ANZCTR search results

It has been well established in the literature that snoring sounds can be used to detect the presence of obstructive sleep apnoea (OSA). Currently the gold standard in the diagnosis of obstructive sleep apnoea is Type I Polysomnography (PSG), which is both time and resource intensive. Streamlining the diagnostic process for patients with OSA is of great significance given the increasing prevalence and awareness of the condition. Retrospective pilot studies have been conducted previously through our unit to assess the utility of analysing snoring sounds as a predictor for obstructive sleep apnoea. Our proposed study aims to systematically explore the performance of our snore/breathing sound technology algorithm against Type I PSG by conducting a statistically powered study in a sleep laboratory as well as a home setting. We hypothesise that breathing sounds (including snoring), when analysed using appropriate mathematical methods and machine learning techniques, can provide sufficient information to detect OSA at a sensitivity and specificity >92% simultaneously, with respect to Type 1 PSG. It is planned to prospectively recruit up to 50 patients with suspected sleep disordered breathing who are already listed for diagnostic PSG study in our sleep lab. These patients will undergo the sleep study as planned, and will undergo a slightly modified protocol with additional sound measurements, along with oesophageal pressure monitoring. The patient will then proceed to have another 7 nights data collected with a portable sound recorded (stored as an "app" on a provided smart phone) to further validate data against PSG. Analysis of the recorded snoring sounds using the externally developed algorithim will then be correlated against Apnoea-Hypopnoea Index (AHI) as measured during the PSG, which is considered the current diagnostic gold standard. Ideally this information will aid in the validation of a streamlined technique to be used in the diagnosis of sleep disordered breathing.

Vitamin A is required for the development and growth of lungs in premature babies who are born with low vitamin A body stores. Supplementing premature babies with additional doses of vitamin A by intramuscular injections decreases bronchopulmonary dysplasia (BPD - a chronic lung disease related to premature birth). As intramuscular injections are painful, the supplementation has not been widely practiced. Oral vitamin A, especially fat soluble form, is poorly absorbed by premature babies and therefore may be less effective. This study aims to investigate if supplementation of water soluble form, which is better absorbed, to extremely premature babies decreases risk of BPD. As a part of the study we are also looking at if we can use saliva to assess vitamin A status instead of blood in the babies. .

Successful transition to home dialysis and maintenance of a home based therapy is influenced not only by medical and demographic factors but also by psychosocial stressors. There is evidence from other medical conditions that coping skills influence patients’ psychological well-being. Our previous research has suggested that people with adaptive coping skills, such as problem solving and active coping, are more likely to sustain home haemodialysis. Based on this research, we believe that by providing home haemodialysis patients with additional adaptive coping skills they are more likely to sustain the use of a home therapy. A coping skills intervention program has been modified for use by people learning home haemodialysis. The program has been developed by psychologists who work with patients of a nephrology department, and is designed to be delivered by any health practitioner. It includes basic skills in stress management, problem solving, mindfulness and healthy thinking. It is designed to be able to be incorporated into the existing education provided to learners during home haemodialysis training, delivered chair-side during dialysis over six one hour sessions. This coping skills intervention will be compared with treatment as usual with home haemodialysis learners. The outcomes to be tested are a) sustainability of home dialysis after training, b) change in levels of reported distress, and c) change in reported use of adaptive coping strategies. The intention of this intervention is to enhance the patient experience of this home based treatment and improve their quality of life.

The purpose of this project is to investigate whether an ‘optimised’ form of Magnetic Seizure Therapy (MST) is a successful treatment for patients with treatment resistant depression compared to the standard form of MST that has been used to date. MST involves the induction of a seizure for therapeutic purposes. It is similar to electroconvulsive therapy (ECT) but with MST the seizure is induced through the use of magnetic stimulation rather than direct electrical currents as occurs with ECT. By avoiding the use of direct electrical current when inducing the seizure, it is thought that MST will result in an improvement in depressive symptoms whilst reducing memory related side effects (i.e. difficulties in remembering recent events) which can occur with ECT. The standard from of MST that has been investigated to date is 100Hz MST to the vertex, or the ‘motor area of the brain’. 100Hz MST has been shown to improve depression in some people and to not have any of the memory side effects often seen with ECT. We will be comparing this form of MST to 25Hz MST to the prefrontal cortex, or the ‘front part of the brain’ to investigate whether this type of MST results in greater improvement in depression than the 100Hz MST.

