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Abstracts Keynote address Professor Stephen Davis AM Saving brain and improving outcomes after stroke Stroke is a massive global health challenge, with 17 million new strokes each year, 6 million deaths and is a leading cause of chronic disability. Effective acute stroke therapies are based on modification of the evolving pathophysiology in the stroke process. Following arterial occlusion, most patients have a mismatch between the region of hypoperfusion and the ischemic core, termed the ischemic penumbra and the target of acute stroke therapy. Reperfusion strategies that attenuate infarct growth include IV tPA and now endovascular thrombectomy for large artery occlusion. Our pathophysiological research has confirmed the principle that ‘time is brain”. The ischemic penumbra can be identified in real time using advanced imaging techniques and used to select treatment responders to reperfusion therapies at delayed time windows.

Closing Plenary Irene Ruderman Changes in Bone and Mineral Markers after cessation of Cinacalcet in dialysis patients with secondary hyperparathyroidism RUDERMAN I (1,2), Hewitson T (1,2), Smith E (1,2), Toussaint T (1,2), Holt S (1,2) 1- Department of Nephrology, The Royal Melbourne Hospital, 2-Department of Medicine, The University of Melbourne

Aim: Removal of PBS funding for cinacalcet in Australian has provided a unique opportunity to assess changes to biochemical and clinical outcomes in dialysis patients following the cessation of this medication. Background: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) and is associated with significant abnormalities in bone metabolism. Management of SHPT is challenging and involves correction of mineral abnormalities or more direct interventions with either the calcimimetic cinacalcet or parathyroidectomy. Methods: Dialysis patients at The Royal Melbourne Hospital whom had cinacalcet withdrawn between August 2015 and March 2016 were included in a prospective observational study. Blood tests were taken at time of cessation and at 1, 3, 6 and 12 months thereafter. Results: Of 128 patients on cinacalcet, 62 patients consented for this study. Mean age was 67 ± 13 years (mean± SD) with 55 patients on haemodialysis and 7 on peritoneal dialysis. Biochemical changes over the 12-month follow-up included increases in serum parathyroid hormone from 51.5 (IQR 33.8-92.8) pmol/L at baseline to 114 (IQR 71-155) pmol/L at 12 months (p<0.0005), serum calcium from 2.30±0.2mmol/L to 2.50±0.1mmol/L (p<0.0005), and alkaline phosphatase 131(IQR 103-173)U/L to 146(IQR111-209)U/L (p=0.049). Serum albumin decreased from 35±4.5 g/L to 33±4.5 g/L (p=0.033). Over 12 months there were two fractures, five cardiac events, one episode of calciphylaxis, and two parathyroidectomies in this cohort. The mortality rate was 19%(n=12). Five patients recommenced cinacalcet, meeting criteria under a special access scheme.

Conclusion: Biochemical changes in our cohort represent worsening SHPT following withdrawal of cinacalcet. Longer term follow-up will allow us to identify if this translate to increased rates of parathyroidectomies and cardiovascular mortality and morbidity.

Basic Science Research 1 Holly Anderton Inhibitor of APoptosis proteins (IAPs) limit inflamation in the skin ANDERTON H(1,2), Rickard J(1,2), Varigos G(3), Lalaoui N(1,2), Silke J(1,2) (1) Cell Signalling and Cell Death Division, The Walter and Eliza Hall Institute for Medical Research; (2) Department of Medical Biology, University of Melbourne; (3) Department Dermatology, Royal Melbourne Hospital

Aims: To explore the role of Inhibitor of APoptosis (IAPs) proteins in skin development and homeostasis, furthering our molecular understanding of inflammatory signalling in the skin. Background: IAPs are critical regulators of cell death and survival pathways. Mice lacking cellular IAP (cIAP) 1 and either cIAP2 or X-linked IAP (XIAP) die in utero, and myeloid lineage-specific deletion of all IAPs causes sterile inflammation; however their role in the skin is unknown. Methods: To investigate the role of IAPs in skin development we generated epidermal-specific IAP-deficient mice and analysed the emerging phenotypes biochemically and histologically. To investigate their role in skin homeostasis we injected a highly specific IAP antagonist compound (Smac-mimetic) subcutaneously into adult wild-type mice and a panel of genetic knock-outs. To explore the contribution of bacteria to the Smac-mimetic inflammatory response we injected wild-type mice born and raised in an abiotic (germ-free) environment, and wild-type mice after treatment with antibiotics. Results: We found that combined genetic deletion of cIAP1 in keratinocytes and ubiquitous cIAP2 deletion (cIap1EKO/EKO.cIap2-/-) caused profound skin inflammation and keratinocyte cell death, that was lethal by post-partum day 10. Injection of Smac-mimetic induced a Toxic Epidermal Necrolysis (TEN) like local inflammation characterised by keratinocyte cell death, immune cell infiltration, and production of pro-inflammatory cytokines. The severity of the skin reaction was reduced in Tnf-/- and Ifng-/- mice and almost absent in Tnf-/-Ifng-/- double knock-out mice, Tnfr1-/-, and FasLgld/gld mutant mice. Mice deficient in Myd88, which is required for an inflammatory response to bacterial products, also had a reduced reaction to Smac-mimetic injection. This prompted us to inject germ-free mice which we found had no response to Smac-mimetic. Germ-free mice became sensitive to the injections within days of transfer into a Specified Pathogen Free (SPF) facility. Administration of antibiotics to SPF mice also reduced the inflammatory response induced by Smac-mimetic injection. Conclusions: Both the genetic and pharmacological models of IAP loss demonstrate a vital role for the IAPs in maintaining epidermal homeostasis and host-microbe symbiosis. TNF, IFNg and FasL cytokines have all been proposed to play a causal role in TEN and our results suggest Smac-mimetic injection as a model to investigate this poorly understood condition. Our results also suggest that, contrary to the current dogma, normal skin flora can contribute to skin inflammation and might play a role in TEN. This work may ultimately lead to identification of new therapeutic targets for skin diseases such as TEN.

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2 Ka Yee FUNG Immunoregulatory role of IL-11 in autoimmune inflammation Fung KY (1), Burstroem L (1), Preaudet A (1), Leung PS (1), Zhang X(2), Markovic-Plese S (2), Putoczki TL (1) (1) Walter and Eliza Hall Institute of Medical Research, Inflammation Division, Melbourne, VIC (2) Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

AIMS: To investigate the immunoregulatory role of Interleukin (IL)-11 in autoimmune inflammation. BACKGROUND: IL-11 is a member of the IL-6 family of cytokines that signals through transmembrane glycprotein-130 (Gp130) beta-subunits resulting in activation of the transcription factor, STAT3. While IL-6 has been the subject of intense investigation, there has been very little research into the function of IL-11. Since both STAT3 and IL-6 play an important role in polarising IL-17 producing helper T (Th17) cells, which is a subset of CD4 T helper cells that play a vital role in inflammation. Therefore, we investigate whether IL-11 can also polarize Th17 cells and its role in Th17-dependent autoimmune inflammation. Methods: We used In vitro T cell culture system to differentiate Th17 cells in the presence and absence of IL-11. We also used the 'gold standard' Th17 cells-dependent experimental autoimmune encephalomyelitis (EAE), mouse model for Multiple Sclerosis (MS) to examine the in vivo role of IL-11 in regulating Th17 cells during inflammation. RESULTS: We identified that IL-11 can induce the differentiation of both mouse and human Th17 cells in a manner that is independent of the 'typical inducer' IL-6. We have further shown that mice deficient for IL-11 receptor (il11r-/-) are less susceptible to the Th17 dependent EAE model of MS, with reduced weight-loss and clinical scores compared to their heterozygote and wild-type littermates. The disease resistance in il11r-/- mice was associated with a decrease in pathogenic Th17 cell infiltration into the spinal cord and brain and reduced serum IL-17A. Similarly, treatment of wild-type mice with an IL-11R neutralising antibody reduced disease severity and serum IL-17A, while the treatment of wild-type mice with recombinant IL-11 accelerated EAE and was associated with an increase in Th17 cell infiltration in the spinal cord and serum IL-17A production. CONCLUSION: Taken together, these results suggested that IL-11 contributes to drive Th17 cells differentiation both in vivo and in vitro. Most importantly, targeting Il-11 signalling could be a possible therapeutic strategy for treating MS patients.

3 Pablo Casillas-Espinosa Anti-epileptogenic effects of a selective T-type Ca2+ channel antagonist, Z944, in the post-status epilepticus model of temporal lobe epilepsy CASILLAS-ESPINOSA PM(1), Braine EL(1), Shultz SR(1), Jones NC(1), Snutch TP(2), O’Brien TJ(1), Powell KL(1). (1) The Department of Medicine, The University of Melbourne, Royal Parade, Parkville, VIC. 3050, VIC, Australia. (2)Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada

Aim and background: Current pharmacotherapy for TLE is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. T-type Ca2+ channels have been strongly implicated in the pathogenesis of TLE. Therefore, in this study we set out To evaluate the effects of Z944, a potent and selective T-type Ca2+ antagonist, on epileptogenesis and epilepsy-related behavioural comorbidities in the post-status epilepticus (post-SE) model of TLE. Methods: Rats underwent implantation of EEG recording electrodes and kainic acid induced SE for 4 hours. SE was terminated with diazepam and animals were assigned to one of five treatment groups: post-SE + Z944 (60mg/kg/day, n=8);

post-SE + levetiracetam (200mg/kg/day, n=9); post-SE + vehicle (n=8); sham + vehicle (n=6) or sham + Z944 (60mg/kg/day, n=6). Treatments were delivered by continuous subcutaneous infusion for four weeks. Four weeks after completion of treatment, the animals had two weeks of continuous video-EEG monitoring to evaluate the effects of the different treatments on epileptogenesis. Behavioural tests were performed to evaluate anxiety, depression, learning and memory, and brain tissue was collected for molecular analysis. Results: Following drug washout, post-SE + vehicle animals had the highest average number of seizures per day (0.77±0.09), followed by post-SE + levetiracetam (0.536±0.076). Treatment with Z944 greatly reduced the number of seizures per day (0.017±0.012) which was significantly different when compared to vehicle and levetiracetam treated animals (p<0.0001). Only two of the eight post-SE + Z944 animals had seizures recorded (one seizure each during the two weeks of recordings), whereas all the animals in the other post-SE groups had several seizures. Depressive-like behaviour was assessed using the sucrose preference and the force swim test (FST). The post-SE + vehicle rats had reduced sucrose preference (and indicative of anhedonia) when compared to shams (p < 0.05). For the FST, post-SE + vehicle rats spent significantly more time immobile (p <0.05) that shams, which is an indicative of despair. In contrast, treatment with Z944 after SE normalised the pathological behaviour on both tests. Conclusion: Treatment with Z944 has a powerful anti-epileptogenic effect in the post-SE model of TLE and reduces comorbid depressive-like behaviour associated with this disorder. This indicates that pharmacologically targeting T-type Ca2+ channels may be an effective disease-modifying treatment for TLE. Z944 has been found to have a favourable safety profile in early phase clinical trials for pain facilitating the translation of the results of this preclinical study into a clinical anti-epileptogenesis trial.

4 Paul Nguyen IL-18 is associated with the onset and progression of gastric cancer NGUYEN P(1), Busuttil R(2), Mielke L(1), Belz G(1), Boussioutas A(2), Ernst M(3), Putoczki T(1). (1) Walter and Eliza Hall Institute of Medical Research, (2) Peter MacCallum Cancer Centre, (3) Olivia Newton-John Cancer Research Institute

Introduction: Gastric cancer (GC) is the fourth most prevalent, and the third most common cause of cancer-related death worldwide. The disease is generally asymptomatic, and consequently is often diagnosed at an advanced stage when metastasis is present, and limited treatment options are available. Chronic inflammation is recognised as an integral component in the development and progression of GC, and is associated with increased infiltration of immune cells into the tumour microenvironment. The production of pro-inflammatory cytokines by these cells may contribute to tumour progression through activation of pathways promoting tumour cell survival and proliferation. Previous work from our lab has shown that therapeutic inhibition of the inflammatory cytokine interleukin (IL)-11 is effective in ameliorating disease progression in gastrointestinal cancer, however, it is unclear what role other pro-inflammatory cytokines, such as IL-18, might have in disease progression. Methods: To characterise the role of different pro-inflammatory cytokines in GC, we first analysed microarray and qRT-PCR data of from human GC specimens and adjacent non-tumour tissue. Following the generation of a candidate list of cytokines deregulated in human GC, the role of individual cytokines in disease progression was examined using a validated mouse model of intestinal-type GC, referred to as Gp130Y757F, by crossing into cytokine knock-out strains and monitoring tumour

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burden and the expression of genes and proteins classically associated with tumorigenesis. Results: We found that the expression pro-inflammatory cytokines including IL-1β and IL-18 were significantly elevated in the tumours of human GC patients compared to non-tumour tissue. In Gp130Y757F mice, genetic ablation of IL-18, but not of IL-1β significantly reduced gastric tumour burden, which was associated with a reduction in the number of intratumoral macrophages, but not lymphocytes. This observation correlated with decreased expression of pro-inflammatory (Ifng, Tgfb1), antimicrobial (Reg3b, Reg3g), and tissue remodelling (Mmp9) genes in these mice. Conclusion: Our results demonstrate that IL-18 has an important role in GC disease progression, and may serve as a potential therapeutic target.

5 Peter Revill Splice Variants of hepatitis B virus are strongly associated with liver cancer. Pan M-H(1), Mason H(2), Bayliss J, Hu H-H(1), Lin Y-L(1), Littlejohn M(2), Sozzi V(2), Locarnini S(2), Yang H-I(1), Revill PA(2) (1) Genomics Research Center, Academia Sinica, Taipei, Taiwan; (2) Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity

Introduction: Over 240 million people live with chronic hepatitis B, resulting in up to 780,000 deaths annually due to cirrhosis and liver cancer. Chronic HBV (CHB) is incurable, and infected persons have a life-long risk of developing liver cancer, the 5th most common cancer and 3rd leading cause of cancer-related mortality. Cases of HBV-related liver cancer in Australia are projected to double over the next two decades, and identifying mechanisms by which HBV causes liver cancer is of paramount importance. We have previously shown in a small pilot study that HBV splice variants were strongly associated with liver cancer(1). The purpose of the current study was to validate these findings using a large international cohort of patients HBV-mediated liver cancer, from the REVEAL study(2) in Taiwan. Method: HBV DNA in serum was purified from 231 samples from 152 patients with liver cancer and 411 samples from 378 control patients who had chronic HBV but had not developed liver cancer. The ratio of splice variant to wild-type HBV was quantified by real time PCR and associations between the relative abundance of splice variants and liver cancer determined by univariate and multivariate analysis. Results: Quantitative real time PCR for splice and wild-type HBV DNA was performed on over 600 samples, the largest study of splice variants associated with live cancer performed to date. After adjustment for the influence of other HCC-related risk factors, subjects with spliced HBV DNA level >10% were 3.3 times more likely to develop HCC than patients with lower levels of splice variants after adjustment of serum levels of HBV DNA and α-fetoprotein, and HBV genotype. Discussion/Conclusion: The mechanisms by which HBV causes liver cancer are yet to be determined, but our previous pilot study of Australian patients suggested that splice HBV variants were strongly associated with liver cancer. We have now validated this finding from over 200 patients with liver cancer (and almost 400 control patients), from a highly characterised Taiwanese cohort, showing that patients with greater than 10% of the viral quasispecies pool in serum represented by splice variants were more likely to have liver cancer than patients with low levels of splice variants. Current studies are focusing on identifying the mechanism for this association.

Cardiorespiratory Research 6 Thomas Moran Patient and carer perceptions regarding the advanced lung disease service – a new model of integrated respiratory and palliative care MORAN T(1), Thompson M(2), Le B(3), Irving L(2), Smallwood N(2). 1. Department of Medicine, University of Melbourne; 2. Department of Respiratory and Sleep Medicine, Melbourne Health; 3. Department of Palliative and Supportive Care, Melbourne Health.

Background: The Advanced Lung Disease Service (ALDS) is a unique, new model of integrated respiratory and palliative care that aims to address the unmet needs of patients with advanced, non-malignant, lung disease. Aim: To explore patients’ and carers’ experiences and satisfaction with the ALDS. Methods: All current ALDS patients and their carers were invited to complete an anonymous, confidential questionnaire with a researcher who was independent of the ALDS team. Results: Eighty-eight responses were received, from 24 carers and 64 (80.0%) of 80 eligible patients. Respondent patients’ median age was 75 years, 34 (53.1%) were male and 25 (39.1%) lived alone. 58 patients (90.6%) had a primary diagnosis of severe Chronic Obstructive Pulmonary Disease. The median number of ALDS clinic visits was 9, and 52 (81.3%) patients saw both respiratory and palliative care staff in the clinic. 66 (75.0%) respondents rated the ALDS as excellent, 18 (20.5%) as very good and 85 (96.6%) would recommend the ALDS to others. 88 (100%) respondents found the ALDS helpful, with 87 (98.9%) feeling more confident self-managing their symptoms, and 87 (98.9%) reporting the ALDS team listened to them carefully. Aspects of the ALDS which were important to respondents included: continuity of care from the same doctors and nurses - 82 (93.2%), long term care - 77 (87.5%), access to urgent clinic reviews - 63 (71.6%), and respiratory nurse home visits - 53 (60.2%). Commonly reported themes were staff warmth, kindness and friendliness, optimal disease management, patient self-management education, and opportunities to discuss all aspects of care, including future care wishes. Conclusion: ALDS patients and their carers express high levels of satisfaction with this new model of integrated respiratory and palliative care, with the empathic, caring nature of staff and long term care being highly valued.

7 Vara Perikala Case study: Obstructive Sleep Apnoea, Obesity hypoventilation, Trisomy 21 and intellectual disability in a 19 year old female PERIKALA V(1,2) Respiratory Medicine, RMH(1) Medicine and Community, RMH(2)

Introduction: Obesity Hypoventilation Syndrome (OHS) is estimated to occur between 10-20% of patients with Obstructive Sleep Apnoea (OSA) (Mokhlesi B, et al; 2008). The most common signs and symptoms are excessive daytime sleepiness, loud snoring, choking during sleep, fatigue, hypersomnolence, impaired concentration and memory, a small oropharynx, and a thick neck (Nowbar S, et al; 2004).Non-invasive ventilation (NIV) is an effective form of treatment in patients with OHS and OSA (Salord N,et al;2013). Case study: A 19 year female Ms G with a BMI of >60 was presented to the hospital with 5 days of cough, rhinorrhoea tachypnoea, nil fevers or sweats, increasing breathlessness at home. She was brought to emergency. Flu swab was negative, chest x-ray showed fluid over load and was treated with frusemide.

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Routinely the patient sleeps while in a sitting position where Sao2 is 92% an room air. During the night, the patient was de saturating to 70% on room air. No baseline data was available, only VBG : PH: 7.37, Paco2: 52, Hco3: 29, Pao2: 42, Sao2:75. Aim of the case study: Review of Implementing NIV in difficult patient population Method: Patient admitted from ED to the ICU for CPAP implementation, but was not tolerating CPAP. ENT referral was made to exclude abnormalities and foreign bodies in the neck, but nothing was found. Later the patient was discharged to the Respiratory Care Unit for further management. On arrival to the patient did not use NIV and pulled out her face mask. The next day, with the help of her sister around bed side, Resp CNC implemented NIV via Nasal pillows and stayed with patient for 10minutes. Low pressures were started such as peep 5 cmH2o and slowly increased to 15 cm h2o.The patient tolerated it well and slept on her back for first time in 15 years. No de saturations were noted. Overnight she had an oximetry study and auto CPAP, most of the time she used 8 -11 cmh2o pressures. Results: Set pressures were given, 11 cm h2o CPAP and discharged back home. Conclusion: Not only is identifying the correct NIV masks crucial the for success of NIV therapy, but starting lower pressures and staying with the patient are important in the success of this case. Discussion: Identifying these patients in ED and ICU, early referral to respiratory specialists and early implementation of NIV, not only will reduce the length of hospital stay but also the cost.

8 John Politis General Practitioners' beliefs and experiences when caring for patients with severe COPD and refractory breathlessness POLITIS J (1), Eastman P (2), Le B (2), Furler J (3), Irving L (1), Smallwood (1) 1. Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital. 2. Department of Palliative & Supportive Care, The Royal Melbourne Hospital. 3. Department of General Practice, The University of Melbourne

Introduction/Aim: Refractory breathlessness is common and undertreated in patients with advanced Chronic Obstructive Pulmonary Disease (COPD). Breathlessness management is complex and may include opioids, however there is a perceived reluctance to prescribe opioids. This study aims to understand the approaches to symptom management and palliative care undertaken by General Practitioners (GP) when caring for patients with severe COPD. Methods: GPs were invited by email and at educational events to complete a case-vignette based survey. Results: One hundred and forty-eight GPs completed the survey. In the described case of a stable, optimally managed COPD patient with severe refractory breathlessness, 90 (66%) GPs recommended adding a new medication to treat dyspnoea, of whom 38 (42.3%) recommended using an opioid. While 75 (55%) GPs thought opioids had a role in treating breathlessness in patients with severe COPD (but not in the terminal phase of their illness), in practice only 66 (49%) GPs had previously initiated or continued an opioid prescription started by another doctor for the treatment of refractory breathlessness. Only 67 (55%) GPs felt comfortable providing general palliative care themselves to their COPD patients, with these GPs being more likely to initiate opioids themselves or continue an opioid prescription to treat refractory breathlessness (p = 0.001). One hundred and twenty (88%) GPs wanted more training or

ongoing education regarding managing patients with severe COPD and refractory breathlessness. Conclusion: Most GPs recognise and are willing to add specific treatments for refractory breathlessness. However, many GPs recommend treatments for which there is no evidence or which are not included in current guidelines. Experience prescribing opioids for refractory breathlessness is low and half of GPs feel uncomfortable providing general palliative care to patients with COPD. These findings highlight current gaps in knowledge and training, which GPs themselves recognise and would like to address.

9 Sandeep Prabhu Ventricular fibrosis regresses following AF ablation in patients with persistent AF and heart failure – A multi-centre prospective study PRABHU S (1,2,3,4, 5), Costello B (2,3), Mclellan AM (2,3), Voskoboinik A (1,2,3,4, 5), Lockwood SM (4), Stokes MB (4), Pathik B (1, 5), Nalliah C (1,5), Wong GR (1,5), Azzopardi S (2,3), Gutman S (2,3), Lee G (1), Mariani J (2,3), Kaye DM (2,3), Ling L ( 1. Melbourne Health, 2. Alfred Health, 3. Baker Heart and Diabetes Institute, 4. MonashHeart, 5. University of Melbourne

Aim: To determine the reversibility of diffuse ventricular fibrosis associated with idiopathic dilated cardiomyopathy (IDCM) and persistent AF following the restoration of sinus rhythm and the improvement in ejection fraction. Introduction: AF ablation improves symptoms and systolic function in patients with comorbid persistent AF and IDCM. However, whether diffuse ventricular fibrosis associated with cardiomyopathy, as measured by cardiac MRI, improves in concert with LVEF following catheter ablation is unknown. Methods: Patients with IDCM (LVEF≤45%) and persistent AF with previously failed medical rhythm control, and no contraindication to cardiac MRI (CMR) were prospectively enrolled and underwent AF ablation and implanted with loop recorders, for AF monitoring. All patients underwent CMR with native ventricular T1 mapping, a histologically validated index of diffuse ventricular fibrosis, and BNP, prior to and at 6 months post ablation. Results: 18 patients were enrolled across 3 centres (Melbourne Health, Alfred Health and MonashHeart): (age 59±13, 92% male, mean continuous AF duration 12±5.4 months, NYHA class 2.5±0.5, mean 24 hour heart rate 81±12bpm and LA size: 34±4.0cm2) All patients underwent catheter ablation (PVI and posterior LA isolation) and were in SR at 6 month follow up (AF burden <5% in 94% patients). Compared to baseline, there was a significant increase in left ventricular ejection fraction (baseline vs 6 months: 33±8.0% vs 47±11%, p<0.001), reduction in indexed left ventricular end systolic volume (80±34ml/m2 vs 63±34ml/m2, p<0.001), reduction in BNP (-351±213ng/L vs 109±100ng/L, p<0.001) and NYHA functional class (2.5±0.5 vs 1.3±0.6, p<0.001) at 6 months. This was associated with reduction in native T1 time from baseline to 6 months (1260±120ms vs 1199±77ms, average ∆T1 mapping time =-62±123ms, p=0.002). Conclusion: Recovery of LVEF in patients with PeAF and IDCM undergoing AF ablation is associated with a shortening of native T1 times consistent with regression of diffuse ventricular fibrosis. Ventricular structural remodelling associated with a presumed arrhythmia mediated cardiomyopathy, may be reversible by the restoration of sinus rhythm.

