ANZCTR search results

Hepatitis C virus (HCV) leads to cirrhosis and/or hepatocellular carcinoma in 20-40% of those infected after 30 years. It is unclear whether the remaining 60-80% of those with HCV derive an objective physical health benefit from the treatment and cure of HCV infection. HCV infection appears to be associated with increased cardiovascular risk, however this is controversial, and it is unclear whether the mechanism is through HCV-induced metabolic syndrome and diabetes, or through chronic inflammation and endothelial dysfunction. The aim of this study if to determine feasibility of using RH-PAT to measure change in endothelial function over time during HCV treatment, to refine assumptions and to seek a signal of effect. These data will then be used to determine if a larger multicentre trial is justifiable and to inform its design.

This study is a translational research project that will generate qualitative data to inform changes to clinical practice in a Cardiovascular acute care setting. Aims: 1 To explore the practical aspects of applying a depression screening protocol 2. To conduct behavioural analysis using the COM-B theorectical model to explore capability, opportunity and motivation of staff to change practice.

Hyperglycaemia in hospitalised patients is independently associated with increased morbidity and mortality in a wide range of patient groups, including the critically ill. The association between hyperglycaemia and poor inpatient outcomes is strong in patients without diabetes. However, despite a greater elevation in plasma glucose concentration and poorer prognosis, hyperglycaemia is a weaker predictor of morbidity and mortality in patients with diabetes. A high plasma glucose concentration in a hospitalised patient can occur because of chronic poor diabetes control and be “normal” for that patient, represent a transient physiologic response to an inter­current illness (stress hyperglycaemia), or be a combination of the above. Stress hyperglycaemia arises because of the inflammatory and neuro­hormonal derangements that occur during a major illness. Therefore, stress hyperglycaemia develops in proportion to the severity of an inter­current illness, and an association between hyperglycaemia and adverse patient outcomes will be, at least in part, a reflection of this. However, stress hyperglycaemia may also directly contribute to adverse outcomes by inducing endothelial dysfunction and oxidative stress. The Endocrine Research Unit, Southern Adelaide Diabetes and Endocrine Services recently developed a metric for stress hyperglycaemia. Estimated average glucose concentration was calculated from glycosylated haemoglobin in 2290 patients acutely admitted to Flinders Medical Centre, Adelaide. Relative hyperglycaemia was defined by the stress hyperglycaemia ratio (SHR), calculated by dividing admission glucose by estimated average glucose. Thus, a patient with a SHR of 1.5 has an admission glucose concentration 50% higher than their average glucose over the prior 3 months. Using data gathered from a research primarily focused on validating the use of HbA1c for diagnosis of diabetes mellitus, a multivariable analysis including glucose, SHR and other potential predictors of poor outcome (e.g age, sex, renal function), the odds ratio for in­-hospital death or ICU admission per 0.1 SHR increment was 1.20 (p<0.001). In contrast, the odds ratio per one mmol/L glucose increment was 1.03 (p=0.31). In contrast to glucose, the association between diabetes and SHR was not affected by diabetic status. These data suggest that SHR is a better predictor of adverse outcomes than glucose and that SHR is associated with poor outcomes in patients with and without diabetes. In this study, we will evaluate whether SHR is more strongly associated with in-­hospital mortality in critically ill patients than absolute glucose. If true, this may create a new paradigm whereby patients in ICU are selected for glucose­lowering therapy based on relative, rather than absolute, hyperglycaemia.

Botulinum toxin type-A (BoNT-A) is a current standard treatment used to reduce muscle spasticity in children with cerebral palsy (CP). Intramuscular BoNT-A treatment results in temporary chemo-denervation of the injected muscle creating a muscle that is “weakened” for 2-5 months. Clinical trials in ambulant children with spastic type CP to date indicate that intramuscular BoNT-A injections to the calf muscles reduce spasticity and have a moderate influence in improving gait. In the long term, there is some evidence that BoNT-A injection may delay and reduce the requirement for surgery to treat musculoskeletal deformities and, provide modest functional benefits, however BoNT-A does not seem to prevent the development of muscle contracture. Studies of BoNT-A in animal models have shown reduced spasticity and muscle length maintenance however these adaptations occurred with a concomitant deterioration in muscle volume and strength. In humans significant atrophy in muscles of two healthy volunteers as well as a one child with spastic type CP has been reported. Recently, in older children with spastic type CP (not naive to BoNT-A), it was found that the volume of the injected calf muscle remained decreased 5 weeks following intramuscular BoNT-A injection. Furthermore, it has been reported that spastic type CP muscle volume grows at a much slower rate after BoNT-A injections (regardless of injection frequency) compared to typically developing controls. However neither of these recent studies involved a spastic type CP control group, receiving no BoNT-A, and therefore it was not possible to reconcile whether this slower growth rate is due to the BoNT-A injection or the underlying mechanisms that lead to reduced growth in spastic type CP in general. Muscle weakening from BoNT-A appears to be beneficial in the short-term for children with spastic type CP however until we know the precise time-course of changes which occur in muscle in response to BoNT-A in these children, it is difficult to predict the long term effect BoNT-A injections has on strength and subsequent function. This reasoning underpins the concerns expressed in the literature regarding the possible detrimental long-term effects of BoNT-A injections on muscle structure and function. It is proposed that this randomised controlled trial will assess the impact of BoNT-A injections treatment to the calf muscles. The research plan will provide a comprehensive picture of calf muscle growth in young children naive to BoNT-A and following their first treatment.

