Melbourne Dental School - Theses
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ItemA study of endodontically-related bacteria(University of Melbourne, 2008)
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ItemInsertion sequence ISPg4 as a genetic virulence marker for porphyromonsa gingivalis in chronic periodontitis patients(University of Melbourne, 2006)
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ItemThe saliva- a functionally active body juice(University of Melbourne, 1937)
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ItemThe microscopical pathology of pyorrhoea alveolaris(University of Melbourne, 1935)
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ItemPsychosocial Wellbeing of Children Born with Cleft Lip and/or Palate( 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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ItemDental Implant Outcomes in Clinical Practice – Translation of Retrospective Findings for a Prospective Implant Registry.( 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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ItemThe Role of Hyaluronic Acid in the Prevention of Neoplastic Therapy-induced Oral Mucositis( 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.
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ItemAn investigation of cyclic resistance of files with different working part lengths and electrical resistivity as a possible predictor of niti instrument fracture( 2022)Introduction: Fracture of rotary nickel-titanium (NiTi) instruments is an unpredictable incident that may prevent adequate cleaning and shaping of the root canal system and compromise the outcome of endodontic treatment. Management of a fractured instrument is a sophisticated time-consuming process and sometimes it is impossible. Improvements in instrument design have been attempted as one important way to reduce the risk of fracture of rotary NiTi instruments. However, there have been no previous studies that investigated the effect of changing the active working part length or the shaft length of an instrument on cyclic fracture resistance. Further, electrical resistivity may be a good physical property for investigating the microstructural characteristics of the alloy because it depends on the formation and disappearance of electron-scattering entities in the material during any change or defect in the matrix of the material. Aims and objectives: The aim of this thesis was to investigate cyclic fatigue fracture in rotary NiTi instruments and to develop new methods or approaches to reduce and/or predict fracture. The first objective of this thesis was designed to study the effect of different active working part lengths (AWPL) and shaft lengths (SL) of rotary NiTi instruments on cyclic fatigue resistance. To achieve this objective, the effect of two active working part and shaft lengths of Mtwo instruments on the cyclic fatigue resistance was studied. The second objective was to investigate whether electrical resistivity could predict fracture of rotary NiTi instruments. This included measuring electrical resistivity of rotary NiTi instruments at fracture during cyclic fatigue testing by studying the electrical resistance behaviour of the rotary NiTi instruments during this test. Material and methods: The method used to realise the first objective of this thesis included using a total of 40 Mtwo instruments (VDW, Munich, Germany) of 0.25 mm size, 25 mm length and 0.06 taper. These instruments were divided into two groups of 20 instruments. The first group contained Mtwo instruments with 21 mm AWPL + 4 mm SL, while the second group has 16 mm AWPL + 9 mm SL. The testing apparatus used in this study was a cyclic fatigue testing jig (ISO jig) that was fixed onto a hard wooden base. The simulated canal for this study had a radius of 5 mm and an angle of curvature of 60 degrees. The rotary handpiece was fixed in a mobile supporting device that allowed a precise and reproducible insertion path. The time to fracture was recorded to calculate the number of cycles to fracture (NCF). The method used to address the second objective of this thesis included using simulated curved canals made of glass tubes with internal diameter of 1.2 mm, radius of curvature of 5 mm and angle of curvature of 60 degree. A total of 60 ProTaper Next instruments of 25 mm length, 0.25 size and 0.06 taper were divided into three equal groups, for cyclic fatigue testing. Changes in the electrical resistance were measured during instrument preparation. The instruments in Group 1 were used to measure the initial electrical resistance, electrical resistance at fracture and the NCF during cyclic fatigue testing. The instruments in Group 2 were used in the same