Methods For Evaluating The Therapeutic Impact Of Diagnostic Tests - Development Of Guidelines
Funder
National Health and Medical Research Council
Funding Amount
$132,325.00
Summary
New diagnostic tests are frequently adopted in clinical practice without any evidence that they improve patient outcomes. This project will produce the first guidelines about the role and optimal design of studies assessing the impact of a new test on therapeutic decisions for conclusions about its clinical value. This work will inform researchers and clinicians to improve evidence-based diagnostic practice and promote the more efficient use of limited health care resources.
Consumer Information Materials And A Communication Aid For Diagnostic Tests For Breast Disease
Funder
National Health and Medical Research Council
Funding Amount
$105,863.00
Summary
Many studies have now shown that the majority of patients want to participate in clinical decisions about medical treatments they might receive. As a result, information materials are being developed to help consumers and doctors work together to reach satisfying treatment decisions which are based on the best available evidence and also reflect the individual patient's needs and preferences about the treatment options. Very little is known, however, about whether consumers also want to particip ....Many studies have now shown that the majority of patients want to participate in clinical decisions about medical treatments they might receive. As a result, information materials are being developed to help consumers and doctors work together to reach satisfying treatment decisions which are based on the best available evidence and also reflect the individual patient's needs and preferences about the treatment options. Very little is known, however, about whether consumers also want to participate in decisions about whether to have a medical test. Tests can be trivial, such as a blood or urine test, or quite major and invasive, such as a biopsy or a colonoscopy. People considering a medical test might want to know the answers to the following questions: What is my chance of having the disease being tested for? If the test result is positive what is the chance I have the disease? If the test result is negative what is the chance I have the disease anyway? How will the test result influence treatment of my condition? What are possible side-effects of the test? Generally information materials about medical tests only describe the test itself, and do not contain the information people need to answer these questions. Even doctors may not have to hand the data needed to answer these questions. Yet without this information, consumers cannot make truly informed and rational choices about whether to have the test. This project aims to find out whether consumers want to participate in decisions about medical tests, what information they would want to do this, and to develop and trial information materials and a communication aid for a small number of breast cancer tests. We will use tests for diagnosing breast cancer as our model but we anticipate the work will be applicable across a wide range of medical tests.Read moreRead less
Infrared Spectroscopic Imaging In The Diagnosis Of Cervical Cancer
Funder
National Health and Medical Research Council
Funding Amount
$291,600.00
Summary
In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to pro ....In Victoria alone around 500000 Pap smears a year are examined for evidence of cancer of the cervix or conditions that may lead to cancer. This is a time consuming, labour intensive and costly process with a relatively high failure rate. A number of alternative techniques have been explored in the last decade with a view to providing a diagnostic technique that is free of human error, more reliable than the Pap method and easily used. An alternative technique based on using infrared light to probe smears shows promise in providing such an easily automated reliable method. We, and others have spent a number of years exploring this technique and have solved a number of the problems associated with it. Based on our work in the field and the work of others we now wish to develop a methodology using an infrared micro-imaging spectrometer combined with multivariate statistics that can be used to diagnose cervical cancer and the conditions that lead to cervical cancer.Read moreRead less
A SYSTEMS BIOLOGY APPROACH TO SCREENING, DIAGNOSIS AND PROGNOSIS FOR LYSOSOMAL STORAGE DISORDERS
Funder
National Health and Medical Research Council
Funding Amount
$900,781.00
Summary
Lysosomal storage disorders (LSD) are inherited and, at present, can only be detected in children after symptoms are obvious. We are developing newborn screening for LSD to detect affected babies before the onset of irreversible symptoms. As most LSD babies appear normal at birth it is important to be able to predict disease severity or rate of disease progression; this will help doctors know when to give therapy, which therapy is best and provide families with appropriate genetic counseling.
