Melbourne Dental School - Theses

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    A study of endodontically-related bacteria
    Chivatxaranukul, Pavena. (University of Melbourne, 2008)
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    The saliva- a functionally active body juice
    Douglass, Arthur. (University of Melbourne, 1937)
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    The microscopical pathology of pyorrhoea alveolaris
    Ellis, David, Ph. D. (University of Melbourne, 1935)
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    Psychosocial Wellbeing of Children Born with Cleft Lip and/or Palate
    Branson, Emma ( 2023-09)
    Background Oral clefts are the most common craniofacial abnormality worldwide with an estimated prevalence of approximately 1 in every 700 live births and can affect multiple areas of a child’s life, including psychological health and wellbeing. Levels of wellbeing may be impacted by the increased incidence of negative social interactions including bullying, communication difficulties, lower self-esteem due to facial differences and increased need for medical treatment. COVID-19 was announced as a global pandemic in March 2020 and in an attempt to suppress the spread of the virus, significant restrictions were imposed to limit social interaction. Research on the impact of the COVID-19 pandemic has indicated that this had a negative influence on the wellbeing of children. In response to the COVID-19 pandemic, the Royal Children’s Hospital (RCH), Melbourne and Murdoch Children’s Research Institute rapidly developed a campus wide study investigating the impact of the COVID-19 pandemic on the wellbeing and mental health of children, including those with cleft lip and/or palate, who were current patients of the RCH. Aims The aims of this project were (1) to systematically review the literature to determine if children born with cleft lip and/or palate (CL/P) are at increased risk of psychological and peer difficulties, and if so, in which domains, and (2) investigate the wellbeing of children born with CL/P during the initial stages of the COVID-19 pandemic in Victoria, Australia. Methods (1) A systematic review was undertaken, with three databases searched for studies investigating the psychological outcomes and peer function of children with non-syndromic CL/P. A meta-analysis was conducted on studies which used the Strengths and Difficulties Questionnaire (SDQ) as the psychosocial tool. (2) A longitudinal cohort study was performed. The Royal Children’s Hospital (RCH), Melbourne, Australia, cleft service database was utilised to identify children born with isolated CL/P. Eligible families were asked to complete the SDQ at two different time points during the COVID-19 pandemic. The outcomes for this cohort were compared to those of a previously published independent study of typically developing Australian children during the COVID-19 pandemic. Results Results from the systematic review and meta-analysis indicated that children born with CL/P have similar psychological outcomes when compared to the typically developing population. There are minor differences between self and parent reported outcomes, with parents generally reporting increased emotional, conduct and hyperactivity problems in children born with CL/P. The clinical study revealed that Victorian children born with CL/P had lower SDQ scores, and fewer difficulties for all outcome domains, when compared to the typically developing population during the COVID-19 pandemic. Discussion and Conclusion Levels of overall psychosocial wellbeing in children born with CL/P appear similar to the typically developing population, with only slightly increased levels of psychological symptoms such as depression and anxiety. Despite the very severe social restrictions imposed during the COVID-19 pandemic in Victoria, children born with CL/P had higher levels of wellbeing when compared to a typically developing Australian population. However, the longer term impact of the pandemic on these children, and how a return to normal life may influence their wellbeing remains unclear. It is therefore important to continue to monitor and support these children and their families.
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    Dental Implant Outcomes in Clinical Practice – Translation of Retrospective Findings for a Prospective Implant Registry.
