Predictive Models And Interventions For Coronary Heart Disease In Aboriginal And Torres Strait Islander People
Funder
National Health and Medical Research Council
Funding Amount
$203,125.00
Summary
The main causes of heart disease in western countries are smoking, high blood pressure and high cholesterol. However, in indigenous populations, other factors may be more important. We propose to look at these conventional risk factors and others like diabetes, blood clotting disorders and inflammation to see which are best for predicting heart attack in Aboriginal and Torres Strait Islander people . We will also examine the effect of heart disease prevention programs run by communities, to see ....The main causes of heart disease in western countries are smoking, high blood pressure and high cholesterol. However, in indigenous populations, other factors may be more important. We propose to look at these conventional risk factors and others like diabetes, blood clotting disorders and inflammation to see which are best for predicting heart attack in Aboriginal and Torres Strait Islander people . We will also examine the effect of heart disease prevention programs run by communities, to see if they can improve these risk factors. Finally, we will use this information to produce educational materials and clinical tools for health services.Read moreRead less
Cataract Surgery And Risk Of Age-related Macular Degeneration (AMD)
Funder
National Health and Medical Research Council
Funding Amount
$339,750.00
Summary
Cataract surgery currently ranks as one of the most frequently performed and successful surgical procedures in Australia (125,000 operations-year). Age-related macular degeneration (AMD) is the principal cause of moderate visual impairment and blindness, currently accounting for blindness in between 17,300 and 30,400 Australians. Past studies have not shown a definite relationship between cataract and AMD. Follow-up data from clinical case series and from two older population-based studies (the ....Cataract surgery currently ranks as one of the most frequently performed and successful surgical procedures in Australia (125,000 operations-year). Age-related macular degeneration (AMD) is the principal cause of moderate visual impairment and blindness, currently accounting for blindness in between 17,300 and 30,400 Australians. Past studies have not shown a definite relationship between cataract and AMD. Follow-up data from clinical case series and from two older population-based studies (the Beaver Dam and Blue Mountains Eye Studies) suggested that cataract surgery might increase the risk of subsequent development of AMD in operated eyes of older persons. Such an increased AMD risk in eyes after cataract surgery appears to be both short term (observation from clinical case series) and long term (evidence from population-based studies), and persists after taking into consideration age, sex, smoking, preexisting early stage lesions of the disease and correlation between both eyes. The proposed study is to follow a large number of older patients who are undergoing cataract surgery in Western Sydney Eye Hospital and in two ophthalmologists' private rooms. Rates of subsequent development of AMD will be compared between operated and non-operated eyes, and also between the surgical cohort and the Blue Mountains Eye Study cohort. We will document macular conditions carefully before and after surgery to exclude the possibility of confounding issues. We will also investigate whether the increased risk occurs in certain subgroups of patients at high risk of AMD. If an increased AMD risk from cataract surgery is confirmed in subgroups of patients, a modified clinical practice may be indicated, to maximize cataract surgery benefit and minimize the risk of vision loss from AMD after surgery. Changes may include additional patient information and consent about this risk, delayed cataract surgery within limits of visual function, and close postoperative follow up.Read moreRead less
Schizophrenia affects, on average, 1% of the population over a lifetime and accounts for 2.6% of the global burden of disease and disability, according to a joint study by the World Health Organization and the World Bank. It is a complex disorder involving both genetic and environmental risk factors, but the specific causation remains poorly understood. People with schizophrenia experience symptoms such as delusions and hallucinations, distorted perception of reality, and progressive loss of mot ....Schizophrenia affects, on average, 1% of the population over a lifetime and accounts for 2.6% of the global burden of disease and disability, according to a joint study by the World Health Organization and the World Bank. It is a complex disorder involving both genetic and environmental risk factors, but the specific causation remains poorly understood. People with schizophrenia experience symptoms such as delusions and hallucinations, distorted perception of reality, and progressive loss of motivation, which disrupt personal development. Recent research demonstrates that underlying cognitive impairments, affecting reasoning, memory, planning ability and information processing, are at the core of the disorder and account for a high proportion of these handicaps. In a study involving 112 families with members suffering from schizophrenia, Western Australian researchers carried out detailed investigations of brain cognitive functioning, coupled with a complete genome scan. They identified, in about 50% of these families, a variety of schizophrenia characterized by multiple cognitive deficits, which turned out to be linked to a particular segment of chromosome 6. It was exactly in the chromosomal region where US investigators had previously found genetic linkage with the symptoms of schizophrenia in a large series of Irish families. In this project, the Western Australian and US teams, together with a group of Dutch researchers, will embark on a joint search for the gene (or genes) on chromosome 6, contributing to cognitive deficits in schizophrenia. They will assess a further large series of patients and controls, and conduct molecular genetic studies aiming to pinpoint the specific gene defect or variant. If successful, the project will have far-reaching implications for defining novel drug targets and treatment strategies for this disabling disorder.Read moreRead less
