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.
IGF BINDING PROTEIN-2 A MODULATOR OF IGF ACTION IN DEVELOPING AND NEOPLASTIC NEURONAL CELLS.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged ....In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged brain, and in tumours, plays a key role on the surface of neurons in regulating IGF availability. We have shown that IGFBP-2 associates with a specialised protein on the nerve cells, where it is further processed to smaller fragments. We believe that these processes are reactivated following brain injury or in cancer states where IGFBP-2 is highly abundant. We propose to determine how IGFBP-2 influences IGF action on the nerve cell surface, and to further ascertain the function of each step in this process. We will achieve this by examining the effects of the mutated version of IGFBP-2, designed to either prevent its binding to the cell surface or its processing to smaller fragments. We will use various human and mouse nerve cell for these studies, which will not only provide greater understanding of the regulation of IGF availability to developing brain cell, but also point to how these processes may be involved in enhancement of recovery from injury or stroke, or possibly in acceleration of tumour growth. The finding of this study will offer the potential for new and exciting treatment designed to alter the function of the IGF system, to either make it more active in response to brain injury or stroke, or less active in brain tumours.Read moreRead less
Reducing The Burden Of Orthostatic Intolerance - Delineating Mechanisms And Improving Therapy
Funder
National Health and Medical Research Council
Funding Amount
$411,735.00
Summary
Orthostatic intolerance (OI) represents a heterogenous group of complex disorders which are poorly understood and lack effective treatment. They are frequently disabling and may severely impact on quality of life. In the proposed project, we will undertake a systematic investigation of _sympathetic nervous system� in OI patients and assess the clinical effect of a drug _L-DOPS� in subjects suffering from OI.
A Randomised, Double Blinded Intervention Study To Assess Health Effects Of Drinking Water From Rainwater Tanks
Funder
National Health and Medical Research Council
Funding Amount
$860,510.00
Summary
We are planning to perform a study in Adelaide to assess if drinking untreated rainwater causes a health risk. Eight years into a drought Australia's water sources are becoming increasingly depleted, so we need to reduce water consumption and consider using alternative sources of water. Increased use of rainwater is one of a number of solutions available. However, current recommendations state that rainwater can be safely used for purposes other than drinking, but because of potential contaminat ....We are planning to perform a study in Adelaide to assess if drinking untreated rainwater causes a health risk. Eight years into a drought Australia's water sources are becoming increasingly depleted, so we need to reduce water consumption and consider using alternative sources of water. Increased use of rainwater is one of a number of solutions available. However, current recommendations state that rainwater can be safely used for purposes other than drinking, but because of potential contamination and limited evidence regarding safety, drinking untreated rainwater is not approved by state health departments. The main outcome of this study will be to determine whether drinking untreated water from rainwater tanks poses a significant health risk. Additionally, we will determine if specific tank or maintenance characteristics can be identified that increase illness risk. The study design consists of following the health of 300 families who drink unboiled rainwater. Families will have a special tap installed that draws water through a water treatment unit (WTU). Half the families will have a working WTU and half will have a sham unit identical in appearance. The functional units sterilise water to remove any microorganisms present, while the sham filters have no effect. All participating families will keep a health diary for one year to record how often they suffer gastroenteritis. Neither the families nor the research workers will know which type of filter has been fitted. Water samples will be collected from selected households. At the end of a year the number of illnesses in the two groups will be compared. If those drinking rainwater from a sham filter suffer more often, then rainwater would be implicated as a source of gastroenteritis. This study will provide health authorities with a better understanding of the relationship between rainwater consumption and human health, and will provide data regarding safe uses of this alternative water source.Read moreRead less
Understanding Influenza Mortality And The Effects Of Vaccination In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$446,877.00
Summary
We will analyse mortality from influenza and other causes to estimate the numbers of deaths from other causes that are triggered by influenza in elderly persons, and to test the value of vaccination in preventing those deaths. Our results will help to decide whether an expensive clinical trial is really needed to show the benefit of influenza vaccination on all-cause mortality in the elderly.
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