Pathophysiology And Alternative Preventative Strategy For Breast Cancer Chemotherapy-induced Bone Loss
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Combination cytotoxic chemotherapy is the current optimal approach for treating breast cancer in premenopausal women. However, long-term skeletal defects (osteoporosis and fractures) caused by the chemotherapy have become an increasingly serious problem due to its intensified use and improved patient survival rate. This project seeks to elucidate the mechanisms for chemotherapy-induced bone defects and to initiate development of a preventative treatment using natural bioactive micronutrients.
Measuring Adverse Events: Development Of A Patient-Centred Adverse Event Reporting Tool (PAET)
Funder
National Health and Medical Research Council
Funding Amount
$454,721.00
Summary
The decision to treat a patient depends on knowing whether the treatment does more good than harm. If it is likely that the treatment will work as well as or better than other treatments and will have minimal associated risks, then that treatment would be recommended unless unavailable or prohibited by cost. Given two equally effective treatments the one with fewer side effects and greater tolerability would be preferred by all. In the process of acquiring knowledge on treatment benefit and trea ....The decision to treat a patient depends on knowing whether the treatment does more good than harm. If it is likely that the treatment will work as well as or better than other treatments and will have minimal associated risks, then that treatment would be recommended unless unavailable or prohibited by cost. Given two equally effective treatments the one with fewer side effects and greater tolerability would be preferred by all. In the process of acquiring knowledge on treatment benefit and treatment harm we rely on evidence from clinical trials. However, the evaluation of benefit versus harm is not symmetric in this setting. Much more effort (e.g. study design, study power, standardisation of efficacy outcome measures) goes into the assessment of whether a treatment works and rather than its potential harm, as measured by adverse events. Adverse event ascertainment and reporting is poorly standardised . There is no standardised measurement process that elicits adverse event information. There is no standardised method for quantifying adverse event information into an index or profile scores equivalent to instruments developed to measure health status, quality of life and other benefits of treatment. Developing astandardised Patient-centred Adverse Event Questionnaire will benefit multiple stakeholders. For Patients: An easy to understand summary measure of treatment harm aids patient understanding of the benefit versus risk. For Doctors, allied health professionals: The Questionnaire includes drug profiles, to align a drug profile with an individual patient's clinical profile. This leads to better patient care. In health policy: All of the above has flow-on effects for policy. Better adverse event data will facilitate information and understanding generally of risks of treatments, risk-benefits of treatments, and cost-effectiveness of management strategies.Read moreRead less
TIR Signalling Pathway Pharmacogenomics And Opioid Response: Beyond The Mu Opioid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$246,396.00
Summary
This project will identify why some people respond poorly and others have toxic side effects to the major group of pain relieving medications, the opioids. The basis will be the genetics of the immune system and both acute postoperative and chronic cancer pain patients will be studied in this international pharmacogenetics project.
Clinical Pharmacology Of Methadone During Induction Onto Maintenance Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$422,310.00
Summary
Heroin addiction can be very successfully treated by substituting heroin with methadone. The transition of stopping heroin and starting methadone is risky and can be associated with death. This application seeks to explore the mechanisms of the increased risk during this transition period so that appropriate management strategies might be instituted.
