Melbourne Health Research Week 2014

Letter from the Executive Director of Research

Research week provides a focus on research where we can reflect on the value of research and celebrate advances in health and sciences. This year’s program promises to have something for everyone. To provide a taste of the diverse research activities at Melbourne Health we invite Professors Jo Douglass, Stephen Holt and Dennis Velakoulis to talk about their respective departments’ activities. Activities continue with the MH Research Symposium, a range of research education and information sessions as well as the Melbourne Academic Centre Research Symposium. The much-anticipated debate brings light relief to the festivities.

I would like to thank the efforts of those involved in reviewing abstracts and posters and the session chairs during Research Week. Your time and expertise is greatly appreciated. I would also like to thank the Research Week Committee for pulling together a wonderful program.

Thank you

Professor Ingrid Winship Executive Director Research

Research Week Committee 2014 Professor Ingrid Winship (Chair) Professor Terry O’Brien Ms Carol Jewell Professor Nick Santamaria Ms Catherine Lander Ms Jessica Savage Professor Danny Liew Professor Judith Savige Ms Angela Magira Dr Angela Watt Dr Ashley Ng

Day 1 – Thursday 12 Jun e 2 014 Opening Session 1.00 – 2.00 pm, Charles La Trobe Lecture Theatre, Function and Convention Centre, Ground Floor (Lunch at 12.30 pm)

Opening: Professor Ingrid Winship, Executive Director of Research, Melbourne Health Invited presentations on various research activities at Melbourne Health » Professor Jo Douglass, Head, Department of Immunology and Allergy » Professor Stephen Holt, Director of Nephrology » Professor Dennis Velakoulis, Director of the Neuropsychiatry Unit

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Day 2 – Friday 13 June 2014 Research Symposium

CONCURRENT SESSIONS: 9 . 1 5 – 1 0 . 1 5 A M

Session 1 Session 2 Session 3 Charles La Trobe Lecture Theatre Seminar Room 1 Seminar Room 2

1 Bernarda Cavka, Reducing LOS 5 Priscilla Auyeung, Autoreactive T cells 9 Tomas Kalincik, Comparative efficacy following primary elective hip and in chronic idiopathic urticaria target of switch to natalizumab or knee replacement surgery through the high-affinity IgE receptor Iα fingolimod in active relapsing- implementation of a standardised subunit (FcεRIα) remitting multiple sclerosis clinical pathway 6 Justin Denholm, Adverse effects of 10 Bruce Campbell, Generalizability of 2 Peita Price, Evaluation of the isoniazid preventative therapy: a real- imaging selection for intra-arterial effectiveness of the HARP Chest Pain world prospective cohort study. therapy in ischemic stroke – up to Pilot program on reducing hospital 7 Melinda Hardy, Cross-reactivity of a 30% of tPA patients are potentially utilisation and costs: A case-control ubiquitous barley-specific T cell eligible. study. population accounts for the immuno- 11 Tim Spelman, Seasonal variation of 3 Caroline Marshall, It’s a matter of stimulatory effects of oats in celiac relapse rate in MS is latitude- attitude! An antimicrobial disease dependent stewardship survey among visiting 8 Benjamin Cowie, The global burden 12 Nawaf Yassi, Stroke Location Predicts specialists, nurses and pharmacists of liver disease attributable to Functional Outcome After Stroke 4 Matthew Lowe, The Northwick Park hepatitis B, hepatitis C, and alcohol: Independently of Lesion Volume Dependency Scale Hospital Version increasing mortality, differing causes (NPDS-H) employed as a tool to reduce nursing absenteeism and positively affect outcomes in patient care in the rehabilitation setting

CONCURRENT SESSIONS: 1 0 . 3 0 – 1 1 . 3 0 A M

Session 4 Session 5 Session 6 Charles La Trobe Lecture Theatre Seminar Room 1 Seminar Room 2

13 Marie Gerdtz, Improving transitions 17 Stephen Edwards, Life Stressors and 21 Sila Genc, Investigating longitudinal from the emergency department: the Mental Health amongst adults with changes in fractional anisotropy in effect of an evidence-informed intellectual disability Alzheimer’s disease using different protocol on safety and quality of care 18 Ilana Ackerman, The substantial registration methods 14 Theresa Vassiliou, Improving personal burden of hip and knee 22 Julianne Bayliss, Spliced HBV consistency of emergency osteoarthritis among young people. genomes and truncated surface department triage categorisation: 19 David Canty, Ultrasound simulator proteins are associated with ground machine learning applied to clinical assisted teaching of cardiac anatomy glass hepatocytes, the neoplastic notes. to pre-clinical anatomy Students: A precursors to HBV associated 15 Kate Fetterplace, Measured energy pilot randomised trial of a three hour hepatocellular carcinoma expenditure compared with learning exposure. 23 Wayne Ng, LPA is involved in estimated energy requirments and 20 Paul Wraight, Percutaneous isolated modulating glioma stem cell acelerometry limb perfusion of the infected diabetic migration 16 Catherine Granger, Determinants Of foot 24 Monique Topp, Translating tumour The 6-Minute Walk Distance In profiles into targeted therapeutic Individuals With Lung Cancer approaches using pre-clinical patient models of epithelial ovarian cancer

Poster Viewing Session 11.45 am – 12.45 pm, Function and Convention Centre, Ground Floor, RMH Melbourne Health Research Week 2014 will display over 120 posters representing the diverse research activities throughout the organization and the Parkville precinct.

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LUNCH: 12.00 – 1 . 0 0 P M

The Great Parachute Debate 1:00 – 2:00 pm, Charles La Trobe Lecture Theatre, Function and Convention Centre, RMH

A deadly virus is unleashed… Six researchers survive… Only ONE can make it out ALIVE…

Melbourne Health has called together some of the greatest minds of our eminent institution to use their intellect to argue for their right to survive.

Master of Ceremonies (MC) Panelists » Professor Ingrid Winship, Executive Director » Prof Kate Leslie, Head of Anaesthesia Research Research Role: Genomicist Judges » Prof Nick Santamaria, Head of Nursing Research » Ms Sharon McGowan, Executive Director Role: Hospital Director of Finance Communications and Community Relations » Dr Emma O’Brien, Allied Health Divisional Manager » Professor Ruth Vine, Executive Director for NCIM & Manager NorthWestern Mental Health Role: Neurosurgeon » A Professor Rodney Judson, Director of » AProf Kate Drummond, Divisional Director Trauma Service Neurosciences, Haematology, Medical Oncology and Infectious Diseases Role: Bioethicist » Prof Danny Liew, Director, The Melbourne EpiCentre Role: Fertility Expert » Dr Ashley Ng, Consultant Haematologist, RMH Role: Biostatistician

Day 3 – Saturd ay 14 June 2014 Surgical Research Forum 8.30 – 9.30 am, Ewing Lecture Theatre, Level 5, Clinical Sciences Building

Chair: Professor Andrew Kaye, Professor of Surgery, University of Melbourne

25 Emma Gannan, Management of Early Stage Node-Positive 28 Wayne Ng, LPA is involved in modulating glioma stem cell Breast Cancer in Australia: A Multi-Centre Study migration 26 Michael Hong, Administrative Coding for Diverticulitis: 29 Emma Tully, Comparison of the management of acute biliary How accurate is it? tract pathology in the pre and post-emergency general surgery 27 Ashleigh Poh, Constitutive Hck activation promotes the era development and progression of colorectal cancer in mice

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Day 4 – Mon day 16 June 2014 How to Undertake Small Clinical Studies Pt. 1 9.00 am – 12.00 pm, Seminar Room 1, Function and Convention Centre, RMH

Study designs and basic epidemiological and statistical concepts

» Dr Megan Bohensky, Research Fellow, Melbourne EpiCentre, University of Melbourne » Dr Alex Gorelik, Senior Statistician, Melbourne EpiCentre, Melbourne Health

This session is coordinated by the Melbourne EpiCentre. Registration is required for this session as there are limited places. To register, please send an email to: [email protected] or telephone 9342 8772.

Research Education 1.00 pm – 2.00 pm, Seminar Room 1, Function and Convention Centre, RMH

Life after Ethics and Governance Approval: Tips on Managing Projects Post-Approval

» Dr Nitya Jani, Manager of Research Integrity and Ethics, Office for Research

Coordinated by the Office for Research, this is a troubleshooting session outlining common errors made when submitting post-approval documents and provides tips on how to get your amendments, progress reports and safety updates reviewed as quickly as possible. For planning purposes, register your attendance via email to Jessica Savage at: [email protected].

Day 5 – Tu esd ay 17 Jun e 20 14 How to Undertake Small Clinical Studies Pt. 2 9.00 am – 12.00 pm, Computer Lab, RMH Library, Ground Floor

Data analysis using Microsoft Excel

» Dr Alex Gorelik, Senior Statistician, Melbourne EpiCentre, Melbourne Health

This session is coordinated by the Melbourne EpiCentre. Registration is required for this session as there are limited places. To register, please send an email to: [email protected] or telephone 9342 8772.

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Day 5 – Tuesday 17 June 2014 Research Education 1.00 pm – 2.00 pm, Seminar Room 1, Function and Convention Centre, RMH

Genetic Issues in Ethical Research

» Dr Michael Bogwitz, Genetic Counsellor » Dr Adrienne Sexton, Genetic Counsellor » Professor Ingrid Winship, Head of Genetics

Your guide to alternate funding and development opportunities! » Steve Christov, Director Business Development

Coordinated by the Office for Research, two presentations on issues affecting research at Melbourne Health. For planning purposes, register your attendance via email to Jessica Savage at: [email protected].

Day 6 – W edn esd ay 18 June 2014 Research Skills Interactive Workshop 9.00 am – 12.30 pm, Seminar Room 1, Function and Convention Centre, Ground Floor, RMH

Qualitative Research: “How, When and Why?”

» Dr Ilana Ackerman, Senior Research Fellow, Melbourne EpiCentre

Dr Ilana Ackerman is a musculoskeletal researcher and experienced orthopaedic physiotherapist who has conducted a range of mixed methods studies across clinical and community settings. Her publications have been extensively cited and she has received funding from the NHMRC, Arthritis Australia and the Physiotherapy Research Foundation to support her research involving people with arthritis. Dr Ackerman will be providing an overview of: » The role of qualitative and mixed method research designs and their application to the clinical setting » Methods for undertaking qualitative research and data analysis » Assessing the rigour of qualitative research papers To register, please send email to: [email protected].

Laboratory Skills Workshop 2.00 pm – 5.00 pm, Fourth floor, Clinical Sciences Building, Grattan Street, RMH

Hands on PCR Workshop

» Professor Judy Savige, Physician, Royal Melbourne Hospital; Professor of Medicine, University of Melbourne

Hold some DNA, make DNA using the polymerase chain reaction, and learn to identify mutations from next gen sequencing readouts. This workshop provides practical experience of current technology and is suitable for physician trainees and other hospital staff. No previous lab experience required.

Please register via email with Prof Judy Savige at: [email protected].

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Day 7 – Thu rsd ay 19 Jun e 2 014 Melbourne Academic Centre Research Symposium 9.00 am – 12.30 pm, Charles La Trobe Lecture Theatre, Function and Convention Centre, RMH

Towards Precision Medicine

Chair: Professor Ian Everall, Cato Professor of Psychiatry and Head, Department of Psychiatry, University of Melbourne Opening: Dr David Alcorn, Executive Director, Royal Melbourne Hospital Keynote Lecture: Professor Fernando Sanchez, Adjunct Professor at the Department of Computing and Information Systems, Melbourne School of Engineering New sources of big data for precision medicine: Are we ready?

Session 1 Session 2 Chair: Professor Peter Rodgers Chair: Professor Christos Pantelis 10.00 – 10.15 Dr Frank Gaillard, Improving new MS lesion 11.00 – 11.15 Dr Andrew Morokoff, Mapping neural predictors detection using a novel semi-automated of treatment response in youth depression: computer aided process introduction to YoDA trial 10.15 – 10.30 Dr Harry Georgiou, Novel biomarkers to predict 11.15 – 11.30 A/Prof Chris Hovens, Intra-metastatic preterm labour heterogeneity and prostate cancer: Will the real Morning Tea 10.30 am to 11.00 am lethal subclone please stand up? 11.30 – 11.45 Prof Patrick Kwan, Test n’ Throw: Express disposable point-of-care molecular diagnostics 11.45 – 12.00 Dr Tom Oxley, Feasibility for an Endovascular Brain Machine Interface 12.00 – 12.15 Dr Sarah Whittle, Biological sensitivity to context: Implications for adolescent depression

Closing Comments: Professor Ingrid Winship, Chair, Clinical Genetics, Department of Medicine, RMH, University of Melbourne; Executive Director Research, Melbourne Health

LUNCH: 12.30 – 1 . 0 0 P M

Closing Ceremony 1.00 – 2.00 pm, Charles La Trobe Lecture Theatre, Function and Convention Centre, RMH

Chair: Professor Ingrid Winship, Executive Director Research Plenary: Dr Michael Wong, Influence of the Long Interdialytic Period (IDP) on the Incidence of Serious Arrhythmias and Sudden Cardiac Death in Patients with Chronic Kidney Disease undergoing Haemodialysis Final presentation for Research Week followed by the annual awarding of the Research Week prizes handed out by the Executive Officer of Melbourne Health, Dr Gareth Goodier. Prizes will be awarded for best oral and poster presentations as well as the winner of this Cleveland Young Investigator Award 2014.

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1 MS BERNARDA CAVKA event, and those frequently attending hospital within 12 months with Chest Pain and or complex needs. 95 patients were recruited as the ‘case group’, Reducing LOS following primary elective hip and knee with 97 patients recruited as the ‘control’ group. replacement surgery through implementation of a The case patients were phone “coached” to support the patient to self standardised clinical pathway manage their Chest Pain management. Hospital utilisation information prior to CAVKA B, Bucknill A, Hogg M, Moore D, Shanahan C, Tacey M and post their recruitment was obtained from Hospital administrative data and costs were obtained from the clinical costing unit. Following descriptive and Royal Melbourne Hospital univariate analysis, multivariate analysis was conducted to statistically adjust Aim: In 2011 / 2012, The Royal Melbourne Hospital’s (RMH) average LOS for noted differences between the case and control groups. following elective primary THR and TKR was 6.7 days which compared unfavourably with exemplar organisations. The aim of the project was to Results: The rate of re-presentations to ED within 30 days of index admission reduce LOS through implementation of a standardised evidence based is significantly less for the case group (14.1%) when compared to the control clinical pathway aimed at minimising variation in practice. group (27.7%). After adjusting for the Baseline differences we find that the case patients are more than 2 times less likely to have re-presentations than Method: The process to identify factors affecting LOS included the following: the control group (OR=0.44, p=0.049). After adjustment for baseline inpatient » Analysis of retrospective data from 288 consecutive patients (July 2011 costs (i.e. during 6-month period prior to recruitment) and differences in – March 2013) following primary elective THR or TKR surgery including baseline characteristics, the estimated reduction in inpatient costs for the post operative complications, wait time for surgery, discharge case group was $1967 (95% CI: $4827 reduction to $893 increase) when destination compared to the control group, although this change was not statistically » Focus groups with key stakeholders significant (p=0.177). » Patient interviews regarding their experiences Conclusion: A phone based integrated disease management program with » Literature reviews targeted interventions can be highly effective in reducing hospital Solutions to the confirmed contributing factors to increased LOS were readmissions and consequent cost savings in a broad patient population with generated by over 40 staff including patient education brochures, blood “Chest Pain”. management guidelines to reduce RBC transfusion rates, multi modal analgesia reducing use of opiates and day of surgery mobilisation. 3 A/PROF CAROLINE MARSHALL Results: The pilot was conducted between November 2013 – April 2014 and included 85 consecutive patients undergoing primary elective THR or TKR It’s a matter of attitude! An antimicrobial stewardship surgery. There was a significant reduction in LOS of 2.1 days (p<0.001) which survey among visiting specialists, nurses and pharmacists was not influenced by discharge destination (home versus rehabilitation). COTTA MO, Robertson MS, Tacey M, Marshall C, Thursky KA, Liew D, Buising Several secondary variables demonstrated encouraging data as listed below. KL » Thirty two patients (42.7%) were mobilised on the day of surgery Department of Medicine, University of Melbourne; Infectious Diseases Service, Royal compared to an estimation of <5% at baseline Melbourne Hospital; Epworth HealthCare, Victoria, Australia » Reduction in post operative RBC transfusions from 16.9% at baseline to Background: An effective hospital-wide antimicrobial stewardship (AMS) 9.4% program requires engagement with all healthcare professionals involved in » Reduction of PCA use from 95% at baseline to 16.5% antimicrobial use. It is therefore useful to consider attitudes towards » Reduced incidence of post operative nausea and vomiting (12.4%) antimicrobial resistance, antimicrobial prescribing and proposed AMS » Reduced waiting time for transfer to a sub acute setting by 3.7 days interventions prior to program implementation. There was high compliance from anesthetists with post operative prescription of the multi modal analgesics meloxicam, Targin, Gabapentin, oxycodone and Methods: A 26-item attitudinal survey was distributed to visiting specialists, paracetamol (95.3%) and intra operative administration of IV tranexamic acid nurses and pharmacists at a large (500 bed) private hospital in Melbourne. (76.5%). Survey questions utilised a “Yes/No” responses and a 7-point Likert scale ranging from “strongly agree” to “strongly disagree”. Descriptive analyses Conclusion: The implementation of a standardised evidence based pathway were performed and chi-squared tests conducted. for primary elective THR and TKR surgery has resulted in process efficiencies evident through a significant reduction in LOS, reduced post operative Results: There were a total of 331 respondents (80 physicians, 58 surgeons, complications, reduced requirements for RBC transfusions and improved 78 anaesthetists, 105 nurses and 10 pharmacists). multidisciplinary collaboration. Surveys of the patient experience are currently A larger proportion of respondents believed that antimicrobial resistance was being undertaken. a serious problem in other hospitals compared to their own (p<0.001). Fifty eight percent agreed that improving prescribing at the hospital would reduce 2 MRS PEITA PRICE antimicrobial resistance. Evaluation of the effectiveness of the HARP Chest Pain Eighty per cent of pharmacists believed there the majority of antimicrobial Pilot program on reducing hospital utilisation and costs: A prescribed for general use and surgical prophylaxis in the hospital was not case-control study. compliant with national prescribing guidelines. These proportions of surveyed pharmacists were significantly higher compared to the other professions Price P, Tacey M, Vincent R, Grigg L (p=0.007 and p=0.019, respectively). HARP- Merri Community Health Service, Coburg, Victoria; Royal Melbourne Hospital; Melbourne EpiCentre, Department of Medicine, University of Melbourne. Twenty nine percent of respondents had previous exposure to AMS, with pharmacists and physicians more likely to have heard of AMS compared to Background: The Tollgate Cardiology Length of stay Project (2009) surgeons, anaesthetists and nurses (p=0.016 and p<0.001 respectively). demonstrated that within 6 months 25% of 12 – 14 hour stayers in the Royal Melbourne Hospital (RMH) Emergency Department (ED) with Chest Pain Just 50.5% of respondents were willing to participate in proposed AMS were admitted back to ED and that 5 – 10% of the population who have interventions, but notably all surveyed pharmacists responded positively Percutaneous Intervention (PCI) presented back to ED with atypical Chest (p=0.002). Pain. These patients who frequently attend ED with Chest Pain do not Conclusion: Pre-existing awareness of issues around AMS was low among always “fit” into established pathways for those having an Acute Myocardial respondents. This study highlights the challenge of making antimicrobial event and are often discharged from the ED to home with short lengths of resistance a local issue and engaging staff prior to implementing change. In stay and are unlikely to be enrolled in mainstream support programs. particular, nursing staff, surgeons and anaesthetists had low levels of Aim: To assess the impact on Hospital presentations, admissions and costs awareness and should be targeted for education. Conversely, pharmacists of a phone-based “coaching” program for patients frequently attending the represent likely proponents of any newly introduced stewardship program. RMH ED with Chest Pain Methods: The study population consisted of consecutive patients recruited over a 12 month period to the HARP Chest Pain pilot that met the recruitment criteria of those that represented with Chest Pain within 6 months of a cardiac

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ongoing database of LTBI treatment outcomes, particularly related to adverse 4 MR MATTHEW LOWE effects and treatment adherence. 12 months after initiation of therapy, an The Northwick Park Dependency Scale Hospital Version additional retrospective chart review was performed to document whether (NPDS-H) employed as a tool to reduce nursing treatment had been successfully completed. absenteeism and positively affect outcomes in patient care Results: Data on the first 100 patients who were prescribed IPT are in the rehabilitation setting presented. 56 patients reported at least one adverse effect at some stage during treatment, with 6 experiencing at least one grade 3-4 adverse effect. LOWE M, Rowe L, Santamaria N, Tacey M Increased age was significantly associated with risk of adverse effects (OR Royal Melbourne Hospital 1.05 per year, 95% CI 1.02-1.08). 85 patients had documented completion of This study aims to examine the effectiveness of the Northwick Park therapy locally, with 10 ceasing due to adverse effects. Dependency Scale Hospital version (NPDS-H) in managing nursing workforce Discussion: This report highlights a variety of somatic adverse effects that needs and improving patient outcomes on the Rehabilitation Inpatient Unit, occurred in a real-world cohort of patients receiving IPT. While adverse Royal Melbourne Hospital, Royal Park Campus. The eight-month study was effects were frequently identified in this study, the considerable majority were divided into two four-month stages. In Stage One the NPDS-H established low grade and transient. Despite frequent adverse effects, this study has also the Rehabilitation Unit’s baseline level of patient dependency. In Stage Two demonstrated high levels of treatment adherence and completion in our the NPDS-H was a trigger for enlisting additional staff to assist with the unit’s cohort. workload. The performance and outcome measures utilised in the study included: nurses’ personal leave hours; Functional Independence Measure 7 DR MELINDA HARDY (FIM) and the Length of Stay (LOS) in four diagnostic groups – stroke, multiple sclerosis, hip replacement, and above and below knee amputations. Cross-reactivity of a ubiquitous barley-specific T cell Quality and safety indicators evaluated comprised of medication errors and population accounts for the immuno-stimulatory effects of patient falls. Accordingly, the results obtained demonstrated that personal oats in celiac disease leave significantly decreased from the fourth week of the Stage Two period by HARDY M 1-2, Tye-Din J 1-3, Stewart J 1, Schmitz F 1, Dudek N 5, Hanchapola I an average of 17.4 hours per week (p=0.046). Additionally the average 5, Purcell A 5, Anderson R 1,4. NPDS-H score was recorded to be higher in the Stage Two, indicating that the unit was comparatively busier during this stage. Hence, the results of the 1 Immunology Division, The Walter and Eliza Hall Institute of Medical Research. 2 Department of Medical Biology, The University of Melbourne.3 Department of study indicated that the NPDS-H may be a valid tool to manage the nursing Gastroenterology, The Royal Melbourne Hospital. 4 ImmusanT, Inc., One Kendall Square, workforce by reducing staff personal leave; however, no quantitative evidence Building 200, LL, Suite 4, Cambridge, MA 02139, USA. 5 Department of Biochemistry and of improvements in patient outcomes was observed. Molecular Biology, Monash University. Background and aims: Pure oats consumption rarely causes clinical disease 5 DR PRISCILLA AUYEUNG relapse in celiac disease (CD), but many patients exclude oats from their Autoreactive T cells in chronic idiopathic urticaria target diets because of concerns regarding potential immunotoxicity. the high-affinity IgE receptor Iα subunit (FcεRIα) Comprehensive epitope mapping has been performed for the toxic grains wheat, rye, and barley, but there is limited evidence that T cells specific to AUYEUNG P, Mittag D, Hodgkin P, Harrison L oats avenin exist in CD patients. Therefore, we examined the in vivo avenin- Walter and Eliza Hall Institute; Royal Melbourne Hospital specific T cell response in CD patients. Background: Chronic idiopathic urticaria (CIU) is the recurrence of “hives” Methods: We utilized short-term oral oats challenge and measured the without an apparent trigger. 50% of CIU patients have IgG autoantibodies to polyclonal avenin-specific T cell responses to peptides contained within the FcεRIα on dermal mast cells and basophils, which upon activation release comprehensive avenin peptide libraries in 73 HLA-DQ2.5+ CD patients. Grain mediators responsible for the formation of urticaria. T cells are present in the cross-reactivity was investigated using oral challenge with wheat, barley, and skin lesions but autoantigen-specific T cells have not been identified in CIU. rye. Aims: We aimed to identify autoreactive T cells to FcεRIα in CIU, to help Results: Avenin-specific responses were observed in 6/73 HLA-DQ2.5+ CD elucidate the pathogenesis and to improve the diagnosis of this disease. patients (8%), against four closely related, partially deamidated avenin- Methods: Peripheral blood T-cell responses to FcεRIα were assayed in 56 derived peptides. Due to strong peptide homology, oral barley challenge CIU and 40 control subjects. Cell proliferation was measured by CFSE dye efficiently induced cross-reactive avenin-specific T cells in most CD patients, dilution. IFN-γ, IL-5 and IL-13 secretion were measured by ELISpot. Serum whereas wheat or rye challenge did not. Pronounced cross-reactivity was also autoantibodies to FcεRIα were measured by immunoprecipitation of 125I- evident when T cell clones raised to homologous peptides responded to both labelled FcεRIα. oat and barley peptides. The most immunogenic avenin peptides were highly susceptible to digestive endopeptidases and showed poorer HLA-DQ2.5 Results: We detected significant CD4+ T-cell proliferation to FcεRIα in 29% of binding stability in vitro compared to homologous barley peptides in vitro. CIU 0% of control subjects. IFN-γ responses were detected in 58% of CIU subjects, while IL-5 and IL-13 responses were detected in 29% and 37% of Conclusions: Our findings indicate that most CD patients possess avenin- CIU subjects, respectively. We detected autoantibodies to FcεRIα in 45% of reactive T cells that preferentially recognize barley-derived epitopes. CIU and 0% of control subjects. Overall, at least one FcεRIα-specific However, these cross-reactive T cells are more efficiently activated in vivo by response was detected in 100% of CIU and only 5% of control subjects. dietary barley than by oats. We conclude that oats do activate gluten-reactive T cells in occasional CD patients in vivo, but their presence does not Conclusion. Autoreactive CD4+ T cells specific for FcεRIα were detected in a necessarily indicate that oats are toxic or should be excluded from the diet. proportion of subjects with CIU and, in combination with the assay for autoantibodies to FcεRIα, may improve the diagnosis of CIU. 8 DR BENJAMIN COWIE 6 DR JUSTIN DENHOLM The global burden of liver disease attributable to hepatitis B, Adverse effects of isoniazid preventative therapy: a real- hepatitis C, and alcohol: increasing mortality, differing causes world prospective cohort study. COWIE BC, MacLachlan JH DENHOLM JT, McBryde ES, Eisen DP, Pennington JS, Chen C, Street A WHO Regional Reference Laboratory for Hepatitis B, Victorian Infectious Diseases Reference Laboratory; Department of Medicine, University of Melbourne. Victorian Infectious Diseases Service, Royal Melbourne Hospital Background: Establishing the relative contributions of the underlying causes Introduction - Isoniazid preventative therapy (IPT) is a widely used of liver cancer and cirrhosis deaths is essential for appropriate targeting of intervention for treatment of latent tuberculosis infection, particularly in public health and clinical responses at global, regional and national levels. patients at high risk for reactivation. While treatment-limiting adverse effects have been well-studied, few prospective studies have considered the broader Methods: Using country-level and regional cause of death data released by range of adverse effects that patients may experience in association with IPT. the Global Burden of Disease Study 2010 (GBD 2010), we analysed the proportion of cirrhosis and liver cancer deaths attributable to HBV, HCV, Methods: From June 2011, all patients commencing treatment for latent alcohol, and other causes globally, but also in the USA, Western Europe, tuberculosis infection at a single TB clinic were prospectively enrolled in an India, China and Australia. Results: According to GBD 2010 data, there were Page | 8

an estimated 752 000 deaths from liver cancer and 1.03 million deaths from Neurology, Box Hill Hospital, Monash University; Department of Neurology, Auckland cirrhosis in 2010, making chronic liver disease a leading cause of human Hospital, University of Auckland. mortality. In the USA in 2010, approximately 70,000 people are estimated to Background: Recent trials have shown no benefit of endovascular therapy have died from these causes. On a global basis, HBV is estimated to be over tPA. Enhanced selection in ongoing trials includes non-invasive responsible for 45% of liver cancer deaths and 30% of cirrhosis deaths, and angiography/perfusion imaging but the effects on generalizability have been HCV for 26% and 28%, respectively. Alcohol abuse is estimated to be controversial. We investigated the effect of imaging selection on potential responsible for approximately one quarter of liver cancer and cirrhosis deaths. recruitment and generalizability. With respect to regional estimates, HCV was the predominant cause of liver Methods: Screening data from the EXTEND-IA trial listing primary reason for cancer/cirrhosis deaths in the USA (40/41%) and Western Europe (36/40%), exclusion were reviewed. Prevalence of each exclusion criteria was assessed with HBV predominating in China (54/46%) and India (48/35%). In Australia, at a single centre. Imaging eligibility requires internal carotid (ICA) or proximal leading causes of liver cancer and cirrhosis deaths were discordant; HBV (M1 or M2) middle cerebral artery occlusion and CT perfusion (CTP) lead as a cause of liver cancer deaths (41%) but alcohol was the predominant mismatch/ ischemic core volume <70mL. cause of cirrhosis deaths (33%). Results: Over 17 months, 350 patients received tPA at 5 centres and 37 Conclusions: These data from the GBD 2010 indicate that liver cancer and (11%) were randomized. Most exclusions were due to no vessel occlusion cirrhosis result in the deaths of 1.75 million humans each year, with chronic (30%), poor pre-morbid function (mRS>1, 25%) and presentation out-of-hours viral hepatitis causing approximately three quarters of these deaths. This (23%). Examining detailed data from the highest recruiting centre, analysis is drawn from a single study – the GBD 2010 – and must be 115/613(19%) of ischemic stroke patients received tPA and 14/115 (12%) considered together with other available data on causes of chronic liver were randomized. ICA/M1/M2 occlusion was present in 44/115 (38%). CTP disease worldwide. However the ability to systematically assess causes of mismatch criteria excluded 5/44 (11%) with vessel occlusion (all due to disease and death using the same methodology across all regions and ischemic core>70mL). If trial operating hours were extended and premorbid countries is an essential strength of GBD 2010. Greater priority to chronic mRS criteria relaxed, up to 33/115 (29%) of tPA patients could have been viral hepatitis and other causes of liver disease is clearly needed to address suitable for endovascular therapy. Adding patients with tPA contraindications this large burden of disease and death. The differing predominant causes of made 41/236(17%) of all ischemic stroke patients presenting within 4.5hr chronic liver disease identified across different regions requires prioritisation potentially eligible for endovascular treatment. of prevention responses to address this emergent global health priority. Conclusions: Approximately 38% of patients treated with tPA have a vessel 9 DR TOMAS KALINCIK occlusion amenable to clot retrieval with ~5% excluded due to >70mL core. Lack of 24h proceduralist availability and strict pre-morbid functional status Comparative efficacy of switch to natalizumab or criteria excluded a further 17%, leaving 12% of tPA patients randomized in fingolimod in active relapsing-remitting multiple sclerosis EXTEND-IA. If randomized trials provide evidence and lead to improved KALINCIK T, Butzkueven H, on behalf of the MSBase Study Group resources, endovascular therapy could be applicable in a substantial Melbourne Brain Centre, Department of Medicine, University of Melbourne; Department proportion of patients. of Neurology, Royal Melbourne Hospital Background: In patients suffering multiple sclerosis activity despite treatment 11 DR TIM SPELMAN with interferon β or glatiramer acetate, clinicians often switch therapy to either Seasonal variation of relapse rate in MS is latitude- natalizumab or fingolimod. However, no studies have directly compared the dependent outcomes of switching to either of these two agents. TIM SPELMAN1, Orla Gray2, Maria Trojano3, Thor Petersen4, Guillermo Methods: Using MSBase, a large international, observational multiple Izquierdo5, Alessandra Lugaresi6, Raymond Hupperts7, Roberto sclerosis registry, we identified patients with relapsing-remitting disease Bergamaschi8, Pierre Duquette9, Pierre Grammond10, Giorgio Giuliani11, experiencing relapses or disability progression within the 6 months Cavit Boz12, Freek Verheul13, Helmut Butzkueven1 immediately preceding switch to either natalizumab or fingolimod. Quasi- 1 Department of Neurology, Royal Melbourne Hospital; 2 Craigavon Area Hospital, randomisation with propensity score-based matching was used to select sub- Portadown, Northern Ireland; 3 Department of Basic Medical sciences, Neuroscience and populations with comparable baseline characteristics. Relapse and disability Sense Organs, University of Bari, Italy; 4 Kommunehospitalet, Arhus C, Denmark; 5 outcomes were compared in paired, pairwise-censored analyses. Hospital Universitario Virgen Macarena, Sevilla, Spain; 6 MS Center, Department of Neuroscience and Imaging, University ‘G. d’Annunzio’, Chieti, Italy; 7 Results: Out of the 792 included patients, 578 patients were matched Maaslandziekenhuis, Sittard, The Netherlands; 8 Neurological Institute IRCCS Mondino, (natalizumab n=407, fingolimod n=171). Mean on-study follow-up was 12 Pavia, Italy; 9 Hôpital Notre Dame, Montreal, Canada; 10 Center de réadaptation déficience physique Chaudière-Appalache, Levis, Canada; 11 Ospedale di Macerata, months. The annualised relapse rates decreased from 1.5 to 0.2 on Macerata, Italy; 12 Karadeniz Technical University, Trabzon, Turkey.13 Groene Hart natalizumab and from 1.3 to 0.4 on fingolimod, with 50% relative post-switch ziekenhuis, Gouda, The Netherlands difference in relapse hazard (p<0.001). The change in disability burden Introduction: Previous studies into seasonal variation of relapses in multiple (quantified as area under disability-time curve) differed between natalizumab sclerosis have had conflicting results. Small relapse numbers, differing and fingolimod ( 0.12 vs. 0.04 per year, respectively, p=0.002). This was diagnostic criteria, differing relapse definitions and single region studies limit largely due to a 67% higher rate of sustained disability regression after switch the generalizability of results. However, a large meta-analysis found that to natalizumab versus fingolimod (p=0.03). No difference in the rate of relapse onset probability varies seasonally, with a spring peak and winter sustained disability progression events was observed between the groups. trough. Conclusions: In patients with active multiple sclerosis during treatment with Objective: The aim of this study was to determine if there is a temporal injectable disease modifying therapies, switch to natalizumab is more variation in onset of relapses in both the northern and southern hemispheres effective than switch to fingolimod in reducing relapse rate and disability and to investigate whether the lag between location-specific seasonal ultra- burden. The probability of disability progression events is similar between the violet radiation trough and subsequent relapse peak varied with latitude. two switch strategies. Methods: Relapses from the MSBase registry were analyzed by hemisphere 10 DR BRUCE CAMPBELL and latitude. Relapses per month for each location were calculated. All analyses were weighted for the number of patients contributed by each Generalizability of imaging selection for intra-arterial center. A sine regression model consisting of one sine and one cosine therapy in ischemic stroke – up to 30% of tPA patients are function, describing a single annual cycle with one peak and one trough potentially eligible. separated by six months, was used to model relapse onset and UVR CAMPBELL B, Mitchell P, Yassi N, Kleinig T, Dewey H, Bladin C, Barber PA, seasonality. Linear regression was used to investigate associations between Donnan G, Davis S for the EXTEND-IA Investigators. latitude and lag between UVR trough and subsequent relapse peak. Department of Medicine and Neurology, Royal Melbourne Hospital, University of Results: 32,762 relapses from 9811 patients in 46 centers across 30 Melbourne; Department of Radiology, Royal Melbourne Hospital, University of countries were analysed. Relapse onset followed an annual cyclical Melbourne; Florey Institute of Neuroscience and Mental Health, University of Melbourne; Department of Neurology, Royal Adelaide Hospital, University of Adelaide; sinusoidal pattern with peaks in early spring and troughs in autumn in both Department of Neurology, Austin Hospital, University of Melbourne; Department of hemispheres. This seasonal variation was statistically significant, with the phase-shift across all relapses estimated at -24.83 (95% CI -45.81, -3.92) Page | 9

which translated into an estimated relapse peak of the 7th March (95% CI 10th February, 28th March) in the northern hemisphere and 5th September 13 A/PROF MARIE GERDTZ (95% CI 10th August, 26th September) in the southern hemisphere. There Improving transitions from the emergency department: was no difference in this pattern by hemisphere (test of interaction p=0.254). the effect of an evidence-informed protocol on safety and Every 10 degrees of latitude away from the equator was associated with a quality of care mean decrease in ultra-violet radiation trough to subsequent relapse peak lag of 28.5 days (95% CI 3.29, 53.71, p=0.028) and controlling for absolute UVR 1. GERDTZ M, 2. Dean A, 3. Vassiliou T, 4. Waite R, 5. Santamaria N, 6. Virtue at each location. There was no difference in this association by hemisphere E, Knott J, Harrod R (p=0.811). 1, 4, 5. The University of Melbourne and Melbourne Health, Level 1 Royal Melbourne Hospital Emergency Department, Grattan Street Parkville Victoria Australia 3050; 2, 3, 6, Conclusions: In our large, multinational study of MS outcomes, we confirm 7, 8. Melbourne Health, Level 1 Royal Melbourne Hospital Emergency Department, prior meta-analyses showing a strongly seasonal relapse probability in the Grattan Street Parkville Victoria Australia 3050. northern hemisphere, and extend this observation to the southern Background: In Australian emergency departments increasing demand for hemisphere. We demonstrate for the first time that there is a statistical resources, overcrowding and the National Emergency Access Target (NEAT) relationship between seasonal UVR trough and relapse onset peak that is all limit the nursing time available for the documentation of patient’s clinical latitude-dependent, with increasing latitudes associated with shorter gaps. status at the point of discharge. Research indicates that rapid emergency department throughput increases the risk for clinical errors, adverse and 12 DR NAWAF YASSI sentinel events. Re-attendance rates have also been linked to sub-optimal Stroke Location Predicts Functional Outcome After Stroke discharge processes. Independently of Lesion Volume Aims: To evaluate the effect of an evidence-informed protocol for: (1) YASSI N, Churilov L, Campbell B, Bammer R, Sharma G, Desmond P, Parsons documentation of vital signs; (2) unscheduled ED re-attendances < 72 hours. M, Albers G, Donnan G, Davis S Method: A mixed methods design was used. A retrospective analysis of 12 Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal months of data was conducted to describe current practice and characterise Melbourne Hospital, The University of Melbourne, Parkville, Australia (NY, BC, SD); Florey unscheduled re-presentations. A before and after study design was utilised to Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, evaluate the effect of the protocol on documentation rates and unscheduled Australia (LC, GD); Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (GS, PD); Department of Neurology and Neurological ED re-attendance < 72 hours for those patients who were discharged home. Sciences and the Stanford Stroke Center, Stanford University Medical Center, Stanford Results: For the 12 month period immediately prior to implementation 44,575 California (RB, GA); Priority Research Centre for Translational Neurosciences and Mental Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, New live patients attended the department, 19.7% had multiple presentations, South Wales, Australia (MP). 6.7% returned within 1 month of the index visit and 4.2% within 72 hours of discharge; of which 3.9% were unscheduled re-presentations. We observed a Background: Stroke lesion volume is strongly associated with functional significant improvement in nurses’ documentation of both vital signs after outcome, but there has been limited study of the independent effect of lesion implementation of the protocol. location. We studied the effect of stroke location on recovery in a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) Conclusion: We developed: (1) an evidence based discharge protocol (2) a and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke method for embedding the protocol in nursing practice (3) an evaluation of the Evolution (DEFUSE) study. effect of the change on documentation rates of vital signs and on unscheduled re-attendances to the emergency department. Methods: Stroke lesions were identified using manual segmentation of the post-treatment diffusion weighted imaging (DWI) scans. To allow comparison 14 MS THERESA VASSILIOU between different patients, images were subsequently transformed into standard space using the Functional MRI of the Brain (FMRIB) Linear Image Improving consistency of emergency department triage Registration Tool (FLIRT). A novel composite brain atlas derived from 3 categorisation: machine learning applied to clinical notes. standard brain atlases and encompassing 132 cortical and subcortical 1. VASSILIOU T, 2. Jimeon A, 3. Gerdtz M, 4. Knott J, 5. Wynne R, 6. Verspoor K structures, was used to segment the transformed lesions into different brain 1. 4. The Royal Melbourne Hospital Emergency Department; 2. 6. Department of regions, and calculate the percentage of each region infarcted. Classification Computing and information systems, The University of Melbourne; 3. 5. Royal Melbourne and Regression Tree (CART) analysis was performed to determine the Hospital Emergency Department and Department of Nursing The University of important regions in each hemisphere associated with non-favourable Melbourne. outcome at day 90 (modified Rankin score [mRS]>1). A 10-fold internal cross- Background: In Australian Emergency Departments (EDs) the Australasian validation was used with total infarct volume included in the model to account Triage Score (ATS) is a valid and reliable tool used to prioritise urgency and for its potential confounding effect. time to treatment for all incoming patients. Acute pain is a feature of Results: Overall, 152 patients (82 left hemisphere) were included. Median approximately 70% of all ED presentations (1).The subjective nature of acute DWI lesion volume was 37.0mL (interquartile range [IQR] 15.2-96.6mL). pain makes it difficult at times to assign a triage category and creates a Median baseline National Institute of Health Stroke Score was 13 (IQR 8-17). barrier for the delivery of effective pain management (2). The ED at Royal Median day 90 mRS was 3 (IQR 1-4). There were no significant differences Melbourne Hospital is one that mandates electronic recording of pain using between left and right hemisphere patients in baseline characteristics or the numerical rating score (NRS) at triage (3). Learning more about the outcome. In the left hemisphere, the strongest determinants of non-favourable context of pain presentations from unstructured clinical notes of triage nurses outcome were infarction of the uncinate fasciculus, followed by precuneus, may assist in understanding how variation in triage classification could be angular gyrus and total DWI volume. In the right hemisphere, the strongest reduced (3).In this study, we explore the application of machine learning determinants of non-favorable outcome were infarction of the parietal lobe methods based on the language of the clinical notes recorded by triage followed by the putamen. nurses. Conclusion: Assessment of stroke location using CART provides information Method: We conducted a retrospective file audit of 12 months of episodes of additional to total lesion volume, which may improve the prediction of stroke triage (N = 57,984). We trained several machine learning algorithms to predict outcome. Prognostically important locations include limbic, default-mode and the triage score based on a combination of features extracted from the ED language areas in the left hemisphere, and visuospatial and motor regions in visits, including the presenting complaint and notes text. The predictions were the right hemisphere. This type of decision tree analysis may allow more then compared to the triage categories assigned by the nurses. specific prediction of patient outcomes based on baseline imaging Results: The triage category is predicted with a good F1 score (balanced characteristics and may play a role in the design of clinical trials by allowing a precision/recall) of 0.88 for the urgent group (ATS=2) in the pain-relevant more informed consideration of the likely outcome and hence a reasonable visits group while the system could not discriminate well between lower level interpretation of treatment effect. of urgency categories, with F1 between 0.58 (ATS=3) and 0.62 (ATS=4). Lower levels of urgency are better predicted for patients with no pain related complaints (F1=0.73, ATS=4) while the classifier has more trouble for the

higher urgency categories in this group (F1=0.43, ATS=2; F1=0.59, ATS=3). The results demonstrate that urgency is more obvious in patients with pain-

