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Hypertension is the most common chronic disease, with a global diagnosed prevalence of 70% by age seventy. Blood Pressure (BP) measures systemic arterial pressure and tends to increase with age from middle into older age. Higher BPs are clearly associated with higher cardiovascular and overall mortality in middle and early old age. However, BP trends and outcomes at advanced ages (over 75 years) have been less clear. This thesis aimed to: 1. estimate long term BP trajectories in older populations, including with proximity to death; 2. test associations between longer term BP decline and clinical outcomes, including in population-representative older adults with specific co-morbidities; 3. test whether declining BP is an independent predictor of outcomes, after accounting for commonly used clinical measures of impaired BP homeostasis. The thesis reports epidemiological analyses ranging from large-scale, representative primary care populations to detailed research cohorts with systematic BP measures. The results show that BP tends to peak at advanced ages, followed by a decline lasting 9 or more years before death. This pattern of decline occurs irrespective of anti-hypertensive treatment. BP declines are more marked in frail groups, and with certain diseases including dementia. Older groups (aged over 75 years) with systolic BPs lower than 130mmHg experienced increased overall mortality compared to those with systolic BP 130 to 140 mmHg consistently across analyses. Declining BP over several years may be a better predictor of mortality outcomes than orthostatic hypertension. The results suggest that declining blood pressures at advanced ages may constitute a distinct syndrome. Older people with a diagnostic label of hypertension without current elevated clinical BPs who have declining BP trends may be at increased risk of adverse outcomes and may require a different approach to clinical management.

Type 2 diabetes is a progressive disease characterised by raised blood glucose levels. Lowering of blood glucose is required to prevent symptoms of diabetes and to reduce the risk of people with type 2 diabetes developing diabetes-related complications. Metformin is the initial drug of choice to lower blood glucose for most people. However, for many people metformin eventually fails to control blood glucose and additional medication is required. At least four different types of glucose-lowering medication are recommended after metformin in current type 2 diabetes treatment guidelines. Choosing the best medication is left to the clinician and patient and is a major clinical dilemma. The degree of glucose-lowering appears to vary greatly between people for all the medication options. The same medication may appear to have a marked effect in one patient but little effect in another. Similarly, only some people develop side-effects. Despite this apparent variation it is largely unknown whether differences in treatment response and risk of side-effects can be predicted based on an individual patient's characteristics. The aim of this thesis is to establish whether simple patient characteristics are associated with differences in treatment effect for common glucose-lowering medications. If they are, this could inform a precision medicine approach in type 2 diabetes, where medications are targeted to those people most likely to benefit.

Vaccination of older adults is a key component of public health policy, but further evidence is required to understand its effectiveness in practice. Electronic health records (EHRs) present a potential alternative to the gold-standard evidence of clinical trials, particularly for populations, such as older adults, who may be under-represented in trials due to ethical and practical constraints in recruitment. Importantly, EHRs also allow the real-world study of an intervention as it is delivered in practice, and its effect in clinically important sub-groups. However, EHRs are not purposed to collect informaton on confounders, which may bias results from the analyisis of routinely-collected data. This motivated my review of quasi-experimental (QE) methods as a means of indirectly adjusting for confounding. My published methodological review found that the longitudinal information available in EHRs offer many opportunities for mitigating against confounding bias, but many methods may be under-utilised. The prior event rate ratio (PERR) and its alternative formulation, described under the Pairwise framework, is a recently developed method that utilises longitudinal information. This before-and-after approach can be applied to rate and survival data, allowing an easy comparison to many trial results. The data on vaccination in UK older adults was also the basis for further study of the performance and limitations of the method beyond exisiting simulation studies. Through comparison to weighted regression, I demonstrated how the source of confounding and robustness of the results could be explored. In a novel application of the PERR and Pairwise methods to interactions, I investigated the effectiveness of the pneumococcal vaccine in older patients, and found evidence for an increase in effectiveness with age across the years of policy implementation, 2003-2005. In my investigation of the influenza vaccine in annual cohorts from 1997 to 2011, I found consistent evidence of a moderately protective effect against myocardial infarction, but that this may decrease with age. The evidence also indicated a protective effect against influenza itself, but no age trend in its effectiveness was detected.

Childhood mental health problems are common (8-18% of the school age population), persistent, seemingly increasing, and can lead to a range of negative outcomes including adult mental illness, risk-taking behaviour, educational failure, and criminality (Costello, Egger & Angold, 2005). The effectiveness of child mental health care is therefore of great importance. This study examined the effectiveness of child and adolescent mental health services (CAMHS). This study explored the relationship of clinical outcome as reported by different informants and parental experience of the service and satisfaction, and the outcomes of children receiving evidence-based interventions for their disorder(s) were compared with children receiving interventions that lacked an evidence base, and the influence of case-complexity on both outcome and clinician workload was explored. A sample of 302 children from two participating CAMHS was recruited. Parents completed the Development and Well-Being Assessment (DAWBA), and the Strengths and Difficulties Questionnaire (SDQ) at baseline, and the SDQ, and the Experience of Service Questionnaire (ESQ) every six months for two years. The practitioners completed questionnaires describing the child’s difficulties and used the Child Global Assessment Scale (CGAS) as an indication of the child’s level of functioning at baseline while the child attended the clinic. From the first follow up, practitioners completed a questionnaire about any interventions offered. This study found that there was little agreement between the parents and practitioners on the outcomes of the children in the sample, and that overall the outcomes of the children in this sample were poorer than would be expected if left untreated in the community. It was also found that evidence based practice did not appear to have an impact upon outcome, nor did workload. Case complexity did appear to have a negative impact upon outcome. This study suggests that perhaps baseline case complexity plays a larger role in determining the outcomes of children than the workload this creates or the interventions that are given. This study also found that parental satisfaction was not highly correlated with outcome, suggesting that satisfaction may not be a reliable indicator of the quality of a service.