Hobart, Australia
Hobart, Australia

The Menzies Research Institute Tasmania is a research institute of the University of Tasmania based in Hobart. The institute conducts innovative, world-class medical research to improve human health and well-being. Wikipedia.

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Palmer A.J.,Menzies Research Institute
Value in Health | Year: 2013

Objectives: The Mount Hood Challenge meetings provide a forum for computer modelers of diabetes to discuss and compare models, to assess predictions against data from clinical trials and other studies, and to identify key future developments in the field. This article reports the proceedings of the Fifth Mount Hood Challenge in 2010. Methods: Eight modeling groups participated. Each group was given four modeling challenges to perform (in type 2 diabetes): to simulate a trial of a lipid-lowering intervention (The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus [ASPEN]), to simulate a trial of a blood glucose-lowering intervention (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation [ADVANCE]), to simulate a trial of a blood pressure-lowering intervention (Cardiovascular Risk in Diabetes [ACCORD]), and (optional) to simulate a second trial of blood glucose-lowering therapy (ACCORD). Model outcomes for each challenge were compared with the published findings of the respective trials. Results: The results of the models varied from each other and, in some cases, from the published trial data in important ways. In general, the models performed well in terms of predicting the relative benefit of interventions, but performed less well in terms of quantifying the absolute risk of complications in patients with type 2 diabetes. Methodological challenges were highlighted including matching trial end-point definitions, the importance of assumptions concerning the progression of risk factors over time, and accurately matching the patient characteristics from each trial. Conclusions: The Fifth Mount Hood Challenge allowed modelers, through systematic comparison and validation exercises, to identify important differences between models, address key methodological challenges, and discuss avenues of research to improve future diabetes models. © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Marwick T.H.,Menzies Research Institute
Heart | Year: 2013

The last decade has produced a proliferation of techniques for the assessment of left ventricular systolic function, and there now seems to be more choice than seems rational for the questions that we need answers to. In some instances, simple estimation is all that is required-the risk stratification process is inexact, as emphasised by the variety of modalities used to characterise ejection fraction (EF) in studies that validated the efficacy of treatments selected on the basis of EF. Nonetheless, while technical advances often cause disruption and confusion, it would be wrong to dismiss them as lacking benefit. The purpose of this review is to try to provide rational grounds for selecting both test modality and physiological parameter in various specific clinical situations.

Winzenberg T.M.,Menzies Research Institute
Cochrane database of systematic reviews (Online) | Year: 2010

Results of randomised controlled trials (RCTs) of vitamin D supplementation to improve bone density in children are inconsistent. To determine the effectiveness of vitamin D supplementation for improving bone mineral density in children, whether any effect varies by sex, age or pubertal stage, the type or dose of vitamin D given or baseline vitamin D status, and if effects persist after cessation of supplementation. We searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2009), MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), AMED (1985 to present) and ISI Web of Science (1945 to present) on 9 August 2009, and we handsearched key journal conference abstracts. Placebo-controlled RCTs of vitamin D supplementation for at least three months in healthy children and adolescents (aged from one month to < 20 years) with bone density outcomes. Two authors screened references for inclusion, assessed risk of bias, and extracted data. We conducted meta-analyses and calculated standardised mean differences (SMD) of the percent change from baseline in outcomes in treatment and control groups. We performed subgroup analyses by sex, pubertal stage, dose of vitamin D and baseline serum vitamin D and considered these as well as compliance and allocation concealment as possible sources of heterogeneity. We included six RCTs (343 participants receiving placebo and 541 receiving vitamin D) for meta-analyses. Vitamin D supplementation had no statistically significant effects on total body bone mineral content (BMC), hip bone mineral density (BMD) or forearm BMD. There was a trend to a small effect on lumbar spine BMD (SMD 0.15, 95% CI -0.01 to 0.31, P = 0.07). There were no differences in effects between high and low serum vitamin D studies at any site though there was a trend towards a larger effect with low vitamin D for total body BMC (P = 0.09 for difference). In low serum vitamin D studies, significant effects on total body BMC and lumbar spine BMD were approximately equivalent to a 2.6% and 1.7 % percentage point greater change from baseline in the supplemented group. These results do not support vitamin D supplementation to improve bone density in healthy children with normal vitamin D levels, but suggest that supplementation of deficient children may be clinically useful. Further RCTs in deficient children are needed to confirm this.

Kalam K.,Menzies Research Institute | Otahal P.,Menzies Research Institute | Marwick T.H.,Menzies Research Institute
Heart | Year: 2014

Background Global longitudinal strain (GLS) is a robust, well validated and reproducible technique for the measurement of LV longitudinal deformation. We sought to assemble evidence that GLS is an accurate marker in predicting cardiovascular outcomes, compared to LVEF. Methods We undertook a systematic review of the evidence from observational studies which compared GLS against LVEF in predicting major adverse cardiac events. The primary outcome was all-cause mortality. The secondary outcome was a composite of cardiac death, malignant arrhythmia, hospitalisation due to heart failure, urgent valve surgery or heart transplantation, and acute coronary ischaemic event. A random effects model was used to combine HR and 95% CIs. A meta-regression was undertaken to assess the impact of potential covariates. Results Data were collated from 16 published articles (n=5721 adults) comprising 15 prospective and 1 retrospective observational studies. The underlying cardiac conditions were heart failure, acute myocardial infarction, valvular heart disease, and miscellaneous cardiac diseases. Mortality was independently associated with each SD change in the absolute value of baseline GLS (HR 0.50, 95% CI 0.36 to 0.69; p<0.002) and less strongly with LVEF (HR 0.81, 95% CI 0.72 to 0.92; p=0.572). The HR per SD change in GLS was associated with a reduction in mortality 1.62 (95% CI 1.13 to 2.33; p=0.009) times greater than the HR per SD change in LVEF. Conclusions There is strong evidence of the prognostic value of GLS, which appears to have superior prognostic value to EF for predicting major adverse cardiac events. © 2014 BMJ Publishing Group Ltd & British Cardiovascular Society.

