Doctor of Philosophy in Pharmaceutical Sciences (PhD)
Addressing equity considerations in research and care of patients with inflammatory arthritis
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Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
Objective:The overall aim of this dissertation was to provide a better understanding of adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF). Methods:Meta-analysis was used to summarize the current evidence on patients’ adherence. Population-based administrative data of British Columbia (BC) was used to develop a cohort of adults with AF. Random-effects multivariable regression modeling was used to develop and validate a method, called REWarDS, to estimate patient’s individualized daily dose of warfarin and facilitate measurement of adherence to this medication. OAC adherence was measured over follow-up by creating time windows. Group-based trajectory modeling was used to characterize adherence trajectories. Regression analyses were used to identify the factors associated with adherence, and adherence trajectories. Results:Systematic review and meta-analysis found that one year after therapy initiation patients, on average, miss 27% of their doses. REWarDS was found to be accurate with superior performance over current methods for estimating exposure to warfarin. 54% of the patients in the cohort were found to be nonadherent to their OAC, missing, on average, 32% of their doses. The greatest decline in adherence was observed in the first year of therapy. Patients were found to exhibit four distinct long-term adherence trajectories. Being on Vitamin K Antagonist (VKA) was associated with statistically significantly 13% higher adherence compared to being on Direct Oral Anticoagulants (DOAC). Over time, however, adherence increased for DOAC but decreased for VKA. Clinical and demographic factors, while readily available in administrative databases, do not have adequate discriminatory power to predict patients’ adherence trajectories. Conclusion:Adherence in patients with AF was found to be worse than previously understood. Identification of distinct long-term adherence trajectories revealed heterogeneity among nonadherent patients and compels tailoring interventions for different kinds of nonadherence patterns. Findings on the impact of drug class on adherence suggest that prescribers should not assume better adherence for DOACs based on their convenience. Overall, very few variables were identified to be independently associated with any specific adherence trajectory. Altogether, findings call for urgent interventions to improve adherence in patients with AF on both VKA and DOAC, particularly early after therapy initiation.
Objectives: To examine biologic use before or during pregnancy among women with autoimmune inflammatory disease by: 1) Describing the patterns of use, discontinuation, and 10-year secular trends; 2) Evaluating the association between biologic exposure before or during pregnancy and adverse maternal and infant outcomes including: preterm deliveries, small-for-gestational-age (SGA) births, congenital anomalies, and serious infections; and 3) Reviewing existing literature and meta-analyzing my findings with published results. Methods: Using provincial population-based administrative health data linked with the perinatal registry and prescription dispensations database, a cohort of women with autoimmune inflammatory disease who had at least one pregnancy during 2002-2012 was identified. Descriptive statistics, multivariable modeling, and high-dimensional propensity score (HDPS) methods were used to describe the patterns of perinatal biologic prescriptions and assess associations with outcomes of interest. Results were meta-analyzed with findings from existing literature.Findings: 1) Perinatal biologic use has increased significantly over 10 years, comprising 5.7% of all pregnancies in this population by 2012. Most often women discontinued their biologic in the first (31%), or second (38%) trimesters, while 98% of those on treatment during the second trimester continued through to delivery. Only disease type was associated with discontinuation. 2) After applying HDPS matching, there were no associations observed between biologic use before or during pregnancy and risk of preterm deliveries (OR 1.13, 95% CI 0.67 to 1.90); SGA (OR 0.91, 95% CI 0.46 to 1.78); or congenital anomalies (OR 1.06, 95% CI 0.46 to 2.47). The theoretical concern of serious infections due to immunomodulatory effects of biologics was not observed. 3) Meta-analysis of unadjusted risk estimates showed significantly increased risks of congenital anomalies, preterm deliveries, and low birth weight babies associated with biologic exposure. However, pooled adjusted risk estimates showed no significant associations. Conclusions: Using novel methods to address potential confounding and pooling existing evidence, the findings from this thesis demonstrated that treatment with biologics before or during pregnancy are not associated with a number of important perinatal outcomes. These findings help patients and clinicians weigh risks and benefits of treatment options in pregnancy, and support difficult decision making around using biologics in a vulnerable population.
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
INTRODUCTION: Despite recent guidelines for managing rheumatoid arthritis (RA) in pregnancy, high rates of discontinuing medications compatible with pregnancy during the first trimester among patients may suggest a translation gap of emerging clinical knowledge. This thesis aims to provide an understanding of how female patients with RA engage in making medication and reproductive decisions.OBJECTIVES: To understand the perspectives and experiences related to pregnancy and early parenting among female patients with RA and healthcare providers involved in their care (Part 1); and to understand how female patients with RA form decisions related to having children, pregnancy, and medication use (Part 2).METHODS: Part 1: I conducted a systematic review and thematic synthesis of literature about pregnancy and early parenting amongst female patients with inflammatory arthritis, including RA, and their healthcare providers. Part 2: I employed a constructivist grounded theory design and used semi-structured interviews to explore medication and reproductive decision-making in the context of living with RA among a purposive sample of participants. Data collection and analysis were iterative, employed theoretical sampling, and peer debriefing, and culminated in a theoretical model.RESULTS: Part 1: I identified 5 analytical themes among patients – making reproductive and family building decisions; experiencing pregnancy and parenting; navigating caregiving with chronic disease; seeking information and resources for pregnancy planning; and interacting with healthcare providers – and 3 additional analytical themes among providers – providing reproductive health care; interacting with patients; and coordinating patient care with other providers. Part 2: Participants dynamically engaged in four decision-making processes: using medications, having children, planning pregnancy, and parenting. These processes were complexly influenced by their intersecting identities and contextual factors within their decision-making environment, particularly attitudes towards health and medications, disease onset and severity, familial support system, and healthcare provider relationship.CONCLUSION: This thesis provides insight into how patients make reproductive decisions in the context of managing RA with particular emphasis on the patient identity and care experiences. A patient-centred care approach is suggested to support female patients with RA in making better reproductive and medication choices aligning with their individual desires, needs, and values.
