Medicine (RMH) - Theses
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ItemImproving clinical outcomes for patients with diabetes related foot complications( 2005)Background: Individuals with diabetes have a 15% lifetime risk of developing a foot ulcer, which are ultimately responsible for over 100,000 amputations being performed each year in the United States. Although it has been well documented that we currently have the available knowledge to successfully heal approximately 90% of such ulcers, amputation and admission rates for these conditions continue to increase. Aim: To determine if management approaches and clinical outcomes (length of stay, amputation rate), for individuals with diabetes related foot complications, can be improved with the introduction of a novel evidence-based clinical guideline by a multidisciplinary team of health professionals. Theories regarding guideline dissemination and implementation will be explored in an attempt to identify strategies that are more effective in achieving sustained clinical change. Methods: A novel evidence-based clinical guideline was created, by reviewing 266 articles specific to the area. The guideline was specifically designed to encourage a systematic and global approach to the clinical assessment, investigation and management of individuals with diabetes related foot complications. The clinical guideline was initially introduced into the pre-existing environment of the hospital, drawing upon published dissemination and implementation strategies / theories. Two-month prospective studies were undertaken both prior and post guideline implementation, evaluating the extent of guideline uptake and the corresponding changes to clinical care. In response to these findings, efforts were made to further improve guideline utilisation by specifically addressing identified barriers to implementation in a second launch of the guideline. A further two-month prospective study was undertaken, 1-year post the initial launch. As sustained changes to health care provision were not achieved at this time, a final strategy to be employed was to use a multidisciplinary team of health professionals, including representatives from endocrinology, podiatry, vascular surgery, infectious diseases, diabetes educators, dietician, clinical psychology, rehabilitation and radiology, to implement the clinical guideline as a part of a newly created, centralised Diabetic Foot Unit (DFU). Results: The evidence-based clinical guideline was insufficient, in itself; to encourage health professionals to change their clinical approach when managing someone with a diabetes related foot complication. Despite identifying many barriers preventing the more widespread uptake of the guideline and multidisciplinary team (professional autonomy, knowledge deficits, environmental and patient barriers) the only approach that achieved significant change was the creation of a centralised, multidisciplinary, diabetic foot unit. With the introduction of the DFU, a complete clinical examination of the foot was undertaken in all patients, investigations were tailored to the specific condition, mean length of stay was reduced by 5 days per admission and there was a significant reduction in the amputation rate. Conclusion: Implementation of (i) an evidence-based clinical guideline, (ii) a multidisciplinary team, and (iii) centralised DFU, can improve all aspects of health provision, with corresponding reductions in length of stay and amputation rates. The development of this complete package for health provision suggests that similar results should be achievable with the introduction of this approach to other health institutions.
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ItemChronic pain in older people( 2001-04)Despite the expansion of research into chronic nonmalignant pain, a majority of reported studies are based on patient populations of specialised pain management clinics, which may not adequately represent older people with chronic nonmalignant pain in the general community. Therefore, the overall aim of the present thesis was to fill some gaps in this knowledge base. The findings of the present thesis support the notion that older people who attend multidisciplinary pain management centres are probably not representative of those with pain who live in the general community but do not attend specialised treatment centres. Indeed a conceptual framework developed from the findings suggest that less than 3 percent of a random community sample of older people with chronic pain share the profile of those who attend a multidisciplinary pain management centre. The majority (86 percent) of the community sample were found to have mild chronic pain that can be adequately managed in the community. However, about 11 percent of the community sample have moderate chronic pain, and it is probable that additional community-based pain management services can improve the management of pain. Development of instruments to measure the perceived helpfulness and use of pain management strategies by community-dwelling older people with chronic pain is another area that has not received adequate attention. A preliminary survey questionnaire was developed to measure the use and perceived helpfulness of pain management strategies in community dwelling older people. The findings have provided new insight from the user’s perspective regarding the relative effectiveness of different pain management strategies, and highlighted the potential clinical application of strategies that are less commonly used, such as TENS (transcutaneous electrical nerve stimulation), and relaxation techniques that are beneficial for specific subgroups of older people with chronic pain. The evaluation of the efficacy of a community-based intervention program that provides free choice of intervention for improving outcomes for older people with chronic pain showed that the program was successful in reducing pain and improving level of physical activity for those who completed the program when they were compared with matched subjects who did not participate. The findings also suggest that an educational seminar can have a positive impact that empower participants to make a more informed choice regarding interventions for managing pain. However, the long-term effect of the program has not been established. Therefore, further research will be needed to evaluate whether this approach is a viable alternative clinical option for effective, accessible, and low cost pain management for the general community of older people with chronic pain. The pain management service model was developed based on a synthesis of the findings. The model was based on a targeted approach that focuses on community-based interventions designed to improve access and outcomes for the majority of community-dwelling older people with chronic non-malignant pain who do not use specialised pain management services. Overall, the findings of the present thesis have enhanced our understanding of the management of chronic non-malignant pain in community-dwelling older people, which has important implications for the development of services, and has generated hypothesis for future research that may contribute to improve outcomes for older people with chronic non-malignant pain.
