Prophylactic salpingo-oophorectomy, the preventive removal of the ovaries and fallopian tubes, is recommended to women who carry a BRCA1 or BRCA2 mutation in order to reduce the risk of breast, ovarian and fallopian tube cancer. The short and long term health and quality of life effects of this procedure are not well understood. We examined the actual and perceived reduction in cancer risk associated with this surgery. The impact of prophylactic salpingo-oophorectomy on health-related quality of life, psychological distress, cancer worry, menopausal symptoms, and sexual function during the year following surgery was also evaluated. In our prospective study, prophylactic salpingo-oophorectomy was associated with an 80% reduction in ovarian and fallopian tube cancer risk. The residual risk for primary peritoneal cancer was 0.2% per year or 4.3% at 20 years after salpingo-oophorectomy. Most women accurately perceived their risk of breast cancer. However, the risk for ovarian cancer was overestimated, particularly by women who carry a BRCA2 mutation. Physical and mental health-related quality of life did not decrease in the year following surgery; and psychological distress was similar to levels experienced by the general population. Most women were significantly less worried about cancer after the surgery, however, a subset of women continued to experience significant cancer specific distress after prophylactic salpingo-oophorectomy. Women who underwent prophylactic salpingo-oophorectomy when premenopausal experienced a significant worsening of vasomotor symptoms and a decline in sexual functioning. Hormone replacement therapy mitigated these symptoms, but not to pre-surgical levels. Dyspareunia was somewhat alleviated by hormone replacement therapy, however, the decrease in sexual pleasure was not. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy was high regardless of these symptoms. These studies will provide women who are considering prophylactic salpingo-oophorectomy with information about the reduction in cancer risk associated with the surgery and the possible effects experienced during the year following surgery.

Multidisciplinary cancer conferences (MCCs) provide an opportunity for health professionals to discuss diagnosis and treatment options with the goal of providing optimal patient management. No prior studies have explored the experiences of adopting and implementing MCCs in Canada. Methods: Using a grounded theory approach, interviews, participant-observation, and document analysis were triangulated to explore the experiences of implementing MCCs at four hospitals in Ontario, Canada. Constant comparative analysis was used to identify themes and assimilate them into a theoretical understanding of policy, administrative/organizational, and participant contributions to implementing MCCs. Results: Thirty-seven MCCs, in three hospitals, were observed, and 48 interviews were conducted. The core conceptual category was a perceived value for time balance, which was influenced by policy and administrative factors, and themes related to MCC structure and participant interaction. Conclusions: MCC implementation in Ontario is inconsistent. Future efforts should concentrate on a systematic implementation plan involving clinicians and administrators.

Background: Self-rated health (SRH) is among the most frequently assessed health perceptions in epidemiological research. While the predominant focus has been the predictive relevance of SRH, there is increasing interest in understanding the nature of SRH. Recently a conceptual interpretation of SRH was proposed. Purpose: To assess the tenability of the recently proposed distinctions of self-rated health, as a spontaneous assessment of overall health, or as an enduring self-concept, or both, and to determine the significance of mental well-being, physical and social health for SRH. Methods: A cohort of individuals undergoing total joint replacement (TJR) for hip or knee osteoarthritis (OA) was followed over 6 months of recovery. Participants (n=449) completed (pre-surgery, 3 and 6 months post-surgery) measures associated with physical health: pain, physical function, sports/recreation, fatigue; mental well-being: anxiety, depression; and social health: social participation, passive/active recreation, community access. Using structural equation modeling, confirmatory factor analyses (CFA) investigated 3 latent health variables, and the responsiveness of SRH to current and changing health status, as well as its predictive significance for future health status was investigated. Results: CFA analyses confirmed relationships between observed health measures and hypothesized latent health dimensions. SRH was responsive to current and changing mental well-being. The effects of physical and social health were mediated through mental well-being. SRH was a strong predictor of future SRH and future health status. Conclusion: SRH displayed features of both an enduring self-concept and spontaneous assessment of health status; evidence is provided that both operate simultaneously. While aspects of physical health have always been perceived as the major determinants of SRH, these findings indicate that mental and social health explain much of the relationship between physical health and SRH. These results are particularly unexpected since this is a sample of individuals undergoing TJR surgery, for which pain and restricted physical function are primary indicators. Since SRH is a significant predictor of health status, TJR outcomes, health care utilization and mortality, this study suggests that health research and care, treatment and management modalities should consider a broad range of health dimensions, not only physical aspects of health, and SRH.

