ANZCTR search results

Sepsis is a serious life threatening condition. Septic patients have significant organ impairment. Prompt administration of right dose of antibiotics is an important cornerstone of resuscitation of sepsis. Currently, doses of beta-lactam antibiotics at administered at a fixed dose or adjusted to renal function. Septic patients have marked alterations in their physiology that affect the pharmacokinetics of beta-lactams. Fixed doses of beta-lactams in sepsis lead to unpredictable variability in plasma concentrations. Septic patients are likely to have complex comorbidities such as immune compromise, infections with resistant organisms and deep-seated infections such as meningitis or endocarditis. Previous studies have demonstrated variable (sub and supra-therapeutic) concentrations of beta-lactam antibiotics when standard dosing is used. Sub-therapeutic concentrations carry the risk of treatment failure and supra-therapeutic concentrations can lead to toxicity, both scenarios can lead to poor clinical outcomes. Beta-lactam antibiotics are the most commonly prescribed antibiotics in the treatment of sepsis in the ICU. Therapeutic drug monitoring (TDM) guided dosing involves individualising doses based on plasma concentrations. Over the last decade, TDM of beta-lactams has been increasingly recommended in the literature due to the pharmacokinetic variability seen in critical illness. However, only a few centres have implemented this test. A knowledge gap exists in literature on implementation of beta-lactam TDM. In this RCT we aim to pilot the implementation of beta-lactam TDM in the ICU in the management of patients with suspected or proven sepsis. We will study the process steps in implementation, the feasibility of randomisation, recruitment and acceptability of variable dosing of beta-lactams. In addition we will compare the dosing advice from software, TDMx with that of researcher recommendation. This study will provide important information on dose adaptation. The knowledge gained from this study can used to inform implementation of beta-lactam TDM as a clinical service.

Endoscopic ultrasound-portal pressure gradient (EUS-PPG) is a novel therapeutic goods administration (TGA) -approved alternative to hepatic venous pressure gradient (HVPG) that has been shown in pilot studies to be safe and technically successful for the evaluation and determination of portal hypertension. EUS-PPG can be performed simultaneously with routine variceal surveillance and can be repeated to provide longitudinal HVPG measurements. Data regarding use in clinical practice is limited. This prospective registry seeks to evaluate the clinical utility of EUS-PPG assessment across multiple tertiary centres. Aims: to evaluate the feasibility and utility of EUS-PPG in clinical practice, safety, clinical applications and the potential for EUS-PPG data to inform clinical management. Correlate EUS-PPG measurements with longitudinal risk of liver-related events, and with a range of non-invasive biomarkers and clinical findings.

Asthma is an inflammatory disease of the airways that affects over 7% of the world’s population (Papi et al., 2018). Exercise-induced bronchoconstriction (EIB) is a type of asthma which is defined as a transient narrowing of the airways in response to exercise and affects 90% of asthma sufferers and up to 15% of non-asthmatic individuals (Bonini & Usmani, 2018). Asthma and EIB can be managed either by rapid bronchodilatation to relieve respiratory symptoms or long-term suppression of inflammation. However, frequent use of reliever medicines can lead to the user becoming tolerant to the treatment and long-term control medicines have several undesirable side effects. Dietary and supplement interventions have been reported to reduce the effects of asthma and EIB (Williams et al., 2016). These may represent a cost-saving, effective and safe method for reducing the incidence of asthmatic attacks. Anthocyanins are coloured pigments that are responsible for the colours red, purple and blue in fruits and vegetables. Current animal studies have found that after consumption of anthocyanins, inflammation was reduced, and lung function was improved (Park et al., 2007). Whether anthocyanins could improve respiratory symptoms and lung function in otherwise healthy humans with EIB is unknown. This will be the first study to determine the role anthocyanins have on lung function and inflammation in individuals with EIB. It is hypothesised the anthocyanin supplementation with increase lung function following eucapnic voluntary hyperpnoea.

The purpose of this trial is to investigate the dose-related effects of intraduodenal administration of the bitter agonist, quinine on energy intake from a palatable milkshake, plasma gut hormone concentrations, and appetite perceptions in healthy individuals, We have found in one of our recent studies that quinine, given as a bolus in doses of 300 or 600 mg (in 10 ml water), potently slowed gastric emptying and lowered postprandial blood glucose. Moreover, we observed more potent blood glucose lowering effects when quinine was administered intraduodenally than intragastrically, suggesting that interaction of quinine with small intestinal receptors is required for potent effects. Therefore, based on these findings, this study aims to characterise the dose-related effects of intraduodenal quinine at these doses, on energy intake.

Despite the benefits of physical activity, over half of Australian adults fail to meet the minimum recommended levels. Pedometers are an effective means of increasing physical activity, allowing instant feedback about the amount of activity accumulated. Recently, a number of new generation pedometers have been released that offer a variety of additional assessment and online feature, however the added value of these features has not been investigated. The aim of this study is to compare the effectiveness of two activity trackers and a traditional pedometer in increasing physical activity and reducing sedentary behavior in healthy, inactive adults. It is hypothesised that the activity trackers will have increased comparative effectiveness for increasing physical activity and reducing sedentary behaviour, than the pedometer. The outcomes of this study provide exploratory evidence of the effectiveness and feasibility of these new devices. Improving movement behaviors in the population can significantly reduce the risk of chronic disease and in turn, relieve the associated economic burden.

