In a series of three parts, this thesis explores the available approaches to analyze post-randomized ineligible patients. Part one: a comprehensive systematic review yielding 18 unique articles from the Medline and the Cochrane Methodology Register databases. Part two: the methods found from the review were applied to a dataset where 23% of the patients in the experimental treatment group were found to be post-randomized ineligible patients. The results of this exercise revealed that little can be done when these patients exist and the best approach to dealing with them is to carefully choose an approach and accurately report how these patients were analyzed. Part three: Influenza was explored to further illustrate the importance of accurate reporting and the broader impact of this analytic issue. In sum, no firm conclusion could be reached on one "best" approach to take for randomized ineligible patients, however prevention and accurate reporting were surrogate recommendations.

Survivors of pediatric cancer should avoid smoking and heavy alcohol use due to health risks associated with intensive cancer treatments they received. Data were analyzed from a multi-centre, population-based study of pediatric cancer survivors in Canada (n=1231) and a frequency matched control group (n=1372). Logistic regression analyses showed that survivors were significantly less likely to be smokers and alcohol drinkers than the controls. Still, a substantial proportion of survivors were smokers (23%), binge drinkers (25%), alcohol drinkers (69%) and concurrent users (20%). Low education, poor life satisfaction, and high stress were the most consistent predictors of substance use. Results from the structural equation modeling analysis to describe pathways to concurrent smoking and alcohol use showed significant pathways from education and chronic stress to concurrent use in the cancer survivors. This study identifies potential risk factors for smoking and alcohol use in cancer survivors and suggests a need for preventive education.

Statement of the problem. Children with neurogenic bladders and poor bladder compliance are usually managed with bladder catheterization and oral anticholinergic medication. They may become non-responders to the drug or present with severe harms. Oxybutynin intravesically is an alternative therapy. Methods. CHEO experience (case series) with intravesical oxybutynin. Systematic review of the literature of intravesical oxybutynin in children with neurogenic bladders. Protocol for a RCT is proposed. Results. CHEO case series and the systematic review suggest intravesical oxybutynin is effective and well tolerated. There was a significant improvement in urinary incontinence and urodynamic outcomes. Published studies are of low level of evidence, and there was no RCT. The incidence of harm was low. Conclusion. Based on the evidence collected, there is not sufficient justification to recommend this therapy for children with neurogenic bladder. Research with a more sound study design, such as RCT, should be conducted to assess the efficacy of this intervention in children.

HIV infection leads to a profound T cell dysfunction well before the clinical onset of AIDS. This study investigated whether alterations in the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathway in CD4+ and CD8+ T cells from HIV-infected patients induced by the growth promoting cytokines IL-2, IL-4, IL-7, IL-10, and IL-15 may be involved. IL-2 and IL-15 induced STAT5 phosphorylation (P-STAT5) in CD4+ T cells but there was a clear separation of cells into P-STAT5- and P-STAT5+ populations to similar proportions in HIV- and HIV+ patients. In response to IL-7, the proportion of P-STAT5- cells was significantly higher in HIV+ patients compared to HIV- controls. The IL-7 dependent P-STAT5- CD4+ T cells appeared to correlate with a lack of IL-7Ralpha chain expression. However, the P-STATS- cells observed did not correlate significantly with other cytokine receptor components. Cytokine-induced P-STAT5 in the CD8+ T cells from HIV+ patients was clearly detected. However, IL-2 and IL-15 stimulation revealed a P-STATS- CD8+ T cell population, which was not detected in HIV- subjects. P-STATS- CD8+ T cells were observed in all HIV+ patients studied in response to IL-2 and IL-15, irrespective of HAART. Defects in the IL-2 and IL-15 mediated signaling pathways appeared to exist downstream of cytokine receptor expression. In response to IL-7, P-STATS- cells were observed in both HIV+ and HIV- patients. However, their proportion was higher in HIV+ patients and returned towards that of HIV- controls under HAART and correlated inversely with IL-7Ralpha chain expression. The presence of P-STATS- CD8+ T cells did not correlate with the expression of other cytokine receptor chains. The P-STAT5- T cells observed in response to these cytokines may represent cells at distinct differentiation stages and functional capacities that arise in response to chronic HIV infection and may contribute to the eventual insufficiency of the cell mediated immune response.

The Ottawa Influenza Decision Aid (OIDA) is a newly developed tool to assist healthcare personnel (HCP) make an informed decision regarding the seasonal influenza vaccine. The primary objective of this thesis is to determine approaches to implementing the OIDA into healthcare organizations by 1) conducting a systematic review of influenza immunization campaigns for HCP; 2) facilitating consultation meetings with healthcare organizers to collect their ideas on using the OIDA within their workplace; and 3) develop an OIDA implementation questionnaire based on the findings from the systematic review and consultation meetings. The systematic review results suggest that education-only campaigns only have a minimal impact on immunization rates. Future studies require improved reporting on the follow-up of HCP and calculation of HCP immunization rates. The consultation meetings identified ten approaches to implementing the OIDA within a healthcare setting. The OIDA Implementation Questionnaire was designed and a survey implementation approach recommended.

Schizophrenia is an illness causing impairment in thinking and functioning in many realms of everyday life. It is considered one of the most disabling of mental illnesses. This thesis considers the impact of schizophrenia in Ontario, including elevated mortality, degree of disability, economic impact. Some known risk factors for schizophrenia are increasingly common in Ontario, such as urban exposure, and a history of immigration. The impact of the illness in Ontario makes schizophrenia a good candidate for surveillance and case registry in this province. This thesis reviews the required elements of a surveillance system, including case definition and potential data sources and applies them to surveillance of schizophrenia in Ontario. The thesis then proposes a surveillance system and linked case registry based on combined OHIP, discharge abstract and mental health care administrative data, and outlines the necessary steps in implementation and evaluation of the system.

Stigma surrounding HIV and AIDS poses a significant threat to the curtailing of the epidemic by acting as a barrier to HIV testing and disclosure of serostatus. Previous research in the United States found personal knowledge of someone with HIV/AIDS to be a predictor of lower levels of HIV/AIDS-related stigma. However, no study to date has examined this relationship in Zimbabweans. Allport's contact hypothesis was hypothesis was the theoretical frame used to assess the effect of direct contact on public attitudes towards people living with the human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in Zimbabweans with the goal of identifying areas of stigma reduction. Stigma surrounding HIV and AIDS poses a significant threat to the curtailing of the epidemic by acting as a barrier to HIV testing and disclosure of serostatus. Previous research in the United States found personal knowledge of someone with HIV/AIDS to be a predictor of lower levels of HIV/AIDS-related stigma. However, no study to date has examined this relationship in Zimbabweans. This study surveyed English-speaking adult Zimbabweans from anywhere in the world. Descriptive statistics, Pearson product-moment correlation coefficients, and hierarchical stepwise multiple regression were used for analysis. Personal knowledge of someone with HIV/AIDS and the beliefs about HIV/AIDS transmission through casual contact emerged as the statistically significant predictors of stigma in the final model (r = -.172, p < .01, and r = .281, p < .001, respectively. There was an inverse correlation between personal knowledge of someone with HIV/AIDS and stigma. Potential positive social change contributions include a mobilized population with a common goal of eradicating HIV/AIDS, seeking HIV/AIDS testing services, disclosure of HIV serostatus, and seeking treatment leading to control of HIV transmission.

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