Narsis Daftarian
Doctor of Philosophy in Experimental Medicine (PhD)
Research Topic
Retinal toxicity and hydroxychloroquine therapy (INTACT): A prospective population-based cohort study
Antonio Avina
Associate Professor
Relevant Thesis-Based Degree Programs
Graduate Student Supervision
Doctoral Student Supervision
Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
Evaluating the association between anti-TNFalpha treatment and multiple sclerosis risk in autoimmune conditions: insights from health administrative data and methodological challenges (2024)
Objectives: This dissertation aims to compare the risk of multiple sclerosis (MS) in anti-tumor necrosis factor alpha (TNFα) users with nonusers among patients with rheumatic disease (RD) or inflammatory bowel disease (IBD). It also aims to uncover methodological biases in existing research and explore statistical strategies to address these biases, with a particular focus on the issue of sparse data bias.Methods: Utilizing population-based health administrative data from four Canadian provinces, a nested case-control study was conducted among patients with RD and IBD (2000 to 2018). Any anti-TNFα dispensations in the two years prior to the index date (MS onset) were identified. Causal directed acyclic graphs (cDAGs) were utilized to illustrate biases like confounders, mediators, and collider-stratification bias, which may influence the relationship between anti-TNFα therapy and MS risk. Advanced statistical techniques were applied to mitigate sparse data biases. These techniques included Firth bias adjustment, data augmentation, Markov Chain Monte Carlo (MCMC), Least Absolute Shrinkage and Selection Operator (LASSO), and Ridge regression, and their results and performance were compared against traditional models via simulation studies.Results: 1) The study found that anti-TNFα therapy was associated with an increased risk of MS in RD patients (pooled incidence rate ratio [IRR]=2.05 [95% confidence interval {CI}, 1.13-3.72]) after adjusting for potential confounders. The number needed to harm was calculated at 2,268 for RD patients. While an increased risk was also observed in IBD patients, the CI was wider (pooled IRR=1.35 [95% CI, 0.70-2.59]). Sensitivity analyses and the computation of E-values were conducted to strengthen the findings. 2) When applying various statistical methods to address sparse data issues, data augmentation and MCMC approaches demonstrated superior performance in bias and mean squared error reduction in simulation studies.Conclusions: The use of anti-TNFα was associated with an increased risk of MS compared with nonusers, especially among patients with RD. The innovative use of cDAGs offers a new perspective on assessing causal relationships and addressing methodological challenges in pharmacoepidemiology. Data augmentation and MCMC approaches should be considered in pharmacoepidemiologic studies with sparse data to avoid drug effect overestimation, which can influence clinical decision-making and public health policies.
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Exploring health care encounters and treatments for mental disorders in individuals with inflammatory arthritis: epidemiologic and health services research studies (2024)
The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
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Population-level studies of the incremental economic burden of systemic autoimmune rheumatic diseases (2018)
In systemic autoimmune rheumatic diseases (SARDs), immune dysregulation leads to systemic inflammation, organ damage, complications, and disability. I examined the longitudinal, incremental direct medical costs of newly-diagnosed SARDs, incremental productivity costs, and impact of socioeconomic status (SES) on costs, at the general population level.Methods: Nine population-based cohorts, one for each SARD, were identified from the administrative health databases of the province of British Columbia (BC), Canada. Nine non-SARD comparison cohorts were selected from the general population of BC, and matched to each SARD cohort on age, sex, and index-year. Direct Medical Costs: Administrative data captured provincially-funded outpatient encounters and hospitalisations, and all dispensed medications. From these data, I estimated direct medical