Degenerative disease of the lumbar spine (DDLS) is a common condition for which surgery is beneficial in selected patients. Wide variation in surgical referral and rates of surgery has been observed contributing to unequal access to care. Our objectives were to examine (1) the variation in preferences for referral and surgery among surgeons, family physicians (FPs) and patients, (2) how FP referral practices compare with preferences and guideline recommendations, and (3) how the ‘enthusiasm’ of patients and physicians influence regional variation in surgical rates. We used conjoint analysis in a mailed survey to elicit preferences based on clinical vignettes from surgeons, FPs and patients. A Delphi expert panel provided consensus guideline recommendations for surgical referral to compare with actual FP referral practices. Rates of surgery for DDLS, obtained from Ontario hospital discharge data, were used to quantify regional variation and regression models assessed the relationship with patient and physician enthusiasm. We identified significant differences in preferences for referral and surgery between patients, FPs and surgeons. Surgeons placed high importance on leg-dominant symptoms while patients had high importance for quality of life symptoms (i.e. severity, duration, walking tolerance). Surgical referral practices were poorly predicted by individual FP preferences and guideline recommendations based on clinical factors alone. Variation in Ontario surgical rates was higher than that of hip or knee replacements and was highly associated with the enthusiasm of surgeons (p<0.008), rather than FPs or patients. By appreciating the variation in preferences between patients and physicians, and exploring other non-clinical factors that influence referrals, we may be able to improve the efficiency of referrals and enhance the shared decision making process. With an understanding of the influence that surgeons have in driving variation in surgical rates, further research may allow us to direct strategies to improve access and allow for a more equitable delivery of care for patients suffering from DDLS.

Osteoporosis is a major public health concern, affecting over 200 million people worldwide. There is valid evidence outlining how osteoporosis can be diagnosed and managed, but gaps exist between evidence and practice. Graham’s “Knowledge to Action” (KTA) process for knowledge translation and the Medical Research Council (MRC) framework for complex interventions were used to address these gaps. The first 4 KTA steps were collapsed into 3 phases of the PhD research plan. In PhD Phase 1, a systematic review was conducted to identify tools that facilitate decision making in osteoporosis disease management (DM). Results showed that few DM tools exist, but promising strategies were those that incorporated reminders and education and targeted physicians and patients. PhD Phase 2 used the findings from the systematic review and consultation with clinical and human factors engineering experts to develop a conceptual design of the tool. Multiple components targeted to both physicians and patients at the point of care, and which could be used as a standalone system or modifiable for integration with electronic health record systems were outlined. PhD Phases 3a and 3b were devoted to the assessment of the barriers to knowledge. In Phase 3a, a qualitative study of focus groups was conducted with physicians to identify attitudes and perceived barriers to implementing decision support tools in practice, and to identify the features that should be included in the design. Findings from 4 focus groups combined with aging research, and input from design and information experts were used to transform the conceptual design into a functional prototype. In Phase 3b, each component of the prototype was tested in 3 usability evaluation studies using an iterative, participant-centered approach to assess how well the prototype met end users’ needs. Findings from the usability study informed the final prototype, which is ready for implementation as part of the post PhD plan to fulfill the requirements of the remaining steps of the KTA and MRC frameworks.