Background: Despite thrombolytic therapy using intravenous tissue Plasminogen Activator (tPA) being a recommended treatment for appropriately selected ischaemic stroke patients, use of this treatment remains low. tPA is only provided to 7% of ischemic stroke patients within Australia. A number of factors including, risk of haemorrhage, limited time-frame of 4.5 hours from stroke onset in which the treatment can be given, and difficulties obtaining informed consent, may be factors limiting the administration of this therapy. Patients with acute stroke are often mentally and physically unable to discuss treatment options, and the challenge of obtaining informed consent is only exacerbated in situations that require immediate action. In such situations alternative forms of consent must be sought and the treatment decision may become the responsibility of the patient’s next of kin. Little attention has been paid to the decision making process for patients and their families in such situations. Given the need for an immediate treatment decision to be made, clinicians need to convey the potential benefits and risks of tPA treatment in order for family members to provide informed consent. Employment of best practice communication guidelines may aid the decision making process for family members and help clinicians to clearly convey the recommended treatment for ischaemic stroke patients. Aims: The purpose of the study was to compare, using a randomised controlled crossover trial among hospital out-patients, the effect of an expert consensus communication strategy compared to a usual care communication strategy (shown via video) on 1) participant knowledge of stroke treatment; 2) treatment decisions for tPA treatment for a) patients and b) a family member; 3) the acceptability of the communication strategies; and 4) the preferred communication strategy.

Stroke is the leading cause of adult disability and mortality in Australia, with the incidence set to rise as our population ages. The majority of strokes are ischaemic in nature and occur when a blood vessel to the brain is occluded, either by a clot or narrowing of the artery. Cerebral blood flow in acute ischaemic stroke is highly dynamic, and factors that either impair or promote cerebral blood flow during the acute phase may directly affect the infarct size and associated clinical deficit. Lowering the head of the bed in the early hours of stroke may theoretically assist flow to the ischaemic tissue, conversely, there is growing support for early mobilisation (getting up) after stroke, with a number of large clinical trials underway. Currently there is no consensus and no clinical guidelines on the safety of early upright posture when caring for acute stroke patients. We are therefore evaluating the extent and clinical relevance of orthostatic changes in cerebral blood flow in acute ischaemic stroke during position changes using transcranial Doppler ultrasound (TCD). The proposed study is a prospective, cohort study of patients with confirmed ischemic (due to a clot) stroke admitted within 24-48 hours of stroke onset to Austin Health. TCD examination is routine for people with stroke at Austin Health. It is performed flat (0 degress) of with the head slightly elevated. In this study, in recruited patients we will extend the current standard care TCD protocol to include measurement of cerebral blood flow velocity in 4 new positions: 30 degrees, 70 degrees, 90 degrees sitting (unsupported) and 90 degrees, standing (if possible). The primary outcome in this study is change in mean cerebral blood flow velocity (CBFVmean) in the middle cerebral artery on the affected stroke hemisphere with change in position from 0 degrees to 90 degrees sitting within the first 24-48 hours of stroke. The assessor of this outcome will be blinded to patient and position. This study will determine whether changing position to upright at 24-48 hours post stroke influences blood flow velocity in the affected hemisphere and whether this response modifies over the first week after stroke. A better understanding of orthostatic changes in blood flow may have significant clinical impact by providing a physiologic basis to guidelines on early head of bed elevation, positioning, and mobilisation of patients with acute anterior circulation stroke. The information from this study will therefore help inform practice and provide pilot data for a larger study that will aim to more clearly identify best practice protocols in subgroups of patients with different stroke characteristics and risk of impaired cerebral autoregulation.

