This thesis documents the development and evaluation of an mHealth intervention for sexual and reproductive health (SRH) referral from drugstores to health facilities in Mwanza Tanzania. SRH is an important factor for human development. Over the last 2 decades, provision and accessibility to SRH services has benefited from international and national health promotion interventions. In developing countries, use of close to community providers (CTC providers), such as village health workers, has been a key component of health promotion. This has been especially true in Tanzania where up to 70% of formal primary health care facilities lack health staff. CTC providers have been promoted through international initiatives such as the World Health Organization’s (WHO) task-shifting initiative. WHO’s recognition of CTC providers ranges from cadres at the grassroots level such as village health workers and drugstores to formal auxiliary providers based in health facilities, such as medical aides and nurses. In Tanzania, drugstores provide a range of SRH services ranging from simple advice on how to use a condom to complex prescriptions of antibiotics for STI treatment. Evidence has shown that drugstores – though more likely to have health-related training than any other informal CTC providers – lack skills necessary for provision of SRH services. This may contribute to poor SRH outcomes, such as increase in prevalence of sexually transmitted infections (STIs)/human immunodeficiency virus (HIV) and antibiotic resistance. Accessing SRH services at the formal health facility level is key to improving these outcomes. To create SRH service linkages and integration between drugstores and health facilities in Mwanza, Tanzania, an intervention that pioneered an mHealth SRH referral from drugstores to health facilities was designed and implemented for 18 months from September 2012 to February 2014. Referral between these two SRH providers using mHealth tools had not been attempted before. The intervention provided an electronic platform accessible to 52 drugstores and 18 health facilities in two districts of Mwanza region. Through a toll-free number and password, drugstores referred patients with SRH conditions to health facilities using the text-messaging feature on their mobile phones. From the platform’s in-built data collection tool, SRH uptake data demonstrated that 38% of patients referred from drugstores accessed HIV, STIs, family planning and maternal health services at the health facility level. A follow-up randomised household survey found that 72% of the participants would accept such type of referral in future, and among those who had ever visited drugstores for SRH services, 15% had heard about the intervention. At the end of the intervention, drugstores and health facilities confirmed that it was beneficial to their SRH service provision and that they would like to continue implementing it. In conclusion, this text messaging intervention pioneered community referral from drugstores to health facilities for SRH treatment by using mobile phones which appeared to be acceptable and effective in Mwanza Tanzania. With the growing use of mobile phones in Africa and the need to provide SRH services beyond the Millennium Development Goals (MDGs) era, mobile phone-based community referral through CTC providers, such as drugstores, could make an important contribution to achieving Universal Health Coverage targets.

This thesis examines issues related to cervical cancer epidemiology and prevention through screening, with the aim of informing policy regarding setting up an organised cervical screening programme in Hong Kong. There are five studies described here. The first, a case control study, indicated that screening is effective in preventing invasive cervical cancer among Chinese women. In addition, the main risk factors identified in other studies, were confirmed as risk factors in this population. Secondly, a cross-sectional study examined the pattern of cervical screening in Hong Kong. The screening system at that time achieved poor coverage, was inefficient, inequitable and potentially harmful. Thirdly, a cross-sectional study of practitioners showed the diversity in provision of services and the lack of consensus among practitioners in the management of abnormal smears. Fourthly, the use of an industrial quality management technique in monitoring quality, using inadequate smear rates as an indicator is assessed. It demonstrated that this is an efficient and useful method that can be applied to monitoring a screening programme. The last study was a randomised controlled trial showing that when women are given balanced information on cervical screening, with information on both the harms and benefits, relatively fewer chose to attend. The implications of these studies in relation to setting up a screening programme are discussed.

The increasing prevalence of obesity has been accompanied by an increase in the number of individuals at the extreme end of the obesity spectrum. The detrimental impacts of extreme obesity, defined as BMI ≥ 40.0kg/m2, on affected individuals' physical and psychological health have not been fully established. Furthermore, it remains unclear whether medical and behavioural interventions are effective at facilitating weight loss for individuals with extreme obesity. The efficacy of two treatment pathways within the Heart of England NHS Foundation Trust Specialist Weight Management Service were examined, with both demonstrated to facilitate clinically and statistically significant weight loss. A detailed profile of the characteristics of individuals entering the service highlighted the substantial physical and psychological co-morbidity associated with extreme obesity, revealing widespread impairment in quality of life and mental health. A systematic review of primary research examining the efficacy of medical and behavioural weight management interventions within lesser-researched extreme obese populations demonstrated the value of medically-supported programmes and also revealed the limited body of good quality research. This thesis has enhanced current understanding of extreme obesity, and recommendations generated from this work have been made in order to improve primary research examining weight management interventions and service provision for affected individuals.

Introduction: Smoking is a major risk factor for development of serious disease and smoking cessation greatly reduces this risk. The association between smoking, smoking cessation and mental health however, is less clear-cut, therefore this thesis aimed to further investigate this association. Methods: The first part of the thesis reports a systematic review and meta-analysis of longitudinal studies to determine the difference in change in mental health between quitters and continuing smokers. The second part of the thesis reports three prospective analyses of individual level-patient data from five trials for smoking reduction treatment. The first analysis examined the association between cessation and change in mental health using propensity score matching (PSM). The second analysis examined the association between cessation and risk of psychiatric disorder using PSM. The final analysis examined the association between change in mental health after quitting and odds of relapse. Results and interpretations: Cessation was associated with improvements in mental health compared with continuing smoking; there was no association between cessation and risk of psychiatric disorder, and no association between change in mental health after cessation and future relapse. Results support the misattribution hypothesis, and have implications for future research, smoking cessation treatment and public health policy.

Introduction: Obesity has been recognized as a major public health problem worldwide that requires preventive action. Prevention is best targeted at children, there is lack of quantitative and qualitative research on obesity prevention in children and most have been conducted in western countries. The aim of this study is to describe the prevalence of obesity among 6-7 years old school children, investigate contributing factors and identify potential components for an intervention programme to prevent obesity amongst children in the State of Qatar. Methods The study consisted of two distinct parts: cross sectional survey and focus groups with a range of stakeholders. Results: Whilst there was a high prevalence of overweight and obesity 16%, underweight was also prevalent (21.7%). The results of the focus group discussions indicate that causes of childhood obesity are multifactorial, and a multi-sector approach to prevention would be acceptable. Some of the important barriers that need to be considered in developing interventions were highlighted. Conclusion: In Qatar there is coexistence of underweight and obesity in primary school children. Qualitative results suggest that a multi-sector approach to prevention would be acceptable toward dietary and physical activity, and suggested potential components for an intervention programme in preventing obesity amongst children in the State of Qatar.

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.