This study builds on previous research showing that breast cancer survival is poorer for First Nations (FN) women compared to other Ontario women. Few studies have examined breast cancer survival in Indigenous populations compared to general populations; all of these report poorer survival among Indigenous people. Fewer still have examined potential factors related to the poorer survival, but these often suggest poorer prognosis even after adjustment for them. Study objectives were: to compare the distribution of demographic, prognostic and treatment factors between FN and non-FN women; to investigate factors associated with later diagnosis in FN women; to compare stage specific survival for FN and non-FN women controlling for important factors potentially associated with breast cancer survival; and to examine potential determinants of survival for FN women by stage at diagnosis. A case-case design was employed to compare FN women (n=287) diagnosed with invasive breast cancer to a frequency-matched random sample of women (n=671) from the general population diagnosed with breast cancer within the Ontario Cancer Registry. Women were matched (2:1) on period of diagnosis (1995-1999 and 2000-2004), age at diagnosis (<50 vs. 50≥), and Regional Cancer Centre (RCC). Stage at diagnosis and data relevant to the determinants of breast cancer survival were collected from medical charts at the RCCs. FN women were diagnosed with breast cancer at later stages compared to non-FN women. Having a non-screened method of detection and increasing BMI were associated with a later breast cancer diagnosis. FN women with comorbidity however were less likely to be diagnosed at a later stage. An unforeseen novel finding was that the survival disadvantage occurred after an early breast cancer diagnosis, whereas the survival experiences for those diagnosed at stages II+ were similar. In a multivariate analysis, elevated risk was observed for FN women in stage I, and significant risk was seen in women with comorbidity. These findings are actionable and can be used to improve the prognosis of FN women with breast cancer. It is likely that the same or similar factors are largely responsible for the survival disadvantage observed among Ontario FN people for most other major cancers.

Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes, and low vitamin D levels have been associated with several chronic and infectious diseases. Previous studies have reported that many otherwise healthy adults of European ancestry living in Canada have low vitamin D concentrations during the wintertime. However, individuals of non-European ancestry are at a higher risk of having low vitamin D levels. This thesis examined vitamin D status in a sample of young adults of diverse ancestry living in the Greater Toronto Area. In my research I found that: 1) vitamin D levels (measured as 25(OH)D concentrations) are low in Canadian young adults, particularly in those of non-European ancestry; 2) vitamin D intakes, which were estimated to be on average higher than current Health Canada recommendations of 200 International Units (IU) per day, were inadequate to maintain optimal vitamin D levels year-round; 3) vitamin D levels undergo large seasonal changes. Winter 25(OH)D concentrations are substantially lower than those observed during the fall; 4) vitamin D intake is an important year-round predictor of 25(OH)D concentrations, but skin pigmentation and sun exposure are also important predictors during the times when UVB is adequate for cutaneous synthesis; and 5) vitamin D binding protein (VDBP) polymorphisms are significant predictors of 25(OH)D concentrations, but their effects vary by ancestry and season, indicating gene-environment interaction effects. My research shows that higher vitamin D intakes are needed to offset the seasonal drop in vitamin D levels and to ensure adequate vitamin D levels year-round for those at higher risk of insufficiency.

Prophylactic salpingo-oophorectomy, the preventive removal of the ovaries and fallopian tubes, is recommended to women who carry a BRCA1 or BRCA2 mutation in order to reduce the risk of breast, ovarian and fallopian tube cancer. The short and long term health and quality of life effects of this procedure are not well understood. We examined the actual and perceived reduction in cancer risk associated with this surgery. The impact of prophylactic salpingo-oophorectomy on health-related quality of life, psychological distress, cancer worry, menopausal symptoms, and sexual function during the year following surgery was also evaluated. In our prospective study, prophylactic salpingo-oophorectomy was associated with an 80% reduction in ovarian and fallopian tube cancer risk. The residual risk for primary peritoneal cancer was 0.2% per year or 4.3% at 20 years after salpingo-oophorectomy. Most women accurately perceived their risk of breast cancer. However, the risk for ovarian cancer was overestimated, particularly by women who carry a BRCA2 mutation. Physical and mental health-related quality of life did not decrease in the year following surgery; and psychological distress was similar to levels experienced by the general population. Most women were significantly less worried about cancer after the surgery, however, a subset of women continued to experience significant cancer specific distress after prophylactic salpingo-oophorectomy. Women who underwent prophylactic salpingo-oophorectomy when premenopausal experienced a significant worsening of vasomotor symptoms and a decline in sexual functioning. Hormone replacement therapy mitigated these symptoms, but not to pre-surgical levels. Dyspareunia was somewhat alleviated by hormone replacement therapy, however, the decrease in sexual pleasure was not. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy was high regardless of these symptoms. These studies will provide women who are considering prophylactic salpingo-oophorectomy with information about the reduction in cancer risk associated with the surgery and the possible effects experienced during the year following surgery.