    Liau, Isaac Jian Xiang ( 2023-03)
    Background Dental implant treatment is a continuously evolving subdiscipline of clinical dentistry that is being undertaken in an increasingly diverse patient population. The rapid growth of new technologies and techniques in this field, combined with the heterogeneity of the treatment population, has led to a lack of high-level evidence to inform the creation of clinical practice guidelines for dental implant treatment in the Australian population. A large-scale, practice-based retrospective cohort study was previously undertaken by a research group at the University of Melbourne in collaboration with the eviDent Foundation, investigating the clinical treatment profiles and complications associated with dental implant treatment in the private practice setting. This dataset was used to generate studies relating to medical comorbidities in the dental implant demographic, bone augmentation procedure outcomes, restorative profiles and complications of short-span prostheses, and restorative profiles and complications of long-span prostheses. The findings and experience of these studies identified a heterogenous dataset, highlighting the need for a comprehensive prospective longitudinal study design to obtain further practice-based data. A clinical quality registry is a powerful data acquisition medium well suited to fulfil this role. Clinical quality registries (CQRs) are validated tools to record and investigate outcomes associated with treatments across a range of healthcare fields. CQRs have been demonstrated to improve clinical outcomes, improve the cost-effectiveness of healthcare, and to identify adverse effects associated with devices. To date, few dental implant registries are in active use worldwide. Aims This thesis aims to translate the knowledge and understanding gained though previous retrospective practice-based cohort studies on dental implant treatment outcomes in clinical practice, into the development and establishment of a proof-of-concept prospective electronic dental implant clinical quality registry. Methods Critical appraisal of the preceding retrospective studies undertaken by the eviDent Project 002 research group was undertaken with comparison to concordant broader scientific literature, to ascertain clinical variables suitable for further investigation in a prospective clinical quality registry. A narrative literature review was undertaken to determine the experience of developing clinical quality registries in the broader healthcare sector, and to describe the strategic framework principles necessary for the establishment of a strong clinical quality registry for dental implants. An electronic pilot trial dental implant clinical quality registry was constructed utilising the REDCap clinical database development application, with database variables identified through the preceding critical appraisal of the literature. Proof-of-concept viability was undertaken with a test data representing non-live patient case files (n=15) entered in parallel by multiple clinicians (n=10) to confirm for internal validity of data entry. Results and Discussion This study blended variables identified in earlier retrospective implant studies with those from the broader scientific literature to create a comprehensive, evidence-based database of implant-related clinical variables relevant to implant-related complications. The database formed the scaffold for a pilot online registry which, when trialled, demonstrated a high level of inter-clinician accuracy with regards to data entry (98.2%) and a high ease of use. The pilot registry was suitable for implementation into live production status as a clinical quality registry. The challenges and future directions associated with the establishment of a functional clinical quality registry are discussed to inform future work on the establishment of this as a powerful clinical audit and research tool.
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    The Role of Hyaluronic Acid in the Prevention of Neoplastic Therapy-induced Oral Mucositis
    Mohammed, Ali Ibrahim Mohammed ( 2022)
    ABSTRACT GENERAL SUMMARY Mucositis is a common and most debilitating complication associated with cancer therapy. Approximately 30–40% of cancer patients treated with chemotherapy develop mucositis; this percentage rises to 60–85% for patients receiving conditioning regimens before hematopoietic stem cell transplantation (HSCT) and can increase to almost 100% for head and neck cancer (HNC) patients receiving radiotherapy concomitant with chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus, causing ulceration and severe pain in both the oral cavity and intestinal tract. The consequences of mucositis are far reaching and can lead to a delay or even cessation of otherwise durable cancer treatment and negatively impacting the benefits of chemoradiation. Mucositis is not only an important driver of patients’ symptoms and infection risk, but its onset is also associated with poor health outcomes, the use of health resources, and incremental costs. Given that mucositis is ultimately a predictable and potentially preventable condition, this project aimed at optimising a pre-clinical model of mucositis and testing the protective effect of a natural compound on chemotherapy-induced mucosal injury. Chapter 1 discusses the generalities of mucositis, its causative agents and risk factors, its pathophysiology diagnosis, and management. After recalling basic concepts of cancer treatment (causative factor) and mucosal structure (target tissue), in this chapter I explain the clinical relevance and economic implications of mucositis. A