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related presenting complaints, and that the classifier can effectively rule out months later. Minimal important decline in the 6MWD was set at 30m. urgency for other patients. The best results are achieved when both the Additional measures included; Colinet comorbidity score, Eastern presenting complaints and the notes text from the ED visit are considered as Cooperative Oncology Group Scale (functional status), hand-held features for classification however the presenting complaint alone was not dynamometry (quadriceps strength) and questionnaires (level of physical specific enough to accurately predict the triage category. activity, symptoms, mood and health-related quality of life [HRQoL]). Conclusion: Our results demonstrate that machine learning methods have the Correlations and linear regression were used to identify relationships between potential to support triage decision making in the natural ED workflow. Such a variables. tool may be more sensitive to subjective descriptors of pain captured in Results: The mean ± SD 6MWD at baseline was 408 ± 106m. There was a nurses’ electronic notes, due to its consideration of the words and context. small positive relationship between the 6MWD and age (r=0.35, p=0.028) but no relationship between 6MWD and cancer stage or Colinet comorbidity 15 MS KATE FETTERPLACE score. The 6MWD correlated positively with ECOG functional status (r=0.60, Measured energy expenditure compared with estimated p<0.0005), quadriceps strength (r=0.61, p<0.0005) and level of physical activity (r=0.51, p=0.001); and negatively with fatigue (r=0.50, p=0.002), energy requirments and acelerometry dyspnoea (r=0.54, p=0.001), pain (r=0.38, p=0.021), distress (r=0.39, FETTERPLACE K (1) ,Beach L(1), Edbrooke L(2), Parry S(2), Curtis R(1), p=0.016) and depression (r=0.49, p=0.003). There was no relationship with Rechnitzer T(1), Berney S(3), Denehy L(2) global HRQoL. The 6MWD declined significantly from baseline by a mean 1. Royal Melbourne Hospital, Melbourne Health, Melboune; 2. The University of [95% confidence interval] of 78m [5 – 148] p=0.037. 62% of participants had a Melbourne, Melbourn; 3. Austin Health, Melbourne decline in 6MWD >30m: these participants had greater comorbidities Rationale: Indirect calorimetry (IC) is the gold standard to measure energy (p=0.009); worse functional status (p=0.030); higher levels of pain (p=0.006), expenditure however it is not widely available in intensive care units (ICUs). anxiety (p=0.18) and distress (p=0.017); and lower levels of physical activity (1) Most ICUs are heavily reliant on estimation equations to determine (p=0.024) at baseline compared to participants whose 6MWD declined <30m patients’ energy requirements, these equations have been shown to be over six months. Pain and comorbidities were independent predictors, unreliable. Accelerometry has not previously been used to estimate energy explaining 17.2% of variance and together correctly classifying 76% of requirements in ICU. Aim: To compare measured energy expenditure (MEE) participants whose functional capacity declined. using IC in critically ill patients with estimated requirements and energy Conclusion: The 6MWD is closely related to physical performance, expenditure measured using accelerometry. comorbidities and symptoms in individuals with NSCLC. Methods: Prospective observational study; 60 adult patients who were mechanically ventilated for a minimum of 48 hours and were expected to stay 17 MR STEPHEN EDWARDS a further 5 days, were recruited from a tertiary Australian ICU. Estimated Life Stressors and Mental Health amongst adults with requirements were determined using the Schofield Equation (SE) and weight intellectual disability based equations, indirect calorimetry was performed using the Deltatrac Metabolic cart on day 1, day 3 and day 5 of admission. The Sensewear MF EDWARDS S, Jackson H armband accelerometer was applied on day 1 for 5 days. University of Melbourne Results: Demographic characteristics: Mean (SD) age (years) 57.5 (16.07), Background: Little attention has been paid to the mental health of adults with APACHE II 22.95 (7.5) and median (inter-quartile range (IQR)) BMI 27.9 (25.3 intellectual disability in either clinical or research domains. Positive - 33.1). Thirty-nine patients had a least one metabolic cart measure correlations have been found between life events (LEs) and signs of mental performed. There was a strong correlation between MEE and SE at day 3 and health problems on subscales of measures completed by a person who day 5 respectively (rho=0.777 p=0.000, rho=0.924 p=0.000) and weight knows the participant well (informant). However, little data is available on the based equations at day 3 (rho = 0.805 p=0.000). There was a moderate relationship between LEs and symptoms of mental health problems reported correlation between MEE and SE at baseline (rho=0.0537 p=0.001) and by participants (respondents) themselves. It is also unclear whether specific weight based equations at baseline (rho=0.533 p=0.001) and day 5 types of LEs (i.e. loss and trauma) are related to specific types of symptoms (rho=0.693 p=0.001). The SE using a median (IQR) stress factor (SF) of 1.3 (i.e. depression and anxiety), as general population studies suggest, and (1.2-1.3) appeared to overestimate MEE by 16%. The SFs seen when whether ability correlates with the number of symptoms a respondent reports. compared to BMR (using SE) at day 1, 3 and 5 were (median IQR) 1.1 (0.98- Method: Fifty-eight adults from a disability support service, whose receptive 1.24) and (mean (SD)) 1.17 (0.22) and 1.23 (0.16) respectively. There was a language had been assessed, passed screening for scoring ability and gave strong correlation between accelerometer measurers and MEE at day 3 (n = valid interviews where they rated symptoms of anxiety and depression on 17) (rho=0.795 p=0.001). modified measures. Loss related and trauma related LEs were identified by Conclusion: The SE appeared to be the best predictor of MEE at day 3 and informants on a measure incorporating signs of mental health problems day 5 of admission, however over estimated MEE on day 1. When using the including anxiety and depression. SE more conservative stress factors should be applied, particularly early in Results: Total LEs were significantly positively correlated with all subscales the ICU stay. The Sensewear accelerometer may be a useful tool for on the informant measure. Importantly, they were not correlated with determining energy expenditure however more validation is required. respondent measures of anxiety and depression and neither were informant signs. Significant positive correlations were found between loss related LEs 16 DR CATHERINE GRANGER and informant anxiety as well as trauma related LEs and informant Determinants Of The 6-Minute Walk Distance In depression but neither type of LE was related to scores on the respondent Individuals With Lung Cancer measures. Whilst scoring ability was related to verbal ability, neither respondent anxiety nor depressive symptoms were related. GRANGER C (1-3), McDonald C (3-4), Irving L (5), Denehy L (2-3). Discussion: An important finding is the lack of relationship between the 1 Department of Physiotherapy, Royal Melbourne Hospital; 2 Department of Physiotherapy, The University of Melbourne; 3 Institute for Breathing and Sleep; 4 symptoms of anxiety and depression disclosed by participants and the LEs Department of Respiratory and Sleep Medicine, Austin Health; 5 Department of and signs of mental health problems identified by informants that know them Respiratory and Sleep Medicine, Royal Melbourne Hospital. well. Additionally, the symptom specific effect of loss and trauma LEs is Introduction: Non-small cell lung cancer (NSCLC) is associated with high dissimilar to findings in the general population and despite common disease burden and physical hardship. The 6 Minute Walk Distance (6MWD) expectations, self-rated symptoms are not related to ability. is the most commonly used measure of functional capacity in NSCLC, Conclusion: Researchers and clinicians should ascertain the subjective however limited information is available about its clinical determinants in this experience of adults with an intellectual disability when studying or treating population. mental health problems. Aims: To identify: 1) the relationship between the 6MWD, demographic and disease-related factors and 2) the clinical profile of participants whose 6MWD declined over six months post-diagnosis.

Methods: Fifty participants (32 male, mean ± SD age 68 ± 9years) with stage I-III NSCLC completed the 6MWD at diagnosis prior to treatment and six Page | 11

Methods: After a single cardiac anatomy lecture, 50 university anatomy 18 DR ILANA ACKERMAN students participated in a three-hour supervised self-directed learning The substantial personal burden of hip and knee exposure in groups of five, randomised equally to either an ultrasound osteoarthritis among young people. simulator or human cadaveric specimens and plastic models. Pre and post- tests were conducted using pictorial and non-pictorial MCQs. Baseline ACKERMAN I, Roberts C, Bucknill A, Cavka B, Page R, Schoch P, Broughton N, knowledge was compared by using Student’s t-test of the pre-test scores. The Brand C learning effect was compared using repeated measures ANOVA of the pre Melbourne Health; Barwon Health; Peninsula Health; The University of Melbourne and post-test scores. Simulator students completed a survey on their Background: Osteoarthritis (OA) has traditionally been considered a condition experience. of older age. However, young people are also affected by hip and knee OA, Results: Four simulator and seven cadaver group students did not attend often as a result of sporting, transport and work-related injuries. Little is after randomization leaving data from 39 students for analysis. Simulator use known about the experience of young adults with hip or knee OA who can in groups of five students was feasible and feedback from participants was face a distinct set of pressures including work responsibilities and parenting very positive. Baseline test scores were similar (P = 0.9) between groups. roles. This study aimed to: After the learning intervention, there was no difference between groups in compare the Health-Related Quality of Life (HRQoL) of young people » change in total test score (P = 0.37), whether they were pictorial (P = 0.6) or with hip or knee OA to age- and sex-matched population norms; and non-pictorial (P = 0.21). In both groups there was an increase in total test » evaluate psychological distress and work limitations among this group. scores (simulator +19.8 ±12.4%% and cadaver: +16.4% ±10.2, P < 0.0001), Methods: People aged 20-55 years with hip or knee OA were recruited from 3 pictorial question scores (+22.9 ±18.0%, 19.7 ±19.3%, P < 0.001) and non- major public hospitals in Victoria (including the Royal Melbourne Hospital) pictorial question scores (+16.7 ±18.2%, +13 ±15.4%, P = 0.002). following screening of orthopaedic outpatient clinic lists and referrals, and through community-based advertisements. Health-Related Quality of Life was Conclusion: The ultrasound simulator appears equivalent to human cadaveric evaluated using the Assessment of Quality of Life instrument (score range - prosections for learning cardiac anatomy. 0.04 to 1.00; scored worst-best); the Kessler K10 instrument was used to assess psychological distress and the Workplace Activity Limitations Scale 20 A/PROF PAUL WRAIGHT (WALS) was used to assess work limitations. HRQoL data were compared to Percutaneous isolated limb perfusion of the infected age- and sex-matched Australian population norms using two-sample t-tests, diabetic foot and psychological distress and work limitations data were analysed descriptively. Recruitment was ceased before reaching the planned sample WRAIGHT P, Christov S, Smith K, Byrne M, McCann J, Dowling R, Mitchell P, size after preliminary analyses showed a larger than expected reduction in Kaye D HRQoL, compared to population norms. The Royal Melbourne Hospital, Melbourne, Australia; Baker IDI Heart and Diabetes Institute (Byrne, Kaye). Results: Data were available for analysis from 147 participants (n=126 from hospitals and n=21 from community-based recruitment). Comparison with Introduction: Inoperable peripheral arterial disease (PAD) and extensive pedal population norms revealed a large and clinically important reduction in infections act as major barriers to achieving wound healing. Pre-clinical HRQoL for the overall sample (mean reduction -0.35 AQoL units, 95%CI - studies demonstrated that antibiotics delivered locally at high continuous 0.40 to -0.31) and for individual age groups. Females reported a greater levels utilizing percutaneous isolated limb perfusion (PILP) resulted in higher reduction in HRQoL than males (mean reduction -0.39 AQoL units, 95%CI - deep tissue antibiotic levels. 0.45 to -0.33). The prevalence of high psychological distress among the Objectives: To determine safety of the PILP procedure in patients with sample was substantially greater than for the general population aged 18 to diabetes-related foot infections and to investigate the effectiveness of 54 years (31% vs 8%), as was the prevalence of very high distress (17% vs recirculating ticarcillin / clavulanic acid (Timentin) on microbiological load. 4%). Sixty-seven per cent of participants reported moderate or considerable Methods: Five individuals with diabetes, pedal infection and PAD requiring difficulty with work activities due to their OA. peripheral angiography were recruited. The antegrade femoral artery Conclusions: This study highlights the substantial personal burden of hip and catheter from the peripheral angiogram, retrograde Venous Recovery knee OA among young people, characterised by large reductions in HRQoL, Catheter and Venous Support Device were connected to an oxygenator, high levels of psychological distress and significant work limitations. These heater and paediatric cardiac perfusion pump. Circulation of the limb was data provide important new evidence to support the provision of targeted isolated by external tourniquet. All individuals underwent a single 30 minute services for people of working age to maximise work participation and PILP treatment episode. Biochemistry, antibiotic levels and tissue samples improve HRQoL. for microbiological assessment were collected during and following the procedure. 19 DR DAVID CANTY Results: No alteration in vital signs or biochemical parameters from the limb Ultrasound simulator assisted teaching of cardiac anatomy or systemic circulation, were recorded during the procedure or 28 day follow- to pre-clinical anatomy Students: A pilot randomised trial up. There was approximately a 10-fold increase in ticarcillin concentrations in of a three hour learning exposure. the lower limb circuit as compared to systemically at the end of the procedure (mean circuit concentration 96 μg/mL compared to mean systemic CANTY D, Hayes J, Story D, Royse C concentration of 3.71 μg/mL). 1. University of Melbourne - Ultrasound Education Group Department of Surgery, Department of Anatomy and Neuroscience, and Anaesthesia, Perioperative and Pain Large reductions in quantitative bacterial levels were observed within 6 hours Medicine Unit; 2. Royal Melbourne Hospital - Department of Anaesthesia and Pain following the procedure. Subject 1 initally had two bacterial species isolated, that were too few to quantify at both 6 hours and 3 days post. Subject 2 had Background: Traditional learning of anatomy uses human cadavers, which three bacterial species isolated, with a 1 log reduction in Colony Forming have limitations including deterioration in appearance and loss of organ Units (CFU) at 6 hours post PILP and eradication of one of the three species relations from preservation and dissection requiring recurring costs and by day 3. Subject 3 initially had 4 bacterial species isolated, with a log maintenance with laboratory staff. The demonstration of a moving (‘living’) reduction in CFU at both 6 hours and 3 days post and only one of the original anatomy with the use of ultrasound in teaching anatomy is gaining popularity isolates was identified at day 3. Subject 4 had a narrow sinus to underlying as it but is restricted by the need for expert tuition, volunteer models and pedal osteomyelitis which prevented adequate tissue from being collected. artifacts that impair image quality. A new ultrasound simulator overcomes Subject 5 had two wounds assessed, with two bacterial isolates initially being many of these limitations and has not previously been reported. The simulator identified in each but CFU's became undetectable in both wounds by 6 hours allows students to independently virtually explore and learn internal anatomy post. by producing accurate, moving, color, three-dimensional rendered slices from any angle or approach leaving the organs and their relationships intact Conclusions: This first in human study suggests that the recirculation of without requirement for consumables or restriction to a supervised laboratory. Timentin via PILP is both safe and achievable. The results demonstrate The aim was to determine the feasibility and efficacy of self-directed learning significant reductions in quantitative bacterial levels within 6 hours of PILP of cardiac anatomy with an ultrasound simulator compared to cadavers and and encourages the need for larger, randomised studies. plastic models.

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populations of GGH were isolated through laser capture microdissection 21 MISS SILA GENC (LCM) of HBsAg positive cells. Quantitative real time PCR (qPCR) was used Investigating longitudinal changes in fractional anisotropy to compare relative DNA levels for wild type (wt) and spHBV DNA in serum, in Alzheimer’s disease using different registration methods whole tissue extract and LCM isolated GGH. An ultradeep pyrosequencing assay was used to detect presence of the truncated HBsAg variants sW172* GENC S, Steward C, O'Brien T, Desmond P. and sW182*. Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne Results: spHBV DNA was detected at low levels in the serum from all Purpose: Diffusion tensor imaging (DTI) has the potential to non-invasively patients, with HCC patients demonstrating significantly higher median spHBV detect microstructural changes in white matter before they present clinically levels than cancer free patients (8.26% (6.01%- 23.093%) vs. 0.625% and few studies exist in the literature that has investigated the longitudinal (0.121%- 8.943% for HCC and HCC-free respectively; p< 0.01). There were changes in diffusion metrics such as FA in Alzheimer’s disease (AD). Many no significant differences in the proportion of spHBV detected in serum as studies use the freely available Tract-based spatial statistics (TBSS) in compared to liver tissue as compared to LCM isolated GGH. HBsAg variant FSL[3], which generates a WM skeleton common to all inputted brain images, detection within serum varied significantly between patients (range: 0%- highlighting changes in FA between populations or time. Recent studies have 96.7%), likely reflecting the impact of antiviral therapy prior to transplantation. shown that enhancing TBSS with an altered pipeline, namely improving sW172* and sW182* were detected in whole tissue extracts from 68% (17/25) registrations, can implicate the specificity of results[2, 4]. The aim of this study and 44% (11/25) of patients respectively. sW172* was present at significantly was to modify the TBSS pipeline using ANTs registrations to investigate how higher levels as compared to sw182* (p= 0.01) and in HCC patients as this would affect the spatial distribution of FA change in the core WM tracts compared to HCC-free patients (p= 0.02). sW172* and sW182* were for AD patients within six months. Herein, Standard TBSS was compared with detected at significantly higher levels in LCM isolated GGH as compared to TBSS enhanced with ANTs registrations[5], and with a study ANTs-derived whole tissue extract (p= 0.05). specific template. Conclusion: The results of this study confirm previous associations between Methods: This imaging study was part of the Velacor study, which was HBV splicing and development of HCC. This is also the first study to confirm approved by the Human Research Ethics Committee at Melbourne Health. In the role of truncated HBV surface proteins in HBV pathogenesis in vivo. total, 9 mild-moderate Alzheimer’s disease patients were included in this study. All participants underwent MR imaging on a Siemens 3.0T Tim Trio. All 23 DR WAYNE NG 9 participants underwent MR imaging at two time points, upon initial recruitment and 6 months following. FA maps were generated using the Fdt LPA is involved in modulating glioma stem cell migration diffusion toolbox in FSL, and three different approaches were used for NG W, Pebay A, Drummond KJ, Burgess AW, D'Abaco GM, Luwor R, Kountouri analysing the FA maps: standard TBSS, TBSS combined with ANTs, and N, Brown DV, Frisca F, Zhou HJ, Kaye AH and Morokoff AP creating a study-specific template. Royal Melbourne Hospital; University of Melbourne Results: The accuracy of registrations were determined visually, and with the Background: Currently, much of GBM research concentrates on targets Measure Image Similarity algorithm in the ANTs registration suite[5] using the related to cytotoxicity, survival or angiogenesis, rather than mechanisms of Mutual Information (MI) metric. The best registrations were to the study- invasion. Lysophosphatidic acid (LPA) signalling has been putatively specific template (MI=0.8370), however all methods gave similar quality described as having a mechanistic role in invasion. Initially described for its registrations to their respective templates (table 1). The volume promotile effects in melanoma cells, it has since been ascribed a role in (23378±714.76mm3) and the mean and standard deviation of significant FA breast and ovarian cancer metastasis.(Stracke et al., 1992; Zhang et al., change in the WM skeleton were similar (figure 2, table 1) in all three 2009) Autotaxin (ATX)/LPA receptor expression can be dysregulated in GBM methods. and can be differentially higher at the invasive edge, suggesting LPA Discussion: Despite improved registrations using ANTs in methods 2 and 3, signalling modulates glioma cell invasion.(Hoelzinger et al., 2007; Kishi et al., the areas of significant FA decrease in the WM skeleton using the three 2006) LPA1 receptor is reported as being pro-tumourigenic and has been registration methods were consistent. implicated in cell motility, invasion, survival and proliferation. Conclusion: The consistencies between the standard TBSS, ANTs-modified Methods: Tumour derived explants were grown in stem cell neurosphere TBSS, and study-specific template results suggests that running the simple conditions and tagged with luciferase. Relative expression of ATX/LPA was TBSS pipeline may be sufficient for longitudinal analyses in complex measured using RT-qPCR. Migration assays were performed using 24 well pathologies such as Alzheimer’s disease, however further studies with greater transwell plates and a luciferase reporter gene assay. sample size are required to confirm these findings. Results: LPA receptors are differentially expressed in our panel of glioma stem cells (GSC). In particular, LPA1 and LPA4 are overexpressed compared 22 DR JULIANNE BAYLISS to control neural stem cells (p<0.05). We show that GSC exhibit dose- Spliced HBV genomes and truncated surface proteins are dependent migration in response to LPA stimulation. Relative to control associated with ground glass hepatocytes, the neoplastic (100% cells seeded to bottom chamber), we observed migration rates of LPA 0.1uM 4.3% +/- 1.7; p=NS, LPA 1uM 24% +/- 1.7; p<0.05 and LPA 10uM precursors to HBV associated hepatocellular carcinoma 46.5% +/- 3.7; p<0.05 (mean +/- SEM; p-value). This response can be BAYLISS J, Walsh R, McLean CA, Lim L, Angus P, Revill P, Locarnini SA, Warner N abolished with a selective LPA1/3 antagonist (Ki16425). We also show that Division of Molecular Research and Development, Victorian Infectious Diseases an LPA1 dominant cell line can migrate in response to LPA stimulation, Reference Laboratory, North Melbourne, VIC 3051; Department of Anatomical whereas an LPA4 dominant cell line exhibits a severely attenuated migration Pathology, Alfred Hospital, Prahran VIC 3051; Department of Gastroenterology, Austin response. Hospital, Heidelberg VIC 3084 Conclusion: LPA1 is an important regulator of LPA induced migration in GSC. Background: Overproduction and sequestration of hepatitis B surface antigen LPA may represent a novel target for GBM therapy. (HBsAg) in chronically infected hepatocytes results in the appearance of “ground glass” hepatocytes (GGH). GGH are believed to represent clonally- 24 MONIQUE TOPP proliferated, pre-neoplastic lesions within which hepatitis B virus (HBV) replication promotes the development of hepatocellular carcinoma (HCC). Translating tumour profiles into targeted therapeutic We hypothesise that aberrant HBsAg and/or spliced HBV variants drive approaches using pre-clinical patient models of epithelial cellular transformation and will be increased in patients who develop HCC. ovarian cancer The current study aimed to determine the profile of spliced HBV DNA and HBsAg variants in serum and tissue of patients with chronic liver disease in MD TOPP 1 2, L Hartley 1, M Cook 1, V Heong 1 3 4, E Boehm 1, L McShane 1, J Pyman 3, O McNally 3, S Ananda 3, MI Harrell 5, D Etemadmoghadam 6 7 8, comparison to patients who develop HCC. L Galetta 6, K Alsop 6, G Mitchell 6, SB Fox 6 8, JB Kerr 2, KJ Hutt 2 9, SH Methods: Matched serum and tissue samples were collected from 25 Kaufmann 10, AOCS Australian patients undergoing liver transplantation surgery. This included 15 patients 1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australi; with HCC and 10 patients with end stage liver disease alone. In the current 2. Department of Anatomy and Developmental Biology, Monash University, Melbourne, study, three specific compartments of HBV were considered for each patient; Victoria, Australia; 3. The Royal Women's Hospital, Melbourne, Victoria, Australia; 4. serum (n= 25), whole tissue extract (n= 25) and GGH (n= 14). Pure Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia; 5. Department of Obstetrics and Gynaecology, School of Medicine, University of Page | 13

Washington, Seattle, Washington, United States of America; 6. Peter MacCallum Cancer demographics, tumour characteristics, treatments, and nomogram risk of Centre, Melbourne, Victoria, Australia; 7. Sir Peter MacCallum Department of Oncology, additional nodal metastasis were recorded. University of Melbourne, Melbourne, Victoria, Australi; 8. Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia; 9. Prince Henry's Institute of Results: A total of 800 positive SLNBs were identified. Primary tumours were Medical Research, Melbourne, Victoria, Australia; 10. Department of Molecular invasive ductal carcinoma (81.4%), 2.0cm in median diameter, hormone Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, receptor positive (90.4%) and HER2 negative (86.0%). There were 452 United States of America; 11. Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, and Departments of Gynaecological (56.5%) cALNDs, 110 (25.5%) for micrometastasis in SLNBs and 314 Oncology, Westmead Hospital, Sydney, New South Wales, Australia; 12. Queensland (72.7%) for macrometastasis. Positive nodes were identified in 153 (33.8%) Institute of Medical Research, Brisbane, Queensland, Australia; 13. Department of cALNDs. For 154 (45.3%) SLNBs with micrometastasis and 99 (29.1%) with Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Victoria, macrometastasis no cALND was performed. Those undergoing cALND Australia; 14. Departments of Genetics, University of Melbourne, Melbourne, Victoria, tended to be younger with a higher risk of additional metastasis and received Australia. more aggressive treatments. The overall cALND rate decreased overtime, yet Background: Treatment options for women with ovarian cancer remain very the nomogram risk of additional metastasis remained stable. limited and acquired resistance to current therapies is the norm. Molecular characterisation of high-grade serous ovarian cancer (HG-SOC) may uncover Conclusion: Although early node-positive breast cancer in Australia is potential drug targets and possible mechanisms of drug resistance. increasingly managed with SLNB only, there is a high-risk subset of patients Additionally, altered DNA repair capability may underlie response to both for whom cALND continues to be frequently performed. standard therapy and PARP inhibitors, one of few single agent targeted therapies shown to improve progression free survival in ovarian cancer. 26 MR MICHAEL HONG However, improvement in the ability to target underlying drivers and Administrative Coding for Diverticulitis: How accurate is it? vulnerabilities of ovarian cancer requires the development of molecularly HONG M, Skandarajah A, Tomlin A, Hayes I annotated preclinical models reflective of the clinic. Colorectal Surgery Unit, Department of Surgery (The University of Melbourne), The Royal Methods: A patient-derived xenograft (PDX) cohort has been generated from Melbourne Hospital; Melbourne EpiCentre, Melbourne Health and the University of consecutive, chemotherapy-naïve human HG-SOC and stratified according to Melbourne DNA repair capability and molecular characteristics, including next generation Background: The use of administrative coding data for health research and sequencing (by Foundation Medicine). In vivo response to standard quality assurance is increasing as it allows comparisons to be made at chemotherapy and PARP inhibitor therapy was determined and further in vivo national and international levels. The link between administrative diagnostic studies using carefully selected inhibitors and drug combinations, codes and the clinical condition under investigation is often unclear. This personalised to each PDX tumour profile is underway. Resistance to therapy includes acute colonic diverticulitis, a common surgical emergency. As a is driven by re-treating relapsed PDX in vivo, providing invaluable “paired precursor to larger studies, we aim to determine the accuracy and usefulness samples” (pre and post drug treatment), which are difficult to obtain from of the Australian diagnostic codes in representing symptomatic diverticular patients, to allow clonal evolution analysis of mechanisms of drug response disease. and resistance. Method: All Australian inpatient admissions are coded according to the Results: Ten HG-SOC PDX have been generated (xenograft success rate International Classification of Disease, 10th revision, Australian Modification 83%). All exhibited mutations in TP53, five had mutations BRCA1/2 (two of (ICD-10-AM). The codes for diverticular disease begin with K57. There are 32 which were germline) and two were methylated for BRCA1. In vivo cisplatin five-character codes to represent potential complications of diverticular response, determined as platinum sensitive (progression-free interval (PFI) disease. To determine the most useful codes, we made a frequency table ≥100 d, n=4), platinum resistant (PFI <100 d, n=3) or platinum refractory based on emergency patient admissions to the Royal Melbourne Hospital (n=3), was largely consistent with patient outcome. Three of four platinum between July 2005 and June 2013, each with the stem K57 as their principal sensitive HG-SOC PDX contained DNA repair gene mutations, and the fourth diagnosis. Individual codes which represented over 1% of the total sample was methylated for BRCA1. In contrast, all three platinum refractory PDX were grouped into three clinically meaningful groups: uncomplicated overexpressed dominant oncogenes (CCNE1, LIN28B and/or BCL2). PDX diverticulitis, complicated diverticulitis and diverticular bleeding. To determine PARP inhibitor response also reflected the spectrum of responses seen in the accuracy of these codes, medical records for 153 admissions between July clinic, with some PDX displaying durable responses to 1st and 2nd line PARP 2012 and June 2013 were examined and clinical diagnoses were assigned. inhibitor. Molecular analysis of this cohort has revealed actionable targets for The diagnostic codes were then compared with these clinical diagnoses to novel therapeutic strategies and guided combination studies designed to determine their sensitivity and positive predictive value (PPV). overcome platinum or PARP inhibitor resistance. Results: 836 patients were admitted with a diagnosis code starting with K57 Conclusion: PDX with histologic, molecular and therapeutic annotation, as over 8 years. Uncomplicated diverticulitis was represented by the codes well as clinical outcome data, provide outstanding utility for understanding K57.32 and K57.92, and the sensitivity of these codes was 0.92 (PPV 0.69). how cancer susceptibility proteins and tumour suppressors, as well as the Complicated diverticulitis was represented by K57.22 with no ability to contribution of defective DNA repair, affect treatment outcomes. This will differentiate abscess, perforation or stricture based on coding alone improve targeting of novel therapies and the design of clinical trials for (sensitivity 0.69, PPV 0.92). 30% of patients with diverticulitis had women. complicated disease. Diverticular bleeding was represented by K57.31 and K57.91 (sensitivity 0.93, PPV 0.57). Some K57 codes have no clinical 25 DR EMMA GANNAN correlate, and are rarely used. Management of Early Stage Node-Positive Breast Cancer in Conclusion: Australian ICD-10-AM coding for diverticular disease can be used Australia: A Multi-Centre Study to differentiate between the three main clinical forms of the condition. The GANNAN E, Khoo J, Nightingale S, Suhardia T, Lippey J, Keane H, Tan K, Collins accuracy of coding for diverticulitis is better than for diverticular bleeding. J Murugasu A, Fox J, Clouston D, Henderson M, Speakman D, O’Brien J, Ewing H, Baker C, Walker M, Gorelik A, Mann GB 27 MISS ASHLEIGH POH The Breast Service, The Royal Melbourne Hospital & The Royal Women’s Hospital; Focus Constitutive Hck activation promotes the development and Pathology; The Peter MacCallum Cancer Centre; Monash Medical Centre; The Austin progression of colorectal cancer in mice Hospital; The Alfred Hospital; St Vincent’s Hospital Melbourne; The Northern Hospital POH A, Preaudet A, Ernst M, O'Donoghue R Background: Surgical management of breast cancer with limited disease in the sentinel node is controversial. Standard practice of completion axillary Walter and Eliza Hall Institute of Medical Research dissection (cALND) was recently challenged by The American College of Background: Colorectal cancer is the second most commonly diagnosed Surgeons Oncology Group’s Z0011 trial. We sought to examine current cancer worldwide, and may develop sporadically or as a result of chronic practice patterns in Melbourne, Australia. inflammation (colitis-associated cancer). Macrophages are a major component of the tumour micro-environment in colorectal cancer and may be Methodology: This multi-centre retrospective analysis included all patients broadly classified into two groups: M1 (classically-activated) and M2 with T1-2 breast cancer and a positive sentinel lymph node biopsy (SLNB) (alternatively-activated) macrophages. M1 macrophages assist in anti- between January 1st 2009 and December 31st 2012. Data was collected from microbial and tumouricidal activities, while M2 macrophages promote 7 hospital-based breast units and 1 private pathology provider. Patient angiogenesis, wound healing and matrix remodelling. Haematopoietic Cell Page | 14

Kinase (Hck) is a Src family kinase expressed within macrophages that is Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria; Department involved in macrophage polarisation and aberrant activation has been shown of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria; Department of Medicine, University of Melbourne, Parkville, Victoria; Department of Cardiology, Western Hospital, to correlate with a poor prognosis in human colorectal cancer. Melbourne, Victoria Methods: We investigated the role of Hck in tumourigenesis using two mouse Background: Chronic kidney disease (CKD) patients on haemodialysis (HD) models of colorectal cancer. Firstly, Hck mutant mice that express a have a high risk of sudden cardiac death (SCD). A unique risk factor may be constitutively active form of Hck (HckF/F) were subjected to the the longer IDP between HD sessions. Inherent in conventional HD (thrice- azoxymethane/dextran sodium sulphate (AOM/DSS) model of colitis- weekly) are two 48-hour (short) breaks and one 72-hour (long) break between associated cancer. To model sporadic colorectal cancer, HckF/F mice were the start of HD sessions. We used an implantable cardiac monitor (ICM) to administered a weekly injection of AOM for six consecutive weeks. define the incidence and timing of significant arrhythmias in a HD population Results: In both tumour models, HckF/F mice exhibited increased tumour (Event Time Distribution-ETD). Repeat 24-hour Holter monitoring was also frequency and multiplicity compared to wild-type (WT) animals, in addition to performed to record and analyse various electrocardiographic markers of mucosal invasion which was absent in WT mice. Western blotting and arrhythmic risk. immunohistochemical analysis revealed a significant increase in tumour Methods: 50 CKD patients on HD had an ICM inserted with intensive follow- proliferation in HckF/F mutants compared to WT animals, consistent with an up. Patients with LVEF < 35% were excluded. The primary end-point was increased abundance of phosphorylated Stat3, Erk, Akt and S6 cytoplasmic SCD or significant arrhythmias according to the ETD. Ambulatory 24-hour signalling proteins. Although a difference in the total macrophage component Holter measurements of ventricular repolarization (VR): corrected QT interval was not observed between both genotypes, qPCR analysis on purified tumour (QTc), T wave alternans (TWA); & measures of autonomic tone (AT): heart macrophages showed a two-to-three fold increase in M2-associated genes rate variability & turbulence (HRV, HRT) were compared during the long vs Il10, Arg1 and Ym1 in HckF/F mice compared to WT animals. short IDP. Conclusions: Collectively, these results demonstrate that aberrant Hck Results: Mean age 66±11 yrs; 72% male; follow-up 8±3 mths. There were 4 activation is able to drive gastrointestinal tumourigenesis in the presence and SCD (8%), all during the long IDP. The terminal event was severe absence of chronic inflammation by increasing epithelial proliferation and the bradycardia with asystole in 3 (terminal event in 4th patient not available). polarisation of macrophages towards a tumour-promoting phenotype. Significant arrhythmias occurred in 16 patients (32%) including: bradycardia Additionally, these findings suggest that the therapeutic inhibition of parallel (≤40bpm ≥4 beats) in 7 (14%); sinus arrest (pauses ≥3secs) in 4 (8%); 2°AV non-oncogenic pathways, such as Hck signalling, could improve prognosis block in 1 (2%); non-sustained ventricular tachycardia (>16 beats <30secs) in and/or survival for cancer patients. 8 (16%). During the Long IDP, 385/615 (63%) of all arrhythmic events occurred (p<0.001) & more adverse changes were noted in HRV [time 28 WAYNE NG (SEE #23) domain measures reflecting HRV fluctuations: SDNN 83±26ms (p<0.002), SDANN 73±24ms (p<0.04); frequency domain measures reflecting sympathovagal imbalance: low frequency 10±8 (p<0.003), very low frequency 29 DR EMMA TULLY 17±8 (p<0.02), low frequency/high frequency ratio 1.1±0.4 (p<0.05)]; HRT indicating loss of normal autonomic regulation [turbulence slope Comparison of the Management of Acute Biliary Tract 2.1±2.1ms/RR (p<0.005), turbulence onset 1.3±2.7% (p<0.001)]; TWA as a Pathology in the Pre and Post-Emergency General Surgery marker of malignant arrhythmic risk 67±18µV (p<0.04); higher serum K+ level Era 5.2±0.6mmol/L (p<0.0001). Intradialytic QTc prolonged during both long IDP TULLY E, Shakerian R. [466±28ms vs. 489±32ms (p<0.001)] and short IDP [470±24ms vs. 494±25ms (p<0.001)]; however, pre- and post-HD session QTc were not The Royal Melbourne Hospital significantly different (p<0.16) when compared during the long IDP vs. short Background: The development of Emergency General Surgical (EGS) Units in IDP. No episodes of polymorphic or sustained monomorphic VT occurred. recent years has brought about considerable interest in the efficacy and cost- Conclusions: Risk of sudden cardiac death, significant arrhythmias and effectiveness in managing common surgical pathologies. Acute appendicitis abnormalities in ventricular repolarization/autonomic tone were greatest has been extensively studied, using benchmarks such as length of stay, time during the long IDP. The mechanism and prevention of severe lethal to operation and costs involved. Biliary tract pathology is a common surgical bradycardia in these patients deserves further evaluation. presentation which at times challenges the general surgeon; this has yet to be studied in the context of these benchmarks. 30 DR SVEN-JEAN TAN Method: Royal Melbourne Hospital Administrative database was used to identify patient discharged with biliary colic or Cholecystitis (as identified by Biological variation and analytical stability of serum ICD codes) in Pre-EGS (2009/2010) and Post-EGS Periods (2011/2012). soluble α-Klotho in healthy volunteers Number and cost of radiologic investigations, surgery during index admission, TAN SJ 1,2, Smith ER 1,3, Holt SG 1,2, and Toussaint ND 1,2 time to surgery and length of stay were compared across the two groups. 1 Department of Nephrology, The Royal Melbourne Hospital, Parkville; 2Department of Results: In the 2 years pre-EGS 232 pts were admitted with biliary colic or Medicine (RMH), The University of Melbourne, Parkville; 3Monash University, Clayton. cholecystitis, of which 110 (47.4%) underwent operative management. By Aim: To investigate the biological variability and analytical stability of soluble comparison in 2011/2012 282 pts were admitted, with 167 pts (59.2%) α-klotho in serum. undergoing surgery. During 2009/2010 a total of 324 imaging studies were Background: Recent evidence suggests that the cleaved extracellular domain performed on these patients (1.40 studies per pt) compared with 344 (1.22 of the α-klotho receptor, soluble α-klotho (sKl), has effects on phosphate studies per pt) in the post-EGS period. Length of stay between the two groups homeostasis, ion channel regulation and anti-fibrotic/anti-oxidant pathways. differed by 2.12 days (6.04 days Pre-EGS vs. 3.92 days post-EGS). However, measurements of serum sKl in healthy individuals and in cohorts of Conclusion: Preliminary results suggest that a rationalisation of biliary tract patients with renal disease have yielded inconsistent results with respect to investigations has occurred in the Post-EGS period, with an increase in the their relationship with renal function, other markers of mineral metabolism and number of patients being operated on in during their index admission and patient outcome. Pre-analytical factors such as biological variation and concurrent decrease in length of stay. analyte stability may affect the interpretation of sKl results but have yet to be formally assessed. 30 DR MICHAEL WONG Methods: For assessment of biological variability, serum samples were Influence of the Long Interdialytic Period (IDP) on the collected from four healthy volunteers at three time-points during the day Incidence of Serious Arrhythmias and Sudden Cardiac (morning, midday and afternoon). For assessment of analytical stability, Death in Patients with Chronic Kidney Disease undergoing separate aliquots from morning samples were allowed to stand at room Haemodialysis temperature for 30, 60 and 120 minutes, prior to centrifugation and processing. All samples were stored at -80°C until batched analysis. sKl was WONG M, Kalman J, Pedagogos E, Toussaint N, Joseph S, Halloran K, Vohra J, measured using a commercial ELISA kit (Immuno-Biological Laboratories Sparks P, Morton J Co., Gunma, Japan) according to the manufacturer’s protocol. Biological and analytical stability was assessed using repeated-measures ANOVA. Page | 15

Results: Delayed separation of samples yielded mean(±SD) sKl levels of 222 coefficients, multiple regression analysis and Bland-Altman plots were used to (±69)pg/mL, 208(±99)pg/mL and 193(±72)pg/mL, at 30, 60 and 120 minutes, assess agreement between spot uPiCr and UPE. respectively, revealing a small but non-significant trend towards analyte Results: 65 CKD patients (49 male) were studied, median age 67yrs (IQR 53- degradation over time. Mean(±SD) sKl levels were 222 (±69)pg/mL, 74) and mean(±SD) serum creatinine 182(±84)μmol/L. Mean(±SD) spot uPi, 220(±51)pg/mL and 207(±69)pg/mL at morning, midday and afternoon time- spot uPiCr and total UPE were 12.6(±6.2)mmol/L, 1.58(±0.55)mmol/mmol points, respectively showing no evidence of significant diurnal change. and 24.5(±11.7)mmol/d respectively. There was no significant correlation Conclusion: Prompt processing of serum samples for sKl measurement is between spot uPiCr and UPE (r=0.116, p=0.336). Spot uPi correlated with 24- advisable, although the magnitude of analyte degradation over 2 hours hour UPE significantly (r=0.306, p=0.019). Bland-Altman analysis of 24-hour appears small. In health, sKl displays minimal variation throughout the day. versus spot uPi showed acceptable agreement with bias +0.2mmol/L (95%CI -1.2284 – 1.6508). Multiple regression analysis was undertaken to predict UPE from gender, sPi, spot uPi and eGFR. Apart from eGFR, these variables 31 DR KRISTEN KELYNACK significantly predicted UPE, F(3,51)=5.321, p=0.003, R2=0.238. Gender, sPi Calciprotein particles induce mineralisation of murine and spot uPi added significantly to the prediction, p<0.05. aortic vascular smooth muscle cells in vitro Conclusion: This study suggests that normalisation of uPi to uCr on spot urine samples may not be appropriate when evaluating urinary phosphate excretion KELYNACK KJ (1), Smith ER (1,2), Wigg B (1), Hewitson TD (1,3), Holt SG (1,3) in adults with CKD. 1 Department of Nephrology, The Royal Melbourne Hospital, Parkville; 2 Monash University, Clayton; 3 Department of Medicine (RMH), The University of Melbourne, 33 DR ANDREW TALBOT Parkville. Severity of Fabry Nephropathy as a Marker of Aim: To investigate whether fetuin-A containing calciprotein particles (CPP) can induce vascular smooth muscle cell (VSMC) mineralisation in vitro. Cardiovascular Outcome: 10 year data from an Australian Cohort on Enzyme Replacement Therapy. Background: Vascular calcification is associated with greatly increased risk of premature cardiovascular mortality in patients with Chronic Kidney Disease TALBOT A, Nicholls K (CKD). VSMC mineralisation is thought to be central to this process. Department of Nephrology, Royal Melbourne Hospital; Department of Medicine, Circulating CPP levels are elevated in CKD and are associated with aortic University of Melbourne. stiffening and poor outcome in this setting. Previous work by our group Introduction: Fabry Disease (FD) is an X-linked lysosomal storage disease showed that CPP are taken up by macrophage via the class A scavenger caused by deficiency in the enzyme α–galactosidase A. Renal involvement receptor (SR-A) and induce a pro-inflammatory response at high results from progressive glomerular podocyte injury causing proteinuria, concentration. We hypothesised that CPP might have direct effects on VSMC leading to focal segmental glomerulosclerosis and ultimately end-stage mineralisation propensity. kidney disease (CKD5). Renal disease is a major risk factor for Methods: Murine aortic VSMC (MoVas) were cultured and characterised. cardiovascular disease. Confluent MoVas monolayers were grown in DMEM + 10% FCS Methods: We performed a retrospective analysis of the long-term outcomes of supplemented with CPP (50 or 100 μg/mL) or equivalent concentrations of male FD (n=25) patients after 10 years on enzyme replacement therapy CaCl2 as control. Calcium and phosphate deposition was determined by (ERT). Clinical outcomes were separated into those with CKD5 (n=10) and alizarin red/von Kossa staining and quantitative colorimetry after 7 days in those without (n=15). culture. Uptake of fluorescently-labelled CPP was visualised by confocal Fabry nephropathy was monitored by degree of proteinuria and change in microscopy. Blockade of SR-A was assessed using a function-blocking nuclear Cr-51 EDTA glomerular filtration rate (GFR). Fabry cardiomyopathy monoclonal antibody. was assessed by changes in echocardiographic parameters and frequency of Results: MoVas expressed molecular markers consistent with a SMC cardiovascular events (death, arrhythmia, pacing device, systolic phenotype. Mineralisation was observed nodules after treatment with CPP- dysfunction). generating high calcium and high phosphate media (both 2mM) over 21 days. Results: There was no change in GFR in the non-CKD5 cohort from baseline CPP were internalised rapidly by MoVas and induced significant deposition of to 10 years (86.9 ± 16.6 versus 82.2 ± 25.4 ml/min/1.73m2, p=0.57). calcium and phosphate (p<0.05, n=3 vs. compared to controls) at high Proteinuria was also stable to 10 years follow-up (baseline 0.37 ± 0.33 g/day concentration (100 μg/mL) within 7 days. SR-A blockade only resulted in versus 0.46 ± 0.42 g/day, p=0.42). modest reduction in mineral deposition (<20%, P=0.06). Cardiovascular events including mortality, both new onset and accumulated Conclusion: High levels of CPP may have a role in VSMC mineralisation and burden, were higher in patients with CKD5 over 10 years follow-up (100% the pathogenesis of vascular calcification but this appears to be independent versus 33%, p<0.001). Left ventricular mass index in CKD5 patients of the SR-A. increased by 89.4 ± 78.3 g/m2 versus 18.6 ± 29.1 g/m2 p=0.014, in non- CKD5, driven by changes in interventricular wall thickness (7.7 ± 5.5mm 32 DR SVEN-JEAN TAN versus 1.5 ± 2.0mm, p=0.004). Relationship between timed urine and spot urine Conclusions: Severity of Fabry Nephropathy at commencement of ERT is a collections for measurement of phosphate excretion strong marker of cardiac involvement and outcome. CKD5 is associated with TAN SJ 1,2, Cai MMX 1,2, Kelynack KJ 1, Wigg B 1, Pedagogos E 1, Smith ER worse baseline cardiovascular parameters and significant progression despite 1,3, Holt SG 1,2, Hewitson TD 1,2, Toussaint ND 1,2 ERT. Mild renal disease at commencement ERT is associated with stable 1 Department of Nephrology, The Royal Melbourne Hospital, Parkville; 2 Department of long-term renal function and reduced cardiac progression. Medicine (RMH), The University of Melbourne, Parkville; 3 Monash University, Clayton. 34 DR ASHISH SHARMA Aim: To determine the relationship between spot urine phosphate:creatinine ratio (uPiCr) and total urinary phosphate excretion (UPE) in chronic kidney The utility of serum aluminium testing in dialysis patients disease (CKD) patients. SHARMA AK 1, 2, TOUSSAINT ND 1, 2, PICKERING J 1, BEESTON T1, HOLT SG 1, 2 Background: Twenty-four hour UPE reflects intestinal phosphate absorption in 1 Department of Nephrology, The Royal Melbourne Hospital, Parkville, VIC; 2 steady state and can be used to evaluate effects of phosphate-lowering Department of Medicine (RMH), The University of Melbourne, Parkville, VIC. interventions. UPE may be more informative than serum phosphate (sPi) in Aim: To audit routine serum aluminium (Al) levels in dialysis patients. assessing phosphate homeostasis. However, timed urine collections are cumbersome and prone to inadequate collection. Spot uPiCr assessment Background: Serum Al is routinely tested in many dialysis units. Al exposure may be a useful, simple surrogate for UPE, but is yet to be systematically may lead to acute and chronic toxicity including dementia, osteodystrophy evaluated in CKD. and anaemia and levels in excess of ~2.2µmol/L (60ng/ml) should be avoided. Historically toxicity has been caused by excessive dialysate Al but Methods: Blood samples, spot and 24-hour urine were collected from patients modern reverse osmosis (RO) water should be Al free. Al assays are with CKD (Stages 1-5). Serum biochemistry was analysed. Urine phosphate sensitive and subject to contamination. Nevertheless we have continued to concentration (uPi) and creatinine concentration measurements were perform annual Al levels on dialysis patients, with 6 monthly tests for those on performed on spot and 24-hour urine collections. Pearson’s correlation Al-based binders. Page | 16

