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Hawkes E.A.,Austin Hospital | Hawkes E.A.,Eastern Health | Hawkes E.A.,Monash University | Grigg A.,Austin Hospital | And 4 more authors.
The Lancet Oncology | Year: 2015

Cancers can evade the host immune system by inducing upregulation of immune inhibitory signals. Anti-programmed cell death-1 (PD-1) monoclonal antibodies block these inhibitory signals allowing the host to mount an immune response against malignant cells. This class of drugs is active in solid tumours, where upregulation of cell-surface PD-1 ligand proteins is nearly uniform. Because lymphoma is a malignancy of immune system cells, the role of the PD-1 pathway in these neoplasms is more complex. However, early clinical trials using PD-1 inhibitors have shown significant clinical activity in various subtypes of relapsed lymphoma. In this Review, we assess the scientific literature on the role of the PD-1 pathway in lymphoma, the relevant clinical data for PD-1 inhibition, and future strategies for this next generation of anticancer agents. © 2015 Elsevier Ltd.


Ogeil R.P.,Monash University | Ogeil R.P.,Eastern Health | Phillips J.G.,Auckland University of Technology
Drug and Alcohol Dependence | Year: 2015

Background: Caffeine and nicotine are commonly used stimulants that enhance alertness and mood. Discontinuation of both stimulants is associated with withdrawal symptoms including sleep and mood disturbances, which may differ in males and females. The present study examines changes in sleep quality, daytime sleepiness and psychological distress associated with use and dependence on caffeine and nicotine. Methods: An online survey comprising validated tools to assess sleep quality, excessive daytime sleepiness and psychological distress was completed by 166 participants (74 males, 96 females) with a mean age of 28 years. Participants completed the study in their own time, and were not offered any inducements to participate. Results: Sleep quality was poorer in those dependent upon caffeine or nicotine, and there were also significant interaction effects with gender whereby females reported poorer sleep despite males reporting higher use of both stimulants. Caffeine dependence was associated with poorer sleep quality, increased daytime dysfunction, and increased levels of night time disturbance, while nicotine dependence was associated with poorer sleep quality and increased use of sleep medication and sleep disturbances. There were strong links between poor sleep and diminished affect, with psychological distress found to co-occur in the context of disturbed sleep. Conclusions: Stimulants are widely used to promote vigilance and mood; however, dependence on commonly used drugs including caffeine and nicotine is associated with decrements in sleep quality and increased psychological distress, which may be compounded in female dependent users. © 2015 Elsevier Ireland Ltd.


Gururajan A.,Monash Institute of Pharmaceutical Sciences | Taylor D.A.,Eastern Health | Malone D.T.,Monash Institute of Pharmaceutical Sciences
Journal of Psychopharmacology | Year: 2012

Recently, a novel paradigm has been designed to assess social investigative behaviour in pairs of Sprague-Dawley rats, which involves physical separation whilst ensuring they are able to maintain contact through other social cues. We have modified this set-up in order to assess not just social behaviour but also locomotor activity of the rats. Results showed that the MK-801- (0.3 mg/kg) treated rats displayed reduced social investigative behaviour, hyperactivity as well as reduced attention span. Pretreatment with the phytocannabinoid cannabidiol (3 mg/kg) not only normalised social investigative behaviour but increased it beyond control levels. Pretreatment with clozapine (1, 3 mg/kg) also normalised social investigative behaviour. Both cannabidiol and clozapine inhibited MK-801-induced hyperactivity. However, there were no effects of pretreatment on impairments to attention span. Our findings reinforce several aspects of the validity of the MK-801-induced model of social withdrawal and hyperactivity and also support the use of this novel set-up for further investigations to assess the antipsychotic potential of novel compounds. © The Author(s) 2012.


McGrice M.A.,Eastern Health | Porter J.A.,Eastern Health
Obesity Surgery | Year: 2012