large section is devoted to the pathophysiology of mucositis as this represents the starting point for the development of novel mechanism-based preventative and therapeutic strategies. The chapter then focuses on oral mucositis and, in this context, types of assessment and scoring scales are extensively discussed. Current management strategies of mucositis are scrutinised in the final part of Chapter 1. Despite its clinically devastating consequences, there is currently little to offer patients in the way of effective treatment to prevent or mitigate mucositis, and this provided the rationale for developing the aims of this project. General materials and methods are detailed in Chapter 2. The experimental design included in vitro experiments using an oxidative stress-induced model of human oral mucosal injury and an in vivo dual murine model of 5-FU-induced oral/intestinal mucositis. Formulations of hyaluronic acid (HA) tested in these models included Mucosamin, cross-linked (xl-), and non-crosslinked high molecular weight HA (H-MW-HA). Cell lines, culture conditions, morphological, functional and molecular assays (e.g. cell viability, cytotoxicity, and proliferation; intracellular ROS production, superoxide dismutase enzyme activity) are described. For the animal study, methodology for clinical, histopathological and morphometric assessment of oral and intestinal mucositis is reported in detail. Specific materials and methods are additionally described in the relevant chapters. In the experiments described in Chapter 3, we aimed to develop and characterise an in vitro model of oral mucosal injury that could mimic the initial events that trigger oral mucositis. Since the molecular mechanisms underlying chemotherapy and radiotherapy-induced oral mucositis involve the production of ROS at early stages and consequent activation of oxidative stress pathways, we established an oxidative stress model on human oral keratinocytes cultures whereby were able to identify optimum concentrations of hydrogen peroxide and incubation period for each of the cell line tested. Such a model allowed the screening of potentially xxx drugs reported later in this thesis. In Chapter 4, the biocompatibility of several hyaluronic acid derivatives in our in vitro cell model system was assessed through an extensive series of experiments. We defined the optimal concentrations of the following compounds: Mucosamin (1%, 5%, 7% and 10% v/v), native high molecular weight HA (H-MW-HA; 0.01%, 0.03%, 0.05%, 0.07% and 0.1% w/v), and cross-linked (xl-) HA (0.01% v/v of xl-HA 5/5, xl-HA 30/30, and xl-HA 100/100). Oral keratinocytes were incubated for 24, 48, and 72 hours in the presence of these HA products and a dose-response curve was developed. All HA compounds tested significantly promoted oral epithelial cell proliferation compared to control, except for Mucosamin; this commercial preparation did not affect cell growth at concentrations of up to 5% (v/v) and was cytotoxic at higher concentrations. Drawing on the results of the pilot experiments described in the previous chapters, in Chapter 5 we tested the protective effects of HA in a model of oxidative stress-induced oral mucosal injury. OKF6 cells were incubated with 400 uM (IC50 value) hydrogen peroxide (H2O2) and the effects of Mucosamin, H-MW-HA, Xl-HA 5/5, Xl-HA 30/30, and Xl-HA 100/100 were tested. While all HA compounds could attenuate to some extent the detrimental effects of ROS, the most marked effects were obtained with H-MW-HA. Specifically, pre- and then co-incubation of OKF6 cells with 0.01 % (w/v) H-MW-HA for 24 hours resulted in a sizeable increase in cell viability when compared to H2O2- treated cells. Remarkably, H-MW-HA also reduced the intracellular level of H2O2-induced ROS production, as measured by the ability of cells to oxidize CM-H2DCFDA. Hence, H-MW-HA at 0.01 % (w/v) was selected for the animal study. Chapter 6 describes a detailed set of experiments to show that HA prevents oral and intestinal mucositis induced by chemotherapy in vivo. To overcome the limitations of current models, whereby oral and intestinal mucositis are studied separately using different, organ-specific models, we first characterized a pre-clinical dual (oral and intestinal) murine model of mucositis by using intravenous 5-FU injections (50 mg/kg) every 48 hours for 2 weeks. In the test group, the mice were pre-treated one day prior to the initial 5-FU treatment and then daily thereafter with high molecular weight HA (H-MW-HA) (0.01 % w/v) in drinking water. Mice were monitored clinically for weight loss, diarrhea (as a surrogate of intestinal injury), and incidence and extent of oral mucositis. Microscopically, histomorphometric analyses of the tongue and intestinal tissues were conducted. The results strongly indicated that H-MW-HA prevented 5-FU-induced damage to the intestinal mucosa and tongue epithelium. We also demonstrated that H-MW-HA enhanced the activity of the SOD enzyme in the blood serum of 5-FU treated mice. This thesis comes to a conclusion with Chapter 7, where our results are discussed in light of current literature. These results reported in this thesis provide an experimental rationale to develop a novel HA-derived treatment as a therapeutic agent to protect against oral and intestinal mucositis associated with chemotherapy in cancer patients. We note that systemic administration of HA as a preventive or therapeutic tool in oral and intestinal mucositis may have profound clinical implications in patients, such as potential interference with cancer treatment, that require further elucidation. Future studies will address this important aspect of our research.