Methods: We retrospectively analysed all the serum Al levels tested for our gene (CFH), as well as other genes. Retinal drusen have been described in dialysis population from Jan 2010-Dec 2013 using our database (Nephworks DDD, and we describe here retinal abnormalities in DDD and atypical HUS. 6) as well as RO and water feed levels. Investigation of high levels was Methods: All individuals with DDD were examined by an ophthalmologist, and undertaken by reviewing data on nephworks as well as medical history. together with the patients with atypical HUS underwent retinal imaging and Results: 2058 Al tests in 755 patients (62% male, mean age 64yrs) were optical coherence tomography (OCT). reviewed showing mean (std.dev) of 0.41(0.30)µmol/L. 57 (2.8%) tests from Results: Ocular symptoms in patients with DDD included impaired night 35 patients had Al levels >1.0µmol/L and 27 (77%) of these patients were or vision, which was common and occurred early, and impaired peripheral had been prescribed aluminium hydroxide (AlOH). 7 patients had Al vision. Individuals with DDD had multiple small basal laminar drusen (<125 >2.2µmol/L. In 3 of these patients, no source of Al was identified; at least one um), large soft drusen, or both. Drusen were first seen in adolescence, with patient was dialyzing at home before being transplanted. 182 patients taking pigmentation and haemorrhage occurring later. Optical coherence AlOH (87% of all patients on AlOH) had levels ≤1.0µmol/L, but the OR of tomography (OCT) demonstrated the drusen location beneath the retinal serum Al >1.0µmol/L on AlOH was 9.98. The cost of serum Al assay is pigment epithelium, secondary atrophy of the neuroretina in about half the $30.60, thus costs were $62,974.80 over the study period or over individuals, and, in one, the further complications of sub-retinal choroidal $1300/month. Despite RO feed water Al levels as high as 48µmol/L neovascular membranes, pigment epithelial detachment and atypical serous (1300ng/mL), Al output from the RO was almost always undetectable retinopathy. (<0.3µmol/L). We have detected dialysate Al levels >2.2µmo/L only 5 times One of the two individuals with atypical HUS had large soft macular drusen (> since 2009, and never in last 3 years. 125 um) identical to those seen in DDD. Conclusion: The role of serum Al monitoring in dialysis patients needs re- Conclusions: Individuals with C3 nephropathy should be assessed evaluation but blanket screening appears unnecessary and expensive. ophthalmologically for macular disease at diagnosis, and monitored annually Targeted and selected screening should be considered in these patients. thereafter. They should be advised to present immediately if their vision 35 D WANG deteriorates. Laser therapy prevents some retinal complications, and biological treatments offer further hope. How missense mutations in the COL4A5 gene cause X- linked Alport Syndrome and the effect of chemical 37 D COLVILLE chaperones Retinal drusen are increased in patients with IgA 1WANG D, 1,2 Mohammad M, 1 Wang YY, 1 Tan R, 1 Rigby L, 1 Dagher H, glomerulonephritis and renal failure 1Savige J , COLVILLE D, Catran A, 1 Ierino F, Deva R, Gani L, Wang Y, Rigby L, 2 Baird PN, 1The University of Melbourne Department of Medicine (Northern Health and Melbourne Savige J, Health) Melbourne, Australia; 2 International Islamic University Malaysia The University of Melbourne Department of Medicine, Northern Health, Melbourne Background: Forty % of mutations in X-linked Alport syndrome are caused by Health and 1 Austin Health; 2 Centre for Eye Research Australia, East Melbourne 3001, missense variants in the COL4A5 gene. These result in an abnormal collagen Australia Background. Retinal drusen or white dots are deposits of immunoglobulin and Aim: This study examined the effects of COL4A5 missense mutations on the complement beneath the retinal pigment epithelium. These have an identical cell, and the consequences of treatment with a chemical chaperone. composition to the glomerular immune deposits seen in some forms of Patients and Methods: Cell lines were produced from skin fibroblasts from two glomerulonephritis. Occasional drusen occur normally in middle-age, and male and four female subjects with X-linked Alport syndrome caused by large soft drusen due to macular degeneration are increased in renal failure. missense mutations, and from 4 non-hematuric controls. Levels of Drusen are also found in the C3 nephropathies, and there is a single report of drusen in membranous and post-streptococcal glomerulonephritis. This study blots, and the corresponding mRNA quantitated using RT-PCR (Applied determined the prevalence of widespread retinal drusen in patients with Biosystems 7500). Growth curves were examined over five days. Levels of glomerulonephritis. mRNA corresponding to ER stress (BiP, CHOP and ATF6), autophagy Patients and methods. Eighty-nine patients with glomerulonephritis, including (ATG5, BECN1 and ATG7) and the pro- and antiapoptotic pathways (caspase IgA disease (n=47), focal segmental glomerulosclerosis (FSGS, n=21), and 3, BAD and Bcl2) were also quantitated. miscellaneous forms (n=21) were studied. One hundred and eighteen patients ER size in electron micrographs, and mRNA corresponding to ER stress, with renal failure due to non-glomerular disease and 147 individuals with autophagy and apoptosis markers were measured at baseline and after normal renal function were also examined. Each provided a brief medical treatment with 10 mM 4-PBA. history, and underwent retinal photography with a non-mydriatic camera (Zeiss). In some cases, any drusen were examined with optical coherence Results: Cell growth rates were reduced in the affected male but not female tomography (Topcon OCT). In addition, DNA was tested with the cell lines. Affected male and female cell lines had larger ER than normals, SEQUENOM iPLEX assay for the Complement Factor H Y402H risk allele. and increased mRNA corresponding to ER stress, autophagy and apoptosis markers. Treatment with PBA reduced the size of the ER but also increased Results. Widespread retinal drusen were present in seven patients with IgA apoptosis markers. glomerulonephritis (15%), all of whom had renal failure. In one case with familial IgA disease, only the individual with renal failure had drusen, and not Conclusions: Missense COL4A5 mutations have an adverse effect on cell the other three affected family members. Drusen were not seen in other forms growth and ER stress. Treatment with chemical chaperones reduces the of glomerulonephritis. However drusen were present in one patient with renal failure due to lithium and another with an unknown cause (2%). Drusen were effects. not present in patients with renal failure due to polycystic kidney disease or 36 D COLVILLE vesicoureteric reflux. Drusen were also present in 2 individuals with normal renal function (2%). The drusen were confirmed beneath the retinal pigment Retinal abnormalities in the C3 nephropathies and the risk epithelium by OCT and were not associated with an increased prevalence of of visual impairment Y402H (4/16 compared with 181/508 alleles, p NS). Conclusions. Retinal drusen are increased in patients with IgA 1COLVILLE D, 1Amos L, 3Hughes P, 3Nicholls K, 2 Mack H, 1,2 Symons RC Andrew, Smith JD, and 1 Savige JA glomerulonephritis and renal failure. Drusen are much larger than glomerular immune deposits but are likely to share a common pathogenesis. 1The University of Melbourne Department of Medicine, Melbourne Health and Northern Health; 2 Eye Surgery Associates, East Melbourne; 3 Department of Nephrology, Royal Melbourne Hospital. 38 L CHENG Aims: To determine retinal abnormalities in 8 affected individuals from 7 Retinal small vessel changes and angiographically-proven families with DDD and two unrelated individuals with atypical HUS. coronary artery disease: a cross-sectional observational Background: The C3 nephropathies comprise dense deposit disease (DDD, study formerly known as membranoproliferative glomerulonephritis type II), C3 CHENG L, Barlis P, Colville D, 1 Lamoureux E, 1Wong TY, Hutchinson A, glomerulonephritis and atypical haemolytic uraemic syndrome. All these Gleason G, VanGaal W and Savige J diseases may be associated with mutations in the Complement Factor H Page | 17

The University of Melbourne Department of Medicine, Northern Health, VIC 3076; Melbourne Health, VIC 3050, AUSTRALIA; 1 Singapore Eye Research Institute, University 40 DR SARAH HANIEH of Singapore, Singapore. Maternal vitamin D deficiency affects early infant language Background: Although traditional vascular risk factors, such as hypertension development in rural Vietnam: A prospective cohort study and diabetes, identify individuals with an increased likelihood of cardiac events, only coronary angiography indicates the immediacy and severity of HANIEH S, Ha T, Simpson J.A, Thuy T.T, Khuong N, Thoang D, Tran T.D, Tuan T, this risk. This study examined how well retinal vascular abnormalities Fisher J.Biggs B.A. predicted angiographically-proven coronary artery disease. Department of Medicine, Melbourne Academic Centre, at the Doherty Institute; Research and Training Centre for Community Development (RTCCD), Hanoi, Vietnam; Patients and Methods: This was a cross-sectional observational study of 146 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne consecutive patients who underwent coronary angiography for clinical School of Population and Global Health, University of Melbourne; Provincial Centre of indications at a single centre. Participants were assisted to complete a Preventive Medicine, Hanam Province, Vietnam; The Jean Hailes Research Unit, School of Public Health and Preventive Medicine, Monash University; The Victorian Infectious medical questionnaire and angiograms were coded, reviewed and graded Diseases Service, Royal Melbourne Hospital. according to the Leaman score by a cardiologist. This score assessed the number of affected vessels, and the severity of stenoses including in the left Introduction: Vitamin D deficiency affects more than 1 billion people, and is anterior descending artery. now recognised as a major public health problem. Important biological functions involving growth and developmental outcomes have been attributed Participants also underwent retinal photography using a Canon or KOWA to vitamin D, and deficiency during pregnancy may result in important health camera, and retinal images were graded for microvascular abnormalities consequences for both mother and child. We conducted a prospective cohort (Wong and Mitchell classification), and diabetic retinopathy (modified Airlie study, in a rural province representative of many areas of Vietnam, to House scheme). The caliber of retinal arterioles and venules was graded determine the association of vitamin D in late pregnancy with infant growth using a computer-assisted method and Knudtson’s modification of the Parr- and developmental outcomes at 6 months of age. Hubbard formula. Statistical analysis was performed using Stata version 11.2 Methods: This was an observational cohort study of 960 infants, born to software (Stata Corp). women who had previously participated in a double-blind cluster randomized Results: The Leaman score was higher in those with retinal hemorrhage controlled trial of antenatal micronutrient supplementation in rural Ha Nam (p=0.012), moderate microvascular retinopathy (p=0.075), or a moderate or province, Vietnam. Our main exposure of interest was maternal vitamin D proliferative diabetic retinopathy (p=0.04). concentration (25-OHD )at 32 weeks gestation. A Waters TQD mass Arteriolar caliber was not different in individuals with three or more diseased spectrometer was used to quantify 25-OHD concentration. Vitamin D levels coronary arteries compared with those with normal vessels (133.6 + 14.6 µm were categorized as replete (≥75nmol/L), insufficient (≥37.5nmol/ and < and 133.3 + 15.2 µm, p=0.99). However the venular calibre was increased 75nmol/L) or deficient (<37.5nmol/L). Our primary outcomes of interest were (205.7 + 21.6 µm in individuals with 3 or more diseased vessels) compared infant developmental scores and infant length for age z scores at 6 months of with 193.2 + 21.1 µm in those with none, p=0.03). age. Conclusions: Moderate microvascular retinopathy and diabetic retinopathy Results: Sixty percent (582/960) of women had vitamin D concentrations less correlated with worse coronary artery disease. Venular calibre was increased than 75 nmol/L in late pregnancy. Infants born to women with 25- in patients with triple vessel disease. This latter observation is consistent with hydroxyvitamin D deficiency ( < 37.5nmol/L) had reduced developmental the increased venular caliber in individuals with increased cardiac risk in language scores compared to those born to women who were vitamin D epidemiological large population based studies. The technique of retinal small replete (≥75nmol/L) (Mean Difference (MD) -3.48, 95% Confidence Interval vessel imaging represents a potential non-invasive and inexpensive method (CI) -5.67 to -1.28). For every 25nmol increase in 25- hydroxyvitamin D to assess cardiac macrovascular risk. concentration in late pregnancy, infant length-for-age z scores at 6 months of age decreased by 0.08 (95% CI -0.15 to -0.02). 39 MRS JO-ANNE MOODIE Conclusions: Our study indicates that low levels of vitamin D during Use of time on therapy for peritoneal dialysis planning at pregnancy are of concern in rural Vietnam, and are associated with reduced language developmental outcomes at 6 months of age. Our results one Victorian centre strengthen the evidence for giving vitamin D supplementation during MOODIE J(1), Holt SG (1,2), Safe M (1), Toussaint ND (1) pregnancy. 1 Department of Nephrology, The Royal Melbourne Hospital, Parkville, VIC; 2 Department of Medicine (RMH), The University of Melbourne 41 DR SARAH HANIEH Aim: To determine outcomes of patients commencing peritoneal dialysis (PD) Predictive factors of early child growth in rural Vietnam: A at our institution and establish the average duration of this therapy. prospective cohort study Background: Time on therapy (TOT) is a helpful tool for analysing causes of HANIEH S, Ha T.T, De Livera A, Simpson J.A, Thuy T.T, Khuong N, Thoang D, treatment failure and service planning. Victoria has seen a growth in the Tran T, Tuan T,Fisher J, Biggs B.A uptake of PD, but there are worries about technique longevity. Department of Medicine, Melbourne Academic Centre, at the Doherty Institute; Training Methods: We retrospectively analysed our TOT for every PD patient on our Centre for Community Development (RTCCD), Hanoi, Vietnam; Centre for Molecular, PD programme between June 2010 and Feb 2014 (44 months). TOT is given Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population and Global Health, University of Melbourne; Provincial Centre of Preventive Medicine, as mean patient months(pm)(Standard error). Hanam Province, Vietnam; The Jean Hailes Research Unit, School of Public Health and Results: 221 patients were on PD during the study period. 12(5%) were lost to Preventive Medicine, Monash University; Victorian Infectious Diseases Service, Royal follow-up(LTFU), 58 (26%) were transferred to haemodialysis(HD), 41(18%) Melbourne Hospital were transplanted and 24(11%) patients died on PD. The remainder 86(39%) Introduction: A child’s future growth is largely determined by conditions that remain on PD. 21 patients have spent <90 days on PD; 8(4%) transferred to occur within the first one thousand days of life. Adverse growth and nutritional HD (i.e. failed PD), 5 were transplanted quickly, none died and 8 had not yet outcomes occurring during this period may be irreversible, and have reached day 90. consequences for the future health, development and economic potential of the child. We sought to determine which antenatal and neonatal factors were When censored for patients on PD<90 days, 12 (6%) were LTFU after associated with infant length for age z scores at 6 months of age in rural ~25(8)pm but were alive and on PD when they transferred out of the unit. Vietnam. 78(29%) remain on PD, 36(18%) were transplanted after an average of 22(4)pm and 24(13%) died with an average of 29(5)pm on PD. Only 50(25%) Methods: An observational cohort study was conducted in Ha Nam province, eventually went onto HD after an average of 25(4)pm. 1,2&3 year technique North Vietnam. Length for age z scores of 1046 infants were measured at 6 survival on PD were 65%, 35%, 20% respectively when censored for months of age, and data concerning maternal and infant factors was transplantation and <90 days on PD. The longest duration on PD was 10 collected. Participants were infants born to women who had been previously years. randomised to one of three micronutrient regimes during pregnancy as part of a cluster randomized trial. Conclusion: In order to plan dialysis and advise patients appropriately it is important to know locally how long patients spend on PD and understand the Results: Mean length-for-age z score was -0.58 (Standard Deviation (SD) reasons why patients come off this modality. 0.94) and stunting prevalence was 6.4%. Maternal body mass index (MD 45.6

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kg/m2; 95% CI 34.2 to 57.1), weight gain during pregnancy (MD 21.4 kg; 95% network theory. In particular, it focuses on the relationships between groups CI 12.6 to 30.1), and maternal ferritin concentration at 32 weeks gestation of individuals and the resources to which membership of these groups (MD -41.5per two-fold increase in ferritin ; 95% CI -78 to -5.0) were indirectly facilitate access. While social network analysis has been used in the context associated with infant length-for- age z scores at 6 months of age via of Australian mental health services before, this study is the first time it will be birthweight. applied to the specific topic of evidence based practice. Conclusions: Maternal nutritional status is an important predictor of early A survey of all occupational therapists at North Western Mental Health (n=83) infant growth. Our findings highlight the need to develop a comprehensive was conducted as part of a workforce wide review of research and evidence and targeted approach to reducing impaired growth in early childhood, that based practice. A section of this survey asked clinicians to identify who they includes the antenatal period. speak to regarding evidence and systems application, and how often these interactions occur. De-identified data was entered into NodeXL, when enables 42 MR STEVE HALPERIN its conversion into a network graph. The connections were then be analysed Implementation of the Victorian Youth Justice Mental as a complete network (i.e. both those in and outside of occupational Health Initiative at a Youth Mental Health Service: Findings therapy), with particular reference to the following metrics – cohesion (distance, reachability, density), subgroups and centrality (degree, closeness, from 2010-2013 betweeness). HALPERIN, S., Hancox, S., Purcell, R., Reid, D., Albiston, D. & Greenwood- Results: The majority of network connections for occupational therapists at Smith, C. North Western Health were with other occupational therapists, in regards to Orygen Youth Health - Clinical Program; Swinburne University of Technology; both evidence and systems application. While senior clinicians were Forensicare, Victorian Institute of Forensic Mental Health. connected with more people in the network, some junior clinicians were also In the community, rates of violence and offending peak in adolescence and recognised as key contacts. Many of these interactions occurred on a monthly young adulthood. It also during this (period between early adolescence to basis, with few respondents reporting talking about evidence based practice young adulthood) that the onset of the majority of the severe mental illness more frequently. occurs. Whilst the interaction between these developmental processes are Conclusion: Social network analysis is a valid and informative method for not well understood, the relationship between experiencing severe mental exploring the human dimension of evidence based practice. The findings of illness, particularly psychosis, and increased rates of violence has been this study will be used to develop a research strategy for the discipline which repeatedly demonstrated. maximises and builds capital in the network. Interventions to reduce violence and offending among the severely mentally ill are now well established in Victoria, but they are currently organised 44 DR REJHAN IDRIZI according to the traditional adult (AMHS) vas child (CAMHS) divide. The challenge for the emerging Youth Mental Health sector is to develop new Investigating the Role of Betacellulin in the Plasma of approaches to service delivery and treatment for young people with both Schizophrenia Patients Treated with the Antipsychotic mental health and offending issues. Clozapine The Youth Justice Mental Health Initiative (YJMHI) was a Victorian IDRIZI R, Sujeevan S, Sathiyamoorthy S, Pereira A, Sundram S Government reform launched in July 2010. The aims of the initiative was to Department of Molecular Psychopharmacology, The Florey Institute of Neuroscience and improve youth justice client’s access to mental health services, and enhance Mental Health, Melbourne Brain Centre, The University of Melbourne, Parkville 3010 the capacity of Youth Justice and Youth Mental Health staff to effectively Victoria, Australia Department of Psychiatry, Northern Psychiatry Research Centre, the Northern Hospital, Cooper Street, Epping 3067, Victoria Australia meet the needs of youth justice clients requiring mental health assessment and treatment. Within Orygen the YJMHI focused on building staff capacity Background: Schizophrenia is a complex neuropsychiatric disorder of (both allied health and medical) for assessing and managing risk of violence unknown aetiology however recent studies have implicated epidermal growth and offending in the most at risk population within the youth mental health factor (EGF)/ErbB-system dysfunction. Betacellulin (BTC) is an EGF family sector. ligand for ErbB1 and ErbB4 receptors and has been demonstrated to be elevated in the serum of schizophrenia patients. Furthermore our previous in- This paper will outline how the YJMHI clinician role has been operationalized vitro, in-vivo and clinical data support clozapine’s augmentation of deficient within Orygen Youth Health and the North Western Metropolitan region of the ErbB1 signalling suggesting a mechanism for its therapeutic efficacy. We Department of Youth Justice. We will also report on the number and types of therefore postulated that BTC levels are altered in schizophrenia and that interventions and consultations delivered to date. Findings include: 1. There they may be influenced by clozapine treatment. has been a significant increase in the number of primary consultations delivered within Youth Justice, facilitating early intervention and referral and Objectives: In this study we sought to prospectively evaluate plasma BTC thus mitigating the risk of serious mental illness and violent offending. 2. levels in a clozapine-treated schizophrenia cohort over a 26-week treatment There has been a significant increase in the uptake of forensic secondary period and in healthy control subjects. consultantions at Orygen Youth Health indicating a greater wawreness of risk Methods: We used an ELISA assay to measure plasma concentrations of and request for risk management planning. Conclusions include: It is both BTC in schizophrenia patients prior to (n=39), 2-weeks (n=22), 6-weeks feasible and acceptable to both clients and families and staff to enhance the (n=21) and 26-weeks (n=38) after clozapine treatment and also in age/gender attention given to forensic issues, particularly risk of violence to others , within matched healthy controls. The Positive and Negative Syndrome Scale a Youth Mental Health setting. (PANSS) and Clinical Global Impression (CGI) were administered at baseline, 6 and 26 weeks of treatment. 43 MISS DANIELLE HITCH Results: Mean BTC levels were significantly lower in patients at baseline Evidence Based Practice in Allied Health - Exploring the (2280±3496pg/ml, mean±SD), 2-weeks (1782±2749), 6-weeks (1938±2939) Human Dimension through Social Network Analysis and 26-weeks (2195±3938) compared to controls (2536±1585). Post- HITCH D treatment BTC levels at 26-weeks significantly correlated with PANSS positive score (r2=0.176; P<0.05; N=35) and with PANSS change % NorthWestern Mental Health (r2=0.143; p<0.05; N=38). Furthermore at 26-weeks there was a significant Background: Evidence based practice has become an imperative in allied difference in BTC levels between responders (n=19) (symptom improvement health in recent years. While many initiatives to increase its adoption have of ≥20%) and non-responders (n=19; P=0.034). focused on developing clinician’s skills, there has been little focus on the interpersonal factors which enable the implementation of new practices. Conclusions: Schizophrenia patients on antipsychotic drugs have Evidence based practice is enacted by networks of clinicians within significantly lower BTC levels compared to healthy controls. It would appear organisations, who use and learn from each other’s expertise and that the lower the BTC value the greater the treatment response in particular understanding of local conditions. The knowledge they share is around both with reference to positive symptoms. This suggests that BTC activation of the evidence to be applied, and the systems it is applied within. ErbB1 and/or ErbB4 may adversely impact on treatment respsonse. Given our previous clozapine findings, we hypothesise that adverse BTC effects Methods: Social network analysis has emerged as a method from social may be principally mediated through ErbB4. science in recent years, and aims to consider social relationships in terms of

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45 MR STEPHEN EDWARDS participants reported higher CT than controls. Intraclass correlation coefficients suggested strong agreement between CT reports at baseline and Who benefits from psychological assistance for high follow-up for FEP participants (0.75) and almost perfect agreement (0.90) for prevalence mental disorders in homeless men’s crisis controls. Patterns of reliability and relationships with psychopathology are shelters. described. EDWARDS S, Fischer-Burgess J. 47 DR MARK DOWLING Inner West Area Mental Health Games of chance in the immune system and cancer – a Background: Homelessness contributes to and can be caused by mental mathematical approach to immune regulation and health problems. Research confirms high rates of mental disorders amongst men who are homeless and the literature highlights a number of service chemotherapy models for detecting and treating these in a population that is consistently MARK DOWLING (1,2,3), Jie Zhou (2,3), Andrey Kan (2,3), John Markham (4), difficult to engage with traditional methods. Innovative models have been Cameron Wellard (2,3), Edwin Hawkins (5), Susanne Heinzel (2,3), Julia developed in public mental health services to work with men who are Marchingo (2,3), Ken Duffy (6), and Philip Hodgkin (2,3) homeless and have psychotic, severe mood and substance disorders. 1 Intern, Melbourne Health; 2 Walter and Eliza Hall Institute of Medical Research, However, limited attention has been given to the higher prevalence disorders Melbourne, Victoria, Australia; 3 Department of Medical Biology, University of of anxiety and depression or challenging behaviour related to ability or Melbourne, Melbourne, Victoria, Australia; 4 Victoria Research Laboratory, National Information and Communications Technology Australia, University of Melbourne, personality problems. Whilst anxiety and depression respond to psychological Melbourne, Victoria, Australia; 5 Imperial College London, Sir Alexander Fleming Building, intervention for motivated clients, challenging behaviour can be enduring and SW72AZ, London, United Kingdom; 6 Hamilton Institute, National University of Ireland, therefore taxing on case workers in crisis accommodation services. Maynooth, Ireland The Psychological Assessment and Treatment in the Homeless Setting The study of cellular differentiation and fate selection at the single cell level is (PATHS) response is a component of the Inner West Area Mental Health fundamental to understanding the normal physiology of many organ systems Service Community Team based in the Melbourne CBD. Case workers in the and pathophysiology in various disease states. In many systems the overall Crisis Supported Accommodation Services (CSASs) can refer men for direct outcome can be reduced to understanding the intricate balance between cell assessment and treatment but can also request formal or informal secondary division, death by apoptosis and differentiation to other cell types. Using the consultation to help with management of challenging behaviour, traversing immune system as a model system, our laboratory focuses on developing service pathways, skill development, advice about specific clinical matters experimental techniques for observing and timing cellular events in single and referrals to primary health care. Where men accept direct assessment, a cells, as well as mathematical models for interpreting such data and shedding feedback letter is sent to the case worker and general practitioner containing light on the dynamics of intracellular processes. Using these approaches, we a diagnostic summary as well as the recommendations that were given to the have found evidence for significant heterogeneity in cellular outcomes at the client at interview. As well as these clinical options, a bi-monthly education single-cell level, even within a seemingly homogeneous population of cells service is also provided for case workers. exposed to identical stimuli. These results demonstrate an element of chance in determining each cell’s fate, in contrast to the common view that a cell’s Methods:A questionnaire elicited feedback from caseworkers about the utility fate is fixed by the stimuli it receives. Mathematical modeling has yielded the of the PATHS service for their work as well as the impact they perceived for surprising insight that each cell may pursue many fates simultaneously but at their clients. They were asked what they thought of the referral process, different rates, with the final result determined by the fate that is reached first informal as well as formal secondary consultation and about – a type of intracellular “competition” or “race”. recommendations contained the feedback letters. They were also asked about whether they thought the assessment and recommendations were These ideas will be illustrated using a simple system of naïve B cells helpful for their clients. stimulated in vitro to mimic the effect of T-cell co-stimulation in vivo. The B cells are induced to pursue a large number of distinct fates important for Results: Thirty responses were received from case workers in the two CBD immune regulation, including expansion in total cell number, isotype switching CSASs with analysis paying particular attention to the feedback from case to produce different classes of antibody, and maturation to antibody secreting workers about the relative value of the service to them and to their clients. cells. Using live cell fluorescence microscopy and fluorescent reporters for Conclusion: The PATHS model is a unique service response to high differentiation events, we observed the fate thousands of single cells isolated prevalence mental disorders in men’s crisis accommodation services in the in microwells in culture. The correlations observed in the data provide Melbourne CBD. The results will contribute to quality improvement activities evidence for intracellular competition for fates, and “censorship” of for the clinical component of the service. incompatible fates. 46 DR SARAH BENDALL We are currently using these experimental systems and mathematical models to study tumour cell (leukaemia and lymphoma) lines that have undergone Stability of Retrospective Self-reports of Childhood Trauma malignant transformation, and the effects of traditional chemotherapy drugs in Early Psychosis. and novel molecularly-targeted agents. We are aiming to develop a BENDALL S1, Simpson S2, Baksheev, G3, Garner, B1, Markulev, C1, theoretical basis for understanding the effects of different drugs on distinct Phassouliotis, C4, Yun, Y1, McGorry, P1; Phillips, L2 elements of cellular response. This approach may prove useful for understanding the synergistic effects of different drugs, as well as for 1. Orygen Youth Health Research Centre and Centre for Youth Mental Health, University of Melbourne; 2. School of Psychological Sciences, University of Melbourne; 3. Centre for predicting novel combinations that may prove useful in the clinic. Mental Health and Wellbeing Research and School of Psychology, Deakin University; 4. Melbourne Neuropsychiatry Centre, University of Melbourne 48 MS EMMA BOEHM Over the last 10 years, it has become increasingly apparent from well- Breaching the Last Bastion of Resistance to DNA-Damaging conducted research studies that childhood trauma (CT) is a risk factor for Drugs in vivo in DNA repair defective High-Grade Serous psychosis. Many studies rely on the use of retrospective self-reports to Ovarian Cancer Patient-Derived Xenografts. estimate the prevalence of CT. However, concerns have been raised that individuals experiencing psychosis may not be able to accurately report their BOEHM E1, Topp MD1 2, Heong V1 3 4, Khambatta V1, McNally O3, Bowtell experiences of CT, calling into question the validity of such research. DD5 6 7, Swisher EM8, Kaufmann SH9, Wakefield MJ1 4 10 and Scott CL1 3 4. Furthermore, people with psychotic disorders in psychiatric settings are less 1. The Walter and Eliza Hall Institute of Medical Research, Melbourne; 2. Department of likely to be asked about abuse, partly because their responses are Anatomy and Developmental Biology, Monash University, Melbourne; 3. The Royal Women's Hospital, Melbourne; 4. Department of Medical Biology, University of considered to be unreliable. While there is preliminary evidence that Melbourne, Melbourne; 5. Peter MacCallum Cancer Centre, Melbourne; 6. Department individuals experiencing psychosis report CT reasonably reliably across time, of Pathology, University of Melbourne; 7. Department of Biochemistry and Molecular further research is required. This study aimed to investigate the test-retest Biology; 8. Department of Obstetrics and Gynaecology, School of Medicine, University of reliability of CT reports in young people experiencing first-episode psychosis Washington, Seattle, Washington, USA; 9. Department of Molecular Pharmacology and (FEP) at two time points (during the acute first episode and three months Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA; 10. Departments of Genetics, University of Melbourne. later), compared to a non-psychiatric control group. There were 25 FEP participants and 31 non-psychiatric controls, all aged 15-25 years. FEP Objective: To investigate the tolerability and utility of therapy targeting DNA repair polymerase activity in high-grade serous ovarian cancer (HG-SOC) Page | 20

patient-derived xenograft (PDX) models which are resistant to standard Conclusions: Reduction of androstenedione to testosterone by the canonical platinum chemotherapy and poly(ADP-ribose) polymerase 1 (PARP) inhibitor HSD17B AKR1C3 is the predominant source of signalling androgens in therapy. hormone refractory prostate cancer. Background: HG-SOC accounts for 65% of mortality for ovarian cancer. ~50% 50 DR RACHEL KOLDEJ of HG-SOC are thought to be defective for the high fidelity DNA repair pathway of Homologous Recombniation (HR) and may be responsive to the Clinically relevant biomarker discovery - Incorporating novel PARP inhibitors which inhibit base excision repair (BER). For response translational research questions into clinical trials of HR-defective HG-SOC to PARP inhibitors, the highly error-prone DNA KOLDEJ R, Ripley J, Lim A, Hockridge B, Boyd J, Ritchie DS repair pathway of non-homologous end joining (NHEJ) may be essential, driving genomic instability, which results in cell death. Indeed, in HG-SOC ACRF Translational Research Laboratory, Royal Melbourne Hospital; Bone Marrow Transplant Unit, Royal Melbourne Hospital; Department of Medicine, University of which are HR and NHEJ defective, resistance may emerge. We propose that Melbourne; Cancer Immunology Research, Peter MacCallum Cancer Centre. in HR and NHEJ defective HG-SOC, targeting increased reliance on BER (with PARP inhibitors) and error prone DNA polymerases (with DNA repair Increasingly, clinical trials are testing new therapeutic strategies that are polymerase inhibitors) may prove effective. The PDX model of HG-SOC has effective only in a subset of patients. Identifying who will benefit most from been shown to be a reliable method of preclinical study, providing the these therapies is the basis of personalised medicine. Important factors in the opportunity to devise rationalized, targeted therapies. design of biomarkers for clinical application are ready access to suitable tissue, high levels of sensitivity and specificity, ease of incorporation into Methods: Mice bearing subcutaneous HG-SOC PDX were treated with a DNA diagnostic laboratory practice and, where possible, provision of insight in the repair polymerase inhibitor via the intraperitoneal route daily for 21 days. The mechanisms of disease and/or response. mice were inspected visually and weighed before each treatment, with loss of >15% pre-treatment body weight indicative of significant toxicity. PDX tumour The aim of this project is to use both immunological and molecular techniques volume was monitored twice-weekly (measurement of perpendicular to develop response biomarkers to identify which patients will respond to a diameters using calipers). Mice bearing tumours > 0.7cm3 were sacrificed particular treatment. This approach will prevent side effects from ineffective, and tumours harvested for analysis. potentially toxic, and often expensive medications, allow for better treatment choices and reduce the treatment cost. Results: The DNA repair polymerase inhibitor was well tolerated at the dose delivered in NOD-SCID-IL-2rγ mice. Preliminary results will be presented. The strategy can easily be incorporated into any clinical trial through the collection of relevant patient samples for analysis. Blood samples are Conclusion: Targeting DNA repair polymerases in this context represents collected at baseline, after a period of treatment (usually 1-3 months) and at taking out the final bastion of resistance to DNA-damaging therapy. DNA disease progression/relapse. They are processed to isolate PBMCs and repair polymerase inhibitor therapy is well tolerated in a PDX model of HG- serum. Other samples such as tumour or BM biopsies can be collected if SOC. This will facilitate the analysis of such therapy in combination with relevant to the disease in question. These samples can then analysed using a PARP inhibitors in HG-SOC PDX carefully chosen, based on molecular number of techniques including FACS analysis to determine immunological characterization of DNA repair capability. This study of DNA repair profile, immunological function tests, cytometric bead array and ELISA to polymerase inhibitor therapy represents a novel approach to overcoming determine cytokine levels, RNA-seq or nanostring analysis to determine gene resistance to DNA-damaging therapy in HG-SOC. expression profiling and serum microRNA expression. The results of these analyses are then correlated to the clinical patient data including disease 49 DR NIALL CORCORAN severity, response to treatment, the development of serious side effects and Canonical Androstenedione Reduction is the Predominant overall survival to identify significant biomarkers. Source of Signalling Androgens in Hormone Refractory Through the application of these biomarkers we will determine a pre- Prostate Cancer treatment profile, which best selects which of these costly therapies is most likely to benefit individual patients. When applied to the clinic, this avoids Matthew Fankhauser1, Yuen Tan1, Geoff Macintyre2, Izhak Haviv2, Matthew K.H. Hong1, Anne Nguyen1, John S. Pedersen3, Anthony J. Costello1,4, patients from being exposed to side effects from ineffective medications and Christopher M. Hovens1,4, NIALL CORCORAN1,4 allows for better choices of treatments. Furthermore, identification of markers that limit responses to existing therapies will provide a list of candidate targets 1. Departments of Urology and Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville; 2. NICTA Victoria Research Laboratory, University of Melbourne, (genetic and immunological) for the rational development of new therapies. Parkville; 3. TissuPath Specialist Pathology, Australia, and the Faculty of Medicine, Monash University; 4. Australian Prostate Cancer Research Centre Epworth. 51 DR JOANNE DAVIS Background: It has been recognised for almost a decade that concentrations A radioresistant lymphoid population controls donor of signalling androgens sufficient to activate the androgen receptor are engraftment and onset of graft-versus host disease in a present in castration resistant prostate cancer tissue. The source of these perforin-dependent manner. androgens is highly controversial, with 3 competing models proposed. We therefore wished to determine the androgenic potential of human benign and DAVIS J, Harvey M, Neeson P, Huntington N, Godfrey D, Trapani J, Ritchie D. malignant (hormone-naïve and treated) when incubated with various 1 ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, precursors, and examine concomitant changes in enzyme expression. Victoria, Australia; 2 Haematology and Immunology Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne; 3 Sir Peter MacCallum Department of Methods: Freshly harvested prostate tissue (benign, hormone-naïve & Oncology, University of Melbourne; 4 Walter and Eliza Hall Institute of Medical Research, hormone refractory prostate cancer) was incubated in excess concentrations Melbourne; 5 Peter Doherty Institute, Melbourne; 6 Bone Marrow Transplant Unit, Royal of cholesterol, progesterone, DHEA, androstenedione, or testosterone for 96 Melbourne Hospital. hours, and steroid concentrations in the conditioned media measured by GC- Immunosuppressive pre-transplantation conditioning is essential for donor MS. Changes in the expression of androgen synthetic and/or degradative marrow and T cell engraftment in allogeneic bone marrow transplantation enzymes was determined by expression microarray and qPCR. Significant (BMT). The role of residual post-conditioning recipient immunity in changes were confirmed in an independent dataset. determining engraftment is poorly understood. In this study, we examined the Results: Of the precursor molecules tested, only incubation with role of recipient perforin in the kinetics of donor cell engraftment using mouse androstenedione gave rise to significant concentrations of signalling models of BMT. androgens. Although this was observed in all tissue types, it occurred to a Two HLA major-mismatched BMT mouse models were utilized; C57BL/6 significantly greater degree in hormone refractory compared to hormone (H2Kb) into BALB/c (H2Kd) recipient mice, or BALB/c into C57BL/6 naïve cancer. Consistent with this, GSEA of the expression microarray data recipients. Lethally irradiated mice (wild type (WT) or perforin knockout (pfn-/- revealed significant upregulation of 17HSD17B activity, with overexpression )) received an iv injection of WT T cell-depleted BM (5e6) on day 0, and WT of the canonical enzyme AKR1C3 confirmed by qPCR in the same samples donor T cells on day 2. Donor lymphoid engraftment was measured in and in a publically available expression dataset. Importantly we found no recipient spleen, BM and lymph nodes from days 5-7 post BMT by histology evidence to support a significant contribution form either the ‘backdoor’ or ‘5-α and flow cytometry. In pfn-/- recipients, both the rate and proportion of donor dione’ pathway. haematopoietic and T cell engraftment were significantly increased, and serum levels of pro-inflammatory cytokines, including IL-6 and IFNg, were

