Development and synthesis of innovative approaches to the surgical assessment of articular cartilage degeneration

This research has established, through ultrasound, near infrared spectroscopy and biomechanics experiments, parameters and parametric relationships that can form the framework for quantifying the integrity of the articular cartilage-on-bone laminate, and objectively distinguish between normal/healthy and abnormal/degenerated joint tissue, with a focus on articular cartilage. This has been achieved by: 1. using traditional experimental methods to produce new parameters for cartilage assessment; 2. using novel methodologies to develop new parameters; and 3. investigating the interrelationships between mechanical, structural and molec- ular properties to identify and select those parameters and methodologies that can be used in a future arthroscopic probe based on points 1 and 2. By combining the molecular, micro- and macro-structural characteristics of the tissue with its mechanical properties, we arrive at a set of critical benchmarking parameters for viable and early-stage non-viable cartilage. The interrelationships between these characteristics, examined using a multivariate analysis based on principal components analysis, multiple linear regression and general linear modeling, could then to deter- mine those parameters and relationships which have the potential to be developed into a future clinical device. Specifically, this research has found that the ultrasound and near infrared techniques can subsume the mechanical parameters and combine to characterise the tissue at the molecular, structural and mechanical levels over the full depth of the cartilage matrix. It is the opinion in this thesis that by enabling the determination of the precise area of in uence of a focal defect or disease in the joint, demarcating the boundaries of articular cartilage with dierent levels of degeneration around a focal defect, better surgical decisions that will advance the processes of joint management and treatment will be achieved. Providing the basis for a surgical tool, this research will contribute to the enhancement and quanti�cation of arthroscopic procedures, extending to post- treatment monitoring and as a research tool, will enable a robust method for evaluating developing (particularly focalised) treatments.

Developing a model of care to improve the health and well-being for Indigenous people receiving renal dialysis treatment

The high levels of end-stage renal disease among Indigenous Australians, particularly in remote areas of the country, are a serious public health concern. The magnitude of the problem is reflected in figures from the Australian and New Zealand Transplant and Dialysis Registry that show that Indigenous Australians experience end-stage renal disease at a rate almost 9–10 times higher than other non-Indigenous Australians. A majority of Indigenous Australians have to relocate to receive appropriate renal dialysis treatment. In some Australian states, renal treatment is based on self-care dialysis which allows those Indigenous Australians to be treated back in their community. Evidence clearly shows that reuniting renal patients with community and family improves overall health and well-being for those Indigenous Australians. With the appropriate resources, training, and support, self-care management of renal dialysis treatment is an effective way for Indigenous people with end-stage renal failure to be treated at home. In this context, the study was used to gain insight and further understanding of the impact that end-stage renal disease and renal dialysis treatment has had on the lives of Indigenous community members. The study findings are from 14 individually interviewed people from South East Queensland. Data from the interviews were analysed using a combination of thematic and content analysis. The study methodology was based on qualitative data principles where the Indigenous community members were able to share their experiences and journeys living with end-stage renal disease. Many of the experiences and understanding closely relate to the renal disease pattern and the treatment with other outside influences, such as social, cultural, and environmental influences, all having an equal impact. Each community member’s experience with end-stage renal disease is unique; some manage with family and medical support, while others try to manage independently. From the study, community members who managed their renal dialysis treatment independently were much more aware of their renal health status. The study provides recommendations towards a model of care to improve the health and well-being is based on self-care and self-determination principles.

Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life

Background: Impairments in upper-body function (UBF) are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL) remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. ---------- Methods: Australian women (n = 287) with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS). Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy- Breast questionnaire were used to assess self-reported UBF and QoL, respectively. ---------- Results: Although mean UBF improved over time, up to 41% of women revealed declines in UBF between sixand 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least twofold (p < 0.05). Lower baseline and declines in perceived UBF between six- and 18-months PS were each associated with poorer QoL at 18-months PS (p < 0.05). ---------- Conclusions: Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.

Children and consent to medical treatment

This chapter deals with the law concerning children and consent to medical treatment. Where a child under the age of 18 requires medical treatment, issues arise as to who may lawfully consent to the treatment and under what circumstances. Depending on the circumstances, consent may be given by the child’s parent or guardian; the child; or a court. The chapter provides a thorough treatment of Australian law about these issues and circumstances.

Finding a way through the ethical and legal maze : withdrawing medical treatment and euthanasia

This article examines Finnis' and Keown's claim that the intention/foresight distinction should be used as the basis for the lawfulness of withholding and withdrawing medical treatment, rather than the act/omission distinction which is currently used. I argue that whilst the intention/foresight distinction is sound and can apply to palliative pain relief hastening death, it cannot be applied to withholding and withdrawing medical treatment. Instead, the act/omission distinction remains the better basis for the lawfulness of withholding and withdrawal, and law reform is consequently unnecessary.

