ANZCTR search results

Atherosclerosis is the build-up of cholesterol deposits (plaque) within the walls of the coronary arteries which are the blood vessels supplying heart muscle. If the plaque ruptures, it can cause a reaction and block off the vessel causing a heart attack. Vessel inflammation is a major contributor to both plaque formation and rupture. The fat (adipose tissue) surrounding the coronary arteries is a rich source of inflammatory chemical messengers, many of which are the same as those found in plaques, and in particular plaques considered to be vulnerable to rupture, called high risk plaques (HRP). Computed tomography coronary angiography (CTCA) is a widely used investigation for the assessment of plaque as well as HRP. Inflammation of the coronary arteries, however, is not as easily assessed. Specialised imaging methods are limited by cost, availability and image resolution. Circulating blood markers of inflammation do not reflect what happens at the level of the vessel. Therefore, the ability to measure a regional marker of inflammation is highly desirable and may improve risk prediction beyond the current measures that CTCA provides. Pericoronary adipose tissue (PCAT) is the layer of fat immediately adjacent to the coronary artery wall. It has been demonstrated that inflammatory chemical messengers cross between the vessel and adjacent fat in both directions. Therefore, PCAT may act as a sensor of vessel inflammation, as well as a driver of plaque formation. A recent seminal scientific study showed that exposure to inflammatory chemical messengers stops fat cells from maturing. The density (attenuation) of PCAT can be accurately assessed on CTCA, and has been validated as a marker of inflammation. A more negative fat attenuation represents less inflammation (fat-rich tissue) whereas higher values suggest greater inflammation (less fat maturation). With increasing evidence of the benefits of anti-inflammatory medications to reduce cardiovascular events, the use of CTCA to detect vascular inflammation as well as its established role in plaque analysis represent an ideal tool for a single, non-invasive imaging test to guide future research into coronary plaque formation and vulnerability. Our hypotheses are: 1. Patients with heart attacks will demonstrate lower PCAT attenuation than stable and asymptomatic patients. 2. Persisting high PCAT attenuation predicts plaque progression and vulnerability. 3. The baseline PCAT attenuation at sites of HRP predicts future heart attacks. This study aims to demonstrate that PCAT attenuation will exhibit a gradient of increasing inflammation from normal vessel to HRP. We will aim to define a threshold at which PCAT attenuation predicts HRP presence and progression, to then guide future studies using anti-inflammatory medications. The long-term goal is the ability to detect inflammation in normal vessels free of plaque and therefore are at risk of accelerated plaque progression.

The Transplantation Standardised Outcomes of Nephrology initative has identified infection as a core outcome. Infections are a common complication following kidney transplantation, occurring in more than 65% KTR in Australia, and 40-50% of transplant recipients worldwide. It is expected that the burden of infectious complications will continue to rise based on the growing prevalence of diabetes mellitus and increasing potency of immunosuppressive regimens. Infectious complications following kidney transplantation are associated with significant mortality. Infection-related mortality occurs in approximately 15-20% of KTR worldwide. In Australia, infection accounts for approximately 22% of deaths in the KTR population, with 75% of these deaths occurring in individuals with a functioning graft. Infectious complications are associated with prolonged length of hospital stay, admission to intensive care unit and post-acute care, and early hospital readmission. Treating infectious complications following kidney transplantation has been estimated to cost the Australian Government approximately $8 billion between 2009 and 2020, and places additional strain on healthcare providers. The development of strategies to mitigate infectious complications following kidney transplantation is therefore of great importance. It has been hypothesised that an individual’s gastrointestinal microbiota may modify the risk of infectious complications in KTR. A study of ileal microbiota from nineteen small bowel transplant recipients has highlighted that the relative compositions of multiple bacterial taxa were diagnostic of infectious illness and acute rejection. Additionally, marked disruption of intestinal flora in human recipients of allogenic stem cell grafts was informative of the risk for bacteraemia. There has been minimal work done on the microbiota of KTR and the underlying pathogenesis, clinical consequences and potential for therapeutic manipulation are poorly understood. As the gastrointestinal microbiota is intimately influenced by diet, the discovery of this relationship between the kidney and gastrointestinal microbiota, known as the kidney-gastrointestinal axis, may be a therapeutic opportunity for nutritional intervention. Thus, this study will explore the benefit of manipulation of the gastrointestinal microbiota, via prebiotic supplementation, examining the feasibility of performing a randomised controlled trial of prebiotic supplementation in reducing infections and gastrointestinal upset in kidney transplant recipients.