way as the instruments in Group 1, with a 7-minute fatigue time and a 15-minute rest interval, while the instruments in Group 3 included two 15-minute rest intervals and an additional 3-minute fatigue time. The electrical resistivity was measured and calculated as a function of the electrical resistance and dimensions of the instruments during cyclic fatigue testing. The rotary handpiece was fixed in a mobile supporting device that allowed precise and reproducible insertion. A Dentsply endodontic motor (Dentsply ATR Tecnika, Pistoia, Italy) with a digital torque control motor and 16:1 contra-angle handpiece was used for all test groups, with a speed of 300 rpm and torque of 100 g.cm according to the manufacturer’s recommendation. The electrical resistance was measured using a four-point probe method that included Kelvin clips and a Fluke 8840A digital multimeter (Fluke Corporation, Everett, WA, USA). The results were analysed using the following statistical methods: Descriptive statistics including means, standard deviations and graphical representations. Inferential statistics including one way analysis of variance, Tukey’s post hoc test, Weibull reliability and probability of failure. Results: The findings of the first study revealed that the mean values of the time to fracture, NCF and fragment length in Group 1 were 1.38 minutes, 415 , and 4.4 mm respectively, and in Group 2, they were 0.86 minute, 258 and 6.7 mm, respectively. There was a statistically significant difference in the time to fracture, NCF and fragment lengths between the two groups. The results of the second study revealed that Group 1 had an initial electrical resistance of 0.085 ohm. The electrical resistance of the instruments increased gradually until fracture. The mean electrical resistance at fracture was 0.221 ohm. The mean of the time from starting cyclic fatigue test until fracture was 9.13 minutes. The mean of the NCF was 2738.1. The electrical resistivity at fracture was calculated as 210.207 micro ohm cm. To study the electrical resistance behaviour of ProTaper Next instruments during cyclic fatigue testing, the test was stopped just before fracture occurrence at 7 minutes and a rest interval of 15 minutes taken (Group 2). The electrical resistance decreased gradually during the 15 minutes of rest until it stabilized at 0.107 ohm. The electrical resistance, after the rest interval increased at a faster rate until instrument fracture at 0.222 ohm with a mean time of 5.340 minute. The total mean time to fracture and NCF in the second group were higher than that when there was no rest interval in the first group. The electrical resistivity at fracture for Group 2 was 211.348 micro ohm cm. For Group 3, a second fatigue time interval of 3 minutes was selected. The electrical resistance value decreased gradually during the second rest interval until it stabilized at 0.115 ohm. The electrical resistance after the second rest interval was higher than that after the first rest interval and the original value at the start. After the second rest, the electrical resistance increased at a faster rate until fracture at 0.223 ohm. The total mean time to fracture and NCF in this group were higher than those when there was only one rest interval in Group 2. The electrical resistivity at fracture for Group 3 was 211.728 micro ohm cm. The one-way ANOVA and Tukey HSD tests revealed that there was no significant difference in the electrical resistance at fracture between and within groups. The electrical resistivity values for all groups were close to each other. There was a highly statistically significant difference in the time to fracture and NCF among groups. These significant differences were very prominent between Groups 1 and 2, and between Groups 1 and 3. The lifetime of the instruments increased and depended on the history of the instruments as to whether one or two rest intervals had been used in the cyclic fatigue test. Group 3 showed a higher Weibull modulus (16.49) compared with Group 1 (9.01) and Group 2 (11.80). This correlated with a high reliability and high probability of survival. When comparing the Weibull characteristic life of the groups, it was found that Group 1 failed at a higher level compared with Groups 2 and 3. Conclusions: This suggests that the AWPL may influence the cyclic fatigue resistance of the instrument. A specific value of electrical resistivity (211.1 micro ohm cm) was found at which fracture of ProTaper Next instruments occurred. There was an inverse correlation between the initial starting resistance of a used instrument and the additional NCF. Measuring electrical resistivity may be used to predict fracture of rotary NiTi instruments. Further studies are needed in this area.