costs of each SARD and non-SARD cohort for up to five years after diagnosis/index date. I used generalised linear models to determine incremental costs of each SARD overall, and by SES group, controlling for covariates, and incremental costs of systemic lupus erythematosus (SLE, the most common SARD) before diagnosis.Productivity Costs: Random sample of the population-based cohorts completed a survey on absenteeism and presenteeism (working at reduced levels/efficiency) from paid and unpaid work. Survey data were used to determine adjusted, incremental lost productivity costs of three SARDs: SLE, systemic sclerosis (SSc), and Sjogren’s (SjS).Results:Direct Medical Costs: I identified 8,858 incident adult SARD cases for the years 1996-2010 (79.8% female) and 32,727 non-SARDs (79.0% female). Adjusted mean per-person-year incremental costs (over-and-above non-SARDs’) ranged from $7,851 to $54,061 2013 CDN, mainly from hospitalisations. For nearly every SARD, incremental costs of the low-SES exceeded the high-SES, by ~$2,000-$3,000 per-person-year. In each of the five pre-index years, adjusted costs for SLE were significantly greater than non-SLE; male sex and low SES were associated with greater costs among SLE. Productivity Costs: 671 surveys were completed: SLE=167, SSc=42, SjS=90, and non-SARDs=375. Adjusted incremental productivity costs averaged $4,494, $3,582, and $4,357 annually for SLE, SSc, and SjS, respectively. Major contributors were unemployment, presenteeism from paid work, and impairments with unpaid work. Conclusion: These novel findings should inform health resource allocation, and ongoing research to improve outcomes and reduce costs in these chronic diseases.
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Master's Student Supervision
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
All-cause and cause-specific mortality risks in granulomatosis with polyangiitis (2017)
BackgroundGranulomatosis with polyangiitis (GPA) is a form of ANCA-associated vasculitis (AAV), a heterogenous group of small vessel vasculitides associated with anti-neutrophil cytoplasmic antibodies (ANCA). There is still significant disease mortality despite advances in treatment of GPA. Furthermore, longitudinal data on secular trends in GPA mortality are scarce and most are from selected populations. We aim to determine all-cause and cause-specific mortality risks in GPA patients compared to the general population, as well as to estimate the difference in mortality risks in GPA patients between 1997-2004 and 2005-2012. MethodsChapter 2 was a systematic review and meta-analysis of observational studies in GPA. An extensive literature search was performed on the EMbase and Medline databases. Data was extracted for a pooled meta-analysis of standardized mortality ratios (SMR). Heterogeneity between studies was assessed using I2. Chapter 3 was a matched cohort population-based study using an administrative health database, comparing incident GPA cases and non-GPA individuals randomly selected from the general population. Primary outcome was death during the follow up period, 1997-2012. Cohorts were subdivided to early cohort (1997-2004) and late cohort (2005-2012). Hazard ratios (HR) were estimated using Cox proportional hazard regression models. ResultsFrom the meta-analysis, we found a 2.7-fold increased risk of death in AAV patients when compared to the general population. Subgroup analyses showed that mortality risks were higher in older cohorts with a trend towards improvement over time (i.e., midpoint of enrolment periods 1980-1993 and 1994-1999, vs. 2000-2005). From the matched cohort study, 370 GPA patients and 3,700 non-GPA individuals were included, with 68 and 310 observed deaths, respectively. Overall, the age, sex and entry time-adjusted all-cause mortality HR in the GPA cohort was 3.12 (95%CI 2.35-4.14). There was excess mortality from CVD causes, but not cancer, in the GPA cohort. All-cause mortality significantly improved between the early and late GPA cohorts (HR 5.61 vs. 2.33, respectively; p = 0.017).ConclusionThere was a 3-fold increase in all-cause mortality risks in GPA patients, with excess mortality from CVD causes. There was a significant improvement in all-cause mortality risks over time but remained elevated compared to the general population.