Role Of An Endogenously Synthesised Sterol In Regulating Cholesterol Removal From The Macrophage
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Heart disease remains the greatest killer of Australians and involves accumulation of cholesterol in the artery wall. Cholesterol accumulates in a specific cell-type called the macrophage (literally means ' big-eater'). Once macrophages accumulate cholesterol, they become bloated cholesterol-filled foam cells. The early and persistent appearance of foam cells in diseased artery suggests that foam cells are active participants in the development of heart disease. Prevention or reversal of their f ....Heart disease remains the greatest killer of Australians and involves accumulation of cholesterol in the artery wall. Cholesterol accumulates in a specific cell-type called the macrophage (literally means ' big-eater'). Once macrophages accumulate cholesterol, they become bloated cholesterol-filled foam cells. The early and persistent appearance of foam cells in diseased artery suggests that foam cells are active participants in the development of heart disease. Prevention or reversal of their formation is therfore an attractive target for new therapies to treat heart disease. In this proposal, we address specific questions which will increase our understanding of how best to prevent or reverse foam cell formation. This work may indicate new therapeutic possibilities for combating heart disease.Read moreRead less
High Risk Prescribing In Older Australians: Prevalence, Outcomes And Potential For Intervention
Funder
National Health and Medical Research Council
Funding Amount
$595,628.00
Summary
Older people are the most likely to be prescribed medicines yet they are the most likely to be harmed by their medicines. The extent of and trends in high risk prescribing among older Australians are not known. This project will use large-scale linked data to determine the prevalence, risk factors, clinical consequences and costs of high risk prescribing among older people in Australia. The findings of this project will be used to identify targets for minimising harm relating to use of medicines ....Older people are the most likely to be prescribed medicines yet they are the most likely to be harmed by their medicines. The extent of and trends in high risk prescribing among older Australians are not known. This project will use large-scale linked data to determine the prevalence, risk factors, clinical consequences and costs of high risk prescribing among older people in Australia. The findings of this project will be used to identify targets for minimising harm relating to use of medicines.Read moreRead less
Medicine-associated Dementia And Cognitive Impairment: Identifying The Problem, Reducing The Harm
Funder
National Health and Medical Research Council
Funding Amount
$513,116.00
Summary
Several studies have shown an association between use of anticholinergic or sedative medicines and increased risk of dementia. Questions remain about whether these medicines cause dementia (or are just used by people already at risk), whether or not cognitive function improves if the medicines are stopped or if the dose is reduced, and the characteristics of patients most likely to use these medicines. This program of research aims to answer these questions.
Pathogenesis Of Antiretroviral Induced Sub-cutaneous Fat Wasting
Funder
National Health and Medical Research Council
Funding Amount
$331,650.00
Summary
The use of potent antiretroviral therapy has resulted in great clinical and survival benefit in patients with HIV infection and has in most cases, outweighed the risk of short term side effects. However, not that survival of patients with AIDS has considerably improved the long-term complications of chronic therapy have become a critical issue. Lipodystrophy syndrome(s) is the name given to a set of changes to blood lipids, glucose levels and body habitus and typically occurs in those successful ....The use of potent antiretroviral therapy has resulted in great clinical and survival benefit in patients with HIV infection and has in most cases, outweighed the risk of short term side effects. However, not that survival of patients with AIDS has considerably improved the long-term complications of chronic therapy have become a critical issue. Lipodystrophy syndrome(s) is the name given to a set of changes to blood lipids, glucose levels and body habitus and typically occurs in those successfully treated with anti-HIV therapy. The facial and body habitus changes are common, progressive and are frequently disfiguring. Aside from the psychological and social effects of such changes, many patiens are not able to retain their anonymity as HIV infected individuals. In addition, changes to blood lipids may lead to atherosclerosis. Already there have been several case reports of premature coronary disease in young HIV infected patients. It is increasingly difficult for patients to remain strictly adherent to chronic therapy because of all these concerns. There is an urgent need to understand the exact biological cause(s) of lipodystrophy syndrome(s) in HIV infected patients in order to help identify which of our currently available antiretroviral therapies will offer the long term clinical and survival benefit of strong viral suppression without increasing risk of vascular disease. Based on results of our previous studies on lipodystrophy syndrome, we have proposed that lipodystrophy may be the result of antiviral drugs depleting the DNA content of mitochondria within fat cells. We propose to examine sequential fat biopsy specimens from HIV infected volunteers to determine whether antiretroviral therapy has had adverse effects on mitochondrial DNA content and-or function.Read moreRead less
The Role Of The Osteoblast In Mediating Glucocorticoid-Induced Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$825,254.00
Summary
Glucocorticoids (GC) exceed most other drugs in terms of numbers of patients treated and indications. Preventing or attenuating the deleterious effects of GC on fuel metabolism is therefore of great clinical significance. Our studies will create new knowledge regarding the mechanisms of GC-induced diabetes and osteoporosis, and will contribute to the development of new approaches that are essential to tackle the pressing medical problem of GC-induced disease.
IgA nephropathy is one of the most common causes of kidney failure in Australia and around the world, but there are currently no specific treatments proven to prevent kidney failure. The SIGNAL trial, jointly led by Australian and Chinese researchers, will bring together leading experts from around the world to reliably ascertain the effects of steroid therapy in this condition, and could potentially prevent many people from developing kidney failure in the future.