Background: Ethnic and immigrant groups represent a large and growing segment of the Canadian population, however, little is known about how these groups differ in their cardiovascular risk factor profiles when compared to the White population. This thesis describes three large, population-based studies examining cardiovascular risk among people of White, South Asian, Chinese and Black ethnicity living in Ontario. It was hypothesized that ethnic groups would differ significantly in their cardiovascular risk factor profiles. Methods: The study population included 154 653 White, 3364 South Asian, 3038 Chinese, and 2742 Black subjects derived from Statistics Canada’s National Population Health Survey and Canadian Community Health Surveys. In Project 1, the age- and sex-standardized prevalence of cardiovascular risk factors, heart disease, and stroke were compared across the four ethnic groups. In Project 2, the degree to which cardiovascular risk factor profiles differed between recent immigrants and long-term residents was compared across ethnic groups. In Project 3, a subsample of the study population was used to compare the ethnic-specific incidence and age at diagnosis of diabetes. We also derived ethnically appropriate body-mass index (BMI) cutoff values for obesity for assessing diabetes risk. Results: Ethnic groups living in Ontario differ strikingly in their cardiovascular risk profiles. The Chinese group had the most favourable cardiovascular risk factor profile, with 4.3% of the population reporting ≥2 major cardiovascular risk factors (i.e., smoking, obesity, diabetes, hypertension), followed by the South Asian (7.9%), White (10.1%) and Black (11.1%) groups. For all ethnic groups, cardiovascular risk factor profiles were worse among those with longer duration of residency in Canada. Nonwhite subjects developed diabetes at a higher rate, at an earlier age, and at lower ranges of BMI than White subjects. For the equivalent incidence rate of diabetes at a BMI of 30 in White subjects, the BMI cutoff value was 24, 25, and 26 in South Asian, Chinese, and Black subjects, respectively. Interpretation: These findings highlight the need for designing ethnically tailored cardiovascular disease prevention strategies and for lowering current targets for ideal body weight for nonwhite populations.

Background: Ethnic and immigrant groups represent a large and growing segment of the Canadian population, however, little is known about how these groups differ in their cardiovascular risk factor profiles when compared to the White population. This thesis describes three large, population-based studies examining cardiovascular risk among people of White, South Asian, Chinese and Black ethnicity living in Ontario. It was hypothesized that ethnic groups would differ significantly in their cardiovascular risk factor profiles. Methods: The study population included 154 653 White, 3364 South Asian, 3038 Chinese, and 2742 Black subjects derived from Statistics Canada’s National Population Health Survey and Canadian Community Health Surveys. In Project 1, the age- and sex-standardized prevalence of cardiovascular risk factors, heart disease, and stroke were compared across the four ethnic groups. In Project 2, the degree to which cardiovascular risk factor profiles differed between recent immigrants and long-term residents was compared across ethnic groups. In Project 3, a subsample of the study population was used to compare the ethnic-specific incidence and age at diagnosis of diabetes. We also derived ethnically appropriate body-mass index (BMI) cutoff values for obesity for assessing diabetes risk. Results: Ethnic groups living in Ontario differ strikingly in their cardiovascular risk profiles. The Chinese group had the most favourable cardiovascular risk factor profile, with 4.3% of the population reporting ≥2 major cardiovascular risk factors (i.e., smoking, obesity, diabetes, hypertension), followed by the South Asian (7.9%), White (10.1%) and Black (11.1%) groups. For all ethnic groups, cardiovascular risk factor profiles were worse among those with longer duration of residency in Canada. Nonwhite subjects developed diabetes at a higher rate, at an earlier age, and at lower ranges of BMI than White subjects. For the equivalent incidence rate of diabetes at a BMI of 30 in White subjects, the BMI cutoff value was 24, 25, and 26 in South Asian, Chinese, and Black subjects, respectively. Interpretation: These findings highlight the need for designing ethnically tailored cardiovascular disease prevention strategies and for lowering current targets for ideal body weight for nonwhite populations.