Introduction: Recent evidence suggests that the risk of young-onset colorectal cancer (yCRC) is significantly increasing. Furthermore, the information needs of this population are not well understood. Unmet information needs are associated with ineffective disease self-management and negative health outcomes. Therefore, it is pertinent to understand the changing epidemiology of yCRC and the information needs of this population.Objectives: This thesis aims 1) to systematically review the literature on the incidence and prevalence trends of yCRC; 2) to determine the information-seeking behaviours of individuals with yCRC; and 3) to determine the information needs of individuals with yCRC. Methods: To address Objective 1, a systematic review was conducted. Databases were searched for studies that: used an epidemiologic design, assessed trends in yCRC incidence or prevalence, and published in English. To address Objective 2, descriptive statistics and proportions of information-seeking behaviours were reported. Lastly, Objective 3 was addressed by reporting proportions of information items unmet. Predictors of corresponding unmet information needs were assessed using multivariable logistic regression models. Results: 1) The search returned 8,695 articles with 40 studies from 12 countries across five continents. Thirty-nine studies assessed trends in yCRC incidence and only one study prevalence trends. Noteworthy, 17 studies from North America and Oceania consistently reported increasing incidence trends in yCRC. Among studies assessing cancer site, nine (of 14) showed an increased risk of rectal cancer in adults less than 50 years. 2) A sample of 366 yCRC respondents, predominantly consisting of highly-educated white women, was analyzed. At respondents’ most recent search of yCRC information (N= 323), 143 respondents relied on the Internet. 3) Among 39 information need items, 26 unmet information needs were found. Conclusion: This thesis provided evidence that risk of yCRC is increasing predominantly in North America and Oceania, driven by rising rectal cancers in younger adults over the past two decades. In addition, this thesis reports that the information needs of the recruited sample were substantially unmet.
Introduction: Suboptimal medication adherence and poor health outcomes in patients with gout, the most common inflammatory arthritis, has prompted efforts to optimize care delivery. The Virtual Gout Clinic, an electronic health technology supported collaborative care model for gout involving rheumatology, pharmacy, and dietetics, offers a promising solution. The purpose of this thesis is to gain an in-depth understanding of how individuals engage in managing their gout and also explore the complexity of the Virtual Gout Clinic using mixed methods to optimize the context and delivery of this care model.Objectives: 1) To explore individual experiences with gout in a Canadian population and to understand the phenomenon of becoming actively engaged in the management of gout with an emphasis on factors which facilitate management; and 2) to explore how participants with gout experience the Virtual Gout Clinic and to understand and explain quantitative outcomes from the evaluation of this care model.Methods: For the first objective, I used a constructivist grounded theory design and conducted semi-structured telephone interviews with participants diagnosed with gout completing the Virtual Gout Clinic. I applied an explanatory sequential mixed methods design for objective 2, as this design enables interview questions used in the qualitative component to be informed by quantitative outcomes of the Virtual Gout Clinic (adherence, serum uric acid) for a comprehensive final interpretation. Results: 1) Analysis of 12 interviews constructed four themes: describing the severity of gout; processing the diagnosis and management of gout; interfering with management of gout; and facilitating management of gout. 2) The experience of the Virtual Gout Clinic was described by three conceptual categories: learning through the Virtual Gout Clinic; receiving personalized support; and knowing someone cares. Suboptimal health outcomes were explained by practical and perceptual barriers to gout management, such as lacking knowledge and fearing side-effects of medications. Conclusion: This thesis provided novel insight into the process of patients becoming actively engaged in the management of gout with an emphasis on facilitating factors. An interdisciplinary model of care is a promising approach to optimize care delivery by providing both emotional and practical support as well as ongoing individualized education.
Introduction: This thesis comprises a systematic review and a pharmacoepidemiological study aimed at improving the understanding about medication non-adherence to antimalarials (AM) in Systematic Lupus Erythematosus (SLE). AM is the conventional and effective long-term treatment option that has resulted in substantial decreases in deaths associated with SLE disease activity. However, there seems to be no such decline in the deaths associated with the sequelae of SLE (such as circulatory disease). Since deriving therapeutic effects from AM depends not only on physicians prescribing the appropriate treatment, but also on patients’ adherence with selected treatment, there is the need for a better understanding of medication non-adherence to AM in SLE.Objective: 1) To systematically review and synthesize the literature on medication adherence in SLE to identify key gaps in the literature; and 2) to evaluate the burden and determinants of medication non-adherence to AM in SLE.Methods: To address Objective 1, I have conducted a systematic review. I conducted a mapped search of Medline, Embase, and Web of Science to identify original, observational studies that indicated the data source and measurement tool to assess medication adherence in a SLE patient sample. To address Objective 2, I have conducted a longitudinal pharmacoepidemiological study of a population-based SLE cohort. I used a Cox’s proportional hazard ratio model to examine factors that were significantly associated with discontinuation of AM. Results: 1) 11 studies were included in the systematic review, and the majority of these studies reported that less than 50% of SLE patients are sufficiently adherent to their medications; 2) After five years, only 33% of patients remained on AM therapy; and 3) Higher SES and the following time-varying covariates updated monthly: glucocorticoids use, traditional NSAIDs use, rate of rheumatologist visits, and rate of dermatologists were statistically significantly protective against discontinuation of AM therapy. Conclusion: Altogether as a collective work, this thesis provides evidence that demonstrates medication non-adherence is a substantial problem in SLE. In addition, it highlights the importance of developing adherence interventions to help support patients taking their medications as prescribed.