We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
Measuring The Productive Efficiency Of Hospitals - A Comparison Of Parametric And Non-parametric Approaches
Funder
National Health and Medical Research Council
Funding Amount
$61,815.00
Summary
In the face of rising health service costs, an ageing population, and falling private health insurance rates, the efficient use of scarce health service resources has become a central theme in health system reform. Productive (or technical) efficiency is a key aspect of health system reform - that given health services are produced with the minimum feasible amount of resources. Despite the importance of technical efficiency there have been few published studies in Australia which measure technic ....In the face of rising health service costs, an ageing population, and falling private health insurance rates, the efficient use of scarce health service resources has become a central theme in health system reform. Productive (or technical) efficiency is a key aspect of health system reform - that given health services are produced with the minimum feasible amount of resources. Despite the importance of technical efficiency there have been few published studies in Australia which measure technical efficiency in the health sector. This study will develop theoretical and empirical approaches to measuring technical efficiency in the production of hospital services using data from Victoria. Measures of hospital technical efficiency will be developed using two quantitative modelling approaches: stochastic frontier modelling and data envelopment analysis. Results will be used to investigate the impact of patient and hospital characteristics on efficiency, and to identify economies of scale and scope in the provision of hospital services. The robustness of results to changes in variables, the sample of hospitals studied, and model assumptions will be tested, and two techniques will be compared to assess their appropriateness in the health services context which has not previously been done. Criteria for assessing the approaches include the degree to which: assumptions affect the robustness of results; the techniques capture the salient features of health services production; and the techniques produce similar rankings and estimates of inefficiency. The methods used will represent a significant contribution to international knowledge of hospital efficiency measurement, and the relationships between hospital characteristics, casemix, and efficiency. The study wil provide improved measures of hospital efficiency in Victoria, and will inform debate on hospital funding policy.Read moreRead less
A Parent Education And Skills Training Intervention For Young Adolescents With Autism
Funder
National Health and Medical Research Council
Funding Amount
$436,500.00
Summary
Autism is a most severe and prevalent lifelong developmental disorder affecting approximately one in every thousand children and their families. Autism is associated with personal suffering and is a significant burden and stress for parents, families and carers and cost to the community. In earlier work we have demonstrated that providing a structured program of parent education and guidance to families with preschool children with autism leads to improved parental adjustment and mental health. ....Autism is a most severe and prevalent lifelong developmental disorder affecting approximately one in every thousand children and their families. Autism is associated with personal suffering and is a significant burden and stress for parents, families and carers and cost to the community. In earlier work we have demonstrated that providing a structured program of parent education and guidance to families with preschool children with autism leads to improved parental adjustment and mental health. The program also led to behavioural and developmental benefits for the child. The early secondary school years bring further stress and difficulty to adolescents with autism and their families. This project aims to assess the effectiveness of a parent education and training program for parents with autistic adolescents aged 12-14 years. If shown to be effective, this manual based intervention can be readily used by professionals to promote parent mental health, family adjustment and improve the wellbeing and outcome for adolescents with autism. As a result, family stress and the necessity of out of home care may be reduced and school participation improved.Read moreRead less
LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.Read moreRead less
Supply, Demand And The Distribution Of Health Services In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,038.00
Summary
The distribution of medical services and its impact on access and equity is widely recognised as a key concern of the Australian community. Access and equity are key indicators to the public of the performance of a health system. These concerns have led to the adoption of major policy goals under Medicare relating to equitable access to medical services for the population as a whole. Furthermore, both the community and policy makers have expressed high levels of concern over the distribution of ....The distribution of medical services and its impact on access and equity is widely recognised as a key concern of the Australian community. Access and equity are key indicators to the public of the performance of a health system. These concerns have led to the adoption of major policy goals under Medicare relating to equitable access to medical services for the population as a whole. Furthermore, both the community and policy makers have expressed high levels of concern over the distribution of medical services between sub-markets and sub-populations, in particular, in the distribution of medical services between urban and rural-remote areas. This project, for the first time, comprehensively examines the performance of Medicare in terms of access to medical services over time. Australian data sets, largely untapped by economic modelling, will be used for analysis of the relationships between the distribution of, access to, and demand and fees for Australian medical services and their impact upon mortality over time. The study will result in the first comprehensive Australian description of access and supply of different medical services by social group and by geographic location over time. Furthermore it will provide evidence on the key determinants of distribution and changes in the distribution of medical services and estimates the likely effects of policy instruments designed to address the distribution of, and access to, medical services.Read moreRead less
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less
A Trial Of A Multidisciplinary, Group Based Intervention To Meet The Needs Of Men With Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$524,285.00
Summary
This study will test an innovative approach to meeting the physical and psychosocial needs of men with early stage prostate cancer using a randomised controlled trial. This novel approach involves a combination of individual and group-based consultations which encourages peer-to-peer support, promotes self-care and enhances appropriate multidisciplinary referrals and communication. It provides a new model of care for patients with chronic diseases that can be translated into clinical practice.
Development Of Novel Medical Therapies To Cure Ectopic Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$601,156.00
Summary
Ectopic pregnancies are conceptions implanting outside the womb, mainly the fallopian tube. They are pathological, and can erode straight through the tube into large blood vessels causing fatal bleeding and death. We plan to assess three medication based approaches to treat this condition that would avoid surgery entirely. If we succeed, and subsequently translate one or more of these treatments to the clinic, it would revolutionise management of this serious gynaecological emergency.
Radiostereometric Analysis Of The Effect Of A Large Articulation On Prosthetic Wear And Migration After Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$192,186.00
Summary
At total hip replacement, there has been a recent trend to use prostheses with a larger ball and liner in the socket. This may decrease the risk of post-operative dislocation, but may also increase the amount of wear, leading to bone loss and loosening of prostheses, which may then require replacement. This project will use a special type of x-ray to determine whether wear and movement of these new prostheses is clinically acceptable, so that they can be used with confidence in patients.
The Risks And Benefits Of Contemporary Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$493,530.00
Summary
The number of hip replacements undertaken in Australia is steadily increasing. The most common complications of hip replacements are dislocation and loosening due to bone loss around the implant, requiring complex and expensive revision surgery. This study will investigate the incidence of dislocation and, using a new diagnostic imaging technique, the incidence and amount of bone loss around a relatively new prosthetic material, the outcomes of which are not known despite its increasing use.