Aims: To determine the test-retest reliability and responsiveness of a new computerized 20-item pain measure, SUPER-KIDZ, in children with juvenile idiopathic arthritis (JIA). Methods: A single centre prospective cohort study of JIA patients aged 8-18 years was performed. For each SUPER-KIDZ item, test-retest reliability analysis was done in patients expected to have stable pain, and responsiveness was evaluated after intra-articular steroid injection(s). Results: Fifty-one subjects were included. Good internal consistency (α=0.73-0.92) was demonstrated for the 3 SUPER-KIDZ domains. Acceptable test-retest reliability (intraclass correlation coefficient or kappa ≥0.80) was found for 15 SUPER-KIDZ items. At 2 weeks post-injection, 16 items were responsive to change in pain (standardized response mean=0.66-0.82, significant Wilcoxon signed rank and linear mixed model). Conclusions: The majority of the SUPER-KIDZ items have acceptable test-retest reliability and responsiveness properties. If validity is demonstrated, this measure could be implemented as a standardized comprehensive pain tool for JIA patients.

Aims: To determine the test-retest reliability and responsiveness of a new computerized 20-item pain measure, SUPER-KIDZ, in children with juvenile idiopathic arthritis (JIA). Methods: A single centre prospective cohort study of JIA patients aged 8-18 years was performed. For each SUPER-KIDZ item, test-retest reliability analysis was done in patients expected to have stable pain, and responsiveness was evaluated after intra-articular steroid injection(s). Results: Fifty-one subjects were included. Good internal consistency (α=0.73-0.92) was demonstrated for the 3 SUPER-KIDZ domains. Acceptable test-retest reliability (intraclass correlation coefficient or kappa ≥0.80) was found for 15 SUPER-KIDZ items. At 2 weeks post-injection, 16 items were responsive to change in pain (standardized response mean=0.66-0.82, significant Wilcoxon signed rank and linear mixed model). Conclusions: The majority of the SUPER-KIDZ items have acceptable test-retest reliability and responsiveness properties. If validity is demonstrated, this measure could be implemented as a standardized comprehensive pain tool for JIA patients.

Since the publication of the Framingham algorithm for heart disease, tools that predict disease risk have been increasingly integrated into standards of practice. The utility of algorithms at the population level can serve several purposes in health care decision-making and planning. A population-based risk prediction tool for Diabetes Mellitus (DM) can be particularly valuable for public health given the significant burden of diabetes and its projected increase in the coming years. This thesis addresses various aspects related to diabetes risk in addition to incorporating methodologies that advance the practice of epidemiology. The goal of this thesis is to demonstrate and inform the methods of population-based diabetes risk prediction. This is studied in three components: (I) development and validation of a diabetes population risk tool, (II) measurement and (III) obesity risk. Analytic methods used include prediction survival modeling, simulation, and multilevel growth modeling. Several types of data were analyzed including population healthy survey, health administrative, simulation and longitudinal data. The results from this thesis reveal several important findings relevant to diabetes, obesity, population-based risk prediction, and measurement in the population setting. In this thesis a model (Diabetes Population Risk Tool or DPoRT) to predict 10-year risk for diabetes, which can be applied using commonly-collected national survey data was developed and validated. Conclusions drawn from the measurement analysis can inform research on the influence of measurement properties (error and type) on modeling and statistical prediction. Furthermore, the use of new modeling strategies to model change of body mass index (BMI) over time both enhance our understanding of obesity and diabetes risk and demonstrate an important methodology for future epidemiological studies. Epidemiologists are in need of innovative and accessible tools to assess population risk making these types of risk algorithms an important scientific advance. Population-based prediction models can be used to improve health planning, explore the impact of prevention strategies, and enhance our understanding of the distribution of diabetes in the population. This work can be extended to future studies which develop tools for disease planning at the population level in Canada and to enrich the epidemiologic literature on modeling strategies.