The purpose of this pilot study is to determine whether providing quit incentives ('paying' [with vouchers'] for abstinence) to pregnant smokers will motivate them to quit during their pregnancy and stay quit once the baby is born. The study will determine if such an incentives intervention is more effective than the current 'usual care' smoking cessation protocols used in public hospital antenatal clinics in Tasmania. Furthermore, the proposed research will determine if incentivising partner support, that is, paying the partner of the pregnant smoker to be a more effective and active 'quit buddy', is more effective than providing cessation-contingent incentives to the expectant mother alone. All participants, during the initial study enrolment visit, will receive publicly available self-help quit materials developed especially for pregnant smokers, as well as a ‘partner pack’ containing materials especially designed for supporters of people trying to quit. At the completion of the initial enrolment visit, participants will be allocated to one of two groups: Control group (CG) or Treatment group (TG). For participants allocated to the Control group, only the participant (pregnant smoker) will be eligible to receive a monthly $50 voucher incentive if they verify (via exhaled breath carbon monoxide [CO] sample < 7ppm) as quit; for participants allocated to the Treatment group, both participant and nominated support person (where possible, spouse) will each be eligible to receive a monthly $50 voucher incentive if the participant verifies (CO sample < 7ppm) as being quit. After the initial enrolment visit (V1), where baseline measures, quit materials, and group allocation takes place, the researcher will telephone the participants on a monthly basis to determine smoking status. If during these calls the participant self-reports as quit, they will be invited to attend the study centre where, upon verification (via CO monitor) of their quit status, they will receive the $50 voucher incentive (plus partner incentive if in the TG). As well as participating in monthly telephone calls until 6 months postpartum (approximately 10 telephone calls), participants, regardless of smoking status, will be required to attend study visits at the end of pregnancy (V2; approximately 8 months gestation) and at 2 months postpartum (V3). During these study visits, participants will be asked to complete follow-up questionnaires (e.g., intention to quit, reasons for quitting, partner interaction questionnaire, smoking knowledge quiz) and have their smoking status verified (via CO monitor). If the participant quits smoking after the initial enrolment visit they may be eligible for a total incentive amount of $570 (plus a further $550 for TG partners). Participants will also participate in a final 12-month follow-up telephone call to determine long term quit status.

CEDRiC (Care coordination through Emergency Department, Residential Aged Care and PrImary Health Collaboration) is an innovative model of service delivery which aims to reduce RACF resident trauma and distress by reducing inappropriate transfer to the hospital emergency department (ED) and to maximise the care and efficiency of care where transfer to ED is appropriate. CEDRiC has two interconnecting components: (i) the Health Intervention Program for Senior (HIPS) the provision of proactive care in the Residential Aged Care Facility (RACF) via a Nurse Practitioner Candidate (NPC) working closely with GPs and RACF staff; and (ii) Geriatric Emergency Department Intervention (GEDI) program advanced practice nurses in the ED who case manage older adults in the ED. The aim of this trial is to determine the effect of the intervention via the outcomes. The trial aims to: 1. Determine ED re-presentation rates up to 72 hours and 28 days for patient cohort seen by GEDI nurses compared with this not seen by GEDI nurses 2. Determine number of RACF transfers avoided via NPC model of care 3. Determine cost effectiveness and sustainability of the GEDI and NPC model of care 4. Measure the ED length of stay on patient cohort seen by GEDI nurses compared with this not seen by GEDI nurses 5. Measure the number of hospital admissions on patient cohort seen by GEDI nurses compared with this not seen by GEDI nurses Group matching will be undertaken from hospital data for the 12 months prior to implementation of interventions.

The primary purpose of this study is to evaluate the safety and efficacy of tanibirumab in participants with recurrent glioblastoma multiforme (GBM). Who is it for? You may be eligible to join this study if you are aged 19 or over, and have been diagnosed with recurrent GBM following treatment with temozolomide chemotherapy with radiotherapy. Study details Tumour angiogenesis is the process that leads to the formation of blood vessels in a tumour, which in turn support cancer cell survival, local tumour growth, and the development of distant metastasis. The investigational drug tanibirumab (TTAC-0001) interferes with the angiogenesis process, inhibiting the formation of the blood vessels and thereby starving the tumour cells of the nutrients and oxygen required for growth. Participants in this study will be enrolled sequentially to arm 1, 2 or 3 with participants enrolled to arm 2 and 3 only after a safety evaluation of the previous arm. Each patient will only be allocated to one arm depending on the time of enrolment. All participants will receive tanibirumab in 3 or 4 doses, one per week, per cycle, for a total of up to 1 year, disease progression or study withdrawal. Throughout the study safety will be assessed by monitoring and assessment of adverse events, vital signs, laboratory tests including testing for immunogenicity (the ability of the study drug to provoke an immune response). Tumour response will be assessed by evaluating MRI scans performed every 8 weeks during treatment and at treatment termination. Blood sampling for drug interaction and distribution within the body will also be collected. It is hoped that the findings of this trial will develop our understanding of the safety of tanibirumab and of it's efficacy as a potential drug treatment for recurrent glioblastoma.

Progressive resistance training (PRT) is a powerful but underutilised tool in the battle against later life disability. With regular and ongoing PRT older adults can reduce their decline into dependency and disability. This has important implication for an individual's quality and dignity of life and for the national healthcare budget. The primary objective of this project is to evaluate evidence-based PRT as a service delivery option for community-dwelling older adults receiving government subsidised home care assistance. A comparison will be made between PRT participation and wait list control participants. Given the strength of evidence we hypothesise that with regular PRT, participants will reduce their trajectory of health decline, improve and prolong their wellbeing, with benefits retained for up to 24 weeks after the training period. Three hundred adults 65 years and older residing in north Brisbane and receiving a government subsidised home care assistance will be randomised to twice weekly PRT or a wait list control group. Participants will be bussed to and from their training and assessment sessions. All assessments and training session will be supervised by accredited exercise physiologists with special population expertise in disability and gerontology prescription. Data will be collected prior to and following long-term participation (24 weeks), and following a long-term period of non-participation (24 weeks), so the residual impact of PRT can be evaluated.