Esophageal squamous cell carcinoma (ESCC) is a common cancer in the northeast of Iran. In a series of studies we explored the genetic basis for this. First we showed the risk to age 75 of esophageal cancer in the first-degree relatives of patients with esophageal cancer was 34%, versus 14% for the first-degree relatives of the controls (hazard ratio = 2.3, 95%CI = 1.7-3.1; P = 3 x 10 – 8). Second, in a candidate-gene association approach, we showed that the ADH1B p.Arg48His mutation was associated with a significantly decreased risk of ESCC (OR = 0.41, 95%CI = 0.29-0.76; P = 4x10-4) under a recessive mode of inheritance, although our study subjects were not alcohol drinkers. Third, we showed the BRCA2 p.Lys3326X variant to be associated with increased risk of ESCC (OR = 3.38, 95%CI = 1.97-6.91; P = 2x10-4). Then, we hypothesized that the genes for Fanconi anemia may be candidate genes for ESCC and sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNA of 190 ESCC cases. We identified three heterozygous insertion/deletions in FANCD2, FANCE and FANCL. All three patients had a strong family history of ESCC. In addition, we found two homozygous patients for the deleterious FANCA p.Ser858Arg mutation. We found two more homozygotes in 556 more ESCC patients, but in none of 1373 matched controls (OR = 16.7, 95%CI = 6.2-44.2; P = 0.01). Finally, we implemented a pilot genome-wide association study in ESCC using 182 cases and 177 matched controls. None of the 1.2 M observed and imputed SNPs showed an association with ESCC at a genome-wide significance level. This showed that an ESCC susceptibility allele with OR>3 estimated from our familial risk study, is unlikely to be identified among common variants of the human genome and we should look for it among rare variants.

The goals of this dissertation were to investigate aspects of the health services utilization of marginalized persons living with HIV (PLWH), including women, recent immigrants, heterosexual men and individuals living in low income neighborhoods. In the first study, an algorithm of three physician claims for HIV-infection within a three-year period was validated for case-ascertainment of PLWH in administrative databases. The sensitivity and specificity of the algorithm were 96.2% [95% confidence intervals (CI) 95.2% to 97.9%] and 99.6% (95% CI 99.1% to 99.8%), respectively. The algorithm was used to conduct a population-based study examining rates of hospitalization among all PLWH receiving care in Ontario. The introduction of combination antiretroviral therapy was associated with more pronounced reductions in rates of total (-89.9 vs. -60.5 per 1000 PLWH; p = 0.003) and HIV-related hospitalizations (- 56.9 vs. -36.3 per 1000 PLWH; p < 0.001) among men relative to women. Between 2002 and 2008, higher rates of total hospitalization were associated with female sex [adjusted relative rate (aRR) 1.15; 95% CI: 1.05 to 1.27] and low socioeconomic status (aRR 1.21; 95% CI: 1.14 to 1.29). Higher rates of HIV-related hospitalizations were associated with low socioeconomic status (aRR 1.30; 95% CI: 1.17 to 1.45). Recent immigrants had lower rates of both total (aRR 0.70; 95% CI 0.61 to 0.80) and HIV-related hospitalizations (aRR 0.77; 95% CI 0.61 to 0.96). Finally, a theoretically-informed qualitative study was conducted to characterize the help-seeking experiences of heterosexual men living with HIV. The results indicate that without the symbolic appeal of women and the social connections of gay men, heterosexual men lack the composition of capital required to benefit fully from or improve their positions within the existing HIV health and social service fields. The findings of this dissertation illustrate important disparities in health services utilization among PLWH in Ontario.

High satisfaction rates and the lack of response variability are problematic areas in survey research. An important area of methodological concern for self-report survey is the sensitivity and reliability of the instrument. This research examines the effects of a positive (right) centred scale on the distribution and reliability of satisfaction responses in a positive respondent population. A total of 216 participants were randomly assigned to one of the following three experimental Likert scale conditions: 5–point equal interval balanced scale; 5–point positive (right) packed scale; 5–point positive (right) centred scale. The distribution of responses occurred in the direction hypothesized. Comparable discrimination was found across the three conditions. Although, the study findings did not prove to be significant, the equal interval balanced scale produced the lowest mean score, contrary to previous research findings.

Osteoporosis is a major public health problem resulting in substantial hip fracture related morbidity. Using healthcare utilization data, we determined the 1- and 2-year direct attributable healthcare costs associated with hip fractures among Ontario seniors in comparison to a matched non-hip fracture cohort. Over a four-year period (2004-2008) we identified 22,418 females and 7,611 males with an incident hip fracture. Approximately 22% of females and 30% of males died in the first year after fracture. The mean attributable cost in the first year was $36,929 ($52,232 vs. $15,503) among females and $39,479 ($54,289 vs. $14,810) among males. Primary cost drivers included acute hospitalizations, complex continuing care, and rehabilitation. Attributable costs remained elevated into the second year, particularly among those who survived the first year ($9,017 females and $10,347 males). Results from this study will aid policy decision makers in allocating healthcare resources and help feed into future health economic analyses.