New Methods Of Pain Assessment In Demented Older Persons
Funder
National Health and Medical Research Council
Funding Amount
$306,000.00
Summary
There are substantial risks of inadequate pain assessment and management in persons with cognitive impairment and particularly in those with communication problems. Undetected or under-treated pain can have serious adverse effects on frail older adults including poorer cognitive performance, increased levels of depression, anxiety and disruptive behaviours, a reduced quality of life and higher levels of functional disability. These adverse effects contribute to greater demands for daily nursing ....There are substantial risks of inadequate pain assessment and management in persons with cognitive impairment and particularly in those with communication problems. Undetected or under-treated pain can have serious adverse effects on frail older adults including poorer cognitive performance, increased levels of depression, anxiety and disruptive behaviours, a reduced quality of life and higher levels of functional disability. These adverse effects contribute to greater demands for daily nursing care and a corresponding increase in health care costs. The present proposal aims to develop more sensitive, reliable and valid questionnaire and non-verbal measures of pain in older adults with cognitive impairment and particularly in those with verbal communication problems. By completion, the present studies should provide much needed information on the reliability and validity of several different types of verbal and non-verbal indicators of possible pain. This research should lead to improved pain assessment and management for the growing segment of the population who suffer from pain and impaired cognitive function.Read moreRead less
Transposable Element Mobility And Chromosomal Rearrangement In The Fungal Pathogen Cryptococcus During Human Infection
Funder
National Health and Medical Research Council
Funding Amount
$322,028.00
Summary
Pathogenic fungi present in the environment have emerged as an increasingly common threat to human health. Cryptococcus neoformans and the closely related species Cryptococcus gattii are the leading causes of life-threatening fungal meningitis, and Australia is one of the few countries where both species are prevalent. Although C. neoformans is an increasingly common cause of infection in immunocompromised patients such as those suffering from AIDS, approximately one in four infected individuals ....Pathogenic fungi present in the environment have emerged as an increasingly common threat to human health. Cryptococcus neoformans and the closely related species Cryptococcus gattii are the leading causes of life-threatening fungal meningitis, and Australia is one of the few countries where both species are prevalent. Although C. neoformans is an increasingly common cause of infection in immunocompromised patients such as those suffering from AIDS, approximately one in four infected individuals has no apparent immune system defect. For patients with AIDS, in the absence of antiretroviral therapy cryptococcal infection is incurable and requires lifelong treatment with antifungal medication to keep the infection in check. During infection, Cryptococcus is under tremendous stress enforced not only by the immune system and the presence of antifungals, but also by the high temperature, nutrient limiting environment encountered in the host. The proposed research will reveal how Cryptococcus evolves in this environment to enable persistence of infection despite medical intervention. I propose that naturally occurring mobile genetic elements present in the Cryptococcus genome cause chromosomal rearrangements during long term infection to produce gene deletions and duplications that facilitate survival. By characterising these changes and the genes associated with them, the research will identify novel genes involved in pathogenesis and will increase our understanding of the infection process. The expected outcome of this project is a detailed understanding of the roles mobile element movement and chromosomal rearrangement play in Cryptococcus during infection, and how these affect genes that contribute to the pathogenic process. The fundamental knowledge gained from this study will facilitate studies designed to combat infections in the clinical setting, provide new drug targets and help foster the development of more effective therapies.Read moreRead less
Impact Of Oesophageal Afferent Processing On Regulatory And Protective Reflexes, And Perception Of Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$247,500.00
Summary
Symptoms of acid reflux, heartburn and regurgitation, are extremely common, occurring weekly in 20% of the population. Curiously, about 1-4 of people with heartburn don't have any more acid exposing their oesophagus than do normal people. We do not understand this apparent increased sensitivity. Many patients with reflux present with cough, asthma, hoarseness, sore throat or even lung fibrosis. Regurgitation of acid causes some of these conditions. It is estimated that 60% of adult asthmatics ha ....Symptoms of acid reflux, heartburn and regurgitation, are extremely common, occurring weekly in 20% of the population. Curiously, about 1-4 of people with heartburn don't have any more acid exposing their oesophagus than do normal people. We do not understand this apparent increased sensitivity. Many patients with reflux present with cough, asthma, hoarseness, sore throat or even lung fibrosis. Regurgitation of acid causes some of these conditions. It is estimated that 60% of adult asthmatics have reflux for example. The purpose of this research is to examine the notion that the sensory nerves coming from the oesophagus are somehow tuned up to fire off too readily. If true this phenomenon may well underlie the inappropriate relaxation of the oesophageal valve mechanisms that normally prevent acid flowing up into the throat and into the airways. Additionally it may explain why so many sufferers seem to be hypersensitive to even small amounts of acid. These studies will better define the nerve pathways involved in heartburn and regurgitation and help us target these diseases with specific drugs in the future.Read moreRead less
