A Randomised Controlled Trial Comparing Intraoperative To Conventional Radiotherapy In Women With Early Beast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$874,046.00
Summary
With the advent of breast screening in Australia many women are diagnosed with small low risk cancers that can be treated with breast conserving therapy with good outcomes. Surgery and radiotherapy in this situation are used to minimise the risk of local recurrence. It is now being questioned whether we can tailor radiotherapy to suit individual patients rather than recommending the daily 6-7 weeks of standard external beam radiotherapy to all patients. This trial aims to answer this question as ....With the advent of breast screening in Australia many women are diagnosed with small low risk cancers that can be treated with breast conserving therapy with good outcomes. Surgery and radiotherapy in this situation are used to minimise the risk of local recurrence. It is now being questioned whether we can tailor radiotherapy to suit individual patients rather than recommending the daily 6-7 weeks of standard external beam radiotherapy to all patients. This trial aims to answer this question as a new device which can deliver radiotherapy intraoperatively in a single session has now been tested and proven safe to use in the breast. The main objective of this trial is to demonstrate that a single dose of radiotherapy delivered intraoperatively (IORT) gives an equivalent local control rate to standard external beam radiotherapy in women with early low risk breast cancer who are suitable for breast conserving therapy. Other objectives include comparing the two treatments with respect to; disease-free-overall survival, cosmetic outcome, patient satisfaction-preference, quality of life and cost benefit. If the study finds that IORT alone after breast conserving surgery is as effective in achieving local control as standard external beam radiotherapy, a major benefit to patients would be shorter treatment duration by avoiding the 6-7 weeks of standard radiotherapy. A reduction in the number of early breast cancer patients requiring access to standard radiotherapy would also benefit treatment centres and other cancer patients by reducing the waiting times for radiotherapy. Consumer groups have supported the concept from the beginning and there has been recent increase in level of support by originally unsupportive groups. Of great significance is this trial offers an opportunity to formally investigate the efficacy of delivering IORT in the safe confines of a clinical trial, before allowing it to become a standard treatment which is occurring in other countries.Read moreRead less
Improving Muscle Function After Injury: Novel Tissue Engineering Strategies For Exercise, Surgery And Sports Medicine
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel thera ....Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel therapeutic approach to restore muscle structure and function to damaged muscles after injury or disease. Our recent research using controlled release of growth factors from biodegradable hydrogels has exciting application for muscle repairafter injury. We will utilize these cutting edge tissue engineering strategies to deliver to damaged muscles a hydrogel containing controlled delivery (slow release) microcapsules loaded with an anabolic agent (the beta-agonist, formoterol) and-or a growth factor (IL-15) designed to enhance functional muscle repair after three distinct but clinically relevant models of muscle injury: a) crush injury: A model for muscle injuries on the sports field, in the workplace, and those associated with road trauma; b) ischaemia-reperfusion injury: a model for muscle damage associated with surgical interventions, muscle transfers for functional restoration, and other injuries associated with plastic and reconstructive surgery; and c) contraction-induced injury: a model for strain injuries such as hamstring muscle tears that can occur on the sports field. After injury we will assess functional muscle repair using a comprehensive series of histological, biochemical, molecular, immunochistochemical, and physiological techniques. The research has broad application to exercise and clinical medicine; including sports, emergency and rehabilitation medicine, and plastic, reconstructive, and orthopaedic surgery.Read moreRead less
Randomised Controlled Trials Of Laparoscopic Techniques For Antireflux Surgery
Funder
National Health and Medical Research Council
Funding Amount
$1,031,381.00
Summary
Gastro-oesophageal reflux is common, with approximately 10% of Australians now using medication to control symptoms. Many Australians will need this medication for life, unless they undergo surgery. The cost of treating reflux is growing. Since 1992 the annual growth rate of the Pharmaceutical Benefits Scheme expenditure on reflux medication has been 13%, and the annual cost for the treatment of reflux now exceeds $1 billion. Not all patients with reflux are satisfied with medication, as some co ....Gastro-oesophageal reflux is common, with approximately 10% of Australians now using medication to control symptoms. Many Australians will need this medication for life, unless they undergo surgery. The cost of treating reflux is growing. Since 1992 the annual growth rate of the Pharmaceutical Benefits Scheme expenditure on reflux medication has been 13%, and the annual cost for the treatment of reflux now exceeds $1 billion. Not all patients with reflux are satisfied with medication, as some continue to experience symptoms. Surgery is the only treatment which will cure reflux. It has a clear role in the treatment of patients with ongoing symptoms, those who don t want to take tablets, and patients with a large hiatus hernia in whom symptoms occur due to the relocation of the stomach from