10 Dominica Zentner A rapid scoring tool to assess mutation probability in patients with inherited cardiac disorders ZENTNER D(1,2), Thompson T(2), Taylor J(2), Bogwitz M(2), Trainer A(2), Vohra J(1,2), Winship I(2), James PA(2)

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1 Dept of Cardiology, Royal Melbourne Hospital; 2 Genomic Medicine, Royal Melbourne Hospital

Aim: To ascertain whether clinical and family history variables can assist decision making about genetic testing in the population of patients presenting to a cardiac genetic clinic (CGC). Background: The development of massive parallel sequencing (MPS) in genetics remains an expensive test and has variable yield across the spectrum of inherited cardiac diseases. Genetic testing in this area remains unfunded. The CGC determined to explore whether clinical and family history variables might predictively assist with calculation of pre test probability of positive mutation detection outcome. This would improve the process of patient counselling and assist the clinic in offering access to testing in an equitable manner. The population attending CGC represent the broad spectrum of inherited cardiac disease, and the decision was made to explore a non disease specific tool. Methods: Utilising CGC transition from single gene/ small number of candidate gene testing to MPS, consecutive MPS cases were identified (Sept 2014 - Dec 2015, n = 126). Cases were scored for the presence of pre-determined clinical and family history variables, blinded to MPS results. Subsequent unblinding allowed ascertainment of the odds ratio (OR) between each variable and positive mutation detection. A clinical tool was developed and variables with higher OR association given a higher weighting. The revised tool was subsequently validated in a cohort of 40 patients. Results: Mean tool score in the derivation cohort was 3.94, mutation positive subgroup: 4.74 and mutation negative subgroup: 3.49 (t test, p < 0.0001). As the clinical tool score increased, there was a strong linear correlation with an increasing probability of detecting a mutation (r2 = 0.88). The maximal enrichment for individuals carrying a mutation occurred with a threshold clinical tool score of 3 (OR 5.63, CI 1.59 - 19.92, p = 0.004) with a sensitivity of 93% and a negative predictive value of 88% but a positive predictive value of only 43%. Had MPS testing only being offered to patients with a clinical tool score greater than or equal to 3 (derivation cohort) testing would have been undertaken in 100 individuals with 3 mutations missed. Conclusion: Routinely collected information on probands and their family history allows identification of individuals with a greater chance of positive mutation detection, with state of the art testing and current genetic understanding. This improves pre test counselling, allows equitable offer of testing and can be calibrated to a predictable ratio of positive mutation and missed opportunity cases for individual health services.

Health Services Research 11 Wendy Bower Patient reported outcome measures for nocturia BOWER WF(1), Rose G(1), Denys M(2), Kumps C(2), Whishaw D(1), Khan F(3), Everaert K(2) 1. Department of Medicine & Community Care, Royal Melbourne Hospital; 2. Department of Urology, Ghent University Hospital; 3. Department of Rehabilitation, Royal Melbourne Hospital

Aim: The aims of this study were to i) investigate predictors of nocturia bother and episode frequency and ii) identify variables that can be individualized as outcome measures of treatment efficacy. Background: Change in voiding frequency is the current marker of treatment efficacy for nocturia. However, nocturia can change from night to night in response to clinically relevant comorbidities. As such nocturia frequency may be an insufficient outcome measure. Methods: Prospective data from 113 patients ≥18 years of age with nocturia ≥ 1/night attending the Continence Clinic at Royal

Melbourne Hospital was merged with data collected from the 91 similar participants presenting to Ghent University Urology Clinic, Belgium. Exclusion criteria were end-stage renal failure, bladder cancer, pelvic radiotherapy, terminal malignancies, and urinary catheterisation. Items in the datasets were derived from the Pittsburgh Sleep Quality Index, ICIQ-Overactive Bladder, ICIQ-Female Lower Urinary Tract Symptoms Long Form, ICIQ-Male Lower Urinary Tract Symptoms Long Form and Nocturia Quality of Life patient-completed metrics. Approval was obtained from the Human Research Ethics Committee at each institution. Descriptive analysis, univariate and multivariate logistic regression were performed. Variables independently predictive of high i) nocturia frequency and ii) nocturia-related bother were developed into patient-reported outcome measures (PRO). Results: Variables predictive of nocturia ≥2 per night: high bother (OR 7.34); daily urgency (OR 5.29); short time to first waking (OR 0.26); low sleep efficiency (OR 2.37); breathing dysfunction (OR 5.94) and poor sleep quality (OR 2.37). Independent predictors that explained 44-61% of the variance of high frequency nocturia were short time to first waking to void, bother and daily urgency. Predictors of high nocturia-related bother were: poor sleep quality (OR 4.13), short time to first waking (OR 0.60), daily urgency (OR 2.78), high nocturia frequency (OR 1.70) and weekly use of sleep medication (OR 2.24). High bother related to a single episode of nocturia was associated with impaired quality and total hours of sleep, use of sleep medication and daytime fatigue. Older age, male gender and urgency were protective against high bother despite multiple episodes of nocturia. Eight individualised outcome measures addressing the 3 domains of: sleep (efficacy, quality, need for medication), lower urinary tract (urgency, time to first waking) and wellbeing (nocturia-related bother, daytime sleepiness and loss of enthusiasm) were developed. Conclusions: This is the first study to report items to measure change in variables of importance to patients with nocturia. These measures sit alongside self-report of nocturia frequency.

12 Catherine Granger Preoperative exercise training for patients with non-small cell lung cancer: A Cochrane Systematic Review GRANGER C(1,2), Cavalheri V(3,4,5). 1 Royal Melbourne Hospital; 2 The University of Melbourne, Victoria; 3 Curtin University, Western Australia; 4 Cancer Council Western Australia, Western Australia; 5 Institute for Respiratory Health, Western Australia

Aim: To determine the effect of preoperative exercise training on postoperative outcomes including risk of developing a postoperative pulmonary complication, postoperative duration of intercostal catheter and length of hospital stay in adults scheduled to undergo lung resection for non-small cell lung cancer (NSCLC). Background: Surgical resection for early stage NSCLC offers the best chance of cure, but is associated with a risk of postoperative pulmonary complications. It is currently unclear if preoperative exercise training, and the potential resultant improvement in exercise capacity, may also improve postoperative outcomes such as the risk of developing a postoperative pulmonary complications, the length of postoperative intercostal drainage or the length of hospital stay. Methods: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PEDro and SciELO (The Scientific Electronic Library Online) up to November 2016. Randomised controlled trials (RCTs) were included in which study participants who were scheduled to undergo lung

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resection for NSCLC were allocated to receive either preoperative exercise training or no exercise training. The two review authors independently screened and assessed studies for inclusion. Risk of bias was assessed using the Cochrane seven evidence-based domain table Meta-analyses were conducted were possible. Results: Five RCTs involving 167 participants were identified. Overall, the risk of bias in the included studies was high. Pooled data from four studies demonstrated that preoperative exercise training reduced the risk of developing a postoperative pulmonary complication by 67% (RR 0.33; 95% CI 0.17 to 0.61). Compared to the control group, the number of days patients in the intervention group needed intercostal catheters was lower (MD -3.33 days; 95% CI -5.35 to -1.30 days) (pooled data from two studies), and postoperative length of hospital stay was also lower in the intervention group (MD -4.24 days; 95% CI -5.43 to -3.06 days) (pooled data from four studies). Conclusion: Preoperative exercise training appears to reduce the risk of developing a postoperative pulmonary complication, the duration of intercostal catheter and postoperative length of hospital stay in people undergoing lung resection for NSCLC. The findings of this review should be interpreted with caution due to disparities between the studies, methodological limitations, risk of bias and small sample sizes. This systematic review emphasises the need for larger RCTs. Grant Support: Catherine Granger is supported by a Victorian Cancer Agency Clinical Research Fellowship. Vinicius Cavalheri is supported by a Cancer Council WA Postdoctoral Fellowship.

13 Lisa Hebel Adult Mental Health: Implications for their dependent children HEBEL L (1,2) Joubert L (2,1) 1. NorthWestern Mental Health, Melbourne Health; 2 University of Melbourne, School of Social Work

Aim: To investigate the formal and informal social networks of parent clients of adult mental health services and to determine the identification, assessment and interventions of the needs of the dependent children in order to explore options for improving work between the various systems that can offer support and help to these children parents and families. Background: In Australia there has been 15 years of COPMI (Children of Parents with a Mental Illness) and FaPMI (Families where a Parent has a Mental Illness) initiatives plus 10 years of focus on Victoria’s Vulnerable Children post the enactment of the Children's Youth and Family Act. There are recent examples of concern, including a 10 year old child not attending school for over a year, a child witnessing their mother cutting her own throat with no documented follow up for this child and a 3 year old child’s whereabouts not being known overnight when mother admitted to hospital. Early trauma is a risk factor for later mental health problems and prevention and early intervention are the most effective ways to reduce the impact of trauma. Having a mental illness does not make someone a bad parent however these children can be at risk. Methodology: In 2015 a clinical data mining (CDM) project was carried out with 25 files of clients who were parents, randomly selected from 4 adult mental health services (100 in total). A 26 question quantitative CDM tool focused on demographics, psychosocial needs as well as the formal and informal supports of parent clients. Of those 25 files from each service, 10 were randomly selected (40 in total) for a more in-depth review, answering 10 specifically designed qualitative questions investigating the documented identification, assessment and interventions of the needs of the dependent children of registered clients.

Results: Themes of social isolation, limited formal and informal social supports, poverty, violence and trauma were found. The impact on the clients’ ability to parent and have potential to cause direct or indirect harm to the children will be described. Conclusions: There is still more to do to recognise the children are there and to support the parents who have heightened isolation and cumulative social distress. The service system does not make it easy for the clinicians involved with these parents, to access the most appropriate help for these children in a timely manner.

14 Margaret Pozzebon Spousal recollections of early signs of primary progressive aphasia Pozzebon, Margaret (1,2,3), Douglas, Jacinta (1,4) and Ames, David (3,5,6) (1) School of Allied Health, La Trobe University; (2) Speech Pathology Department, Royal Melbourne Hospital; (3) Cognitive Dementia and Memory Service, Royal Melbourne Hospital; (4) Summer Foundation, Victoria; (5) The National Ageing Research Institute and University of Melbourne; (6) Department of Old Age Psychiatry, University of Melbourne.

Background: Although primary progressive aphasia (PPA) is known to be characterised by progressive loss of language abilities, knowledge about the earliest symptoms is limited. Aim: This study sought to explore spousal recollections regarding the earliest manifestations of PPA and to compare the nature of the earliest perceived symptoms across the three PPA variants. Method: In-depth interviews focusing on earliest symptoms of illness onset were conducted with 13 spouses whose partners were diagnosed with PPA. The data was collated, analysed and key themes identified and compared across the PPA variants. Results: Spousal retrospective accounts indicated the 3 PPA variants (non-fluent, logopenic and semantic) had a signature profile announcing illness onset. The findings suggest the possibility that PPA initially presents as subtle changes in interpersonal-relational contexts for svPPA and nfvPPA rather than overt receptive and expressive language impairments. The initial symptoms for partners with nfvPPA were speech production and fluency issues. The nuances revealed through personal narratives illustrate the challenges associated with early identification, particularly as very early manifestations of PPA are unlikely to be easily captured in standardised clinical assessments, scales and questionnaires. Conclusion: Understanding the nature of symptoms perceived in the earliest stages of PPA has potential to inform earlier and accurate diagnosis and interventions to assist those living with the illness.

15 Lauren Ross Palliation and the use of diagnostic tests in patients dying in hospital from COPD ROSS, L(1), Taverner, J.(1.), Bartlett, C.(1), Irving, L.(1), Philip, J.(2), and Smallwood, N.(1) 1. Department of Respiratory Medicine, Royal Melbourne Hospital 2. 2. Department of Palliative Care, St. Vincent’s Hospital Melbourne.

Background: COPD is an incurable, progressive illness, with associated significant morbidity and mortality. Accurately determining prognosis in severe COPD is well-recognised to be challenging, as is diagnosing “active dying”. Aim: To audit the use of diagnostic tests in both recognising active dying and after establishing the “Goal of Care” (GOC) was palliation in COPD patients dying in hospital. Method: A retrospective audit of 475 consecutive patients who died from COPD at an Australian teaching hospital between 2004-2016.

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Results: Of 221 patients included: 136 (60%) male, median age 80 years; median respiratory function: FEV1 0.8L (41%), FVC 2.0L (73%) and DLco 9 (41%); and 109 (49%) used home oxygen. 63 (29%) patients had palliative care involvement prior to the final admission. During the terminal admission patients received on average 7 episodes of venepuncture, 9 Arterial Blood Gas tests and 3 chest radiographs. Receiving increased diagnostic tests was associated with age <70years, admission under respiratory medicine team, ICU admission, and radiological evidence of pneumonia on admission. For 187 (85%) patients, the GOC was documented as palliation during the final admission, a median of 1.8 days prior to death. 131 (70%) patients had diagnostic tests performed on the day palliation was initiated, and despite the change in GOC 22 (12%) patients had further tests following palliation. 70 (32%) had tests on the day they died. Conclusion: Excessive, unnecessary diagnostic tests were performed in one third of inpatients dying from COPD, including those following a clear decision to palliate. Failure to clinically diagnose active dying imposes an unnecessary burden of diagnostic tests on those in their final hours.

Public Health Research 16 Justin Denholm SIRCLE – a randomised controlled cost comparison of self-administered Short-course Isoniazid and Rifapentine for Cost-effective Latent tuberculosis Eradication JUSTIN T DENHOLM (1-3), Emma S McBryde (4), Damon Eisen (5), Alan Street (2), Elizabeth Matchett (2), Caroline Chen (6), Thomas Shultz (2), Beverly Biggs (2), Karin Leder (2,7) 1.Victorian Tuberculosis Program, Melbourne Health 2. Victorian Infectious Diseases Service, Royal Melbourne Hospital 3. Department of Microbiology and Immunology, University of Melbourne 4. James Cook University 5. Townsville Hospital 6. Pharmacy Department, Royal Melbourne Hospital, 7. School of Public Health and Preventive Medicine, Monash University

Aim: To evaluate the comparative cost-effectiveness of standard and short-course therapy for LTBI in an Australian context Background: Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A three-month course of weekly isoniazid and rifapentine (3HR) has been shown to be as effective as nine months of daily isoniazid, and associated with less hepatotoxicity however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost effectiveness of this new therapeutic approach is uncertain. Methods: Single centre randomised controlled trial, conducted between December 2013- March 2016. Participants underwent 1:1 randomisation to either a 9 month course of daily isoniazid or 12 week course of weekly isoniazid and rifapentine. Primary outcome measure was total healthcare system costs (AUD) per completed course of LTBI therapy. Secondary analyses were performed to consider cost-effectiveness under varying assumptions regarding commercial cost of rifapentine. Results: Overall, 34 of 40 participants in the 9H group (85%) and 36/40 in the 3HR group (90%) completed therapy. One patient in the 3HR group was hospitalised for a febrile illness; no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HR was significantly lower at 511 AUD (p<0.01). Conclusions: This study provides evidence that short-course INH/RPT is a well-tolerated and cost-effective tool for the treatment of LTBI in an Australian context.

17 Kudzai Kanhutu Postcards from the digital health frontier; using telehealth for Hepatitis C care Schulz T1, KANHUTU K1,2,3, Sasadeusz J1, Watkinson S1, Biggs BA1,2 1 Royal Melbourne Hospital, 2 University of Melbourne Faculty of Medicine, Dentistry and Health Sciences 3 Health Informatics Society Australia

Aim/Background: The Victorian Infectious Diseases Service based at the Royal Melbourne Hospital currently provides telehealth care for rural and regional patients with hepatitis C. Telehealth is defined as the ‘use of telecommunication techniques for the purpose of providing telemedicine, medical education, and health education over a distance".1 There is evidence to suggest that patients from rural and regional sites are subject to worse outcomes from chronic hepatitis C when compared with their urban counterparts. The progressive roll out of the national broadband network and increasing availability of web based videoconferencing platforms and mobile devices have provided unprecedented capacity to manage patients remotely.The primary outcome of this study is to demonstrate that telehealth delivered hepatitis C management achieves comparable virological outcomes to standard face to face care. Methods: The study is part of a quality audit of the hepatitis service. Key outcome and process measures include: Proportion of patients achieving a sustained virological response (SV); Failure to attend rate (FTA); Frequency of technical difficulti; Consult duration tie. Results: In the 12 months since March 1st 2016, over 50 patients have been managed via telehealth. Of those who have so far completed therapy an SVR rate of 94% of has been achieved. Expected SVR genotype 1 ( >95% ); genotype 3 ( >85% ). Technical difficulties occurred in less than 10% of consultations with FTA of 17%. Consult duration was on average 15 minutes or less. Conclusion: Our completed patient cohort results suggest comparable outcomes for telehealth managed patients as compared to traditional modalities even when adjusted for age, gender, hepatic fibrosis status and co-existent co-morbidities. In the context of increasing state and federal government prioritisation of telehealth as a means of delivering patient centred care; we discuss the challenges and benefits of outpatient telehealth services as we enter the era of accelerating digitally enabled healthcare.

18 Philippe Lachapelle The Royal Melbourne Hospital thunderstorm asthma cohort LACHAPELLE P, Harun NS, Irving L, Douglass JA The Royal Melbourne Hospital

Aim and Background: The 21st of November 2016, an asthma epidemic occurred in Melbourne which lead to unprecedented numbers of asthma presentations to emergency department (ED), hospitalisations and deaths. While similar thunderstorm asthma episodes have been reported previously, it is still unclear why some patients developed life-threatening asthma exacerbations. Methods: We prospectively followed patients who had a thunderstorm asthma exacerbation on the 21st-22nd of November 2016 and who agreed to be seen at the RMH asthma clinic. All patients who presented to RMH ED with asthma symptoms between 15:30 and noon the next day were contacted. Subjects were offered to attend for a complete asthma evaluation with lung function, SNOT-22 and asthma control questionnaire (ACQ), fraction exhaled nitric oxide (FeNo), blood eosinophils, total IgE and specific IgE to allergens (RAST) measurement. Characteristics between the

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more severe hospitalised patients and the non-hospitalised subjects were compared using person Chi-Square analysis. Results: Of the 241 patients (49% female, mean (±SD) age=36±13) who presented at RMH ED, 49 declined the appointment, 45 had no or incorrect contact details and 89 are as yet uncontactable. To date, a total of 58 subjects (50% female, mean age=35±10) were evaluated at the asthma clinic. Subjects were majority non-Caucasian (60%), Australian-born (62%), non-smokers (71%) and had allergic rhinitis (95%). Subjects were of mean ACQ score=1.36 ±1, SNOT-22 score=31±19, blood eosinophils=0.37±0.3, FeNo=58±42ppb and FEV1=92±17L. Only 10 subjects (17%) had no prior asthma diagnosis and had never reported asthma symptoms after a careful history was taken. A total of 20 patients (34%) were hospitalised and 38 (66%) were discharged from ED. In the hospitalised group, 75% had known asthma and 63% had current asthma symptoms compared to 63% and 47% in the non hospitalized subjects (p=0.4, p=0.2 respectively). Thirteen hospitalised patients (65%) left the ED with an inhaled corticosteroids (ICS) prescription compared to 6 subjects (16%) in those not hospitalised (p<0.01). Of the 39 patients (67%) who left hospital without ICS prescription, only 8 were subsequently put on ICS by their family doctor. All subjects had specific RAST testing to ryegrass. Hospitalised group had greater proportion of “extremely” high RAST to ryegrass, defined as IgE ≥ 100 kUA/L, compared to the non hospitalised (64 vs 42%, p=0.2). Conclusion: RMH’s patients who suffer from a thunderstorm asthma exacerbation were all sensitized to ryegrass. Specific ryegrass IgE titer were higher in those severely affected.

19 Ebenezer Owusu Adjah Association of adiposity level at diagnosis of type 2 diabetes with cardiovascular and mortality risk: Ethnicity-specific real world study OWUSU ADJAH E (1,2) , Paul S (1,3) 1. Melbourne Epicentre; 2.QIMR Berghofer Medical Research Institute; 3. University of Melbourne

Aim: To compare the association of body mass index (BMI) at the time of diagnosis of type 2 diabetes mellitus (T2DM), with the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in White Europeans (WE), African-Caribbeans (AC), and South Asians (SA). Background: While the risk of developing diabetes is known to vary over the adiposity levels among different ethnic groups, the ethnicity-specific long-term CVD and ACM risks at different levels of BMI in patients with T2DM have not yet been studied. Methods: From a nationally representative UK primary care database, 56443 WE, 4370 AC, and 8844 SA patients who were diagnosed of T2DM (after 1999), aged 18 – 70 years, and without history of CVD, kidney disease, and cancer were identified. CVD was defined as first occurrence of heart failure, stroke or ischemic heart diseases. The adjusted CVD and ACM risk in different BMI categories, compared to grade 1 obesity (30-35 kg/m^2), were estimated for the three ethnic groups. Results: The mean age / BMI at diagnosis in WE, AC, and SA were 54 years / 33.0 kg/m^2, 49 years / 31.4 kg/m^2 and 48 years / 29.9 kg/m^2 respectively. The proportions of obese patients were 69%, 60%, and 48% respectively. African-Caribbean patients had the highest HbA1c and LDL-cholesterol levels at diagnosis compared to WE, and SA patients. The median follow-up time was similar (7 years) across the ethnic groups. Among WEs, compared to patients with grade 1 obesity at diagnosis (mean time to CVD 4.4 years), normal weight patients developed CVD significantly earlier by 0.5 years (95% CI: 0.2, 0.9 years).

With a mean time to death of 7.1 and 7.5 years among grade 1 obese WEs and SAs respectively, those with normal body weight at diagnosis were significantly more likely to die earlier by 0.8 years (95% CI: 0.3, 1.4 years) in the WE group and by 2.0 years (95% CI: 0.4, 3.6 years) in the SA group. Conclusion: This study in newly diagnosed patients with T2DM, without history of CVD, renal complications and malignancies at diagnosis, suggests significantly different patterns of association of adiposity levels with cardiovascular and mortality risks in different ethnic groups. Normal weight WEs and SAs appears to have significantly higher mortality risk compared to those with grade 1 obesity at the time of diabetes diagnosis. However, this paradoxical association of lower adiposity level and higher mortality risk was not observed among the AC people.

20 Marie Parsons Identification of clinically relevant colon cancer genes predictive of improved relapse free survival Parsons M (1, 2), Mouradov D (1,3), Ward.R (4), Gibbs P (1), Hawkins N (5) and Sieber O (1,3) 1. Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research. 2.Department of Surgery, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne. 3.Department of Medical Biology, University of Melbourne. 4. Office of the Deputy Vice-Chancellor (Research), The University of Queensland. 5. School of Medicine, The University of Queensland.

Colorectal cancer (CRC) is the third most common cancer worldwide, affecting over 15,000 individuals in Australia each year. While CRC is often detected at a stage where resection of the primary tumour is possible, approximately 50% will relapse and die from metastatic disease. Prognostication is mainly determined by tumour depth (T), lymph node stage (N) and the extent of cancer spread (M). However, clinical outcomes of patients with the same TNM stage can be heterogeneous. Therefore, there is a need to identify markers to better predict prognosis and stratify patients for treatment regimes. A panel of 113 candidate CRC genes were identified as significantly mutated in whole genome and whole exome sequencing studies from 361 MSS colon cancers and 63 CRC cell lines. Custom amplicon panels for target enrichment were designed for use with the HaloPlexTM target enrichment system. Sample libraries were prepared for 274 patients with stage II/III CRC using the automated Bravo liquid handling platform followed by next-generation sequencing (NGS). Functional analysis was then performed using a high-throughput siRNA screen for migration and proliferation. Analysis of the 113 candidate genes identified 31 genes recurrently mutated above 10 percent in our discovery cohort. We identified 4 genes previously reported as colon cancer genes (APC 68%, TP53 60%, KRAS 30% and PIK3CA 20%), confirming APC, TP53 and KRAS as the most frequently mutated genes in CRC. To identify novel and clinically relevant genes, the 31 genes in our discovery cohort were tested for association with clinical features. In the discovery cohort, 24/31 genes were significantly associated with right sided CRC, 10/31 with mucinous CRC, 9/31 with stage II CRC and 7/31 with improved relapse free survival (RFS). Of these significantly associated genes, 10/24 genes were validated as significantly associated with right sided CRC, 3/9 with stage II and 3/10 with mucinous CRC in the validation cohort. Five of these genes were selected for further investigation as they were significantly associated with improved RFS, together with one or more clinical feature. In a primary screen 4 transfected cell lines were assessed for cell viability and migration. A total of 10/31 of the top mutated genes showed decreased proliferation and 4/31 genes showed increased proliferation. For migration, 10/31 genes showed

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increased migration while 5 genes showed decreased migration. Identification of novel recurrently mutated genes is key to a better understanding of the molecular mechanisms of CRC and development of novel therapeutics.