Preterm infants are highly susceptible to bacterial late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), both are major causes of systemic inflammation and contribute to brain injury and long-term disability in premature infants. Treating LOS and NEC are essential for survival, but suppressing systemic inflammation can also help reduce mortality, hospital stay and disability due to brain injury. The current treatments for NEC and LOS are limited to antibiotics, supportive care and surgery in some NEC cases, all of which do not aid in reducing systemic inflammation, therefore there is a need to reduce systemic inflammation. Pentoxifylline is a safe, low-cost, non-steroidal drug with potent immune-modulating activity with the potential of suppressing systemic inflammation induced by LOS or NEC. A recent Cochrane Review of 6 randomised controlled trials (RCT) suggests that PTX, given with antibiotics in neonatal sepsis, reduces mortality and length of hospital stay. We are conducting an international multicentre trial that will enrol and consent approximately 1,800 preterm infants (born <29 weeks gestational age). The primary aim is to evaluate the effect of treatment with intravenous Pentoxifylline versus placebo, starting within 6 hours from blood culture taken for suspected LOS or NEC. After 48 hours treatment will cease if diagnosis is refuted or will continue for 4 days if diagnosis is proven. The primary outcome to measure effectiveness is survival without disability at 18-24 months of age (corrected for gestation).

Cerebral palsy (CP) is the most common physical disability of childhood, affecting 2 per 1000 live births across the world. CP describes permanent non-progressive motor disorders arising from damage to the developing brain. CP is often associated with epilepsy, difficulties in speech, sight, hearing, sensation, perception, behaviour or cognition. There is no cure for CP. Preclinical studies of different types of stem cells in models of acute brain injury similar to CP have shown significant functional improvement. The variety of stem cells available in umbilical cord blood (UCB), an ethically uncomplicated source of stem cells, has led to a focus on UCB stem cell therapy as a quick-to-clinic option. Previous studies indicate that autologous or unrelated donor UCBC infusion is safe and feasible for children with CP, and may lead to improved motor functioning, but there is no information about the safety and effects of matched sibling cord blood available. Therefore, this trial will study the safety of infusing matched sibling cord blood cells to children with cerebral palsy. Additionally, we will assess how long the cells remain within the recipient through sensitive chimerism assays, as we hypothesise that the cells may be rejected within 24 hours of infusion. Finally, we will trial the use of a range of outcome measures in this context.

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity and is known to contribute to cognitive impairment, a condition common in CVD patients. Cognitive impairment has been demonstrated to occur in 25-50% of heart failure patients and atrial fibrillation patients have a 42% increased hazard of dementia, a risk which increases with advancing age. However, little is known about cognitive impairment in acute coronary syndrome (ACS) survivors. Cognitive impairment is important to detect, manage and accommodate because it limits the capacity of these patients to engage in appropriate self-care. A potential platform to improve detection and treatment for cognitive impairment is cardiac rehabilitation (CR), because it includes routine screening and services for this population. Also, the regular exercise delivered in CR offers a potential means to attenuate cognitive decline, however this potential has not been investigated. There is a gap in the literature for a research study that will examine ACS patients attending CR for: 1) the prevalence of cognitive impairment, 2) the association between cognitive impairment and level of physical activity and attendance rate, and 3) the effect of CR on cognitive function. Cognitive impairment is prevalent in cardiovascular disease patients and important to detect, manage and accommodate because, even when mild, it can limit self-care capacity and engagement in secondary prevention behaviours. Mild cognitive impairment is likely to go undetected unless screening is undertaken. This study will investigate the prevalence of cognitive impairment in acute coronary syndrome survivors. The sample will be drawn from Royal North Shore Hospital in Northern Sydney Local Health District. Cognitive function will be assessed in the areas of processing speed, executive function and memory. Physical activity and moderate-vigorous exercise have been demonstrated to ameliorate cognitive changes in older adults in the general population and heart failure patients. The impact of comprehensive cardiac rehabilitation, which includes an 8-week structured physical activity program, will be determined by comparing cognition at baseline and completion and follow-up (8 and 16 weeks). The relative influence of physical activity will be assessed by measuring engagement in physical activity using new technology (Fitbit), while accounting for baseline exercise capacity, activities of daily living, depression, education level, age and gender. Sample size of 127 patients is calculated on a moderate effect on executive function, power of 0.8, allowing 20% loss to follow up. Study Aims & RESEARCH QUESTIONS Aims and objectives: 1. To investigate the prevalence of altered cognitive function in coronary heart disease patients ENTERING a comprehensive cardiac rehabilitation program 2. To explore the relationship between physical activity and cognitive function over 16 weeks in coronary heart disease patients attending a com

The aim of this research is to evaluate the role of dysbiosis and probiotics and orotic acid as a treatment for depressive illness that does not respond to standard medication treatment. The mechanisms of probiotics in the treatment of dysbiosis and systemic inflammation and orotic acid as a treatment for resistant depression will also be evaluated. Significance: Developing effective and safe treatments for resistant depression is essential as this group presents a significant burden of care to the health system and generally have poorer vocational and quality of life outcomes and are at increased risk of morbidity and mortality. Dysbiosis and ensuing systemic inflammation has been strongly implicated in depression that has a poor treatment response. Orotic acid rapidly metabolises into uridine which has proven antidepressant effects through mechanisms different to antidepressant medication. Orotic acid demonstrated efficacy in our previous pilot work. The expected outcome of this study is to provide preliminary efficacy and safety data, and elucidate the mechanism of probiotics and orotoic acid as an adjuvant therapy with one class of standard medication.