the abdomen into the chest. Approximately 5,000 Australians per year undergo surgery for reflux. The standard operation achieves a good outcome in approximately 90%, although some patients are troubled by side effects. To reduce the risk of this, the original procedure has been modified. However, the evidence supporting modifications has until recently been limited. The best way to compare different operations is in randomised trials. The majority of the largest and best trials addressing this area have been undertaken in Adelaide. We have already entered 504 patients into 5 randomised trials, 4 conducted entirely in Adelaide, and one across multiple sites with the cooperation of 15 Australasian surgeons. These trials have provided a more reliable evidence base for surgeons undertaking surgery for reflux. However, long term follow-up is required to ensure that conclusions drawn are valid at late follow-up. In addition we are establishing 2 new randomised trials, which will determine how best to perform surgery for reflux, and how best to repair a large hiatus hernia. These studies will be undertaken in collaboration with more than 25 other surgeons throughout Australia.Read moreRead less
Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have b ....Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have been used extremely successfully in the treatment of some leukaemias. Unfortunately, retinoids have not worked as well in other cancers. We have identified an important role for abnormal retinoid function in the evolution of pancreatic cancer, which may be responsible for the lack of effective response to retinoid treatment. This project focuses on identifying if these abnormalities in retinoid function can be reversed with adding specific pharmaceuticals so that retinoid based therapies will be effective in pancreatic cancer.Read moreRead less
Delayed Phase Of Remote Ischemic Preconditioning: Clinical Application And The Role Of Kallikrein-kinin Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$159,197.00
Summary
Brief episodes of interruption of blood flow to the arm or leg provide strong protection against prolonged interruption of blood flow to a target organ (e.g., heart or lung). This is known as remote ischemic preconditioning (RIPC). The strongest protection occurs 24 hours after blood flow interruption to the limb and may be mediated by a humoral cascade known as kallikrein-kinin. RIPC may provide protection against heart attack and stroke.
Perioperative Beta-blockade To Prevent Cardiac Morbidity In High-risk Patients Undergoing Surgery (The POISE Study)
Funder
National Health and Medical Research Council
Funding Amount
$189,625.00
Summary
Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a subst ....Non-cardiac surgery is associated with significant risk of complications and death, particularly in elderly patients who are known to have heart disease, or who have risk factors for it (ie smoking, high blood pressure). About 11% of the Australian population are currently taking medications for heart disease or high blood pressure and about 80% have at least one risk factor for heart disease. As more than 2 million Australians have general anaesthesia for non-cardiac surgery every year, a substantial group of patients are therefore at risk of an adverse outcome following surgery. Despite the magnitude of this problem, however, few studies have established treatments to decrease the risk of complications and death following surgery. Beta-blockers are a group of drugs which have been used for decades in the treatment of heart disease and high blood pressure. Beta-blockers are known to improve the way the heart copes with the stress of surgery. They decrease the heart rate, make the heart more efficient at using energy and reduce the likelihood of imbalance between oxygen supply and demand. Some previous studies showed that beta-blockers may reduce the risk of heart attack and death for up to 2 years after surgery. However, other studies have shown no effect of beta-blockers on outcome. These previous studies have involved small numbers of patients who may not represent the broader population having surgery. We therefore propose to undertake a large trial to definitively answer the question about whether beta-blockers improve the outcome after non-cardiac surgery in patients with, or at risk of, heart disease. Even if the effect of beta-blockers is relatively modest, because such large numbers of patients with heart disease have surgery, the overall effect on the rate of complications and death in the population could be very significant. The results of this study could have major implications for the success of, and cost of, surgery worldwide.Read moreRead less
QUANTITATIVE ASSESSMENT OF LOOSENING IN HIP ARTHROPLASTIES USING MECHANICAL VIBRATION DIAGNOSTICS
Funder
National Health and Medical Research Council
Funding Amount
$185,665.00
Summary
Recent advances and improvements made to the mechanical design of artificial joints have led to greater strength, fatigue life and wear resistance. However, this extension to the working life of joint replacements has led to patients becoming increasingly vulnerable to the problem of joint loosening. There are over 500 000 hip joint replacements performed every year, on a worldwide basis. Of these 7 to 13% will require revision surgery because of loosening at some stage of their working life. Th ....Recent advances and improvements made to the mechanical design of artificial joints have led to greater strength, fatigue life and wear resistance. However, this extension to the working life of joint replacements has led to patients becoming increasingly vulnerable to the problem of joint loosening. There are over 500 000 hip joint replacements performed every year, on a worldwide basis. Of these 7 to 13% will require