Medicine (St Vincent's) - Theses
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ItemCreating a state-wide registry to drive new epidemiological, forensic and clinical insights into sudden cardiac arrest in young Australians( 2022)Sudden cardiac arrest (SCA) is a leading cause of death globally, accounting for approximately half of all deaths from cardiovascular disease. As demonstrated in this thesis, in young Australians it accounts for one-quarter of all deaths and is associated with approximately 90% mortality. Despite the condition’s high mortality rate and prevalence, systematic and adjudicated data collection remains lacking. As indicated in Chapter 1, only a few registries worldwide provide comprehensive multi-source surveillance of all SCAs, and many important questions in the field of SCA remain unanswered. The substantial economic cost imposed by young SCA in Australia is calculated for the first time in this thesis and provides an economic as well as medical imperative to better understand SCA. In Chapter 2, the aims of this PhD project are established as being to design a multi-source SCA registry with comprehensive case capture and adjudication. Such a registry would enable the secondary aims of identifying epidemiological and forensic insights, as well as creating an opportunity to highlight the experiences of selected patient groups. Chapter 3 of this thesis describes in detail the process of establishing the End Unexplained Cardiac Death (EndUCD) registry including its hierarchical consent process, data flow, data quality control and governance processes. From the establishment of the EndUCD registry, large-scale epidemiological assessments have been undertaken (Chapter 4). These include delineating overarching features of the entire patient group such as causes of arrest, the role of obesity and the role of rural residence. We have also identified variations in administrative data coding that will create under-appreciation of the community burden of SCA. The registry also enabled several projects to be undertaken in close collaboration with the Victorian Institute of Forensic Medicine (Chapter 5), yielding novel forensic information in the investigation of young sudden cardiac death (SCD). These projects include identifying rates of referral and potential under-referral of young SCD for forensic investigation, investigating a novel approach of performing post-mortem coronary artery calcium scores to assist cause of death determination, and examining the diagnostic yield of post-mortem interrogation of implanted cardiac devices such as pacemakers. The EndUCD registry’s unfortunately substantial number of patients created an opportunity to examine multiple relevant clinical questions (Chapter 6). These include more targeted clinical scenarios such as the outcomes of pregnant women experiencing SCA, those with coronary artery anomalies and unusual cases such as IgG4 coronary arteritis causing SCA. Two registry participants also graciously waived their anonymity and shared their experiences in being affected by SCA. In conclusion, the EndUCD registry has been established in line with best practice globally, and successfully commenced operations. Data from this registry has enabled diverse important projects providing new insights into the management of SCA on epidemiological, forensic and clinical levels.
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ItemPopulation level outcomes of advancements in diabetes care( 2021)The development of diabetes-related complications is a major healthcare problem. The overall aim of this thesis is to document trends in the incidence of diabetes-related complications, focusing on those related to cardiovascular and renal disease. Diabetes care has improved significantly over past decades, resulting in improved glycaemic control and an increase in the number of patients achieving various metabolic goals. Indeed, the application of multifactorial, target driven interventions has been shown to reduce the development and progression of diabetes related complications in the clinical trial setting. Furthermore, novel glucose lowering medications have recently been shown to reduce the development of cardiovascular and renal complications in recent clinical trials. It is possible that these recent improvements in diabetes management have contributed to reductions in complications in the general diabetes population. In this thesis I examined changes in rates of diabetes related complications in people with and without diabetes over time in Victoria, Australia. The research described in this thesis is mainly centred on an analysis of trends in hospital admissions in Victoria, Australia for various diabetes related complications. This thesis shows that there was a significant decline in the cardiovascular outcomes of, incident AMI, stroke and heart failure presentations for patients with type 1 diabetes, type 2 diabetes and without diabetes between 2004 and 2016. The greatest rate of decline was observed in patients with type 2 diabetes, followed by patients with type 1 diabetes. My research also demonstrates that there was a significant decline in end stage renal disease presentations (separate to those for dialysis and transplantation) for patients with type 1 diabetes, type 2 diabetes or no diabetes. However, rates of admissions for diabetic nephropathy and specifically for dialysis and transplantation remained stable. This lack of translation of a reduction in ESRD presentations to reduced rates of dialysis and transplantation may be due to changes in clinical practices, such as greater access and eligibility for renal replacement programs. The continuing large number of patients with diabetic nephropathy represent an opportunity for the better implementation of best practice guidelines aimed at slowing the development and progression of diabetic kidney disease. In addition, I was able to show that overall rates of lower extremity amputations (LEA) declined for patients with type 2 diabetes, compared to those with type 1 diabetes who did not experience such a decline. Concerningly, a significant rise was seen in all types of LEA for younger patients with type 1 diabetes, whereas pleasingly, older patients with type 2 diabetes saw a decline in rates of LEA. While there is a large amount known on the numbers of people that experience cardiovascular events, less is known about the intravascular burden of coronary artery disease in people with and without diabetes. I was able to show a significant increase over time in the burden of coronary artery disease for patients with type 2 diabetes, compared to those without diabetes in whom no change was observed. A key finding was that following adjustment for the use of traditional cardiovascular protective medications such as statins, renin-angiotensin system inhibitors and anti-platelet drugs, there was no significant difference in the extent of intra-coronary artery disease between patients with and without type 2 diabetes. The implication of this finding is that the aggressive use of traditional preventative therapies can greatly help to reduce the excess burden of disease within the coronary arteries of patients with type 2 diabetes. The improvement in rates of traditional diabetes related complications has led to a corresponding increase of non-traditional complications, including malignancies. In the last results chapter of this thesis, I was able to show that for patients with type 2 diabetes and malignancies there was a significantly increased risk of emergency department presentations, inpatient admissions and all-cause mortality compared to patients with malignancies but without diabetes. This thesis adds to a growing body of evidence of the negative impact of diabetes, on patient outcomes and the importance of risk factor modification and multifactorial interventions. It highlights that although improvements in hospital admission rates for many diabetes related complications are occurring, the overall burden of complications still remains a major public health problem. Unfortunately, my work also shines a light on the changing face of diabetes complications and the potential problems associated with the emergence of non-traditional complications, such as malignancies.