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ItemScreening for Type 2 Diabetes Mellitus initiated through the dental setting: a cost-effectiveness analysis( 2019)Background. Diabetes Mellitus (DM) is the fastest growing chronic condition in Australia. Approximately, 30% of DM in Australia is undiagnosed. Early identification may delay or prevent the onset of DM with minimal complication. In the Western Pacific (WP) region, Australia has the highest per capita spending on DM. With the rising cost of healthcare, increasing emphasis is being made to ensure that health interventions are not only practical but also cost-effective that can save resources which otherwise may have to be spent on complication and hospital admission. By stretching the number of contact points between health care providers and individuals seeking care, there is plenty of opportunity for early identification of asymptomatic individuals with Type 2 Diabetes Mellitus (T2DM). With this link between DM and periodontal disease, dentists may have an unrealized opportunity to identify risk groups and refer them to physicians for further care. For any screening activity in the dental setting, the participation of Oral Health Professionals (OHP) is important. Little is known as to how well oral health professionals incorporate into practice on the evidence supporting the link between DM and periodontal disease. Besides that, no previous studies have reported the cost-effectiveness of opportunistic screening using a diabetes risk assessment tool in the dental setting. As such, the aim of the thesis is twofold. To explore the Victorian oral health professionals (OHP) knowledge, attitude and practice (KAP) around DM and to evaluate the overall economic justification of screening for diabetes and pre-diabetes in the dental setting. Methods. A cross-sectional survey of Victorian OHP was conducted. The questionnaire consisted of sociodemographic, practice characteristics and diabetes-related KAP. Descriptive statistics with frequencies and percentages were used to summarize the variables. A Mann-Whitney and Kruskal-Wallis test was performed to determine differences in OHP response to the KAP questions. The screening model consists of a decision tree and a disease progression Markov model to identify the risk of T2DM over a ten-year period. Literature data were used for the risk categorisation and disease transition for health states. The cost-effectiveness of screening was compared to no screening option. A hypothetical population of 40 to 74-year-old Victorian dental patients with no previous history of DM were screened with the Australian type 2 Diabetes Risk Assessment Tool (AUSDRISK). Those identified as high-risk follow-up with the physician for screen diagnosis using Fasting Plasma Glucose (FPG). Based on the previous finding from two-step screening in the dental setting the model made an assumption that 21.5% of the dental patient identified as high risk follow up with the physician. The cost-effectiveness was analysed from a societal perspective. The main outcome measure includes cost per case detected as undiagnosed T2DM, new cases of T2DM. A univariate sensitivity analysis was performed to determine the effect of different physician follow-up rate from the dental setting to identify undiagnosed T2DM. Results. The survey analysis included 197 OHP. General and specialist dentist constitute 65% and 11% of the response and the remainder were dental hygienist and therapist. Around 86% of the OHP showed adequate knowledge of DM. Further 93% and 81% of the OHP expressed positive attitude and practice behaviour towards T2DM screening and management. For OHP to perform chair-side screening for DM, 58% felt it was essential, and 70% felt it was appropriate. More female (67%) and public sector OHP (79%) felt it is important to conduct chair-side screening for T2DM. The majority (65.4%) of the OHP agreed on consent as the most important and insurance coverage as the least important (43%) consideration for T2DM screening. Under model assumption, the number of dental patients identified as undiagnosed T2DM and pre-diabetes were 4,108 (0.3%) and 10,072 (0.8%). The cost incurred for one new case of undiagnosed T2DM and pre-diabetes were AUD 15,508 and AUD 6,325. The Number Needed to Screen (NNS) to identify one new case of undiagnosed T2DM and pre-diabetes were 288 and 117. Among those followed up with the physician, at the end of five years, 81.5% had Normal Glucose Tolerance (NGT), 8.1% had Impaired Fasting Glucose (IFG), 6.9% had T2DM, and the all-cause mortality was 3.5%. At the end of the ten-year period, 10% had T2DM. The overall and disease-free survival was 92.8% and 82.8%. Discussion. Majority of OHPs had adequate knowledge and a positive attitude towards T2DM screening in the dental setting. The survey identified patient willingness as the most important consideration among the OHPs for implementing T2DM screening in the dental setting. The screening model identified several methodological challenges due to incongruent data and unsuitable comparator. Despite that, opportunistic screening with AUSDRISK was found to be neither clinically effective nor cost-effective compared to screening in the medical setting. High screening cost, poor predictive ability of AUSDRISK, low prevalence of the disease, unnecessary physician referral besides uncertain benefits, fear of over diagnosis and poor patient compliance makes screening for T2DM in the dental setting difficult to justify. The model findings are in line with previous estimates on AUSDSRISK as a screening tool. In financially constrained health system resource allocation will need to be based on favourable evidence that screening can reduce disease levels in the community, demonstrate health benefits at an acceptable cost. A two-step opportunistic screening that includes a risk assessment followed by a Point-of-Care (PoC) HbA1c may offer some benefits in the low- and middle-income countries.