Background: There is a paucity of evidence-based dietary management guidelines for patients post-laparoscopic adjustable gastric banding, including no consensus recommendations for macronutrient intake. We examined the macronutrient intake across a multi-centre cohort of post-bariatric surgery patients and compared these intakes to post-bariatric surgery and population-based dietary guidelines. Methods: Two hundred and fifteen patients from three bariatric surgery centres in Melbourne, Australia were invited to complete a validated Food Frequency Questionnaire 12 months post-operatively. Results: Energy intakes of the 52 participants ranged from 1,140 to 13,200 kJ/day, with an average of 4,890 kJ/day (±2,360 kJ/day). Many patients did not meet minimum population recommendations for macronutrients. The average fibre intake was only 14 g/day (compared to the recommendations of 25 g for women and 30 g for men). The average diet 1 year post-operatively was 36 % total fat compared to the recommendations of 20-25 %, with 14 % of intake from saturated fat. Conclusions: Patients' dietary intakes vary significantly 1 year post-laparoscopic adjustable band surgery, with many patients not meeting recommendations. These results suggest that patients decrease their total energy intake; however, eating habits may not improve as they consume a diet high in saturated fat. It is recommended that all patients receive dietary education about diet quality post-laparoscopic adjustable gastric band surgery to assist them in improving their diet quality as well as quantity for optimal health and weight loss. Specific international guidelines for nutrient intakes for people undergoing bariatric surgery are needed. © 2012 Springer Science + Business Media, LLC.


Yao W.,Eastern Health
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2013

We propose an approach to determining optimal beam weights in breast/chest wall IMRT treatment plans. The goal is to decrease breathing effect and to maximize skin dose if the skin is included in the target or, otherwise, to minimize the skin dose. Two points in the target are utilized to calculate the optimal weights. The optimal plan (i.e., the plan with optimal beam weights) consists of high energy unblocked beams, low energy unblocked beams, and IMRT beams. Six breast and five chest wall cases were retrospectively planned with this scheme in Eclipse, including one breast case where CTV was contoured by the physician. Compared with 3D CRT plans composed of unblocked and field-in-field beams, the optimal plans demonstrated comparable or better dose uniformity, homogeneity, and conformity to the target, especially at beam junction when supraclavicular nodes are involved. Compared with nonoptimal plans (i.e., plans with nonoptimized weights), the optimal plans had better dose distributions at shallow depths close to the skin, especially in cases where breathing effect was taken into account. This was verified with experiments using a MapCHECK device attached to a motion simulation table (to mimic motion caused by breathing).


Speed L.,Eastern Health | Harding K.E.,Eastern Health
Journal of Critical Care | Year: 2013

Purpose: Multidisciplinary tracheostomy teams have been implemented in acute hospitals over the past 10 years. This systematic review of the literature and meta-analysis aimed to assess the effect of tracheostomy teams on patient outcomes. Materials and Methods: We conducted an electronic search of the literature in the following databases: MEDLINE, CINAHL, EMBASE, and AMED. Inclusion/exclusion criteria were applied, and included articles were assessed against quality criteria. Qualitative synthesis and meta-analysis were completed. Results: Seven studies were included. The studies were all pre-post cohort designs of low-moderate quality. Meta-analysis showed that tracheostomy teams were associated with reductions in total tracheostomy time (4 studies; mean difference, 8 days; 95% confidence interval, 6-11; P < .01; I2 = 0%) and hospital length of stay (LOS) (3 studies; mean difference, -14 days; 95% confidence interval, -39 to 9; P = .23; I2 = 50%). Reductions in intensive care unit LOS (3 studies) and increases in speaking valve (3 studies) use were also reported with tracheostomy teams. Conclusion: There is low-quality evidence that multidisciplinary tracheostomy care contributes to a reduction in total tracheostomy time and increase speaking valve use for patients leading to improved quality of life. There is insufficient evidence to determine that multidisciplinary tracheostomy teams reduce hospital or intensive care unit LOS. © 2013.


Croagh C.M.N.,Eastern Health | Lubel J.S.,Eastern Health | Lubel J.S.,Monash University
World Journal of Gastroenterology | Year: 2014

Chronic hepatitis B (CHB) is a condition of global prevalence and its sequelae include cirrhosis and hepatocellular carcinoma. The natural history of CHB is a complex interplay of virological, environmental and host factors. The dynamic relationship between the virus and host evolves over the duration of the infection and different phases of the disease have been observed and described. These have been conceptualized in terms of the state of balance between the host immune system and the hepatitis B virus and have been given the labels immune tolerant, immune clearance, immune control and immune escape although other nomenclature is also used. Host factors, such as age at infection, determine progression to chronicity. Virological factors including hepatitis B viral load, mutations and genotype also have an impact on the adverse outcomes of the infection, as do hepatotoxic cofactors such as alcohol. Our understanding of the natural history of CHB has evolved significantly over the past few decades and characterizing the phase of disease of CHB remains an integral part of managing this virus in the clinic. © 2014 Baishideng Publishing Group Inc. All rights reserved.