Cancer Research 21 Suad Abdirahman Establishing human colorectal cancer patient derived xenografts for pre-clinical drug trials ABDIRAHMAN S, Preaudet A, Sieber O, Putoczki T The Walter and Eliza Hall Institute of Medical Research

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and affects approximately 15,000 Australians every year. When the cancer is detected early, it is often resectable; however, approximately 50% of the patients will experience a relapse and succumb to metastatic disease. Despite many advances in cytotoxic and targeted therapies in recent years, the development of resistance remains a challenge. Standard cell line xenograft models used to study it do not accurately recapitulate heterogeneous nature of the human disease, and as a result many pre-clinical drug targets fail in clinical trials. In addition, using cell lines in cell culture to determine the efficacy of new drug targets has revealed inconsistent results when compared to patient treatment response. As a result, the lack of appropriate animal models to accurately predict the response of anticancer drug targets limits most research opportunities. Aim: Our aim was to establish and characterise a series of CRC patient derived xenografts (PDXs) for use in anticancer drug studies. Methods: PDXs were created when fresh human tumour samples were engrafted into immunocompromised mice directly after patient surgery. The tumour engraftment and growth rates of the PDXs were then monitored over time. Haematoxylin and Eosin staining, immunohistochemical staining and western blotting were used to compare the stability of the mouse tumours relative to the original patient tumours after serial transplantation. Results: We have successfully generated 21 PDXs representing different stages of CRC samples. Our tumour engraftment rate is 70% following subcutaneous implantation and our preliminary histopathological analysis shows that the features of the original patient tumour are retained in the mouse xenografts after serial transplantation. Conclusion: PDXs are physiologically relevant pre-clinical models where the patient tumour heterogeneity, genetic profile, and gene expression patterns are retained. Our established PDXs will serve as a platform to study the effects of novel targeted therapies.

22 Dan Buchanan Somatic causes of tumour mismatch repair-deficiency in Lynch-like colorectal and endometrial cancers BUCHANAN DD(1,2,3), Mark Clendenning, Christophe Rosty, Harindra Jayasekara, Jihoon E. Joo, E. Ming Wong, Rhiannon J. Walters, Neil O’Callaghan, Susan Preston, Khalid Mahmood, John L. Hopper, Roger L. Milne, Graham G. Giles, Dallas R. English, Melissa C. 1 Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne 2 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne 3 Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital.

Aim: The aims of this study were to investigate somatic causes of tumour MMR-deficiency and to study survival in individuals with LLS.

Background: A high proportion of individuals affected with colorectal cancers (CRCs) or endometrial cancers (ECs) that demonstrate tumour mismatch repair (MMR) deficiency are categorised as having “Lynch-like syndrome”(LLS), due to the absence of tumour MLH1 methylation or germline MMR gene mutations after standard screening approaches. Methods: Study participants with incident MMR-deficient CRC (n=193; ACCFR and MCCS) or EC (n=197; ANECS and MCCS) were categorised as either Lynch Syndrome (LS) (germline MMR gene mutation), or having MLH1 methylation or LLS. Lynch-like tumours were tested for somatic MMR gene mutations using AmpliSeq-Ion Proton custom capture sequencing and for MSH2 or MSH6 gene promoter methylation. Overall survival for LLS CRCs were compared to LS related CRCs using Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) adjusting for age at diagnosis, sex, stage and grade. Results: Across all the MMR-deficient CRCs and ECs, LLS tumours comprised 32% (63/193) and 23% (45/197), respectively, compared with 27% and 15% for the LS group and 41% and 62% for MLH1 methylated tumours. Of the LLS CRCs and ECs tested, two somatic mutations were identified in 37% (18/49) and 48% (11/23), respectively. MSH2-deficient CRCs and ECs had the highest frequency of double somatic mutations across the different patterns of MMR IHC loss (40% and 64%, respectively). The mean age at diagnosis for the LLS CRCs with double somatic mutations was 49.7 ± 15.8 years, not significantly different from LS CRCs (n=52; 45.4 ± 11.3years; p=0.2) but was significantly different to the MLH1 methylated CRCs (n=83; 70 ± 8.9years; p=0.0001). No evidence of tumour MSH2 or MSH6 gene promoter methylation was identified in either MSH2-deficient or MSH6-deficient LLS CRCs or ECs tested (n=34 and n=12, respectively). LLS CRCs with double somatic mutations showed an overall poorer survival compared with LS CRCs but did not reach statistical significance (HR=2.58, 95% CI, 0.77-8.67; p=0.1). Conclusions: Double somatic mutations in the MMR genes represent a significant proportion of the unexplained LLS MMR-deficient subtype of CRC and EC in the population. Clinical triaging strategies used to identify Lynch syndrome for both CRC and EC should include tumour testing for somatic mutations in the MMR genes.

23 Karen Doggett Minor class splicing represents a novel target for cancer treatment DOGGETT K (1), Williams B (1), Morgan K (1), Markmiller S (1), Gong Z (2), Heath J (1) 1. Walter and Eliza Hall Institute of Medical Research, Melbourne. 2. Department of Biological Sciences, National University of Singapore

Aim: To identify a novel therapeutic target to a broad spectrum of cancers. Background: A small sub-set of genes in the human genome (~700) harbour distinctive introns that require recognition by the minor class spliceosome for their correct expression. These genes include prominent human cancer genes, such as key components of the MAPK and PI3K mitogenic pathways, and other ‘information processing genes’ essential for the growth and division of rapidly proliferating cells. Therefore, we hypothesized that efficient minor class splicing will also be crucial for cancer cells and minor class splicing may represent a novel, clinically relevant, target for cancer treatment. Methods: To test this we generated zebrafish and mouse genetic models of Rnpc3 deficiency, a unique protein component of the minor class spliceosome. We found that zebrafish and mice carrying two constitutive loss-of-function alleles die during development however heterozygous animals develop normally with no obvious phenotype. We then

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examined the impact of loss of one allele of rnpc3 in a variety of tumour-prone animal models. Results: Remarkably, we found that rnpc3 heterozygosity can decrease gastric tumour burden in mice and also Pten heterozygous mice which spontaneously develop large lymphomas. Moreover, homozygous deletion of conditional Rnpc3 alleles significantly prolonged the survival of AML carrying mice and decreased the growth of lung adenocarcinomas caused by the conditional expression of oncogenic K-RAS (K-RASG12D). We also obtained similar results with a zebrafish model of hepatocellular carcinoma (HCC) driven by krasG12V. Conclusion: Our results indicate that minor class splicing represents an attractive clinically relevant target for a broad spectrum of cancer types with a therapeutic window that could be exploited clinically to restrict the growth of cancer cells without affecting normal tissues. We believe inhibiting the process will be particularly highly effective against tumours carrying activating mutations in RAS genes which have until now remained difficult to treat.

24 Paul James The contribution of rare variants, polygenic risk, and novel candidate genes to the hereditary risk of breast cancer in a large cohort of Breast Cancer families. JAMES PA(1,2,3), Li N(1), Rowley S(1), Goode D(2), Devereux L(1), McInerny S(2), Grewal N(2), Trainer(2,3), Lifepool Study, Scott R(4), Campbell I(1) 1) Research Division, Peter MacCallum Cancer Centre 2) Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre 3) Genomic Medicine, Royal Melbourne Hospital 3) Division of Genetics, Hunter Area Pathology Service.

Identifying the missing hereditary factors underlying the familial risk of breast cancer could have a major and immediate impact on managing the breast cancer risk for these families. Methods: We identified candidate breast cancer predisposition genes through whole exome sequencing of BRCAx families, and sequenced, up to 1325 genes, along with 76 common variants associated with breast cancer, in index cases from 5,900 BRCAx families and 5,600 cancer free women (ethnically matched on PCA). Results: The role of recently described (PALB2) or suspected (MRE11A) moderately penetrant genes was confirmed. Conversely, the size of the cohort means that the absence of enrichment for LoF mutations provides strong evidence against other reported breast cancer genes (BRIP1, RINT1, RECQL). For further moderate risk variants (in CHEK2, ATM, BRCA2) we observed significant risk modification based on the polygenic risk score (PRS - calculated from the common variant data), with the risk restricted to the co-occurrence of the rare variant and high PRS. Novel candidate genes were identified based on LoF mutations, including NTHL1 (38 cases versus 15 controls, OR 2.5 p=0.002): a member of the base excision repair (BER) pathway. We analysed data from additional genes in the BER pathway, along with somatic sequencing, tumour mutation profiling and familial segregation to examine this association. Conclusion: Our data shows that the effect of rare variation in established and novel breast cancer genes, along with consideration of the background polygenic risk together explains a substantial component of the heritable risk of breast cancer in our cohort.

25 Eric Joo Tumour DNA methylation signature defines colorectal cancers from biallelic MUTYH mutation carriers JE J, Wong EM, Rosty C, Clendenning M, Macrae F, Winship IM, Win AK, Newcomb P, Lindor N, LeMarchand L, Haile R, Casey G, Gallinger S, Hopper JL, Milne RL, Giles GG.

Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne; Colorectal Medicine, RMH; Familial Cancer and Genetic, RMH.

Aim: We aimed to identify a methylation signature within colorectal cancers (CRCs) that could discriminate CRCs from MUTYH biallelic mutation carriers. Background: Carriers of germline biallelic mutations in the base excision repair gene, MUTYH, have an increased risk of developing CRC by up to 100-fold. Given the well-understood role of DNA methylation in colorectal tumourigenesis, we hypothesised that there are DNA methylation signatures associated with colorectal tumours of MUTYH germline biallelic mutation carriers that can discriminate them from other sporadic CRCs. Method: Using the Illumina Infinium HumanMethylation450K (HM450K), we measured genome-wide methylation on a test set of 192 formalin-fixed paraffin embedded tumour and matched normal samples from 96 CRC-affected patients. Nine of those 96 CRC-affected individuals were biallelic carriers of a germline mutation at the MUTYH locus, recruited from the Colon Cancer Family Registry Cohort (Colon-CFR). Sixty-nine individuals were late-onset “sporadic” cases, recruited through the Melbourne Collaborative Cohort Study (MCCS). The remaining 12 cases were either MLH1 epimutation carriers or carried germline mutations in the DNA mismatch repair genes (Lynch syndrome). The replication group comprised 13 CRCs from biallelic MUTYH mutation carriers (Colon-CFR) and 552 unselected CRCs from the MCCS. The HM450K data was processed using the minfi Bioconductor package. Differentially Methylated Probes (DMPs) were assessed by performing a regression analysis using the limma Bioconductor package. Results: We successfully measured methylation at >450,000 CpG probes from all 192 tumour and matched normal samples. We observed extensive DNA methylation differences between all tumour and matched normal samples with a set of >250,000 statistically significant DMPs (FDR adjusted p-value < 0.01). Further analysis identified 15 differentially methylated probes specific to the CRCs from MUTYH biallelic mutation carriers (i.e. not present or much weaker in sporadic CRCs). These probes overlapped the MRSB3, TNFRSF4, GIMAP5, RNASE9, ZC3H3, PTBP2, HAUS5, PGCP, CD109, C7orf58, FAM184A, and UNC50 genes, where tumours were consistently more methylated than normal tissues. We further tested methylation at these CpG probes in a replication group of 13 MUTYH biallelic CRCs and 552 sporadic CRCs. We found significant methylation differences between the two groups for 4 of these 15 CpG probes (c7orf58, PTBP2, MSRB3, PGCP). Conclusion: We identified a DNA methylation signature in CRCs from biallelic MUTYH mutation carriers that can differentiate this clinically important subgroup of patients from those with sporadic tumours or from other inherited CRC syndromes and, if validated, has the potential to be used to identify MUTYH carriers.

Continuing Care Research 26 Frances Batchelor Do people think they will fall when they are in hospital? F BATCHELOR(1), S Williams(1), R Lewin(2), K Mackenzie(2), L Harvey(2), V Lui(2), P Lange(2), C Said(3,4) * 1. National Ageing Research Institute 2. Royal Melbourne Hospital 3. Austin Health 4. University of Melbourne. *On behalf of members of the Melbourne Ageing Research Collaboration (MARC)

Aim: To investigate the falls prevention knowledge and attitudes towards falls of hospital inpatients. Background: Translation of falls prevention evidence in hospitals has focussed on interventions and strategies shown to decrease the rate of falls. Although person-centred practice

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is part of hospital care, patients’ knowledge and attitudes about falls have not driven this translation. Preliminary data of one unit (AMU) showed that 77% of hospital inpatients do not think they are at risk of falling. The main reason for this was that patients felt that the staff would ensure their safety. These findings led the project team to ask if this high response of not being at risk of falling was a hospital wide perception or specific to one unit. This sub-study, part of a larger falls prevention project, investigates knowledge and attitudes towards falls in hospital inpatients. Method: All patients (greater than 500) at a Royal Melbourne Hospital (2 campuses) were surveyed once. Patients were asked about their perception of falls risk while in hospital and whether they could identify falls prevention strategies relevant to their hospital stay. Descriptive analysis was undertaken, and responses grouped according to emerging themes. Results: Five-hundred and seventy-one (571) beds were surveyed across 22 units. Consent was obtained from 49% of patients. Sixty-six percent of all hospital patients surveyed did not think they were at risk of falling. There was a statistically significant difference between acute and subacute wards (p=0.001). Few patients (29%) could identify more than one falls prevention strategy. Of the strategies identified, the majority were generic, such as the nurses always being there to help. Conclusion: Falls prevention interventions need to include patient perceptions and focus more on the knowledge and attitudes of patients. For strategies to be effective, the combined involvement of both staff and patients in being responsible for falls prevention needs to occur.

27 Mervyn Kyi A Randomised trial of a Proactive Inpatient Diabetes Service (RAPIDS) demonstrates decreased adverse glycaemia and hospital-acquired infections KYI M(1,2,3), Colman PG(1), Wraight PR(1), Reid J(1), Galligan A(1), Kumar S(1), Rowan LM(1), Nankervis A(1), Gorelik A(4), Marley KA(1), Russell DM(2), Fourlanos S(1,2) 1. Diabetes & Endocrinology, RMH. 2. Department of General Medicine, RMH. 3. University of Melbourne, Department of Medicine RMH. 4. Melbourne EpiCentre, RMH

Background: In hospitalised patients, both hypoglycaemia and significant hyperglycaemia are associated with adverse outcomes. We hypothesised a proactive inpatient diabetes service (IDS), which electronically identifies inpatients with diabetes and provides immediate management, will decrease the incidence of adverse glycaemia & hospital complications. Methods: RAPIDS (ACTRN12616000265471) was a cluster-randomised trial on 8 wards of a Royal Melbourne Hospital. Consecutive inpatients with diabetes or new-onset hyperglycaemia (random blood glucose [BG] ≥11.1 mmol/L without known diabetes) were recruited. Networked glucose meters were used to record capillary BG measures from admission until discharge, or day 14 for long-stayers. There was a 10-week baseline observational phase followed by a 12-week active phase during which the wards were cluster-randomised into 4 intervention and 4 control wards. Intervention wards received proactive IDS (endocrinologist or nurse practitioner who aimed to see patients within 24h of admission), while control wards continued usual care (a referral-based consultation service). Primary outcome (incidence of adverse glycaemic days [AGD]: patient-day with any BG <4.0 or >15.0 mmol/L) and secondary outcomes (patient-day mean glucose, hospital-acquired infections and length of stay) were compared between baseline and active phases within each group and subjected to multivariable analysis, adjusting for patient clinical features. Results: We investigated 1002 patients (87% type 2 diabetes; 29% insulin-treated; HbA1c: 7.5±1.7%) totalling 5447 patient-

days & 19062 BG measures. Incidence of AGD decreased significantly in the intervention wards (243 vs. 186 per 1000 patient-days [23% decrease], p < 0.001), but there was no significant change in the control wards (291 vs. 261 per 1000 patient-days, p= 0.08). On multivariable analysis, proactive IDS was independently associated with 24% decrease in the incidence of AGD (p=0.005). Proactive IDS also decreased the patient-day mean glucose (mean [SD]: 9.0 [2.7] vs. 9.5 [3.2] mmol/L, p<0.001), and the incidence of hospital-acquired infections (crude incidence: 8% vs. 3%, p=0.02; adjusted odds ratio: 0.28, 95% CI: 0.11-0.74, p = 0.01). There was no difference in hospital length of stay. Conclusion: This large randomised trial of a proactive inpatient diabetes service decreased the incidence of adverse glycaemia and hospital-acquired infections. This proactive treatment paradigm may change the approach to inpatient diabetes care.

28 Katie Marley HbA1c reduction and engagement in an ambulatory insulin stabilisation program MARLEY K, Tsan J, Dawson W, Kyi M, Rowan L, Urban E, Thien C, Hill E, Parlapiano C, McManus F, Colman P Background and Aim: The Royal Melbourne Hospital Diabetes Education Service implemented a number of improvement measures for its ambulatory insulin stabilisation program over the last 2 years. We aimed to establish whether a link exists between engagement in our program and improvement in diabetes control. Methods: A retrospective audit was performed on all referred patients on the program (n=355) throughout 2015 looking at referral reason, discharge reason, engagement and HbA1c before and after participation. The closest available HbA1c within 6 months prior to referral and 6 months after discharge was included. Engagement was defined as ≥1 contact with a Diabetes Educator involving addressing insulin dose management. Results: The most frequent documented referral reason was hyperglycaemia n=64 (35%), new commencement of insulin n=35 (19%) and change of insulin/ treatment regimen n=33 (18%). Of the 355 patients, before and after HbA1c were available in 166 patients. In this group there was a statistically significant reduction in HbA1c from 9.6% pre- to 8.5% post-intervention (p <0.001). There was a trend to a greater HbA1c reduction in those who remained engaged [1.2% reduction versus non engaged 0.6% reduction (p = 0.160)]. Patients who remained engaged, had a mean of 3.5 ± 3.8 contacts, with an association between a greater number of contacts and a reduction in HbA1c (Pearson’s r = -0.231, p = 0.003). The most common discharge reason was failing to maintain contact n=76 (40%) while 34 (19%) reached completion. Conclusion: Patient referral to our program (predominantly for hyperglycaemia) reduced HbA1c and there was a trend indicating a greater HbA1c reduction in those who remain engaged. While there is a high drop-out rate, we conclude that a small number of contacts can return desirable results and improvement measures should be targeted at establishing initial engagement.

29 Zoe Milner Complex regional pain syndrome: a new model of care improving patient outcomes MILNER Z (1), Hogg M(2), O'Sullivan H(1), White B(3) 1 Hand therapy RMH, 2 Head of pain services Melbourne Health, 3 Pain Fellow Melbourne Health

Aim: To implement a new innovative model of care to faciliated early access to care for patients presenting with signs and symptoms of complex regional pain syndrome (CRPS). By

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providing care in a co-ordinated approach, variation in care and healthcare utilisation will be reduced, whilst improving patient outcomes. Background: Current literature indicates early recognition of CRPS can improve patient outcomes, yet ‘early’ recognition is yet to be well defined. Furthermore, less than 50% of patients diagnosed with CRPS return to the workforce, in part due to delayed diagnosis and management. Patients presenting with CRPS within Royal Melbourne Hospital (RMH) were frequently not identified, resulting in multiple presentations to the emergency department and high healthcare utilisation. These patients received variable care in silos lacking co-ordination. Many patients that presented with CRPS suffered persistent pain and poor hand function. Methods: With the support of a Department of Health & Human Services Allied Health Workforce Advanced Practice grant a new management pathway was developed and implemented at RMH. Developed and implemented clinician resources; Established an early and direct referral pathway to assist clinicians in key hospital areas to identify patients and implement management. Results: Data analysis for the 65 patients referred to the program between July 2015 and June 2016, indicates positive outcomes. 33 of the referred patients met the Budapest diagnostic criteria (clinical) at their initial assessment. Comparisons have been made with a pre-pathway cohort with CRPS. Statistical significant changes were apparent in: reducing healthcare utilisation including ED presentations and IP admissions for pain, Surgical consults, Pain consults and allied health consults; 88% of patients returned to work; patient rated pain scores and functional outcomes also showed statistically significant improvements. Conlusion: Hand therapy in collaboration with pain management services, developed and implemented an innovative clinical approach to the management of patients with CRPS at RMH. This pathway provides a single point of contact for this complex patient cohort and enables early access to specialised care. This pathway has demonstrated its effectiveness by reducing healthcare utilisation, improving patient access to care, whilst also improving patients’ pain and functional outcomes. Early identification of signs and/or symptoms of CRPS in an acute hospital, together with early access to skilled clinicians and pain management, can result in improved clinical outcomes. Furthermore, this pathway has demonstrated that early co-ordinated care reduces the healthcare service demands from this complex cohort.

30 Joanne Young Pharmacist-facilitated e-learning module versus standard pharmacist-delivered education for warfarin naive patients: a randomised controlled study YOUNG J(1)¸ Nalder M(1), Elliott R(2,3) 1) Melbourne Health 2) Monash University 3) Austin Health

Background: Interactive e-learning is a relatively new electronic-based education delivery mode that has not been evaluated for its effectiveness in imparting warfarin knowledge to patients. Aims: To compare the effectiveness of a pharmacist-facilitated interactive warfarin e-learning module with standard pharmacist-delivered warfarin education on patients’ or their carers’ knowledge of warfarin. Secondary aims were to compare participants’ satisfaction with the warfarin education provided; to compare the time spent by pharmacists delivering warfarin education; and to assess pharmacists’ satisfaction with the warfarin education delivery modes. Methods: Adult English-speaking hospital inpatients commenced on warfarin for any indication (or their carers)

were eligible to participate in this study. Participants were randomised to receive either face to face verbal warfarin education by a pharmacist (control) or warfarin education via an interactive e-learning module (intervention). All participants were provided with a written warfarin booklet and given the opportunity to ask a pharmacist questions. Participant knowledge was measured at least two weeks after education using the Oral Anticoagulation Knowledge (OAK) test. Time spent providing warfarin education was self-measured by pharmacists. Participant and pharmacist satisfaction was measured via surveys. Results: A total of 54 participants completed the study (27 control and 27 intervention). There was no statistically significant difference in participant warfarin knowledge between the two groups (median correct OAK test scores, 80% [control] vs. 85% [intervention], p=0.14). Both warfarin education delivery modes were generally well-received by participants, with the majority in both groups satisfied with how the information was presented, that the information was clear and easy to understand, and that they had the opportunity to ask questions. Warfarin education delivered via e-learning took slightly less time compared to standard education (25.5 minutes vs. 33 minutes, respectively) but this reduction in time did not reach statistical significance (p=0.05). The e-learning module was well-received by pharmacists (n=12), however their overall preference for warfarin education delivery mode was variable. Pharmacists stated that individual patient factors, such as familiarity with computers or iPads and age, were important to consider when selecting education delivery mode. Conclusion: Warfarin education delivered via a pharmacist-facilitated e-learning module was non-inferior, in terms of patient or carer warfarin knowledge, compared to standard pharmacist-delivered education. The e-learning module did not significantly impact participant satisfaction with warfarin education or time to deliver education, and may be considered a useful alternative education mode.

Surgical Research Forum 31 Clarissa Whitehead Targeting invadopodia to treat glioblastoma invasion Whitehead CA (1), Mao L (1), Paradiso L (1), Kaye AH (1,2), Luwor RB (1,2), Stylli SS (1,2) 1) Department of Surgery, University of Melbourne, Royal Melbourne Hospital, 2) Department of Neurosurgery, Royal Melbourne Hospital

Aim: We screened a number of FDA approved drugs to examine their therapeutic efficacy and ability to reduce the invasiveness of glioma cell lines by targeting invadopodia activity. Background: Primary brain tumours are responsible for about 2% of all deaths from cancer, with glioblastoma multiforme (GBM) being the most prevalent form of adult glioma. Patients with this type of cancer face a poor prognosis. Even after the mass of the tumour is surgically removed, the invasive nature of GBM means that microscopic disease is still present, making surgical cure impossible. Standard treatment for GBM patients involves surgical resection, followed by post-operative radiotherapy (RT) and Temozolomide (TMZ). This approach provides a modest increase in survival producing a median survival of only 15 months and a 5 year survival rate of only 10%.Therefore, there is an urgent need for an evolution in the treatment of patients to improve their survival outcome. The invasive potential of glioma cells has been shown to be facilitated by structures on the cell membrane known as invadopodia. We have shown that invadopodia proteolytically degrade the extracellular matrix via the activities of numerous proteases, facilitating GBM cell invasion. Methods: We utilized a cell viability assay to examine the therapeutic efficacy of the FDA approved drugs on GBM cells.