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elevated. Additionally, rapid differentiation of engrafted donor T cells to an University of Melbourne; 3. Department of Medical Oncology, The Royal Melbourne effector memory T cell phenotype was observed. Hospital, Parkville. In WT recipients, the rate and degree of donor lymphoid engraftment could be The TNF superfamily member RANKL and its cognate receptor RANK are enhanced to that seen in pfn-/- recipients, by depleting natural killer cells (NK) essential for the formation of a functioning, lactating mammary gland. prior to BMT. This demonstrates that a perforin-dependent, NK-mediated Progesterone-induced RANKL signalling has recently been identified as the host-versus graft effect limits the rate of donor cell engraftment and T cell key driver of mouse mammary stem cell proliferation and expansion during activation. We found that a radio-resistant NK cell subset, NKT cells, pregnancy and has been implicated in the development of hormone-driven survived in the BM of lethally irradiated mice, and may contribute to the host- mammary carcinogenesis. versus graft effect. Furthermore, reduced pre-transplant irradiation doses in To further investigate the role of RANK signalling in the early stages of breast pfn-/- recipients permitted long-term donor haematopoietic and T cell tumorigenesis, we have analysed the expression of the RANK receptor in engraftment. both normal human breast and preneoplastic BRCA1-mutated tissue by flow These findings suggest that suppression of perforin activity or selective cytometry. Approximately 15% of luminal progenitor cells (Lin- depletion of recipient NK cells prior to BMT could be utilized to improve donor EpCAM+CD49f+) express RANK on their surface in both normal and BRCA1- stem cell and T cell engraftment, and should allow for reduction of the mutated breast tissue, and these RANK-positive cells have a higher intensity of pre-transplant conditioning. proliferative capacity in vitro compared to their RANK negative counterparts. Cohorts of BRCA1-mutant primary tumour xenografts were established and 52 DR STANLEY STYLLI treated weekly with the RANKL inhibitor OPG-Fc or a matched isotype control antibody to study the effectiveness of RANKL inhibition for the treatment of EGFR and Cortactin - dual targets in GBM patients ? established BRCA1-mutated breast cancer. Tumour formation was attenuated STYLLI SS 1,2, Ware T 1, Paradiso L 1, Kaye AH 1,2, Luwor RB 1. in mice treated with the inhibitor compared to the control. To assess the 1 Department of Surgery, The University of Melbourne, Royal Melbourne Hospital, usefulness of RANKL inhibition for chemoprevention, we are currently treating Parkville, VIC, Australia; 2 Department of Neurosurgery, The Royal Melbourne Hospital, cohorts of BRCA1-deficient mice shown to express high levels of the RANK Parkville, VIC, Australia. receptor with OPG-Fc and monitoring the onset of tumorigenesis. Taken Primary brain tumours are responsible for about 2% of all deaths from cancer together, these results show promise for the critical role of RANKL signalling with the glioblastoma multiforme (GBM) being the most common and in the onset of BRCA1-associated tumorigenesis, and ongoing studies will aggressive primary adult brain tumour. The current standard of care involves assess both the functional regulation of luminal progenitor cells by RANKL maximal surgical resection followed by radiation therapy (RT) combined with and the effectiveness of OPG-Fc as a novel chemopreventative agent. concurrent and adjuvant temozolomide (TMZ). This combinatorial approach provides a modest increase in survival producing a median survival of only 54 DR WAYNE NG 14.6 months and a dismal overall prognosis with a patient 5-year survival less LPA is involved in modulating glioma stem cell migration than 5%. NG W, Pebay A, Drummond KJ, Burgess AW, D'Abaco GM, Luwor R, Kountouri Control of growth factor receptor signalling is fundamental to a wide variety of N, Brown DV, Frisca F, Zhou HJ, Gogos A, Lim T, Kaye AH and Morokoff AP. cellular processes including cell growth, differentiation, motility and survival. Royal Melbourne Hospital; University of Melbourne; Centre for Eye Research Australia; Therefore, molecular targeted agents against key growth factors and Walter and Eliza Hall Institute of Medical Research components of related signalling pathways in GBM have been the focus of Background: Currently, much of GBM research concentrates on targets research for a number of years. The inappropriate activation or aberrant related to cytotoxicity, survival or angiogenesis, rather than mechanisms of signalling by particular growth factor receptors is linked with a number of invasion. Lysophosphatidic acid (LPA) signalling has been putatively diseases including cancer. In particular, the epidermal growth factor receptor described as having a mechanistic role in invasion. Initially described for its (EGFR) appears to play a pivotal role in a number of cellular processes, promotile effects in melanoma cells, it has since been ascribed a role in ultimately leading to therapeutic resistance. Dysregulated EGFR signalling breast and ovarian cancer metastasis.(Stracke et al., 1992; Zhang et al., can result from mechanisms such as cell-surface overexpression, autocrine 2009) Autotaxin (ATX)/LPA receptor expression can be dysregulated in GBM activation and EGFR gene mutation. Amplification of the EGFR gene, and can be differentially higher at the invasive edge, suggesting LPA resulting in overexpression of EGFR protein is seen in approximately 40% of signalling modulates glioma cell invasion.(Hoelzinger et al., 2007; Kishi et al., GBM cases. A high percentage of GBM patients that overexpress EGFR are 2006) LPA1 receptor is reported as being pro-tumourigenic and has been known to express both wild-type EGFR as well as a mutated EGFR. The most implicated in cell motility, invasion, survival and proliferation.(Yanagida et al., common mutated form is known as EGFRvIII, which is the result of a 2011) truncated extracellular domain that leads to ligand-independent constitutive tyrosine kinase activity that activates and sustains mitogenic, anti-apoptotic Methods: Tumour derived explants were grown in stem cell neurosphere and pro-invasive signalling pathways. conditions and tagged with luciferase. Relative expression of ATX/LPA was measured using RT-qPCR. Migration assays were performed using 24 well Cortactin is a ubiquitously expressed Src substrate that engages in several transwell plates and a luciferase reporter gene assay. protein-protein interactions that may be relevant to tumour cell motility and tumoural progression. The cortactin gene CTTN resides on chromosome Results: LPA receptors are differentially expressed in our panel of glioma locus 11q13 and is frequently amplified in human cancers such as head and stem cells (GSC). In particular, LPA1 and LPA4 are overexpressed compared neck carcinomas and colon cancer, but has not been extensively studied in to control neural stem cells (p<0.05). We show that GSC exhibit dose- glioma. A growing list of cortactin-binding partners has been identified dependent migration in response to LPA stimulation. Relative to control including proteins that regulate receptor clustering, endocytosis, and vesicle (100% cells seeded to bottom chamber), we observed migration rates of LPA transport. It is therefore highly conceivable that cortactin overexpression in 0.1uM 4.3% +/- 1.7; p=NS, LPA 1uM 24% +/- 1.7; p<0.05 and LPA 10uM cancer or the interaction with relevant binding partners may influence EGFR 46.5% +/- 3.7; p<0.05 (mean +/- SEM; p-value). This response can be or EGFRvIII activity. The overexpression of cortactin in specific cancers, abolished with a selective LPA1/3 antagonist (Ki16425). We also show that coupled with its involvement in endocytic events and vesicle trafficking, led us an LPA1 dominant cell line can migrate in response to LPA stimulation, to investigate the involvement of cortactin expression on the EGFR in glioma whereas an LPA4 dominant cell line exhibits a severely attenuated migration cells. response. 53 MISS EMMA NOLAN Conclusion: LPA1 is an important regulator of LPA induced migration in GSC. LPA may represent a novel target for GBM therapy. Investigating the role of RANKL signalling in the development of BRCA1-associated breast cancer. 55 DR HUI-LI WONG NOLAN E; Vaillant F and Visvader J are affiliated with institutions 1&2 (WEHI Resection of colorectal cancer (CRC) metastases in routine and Department of Medical Biology). - Lindeman G is affiliated with all three practice listed institutions (WEHI, Department of Medical Biology and Department of Medical Oncology WONG H (1), Field K (2), Tran B (1-3), Tie J (1-3), Shapiro J (4), Wong R (5), Yip D (6), Nott L (7), Richardson G (4), McKendrick J (5), Gibbs P (1-3,8) 1. VBCRC Breast Cancer Laboratory, ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville; 2. Department of Medical Biology, (1) Walter and Eliza Hall Institute of Medical Research, Parkville; (2) Royal Melbourne Hospital, Parkville; (3) Western Hospital, Footscray; (4) Cabrini Health, Malvern; (5) Page | 22

Department of Medical Oncology, Eastern Health, Box Hill; (6) The Canberra Hospital, Garran ACT, (7) Royal Hobart Hospital, Hobart, TAS; (8) BioGrid Australia, Melbourne 57 MS ANTHEA UDOVICICH Background: The optimal management of metastatic colorectal cancer Meeting an unmet need: Facilitating guided relaxation for (mCRC) involves a multimodality approach. Complete resection of limited cancer patients in a busy acute setting. metastatic disease is a critical, potentially curative intervention for a minority UDOVICICH, A of patients. Data on resection rates and outcomes in routine clinical practice are limited. Royal Melbourne Hospital - Occupational Therapy Department Background: Guided relaxation has been proven to assist with stress and Methods: Analysis of patients prospectively entered onto the TRACC anxiety, common symptoms to cancer patients. At the Royal Melbourne (Treatment of Recurrent and Advanced Colorectal Cancer) database, a hospital, caseload demands and the need to prioritize discharge planning multisite Australian mCRC registry. Data collection commenced in July 2009 have been barriers to facilitating this. In response, a quality project was and is ongoing at 14 centres. Treatment intent was recorded at initial patient commenced to investigate using the OT allied health assistant to assist in review as curative, potentially curative or palliative. providing guided relaxation. Results: At median follow-up of 20.9 months, 213 (21%) of 1012 patients Method: have undergone metastasectomy, including 179 (84%) R0 resections. Liver 1. Benchmarking email to members of OT Australia Oncology and Palliative (55.4%) and lung (20.2%) were the commonest resected disease sites. For Care SIG (revealed that busy caseloads were also an issue for them in 26 (12.2%) patients the initial treatment intent had been palliative. Patients providing relaxation). who had metastases resected were younger (median age 63 vs 70 years, 2. Literature review. p<0.0001), of better performance status (PS0-1: 97.7 vs 75.5%, p<0.0001), 3. Survey conducted for patients on the oncology ward to gage their interest had fewer comorbidities (Charlson Index ≤3: 75.1 vs 55.9%, p<0.0001) and in participating in guided relaxation. fewer sites of disease (single site: 79.8% vs 52.5%, p<0.0001). A significantly 4. Education sessions with OT AHA on facilitating guided relaxation with higher proportion of patients treated in private than public hospitals underwent patients. resections: 143/548 (26.1%) vs 70/459 (15.3%), p<0.0001. At initial 5. Post relaxation sessions, a survey is being provided to patients to gage presentation, more private patients had PS0-1 (82.8% vs 77.8%, p=0.0459) their satisfaction in the session and whether it assisted with their and single disease site (61.3% vs 54.5%, p=0.0291) than public patients, but symptoms. the median age of private patients was higher (70 vs 67 years, p=0.041). Outcomes: The pre-survey revealed that cancer patients on the ward Overall survival was equivalent for resected patients in both groups (median experience issues with sleep, stress/anxiety and muscle tension. Over half of not reached, HR 0.96, 95% CI 0.45-2.06, p=0.9189). those surveyed were interested in guided relaxation. Based on the literature, Conclusion: A substantial proportion of mCRC patients in routine practice benchmarking email and survey outcomes, guided relaxation with the OT undergo resection of distant metastases, including some patients initially AHA has commenced. Surveys were completed post the relaxation and all considered incurable. Significant variation between sites has been noted, feedback was positive with patients noting it assisted with their symptoms and which may relate to differences in patient population and/or a more gave them a chance to have 'time on their own'. Patient suggestions were aggressive treatment approach. Multivariate analyses and review of individual also considered in improving future sessions. centre data are planned to explore reasons for potential underutilisation of Conclusion: Occupational Therapy plays a role in providing strategies to this critical intervention. assist patients with symptom management. Utilizing an OT AHA to facilitate 56 MR ALEXANDER DAVENPORT guided relaxation can assist in the management of stress, anxiety and issues with sleeping in the context of a busy acute hospital. Investigating immunological killing kinetics and synapse formation by CD8+ t cells expressing a chimeric antigen 58 DR NIALL CORCORAN receptor Phase-II study of neoadjuvant ‘supercastration’ in men ALEXANDER DAVENPORT1,2,3,Misty Jenkins2, Michael Kershaw3, Phil Darcy3, with high-risk prostate cancer Paul Neeson3, David Ritchie1,2, 3 NIALL CORCORAN1,2,3, Nicholas Howard1, Pat Bugeja1,2, Michael Kerger1, 1 University of Melbourne, Department of Medicine; 2 Royal Melbourne Hospital; 3 Peter Dan Moon4, David Clarke2, Jeremy Grummet5,6, Chris Hovens1,3,, Justin MacCallum Cancer Centre. Peters2,3, Tony Costello1,2,3, John Pedersen6,7, Andrew Ryan7, Phil Chimeric antigen receptor (CAR) therapy is a revolutionary concept allowing Dundee1,2, Paul Ruljancich8 and Phillip Parent for the reprogramming of autologous T cells to otherwise undetectable cancer 1 Australian Prostate Cancer Research Centre Epworth, Richmond; 2 Royal Melbourne antigens. Unlike MHC class I antigens, that can be recognized by Hospital, Parkville; 3 University of Melbourne, Parkville, VIC; 4 Epworth Healthcare, conventional T cell receptors (TCRs), CARs are not restricted and can be Richmond; 5 Alfred Hospital, Prahran; 6 Monash University, Clayton; 7 TissuPath Pty Ltd, designed against an unlimited number of tumour-associated antigens. Recent Mt Waverley; 8 Eastern Health and Epworth Eastern, Box Hill. reports have highlighted the effectiveness of CAR therapy in both Chronic Introduction & Objectives: Men with high-risk prostate cancer are at increased Lymphocytic Leukaemia and Acute Myeloid Leukaemia. risk of disease relapse post-prostatectomy. Previous neo-adjuvant studies demonstrate reductions in positive margin rates, but a low pT0 response rate In this study, we investigate the activation of T cells via the TCR and and no improvement in biochemical recurrence-free survival. With the advent subsequent formation of the Immune Synapse (IS) and the kinetics of the of more effective hormonal agents we wished to determine if a delivery of the lethal hit via the CAR. To do this, we have generated a ‘supercastration’ combination led to an increased pT0 response rate transgenic mouse model expressing a CAR (anti-human HER2) crossed with compared to historical controls. the well characterized OT-I (OVA) model system. We have compared the activation potential and cytotoxicity of a classic TCR/MHC synapse with the Methods: This is an open label non-randomised Phase II study neoadjuvant CAR/antigen synapse, using a H2-kb expressing target cell line that has also study of ‘supercastration’ in men with high-risk clinically localized prostate been transduced to express the CAR antigen. cancer. Treatment consists of Degarelix 240/80mg q 1/12, Abiraterone 1000mg OD, Bicalutamide 50mg OD and Prednisolone 5mg OD for 24 Using live cell time-lapse microscopy we have shown that the kinetics of weeks. The primary endpoints are safety/tolerability and pT0 response rate. perforin pore formation are equivalent to that of conventional TCR-mediated Secondary endpoints include correlative molecular and hormonal studies. synapses and that CAR T cells can serially kill targets. Importantly we have Using an optimal 2-stage design, the trial is powered to detect a pT0 shown that despite CAR cell surface expression being 60 fold lower than response rate of 25%, with at least one pT0 response required in the first 9 TCR, functional cytotoxicity is equivalent, highlighting the efficiency of CAR- patients required to trigger recruitment to the second phase. The final mediated T cell responses. This work will allow for development of CAR- anticipated sample size is 12-17. restricted T cells with optimal activation and cytotoxicity, for use in adoptive therapies. Results: To date 17 patients have been recruited. The combination treatment has been well tolerated, with hot flushes and fatigue being the most

commonly reported side effects. Six patients with asymptomatic elevation of liver transaminases required Abiraterone dose reductions, and there have been no unexpected toxicities. One patient in the first phase had a complete

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pathological response, with complete resolution of high-grade disease 61 MR NICHOLAS YEE observed in a second patient. Conclusions: This ongoing Phase II trial will offer insights into the role of Role of PI3K and mTOR inhibitors in glioma stem cells neoadjuvant ‘supercastration’ in men with high-risk prostate cancer. YEE N, Ng W, Kountouri N, Drummond K, Morokoff A. Correlative molecular studies will be performed to elucidate molecular Department of Surgery, Royal Melbourne Hospital; Department of Medicine, Royal mechanisms of resistance in persistent tumour tissue. Melbourne Hospital, University of Melbourne Background: Glioblastoma multiforme (GBM) is the most common and 59 MR TEDDY KAI ZHEONG LIM malignant primary brain tumour in adults. GBM has a very dismal prognosis The role of focal adhesion kinase in glioma stem cell as a result of extensive tumour heterogeneity as well as a high rate of migration and invasion recurrence. Median survival of patients with GBM is approximately 14-16 months. Glioma stem cells have been described as the cause for this LIM TKZ, D’Abaco GM, Kountouri N, Ng W, Dimou J, Malaterre J, Nowell C, disease's recurrence. We have recently collected and cultured glioma stem Johns T, Kaye AH, Drummond KJ, Morokoff AP cells derived directly from GBM patients' tumours to study this subpopulation 1. Department of Surgery, University of Melbourne, Parkville; 2. Peter MacCallum Cancer of cells in terms of their survival mechanisms. Centre, East Melbourne; 3. Monash Institute of Pharmaceutical Sciences, Parkville; 4. Monash Institute of Medical Research, Centre for Cancer Research, Clayton; 5. Faculty of Phosphoinositide 3-kinase (PI3K) is an important enzyme which forms part of Medicine, Health & Sciences, Monash University, Clayton. a crucial intracellular pathway first thought to determine cell survival via Background: Despite standard chemotherapy with temozolomide plus downstream bcl-2 apoptotic signalling pathway. Hence, its role in cancer and radiotherapy, Glioblastoma multiforme (GBM) has a poor median survival of more recently in GBM is currently being investigated in terms of dysregulation 14 months. Focal adhesion kinase (FAK) is a 125kDa non-receptor kinase of this signalling pathway. Dual inhibition of PI3K as well as downstream that mediates cell-matrix interaction as well as growth, survival, and migration mammalian target of rapamycin (mTOR) has been shown to induce in cancers. Overexpression of FAK is linked to poorer prognosis in GBM. differentiation on glioma stem cells and as a result the self-renewal capacity Using an in vitro glioma stem cell model, we have previously shown that FAK of the stem like glioma cells is unable to be maintained. Thus, the utilisation of and phosphorylated FAK is over-expressed and that specific inhibition of FAK the inhibitors can be useful in elucidating properties of glioma stem cells in by a kinase inhibitor Y15, unlike temozolomide, prevents neurosphere the context of cancer signalling pathways. formation and leads to apoptosis. Methods: We aim to investigate the cytotoxic effect of a dual PI3K-mTOR Aims: We further explore the role that FAK plays in glioma stem cells with inhibitor as well as a partial PI3K inhibitor by using a PTEN retained and respect to their ability to migrate and invade in vitro and in vivo. We also aim PTEN deleted cell line of glioma stem cells and LDH cytotoxicity assays. We to determine whether the FAK pathway is important in tumour recurrence. will confirm intracellular signalling with western blots for PTEN, Akt/pAkt, PARP/cleaved PARP, GFAP, olig2 and β3-tubulin. We will also validate the Methods: Transwell migration will be used to assess migration. A fluorescein action of PI3K/mTOR inhibition in glioma stem cells using PIP3 assays. isothiocyanate (FITC)-degradation assay with Matrigel emulating the extracellular matrix will be used to assess invasion. Orthotopic xenograft GSC Conclusions: We hope to show that inhibition of PI3K and mTOR pathways mouse models will be used in conjunction with bioluminescence imaging and synergistically lead to cancer cell cytotoxicty and induces differentiation in H&E staining to investigate the effect of Y15 in vivo. FAK/p-FAK and glioma stem cells. response to inhibition will be assessed in recurrent tumours using the glioma stem cell model as well as comparison of primary vs recurrent GBM tissue 62 MS VENETIA KHAMBATTA from surgical resection. Using patient-derived xenografts to design targeted Conclusion: FAK plays a key role in driving malignant stem cell behaviour in therapies to treat oncogene-driven high-grade serous GBM and that targeting FAK may be a stem cell- specific therapeutic strategy. ovarian cancer. 60 MR RYAN ATKINS KHAMBATTA V, Heong V, Topp MD, Boehm E, McNally O, Swisher EM, Haber M, Norris M, Wakefield MJ, Bowtell DD and Scott CL. Quiescence as a marker of treatment resistance in Walter and Eliza Hall Institute; The Royal Women's Hospital glioblastoma multiforme Background: High-grade serous ovarian cancer (HG-SOC) continues to be ATKINS RJ, Stylli SS, Luwor RB, Kaye AH, Hovens CM. one of the leading causes of cancer mortality in women. The efficacy of Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, platinum chemotherapy, the mainstay of treatment for HG-SOC, is of limited Parkville; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville; Australian Prostate Cancer Research Centre at Epworth, Richmond. duration for the majority of women and no novel therapies targeted to HG- SOC have been approved. Molecular sub-classification of HG-SOC has the Gliomas are tumours of the brain, and despite decades of intense research, potential to reveal new drug targets. Of interest is the C5 HGSC subgroup, still maintain a dismal prognosis. Glioblastoma multiforme represents the with over-expression of the proto-oncogene, MYCN, a member of the MYC most malignant (WHO grade IV) incarnation of this tumour, with a median family of oncogenic transcription factors, which play essential roles in patient survival of ~16 months, and novel therapeutic approaches are tumorigenesis. Inhibition of MYCN in C5 HG-SOC may reduce cellular required to improve patient outcomes. The cancer stem cell (CSC) pool within proliferation and the ability of HG-SOC to evade therapy. the tumour that resist treatment, causes recurrence and ultimately mortality shares properties with normal stem cells, including high resistance to Aim: Utilising a “C5-like” patient-derived xenograft (PDX) cohort to document chemoradiotherapy and a low mitotic index. By isolating these resistant whether MYCN-high HG-SOC respond to novel MYCN inhibitors. quiescent cells and analysing their expression profiles it is hoped that novel Methods: Human HG-SOC PDX have been characterised by the host therapeutic targets will be revealed that may improve patient outcomes. laboratory, including with in vivo drug response to standard platinum-based In this study the fluorescent dye Oregon Green was used to label glioma cell chemotherapy and relevant molecular characteristics. “C5-like” PDX in which lines in a 7-day pulse-chase assay. Oregon Green ubiquitously labels cells, the MYCN-pathway (MYCN, LIN28B and HMGA2) appears to be over- and with each the cell division the fluorescent signal is divided 50:50 between expressed, have been identified, most of which do not have DNA repair gene each daughter cell. After 7 days the brightest (and thus the least proliferative) mutations. Appropriate regimens of putative novel MYCN inhibitors are being fraction of cells can be identified using flow cytometry or fluorescence determined in mice bearing C5 PDX. When tumour volume reaches 0.2 cm3, imaging. delivery of appropriate doses, starting with those from relevant models in the It was found that cells that retain the highest concentration of Oregon Green literature where available, is being compared with vehicle administration to are more resistant to chemotherapy (temozolomide), radiotherapy, and determine tolerable, efficacious regimens. A subset of mice will be harvested combination chemoradiotherapy. The quiescent cells are also more migratory after 48 hours of treatment for biomoarker analysis. For the remaining cohort than their proliferative counterparts. of mice, tumour volume will be measured twice-weekly and mice will be euthanized when tumour volume reaches 0.7 cm3, after which the mice will be We have shown that quiescent cells are innately resistant to the current GBM heart bled to retrieve plasma and tumours processed. This preliminary work standard treatments and are more migratory than rapidly dividing cells. We will allow generation of PDX samples for future histologic, western blot, qRT- have provided a platform for quickly and easily isolating this quiescent fraction of cells for further analysis.

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PCR and genomics analysis, to identify molecular features of response and 22 min, p=0.02. Patients with no prenotification which prevented transfer resistance. direct to CT had significant delays (median DNT 51 min; p<0.001 vs. pre- Results: Regimens are being analysed and will be presented for PKI-587 a notification). After-hours where the system remained unchanged there was no dual-pathway PI3K/mTOR pathway inhibitor; JQ1, a bromodomain inhibitor change in DNT (median 67 min vs. 65 min; p=0.87). Patients possibly taking and vinorelbine, a tubulin polymerase inhibitor. warfarin previously required laboratory INR pre-tPA (median DNT 77 min; range 38-92 min). Subsequently 6/80 (7.5%) patients were treated after Conclusion: By exploring the impact of MYCN inhibition in a cohort of “C5- confirming sub-therapeutic POC-INR (25 min; range 14-34 min). like” PDX, a novel approach to treatment for women with C5 HG-SOC may be Conclusions: Pre-notification and going direct to CT have the greatest impact elucidated. in reducing treatment delays. Combined, these simple, resource-neutral 63 WITHDRAWN procedures halved our median DNT. The optimal pre-notification includes patient details, allowing pre-registration, pre-ordering of CT, and access to prior medical history during transport. POC-INR is helpful in select patients. 64 DR ANDREW TALBOT 66 MISS MONICA LIN Anti-Epileptic Medications Increase Osteoporosis Risk in CYP2C19 polymorphisms and clinical outcome in Male Fabry Patients: Bone Mineral Density in an Australian endovascular treatment of cerebrovascular disease Fabry Cohort. Monica Lin1, Marian Todaro2, Jian Xiong Chan2, Leonid Churilov3, Wu Sheng TALBOT A, Ghali J, Nicholls K. Zhu1, Sangeetha Ramdave2, Diana Chung1, Stefan Guerra2, Peter J. Mitchell4, Department of Nephrology, Royal Melbourne Hospital; Department of Medicine, Richard J. Dowling4, *Patrick Kwan2,5, *Bernard Yan University of Melbourne 1 Melbourne Brain Centre, Royal Melbourne Hospital, Department of Medicine, Background: Fabry Disease (FD) is an inherited X-linked lysosomal storage University of Melbourne; 2 Department of Medicine, The University of Melbourne; 3 disease with widespread clinical manifestations. Small prospective studies Florey Institute of Neurosciences and Mental Health, Melbourne Brain Centre (Austin Campus), Heidelberg; 4 Department of Radiology, The Royal Melbourne Hospital; 5 have shown increased osteopenia and osteoporosis in male FD patients. Department of Neurology, The Royal Melbourne Hospital. Limited information however exists about bone metabolism and osteoporotic risk factors within this group. We reviewed osteoporotic risk factors within our Background: Clopidogrel is commonly prescribed for the prevention of cohort. ischaemic events after endovascular coiling or stenting of intracranial aneurysms. Clopidogrel is a pro-drug that requires conversion to its active Methods: A retrospective analysis of bone mineral density (BMD) results and metabolite by the cytochrome P450 (CYP) 2C19 enzyme. The incidence of fracture incidence in 44 patients, (22 Males and 22 Females), was ischaemic events may be attributed to common CYP2C19 polymorphisms undertaken. Dual X-Ray absorptiometry scans were performed at the Lumbar which are associated with differing clopidogrel responsiveness. Among them, Spine, Hip and Femoral Neck. The impact of risk factors including renal CYP2C19*2 and CYP2C19*3 are associated with reduced response to function, anti-epileptic drug (AED) analgesia and vitamin D levels were clopidogrel and increased risk of ischaemia, while CYP2C19*17 has been assessed. less well studied. We examined the relationship between the polymorphisms Results: Male FD patients had low T scores at all sites (Spine -1.2 ± 1.06, of the CYP2C19 gene and the clinical outcomes of patients treated with Hip -1.6 ± 0.9, Femoral Neck -2.23 ± 1.01). Female T scores showed more clopidogrel therapy after endovascular treatment for intracranial aneurysms. typical distribution (Spine -0.07 ± 1.47, Hip 0.02 ± 1.14, Femoral Neck -0.49 Methods: This was a prospective, longitudinal, observational study. Patient ± 1.31). A higher incidence of osteopenia and/or osteoporosis occurred in demographics and cerebrovascular status were collected. CYP2C19 males versus females (Spine 46.9% versus 31.8%, Hip 75.5% versus 18.2%, genotyping was undertaken by PCR-RFLP. Three month follow-up data and Femoral Neck 86.4% versus 45.5%). Multiple regression analysis included vascular complications, mortality and Modified Rankin Score (mRS). showed a 50.8% (p<0.001) reduction in femoral neck BMD with AED usage, Clopidogrel responsiveness was tested by VerifyNow P2Y12 assay. after adjustment for age, gender, and renal function. Correlations were made between CYP2C19 polymorphism, clopidogrel Conclusions: Low bone density was highly prevalent in male patients with responsiveness and clinical outcome. increased incidence of non-traumatic fractures. AED usage significantly Results: One hundred and eight participants were included in the study. reduces BMD. Treatment to prevent BMD deterioration will depend on Median age was 56 years (interquartile range, IQR: 48.8 – 65.0), and 32.4% determining the bone turnover status. were male. Participants carrying at least one CYP2C19*17 polymorphism (n=28) had an increased risk of developing an ischaemic event compared to 65 DR BRUCE CAMPBELL those who carried CYP2C19*1/*1 (32.1% vs. 11.4 %), OR 3.7 (95% CI 1.1- Achieving sub-20min tPA door-to-needle times – the 12.6). This remained significant after adjustment for age and clopidogrel importance of patient details on pre-notification and responsiveness testing. point-of-care INR Conclusion: Our results suggest an increased risk of ischaemic events associated with CYP2C19*17 polymorphism in patients receiving clopidogrel CAMPBELL B, Yassi N, Weir L, Ugalde M, Hand P, Yan B, Hocking G, Truesdale after endovascular therapy. M, Davis S, Meretoja A Department of Medicine and Neurology, Melbourne Brain Centre at the Royal 67 MRS SAMANTHA PLUMB Melbourne Hospital, University of Melbourne, Parkville; Ambulance Victoria, Melbourne, Australia; Emergency Department, Royal Melbourne Hospital, Parkville; Department of An exploratory study to identify the needs of stroke Neurology, Helsinki University Central Hospital, Helsinki, Finland. patients in an outpatient clinic setting 2 to 3 months post Background and purpose: Institutions around the world have re-engineered stroke acute stroke care to achieve dramatic reductions in tPA door-to-needle times (DNT). We investigated the effects of specific process elements on DNT. PLUMB S, Marr L, Hand P Methods: The “code stroke” system at Royal Melbourne Hospital was Royal Melbourne Hospital systematically evaluated and redesigned in 2012 to take patients directly from Background: Recent advances in acute stroke care have improved stroke triage to CT on ambulance stretchers and deliver tPA on the CT table. We mortality and morbidity, however the optimum care for these patients post studied the 12 months post implementation data within business hours (when discharge is still to be determined. An ageing population and increased stroke team members were located in the hospital) for effects of variably longevity of stroke survivors demands that continuity and coordination of care utilized key components of the new system – ambulance pre-notification are priority areas for service improvement. Patients currently attend the stroke including patient name and date of birth (allowing transfer direct to CT), and clinic at the Royal Melbourne Hospital (RMH) 3 months post stroke where the point-of-care (POC)-INR. main focus is secondary prevention with pharmacological management. Results: In the 12 months post-implementation, 40/80 (50%) of patients who Physiotherapy care in these clinics is not standard practice in Australia. received tPA were treated in-hours. In-hours DNT reduced from pre- Method: All patients with a diagnosis of stroke were screened by a implementation median 43 min to 23 min (p<0.001). However, only 33% of physiotherapist prospectively for 6 months at RMH. For patients that met the the patients had full pre-notification including name and date of birth. In these inclusion criteria, quantitative and qualitative data were collected to determine patients median DNT was 16 min vs. pre-notification without personal details needs of patients at the time of clinic attendance. Objective measures Page | 25

included the step test (balance), Tardieu (spasticity) and sickness impact Methods: We included consecutive acute ischaemic stroke patients who profile (SIP) (quality of life). received IVT between 2007 and 2011. The following data were included: Results: 25 patients (16 males, mean age 64.8 yrs (SD 15.7)) were included. demographics, vascular risk factors, stroke type, National Institutes of Health The most frequently reported problems were gait (56%), fatigue (44%) and Stroke Scale (NIHSS) at onset and at 24 hours post IVT. Baseline CT brain not driving (36%). Of the 25 patients, 3 were waiting for an initial scans were analysed. Two blinded assessors rated the CT scans using the physiotherapy appointment and 9 had not been referred. All 12 patients had van Sweiten score (vSS) for leukoaraiosis. Median regression was used to an identified need for physiotherapy including issues related to falls and assess the relationship between leukoaraiosis and neurological recovery. balance. Patients who were not seeing a physiotherapist had significantly Results: We included 158 patients. The median (IQR) age was 77 (68-84) poorer quality of life (SIP, mean difference 22.0, 95% CI 7.3-36.7, p=0.005). and 71 (45%) were female. The median (IQR) NIHSS was 13 (7-18.75) at Conclusion: A targeted physiotherapy assessment and management program baseline and 7.5 (2-16) at 24 hours. After taking into account variables within stroke clinic addressing consumer led needs, is a model of care that independently associated with leukoaraiosis, median regression analysis should be implemented. failed to demonstrate the association between the presence of leukoaraiosis and early neurological recovery (NIHSS relative 1) after IVT, for either of the 68 DR BRUCE CAMPBELL three pre-specified dichotomization-based definitions of leukoaraiosis. EXtending the time for Thombolysis in Emergency Conclusions: In our sample, there was no evidence of the association between the degree of leukoaraiosis and early neurological recovery post Neurological Deficits – Intra-Arterial: the EXTEND-IA Trial IVT. CAMPBELL B, Mitchell P, Yan B, Churilov L, Ma H, Parsons M, Donnan G, Davis S for the EXTEND-IA Investigators 70 DR TIM SPELMAN Department of Medicine & Neurology, Royal Melbourne Hospital, University of Updated Comparison of Switching to Natalizumab Versus Melbourne; Department of Radiology, Royal Melbourne Hospital, University of Remaining on Interferon-Beta or Glatiramer Acetate after Melbourne; Florey Institute of Neuroscience and Mental Health, University of Melbourne; Department of Neurology, John Hunter Hospital, University of Newcastle, On-Treatment MS Relapse Using Propensity-Matched Newcastle. Registry Data Background: The proven benefits of tPA within 4.5 hours of stroke onset are Tim Spelman,1 Tomas Kalincik,1 Fabio Pellegrini,2 Annie Zhang,3 Maria limited by modest reperfusion rates in patients with major vessel occlusion. Trojano,4 Heinz Wiendl,5 Ludwig Kappos,6 Robert Hyde,3 Shibeshih Endovascular mechanical clot retrieval may increase reperfusion rates in Belachew,3 Freek Verheul,7 Francois Grand-Maison,8 Guillermo Izquierdo,9 these patients. Helmut Butzkueven,1 on behalf of the MSCOMET (a Objective: EXTEND-IA will test the hypothesis that dual target vessel 1 Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, occlusion and penumbral mismatch can select patients with favourable University of Melbourne; 2 Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Chieti, Italy; 3 Biogen Idec Inc., Weston, MA; 4 Department of response to reperfusion using mechanical clot retrieval after standard IV Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy; 5 tPA<4.5hrs from stroke onset. EXTEND-IA will provide much needed Department of Neurology, University of Münster, Münster, Germany; 6 Departments of randomized evidence about the effectiveness of clot retrieval in a responder Neurology and Biomedicine, University Hospital Basel, Basel, Switzerland; 7 Groene Hart population defined by CT or MR mismatch. Ziekenhuis, Gouda, The Netherlands; 8 Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec, Canada; 9 Hospital Universitario Virgen Macarena, Sevilla, Spain Design: Investigator-initiated, prospective, randomised, open-label, blinded- endpoint (PROBE) phase 2 trial. Objective: To investigate time to first relapse, treatment discontinuation, and Expanded Disability Status Scale (EDSS) progression in propensity-matched Population studied: Patients with ischemic stroke <4.5 hours from onset who samples of MS patients who relapsed on interferon-beta (IFN) or glatiramer are receiving tPA. Eligibility for the trial requires vessel occlusion of the ICA or acetate (GA) and switched to natalizumab (NAT) or stayed on IFN/GA. MCA (M1/M2) and CT or MR “mismatch” using a perfusion threshold of Tmax>6sec and a perfusion:ischemic core lesion volume ratio of >1.2. Background: Outcomes in patients switching to NAT versus remaining on Ischemic core volume, assessed using MR-DWI or CT-relative cerebral blood IFN or GA after an on-treatment relapse are not known. flow, must be <70mL. This is assessed using a fully automated software DESIGN/METHODS: MSCOMET is a longitudinal MSBase registry substudy package (RAPID, Stanford University). of 1000 IFN- and GA-treated patients with on-treatment relapse activity from Intervention: Mechanical clot retrieval (Solitaire FR device, Covidien) after IV 14 countries. TOP is an observational study of 4821 patients commencing tPA vs tPA alone. natalizumab treatment in 16 countries. All patients included in the analysis had on-treatment relapses in the 12 months prior to baseline. Characteristics Outcome measures: The co-primary endpoint is reperfusion at 24hr and at study entry (baseline) used for 1:1 propensity matching included sex, age, favourable clinical response (≥8 point reduction in National Institutes of disease duration, EDSS score, and prebaseline treatment and relapse Health Stroke Scale or reaching 0-1) at 3 days with secondary endpoints activity. Matching success was assessed via a McNemar test or Wilcoxon including recanalization, symptomatic hemorrhage and functional outcome signed-rank test. Time to first relapse and treatment discontinuation over 1 (modified Rankin score at 90 days). year were analyzed using a clustered marginal Cox model, with simultaneous Analysis: Intention to treat. censoring of the matched pairs. Trial Status: Recruitment commenced in August 2012 with 12 centres now Results: A total of 759 MSCOMET patients were successfully matched to 759 open in Australia and New Zealand and a further 3 sites planned to open in TOP patients. The rate of first relapse in patients continuing IFN or GA was 2014. Trial Registry Number: ClinicalTrials.gov NCT01492725 registered 2.35 (95% confidence interval [CI]: 1.93–2.85) times the rate of first relapse in 20/11/11 switch-to-NAT patients. The rate of treatment discontinuation in patients treated with IFN or GA was 2.10 (95% CI: 1.72–2.50) times the rate of 69 DR HEIDI MCALPINE treatment discontinuation in switch-to-NAT patients. Annualized relapse rate and confirmed EDSS progression in IFN- or GA-treated patients compared Leukoaraiosis and early neurological recovery post with NAT-treated patients over >1 year will also be presented. intravenous thrombolysis Conclusions: The efficacy of NAT switch, as assessed by time to first relapse MCALPINE H, L Churilov, P Mitchell, R Dowling, S Teo, B Yan and time to treatment discontinuation, was superior to that of remaining on 1. Royal Melbourne Hospital, Melbourne Australia; 2. Florey Institute of Neuroscience IFN or GA in propensity-matched MS patients. Propensity matching is useful and Mental Health, Melbourne, Australia; 3. Department of Mathematics and Statistics, to inform treatment decisions when randomized trial evidence is lacking. The University of Melbourne, Australia Purpose: Early neurological recovery post intravenous thrombolysis (IVT) is 71 DR TIM SPELMAN associated with favourable outcome post acute ischaemic stroke. Leukoaraiosis, a marker of chronic ischaemia, is a possible negative After a relapse, patients who switch to natalizumab have predictive factor of early recovery. However, its negative attenuating effects better outcomes than those who switch between platform remain inadequately studied, leading to uncertainty in the prediction of therapies outcomes post IVT. We aim to determine the influence of leukoaraiosis on Tim Spelman,1 Maria Trojano,2 Tomas Kalincik,1 Annie Zhang,3 Heinz early neurological recovery. Wiendl,4 Ludwig Kappos,5 Shibeshih Belachew,3 Robert Hyde,3 Freek Page | 26

Verheul,6 Francois Grand-Maison,7 Guillermo Izquierdo,8 Helmut of stroke hemisphere versus contralateral hemisphere was investigated using Butzkueven,2 on behalf of the MSBase Investigators and the Freesurfer software (Boston, USA). 1Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, Results: Mean patient age was 69yr (Standard deviation [SD] 10), Median University of Melbourne, Victoria, Australia 2Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy, 2Department of Medicine baseline National Institute of Stroke Score (NIHSS) was 10 (interquartile and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, range [IQR] 5-14). Mean peri-infarct NAA concentration was 6.2mM (SD 1.3) Victoria, Australia 3Biogen Idec Inc., Weston, MA 4Department of Neurology, University compared with 7.0mM (SD 1.0) in the contralateral hemisphere (p<0.05, of Münster, Münster, Germany 5 Departments of Neurology and Biomedicine, University Paired Samples t-test). There was a significant correlation between age and Hospital Basel, Basel, Switzerland 6Groene Hart Ziekenhuis, Gouda, The Netherlands baseline grey-matter volume (r=-0.84, p<0.001) but not with white-matter 7Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec, Canada 8Hospital Universitario Virgen Macarena, Sevilla, Spain volume. Introduction: There are no randomized, statistically-powered clinical trials that Lower concentrations of peri-infarct NAA were significantly associated with compare treatment outcomes after patients relapse on platform therapies white-matter volume loss between 1 and 3-months (r=0.69, p<0.005) but not (interferon-beta [IFN-beta] or glatiramer acetate [GA]). Propensity-matching with grey-matter volume change. There was a similar trend detected using techniques closely approximate randomization by comparing patients with freesurfer (r=0.51, p=0.06) and this was driven mainly by changes in the similar baseline characteristics. Using propensity-matched groups, treatment stroke hemisphere (r=0.69, p=0.007). continuation and clinical outcomes were compared between patients who Conclusions: Estimation of peri-infarct NAA using MRS may signify varying switched to natalizumab and those who switched between IFN-beta and GA degrees of neuronal damage after stoke which may correlate with the severity after an on-treatment relapse. of axonal degeneration and subsequent white-matter atrophy. Correlation with Methods: From MSBase and TOP observational studies, 578 patients who clinical outcomes is required. switched from IFN-beta to GA and 165 patients that switched from GA to IFN- beta were successfully propensity-matched (based on age, sex, disease 73 DR TIM SPELMAN duration, EDSS score, prior number of treatments and relapse history) to Defining Secondary Progressive Multiple Sclerosis – Is it equivalent numbers who switched to natalizumab (table 1); treatment possible to diagnose early? switches occurred <=12 months after relapse. Time to next relapse on treatment and treatment discontinuation were compared using Cox time-to- Tim Spelman1, Maria Trojano2, Pierre Duquette3, Guillermo Izquierdo4, event analysis with propensity-matched patients jointly censored (mean Alessandra Lugaresi5, Pierre Grammond6, Francois Grand’Maison7, Raymond Hupperts8, Roberto Bergamaschi9, Giorgio Giuliani10, Maria Edite Rio11, follow-up=1.69-2.24 years). Celia Oreja-Guevara12, Vincent Van Pesch1 Results: Switching to natalizumab reduced relapse risk by 63% (figure 1) and 1 Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, discontinuation risk by 62% (figure 2) compared to switching from IFN-beta to University of Melbourne, Victoria, Australia; 2 Department of Basic Medical sciences, GA. Switching to natalizumab reduced relapse risk by 53% (HR=0.47; Neuroscience and Sense Organs, University of Bari, Italy; 3 Hôpital Notre Dame, 95%CI=0.30-0.74; P<0.001) and discontinuation risk by 48% (HR=0.52; Montreal, Canada; 4 Hospital Universitario Virgen Macarena, Sevilla, Spain; 5 MS Center, Department of Neuroscience and Imaging, University ‘G. d’Annunzio’, Chieti, Italy; 6 95%CI=0.36-0.75; P<0.001) compared to switching from GA to IFN-beta. Centre de réadaptation déficience physique Chaudière-Appalache, Levis, Canada; 7 Conclusions: When considering treatment sequence for MS patients who Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec, Canada; 8 Maaslandziekenhuis, relapse on platform therapies, switching to natalizumab rather than switching Sittard, The Netherlands; 9 Neurological Institute IRCCS Mondino, Pavia, Italy; 10 Ospedale di Macerata, Macerata, Italy; 11 Centro Hospitalar de São João, Porto, Portugal; between IFN-beta and GA may improve clinical outcomes and further 12 Hospital Clínico San Carlos, Madrid, Spain; 13 Cliniques Universitaires Saint-Luc, treatment continuation. In the absence of randomized clinical trials, Brussels, Belgium; 14 Groene Hart ziekenhuis, Gouda, The Netherlands; 15 John Hunter propensity-matching techniques can estimate the risks associated with Hospital, Newcastle, Australia; 16 Ospedali Riuniti di Salerno, Salerno, Italy; 17 various treatment decisions in a clinical practice setting. Department of Neurology University of Florence, Florence, Italy; 18 AORN San Giuseppe Moscati Avellino, Italy; 19 Karadeniz Technical University, Trabzon, Turkey. 72 DR NAWAF YASSI Introduction: Conversion to secondary progressive course of multiple Baseline Peri-infarct N-Acetylaspartic Acid Concentration sclerosis is associated with significantly poorer prognosis. However no single definition of Secondary Progressive Multiple Sclerosis (SPMS) is widely Correlates with Regional White Matter Atrophy after employed in clinical practice. Ischaemic Stroke Objective: To use a large, international, observational MS registry to assess YASSI N, Bivard A, Campbell B, Parsons M, Desmond P, Davis S the frequency and overlap of patients satisfying three distinct definitions of Departments of Medicine and Neurology, Melbourne Brain Centre @ The Royal SPMS . Melbourne Hospital, University of Melbourne, Parkville, Australia (NY, AB, BC, SD); Priority Research Centre for Translational Neuroscience and Mental Health, University of Methods: The MSBase study is a global, longitudinal, observational registry Newcastle and Hunter Medical Research Institute, Newcastle, Australia (MP); for Multiple Sclerosis. At time of extraction, the registry contained 21,348 Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, patients from 60 centres in 26 countries adhering to a unified observational Parkville, Australia (PD) plan. Three Definitions (D) of SPMS onset were used: D1) Physician Background: Longitudinal changes in cerebral volume have been described designation, D2) first EDSS of 4 or more and D3) first EDSS of 3 or more after ischaemic stroke and may correlate with long-term outcome, particularly associated with at least one 1-point EDSS progression event within the 2 with the risk of post-stroke cognitive impairment. We tested the hypothesis years prior to this onset date. Baseline EDSS scores recorded within 60 days that baseline peri-infarct concentration of the neuronal metabolite N- of relapse onset were excluded. Specificity of each definition was tested by Acetylaspartic Acid (NAA), measured non-invasively using magnetic assessing the proportion of patients classified by each definition who resonance spectroscopy (MRS), correlates with cerebral volume change experienced EDSS regression below baseline EDSS during follow-up. after stroke. Results: A total of 3551 patients satisfied at least one of the SPMS definitions, Method: Fifteen patients with supratentorial ischaemic stroke underwent 3 1552 for D1, 2543 for D2 and 957 for D3. There was no significant difference Tesla MRI within 1 week of stroke onset and subsequently at 1 and 3 months. in median follow-up in SPMS state for each group (9.4, 8.5 and 8.2 years in High resolution structural imaging involved a T1-weighted axial MPRAGE D1, D2 and D3 respectively). Disease duration at last visit in D3 was 15.9 (1mm slices, TR 1.9s, TE 2.82msec). NAA estimation was performed at the years, representing a difference of 7.1 years compared with D1 (23.0 years.) baseline scan using single voxel spectroscopy (TE30msec, voxel dimensions and 3.2 years compared to D2 (19.1 years). At the end of follow-up in SPMS, 2x2x2cm) with the voxel placed in the peri-infarct region as determined by the overall proportion of patients remaining relapse free after SPMS onset assessment of the diffusion-weighted image by the investigator. Quantitative ranged from 51% for D1 to 21% for D3, whilst the proportion of patients on a spectroscopic analysis was performed using LCmodel software. Longitudinal disease-modifying drug (DMD) ranged from 24% for D1 to 61% for D3. cerebral volume change was determined between 1 and 3 months due to Median EDSS at end follow-up was 6.5 for D1, 6.0 for D2 and 4.0 for D3. anticipated effects of oedema on brain volume at the baseline scan. Total EDSS regression below baseline during follow-up was observed for 78% of grey and white-matter volume, normalised for subject head size, was patients fulfilling D3, 57% for D2 and only 28% for D1. Baseline EDSS was determined using the Cross-sectional Structural Image Evaluation, using available for all of D2 and D3 (by definiton) and 48% of D1 within 6 months of Normalisation, of Atrophy tool (SIENAX) (part of FMRIB's Software Library - date of onset. FSL, Oxford UK). The result was subsequently validated and the contribution

