ANZCTR search results

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

This study sought to determine whether 3IU oxytocin was comparable to standard 5IU regarding postpartum blood loss in pregnant women undergoing elective caesarean delivery under spinal anaesthetic, but could reduce blood pressure elevating medication (vasopressor) requirements and adverse events. We hypothesized that patients receiving 3IU oxytocin would be non-inferior to 5IU regarding postpartum blood loss and superior regarding uterine tone, incidence of low blood pressure (hypotension), blood pressure elevating medication (vasopressor) requirements and adverse events.

Approval # H11321 Approved by the Human Research Ethics Committee at Western Sydney University Type 2 diabetes (T2D) is an increasing health and economic burden in Australia that is frequently associated with depression and psychological distress. The annual incidence of T2D in Australia could be higher than 10% for adults with depression who have impaired glucose regulation (‘pre-diabetes’). Lifestyle programs aimed at achieving and maintaining a healthy weight are recommended for the primary prevention of T2D, especially for people with pre-diabetes. Lifestyle guidelines, based on findings of several large-scale clinical trials that excluded people with prevalent psychopathology, cannot be generalised to people with depression, who are least likely to engage in or adhere to healthy lifestyle recommendations and may be taking diabetogenic medications (e.g. some anti-depressants). Depression presents a major barrier to effective and sustained healthy lifestyle changes (especially exercise) that needs to be addressed to prevent T2D in this high-risk population group. While both collaborative, multidisciplinary care (‘team-based care’) and lifestyle programs are known to be effective interventions for depression treatment and diabetes prevention, respectively, there is a lack of information on how to effectively prevent T2D in community-based patients with co-morbid depression and pre-diabetes in the Australian primary health care system. Specific aims 1.To provide preliminary evidence on the effectiveness of collaborative, multidisciplinary health services covered by the Medicare Benefits Schedule (MBS) for preventing T2D in community-based patients with co-morbid depression and pre-diabetes (DPD care) compared with usual general practitioner (GP) care 2.To assess the feasibility of conducting a large, full-scale study

Volunteer home visiting is a place-based strategy for strengthening vulnerable families, facilitating civic participation, and establishing inclusive community networks among individuals and service organisations. A research trial across four Australian states in partnership with three leading non-Government organisations, will provide a robust assessment of its effectiveness and opportunities to mobilise communities in this way to support improved well-being and social connectedness outcomes for families as well as volunteers. This innovative trial will directly inform national strategic research priorities relating to population well-being and participation. It will also establish social return on public investment in this strategy.