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An invadopodia assay was then used to determine the ability of the drugs to reduce invadopodia formation / activity. Drugs which showed promising results with these two assays were then tested alongside TMZ and RT to establish their effect when used in conjunction with RT and TMZ. Finally, we also used western blot analysis (invadopodia protein expression) and zymograms (protease secretion/activity) of the treated GBM cells to further explore the overall effect of the FDA approved drugs. Results: We determined that our GBM cell lines secreted MMP-2 as the primary protease. Also, we observed that a single RT and TMZ treatment resulted in an increase in invadopodia activity and invasion in a 3D matrix assay. We identified a number of FDA approved agents that had both a cytotoxic effect on GBM cells and were also able to significantly reduce RT and TMZ induced invadopodia activity. Conclusion: Repurposed FDA approved drugs, not initially intended for the treatment of GBM, can have the potential to display both a cytotoxic and an anti-invasive (anti-invadopodia) effect on GBM cells. Further research will allow us to potentially discover new agents for the treatment of glioma patients.

32 Nigel Da Silva Accuracy of administrative coding data to determine lymph node & metastasis status in colorectal cancer NIGEL DA SILVA(1,2) Caroline McCallum(1,2) Ian Hayes(1,2) Anita Skandarajah(1,2) 1. Department of Surgery, RMH; 2. The University of Melbourne

Aim: This study aims to determine the accuracy of administrative data coding of lymph node and metastasis status and ASA PS grades of patients, after a colorectal cancer resection when compared to the clinical sources. Background: Research into colorectal cancer requires the maintenance of cancer databases with complex datasets. Administrative data is routinely captured for each patient admission and may serve as an alternative source to a database. Methods: A retrospective study of all colorectal cancer resections between 1st of January 2008 to 31st of December 2013 was conducted at Melbourne Health. Clinical data for all patients (Lymph node involvement & metastasis status), was derived from the hospital utilised web-based results viewing system, Clinical Information System (CIS). Local administrative data, coded as per ICD-10 AM and ACHI, pertaining to lymph node and metastasis status was then compared with this clinical information for accuracy. Results: A total of 437 patients were identified. 296 out of 437 patients had a specific ASA PS grade noted. Administrative data matched in 268/296 cases (90.54%) with regards to Lymph node status. This resulted in an accuracy of 93.33. 249 (84.12%) patients out of the cohort had an accurate record of their metastatic status. Conclusion: Administrative data can provide information on staging of colorectal cancer with an accuracy comparable to that of clinical notes. It demonstrates the utility of administrative data to populate a cancer database.

33 Ruth Mitchell The structure, function and inhibition of Epidermal Growth Factor Receptor in Glioblastoma MITCHELL R(1,2,3), Luwor R(1), Burgess A(1,2) 1. Department of Surgery (The Royal Melbourne Hospital), The University of Melbourne 2. Walter and Eliza Hall Institute 3. Department of Neurosurgery, The Royal Melbourne Hospital.

Aim and Background: Glioblastoma is the most common malignant brain cancer in adults, with a dismal prognosis. Current therapies for glioblastoma, which have been in use for a decade, are unsatisfactory. The epidermal growth factor

receptor (EGFR) is heavily implicated in glioblastoma, and is frequently amplified (40% of cases), mutated (45%) and/or over-expressed (50%). These alterations lead to cancer cell proliferation, survival and drug resistance. Many of the available anti-EGFR therapeutic agents (used in other cancers) have been investigated clinically in glioblastoma but to date none have been found to have adequate benefit. The purpose of this project is to shed new light on the structure and function of the EGFR to improve therapeutic targeting in glioblastoma. Methods: The present project has been designed to assess the structure and function of EGFR by purifying full-length EGFR and placing it in phospholipid bilayer constructs named nanodiscs. The nanodisc-bound receptor can then be characterised both structurally, by means of cryo-electron microscopy, and functionally by means of assays of kinase activity and binding. Importantly the nanodisc-receptor complex provides a biologically relevant platform where true-to-life receptor structure and function are assessed in the presence of novel therapeutic agents. Results: The function of EGFR will be demonstrated, both in free solution and in nanodiscs. The impact of selected agents, both novel (polyIC-conjugated affibodies) and established monoclonal antibodies and tyrosine kinase inhibitors on the function of the receptor will be detailed. The action of EGFR targeting agents (eg. PolyIC-anti-EGFR affibodies) will be described. Progress towards the structure of nanodisc-bound full-length EGFR will also be shown also. Conclusion: Novel structural and functional insights into the EGFR enable improved targeting of this receptor in glioblastoma.

34 Joshua Wong Factors influencing re-excision following breast conserving surgery WONG J(1), Philpott A(1), Elder K(1,2), Gorelik A(4), Mann B(1,2,3), Skandarajah A(1,2,3) Royal Melbourne Hospital Breast Service (1), Royal Womens Hospital Breast Service (2),Victorian Comprehensive Cancer Centre (3), EpiCentre(4)

Intro: Re-excision rates following breast conserving surgery (BCS) vary between 10-46%. The rate at our institution was 19.5%. Prior to 2014, our policy was to re-excise when cancer/in situ carcinoma was within 2mm of the surgical margin. After the 2014 SSO/ASTRO guidelines we adopted “no ink on tumor” as adequate margin for invasive cancer. In January 2015 we introduced routine intraoperative specimen X-ray (Faxitron) at one site. Aim: We aim to identify the influence of these events on re-excision rate at our centre. Method: All 562 patients who underwent BCS for core-biopsy proven in situ or invasive breast cancer at the Royal Melbourne Hospital from 2013-2015 and Royal Women’s Hospital from 2013-2014 were included in our study. Medical records, radiology, pathology and our electronic database were retrospectively reviewed to identify patients who underwent reexcision (re-excision or total mastectomy) within 100 days of their primary procedure. Results: There was a trend in reduction of re-excision rate from 25% to 17% (p=0.05) with the introduction of SSO/ASTRO guidelines and 17% to 16% (p=0.73) with the introduction of Faxitron. On multivariate analysis the factors which significantly increased re-excision rate were presence of multifocality on mammogram (p<0.01), smaller volume of surgical resection (p<0.01), and larger lesion size (p<0.01). Conclusion: As expected, there has been a trend in reduction of re-excision rates since 2014 SSO/ASTRO guidelines and our introduction of Faxitron, but neither were significant. Other influential factors are the presence of multifocality on mammogram, volume of surgical resection and lesion size.

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35 Ryan Stuchbery A transcriptional field effect in fat can be used to predict tumour grade in localized prostate cancer STUCHBERY R1, Mangiola S1,2, Macintyre G3,4,5, Clarkson MJ1, Peters JS6, Costello AJ1,2.6, Hovens CM1,2,7, Corcoran NM1,2,7,8 1 Australian Prostate Cancer Research Centre Epworth; 2 Department of Surgery, University of Melbourne; 3 Centre for Neural Engineering, Department of Computing and Information Systems, University of Melbourne; 4 Cancer Research UK Cambridge Institute, University of Cambridge, UK; 5 Diagnostic Genomics, NICTA, Victoria Research Laboratory, University of Melbourne; 6 Electrical and Electronic Engineering, Melbourne School of Engineering, University of Melbourne; 7 Departments of Urology and Surgery, Royal Melbourne Hospital; 8 Dept of Urology, Frankston Hospital

The decision to treat clinically localised prostate cancer is critically dependent upon an accurate estimation of the risk of progression within a patient’s lifetime. Due to sampling error, prostate biopsy may miss completely a clinically important tumour, or significantly underestimate its potential aggressiveness. Over the last decade, accumulating evidence suggests that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. Given the potential role of the local fat depot in prostate cancer progression, as well as the ongoing need for new strategies to improve risk stratification at the time of diagnosis, we investigated the possibility that alterations in peri-prostatic adipose may be associated with disease risk as well as response to treatment. We performed RNA sequencing on peri-prostatic adipose tissue obtained at the time of prostatectomy from patients with low and high risk disease, to determine if there existed a transcriptional signature that would allow differentiation between groups of patients at high- or low-risk of progression. We found significant alterations in expression affecting 677 genes, although the majority were not abundantly expressed and the dynamic range was low. However despite this a distinct signature was present which we could confirm by qPCR in an expanded cohort, and potentially translate into a clinically usable test. Analysis of the genes involved suggest that differential expression is due to immune based reactive changes within the tissue rather than local adipose tissue acting as a distinct driver of tumour progression.

Neurosciences and Mental Health Research 36 Bruce Campbell Prognostic and treatment impact of CT perfusion imaging in pooled analysis of randomized trials of endovascular thrombectomy CAMPBELL BCV(1), Mitchell PJ(2) for the HERMES Collaborators (1) Department of Neurology and (2) Department of Radiology, Royal Melbourne Hospital

Aim: To investigate the association of CT perfusion (CTP) with treatment effect and functional outcome after endovascular stent-thrombectomy Background: The role of CTP in patient selection for endovascular thrombectomy remains uncertain. Methods: Patient-level imaging data from the MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE and THRACE trials were pooled (HERMES Collaboration). CTP data were reprocessed using RAPID (research version, IschemaView) as used in the EXTEND-IA and SWIFT PRIME trials. Irreversibly injured ischemic core was estimated using a relative cerebral blood flow threshold<30% of normal brain. The association between pre-treatment core volumes and the 90-day modified Rankin scale (mRS) was examined by treatment status and reperfusion status. The number needed to treat (NNT) to achieve independence (mRS 0-2) or at least 1 unit improvement in mRS with endovascular treatment versus

control was calculated for a range of ischemic core volumes, based on model-derived treatment effects adjusted for age, sex, baseline stroke severity, time from symptom onset to randomization, baseline CT ischemic changes, baseline site of arterial occlusion, whether a patient received intravenous thrombolysis and a random effects term for trial of origin. Results: There were 591/1764 (34%) patients in the pooled trials who had CTP, 289 treated with endovascular thrombectomy and 302 controls. Baseline characteristics were well matched between treatment groups and representative of the overall trial characteristics. Increasing core volume was independently associated with reduced independent functional outcome in both endovascular treatment (OR 0.79, 95%CI 0.69-0.90 per 10mL core) and standard care groups (OR 0.71, 95%CI 0.56-0.90 per 10mL core), after adjustment for baseline prognostic variables. However, the interaction between core volume and treatment was not significant (p=0.26). This translated to a NNT to achieve independence <10 for core volumes <125mL. For at least 1 point improvement in mRS, NNT remained <5 for core <125mL. In multivariate analysis in the subgroup of patients who had successful endovascular reperfusion (n=186), core volume (OR 0.82, 95%CI 0.73-0.92 per 10mL, p=0.001), age (OR 0.83, 95%CI 0.72-0.94 per 5 years) and time from imaging to reperfusion (OR 0.79, 95%CI 0.66-0.95 per 30min, p=0.01) were independently associated with outcome. Onset to imaging time and NIHSS were not independently associated with outcome. Conclusions: CT perfusion core volume was strongly prognostic but potentially meaningful treatment benefit may persist even at large core volumes. Integration of core volume with age and expected time to reperfusion improves prognostic specificity which has direct relevance to patient selection for therapy.

37 Tomas Kalincik Fingolimod, dimethyl fumarate and teriflunomide for relapsing-remitting multiple sclerosis KALINCIK T(1,2), Spelman T(1,2), Jokubaitis V(1,2), Butzkueven H(1,2) (1) Department of Neurology, Royal Melbourne Hospital (2) Department of Medicine, University of Melbourne.

Aim: To compare the efficacy of the oral immotherapies for multiple sclerosis. Background: Oral immunotherapies are becoming a standard treatment in relapsing-remitting multiple sclerosis. Relapse and disability outcomes have not been directly compared between these therapies. Methods: We identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod in the global MSBase cohort study with the minimum 6-month treatment persistence and disability follow-up. Patients were matched using propensity scores and pairwise censoring. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models) over a 2-year follow-up. Sensitivity analyses were completed. Results: The eligible cohorts consisted of 450 (teriflunomide), 599 (dimethyl fumarate) or 1936 (fingolimod) patients. Annualised relapse rates were higher on teriflunomide compared with dimethyl fumarate (0.26 vs. 0.17; p=0.005) and fingolimod (0.18 vs. 0.24; p=0.009) and similar on fingolimod and dimethyl fumarate (0.21 vs. 0.24; p=0.1). No differences between the effect of the therapies on disability accumulation or improvement were found (p>0.1). Patients were less likely to discontinue fingolimod vs. teriflunomide or dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.9). Sensitivity analyses, including

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secondary progressive disease, different matching strategies, different prior disease activity and matching on MRI, largely confirmed the outcomes of the primary analyses. Conclusion: Fingolimod and dimethyl fumarate are associated with a similar effect on reducing relapse activity, which is superior to that of teriflunomide. The effect of the three oral therapies on disability outcomes is similar during the initial two years.

38 Bernd Merkel Timing of high-efficacy disease modifying therapies for relapsing-remitting multiple sclerosis MERKEL B(1), Jokubaitis V(1,2), Spelman T(1,2), Butzkueven H(1,2,3), Kalincik T(1,2), on behalf of the MSBase Study Group (1) Department of Medicine, University of Melbourne (2) Department of Neurology, Royal Melbourne Hospital (3) Department of Neurology, Box Hill Hospital, Monash University.

Aim: The study evaluated the effect of early treatment with high-efficacy disease modifying therapies (DMTs) on disease outcomes in relapsing-remitting multiple sclerosis (MS). Background: It has been shown that treatment with high-efficacy immunomodulatory agents prevents accumulation of permanent disability in MS. However, the most common treatment strategy is to commence first-line therapies, followed by treatment escalation in patients who continue to experience on-treatment disease activity. The evidence in support of the hypothesis, that early initiation of high-efficacy DMTs may result in improved long-term disease outcomes compared to their later commencement and/or prior initiation of first line DMTs, is still needed. Methods: We have used the global MSBase cohort study to compare relapse and disability outcomes in patients who have commenced (i) high-efficacy DMTs (alemtuzumab, natalizumab or fingolimod) vs. low-efficacy DMTs (interferon-beta, glatiramer acetate or teriflunomide) within 4 years of their diagnosis of MS, or (ii) high-efficacy DMTs within 4 years vs. after 6 years from MS diagnosis. Finally, we have evaluated the association between the time of commencing therapy and the magnitude of the difference in disease outcomes between high-efficacy and low-efficacy DMTs. The study used propensity score matching with pairwise censoring to mitigate indication and attrition bias, intention-to-treat approach to mitigate the effect of informed censoring, analysis of robustness to unmeasured confounding and multiple sensitivity analyses. Results: 396 and 1172 matched patients commenced high-efficacy or low-efficacy DMTs within 4 years of the diagnosis, respectively. The patients treated early with high-efficacy DMTs experienced less relapses (annualised relapse rate 0.22 vs. 0.41, p<.0001). 576 and 1099 matched patients commenced high-efficacy DMTs within 4 years (early) and after 6 years (late) of their diagnosis, respectively. Patients in the late high-efficacy group had higher annualised relapse rates (0.29 vs. 0.22, p<.0001). Finally, 468 and 1795 patients commenced high-efficacy or low-efficacy DMTs (irrespective of the date of commencement), respectively. The difference in annualised relapse rate between the high- and low-efficacy DMTs was diminishing with time. In contrast, no time-dependent flux in recovering from disability was observed. Finally, we conducted sensitivity analyses by (i) only including patients with available baseline MRI and (ii) using a different matching ratio, which largely confirmed the above mentioned results. Conclusion: Early commencement of high-efficacy DMTs in relapsing-remitting multiple sclerosis provides a superior control over relapse activity than their delayed commencement. Further outcomes in sub-cohorts, stratified by different clinical and demographic variables, will be explored.

39 Maria Di Biase PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia DI BIASE M 1,2, Zalesky A 1,2,3, O'keefe G 4, Laskaris L1,2, Baune BT 5, Shannon Weickert C 1,6,7,8, Olver J 2,4, McGorry P 10, Amminger P 9, Nelson B 9, Scott AM 4, Hickie I 11, Banati R 12, Turkheimer F 13, Yaqub M 14, Everall IP 2,15,16,17,18, Pantelis C 1,2 1 Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health 2 Department of Psychiatry, The University of Melbourne 3 Melbourne School of Engineering, The University of Melbourne 4 Department of Molecular Imaging and Therapy, and Department of Medicine, University of Melbourne, and La Trobe University, Austin Hospital 5 Discipline of Psychiatry, The University of Adelaide 6 Neuroscience Research Australia 7 Schizophrenia Research Institute 8 Sachool of Psychiatry, University of New South Wales 9 Orygen, The National Centre of Excellence in Youth Mental Health 10 Centre for Youth Mental Health, The University of Melbourne 11 Brain & Mind Centre, The University of Sydney 12 Medical Radiation Sciences, The University of Sydney 13 Department of Neuroimaging, King’s College London, UK 14 VU University Medical Center, Amsterdam Netherlands 15 North Western Mental Health, Melbourne Health 16 Florey Institute for Neurosciences and Mental Health 17 Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne 18 Cooperative Research Centre for Mental Health.

Background: Schizophrenia is associated with progressive grey and white matter loss, especially in frontal and temporal regions. Brain change may reflect axonal degeneration or neuronal loss, which we hypothesised to be accompanied by microglial activation - an inflammatory response in the central nervous system (CNS). In vivo positron emission tomography (PET) imaging can quantify microglial activity and potentially elucidate the neurobiology underlying brain changes observed across the course of schizophrenia. Aim: We examined putative microglial activation as a function of illness course in schizophrenia. Methods: Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) PET imaging in: i) 10 individuals at ultra-high risk (UHR) of psychosis; ii) 18 patients recently diagnosed with a schizophrenia-spectrum disorder; iii) 15 patients chronically ill with schizophrenia; and, iv) 27 age-matched healthy comparison subjects. Regional binding potential (BPND) was calculated using the simplified reference tissue model (SRTM) with four alternative reference inputs: cerebellar grey matter, white matter, grey matter with lowest standardized uptake and reference voxels delineated with supervised clustering. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to test for between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis was performed to test for BPND associations with grey matter volume, peripheral cytokines and clinical variables. Results: The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison for any of the 6 regions. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, p=.008, false discovery rate). Conclusion: We found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. However, we cannot exclude the possibility of patient subgroups, characterized by increased microglial activation.

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40 Mastura Monif Interleukin-1β has trophic effects in microglia and its release is mediated by P2X7R pore. Implications in multiple sclerosis and other neuroinflammatory conditions MASTURA MONIF (1,5) , Christopher A. Reid (2), Kim L Powell (3), Katherine J Drummond (3), Terrence J. O’Brien (3), David A Williams (1) 1. Department of Physiology, The University of Melbourne 2. Howard Florey Institute, The University of Melbourne 3. Department of Medicine, Royal Melbourne Hospital, The University of Melbourne 4. Department of Surgery, Royal Melbourne Hospital, The University of Melbourne 5. The Department of Neurology, The Royal Melbourne Hospital

Aim: Our overarching aim is to investigate the role of a purinergic P2X7 receptor (P2X7R) in microglial activation, and the ensuing downstream neuroinflammatory cascades. The ultimate hope is to find therapeutic targets that can be used in neuroinflammatory conditions such as multiple sclerosis (MS) and autoimmune epilepsy. Background: In the neuroinflammatory foci of a number of neurological conditions such as MS and autoimmune epilepsy, there is enhanced expression of P2X7R where increased microglial activation is a co-existing feature. P2X7Rs can function either as a cation channel, or upon continued stimulation, a large pore. P2X7R-overexpression alone is sufficient to drive microglial activation and proliferation in a process that is P2X7R pore-dependent, although the biological signalling pathway through which this occurs remains unclear. Once activated microglia are known to release a number of bio-active substances that include the proinflammatory cytokine interleukin 1β (IL-1β). Previous studies have linked P2X7R stimulation to the processing and release of IL-1β, but whether the channel or pore state of P2X7R is predominant in driving IL-1β release is unknown and is a major aim of this study. In addition we will determine whether IL-1β has trophic effects on surrounding microglia? Methods: Electron microscopy and immunohistochemistry was used to delineate the sub-cellular localization of P2X7R and IL-1β in primary hippocampal rat cultures. FM1-43 fluorescent dye and confocal microscopy were used to quantify vesicular exocytosis from microglia expressing the pore forming P2X7R versus a non-pore forming point mutant, P2X7RG345Y. IL-1β in culture was quantified with an enzyme linked immunosorbent assay (ELISA). IL-1β intracellular processing was blocked with inhibition of caspase 1 (with a synthetic peptide antagonist) and its extracellular form neutralized with an IL-1β neutralizing antibody. Microglial activation and proliferation was quantified immunohistochemically with confocal microscopy. Results: P2X7R and IL-1β were co-localized in lysosomes. Vesicular exocytosis was higher in microglia expressing the pore forming P2X7R compared to those expressing the non-pore forming mutant. There was increased IL-1β in cultures expressing the pore forming P2X7R and this proinflammatory cytokine was found to mediate the trophic effects of P2X7R pore in microglia. Inhibition of IL-1β production and function resulted in a significant decrease in P2X7R-mediated microglial activation and proliferation. Conclusion: IL-1β is a mediator of microglial activation and proliferation and its release/production is P2X7R pore dependent. Blockade of P2X7R pore could serve as a therapeutic target in alleviating the degree of inflammation seen in conditions such as MS and autoimmune epilepsy.

University of Melbourne RMH Symposium MD1 Morgan Hepburn-Brown Early decision making in acute pulmonary embolism: a retrospective clinical audit HEPBURN-BROWN M(1), Hammerschlag G(2) (1)The Royal Melbourne Hospital Clinical School, University of Melbourne; (2)Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital

Aim: To provide real world data on the risk profile of patients assessed from 2012 to 2016 for discharge and admission decisions, management and follow-up. Background: The evolution of the Direct Oral Anticoagulants has allowed a paradigm shift in the management of patients with acute Pulmonary Embolism deemed “low risk”, allowing early discharge from hospital. Early discharge results in lower costs to the healthcare system, decreased demand on inpatient beds and increases patient autonomy. Methods: 665 patients with the discharge diagnosis “Pulmonary Embolism with or without right heart strain” were evaluated. 438 were excluded due to inappropriate coding, 8 due to a co-morbidity requiring admission and 17 due to unavailable patient files. Remaining files were assessed for criteria determining risk, mainly the simplified Pulmonary Embolism Severity Index (sPESI), management decisions and the investigations performed. Results: A total of 202 patients were assessed as per the 2014 European society of Cardiology Guidelines for low risk Pulmonary Emboli, i.e sPESI<1 and high risk i.e. sPESI≥1, and for evidence of right ventricular dysfunction. 70 patients were classified as low risk: Of these, 6 were admitted (8.57%) and 64 were discharged (91.43%). 132 patients were classified as high risk: Of these, 105 were admitted (79.55%) and 27 were discharged (20.45%). Overall, 97 patients were discharged on Rivaroxaban and 83 on Warfarin, with 173 patients receiving at least one therapeutic dose of Enoxaparin during admission. Investigations for right heart strain included 192 ECG, 132 Troponin, 28 Transthoracic echocardiography and 0 Brain natriuretic peptide. After discharge, 190 patients were referred to General Practice, 127 to Respiratory clinics and 37 to Haematology clinics. Conclusion: Patients diagnosed with acute pulmonary embolism are being appropriately risk stratified by the sPESI and evidence of right ventricular strain. However, 20.45% of high-risk patients were discharged inappropriately. With evidence showing substantial mortality in high-risk patients who are discharged early, this presents an area for further focus.

MD2 Qi Yang Damien Qi The RMH Pro-Diab Perioperative Study: a structured perioperative diabetes management plan improves medication usage and glycaemia QI QYD (1), Pemberton E (2), Kyi M (3), Colman PG (3), Fourlanos S (3) (1) Royal Melbourne Hospital Clinical School; (2) Department of Pain and Anaesthesia, RMH; (3) Department of Diabetes and Endocrinology, RMH.

