Medicine & Health

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Now showing 1 - 10 of 87
  • (2022) Ho, Jacqueline
    Thesis
    Eosinophilic chronic rhinosinusitis (eCRS) or type 2 dominant chronic rhinosinusitis (CRS) is a complex inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Management of this condition is often difficult, requiring multimodal approaches with local and systemic medications as well as surgical therapy. Biologic therapies, including mepolizumab (a monoclonal antibody targeting IL-5), have been successfully used in eosinophilic asthma and are emerging as a new treatment in CRS and eCRS, however there is limited data in this field. This thesis focuses on biomarkers and biologics in CRS. Firstly, identifying and assessing clinical biomarkers that are available to the guide management in patients with CRS and eCRS. Secondly, a prospective open-label single-arm single-centre study of the effectiveness of mepolizumab in patients with eCRS was performed. In this study, biomarkers as well as clinical, functional, and patient reported outcomes are assessed to determine the utility of mepolizumab as biologic treatment for eCRS.

  • (2021) Tran, Huy
    Thesis
    Aim: To determine the role of topical Caffeine, a Xanthine derivative in slowing myopia either as a single-drug or in combination with Atropine. Methods: A systematic review and meta-analysis for Atropine in myopia control was followed by a short-term dispensing trial to select a single Atropine concentration to use in combination with Caffeine. In a prospective, randomized, dispensing trial, children with myopia were assigned to daily use of either Caffeine-2%, Atropine-0.02% with Caffeine-2% or Atropine-0.02%. A parallel non-randomised group of spectacle lens wearers were controls. The six-month change in spherical equivalent, axial length, pupillary diameter, and accommodative amplitude were compared between groups. Finally, a validation trial monitored pupillary and accommodative amplitude changes over 24 hours with various concentrations of Atropine and Caffeine, either single or combined. Comparison between groups were performed using repeated measures Analysis of Variance with significance set at 5%. Post-hoc multiple comparisons conducted using Bonferroni correction. Results: Meta-analysis confirmed dose-dependent efficacy and side effects for all concentrations of Atropine excepting 0.01%. Similarly, short-term trial demonstrated no pupillary diameter/accommodative change with Atropine-0.01% in approximately 30% of eyes. Atropine-0.02% was selected to be used in combination with Caffeine and at six months, change in spherical equivalent/axial length was -0.20±0.34D/0.08±0.11mm, -0.20±0.30D/0.11±0.11mm, -0.39±0.38D/0.19±0.15mm and -0.33±0.29D/0.18±0.11mm with Atropine-0.02%, Atropine-0.02% with Caffeine-2%, Caffeine-2%, and single vision spectacles respectively. The pupillary diameter increase/reduction in accommodative amplitude was 1.20±0.85mm/-3.14±4.08D, 0.76±0.58mm/-2.84±4.35D, -0.07±0.47mm/-0.78±3.43D and -0.10±0.32mm/-0.22±3.81D respectively. Temporal observations of pupil diameter indicated, a) no significant variation with Caffeine, b) Post instillation to 60 minutes – Caffeine-2% combined with 0.05% and 0.1%-Atropine resulted in significantly fewer eyes reaching higher pupillary diameter compared to monotherapy with 0.05% and 0.1%-Atropine. There were no significant changes for accommodative amplitude. Conclusion: Caffeine-2% did not slow myopia when used either individually or in combination with Atropine. However, Caffeine in combination with Atropine significantly minimised the increase in pupillary diameter that occurs with use of Atropine.