Dawkins E.,Menzies Research Institute | Small D.H.,Menzies Research Institute
Journal of Neurochemistry | Year: 2014

The β-amyloid precursor protein (APP) has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ) of Alzheimer's disease. However, the normal function of APP remains largely unknown. This article reviews studies on the structure, expression and post-translational processing of APP, as well as studies on the effects of APP in vitro and in vivo. We conclude that the published data provide strong evidence that APP has a trophic function. APP is likely to be involved in neural stem cell development, neuronal survival, neurite outgrowth and neurorepair. However, the mechanisms by which APP exerts its actions remain to be elucidated. The available evidence suggests that APP interacts both intracellularly and extracellularly to regulate various signal transduction mechanisms. © 2014 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

Wang S.,Menzies Research Institute | Young K.M.,Menzies Research Institute
Neuroscience | Year: 2014

CNS white matter is subject to a novel form of neural plasticity which has been termed "myelin plasticity". It is well established that oligodendrocyte generation and the addition of new myelin internodes continue throughout normal adulthood. These new myelin internodes maybe required for the de novo myelination of previously unmyelinated axons, myelin sheath replacement, or even myelin remodeling. Each process could alter axonal conduction velocity, but to what end? We review the changes that occur within the white matter over the lifetime, the known regulators and mediators of white matter plasticity in the mature CNS, and the physiological role this plasticity may play in CNS function. © 2013 IBRO.

Chang A.B.,Menzies Research Institute
Cochrane database of systematic reviews (Online) | Year: 2011

Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2)-antagonist and proton pump inhibitors (PPI)) and fundoplication. To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease, i.e. non-specific chronic cough. We searched the Cochrane Airways Group Specialised Register, the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, review articles and reference lists of relevant articles. The date of last search was 8 April 2010. All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease. Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information. We included 19 studies (six paediatric, 13 adults). None of the paediatric studies could be combined for meta-analysis. A single RCT in infants found that PPI (compared to placebo) was not efficacious for cough outcomes (favouring placebo OR 1.61; 95% CI 0.57 to 4.55) but those on PPI had significantly increased adverse events (OR 5.56; 95% CI 1.18 to 26.25) (number needed to treat for harm in four weeks was 11 (95% CI 3 to 232)). In adults, analysis of H(2) antagonist, motility agents and conservative treatment for GORD was not possible (lack of data) and there were no controlled studies of fundoplication. We analysed nine adult studies comparing PPI (two to three months) to placebo for various outcomes in the meta-analysis. Using intention-to-treat, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough (OR 0.46; 95% CI 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). We only found significant differences in sensitivity analyses. We found a significant improvement in change of cough scores at end of intervention (two to three months) in those receiving PPI (standardised mean difference -0.41; 95% CI -0.75 to -0.07) using generic inverse variance analysis on cross-over trials. Two studies reported improvement in cough after five days to two weeks of treatment. PPI is not efficacious for cough associated with GORD symptoms in very young children (including infants) and should not be used for cough outcomes. There is insufficient data in older children to draw any valid conclusions. In adults, there is insufficient evidence to conclude definitely that GORD treatment with PPI is universally beneficial for cough associated with GORD. Clinicians should be cognisant of the period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double-blind, randomised controlled and parallel-design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.

OBJECTIVE: The aim of this study was to describe the associations between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity, inflammatory cytokines and bone loss/erosions in patients with RA.METHODS: The study included 130 patients with RA and 80 healthy controls. Serum 25(OH)D, IL-17 and IL-23 levels were detected by ELISA. Radiographic bone erosion was assessed using the van der Heijde modified Sharp score and BMD was measured using DXA.RESULTS: There were no significant differences in age, gender and BMI between the RA and control groups. Serum level of 25(OH)D was markedly lower in the RA group than in the control group [43.12 nmol/l (s.d. 15.59) vs 57.93 (15.95), P < 0.01]. In RA patients, 25(OH)D levels were significantly and negatively associated with clinical parameters of disease activity including swollen joint count, tender joint count, joint pain degree, morning stiffness time and HAQ score and laboratory measures including platelets and ESR after adjustment for gender, age and BMI. They were also negatively associated with serum levels of IL-17 and IL-23. While 25(OH)D levels were not associated with radiographic bone erosions of RA, they were significantly lower in those with osteopenia and osteoporosis than in those with normal BMD (P < 0.01).CONCLUSION: 25(OH)D levels were reduced in patients with RA and were negatively associated with disease activity, IL-17/IL-23 and bone loss in RA. These suggest that vitamin D deficiency may play a role in the aetiology of RA. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Menzies Research Institute | Date: 2012-02-01

The present invention relates to neural cell survival, differentiation and proliferation promoting peptide fragments derived from metallothioneins (MT), pharmaceutical compositions comprising said peptide fragments and uses thereof for treatment of diseases and conditions where the effects of stimulating neural cell proliferation, differentiation and/or survival, and/or stimulating neural plasticity associated with learning and memory are beneficial for treatment.

Menzies Research Institute | Date: 2012-02-01

The present invention relates to neural cell survival, differentiation and proliferation promoting peptide fragments derived from metallothioneins (MT), pharmaceutical compositions comprising said peptide fragments and uses thereof for treatment of diseases and conditions where the effects of stimulating neural cell proliferation, differentiation and/or survival, and/or stimulating neural plasticity associated with learning and memory are beneficial for treatment.

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