Background: The perioperative management of inpatients with diabetes is complex. Suboptimal glycaemia in the perioperative period is common, and associated with increased morbidity and mortality. Aim: To determine the effect of a structured perioperative diabetes management plan (PDMP) on the appropriate recommendation, prescription, and administration of diabetes medications in the perioperative setting. Methods: A multidisciplinary team developed a novel structured PDMP endorsed by the Departments of Diabetes &

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Endocrinology and Pain & Anaesthesia. This observational study consisted of pre- and post-intervention periods, where pre-intervention care for perioperative diabetes management (non-structured) was audited for 4 months (Feb-May 2016) and then re-audited for 4 months (Feb-May 2017) post-intervention (structured plan). The primary outcome measure was documentation of appropriate recommendation, prescription and administration of diabetes medications in the perioperative setting according to the PDMP. Secondary outcome measures included glucose monitoring practice and glycaemic measures. Results: The pre- and post-intervention groups comprised 138 and 84 patients respectively, all of whom were seen in preadmissions clinic and the majority admitted on the procedure day. The two groups were not significantly different in their clinical characteristics. In the intervention group, the PDMP was completed correctly in 71% of patients. The appropriate recommendation, prescription, and administration of diabetes medications occurred in 63% of cases in the post-intervention group compared to 30% in the pre-intervention group (p<0.001). In the post-intervention group, appropriate glucose monitoring increased significantly in both the preoperative (p<0.001) and postoperative (p=0.002) periods. The post-intervention group also had significant improvements in glycaemia in the preoperative (p=0.005) and postoperative (p=0.003) periods. These improvements were even greater in the subset of patients who had the PDMP completed correctly. Conclusion: This novel structured perioperative diabetes management plan used in elective surgery significantly improved the appropriate recommendation, prescription and administration of diabetes medications, glucose monitoring, and glycaemia.

MD3 Tal Koren Patients with epilepsy exhibit changes in expression of cardiac ion channels KOREN T(1), Todaro M(1), Powell K(1), Royse C(1), O'Brien T (1) Royal Melbourne Hospital

Background: A growing amount of evidence suggests a link between epilepsy and cardiac disease, which may help explain some cases of Sudden Unexpected Death in Epilepsy (SUDEP), an important but poorly understood cause of death in patients with epilepsy. Animal models with both genetic and acquired epilepsy have revealed cardiac dysfunction and changes in the cardiac expression of the ion channels HCN2, Cav3.2 and Kv4.2, which are known to increase the susceptibility for cardiac arrhythmias. Similarly, patients with genetic mutations in potassium channels, such as Kv7.1 and Kv11.1 and in sodium channels Nav1.1 and Na¬v1.5, often co-exhibit epilepsy and cardiac arrhythmias. Aim: This study aimed to determine whether HCN2 and Cav3.2 mRNA expression changes in patients with epilepsy (previously published by our lab) correspond with changes in protein expression. Additionally, cardiac mRNA expression of the ion channels Nav1.1, Nav1.5, Kv4.2, Kv7.1, Kv11.1 and the Na¬+/Ca2+ exchanger in patients with epilepsy were investigated, and whether these changes correlate with changes in cardiac function. Methods: Heart tissue from patients with epilepsy undergoing open-heart surgery and from matched controlled patients was collected over a three-year period. Changes in mRNA expression of the genes SCN1A, SCN5A, KCNQ1, KCND2, KCNH2 and SLC8A1 corresponding to ion channels listed above were analysed using quantitative PCR. Cardiac protein expression changes in Cav3.2 and HCN2 was analysed using western Blotting. ECG and Echocardiography reports were analysed for corresponding changes in cardiac function and rhythm. Results: mRNA expression of SCN5A and KCNQ1, corresponding to Nav1.5 and Kv7.1 respectively, was

significantly reduced in patients with epilepsy (n=8) compared to controls (n=16), (p=0.0268 and p<0.0001 respectively). HCN2 protein expression was significantly reduced (p=0.0392) in epilepsy patients (n=7) compared to controls (n=14). However, ECG and echocardiogram reports did not reveal any significant difference in cardiac function or rhythm. Conclusion: These results show that cardiac mRNA expression of Nav1.5 and Kv7.1 is reduced in patients with epilepsy. Additionally, there was concordance between changes in protein expression of HCN2 channels and previously published reduction in mRNA expression. Larger sample sizes are required to ascertain whether these changes correlate with clinically significant difference in cardiac function. Nevertheless, changes in these important ion channels may contribute to cardiac dysfunction seen in patients with epilepsy and may be important to further understanding SUDEP pathogenesis.

MD4 Ken Teng Longitudinal post-operative quality of life and cognition in acoustic neuroma, meningioma and low-grade glioma TENG K (1,2), Toor G (1,2), Drummond K (1,2) (1) Department of Neurosurgery, The Royal Melbourne Hospital. (2) Melbourne Medical School, The University of Melbourne

Aim: To assess HRQoL, how it changes over time, and the relationship between perceived and objective cognition in patients with acoustic neuroma (AN), meningioma (M) or low-grade glioma (LGG). Background: AN, M and LGG are slow growing brain tumours amenable to management via surgical resection. Advances in surgical technique and technology have led to extended survival after treatment. The quality of that survival is at least equally as important as the duration. Therefore, it is important to assess the health-related quality of life (HRQoL) in this population. HRQoL is a patient-reported measure that encompasses physical, psychological, and social wellbeing. Brain tumour patients often report poor cognition and it is widely accepted that cognition is intimately related to HRQoL. Methods: 501 unselected post-operative outpatients with histologically-confirmed brain tumour (AN: 131, M: 241, LGG: 129) have been recruited from the Royal Melbourne Hospital as part of an ongoing study. HRQoL was assessed using the EORTC QLQ-C30 and QLQ–BN20 questionnaires. A thoroughly validated computerised test battery from Cogstate was used to assess cognition. Results: We found considerable HRQoL deficit in the different tumour types across all domains (p<0.05) with the exceptions of emotional domain for AN patients and physical domain for LGG patients. HRQoL scores remained stable over time when comparing participants as a group but were variable when analysing participants individually. Cogstate testing on 81 patients showed statistically significant impairment for processing speed tasks but the scores lie within one standard deviation of the reference population mean. Interestingly, comparison of objective and perceived cognitive scores revealed 51 patients with low perceived cognitive score but high objective cognitive score. Emotional functioning, future uncertainty, communication deficit, pain and fatigue were moderately correlated with perceived cognition. Conclusion: Our results demonstrate significant HRQoL impairment for AN, M and LGG patients and complex change in HRQoL over time. Patients attained lower scores for processing speed on Cogstate but the clinical significance of this remains unclear. Nearly two-thirds of these patients reported poor perceived cognition but performed well on cognitive testing. We found a number of factors related to perception of cognition with emotional functioning showing the strongest correlation. Further investigation of such factors is

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warranted to resolve this discord and adopt appropriate interventions to optimise HRQoL in this population.

MD5 Adam Fambiatos Risk of secondary progressive multiple sclerosis: a longitudinal study FAMBIATOS A(1), Jokubaitis V(2,3), Spelman T(2,3), van der Walt A(2,3), Butzkueven H(2,3,4), Kalincik T(1,3), on behalf of the MSBase Study Group 1. CORe Unit, Department of Medicine; 2. Department of Medicine, University of Melbourne; 3. Department of Neurology, Royal Melbourne Hospital; 4. Department of Neurology, Box Hill Hospital, Monash University

Aim: To determine the demographic, clinical and paraclinical features that influence the risk of conversion to SPMS. Background: The ability to estimate individual risk of conversion to secondary progressive multiple sclerosis (SPMS) represents an area of unmet need. We have examined factors associated with SPMS conversion using a time-sensitive survival model, objective definition of SPMS and the multinational MSBase cohort. Methods: Patients with adult-onset relapsing-remitting multiple sclerosis, at least three visits (with ≥6 months between the first and second visit and ≥3 months between the second and final visit), a minimum dataset and sufficient magnetic resonance imaging (MRI) data were selected from MSBase. The risk of objectively defined SPMS conversion was re-evaluated at multiple timepoints per patient using multivariable marginal Cox regression models. Sensitivity analyses with additional prognostic markers, minimum follow up requirements and stringent data quality standards were performed. Results: 6,145 patients contributing 35,340 visits and 39,360 patient-years of follow up were included in the primary analysis. Older age (HR: 1.02, 95% CI: 1.01-1.04), longer disease duration (HR: 1.03, 95% CI: 1.01-1.05), a higher expanded disability status scale score (HR: 1.30, 95% CI: 1.21-1.41) and more rapid disability trajectory (HR: 2.58, 95% CI: 1.39-4.81) were independently associated with an increased risk of SPMS, while an improving disability trajectory (HR: 0.31, 95% CI: 0.12-0.88) was associated with a reduced risk of SPMS. Recent MRI evidence of disease activity in the brain, radiological evidence of lesions in the spinal cord and the presence of oligoclonal bands in the cerebrospinal fluid did not independently influence the risk of SPMS. Pre-baseline exposure to disease modifying therapy lowered the risk of SPMS in a larger cohort of patients for whom MRI data was not required (n = 15,717; HR: 0.70, 95% CI: 0.54-0.91). Conclusion: Risk of SPMS increases with age, duration of illness and worsening disability, and decreases with improving disability. Recent MRI evidence of disease activity in the brain, spinal cord lesions and oligoclonal bands in the cerebrospinal fluid do not influence the risk of conversion to SPMS. Therapy may delay the onset of SPMS, although further work is required to confirm this result.

MD6 Olivia Galante Cerebral Microbleeds and Intracerebral Haemorrhage GALANTE O (1) , Cody R (2) , Wu T (1) , Shah D (1) , Pesavento L (1) , Sharma G (1) , Yates P (2) , Yassi N (1) 1.Department of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne;2. Department of Aged Care, Austin Health, University of Melbourne

Background: Cerebral microbleeds (CMB) are associated with intracerebral haemorrhage (ICH). However, the relationship between CMB burden and ICH characteristics is unclear. Aim: To characterise the association between CMB number/location and ICH volume/aetiology. Methods: 78 ICH patients presenting to the Royal Melbourne Hospital between January 2011 and August 2016 underwent 3T-MRI and CT. Aetiology was defined according to SMASH-U

criteria. ICH and CMB location were classified as lobar, deep or infratentorial. CMBs were assessed on susceptibility weighted imaging. ICH volumes were calculated using semi-automated planimetry on baseline CT. Results: Seventy-eight patients (mean age 62 years, 43.6% female) were included. The most common ICH aetiologies were cerebral amyloid angiopathy (CAA) (33.2%) and hypertension (30.8%). ICHs were lobar in 46.2%, deep in 32.1% and infratentorial in 21.8%. CMB prevalence was 61.5% (median 1, IQR 0-4.25). When present, CMBs were noted in multiple locations in 54.2% of cases. Age was associated with number of CMBs in all locations (p<0.05). Hypertensive and medication-induced ICH exhibited more deep CMBs (p=0.025), as did patients with infratentorial ICH (p=0.02). Median ICH volume was 6.8mL (IQR 2.5mL-13.1mL). There was no correlation between CMB number and ICH volume (p>0.05) overall. However, in patients with probable CAA, there was a significant correlation between ICH volume and number of lobar CMBs (p=0.048). Conclusion: CMBs are common in patients with ICH. In CAA patients, volume of ICH was associated with number of lobar CMBs. CMB burden may reflect severity of underlying vasculopathy which could have treatment implications for patients with ICH.

MD7 Tran Binh (Andrew) Giang Functional analysis of monogenic candidates in families with CVID GIANG TB(1,2,3), Slade C(1,2,3), Bryant V(1,2,3), Douglass J(1,2,3,4) (1) Division of Immunology, Walter and Eliza Hall Institute of Medical Research;(2) Department of Medical Biology, The University of Melbourne; (3) Department of Clinical Immunology and Allergy, Royal Melbourne Hospital; (4) Department of Medicine, The University of Melbourne.

Aim: To demonstrate functional immune deficits of candidate mutations identified in patients with CVID. Background: Common Variable Immunodeficiency (CVID) is a primary immune deficiency characterised by defective antibody production resulting in hypogammaglobulinaemia and impaired vaccination responses. It remains among the most clinically relevant and prevalent primary immune deficiencies, affecting between 1 in 10,000-50,000 individuals. Paradoxically, despite its relatively high prevalence in comparison to other rarer forms of primary immunodeficiency (such as X-linked agammaglobulinaemia or Severe Combined Immunodeficiency), our understanding of the underlying genetic aetiologies and pathophysiology is poorly defined, leading to a delay in diagnosis and access to appropriate therapies. We, and others, recently identified genetic defects in the NF-kB pathway as the underlying cause of disease in a significant proportion of CVID patients. Here, we investigated a cohort of Victorian patients with CVID, in whom candidate mutations in NF-kB genes were identified by whole-exome sequencing (WES). To better understand how these mutations result in clinical disease, we tested the functional consequences of these novel variants using in vitro techniques and examined their impact on up-stream and down-stream signalling events/molecules in the NF-kB pathway. Methods: Mutations in NFKB1 or NFKB2 were identified, via whole-exome sequencing, in 8 CVID patients from 5 families. Peripheral blood mononuclear cells (PBMCs) were isolated in each individual from whole blood samples taken. The pathogenicity of novel variants was assessed via analysis of protein expression in patient cells and in vitro analysis of mutant protein function via immunoprecipitation, assessing key molecules involved in the NF-kB signalling pathway. Results: We confirm reduced protein expression and phosphorylation of NF-kB1-related proteins, in NF-kB1

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deficient patients, as previously published, and also demonstrated a defect in NF-kB2 signalling in these patients. For patients carrying novel variants in NFKB2, we demonstrated reductions in both protein expression and phosphorylation of NF-kB2 proteins, with subtle changes in NF-kB1 protein levels, suggesting the cross-talk between these two pathways is largely unidirectional. Conclusions: We demonstrated altered expression and phosphorylation of key NF-kB pathway signalling molecules in patients with mutations affecting NF-kB1 or NF-kB2, thus identifying 4 new disease-causing mutations in 4 CVID families. We also showed biological evidence of immune cell dysfunction resulting from these novel genetic defects, providing important insights into the potential pathogenic mechanisms of disease in these patients, paving the way for improved patient management and targeted therapies.

MD8 Fathima Nazha Nazeem High flow humidified nasal oxygen to prevent desaturation during endobronchial ultrasound – a randomised controlled trial. NAZEEM F (1), Ng I (2) 1. The University of Melbourne 2. Melbourne Health

Background and Aims: Endobronchial ultrasound (EBUS), commonly performed under sedation, is a largely safe procedure indicated for the diagnosis of lung pathology. However, complications such as desaturation can occur due to underlying respiratory disease and hypoventilation from sedative agents. Anaesthetic management can be modified to mitigate this risk. In particular, optimizing oxygenation during EBUS may reduce the occurrence and severity of desaturation. Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE, delivered by Optiflow; Fisher & Paykel, Auckland, New Zealand) is an oxygen delivery device that provides heated, humidified oxygen up to 70L/min through nasal prongs. It has been shown to improve oxygenation in a variety of clinical settings, although it’s use in EBUS has not been widely reported. The aim of our study was to evaluate OptiFlow THRIVE’s role in oxygenation during EBUS. Methods: 60 patients presenting for EBUS under sedation were randomized to receive standard oxygenation via bite block (n =30, oxygen flow of 10 - 15L/min) or high flow oxygenation via THRIVE (n = 30, oxygen flow of 30 – 70 L/min) during the procedure. Anaesthetic depth was targeted to “Modified Observer’s Assessment of Alertness/Sedation Scale”, OAA/S = 4. The primary outcome was the proportion of participants who experienced procedural desaturation (SpO2 < 90%). Secondary outcomes included SpO2 after pre-oxygenation, lowest oxygen saturation, number of hypoxic episodes, duration of hypoxia, satisfaction scores, total procedural time, anaesthetic agents used and procedural complications. Data was analysed as per protocol. Results: Baseline characteristics were similar between groups. More patients in the control group experienced desaturation during the procedure than in the THRIVE group (10 vs 4 patients), although not statistically significant. SpO2 after pre-oxygenation and prior to sedation was significantly higher in the THRIVE group compared to the control group (98 [97-99]% vs 100 [99-100]%, p<0.01). Lowest procedural SpO2 was significantly lower in the control group than in the THRIVE group (92 [88-95]% vs 97.5 [94-99]%, p < 0.01). There were no statistically significant differences in other secondary outcomes. Conclusions: Although our primary outcome was not statistically significant, 33% of patients experienced desaturation on standard oxygenation compared to only 13% on THRIVE. In addition, THRIVE was associated with a higher SpO2 after pre-oxygenation and higher lowest SpO2 value, showing a stable maintenance of oxygenation during EBUS.

These promising results establish a pre-requisite for larger studies to confirm that THRIVE may aid the safety of EBUS via prevention of desaturation.

MD9 Benjamin Johnstone Determinants of psychiatric comorbidities and quality of life in patients with drug-resistant epilepsy or psychogenic non-epileptic seizures JOHNSTONE B (1), Velakoulis D (1,2), Malpas C (1,2), O'brien TJ (1,2) The University of Melbourne, The Royal Melbourne Hospital

Aim: This study aimed to examine the nature and prevalence of psychiatric comorbidity within specific epileptic syndromes, and to investigate the relationship between psychiatric comorbidity, drug-resistant epilepsy, psychogenic non-epileptic seizures (PNES) and quality of life in a video-electroencephalogram monitoring (VEM) unit. Background: The prevalence of psychopathology in patients with drug-resistant epilepsy and PNES has been reported to be significantly higher than the general population. Methods: Four hundred fifty-one patients were recruited from the Royal Melbourne Hospital VEM unit between February 2009 and November 2016. The diagnostic breakdown of this group was: temporal lobe epilepsy (TLE) (107), extra-temporal focal epilepsy (64), generalised epilepsy (33), PNES (118), both epilepsy and PNES (29), and uncertain diagnosis (100). The lifetime history of Axis I psychiatric disorders was determined by formal neuropsychiatric assessment. All patients completed questionnaires assessing psychiatric symptomatology (SCL-90-R), Anxiety and Depression (HADS), quality of life (QOLIE-89) and cognition (NUCOG). Pearson’s Chi-Square test was used to compare prevalence of psychiatric comorbidity between VEM diagnostic groups. Comparison of questionnaire data between diagnostic groups was determined using One-Way ANOVA analysis. Statistical significance was defined as p<0.05 for all analyses performed. Results: The prevalence of psychiatric comorbidity was significantly higher in patients with PNES (70.3%) or both PNES and epilepsy (62.1%) compared to patients with epilepsy alone (41.2%) (p<0.001). There were no significant differences in prevalence of psychiatric disorders between patients with TLE, extra-temporal focal epilepsy and generalised epilepsy. Patients with PNES had significantly worse quality of life, and scored higher on measures of psychiatric symptomatology, compared to patients with epilepsy alone (all comparisons p < .001). A general linear model was computed to identify predictors of quality of life. VEM diagnosis (p=.002), HADS depression score (p<.001), SCL-90-R positive symptoms total (p<.001), and NUCOG total score (p<.001) were significant predictors, together explaining 65% of variance in quality of life. Conclusion: This study supports emerging evidence that patients with TLE do not possess higher prevalence of psychopathology than patients with other types of epilepsy. Patients with PNES with or without comorbid epilepsy had significantly higher prevalence of psychiatric comorbidity and poorer quality of life than patients with epilepsy alone. This may be due to a common mechanism that predisposes individuals to development of both PNES and psychiatric disorders. Psychometric questionnaire data was found to correlate significantly with quality of life, suggesting routine clinical use within epilepsy and PNES populations may serve as an effective component of management.

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Big Ideas Symposium BI-1 Kate Storer Colouring away mental illness STORER K As 1/4 people within Australia suffer from a mental illness at some point in their life, I believe anything that is able to help those who are suffering from a mental health issue as well as physical issue within a hospital setting is needed. After talking to my grandfather, who has spent some time in hospitals over his years, he suggested something as simple as colouring in. I listened, but at that time it went in one ear, and out the other. That was until today, and after completing the mental health placement. The impact colouring in has in reducing anxiety and allowing people to have time to sit and just concentrate on colouring in within the lines was proven to have such a great impact on those within the facility so why couldn't it work within an acute hospital setting. That is why I believe an introduction of colouring in books, or simple print outs would be useful, in not only keeping the patient preoccupied for a while but also giving them time to tune out, and forget about where they are. Pictures such as animals, scenery's such as beaches, and things such as mandalas could be incorporated within the book to try and appeal to a wide audience.

BI-2 Janelle Bond and Mike Chmiel The Royal Rocket Food Truck BOND J, CHMIEL M Aim: To supply a variety of food that is fresh, hot, tasty and in line with patient’s lives outside of hospital. Starting 2 days a week on Tuesday’s and Thursday’s for breakfast, lunch and dinner on those days. What it will achieve: Normalisation during their stay whilst empowering and providing clients with an option to have non hospital food as they would at home. Hospital food can be bland, visually unappealing whilst also contributing to decreasing client’s appetites. The Royal Rocket allows the clients to have a greater choice of healthy but visually appealing and tasty food options aligned to their individual intake requirements. Improvement in patient satisfaction, as one of the biggest complaints is the food is awful or cold. Increased revenue as patients will pay this service. Background of the issue: Patient’s admitted for at least 3 days or more in a hospital setting generally complain about the quality of food. Anecdotally patients regularly report they have a decreased appetite which further complicates accurate assessment of their medical condition. The Royal Rocket food truck Big Idea provides an option that is hot and allows the patient to enjoy the experience of “going out for lunch” whilst still in hospital. Method of achieving and measuring goal: Patient survey to be conducted about current hospital food and what food options would be preferred out of a range of food truck possibilities. This survey should include impacts on health and medical condition from a diet and environment perspective. From this a plan of food choices agreed upon utilising the dietician team expertise. Inform patients of option for set days. The Royal Rocket food service staff would track exact numbers of participants and food tally to confirm successful trial. Where to from here: Complete survey; Find local supplier (possibly a local café may want to take on new business venture) or new part time position in RMH; Fulfil Tuesday and Thursday commitments; Review with Survey; Increase days if popular.

BI-3 Homairah Jasat Long-term regular paracetamol (Acetaminophen) administration. JASAT H(1), Mosley I (1) La Trobe University (1)

Aim - The aim of this proposal is to explore the prescribing decisions for the safe use of paracetamol in a rehabilitation environment. Furthermore, we seek to identify the incidence of prescribing regular long-term paracetamol administration (QID) in the absence of a pain assessment. Background - Paracetamol (acetaminophen) is used to treat mild to moderate pain and reduce fever. Due to its minimal adverse effects, paracetamol is frequently prescribed. Other medication for hypertension, cardiac conditions, for example, are reviewed to ensure the appropriate therapeutic dose for the patient’s specific health condition. However, routinely prescribed regular administration of paracetamol may continue in the absence of a regular pain assessment. Paracetamol is not only used to treat mild to moderate pain but also has an antipyretic effect. The long-term use of paracetamol may interfere with body’s natural defence response to infection, particularly in older adults. Moreover, literature also shows that long-term use of paracetamol can cause hypertension, false glucose reading, gastrointestinal issues and an increase in tolerance to the drug. Methods - A retrospective analysis of medical records will be undertaken to identify the incidence of regular paracetamol administration in the absence of a pain assessment (QID administration and not PRN), length of time prescribed, diagnosis and if the patient was discharged with regular administration will be recorded. Hospital and pharmacy protocols for pain relief will be investigated and documented. Semi structured interviews will be conducted with Medical prescribing staff, hospital pharmacy staff and nursing staff in the rehabilitation ward. These interviews will seek to understand the prescribing patterns and rational for prescribing regular paracetamol administration. At interview, other factors associated with prescribing regular paracetamol in the absence of a pain assessment will be discussed along with knowledge of long-term paracetamol use, adverse effects and that pain assessments will be undertaken appropriately. Where to from here? - The outcomes of this study will provide a snapshot of incidence, prescribing patterns and rational for prescribing long-term routine paracetamol in a rehabilitation environment. The results will inform the development of recommendations for the safe, effective and timely prescribing of long-term paracetamol. In turn, reducing side effects, adverse effects and providing appropriate pain relief for patients.

BI-4 Wendy Bower Is there a Central Driver for Nocturia and Common Comorbidities? BOWER WF(1), Ervin C(1), Rose G(1), Goldin J(2), Whishaw M(1) 1. Continence Service, Dept of Medicine and Community Care 2. Dept of Respiratory and Sleep Medicine

Aim: Nocturia comorbidities share central neural control. Areas such as the pontine micturition centre, the reticular activating system (specifically the locus coeruleus), the spinothalamic tracts, and the vasomotor centre are implicated in autonomic regulation of variables co-existing with nocturia. We hypothesize that a generalised hypofunction of the brainstem may underlie co-existing symptoms seen in patients with non-monosymptomatic nocturia and that improvement or resolution of one symptom may reduce the severity of comorbid dysfunctions.

