meta-analysis demonstrated the effectiveness of the polysaccharide vaccine against invasive pneumococcal disease among healthy elderly, to whom vaccination was not recommended at the start of this work. Using this result, a costeffectiveness analysis assessed the economic acceptability of such a programme, from the public health perspective. A better understanding of pneumococcal carriage and transmission is required to assess the effectiveness and cost-effectiveness of mass vaccination strategies with the pneumococcal conjugate vaccine. A novel model framework was developed and fitted to a longitudinal dataset of carriage in UK families. The results demonstrated an inverse relationship between duration of carriage and age and highlighted the importance of both family size and composition for persistence in a household. Great dissimilarities were estimated among the specific serotypes in terms of transmissibility, duration of carriage and level of competition. Realistic age structured dynamic models were developed and used to investigate the impact of a range of vaccine strategies. The importance of serotype replacement, as a consequence of vaccination, was demonstrated. The economic acceptability of alternative interventions with the conjugate vaccine depended on the magnitude of its indirect effects. Herd immunity had a considerable impact on the overall cost-effectiveness of the programmes since it may substantially reduce the burden of disease in older age groups. However, serotype replacement may counterbalance this reduction and lead to a non cost-effective result.

This thesis presents a study of the transmission dynamics of nosocomial pathogens in hospital wards, with particular reference to methicillinresistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The work makes use of mathematical models, and observational and epidemiological studies. Transmission dynamics of a potential pathogen are first explored using a stochastic host-vector epidemic model, where health-care workers' hands are assumed to be the vectors. Consequences of changes in patient management are presented, and stochastic effects are shown to be essential to an understanding of ward dynamics. Observations of carer handwashing behaviour and carer-patient contact patterns are described, and the factors associated with hand washing compliance and contact rates explored using statistical models. Patient-carer mixing patterns are investigated. Refinements to the host-vector model are used to show how different aspects of observed contact patterns may both increase and decrease the spread of nosocomial pathogens. For contact patterns typical of intensive care units, the model predicts that infection rates will increase as the staff-to-patient ratio decreases, so understaffing may result in more cross-infection even if handwashing levels do not change. The effect of antibiotic treatment on the spread of resistant strains is studied using a two-strain model. Changing patterns of antibiotic use are shown to be capable of causing large and rapid changes in ward prevalences of resistant strains. To investigate possible fitness costs, growth kinetics of methicillin-sensitive and methicillin-resistant S. aureus strains are compared. No evidence for differences in growth rates is found, though there is a suggestion that MRSA stains may have longer lag periods. Finally, a Markov chain Monte Carlo (MCMC) approach is developed to enable model parameters to be estimated from the incomplete data typical of ward-based epidemiological studies. The approach is used to estimate parameters using S. aureus and VRE transmission data. With the latter data, transmission rates were related to patient antibiotic use. All antibiotic combinations considered were associated with increased acquisition rates, the effect being strongest for cephalosporins.

A forward projection model was used to estimate the numbers of, both current and former, IDUs who acquired HCV infection and progressed to mild, moderate and severe HCV disease in Glasgow and Scotland between 1960 and 2030. The model was developed initially for Glasgow because more epidemiological information exists for this region, than elsewhere in Scotland, to calibrate model outcomes with local data relating to HCV and its consequence. Insights gained from the model fitting process in Glasgow were then used to extend the model to the rest of Scotland. First, the incidence and cessation of injecting drug use in Glasgow during 1960-2000 were derived through the use of a modified Delphi approach. Instead of the usual iterative process to refine experts’ estimates, the elicitation of IDU incidence and cessation provided an opportunity to combine these data and examine coherence with capture-recapture IDU prevalence estimates. Coherent estimates indicated that incidence (median: 28 to 49) and cessation (1 to 24%) remained low and stable during 1960-1975, rose steeply between 1975-1985 (incidence from 49 to 1,335; cessation from 2% to 6%), and by 2000 there had been a decline in incidence (1,195) but a further rise in cessation (15%). Secondly, stochastic simulation was used to model the transmission of HCV among current IDUs in Glasgow, according to their injecting risk behaviours, and estimate the past incidence of HCV infection. The model that considered higher infectivity during acute viraemia following infection produced seroprevalences (median: 62-72%) and incidences (18-30 per 100 susceptible injector-years) consistent with observed data during the 1990s. The annual number of new HCV infections among current IDUs in Glasgow was estimated to be low during 1960-1976 (median: 10-60), rise steeply during 1960-1976 (median: 10-60), rise steeply during the early 1980s to peak in 1985 (1,120), stabilise during 1991-1997 (510-610) and rise again during 1998-2000 (710-780). Scenario analyses indicated that potentially as many as 4,500 HCV infections (10th and 90th percentiles: 2,400-7,700) had been prevented in Glasgow during 1988-2000 as a result of harm-reduction measures. Scenario analyses also permitted the gauging of changes in risk behaviours required to effect appreciable reductions in the incidence of HCV infection. Incidence can be successfully reduced if IDUs who, unavoidably, share needles/syringes confine their borrowing to one person; with this strategy alone, an estimated 5,300 HCV infections (10th and 90th percentiles: 4,100-6,700) could have been averted in Glasgow during 1988-2000. Such insights will inform those responsible for developing new ways to prevent HCV transmission among IDU populations. Thirdly, linkage of laboratory data on diagnosed HCV antibody positive persons in Scotland to clinical data from hospital and death records provided a unique national epidemiological dataset to estimate the number who had progressed to severe HCV disease.

Thesis (M.P.H.M.(Primary Health Care Management))--Mahidol University.

Made available in DSpace on 2014-10-09T12:28:23Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:27Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia) / IPEN/D-MPLO / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP; Faculdade de Odontologia, Universidade de Sao Paulo, Sao Paulo