Targeting Hypermutable ‘superbugs’ In Chronic Respiratory Infections By Optimised Antibiotic Combination Dosage Regimens
Funder
National Health and Medical Research Council
Funding Amount
$697,731.00
Summary
Many bacterial ‘superbugs’ can increase their mutation rate, i.e. become hypermutable, and thus rapidly become resistant to multiple antibiotics. Chronic lung infections with hypermutable bacteria cause increased ill-health and death in patients and current treatments do not work well. We will develop improved treatments using combinations of available antibiotics. This project will provide guidance to doctors on how to treat infections more effectively and minimise emergence of resistance.
Developing Irreversible Electroporation Non-Thermal Tumor Ablation For Organ-Confined Prostate Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$290,512.00
Summary
IRE is technique for targeted tissue ablation. Electrodes placed into the targeted area deliver intense, brief electric pulses. Nano-scale pores are created in the cell membrane killing the cells but preserving the extracellular matrix. The pulses do not affect sensitive structures including neurovascular bundles, major vasculature and ductal systems preserving their function. It may address prostate regions implicated in prostate cancer without damaging vital structures, reducing side effects.
Optimisation Of The Safety And Efficacy Of Protein Kinase Inhibitors Using Endogenous And Dietary Biomarkers
Funder
National Health and Medical Research Council
Funding Amount
$384,360.00
Summary
Many new cancer medicines are part of the 'kinase inhibitor' group of drugs. Although these drugs are effective in treating a range of different cancers, opportunities remain to improve the effectiveness and safety by more intelligently deciding the dose of the drug that a specific individual should receive. The research aims to assess whether the levels of chemicals normally present in the blood of individuals being treated can be used to guide the best dose an individual should receive.
Promoting Upper Limb Recovery After Stroke In People With Severe Paresis.
Funder
National Health and Medical Research Council
Funding Amount
$348,948.00
Summary
Stroke survivors with severe arm disability have poor potential for functional recovery. Yet, an incomplete understanding of indicators of good potential currently dictate clinical decisions concerning referral to rehabilitation and therapy provision. The proposed research aims to characterise the dynamic capacity of the severely damaged brain to recover. This research will provide the foundations for more personalized health care options and extend our understanding of this growing cohort.
Combating Bacterial 'superbugs' By Innovative Antibiotic Combination Strategies
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
Resistant bacteria are among the 3 most serious threats to human health. This project will substantially improve our quantitative understanding of how bacteria survive antibiotics and enable the design of innovative antibiotic combination therapies to combat resistant ‘superbugs’. My research outcomes will inform clinicians how to optimally use available antibiotics and greatly support rational development and optimisation of new antibiotics in collaboration with pharmaceutical industry.
Clinical And Physiological Evaluation Of Chinese Herbal Medicine For Constipation Predominant Irritable Bowel Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$592,705.00
Summary
This innovative study examines the effectiveness, safety and mechanisms of action of a complex Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS). IBS is the most common chronic medical disorder of the digestive tract with 10% prevalence in the Australian population. Characterised by abdominal pain and altered bowel habits, it significantly affects quality of life and has major socioeconomic implications. IBS is increasingly recognized as a complex multi-factorial condition with ps ....This innovative study examines the effectiveness, safety and mechanisms of action of a complex Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS). IBS is the most common chronic medical disorder of the digestive tract with 10% prevalence in the Australian population. Characterised by abdominal pain and altered bowel habits, it significantly affects quality of life and has major socioeconomic implications. IBS is increasingly recognized as a complex multi-factorial condition with psychogenic, hormonal and immune components. It is poorly addressed by current pharmaceutical treatments. Medical treatment of IBS remains unsatisfactory, with incomplete benefits offered by a single drug approach. The multi-factorial nature of IBS renders it an ideal candidate for evaluation with a more complex mix of low dose agents offered by herbal medicine. Specifically, CHMs by their complex chemical nature have substantial potential in the treatment of IBS because of their range of physiological effects on both bowel function and the central nervous systems We will perform a clinical trial of 8 weeks to determine the effectiveness of a chemically standardised CHM preparation in 160 patients with constipation predominant IBS patients compared to an identical placebo (sham). This project builds on our previous studies that demonstrated an effectiveness of CHM for IBS superior to current interventions. We’ve validated methods to ensure chemical standardisation of herbal medicines; validated approaches to psychosocial assessment of cognitive and behavioural changes in IBS patients; and have validated physiological, mechanistic evaluation of the lower bowel in response to treatment. The significance of the current proposal lies in its ability to provide a standardised, multi-component CHM (8 herbs) for the comprehensive clinical evaluation of the efficacy and safety of this type of therapy for IBS, and to provide insight into the relevant mechanisms of action. This project draws together the unique skills and previous studies from the Centre for Complementary Medicine Research (UWS), and the Gastrointestinal Investigation Unit of RNSH, USYD. This innovative project is medically important because it addresses a common gastrointestinal disorder with high socioeconomic implications for which conventional western medicine has failed to produce a cure or adequate palliative treatment.Read moreRead less
The Pharmacokinetic, Pharmacodynamic And Pharmacogenomic Outcomes Of Reduced Dosage Of Efavirenz: The Encore1 Study
Funder
National Health and Medical Research Council
Funding Amount
$1,234,943.00
Summary
Our primary aim is to assess blood concentrations of a drug called efavirenz, an important drug used in the treatment of HIV infection and associate these with variability of genes that control metabolism of the drug. A better understanding of gene variability and how it relates to safety and efficacy outcomes at a reduced, compared to a standard dose of efavirenz could support improved treatment of HIV disease.
Redefining Antibiotic Dosing To Reduce Bacterial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$474,513.00
Summary
>3000 Australians die every year from severe infections (nearly 3-fold higher in number than our annual road toll). These treatment failures are due to sub-optimal antibiotic dosing from a poor understanding of why concentrations are different in these patients. I will use my laboratory to define what antibiotic concentrations we need to achieve and perform clinical studies with my collaborative network to demonstrate that we can redefine antibiotic dosing to reduce the emergence of superbugs ....>3000 Australians die every year from severe infections (nearly 3-fold higher in number than our annual road toll). These treatment failures are due to sub-optimal antibiotic dosing from a poor understanding of why concentrations are different in these patients. I will use my laboratory to define what antibiotic concentrations we need to achieve and perform clinical studies with my collaborative network to demonstrate that we can redefine antibiotic dosing to reduce the emergence of superbugs.Read moreRead less
Improving The Therapeutic Use Of Anti-infective Agents: Application Of Pharmacometrics For Rational Dosing Regimen Design
Funder
National Health and Medical Research Council
Funding Amount
$313,390.00
Summary
There is no field of medicine in which the individualisation of medicines is more important than in infectious diseases – appropriate doses must be administered to maximise efficacy and to minimise side effects and the emergence of drug-resistance. This fellowship will use the emerging science of pharmacometrics to investigate factors contributing to the variability in response to anti-infective medications and to optimise dosing regimens for the best use of these drugs in clinical practice.
This project will improve our understanding of how painkiller medicines work in very old and frail people which will improve the use of these medicines in pain management. This study will carefully examine pain control with two of the most commonly used pain killer medicines - paracetamol and oxycodone. By understanding all the factors that influence an older persons pain control we will be able to improve the safe and effective use of painkiller medicines in this special group of people.