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Background: Individuals with nocturia have up to a threefold increase in utilisation of health care services, making the personal and health cost of this symptom considerable. There are significant interactions between voiding at night and metabolic, cardiovascular, hormonal, mental health, sleep and inflammatory changes. We have noted a high prevalence of co-existing pain, hypertension, postural hypotension, urinary urgency, depression, insomnia and sleep disordered breathing in patients with nocturia > once per night. Our team has studied the direct and indirect pathways to nocturia and question whether it shares a common central control area with co-existing comorbidities, possibly in the brainstem. One way to investigate any clinically relevant interaction is to capture change in comorbid systems after successful treatment of single disorders on the causal pathway of nocturia. Methods: We will consider the two conditions of sleep disordered breathing (SDB) and urinary urgency or urgency incontinence (UUI) that sit directly on the causal pathway of nocturia. Gold standard treatment of either SBD or UUI will be offered to symptomatic patients who also have nocturia. Efficacy of the index treatment, nocturia frequency and brainstem- controlled comorbidities will be evaluated pre and post treatment. The primary outcome will be number of episodes of nocturia per night over a one-week period. Secondary outcomes will measure change in: Overnight urine production, severity of UUI, quality of life, time to first nocturia episode, hypersomnolence, sleep latency, sleep quality, anxiety, depression, self-reported health status, systolic blood pressure and postural hypotension. for SDB or UU will also be evaluated. Where to from here?: Findings from the current study will clarify whether co-existing symptoms in patients with nocturia are centrally controlled and interconnected. We will understand whether improvement in one comorbid variable may regulate other dysfunctions toward a more normal status. Clinically this will indicate whether nocturia treatment should be multi-modal or can be specifically targeted to a specific symptom. This may optimise clinical care of patients with nocturia.

BI-5 Emma Biggar Assessment of the barriers to accessing appropriate treatment and support for families experiencing breastfeeding difficulties relating to infant tongue and lip tie BIGGAR E, Mosley I La Trobe University

Aim: To improve health service delivery to support the mother-baby dyad experiencing breastfeeding complications resulting from infant tongue and lip ties and improve overall breastfeeding outcomes. Background: Breastfeeding is accepted as the normal biological way of feeding an infant child. It provides more than just a valuable source of nutrition and immunological benefit to the infant. Appropriate education and support enables almost all mothers and babies to overcome any breastfeeding challenges that may arise. One such challenge is that of infant tongue and lip ties. There is controversy surrounding the discussion of tongue and lip ties in relation to their impact on breastfeeding. Disagreements are found in many areas including definition of what constitutes a tie, the criteria determining the presence, severity and impact of the tie, the assessment tools used, the treatment options and the long term outcomes and consequences. There remains much debate as to whether a tie is purely a normal variation or an anomaly that must be treated. With all this it is easy to understand why parents may find difficulties in accessing appropriate support and treatment for their infant with suspected tie related breastfeeding difficulties. We may

speculate on what those barriers might be, however, a search of the current literature indicates no clear and consistent evidence on managing tie related breatfeeding difficulties. In order to improve services and ultimately improve breastfeeding outcomes we need to determine the specific barriers experienced by families in accessing support and treatment of tongue and lip ties in the breastfeeding infant. Additionally, it is important to determine the extent these barriers pose on families. Methods: I propose a mixed methods approach. The first part of this research will be a qualitative study using semi structured interviews of mothers who have achieved breastfeeding improvements following appropriate treatment of infant tongue tie. Participants will continue to be recruited and interviewed until saturation of the data is achieved. Once this is completed and common themes have been identified a quantitative survey will be composed. Participants for the survey will be recruited through services that provide tongue and lip tie treatment and support. Where to from here: Once barriers have been identified, service improvements can be developed and implemented in order to improve ease of access to treatment and support for consumers. This will lead to improved service delivery, decreased time-wastage and ultimately achieve greater positive outcomes in breastfeeding.

BI-6 Nompilo Moyo Tuberculosis screening in an aged care residential facility in a low-incidence setting Moyo N(1), Trauer J(2), Trevan P(1), Baker A(1), Musemburi J(1), McGrath K(1), Nolan A(1), McIntyre E(1), Hulls J(1), Denholm JT(1,3) 1. Victorian Tuberculosis Program, Melbourne Health; 2. School of Public Health and Preventive Medicine, Monash University; 3. Department of Microbiology and Immunology, University of Melbourne

Aim: Reviewing a contact tracing exercise in an aged care residential facility following exposure to tuberculosis, to assist in refining practical and optimal approaches to contact tracing in such environments. Background: Residents in long-term aged care residential facilities (ACRF) have long been recognised as having higher incidence of tuberculosis than the general community in many settings. However, despite this, they are a difficult group to screen and the best approach is not known. Methods: This is a retrospective cohort study of tuberculosis contact tracing and screening in an elderly residential facility in Victoria. In the absence of specific guidelines regarding an optimal test for this population, 18 residents were tested with both tuberculin skin test (TST) and interferon-gamma release assay (IGRA), and all underwent symptom assessment and chest x-ray (CXR). Results: A total of 19 residents with epidemiological contact were identified for contact tracing, with 18 consenting to evaluation. Residents with a positive IGRA were more likely also to be positive on TST (5/18 versus 2/18; 11%, Pearson χ2=5.85, p=0.016). No resident with negative IGRA was found to have a positive TST. CXR identified abnormalities in 4/18 (22%), with all of these individuals also having positive IGRAs (Pearson χ2=13.87, p<0.001). Both TST positives had abnormal CXRs. Screening with CXR was problematic in this group, particularly due to many co-morbidities and incidental findings on CXR (especially malignancy). Qualitative feedback from clinical nurse consultants was collected and reviewed. Consistent themes were that: 1. TST administration was difficult due to fragile skin and loss of skin elasticity. 2. It was noted that some residents were not able to cooperate with the procedure, most frequently due to behavioural issues secondary to dementia. 3. Similarly, IGRA collection was also considered problematic due to requirement

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for phlebotomy. 4. Nursing staff reported a range of additional issues, including challenges with identifying appropriate persons responsible for healthcare decision-making for those residents not able to independently provide consent to testing. Where to from here: This study identified challenges of tuberculosis screening inherent in ACRF, and has informed local policy and practice. Tests for LTBI appeared to have little impact on management in this cohort, and in future surveillance for active disease rather than LTBI testing will be prioritised. The challenges illustrated in this report encourage alternative approaches to reducing the incidence and impact of TB in ACRF.

BI-7 Angela Rogers Easy access to guided meditation for all inpatients. ROGERS A(1) Aim: Easy access to guided meditation for all inpatients. Background: Music therapy can assist with stress management and can promote harmony between the mind and body (Jane Collingwood, 2016). Music can effectively relax a person and decrease stress levels. It can lower blood pressure and improve pulse and heart rates (Jane Collingwood, 2016). Electroencephalography (EEG) and magnetic resonance imaging (MRI) have indicated that meditation can alter the brain’s activity (Department of Health & Human Services, 2016). From lived experience, I know that listening to a guided meditation cd allows a clearing of the mind. A sense of calmness is enhanced and one becomes focused in the now. There are different types of guided meditation that are available such as: concentrating on one’s breath, grounding and mindfulness, emptying your mind, looking at an object, movement, or using a mantra (Department of Health & Human Services, 2016). Method: My Big Idea would be to make it possible for all inpatients to have easy access to an array of guided meditation audio from their hospital bed. This could be easily accessed from the patient’s TV/Radio system. Ideally, it would be fabulous if patients received a set of disposable headphones with their admission into hospital. However, this would be an expensive consumable for the hospital to maintain. However, patients could bring their own headphones into hospital. The Royal Melbourne Hospital could possibly set up two “Meditation” rooms somewhere in the hospital that is not busy and disruptive. This would cater for patients, who wish to meditate away from the surrounds of their hospital bed. These “Meditation” rooms would be equipped with possibly six to eight recliners so that patients could take advantage of either sitting or reclining in comfort. In these rooms a compact disk player would be used to play the guided meditation. These meditation sessions would run on a diary/timetable basis, so as to maintain order and ensure that patients can book a meditation session with ease. Where to from here?: The priority is to approach the hospital’s audio visual technicians regarding this idea of including some meditation material to the current hospital system. Would it be possible and feasible for patients to access this content from their bed?

BI-8 Louise Guerin Implementation of group-based education to improve patient quality of care, satisfaction and health outcomes GUERIN L Aim: To offer group-based education to patients and their families in the hospital setting on various clinical topics. Benefits for patients include social learning, self-efficacy, and improved quality of care, satisfaction and health outcomes. Benefits for Melbourne Health staff include enhanced

collaboration between staff and providing opportunities for professional development for nurses. Background: Patient education is currently provided to patients individually by their nurse. While this type of education has benefits such as the ability to tailor learning to the individual patient, there are also disadvantages such as the time it takes to educate patients individually and inconsistencies in the quality of the education. Group-based education can improve social learning as it allows the patient and their family to share their own experiences and learn from the experiences of others. It also builds self-efficacy in the patient to enable them to better self-manage. Further, it provides a structured and consistent quality of education. Equipped with solid foundational knowledge, the patient should be able to better engage in planning their care, and ultimately improve their health outcomes. Both patient and family satisfaction with the level of care provided by Melbourne Health would be enhanced. There would also be benefits for Melbourne Health. This includes enhanced collaboration between senior and junior staff and providing opportunities for professional development for nurses who aspire to roles in leadership, health promotion, or clinical education. Method: This initiative could be implemented at Melbourne Health in the function centre. Topics should be determined based on patient interest and educator expertise such as living with type 2 diabetes, how to manage chronic pain, and living with dementia for example. A different topic could be selected each month and offered at several different times to allow family member participation (e.g. day and evening). Group-based learning requires strong communication and facilitation skills. A Clinical Nurse Specialist (CNE) could facilitate the group-based education with a junior staff member. For patients with mobility issues, family members could accompany them to the session or the education component could be recorded and made available as a podcast. Where to from here? A pilot with a single topic and group of eligible patients is recommended initially. Baseline measures should be taken from participants before the pilot including both clinical measures (e.g. vital signs, HbA1c glycated haemoglobin test, lipid profile, medication adherence, current diet etc.) and measures of patient and family member satisfaction with hospital care. Following the pilot, these measures could be reassessed at different time intervals.

BI-9 Sarah Kleemann Process of Care for Spinal Cord Injury Patients KLEEMANN S(1), Mosley I(1) (1)La Trobe University

Aim: We seek to identify the process of care for patients presenting with SCI. Specifically, map the pathways of care, timelines, activities, investigations and procedures. Background: Spinal Cord Injury (SCI) is a most devastating event. It is typically associated with healthy young men, resulting in paralysis. Authors of recent studies recommend a reduction in time from spinal cord injury to surgical decompression in order to reduce secondary spinal injury and improve patient outcomes. Methods: A retrospective review of trauma records was undertaken for all patients who presented to the Alfred Major Trauma Service with a diagnosis of SCI over three years. SCI was identified using Abbreviated Injury Scale (AIS) injury and severity codes. Results: 119 patients were identified with an AIS spinal severity code >3 (complete n=54, incomplete n=65). Patients presenting via a referral hospital 29% (n=34). Average age 52 years with 84% Male. Median Injury Severity Score (ISS) 25, IQ(17-36). Median injuries per patient 4, IQ(2-8). 678 procedures were undertaken at an average of 6.7 per patient. 234 surgical operations performed at an average of 3.2 per

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patient. Median “Injury to Alfred Surgical Operation” time 17.5 hours IQ(9.2 – 42.5). Median “Door to Alfred Surgical Operation” time 12.9 hours IQ(5.3 – 25.3). Where to from here?: Early surgical decompression combined with innovations like therapeutic hypothermia could potentially improve outcomes for patients with traumatic SCI. The results reported here quantify the operational and logistical events that occur after SCI. This study contributes to our knowledge by outlining priorities, timelines, procedures and potential opportunities for time reductions. We found that the vast majority of patients experienced co-existing injuries. A diverse and complex mix of procedures were undertaken from point of injury to the operating room including in the ambulance, the referral hospital and the trauma unit. Median injury to operation time was found to be below previously reported times of 24 hours. Further research is required to test interventions aimed at reducing time to surgical operations and in turn improving patient outcomes.

BI-10 Elizabeth Barson The feasibility and acceptability of embedding mental health screening into referrals to a general hospital Clinical Psychology service BARSON E(1), FISHER C(2) Aim: To establish best practice mental health screening in the Clinical Psychology service Background: The complex and bidirectional relationship between mental health and physical illness is well documented. Poor mental health is associated with an increased risk of physical illness. Physically-ill patients with comorbid mental health conditions have: reduced treatment adherence, increased symptom burden, poorer prognosis, increased mortality, reduced quality of life and higher utilisation of services. Integrated mental and physical healthcare can improve outcomes and reduce service use and healthcare costs. However, mental health problems frequently go undetected in busy physical healthcare settings. This has been attributed to stigma around mental illness, lack of time and accessible resources, and concerns about how any mental health problems discovered would be addressed. Therefore, despite strong empirical and policy support for embedding of mental health screening into routine practice, implementation has continued to lag behind the evidence. The Clinical Psychology service at Royal Melbourne Hospital is a small service that has evolved in response to requests and funding opportunities to provide assessment and intervention to specific wards and departments. The process of referral has developed in a similarly organic manner via collegiate networks and does not currently include any structured mental health screening tools. Demand for Clinical Psychology services within the hospital is currently exceeding capacity and growing. Therefore, there is a strong imperative to ensure the effective and efficient allocation of resources. A clearer understanding of the mental health concerns of our referred clients will allow us to enhance our existing referral pathways, prioritise service delivery, target service development and capacity building initiatives, and build a robust framework for service evaluation. Method: The first stage is a systematic review of mental health screening tools used in general hospital settings. The second stage is a qualitative review of the barriers and enablers of mental health screening within the Clinical Psychology Service and referring departments and wards. The third stage is a time-limited trial implementing the selected screening tool and protocol to evaluate the acceptability (via number of administrations and clinician and client feedback), feasibility (via changes to referral patterns and clinician feedback) and usefulness (via information provided by the tool regarding symptom type and severity and clinician feedback).

Where to from here?: The next step is conducting the systematic review of the literature and developing the qualitative interview for clinicians and referrers regarding the protocol.

BI-11 Michael Chmiel Implementation of a student nurse volunteer pool to enhance patient-centred care and increase clinical exposure for students. CHMIEL M(1,2), Guerin, L(1,2). 1) La Trobe University; 2) Melbourne Health

Aim: To recruit a student nurse volunteer pool which would both enhance the experience of Melbourne Health patients and provide valuable exposure to the clinical environment for La Trobe undergraduate students. Background: In 2016, Melbourne Health piloted a program involving La Trobe Bachelor of Nursing undergraduates employed as Health Assistants in Nursing (HANs). This program supported the nursing team in the delivery of high-quality and safe patient-centred care, primarily through undertaking constant supervision of patients with delirium, dementia, or those at high risk of falls. For many such patients, company and conversation may be regarded as frontline interventions. However, the benefit of this support is not limited to elderly or frail patients. Melbourne Health is currently recruiting for additional HANs, and the experiences of existing HANs involved in the 2016 pilot have been largely positive. The proposed student volunteer pool would enable additional students to gain valuable exposure to the clinical and sub-clinical hospital environments in their second year of undergraduate study, whilst not adding any significant additional cost to Melbourne Health. Such exposure is of direct benefit to participating students, yet also provides ongoing benefits to patients in the future as students progress through their training. This pre-screened pool of volunteers could also be used for recruitment for HANs when additional staff is required. Method: The student volunteer pool role would not involve any clinical duties, precluding the need for direct supervision. It could involve patient support such as accompanying patients to the ground floor food court, post office, or shops at the Royal Melbourne Hospital, making purchases on their behalf if they cannot leave the ward, delivering flowers to the bedside, reading to the patient, procuring and returning library books, refilling water jugs, maintaining a safe and tidy environment around the bed, facilitating TV connection, or helping with mobile phone and web technologies. In addition, volunteers could assist the healthcare team by ensuring relevant stock levels are maintained on the ward, picking up dressings or stock from other wards if required, or cleaning equipment. Where to from here?: It is recommended that a pilot be conducted with a small group of volunteers initially, selected from students allocated to the Royal Melbourne Hospital clinical school. Recruitment could be integrated with existing volunteer selection and training programs, and availabilities structured around students’ existing work and study commitments.

BI-12 Kate Storer Including the patient in their care through digital screen schedules. STORER K The aim of this idea is to help the patient feel more included within their care during their time at the hospital. During placements, and hearing stories from family members, one of the biggest issues while in hospital is the general lack of communication and not knowing what is happening. It is hard sometimes to be able to inform the patients of every single

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thing, especially as times of appointments and varies other things constantly change. That is why I believe an introduction of digital screens within the patients room would be useful. These screens will have a schedule on it when doctors are coming in, when medication, observations, scans and other appointments are due. Therefore the patient is aware of what has been planned for that day. As things change the system can be updated, which will change the screen, so the patient is always kept up to date in relation to what is happening. This will also allow patients to plan their day, including organising when visitors are coming in. Things can also be added as needed depending on what ward, for example on oncology, the latest blood readings can be seen by the patient as soon as they are in. I believe this will improve the patients experience within the hospital setting as they will feel more included within their care, and feel less anxious as they know what is happening for the day.

BI-13 Claire Ervin Does leg elevation reduce nocturia in patients with co-existing cardiovascular disease and lower leg oedema? ERVIN C(2),Whishaw M(1), Ong Tj(1)Rose,G(1), Bower W(1) La Trobe University

Aim: The aim is to identify if community dwelling participants ≥60 years of age with lower leg oedema and nocturia can increase the redistribution of peripheral oedema fluid by resting supine for 90 minutes before bed at night. Reduction of fluid redistribution overnight may alter nocturnal urine volume, reduce nocturia episodes and improve self-reported health-related quality of life Background: Nocturia, the act of waking from sleep to pass urine and returning to sleep more than once per night, affects up to half the population over 50 and increases in severity as people age. The burden of nocturia also increases similarly, with nocturia identified as a significant problem that can impact negatively on people’s life. In older patient populations, chronic heart failure can result in night-time evacuation of 3rd space fluid, making peripheral oedema one of the most common causes of nocturnal polyuria in the older population The continence literature on conservative lifestyle management of nocturia, widely recommends rest with legs elevated, but there is little consensus around the recommendations. Noninvasive and well tolerated treatments require further investigation, as nocturia negatively impacts quality of life in an aging population. Methods: We aim to identify if leg elevation reduces nocturia by recruiting 19 eligible participants to record baseline measures of lower leg circumferences and a 3 day bladder diary, and then again after resting in a supine position for ninety minutes prior to bed. An actigraphy body worn device will also be employed to track sleep patterns. This will be a pretest post-test design using each participant as their own control. The primary outcome of episodes of nocturia will compared to evaluate the effectiveness of a commonly recommended strategy to reduce nocturia. Secondary outcomes of nocturnal urine volume, first uninterrupted sleep time (FUST); and nocturia-related quality of life, will also be compared. Where to from here?: Lifestyle strategy education can increase an individual’s involvement in their shared healthcare plan and positively impact on reported outcomes. Improved outcomes may be achieved if robust research has informed specific instructions. People may succeed with lifestyle strategies if they know how long and at what time they should elevate their legs to see improvement in nocturia. Benefits of this non-invasive intervention may include; increased fluid redistribution prior to bed, lower nocturnal urine volume, less nocturia episodes and improved quality of life.

BI-14 Tara Dehm Nurses’ perceptions of changes to emergency stroke care procedures with the implementation of dedicated stroke ambulances in a metropolitan tertiary hospital DEHM T(1) La Trobe University

Aim: The aim of this proposed study is to explore how nurses’ believe their role in emergency stroke care will change with the implementation of mobile stroke units. What barriers and enablers are identified that may hinder or assist changes in clinical practice to support the Mobile Stroke Unit. The information gleaned from this study will inform researchers and policymakers in developing strategies to optimise acute stroke pathways of care between the mobile stroke unit, and the tertiary metropolitan hospital. Background: Following the trials of mobile stroke units implemented in Germany and American, the Royal Melbourne Hospital is introducing Australia’s first mobile stroke unit in the North-Western region of Melbourne, in order to reduce the time involved in the diagnosis and treatment for patients suffering from strokes. The implementation of mobile stroke units could allow for expedited access to the necessary CT scans and thrombolysis, thus decreasing time from stroke onset to both treatment and presentation to hospital, and improving patient outcomes (Hacke et al., 2008; Bray, Mosley, Bailey, Barger & Bladin, 2011). Walter, Kostopoulos, Haass, Keller and Lesmeiste (2012) reported the benefits of a mobile stroke unit. However, one important limitation of mobile stroke management studies was how the implementation of stroke ambulances influenced the nursing care provided once they were transported to the hospital. Mocco et al., (2015), identified in their comparative study of neurothrombectomy devices, that patients should be treated in facilities with efficient, team-based and organised facilities that engage in continuous quality improvement processes. Method: The research proposed would be conducted using semi-structured interviews with registered nurses in the emergency department and perioperative department of the hospital – (those nurses most involved with emergency stroke care). Study participants will be provided with an outline of the current proposed plans for mobile stroke unit implementation in Victoria. The semi-structured interview will involve exploring the participants’ current role in emergency stroke care, the positives, negatives and gaps they can identify within the outline, and their beliefs about how their role in stroke care may be affected. Where to from here?: Identification of Key Staff ; Identification of proposed procedures for MSU?; Identify variances from current practice and planned implementation of new practice for the MSU study; Pilot test questionnaire.

BI-15 Kate Storer Digital touch screen – map of where to go STORER K On entering a hospital it can be a quite daunting experience, whether it is your coming for your own treatment or to visit a loved one. The added stress of not knowing where to go can amplify those emotions causing unneeded angst. This is why a simple addition of digital touch screens, as seen in many of the big shopping centres, can make a huge difference in reducing anxiety levels. From my short experience at The Royal Melbourne Hospital and being lost myself, while also having patients ask me how to get to a certain area, I can see that the addition of a few of these screens would make a huge impact on everyone getting to where they need to go a lot quicker and calmer. The screens would have a list of the different areas eg. Cardiac, orthopaedic, palliative, oncology etc. as well as a

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search bar. The patient and their family will be able to search for the area they are looking for and a map will be bought up showing them the way to get there. I believe a short survey of how people find travelling around the hospital will be sufficient in gaining data as to whether the implementation of these digital screens would make an impact. I would suggest installing one at the entrance and trailing how it goes, and installing more thereafter once the success of these screens are shown.

BI-16 Kayla Arkinstall Pre-operative education ARKINSTALL K(1) Latrobe University

Background: Pre-operative surgery is a time of high anxiety for patients, as fear of the unknown and ‘going under the knife’ is a stressful experience. Thus patient anxiety can become problematic, particularly during pre-operative appointments, as it can make it difficult for the patient to understand and remember the information that’s provided. Studies have also noted that anxiety can make pain associated with the procedure harder to cope with and potentially worse than it might have been if patient anxiety levels had been addressed and adequately dealt with in the initial stages. Aim: In order to address this problem my aim would be to provide a central location for health information relevant to the patient’s procedure, which would be delivered in the form of a hospital app. The purpose of this app would be to provide educational resources to patients about their specific procedure that they may access after pre-operative appointments. This app’s ultimate goal would be to provide more information and educate patients electing to undergo surgery in an attempt to alleviate anxiety and concerns associated with the process. Methods: The app would achieve these aims by educating the patient during the pre-operative period on their procedure through platforms like approved videos detailing what will occur, the potential complications, relevant anaesthesia information and what to expect post-procedure. This platform could also be used to provide links to information brochures/leaflets/posters that will aid in reducing patient anxiety. It will also provide information on what is needed to be done prior to the procedure including a checklist that highlights all necessary documentation, information on additional requirements like fasting times, and documents that will need to be brought on the day of the procedure. Post-operatively the app can detail information about what to expect and what serious symptoms to look out for and when to contact their doctor in regards to same. This app will also provide information in regards to any required follow-up appointments, what to bring, the appointment date and time and associated reminders. The app would provide a feedback questionnaire on its effectiveness at reducing anxiety and providing information about the procedure in order to determine its overall effectiveness and to suggest improvements for future users. Where to from here?: Development and trial of a prototype app that will determine whether the app has merit in terms of alleviating anxiety and providing information.