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Trends of venous thromboembolism risk before and after diagnosis of gout : a population-based study (2017)
Background: Previous studies have shown that gout is an independent risk factor for cardiovascular diseases. Venous thromboembolism (VTE, including deep venous thrombosis [DVT] and pulmonary embolism [PE]) represents the third most common form of cardiovascular disease among the general population. However, data on the risk of VTE in gout patients are scarce. Objectives: 1) To estimate the overall risk of VTE, DVT, and PE before and after gout diagnosis in an incident cohort of individuals with gout; 2) To access the temporal trend of VTE, DVT, and PE before and after gout diagnosis compared with the general population.Methods: I conducted a 1:1 matched cohort study using a province-wide population-based administrative health database from British Columbia, Canada. I calculated incidence rate ratios and multivariable adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of VTE, DVT, and PE before and after gout diagnosis. Results: Among 124,306 individuals with newly diagnosed gout (65% male, mean age 60 years), VTE developed in 1,594 patients, DVT in 989 patients, and PE in 813 patients. Incidence rates were 2.44, 1.51, and 1.24 per 1,000 person-years, respectively. The corresponding incidence rates among non-gout individuals were 1.37, 0.83, and 0.75 per 1,000 person-years, respectively. The final aHRs (95% CI) for VTE, DVT, and PE were 1.34 (1.23-1.46), 1.38 (1.24-1.54), and 1.27 (1.13-1.42), respectively. For the entire pre-gout period, compared to general population, the final aHRs (95% CI) were 1.56 (1.41-1.71), 1.55 (1.38-1.75) and 1.53 (1.34-1.76) for VTE, DVT and PE, respectively. During the 3rd, 2nd, and 1st years preceding the gout diagnosis, the final aHRs for VTE were 1.51, 1.61, and 1.74, respectively. During the 1st, 2nd, 3rd, 4th, and 5th years after the gout diagnosis, the final aHRs were 1.46, 1.44, 1.37, 1.36, and 1.32. Similar trends were also seen for DVT and PE. Conclusion: Increased risks of VTE, DVT, and PE were found both before and after gout diagnosis. The risk increased gradually before gout diagnosis, peaking in the year prior to gout diagnosis, and then progressively declined following the diagnosis. Gout associated inflammation may contribute to VTE risk.
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Population-Based Epidemiologic Studies of Gout in British Columbia, Canada (2016)
Introduction: This thesis contains original analyses aimed at better understanding the burden of gout, an excruciatingly painful form of inflammatory arthritis, in the Canadian context. While gout is increasingly recognized as the most common form of inflammatory arthritis worldwide (e.g., reported prevalence of 3.9% and 2.5% in the United States and United Kingdom, respectively), no Canadian trend data are available. Objectives: 1) To evaluate the contemporary prevalence and incidence of gout over the past decade, as well as gout treatment patterns and comorbidity burden. 2) To evaluate the burden of hospitalized gout and corresponding inpatient costs as compared to rheumatoid arthritis (RA), another inflammatory joint disease known to incur substantial resource use. Methods: To address both objectives, I used PopulationData BC, a large administrative database spanning the province of British Columbia (BC). For Objective 1, I used physician and hospital visits to identify gout cases and estimate the annual trends in prevalence and incidence among the general population. I additionally used data from PharmaNet, BC’s prescription drug database, to examine gout treatment patterns (i.e., urate-lowering therapy, colchicine, glucocorticoids, and non-steroidal anti-inflammatory drugs) over the same time period. For Objective 2, I used hospital diagnoses and procedure codes to assess annual trends in hospitalizations and joint surgeries as well as inpatient costs for both gout and RA. Results: 1) Both the prevalence and incidence of gout have increased over the past decade (i.e., a 59% and 48% increase, respectively), while the prescription of gout treatment remains low. 2) The hospitalization rates for gout have doubled over the past decade, while those for RA have declined by 49%. The inpatient costs also reflected the hospitalization trends, with a 40% decrease in RA hospital costs, while gout costs more than doubled over the study period. Conclusion: Altogether, this thesis provides evidence that the burden of gout in Canada is substantial and increasing. These findings are further contrasted against the hospitalization burden of RA, which has decreased considerably over the same period. This thesis highlights the critical need to improve gout prevention and care to mitigate its rising disease burden in Canada and beyond.
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