Clinical Impact Of Clonal Pseudomonas Aeruginosa In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$547,238.00
Summary
In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on ....In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on the major bacterial problem, Pseudomonas aeruginosa. Several studies from Australia and the UK, including our own have shown that about 30% to 45% of patients share the same strain of Pseudomonas aeruginosa within a centre. We know that two dominant strains of Pseudomonas aeruginosa are found in CF centres on the eastern board of Australia. This is unexpected as this bacterium is usually acquired from the environment. The emergence of these clonal strains is causing increasing anxiety in the CF community. This study is designed to provide vitally needed information on the clinical implications of being infected by an clonal strain of Pseudomonas aeruginosa and the risk factors for the acquisition of an clonal strain. This new information will provide a rationale basis for the need for changes to infection control policies (including patient segregation), better outcome predictors for patients infected with clonal strain of Pseudomonas aeruginosa.Read moreRead less
Health Services Research: A Randomised Controlled Trial To Evaluate A Model Of Comprehensive Stroke Care
Funder
National Health and Medical Research Council
Funding Amount
$519,150.00
Summary
This study compares the length of stay and patient outcomes between two stroke care models - co-located acute-rehabilitation and dislocated acute-rehabilitation stroke care. In participating hospitals, acute stroke patients admitted to the emergency department will be randomly allocated to either model of care. Length of hospital stay and clinical outcomes will be examined 90 days post-stroke. Study results will provide high level of evidence for future stroke care model development.
Outcome Of Childhood Asthma In Adult Life And The Interaction With COPD
Funder
National Health and Medical Research Council
Funding Amount
$503,549.00
Summary
The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approac ....The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approaches to treatment of paediatric asthma nationally and internationally. The results of the study have been published widely over the years and cited extensively. The members of this cohort turn 50 in 2007 and will be invited to participate in a further review to reassess their clinical outcome to examine the relationship between long standing asthma and the development of COPD. Those members of the cohort who have had asthma persisting through their adult years have a degree of fixed obstruction on their tests of lung function and are potentially at risk of developing COPD. Some are at increased risk as approximately 30% of the members are regular smokers. In this review, at age 59 years, there is an excellent opportunity to examine the interaction of asthma and COPD and to compare the inflammatory processes between those who have continuing asthma, those whose asthma has resolved and in each group examine the effect of smoking. We will also look at a numbers of genetic markers associated with COPD to identify those who are more susceptible to the development of COPD. A second area of interest is the components of the immune system that influence asthma.. In an earlier study we identified one component of the immune system, known as the T cell system, that had returned to normal in those whose asthma had resolved. In this review, we plan to examine the T cell system in detail to understand what mechanisms may be responsible for resolution of childhood asthma.Read moreRead less
Evaluation Of Nitrous Oxide In The Gas Mixture For Anaesthesia: A Randomised Controlled Trial (The ENIGMA Trial)
Funder
National Health and Medical Research Council
Funding Amount
$490,125.00
Summary
There are about 2 million anaesthetics given each year in Australia (1:10 Australians), with more than 1 million Australians being exposed to nitrous oxide (laughing gas). Despite being around for more than 150 years, there has yet to be a large trial of the safety and benefits of nitrous oxide, particularly when compared with newer (safer?) anaesthetic drugs. Nitrous oxide is not a particularly strong anaesthetic and so it must be mixed with other drugs. Current practice in Australia and around ....There are about 2 million anaesthetics given each year in Australia (1:10 Australians), with more than 1 million Australians being exposed to nitrous oxide (laughing gas). Despite being around for more than 150 years, there has yet to be a large trial of the safety and benefits of nitrous oxide, particularly when compared with newer (safer?) anaesthetic drugs. Nitrous oxide is not a particularly strong anaesthetic and so it must be mixed with other drugs. Current practice in Australia and around the world is to give 70% nitrous oxide in oxygen along with another anaesthetic gas in order to produce a depth of anaesthesia sufficient for surgery. This is despite knowledge that nitrous oxide interferes with the production of DNA. DNA is used to programme cell division and function - it is the building block of cell and tisue growth. It is known that nitrous oxide can impair some tissue functions, such that anaemia and, possibly birth defects can occur. Such effects are rare, but recent evidence suggests that milder abnormalities may occur more commonly than previously thought. There is also good evidence that nitrous oxide increases the risk of severe nausea and vomiting after surgery. The adverse effects on DNA production raises the possibility of nitrous oxide causing immune deficiency, heart ischaemia, (angina), nerve and spinal cord damage, and increased cancer risk in hospital staff chronically exposed to low levels of nitrous oxide. The prevailing view is that nitrous oxide is a cheap, relatively safe drug that can reduce the exposure to other anaesthetic drugs. However, the development of many new anaesthetic drugs demands a re-evaluation of the role of nitrous oxide in current anaesthetic practice.Read moreRead less
Progression Of Influenza Virus Within The Respiratory Tract
Funder
National Health and Medical Research Council
Funding Amount
$513,716.00
Summary
We are exploring how influenza virus moves down the respiratory tract after infecting the nose. We have identified a component of mouse saliva that can halt the progression from the nose to the trachea and lungs and will determine how it binds to the virus to stop infection. We will also examine how human and highly lethal avian viruses move from the upper respiratory tract to other organs in the mouse and also in the ferret, which is a much better model for mimicking what happens in man.