revision surgery because of loosening at some stage of their working life. This is becoming a major concern to health services around the world since revision surgery is associated with a higher risk to the patient and costs are far greater than for the primary operation. Current diagnostic techniques using radiographic imaging are both invasive and lack diagnostic accuracy. The ability to detect joint loosening and to discriminate between the various causes of joint loosening following arthroplasty is of great importance to the success of subsequent care plans. This study will be the first in the world to assess the validity of a new diagnostic test that uses low energy mechanical vibration to quantify the degree of loosening in both components of the implanted hip joint. Once the technique has been proven it could readily be extended to evaluate the degree of fixation of other implanted prostheses used to replace the knee, ankle or joints of the upper limbs.Read moreRead less
Clinical Feasibility Study Of Omega-3 PUFA Therapy For The Reduction Of Post-cardiac Surgery Atrial Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$442,092.00
Summary
The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be li ....The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be linked to low incidence of AF. The main aim is to provide a cheap and safe preventative therapy against post-operative atrial fibrillation (AF), a key heart rhythm disorder that occurs in at least 1 in 4 patients after heart surgery and increases post-operative complications, limits recovery and increases hospital stay and cost. Biochemical study elements are important to gain valuable insight into the molecular mechanisms (directly in human heart) that underlie post-operative heart rhythm disorder and may delineate new more precise molecular targets for therapy. No previous clinical study has ever examined whether omega-3 PUFA therapy prevents post-operative heart rhythm disorder. Use of 3g-day omega-3 PUFA pre-treatment in the surgical setting has been shown to be safe in a number of small studies, including our own. Our preliminary data indicates that therapy increases heart and blood content of omega-3 PUFA ~2-fold, and reduces the incidence of AF. Post-operative AF is an expensive resource burden in all cardiothoracic surgery units of Australian hospitals and targets key health priorities. Due to the non-patentable nature of omega-3 PUFA, significant industry based support for clinical research is limited. A positive outcome would rapidly pave the way for widespread use in elective surgery. Reduced length of hospital stay, cost-savings, and the increase in productivity as healthy individuals return to their communities would nationally repay the investment many fold.Read moreRead less
Evaluation Of Aspirin And Tranexamic Acid In Coronary Artery Surgery: The ATACAS Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,185,000.00
Summary
This large study will compare two types of drug treatment in 4600 patients undergoing heart surgery, to see whether either can reduce the risk of death or major complications. The complications after surgery we are measuring include heart attack, stroke, lung embolism, bleeding around the heart, breathing failure, kidney failure, major haemorrhage, serious wound infection, and death. The first drug being tested is low-dose aspirin. It is believed that aspirin can reduce the risk of a further hea ....This large study will compare two types of drug treatment in 4600 patients undergoing heart surgery, to see whether either can reduce the risk of death or major complications. The complications after surgery we are measuring include heart attack, stroke, lung embolism, bleeding around the heart, breathing failure, kidney failure, major haemorrhage, serious wound infection, and death. The first drug being tested is low-dose aspirin. It is believed that aspirin can reduce the risk of a further heart attack or stroke in patients with pre-existing heart disease. There is some evidence that aspirin may have similar effects in people undergoing heart surgery, but such use is constrained by a concern that there may be an increased risk of bleeding after surgery. For this reason, most patients having heart surgery are advised to stop their aspirin about one week before surgery. But patients could be missing out on aspirin's beneficial effects. At present, we do not know whether the benefits of aspirin could outweigh the risk of excesive bleeding. The second drug being tested is tranexamic acid. This drug prevents blood clot being broken down at the stitching sites of surgery, and probably reduces the amount of blood loss during and after heart surgery. It is known that use of this drug reduces the need for a blood transfusion. It is possible that this could avoid other more serious complications after surgery. Both of these drugs are being tested individually, but in addition we are testing whether they may have an extra beneficial effect when used together. The study is being done by a partnership of anaesthetitsts and surgeons at more than 20 hospitals around Australia.Read moreRead less
Finding The Optimum Target And Predictors Of Outcome In Deep Brain Stimulation Of Older Patients With Parkinsons Disease
Funder
National Health and Medical Research Council
Funding Amount
$428,392.00
Summary
Parkinson's disease treatment has been revolutionised by the advent of deep brain stimulator surgery. The major benefits come from improved motor function and quality of life. We aim to test the relative benefits of two different targets for brain stimulation and compare their effects on quality of life and cognition. We will also use some of Australia's expertise in brain scanning technology to look for pre-operative predictors of treatment outcomes in this group of older patients with PD.