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Conclusion: Identification of the secondary progressive phase by physicians The seizure-prone (FAST) and seizure-resistant (SLOW) rat strains were occurs 4 to7 years later when compared with pure EDSS based definitions. originally derived, from parent populations of Long Evans Hooded (LEH) and Physician designation of SPMS is more specific than EDSS-based definitions Wistar rats, using selective breeding processes based on a differential but will delay diagnosis and potentially limit treatment choices if these vulnerability to amygdala kindling. Remarkably, as kindling sensitivity become available. increased over successive generations in the FAST strain, additional traits naturally evolved that are highly reminiscent of those observed in ASD and 74 MR TIMOTHY GOLDSMITH ADHD including hyperactivity, impulsivity, learning deficits, repetitive Quality of Life Outcomes in Low-Grade Glioma and Benign behaviors and delays in visuomotor and social development. Brain Tumours Strong evidence has indicated that neuroanatomical alterations are associated with epilepsy, ASD and ADHD. Accordingly, in this study we GOLDSMITH T, KEEKA M, TEH J identified neuroanatomical discrepancies in FAST versus SLOW rats using Melbourne Brain Centre; Royal Melbourne Hospital; University of Melbourne magnetic resonance imaging (MRI). FAST rats were found to have larger Background:Health-related Quality of Life (HR-QoL) is a multi-dimensional white matter volumes. Given the large differences in white matter volume we construct used to measure the effects of illness and treatment on overall well- also compared levels of two primary myelin proteins in FAST versus SLOW being. Little is known of the distribution and determinants of QoL in patients rats using western analysis. Myelin-basic protein (MBP) is responsible for with low-grade glioma (LGG), meningioma and vestibular schwannoma (VS). myelin sheath organisation and proteolipid protein (PLP) is a transmembrane Well-powered, longitudinal studies would benefit these patients by enabling protein responsible for the compaction of central nervous system myelin. Both the evaluation of current and future treatment regimens. proteins were found to be significantly reduced in FAST versus SLOW myelin, HR-QoL domains that have been shown to be important include global health suggesting that FAST myelin may be of inferior quality. Given that larger status and symptom burden, as well as functional scales including physical, white matter volumes have been reported in children with epilepsy and ASD, emotional, cognitive and social. We compare HR-QoL in our sample with the enlarged white matter volumes and altered myelin microstructure may be normative population data as well as data collected from a spinal surgery related to the profound developmental delay, abnormal behavioral patterns reference group. and heightened seizure susceptibility in FAST versus SLOW rats. Methods: Participants are recruited from the Neurosurgical and Neuro- 76 MR ZHEN ZENG Oncology clinics of the Royal Melbourne Hospital. They are identified by operation and histology reports, and then invited to participate if they are 18 Differential Slow Inactivation properties of Human Nav1.1 years or older, literate in English and have a histologically confirmed and 1.2 and effect of phenytoin on these channel subtypes diagnosis of LGG, VS or meningioma or have had spinal surgery. Incomplete ZENG Z, Miller S, French C surveys, patients with multiple tumour types and those who had both spinal The University of Melbourne, The Royal Melbourne Hospital surgery and a brain tumour were excluded. Background: Nav1.1 and Nav1.2 are two of the main voltage-gated sodium HR-QoL is assessed using the European Organisation for Research and channel subtypes expressed in central neurons. It is likely that there is a Treatment of Cancer Quality of Life Questionnaire (EORTC- QLQ-C30) and functional separation of these subtypes in that Nav1.1 is thought to be the the EORTC- Brain Cancer Module (BN-20) questionnaire. Additional predominant type in rapid spiking interneurons and Nav1.2 in pyramidal questions are also used to further evaluate tumour-specific symptoms, patient neurons. Sodium channels can enter the classical fast inactivated state, as demographics and treatment regimens. The questionnaires are administered well as one or more “slow” inactivated states. Many anti-epileptic drugs such in Neuro-oncology and Neurosurgery outpatient clinics at the Royal as phenytoin (PHT) are believed to modulate Nav channel inactivation. Melbourne Hospital. Characterisation of the inactivation properties and drug responsiveness of Results: At present, data have been collected from 126 patients (14 VS, 22 these Nav subtypes may clarify important therapeutic issues such “drug LGG, 24 meningioma, 37 spinal) with 29 excluded. Preliminary analysis refractoriness” and paradoxical exacerbation of seizures with anti-epileptic revealed no statistically significant differences in mean global health status medications. scores (VS 74, LGG 72, meningioma 64, spine 58). The functional scale of Methods: HEK293T cells expressing human Nav1.1 and Nav1.2 alpha the EORTC is divided into 5 domains: physical, role, emotional, cognitive and subunits were used. Sodium currents were recorded in the whole cell social functioning. Physical and role function scores were lower in the spinal configuration under voltage clamp. Conventional activation, inactivation, group and comparable amongst those with brain tumours. The 3 tumour equilibrium, dynamic transitions between inactivated states as well as the groups demonstrated minimal difference across the 9 symptom domains effects of PHT on the properties of inactivation were examined. surveyed. Results: n=68. Steady state inactivation parameters were measured with 50, Conclusion: The current data have not yet shown statistically significant 500 and 10000ms conditioning pulses (CP). Interestingly, increasing duration differences in Global Health Scores between groups. Functional Domain of CP resulted in a negative shift in the h∞ curves, which were similar for both scores are distributed similarly across the three tumour types, with lower channel types (n=11, 12 for Nav1.1 and 1.2 respectively). Nav1.1 had about scores for spinal patients in some domains. With further data collection we 40% less channels (n=7) inactivated with transitions from -100 to -70 mV than aim to identify which variables affect the HR-QoL in each tumour subtype, Nav1.2. Nav1.1 enters inactivated state faster than Nav1.2 with transition compare our results with normative population data and identify any emerging from -70 to -100 (n=7). Nav1.1 was less affected by use-dependent statistically significant differences between groups. inactivation elicited by 40 Hz depolarization (n=6). Additionally, Nav1.1 (n=5) is less affected by slow inactivation with 10s pulses compared with Nav1.2 75 MS PRAGATI SHARMA (n=3). PHT caused a 5 to 6mV negative shift of V0.5 in 10000ms CP on both Understanding Neuroanatomical and Neurostructural channel subtypes but more so with Nav1.1 (Nav1.1, n=3; Nav1.2, n=4). PHT Contributions to Relative Seizure Disposition and slowed the time constants of use-dependent inactivation at both 25Hz on both channel subtypes without obvious differences between the two subtypes Associated Behavioural Profiles: Lessons from FAST and (n=4-5). Dose-response study had found that IC50 of Nav1.1 is higher than SLOW Rats 1.2 which translated into a 26µM difference (n=7). SHARMA P, Powell KL, Wlodek M, O'Brien TJ Conclusion: Nav1.1 channels are less affected by slow inactivation processes Melbourne Brain Centre, The Royal Melbourne Hospital, The University of Melbourne. and use dependent inactivation than Nav1.2. These differences may underlie Epilepsy and interrelated neurodevelopmental disorders such as Autism for the high frequency firing behavior seen in the majority of interneurons Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder which have a predominance of Nav1.1 subtype. PHT shifted the 10s CP h∞ (ADHD), often share both primary and comorbid symptoms. Common traits V0.5 by ~5mV in both channel types. Our data suggested PHT affecting associated with these disorders include seizures, developmental delay, slower inactivation processes in Nav1.2. The difference in IC50 of PHT is hyperactivity, impulsivity, aggression and intellectual impairment. The degree intriguing. of clinical overlap is believed to signify a ‘spectrum of vulnerability’ that arises out of an early common dysfunction in central nervous system development. 77 DR PABLO CASILLAS-ESPINOSA

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Developmental expression profile of Transmembrane for the duration of their three month recovery period. After a three month AMPA Receptor Regulatory Proteins and AMPA receptor recovery period, rats underwent behavioural testing to assess cognitive, subunits in Genetic Absence Epilepsy Rats from sensorimotor, and emotional function. Rats then underwent in vivo anatomical magnetic resonance imaging and diffusion weighted imaging to assess Strasbourg. structural damage and axonal injury. Post-mortem western-blot and CASILLAS-ESPINOSA PM, Barmanray R, O’Brien TJ, Powell KL immunofluorescence analyses were conducted on brain tissue to assess Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, protein phosphatase 2A and hyperphosphorylated tau. Sodium selenate Victoria, Australia treatment was found to significantly increase protein phosphatase 2A, Objective: Absence epilepsy is characterized by a temporary loss of decrease hyperphosphorylated tau, and decrease brain damage in rats given awareness and spike-and-wake discharges on the EEG. Studies in the well three mild fluid percussion injuries compared to their vehicle-treated validated Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model counterparts. Sodium selenate treatment also significantly reduced the have identified that absence seizures arise due to abnormal cognitive and sensorimotor deficits in rats given three mild fluid percussion hypersynchronous activity within the thalamocortical circuit. The α-amino-3- injuries compared to those treated with vehicle. These findings indicate that hydroxy-5-methyl-4-isoxazolepropionic receptors (AMPARs) mediate most of protein phosphatase 2A and hyperphosphorylated tau may be important fast excitatory synaptic neurotransmission. Transmembrane AMPAR factors in the pathogenesis of repeated concussion. Furthermore, sodium regulatory proteins (TARPs), stargazin (γ2), γ3, γ 4, γ5, γ7 and γ8, are a selenate treatment is capable of modulating these factors, has family of proteins that regulate AMPARs trafficking, expression and neuroprotective effects in a rat model of repeated concussion, and may biophysical properties. Stargazin has been shown to be increased in the represent a novel approach to treat concussions and chronic traumatic somatosensory cortex (SCx) of GAERS compared to NEC controls. In this encephalopathy. study we investigate the expression of TARPs and AMPARs in different developmental ages, 7-day (pre-epileptic), 7-week (early epileptic) and 22- 79 DR GEORGIA MCCLUSKEY week (epileptic) to determine if expression changes are causative or a 'The relationship of brain amyloid to subjective cognitive consequence of the epilepsy. Methods: GAERS (n=10) and non-epileptic impairment: data from the Women's Healthy Ageing control rats (NECs, n=10), aged 5 and 20-week underwent surgery to implant Project EEG recording electrodes for confirmation of the epileptic phenotype. 2 x 4hr EEG recordings were acquired over a week after which time the animals were MCCLUSKEY G E, Yates P, Lee C and Szoeke C. culled, and the SCx, motor cortex (MCx) and thalamus were dissected, snap- The University of Melbourne; The Royal Melbourne Hospital, Centre for Medical frozen over liquid nitrogen and stored at −80 °C. GAERS (n=10) and NECs Research; The Austin Hospital, Nuclear Medicine and Centre for PET. (n=10) 7 day old pups were obtained for brain dissections but these animals Background: Long considered the pathological hallmark of Alzheimer’s did not have EEG recordings. For molecular analysis, mRNA expression disease (AD), β-amyloid accrual is thought to begin decades before the onset levels were assessed in the MCx, SCx and thalamus using qPCR for the of clinical disease. The utility of subject memory impairment (SMI) in TARPs, (stargazin, γ3, γ 4, γ5, γ7, γ8); AMPARs subunits GluA1 to GluA4. signifying those at risk of developing AD has received attention. SMI appears Results: There was no significant difference in stargazin mRNA expression in related to mood, rather than cognition on cross sectional studies. However, the SCx, MCx and thalamus in 7-day old GAERS that are not having there is some evidence for an association of SMI with amyloid and future spontaneous absence seizures compared to NEC rats. However, in 7-week cognitive performance. To our knowledge, no study has looked at the old GAERS as seizures begin to manifest, stargazin mRNA is significantly relationship between SMI and amyloid load a decade later. In this study we increased in the SCx, MCx and thalamus (p<0.05 for the 3 regions). In adult aimed to assess the clinical value of SMI through assessing the relationship epileptic GAERS the changes are more pronounced. In MCx, stargazin between β-amyloid and SMI measured 10 years earlier and SMI measured at (p<0.05), γ3 (p<0.01), γ5 (p<0.001), and GluA4 (p<0.05) are increased, in the time of PET scanning. SCx stargazin (p<0.05), γ3 (p<0.01), γ5 (p<0.01), γ8 (p<0.001) and GluA4 Methods: We examined the associations between current and prior SMI (p<0.01) are increased. In thalamus γ4 (p<0.05) and γ5 (p<0.0001) are determined in 2002 and 2012 (using specific questions on self-perceived increased. Conclusion: These results indicate that changes in TARP cognition and the MAC-Q in 2012), in 93 cognitively normal subjects. expression occur as seizures begin to manifest given that GAERS do not Participants also had cerebral β-amyloid load measured by 18F- begin to express seizures until around 7 weeks of age, these findings Fluorobetaben PET in 2012. establish a temporal association between increased TARPs expression and seizures Results: No significant associations were found between the SMI groups identified using 3 questions on memory asked in 2002 and SUVR measured 78 MR XIN LIN TAN 10 years later. Correlations were found between SMI and depression and anxiety. Subjects who confirmed they had felt confused in the last week had Sodium selenate reduces hyperphosphorylated tau and higher β-amyloid load on scanning in the same year (sig.<0.05). Further improves outcomes in an animal model of chronic analysis revealed the association was significant with amyloid in the traumatic encephalopathy ventrolateral prefrontal region (sig.<0.05) and lateral temporal lobe Tan X-L, Wright DK, Jones NC, Hovens C, O’Brien TJ, Shultz SR (sig.<0.01). Department of Medicine, The Royal Melbourne Hospital, The Melbourne Brain Centre, Conclusion: Subjective memory impairment was found to have no relationship The University of Melbourne, Melbourne VIC; The Florey Institutes of Neuroscience and with amyloid load determined a decade later, suggesting limited clinical use in Mental Health, Melbourne, VIC very early detection of disease. The cross-sectional association between Brain concussions account for the majority of traumatic brain injuries, and those who felt confused and higher β-amyloid in the prefrontal and temporal repetitive concussions may result in cumulative damage and chronic regions, suggests that this cognitive complaint may be related to early AD traumatic encephalopathy. Hyperphosphorylated tau has been implicated in neuropathology. The lack of significance found for SMI identified by the MAC- the pathogenesis of concussion and chronic traumatic encephalopathy. Q and other questions used in this study suggest that some forms of cognitive Protein phosphatase 2A is the major tau phosphatase in the brain, and is self-awareness may be more clinically useful than others. Further research is decreased in tauopathies and after brain insult. Thus, protein phosphatase 2A needed to fully explore the significance of early SMI and brain amyloid on may be targeted pharmaceutically to reduce hyperphosphorylated tau. cognitive and functional outcomes. Sodium selenate is a compound shown to increase the activity and expression of protein phosphatase 2A, and dephosphorylate tau. The current 80 PROF FRANK VAJDA study investigated whether treatment with sodium selenate would increase Antiepileptic drug therapy and the unborn child protein phosphatase 2A, reduce hyperphosphorylated tau, and improve outcome in a rat model of repeated concussion and chronic traumatic VAJDA F, Graham J, Davis S, O'Brien T encephalopathy. 41 young adult male Long-Evans rats were given either University of Melbourne , The Royal Melbourne Hospital three mild lateral fluid percussion injuries or three sham-injuries. Each of the Background :The Australian Epilepsy and Pregnancy Register, affiliated with repeated injuries was separated by five days. After the first injury rats were the European International Regster has been collecting data on antiepileptic assigned to receive either continuous sodium selenate or saline-vehicle drug (AED) teratogenicity and seizure control in pregnancy. treatment (1 mg/kg/day), administered via subcutaneous osmotic mini-pump,

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Method: Currently 2300 women providing data by 4 structured interviews, in blinded to clinical information using the Age-Related White Matter Changes each trimester and 12 months after delivery (ARWMC) scale. Five regions (frontal, parietal-occipital, temporal, basal Results: AEDs have been shown to teratogenic, representing a major burden ganglia and infratentorial) of the two hemispheres were rated separately (0: of epilepsy. The effects have been assessed prospectively, with informed no lesions, 1: focal lesion, 2: beginning confluence of lesions, 3: diffuse consent and ethical approval. The effects on the foetus are both physical changes). Wilcoxon rank-sum test was applied. In phase 2, patients all with malformations and cognitive challenge.. Monotherapy data indicate that 3T MRI (thickness was 1 mm) were collected. valproate is the most teratogenic AED, and teratogenicity is dose- related. It Results: Of the 84 subjects in phase 1, 56% (47) were categorized into the has been shown that polytherapy per se is no more teratogenic than drug-resistant epilepsy group, and 44% (37) were in the new-onset epilepsy monotherapy, and that it is the content of polytherapy is relevant. Second group. The median age was similar (38 vs. 35, P=0.165). Females were more generation AEDs, comprising lamotrigine, levetiracetam, topiramate, in the new-onset group (57.5% versus 29.7%, P=0.011). Interclass correlation gabapentin and zonisomde are no more teratogenic that traditional ones. coefficient between the two raters was 0.95(95% confidence interval: 0.92– With the exception of valproate , the major AEDS are comparable in their 0.96, P<0.001). The median ARWMC score of drug-resistant group was 1 effects in causing physical malformations. Cognitive challenge may manifest (25th-75th percentiles, 0-3) which was significantly higher than the new-onset as language difficulties, impairment of executive function, and autism may be group (0(median), 0-1 (25th-75th percentiles), P=0.032). However, more involved Specific malformations are identified with specific agents and the drug-resistant patients underwent 3T MRI than new-onset ones (74.5% severity of specific malformations is also dose- related . Folate administration versus 37.8%, P=0.001). is advised for women contemplating pregnancy, but its effect on the foetus In phase 2, 273 cases have been included with 3T MRI. 43.8% were in the have not been decisively proven. drug-resistant group. The median age and female proportion were similar Conclusion; AED therapy needs to strike a fine balance between seizure between the groups (35 versus 35, P=0.971; 51% versus 50%, P=0.925; control and protection of the foetus from foetal malformations. respectively). Clinical data collection and MRI assessments are in process. 81 MR ADRIAN TALIA Conclusion: People with drug-resistant epilepsy may have increased burden of WMH than patients with new-onset epilepsy in our pilot study. Further Safety of instrumentation and fusion at the time of research is required to confirm our findings due to an unequal distribution of surgical debridement for spinal infection: A retrospective the quality of MRI images, which could result in an underestimation of white cohort analysis. matter changes in new-onset patients. Vascular risk factors also need be adjusted. TALIA AJ, Wong ML, Lau HC, Kavar B, Kaye AH Measurements of the burden of WMH will be helpful for identifying patients Dept of Neurosurgery, Royal Melbourne Hospital; University of Melbourne with epilepsy at a higher risk of stroke. Objectives: The present study aims to assess the results of single-stage instrumentation and fusion at the time of surgical debridement of spinal 83 PROF CHRISTINE TJEN infections, vertebral osteomyelitis or epidural abscess. Survey on Intraoperative Intravenous Fluid Preferences in Methods: 9 cases of spinal infection were treated with instrumentation and Neurosurgical Patients fusion after radical debridement in a single-stage operation. Predisposing factors and comorbidities, pain, ASIA scores, primary pathologies, TJEN C*, Leslie K*#, Story D# microbiology and perioperative markers were recorded. *Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Australia; #Anaesthesia Perioperative and Pain Medicine Unit, Melbourne Results: 7 cases of pyogenic and 2 cases of tuberculous spinal infection were Medical School, University of Melbourne, Melbourne, Australia encountered, the most common pathogen being Staphylococcus aureus. 5 Introduction: The choice of fluid therapy in neurosurgical patients is patients were predisposed to infection because of their diabetes mellitus. controversial, including use of colloids generally and albumin in traumatic Antibiotic duration lasted up to 12 months. 6 patients had thoracic infection, 2 brain injury. There is also increasing interest in more physiological fluids to lumbar and 1 thoracic. The mean operative time was 386 minutes. No post- avoid the chloride burden of 0.9% saline. The aim of this survey was to operative complications were encountered. There was a significant reduction determine routine and resuscitation fluid preferences among in pain scores compared to pre-operatively. All patients with neurological neuroanaesthetists for elective and emergency neurosurgical patients. symptoms improved post-operatively. Despite introduction of hardware, no patients had a recurrence of their infection in the 12 months follow up period. Methods: With approval, an anonymous on-line survey was sent to members of the ANZCA/ASA/NZSA Neuroanaesthesia Special Interest Group. Data Discussion: Single stage debridement and instrumentation appeared to be a were collected on demographics and fluid choices for intracranial safe and effective method of managing spinal infections. The combination of neurosurgery patients in elective and emergency settings. Statistical debridement and fusion has the dual benefit of removing a focus of infection differences were evaluated using chi-squared test. and stabilising the spine. The current series confirms that putting hardware into an infected space is safe in a majority of cases. Stabilisation and Results: The response rate was 29% (136/468). Seventy-seven percent of correction of spinal deformity reduces pain, aids neurologic recovery and respondents worked in Australia and 57% worked exclusively in the public improves quality of life. However its small patient population and retrospective sector. About half used saline as their initial fluid in elective (50%) and nature limit the present study. emergency (56%) cases. The greatest influence on fluid choice was osmolality in elective (48%) and emergency (55%) cases, although a third of 82 DR YITING MAO respondents considered electrolyte composition the most important factor in both settings. Over half of respondents used 1-2 L throughout a case in either White Matter Lesions in People with Epilepsy setting, whilst 57% avoided colloids in elective cases and 47% in MAO Y, Goh E, McIntosh A, Churilov L, Yan B, Kwan P. emergencies. Most saline users were Australian with a significant regional 1 The Melbourne Brain Centre at the Royal Melbourne Hospital; 2 Department of difference in elective cases: New Zealand 0% vs. Australia 58%, difference Medicine, the University of Melbourne; 3 Department of Neurology, The Royal 58%, 95%: CI 40 to 68%, P<0.0001). In both settings, saline users were most Melbourne Hospital influenced by osmolality (66%) and non-saline users by electrolyte Background: People with epilepsy have increased risk of stroke, the reason of composition (57%) (p<0.001). which is unclear. White matter hyperintensities (WMH) on T2-weighted Fluid- Conclusions: The response rate was comparable to other ANZCA web Attenuated Inversion Recovery (FLAIR) sequence on brain magnetic surveys. Most neuroanaesthetists surveyed favoured using saline in resonance imaging (MRI) are a marker for burden of cerebrovascular neurosurgical patients, due to its osmolality. However, there appear to be disease. The aim of this project is to explore the relationships between WMH, significant regional differences, with New Zealanders preferentially avoiding epilepsy and stroke by comparing the burden of WMHs between people with saline. With the relatively small volumes predicted to be used, the new-onset epilepsy and chronic drug-resistant epilepsy. significance of undesirable effects of saline is unclear. Despite controversy on Methods: Eligible subjects were identified from epilepsy database at Royal colloids, over half of respondents use them in emergency cases. Melbourne Hospital from 01/06/2009 to 01/06/2013. In phase 1, to assess the inter-rate reliability, WMHs of 84 people with 84 DR SANDRA PETTY epilepsy were measured by two experienced neurologists (P.K. and B.Y.) Page | 30

Carbamazepine Inhibition Of Native Sodium Currents In Respiratory Registrar. Prior to the establishment of the RCU, patients with Murine Osteoblasts moderate to severe acute respiratory problems could only be cared for in the emergency department (ED), or in the Intensive Care Unit (ICU).To evaluate PETTY, S.J., Milligan, C.J., Todaro, M., O’Brien, T.J., Wark, J.D., Mackie, E.J., the effectiveness of BIPAP for Acute Exacerbations (AE) of Chronic Petrou, S. obstructive Pulmonary disease(COPD) patients in RCU a prospective (1) Melbourne Brain Centre at The Royal Melbourne Hospital, The University of observational 12 months study was undertaken. Melbourne, Parkville; (2) Ion Channels and Disease Group, Epilepsy Division, The Florey Institute of Neuroscience and Mental Health, Parkville; (3) Department of Medicine Aim: To examine the efficacy of NIV for treatment of AECOPD patients RMH, The University of Melbourne; (4) The Royal Melbourne Hospital Bone and Mineral complicated by acute respiratory acidosis. Medicine; (5) Faculty of Veterinary Science, The University of Melbourne. Inclusion criteria: Adult patients admitted with AECOPD by standard criteria Background: An increase in fracture risk is well established in patients with (GOLD, 2007) complicated by acute respiratory acidosis (pH < 7.35, PaCO2> epilepsy. However, the mechanism for this association is less well defined. 45 mmHg) managed with BPAP. Our aim was to isolate sodium channel currents in mouse primary calvarial osteoblasts using whole-cell patch-clamping and also to examine whether the Exclusion criteria: Indications for mechanical ventilation (PH<7.2 and low antiepileptic medication carbamazepine (CBZ) blocks these currents. GCS) and weaning post-mechanical ventilation. Methods: Primary osteoblasts isolated from the calvariae of C57BL6 mice at Methods: postnatal day 2 (P2) were used to examine the impact of CBZ on sodium 1. Prospective observational 12 months study. (March 2011-March 2012) channel currents using automated whole-cell planar electrode voltage clamp 2. 28 patients met inclusion criteria and an in depth audit was conducted recordings (Patchliner, Nanion, Germany). Currents were elicited from a focusing on in-patient management and clinical outcomes. holding potential of -80 mV using a voltage protocol stepping from -100 mV to 3. Severity of BAP 65 score as calculated by class II to class V +60 mV in 10 mV increments, for 20 ms. CBZ (50 μM) was applied to the Results: A Total of 28 patients with 30 encounters (two patients readmitted) cells in the continued presence of external tetraethylammonium (10 mM) and received NIV. Patient characteristics were age (70±10yrs), M: F (20:8), FEV1 internal Cs+. Following washout of CBZ, 10 μM tetrodotoxin (TTX) a known (0.84±0.35L), initial pH (7.29±0.08) and PaCO2 (72±22mmHg). BAP 65 voltage-gated sodium channel blocker was applied. score admission diagnosis Class II to class V and risk of mortality was 1.4- 26.2%. There were 20 patients with both COPD and CHF and 8 patients were Results: TTX sensitive (mean block of 89.96 ± 2.14 %; n = 6; p<0.0001) purely COPD. The Inspiratory Positive Airway Pressure (IPAP) range 10- voltage-activated inward sodium currents were readily observed in P2 27cmH2O, Expiratory Positive Airway Pressure (EPAP) range 5-14 cmH2O. osteoblasts and bath application of CBZ (50 μM) significantly inhibited these currents (mean block of 31.6 ± 5.9 %; n = 7; p<0.001). With NIV there was a significant improvement in ventilation parameters with baseline pH increasing (0.12±0.07) and PaCO2 falling (12±18mmHg) Conclusion: Mouse osteoblasts express native voltage-activated sodium (p<0.001) resulting in resolution of acute respiratory acidosis in all patients. channels, which are sensitive to CBZ and TTX. This novel demonstration of There was one death due to end stage COPD and there were no significant an inhibitory effect of CBZ on primary osteoblast sodium currents utilising complications. Average length of stay was in RCU 2.8 days. Patchliner, paves the way for semi-automated screening of anti-epileptic drugs, enabling further study to determine whether the effects on ion channel Conclusion; Findings indicate that the use of BIPAP in Acute Type 2 activity observed here translate to effects on signal transduction in respiratory failure patients results in reduced acute respiratory failure and osteoblasts, inhibition of osteoblast activity and clinically-relevant changes in improves the physiological parameters of pH and PaCo2 without significant bone quality. morbidity. 85 PROF NICK SANTAMARIA 87 MRS LISA BEACH Pressure injury prevention research: evidence and clinical Low Physical Activity Levels And Poorer Muscle Strength experience Are Associated With Reduced Physical Function At SANTAMARIA N, Gerdtz M, DeVincentis S, Ng AW, Sage S, Liu W, Vassiliou T, Intensive Care Unit Discharge: An Observational Study McCann J, Tudor H, Morrow F, Smith K, Knott J, Liew D. BEACH L, Fetterplace K, Edbrooke L, Parry S, Rechnitzer T, Berney S, Denehy L. University of Melbourne The Royal Melbourne Hospital; The University of Melbourne; Austin Health. Pressure injury prevention is a complex and challenging task for clinicians. Rationale: Critical care admissions are often associated with the development This paper presents the research evidence fron one RCT and one of clinically significant weakness that impacts health related quality of life. prospective cohort study into the use of silicone dressings to prevent hospital Early mobility may attenuate this weakness, improve function and reduce acquired pressure injuries (PI) in 600 ICU patients at Melbourne Health. hospital length of stay (LOS). However no published studies have objectively Critally ill patients were recruited from the Emergency Department and 372 documented baseline activity levels of patients while in the intensive care unit were treated with prophylactic dressings applied to their sacrum and/or heels. (ICU). Aims: 1) To describe physical activity (PA) levels during an ICU The rates of PI were significantly reduced compared to control patients (p admission and barriers to PA. 2) To describe the relationship between PA, <0.01) and const benefit analysis revealed that patients treated with the muscle strength and physical function at ICU discharge. 3) To describe the dressings were 3.6 times less costly to treat than controls. These studies relationship between muscle strength, physical function and ventilator free combined with emerging international evidence suggest that the use of days and between PA levels and ICU/hospital LOS. Methods: Prospective prophylatic silicone dressings are a valuable adjuct to existing PI prevention observational study; 48 participants (54% male, mean age 59.5(15.4), mean strategies. APACHE II 23.9(7.3)) who were mechanically ventilated for at least 48 hours and anticipated to require a further 5 days of ICU care were recruited from 86 MRS VARA PERIKALA RMH ICU. Outcome measures: Accelerometry for the first 5 days (metabolic Acute Non-Invasive Ventilation for COPD patients: equivalents [METs], duration of physical activity [defined as > 1 MET] and steps).Daily measures; highest level of PA, barriers to PA and sedation (Riker 12month Prospective observational Study in ward based sedation and agitation scale [SAS]). Muscle strength (medical research Respiratory High dependency Care Unit (RCU) Royal council scale [MRC]), physical function (physical function in intensive care Melbourne Hospital. test -scored [PFIT-s]) were completed at baseline, day 5, weekly thereafter Perikala V1,2 ; Goldin J1 , Assoc Professor Irving L1 and ICU discharge. Results: Accelerometer data are presented as median 1 Departments: Respiratory Medicine; 2 Medicine and community care (IQR); duration of PA (minutes) 9.3 (0.4-151.2), METs 0.9 (0.8-1.0) and steps 3.5 (1.4-5.9) per day. The main barriers n(%) to PA at baseline and day 5 Introduction: The Respiratory Care Unit (RCU) is a four bed specialised unit respectively were sedation 43(93.5); 18(51.5), cardiovascular instability within 5SW. The RCU manages patients with acute respiratory 2(4.3); 4(11.4). There was a moderate correlation between sedation score diagnoses.This involves close respiratory observation and monitoring and PA level at day 5 (rho=0.601, p<0.005). There was a good correlation including arterial blood gas sampling, non-invasive ventilation (NIV– between PA level and physical function (rho=0.707, p<0.005) and an CPAP,BiPAP)and high flow oxygen humidification.The RCU comprises of 1: 2 excellent correlation between muscle strength and physical function nursing ratio, twice daily consultant ward rounds by a Respiratory Physician, (rho=0.870 p< 0.01) at ICU discharge. Ventilator free days was moderately Respiratory Clinical Nurse consultant (background in ICU nursing) and correlated with muscle strength (rho=0.479, p =0.003) and physical function

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(rho=0.503, p=0.002). There was no relationship between PA levels and [MRC]), physical function (physical function in intensive care test -scored ICU/hospital LOS. Conclusion: Patients in RMH ICU have very low levels of [PFIT-s]) at baseline, day 5 and weekly thereafter. PA in the first 5 days; this is supported by the low number of steps taken and Results: Demographic data; Mean (SD) Age 57.6 (16.1), APACHE II 23.0 the high percentage of the day spent sedentary (< 1 MET), comparable to (7.5) and Median (interquartile range (IQR)) BMI 28.0 (25.4-33.1) ICU (LOS( resting metabolic rate. Higher strength scores and PA levels are correlated 7 (4-12). The median (IQR) cumulative calorie debt (kcal) when comparing with better physical function at ICU discharge. Higher levels of PA are not received calories with prescribed calories to ICU day 12 was 2576.50 kcal associated with reduced LOS. (1315.00-3738.00), patients met 77.6% (51.1-88.1) of their daily energy target 88 MS MARTINE HATZI to ICU day 12. There was a significant change in nutritional status (SGA); at baseline 27% were malnourished compared to 34% at discharge (p<0.001). The role of the Intensive Care Unit in severe anorexia There was a moderate correlation between cumulative calorie debt up to day nervosa: A case study report 12 and diagnosis of ICU acquired weakness (ICUAW) at day 5 (rbp 0.391 (p=0.029) and at ICU discharge (rpb 0.448, p 0.001) and a fair correlation with HATZI M, Kaul N ICU LOS (rbp 0.259, p 0.046). Department of Clinical Nutrition, Royal Melbourne Hospital, Melbourne, Parkville, Australia Conclusion: A modest calorie debt was observed in this study, however there Metabolic complications of refeeding syndrome are a significant barrier in the was an increase in malnutrition rates over the ICU stay. Cumulative calorie progression of nutrition restoration in patients with severe anorexia nervosa debt to day 12 was moderately associated with ICUAW, but showed only a (AN). Clinical refeeding guidelines recommend the slow reintroduction of fair association with increased ICU LOS. nutrition, 5-10 kcal per kg, reaching target rate over 4-7 days. However in 90 MRS LISA BEACH patients with a critically low body weight, underfeeding may further exacerbate complications of malnutrition and AN. Physiotherapy Model of Service Delivery of Australian This case study aims to demonstrate the utilization of the Intensive Care Unit Tertiary Trauma Centres with Level III Intensive Care Units (ICU) to facilitate rapid reintroduction of nutrition in a patient with severe AN. BEACH L, Jones J, Jackwitz S, Granger C, Sorohan M A 23 year old female was transferred to the Royal Melbourne Hospital ICU Melbourne Health; Austin Health; Eastern Health; University of Melbourne. from a rural hospital following a hypoglycemic collapse in the community on a Introduction: The survival rates of Intensive Care Unit (ICU) patients have background of a 13 year history of AN. Her weight on admission was 24.1kg, increased in recent decades. In the literature, reductions of quality of life and giving her a body mass index (BMI) of 8.6kg/m2, however the patient was function have been reported in ICU patients up to five years post discharge. fluid overloaded, with a likely true weight of 22kg. She presented with Physiotherapists have a role in the rehabilitation and respiratory management biochemical abnormalities including hyponatraemia, hypokalaemia and of ICU patients. There is limited evidence on ICU physiotherapy models of hypoalbuminaemia. Serum phosphate and magnesium were within normal service delivery however a ratio of one physiotherapist to five beds has been ranges. No respiratory or cardiovascular support was required. Intravenous recommended. electrolyte replacement, 300mg intravenous thiamine and an oral multivitamin Objectives: To investigate ICU physiotherapy staffing ratios and service were commenced. The patient was kept nil orally with the exception of 500ml structures of Australian Tertiary Trauma Centres. of water. A nasogastric tube was inserted and feeds commenced, with concurrent intravenous 10% dextrose providing a combined total caloric Methods: There were 19 Tertiary Trauma Centres in Australia with Level III intake of 22kcal/kg on day 1. The patient was closely monitored and ICUs in 2013. The Physiotherapy Manager or Senior ICU Physiotherapist electrolyte imbalances and metabolic abnormalities were corrected. On day 7 were invited via telephone to participate and subsequently emailed a 30 she was discharged from the ICU to the ward receiving 30kcal/kg, maintaining question electronic survey that was designed and piloted prior to distribution. euglycamia and no longer requiring intravenous electrolyte replacement. The survey questions pertained to the type and size of the hospital, Underfeeding and weight loss may further precipitate metabolic changes physiotherapy ICU staffing and equivalent full time (EFT), the role and EFT of other ICU allied health professionals, and types of treatment administered by associated with refeeding syndrome in patients with critically low body weight. ICU physiotherapists. Senior RMH ICU physiotherapists completed the This case study demonstrates the safe rapid nutrition repletion in a patient survey to provide a comparator for the data. Descriptive statistics were used with severe AN in the ICU. Although elective admissions to the ICU are to report data. uncommon, in cases of severe AN and high refeeding risk, the ICU may assist in rapid nutrition restoration. Further research on this topic is Results: Eleven complete responses were received which equated to a recommended. response rate of 58 percent. The RMH ICU physiotherapy staffing was 0.95 EFT per 10 funded ICU beds. The highest response had an ICU 89 MS KATE FETTERPLACE physiotherapy EFT of 3.30 per 10 funded beds and the mean (SD) was 1.18 Associations between cumulative calorie debt in intensive (0.94). One hospital reported providing the recommended physiotherapy staffing ratio of one EFT per five beds, the remaining hospitals had staffing care: The diagnosis of intensive care unit acquired ratios of less than one physiotherapist to five beds. Eighty-two percent of weakness and length of stay hospitals provided a weekday physiotherapy evening service which was not FETTERPLACE K (1) ,Beach L(1), Edbrooke L(2), Parry S(2), Curtis R(1), available at the RMH. All hospitals reported that senior physiotherapists were Rechnitzer T(1), Berney S(3), Denehy L(2) available. Research related positions were reported by 27 percent of 1. Royal Melbourne Hospital; 2. The University of Melbourne; 3. Austin Health. hospitals. The ICU physiotherapy service structure and staffing ratios were highly varied both within and across states and territories. Rationale: Patients who survive an Intensive Care (ICU) stay often develop clinically significant weakness and malnutrition which impacts outcomes and Conclusions: The majority of Australian Tertiary Trauma Centres with Level III quality of life. In ICU patients often do not receive adequate nutrition and ICUs have physiotherapy staffing ratios that are below recommendations therefore calorie debt accumulates. Cumulative calorie debt is possibly a reported in the literature. Further research is required to explore ICU modifiable risk factor for the development of this weakness. physiotherapy service structures and models of service delivery to provide best patient care. Aims: To describe the relationship between cumulative calorie debt and nutritional markers, muscle strength and physical function at ICU discharge. 91 MR ADAM DE GRUCHY To describe the relationship between cumulative calorie debt and ventilator free days and ICU/hospital length of stay (LOS). Advanced Practice Physiotherapy in an Emergency Methods: Prospective observational study; 60 participants who were Department: Observational study of practice. mechanically ventilated for a minimum of 48 hours and anticipated to remain DE GRUCHY A, Granger C in ICU for 5 days, were recruited from a tertiary Australian ICU. Data University of Melbourne collection included: prescribed energy requirements, weight, Mid Upper Arm Background: Increasing pressure on Emergency Departments (ED) Circumference (MUAC), nutritional status using the Subjective Global throughout the world has meant the introduction of innovative ways of Assessment (SGA), muscle strength (Medical Research Council scale working, such as the advanced practice physiotherapist (APP). Within this role the physiotherapist acts as a primary contact practitioner. There has