BI-17 Danielle Hitch Is it time to move on from Evidence Based Practice? Hitch, D (1) North Western Mental Health, Deakin University

Evidence based practice has been a key concept in health care for the past 20 years, and yet the research / practice gap remains as wide as ever. While attitudes towards using evidence to guide health care are very positive amongst a

range of health professionals, good intentions are clearly not enough to make significant changes. Clinicians are exhorted to up skill their ability to find relevant sources from the hundreds of articles being published every day, conduct literature reviews, critique the research they find, become statistically literate, and devise strategies for adapting and modifying the evidence to their particular setting. Oh, and by the way, they also need to carry full caseloads and ensure they provide top quality care to as many people as possible. Understandably, many prioritise practice over evidence. And so the status quo remains. The aim of this presentation is to critically consider the concept of evidence based practice, and present an alternative framework which seeks to improving patient care by meeting clinicians on their turf. Evidence based practice cannot exist independently of clinical reasoning, and the Integrating Theory, Evidence and Action (ITEA) framework provides a method for bringing the multiple ways of knowing used by clinicians together. Since its development, this framework has supported clinicians and academics to embed their practice in theory, and understand the implicit barriers and challenges around getting evidence into practice. A recent update (including the Person) has strengthened its ability to meaningfully include the practice knowledge of clinicians and personal knowledge of patients into the process. The directions in which this framework may develop into the future will be identified, and the potential for inter-disciplinary collaboration highlighted.

BI-18 Emma Peacock Barriers to implementation of Nurse-Initiated Point of Care Testing and Oseltamivir regimes for Influenza Peacock, E(4) La Trobe University Nursing Student

Aim: This project aims to explore the feasibility of a nurse-initiated point-of-care testing (POCT) protocol for influenza in the setting of long-term care. By identifying barriers to implementation of nurse-initiated POCT, strategies to improve nurse and facility engagement with the protocol might be established. Background: Outbreaks of viral infections, particularly influenza, pose significant dangers to the well-being of residents in long-term care facilities. Nurse-initiated point of care testing for influenza has the potential to facilitate earlier isolation and intervention for residents who have tested positive. By isolating confirmed cases of influenza earlier, outbreaks and further spread might be prevented. Early intervention with the antiviral drug Oseltamivir may lessen viral shedding, severity of symptoms and duration of illness for infected residents. However, cost issues, nurse education, scope of practice concerns, and identifying deteriorating residents who should be swabbed may present potential barriers to effective implementation. By identifying and addressing these barriers, nurse-initiated point of care testing protocols and early intervention with Oseltamivir may be made more viable in long-term care facilities. Methods: Pilot versions of the nurse-initiated POCT protocols have been launched in some of the Royal Melbourne Hospital long-term care facilities. To explore the feasibility of the POCT protocols and barriers to implementation, a mixed-methods approached might be most appropriate. Analysing existing and incoming data surrounding current uptake and efficiency of the protocol will demonstrate if, how and when the protocol is currently being employed and with what effect. Structured interviews may determine nurse perception of the program, identifying barriers to effective implementation and highlighting avenues for improvement of the protocol. Where to from here? By identifying barriers to implementation of the nurse-initiated POCT protocol and Oseltamivir regime, the program may be more successfully implemented in a

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greater range of facilities, and early detection, isolation and intervention into influenza in long-term care facilities might be achieved. A literature review exploring the strengths and weaknesses of existing nurse-initiated POCT protocols, the use of Oseltamivir in ageing residential populations, the human cost of late or inappropriate intervention into influenza in aged care, and the burden of influenza on long-term care facilities will further highlight the need for this research.

BI-19 Nicole & Gordana Clare & Boskovic Our BIG idea CLARE N(1) BOSKOVIC G(1) Latrobe University

The majority of our placements have been in sub-acute hospital environments with elderly patients. With the time we have spent on the ward and observations we have made we noticed that the elderly people had limited social interaction and a lack of mind stimulating activities. The limited socialization and decreased mind stimulation seemed to be due to two main reasons. The first reason being that family and friends are not able to visit their loved ones due to numerous reasons. The second reason being because the patients were in single rooms or had curtains dividing the rooms. To our observations this developed feelings such as boredom and isolation. To our knowledge, isolation and boredom can increase the chance of mental illnesses such as depression and can decrease the drive to get back to good health. The aim of our BIG idea is to ensure a more enjoyable and pleasurable stay to enhance mental health which will assist the patient back to good health. Therefore, with the above in mind our BIG idea is to firstly have an allocated space where the patients from the ward can go and meet, socialize and enjoy their meal times together. This will be something that will be notified to the patient on admission to ensure that the patient feels welcome to join the meal time dining area. For patients that are unable to mobilize to the dining area, with permission from the other patients, the curtains will be opened for meal times so the patients can socialize. The second component to our BIG idea is the establishment of daily activities whilst patients are in hospital. The activities will be targeted at the patient’s current situation, discharge plan, medical conditions and abilities. This can be achieved by the nurse investigating on admission the patient’s most suitable activities and what activities would be most appropriate for the patient. Having a common area or scheduling the activities could also assist in the achievement of this idea. This idea is measured by monitoring interaction of the patient via a daily interaction sheet and then reviewing how effective the activities and meal times are on the patient’s mood and general wellbeing.

BI-20 Angela Rogers Personal hygiene/toiletry packs for inpatients: ROGERS A(1) Aim: Provide personal hygiene/toiletry packs for inpatients containing plastic toothbrush/toothpaste; plastic combs/elastic; soap; deodorant wipes/sachet; sanitary hygiene products. Admission to hospital is never a joyous occasion. From lived experience the feelings of an upcoming planned admission is filled with anxiety and worry and helplessness. These feelings are heightened when admissions are not planned and unexpected. In such instances patients can be unprepared for a stay in hospital. This can cause further stress because often there is a need to rely on the help of loved ones. Sadly, some patients do not have anyone they can call upon. Hence, the idea of providing basic hygiene packs.

Background: In the United Kingdom ‘patient packs’ have been distributed in many community hospitals (Virgin Care, 2012). However, the packs that are offered by Virgin Care include not only basic hygiene essentials, they include a handbook which informs patients and their visitors about important details such as: available services in hospital, hospital policies, visiting hours, and important staff members (Virgin Care, 2012). Included in these patient packs are puzzles and a 3-in-1 magnifying glass to help keep patients mentally active whilst in hospital. These packs come in a plastic bag, which becomes a laundry bag to transport the patient’s washing home and a waterproof pocket inside to keep the toiletries (Virgin Care, 2012). Virgin Care reported that the purpose of the personal packs was to make patients feel welcomed and cared for without having to be reliant on others (Virgin Care, 2012).The feedback regarding these packs has been promising. 80% patients stated it was a good idea and 67% replied that they would continue to reuse the pack upon leaving hospital (Virgin Care, 2012). Methods: Obviously such packs would be costly to introduce and maintain. Large establishments such as airports, airlines, cruising ships, hotels and motels have always stocked consumables within a large scale. Virgin Care is run by Richard Branson. Where to from here: The Royal Melbourne Hospital could possibly approach the procurement branch of an Australian Company such as Qantas Airlines (Qantas) to assist with logistics of introducing such a product. I feel that providing basic toiletry packs would assist patients and enhance their dignity.

BI-21 Kate Storer Beauty - a useful therapy STORER K On coming into hospital there is quite a bit of uncertainty, and one of those uncertainty is how long the admission is going to last for. Some people may be admitted for a day, others months. During that time the patients general appearance seems to get pushed a side, as more important things are dealt with. That is why I believe an introduction of a beauty service would be beneficial to the patients as well as the hospital, as the overall happiness of the patient will improve through a bit of self loving. By becoming affiliated with beauty training facilities around the area, free or reduced cost services will be available for the patients, while the students at the school will receive extra hands on training. Some of the possible services may be manicure, painting nails, facials, and small massages of hands, head and feet. I believe that if people feel good about themselves, their overall health improves, leading to a possible reduction in length of stay.

BI-22 Ian Mosley Does this patient need to be in the ED? MOSLEY I (1), Brown M (2). LaTrobe University Staff (1), LaTrobe University Student (2).

Aim: We seek to identify the incidence of non-urgent Emergency Department (ED) presentations among adults presenting to a major public hospital ED. Furthermore we seek to explore the reasons for attending the ED among people who are assessed at triage as being non urgent. (triage category 5) Background: ED presentations overall are increasing at a rate of 5% per year with over 1.5 million presentations in Victoria in 2014. Of these 10% were categorised as non-urgent with expected waiting times in excess of 2 hours. There is however much difficulty in determining what is an inappropriate, or unnecessary, or non-urgent ED visit. Furthermore, over many years a diverse range of strategies to “De-Market” ED visits

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have been largely unsuccessful. With patients stating the ED was a “one stop shop”. Patients reported presenting to the ED because they believed their condition was serious enough to require ED attendance or because of the time of the day. Methods: Part A: A retrospective analysis of ED records will be undertaken to identify the incidence and presentation patterns of category 5 patients who are discharged home from the ED with a minor or superficial diagnosis and were documented as not requiring investigation, procedures or referral. Part B: Patients identified in the ED as category 5 and have been directed to the waiting room will be interviewed with a semi-structured questionnaire to determine the reason for attendance. GP confidence, diagnostic services access, cost, waiting times, medical history, frequency of attendance, perceived severity and patient demographics among others issues will be discussed at interview. A follow up review of ED records will be undertaken to confirm final discharge diagnosis, length of stay and treatment for included participants. Where to from here: The outcomes of this study may inform strategies to reduce non-urgent presentations among specific patient cohorts. Presentation patterns of non-urgent cases may inform resource allocations and development of alternate care pathways to reduce the impact of non-urgent cases on the ED when they do present.

BI-23 Jodie Swan Using Touchscreen Technology Within Residential Care to Promote Meaningful Activity: Evidence and Implementation SWAN, J, HITCH, D Melbourne Health

Touchscreen table technology (TTT) is a low cost and accessible form of technology, which may provide opportunities for people in residential care to engage in meaningful activity that align with a persons interests and life experience. However, evidence around their use in practice has been sparse to date and the factors that might impact on the implementation of this innovation have not been explored. A comprehensive scoping review of the use of TTT in these settings will be presented, including efforts to evaluate its impact on the health and wellbeing of people in residential care. The Consolidated Framework for Implementation Research (CFIR) will then be used as a framework for discussing past, present and planned research at North Western Mental Health on this topic and how this technology has been implemented into practice. By taking an implementation science approach, the team has been able to successfully implement evidence into practice.

BI-24 Nethmi Subasinghe Encouraging Nutrition Through Volunteers SUBASINGHE N(1) 1: La Trobe University

Aim: To introduce a volunteering program of assisting patients with meals, whether it be feeding, setting up meals, socialising with them, encouraging them to eat and drink adequately or filling in their menu. Too often the nursing stuff do not have the time to patiently continue feeding, assisting all their patients with their meals or encouraging them to eat adequate amounts. The aim of this program is to encourage and help with patients having an adequate dietary intake during hospital stay, so patients do not become undernourished and have significant weight losses. Nutrition impacts their hospital stay, wound healing and mental state. Background: Malnutrition and weight loss is an increasing issue across health facilities and is not highlighted enough to nursing staff, doctors and allied health members as a major

concern during the care and treatment of medical and surgical patients. Essentially, this affects patients' health, becoming undernourished, losing weight, not healing as quickly, creating more health issues and in turn, resulting with a longer hospital stay. Also, some patients have language barriers, difficulty reading menus and, cognitive and physical impairments. Methods: This program should be available for volunteers to partake in, where they feel like and are directly involved in the patients' care and wellbeing. Volunteers want to know that they are making a difference at the hospital, and this program will definitely do so. Nurses and dieticians should initiate which patients in each ward needs extra assistance with meals, whether it be any of the options mentioned earlier. During meal times volunteers should be allowed to come into their specified ward and go to the patients requested by the staff, ask consent from the patients for their assistance, encourage meal intake and socialise with them. Their dietary intakes (diet and fluids) can be recorded by the volunteers, if need be, so nurses, dieticians and other members can monitor their intakes. This program will significantly drop the amount of patients who lose weight during hospital stay. Where to from here: This program should be brought to the Volunteer Board, discussed about with nurses, doctors, dieticians, speech pathologists and volunteers. This program will positively impact the patients' health, not worry families, relieve stress from nurses, decrease the number of those undernourished or malnourished, make volunteers be actively involved in patients' care and feel helpful, lessen dietician consultants and improve quality of care.

BI-25 Dani Moore Shift Planning – Can we optimise the approach for students? MOORE, D (1) 1. LA TROBE UNIVERSITY

Aim: Good time management skills are a requirement for most job applicants. Nursing is certainly no exception and in fact, as students, time management is an aspect of training which we are required to focus on in every placement opportunity. I feel with a little bit of administrative intervention, shift planning could be adjusted slightly for students, to allow them to optimise their daily plan. Ultimately, our ability to effectively plan our shifts will increase our confidence in performing our tasks. This will lead to optimal relationships with our buddy nurses and CNE’s and flow through to excellent patient care. Background: I initially identified this opportunity in my first placement (second year) at RMH. Buddied with a nurse who was sharing a patient load of 8 with another RN, I was a little overwhelmed by time planners and patient loads whilst trying to get my head around handovers, nursing abbreviations and the general running of the ward. Upon reflection, I felt time planning for students could be adjusted slightly to allow for these aforementioned overwhelming elements. I set about creating a newly designed time planner for students. With more placement exposure I noticed that whilst time planning itself remained relatively unchanged from ward to ward and hospital to hospital, adjusting to life on different wards, with different health focuses was an area in which students were likely to fall behind. I created a template which can be used in each different ward for students. Essentially, it contains more detail for students to remind them and refocus them throughout their days. On the back, it contains a snap shot of information relevant to the specific ward, such as common abbreviations and medications. In my recent placement on 4 south, I included a picture of the brain, to remind me of the lobes and their functions.

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Methods: Implementation of ward specific time planners can be simple, effective and easily measured. A rollout across wards would require a short presentation to nurse educators, who can choose to insert their “headline information” on the back for students. Assessing the user friendliness and benefit of the planners could be done via CNE feedback on student proficiency and student feedback on user friendliness. Both sets of feedback could be gained via a survey monkey. Where to now: I would appreciate the opportunity to present my idea and further explain the benefits of student focused time planners.

BI-26 Kate Storer Trolley full of distraction STORER K During ones stay in hospital, time can tick by quite slowly, especially without visitors. That is why I think an introduction of a book trolley would be handy in filling in the time between appointments. A volunteer could be used to push around a trolley to suitable wards, handing out donated books and magazines to those who may want to read to pass some time. The aim of this idea would be to reduce patients boredom, while keeping their mind active with reading. This in turn will hopefully improve the patients stay as they feel they have spent their time doing something rather than nothing.

Poster Abstracts 41 Sarah Eaton High rates of caustic ingestion in migrant populations EATON S, Buckle A, Metz A, Hebbard G, Sood S Melbourne Health, Department of Gastroenterology

Aim and background: Ingestion of caustic substances are uncommon, but can result in serious and life-threatening injuries to the gastrointestinal tract(1) with a mortality of 7-14%(2). Patients often require multiple endoscopic procedures, and represent a significant healthcare burden. Methods: We conducted an audit of caustic ingestion at the Royal Melbourne Hospital (RMH) between 2010-2015 to evaluate the burden of disease, quality of care, and identify high risk groups for caustic injury. Patients were identified through casemix coding, and file reviews undertaken to collect demographic data and clinical outcomes. A chi-squared test with a p-value <0.05 considered significant. Results: 38 adults (18M:20F) were admitted for caustic ingestion over 5 years. The median age was 30.5 years old (range 18-85). More than 60% were due to deliberate ingestion. Common agents included hydrochloric acid (21, 55%) and sodium hydroxide (6, 16%). 37% had pre-existing mental health comorbidities. 2 patients (5%) died as a result of caustic ingestion. Only 13 patients (34%) were born in Australia, with the majority born overseas (25, 66%). The RMH catchment is large and diverse. According to the 2011 census, 36.7% of persons in Greater Melbourne were born overseas(3). Using the chi-square statistic, the number of overseas born persons with caustic ingestion was significantly higher than expected (p<0.001). When migrants from individual countries are analysed, it revealed disproportionally high rates of caustic injury in persons from minority regions. North Africa and the Middle East accounted for 7 (18%) of our study, but only 2.1% of Melbourne's total populations. The same was seen with Southern and Central Asia; who accounted for 6 (15%) patients but only 4.4% of Melbourne's census(3). Conclusion:This audit highlights a concerning number of caustic ingestion injuries in overseas born persons who seems to be at greatest risk. There is need for further investigation and analysis of at risk groups and mortality rates throughout Victoria.

42 Emma Halmos Compliance of gluten free food provided in Melbourne food outlets HALMOS EP(1), Di Bella C(2) Webster R(3) Tye-Din JA(1,4,5) 1) Department of Gastroenterology, The Royal Melbourne Hospital 2) Coeliac Victoria and Tasmania 3) Health and Wellbeing Branch, City of Melbourne 4) Immunology Division, The Walter and Eliza Hall Institute of Medical Research 5) Department of Medical Biology, University of Melbourne

Background & Aims: Effective treatment of coeliac disease is contingent upon a strict gluten free diet but remission is often incomplete. Inadvertent or accidental gluten exposure is considered an important cause of this problem. Patient reports of symptoms triggered by gluten relate mostly to dining out, however the compliance of food outlets providing gluten free food has never been formally assessed. This study aimed to investigate the likelihood of gluten exposure in outlets providing gluten free food by analysing samples of food declared gluten free for gluten content and assessing knowledge of foodservice staff. Methods: Food outlets within the City of Melbourne that declared at least one gluten free item on their menu were

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randomly selected for inclusion. Unannounced site inspections were conducted by City of Melbourne Environmental Health Officers (EHO) (October to December 2016). Each inspection involved i) sampling of at least one gluten free food item for independent qualitative and quantitative analysis of gluten content (Ridascreen® R5 Elisa), and ii) completion of a questionnaire assessing knowledge and implementation of gluten free standards by the manager or most appropriate onsite employee. Gluten free was defined as ‘no detectable gluten’ as per the Food Standards Australia New Zealand (FSANZ) code. Data was compared to retrospectively obtained compliance rates of gluten free food samples tested within a two-month period in both 2015 and 2014 in an overlapping sample of outlets. Results: From the 128 food outlets included in the 2016 audit, 158 food samples were analysed and 14 (9%) had detectable levels of gluten. Of these samples, five had < 20 parts per million (ppm), four had 20-80 ppm and three had gluten content above the measurable limit of 80 ppm (two were from gluten-containing foods mistakenly provided to the EHO as gluten free). Non-compliance rates had improved, being 28/138 (20%) in 2014 and 22/151 (15%) in 2015. Knowledge and practice of gluten free food was generally poor, with the most recent questionnaire results indicating that 95/123 (77%) outlets could not identify gluten-containing grains, including 12 not identifying wheat as gluten-containing. This rate was comparable amongst compliant and non-compliant outlets. 20% of outlets used FSANZ prohibited declarations of ‘gluten friendly’ or ‘coeliac friendly’. Conclusion: Despite improving rates of compliance to provide gluten free menu items, knowledge of gluten and food standards amongst foodservice staff is inadequate. Interventions targeting foodservice staff education could further improve the safe provision of gluten free food.

43 Nick Ternes A new model of care – the implementation and evaluation of the Allied Health Interdisciplinary Professional Practitioner (AHIPP) in General Medicine TERNES N, Edwards S, Marr L, Phan U, Plumb S Royal Melbourne Hospital

Background: Patients admitted to hospital under general medicine units are presenting with increasingly complex problems and comorbidities requiring significant input and expertise from multiple disciplines. This places larger burdens and pressure on the traditional multidisciplinary team (MDT). Evaluation has identified various inefficiencies in service delivery within the MDT including delay in allied health (AH) referrals and commencement of intervention. Other areas for improvement included; reducing duplication of assessment and management across AH disciplines, streamlining discharge planning and coordination of care across the continuum and providing clinical leadership to junior allied health staff. The AHIPP supports an interdisciplinary team (IDT) approach through a clinical leadership role and by completing interdisciplinary screening and assessment ensuring care is provided by the right person, in the right place, at the right time. Methods: The AHIPP was implemented as a feasibility pilot study with initial funding support from the Department of Health and Human Services. Two general medical units received AHIPP intervention and one control group general medical unit received standard care. The AHIPP interventions included screening and early assessment of patients to establish allied health needs and ensure appropriate referrals were in place for timely intervention from each discipline. The AHIPP reviewed patients with a length of stay greater than 7 days to support allied health decision making and discharge planning. Results: The AHIPP was implemented and initially evaluated over a four month period from July to November 2015 with

positive trends seen. The role continued throughout 2016 with further extensive analysis completed. Key findings included a 1 day decrease in median length of stay in AHIPP intervention units compared to control units 7 days (IQR 4-12) versus 8 days (IQR 5-13), (p=0.016), 4.3% increase in proportion of patients discharged directly to their previous place of residence compared to control units and a 10% increase in allied health referrals being made within 48 hours of admission. Conclusion: The AHIPP in General Medicine is an innovative model of care enabling a more responsive allied health service to better meet the challenges of a complex patient caseload.

44 Arleen Watt The prevalence of disordered eating behaviour in adults with type 1 diabetes mellitus attending the Melbourne Health Diabetes Service WATT A (1), Bramley A (1,2), Sandison A (1) 1. Melbourne Health, 2. La Trobe University

Aim: The aim of this study is to establish the prevalence of disordered eating behaviour (DEB) in adults with Type 1 diabetes mellitus (T1DM) attending the Melbourne Health Diabetes Service. Background: Diagnosed Eating disorders (ED) and subclinical disordered eating behaviours (DEB) are a concern for patients with Type 1 diabetes (T1DM) due to the associated risk of poor outcome and mortality. Detection of DEB can be very difficult due to common identifiers, such dietary restraint, weight monitoring, increased activity and self-titration of insulin, being routine factors in the management of diabetes. It has been recommended that regular screening for disordered eating should be incorporated into routine care. The Diabetes Eating Problem Survey - Revised (DEPS - R) was designed as a screening tool to detect DEB specifically in T1DM. Methods: Adults aged 18-65 with T1DM attending the service were invited to complete the DEPS - R. Additional demographic and medical data were obtained including age, sex, BMI, HBa1C, duration of diabetes, number of hospital admission in last 12 months and episodes of DKA. Results: A total of 199 participants completed the DEPS-R, with 31.2% obtaining a score of ≥ 20, indicating DEB. A DEPS-R ≥ 20 was associated with being female (39% vs 23.3%, p=0.016), a high BMI (28kg/m2 (24.5-31.6) vs 25.5 kg/m2 (22.8-28.1), p=0.002) and a high HbA1c (median (IQR) 8.9% (7.8-10.2) vs 8% (7.3-8.7), p<0.001). The prevalence of DEB increased significantly with BMI, from 21.3% (BMI18.5-24.9kg/m2) group to 37.1% (BMI>25/m2) group (p=0.02).Low levels of risky behaviours such as insulin omission (4.8-11.3%), binge eating (11.3%) or purging (1.6%) were observed whilst high scores in desiring to lose weight (58%) and skipping meals (24.2%) were noted. Conclusion: In adults attending the Melbourne Health Diabetes service, 31.2% had a DEPS-R > 20 indicating presence of DEB. A positive correlation between Hba1C, BMI and DEB was observed. A DEPS-R ≥ 20 was mostly driven by questions regarding a desire to lose weight, meal patterns and glycaemic control. Weight loss may be desirable in older patients with higher BMI suggesting reduced sensitivity of the DEPS-R in adults compared to paediatric populations. All patients with diagnosed pre-existing ED had scores ≥ 20 confirming specificity. The interaction between weight, diabetes control and eating behaviour is complex. Although less sensitive in adults the DEPS-R may be a useful tool to identify patients with potential DEB and the need for dietetic intervention.

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45 Lauren Grundy Poor recognition of Malnutrition at Melbourne Health GRUNDY L, Marshall K, Osborne J, Ford J, Watt A, Fetterplace K, Sandison A Clinical Nutrition Department, Melbourne Health

Background: Malnutrition is highly prevalent in the hospital setting, and is associated with poor outcomes and increased health care costs. In accordance with National Accreditation Standards, it is mandatory that all hospitalized patients are screened for malnutrition, and if at risk, referred to a dietitian for assessment and intervention. In 2011, 43% of patients at Royal Melbourne Hospital (RMH) were found to be malnourished. Only 50% of these patients were referred to a dietitian. In 2012, malnutrition screening was introduced at Melbourne Health. Although compliance rates have improved, bedside auditing shows a compliance rate of 79%, (below KPI 90%). The accuracy of screening is also inconsistent, and many malnourished patients are not being referred to a dietitian. Aim(s): To assess the compliance and accuracy of malnutrition screening at RMH, and determine if appropriate referrals were sent to the dietitian; To determine malnutrition prevalence, and identify associations between malnutrition and complications. Methods: In December 2016, the Nutrition Department undertook a one day audit of all patients admitted to RMH, excluding ICU, palliative care and John Cade. Patients were also excluded if they were unable to consent due to cognitive impairment or severity of illness. All patients were screened for malnutrition risk using the Malnutrition Risk Screen (MST). Patients deemed at risk of malnutrition were assessed by a dietitian using the Subjective Global Assessment (SGA) to determine nutritional status. Demographic data, admission diagnosis, dietitian referrals, and nutrition interventions were also collected. Results: At RMH 224 patients were included in the study. The compliance rate for MST screening by nursing staff was 75% (169/224), however, only 58% were accurately completed. Therefore, 42% of patients were either inaccurately screened, or not screened at all. Of the patients screened, 29% (49/169) were determined to be at risk of malnutrition, however, only 56% of these patients were referred to the dietitian. The prevalence of malnutrition was determined to be 36% (78/224). Further analysis will be completed to determine the relationship between malnutrition and complications. A retrospective audit will determine if patients who were diagnosed as malnourished were correctly coded, and if this would alter the Diagnosis Related Group /payment allocated for that admission. Conclusion: Malnutrition screening compliance remains below 90% KPI. The accuracy of screening and dietetic referral rates for malnourished patients has not improved and remains poor. A significant amount of malnourished patients are not being identified, and therefore are not receiving the appropriate care.