The early years of life are critical in development of sleep behaviours and present the optimal window for promotion of healthy sleep patterns and early intervention to prevent and treat sleep problems. During this period, childcare plays a significant role in the lives of children and has demonstrated impacts on lifetime trajectories of health and development. This project focuses on the role of childcare in supporting sleep health of children aged 0-3 years. The majority of Australian children attend childcare and many spend considerable hours in childcare from early life, when sleep patterns are developing. Despite this, little is currently known about impacts of childcare practices on young children’s sleep health. Yet prior to age 3, there are substantial challenges in this context that result from greater variability in child sleep need (including timing, duration and number of sleep periods), settling behaviours, and the complexity of parent demands. This study aims to examine current sleep practices for infants and toddlers (aged 0-36 months) in childcare settings. The focus is on addressing two key questions in establishing the role that childcare plays in younger children’s sleep health: (1) Do childcare environments influence children’s sleep patterns and behaviours? (2) Does consistency between sleep practices in childcare and at home influence the regularity of children’s sleep patterns?

Dietary fibre is important for gut health. Within the large intestine, some dietary fibres are broken down by the gut bacteria (microbiota) in a process called fermentation. A product of fermentation are metabolites called short-chain fatty acids. These can also be found in fermented foods and drinks, such as vinegar. In animal studies, short-chain fatty acids have been associated with reduced inflammation and lower blood pressure. The aims of this research project is to investigate if increasing short-chain fatty acids through increasing fibre and fermentable foods in the diet have effects on: 1. Immune cells and inflammation 2. Blood pressure 3. Gut function To answer these questions, we are asking for healthy volunteers to participate in a dietary intervention study. This will involve consuming a diet with varying levels of fibre and fermented foods. At certain points in the study, Blood and faecal samples will be taken and we will also measure your blood pressure. We aim to recruit 30 healthy participants. This study will help us to understand if dietary fibre and fermentable foods could be used to reduce inflammation and blood pressure in conditions such as asthma, allergy and hypertension in the future. This study has been initiated by A/Prof. Jane Muir, head of Translational research at the Department of Gastroenterology and is being conducted by Mr. Paul Gill as part of his PhD studies

The purpose of this study is to investigate whether rehabilitation in the home services improve health-related quality of life. There has been little research evaluating whether health-related quality of life improves as a result of rehabilitation in the home programs (or similar). Measures of functional status at the start and end of rehabilitation in the home programs do not necessarily show change as these measures are not sufficiently sensitive or responsive over the relatively short duration of a rehabilitation in the home program. We believe measuring health-related quality of life may be a useful tool for evaluating the effectiveness of rehabilitation in the home program.

Both indomethacin and ibuprofen are routinely prescribed to close a patent ductus arteriosus (PDA). However the effect of each medicine on cerebral circulation, is different. These differential effects may be secondary to drug specific alterations in cerebral oxygen kinetics. We propose that in order to fully understand the effect of indomethacin and ibuprofen administration on cerebral haemodynamics, it is critical to interrogate both cerebral oxygen delivery and consumption. We hypothesise that indomethacin, in comparison to ibuprofen reduces cerebral blood flow without adversely altering cerebral oxygen kinetics in preterm newborns with a clinically significant PDA.