The total number of births among immigrants is on the rise and currently exceeds one fifth of live births within industrialized countries. The relation between adverse birth outcomes and migration remains unclear. The objectives of this thesis are to undertake a literature review to clarify the relation between migration and adverse birth outcomes, and to examine the interplay between duration of residence, maternal country of origin, and the residential environment using data on immigrants to Ontario Census Metropolitan Areas. The findings indicate that: a) Analyzing disparities in birth outcomes by migrant status with migrants defined as a single category is not informative. Rather, ethnicity and country of origin are important predictors of birth outcomes among immigrants. b) Duration of residence is linearly associated with low infant birth weight and preterm birth, mainly driven by decreases in gestational age with prolonged stay in Canada. c) The detrimental effects of long duration of residence on preterm birth are modestly attenuated, but not prevented, among immigrants living in urban neighbourhoods characterized by low material deprivation. d) Neighbourhood material deprivation has little, if any, influence on birth outcomes of recent immigrants, and only becomes influential after 15 years of stay in Canada. Maternal world region of origin constitutes a stronger predictor of adverse birth outcomes among recent immigrants. These findings stress the importance of the maternal country of birth and duration of residence as key predictors of immigrants’ health. They also support further research aimed at clarifying the nature of the association between time spent in Canada after migration and decreases in gestational age at delivery, and the identification of immigrant groups at high risk of adverse birth outcomes, based on these two key predictors.

Antimicrobial resistance is a serious threat to the treatment of infectious diseases and a leading public health concern of the 21st century. Antimicrobial resistant E. coli has been detected in many places including domestic livestock, humans, food items, surface water, and drinking water. Although the use of antibiotics is a major contributor to the emergence of resistance, the ingestion of water contaminated with antimicrobial resistant bacteria may contribute to the prevalence of antimicrobial resistance in humans. Purpose: The objectives of the research were to determine the prevalence of human faecal carriage of antimicrobial resistant E. coli in people residing in southern Ontario who used private water sources and to determine whether the use of water contaminated with antimicrobial resistant E. coli was associated with human carriage of same. Method: The study population consisted of people living in Ontario households that submitted water samples from private water sources for bacteriological testing between May 2005 and September 2006. Respondents completed a questionnaire and submitted a self-collected rectal swab. Results: Antimicrobial resistant E. coli were detected in the swabs of 41% of the 699 respondents, with 28% resistant to ampicillin, 25% to tetracycline, and 24% to sulfisoxazole, and 29% that were multi-drug resistant. Subjects from households using untreated water contaminated with antimicrobial resistant E. coli were 40% more likely to carry antimicrobial resistant E. coli in their gastrointestinal system than people from households using uncontaminated water, even after adjusting for the effect of other variables. Implications: The association between the consumption of water contaminated with antimicrobial resistant E. coli and human carriage of resistant E. coli highlights the ongoing risks associated with water contamination and antimicrobial resistance in Ontario. The high rates of resistant E. coli in healthy non-institutional persons provides further rationale for public health programs to reduce antibiotic use in medicine and agriculture.

Injury is the leading cause of morbidity and mortality among Canadian youth. In order to develop successful prevention strategies for this major public health problem, it is necessary to determine injury risk factors. Despite reasons to believe that family structure (parents’ marital and living arrangements) may be associated with youth injury, this link has been largely overlooked in injury research. The objectives of this thesis were to determine whether family structure was associated with youth injury in a manner described by theory, after considering alternative explanations for the observed association and to explore how engaging in high risk behaviour mediated the impact of family structure on youth injury. The association was explored using cross-sectional and longitudinal data. This study was based on a representative, cross-sectional World Health Organization, Health Behaviour in School-aged Children (2006) survey of 9, 068 Canadian students, aged 11–15 years, from 186 schools. A sub-sample of 1, 885 Ontario students surveyed in 2006 and again in 2007 comprised the longitudinal sample. The associations were assessed using generalized estimating equations with classroom clusters and Poisson distribution, adjusting for identified potential confounders and examining mediation by high-risk behaviours. There were three main findings: 1) Family structure was associated with medically treated injury in females, after accounting for confounding. Results showed that females from non-intact families had slightly increased risk of any injury than those from intact families (PR=1.11; 95% CI: 1.04-1.19). However, they had a greater risk of non-sports (PR=1.30; 95% CI: 1.16-1.77) and severe, non-sports (PR=1.46; 95% CI: 1.12-1.91) injury. 2) Only a small portion of the association between family structure and injury was explained by engaging in high risk behaviour. 3) There was an inconsistent relationship between family structure and male non-sports injury (Canadian cross-sectional, PR=1.05; 95% CI: 0.94-1.16; Ontario longitudinal, PR=1.58; 95% CI: 1.20-2.07). The findings of this thesis call attention to the importance of non-intact family structures as a risk factor for youth injury. More research is needed to improve our understanding of the mechanisms through which family structure influences youths' risk of injury in order to guide policy development.