A systematic review was conducted of the evidence for the effectiveness of the outcomes from treatment by multidisciplinary outpatient rehabilitation programs which were provided by more than one allied health or nursing discipline for people diagnosed with Parkinson's disease (PD). The search yielded only 4 studies ranging from poor to good quality, on the outcomes of multidisciplinary rehabilitation. There were no available random controlled trials on short term outcomes although some limited evidence from lower quality studies suggested significant short term gains are achieved in gait speed and step length. No consistent evidence is available for other outcome measures. From the available evidence for longer term outcomes over a period of 4-6 months post intervention the improvements in outcome measures for gait are not significant. The results of this systematic review suggest that there is limited evidence to suggest short term gains in outcomes for people with PD attending multidisciplinary programs but over a 4-6 month period these gains are no longer significant. Overall, there is very limited high level evidence available to show whether multidisciplinary out-patient programs produce effective, either short or long term, outcomes for PD and further research is needed. © 2010 - IOS Press and the authors. All rights reserved.


Wallis J.A.,Eastern Health | Taylor N.F.,Allied Health Clinical Research Office | Taylor N.F.,La Trobe University
Osteoarthritis and Cartilage | Year: 2011

Objective: To determine if pre-operative interventions for hip and knee osteoarthritis provide benefit before and after joint replacement. Method: Systematic review with meta-analysis of randomised controlled trials (RCTs) of pre-operative interventions for people with hip or knee osteoarthritis awaiting joint replacement surgery. Standardised mean differences (SMD) were calculated for pain, musculoskeletal impairment, activity limitation, quality of life, and health service utilisation (length of stay and discharge destination). The GRADE approach was used to determine the quality of the evidence. Results: Twenty-three RCTs involving 1461 participants awaiting hip or knee replacement surgery were identified. Meta-analysis provided moderate quality evidence that pre-operative exercise interventions for knee osteoarthritis reduced pain prior to knee replacement surgery (SMD (95% CI) = 0.43 [0.13, 0.73]). None of the other meta-analyses investigating pre-operative interventions for knee osteoarthritis demonstrated any effect. Meta-analyses provided low to moderate quality evidence that exercise interventions for hip osteoarthritis reduced pain (SMD (95% CI) = 0.52 [0.04, 1.01]) and improved activity (SMD (95% CI) = 0.47 [0.11, 0.83]) prior to hip replacement surgery. Meta-analyses provided low quality evidence that exercise with education programs improved activity after hip replacement with reduced time to reach functional milestones during hospital stay (e.g., SMD (95% CI) = 0.50 [0.10, 0.90] for first day walking). Conclusion: Low to moderate evidence from mostly small RCTs demonstrated that pre-operative interventions, particularly exercise, reduce pain for patients with hip and knee osteoarthritis prior to joint replacement, and exercise with education programs may improve activity after hip replacement. © 2011 Osteoarthritis Research Society International.


Clark I.,Eastern Health | Harding K.,Eastern Health
Nordic Journal of Music Therapy | Year: 2012

Meaningful interventions that enhance psychosocial factors, such as improving mood, reducing anxiety or increasing motivation, have the potential to ameliorate therapeutic outcomes for individuals in therapeutic programs. Singing, with its capacity for social, emotional, cognitive, and physical engagement, demonstrates potential as an accessible intervention that could facilitate such benefits. A systematic review of the literature was conducted to investigate the effectiveness of active singing as an intervention for improving psychosocial measures for people in therapeutic programs. Literature was searched through databases Medline, PsycInfo, Embase, Cinahl, Amed, and PubMed. Key concepts included populations in therapeutic programs, active singing as an intervention and psychosocial outcomes. Fourteen articles were identified that met the inclusion and exclusion criteria. These studies were assessed against quality criteria and data were tabulated for analysis and synthesis of results. Of the 11 quantitative studies, three demonstrated significantly improved psychosocial measures following the active singing intervention, and three further studies showed significant effects for both active singing and a comparison intervention. These findings are inconclusive and indicate that a variety of interventions including active singing demonstrate a capacity to improve psychosocial measures in the populations examined. Evidence from three qualitative papers, however, suggests that active singing may have some less tangible benefits that were not captured in the quantitative data. Further research with random group allocation, validated measurement tools, larger sample sizes and mixed quantitative and qualitative designs might increase the potential for results that capture the psychosocial effects of active singing for therapeutic purposes. © 2012 Copyright Taylor and Francis Group, LLC.

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