  • (2022) Badge, Helen
    Thesis
    Primary total hip arthroplasty (THA) & total knee arthroplasty (TKA) are common, cost-effective surgeries that reduce the pain and disability caused by osteoarthritis. THA/TKA are associated with a small risk of complications, such as venous thromboembolism (VTE) and surgical site infection (SSI), resulting in poorer outcomes. VTE & SSI prophylaxis clinical practice guidelines exist, but it is unclear whether service providers comply, or whether this affects outcomes. Methods A prospective multi-centre cohort study was undertaken in consenting adults with OA having primary TKA/THA at one of 19 high-volume Australian public/private hospitals. Data were collected before and for one-year post-surgery. Compliance was calculated with the National Health & Medical Research Council (NHMRC) & Australian Orthopaedic Association (AOA) VTE clinical guidelines & Therapeutic Guidelines (TG) Antibiotic. Logistic and linear regression were undertaken to explore associations between clinical guideline non-compliance and complications and patient-reported outcomes (Oxford Hip/Knee Scores [OH/KS], EQ-5D), and cephalosporin prophylaxis and SSI. Results Data were analysed for 1875 participants. Clinical guideline non-compliance rates averaged 87% for TG Antibiotic, 65% for NHMRC VTE clinical guideline & 20.1% for AOA VTE clinical guideline. NHMRC VTE clinical guideline noncompliance was associated with an increased VTE risk (adjusted odds ratio [AOR]=2.83, 95%CI=1.59-5.28, p< 0.001) and with lower (worse) 1-year EQ-5D Index scores (β=-0.03, SE=0.008,p=0.002) & an inconsequential reduction in OH/KS (β=-0.76,SE=0.30,p=0.01). AOA VTE clinical guideline non-compliance reduced the risk of symptomatic 90-day VTE (AOR=0.1, 95%CI=0.0-0.4,p=0.01). TG Antibiotic noncompliance was associated with higher SSI risk (AOR=1.98, 95%CI=1.17-3.62,p=0.02) but not with PROMs. Reduced SSI risk was associated with cephalosporin dose (any SSI; AOR=0.68, 95%CI=0.47–0.99, p=0.05) and commencing antibiotics before skin incision (0-60 mins: any SSI, AOR=0.56,95%CI=0.36–0.89,p=0.01; DSSI, AOR=0.56,95%CI=0.36–0.89,p=0.01; ≥60 minutes: AOR=0.35, 95%CI=0.17-0.70,p=0.004; DSSI, AOR=0.35,95%CI=0.17-0.70,p=0.004). Changing dose (AOR=1.76, 95%CI=1.22–2.57,p=0.02) & receiving preoperative non-cephalosporin (AOR=1.35, 95%CI=1.01–1.81,p=0.04) increased SSI risk. Antibiotic prophylaxis duration was not associated with SSI. Summary Non-compliance with NHMRC VTE clinical guidelines & TG Antibiotic increased the risk of VTE & SSI. The contrary NHMRC & AOA VTE clinical guideline findings may be explained by AOA recommending aspirin. Increased compliance with high-quality VTE & antibiotic clinical guidelines may improve THA/TKA outcomes.

  • (2022) Mostyn, Benjamin
    Thesis
    The adoption of the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances 1988 (“the 1988 Convention”) has been widely viewed as the final step in establishing global drug prohibition. This thesis provides an examination of Australia’s decision to support and sign the Convention which has not been analysied before. It also provides a detailed history of the development of the Convention as Australia was a key participant in UN drug meetings at the time. This thesis is based on the first research to access archival files, primarily from Foreign Affairs but also from the AFP and Department of Health. Nearly 180 folders, totalling approximately 35,000 pages, were copied from the Australian archives. These files provide detailed reports of almost all meetings and drafts that progressed the 1988 Convention. Interviews with key participants were also conducted. It provides an interdisciplinary legal history of Australia’s involvement in the 1988 Convention using the lens of the international relations theory of neorealism and the political theory of historical institutionalism. Through process tracing, it uses the theories to examine whether neorealist geopolitical forces and institutional forces caused Australia to support and sign the Convention. The analysis finds that geopolitical considerations trumped early concerns that a third convention was not necessary. The analysis also demonstrates that institutional forces within the UN benefitted financially from drug prohibition and played an unusually strong role in encouraging the development of the 1988 Convention. It also finds that institutional forces within the Australian government, such as the AFP and Foreign Affairs, supported the new Convention to increase their own jurisdiction and powers. Lastly, it looks at whether alternative policies such as regulation or decriminalization were considered by key policymakers. It finds that key individuals did support decriminalization but were overpowered by institutional and geopolitical forces. The significance of the dissertation includes: large amounts of new data to explain the development of the 1988 Convention; it increases knowledge around the institutional forces of criminalization and global criminalization; it significantly increases our knowledge of the role of the United Nations in waging the War on Drugs; and it increases knowledge around how mid-level nations interact with global institutions.

