Surgery (St Vincent's) - Theses
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ItemThe role of digital technology and gamification to improve health literacy in patients undergoing arthroplasty( 2022)Arthroplasty is a high-volume but costly treatment option for end-stage osteoarthritis. This PhD used a mixed methods approach to explore new strategies to better select and prepare surgical candidates for their surgical journey. A narrative review conveyed how health literacy can improve understanding, rationalise expectations and reduce dissatisfaction in arthroplasty through the medium of digital technology and gamification (the use of gaming elements in a non-gaming context). A quantitative analysis of online arthroplasty information quality demonstrated a marked shortage of reliable resources for patients. A scoping review revealed how existing digital interventions can have a positive impact on related aspects of health literacy, such as knowledge and self-management, despite no structured approach or theoretical framework around these designs. An observational study determined the health literacy profile of a patient cohort undergoing arthroplasty, in whom were lacking the abilities to actively manage their health, and find and appraise health information. It also found that participants who utilised the internet often had higher health literacy, and those able to actively self-manage were three times as likely to progress to surgery. Qualitative research with people before and after their orthopaedic surgery consultation, found those with higher health literacy (including the ability to actively self-manage) had already made the decision to undergo surgery and reflected better surgical candidacy to the surgeon. Finally, interviews with patients about their attitudes, usage and opinions towards a digital tool found that the most effective digital education tool included practical clinical, logistical and lifestyle information, including checklists and timelines, combined with nuanced gamified mechanics, such as points, badges and self-tracking data. The findings from these six studies were synthesized into a concept design for a digital, gamified education tool. It is a data-driven design which ultimately aims to improve health literacy in the context of arthroplasty, empowering patients to obtain evidence-based knowledge, and seek and receive the right treatment at the right time.
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ItemAssessing the suitability of Australian general practice electronic health record data for clinical prediction model development: A case study in Osteoarthritis( 2022)Australian general practice electronic health records contain a wealth of patient information. However, the suitability of these data for developing clinical prediction tools is unclear. This research focussed on determining the suitability of these data for prediction model development using osteoarthritis as a case-study. A comprehensive data quality assessment was conducted and a prediction model for total knee replacement surgery developed. The thesis demonstrated that suitability of Australian general practice electronic health record data for prediction model development should be assessed on a case-by-case basis. A decision aid was developed to assist researchers in determining whether their electronic health record data are fit for prediction model development.
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ItemBio-engineering vascularised liver organoids( 2022)Liver organoids are bioengineered constructs that recapitulate native liver tissue, and are used to study liver development, test drugs, and as replacement tissue that can be transplanted to treat liver disease. This thesis focusses on the specific application of liver organoids for use as a cell-based treatment for liver disease via organoid transplantation. It places a particular emphasis on the addition of vascularisation to liver organoids to enhance structure and function, and improve engraftment during in vivo transplantation. Initially, the effect of the addition of endothelial cells to create vascularised liver organoids was assessed using mouse cells. The addition of mouse liver sinusoidal endothelial cells (LSECs) to mouse liver progenitor cells (LPCs) resulted in a striking change in organoid morphology, with the development of hepatobiliary ductular structures and clusters of polygonal hepatocyte-like cells which did not appear when LPCs were cultured alone as organoids. Furthermore, in vitro hepatobiliary gene expression, hepatic synthetic functions (albumin and apolipoprotein E production) and organoid viability was significantly increased by the addition of LSECs. Upon transplantation into vascularised chambers established in Fah-/- Rag2-/- Il2rg-/- (FRG knockout) mice, LPC only organoids had almost zero survival at 2 weeks, whereas LPC/LSEC organoids developed robust hepatobiliary ductular structures with a 115-fold increase in HNF4a+ cells and 42-fold increase in Sox9+ cells. To translate the mouse findings into a humanised platform, human LPCs and LSECs and their human induced pluripotent stem cell (hiPSC)-derived counterparts were characterised. The hepatic differentiation of human primary adult LPCs and hiPSC derived LPCs into hepatocyte-like cells was confirmed based on cell morphology, marker expression, and function (albumin production), and transcriptomic profiling using bulk and single cell RNA sequencing. Concurrently, human primary adult LSECs were compared to hiPSC-derived endothelial cells(iECs). Although in vitro iECs had a generic endothelial phenotype very different to LSECs, when iECs were transplanted into mouse liver they underwent tissue specification to approximate LSECs, highlighting the importance of the liver microenvironment in this process. Subsequently, three types of vascularised human liver organoids were explored using primary human and hiPSC-derived cells. First, primary LPCs, LSECs and adipose-derived mesenchymal stem cells were combined in a human liver-derived extracellular matrix (ECM) hydrogel and seeded into bioabsorbable porous polyurethane scaffolds. Second, iECs were aggregated with hiPSC-derived hepatocyte (iHep) organoids to coat the surface of the iHep organoids. Third, single cell-type organoids were integrated to form a combination organoid created from hepatocyte, cholangiocyte, and vascular organoids. Of the three models, combining organoids of different cell types to create a combination organoid was deemed the best approach to derive complex liver organoids containing well-organised tissue structures such as polarised hepatocytes with bile canaliculi, bile ducts, and blood vessel networks. An overarching theme is that vascularisation is pivotal in the development of transplantable liver organoids. Adding endothelial cells promotes hepatobiliary differentiation, and pre-formed vasculature can significantly enhance the survival of transplanted liver organoids by hastening connection to the host’s blood supply. However, this is not easy to achieve and remains a challenge in the liver organoid field, and the production of well-vascularised liver organoids with sustained development of blood vessels over time in culture remains elusive. Nevertheless, the limitations and challenges identified in this thesis point towards future directions in addressing the issue of vascularisation. For clinical translation of liver organoid transplantation, hiPSC-derived cells are a more reliable source of personalised cells, and the ECM additive should be bio-synthetic and chemically-defined, rather than Matrigel. Ultimately, the results in this thesis support the exciting prospect of stem-cell derived liver organoids being used as a regenerative treatment for liver disease.