Esophageal squamous cell carcinoma (ESCC) is a common cancer in the northeast of Iran. In a series of studies we explored the genetic basis for this. First we showed the risk to age 75 of esophageal cancer in the first-degree relatives of patients with esophageal cancer was 34%, versus 14% for the first-degree relatives of the controls (hazard ratio = 2.3, 95%CI = 1.7-3.1; P = 3 x 10 – 8). Second, in a candidate-gene association approach, we showed that the ADH1B p.Arg48His mutation was associated with a significantly decreased risk of ESCC (OR = 0.41, 95%CI = 0.29-0.76; P = 4x10-4) under a recessive mode of inheritance, although our study subjects were not alcohol drinkers. Third, we showed the BRCA2 p.Lys3326X variant to be associated with increased risk of ESCC (OR = 3.38, 95%CI = 1.97-6.91; P = 2x10-4). Then, we hypothesized that the genes for Fanconi anemia may be candidate genes for ESCC and sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNA of 190 ESCC cases. We identified three heterozygous insertion/deletions in FANCD2, FANCE and FANCL. All three patients had a strong family history of ESCC. In addition, we found two homozygous patients for the deleterious FANCA p.Ser858Arg mutation. We found two more homozygotes in 556 more ESCC patients, but in none of 1373 matched controls (OR = 16.7, 95%CI = 6.2-44.2; P = 0.01). Finally, we implemented a pilot genome-wide association study in ESCC using 182 cases and 177 matched controls. None of the 1.2 M observed and imputed SNPs showed an association with ESCC at a genome-wide significance level. This showed that an ESCC susceptibility allele with OR>3 estimated from our familial risk study, is unlikely to be identified among common variants of the human genome and we should look for it among rare variants.

The goals of this dissertation were to investigate aspects of the health services utilization of marginalized persons living with HIV (PLWH), including women, recent immigrants, heterosexual men and individuals living in low income neighborhoods. In the first study, an algorithm of three physician claims for HIV-infection within a three-year period was validated for case-ascertainment of PLWH in administrative databases. The sensitivity and specificity of the algorithm were 96.2% [95% confidence intervals (CI) 95.2% to 97.9%] and 99.6% (95% CI 99.1% to 99.8%), respectively. The algorithm was used to conduct a population-based study examining rates of hospitalization among all PLWH receiving care in Ontario. The introduction of combination antiretroviral therapy was associated with more pronounced reductions in rates of total (-89.9 vs. -60.5 per 1000 PLWH; p = 0.003) and HIV-related hospitalizations (- 56.9 vs. -36.3 per 1000 PLWH; p < 0.001) among men relative to women. Between 2002 and 2008, higher rates of total hospitalization were associated with female sex [adjusted relative rate (aRR) 1.15; 95% CI: 1.05 to 1.27] and low socioeconomic status (aRR 1.21; 95% CI: 1.14 to 1.29). Higher rates of HIV-related hospitalizations were associated with low socioeconomic status (aRR 1.30; 95% CI: 1.17 to 1.45). Recent immigrants had lower rates of both total (aRR 0.70; 95% CI 0.61 to 0.80) and HIV-related hospitalizations (aRR 0.77; 95% CI 0.61 to 0.96). Finally, a theoretically-informed qualitative study was conducted to characterize the help-seeking experiences of heterosexual men living with HIV. The results indicate that without the symbolic appeal of women and the social connections of gay men, heterosexual men lack the composition of capital required to benefit fully from or improve their positions within the existing HIV health and social service fields. The findings of this dissertation illustrate important disparities in health services utilization among PLWH in Ontario.

High satisfaction rates and the lack of response variability are problematic areas in survey research. An important area of methodological concern for self-report survey is the sensitivity and reliability of the instrument. This research examines the effects of a positive (right) centred scale on the distribution and reliability of satisfaction responses in a positive respondent population. A total of 216 participants were randomly assigned to one of the following three experimental Likert scale conditions: 5–point equal interval balanced scale; 5–point positive (right) packed scale; 5–point positive (right) centred scale. The distribution of responses occurred in the direction hypothesized. Comparable discrimination was found across the three conditions. Although, the study findings did not prove to be significant, the equal interval balanced scale produced the lowest mean score, contrary to previous research findings.

Osteoporosis is a major public health problem resulting in substantial hip fracture related morbidity. Using healthcare utilization data, we determined the 1- and 2-year direct attributable healthcare costs associated with hip fractures among Ontario seniors in comparison to a matched non-hip fracture cohort. Over a four-year period (2004-2008) we identified 22,418 females and 7,611 males with an incident hip fracture. Approximately 22% of females and 30% of males died in the first year after fracture. The mean attributable cost in the first year was $36,929 ($52,232 vs. $15,503) among females and $39,479 ($54,289 vs. $14,810) among males. Primary cost drivers included acute hospitalizations, complex continuing care, and rehabilitation. Attributable costs remained elevated into the second year, particularly among those who survived the first year ($9,017 females and $10,347 males). Results from this study will aid policy decision makers in allocating healthcare resources and help feed into future health economic analyses.