  • (2022) McEniery, Julie
    Thesis
    Background: Queensland’s infant mortality rate (IMR) is higher than other Australian jurisdictions and the disparity is under-researched, particularly for Sudden Unexpected Deaths in Infancy (SUDI). Informed by Triple Risk and Adverse Childhood Events (ACEs) constructs, and with a focus on shared infant sleep, this thesis analyses risk factors to identify opportunities for prevention. Methods: Three analytical chapters include: extraction and reconfiguration of reported demographic data to compare international and Australian jurisdictions; multivariate analysis of linked administrative data (a six-year Queensland births cohort) to analyse pre-natal risk factors for infant death; and analysis of findings from a series of SUDI and post-neonatal deaths, incorporating reviews by the Queensland Paediatric Quality Council expert panel. Results: I confirmed that Queensland’s IMR was significantly higher than the rest of Australia for neonatal, post-neonatal, ill-defined, and non-Indigenous deaths, but not Indigenous deaths. Perinatal factors significantly associated with acquired cause of death after multivariate analysis (young motherhood, higher birth order, smoking in pregnancy, late antenatal care, preterm gestation, maternal obesity, Male infant), were identifiable but not modifiable by mid-pregnancy. Indigeneity and residence in low socio-economic areas were not associated with acquired cause of death after adjustment for other factors. Correcting for post-conceptional age at SUDI shifts the peak incidence to age less than 44-weeks post-conception. Death scene description, post-mortem investigation, and clinico-pathological correlation were inadequate in more than 30 percent of SUDI cases. After panel review, deaths attributed to suffocation and undetermined causes increased, acknowledging the contributory role of unsafe sleep in almost all SUDI, and the rarity of other sufficient causes. SUDI occurred in the setting of high levels of multigenerational social adversity. Conclusion: SUDI is an important contributor to Queensland’s excess infant mortality. The vulnerability to SUDI of infants born before 40-weeks gestation provides a new focus for prevention. The association of maternal pre-natal risk factors with maternal ACEs is consistent with the multifactorial genesis of SUDI and warrants further research. Opportunities for prevention are hampered by inadequate death investigation. SUDI occur in families experiencing multigenerational adversity, for whom engagement and support may help to mitigate highly prevalent risk factors including unsafe sleep.

  • (2022) Cao, Jun
    Thesis
    This thesis focuses on the development and applications of magnetic resonance electrical properties tomography (MREPT), which is an emerging imaging modality to noninvasively obtain the electrical properties of tissues, such as conductivity and permittivity. Chapter 2 describes the general information about human research ethics, MRI scanner, MR sequence and the method of phase-based MREPT implemented in this thesis. Chapter 3 examines the repeatability of phase-based MREPT in the brain conductivity measurement using balanced fast field echo (bFFE) and turbo spin echo (TSE) sequences, and investigate the effects of compressed SENSE, whole-head B_1 shimming and video watching during scan on the measurement precision. Chapter 4 investigates the conductivity signal in response to short-duration visual stimulus, compares the signal and functional activation pathway with that of BOLD, and tests the consistency of functional conductivity imaging (funCI) with visual stimulation across participants. Chapter 5 extends the use of functional conductivity imaging to somatosensory stimulation and trigeminal nerve stimulation to evaluate the consistency of functional conductivity activation across different types of stimuli. In addition, visual adaptation experiment is performed to test if the repetition suppression effect can be observed using funCI. Chapter 6 explores if resting state conductivity networks can be reliably constructed using resting state funCI, evaluates the consistency of persistent homology architectures, and compares the links between nodes in the whole brain. Chapter 7 investigates the feasibility of prostate conductivity imaging using MREPT, and distinctive features in the conductivity distribution between healthy participants and participants with suspected abnormalities.