India houses the world&rsquo;s third largest population of people living with Human Immunodeficiency Virus (HIV) who constitute about 6% of the global HIV burden. In about 2008-9, an estimated 1.9 million [95%CI: 1.5 to 2.5] adults were living with HIV in India. The four southern Indian states of Andhra Pradesh, Karnataka, Maharashtra and Tamil Nadu account for about 60% of estimated HIV infections, although they house only 30% of the adult population. I report that most HIV infections in infected couples in the general population of India (85.4% (95%CI: 80.0, 90.7)) were introduced by the male partner. The per-partnership transmission probability of HIV in the general population was low 29.1% (95%CI: 22.5, 35.7) compared to what has been reported for other STIs. Important theoretical facilitating factors for HIV transmission were associated with HIV infection with nearly equal effect sizes in both genders and across HIV&ndash;risk settings (multiple partnerships (OR: 2.46 (95%CI: 1.98, 3.06) and STIs (ORHSV-2: 5.60 (95%CI: 3.37, 9.33); ORSyphilis: 4.12 (95%CI: 2.35, 7.25)). The strength of association of STIs with HIV was consistent. Intervention spending on, or coverage of, STI treatment-focused sex work interventions (per 1000 total district population) was associated with a reduced annual risk of either HIV (- 1.7%, 95%CI: -3.3, -0.10) or syphilis (-10.9%, 95%CI: -15.9, -5.8) infection in young pregnant women in the high-burden southern states. A decreased annual risk of syphilis iii among young pregnant women attending public prenatal clinics in the high-burden southern states was associated with a unit increase (per 1000 total district population) of intervention spending (-0.009%, 95%CI: -0.014, -0.004), number of STIs treated (-10.9%, 95%CI: -15.9, -5.8), FSWs reached (-3.0%, 95%CI: -5.2, -0.7) and condoms distributed (-0.034%, 95%CI: - 0.053, -0.015). Male sexual behaviour (non-regular partnerships and use of female sex work) is the dominant driver of HIV transmission in the general population of south India. Ulcerative STIs were strongly associated with HIV infection in south India and interventions aimed at treating STIs and promoting safer sex practices for FSWs and their clients have resulted in reductions in HIV and syphilis incidence and prevalence in the general population of south India.

India houses the world&rsquo;s third largest population of people living with Human Immunodeficiency Virus (HIV) who constitute about 6% of the global HIV burden. In about 2008-9, an estimated 1.9 million [95%CI: 1.5 to 2.5] adults were living with HIV in India. The four southern Indian states of Andhra Pradesh, Karnataka, Maharashtra and Tamil Nadu account for about 60% of estimated HIV infections, although they house only 30% of the adult population. I report that most HIV infections in infected couples in the general population of India (85.4% (95%CI: 80.0, 90.7)) were introduced by the male partner. The per-partnership transmission probability of HIV in the general population was low 29.1% (95%CI: 22.5, 35.7) compared to what has been reported for other STIs. Important theoretical facilitating factors for HIV transmission were associated with HIV infection with nearly equal effect sizes in both genders and across HIV&ndash;risk settings (multiple partnerships (OR: 2.46 (95%CI: 1.98, 3.06) and STIs (ORHSV-2: 5.60 (95%CI: 3.37, 9.33); ORSyphilis: 4.12 (95%CI: 2.35, 7.25)). The strength of association of STIs with HIV was consistent. Intervention spending on, or coverage of, STI treatment-focused sex work interventions (per 1000 total district population) was associated with a reduced annual risk of either HIV (- 1.7%, 95%CI: -3.3, -0.10) or syphilis (-10.9%, 95%CI: -15.9, -5.8) infection in young pregnant women in the high-burden southern states. A decreased annual risk of syphilis iii among young pregnant women attending public prenatal clinics in the high-burden southern states was associated with a unit increase (per 1000 total district population) of intervention spending (-0.009%, 95%CI: -0.014, -0.004), number of STIs treated (-10.9%, 95%CI: -15.9, -5.8), FSWs reached (-3.0%, 95%CI: -5.2, -0.7) and condoms distributed (-0.034%, 95%CI: - 0.053, -0.015). Male sexual behaviour (non-regular partnerships and use of female sex work) is the dominant driver of HIV transmission in the general population of south India. Ulcerative STIs were strongly associated with HIV infection in south India and interventions aimed at treating STIs and promoting safer sex practices for FSWs and their clients have resulted in reductions in HIV and syphilis incidence and prevalence in the general population of south India.