Many older people who fracture their hip do not recover to their previous level of function. This study will test whether it is possible to help recovery of function, particularly walking, after hip fracture by using different and more intensive physiotherapy treatment. The treatment will concentrate on exercise when standing, will be provided twice daily and will continue after the person with hip fracture has returned home. Four months after the hip fracture it is expected that walking ability ....Many older people who fracture their hip do not recover to their previous level of function. This study will test whether it is possible to help recovery of function, particularly walking, after hip fracture by using different and more intensive physiotherapy treatment. The treatment will concentrate on exercise when standing, will be provided twice daily and will continue after the person with hip fracture has returned home. Four months after the hip fracture it is expected that walking ability, strength and balance will be improved by the new treatment methods.Read moreRead less
Exercise Self-management To Improve Long-term Functioning And Prevent Falls After Hip Fracture.
Funder
National Health and Medical Research Council
Funding Amount
$848,478.00
Summary
Up to 20,000 older Australians suffer hip fractures each year. Many people don't fully recover. We have designed a self-management training program which incorporates individualised exercise prescription. This novel program is designed for people who have completed usual treatment and rehabilitation for hip fracture. We will conduct a well-designed randomised controlled trial to test the effects of this program on disability, falls and hospital readmissions and to assess its cost-effectiveness.
Functional Genomic Analysis Of The Role Of P53 In Early Embryo Death After Assisted Reproductive Technologies (ART).
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. ART are expensive therapies and much of this cost is related to the relative inefficiency of the technology. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. Consequently the chance of any individual embryo resulting in a successful birth is not high. There has been only ....Assisted reproductive technologies (ART, such as IVF and related techniques) are successful treatments for most forms of infertility. ART are expensive therapies and much of this cost is related to the relative inefficiency of the technology. Much of this is due to the high mortality of the resulting embryos. Typically, 45-80% of embryos produced by ART do not survive the first week. Consequently the chance of any individual embryo resulting in a successful birth is not high. There has been only modest increments in embryo survival in recent years. The low cahnce of individual embryos resulting in a baby means that: (1) generally several treatment cycles are required; (2) superovulation is used to maximise the number of embryos produced giving an accumulation of unwanted cryopreserved embryos; (3) more than one embryo is generally transferred resulting in a significant incidence of multiple pregancies. The high mortality of the early embryo seems to be a general feature of IVF but its causes and effectors are not known. It has recently been established that it largely occurs due to a form of cell 'suicide' known as apoptosis. This form of cell death has important normal functions: its activation allows for cells that are no longer required to be removed, allowing the remodelling of tissues and it also serves to remove cells that are irreversibly damaged. p53 is a protein that has the ability to 'sense' cell stress and damage and to direct the cell to undergo apoptosis if the stress is severe. This project will examine if ART cause increased expression of p53 and whether this elevation of p53 causes embryonic cell death. We will examine the factirs that control p53 expression in the embryo. using mice with mutations that stop the function of p53 and several of its regulatory proteins. Experiments will determine the susceptibility of embryos possessing these mutations and will therefore allow us to define the proteins causing apoptosis after ART.Read moreRead less
Follow-up Of Women On A Randomised Clinical Trial Of Adjuvant Docetaxel And Doxorubicin For Node Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$113,250.00
Summary
This project is testing the use of a drug docetaxel in the post-operative (adjuvant) treatment of women with breast cancer and involved lymph nodes (N+). Until recently the drug doxorubicin was the most active chemotherapy drug for breast cancer, but more recently a new group of chemotherapy drugs called taxanes were identified. One taxane called docetaxel may be even more effective than doxoubicin. Using available treatments that include doxorubicin based chemotherapy, approximately half the wo ....This project is testing the use of a drug docetaxel in the post-operative (adjuvant) treatment of women with breast cancer and involved lymph nodes (N+). Until recently the drug doxorubicin was the most active chemotherapy drug for breast cancer, but more recently a new group of chemotherapy drugs called taxanes were identified. One taxane called docetaxel may be even more effective than doxoubicin. Using available treatments that include doxorubicin based chemotherapy, approximately half the women with N+ breast cancer experience recurrence of their cancer. It is therefore important to test whether the inclusion of docetaxel in adjuvant therapy can reduce relapses. If docetaxel is to be included, it is also important to test whether it is best to combine it with doxorubicin at the same time (which for safety reasons requires the doses of each drug to be reduced), versus giving them sequentially at full dose. Currently, docetaxel is not approved nor funded for use in early breast cancer in Australia. There are several international trials testing the inclusion of taxanes in the adjuvant therapy of breast cancer. However this trial stands out, because all the women in the trial receive chemotherapy of at least 6 months. In some other trials, testing the possible benefit of adding a taxane, women in the control treatment group (who were randomised not to receive the taxane) received only 3 months of treatment, which makes it difficult to distinguish between longer treatment or addition of the taxane drug. This trial has completed international recruitment of 2890 women who will be carefully followed for 10 years. Australian and New Zealand centers recruited 20% of the women in the trial. After the women have been followed-up for 5 years the results of this trial will be analysed, presented and published and should provide reliable evidence about the potential benefit of adding docetaxel into adjuvant chemotherapy.Read moreRead less