  • (2021) Short, Katherine
    Thesis
    Children experiencing social and environmental adversity are at greater risk of language difficulties and the related long-term educational and social life challenges. Early years interventions such as home visiting are designed for this vulnerable group and target a range of factors that may influence language outcomes. Many fixed, less modifiable and more modifiable risk and protective factors are known to influence language development. However, it is not clear which factors influence language outcomes in children experiencing adversity nor how these factors combine, especially in the context of intervention. This thesis used qualitative and quantitative methods to investigate the influence of: i) 16 different risk and protective factors and ii) a home visiting intervention on the language outcomes of two groups of children experiencing adversity (n=234). Data were extracted from three longitudinal studies: the Gudaga birth cohort, the Bulundidi Gudaga study and the Maternal Early Childhood Sustained Home-visiting randomised control trial. Several factors influenced language outcomes in urban Aboriginal children. Receptive vocabulary at 3 years was predicted by the child’s gender, non-verbal cognition, number of children in the home and maternal education, and at 4 years by mothers’ emotional well-being, home visiting intervention and daily book reading. In a low socioeconomic status culturally and linguistically diverse cohort, multiple combinations of cumulative risk and protective factors resulted in ‘good’ and ‘poor’ language development, with and without home visiting intervention. While all factors explored, including toddler development, maternal education, early childhood education, number of children in the home and language spoken, impacted on children’s language outcomes, the pervasive influence of two modifiable factors – maternal psychological resources and responsivity – were key. This thesis details the impact of varying combinations of risk and protective factors and a home visiting intervention on language development in two cohorts of children experiencing adversity. Children’s environments made a difference to their learning. Maternal psychological resources, responsivity, home visiting, book reading, the number of children at home and early childhood education were all important, in varied combinations, in children’s language outcomes. These findings have the potential to inform more precise home visiting early interventions so they can respond to the individual characteristics of children and families.

  • (2022) Aishah, Atqiya
    Thesis
    Obstructive sleep apnoea (OSA) pathogenesis is multifactorial with contributions from anatomical and non-anatomical endotypes. Current anatomical-orientated therapies are often inadequate or poorly tolerated with no pharmacotherapies available for OSA. Recent research shows that a combination of noradrenergic and anti-muscarinic agents increases upper-airway muscle activity (key non-anatomical endotype) and reduces OSA severity. Thus, my thesis aimed to investigate alternate therapies for OSA including novel pharmacotherapies targeted towards non-anatomical OSA endotypes as well as combining with existing anatomical approaches based on OSA endotype characterisation. Study 1 investigated the effects of the noradrenergic agent atomoxetine combined with 2 different anti-muscarinics (solifenacin or biperiden) with different receptor-selectivity profiles. Previous studies combined atomoxetine with the antimuscarinic oxybutynin which has broad receptor-selectivity. The goal was to gain mechanistic insight into specific antimuscarinic receptor subtypes for OSA pharmacotherapy which may also have a better side-effect profile versus oxybutynin. The different anti-muscarinics plus atomoxetine improved upper airway function and perceived next-day sleepiness in people with OSA albeit to a lesser extent compared to oxybutynin. This suggests broad or at least M2 muscarinic receptor selectivity may be important in mediating the efficacy of this drug combination for OSA pharmacotherapy. Previous studies with noradrenergic and antimuscarinic agents have been short term (≤1 week) and have not included different doses. Accordingly, in study 2, I investigated longer term (1-month) safety, tolerability, and efficacy of different doses of atomoxetine plus oxybutynin (ato-oxy) versus placebo. 1-month of ato-oxy was generally well-tolerated with a side effect profile consistent with the known profile of each agent alone. An 80/5 mg dosage combination of ato-oxy reduced key OSA severity metrics by ~50%. In study 3 I aimed to investigate if OSA endotype characterisation can be used to inform targeted therapy to resolve OSA in the clinically relevant group of patients who have an incomplete therapeutic response to oral appliance alone (~50% of patients). In these individuals, I systematically added existing anatomical therapies and emerging non-anatomical therapies (i.e., ato-oxy) according to OSA endotype characterisation. OSA was controlled in 50% of participants with addition of other existing anatomical interventions. Almost all the remaining participants were fully treated with the addition of non-anatomical pharmacotherapies. These novel findings provide important insight for the development of novel pharmacotherapy and combination therapy approaches informed by underlying physiological mechanisms for future treatment and management of OSA.