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been little research into this role beyond identifying patient satisfaction with 93 MR PETER ALARCON MANCHEGO management and time efficiency. In order to appropriately examine the role and develop it further, the APP patient caseload, resource utilisation and Management of mental health patients in Victorian management outcomes requires exploration. emergency departments, a 10 year follow up study Method: Data collection occurred prospectively for 6-months within the Royal ALARCON MANCHEGO P, Knott J, Bartley B, Graudins A, Mitra B. Melbourne ED. Any patient that consented to physiotherapy assessment was University of Melbourne School of Medicine, Royal Melbourne Hospital Emergency included in the study. Patient demographics, assessment times, triage Department, Geelong Emergency Department, Dandenong Emergency Department, categorisation, diagnostic category, hospital resource utilization and Alfred Emergency Department. discharge destinations were recorded and analysed. The most common Background: In the past 30 years there have been ongoing changes to the patient presentations to the APP were compared with the performance of the range of mental health (MH) services Victoria offers as well as to how and ED as a whole. where these services are available. Ten years ago, a comprehensive study Results: 1017 patients (45% female, median IQR age 34 [25-52] years) were evaluated the patient demographics, presentations, clinical managements managed by the APP; the majority (77%) had less urgent triage and dispositions of mental health patients presenting to multiple Victorian categorisation. Median [IQR] patient waiting time to be seen was 19 [7.6 – emergency departments (ED). 42.6] minutes, and median [IQR] treatment time was 63 [42.0 – 97.1] minutes. Objective: To establish a current clinical picture of mental health 46% of the patients seen were managed independently, without any resource presentations to Victorian emergency departments and compare this to that from medical colleagues. 18% of discussions with Emergency Physicians was determined 10 years prior. due to protocol requirements for onward referral or ordering imaging. 13% of Method: A retrospective observational study across multiple Victorian discussions with Emergency Physicians was due to prescription of analgesia. emergency departments. Patients were included in study if presented to ED Most frequent outcome was a referral back to the local medical officer (41%) between May 14th- October 13th 2013 and presentation considered MH in or musculoskeletal outpatient clinics (30%), such as Fracture or Hand and nature as per an ICD-10 discharge diagnosis of a mental health disorder, Wound Clinics. referral to emergency crisis assessment team or with a presenting complaint The most common presentations to the APP were Hand Fractures, Ankle of self-harm or other psychiatric complaint. Variables of interest were Sprains and Lumbar Pain. When comparing the APP with the whole ED extracted from electronic medical records. performance, patient demographics were similar, but the APP was Results: There were approximately 6,000 MH patients enrolled across all ED significantly (p<0.5) more time efficient across all groups. sites (2,900 in 2004), 12.3% were brought in by police (17% in 2004) and Conclusions: This study has identified the APP role as a valuable asset to an 46% brought in by ambulance services (39.9% in 2004.) The mean ED length ED, managing a great deal of their caseload independently and time of stay decreased from 8:07 hours in 2004 to 5:14 hours in 2013, with a efficiently, maintaining an average patient time in ED well under the 4 hour significant reduction in stays over 24 hours from 5.9% to <0.5% of national targets. presentations in 2013. Of those patients presenting with some form of With further development of local protocols for further imaging modalities, intoxication, methamphetamine use increased from 6.6% to 13.3% in 2004 pathology requests, referral to inpatient teams and for administration of and 2013 respectively. analgesia there is a room to expand the scope of practice and hence further Conclusion: There has been an increase in the total volume of MH utilise the expertise of the APP in ED. presentations to emergency departments, however, it appears changes in ED practice, like the wider implementation of short stay units, have allowed for 92 A/PROF MARIE GERDTZ EDs to meet demand and even shorten mean ED length of stay. The ED An evaluation of the outcomes of e-care plans for frequent length of stays were highly variable among different sites and this might be attenders to the emergency department attributed to differences in access to resources or hospital structuring/practice. Finally, while the number of MH patients presenting with 1. GERDTZ M, 2. Virtue E, 3. Baldock S, 2. Dean A alcohol substance abuse was similar to that 10 years prior, the use of 1. The University of Melbourne and Melbourne Health, Level 1 Royal Melbourne Hospital methamphetamines has increased significantly and is of public concern. Emergency Department, Grattan Street Parkville Victoria Australia 3050; 2. Melbourne Health, Level 1 Royal Melbourne Hospital Emergency Department, Grattan Street Parkville Victoria Australia 3050; 3. The University of Melbourne Department of Nursing 94 A/PROF JONATHAN KNOTT Level 6 Alan Gilbert Building The University of Melbourne Understanding practice: the factors that influence Background: Frequent emergency department attenders are a diverse mix of management of mild traumatic brain injury in the people including those with chronic illness and psychosocial issues. Frequent emergency department - a qualitative study using the attenders exacerbate problems of emergency department crowding by increasing demand for services in a climate of limited resources. In our Theoretical Domains Framework emergency department the top 5% of frequent attenders contribute to 20% of 1. Tavender E J, 1. Bosch M, 2. Gruen R L, 3. Green S E, 4. KNOTT J, 5. Francis J the total length of stay. J, 6. Michie S, 3. O’Connor D Aims: To evaluate the outcomes of e-care plans on emergency department 1. National Trauma Research Institute, The Alfred, Monash University, Melbourne, use among frequent emergency department attenders. Australia; 2. Department of Trauma, The Alfred Hospital/Department of Surgery, Monash University/National Trauma Research Institute, Melbourne, Australia; 3. School of Public Methods: We used a mixed methods design comprising document analysis Health and Preventative Medicine, Monash University, Melbourne, Australia; 4. and before and after study of emergency department use for a convenience Melbourne Medical School and Department of Emergency Medicine, Royal Melbourne sample of patients with e-care plans (frequent attenders). Emergency Hospital, Melbourne, Australia; 5. School of Health Sciences, City University, London, UK; 6. Department of Clinical, Educational and Health Psychology, University College London, department presentations and length of stay were measured for each patient London, UK. for 6 months before and 6 months after implementation. Background: Mild traumatic brain injury is a frequent cause of presentation to Results: The visit characteristics and e-care plans of 35 patients were emergency departments. Despite the availability of clinical practice guidelines analyzed. The majority of patients were young male (62.5%), had a primary in this area, there is variation in practice. One of the aims of the Neurotrauma mental health problem (94.2%), were socially isolated (28.5%) of no fixed Evidence Translation program is to develop and evaluate a targeted, theory- address (42.8%) or had drug and alcohol related problems (40%). The care and evidence-informed intervention to improve the management of mild plans addressed five issues: managing behavioral risk, informing the traumatic brain injury in Australian emergency departments. This study is the management of medical care and response at presentation, providing a first step in the intervention development process and uses the Theoretical consist approach to care and guiding the use of the emergency department. Domains Framework to explore the factors perceived to influence the uptake No significant changes were observed in length of stay; however there was of four key evidence-based recommended practices for managing mild an overall reduction in total presentations. traumatic brain injury. Conclusion: The development and implementation of e-care plans for patients who frequently attend and are discharged from the emergency department Methods: Semi-structured interviews were conducted with emergency staff in provides one mechanism for standardizing care and limiting emergency the Australian state of Victoria. The interview guide was developed using the department use. Theoretical Domains Framework to explore current practice and to identify the factors perceived to influence practice. Two researchers coded the interview transcripts using thematic content analysis. Page | 33

Results: A total of 42 participants (9 Directors, 20 doctors and 13 nurses) Aim: The aim of the project was to minimise post operative RBC transfusion were interviewed over a seven-month period. The results suggested that (i) rates through the establishment of a multidisciplinary, multimodal peri- the prospective assessment of post-traumatic amnesia was influenced by: operative blood management program. The guidelines aimed to optimise knowledge; beliefs about consequences; environmental context and patient’s pre operative red cell mass and coagulation status, minimise peri- resources; skills; social/professional role and identity; and beliefs about operative blood loss, including meticulous attention to surgical haemostasis capabilities; (ii) the use of guideline-developed criteria or decision rules to and tolerance of post operative anaemia. The project was led by a senior inform the appropriate use of a CT scan was influenced by: knowledge; physiotherapist with sponsorship from the Executive Director of RMH. beliefs about consequences; environmental context and resources; memory, Method: Retrospective data from 288 consecutive patients (July 2011 – attention and decision processes; beliefs about capabilities; social influences; March 2013) following primary elective THR or TKR surgery was analysed to skills and behavioral regulation; (iii) providing verbal and written patient identify contributing factors impacting on the increased LOS. Patients who information on discharge was influenced by: beliefs about consequences; received a RBC transfusion had a statistically longer LOS than patients not environmental context and resources; memory, attention and decision requiring a transfusion (p<0.05). Strategies to reduce transfusion rates were processes; social/professional role and identity; and knowledge; (iv) the generated in accordance with National Blood Authority guidelines which practice of providing brief, routine follow-up on discharge was influenced by: included; environmental context and resources; social/professional role and identity; » Treating identified pre operative anaemia through referral to a rapid knowledge; beliefs about consequences; and motivation and goals. access haematology clinic. Patients were requested to have blood tests Conclusions: Using the Theoretical Domains Framework, factors thought to completed prior to their preadmission clinic (PAC) appointment to influence the management of mild traumatic brain injury in the emergency facilitate timely management. department were identified. These factors present theoretically based targets » Minimisation of peri-operative blood loss through intra operative for a future intervention. administration of tranexamic acid. » Implementation of transfusion guidelines based on haemoglobin levels 95 A/PROF JONATHAN KNOTT and the patient’s clinical status. Results: The pilot was conducted from November 2013 – March 2014 and A national project seeking to improve pain management in included seventy two patients. The overall RBC transfusion rate decreased the emergency department setting: findings from the from 16.9% (n=49) at baseline to 9.7% (n=7) during the pilot. Sixty nine NHMRC NICS National Pain Management Initiative percent of patients (n=36) who attended PAC and received surgery during the 1. Steven D, 2. KNOTT J, 3. Bennetts S, 4. Jazayeri M, 5.Huckson S pilot had their blood tests completed prior to their PAC appointment. Of these On behalf of National Health and Medical Research Council’s National Institute for patients five were managed by the haematology clinic for anaemia and did Clinical Studies National Emergency Care Pain Management Initiative; 1. VMO Critical not require a post operative transfusion. There was 75% (n=54) compliance Care Tamworth Base Hospital (NSW); 2. Emergency department, Royal Melbourne from anaesthetists with intra operative administration of tranexamic acid. Hospital Melbourne, Australia; 3. Department of Mathematics and Statistics, La Trobe Additionally, high medical compliance with the post transfusion guidelines has University; 4. Manager Centre for Outcome and Resource Evaluation, Australian and New reduced the number of clinically inappropriate transfusions. Zealand Intensive Care Society Conclusion: The implementation of a peri operative blood management Objectives: The National Pain Management Initiative was established by the program has reduced the post operative RBC transfusion rate following National Institute of Clinical Studies to improve analgesic practice across primary elective hip and knee replacement surgery. Australian emergency departments. Methods: A barrier analysis provided information to better implement changes 97 MS LAKE LUCY in analgesic practice. A working party was established and developed a multi-faceted intervention strategy and clinical indicators. An on-line data A point prevalence survey of nurse sensitive indicators collection system was developed and sites collected data at three monthly associated with the management of peripheral intervals for 18 months. A stepped-wedge design was chosen to manage the intravenous cannulae (PIVC) and the prevention of PIVC number of hospitals involved. Clinical Indicators included documentation of associated infection. pain score, time to analgesia, appropriate use of parenteral narcotics and Christie K1, Chieng A1, Xu Q1, Kennedy K1, Lake L1, Ramsay V2, Hobbs L2, effectiveness of analgesia for severe pain. Wynne R3. Results: 16627 patient data sets were entered from 45 metropolitan and 1 Department of Nursing, University of Melbourne; 2 Department of Infection Prevention regional hospitals. There was an increase from 41% to 64% in documented and Surveillance Service, Melbourne Health; 3 Department of Nursing University of pain score (difference in proportions 23%, 95%CI: 20 to 26) and median time Melbourne, Department of Cardiothoracic Surgery Royal Melbourne Hospital to analgesia fell from 61 minutes (IQR: 23 – 122) to 41 minutes (IQR: 15 – Background: Peripheral intravenous cannulae (PIVC) are the most common 95). Appropriate parenteral narcotic use was over 90% for all time points type of vascular access device (VAD) used for intravenous therapy and it is combined. For all patients with severe pain there was no significant change estimated that one in three hospital inpatients have at least one PIVC in situ. in the proportion with a documented reduction of pain within one hour of PIVC are a potential source of healthcare-acquired infection (HCAIs) and presentation. there is minimal evidence describing practice associated outcomes related to Conclusion: Significant improvements in documentation of pain score and these devices. time to analgesia were demonstrated through a national project of targeted Aim: The primary aim of this study was to evaluate the prevalence of PIVCs improvement. Parenteral narcotic use has a high level of adherence to within the inpatient population of the Melbourne Health. Secondary aims were recommended practice. An improvement in the effectiveness of analgesia in to determine patterns of use in relation to nurse sensitive indicators for severe pain has not been clearly demonstrated in this study. infection prevention, as well as the incidence of PIVC associated infection at a single point in time. 96 MS BERNARDA CAVKA Methods: A point prevalence audit of PIVC was conducted over one day at The effect of implementation of peri operative blood the acute care campus of Melbourne Health, the Royal Melbourne Hospital in management guidelines on transfusion rate of patients January 2014. The incidence, characteristics and infection rates associated undergoing primary joint arthroplasty with PIVC use were recorded. CAVKA B, Moore D, Kelsey G, Coventry A, Gardiner J, Cortese S, Cosgriff C, Results: On the day of the audit 431 inpatient bed areas were reviewed to Bucknill A determine whether or not a patient was present and a PIVC was insitu. There Royal Melbourne Hospital were 402 (93.3%) inpatients present and 168 (39%) had at least one PIVC insitu, 181 (42%) patients had no PIVC and 53 (12.3%) patients were Background: In 2011 / 2012 The Royal Melbourne Hospital (RMH) had unavailable at the time of the audit. Of these inpatients 6% (n = 24) showed median length of stay (LOS) of 5 days (IQR 4-7) for elective primary hip and evidence of indicators of infection, however no single patient showed the knee replacements which compared unfavourably with exemplar necessary combination of signs and symptoms to indicate phlebitis. Of the organisations. International literature identifies high post operative red blood nurse sensitive indicators assessed documentation had the poorest rate of (RBC) transfusion rates as a contributing factor for increased hospital LOS. compliance, particularly in regard to re-site or removal requirements for PIVCs. Page | 34

Conclusion: PIVC use was frequent in this setting and rates of associated week for 2hrs (31) and then SCIg 2-3 times per week for 1hr (19). Those not infection were low. This is consistent with evidence that nurses were interested in home based therapy had concerns regarding access to medical compliant with the majority of infection minimization techniques. Despite support, lack of confidence to perform a subcutaneous infusion and a these findings areas for improvement exist, particularly regarding preference for less frequent dosing. The recurring themes for those interested documentation. Development in these areas may provide further benefit for in trialling a home based therapy included convenience, less travel and infection prevention associated with PIVC use. enhanced productivity. 98 MR JOHN POLITIS Conclusions & Clinical Relevance: This survey has demonstrated that home based immunoglobulin replacement is popular, supported by 3/4 of the Overview of Shorthand Medical Glossary (OMG) Study patients with PID attending RMH. POLITIS J, Lau S, Yeoh J, Brand C, Russell D, Liew D 100 MS BERNARDA CAVKA University of Melbourne Background: Shorthand (abbreviations and acronyms) is commonplace in Evaluating waiting time outcomes after implementation of clinical notation. While many abbreviations and acronyms are standard and the Osteoarthritis Hip and Knee Service widely accepted, an increasing number are non-standard and/or CAVKA B, Ackerman A, Tacey M, Brand C unrecognisable. Discharge summaries are critical for communication about The Royal Melbourne Hospital inpatient admissions. This study sought to describe the frequency of Background: The Osteoarthritis Hip and Knee Service (OAHKS) was inappropriate and ambiguous shorthand in discharge summaries. implemented at The Royal Melbourne Hospital (RMH) in 2006 to improve the Method: 80 electronic discharge summaries from the four General Medical management of patients with osteoarthritis through evidence based Units at the Royal Melbourne Hospital (RMH) were randomly extracted from multidisciplinary management and more effective prioritisation of joint the hospital’s electronic records. Extraction was stratified by the four units and replacement surgery. by the four quarters between July 2012 and June 2013 (giving five discharge summaries per unit per quarter). Information regarding doctor gender, patient Aims: This project aims to quantitatively assess the impacts and outcomes of gender and age, primary diagnosis, and total word count were recorded. All the OAHKS on patient wait times using a pre-post historical control evaluation shorthand notes were assigned into one of four categories according to design. Process outcomes of interest include patient wait time from GP appropriateness: i) ‘Universally accepted and understood even without referral to consent for surgery and wait time from consent for surgery to joint context’; ii) ‘Understood when in context’; iii) ‘Understood but inappropriate replacement surgery. and/or ambiguous’; and iv) ‘Unknown’. The categories were determined by Methods: All patients who had undergone a primary elective total hip or total the authors, which included junior and senior medical staff at RMH. knee replacement at RMH between 2003-2012 were identified using the Results: The 80 discharge summaries contained 840 different abbreviations orthopaedic data base and Reporting and Analysis Unit data (n=1704). and acronyms used on 6269 occasions. 20.12% of all words were either an Twenty five patients with referrals from general practice were randomly abbreviation or acronym. Of the 6269 abbreviations and acronyms, 6.76% selected for each year taking into account the proportion of hip versus knee were categorised as ‘Understood but inappropriate and/or ambiguous’ or procedures performed. Patients were excluded if the referrals were sent from ‘Unknown’, equating to 1.36% of all words, and an average of 5.4 words per private orthopaedic surgeons or RMH outpatient clinics. Data was extracted discharge summary. from the medical records including date of GP referral, date of initial outpatient clinic appointment, date of consent for surgery and procedure date, Conclusion: Abbreviations and acronyms are common in electronic discharge patient characteristics (age, gender, requirement for an interpreter), health summaries, occurring at a frequency of 1 in 5 words. While the majority of status, and social support at home. Descriptive statistics and non-parametric shorthand used seems to be ‘appropriate’, the use of inappropriate, statistical tests were performed. ambiguous or unknown shorthand is still frequent. This has implications for Results: After accounting for exclusions and those patients with complete safe and effective patient care, and highlights the need for better awareness and education regarding use of shorthand in clinical notation. data, a total of n=125 patients were considered in the preliminary analysis. There was no significant difference in patient characteristics between the pre 99 DR KYMBLE SPRIGGS (2003-2005) and post (2007-2012) OAHKS implementation periods. When considering the post OAHKS implementation period (2007 to 2012), the Improving treatment delivery in immunoglobulin median wait time from GP referral to surgery for patients triaged to OAHKS deficiency: A Quality Improvement Survey was 365 days (IQR: 226–442) compared to a wait time of 464 days (IQR: Chatelier J,SPRIGGS K, Lichtblau D, McComish J, Nicholls K, Unglik G, 272–590) for patients triaged to the orthopaedic clinic, although this difference Brewerton M, Slade C*, Douglass JA*. was not statistically significant (p=0.072). Whilst the wait times from GP referral to surgery consent were comparable between the OAHKS and Department of Immunology and Allergy, Royal Melbourne Hospital and Department of Medicine, University of Melbourne*. orthopaedic groups, there was a significant difference (p=0.012) in wait time from surgery consent to procedure, with a median wait of 140 days (IQR: 70- Background: Patients with primary immunoglobulin deficiency (PID) have 204) for the OAHKS patients, compared to 214 days (IQR: 121 – 350) for the intravenous immunoglobulin (IVIg) in hospital at 3-4 weekly intervals. Recent orthopaedic clinic patients. treatment developments enable the delivery of subcutaneous immunoglobulin (SCIg) at home at weekly intervals as an alternative. There is limited Conclusion: Preliminary analysis of the impact of the OAHKS implementation information regarding patient experiences and preferences surrounding at RMH identified a reduction in waiting times from date of consent for surgery immunoglobulin replacement. to primary joint replacement for those patients triaged to OAHKS. Objective: To seek to identify patient experiences and preferences with 101 MRS KELLIE LIERSCH immunoglobulin treatment in hospital and to quantify interest in home based SCIg. Evaluation of nursing staff conducting the Abbreviated Methods: Patients with PID receiving immunoglobulin prescribed by the Westmead Post Traumatic Amnesia Scale at The Royal Department of Allergy and Immunology at the Royal Melbourne Hospital were Melbourne Hospital asked to respond to a questionnaire developed and piloted in-house and LIERSCH K, Carey L delivered on an iPad. Factors such as travel time, time spent at the hospital, Background: The Abbreviated Westmead Post Traumatic Amnesia Scale experiences, suggestions for improvement and attitudes to home based (AWPTAS) was introduced at The Royal Melbourne Hospital (RMH) in 2011 therapy options were investigated. The study was approved by the Melbourne following research that it is the most effective way of screening patients for Health Research and Ethics Committee, approval number QA2013119. Post Traumatic Amnesia (PTA) following a potential Mild Traumatic Brain Results: The survey response rate was 82% (n = 61/74), with the majority of Injury (mTBI). This study evaluates the results of nursing staff conducting the patients (n = 53, 72%) reporting lengthy return travel times (108mins) and AWPTAS. time spent in hospital (208mins). Most (n = 47, 77%) showed interest in any The aims of this study were to: form of home based therapy, and could select multiple possible options with » Evaluate current knowledge and clinical practice of nursing staff who IVIg at home most frequently chosen (36), followed by SCIg at home once per are trained to administer the AWPTAS Page | 35

» Ensure relevant patients are being effectively screened and managed on patient care. Student recommendations included the earlier timing of the » Assess the impact this has on mTBI patient’s length of stay (LOS) experience in the curriculum. Method: An audit of all mTBI patients admitted to the trauma wards at RMH These findings supporting the Nurse Buddy days continued use in the MD2 over a 10-day period in August 2013 was completed. A survey of nursing staff curriculum with consideration to the recommendations given by the students. skills and knowledge related to AWPTAS was also conducted, together with a review of LOS for patients fitting the criteria of mTBI from RMH Trauma 103 MISS MELISSA BANTICK Registry. Improving communication with trauma patients Results: Results indicate that some inconsistencies remain between nursing staff knowledge and clinical practice. BANTICK M, Liersch K, Tacey M, Santos R, Judson R A/P, Morrish G and Horrocks, B. Thirty patients met the criteria for AWPTAS. Data analysis indicated 60% The Royal Melbourne Hospital were screened accurately by nursing staff although the questionnaire indicated 89% were ‘confident’ understanding the screening criteria. Aim: To identify the perceptions of patients regarding Trauma Care at one Major Trauma Service (The Royal Melbourne Hospital). Questionnaire results demonstrate that 97% of nursing staff are ‘confident’ in knowing when to provide the mTBI education handout, however only 20% of Method: One hundred and sixty-nine in-hospital patient surveys were nursing staff provided patients with the handout. conducted for trauma admissions at the Royal Melbourne Hospital over a period of 12 weeks in 2013. The survey addressed the themes of General Data obtained from the trauma registry demonstrates a decrease in average Satisfaction, Decision Making, Information and Wards Rounds, with LOS for mTBI patients following the introduction of nursing staff administering respondents asked to give a rating based on a 5-item Likert scale from the AWPTAS. Strongly Disagree to Strongly Agree. Patient responses were assessed Conclusions: This study demonstrates that training nursing staff to conduct across different strata of patient characteristics and clinical information, the AWPTAS with mTBI patients has positively impacted patient LOS. including age, sex and Mechanism of injury (MOI). However, components of nursing staff knowledge are not consistently being Results: While patient perceptions of care, communication, information and transferred into clinical practice. Therefore, this study highlights the ward rounds was high (i.e. Agree and Strongly Agree) across all responses importance of health organisations reviewing implementation of new 93.49%, the results of this survey identified that only 63.9% were satisfied guidelines and initiatives to ensure consistent utilisation and sustainability. with their level of involvement in decision making about their care and 55.6% were satisfied with their level of involvement in discharge planning. Patients 102 MRS LOUISE PALMER reported that despite feeling they receive enough information about their Medical students “Buddy days” with nurses. An injuries, 62.7% felt that the understanding of the injuries they have and how introduction to patient-centred care and the multi- they may impact on daily activities and long term outcomes could be disciplinary team. improved. In addition 21.0% reported feeling frustrated by the lack of information or conflicting information provided. PALMER, L*; Bendrups, A; Morley, P; Heily, M When considering the age of the patients, 90.7% of patients aged 26-40 Clinical School, The Royal Melbourne Hospital, University of Melbourne years (n=40, p=0.039) and 88.5% aged 41-60 years (n=52, p=0.020) were Background: Under the new post-graduate Doctor of Medicine four-year less satisfied with their treatment when compared to those aged greater than medical course, medical students enter a hospital-based campus after one 61 years (n=44, 100%). Patients with a MOI of High Fall (n = 27, 85.2%) were year of university education. Mindful of this, MD course curriculum designers less satisfied than those brought to hospital after a Motor Vehicle Accident have included programs to orientate new second-year students (MD2) to the (n=52, 98.1%, p= 0.026). In addition, men (n=117, 58.1%) were less satisfied patient-centred, multi-disciplinary clinical environment. Following agreement with their level of involvement in decision making than Women (n=52, 76.9%, from The Royal Melbourne Hospital (RMH) and Melbourne Private Hospital p=0.041). A discharge destination of rehabilitation or multiple trips to theatre (MPH) Nursing Executives, Nurse Unit Managers were briefed and supportive also correlated with the perception that information was at times being of the objectives of the clinical experience. deliberately withheld. After four weeks of the 2014 Foundation Term, MD2 students were rostered Conclusion: While patient perceptions of care was high in many areas, the to spend one eight-hour morning shift buddying (or shadowing) with a clinical results of this survey have identified there is a perception amongst trauma ward nurse. The students had already completed core sessions in skills such inpatients that they are not involved in decision making and discharge as Manual Handling and Hand Hygiene. planning as much as they would like. In addition certain patient characteristics Methods: such as sex and MOI correlate with different perceptions regarding elements 1. Immediately following the shift, all students participated in a facilitated of care. This may have implications for the care provided to these specific discussion. groups of trauma patients. 2. Students voluntarily and anonymously recorded their responses to a survey. A five-point Likert Scale (1= Strongly Disagree, 5 = Strongly 104 DR HEIDI MCALPINE Agree) demonstrated the self-reported impact of the experience. Improving Brain Tumour Care Online Students also provided qualitative comments. MCALPINE H, JOUBERT J, MARTIN-SANCHEZ F, MEROLLI M, DRUMMOND, K Results: 38 out of 57 (67%) of students completed the survey. To the question, ‘The placement met my learning needs’ 89% replied Agree or Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Vic, Australia; Health and Biomedical Informatics Centre, University of Melbourne, Vic, Australia; Strongly Agree. To the question, ‘Royal Melbourne Hospital/ Melbourne Department of Social Work, University of Melbourne, Vic, Australia; Peter MacCallum Private Hospital nursing staff were approachable and supportive’ 92% replied Cancer Centre, East Melbourne, Vic Australia Agree or Strongly Agree. Overall the qualitative responses were positive with Background: An increasing number of patients living with cancer has led to students finding the experience valuable to their learning; in particular patient the exploration of innovative options for their long-term support. Online interaction, intra professional communication and understanding. Some interventions have the potential to transgress geographic, physical and respondents reported: psychological barriers to healthcare, and to facilitate treatment, support and » their presence increased the buddy nurse’s workload education for patients within convenient timeframes and their own » buddy nurse was not aware of the medical student’s objectives for the environment. day. Conclusion: Overall, the students reported an increased understanding of the Objective: We have reviewed the evidence-based literature surrounding the difference between a bedside tutorial and a clinical shift caring for a patient. use of online resources for adult cancer patients, including those who are This shift appeared to increase the students’ knowledge of details involved in currently undergoing treatment as well as cancer survivors. The focus was patient care. Some students reported satisfaction in spending a whole shift on resources that connect patients with their treating team, and supportive with a patient, as well as the opportunity to participate in appropriate and educational resources as well as the outcome measures used to assess procedures. Respect for the skills and knowledge of the nursing staff appears their efficacy. to have been enhanced. Working with and seeing interactions of the Methods: The following databases were systematically searched for relevant multidisciplinary team highlighted how one role influences the other impacting literature: MEDLINE, PsychINFO, Cochrane Central Register of Controlled Trials, CINAHL, Inspec and Computers and Applied Science without a Page | 36

specified date limit. Included were studies conducted in an outpatient setting, patient census lists for Pastoral Care, patients are listed as ‘Not specified’ or reporting a measurable clinically relevant outcome, and with a full text ‘Unknown.’ To address this gap action was taken to maximise patient quality available in English. Fourteen studies satisfied the inclusion criteria. of care Results: Types of interventions included those linking the patient and the Method: Pastoral Care surveyed/interviewed these patients during their daily treating team (one), those connecting patients with each other (five) and rounds across various care environments. In addition to this quantitative task, those providing educational resources (two). Six studies assessed there was a qualitative component which more subtly addresses Standard 2. multidimensional interventions. Results of the interventions were varied, with Following identification of religious identity, patients were further organised some demonstrating positive effects on quality of life and related measures, into eight thematically categories, enabling timely clinical application, and and two demonstrating poorer outcomes for intervention participants. The entered on Riskman Q. majority of interventions reported mixed results. Included intervention types Results: Of the surveyed patients, 97% requested that their Identifier be and outcome measures were too heterogeneous for meta-analysis. changed, greatly exceeding our hypothesised 50%. Of these, 79% requested Conclusions: We found the overall benefit of online interventions for cancer a particular faith designation and other 21% requested ‘’No-religion”. Overall, patients to be unclear. Although there is significant promise and a plethora of 57% requested some faith-based (‘religious’) care, and 34% requested interventions reported without analysis, current interventions demonstrate Pastoral Care for emotional/ personal needs. In total, 91% requested mixed efficacy when rigorously evaluated. Pastoral/spiritual care and 9% declined. Following this ‘co-design’ of patient Using funds from a Brain Foundation Australia grant (2013) we are currently needs, religious IDs were altered on system, and appropriate follow-up care undertaking a Human Research Ethic Committee-approved needs arranged. assessment of online resources for brain tumour patients. This will commence Conclusions: This initiative highlighted a significant gap in patient care. The at the Neuro-oncology multidisciplinary clinic at RMH in May 2014. A novel qualitative factor in this research - collaborative design of patient spiritual care iPad questionnaire format has been specifically designed for the survey. With - highlighted potential risk in a considerable number of cases. At the clinical the information gathered we aim to develop an online therapeutic community level, the data captured enabled targeting of those with potential for our brain tumour patients, augmenting outpatient care by providing on-line psychosocial/spiritual risk, and appropriate interventions arranged communication with the treating team, remote measurement of appropriate parameters (e.g. pain, quality of life) and connecting patients online for 107 MS LYNNE DENBY support and education. The efficacy of this online community will be tested in A modified PHEEM as a tool to improve the Educational a randomized controlled trial. Climate in a Teaching Hospital 105 MS LEONIE SHAW DENBY L, Ng L, MacGill K. Weekend allied health services for acute medical / surgical Background: The Post-graduate Hospital Environmental Measure (PHEEM) is patients to improve efficiency and safety of patient care. a tool which originated from the UK, used to measure the educational climate of a hospital and a quality assurance instrument used to evaluate the clinical Leonie Shaw, Terry Haines, Donna Markham, Deb Mitchell, Elizabeth Skinner, learning experiences of junior doctors. It can be used at a unit or institutional Tim Chiu, Lisa O’Brien, Genevieve Juj, Samantha Plumb, Fiona McDermott, level and provides validated and reliable data. The 40 item questionnaire is Kathleen Phillip, David Lescai, Kerry May, Romi Haas, Kelly Bowles completed by junior doctors at the end of each rotation. This instrument has Monash Health, Western Health, Department of Health, NHMRC been used widely in Australia but with variable effectiveness, largely due to Background: There is little evidence supporting the efficacy, safety or cost- the inability of the tool in identifying relevant areas of improvement within effectiveness of allied health services provided on weekends across acute specific units. At a major teaching hospital in Melbourne, it was modified in a medical and surgical units. This means that it is unknown whether resources way that maintained the integrity of the questions but included details such as spent on these services could be better spent in other activities. This the level of training of the responding junior doctor and the provision of free presentation will describe the protocol of a trial aiming to investigate the text responses, allowing for trainees to reflect on their rotational experiences, safety, efficacy and cost-effectiveness of weekend allied health services on their achievements, key learning and what could be improved. provided on acute medical and surgical units. Methods: The PHEEM was administered through an on-line capability linked Design: A novel “roll-in” stepped wedge, cluster randomised controlled trial to an on-line reporting capability over a period of seven years. Junior doctors design will be used. This is the world’s first application of this research from intern level through to Registrar level were encouraged to complete the design. This will be immediately followed by a conventional stepped wedge, PHEEM on-line at the conclusion of each rotation. cluster randomised controlled trial. In parallel with these trials, will be an Results: Response rate was very good from rotational junior medical staff with observational, dose-response study. 400 in a single year out of approximately 700 completing PHEEM in 2013. Participants and setting: 17 acute medical surgical wards across Melbourne PHEEM completion rate by rotating junior medical staff increased from the Health, Western Health and Monash Health. It is anticipated that year of implementation of 180 to 400. Increase in completion numbers approximately 42,500 patients will be involved in this trial. evolved over time and it is important to note completion of a PHEEM is not Intervention: Current weekend allied health services provided on the study compulsory or mandated by the organization. Completion being driven by wards will be investigated using the novel roll-in design. A new stakeholder- many factors such as empowerment by a validated feedback process to driven model (of equivalent expense) will be investigated using the improve the clinical learning environment responding to strengths and conventional stepped wedge trial. Stakeholders will comprise nursing, weaknesses highlighted in PHEEM reports. PHEEM reports were provided to medical and allied health staff at study sites. Units on an annual basis or upon request. Quality improvements were many including specifically tailored orientation and education programs. Outcomes: Cost of patient hospitalisation, re-admission within 28 days, length of stay, patient adverse events (such as falls, deep vein thrombosis). Other Conclusion: The implementation of PHEEM will provide high quality outcomes such as patient satisfaction, functional ability at discharge, and staff constructive feedback from Junior Medical Staff rotational experiences and as satisfaction will be collected from a subset of participants and through an organisation we should be supporting and prompting the need for high qualitative group interviews conducted during the project. quality constructive feedback as a means to providing and ensuring an optimum supportive training environment for junior doctors. 106 MR DAVID GLENISTER 108 MS NIKOLA SOLOMON Can we judge a book by its cover? Clarifying patient religion identifiers and personal spirituality A point prevalence survey of nurse sensitive indicators associated with the management of central venous access GLENISTER D, Prewer M devices (CVAD) and the prevention of central line- Royal Melbourne Hospital associated bloodstream infection (CLABSI). Background: In response to NSQHS Standards 1 and 2 we identified a gap in admission information that could present a risk to patient wellbeing. A Solomon N1, Wong H1, Alexandra T1, Tang C1, Brunacci N1, Nazareth L1, significant number of patients (17%) are not asked their choice of religious Pritchard C1, Richards M2, Hobbs L2, Wynne R3 identifier on admission, for a number of reasons. This means that on daily

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1 Department of Nursing, University of Melbourne; 2 Department of Infection Prevention Conclusion: The prevalence of IDC use at Melbourne Health is less than that and Surveillance Service, Melbourne Health; 3 Department of Nursing University of of larger studies but consistent with previous prevalence surveys in this Melbourne, Department of Cardiothoracic Surgery Royal Melbourne Hospital organisation. While the evidence suggests nurses adhere to best practice Background: Central venous access devices (CVAD) are commonly used in when managing IDCs, in this context there is room to improve relevant health-care settings; however they are also one of the most frequent causes documentation and patient education on IUC management. Further research of health-care associated bloodstream infections. Whilst extensive research investigating interventions to promote the implementation of IUC specific has been complied about the prevention of central line-associated documentation and f patient education is required. bloodstream infection (CLABSI) with recommendations of catheter type, number of lumens and length of therapy, information regarding nursing 110 DR MICHAEL KLUGER practice in the context of CVAD is relatively unknown. Composite assessment of early graft dysfunction and Aims: The primary aim of this study was to identify the prevalence of CVAD in concomitant drug monitoring in patients undergoing liver use within Melbourne Health. The secondary aims of this study were to transplantation describe the current practice of nursing management of CVAD and illustrate the clinical characteristics of patients with CVAD associated infections. KLUGER M, Goryński K, Jerath A, Bojko B, McCluskey S, Pawliszyn J, Wasowicz M Toronto General Hospital, Toronto, ON, Canada; University of Waterloo, Waterloo, ON, Methods: A point prevalence survey of CVAD use amongst an adult Canada; Department of Anesthesia, University of Toronto, Toronto, ON, Canada population at Melbourne Health was undertaken over two days in January 2014. Aim: Demonstrate proof of concept in the application of Solid Phase Microextraction (SPME) to measure multiple parameters important to liver Results: There were 668 patients being assessed during this survey, 54 transplantation. To develop a single technique to simultaneously measure (8.1%) of whom had a central venous access device in situ. CVAD use was tranexamic acid (TXA) and rocuronium levels and identify metabolite changes most prominent in the intensive care unit and oncology ward. Documentation using SPME. for site maintenance was evident in 98% (n=52) of patients, whilst the frequency of dressing change was documented in 52.8 % (n=28) of cases Background: Poor donor graft preservation, ischemic time and reperfusion and the date for when the next dressing change was due was documented in injury contribute to early graft dysfunction (EGD) post liver transplantation. 49% (n=26) of cases. There was variability evident in practice patterns Studies have suggested that prolonged rocuronium-induced neuromuscular associated with documentation related to CVAD. Patients with evidence of blockade could serve as a marker of EGD following liver transplantation. indicators of infection had blood cultures taken (n=13, 24.1%) and 3.7% (n=2) Metabolomics studies in liver transplantation have identified potential were positive. biomarkers to predict EGD. Liver transplantation is associated with abnormal clotting function and significant blood product transfusions. Though Conclusion: Commonly accepted indicators of infection were not always tranexamic acid (TXA) is frequently used to reduce blood transfusion, plasma indicative of CLABSI. Practice improvement within Melbourne Health should TXA levels have not been modelled within this patient group. Solid phase emphasise standardising practice across departments and ensuring adequate micro extraction (SPME) is a newer sampling and extraction technique that documentation of nurse-sensitive indicators for the prevention of infection. allows simultaneous measurement of multiple drugs and metabolites from bio-fluids and tissues. Absorption of compounds within the SPME fiber matrix 109 MS LISSA KWOK quenches metabolic pathways capturing many more short-lived metabolites A point prevalence survey of nurse sensitive indicators compared with previous analytical methods. associated with the management of indwelling urinary Methods: Adults undergoing liver transplantation were administered a bolus catheters (IUC) and the prevention of catheter associated and infusion of TXA during surgery. A 0.6mg/kg bolus of rocuronium was urinary tract infection (CAUTI). given prior to graft reperfusion and return of neuromuscular function was recorded using train-of-four (TOF) monitoring. Concomitant measurement of Kwok E1, Chandi J1, Boit B1, El-Jordi S1, Fitzgerald F1, Kandiman R1, Turner plasma rocuronium, TXA and metabolomics profile was performed using P1, Williams K2, Hobbs L2, Wynne R3 SPME. Initial study included 9 cadaveric liver recipients. 1 Department of Nursing, University of Melbourne; 2 Department of Infection Prevention and Surveillance Service, Melbourne Health; 3 Department of Nursing University of Results: A single testing method was developed for concomitant Melbourne, Department of Cardiothoracic Surgery Royal Melbourne Hospital measurement of rocuronium, TXA and metabolomics using SPME. Background: Almost half of all hospital acquired infections are attributed to Concerning rocuronium, average time to return of TOF was 102 min (SD urinary tract infections (UTIs) and the majority of these infections are 46min). Delayed return to TOF (120 min) occurred in one patient. Plasma associated with indwelling urinary catheter (IUC) use. Infection prevention, peak concentration was greatest and levels declined slowly. This duration and indication for IUC use and the provision of education to patients corresponded with the highest MELD score of 26 and hepatorenal syndrome are key areas addressed by guidelines for the prevention of catheter- (creatinine 226). Global metabolomic profile was analyzed in 4 patients. associated urinary tract infections (CAUTI). Nurses have a critical role in There were significant changes in metabolites pre and post transplant. addressing these areas and as such CAUTI prevention. There is however, Profiles were similar in three patients with alcoholic and non-alcoholic limited research into practice patterns associated with nurse-sensitive cirrhosis. The one patient with cirrhosis due to hepatitis C displayed a trend indicators for the prevention of CAUTI. towards a different metabolic profile. Metabolites displaying significant changes include histidine, bile acids, pyruvate and carbohydrates. Aim: The aim of this study was to determine the prevalence of IUC use within Melbourne Health and to investigate nurse-sensitive indicators for the Conclusions: We have demonstrated proof of concept in developing a single prevention of CAUTI in this context. test that allows simultaneous measurement of multiple pharmacokinetic and metabolomic parameters clinically important in liver transplantation. This will Methods: We conducted a point prevalence survey of IUC across both allow medical management to be tailored to an individual patient Melbourne Health campuses over a one-day period in January 2014. intraoperatively and in the postoperative critical care setting. Results: At the time of the survey 609 (91.2%) inpatient beds were occupied at the Royal Melbourne Hospital (n=492, 73.7 %) and the Royal Park (n=176, 111 MISS JENNIFER HUYNH 26.3%) campus. At the time of the survey (n=61, 10.0%) patients had an IDC IRF6 is essential for the inducible expression of the novel IL-1 in situ that were in the majority a standard Foley catheter (n=49, 86.0%). Of these patients, only 14.8% (n=9) had a urine specimen sent within a 72 hour family member, IL-36G, in response to Porphyromonas window of the time of the survey and 55.6% (n=5) were positive for gingivalis colonisation. At least a single nurse sensitive indicator was detected for HUYNH J, Kwa M Q, Reynolds E C, Hamilton J A, Scholz G M. 70.4% (n=43) patients and when detected, consistent with best practice Bio21 Institute; Oral Health CRC. guidelines. However, a large proportion of patients had no evidence of The epithelial cells of the oral mucosa play important roles in host defense. receiving education regarding the management of their IUC (n=34, 82.9%). They not only act as a physical barrier, but also utilize pattern recognition Documented date of insertion was poor (n=28, 45.9%) as was a documented receptors, such as Toll-like receptors (TLRs), to detect and respond to plan for removal (n=9, 14.8%) or rationale for continued catheterisation (n=12, pathogens. The Interferon regulatory factor (IRF) family of transcription 19.7%). factors are key regulators of TLR signaling. Unlike other members of the IRF family, IRF6 appears to be exclusively expressed in epithelial cells and has Page | 38

been shown to be a critical regulator of keratinocyte differentiation. However, Methods: A total of 60 adult patients were randomized to either having we recently identified a non-redundant role for IRF6 as a regulator of IRAK-1- intubation with the Ascope or Karl Storz fibrescope. The primary outcome was dependent TLR2 responses in human keratinocytes. the Global Rating Scale (GRS) score. Secondary outcomes included Here, we have investigated a role for IRF6 in regulating the inflammatory intubation success, number of intubation attempt and intubation time. Other response of keratinocytes to the oral pathogen, Porphyromonas gingivalis. subjective outcomes including practicality, usability and image quality were Challenge of the human oral keratinocyte cell line, OKF6/TERT-2, with P. also recorded. gingivalis resulted in the robust up-regulation of IRF6 expression, the most Results: There was no significant difference in GRS, intubation success and abundant IRF in these cells. The expression of the other IRFs was modestly intubation time between the use of Ascope or Karl Storz fibrescope. There up-regulated or unaffected. Gene expression profiling identified a number of was fewer number of intubation attempt in the Ascope group. All of the other IRF6-dependent P. gingivalis-inducible genes including IL-36G. The inducible subjective outcomes were similar between the two groups, except that expression of IL-36G by the TLR2 ligand, FSL-1, was also IRF6-dependent. operators found it easier to use the Ascope than the fibrescope. Consistent with its regulation by TLR2 signalling, knockdown of IRAK-1 Conclusions: The Ascope does not have have a significant difference in inhibited P. gingivalis-inducible IL-36G expression. We also present data clinical performance compared with a Karl Storz fibreoptic bronchoscope. describing the effects of IL-36G on inflammatory genes in oral keratinocytes This device has been improved significantly in recent times to its current and monocyte-derived macrophages. version – the Ascope 3. The Ascope has been consistently rated as an easier Collectively, we have for the first time established a key role of IRF6 as a to use device and its disposability and potential for cost savings potentially transcriptional regulator of IL-36G expression in the host inflammatory make it an acceptable alternative to the reusable fibrescope. response of oral keratinocytes to P. gingivalis. 114 PROF KATE LESLIE 112 DR IRENE NG Large Multicentre Trials in Anaesthesia A multicentre audit on difficult airway equipment at LESLIE K, Cotter R, Stewart M, Zingerle N University of Melbourne affiliated hospitals Department of Anaesthesia and Pain Management, Royal Melbourne Hospital Ilyas S, NG I, Segal R, Lee K, Story D The Department of Anaesthesia and Pain Management, Royal Melbourne Royal Melbourne Hospital Hospital, is an active initiator and facilitator of multi-centre trials in Introduction: Suitable airway equipment must be accessible when managing a anaesthesia, perioperative and pain medicine. The Department is affiliated difficult airway. The Australian and New Zealand College of Anaesthetists with the Anaesthesia, Perioperative and Pain Medicine Unit, Melbourne (ANZCA) has developed guidelines on Equipment to Manage a Difficult Airway Medical School, and the Australian and New Zealand College of During Anaesthesia. We used an audit tool to test compliance with the ANZCA Anaesthetists Trials Group. We have recently completed or are recruiting to guidelines among different Victorian hospitals in key locations. four NHMRC-funded trials: Methods: After obtaining ethics approval, a paper audit tool was used to collect 1. The POISE-2 Study data on the equipment in the adult difficult airway trolley, paediatric difficult airway trolley, difficult airway grab bag; and also the storage conditions of the Patients aged 45 years and older, with or at risk of adverse cardiovascular equipment. The auditors assessed the equipment at three different sites of each outcomes and presenting for non-cardiac surgery were randomised to aspirin hospital: Operating Suite (OS), Intensive Care Unit (ICU) and Emergency or placebo and clonidine or placebo. The primary outcome was death and Department (ED). 14 hospitals with a total of 37 locations were assessed. Each myocardial infarction within 30 days. The results will be published shortly. item listed in the guideline if found available was given a score and an overall 2. The ENIGMA-2 Study item score was calculated for each location. The number of additional Patients aged 45 years and older, with or at risk of adverse cardiovascular equipment present on the trolley were also calculated. outcomes and presenting for non-cardiac surgery lasting more than 2 hours Results: It was found that 14 out of the 37 locations (43%) did not have a were randomised to nitrous oxide-containing or nitrous oxide-free separate adult difficult airway trolley and a majority of these locations (93%) anaesthesia. The primary outcome was death and major complications within were either in ED or in ICU. For those locations where a designated adult trolley 30 days. The results will be published shortly. was available, there was only about two thirds of the prescribed equipment 3. The Balanced Anaesthesia Study present as per College guideline (median item score 60% [IQR 56-80]). There was also an average of 24 additional equipment found on the adult trolley. Patients aged 60 years and older, with or at risk of adverse cardiovascular Similarly, a majority of the locations did not have a separate paediatric difficult outcomes and presenting for surgery lasting more than 2 hours are being airway trolley (81%) or airway grab bag (89%). For the paediatric trolley, we randomised to deep or light general anaesthesia The primary outcome is one could only found, in average, half of the College prescribed equipment (median year mortality. Recruiting is ongoing. item score 53% [IQR 50-64]). The number of listed required equipment was 4. The RELIEF Study higher for the grab bag (median item score 71% [IQR 64-81]). However, there was a lot more extra equipment found in the bag (an average of 19 extra items). Patients aged 18 years and older, with or at risk of adverse outcomes, and presenting for major abdominal are being randomised to a liberal or restricted Conclusions: Overall, there was a marked variation in compliance with the fluid strategy. The primary outcome is disability free survival at one year. The ANZCA guidelines for difficult airway equipment. There were some locations results will be published shortly. with multiplications of required equipment and additional equipment, which made it difficult to access crucial airway equipment in an emergency situation. Conclusion: Large multicentre trials in perioperative medicine are contributing While there may be limitations for each location, a review of the current to improved evidence for practice and, hopefully better outcomes, in patients available equipment and potential changes should be made to improve the presenting for surgery. safety of difficult airway management for our patients. 113 DR IRENE NG 115 DR ASHLEY NISBET Randomized controlled trial comparing the Ambu Ascope Pattern and Prevalence of Arrhythmias in a Contemporary with conventional fibreoptic bronchoscope in asleep Cohort of Adults who have undergone Fontan Palliation for orotracheal intubation of adult patients Congenital Heart Disease Chan JK, NG I, Ang JP, Koh SM, Lee K, Mezzavia P, Morris J, Loh F, Segal R NISBET AM, Zentner D, Grigg L, Kalman JM Royal Melbourne Hospital Department of Cardiology, Royal Melbourne Hospital Background: Fibreoptic guided intubation remains an essential skill to master Arrhythmias are common in patients who have undergone Fontan for anaesthetists. In addition to the reusable fibrescope, an alternative procedures. It is unclear whether in a contemporary adult cohort, the type of disposable videoscope has been available. This randomized controlled study Fontan impacts on the pattern and prevalence of arrhythmias. The aim of this aims to compare the use of the Ambu Ascope with the Karl Storz fibrescope study was to determine the pattern and prevalence of arrhythmias in adults in orotracheal intubation in anaesthetised patients. who have undergone Fontan palliation for single ventricle physiology.

