Health Sciences - Theses, Dissertations, and other Required Graduate Degree Essays

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Cancer risk among women living with HIV: Implications for care in the modern cART era

Author: 
Date created: 
2017-06-28
Abstract: 

Following the advent of modern combination antiretroviral therapy (cART) in 1996, a temporal decline was widely observed in AIDS-related morbidity and mortality. In the province of British Columbia (BC), universal provision of cART free-of-charge for people living with HIV (PLHW) has contributed in part to a significant demographic shift, with individuals over 50 years of age comprising over half of all PLHW. In this context there is a need to understand how comorbidities, such as cancer, impact this aging cohort. Within this line of inquiry, it is imperative to look at cancer risk specifically amongst women living with HIV (WLWH). The majority of studies looking at cancer as a co-morbid condition among PLWH fail to conduct sex-stratified analyses, which may obscure the burden of cancer risk specific to WLWH. Using a Life Course Epidemiology framework, the objectives of this PhD dissertation were to: 1) measure cancer incidence among WLWH in BC compared to a general population sample of women; 2) identify the role of early cART initiation in mitigating excess risk of cancer observed among WLWH; and 3) estimate the burden of cancer-related mortality among PLWH. This research utilized administrative health data from Population Data BC (which included data from the BC Cancer Agency and Vital Statistics) and clinical HIV data from the BC Centre for Excellence in HIV/AIDS. Findings suggest WLWH experience an increased risk of certain cancers, notably for certain viral-related malignancies, in comparison to HIV-negative women in the modern cART era. A protective effect of early initiation of cART therapy was found for some types of cancer, suggesting oncological health benefits might be associated with timely initiation of cART after HIV diagnosis for WLWH. Finally, sex stratified age-adjusted cancer-related mortality rates promisingly suggest there may not be significantly different cancer-related mortality outcomes between PLWH and the general population. This dissertation demonstrates that cancer-related morbidity is a healthcare priority for the growing aging demographic of WLWH and subsequently highlights the importance of appropriate and effective routine cancer screening measures as well as comprehensive HIV care inclusive of timely diagnosis and cART initiation.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Robert Hogg
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

Going beyond health-related quality of life for outcome measurement in economic evaluation

Author: 
Date created: 
2017-07-04
Abstract: 

Background: The quality-adjusted life year (QALY) framework has been challenged for use in economic evaluation because of its narrow focus on health-related aspects of quality of life, thus ignoring potential ‘non-health’ benefits associated with treatments and interventions. With the development of new preference-based measures, such as the ICEpop CAPability (ICECAP) instruments that adopt a broader evaluative space, the aim of this thesis was to examine methodological considerations and applied implications for outcome measurement in health economics when applying measures that extend beyond health. Methods: A narrative review provides an overview of challenges involved for broadening the evaluative space of the QALY and the progress that has been made in this area. A critical interpretive synthesis (CIS) is then presented that conceptualized benefits beyond the health-related QALY, followed by three empirical analyses, each using a different dataset: (i) regression analyses testing the complementarity of a preference-based health-related quality of life (HRQoL) measure, the EQ-5D-5L, and a measure of capability wellbeing for older adults, the ICECAP-O, within the context of public health; (ii) exploratory factor analyses investigating the overlap between the ICECAP-A and five preference-based HRQoL measures; and (iii) path analyses to further explore the relationship between two HRQoL measures (EQ-5D-5L and AQoL-8D) and two wellbeing measures (ICECAP-A and subjective wellbeing). Results: The CIS conceptualized non-health benefits into four themes: (i) benefits affecting a person’s wellbeing (psychological wellbeing, subjective wellbeing, empowerment, and capability wellbeing); (ii) benefits derived from the process of health care delivery; (iii) benefits beyond the affected individual; and (iv) benefits beyond the health care sector. Three key findings were made from the empirical analyses that further explored wellbeing measures. Firstly, the ICECAP-O is more sensitive to environmental features (i.e., social cohesion and street connectivity) when compared with the EQ-5D-5L; secondly, the ICECAP-A contains domains in its descriptive system that are not measured by most HRQoL measures, except for the AQoL-8D; and thirdly, HRQoL and wellbeing measures are affected in a different way by different secondary health conditions but a similar relationship was found between the ICECAP-A and AQoL-8D. Conclusion: The thesis concludes that the application of wellbeing measures in economic evaluations requires careful consideration due to the risk of double counting. The capability approach has the potential to extend the QALY but the operationalization of this approach – and other non-health benefits within or outside the QALY framework – requires further research.