  • (2022) Khou, Vincent
    Thesis
    Diabetes is a condition affecting 7.4% of Australians. Individuals with diabetes often develop complications, which include retinopathy, neuropathy, and kidney disease. Consequently, these individuals require multidisciplinary care. The provision of accessible and timely care is critical, especially with retinopathy, where eye examinations are required to prevent and delay visual impairment. Thus, the objective of the thesis was to assess the current standard of eye care and investigate new ways to enhance eye care for individuals with diabetes. This was explored over two sections. The first section comprised of three studies to explore current models and examine the efficacy of new models. The first study investigated wait lists at a public hospital ophthalmology clinic through a review of referrals. This study established that wait lists were encumbered by poorly targeted referrals for chronic ocular conditions, which could potentially delay access to eye care for individuals with diabetes. Subsequently, two studies were conducted to assess changes in access from two recently implemented models. The second study comprised of a randomised clinical trial that evaluated a metropolitan public hospital collaborative optometry-ophthalmology clinic. Low‑risk participants with diabetes examined by an optometrist experienced quicker wait times without affecting diagnostic accuracy. The third study evaluated a nationwide diabetic retinopathy screening programme operated at primary health care facilities. A survey of health care practitioners, and audit of photos graded by an optometry-led service revealed an increase in access to retinopathy screening. Evaluation of these models revealed that optometrists play a vital role in providing alternative pathways, and that the models improve access in both urban and non‑urban regions. The second section of the thesis comprised of two experimental studies investigating new uses of corneal confocal microscopy and optical coherence tomography which visualise the corneal nerves and retinal layers, respectively. Two cross-sectional studies were conducted to examine corneal and retinal changes in individuals with diabetes. These studies indicated reductions in corneal nerve morphology and retinal layer thicknesses. Since optometrists are familiar with these devices, there is potential to enhance eye examinations in the future by utilising these ocular imaging instruments to detect other diabetic complications.

  • (2022) Ulanova, Marina
    Thesis
    Alzheimer’s disease (AD) is the most common neurodegenerative disease characterised by the development of amyloid-beta (Aβ) plaques, neurofibrillary tau tangles and neurodegeneration. Currently, a definitive diagnosis is only possible with positron emission tomography imaging of amyloid-beta or the analysis of cerebrospinal fluid for AD biomarkers. Both approaches have limitations, namely they are expensive, not widely available and having limited repeatability. Magnetic resonance imaging (MRI) using magnetic nanoparticle contrast agents has opened the potential for less invasive and costly diagnosis. Moreover, magnetic particle imaging (MPI) is a novel tracer-based technology, which derives signal from magnetic nanoparticles to produce images with high sensitivity. While this technology is in the preclinical stages, its high spatial resolution and rapid image acquisition renders it a powerful new tool for neuroimaging research and diagnosis of AD. This thesis seeks to develop biocompatible Aβ-targeted magnetic nanoparticle for use as -MRI contrast agent and MPI tracer as tools for early AD diagnosis. Investigations were undertaken to examine the in vitro biocompatibility and imaging efficacy of Aβ-targeted spherical and cube nanoparticles stabilised with a dimercaptosuccinic acid (DMSA) coating and Aβ targeted spherical iron oxide nanoparticles coated with poly(maleic anhydride-alt-1-octadecene) (PMAO). Results indicated superior stability and MRI contrast enhancement of the PMAO-coated nanoparticles, and thus we employed these in subsequent in vivo analyses. Having established the efficiency of PMAO-coated nanoparticles, we sought to determine their in vivo biocompatibility and biodistribution, and evaluate the efficacy of the targeted nanoparticles as a dual-mode MRI and MPI tracer for AD diagnosis using a mouse model of AD. Critically, this study demonstrated that administration of Aβ-targeted PMAO-coated nanoparticles results in hypointensities in the MRI image and signal in MPI scans, which colocalise with Aβ plaques on histology. Furthermore, MPI is demonstrated as an effective and efficient tool for determining and quantifying nanoparticle biodistribution, establishing it as a powerful tool for research and diagnosis. The present work provides compelling preliminary investigation and evaluation of an Aβ-targeted MRI contrast agent which could facilitate more widespread availability early AD diagnosis, opening the window for more effective treatment and prevention of AD.