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Item‘Every bone in my body aches’: A culturally secure exploration of osteoarthritis among Aboriginal and Torres Strait Islander People( 2022)Background As a leading cause of pain and disability worldwide, osteoarthritis is associated with considerable personal, economic and societal toll. Osteoarthritis commonly coexists with chronic diseases such as heart disease, diabetes and mental health challenges and can exacerbate the morbidity and mortality associated with these conditions. The health and social disparities experienced by Aboriginal and Torres Strait Islander people in Australia are well documented and include a greater burden of chronic disease, poorer self-assessed health status and lower life expectancy. Osteoarthritis and the burden of illness among Aboriginal and Torres Strait Islander people represent two substantial public health challenges today, however there is a dearth of research which bring the two together. The limited research available suggests that Aboriginal and Torres Strait Islander people experience a higher prevalence and greater burden of osteoarthritis, yet access health care for osteoarthritis at substantially lower rates than non-Aboriginal people. With no culturally adapted models of osteoarthritis care for Aboriginal and Torres Strait Islander people, osteoarthritis is an unmet health need. This thesis responds to these gaps by exploring osteoarthritis among Aboriginal and Torres Strait Islander people and laying the foundations of culturally secure osteoarthritis research for Aboriginal and Torres Strait Islander people. Cultural security in research occurs when the research is conducted in a way that will not compromise the cultural rights, values, beliefs, knowledge systems and expectations of Aboriginal and Torres Strait Islander people. Objectives To explore osteoarthritis among Aboriginal and Torres Strait Islander people and lay the foundations of culturally secure osteoarthritis research for Aboriginal and Torres Strait Islander people, the aims of this PhD were to; 1) Establish an Aboriginal and Torres Strait Islander community reference group to inform, guide and enable community engagement throughout the research; 2) Examine the access, utilisation and surgical outcomes among Aboriginal and Torres Strait Islander people with hip and knee osteoarthritis undergoing total joint replacement surgery and; 3) Inform and guide the development of culturally secure osteoarthritis care for Aboriginal and Torres Strait Islander people based on their lived experience. Methods To achieve these aims, a mixed-methods approach, situated within methodological pluralism and a pragmatic epistemology was employed. Predominantly qualitative methods were chosen to prioritise the stories and cultural context of Aboriginal and Torres Strait Islander participants. This PhD was also conducted within a culturally secure research framework, which prioritised relationships, community engagement and Aboriginal and Torres Strait Islander cultural values and voices throughout. Four phases of research were conducted: 1. In Phase 1, a review of the literature describing osteoarthritis and health care access, including access to total joint replacement among Aboriginal and Torres Strait Islander people was performed. 2. In Phase 2, a qualitative key informant study was conducted. Research yarning interviews with Aboriginal health stakeholders and Aboriginal and Torres Strait Islander people with lived experience of osteoarthritis were conducted to inform the establishment of a community reference group and terms of reference. 3. In Phase 3, a qualitative dominant mixed-methods study was conducted. First, a retrospective cohort study was conducted to explore the uptake and utilisation of total joint replacement by Aboriginal and Torres Strait Islander people and characteristics of Aboriginal and Torres Strait Islander people undergoing total joint replacement. This was followed by a qualitative exploration of the lived experience of osteoarthritis from the perspective of Aboriginal and Torres Strait Islander people, and; 4. In Phase 4, data collected in Phase 3 were integrated to inform and guide the development of culturally secure osteoarthritis care and to develop the discussion chapter of this thesis. Findings The review of the literature conducted in Phase 1 highlighted a lack of evidence describing osteoarthritis among Aboriginal and Torres Strait Islander people, particularly from a person-centred perspective. Two published manuscripts addressed the paucity of research directed towards this unmet health need. The first publication ‘Tackling the burden of osteoarthritis as a health care opportunity in Indigenous communities – A call to action’ raises the profile of osteoarthritis as an unmet health need for Indigenous communities around the world, placing this public health issue on the research agenda. The second narrative review and call to action titled ‘Addressing surgical inequity for Aboriginal and Torres Strait Islander people in