Document type: 
Thesis
File(s): 
Senior supervisor: 
David Whitehurst
Scott Lear
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

Canadians leaving the Canadian health care system to seek bariatric surgery abroad: Examining patient experience with international bariatric tourism

Date created: 
2017-06-09
Abstract: 

Globally, bariatric surgery, commonly known as weight loss surgery, has grown in popularity among obese individuals as a means to addressing their weight-related negative health when more traditional weight loss programs, such as diet and exercise, fail to elicit long term sustained weight loss. In Canada, however, complex barriers related to social, administrative, and other structural factors restrict access to care domestically, leaving some patients turning to surgical options abroad through the practice of medical tourism. In light of this, it is important that we understand the implications the practice of ‘bariatric tourism’ may hold for Canadians. Using an interview-based approach with former Canadian bariatric tourists, this study examines the patient experience of bariatric tourism. The analyses highlight specific barriers that are motivating patients to seek care internationally and challenges experienced in care obtainment both internationally and domestically that appear to heighten the health and safety risks these patients undertake.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Jeremy Snyder
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

The aryl hydrocarbon receptor nuclear translocator (ARNT) transcriptional co-regulator complex: Effects on estrogen and hypoxia signaling

Date created: 
2016-08-11
Abstract: 

The basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH-PAS) domain family of proteins mediates cellular responses to a variety of stimuli. The bHLH-PAS proteins are heterodimeric transcription factors that are further sub-classified into sensory and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins. The ARNT protein is constitutively expressed and heterodimerizes with hypoxia-inducible factors (HIFs) to mediate oxygen-sensing mechanisms and heterodimerizes with the aryl hydrocarbon receptor (AHR) to combat environmental contaminant exposure. Firstly, a reciprocal disruption relationship exists between AHR ligands, like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and estrogen receptor (ER) ligands, like 17β-estradiol (E2). Ligand-bound ER tethers to the AHR/ARNT transcription factor complex and represses TCDD-inducible gene transcription. However, the tethering paradigm and molecular mechanisms employed by AHR and ARNT at ER-regulated genes remains to be determined. Secondly, thyroid hormone receptor/retinoblastoma-interacting protein 230 (TRIP230) interacts with ARNT and is a coactivator required for hypoxia-regulated transcription. The retinoblastoma protein (Rb) is a negative regulator of the cell cycle and also negatively regulates TRIP230 coactivator potential. Thus, Rb may influence ARNT transcription factor functions via TRIP230. Rb-loss in many solid tumours directly precedes the activation of HIF-regulated genes and correlates with increased angiogenesis and metastasis. As most solid tumours contain regions of hypoxia and only correlative data between HIF/ARNT activity and Rb-loss has been gathered, we have identified a need to rigorously examine the role of Rb-loss in concert with hypoxia in breast and prostate cancer models. In this thesis, I used siRNA technology to knockdown ARNT and AHR expression and found that TCDD-mediated disruption of ER-signalling is AHR-dependent and that ARNT is a coactivator in MCF7 cells and a corepressor in ECC1 cells. Additionally, I used siRNAs and shRNA technology in concert with microarray analysis in LNCaP prostate cancer cells and MCF7 breast cancer cells to delineate the role of the ARNT-TRIP230-Rb transcriptional complex in hypoxia-regulated transcription. I found that Rb-depletion in conjunction with hypoxia exacerbates HIF1-mediated transcription and promotes a more invasive and late stage phenotype in both breast and prostate cancer models. The molecular mechanisms and gene pathways described herein should prove useful for developing chemotherapies for late stage breast and prostate cancers.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Timothy Beischlag
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

Sexual self-efficacy among adolescent men and women living in an HIV-hyper-endemic setting of South Africa