Signal authentication and integrity schemes for next generation global navigation satellite systems

This paper describes a number of techniques for GNSS navigation message authentication. A detailed analysis of the security facilitated by navigation message authentication is given. The analysis takes into consideration the risk of critical applications that rely on GPS including transportation, finance and telecommunication networks. We propose a number of cryptographic authentication schemes for navigation data authentication. These authentication schemes provide authenticity and integrity of the navigation data to the receiver. Through software simulation, the performance of the schemes is quantified. The use of software simulation enables the collection of authentication performance data of different data channels, and the impact of various schemes on the infrastructure and receiver. Navigation message authentication schemes have been simulated at the proposed data rates of Galileo and GPS services, for which the resulting performance data is presented. This paper concludes by making recommendations for optimal implementation of navigation message authentication for Galileo and next generation GPS systems.

Requirements for enhancing trust, security and integrity of GNSS location services

The paper describes a number of requirements for enhancing the trust of location acquisition from Satellite Navigation Systems, particularly for those applications where the location is monitored through a remote GNSS receiver. We discuss how the trust of a location acquisition could be propagated to an application through the use of a proposed tamper-­resistant GNSS receiver which quantifies the trust of a location solution from the signaling used (ie. P(Y) code, Galileo SOL, PRS, CS) and provides a cryptographic proof of this to a remote application. The tamper­-resistance state of the receiver is also included in this cryptographic proof.

New drugs for the treatment of coronary artery syndromes

Background: Acute coronary syndromes are a major cause of mortality and morbidity. Objectives/Methods: The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anti-coagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the anti-platelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. Results: In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Conclusions: Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.

Good results for early treatment of clinically isolated syndrome prior to multiple sclerosis with interferon beta-1b and glatiramer

Background: The first sign of developing multiple sclerosis is a clinically isolated syndrome that resembles a multiple sclerosis relapse. Objective/methods: The objective was to review the clinical trials of two medicines in clinically isolated syndromes (interferon β and glatiramer acetate) to determine whether they prevent progression to definite multiple sclerosis. Results: In the BENEFIT trial, after 2 years, 45% of subjects in the placebo group developed clinically definite multiple sclerosis, and the rate was lower in the interferon β-1b group. Then all subjects were offered interferon β-1b, and the original interferon β-1b group became the early treatment group, and the placebo group became the delayed treatment group. After 5 years, the number of subjects with clinical definite multiple sclerosis remained lower in the early treatment than late treatment group. In the PreCISe trial, after 2 years, the time for 25% of the subjects to convert to definite multiple sclerosis was prolonged in the glatiramer group. Conclusions: Interferon β-1b and glatiramer acetate slow the progression of clinically isolated syndromes to definite multiple sclerosis. However, it is not known whether this early treatment slows the progression to the physical disabilities experienced in multiple sclerosis.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Diagnostic and treatment pathways for men with prostate cancer in Queensland : investigating spatial and demographic inequalities

Background: Patterns of diagnosis and management for men diagnosed with prostate cancer in Queensland, Australia, have not yet been systematically documented and so assumptions of equity are untested. This longitudinal study investigates the association between prostate cancer diagnostic and treatment outcomes and key area-level characteristics and individual-level demographic, clinical and psychosocial factors.---------- Methods/Design: A total of 1064 men diagnosed with prostate cancer between February 2005 and July 2007 were recruited through hospital-based urology outpatient clinics and private practices in the centres of Brisbane, Townsville and Mackay (82% of those referred). Additional clinical and diagnostic information for all 6609 men diagnosed with prostate cancer in Queensland during the study period was obtained via the population-based Queensland Cancer Registry. Respondent data are collected using telephone and self-administered questionnaires at pre-treatment and at 2 months, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months post-treatment. Assessments include demographics, medical history, patterns of care, disease and treatment characteristics together with outcomes associated with prostate cancer, as well as information about quality of life and psychological adjustment. Complementary detailed treatment information is abstracted from participants’ medical records held in hospitals and private treatment facilities and collated with health service utilisation data obtained from Medicare Australia. Information about the characteristics of geographical areas is being obtained from data custodians such as the Australian Bureau of Statistics. Geo-coding and spatial technology will be used to calculate road travel distances from patients’ residences to treatment centres. Analyses will be conducted using standard statistical methods along with multilevel regression models including individual and area-level components.---------- Conclusions: Information about the diagnostic and treatment patterns of men diagnosed with prostate cancer is crucial for rational planning and development of health delivery and supportive care services to ensure equitable access to health services, regardless of geographical location and individual characteristics. This study is a secondary outcome of the randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000233426)

Potential of St John's Wort for the treatment of depression : the economic perspective

The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with complementary and alternative medicines. Meta-analyses of randomized controlled trials have found Hypericum perforatum preparations to be superior to placebo and similarly effective as standard antidepressants in the acute treatment of mild to moderate depression. A clear advantage over antidepressants has been demonstrated in terms of the reduced frequency of adverse effects and lower treatment withdrawal rates, low rates of side effects and good compliance, key variables affecting the cost-effectiveness of a given form of therapy. The most important risk associated with use is potential interactions with other drugs, but this may be mitigated by using extracts with low hyperforin content. As the indirect costs of depression are greater than five times direct treatment costs, given the rising cost of pharmaceutical antidepressants, the comparatively low cost of Hypericum perforatum extract makes it worthy of consideration in the economic evaluation of mild to moderate depression treatments.