Australia’s universal health care system: A call to action’ highlights that Aboriginal and Torres Strait Islander people experience significant barriers to accessing care along the whole of the patient journey to surgical care by drawing examples from the field of osteoarthritis and total joint replacement. The process of establishing an Aboriginal and Torres Strait Islander community reference group and terms of reference in Phase 2 was described in the manuscript (under review) ‘Laying the foundations of community engagement in Aboriginal health research: Establishing a community reference group and terms of reference in a novel research field’. Trust and relationships were considered the most important factors in successfully recruiting ‘the right people’ to an Aboriginal and Torres Strait Islander community reference group. Key informants recommended that representatives of a broad spectrum of expertise should have a seat at the table, including both health service providers and Aboriginal and Torres Strait Islander people with lived experience of osteoarthritis. Community engagement, research steering, knowledge dissemination and advocacy were identified as essential functions of a community reference group. Emphasis was placed on the importance of self-determination, ownership and the decision-making power of the group to negotiate their own terms and conditions. The findings from this study informed the establishment of an Aboriginal and Torres Strait Islander community reference group (comprised of six members) and terms of reference who provided significant input in all subsequent studies in this PhD. The uptake and characteristics of Aboriginal and Torres Strait Islander people undergoing total joint replacement explored in Phase 3 was presented in the manuscript (under review) ‘Total joint replacement may be a valuable treatment for Aboriginal and Torres Strait Islander people with osteoarthritis, but uptake is low’. This manuscript describes the findings from a registry-based retrospective cohort study which compared the sociodemographic, clinical characteristics and surgical outcomes of all Aboriginal and Torres Strait Islander patients and non-Aboriginal patients who underwent primary hip and knee replacement at St Vincent’s Hospital Melbourne between 1996-2019. This exploratory study identified that in the 23-year study period, 49 (0.5%) of procedures were conducted in patients who identified as Aboriginal, Torres Strait Islander or Aboriginal and Torres Strait Islander. St Vincent’s Hospital Melbourne is the largest metropolitan provider of care to Victoria’s Aboriginal community, with over 5000 occasions of care to Aboriginal adults annually. Based on hospital data from the Decision Support Unit, approximately 2.2% of acute hospital admissions at SVHM are patients who identify as Aboriginal, Aboriginal and Torres Strait Islander or Torres Strait Islander. Aboriginal people make up approximately 1.6% of the population in Victoria, excluding metropolitan Melbourne, and 0.5% of the population of Melbourne. The study also found that although Aboriginal and Torres Strait Islander people undergoing total joint replacement were younger, more likely to be overweight and more likely to have a diagnosis of diabetes or multiple chronic diseases, they experienced comparable post-operative quality of life improvements 12-months post-surgery to non-Aboriginal people. The lived experience of osteoarthritis from the perspective of Aboriginal and Torres Strait Islander people, also investigated in Phase 3, was described in the manuscript (accepted for publication) ‘Understanding the impact and tackling the burden of osteoarthritis for Aboriginal and Torres Strait Islander people’. This study identified that osteoarthritis is a multidimensional issue for Aboriginal and Torres Strait Islander people which permeates all aspects of life. Many participants experienced significant psychosocial impacts of osteoarthritis which often occurred within already stressful or complex health or life circumstances. Participants also described multiple negative health care experiences whilst seeking care for their osteoarthritis, which were often characterised by ineffective communication by health care providers. Conclusions As the first in-depth person-centred exploration of osteoarthritis among Aboriginal people and Torres Strait Islander people, this research highlighted the impact of osteoarthritis as a significant health concern which permeates all aspects of life for those affected and validates the importance of addressing the impacts of osteoarthritis within a multidimensional framework. Integrated, multidisciplinary care which is evidence based, culturally secure, individualised to patient need and accessible is required to address the burden of osteoarthritis among Aboriginal and Torres Strait Islander people. By addressing the burden of osteoarthritis among Aboriginal and Torres Strait Islander people, there is an opportunity to improve the health and wellbeing of Aboriginal and Torres Strait Islander communities.