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Methods: Casenotes review of patients who had Fontan palliation, followed Conclusions: Long term “cure” rates after RFA of IART late after Fontan up in the Congenital Heart Disease Clinic in Royal Melbourne Hospital repair are low. However, many patients experience significant palliation with Results: 99 patients: 57 male (57.6%). Patients had mean 3 operations reduction in symptom burden and DCR frequency. The procedure can be (range 1-6). Mean age at initial Fontan: 6.9±5.4 years (2-33): (atriopulmonary performed with low risk. (RA-PA) in 57 (57.6%), intra-cardiac lateral tunnel (LT) in 18 (18.2%), Bjork 117 DR ANDREW TALBOT (RA-RV) in 4 (4%) and extra-cardiac total cavopulmonary connection (TCPC) in 17 (17.2%)). Left Ventricular Filling Pressure (estimated by E/Ea) Bradyarrhythmias were present in 31 (31.3%): sinus bradycardia in 16 Predicts Cardiovascular Events in Fabry Disease: (16.1%), first degree AV block in 3 (3.1%), and complete heart block in 12 Assessment of Long-term Outcomes in an Australian Fabry (12.1%). 16 had permanent pacemakers (PPM) (16.1%) at mean age 15±11 Cohort years (range 0-39). In the RA-PA group, 16 patients (28%) required a PPM. TALBOT A, Lewis N, Nicholls K. There were no PPMs in LT, Bjork or TCPC groups. Department of Nephrology, Royal Melbourne Hospital; Department of Cardiology, Royal Tachyarrhythmias were present in 50 patients (50.5%): 39 intra-atrial Melbourne Hospital; Department of Medicine, University of Melbourne reentrant tachycardia (IART) (78%); 7 atrial fibrillation (AF) (14%), 4 SVT Introduction: Fabry Disease (FD) is an X-linked lysosomal storage disease (8%). DC cardioversion was required in 22 (44%). In the RA-PA group, caused by deficiency in the enzyme α-galactosidase resulting in intracellular tachyarrhythmia prevalence was 68.4% (IART or AF). In the LT group, storage of globotriaosylceramide. Cardiac involvement is associated with left tachyarrhythmia prevalence was 17.6%. In the TCPC group tachyarrhythmia ventricular hypertrophy, conduction defects and diastolic dysfunction that can prevalence was 22.2% (4 patients, 2 AVRT due to accessory pathways, 1 AF, improve with enzyme replacement therapy (ERT). 1 IART). Maze procedure was performed in 3 (6%). His bundle RFA was performed in 2 (4%). 15 patients (30%) underwent RFA: 2 for AVRT; 13 for Objectives: We assessed the long-term progression of cardiomyopathy in a IART. Mean age at RFA: 24.2±6.1 years (12-33) and 18.3±5.8 years post single centre Australian cohort of Fabry patients on ERT. The impact of initial initial Fontan (9-29 years). All patients who underwent RFA for IART had an disease status, diastolic dysfunction, renal function and hypertension on RA-PA Fontan. 60% of patients with a documented tachyarrhythmia had no cardiovascular outcomes was determined. invasive electrophysiological intervention. Surgery to convert an RA-PA to an Methods: Cardiovascular outcomes and renal function of 25 male patients extra-cardiac Fontan was undertaken in 8 patients (14%). Mean age at were analyzed at times 0, 1, 2, 5, 7 and 10 years after commencement of conversion 20.9±8.8 years (8-38). Of these, 75% had a documented enzyme replacement therapy (ERT). The group was separated into those tachyarrhythmia and 37.5% had a PPM. with end-stage kidney disease (CKD5) (N=10) and those with mild renal Conclusion: Modern surgical techniques have substantially reduced the impairment Non CKD5 (N=15). ECGs and clinical assessments were done 6 prevalence of brady- and tachyarrhythmias in the Fontan population. monthly while echocardiography and nuclear GFR were performed However, arrhythmias are not unique to the atrio-pulmonary Fontan patients, 12monthly. Cardiovascular events included cardiac arrest, sudden death, and invasive electrophysiologists face challenges in the management of arrhythmia and pacemaker insertion. arrhythmias in extra-cardiac Fontan patients. Results: After 10 years of ERT the cardiac and renal function of the non CKD5 group remained unchanged. Furthermore these parameters were 116 DR ASHLEY NISBET significantly better than the age matched CKD5 cohort prior to Long Term Outcome of Radiofrequency Ablation for Intra- commencement of ERT. Atrial Reentrant Tachycardia after Fontan Palliation for Patients with CKD5 had worse baseline cardiac parameters and deteriorated Congenital Heart Disease significantly. Cardiovascular events occurred more frequently in CKD5 patients. Left ventricular mass index (LVMI) in CKD5 patients increased by NISBET A, Grigg L, Kalman JM 89.4 ± 78.3g/m2 versus 18.6 ± 29.1 g/m2, p=0.014 in non- Department of Cardiology, Royal Melbourne Hospital CKD5 over 10 years of treatment. The change in LVMI was predominantly Background: Limited acute and long term follow-up data are available for due to increased interventricular wall thickness (7.7 ± 5.5 mm versus 1.55 ± patients who have undergone ablation (RFA) for intra-atrial re-entrant 2.6 mm, p=0.004). tachyarrhythmias (IART) late post Fontan palliation for single ventricle physiology. Recurrence rates of up to 85% at 4 years have been reported. Additionally estimated LV filling pressure (E/Ea) was significantly higher in We describe the acute procedural success and long-term outcome of ablation patients having cardiovascular events (22.3 ± 7.4 versus 12.6 ± 4.4, p=0.002) for IART in Fontan repair patients. irrespective of renal function. Methods: Clinical case notes and procedures reports were reviewed on all Conclusions: End-stage kidney disease was the strongest indicator of patients who underwent radiofrequency ablation for IART at Royal Melbourne cardiovascular disease progression in FD. ERT in early FD appears to Hospital between 1997-2013. stabilize cardiac and renal disease. Cardiovascular deterioration occurs despite ERT in CKD5 patients. Additionally, E/Ea ≥15 may predict increased Results: Thirteen patients (11 male) underwent 16 ablation procedures for risk of cardiac events. IART. Patients underwent 2±1 operations for palliation of single ventricle physiology. First Fontan repair was at age 6 ±6 yrs (atrio-pulmonary (AP) 118 MRS VARA PERIKALA connection in 12, and an RA-RV (Bjork) in 1). 1 patient subsequently underwent a conversion from an AP to an extra-cardiac Fontan. Pacemaker Review of Ward based Respiratory Care Unit - Three years implant was required in 2 patients, at ages 12 and 15. 10 patients required a of Post Implementation of Respiratory Education Module mean of 5.1 cardioversions (DCR) per year prior to ablation. and annual assessments Patients had failed 2.2 ± 1.2 anti-arrhythmic drugs (AADs). Age at RFA was PERIKALA V, Irving L, Smallwood D 26±6 yrs (mean time since Fontan 19±5 yrs). Median of 2.0±1.7 IARTS were Royal Melbourne Hospital mapped. The acute procedural success rate (defined as non-inducibility of Introduction: The Respiratory Care Unit (RCU) is a specialized four bed unit IART) was 75%. Fluoroscopy time - 25±12 mins; RFA duration - 19±14 mins. within Ward 5 South West that manages patients with acute respiratory There were no procedural complications. After the first RFA procedure, IART issues. This involves close respiratory monitoring, arterial blood gas and non- recurred in 7 patients (53.8%) at a mean of 36 months and 3 patients invasive ventilation (NIV). Prior to its establishment in 2004, patients with underwent repeat procedure. At follow up of 65 months (1-166) after the last procedure 9 (56.3%) had recurrence. IART severity score reduced moderate to severe acute respiratory issues could only be cared for in the significantly from mean of 7.5±1.5 pre RFA to 4±2.9 post RFA (P=0.016). emergency department (ED), or Intensive Care Unit (ICU). In 2011, a Patients required 5.1±8.6 DCRs/year pre RFA and 1.5±3.2/year post RFA Respiratory Education Module (REM), practical assessments and annual (P<0.05). 2 no longer required AADs. There was no difference in age at RFA, competencies were introduced for Registered Nurses (RNS). Since this time since first surgery or time since Fontan procedure between the cases implementation, the number of trained RNS able to look after this patient who had recurrence versus those who did not. No patients developed atrial population increased from 16 to 41 (Perikala, V; Irving, L; et al 2012). To fibrillation during follow up. One patient died during follow up from evaluate the effectiveness of the unit (e.g. utilization of beds, impact on hepatocellular carcinoma. Page | 40

patient outcomes), a yearly data collection set was developed in 2012 and Royal Melbourne Hospital; University of Melbourne continued. Background: Continence problems such as urinary urgency, frequency and Aim: To evaluate the utilization of RCU post implementation of the REM, as leakage are more common in older adults, as is chronic heart failure (CHF). evidenced by: We sought to investigate the prevalence and impact of continence problems » Number of patient admitted to RCU (from ED, ICU and other areas of in a cohort of patients with CHF. hospital). Method: A prospective descriptive survey of patients attendng an outpatient » Number of NIV hours used CHF service at a single major metropolitan tertiary teaching hospital in » Length of stay Melbourne, Australia. From November 2012 to 2013, 323 (100%)patients » Adverse events attended this service. Exclusion criteria included, first clinic attendance (n=41, • Pressure injuries; Falls; Critical medication errors; Mortality 12.7%), Transcatheter aortic valve implant candidates (n=33, 10.2%), non- Methods: Prospective data on all patients admitted to RCU in 2012 and 2013 english speaking patients (n=92, 28.5%) and a single patient without a was analysed. bladder (1, 0.7%).56 (17.3%)declined to participate. Results: Total number of patients admitted to RCU was 277 in 2010, 324 in Results: 156 (48.3%) patients were eligible for inclusion and 100 (64.1%) 2011 (increase by 47), and 362 in 2012 (increase by 38). 130 patients were consented to participate.The sample was comprised of 73 men (73%), aged admitted from ED in 2013 (compared to 148 in 2012), while 80 patients were 65.6 (SD 11.9) years with a mean BMI of 30 (SD 7.5)kg/m2. CHF was admitted from ICU in 2013 (compared with 83 in 2012). In 2013, 5 patients diagnosed 45 (Q1 15.5, Q3 100.5) months beforehand and 61% of patients stayed more than 12 days compared to 8 in 2012. Length of longest patient had moderate (EF 30-45%) to severe (EF<30%) left ventricular impairment. stay is reduced by 10 days in 2013 compared to previous years. Mean Mean NYHA Class was 2 (SD 0.7) and median Minnesota Living with Heart duration of stay was 2.8 days. Hours of NIV used increased by 232 hours in Failure Questionnaire (MLHFQ) score was 27 (Q1 14, Q3 43.7) indicative of 2013. There were no significant adverse events, and one episode of nasal CHF having a moderately severe impact on quality of life. Diuretics were bridge pressure injury. Major causes of mortality were end-stage COPD, prescribed for 81 patients. Continence problems were evident in 66 patients severe Pulmonary hypertension, and pulmonary fibrosis. (International Consultation on Incontinence Questionnaire, ICIQ). 43 (65.1%) Conclusions: patients leaked urine secondary to mixed (16, 37.2%), urge (19, 44.2%) or » The implementation of Respiratory Education Module (REM) enables stress (3, 6.9%) incontinence, 5 (1.6%) secondary to post micturition dribble more RNS to care for this patient population and other speciality and 23 (34.9%) secondary to isolated urge incontinence (Questionnaire for patients throught the hospital who require respiratory support. Urinary Incontinence Diagnosis, (QUID). The MLHFQ score differed between » Mean length of RCU patient stay was 2.8 days and mean NIV used patients with (35, SD 20.3) and without (21, SD 16.0) a continence problem; hours were 11.7hours/day. These results indicate that RCU provide Z-3.2, p=0.001. Patients who reported urinary incontinence (n=43) were adequate respiratory support and monitoring. The protected 4 bed RCU moderately (11.6, SD 5.7) bothered (Urge-Urinary Distress Inventory, U-UDI) has greatly improved patient outcomes and reduced admission pressure by this but it caused minimal interference in their daily routine (Med 8, Q1 0, on ICU and ED. Q3 18, Urge- Incontinence Impact Questionnaire, U-IIQ). Patients with continence problems (n=63) were compliant with diuretic therapy and agreed 119 DR GARY HAMMERSCHLAG these medications were beneficial (18.6, SD 3.7, max score possible 25, Beliefs about Medication Compliance Scale, BMCS). Sleep Disturbance in a Male Cohort with Fabry Disease Conclusion: Continence problems are prevalent in patients with CHF and HAMMERSCHLAG G, Garner D, Talbot A, Goldin J, Nicholls K. although bothersome, have minimal impact. In a structured CHF service Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital; Department patients with these conditions manage both well. of Nephrology, Royal Melbourne Hospital; Department of Medicine, University of Medicine 121 DR JESSAMINE LIU Background: Fabry Disease (FD) is an X-linked lysosomal storage disease caused by deficiency in the enzyme alpha-galactosidase resulting in Use of Computed Tomographic Coronary Angiography excessive intracellular storage of globotriaosylceramide. There is a paucity of After Equivocal Stress Tests objective sleep data in FD, however important clinical and physiological LIU J, Lui E, Better N, Heinze S, Langenberg F, Gurvitch R, Joshi S features if FD include pain, renal impairment, obstructive lung disease, Royal Melbourne Hospital, Cardiology Department thickening of the soft and hard palate, cardiomyopathy, cerebrovascular disease and peripheral neuropathy. We hypothesise that these abnormalities Background: Patients with inconclusive cardiac stress test results, depending are likely to increase the prevalence of sleep disorders in FD. on the index of suspicion, traditionally either undergo invasive coronary angiography or are left with uncertainty regarding the diagnosis. Methods: Clinical sleep assessment and analysis of in-laboratory polysomnograms (PSG) of male Fabry patients (n=11) were recruited from Computed Tomographic Coronary Angiography (CTCA) offers another means the Victorian Fabry cohort. Analysis of PSG was conducted by a sleep for evaluation and potentially avoids invasive cardiac catheterisation. scientist and reported by a sleep physician with particular attention to However, one concern is that CTCA could be a redundant layered testing if identifying for sleep-disordered breathing (AHI >5 events/hour) and/or these patients still need invasive coronary angiography downstream. periodic leg movement disorders (periodic leg movements >15/hr). Results: A total of 11 patients (mean ± SD), age 43 ± 8 years completed Current international guidelines recognise CTCA as appropriate following overnight PSG. Baseline characteristics included: BMI = 23.3 ± 3.7, neck prior stress imaging with equivocal results. While symptomatic patients would circumference = 38.95 ± 12.19. Sleep disordered breathing was identified in be covered, this indication is not explicitly stated in the current Medicare 36% (95% C.I. 15.1, 64.6) of patients and periodic leg movements were Benefits Schedule in Australia. This study was designed to evaluate the need present in 91% (95% C.I. 62.2, 98.3) of patients. All patients with sleep- for downstream invasive investigation in patients with equivocal cardiac stress disordered had significant periodic leg movements. Of the tested group 11/11 test results following CTCA. were on enzyme replacement therapy at the time of testing. Methods: Records were reviewed of 243 consecutive patients undergoing Conclusions: Sleep disturbance in FD is likely to be multifactorial with patients CTCA at a single institution between 2009 and 2012. Patients referred for having a higher prevalence of periodic leg movement disorder than the CTCA following an equivocal cardiac stress test were identified based on general population (approximately 4%). The prevalence of sleep-disordered radiology request forms. Results of these CTCA were reviewed. breathing is slightly high than the prevalence in large population studies Results: Thirty-four (34) patients were identified (mean age 55 ± 12 years). (approximately 24%). Interventions are available for these symptoms and Twenty-one patients were of male gender. 38% (13/34) had normal coronary may improve quality of life. arteries; another 38% (13/34) had non-obstructive (<50% maximal diameter) 120 MS ROCHELLE WYNNE stenosis. 24% (8/34) patients had indeterminate or significant (>50% maximal diameter stenosis) findings requiring further clarification or confirmation with The prevalence of continence issues in patients with invasive coronary angiography. chronic heart disease Conclusion: CTCA successfully excluded obstructive CAD in 76% of patients KERLIN M, WYNNE R, Poole K with equivocal stress tests who may otherwise have undergone invasive Page | 41

coronary angiography. Our findings suggest that with good patient selection that required further investigation. Our findings suggest that at our institution from referring physicians CTCA is useful for this patient group and does not CTCA has been used in accordance with the published appropriate use lead to redundant layered testing. criteria. 122 DR KAI'EN LEONG 124 MRS SARA BONANZINGA Comparison of radiation doses between Coronary CT and An SNP affecting the interferon lambda 3 (IL28B) gene also Conventional Coronary Angiography influences thymidine phosphorylase activity LEONG K E, Einsiedel P F, Lui E, Better N, Heinze S B, Neal C R, Langenberg F, BONANZINGA S, Shaw T. Gurvitch R, Eccleston D S, Joshi S B Victorian Infectious Diseases Reference Laboratory, Melbourne Health; Monash Royal Melbourne Hospital University Background: Concerns regarding radiation exposure from coronary CT Background: An estimated 3% of the global human population is infected with angiography (CTA) have led to dose minimization strategies. We compared Hepatitis C virus (HCV), a positive-strand RNA virus that establishes radiation doses from CTA with conventional angiography (CA). persistent infection in a majority of cases. Chronic HCV infection predisposes to subsequent development of potentially fatal cirrhosis and liver cancer and Methods: We reviewed radiation doses from consecutive diagnostic CA and its outcome is affected by the genotypes of both host and virus. The CTA studies (400CA, 100 CTA) performed from 1st January 2012. Bypass combination of pegylated interferon-alpha (pIFN-a) and ribavirin, currently the graft, congenital or right-heart catheterisation cases were excluded. CTA was “standard” treatment for hepatitis C, shows limited efficacy and frequently performed on a 1ST generation dual source CT scanner. Effective radiation produces adverse side effects, but new anti-HCV drugs that have recently doses for CTA and CA were estimated from the dose-length product and the become available have greatly improved prospects for cure. The host dose-area product using the respective chest conversion coefficients (0.014 genotype determines the strength and nature of antiviral immune responses mSv/mGy x cm and 0.20 mSv/mGy x cm2). and the pharmacokinetics, safety and efficacy of antiviral drugs. Single Results: The median effective radiation dose for CTA was 5.2 mSv (IQR 3.5, nucleotide polymorphisms (SNPs) affecting the gene for interferon lambda-3 8.2) vs 9.1 mSv (IQR 6.8, 13.1) for CA (p < 0.001). There was no significant (IFNL3), also known as interleukin-28B (IL28B) have been shown to influence difference in median CA dose between cases with or without left both spontaneous HCV clearance and the viral response to pIFN-a-based ventriculography (8.9 vs 9.7 mSv, p = 0.29). The majority (86%) of patients treatments. The most studied SNP is C/T at rs12971860 in the IFNL3 gene’s undergoing CTA had calcium scoring with a median additional dose of CpG rich promoter region, with the ranked probability of favourable response 0.7mSv. For both CTA and CA, increasing patient weight was correlated with (HCV clearance) being CC>CT>TT. The physiological, biochemical and increasing dose (p < 0.001 for both). In patients < 70 kg, the median CTA genetic mechanisms responsible for this phenomenon are poorly appreciated. dose was 3.6 mSv vs 7.0 mSv for CA (P < 0.001). In patients < 70 kg and < One hypothesis to explain the observed ranking proposes that the T allele 50 years of age, the median CTA dose was 0.7mSv vs 5.3 mSv for CA (p = lowers the threshold for immune activation, consequently raising the threshold 0.03). and reducing the dynamic range available for response to additional Conclusion: With attention to dose minimization strategies, radiation exposure immunogenic stimulation by exogenous IFN-a. Thymidine phosphorylase is with CTA was lower than that for CA at this teaching institution. an evolutionarily conserved enzyme which is induced by oxidative stress and pro-inflammatory cytokines including IFN-a, so that increases in its activity 123 DR JESSAMINE LIU can be regarded as indicative of inflammation and immune activation. If the IFNL3 rs12971860 T allele is associated with increased immune activation, it Evaluation of Appropriate Use of Computed Tomographic may increase TP activity, which is easily measured in blood cells. Coronary Angiography in a Single Tertiary Institution Methods: A simple HPLC-based assay for blood TP activity was devised. TP LIU J, Lui E, Better N, Heinze S, Langenberg F, Eccleston D, Joshi S activity was measured in 300 consecutive whole blood samples for which the Royal Melbourne Hospital IFNL3 genotype was also determined using a PCR-based method. Background: Computed Tomographic Coronary Angiography (CTCA) offers a Results and Conclusions: Remarkably, saturation of blood TP activity noninvasive alternative for definitive diagnosis of coronary artery disease occurred only at concentrations of thymidine almost a million-fold greater than (CAD). However, the advent of CTCA has raised concerns regarding potential the normal plasma concentration (less than 0.5 micromolar). A very large (~7- overuse, particularly when used for general screening in asymptomatic fold) range of TP activity was found. Correlation of TP assay results with patients and routine repeat testing. results of IFNL3 genotyping revealed significant differences in TP activity in This study was designed to examine the indications and evaluate the the order TT>CT>CC, supporting the hypothesis that the rs1291860 T allele appropriateness of CTCA requested at a large tertiary institution. is associated with increased pro-inflammatory activity. These results need to be verified by larger-scale, more rigorous testing. Methods: The radiology request forms for all CTCA studies performed at a single institution between 2009 and 2012 were reviewed to determine the indication of study. The CTCA reports for the asymptomatic patients were reviewed. Results: 243 consecutive CTCA studies were identified (mean age 55 ± 15 125 DR MELISSA GRESLE years, 60% male gender). The most common indication was detection of CAD Do genetic variations associated with Multiple Sclerosis in symptomatic patients (42%), followed by preoperative coronary risk influence gene expression in immune cells? assessment prior to non-coronary cardiac surgery (14%) and evaluation of adult congenital heart disease and coronary arterial anomalies (10%). Other GRESLE M (1,2), Jordan M (3), Spelman T (2), Stankovich J (1), Johnson L (4), indications including risk assessment post revascularization, equivocal stress Laverick L (1), Hamlett A (4), Foo G (1), Field J (4), Baxter A (3), Butzkueven H (1,2). test, evaluation of intra- and extra-cardiac structures, and pericardial disease (31%). Three patients (1%) were excluded from analysis due to missing 1 Department of Medicine University of Melbourne, Royal Melbourne Hospital, Parkville, VIC 3050; 2 Melbourne Brain Centre at Royal Melbourne Hospital, University of records. Melbourne, Parkville; 3 Comparative genomics laboratory, James Cook University, Seven patients (2%) were identified who underwent CTCA for evaluation of Townsville; 4 Florey Institutes of Neuroscience and Mental Health, Parkville. coronary disease who were asymptomatic. Of those, six (86%) had family In recent times, large scale genome wide association studies have identified history of sudden cardiac death or risk factors for CAD and 1 patient (14%) and confirmed 110 genetic variations, known as single nucleotide had known mild CAD. Of those, 6 patients were found to have normal or non- polymorphisms (SNPs), that are each associated with a modest increase in obstructive disease. One patient with risk factor for CAD had indeterminate risk of Multiple Sclerosis (MS). MS associated risk SNPs are not found in result requiring further investigation. protein coding regions of the DNA, but rather, they are found in un-translated Conclusion: In a single tertiary institution, 98% of patients fulfilled appropriate sequences including promoter regions or introns. Hence, it is largely use criteria for CTCA. Two percent were performed in asymptomatic patients, unknown how these risk variants influence biological functions. We but all had family history of sudden cardiac death or known risk factors for hypothesise that some MS risk SNPs will promote immune cell type specific coronary artery disease, and one of those patients had indeterminate result gene expression changes to influence immune cell function. We are using

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gene expression and genotype data to identify if MS risk alleles are Oral Health CRC, Bio21 Institute; Department of Medicine, Royal Melbourne Hospital associated with the differential expression of nearby genes (known as as cis- The Interferon Regulatory Factor (IRF) family of transcription factors serve expression quantitative trait loci or cis-eQTLs) in common immune cell types. important roles in inflammation as well as immune cell differentiation. IRF6 is We have genotyped 110 healthy controls and 80 MS patients at known risk highly expressed in keratinocytes, where it functions as a critical regulator of SNPs by Illumina Immunochip; and have also isolated five peripheral blood differentiation. IRF6 has also recently been described as a novel tumour leukocyte subsets, namely monocytes, NK cells, B-cells and CD4 and CD8 T- suppressor gene. Receptor-Interacting Protein Kinase 4 (RIPK4) functions in cells, for Affymetrix gene expression microarray analyses. For cis-eQTL the protein kinase C (PKC) signalling pathway and, like IRF6, is also a key analyses, we used a list of 136 SNPs that were associated with MS or regulator of keratinocyte differentiation. Given these similarities, we showed suggestive association, and for each SNP, we identified genes within investigated whether IRF6 and RIPK4 may function in the same pathway to 110kb upstream and 40kb downstream of the transcription end site. For each regulate keratinocyte differentiation. SNP-gene pair, we tested whether gene expression was associated with Through the use of gene promoter-reporter assays, confocal imaging, and co- number of risk alleles of the SNP using linear regression models. Three cis- immunoprecipitation, we show that RIPK4 interacted with IRF6, leading to the eQTLs were identified with uncorrected p values of <10-15: rs1323292 robust activation and nuclear translocation of IRF6. Silencing of either RIPK4 associated with Regulator of G-protein signalling-1 (RGS1), rs11154801 or IRF6 expression in oral keratinocytes suppressed the induction of genes associated with Abelson helper integration site 1 (AHI1), and rs11052877 that promote cell cycle arrest (e.g. OVOL1 and MXD1) and differentiation associated with C-type lectin-like 1 (CLECL1). In each case the MS risk allele (e.g. GRHL3). In contrast, overexpression of RIPK4 enhanced the was associated with reduced RNA expression, and the effect was cell type upregulation of OVOL1 and GRHL3 gene expression. Additionally, specific. These results suggest that some MS risk SNPs are likely to knockdown of RIPK4 and IRF6 also negatively affected the expression of pro- modulate gene expression in immune cells. We are now investigating how inflammatory genes (e.g. IL-8 and CCL5). Finally, we demonstrate that the differential expression of these genes could modify the functions of immune activation of IRF6 by RIPK4 is highly dependent on Ser413 and Ser424 in the cells to leave some individuals more susceptible to MS. C-terminal domain of IRF6. Thus, the RIPK4-IRF6 signalling axis may have a dual role in epidermal barrier function and host defense by regulating 126 DR DAYU GAI keratinocyte differentiation and inflammatory cytokine expression. AKT3 gene Deletion and Microcephaly: A Case Study and Literature Review 128 MS JENNIFER MACLACHLAN GAI D, Haan E, Scholar M, Nicholl J, Yu S Epidemiology of blood-borne virus co-infection in people 1 Royal Melbourne Hospital, Parkville; 2 Department of Genetic Medicine, Women’s and diagnosed with chronic hepatitis B in Victoria, 1998-2012 Children’s Hospital, South Australia; 3 Department of Paediatrics, Flinders Medical MACLACHLAN JH, Cowie BC Centre, South Australia; 4 South Australian Clinical Genetics Service, SA Pathology (at Women’s and Children’s Hospital); 5 School of Paediatrics and Reproductive Health, 1. Epidemiology Unit, Victorian Infectious Diseases Reference Laboratory; 2. Department University of Adelaide, Adelaide. of Medicine, University of Melbourne; 3. Victorian Infectious Diseases Service, Royal Melbourne Hospital. AKT3 gene (v-akt murine thymoma viral oncogene homolog 3) is located at Introduction: In people living with hepatitis B, co-infection with other blood- chromosome 1q44 and encodes a 479 amino acid protein, a member of the borne viruses (BBVs) such as HIV, hepatitis C virus (HCV) and hepatitis D protein kinase B (PKB) family. These kinases are serine/threonine-specific virus (HDV) leads to poorer outcomes and complication of clinical protein kinases and are involved in the phosphatidylinositol 3-kinase (PI3K)- management, however incidence and trends are not well understood. AKT signalling pathway. Over or underactivation of the PI3K-AKT signalling pathway has been associated with brain overgrowth or undergrowth Methods: Chronic hepatitis B (CHB) notifications data, including syndromes respectively, demonstrated in knockout mice models and human HIV/HCV/HDV notification status, were obtained from Department of Health case studies. Phenotype and genotype study of patients with 1q44 deletion Victoria. Chi2 tests were used to determine significance of co-infection syndrome has suggested that the AKT3 gene is responsible for the prevalence according to demographic factors. microcephaly phenotype in these patients. However, the relationship between Results: Between 1998-2012, 26,539 CHB notifications were recorded in AKT3 gene deletion and microcephaly has not been fully investigated. Victoria, of whom 1,630 were notified with another BBV: 1,426 (5.4%) with We report a 1q44 deletion involving only AKT3 in a boy and his father. The HCV, 168 (0.6%) with HIV, 84 (0.3%) with HDV, and 48 (0.18%) with multiple boy has microcephaly, hypotonia, feeding difficulties, developmental delay co-infections. and minor dysmorphic features. His father has no microcephaly and is of The proportion of people notified with CHB who had another BBV peaked in normal intelligence. 2002 at 8.0%, and has since declined to below 4%. HCV was most commonly We performed a literature and database search for patients or normal diagnosed before or in the same year as CHB (84.7%), as was HIV (79.2%), individuals with a pure AKT3 deletion. A total of 13 persons have been while HDV was generally diagnosed after CHB (58.3%). reported to carry a pure AKT3 deletion involving at least 1 exon. Six cases Half of those with co-infection were born overseas (49.6%), most commonly (including our own) were from published literature, two cases from patients in Vietnam (11.6%), Sudan (4.9%) and China (2.2%). Those with co-infection the Database of Chromosomal Imbalance and Phenotype in Humans using were also more likely to be Aboriginal and Torres Strait Islander (2.2% Ensembl Resources (DECIPHER) and the remaining five were from normal compared to 0.4%, p<0.001) and to be male (72.4% compared to 53.9%, control individuals in the Database of Genomic Variation (DGV). Of these 13 p<0.001). persons, six displayed microcephaly. Assuming the normal control individuals in DGV did not have microcephaly, the penetrance of microcephaly is 46% Conclusion: Co-infection, mostly with hepatitis C, is a significant issue for (6/13). Parental studies were only performed in three patients including our people living with CHB in Victoria, affecting 5% of those diagnosed. These proband. In all three, the AKT3 deletion was inherited: two were maternal, findings emphasize the importance of universal testing for other BBVs in and our case was paternal. Furthermore, only one out of the three parents those diagnosed with CHB to guide the provision of optimal care. carrying the AKT3 deletion displayed microcephaly. This implies that the AKT3 deletion by itself may not be sufficient to cause microcephaly. 129 MRS ROSE BERNHARD This is the first report to show that microcephaly is only present in 46% of Evaluation of Bruker Daltonics MALDI-TOF MS at The Royal persons carrying a pure AKT3 deletion (incomplete penetrance). In addition, Melbourne Hospital AKT3 deletion is likely to be inherited in contrast to the larger 1q44 deletion, Bernhard R, Giltrap D. which is mostly de novo. This is also the first report of a paternally inherited Microbiology Department pure AKT3 deletion and the second case of a pure AKT3 deletion inherited from a normal parent. Objectives: To evaluate identification of clinical isolates using Bruker Matrix Assisted Laser Desorption Ionisation Time of Flight Mass Spectrometry 127 MISS MEI QI KWA (MALDI-TOF MS) and compare this with previously established methods. These included phenotypic methods and for more difficult organisms, 16S A dual role for RIPK4-activated IRF6 in epidermal ribosomal RNA gene sequencing. differentiation and inflammation KWA MQ, Huynh J, Reynolds EC, Hamilton JA, Scholz GM Page | 43

Method: A total of 727 clinical isolates were identified using previously 131 DR MARIA CHRISTINE THURNHEER established methods and the MALDITOF MS. Of these, 561 were common pathogens isolated in the laboratory. Remote challenges? First evaluation of a hepatitis 16S ribosomal RNA gene sequencing or other phenotypic methods were outreach program in Victoria used to resolve discordant results. THURNHEER MC, Schulz TR, Nguyen T, Sasadeusz J 108 ATCC strains of various bacteria and yeasts were identified using the Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, VIC. MALDI-TOF MS. Background: Assessment of liver fibrosis is an important part of treatment Results: For the 727 isolates tested, there was 96.7% agreement between the evaluation in the setting of chronic hepatitis. In recent years FibroScan® has previous identification methods and the MALDI-TOF MS. For the 561 become the preferred method for non- invasive fibrosis screening. The commonly isolated pathogens there was 99% agreement. There were 9 availability of a portable device allows for wider access to fibrosis screening isolates for which the MALDI-TOF MS gave no reliable identification (ID): and should include clinics in remote areas. » Six were identified to the genus level using 16S ribosomal RNA gene Aims: Improving access to liver disease assessment through an outreach sequencing: Clostridium sp (1), Actinomyces sp (1), Leptotrichia sp (1), program using a mobile FibroScan®. Fusobacterium sp (1), Paenibacillus sp(2). Methods: FibroScan® sessions were held at four different types of locations. » Three were identified to the species level by 16S ribosomal RNA gene sequencing: Micrococcus flavus (1), Odoribacter splanchnicus and These included a tertiary hospital, a community health centre, a health clinic Propionibacterium propionicum. for people who inject drugs (PWID) and four remote clinics located in rural There were 10 discrepant results; for 8 of these 16S ribosomal RNA gene Victoria. Data were collected prospectively using a standardized CRF and sequencing agreed with the MALDI-TOF identification. Two isolates gave no analysed using STATA SE 12. peaks with the MALDITOF. One was identified as Corynebacterium Results: Of the 447 individuals scanned, 110 patients (24.6%) were evaluated tuberculostearicum by 16S ribosomal RNA gene sequencing and the other as during outreach sessions (rural 47 (10.5%); PWID 14 (3.1%); community 49 Cryptococcus neoformans by phenotypic methods. Ninety-five percent of the (11.0%)). The median age of the population was 44 years, and 62 % were ATCC strains were identified correctly to species level and 5% were identified male. While most patients in tertiary or community centres were referred for to genus level using MALDI-TOF MS. assessment of chronic hepatitis B (54.3%; 69.4% respectively), the majority of Conclusion: The data shows that MALDI-TOF MS compared favourably with patients in rural or PWID settings were referred for evaluation of chronic methods that have been used previously for the identification of bacteria and Hepatitis C (76.6% ;100% respectively (among PWID 21% HIV co-infected)) common Candida species. The proportion of patients without marked fibrosis (median stiffness < 7 kPa) was significantly lower in rural settings compared to three other locations 130 DR DING OH (rural 57.1%; tertiary 74.4%; community 85.4%; PWID 63.6%, p 0.026), and a Evaluation of oseltamivir prophylaxis regimens for higher proportion of patients in rural and PWID settings presented with advanced fibrosis/ cirrhosis (F4) (rural 19%; PWID 18.2%; tertiary 6.5%; reducing influenza virus infection, transmission and community 7.3%, p 0.026). disease severity in a ferret model of household contact Conclusions: Distinct, difficult to reach populations can be successfully Ding Yuan OH 1, Sue LOWTHER 2, James MCCAW 3,4, Sheena G. SULLIVAN 1, assessed through an outreach program using mobile FibroScan®. Patients in Sook-Kwan LEANG 1, Jessica HAINING 2, Rachel ARKINSTALL 2, Anne KELSO 1, rural settings and PWID are more often infected with chronic HCV and Jodie MCVERNON 3,4, Ian G. BARR 1,5, Deborah MIDDLETON 2, Aeron C. present with advanced fibrosis, a finding that should promote efforts to HURT 1,5 improve health care provision for these populations. 1. WHO Collaborating Centre for Reference and Research on Influenza; 2. Australian Animal Health Laboratory; 3. Vaccine and Immunisation Research Group, Murdoch 132 DR NADIA CHAVES Childrens Research Institute, Royal Childrens Hospital; 4. The University of Melbourne, Melbourne School of Population and Global Health; 5. Monash University, School of Providing equitable health care for refugees and asylum Applied Sciences and Engineering. seekers: the Refugee and Immigrant Unit at the Victorian Objectives: The emergence of the pandemic influenza A(H1N1)pdm09 virus Infectious Diseases Service in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly Chaves NJ, Gardiner J, Schulz T, Biggs BA transmissible virus. Prior to the pandemic, many countries stockpiled NAIs Victorian Infectious Diseases Service, Royal Melbourne Hospital; Refugee and Immigrant and developed pandemic plans for the use of antiviral drugs, based on either Health Unit, University of Melbourne. treatment of high risk individuals and/or prophylaxis of contacts. However, to Background: Asylum seekers and refugees are one of the most marginalised date there has been a lack of in vivo animal models to test the efficacy of NAI and deprived groups in Australia. Globally, the number of refugees is prophylaxis following exposure to an infected contact, in a household setting. continuing to increase, a reflection of the severity of current conflicts. The Methods: A ferret model of household contact was developed to study the Victorian Infectious Diseases Service has had a State Government supported efficacy of different prophylaxis regimens in preventing infection in contact Refugee Health Fellows program in place since 2008. This program aims to ferrets exposed to influenza A/California/7/2009 A(H1N1)pdm09-infected build capacity in refugee health care by providing: education for health staff, ‘index’ ferrets. Index ferrets were naturally infected by 48 hours exposure to improved clinical services, and, by engaging in research to promote best infected donor ferrets, prior to co-housing with contact ferrets. Prophylaxis practice for refugee health care in our institution and in the wider refugee regimens of contact ferrets consisted of once or twice daily dosing of community. oseltamivir phosphate (5 mg/kg) at 12- or 24-hour pre-exposure, or 24-hour Methods and Results: We describe our unique clinical services model for post-exposure to infected index ferrets. refugees in Victoria which combines RMH outpatient, tertiary outreach and Results: Among the different prophylactic regimens, contact ferrets receiving telehealth refugee health services with the Refugee Health Fellows Program. oseltamivir prophylaxis twice daily from 24 hours pre-exposure or 12 hours We detail our Refugee Clinical Hub and Clinician Assisted Electronic Health post-exposure showed better outcomes than those receiving oseltamivir once Record (CAReHR) which assists hospital-based specialists and GPs to daily. Benefits included a significant delay in the time to secondary infection, manage refugee patients more efficiently, and which has the potential to lower weight loss and higher activity levels. None of the prophylaxis regimens provide real-time access to medical information across four hospital networks prevented infection or reduced the duration of viral shedding, although clinical in Victoria. We outline how we have used CAReHR to audit our health care symptoms did improve in ferrets receiving prophylaxis. practices and to improve documentation of medical issues for our patients. Conclusions: Different oseltamivir prophylaxis regimens did not prevent Conclusion: We discuss the complex health issues faced by refugees who infections nor significantly reduce viral titres. However, oseltamivir prophylaxis attend our service and outline the responsibilities we are trying to fulfil as an did consistently result in a reduction of symptoms in infected ferrets. The organisation to provide care for our asylum seeker and refugee community. combination of improved morbidity but little effect on viral shedding warrants further investigations in human.