Date created: 
2017-04-12
Abstract: 

Adolescent women in South Africa face disproportionate HIV acquisition. In this context, evidence remains mixed on whether sexual self-efficacy (SSE)- one’s perceived control in decision-making regarding safe sex, predicts consistent condom use (CCU). Using cross-sectional survey data from 830 adolescent men and women aged 14-19 living in Soweto, South Africa, this thesis conducted gender-based analyses to examine determinants of high-SSE (study-alpha=0.75) and the association between high-SSE and CCU. Results revealed women have higher SSE than men. High-SSE was associated with CCU use for men, but not women. For women, high-SSE was associated with having an adult in the home, and no history of physical violence. Moreover, lower depressive symptomology among women was more predictive of CCU than SSE, indicating that gender-targeted HIV prevention interventions must move beyond individual-level determinants of behaviour to address socio-structural and relational factors influencing syndemic HIV risk among adolescent women in South Africa.

Document type: 
Thesis
Senior supervisor: 
Dr. Robert Hogg
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

How Much Help? How Much Harm? Working class women’s experiences of prenatal care in East Vancouver

Author: 
Date created: 
2017-03-06
Abstract: 

This project sought to interrogate the institution of prenatal care in East Vancouver through the lived experiences of working class and historically marginalized women. Prenatal care in British Columbia is a complex of institutional policies and practices. This project focused on prenatal visits between pregnant women and their chosen maternity care provider. Through the stories and experiences of nine research participants, this project affords insight into how the work of prenatal care might be improved to better the experiences and health outcomes for working class and historically marginalized women and their newborns. This could include integrating more substantive ways of centering women in the institution of prenatal care and recruiting women as active participants, such as the use of group care and lay health care workers. Pregnancy is a time of great change for working class and historically marginalized women, attempts to reduce social inequity can start with the institutions that provide women care throughout pregnancy.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Nicole Berry
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

Impacts of a new Greenway on older adult mobility: A mixed-methods analysis in Vancouver, BC

Author: 
Date created: 
2017-04-19
Abstract: 

Our population is aging, and life expectancies are increasing globally. One strategy to promote healthy aging is by creating environments that support physical activity. Using a natural experiment study design, this dissertation takes a mixed-methods approach to capture the impacts of a built environment intervention aimed to increase active transportation among community-dwelling older adults. We captured location-specific travel and physical activity using accelerometers and GPS monitors one year before and after the Comox-Helmcken Greenway was developed, and measured change in weekly transportation-related activity, specific activity along the Greenway, and activity along a comparison corridor. Secondly, we interviewed a subset of these older adults to capture their perceptions of the Greenway. We found no change in weekly physical activity levels, but a decrease in the number of trips along the Greenway. Our interview data suggests this may result from confusion of messaging, the steep slope, and a lack of destinations.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Meghan Winters
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

A comparison of self-efficacy between pregnant women who use cigarettes versus electronic nicotine delivery systems: A cross-sectional study of participants in the BC Healthy Connections Project

Date created: 
2016-12-15
Abstract: 

Self-efficacy (SE) has been regarded the strongest cognitive determinant of cigarette use during pregnancy, but has yet to be assessed in pregnant women who use alternative modes of nicotine, including electronic nicotine delivery systems (ENDS). Knowing that nicotine is harmful to the fetus, more research on SE in pregnant ENDS users is warranted. Using data from the BC Healthy Connections Project, the purpose of this research was to identify differences in SE between pregnant: cigarette users; ENDS users; combination users (ENDS and cigarettes); and abstainers (no tobacco or nicotine). The relationship between SE and mode of nicotine was examined using multiple linear regression. Due to small sample sizes, ENDS and combination users were collapsed (ENDS/combination users). SE was significantly higher in ENDS/combination users compared to abstainers. No other significant group differences emerged. Results from this research can be used to tailor interventions aimed at reducing fetal exposure to nicotine.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Charlotte Waddell
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.