The Construction And Validation Of The Assessment Of Mental Health Related Quality Of Life (PsyQoL) Instrument
Funder
National Health and Medical Research Council
Funding Amount
$539,450.00
Summary
Mental Health is one of the national health priority areas as well as one of the largest contributors to burden of disease. WHO projections suggest that by 2020 the burden of depression alone will be second only to cardiovascular disease. New treatments for mental disorders are being developed which must be evaluated. Current research methods do not allow an accurate comparison of the cost effectiveness of these therapies with the cost effectiveness of other medical services as this requires the ....Mental Health is one of the national health priority areas as well as one of the largest contributors to burden of disease. WHO projections suggest that by 2020 the burden of depression alone will be second only to cardiovascular disease. New treatments for mental disorders are being developed which must be evaluated. Current research methods do not allow an accurate comparison of the cost effectiveness of these therapies with the cost effectiveness of other medical services as this requires the measurement of 'utility' or 'quality of life'. The small number of 'generic' 'quality of life instruments' developed to date vary significantly in their 'sensitivity' to different illnesses-their ability to detect change-and none is very sensitive to changes in mental health states. The present project is to overcome this deficit. This will be achieved by refining and expanding an instrument developed in Australia, the Assessment of Quality of Life (AQoL) instrument. This is the only instrument to date which was both constructed using correct psychometric principles of instrument construction and which describes health states in terms of the effect upon a patient's ability to function in a social environment. The new instrument called the PsyQoL will increase instrument sensitivity by including a mental health 'module' to the existing instrument and revising existing items. The methods used will include several methodological innovations in the description of health states and the derivation of utility scores. The project will include a large scale 'validation' study which will include the construction of population 'norms' and also the creation of 'exchange rates' between the PsyQoL and other instrument scores. The significance of the project is that the PsyQoL will allow valid and reliable measurement of health states in a way that creates a 'level playing field' between mental and other health related interventions.Read moreRead less
Risk Factors For Compliance With Command Hallucinations In Psychotic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$180,290.00
Summary
There is widespread public concern about the danger individuals with schizophrenia or related disorders pose to themselves and to the community. Whilst a number of violence risk factors such as being male, exhibiting hostility, and having a prior history of violence are well established, they are of limited use to clinicians in making management decisions. Our study will investigate a different approach to identify individuals and occasions when a sufferer might require more intensive care or ob ....There is widespread public concern about the danger individuals with schizophrenia or related disorders pose to themselves and to the community. Whilst a number of violence risk factors such as being male, exhibiting hostility, and having a prior history of violence are well established, they are of limited use to clinicians in making management decisions. Our study will investigate a different approach to identify individuals and occasions when a sufferer might require more intensive care or observation. Most individuals with schizophrenia experience auditory hallucinations. Amongst these hallucinations, voices that command the individual to undertake a particular action are common; many of these involve significant potential harm to the hallucinator or to other persons. We will attempt to identify those factors that are associated with an individual obeying command hallucinations. Variables to be examined include the characteristics of the hallucinated voices, and the beliefs of the subject about the power of the voices. Subjects will be interviewed to find out whether they have delusions that are consistent with their hallucinations, whether they suffer from Antisocial Personality Disorder, or are dependent on alcohol or drugs. We will also determine whether subjects who report being raised by authoritarian parents, who are dependent on the approval of others, or who see external factors as determining the occurrence of major events in their lives, are more likely to act on their hallucinations. Two groups of 100 patients will be studied. One group will be representative of people living in the community with schizophrenia. The other group will be people with schizophrenia who have been treated by the State Forensic Psychiatric Services. Statistical models will be developed in order to determine the accuracy with which compliance with command hallucinations can be predicted. These models with also reveal which risk factors are the most important.Read moreRead less
Health-Related Quality Of Life In Intractable Paediatric Epilepsy: Using A New Measure To Improve Management
Funder
National Health and Medical Research Council
Funding Amount
$252,940.00
Summary
Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. ....Until recently there was no adequate measure to assess the quality of life of children with epilepsy. Our Australian centre was the first to develop, validate and publish such an instrument; the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). We now aim to collect more data using the QOLCE to gain further understanding of the effects of epilepsy and its treatment on the quality of life of children. We will determine if surgery in children stops seizures and improves quality of life. We also aim to find out if children with different types of epilepsies have unique quality of life issues. Finally, we aim to determine if the quality of a child's life depends on how well they are thinking and learning or how often they are having seizures. We will conduct this study in children with difficult epilepsy recruited from three major children's hospitals (Sydney Children's Hospital, the Children's Hospital, Westmead, Miami Children's Hospital, Florida USA) using a well designed methodology. Each child will have their particular type of epilepsy characterised using video and brain wave analysis. Each parent and older child will receive a quality of life package including the QOLCE to assess life function. In addition, all children will have an assessment of their thinking and learning by a child psychologist. At the completion of this project we will have established whether surgical treatment in children with epilepsy stops seizures and improves quality of life. This will allow clinicians and parents to better understand the effects of surgical treatment in this population. In addition, we will determine if problems in quality of life are associated with specific types of epilepsy. This information can be used to counsel families and tailor interventions and treatments. Finally, we will know whether a child's quality of life is determined by problems with thinking and learning and-or seizures.Read moreRead less
Conditionally Replicative Adenoviruses For Mesothelioma Therapy
Funder
National Health and Medical Research Council
Funding Amount
$260,600.00
Summary
Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy ....Australia has one of the highest incidences of mesothelioma in the world. The clinical outcome for patients with this disease is extremely poor, with median survival of only 6-9 months. The latest developments in chemotherapy, radiotherapy and radical surgery have done little to improve the overall survival rate. New approaches to therapy are thus required. Oncolytic therapy using conditionally replicative adenoviruses (CRAds) is a novel and promising approach to cancer treatment. This strategy relies on selective viral replication in (and therefore death of) tumour cells but not normal cells. In principle, mesothelioma is an attractive target for this therapeutic approach owing to its propensity to remain localised to the pleural space until late in the disease. However, for any CRAd strategy to succeed, viral replication must be limited to the tumour cells so as not to cause unnecessary toxicity to normal tissues. This level of specificity can potentially be achieved by using cell-specific promoters to control the expression of viral genes essential for replication. To date however, there have been no reports evaluating candidate mesothelioma-specific promoters in adenoviral vectors. Furthermore, other issues such as tumour a lack of viral receptors or tumour-associated fibrosis could limit viral spread through a mesothelioma mass and reduce the efficacy of the approach. In this proposal we will contruct and test CRAds which are controlled by promoters which we believe will be highly active in mesothelioma, but very poorly active in other tissues. We will test the ability of these new agents to kill mesothelioma cells in tissue culture, in pieces of mesothelioma tumours removed from patients, and in animal models. If successful, this approach could offer new hope for mesothelioma patients.Read moreRead less
Targeting MYC-driven Cancers By Inhibition Of The MTOR Pathway
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
This proposal will evaluate a new strategy for treating cancers associated with the cancer causing gene MYC. Globally there are more than 1 million cases of MYC-associated cancers diagnosed per year. Based on encouraging early results we will test if turning off the proteins associated with mTOR will be an effective strategy for treating MYC cancers using state-of-the-art cancer models and investigate why these cancers respond.
Testing A Home Based Rehabilitation Program For Survivors Of A Critical Illness: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$447,602.00
Summary
The aim of this study is to evaluate whether a home-based, individually tailored physical rehabilitation program can improve the physical and psychological recovery for survivors of a critical illness. Surviving a critical illness results in physical de-conditioning and emotional sequelae. Many observational studies have demonstrated a delayed recovery, often beyond a six-month period. At present there is a lack of specific service provision for the recovering intensive care patient, and prelimi ....The aim of this study is to evaluate whether a home-based, individually tailored physical rehabilitation program can improve the physical and psychological recovery for survivors of a critical illness. Surviving a critical illness results in physical de-conditioning and emotional sequelae. Many observational studies have demonstrated a delayed recovery, often beyond a six-month period. At present there is a lack of specific service provision for the recovering intensive care patient, and preliminary work by us indicates a need for an outreach follow-up service for ICU survivors that does not require individuals to attend an outpatient clinic. The 8-week program includes prescribed training of lower limb exercises, walking, and upper limb exercises, with the goal of improved physical strength and endurance at study end-point of 26 weeks. The standardised leg and arm exercises will be adjusted according to participant progress, using a specifically designed rehabilitation manual. Physical function, endurance and psychological well-being between the usual care and this program will be compared. Importantly, the project addresses outcomes that are clinically meaningful for the patients. It is designed to evaluate whether physical rehabilitation for people recovering from a critical illness improves physical and psychological recovery, which contribute to how people function and they feel. There appears to be little research in this area, so the innovative aspects of the study are an important consideration. The project addresses one of the National Research Priorities using an exercise-based rehabilitation program. It also provides an important innovation: successful implementation and positive findings from this home-based rehabilitation program will provide a model of care that existing primary care or community services can adopt so that all survivors of a critical illness will have the opportunity to improve their physical and psychological recovery.Read moreRead less