We propose to evaluate an online cognitive behavioural therapy for eating disorders in 125 university students with disordered eating that impairs their quality of life. We will adopt a novel design that can inform translational strategies, with random allocation of people to active conditions (N=100) and wait-list control (N=25). Of the 100 allocated to active conditions, 25 will be randomly allocated to guided self-help (GSH), 25 randomly allocated to pure self-help (PSH), and then the remaining 50 will be allocated to GSH if they have low motivation (GSH-low) and to PSH if they have higher levels of motivation (PSH-high). Hypotheses Significantly better outcomes at end of intervention and follow-up will be produced for the following comparisons, with the first group/s having better outcomes in each case: GSH, GSH-low, PSH-high vs PSH or control; GSH-low vs GSH; PSH-high vs PSH.

The ageing process is characterised by a reduction in bone and muscle mass and strength and an expansion of the adipose (fat) tissue. These changes are not only associated with increased risk of falls and fractures, but also increase risk of diseases such as type 2 diabetes (T2D). Furthermore, T2D is characterised by high glucose (sugar) levels (hyperglycaemia) that can adversely affect both bone and muscle health. We previously demonstrated that bone releases hormones that can improve muscle glucose uptake via a specific cellular pathway, however, how this communication is affected by hyperglycaemia is not clear, but may open the door for new pharmacological targets to treat T2D in the future. Exercise is effective to improve glucose control as well as improve bone and muscle health. As such, exercise can be used as a tool to explore the mechanisms behind the interactions between bone, muscle and fat in these patients with the ultimate goal of improving the health and well-being of patients with T2D. We will assess this following a single session of high intensity cycling exercise, and following 4 and 10 weeks of high intensity cycling training. The study includes blood and urine sampling before and after exercise in the acute exercise session, and following the 4 and 10 weeks of training to assess if certain markers of bone, muscle and fat health that circulate in the blood and urine are modified by exercise. Muscle (thigh muscle) and fat (abdomen) biopsies are optional in this study, and are taken before and after exercise. This project will bring new insights into how exercise can modify the way in which bone-muscle-fat communicates leading to potentially new pharmacological/non-pharmacological interventions important for health in patients with T2D.

Financial incentives (for patients and primary care providers) may be a straightforward strategy for improving the uptake of hepatitis C treatment in primary care. In the MOTIVATE-C project, individuals with hepatitis C will be randomly assigned to usual care (no incentive) or to receive incentives of various dollar values (AUD 0 to AUD 1000), provided in conjunction with/without a co-incentive payment to the participant’s nominated primary care provider, for commencing hepatitis C treatment within the context of a supported treatment framework. By assigning patients to different values of incentive and evaluating their effect on treatment initiation, we aim to directly inform the future implementation of incentives by identifying the most cost-efficient strategy.

This is a randomized, double-blind, placebo-controlled, single ascending dose study. Approximately 56 men and women who fulfill the inclusion and exclusion criteria will be enrolled at one or more sites in Australia. Eligible subjects will be admitted to the clinical research unit on Day -1, dosed on Day 1, discharged on Day 2, and return for outpatient visits through Week 24. In Part A, 8 subjects will be randomized in a 3:1 ratio to receive a single dose of BW-00163 (n=6) or placebo (n=2) on Day 1 in a double-blind fashion. Cohorts 1 to 4 will receive BW-00163 doses of 50, 150, 300, and 600mg, or placebo respectively. In Part B,12 subjects will be randomized in a 2:1 ratio to receive a single dose of BW-00163 (n=8) or placebo (n=4) on Day 1 in a double-blind fashion in each cohort. Cohorts 5 and 6 will receive single dose of BW-00163 300 and 600 mg, or placebo respectively.

Adolescent e-cigarette use has drastically increased in recent years, posing several acute and chronic harms, including poisonings, burns, serious lung injury, and - where nicotine e-liquid is used - the potential to impact brain development and lead to dependence. Effective and scalable preventive interventions are urgently needed, and school-based eHealth interventions are an efficient, effective and economical approach. Yet, there are few school-based preventive eHealth interventions targeting e-cigarettes, and none within Australia. To address this need, we developed the OurFutures Vaping Program. Built on the successful ‘OurFutures’ (formerly ‘Climate Schools’) prevention model, the OurFutures Vaping Program involves 4x40 minute online cartoon-based lessons that are delivered during Year 7/8 health education classes. This study will evaluate the OurFutures Vaping Program via a cluster randomised controlled trial among 42 schools across NSW, QLD and WA. It hypothesized that: • H1 (primary outcome): Students who receive the OurFutures Vaping Program will be less likely to commence e-cigarette use at the 12-month follow-up, compared to students in an active control condition. • H2: The OurFutures Vaping Program will achieve superior outcomes to the control condition on secondary outcomes including: uptake of tobacco smoking, frequency/quantity of e-cigarettes use and tobacco smoking, intentions to use e-cigarettes/tobacco cigarettes, knowledge about e-cigarettes and tobacco smoking, mental health, wellbeing, and quality of life. • H3: Benefits of the OurFutures Vaping Program on primary and secondary outcomes will be sustained over the long-term (up to 36-months post baseline). • H4: The OurFutures Vaping Program will demonstrate cost-effectiveness (up to 36 months post baseline).