The Impact of HIV Non-Disclosure Case Law on the Healthcare Engagement of Women Living with HIV in Canada

Date created: 
2016-06-17
Abstract: 

Introduction: In 2012, the Supreme Court of Canada (SCC) expanded the reach of criminal liability for HIV non-disclosure in Canada when it ruled that people living with HIV (PLWH) who do not disclose their HIV status before sex that has a “realistic possibility” of HIV transmission could face criminal charges, suggesting that condom-protected vaginal sex with a low HIV viral load would incur no legal obligation to disclose. This thesis sought to identify the prevalence and correlates of facing a legal obligation to disclose, and to investigate awareness, understanding and perceived healthcare impacts of the 2012 SCC ruling among the diversity of women living with HIV (WLWH) in Canada, involving WLWH as key research partners.Methods: Quantitative data from men and women enrolled in a cohort of PLWH who use illicit drugs in Vancouver (ACCESS), and women enrolled in a community-collaborative cohort of WLWH in British Columbia, Ontario, and Quebec (CHIWOS), were used to meet the objectives of this thesis. Novel community-driven questions assessing awareness, understanding and perceived impacts of HIV non-disclosure case law were incorporated into data collection instruments of both cohorts. Results: Among ACCESS participants who use injection drugs (n=176), WLWH were more likely to face a legal obligation to disclose compared to men in the wake of the 2012 SCC ruling. Among female ACCESS (n=98) and CHIWOS (n=584) participants, awareness of the 2012 SCC ruling (44% and 74%, respectively) and understanding of the conditions under which PLWH may face a legal obligation to disclose (17% and 35%, respectively) were suboptimal. Although most participants were engaged in HIV treatment and care, discussions about HIV disclosure and the law were lacking in healthcare settings, despite participants expressing a willingness and desire to engage in discussions of this nature with providers. Most participants believed that HIV non-disclosure case law might limit the type of information WLWH would share with providers.Discussion: This thesis identified an urgent need to disseminate information about HIV non-disclosure and the law in community and healthcare settings, to ensure WLWH have fundamental information to avoid prosecution and to optimise their health and rights in the current legal climate.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Angela Kaida
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.

Women and antiretroviral therapy adherence: examining the impact of internalized stigma by gender

Author: 
Date created: 
2016-09-21
Abstract: 

Background: Antiretroviral therapy (ART) and ambitious treatment strategies such as Treatment as Prevention (TASP) and 90-90-90 have reduced HIV-related morbidity and mortality among people living with HIV (PLWH), and substantially decreased the likelihood of transmission of the virus to others. The benefits of ART are not felt equally among all PLWH, as PLWH may not be able to maintain ART adherence. This study examines gender differences in ART adherence and the sociostructural and psychosocial factors associated with such differences in British Columbia, Canada. Methods: Quantitative analyses assessed optimal ART adherence by gender, longitudinally and cross-sectionally, using bivariate, multivariate analyses, as well as structural equation modelling. All analyses used data collected from 2000 onward by the BC Centre for Excellence in HIV/AIDS from BC, Canada, with adherence measured using pharmacy refill compliance data. Findings: Gender-based disparities were evident in ART adherence in BC, with a significantly lower proportion of women attaining optimal (≥95%) adherence relative to men (57.0% versus 77.1; p<0.001) regardless of subgroup. Women also experienced far greater sociostructural and psychosocial disparity than men, however food insecurity was the only variable examined that was independently associated with suboptimal adherence among women (adjusted odds ratio [AOR]: 0.364; 95% confidence interval [CI]: 0.181 to 0.734). Psychosocial variables exhibited different effects and interactions for men and women, however, they explained only a low proportion of the variability observed in ART adherence (1.6% and 3.7%, respectively). Disclosure worries was the only psychosocial variable to affect women’s adherence (standardized regression weight [r]: -0.192; p=0.015). Personalized stigma (r: 0.299; p<0.001) and internalized stigma (r: 0.321; p<0.001), however, did have a significant explanatory affect on depression experienced by women. Discussion: Gender-based disparities must be addressed if women living with HIV are to attain optimal health and if we are to achieve the goals of 90-90-90. Addressing aspects of poverty and the greater adversity that women face in this regard would result in a more salient improvement to ART adherence than interventions addressing stigma.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Cari Miller
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) Ph.D.