COLCARDIO-ACS Main study: Inflammation plays a pivotal role in atherosclerosis, offering new opportunities for the prevention and treatment of coronary artery disease. Colchicine is a commonly used anti-inflammatory medication approved for the treatment of gout, Familial Mediterranean Fever, and acute/recurrent pericarditis. There is an increasing body of evidence in the medical literature supporting a beneficial role of long term colchicine therapy in prevention of cardiovascular disease, via modulation of inflammatory cytokine production and tubulin-mediated mitosis inhibition. This includes both primary prevention in patients treated with colchicine for gout or Familial Mediterranean Fever, and secondary prevention in patients with stable coronary artery disease who are also being treated with statins and anti-platelet agents. Low-dose colchicine use has also been proven to be safe, well tolerated, and is inexpensive and readily available. The aim of this project is to assess the effect of colchicine (0.5 mg/day) in addition to optimal medical therapy on cardiovascular outcomes in ACS patients with evidence of persistent coronary inflammation (based on hsCRP). We hypothesise that addition of colchicine to optimal medical therapy in patients post-ACS, who have biomarker evidence of persistent inflammation will reduce recurrent cardiovascular events. COLCHICINE-COG Sub-study: Dementia affects over 400,000 Australians at a cost to the economy of $30 billion per year and is a Commonwealth Government National Health Priority. It is the third leading cause of death overall and the largest reason for disability in older Australians. Cardiovascular disease (CVD) has been identified as the earliest and strongest pathological marker for dementia. Oxidative stress is characterised by an imbalance in the redox state of cells (either via the overproduction of reactive oxygen species of antioxidant system dysfunction) and is posited to be a key mechanistic pathway underpinning the relationship between CVD and cognitive decline. Importantly, research suggests that the pathology leading to dementia occurs 10-20 years before the onset of clinical symptoms. Therefore, it is critical that interventions target CVD in those ‘at risk’ to prevent onset and reduce cognitive decline. The aim of this study is to examine the effect of long term low-dose colchicine on cognition and brain health patients with established coronary artery disease.

Sedation of children in the Emergency Department (ED) for either urgent therapeutic procedures that may be painful or which require a still and cooperative child (such as wound closure, abscess drainage, foreign body removal, lumbar puncture or fracture reduction) or to obtain critical diagnostic information (for example via medical imaging) is an important aspect of emergency medical practice for which a considerable and evolving body of evidence has developed over several decades. Sedation and analgesia for painful procedures is certainly considered a standard of care that should be offered to all children undergoing painful procedures where possible. While there are some published guidelines there is considerable variation in practice both locally and internationally in terms of choice of sedative agent and conduct of the procedure of sedation. Most of the literature relates to parenteral routes of administration of sedative drugs, typically intravenous (IV) or intramuscular (IM) routes, due to the ability to titrate the dose and the reliability of drug effects when administered via these routes. Study aims 1. Investigate the feasibility of a novel needle-free approach to paediatric sedation in the emergency department 2. Investigate the scientific merit of IN ketamine sedation of children in the emergency department 3. Investigate the practical merit of IN ketamine sedation of children in the emergency department 4. Improve emergency paediatric sedation practices consistent with humane processes of paediatric emergency care 5. Establish a greater evidence base for the intranasal route of sedative drug administration in the emergency department Study hypotheses 1. That IN ketamine sedation will not require significant rates of IV cannulation to safely complete the procedure where an IV cannula is not already considered essential for a patient’s ongoing care 2. That IN ketamine (10mg/kg) will provide non-inferior sedation compared with IV ketamine (1.0-2.0mg/kg) and IM ketamine (4-5mg/kg) 3. That IN ketamine would be associated with higher parental/caregiver satisfaction with the overall procedure and general care in the emergency department 4. That IN ketamine would be associated with greater physician satisfaction with the overall performance of the sedation and the process required to ready the patient for sedation 5. That IN ketamine sedation will lead to earlier readiness for performance of the procedure or diagnostic intervention and hence earlier procedural completion 6. That IN ketamine sedation will not be associated with an overall increase in ED length of stay 7. That IN ketamine sedation will not be associated with an increased rate of emesis, unpleasant psychomimetic effects or other adverse events