This thesis consisted of three major components: 1. A sample of randomized controlled trials of herbal medicines was collected and assessed with a recently developed extension of the CONSORT statement for herbal medicine trials. 2. A methodological review of proposed methods of assessing clinical heterogeneity in meta-analyses of randomized controlled trials, 3. The application of permutation based resampling in meta-regression of multiple covariates. An analysis of 406 RCTs of herbal medicine interventions revealed that these trials are regularly under reporting important aspects of the intervention. Next, the second project showed that there are many resources providing suggestions for investigating clinical heterogeneity in systematic reviews of controlled clinical trials and though there is minimal consensus some recommendations are common across sources. Finally, the third project found that permutation tests result in more conservative, larger, p-values potentially reducing the rate of false positive findings when exploring multiple covariates.

Background: Breast cancer is a diverse disease. Over the past 3 decades it has been increasingly appreciated that therapy should be targeted to specific patient and tumour characteristics. In recent years the evaluation of tailored therapy has been dominated by the development of new drug therapy which when successful has been marketed at a high price. There have been few successful attempts to optimize currently available therapies. This thesis explores the optimization of currently available therapies in three domains: efficacy, toxicity and supportive care. Methods: Three independent studies were undertaken. First, a prospective cohort study was conducted to assess the impact of re-biopsy of recurrent breast cancer on physician choice of therapy and on patient satisfaction. The second study comprised a systematic review and meta-analysis of randomized trials exploring toxicities associated with different endocrine therapy options for early breast cancer with the aim of identification of patients who may be harmed by certain drugs. Finally, a randomized feasibility study was conducted to evaluate de-escalated intravenous bisphosphonates in women with low-risk metastatic breast cancer to bone. Results: All studies met their objectives in showing that the tailored use of available therapies can be optimized. The prospective study of the impact of re-biopsy showed that treatment decisions were modified in 14% of women. Patient satisfaction with the process of re-biopsy was high. The meta-analysis of toxicities of endocrine therapy identified cardiovascular disease as a statistically significant toxicity of aromatase inhibitors, thereby suggesting that those with established cardiovascular disease or risk factors thereof should reduce their exposure to these drugs. Finally, the randomized feasibility study showed that it is possible to conduct randomized trials of de-escalated bisphosphonates in women with low-risk breast cancer and there was no signal that reducing the frequency of treatment was associated with untoward outcomes. Conclusions: It is possible to optimize the tailored therapy of breast cancer using currently available treatments. This may lead to improved patient outcome while using existing resources. Further studies assessing the optimization of other treatments are warranted.

Introduction: There is uncertainty whether low-risk febrile neutropenia (FN) episodes in children with cancer are best managed in the inpatient or outpatient setting. Methods: A cost-utility model was created to compare four different treatment strategies for low-risk FN in pediatric cancer patients. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollar), and incremental cost-effectiveness ratios (ICER). Results: The most cost-effective strategy was outpatient treatment with intravenous antibiotics. It was cost saving ($2,732 versus $2,757) and more effective (0.66 QAFNE versus 0.55 QAFNE) as compared to outpatient treatment with oral antibiotics. An early discharge strategy after 48 hours in hospital was slightly more effective but significantly more expensive than outpatient treatment with intravenous antibiotics resulting in an unacceptably high ICER of more than $130,000 per QAFNE. Inpatient care was the least cost-effective strategy. Conclusions: Outpatient strategies for treatment of low-risk FN in children are more cost-effective than traditional inpatient care.

Social inequalities exist in smoking-attributable mortality rates of males. Change in these social inequalities in the past two decades in developed countries remains uncertain. This study was conducted in Canada, France, Poland, and Switzerland to quantify differences in smoking-attributable mortality rates, at ages 35-69 years, among different social strata in recent years and to examine the changes in social inequalities in these rates between 1986 and 2001. Analyses included 377,878 deaths from a total population of 13,482,210 males of these four countries. Smoking-attributable mortality rates reduced in all strata over the comparative time periods, in all countries, except France. This work specifically focuses to fill the gap in knowledge about whether tobacco control has reached the poor or lower social strata in developed countries. This study will enable follow up research including quantification of effects of the specific tobacco control policies in each country.