Medicine & Health

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  • (2023) Odutola, Michael
    Thesis
    Follicular lymphoma (FL) accounts for one-third of incident non-Hodgkin lymphomas in Western countries, but its etiology is largely unexplained. I performed systematic reviews and meta-analyses, and used a population-based family case-control study to investigate the relationship between lifestyle, environmental and occupational risk factors of FL. Meta-estimates from my random-effect models showed a non-significant association with smoking, heterogeneous results for alcohol, modest increased risk with obesity, and positive associations with exposure to polychlorinated biphenyls (PCBs), chlorinated solvents and dichlorodiphenyldichloroethylene (DDT, a pesticide). The population-based case-control study included 770 FL cases and 490 family controls (siblings, partners). Participants completed a lifetime residential and work calendar and health, lifestyle, and diet questionnaires. I used unconditional logistic regression to examine associations with FL risk, including group-based trajectory modeling to examine associations with body shape and outdoor hours over the life course. I identified deaths using record linkage and applied Cox proportional regression to estimate hazard ratios for all-cause and FL-specific mortality. I observed a positive association between smoking and FL risk and mortality. Associations with recent alcohol intake and FL were null. Being obese 5 years prior to enrolment and higher body mass index 5 years prior to enrolment was associated with a modest increased FL risk, but there was no association with body shape trajectory. Body size was not associated with mortality. I observed an elevated FL risk with consumption of oily fish, but no association with mortality. I found no significant association between occupational exposure to pesticides, or extremely-low frequency magnetic fields, and FL risk. For sun exposure, I observed an inverse association with high cumulative outdoor hours and high outdoor hour maintainers over the life course, and FL risk. Policies on tobacco control, maintaining body weight within normal range, and safe use of solvents and pesticides are crucial in reducing the burden from FL. Sun exposure is not recommended as a cancer control policy, but the association may inform research on targeted therapies for this malignancy. My key findings have advanced our understanding of FL etiology and help guide risk reduction strategies and future research.

  • (2023) Carson, Joanne
    Thesis
    Background: Direct-acting antiviral (DAA) treatment is being scaled up to eliminate hepatitis C virus (HCV) as a major public health threat. Aims: The aim of this research was to assess potential barriers to HCV elimination in Australia, including DAA discontinuation, treatment failure, and HCV reinfection. Specific aims included assessing (1) reinfection incidence in prison; (2) real-world effectiveness of retreatment for reinfection and (3) treatment failure; (4) national trends in retreatment for reinfection and treatment failure; and (5) national trends in treatment discontinuation. Methods: In Chapter 2, HCV reinfection incidence was assessed in a prospective cohort of people treated for HCV in four prisons. In Chapters 3 and 4, the effectiveness of retreatment for reinfection and treatment failure were assessed using standard of care data from a national observational cohort that included a broad range of treatment settings. In Chapter 5, a machine learning model was developed and applied to national pharmaceutical administrative data to assess trends in retreatment for reinfection and treatment failure. In Chapter 6, treatment discontinuation trends were assessed in national pharmaceutical administrative data. Key Findings: High HCV reinfection (13/100 person-years) was observed in prisons. Retreatment for reinfection was highly effective (95%), but high losses to follow-up during treatment (25%) were observed. The effectiveness of retreatment for treatment failure (81%) was not impacted by treatment setting, supporting decentralisation of HCV care. A machine learning model with high predictive accuracy (96%) to classify retreatment reason was developed. When applied, an increasing national trend of retreatment for reinfection was observed. Half of retreatment for treatment failure was among individuals discontinuing treatment. National treatment discontinuation rates doubled between 2016-2021, rising to 15%, despite increasing use of simplified shorter duration DAA regimens. Conclusions: Retreatment of reinfection and treatment failure will be crucial to reduce HCV transmission and HCV-related morbidity and mortality. Retreatment can be effectively delivered through decentralised models of HCV care. Increasing trends of retreatment for reinfection and treatment discontinuation correspond with increasing treatment uptake among people who inject drugs. Additional strategies are needed to ensure vulnerable populations achieve and maintain HCV cure.