Medicine & Health

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Now showing 1 - 4 of 4
  • (2022) Liao, Peiwen
    Thesis
    Background People with intellectual disability are at high risk of developing several health conditions, including epilepsy. Research on the clinical characteristics of people with intellectual disability and epilepsy is abundant. However, their health needs and health service use, which can reflect how they fare in the current health system, remain insufficiently examined. Methods The thesis comprises four studies. The first is a systematic literature review to quantify physical health conditions in people with intellectual disability and derive a detailed understanding of their health status. The remaining retrospective cohort studies were based on linked administrative datasets from health and disability services in the jurisdiction of New South Wales (NSW), Australia. Individuals aged 5-64 years with a diagnosis of epilepsy were identified from NSW hospital admission data, and diagnoses of intellectual disability were ascertained from disability and health service records. The studies examined and compared the risk of rehospitalisation and emergency department (ED) presentation after epilepsy hospitalisation and mortality in people with and without intellectual disability. Factors associated with hospital use and mortality were also investigated for those with both diagnoses. Results The systematic review added new knowledge about the risk of physical health conditions in people with intellectual disability. It identified conditions of the highest risk, including epilepsy, and conditions likely being under-detected. The linked data projects revealed that 1) intellectual disability is independently associated with a higher risk of readmission and ED presentation after epilepsy hospitalisation; 2) lower socioeconomic status and certain comorbidities are associated with an increased risk of repeat hospital use; 3) intellectual disability in people with epilepsy is associated with an increased mortality risk and a different cause of death profile. Disability and health characteristics are the main risk factors for death. Conclusions The studies generated new evidence of disparity in epilepsy-related health service use and outcomes between people with and without intellectual disability. The novel findings provide a foundation for improved clinical services provision. To better understand unmet health needs of people with intellectual disability and epilepsy, future research should investigate the use and the drivers of primary and outpatient care and antiepileptics in this population.

  • (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) Kotevski, Damian
    Thesis
    Head and neck cancer (HNC) is a complex disease with diversity in treatment modality and survival by anatomical site of origin. There is limited knowledge of the utility of oncology information systems (OIS) for the collection and reporting of HNC data during routine clinical practice to investigate prognostic factors and predict head and neck cancer-specific survival (HNCSS). Routinely collected structured data was extracted from an OIS from seven major hospitals in Australia for patients diagnosed with HNC between 2000 and 2017 and treated with definitive radiotherapy. Deaths were obtained from the National Death Index via record linkage, and HNCSS was measured from the date of diagnosis until death from HNC. Open-source machine learning and nomogram models were used to predict HNCSS and perform multivariable analysis to identify prognostic factors. Descriptive and survival analysis was used to identify inter-hospital variation in data collection, primary radiotherapy treatment, and survival. A random sample of clinical radiation oncology documents from an OIS were anonymised using a customised open-source tool (Microsoft Presidio) to evaluate the use of unstructured information for medical research. Not all user-defined fields were routinely completed and not all hospitals relied solely on the OIS, with one hospital collecting disease information in a parallel database. However, structured information collected in a standardised way with minimal missing data during routine clinical practice in an OIS can be used to predict two-year HNCSS with high performance. Evidence of inter-hospital variation in data completeness, primary radiotherapy dose, and five-year HNCSS was detected. The presence of missing data in the OIS reduced the number of predictors for prognostic analysis and prevented exploratory analysis to explain differences in survival by hospital. Lastly, the application of the anonymisation tool on unstructured clinical information sourced from an OIS demonstrated safe and secure use for some fields and a need to improve the detection and removal of person names. Data mining techniques for unstructured data or strategies to improve structured data collection should be explored to enable the development of prediction models using more complete data, patients, and variables, followed by external validation to confirm model performance.

  • (2021) Nguyen, Kim
    Thesis
    Many important processes in lymphocytes are dictated by signalling inputs received by cell surface receptors, which allow the cells to form effective responses to external stimuli. Intracellular signalling pathways also play critical roles in processes that are conceivably more cell intrinsic, such as development and differentiation. Defects in signalling pathways that disrupt any of these functions can compromise the ability to generate robust immune responses. Primary immunodeficiencies (PIDs), or inborn errors of immunity (IEI), are monogenic disorders that impair immune system development or function. To date, variants in >450 distinct genes have been identified to cause immune dysregulation (i.e. inadequate or inappropriate immune responses), manifesting clinically as infectious susceptibilities, autoimmunity, inflammation, allergic disease and malignancy. With the continual discovery of novel gene variants causing PIDs/IEI, improved cellular and molecular characterisation of these disorders is crucial to unravel mechanisms of disease pathophysiology, as well as the fundamental requirements for establishing intact innate and adaptive (humoral and cellular) immunity. In addition to yielding direct therapeutic benefits for the patients in question, such studies also have the potential to illuminate roles for the implicated proteins and pathways in the context of healthy individuals, thus facilitating broader clinical implications. This PhD project has utilised lymphocytes from patients harbouring germline pathogenic mutations in the components of two major cell signalling pathways – phosphatidylinositol 3-kinase (PI3K) and nuclear factor binding to κB sequences in activated B cells (NF-κB) – to dissect the role of these pathways in human immunobiology. Through phenotypic and functional characterisation of patient lymphocytes, we have shown that over- or under-activation of PI3K or NF-κB signalling alters multiple key aspects of lymphocyte biology in vivo and in vitro. Patient B and T cells displayed aberrant functional responses following activation through several key surface molecules. In the context of recent findings relating to these PIDs/IEI, our results provide insights into mechanisms underlying disease pathogenesis that precipitate immune disease in these patients. Comparisons made between the cellular phenotype of these PID/IEI cohorts highlight the tremendous complexity in the regulation of the PI3K and NF-κB pathways. Altogether, this work underscores the importance of balanced intracellular signalling in maintaining immune homeostasis and sustained protection against infectious threats.