PROTEIN PROFILING FOR THE IDENTIFICATION AND MONITORING OF LYSOSOMAL STORAGE DISORDERS AND OTHER NEUROLOGICAL DISEASES
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
Lysosomal storage disorders (LSD) are a group of more than 45 progressive genetic diseases, that result from the absence or impaired function of a specific enzyme in each of the body's cells. Lysosomes rid the cell of excess waste. Impaired enzyme function halts this process and waste begins to accumulate (or 'store') in the cell. Disease severity and patient longevity is variable, but severely affected patients often die by their mid-teens. LSD can affect the skeleton and joints, respiratory an ....Lysosomal storage disorders (LSD) are a group of more than 45 progressive genetic diseases, that result from the absence or impaired function of a specific enzyme in each of the body's cells. Lysosomes rid the cell of excess waste. Impaired enzyme function halts this process and waste begins to accumulate (or 'store') in the cell. Disease severity and patient longevity is variable, but severely affected patients often die by their mid-teens. LSD can affect the skeleton and joints, respiratory and cardiovascular systems, the brain, the eyes, the ears and the airways. As affected children become older, symptoms worsen. Patients often require frequent hospitalisation, and medical and surgical intervention. Approximately 10 to 15% of the general population are affected or carriers of an LSD. In Australia, one LSD child is born in every 5,000 live births. Diagnosis often takes several years, and families often have other children before their affected child is diagnosed. LSD are, therefore, a considerable burden to not only the families but also to the health care system. The goal of the Lysosomal Diseases Research Unit is Diagnosis at birth and effective therapy for lysosomal storage disorders. To this end we have been working toward the development of a newborn screening program for LSD and improved methods for the diagnosis and monitoring of therapy in this group of diseases. In this project we propose to develop and evaluate the use of protein profiling (looking at many diagnostic markers at the same time) to achieve these goals. The technology developed in this project will have potential application beyond LSD. Lysosomal dysfunction has been implicated in Alzheimer's disease and Parkinson's disease; in addition lysosomal proteins are reported to be involved in the spread of some cancers and may be useful markers for early detection. We will collaborate with other research groups to further develop protein profiling in these areas.Read moreRead less
Why Does Peripheral Airway Dysfunction Lead To Broncholitis Obliterans Syndrome In Lung Transplantation?
Funder
National Health and Medical Research Council
Funding Amount
$312,927.00
Summary
The uneven way that airways narrow (heterogeneity) is an important factor affecting the natural history, clinical expression and response to treatment in patients following lung transplantation. In the proposed study we plan to monitor the heterogeneity of the airways in patients immediately following lung transplantation and relate these changes to immunological markers of lung rejection.
How Do Glycosaminoglycans Promote The Propagation Of Prions?
Funder
National Health and Medical Research Council
Funding Amount
$512,270.00
Summary
The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major c ....The prion diseases are a group of transmissible, neurodegenerative disorders affecting both humans and animals. The most common form in humans is sporadic Creutzfeldt-Jakob disease (CJD), although acquired (variant CJD) and inherited (familial CJD) forms are recognised. Prion diseases are transmissible to the same species by inoculation with, or dietary exposure to, infected tissues. The infectious agent, referred to as a prion , has not been identified at the molecular level. However, a major component of purified prions is an abnormal disease associated form of the host encoded prion protein. Understanding how the disease associated form of the prion protein is generated and how host-derived cofactors contribute to its formation will help in our understanding of the infectious nature of these diseases and in the development of effective therapeutic and prophylactic strategies. Glycosaminoglycans are host-derived components of the extracellular matrix that are associated with prion protein plaques found in the brain tissue of patients with prion diseases. Glycosaminoglycans are believed to influence the transmission of prions and the ongoing propagation of infectivity. In this study the importance of glycosaminoglycans in the formation of the disease associated prion protein and the generation of infectivity will be investigated using both cell-free and cell-based models of prion propagation. The understanding gained from this study will be used to develop a high throughput assay that can be used to detect prion infection prior to the development of clinical disease and within a time frame whereby therapeutic intervention may be effective.Read moreRead less