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1. Victorian Infectious Diseases Service, Royal Melbourne Hospital; 2. VICNISS Healthcare 133 DR JASON RAY Associated Infection Surveillance System; 3. University of Melbourne Department of Staphylococcus aureus bacteraemia in a tertiary institution Medicine, Royal Melbourne Hospital; 4. Arcitecta, Northcote. in Australia: a review of epidemiology, patterns of Objective: Telehealth is a rapidly expanding method of delivering health care throughout Australia. In 2011 the Federal government introduced Medicare resistance and patient outcomes item numbers to fund Telehealth consultations for patients outside the public RAY J, Madigan V, Sinickas V, Tacey M, Ratnam I, Giltrap D, Chean R. hospital system. We aim to describe the experiences learnt and the Melbourne Health challenges faced in developing a new Telehealth clinic. We offer This paper is a retrospective review of cases of Staphylococcus Aureus recommendations to enhance and support Telehealth implementation in bacteraemia over 2004-2013 in the Royal Melbourne Hospital. Rates of SAB Australia. and patterns of anti-microbial resistance including methicillin are identified Design, participants and setting: We present an audit of first 120 patients and compared with state and national figures, and show decreasing rates of seen at a new Telehealth clinic, developed for refugee and immigrant patients MRSA. who settle in regional Victoria. The patient was seated with the GP and linked The proportion of cases that are nosocomial or healthcare-associated for the by videoconference to the specialist seated at a tertiary referral hospital. hospital are reviewed and compared, showing decreasing nosocomial A trial of varying bandwidth and latency was also conducted to inform future infections, but increasing numbers of MRSA in the community. choices of videoconferencing equipment and practice. Patient outcome is examined in terms of mortality and ICU admission, Main outcome measures: A successful Telehealth clinic can be developed. showing increasing rates of admission to ICU, and an overall mortality below The two most frequently managed conditions were hepatitis C and latent the national average of 18.8%. Mortality from MRSA bacteraemia remained tuberculosis. Nearly 500 km’s of travel and 127kg of CO2 was avoided per statistically higher then MSSA bacteraemia, at 24.8%. patient review. Information technology issues however were faced in 25% of The familiarity of specialty in-patient units in treating SAB was examined, and consultations. the frequency of presentation to different specialties was determined. Patients We recommend that a successful Telehealth clinic can add a new component admitted under the Victorian Infectious Diseases Service had significantly to of overall patient care. This will require adequate administrative support reduced mortality of 8.1% compared with 19.4% under other specialty teams, and should include provision to see patients in person. We encourage the suggesting scope for improvement in recognition and management of the ongoing support of Telehealth development through both Medicare funding condition. and changes to improve simplicity and standardisation of videoconferencing systems. 134 MS JENNIFER MACLACHLAN Key recommendations: Shifting scales: comparing viral hepatitis and HIV/AIDS 1. Provide resources to administrative support of any Telehealth clinic, mortality data 1990-2010 in the Global Burden of Disease either as a central service or at individual locations. Study 2010 2. Use Telehealth as one component of overall patient care. 3. Ensure the opportunity for in-person review is always available. Cowie BC, MACLACHLAN JH 4. Support moves towards an accepted standard system for over internet 1. WHO Regional Reference Laboratory for Hepatitis B, Victorian Infectious Diseases videoconferencing. Reference Laboratory, Melbourne, VIC, Australia; 2. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia. 5. Ensure a consistent bandwidth of at least 512kps, both upload and download, with a latency of 300ms or less to allow adequate sound and Introduction and Methods: The Global Burden of Disease Study 2010 (GBD picture quality for multipoint videoconferencing. 2010) collated estimates of 67 risk factors, 291 diseases and injuries, and 6. Continue the additional Medicare item numbers for the use of Telehealth 1,160 sequelae for 187 countries and 21 regions to identify the determinants to account for the increased scheduling complexity. of death and disability throughout the world. Using country-level and regional 7. Encourage software (and hardware) vendors to improve the ease of use causes of death data, we analysed mortality attributed to hepatitis B and for non-technical clinicians, until Telehealth is as simple as using the hepatitis C (cirrhosis, liver cancer and acute infections) and HIV/AIDS, both phone. globally and specifically in the USA, Western Europe, India, China and Australia. 136 MS JENNIFER MACLACHLAN Results: Globally, deaths from both viral hepatitis and HIV increased from Temporal and geographic distribution of hepatocellular 1990 to 2010 to be leading causes of human mortality, with HIV ranking 6th carcinoma and chronic hepatitis B in Victoria, Australia, (1.47 million deaths in 2010) and viral hepatitis B and C combined ranking 9th, with 1.29 million deaths in 2010. Whereas HIV related deaths in China 1982 to 2007 and India increased over this time period, in the USA, Western Europe and MACLACHLAN JH, Carville KC, Cowie BC Australia, deaths attributable to HIV/AIDS fell by approximately half following 1 Epidemiology Unit and WHO Regional Reference Laboratory for Hepatitis B, Victorian the introduction of highly active antiretroviral therapy from the late 1990s. Infectious Diseases Reference Laboratory, North Melbourne, Australia; 2 Department of Medicine, University of Melbourne, Australia; 3 Victorian Infectious Diseases Service, As a result of declining HIV deaths but increasing viral hepatitis deaths, it was Royal Melbourne Hospital, Melbourne, Australia. estimated that in 2010, in the USA there were approximately 3 times as many Introduction: As liver cancer is the most rapidly increasing cancer in Australia, hepatitis attributable deaths as there were HIV attributable deaths. In we aimed to identify population groups at greater risk of hepatocellular Australia and Western Europe, an estimated 10 times as many people died carcinoma (HCC), the main primary liver cancer, in Victoria in order to better as a result of viral hepatitis than from HIV/AIDS. target diagnosis and treatment efforts. Conclusions: These results from the GBD 2010 suggest that while HIV/AIDS Methods: Epidemiological analysis of cancer registry data from 1982-2007, undeniably remains a key global health priority, mortality from viral hepatitis is hepatitis B and C virus (HBV and HCV) notifications from the Victorian higher than that of HIV/AIDS in a number of regions. Although the analysis Department of Health 1998-2011, and population data from the Australian presented here is drawn from a single study, and needs to be considered Census. Main outcome measures included ncidence, survival and mortality together with other available data, the release of the GBD 2010 results associated with HCC. provides a unique opportunity to set global and local priorities for health, and address previous imbalances in addressing the major preventable causes of Results: Over 26 years 3496 cases of HCC were identified and incidence human death, among which hepatitis B and C must clearly now be counted. tripled, with an annual increase of 5.2% (95%CI 4.6% to 5.7%) in the metropolitan area and 6.2% (95%CI 5.1% to 7.3%) in rural areas. Over half 135 DR THOMAS SCHULZ (54.7%) were born overseas, with those born in China and Vietnam between Telehealth - Still a long way to go: Experience of the first 8 and 10 times more likely to develop HCC. HCC incidence was higher in geographic areas with a higher proportion of people born overseas and higher 120 consultations delivered from a new Refugee rates of HBV notification, with some association observed with HCV Telehealth clinic. notification rates. Survival was poor, with 30.9% of HCC deaths occurring SCHULZ TR 1,3; Richards M 1,2; Gasko H 3; Lohrey J 4; Hibbert ME 3; Biggs BA 1 3 within 30 days of diagnosis.

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Conclusions: This analysis highlights poor survival and late diagnosis for death and disability globally. Using country-level data we analysed mortality people diagnosed with HCC, and identified areas of greatest burden within attributable to communicable diseases in Australia between 1990-2010. the state of Victoria. These data highlight the imperative of liver cancer Results: Between 1990 and 2010, death rates per 100,000 persons declined prevention and the importance of identifiable risk factors, particularly viral for many notifiable communicable diseases, including meningitis (0.60 to hepatitis. 0.43), tuberculosis (0.53 to 0.34), HIV/AIDS (2.34 to 0.75), and other STIs 137 MR BANG M TRAN (0.20 to 0.13). Increases were seen in deaths due to lower respiratory infections (13.0 to 18.7), diarrheal diseases (0.22 to 0.65), acute viral hepatitis The Hepatitis B Surface proteins may promote the (0.28 to 0.59) and chronic viral hepatitis (5.8 to 7.4). Communicable diseases development of liver cancer via upregulation of Wnt/β- that continued to decline from very baseline low death rates included vaccine- catenin signalling preventable infections such as tetanus, measles, and pertussis. Bang Manh Tran1,2, Stephen Locarnini1, Alex Thompson3, Elizabeth Conclusion: Mortality from communicable diseases in Australia continues to Vincan1,2,4, and Nadia Warner1,2 shift from deaths due to acute epidemics of notifiable childhood infections, to 1 Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne; 2 infective complications more common in those with chronic conditions, and Department of Anatomy and Neuroscience, The University of Melbourne; 3 University of the long-term sequelae of chronic infections. This epidemiological change has Melbourne Department of Gastroenterology, St Vincents Hospital, East Melbourne; 4 implications for priority setting within government departments and policy Curtin University, Perth. makers charged with protecting the health of Australians. Introduction: Chronic infection with hepatitis B virus is the main risk factor for development of hepatocellular carcinoma (HCC) with the presence of 139 MR MENINO OSBERT COTTA infection in approximately 40% to 90% of liver cancer cases. In addition, the How antimicrobial stewardship can be introduced to prevalence of HBV-associated HCC is growing at an alarming rate. The Australian private hospitals: a qualitative study Wnt/β-catenin pathway has been causatively linked to various cancers, including liver cancer, with up to 60% of liver cancers showing active Wnt/β- COTTA MO, Robertson MS, Marshall C, Thursky KA, Liew D, Buising KL catenin signalling. Despite the importance of this pathway in liver cancer, Department of Medicine, University of Melbourne, Victoria, Australia; Victorian there are few studies examining the effect of HBV on Wnt/β-catenin signalling Infectious Diseases Service, Royal Melbourne Hospital, Victoria, Australia; Epworth HealthCare, Victoria, Australia. in HCC. The aims of this study are to (1) characterise the Wnt/β-catenin signalling pathway in two HBV permissive human liver cell lines (Huh7 and Background: Uptake of antimicrobial stewardship (AMS) programs in the HepG2), to determine their suitability for HBV- Wnt/β-catenin signalling Australian private hospital sector is currently limited. This study seeks to studies, and (2) use these cells to examine the potential impact of the HBV explore the likely contributing factors and to investigate how AMS can surface proteins on the Wnt/β-catenin signalling pathway in liver cancer, potentially be implemented. especially the HBV S protein which is the most abundant protein secreted by Methods: A series of focus group discussions (FGDs) was undertaken at one the virus. of Australia’s largest private hospitals. Participants were purposively sampled Methods: To measure Wnt signalling, a TCF/β-catenin transcriptional reporter and included clinical and non-clinical stakeholders. A semi-structured (sTOPflash) was co-transfected into Huh7 and HepG2 cells with or without a interview guide was utilised consisting of open-ended questions and plasmid encoding constitutively active β-catenin. Cells were then stimulated scenarios. Discussions were audio recorded, transcribed verbatim, and a with Wnt3a, and luciferase activity (relative to renilla transfection control) was thematic framework analysis was then undertaken for each FGD. measured using the Promega Dual Luciferase assay. Results: Autonomy of attending specialists was perceived as being of greater Results: (1) We have confirmed that Huh7 cells have an intact, tightly significance in private hospitals compared to public hospitals. Use of an AMS regulated Wnt/β-catenin signalling pathway in three ways; by demonstrating expert team providing antimicrobial prescribing advice and education without activation of TCF/β-catenin transcriptional activity following stimulation of intruding on existing patient-specialist relationships was proposed as being pathway components at the cell surface, cytosol and nucleus. In contrast, effective in delivering AMS. Participants believed there was more opportunity HepG2 cells have high levels of constitutive activation due to mutated β- for nurses and pharmacists to participate in the AMS process, and that catenin. Despite constitutive activation, Wnt signalling in HepG2 cells can be patients themselves could be empowered to drive adoption of AMS practices. further stimulated. (2) Using Huh7 cells, we have shown that co-expression of Opportunities existed for private hospital executive to market AMS to both the HBV S protein greatly enhances receptor/ligand-mediated Wnt signalling. attending specialists and patients. It also further increases the activity of co-transfected constitutively active β- Conclusions: Introducing AMS to Australian private hospitals need to take into catenin. Furthermore, when Wnt signalling is stimulated with Wnt3a account concepts such as autonomy and a strong sense of patient conditioned media, co-transfection of HBs can enhance the signalling responsibility among attending specialists. Provision of education and advice pathway in a dose-dependent manner. More interestingly, we have confirmed from experts, championing by clinical leaders, marketing by hospital executive that treating cells with HBV S protein-containing media alone is sufficient to and involving nurses, pharmacists and patients are important considerations enhance the Wnt signalling pathway. when introducing AMS in the Australian private hospital sector. Discussion: These results suggest that the HBV S protein stimulates additive 140 MR TIM SHAW Wnt/β-catenin signalling from both the receptor and transcription complex. This may be a mechanism by which HBV promotes the development of liver [Re-]Modeling Viral Dynamics Using HOT SOCs and Power cancer. We are in the process of further characterising this interaction. Tools – Simples! 138 DR NICOLE ALLARD SHAW T, Peel A. Victorian Infectiuos Diseases Reference Laboratory; The University of Melbourne The shifting burden of mortality attributable to Background: Regular monitoring of the concentration of virus in plasma as a communicable diseases in Australia, 1990-2010 proxy measure of whole body viral load has become an integral part of clinical ALLARD N, MacLachlan JH, Cowie BC management of chronic viral infections, notably those established by hepatitis 1. Epidemiology Unit, Victorian Infectious Diseases Reference Laboratory; 2. Department B and C viruses and human immunodeficiency virus. Since 1995, the of Medicine, University of Melbourne; 3. Victorian Infectious Diseases Service, Royal resulting data has been used to construct mathematical models that aim to Melbourne Hospital describe and predict responses to therapy. Early models resolved viral Introduction: In Australia there are 71 diseases whose diagnosis is nationally clearance into a fast first phase, followed by a slow second phase. The two notifiable, and among these, some are prioritised for follow-up based on phases were interpreted as corresponding to the rapid elimination of free severity and public health importance. We examined trends in the mortality virus and much slower immune-mediated destruction of infected cells, associated with common notifiable and non-notifiable communicable diseases respectively. More effective treatments, developed recently in parallel with over the past two decades using the Global Burden of Disease Study 2010 more accurate and sensitive viral load assays, have revealed seemingly more (GBD 2010), to determine their relative impact. complex viral clearance kinetics and inspired the creation of correspondingly Methods: GBD 2010 collated estimates of 67 risk factors, 291 diseases and complex mathematical models. Current models require specialist computing injuries, and 1,160 sequelae for 187 countries to identify the determinants of resources and skills to implement and interpret. Whether the parameters that

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they produce are much practical use is debatable, signaling a need for Methods: 30 Royal Melbourne Hospital Dermatology outpatients currently simpler, more useful and comprehensible alternatives. receiving biologic (n=15) and non-biologic (n=15) treatment for psoriasis will Aims and Methods: We sought more biologically rational explanations for viral be asked to complete the CogState Brief Battery, a game-like computerised dynamic phenomena and more facile alternative methods of analysis that cognitive performance test designed to be useful in evaluations of cognitive could be implemented using readily available software. We critically examined function in individual and group studies. The results of this test will be established concepts of viral dynamics and their underlying assumptions, re- compared to participant haemoglobin results, Psoriasis Area and Severity analyzed numerous published data sets with the aid of MatLab and Index scores and Dermatology Life Quality Index Questionnaire results to TableCurve and tested analytical methods using simple spreadsheet further investigate the effect psoriasis may have on cognition. programs. Results: Data collection is ongoing (n=10 as of 08/04/2014) and will be Results, Discussion and Conclusions: Simple power laws can adequately completed in June 2014. The groups will be matched by gender and age. describe fluctuations in viral load. Power law relationships are ubiquitous in Discussion: This study is a preliminary study which may help clarify whether complex systems of every type, where they can arise spontaneously from there is a significant link between psoriasis and cognitive impairment, and both stochastic and deterministic processes. Two concepts that have been whether biologic therapies can potentially influence cognitive status. developed as frameworks to explore the origin of power laws in complex Demonstrating an improvement in cognition would be the first time this has systems – Highly Organized Tolerance (HOT) and Self Organizing Criticality been seen, and may lead the way to novel therapies for dementias such as (SOC) – are particularly relevant to evolutionary biology. Populations of Alzheimer’s disease. viruses that exhibit quasispecies-like behavior as a result of low-fidelity replication and large population size are self-organizing. They exhibit 143 SONJA SOKOLOVSKA characteristics that under different conditions – are compatible with both HOT and SOC. Application of these concepts allows viral dynamics to be modeled Outcomes of Pemphigus treatments at The Royal as scale-free transitions between meta-stable equilibrium states, without Melbourne Hospital over 5 years on immune suppressive invoking assumed variables and underlying mechanisms. Models requiring therapies used over this time: A retrospective analysis four or fewer parameters were devised. They may be implemented using a SOKOLOVSKA S1, Scardamaglia L2, Varigos G2 basic spreadsheet program such as Microsoft Excel. Some examples are presented together with a discussion of their probable biochemical and 1. University of Melbourne; 2. Dermatology Department, Royal Melbourne Hospital. genetic basis and its implications. Background: Pemphigus is a rare, autoimmune blistering condition, resulting 141 ALVIN LIM in significant morbidity and mortality. It warrants treatment by various An investigation of prognostic indicators in thin cutaneous immunosuppressive agents, which also contribute to significant morbidity and mortality. Newer treatment agents, including IVIG and Rituximab may be melanoma: lymphangiogenesis and vitamin D more effective or better tolerated. LIM A1, Shayan R2, Varigos G3 The aim of this study is to determine the patient responses to various 1. University of Melbourne; 2. Department Plastic Surgery, Royal Melbourne pemphigus treatments, and how they have affected our patient’s quality of life Hospital; 3. Dermatology, Royal Melbourne Hospital. over their treatment period. Malignant melanoma is the most lethal skin cancer. New methods of Methods: The medical records of the entire cohort of 21 pemphigus patients detection and novel therapies are needed to improve patient outcomes. This treated at the Royal Melbourne Hospital for pemphigus vulgaris between May study investigates two factors reported to influence melanoma prognosis: 2009 and May 2014 (inclusive) were retrieved for analysis. lymphangiogenesis and vitamin D. Relevant data pertaining to their particular pemphigus treatment and how it A proportion of thin melanomas (≤1mm) harbour occult metastasis; however, affected their quality of life was extracted, as well as details regarding sentinel lymph node biopsy is not routinely indicated in this subgroup. potential confounding factors, including medical co morbidities and concurrent Immunohistochemical analysis of lymphatic vessels has been shown to medications. predict metastasis in primary melanoma. In the present study, the primary aim is to study the association between lymphatic vessel density (LVD) and The PDAI (pemphigus disease activity index) (Murrell et al, 2008) and the metastatic status in thin primary melanomas, using the lymphatic markers D2- ABSIS (autoimmune bullous skin disorder intensity score) (Pfutze et al, 2007) 40 and LYVE-1. We hypothesise that metastatic tumours will have were retrieved from each patient’s record, with their scores being determined significantly higher LVD compared to non-metastatic tumours. As such, we by the lesion extent and severity that was documented in the patient record aim to demonstrate that LVD quantification can serve as a novel prognostic template (Department of Dermatology, Royal Melbourne Hospital). indicator in thin melanoma, to identify tumours early in their metastatic PDAI and ABSIS values were recorded in Excel Database format as progression. documented for each patient before their pemphigus treatment was Vitamin D has been reported to improve survival in melanoma patients. Some commenced, and upon their most current treatment review appointment. studies suggest patients with higher vitamin D status present with less aggressive tumours. The secondary aim is to correlate patient vitamin D level 144 LAUREN ANDERSON with clinical and histological parameters in this sample of thin melanomas, Systemic Treatment Impacts on Disease Severity and including metastatic status and LVD. Quality of Life in an Adult Cohort with Severe Atopic 142 ANGELIQUE ROSS Eczema Anderson L, Varigos G, Ross G. Cognitive Function in Patients with Psoriasis While on University of Melbourne; Dermatology, Royal Melbourne Hospital Biologic Therapies: Pilot Study Background: Atopic dermatitis is a chronic inflammatory skin condition that Angelique Ross, Prof George Varigos, Dr Anna Braue, A/Prof David Darby remains a challenge to modern medicine because of its prevalence, relapsing University of Melbourne; Royal Melbourne Hospital course, complex pathogenesis and burden on quality of life. Although there Introduction: Psoriasis is an immune-mediated, inflammatory disease are effective short-term medications, long-term efficacy remains questionable, affecting primarily the skin and joints. An understanding of the as available systemic treatments are commonly associated with poor immunopathogenesis of psoriasis has led to the discovery of novel biologic outcomes and several side effects. This study analyses the use of systemic agents that alter the TNF-α pathway to treat the disease. Studies looking at treatments at RMH dermatology outpatient clinics and compares efficacy, shared pathways between psoriasis and conditions of impaired cognition tolerability, safety and quality of life in relation to specific systemic don’t illustrate a clear link between the two disease processes. We aim immunosuppressive treatments. Objective: To assess the pattern of use, investigate a potential link between psoriasis and cognition. We hypothesise health related quality of life, disease severity, tolerability and safety in relation that participants with psoriasis treated with biologic agents will achieve higher systemic maintenance treatment for severe adult atopic dermatitis to validate cognitive scores than those treated with non-biologic agents. the potential short-term benefits of systemic immunotherapy and justify the need for more effective long-term treatment options. Methods: We performed a retrospective cohort study in adults with severe atopic eczema who were

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receiving systemic immunosuppressive maintenance therapy between 2012- 2014 at the Royal Melbourne Dermatology outpatient clinic. Survey and chart 146 DR CHUN GAN review data was recorded for each patient for each clinic visit. Primary Applicability of Next Generation Sequencing technology in outcome measures were analyzed using the Wilcoxon test to show mean changes in SCORAD (scoring atopic dermatitis) and DLQI (dermatology life Microsatellite Instability testing. quality index) scores in response to each systemic treatment (azathioprine, GAN C, Love C, Beshay V, Macrae F, Fox S, Waring P, Taylor G. methotrexate, cyclosporine and mycophenolate mofetil). Number of flares, Dept of Pathology, Faculty of Medicine, Dentistry and Health Sciences, University of side effect and toxicity profiles and reasons for treatment cessation are also Melbourne, Parkville; Dept of Colorectal Medicine and Genetics, Familial Cancer Clinic, recorded. Results: We studied a cohort of 49 adults receiving systemic and Melbourne University Dept of Medicine, Royal Melbourne Hospital; Dept of Pathology, Peter MacCallum Cancer Institute, East Melbourne. immunosuppressive maintenance therapy. Data analysis and results will be available in the coming weeks with regards to demographics, pattern of use of Purpose: Microsatellite Instability (MSI) is the molecular hallmark of Lynch systemic therapies in our dermatology clinic. syndrome (LS). MSI is used as an effective screening test for patients with suspected LS. If a patient’s tumour is found to be MSI positive, definitive We hypothesize that treatment will reduce DLQI and SCORAD scores in the germline LS mutation testing will be offered. MSI positive tumours are less short term but that as well as tolerability and safety profiles. Conclusions: We likely to be responsive to 5-Flurouracil (5FU) based chemotherapy and hence, hypothesize that severe atopic dermatitis patients receiving systemic should be offered non-5FU based chemotherapy regimens. immunosuppressive treatment experience a temporary improvement in severity and quality of life scores but their efficacy will is limited by side There is an increasing trend in MSI testing relating to the reasons above. 70% effects and toxicity. More randomized control trials are needed to evaluate of National Cancer Institute in the United States are testing for MSI in the long-term efficacy, safety and tolerability of these immunosuppressive colorectal tumours universally. medications and clinical trials for more advanced drugs, like biologics are Traditional MSI testing employs low-throughput Sanger sequencing indispensable. technology. This method is based on a priority selection approach in which the gene deemed most likely to harbour a disease causing mutation is 145 DR FRANCESCO AMICO sequenced first. If the initial gene tested has not revealed any pathogenic Introduction of colon capsule endoscopy in Australia mutation, additional genes will be subsequently screened. This approach is both time-consuming and expensive. The advantage of NGS technology is Amico F, Mclaughlin E, SEGAL G, Macrae FA that it allows massively parallel sequencing of a panel of genes that could University of Melbourne, Department of Medicine; The Royal Melbourne Hospital, potentially harbour disease-causing mutations. This technology is capable of Department of Colorectal Medicine & Genetics; University of Insubria, Department of Surgery, Varese, Italy. producing millions of sequences at once. The cost for sequencing 1 million bases is $0.05 – $10 and $2000-3000 for NGS technology and Sanger Introduction: After its introduction in clinical practice in 2006 Colon Capsule technology respectively. Endoscopy (CCE) has been widely used especially in clinical trials across Europe. Consensus still has to be met with regard to what has to be In this study, we aim to test the applicability of MSI testing utilizing NGS considered the standard bowel preparation and the standard clinical technology. We present the results of MSI testing in 22 tumour samples here. indication for CCE. Only one cleanliness scale for CCE has been published to Methods: 22 Formalin-Fixed Paraffin-Embedded Colorectal tumours were date. PillcamCOLON2® holds Therapeutic Goods Administration approval at recruited (15 and 7 samples from University of Melbourne and Peter the Australian Department of Health since 2013 and no reports of its use in MacCallum respectively). These samples have previously been tested for MSI Australia are yet available. with the Sanger sequencing approach. We tested 5 MSI markers in this We present the introductory use of CCE in Australia and outline the work experiment (BAT25, BAT26, BAT34c4, D18S55, D5S346). The MSI markers undertaken to identify strategic requirements deemed key for its introduction of the tumour tissues were compared with normal tissue. They are deemed to in Australia. be unstable if they showed expansion or deletion in the Microsatellite regions. Methods: On-line literature and information available through direct contact Results: Utilizing NGS, we were able to determine 6 MSI-High tumours and with world experts was extensively assessed with the purpose of identifying 16-MSI Stable/Low tumours. These results are all concordant with the MSI which bowel preparations might provide the best bowel cleanliness, and at status obtained from the Sanger sequencing approach. the same time be palatable and safe. Literature was also similarly searched to These results suggest that NGS technology is a feasible alternative to Sanger identify the best available cleanliness scale for capsule endoscopy. technology. We are proceeding to test a larger batch of samples in Hands-on training was completed beforehand to achieve competency in collaboration with Peter MacCallum and University of Melbourne. administering and reporting CCE. Ten Colon Capsules were made available by the producing company to perform familiarisation procedures on ten out- 147 MISS RENATE SCHWAB patients. Frizzled7 functions as the stem cell Wnt receptor in the Results: Due to safety concerns Sodium Phosphate was deemed a non- normal intestine primary cleansing agent for CCE. Gastrografin was used as a prokinetic SCHWAB RHM 1, Amin N 1, Malaterre J 2, Phesse TJ 3, Ramsay RG 2, Ernst M agent for CCE bowel preparation. Prucalopride was identified as another 3, Strange D 4, Nowell CJ 5, Barker N 6, Clevers H 4, Vincan E 1. possible prokinetic agent to be used as a booster for CCE bowel preparation. 1 University of Melbourne and Victorian Infectious Diseases Reference Laboratories, CCE was performed on six patients. No safety issues where raised. Two Melbourne, Australia; 2 Peter MacCallum Cancer Centre, East Melbourne, Australia; 3 different types of bowel preparation were used. Two procedures were Walter and Eliza Hall Institute, Melbourne, Australia; 4 Hubrecht Institute of Developmental Biology and Stem Cell Research, Utrecht, The Netherlands; 5 Monash incomplete. Five procedures were performed on patients due for colorectal University, Melbourne, Australia; 6 Institute of Medical Biology, Immunos, Singapore. cancer screening and declining conventional colonoscopy, one procedure was performed on a patient with previous incomplete colonoscopy. Wnt/beta-catenin signaling has multiple functions throughout gut development and plays a critical role in homeostatic control of the intestinal epithelium. Conclusions: Prucalopride and Gastrografin might play a key role as boosters Aberrant activation of the Wnt pathway is observed in all human colorectal in the context of bowel preparation for CCE. cancers (CRC) and it's now evident that this aberrant activation plays pivotal Validation of the currently available CCE cleansing scale might rationalise roles in the initiation, growth and progression of CRC. Importantly, naturally data flow between different centres in Australia and uphold future potential occurring inhibitors of Wnt-Fzd interaction are epigenetically silenced very comparison of different cleansing regimens on a larger scale. early in the transition from normal epithelial stem cell to cancer cell, which implicates a role for Wnt and Fzd in this early transition. Here we investigate After a dedicated team was specifically trained it was possible to the function of Fzd7 in the intestinal epithelium using the Cre/LoxP system as independently perform CCE on six patients. CCE cost related issues will also a means to determine gene function. Using a novel mouse model, which need to be addressed before such procedure is made widely available allows specific and inducible knock-out of Fzd7 in the intestinal epithelium, we through public or private practice in Australia. established a protocol to grow mini-gut organoid cultures from the mouse small intestine. The aim was to delete the Fzd7 gene in the intestinal epithelial cells and assess the effect of Fzd7 loss on intestinal architecture.

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First, we determined the localization of Fzd7 within the epithelium and KLAIC M, Khan F, Galea M, Ng L, Zhang N, Abbott G, Elmalik A showed Fzd7 expression is confined to the Lgr5+ stem cells of the crypt. Royal Melbourne Hospital; University of Melbourne Next, we established in vitro mini-gut organoid cultures from the intestines of Background and Aim: It is estimated that up to 65% of stroke survivors fail to Fzd7.AhCre.LacZ mice. The mini-gut organoid cultures recapitulate the regain functional use of their upper limb (UL). There are a number of features of the intact intestinal epithelium. Passage and maintenance of the contributing factors to this outcome including time constraints, retraining of organoids is absolutely dependent on Wnt. Once the organoids were walking being prioritized over rehabilitation of the UL and early emphasis on established, we induced Cre-mediated Fzd7 gene deletion. The AhCre compensatory techniques. Furthermore, access to specialist clinics, including recombinase targets all epithelial cell types except the Paneth cells. The hand clinics, are limited with extensive wait times. As a result, long term recombinase activity of AhCre is induced by treatment with beta- outcomes for recovery of UL function following a neurological event are often naphthoflavone (BNF). The organoids were imaged before treatment on day 0 poor. and again on day 3 and day 5 post induction. By day 5 the crypt domains of the BNF treated organoids were mostly dying or dead. Control carrier Research on the mechanisms of neuroplasticity following a neurological injury (DMSO) treated organoids continue to grow unhindered. In stark contrast, suggest that intensive and repetitive training of functionally relevant and after passaging, the Fzd7 deleted organoids were not able to regenerate. engaging tasks are essential for the successful rehabilitation of the UL. Growth and passage of the Fzd7-deleted organoids could be rescued by Advances in robotics and gaming technology now provide a basis for activating the Wnt pathway down-stream of Wnt/Fzd (i.e. by inhibiting GSK3). intensive and repetitive training of the UL. The incorporation of such technology increases patient motivation and engagement while providing a These data show Fzd7 maintains intestinal stem cells and their regenerative low-cost means of additional practice of UL tasks for stroke patients. function. Notably, the Fzd7 gene is over-expressed in CRC, as a consequence, these and other functional analyses will give us an This paper describes the development of the Hand Hub – a state of the art understanding about its role in CRC initiation, maintenance and progression. environment that harnesses new technology to rehabilitate the UL following a These insights can then offer novel avenues in treatments to target key neurological event. events during tumor growth and progression. Methods: This project utilises comparative effectiveness research (CER) framework which generates and synthesises evidence comparing benefits of 148 MR DUSTIN FLANAGAN treatments. Inclusion criteria are UL deficit following neurological event. There Rapid loss of gastric epithelial cells upon conditional are no exclusion criteria. Data collection is over 5 years and all participants deletion of the Wnt receptor Frizzled-7. are assessed by an occupational therapist and rehabilitation physician at baseline, immediately post treatment and at 12 months. Assessments include FLANAGAN DJ1, Phesse TJ2, Ernst MRW2, Vincan E1. measures on spasticity, motor function, cognition and perception. Intervention 1. University of Melbourne and Victorian Infectious Disease Reference Laboratories, is a minimum of 12 treatment sessions within a group setting where Melbourne Health; 2. Walter and Eliza Hall Institute, Melbourne. participants practice UL tasks at one of a series of graded workstations using The adult mammalian gastric epithelium undergoes constant self-renewal due virtual reality / gaming technology including the ReJoyce and the Able-X. to unrelenting exposure to harsh chemical and mechanical stresses, and as a Results: The hand hub commenced in August 2013 at the Royal Park consequence is replenished every 10-15 days. The epithelium is organised Campus of the Royal Melbourne Hospital. To date, more than 30 clients have into multiple gastric units resembling flask-shaped pockets. Individual gastric participated in the project. Preliminary results indicate statistically significant units comprise a glandular domain leading into a pit compartment that opens improvements in both objective and subjective measures. out onto the gastric surface epithelium. The gland domain is further divided into an isthmus, neck, and gland base region. The constant turnover of cells Conclusion: The hand hub clinic has strategically used new technology to is maintained by adult resident stem cells. In 2010, cells characterised by the build capacity in the provision of rehabilitation of the UL following a expression of the Wnt target gene Lgr5, found to reside at the base of gastric neurological event. Advantages of this equipment include improved patient units, were shown to be capable of self-renewal and generating all cell outcomes with a marked reduction in therapist one-on-one time. Phase 2 of lineages of the gastric epithelium, fulfilling the requirements of adult stem this study will explore utility of gaming technology with rural/regional patients cells. In addition, these cells demonstrated a high dependency and sensitivity using telerehabilitation. -catenin signalling for their maintenance. However, non-Lgr5 expressing cell populations have also been implicated in the homeostasis of 150 DR LOUISA NG the gastric epithelium. These data suggest the co-existence of multiple stem Let’s talk about sex: a randomised controlled trial on cell populations within the epithelium that work in concert to maintain the sexual rehabilitation after stroke integrity of the gastric epithelium. NG L, Zhang N, Sansom J, Amatya B We sought to determine the requirement of the Wnt receptor Frizzled-7 Department of Rehabilitation Medicine, Royal Melbourne Hospital; 2 Department of (Fzd7) in gastric homeostasis via conditional deletion using transgenic Medicine, University of Melbourne; 3 Royal Melbourne Hospital Clinical School, tamoxifen inducible Lgr5-EGFP-ires-CreERT2 and Tff1-CreERT2 mice to University of Melbourne delete Fzd7 in Lgr5+ cells and the whole gastric epithelium respectively. Background: Sexual activity is an integral part of life and the importance of When Fzd7 is deleted from Lgr5+ cells exclusively, we do not see any effect addressing sexual health after stroke is well accepted. Despite this, a recent on epithelial homeostasis. However, Tff1-CreERT2 mediated Fzd7 deletion Australian National Stroke Audit Rehabilitation Services Report 2012 showed resulted in rapid repopulation of the epithelium characterised by replacement that of 2789 post-stroke patients audited across 111 Australian public and of Fzd7 deficient cells with Fzd7 proficient cells, indicating a strong selective private hospitals, only 17% of patients received information on sexuality. In pressure against Fzd7 deficient cells. Molecular analysis of this repopulation addition, although current guidelines recommend the assessment and process has identified significant increases in proliferation and the expression management of post-stroke sexual dysfunction, little is known about what -catenin target genes. We also observed decreased type of intervention (timing, content, intensity, setting) should be provided and expression of the gastric stem cell marker Troy and the intestinal stem cell how effective these interventions are. marker Lrig1 upon Fzd7 deletion, suggesting that Fzd7 is required for these stem cell populations. Aims: To assess the effectiveness of a comprehensive structured sexual rehabilitation program compared with written information alone, on sexual These findings demonstrate an essential role for Fzd7 during homeostasis of functioning and psychological function (anxiety, depression, stress), in an the gastric epithelium since using Tff1-CreERT2 to drive Fzd7 deletion Australian stroke cohort. The secondary aim will be to assess the efficacy of throughout the epithelium induces a repopulation event. We also show that the sexual rehabilitation program on functional independence and quality of this process does not require Lgr5+ cells since deletion of Fzd7 specifically life. from Lgr5+ cells did not induce gastric repopulation. As Troy and Lrig1 are both downregulated upon Fzd7 deletion, we hypothesise that these may Methodology: A randomised-controlled trial where consecutively admitted represent gastric stem cell populations regulated by Fzd7. stroke patients on the inpatient rehabilitation unit at the Royal Melbourne Hospital will be recruited over a period of 12 months. They will be randomised 149 MS MARLENA KLAIC using a computer-generated sequence with allocation concealment. The treatment group will receive an individualized sexual rehabilitation program The hand hub: Maximising upper limb rehabilitation during their inpatient stay and/or within 3 months of discharge in the following a neurological injury outpatient setting according to patient preference in addition to written Page | 49

educational material (fact sheet produced by the National Stroke Foundation) subsequently fortnightly for a total of 3 months. The control group will receive on sexuality after stroke, which both treatment and control groups will receive. befriending sessions at the same intensity. Assessment time points will be at admission, 6-weeks and 6-months following Expected outcome: It is hypothesized that combining music therapy with intervention. Standardised validated measures will be used to measure standard care will improve language function, quality of life, and mood. sexual and psychological functioning, functional independence and quality of Clinical changes will be mapped to any observable changes in fMRI, further life. The study will be powered based on the primary outcome measuring characterising aphasia recovery post-stroke. This research has significant sexual function and 70 patients will be recruited to ensure a sample of 30 implications in improving understanding of stroke recovery and exploring patients in each group is achieved. targeted multidisciplinary therapies for improving aphasia rehabilitation. 151 MRS ANITA BROWN-MAJOR 153 MR BERND MERKEL Let’s talk about sex: implementing the evidence to stroke survivors undergoing inpatient rehabilitation. White Matter Hyperintensities and Physical Activity in BROWN-MAJOR,A, Cowan, C, Zhang, N. People at Risk of Alzheimer's Disease Australian Centre in Sex, Health and Society, Latrobe University MERKEL B, Lautenschlager NT, Cox K, Ames D, Cyarto E, Ellis K, Phal P, Tran B, Steward C and Desmond P Background:The National Stroke Foundations Clinical guidelines for stroke management (2010) state that patients should be provided with information 1 Radiology, University of Melbourne, Parkville; 2 Radiology, Royal Melbourne Hospital, Parkville; 3 Psychiatry, University of Melbourne, Kew; 4 National Ageing Research about sexuality. A recent study by the Foundation found that only 12% of Institute, Parkville; 5 University of Western Australia, Perth patients were given a copy of the sexuality fact sheet. This project was initiated by the Australian Research Centre in Sex, Health and Society at La During the last decade, research in Alzheimer's Disease has focussed not Trobe University and collaborated with multiply organisations to implement only on optimizing treatment, but also on investigating modifiable risk factors the NSF best practice recommendations regarding sexuality after stroke. This with the aim to slow down the neurodegenerative progression in people at paper reports on the implementation process on the Royal Melbourne increased risk of developing AD. These risk factors include unhealthy diet, Hospital Inpatient Rehabilitation ward at the Royal Park Campus. cerebrovascular risk factors (VRFs) and lack of physical and cognitive activity. White matter hyperintensities (WMHs), which characterize cerebrovascular Method: Quantitative and qualitative data were collected via a medical record disease (CVD) on MR images, are considered to be associated with an audit and online survey monkey with clinical staff regarding their knowledge, increased risk of AD. However, the impact of physical activity (PA) on confidence and level of comfort providing stroke survivors with sexuality cognitive function and CVD remains under-researched. In this work, we information. These results were analysed used descriptive and frequency analyse WMHs of T2-FLAIR MR images and hippocampal (HC) volumes of statistics. older adults with subjective memory complaints (SMC) or mild cognitive Six stroke survivors undergoing rehabilitation discussed how they would like impairment (MCI) and examine their association with different PA to receive information regarding sexuality and intimacy. Interviews were assessments cross-sectionally. Baseline MR images were acquired of 100 analysed using simple content analysis and conceptual themes identified. eligible participants (71 SMC, 29 MCI, mean age: 73.2, min. age: 61), who are enrolled in the AIBL Active trial. After different steps of image processing Results: Medical records audits found nil citations regarding sexuality. (reorientation, normalizing, skull removal, bias field and neck clean up, Results of survey indicated that staff lack knowledge and confidence and resampling), ROIs for the WMHs were drawn on the MR Images (axial view) stroke survivor’s interviews gave us great insight into how patient would like by one tracer and revised by an expert neuroradiologist. HC volumes were to receive sexuality information. Education sessions were presented to staff calculated with automated software tools. Level of PA was measured using and protocols to encourage implementation of NSF recommendations were the CHAMPS (community healthy activities model program for seniors) developed. questionnaire and the 6-minute Walk Test was used to assess cardiovascular Conclusion: This study provides insight into how we can facilitation the endurance. implementation of best practice guideline to provide stroke survivors with In the total data set, both HC volumes (r=-0.443, p<0.01) and WHMs information regarding sexuality. (r=0.214, p<0.05) were significantly associated with age. There were no significant differences in the measurements of volumes (HC, WMH) and PA 152 MR SAM HARVEY between the SMC and MCI subgroup. In the SMC subgroup, corrected for Exploring a multidisciplinary approach to aphasia age, we found a significant correlation between WMHs volume and the 6- rehabilitation: Study Protocol minute Walk Test distance (r=-0.285, p<0.05). However, this finding could not be replicated for the MCI group. The lack of effect in the MCI group may be HARVEY S, Megee F, Campbell B, Bivard A, Turner A, Wier L, Hand P, Desmond related to statistical underpowering due to the smaller number of MCI vs. P, Davis S, O’Brien E, Dr Yassi N. SMC. HC volumes were not associated with PA levels in the subgroups. Dept of Speech Pathology & Audiology, Royal Melbourne Hospital; Dept of Neurology, PA may play a role in reducing the risk of CVD and confer a protective effect Royal Melbourne Hospital; Dept of Medicine, University of Melbourne; Dept of against AD. WMHs provide a measure of cardiovascular health of the brain Psychiatry, University of Melbourne; Dept of Radiology, Royal Melbourne Hospital; Dept of Music Therapy, Royal Melbourne Hospital. and may be influenced by physical activity. Longitudinal studies on SMC or MCI patients undertaking a physical activity program may provide new Rationale: Up to one third of stroke survivors present with aphasia which evidence about the protective effect of PA in patients at increased risk of AD. impacts functional communication and social participation. Prior to 2012, clinicians at the Royal Melbourne Hospital had informally observed the benefits of music therapy for patients with communication impairments post- stroke. This trial investigates the benefit of a multidisciplinary approach to language therapy by combining intensive music therapy with traditional communication rehabilitation. Objectives: To assess the effect of intensive music therapy on clinical and neurological recovery as well as mood and quality of life in patients with expressive aphasia. Methods: A pilot randomised control trial will be performed involving 10 participants with ischaemic stroke and expressive dysphasia over a 2-year period. Language assessment, mood and quality of life questionnaires, and functional-MRI will be performed at baseline and at 3 months (end of study). Language assessment, mood and quality of life questionnaires will also be performed at 2 weeks. The active group will receive intensive music therapy twice daily for two weeks in addition to standard care, followed by weekly sessions for 8 weeks

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Poster Display Map Function and Convention Centre, Ground Floor, RMH

Foyer Clinical School Epidemiology: 40-41 Mental Health: 42-46 Cancer: 47-63

Renal: 30-39

Neurosciences: 64-84 Critical Care: 85-95

Dermatology: 141-144 Gastro-Intest: 145-148 Rehabilitation: 149-152

Infectious Diseases: 128-140 Quality of Care: 96-109 Radiology: 153 Surgery: 110 Dental: 111

Anaesthesia & Pain Mgt: 112-114 Cardiorespiratory: 115-122 Genetics: 123-127

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Notes

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