Multi-centre Phase 2a open-labelled extension study of R-107 in MDD treatment resistant subjects who responded to treatment in the R107-C205 (BEDROC) study. Each subject will participate in up to 3 phases: • A screening phase of up to 3 weeks • An open-label treatment phase for 24 weeks • A 4-week post-treatment (follow up) phase

BTX 1503 contains the active pharmaceutical ingredient, cannabidiol in a topical liquid formulation, and is being developed for the treatment of acne vulgaris by Botanix Pharmaceuticals Limited. CBD is a member of a broader family of compounds known as cannabinoids, a class of compounds originally derived from the cannabis sativa plant. CBD is chemically synthesized under Good Manufacture Practices (GMP) for use in this study. The objective of this study is to assess safety and efficacy of various doses of BTX 1503 in subjects with moderate to severe acne vulgaris of the face. This will be a multi-center, randomized, double-blinded, vehicle-controlled, parallel group, dose-finding study in pediatrics, adolescents and adults (aged 12 to 40 years). Study participants will be enrolled at sites in Australia and United States of America. Not all sites will enrol paediatric participants. Participants will be randomised to one of five treatment arms: BTX 1503 5%, BID:BTX 1503 5%, QD:BTX 1503, 2.5% QD:Vehicle, BID:Vehicle QD) with 90 subjects in each BTX 1503 group and 45 subjects in each vehicle group for a total of 360 subjects. Participants will be provided with instructions for dose administration and will be asked to self-administer for 28 consecutive days. Safety and cutaneous tolerability will be assessed by the collection and review of AEs and application site review, laboratory parameters throughout the duration of the trial. Efficacy measurements will include change in inflammatory and non-inflammatory lesion counts from baseline. Photography of the face will be conducted for some participants.. Participants will remain in follow up until 84 days following the first application of investigational product, with outpatient visits at Days 1, 14, 28, 56 and 84.

Pre-operative anaemia, as defined by the World Health Organisation criteria, has a prevalence in non-cardiac surgery of around 25% and is associated with poorer outcomes peri-operatively. It also increases the chance of transfusion and increases risk of death in cardiac surgery. Blood transfusion is often used to correct peri-operative anaemia and whilst life saving in acute major haemorrhage is a limited resource and, is itself associated with morbidity and mortality. It remains unclear if treating anaemia in the peri-operative period can positively influence morbidity or mortality. However benefit from patient blood management interventions, including pre-operative anaemia optimisation, has been shown to reduce the need for blood transfusion with possible trends towards improved patient outcomes. Guidelines have been published recommending identification and active management of preoperative anaemia. An excellent goal directed review has been undertaken by the Australian National Blood Authority and also supports identification and optimisation of pre-operative anaemia. A preliminary look reviewing colorectal patients over a six month period in 2017 was recently undertaken at St George. Of the 171 elective operative cases found, ninety had a preoperative haemoglobin reported thirty of which were anaemic (33% of those who had a haemoglobin). Eight patients were transfused during the peri-operative period, the majority of whom were anaemic before surgery. This pilot study supports the published literature, and implies the problem of pre-operative anaemia is present at St George and currently insufficiently managed. Pre-operative anaemia may be an optimisable risk factor for our patients at St. George, first however we need to understand which patient groups are at greatest risk, their current management (blood product transfusions) and then how and where to focus our efforts. This work has not been previously undertaken at St George. The primary aim of the proposed study is to document the prevalence of anaemia pre-operatively and transfusion practice for all patients having a procedure in 2017 at St George Hospital. Secondary aims include the documentation of anaemia according to surgical speciality, of pre-operative iron deficiency anaemia, anaemia of chronic disease and of blood product transfusions according to patient demographics and surgical speciality. The study will also examine the timings from booking to surgery and pre-operative assessment to surgery to consider how best to optimise Haemoglobin (Hb) during the patients pre-operative pathway.

Currently, there are significant challenges in delivering health care to chronic disease populations. Our research explores the impact of early multidisciplinary supportive care for the life-limiting chronic disease population on patient and carer outcomes and healthcare resource utilisation and the utility of a multi-disciplinary supportive care clinic for such chronic conditions.