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ItemRegulation of SNARE proteins in macrophages by colony stimulating factor-1( 2007)Macrophages serve key roles in host defence by initiating inflammatory responses to infection and/or injury. They contribute to innate immunity by secreting a range of pro-inflammatory cytokines (e.g. TNF and IL-6) upon activation as well as by phagocytosing pathogens and dead cells, which is necessary for the resolution of inflammation and effective wound repair. Macrophages also contribute to adaptive immunity by functioning as antigen presenting cells.Colony stimulating factor 1 (CSF-1) is the major growth factor governing the differentiation, proliferation and survival of macrophages. Although not as well appreciated, CSF-1 also regulates some of the immune functions of macrophages, such as cytokine secretion and phagocytosis. However, the mechanisms by which CSF-1 governs the immune functions of macrophages are poorly understood. Cytokine secretion, phagocytosis and antigen presentation involve various vesicle trafficking and membrane fusion events, processes in which SNARE proteins play vital roles. Thus, the hypothesis tested in this thesis was that CSF-1 modulates the immune functions of macrophages by regulating the expression and/or activity of SNARE proteins that regulate endocytic and exocytic processes.In this study, the endosomal SNARE protein syntaxin 7 was identified, via microarray analysis, as a CSF-1 inducible gene in primary mouse macrophages. Syntaxin 7 has previously been detected in phagosomal membranes in macrophages. Furthermore, syntaxin 7 has recently been implicated in the secretion of cytokines (e.g. TNF) from macrophages by forming a novel complex with syntaxin 6, Vti1b and VAMP3.
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ItemSleep disordered breathing in stable methadone maintenance treatment patients( 2006-02)Methadone is a long acting mu-opioid and is the most effective treatment for heroin addiction. However, opioids depress respiration and methadone maintenance treatment (MMT) patients have a higher mortality rate than the general population. Teichtahl et al conducted a pilot study and found 6 out of 10 MMT patients had central sleep apnea (CSA). But no definite conclusions were made regarding the prevalence and possible pathogenesis of CSA in the patients due to the small sample size and lack of blood toxicology data. The present project aims to confirm the preliminary results and further quantify the sleep disordered breathing (SDB) in stable MMT patients and to delineate the pathogenesis involved. (For complete abstract open document)
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ItemConceptualising and measuring health literacy from the patient perspective( 2009)The current patient-centred healthcare approach encourages individuals to assume greater roles in decisions about their health. The premise is that patients who are well informed about healthcare options are more likely to adhere to prescribed treatments and achieve better health outcomes. This approach assumes that patients have an adequate level of health literacy. While a range of definitions exist, health literacy is commonly defined as an individual’s ability to seek, understand and utilise health information to make appropriate health decisions. Health literacy is increasingly recognised as a complex multi-dimensional concept which involves interactions between individual abilities and broader environmental factors. However across definitions, there has been little consultation with patients to understand what is important to effectively seek, understand and utilise health information. The lack of a consensual understanding has led to debate as to what health literacy represents and how it should be measured. A range of measures exist with the predominant approach being the testing of individual literacy abilities. However measures do not assess the range of attributes described in definitions. Thus a considerable gap exists between how health literacy is defined and how it is measured. This thesis focused on addressing this gap. The objectives were to: (i) critically appraise existing health literacy measures (ii) develop a conceptual framework from the patient perspective and (iii) use this framework to develop a comprehensive measure of health literacy. A multi-method qualitative and quantitative approach was used: (1) Systematic review and appraisal of the content, development and psychometric properties of health literacy measures. (2) In-depth consultations with patients across healthcare and disease continuums to develop a conceptual framework. (3) Development of a new health literacy measure based on the conceptual framework using a classical test theory approach. A critical appraisal of the literature revealed that the majority of health literacy measures are not based on a conceptual framework and none appeared to adequately measure a person’s ability to seek, understand and utilise health information. Content focussed primarily on reading, comprehension and numeracy skills and scoring was poorly defined. Only five of the 19 measures had evidence of acceptable reliability. The conceptual framework of health literacy from the patient perspective identified 17 key elements: six individual