Characterization Of Neutralizing Antibody Responses In HCV Infected Individuals.
Funder
National Health and Medical Research Council
Funding Amount
$478,076.00
Summary
Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attri ....Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attributed to the development of a strong cellular immune response and antibody is belived to play a monir role in achieving viral clearance. However, measurememnt of antibody responses in HCV infected pateints is routinely performed using conventional diagnostic tests that do not measure antibody that can help neutralize and clear virus. We have developed an assay that accurately measures the level of NAb in patient sera. We have found that chronically infected patients have broadly reactive neutralizing antibodies but that patients who clear virus, naturally or through treatment do not have broadly reactive neutralizing antibodies. Possibly explaining this phenomenon is that early during infection, antibody is frequently specific only to the infecting virus therefore to detect neutralizing antibodies, homologous viral sequences must be examined. In addition, we have found evidence that HCV can evade neutralzing antibodies through masking of sites to which antibodies bind. We propose to explore whether acutely infected patients develop NAb to autologous viral sequences, and how do these viral sequences and the antibody titre change throughout the course of infection and treatment. We also plan to determine the mechanism of neutralization resistance through the use of mutagenesis of resistant HCV glycoproteins. These studies are aimed at gaining a thorough understanding of the true role of antibody in HCV infection and its influence on viral evolution.Read moreRead less
A Multi-centre, Randomised, Controlled Trial Of BAL Directed Therapy In Young Children With Cystic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$571,750.00
Summary
The management of children with cystic fibrosis (CF) aims to delay the inevitable progression of lung disease that results from chronic lower respiratory tract infection (LRTI) and inflammation. Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) are increasingly used as research and clinical tools in the management of LRTI in CF infants and are integral to the monitoring of future drug trials and gene therapy. Early LRTI particularly with Pseudomonas aeruginosa (Pa) in CF is associated ....The management of children with cystic fibrosis (CF) aims to delay the inevitable progression of lung disease that results from chronic lower respiratory tract infection (LRTI) and inflammation. Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) are increasingly used as research and clinical tools in the management of LRTI in CF infants and are integral to the monitoring of future drug trials and gene therapy. Early LRTI particularly with Pseudomonas aeruginosa (Pa) in CF is associated with a decline in pulmonary function and an increase in morbidity and mortality. Many CF centres internationally now treat young children with CF using aggressive antibiotic protocols in an attempt to eradicate infection. Most centres use oropharyngeal specimens to diagnose LRTI with a sensitivity of around 45% and specificity of around 90%. Thus many children miss out on treatment or are exposed unnecessarily to antibiotics. The use of antibiotics themselves may increase the risk of infection with resistant organisms thus complicating the design of drug trials in young children as monitoring for the emergence of resistant new organisms requires BAL. It is thus of key importance that the safety and value of FB and BAL is examined and long term outcomes are obtained. The financial costs of managing patients with CF in Australia may be estimated at more than $85 million-annum. Early intervention strategies may reduce health costs because of improved morbidity or may increase costs due to the intervention. This will be the first time an economic evaluation of early management and the cost effectiveness of an intervention in children with CF has been undertaken which will enable responsible health care planning for this important group of patients. This trial provides a unique opportunity to study the relationship between LRTI and inflammation and long term outcomes such as lung function and radiological scores and will provide key evidence for designing future trials.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