Clinical Trial Of Adjuvant Docetaxel And Doxorubicin For Node Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$185,135.00
Summary
This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+). Every year 3000 women in Australia, and over 400,000 worldwide are newly diagnosed with N+ breast cancer. Using available treatments more than 60% of these (5 per day in Australia, 4,500 each week worldwide) will die from breast cancer. The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview c ....This project is investigating the optimal use of docetaxel and doxorubicin in the treatment of women with breast cancer and involved lymph nodes (N+). Every year 3000 women in Australia, and over 400,000 worldwide are newly diagnosed with N+ breast cancer. Using available treatments more than 60% of these (5 per day in Australia, 4,500 each week worldwide) will die from breast cancer. The efficacy of adjuvant chemotherapy in early breast cancer is well established by the international overview conducted by the Early Breast Cancer Trialist's Collaborative Group (EBCTCG). They have demonstrated the efficacy of adjuvant chemotherapy on reducing mortality and recurrence rates, but current regimens are far from optimal. Docetaxel (Taxotere), a new agent, has effectiveness and manageable side effects in the treatment of advanced breast cancer patients, and can plausibly improve outcomes for patients with early N+ breast cancer by optimal integration into current adjuvant chemotherapy regimens. This clinical trial is designed to compare whether it is advantageous to use docetaxel and-or doxorubicin in combination or sequentially with other currently available chemotherapy drugs.Read moreRead less
Using Evidence To Set Priorities In Health: An Analysis Of Decisions Of The Pharmaceutical Benefits Advisory Committee
Funder
National Health and Medical Research Council
Funding Amount
$174,575.00
Summary
Australia has pioneered the use of rigorous clinical and economic evidence in the evaluation of drugs prior to funding on our nationally subsidised Pharmaceutical Benefits Scheme. In the ten years since the introduction of the requirement that drugs demonstrate cost effectiveness prior to subsidy being granted there has been no formal independent evaluation of the system to assess its performance. This project will examine the recommendations of the Pharmaceutical Benefits Advisory Committee in ....Australia has pioneered the use of rigorous clinical and economic evidence in the evaluation of drugs prior to funding on our nationally subsidised Pharmaceutical Benefits Scheme. In the ten years since the introduction of the requirement that drugs demonstrate cost effectiveness prior to subsidy being granted there has been no formal independent evaluation of the system to assess its performance. This project will examine the recommendations of the Pharmaceutical Benefits Advisory Committee in the last decade and consider the factors that explain those decisions. At times it has been asserted that those decisions have been arbitrary or based on inappropriate considerations such as the financial cost to government or politics of the day rather than the value for money of the drug in question. We will examine the reasons behind the decisions against the objectives of providing access to life enhancing medicines in a cost effective manner. We will look at what are the key determinants of whether a drug is recommended for listing on the PBS or is rejected. A key focus will be on whether those determinants could be described as legitimate in terms of their consistency with the objectives of the scheme. For example whether the main cause of rejection is a lack of high quality evidence on effectiveness- cost effectiveness or simply because of factors such as the high financial cost to government. The project will create a database of all submissions to the PBAC 1992-2004 that will allow us to explore a number of questions about the effectiveness of the decision making process in using evidence on effectiveness and costs in health more broadly as well as those specific to the PBS. In highlighting some of the problems with the evidence and its interpretation the overall aim is to improve the quality of the decision making process in the future.Read moreRead less
Role Of Post-traumatic Hypoxia In The Exacerbation Of Cerebral Inflammatory Response Elicited By Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$397,535.00
Summary
Traumatic brain injury is the major cause of death in the young population below the age of 40 years. Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with considerable family, professional and economic costs. Extensive research has shown that not all brain damage occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may result from various factors including hypoxia (insufficient oxygen) a ....Traumatic brain injury is the major cause of death in the young population below the age of 40 years. Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with considerable family, professional and economic costs. Extensive research has shown that not all brain damage occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may result from various factors including hypoxia (insufficient oxygen) as a consequence of respiratory distress that occurs in about 50% of patients with severe head trauma. Hypoxia is known to significantly worsen the neurological impairment and potentially lead to death. Brain injury and hypoxia have the ability to separately trigger cerebral inflammation. A dual role has been attributed to inflammation: to promote tissue repair but also add further damage through the release of neurotoxic substances. We hypothesise that hypoxia occurring after traumatic brain injury enhances the inflammatory response in the brain and aggravate tissue damage as well as neurological dysfunction. This hypothesis will be tested on a rat model of brain injury whereby the animals will be exposed to moderate-severe hypoxia immediately after trauma. The production of multiple inflammatory mediators will be quantified in the brain tissue and also in cerebrospinal fluid. The concentration of these mediators will be compared with the levels of cellular injury proteins known to increase following injury to determine whether a correlation exists. In a clinical study on patients, we will measure the same inflammatory mediators and proteins in the cerebrospinal fluid and blood of individuals with severe head injury. The suitability of these factors for potential use as diagnostic-prognostic markers of either hypoxia or injury will be determined.Read moreRead less