abilities and 11 broader contextual factors that are important to seek, understand and utilise health information and expanded previous conceptualisations of health literacy. This informed the development of the Health Literacy Management Scale (HeLMS) which measures six generic and potentially modifiable abilities and three specific broader social factors. Overall the HeLMS measures an individual’s ability to seek, understand and utilise health information within the healthcare setting. The HeLMS consists of 29 items across eight domains. Rigorous psychometric testing demonstrates that it possesses strong construct validity and high reliability (coefficient α >0.80 for all eight domains). This research provides unique contributions to the conceptualisation and measurement of health literacy. Limitations in the content and psychometric properties of previously developed measures have been identified through a systematic process. A conceptual framework derived from the patient perspective identifies a range of components that provide new insight into: (i) constructs that should be incorporated to measure health literacy and (ii) areas that need to be addressed to improve health literacy. The development of the HeLMS now allows for a more comprehensive assessment of health literacy. Information from the conceptual framework and the HeLMS are likely to be useful tools to inform the development of public health initiatives to enhance patient participation in the management of their health.
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ItemMechanisms and mapping of ventricular arrhythmias in cardiomyopathy( 2009)Heart failure due to ischemic and dilated cardiomyopathy is a large and expanding public health problem, and ventricular arrhythmias are a common and potentially fatal complication of this condition. Despite extensive investigation, the mechanisms of ventricular arrhythmias in cardiomyopathy remain incompletely understood. This thesis examines these mechanisms, particularly with reference to the potential role of the underlying electrophysiologic substrate. It also evaluates the validity and utility of some of the tools commonly used to assist in the mapping and catheter ablation of ventricular arrhythmias. The central rationale of this thesis is that the mechanisms of ventricular arrhythmogenesis in cardiomyopathy are optimally studied by comparing ischemic and dilated cardiomyopathy patients with spontaneous (rather than inducible) ventricular tachycardia to otherwise similar heart failure patients who have never developed clinical arrhythmias. This has been done in the two largest projects herein. In the setting of ischemic cardiomyopathy, it is demonstrated that there are large differences in the electrophysiologic substrate between the groups such that patients with clinical ventricular tachycardia have substantially greater endocardial scarring as inferred by the presence of low-voltage zones and scar-related electrograms compared to control cardiomyopathy patients with no spontaneous arrhythmias. Furthermore, there appear to be fundamental differences in the nature of the scarring process with ventricular tachycardia patients having more abnormal electrograms per unit area of low-voltage and more scar-related putative conducting channels (which may form critical diastolic isthmuses in tachycardia). This was accompanied by a lower rate of ventricular tachycardia inducibility in the control patients. Taken together these findings point to a major role for the electrophysiologic substrate in ventricular arrhythmogenesis in the setting of ischemic cardiomyopathy. The situation in dilated cardiomyopathy is more complicated and although significant endocardial substrate differences were again seen in this context, there was marked heterogeneity in the group with ventricular tachycardia with some patients having extensive low-voltage zones and others having normal endocardial voltage. As the pericardium could not be accessed for ethical reasons in control patients with no clinical arrhythmia, the precise role of an abnormal epicardial substrate was not able to be defined in this study. Another project in this thesis examines potential improvements (in the form of a multielectrode mapping catheter) to a widely used electroanatomic mapping system that can assist in mapping ventricular tachycardia circuits and the substrates underlying them. A further project compares magnetic resonance imaging and electroanatomic substrate mapping in defining ventricular scarring in the context of cardiomyopathy. And finally, electroanatomic mapping is used to look at endocardial activation patterns and electrical dyssynchrony in cardiomyopathy patients with and without left bundle branch block. The demonstrated variability in these factors may underlie the significant non-response rates to cardiac resynchronization therapy. In summary, it is apparent from this work that the electrophysiologic substrate plays a crucial role in mechanism of the ventricular arrhythmias seen in heart failure patients with ischemic and dilated cardiomyopathy. An improved understanding of these mechanisms may in turn lead to better diagnosis, risk stratification and ultimately management of heart failure patients suffering from, or at risk of developing these potentially lethal arrhythmias.