46 Zoe Milner Sensory-motor retraining program: part of a clinical pathway for management of complex regional pain syndrome MILNER Z1, Hogg M2, O'Sullivan H1, White B3 1. Hand Therapy RMH; 2 Head of Pain Services RMH; 3 Pain RMH

Aim: To develop an integrated sensory retraining program that incorporates both cortical and peripheral activation, to complement existing motor retraining methods. Background: Complex regional pain syndrome (CRPS) is a condition that can affect the limb following injury and is characterised by pain, sensory, vasomotor, sudomotor / oedema and motor / trophic changes. Current literature

suggests early rehabilitation improves function and reduces pain, yet the type of rehabilitation remains uncertain. Despite sensory perception deficits being well described and a significant component of CRPS, evidence is strongly orientated towards motor retraining. Altered sensation significantly reduces hand function and results in sensory cortex changes. Until recently, sensory retraining has focused on peripheral input only. Sensory retraining is defined as retraining the brain through various cognitive techniques. There is emerging evidence for cortical and peripheral input for sensory retraining. Method: A Victorian Department of Health & Human Services Allied Health Workforce Advanced Practice grant supported the development of a sensory-motor retraining program for patients with CRPS. A literature search was undertaken with a focus on sensory re-education, pain theories, hand therapy rehabilitation and the GMI framework of cortical activation. A five stage sensory retraining program was developed to complement existing motor retraining techniques. RMH implemented the sensory-motor program in July 2015, coinciding with the commencement of a new innovative model of care. Data was collected on a range of outcome measures including the Human Activity Profile (HAP), electronic persistent pain outcome collaboration (ePPOC), Semmes-Weinstein monofilaments and specific outcome measures. Results: Preliminary data analysis has been undertaken of the initial 65 patients referred to the CRPS pathway. 33 of these patients met the Budapest clinical diagnostic criteria at initial assessment. 85% of patients presenting with CRPS at initial assessment had altered sensation according to Semmes-Weinstein testing. At discharge only 10% of the CRPS cohort had diminished light touch. All other patients had normal sensation. Functional outcomes have also improved evidenced by improvements on outcome measures. Conclusion: Sensory deficits are well recognised within CRPS literature, however to date intervention has primarily focused on motor retraining. This sensory program, provided alongside existing motor retraining concepts, has resulted in improved patient outcomes evidenced by improvements on outcome measures and 88% of referred patients with CRPS returning to work. Sensory deficits should be addressed early and clinicians must use clinical reasoning to determine the commencement of sensory retraining as well as the balance between motor and sensory intervention.

47 Angela Carnovale Using an iPad in an inpatient palliative care setting to maintain roles and occupations; a mixed-methods study CARNOVALE A, Marston C Monash Univiersity

Aim: To explore patients’ experiences of using ipad devices in an inpatient palliative care setting Background: Participation in valued roles and occupations is vital for the well-being of the palliative patient population. However, due to ongoing decline in function and unexpected hospital admissions, these activities are often disrupted. At the study site, it was identified there was is a need to optimise quality of life and participation through occupational engagement in the hospital setting . On admission to palliative care at Royal Melbourne Hospital, patients can access ipad devices. There is minimal research into patient use of these devices and their overall experiences in this setting. Methods: A mixed-methods design was used. All patients who used the ipad were invited to take part in semi-structured

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interviews exploring their experiences of using the ipad whilst on the ward through numerical rating scales and open-ended questions. Data were analysed thematically and descriptively. Results: 8 participants were recruited. 3 themes were established from the data: 1) Connections; 2) Occupying time; 3) Facilitators to use. Having access to the ipad served to normalise patients’ stay , enabled participants to engage in pre-hospital roles and routines, provided an opportunity for new learning, and was a welcome distraction from the hospital environment. Conclusion: This study demonstrates the potential of using an ipad to enable maintain connections and participate in valued roles and occupations.

48 Nicola Bacon Enhancing stroke rehabilitation Occupational Therapists’ use of Functional Electrical Stimulation : An action research study BACON N(1,2), Klaic M(1), Barr C(2) 1: Department of Occupational Therapy, The Royal Melbourne Hospital; 2:School of Health Sciences, Flinders University

Background: Australian clinical guidelines recommend Functional Electrical Stimulation (FES) for post-stroke upper limb rehabilitation. Despite undergraduate training, occupational therapists (OTs) do not consistently use FES in clinical practice. This includes at the Royal Melbourne Hospital, where a recent survey showed OTs were utilising FES only 8% of the time with patients post-stroke. Similar issues of staff not adhering to clinical guidelines have been documented in Australia and overseas, highlighting serious concerns about the quality of care being provided to patients. The occupational therapy department held workshops to enhance the confidence and skills of its staff in using FES. Improvements were primarily seen with acute-campus OTs, and did not extend to subacute and ambulatory sectors, indicating site-specific barriers existed. Aims: To identify barriers affecting uptake of FES by stroke rehabilitation OTs at Royal Park Campus. 2) To implement a multi-factorial educational package to address these barriers and enhance the use of FES by these stroke rehabilitation OTs. Methods: Six stroke rehabilitation OTs (inpatient and outpatient) were recruited to this 2016 prospective cohort study. A medical record audit, questionnaire and focus group gained information on use and barriers to FES at the site. A six-week intervention was developed using the Action Research model (Lewin, 1946). Outcome measures were repeated two weeks post-intervention. Results: Organisational, patient and clinician-related barriers were identified. Time constraints and decreased clinician confidence were targeted in the intervention which involved group FES tutorials, handouts prompting electrode placement, individual consultations with a local FES champion, and training an assistant to support therapists using FES. There was a statistically significant increase in participants' use of FES post-intervention (p= 0.035) and non-significant improvements in confidence and perceived barriers to FES. Conclusion: Knowledge translation interventions need to be tailored to the local workplace, and although time-consuming, can lead to improved staff use of evidence-based-practice. The Action Research Model was useful here for engaging participants and developing such a tailored, site-specific intervention to address FES use. The results, and the action research model, could help develop similar programs in other departments, to increase clinician use of other recommended interventions.

49 Shaza Abo Functional decline following allogeneic stem cell transplantation may be improved with structured exercise ABO S(1), Ritchie D(2,4), Denehy L(2), Panek-Hudson Y(2,4), Irving L(5), Granger C(1,2) 1 Department of Physiotherapy, Royal Melbourne Hospital; 2 Department of Clinical Haematology and Bone Marrow Transplant, Royal Melbourne Hospital; 3 Department of Physiotherapy, The University of Melbourne; 4Haematology Service, Peter MacCallum Cancer Centre; 5 Respiratory and Sleep Medicine, Royal Melbourne Hospital

Aims: To (1) measure changes in physical function and health related quality of life (HRQoL) in patients from pre- to 60 days post allogeneic stem cell transplantation (alloSCT); (2) investigate the feasibility of an 8-week exercise program commencing 60 days post-alloSCT; and (3) measure changes in patient outcomes before and after the exercise program. Background: Patients undergoing alloSCT experience significant treatment burden which international studies have shown can be improved through exercise. Feasibility of exercise following alloSCT in Australia is yet to be established. Methods: Single site, prospective case series including 43 adult patients (60% male; median [IQR] age 50 [36-56] years) undergoing alloSCT at a major transplant centre in Melbourne, Australia. Outcomes included functional exercise capacity (incremental shuttle walk test (ISWT)), self-reported physical activity (PA) and HRQoL (Functional Assessment Cancer Therapy-Bone Marrow Transplant (FACT BMT)) measured (1) prior to alloSCT; (2) 60-days post-alloSCT before commencing the exercise intervention; and (3) 100-days post-alloSCT (immediately after the exercise intervention). Feasibility (consent, adherence and withdrawal rate) and exercise compliance were also recorded. Intervention was an 8-week outpatient and home-based exercise and education program commenced at 60 days post-alloSCT. Results: The consent rate was 93%. Reasons for non-consent were “too many appointments” and “too preoccupied with health concerns to think about exercise”. Baseline pre-alloSCT functional exercise capacity was already below that of the healthy population (median [IQR] ISWT distance 660meters [470-880] compared to 810meters [572-1030]). From baseline to 60 days post-alloSCT there was significant decline in functional exercise capacity (mean difference 224meters, 95%CI 153-295, p<0.0005), self-efficacy for physical activity (mean difference 294points, 95%CI 136-452, p=0.001) and HRQoL (mean difference 15points, 95%CI 8-21, p<0.0005). 23% (n=10) of participants did not commence the exercise program 60 days following alloSCT due to death, illness or cancellation of alloSCT. From pre to post exercise intervention (n=20), there was significant improvement in functional capacity (mean difference 152metres, 95%CI 76-227, p=0.001) and HRQoL (mean difference 14points, 95%CI 7-20, p=0.001). There were no adverse events. Conclusion: AlloSCT results in significant decline in functional capacity, self-efficacy for PA and HRQoL, which can be improved through an exercise and education program. The high consent rate shows considerable patient interest in exercise in Australia. However, without a control group we cannot confidently attribute the program to the patients’ improvement. Also not all patients were well enough to commence exercise post treatment. Commencing exercise prior to transplantation may improve this. Further research is required.

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50 Patricia Maggs Physiotherapists’ knowledge about dementia MAGGS P, Kay J and Ovaskainen T Physiotherapy Department, Melbourne Health

Aim: To identify and rectify knowledge gaps that exist about dementia amongst physiotherapists working in a major metropolitan hospital. Background: The prevalence of dementia is increasing and is now the second leading cause of death. Patients with dementia have more comorbidities, 5.4 compared to 2.9, in patients over 65 and dementia is 6-7 times more likely to be an additional diagnosis and not the focus of care. It is important that all staff working with patients with dementia have good knowledge regarding the disease trajectory to ensure best practice care is provided. Method: A cross-sectional survey of 50 acute & subacute physiotherapists working within a major metropolitan hospital was completed using The Dementia Knowledge Assessment Tool version 2, a 21 item questionnaire examining knowledge about dementia, administered in a single assessment. Following collation of results, a 45 minute dementia education session was provided by Senior Aged Care physiotherapists and 42 staff were re-surveyed using the DKAT2. Results: Pre-education: Physiotherapists performed well (>95% of the cohort scored it correctly) in the following knowledge areas: Dementia occurs because of changes in the brain (100% N=50 correct), not only older adults develop dementia (100% N=50 correct), exercise can sometimes be of benefit to people who have dementia (96% N=48 correct). However, physiotherapists had limited knowledge (<75% of the cohort scored it correctly) in the following areas: dementia is likely to limit life expectancy (58% N=29 correct), difficulty swallowing occurs in late stages of dementia (66% N=33 correct), movement (e.g walking, moving in a bed or chair) is limited in late stage dementia (72% N=36 correct). Post-education: Physiotherapists demonstrated improvement in knowledge around dementia limiting life expectancy (98%, N=41); in late stages of dementia swallowing difficulties may be present (81% N=34) and movement is limited (88%, N=37). Conclusion: There were key knowledge gaps within physiotherapy regarding dementia, but these could be addressed through targeted education. Patients with dementia are often hospitalised or attend specialist clinics for conditions other than their dementia and will require physiotherapy intervention. Physiotherapists’ lack of knowledge regarding dementia may have implications for clinical decision making and prognostication and may be associated with adverse outcomes or costly futile interventions. Therefore, engaging both senior physiotherapy staff from specialties outside of Aged Care as well as rotating junior staff in ongoing education about the disease is critical for best practice care of dementia patients in the hospital.

51 Olivia Jenvey Need for an extended hours physiotherapy service in the intensive care unit at a major trauma hospital: an observational study JENVEY O, Sheehan J, Granger K, Beach L Aim: To determine the need for an extended hours physiotherapy service to Intensive Care Unit patients after 4pm on weekdays. Method: A prospective longitudinal observational study at a major tertiary trauma hospital was conducted. All Intensive Care Unit patients were screened on weekdays, excluding public holidays from May to August 2016. All patients in the unit were assessed at 4pm by senior physiotherapy staff

to identify those who would be appropriate for cardiorespiratory physiotherapy intervention that evening to prevent deterioration in respiratory status. Data were collected regarding patient diagnosis, extubation status and recommended physiotherapy intervention. Results: From 1535 possible patient episodes, 72 (4.7%) were assessed as warranting an extended hours physiotherapy treatment. This equated to 1.14 physiotherapy episodes per day (range of 1-5). The most common patient diagnostic category for evening review was chest trauma. This was evident for both number of total patients n= 12 (26%) and number of total episodes n=21 (29%). A combined respiratory and mobility intervention for non-intubated patients was the most recommended for n=30 (42.9%) episodes. The number of patients warranting treatment on the day of extubation was n=27 (38.6%), of these nine suffered chest trauma (33.3%). Conclusion/ Key Practice Points: There was an identified need for 1.14 physiotherapy episodes per day outside of standard hours; Patients with chest trauma accounted for 29% of these episodes; These findings support an extended hours physiotherapy service in the Intensive Care Unit.

52 Aruska D'Souza Characteristics of general medical patients referred to Physiotherapy at the Royal Melbourne Hospital D'SOUZA A (1,2), Granger C (1,2), Kay J (1), Said C (2) (1) Royal Melbourne Hospital (2) University of Melbourne

Aim: To determine the case mix, demographics and discharge destination of general medical patients referred to Physiotherapy at the Royal Melbourne Hospital. Background: During the data collection time period of July 2016 to February 2017, General Medicine accounted for 974 admissions, of which approximately 70% required Physiotherapy intervention (n=697). These patients are a varied and complex cohort with a mix of correctable illnesses, chronic disease, palliative care and patients with minimal acute medical needs, but social issues or decline in mobility and cognition. Method: This study forms part of a broader project investigating the association between patient factors (medical and social) and discharge destination. It is a prospective, single site, observational study. Data collected included demographics, co-morbidity (Charlson Co-morbidity Index, CCI), pre-morbid function (Blaylock Risk Assessment Screening Score, BRASS), mobility and function (De Morton Mobility Index, DEMMI and the Alpha Functional Independence Measure AlphaFIM) and cognition (Rowland Universal Dementia Assessment Scale, RUDAS), measured within 72 hours of Physiotherapy initial contact. Data are presented as median [IQR] or frequency (percentage). Results: Two-hundred and fifty patients were recruited between July 2016 and February 2017. Fifty-five percent (n=137) were female, the median age was 82 years [76-87] and 44% (n=110) of the patients required an interpreter. The most common diagnosis-related groups were: Respiratory infections (9.6%, n=24), Heart Failure (6.4%, n=16), Dementia (5.2%, n= 13), Chronic Obstructive Airways Disease (4.4%, n=11) and non-surgical spinal disorders (4%, n=10). On admission, the CCI was 2 [1-3] and BRASS was 13 [10-16]. Admission mobility levels were low compared with previous research in this population, with DEMMI scores being 34.5 [24-37] whilst physical function was similar to previous literature with scores of 30 [24-37]. Similarly, cognition on admission was poor, with a RUDAS score of 23 [19-26]. Length of acute hospital stay was 8 days [5-14]. Fifty-four percent of patients (n=137) returned home on discharge (n=129 home and n=8 where home was Residential Care Facility), while 37% (n=93) required a subacute admission, 4.4% (n=12) were deceased

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and 4.6% (n=8) had other discharge destinations. Twelve percent (n=31) of patients were readmitted within 28 days. Conclusion: General medical patients referred to Physiotherapy are a diverse cohort with a wide range of demographic characteristics and physical and cognitive function. Further research is needed to determine the association between function, demographics and discharge destination.

53 Hannah Davies Profiling the general medicine physiotherapy service delivery models across major acute metropolitan hospitals within Australia DAVIES H(1), Granger C(1) Melbourne Health

Aim: To investigate physiotherapy service delivery for General Medicinal in major acute Australian hospitals and their staff satisfaction. It is often felt that services are understaffed resulting in busy caseloads, potential for inadequate delivery of physiotherapy, staff fatigue and burn out. Design: 40 Item online survey Method: Australian metropolitan hospitals with a General Medical Unit were eligible to participate. Physiotherapy managers from 51 hospitals were approached. The 40-item survey included questions about physiotherapy EFT/case mix, perceived service delivery model adequacy and staff satisfaction. Data are reported as mean ± standard deviation (SD) or median [interquartile range IQR]. Results: Forty two out of 51 hospitals were contactable and 28 (67%) completed the survey. The number of beds allocated to General Medical patients was 89±54, with 86% of respondents reporting a designated General Medical ward. The general medicine physiotherapy EFT was 3.4±1.8 per hospital and grade one (junior) was the most common classification. 33% of respondents perceived they had ‘inadequate’ staffing and therapists noted increases in caseload without associated increases in physiotherapy staffing. Physiotherapists’ caseloads were 15 [14 - 18] patients/day; and they routinely provided treatment to 11±2.5 patients/day. There was a moderate relationship between an increased number of patients seen daily with increased number of hospital beds (rho=0.534, p = 0.01). 100% of respondents reported seasonal increases in workload but only 2 sites (7%) reported associated increased seasonal physiotherapy EFT. 78% of therapists felt satisfied with their job. Conclusion: We have reported the profile of acute physiotherapy service delivery in general medicine and results can be used by hospitals, including the Royal Melbourne, to benchmark. Further work is required to determine the optimal physiotherapy model for patient outcomes.

54 Thao Nguyen Best practice management of the hemiplegic upper limb: Utilising telehealth to provide education to allied health clinicians in regional Victoria Quiney J, NGUYEN T, Plumb S Physiotherapy Department, Royal Melbourne Hospital

Aim: To develop, implement and evaluate an upper limb (UL) management course for regional clinicians using telehealth videoconferencing technologies. This involved the use of regional clinical ‘champions’ to deliver the practical components within the course. Background: Clinicians at the Royal Melbourne Hospital (RMH) have undertaken a number of initiatives to enable best practice management for neurological patients at risk of hemiplegic UL complications. This has included the development and provision of an evidence-based UL management course. The

course has been successfully implemented on nine occasions, with positive feedback from the physiotherapy and occupational therapy participants. However, the metropolitan location for the course appears to be a limitation to access for regional clinicians. Methods: This project involved modifying the implementation of a pre-existing UL management course for delivery to a regional setting. The project involved consultation with key stakeholders, the identification and training of clinical ‘champions’, a focus group with the clinical champions, and feedback from the course participants immediately following the course and after a 3-month period. Participant feedback was compared to feedback obtained from prior courses run on-site at RMH. Results: The UL management course was successfully implemented simultaneously at three regional sites and involved the training of 12 clinical ‘champions’ and 51 course participants. Participant feedback suggested a high level of satisfaction with the telehealth course; however, several scores were lower than those obtained from prior face-to-face courses. Three month evaluation data demonstrated strong satisfaction with the course materials and format, and increased confidence with the assessment and management of hemiplegic ULs. It also demonstrated a change in use of risk assessment and management modalities, which align with the evidence that was presented and may indicate a change in practice as a result of the course. Conclusion: This study highlights the challenge of delivering clinical education via telehealth for allied health clinicians, in particular PT and OT where practical skill, in addition to theoretical knowledge, is important. The practical components and skill development were reliant on the ‘champions’ to deliver and limited any feedback the experts could provide towards the participants’ performance. Face-to-face delivery of the course was rated more positively compared to the telehealth version by participants and the expert educators in regards to quality for most of the presentations. These findings provide further opportunity to modify the course, to better meet the needs of regional physiotherapists and occupational therapists. A phase 2 study is currently underway.

55 Claire Corbett Cognition and health beliefs in patients with diabetes related foot wounds CORBETT C(1), Barson E(1), Jolley J(2), Fisher C(1) 1 - Psychology Department, Allied Health, Royal Melbourne Hospital; 2 - Podiatry Department, Allied Health, Royal Melbourne Hospital

Aim: This study aims to characterise the health beliefs and cognitive functioning of patients with diabetes related foot wounds, as well as investigate the association between health beliefs and cognition. Background: Diabetes is a chronic condition with a myriad of complications, including peripheral neuropathy and arterial disease that can lead to foot ulcers and amputations. For diabetic foot complications to be managed effectively, significant self-treatment, behaviour change, and adherence to medical recommendations is required. Psychological factors impacting on diabetes-related foot wound management have only recently been recognised as an important determinant of outcomes (Hatch et al., 2016). The small amount of research in this area suggests that neurocognitive changes and an individual’s assumptions about their condition may be associated with self-care (Natovich et al., 2016; Perrin et al., 2013). Methods: Inpatients referred to the DFU Clinical Psychology service over a six month period were assessed on the Patient Interpretation of Neuropathy and the Montreal Cognitive

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Assessment, and relevant demographic and medical information was collected. Results: Descriptive and correlation analyses of the results of the cognition and health beliefs assessments will be presented from this pilot data. This will include Montreal Cognitive Assessment results, Patient Interpretation of Neuropathy findings, and correlational analyses between these variables and the collected demographic and medical information. Conclusion: Exploring the cognitive and health belief factors that impact on diabetes related foot wound management is an important area of research that requires further investigation. By increasing knowledge about the factors that contribute to foot wound management problems, interventions can be adapted to more effectively target these underlying factors. This study describes the results of cognitive and health-beliefs assessment in this population and provides discussion about how this may influence the provision of education and services tailored to the needs of the individual. In addition, the challenges associated with clinical research within this setting and population are discussed.

56 Emma Foster Acute seizure management in a private hospital FOSTER E(1,2), Holper S(1), Kwan P(1,2,3). 1 - The Royal Melbourne Hospital. 2 - Cabrini Health. 3 - Department of Medicine (RMH), The University of Melbourne

Aim: To examine the epidemiological features and management of first-ever seizures and untreated recurrent seizures presenting to a comprehensive private hospital in Australia. Background: Seizures are a common neurological problem. Approximately 10% of people have at least one seizure in their lifetime, and one-third of this group eventually go on to be diagnosed with epilepsy. Not surprisingly, therefore, seizures are a common presenting complaint to hospital, accounting for 0.9% of emergency department visits. Managing first-ever seizures and recurrent untreated seizures effectively has important health, economic, and social implications for our community. Methods: We reviewed medical records of patients with ICD-10 codes of G40 (epilepsy) or G41 (status epilepticus) discharged from Cabrini Hospital (Malvern), Melbourne, between 1 Jan 2008 and 30 Nov 2016. Patients were included if they presented with a first ever seizure or untreated, recurrent seizures either to the Emergency Department (ED) or during hospitalisation for other reasons, and were excluded if they had a previous diagnosis of epilepsy or had non-epileptic events. Results: 244 patients were identified. 168 were excluded (pre-existing epilepsy diagnosis [159]; psychogenic non-epileptic seizures [4], vasovagal episode [2], stroke [2], delirium [1]). 76 were included for analysis. 34 and 16 patients presented to ED with first seizures or recurrent, untreated seizures respectively. 15 and 11 had first seizures or recurrent, untreated seizures on the ward, respectively. The median age of patients with first ever seizure was 76 years old. 25/49 patients were male. Seizure were classified as acute symptomatic (19.7%), remote symptomatic (19.7%), association with idiopathic generalised epileptic syndromes (5.3%), and unclassified (55.3%). 80% of patients presenting to the ED had CT brain, most within 2 hours of presentation. 50% had MRI and 60.5% EEG; median time from admission to test was 2 days and 3 days, respectively. EEG resulted in identification of IGE syndromes in 4 patients, leading to medication alteration. Majority of patients presenting with their first ever seizure to ED were commenced on an antiepileptic drug (AED) (82.4%), which increased to 85% at time of discharge. Conclusion: Timely investigations and neurological review are valuable in the diagnosis and treatment of patients with

seizures. Future studies should focus on identifying factors associated with rapid diagnosis that may lead to better treatment choices and improved seizure control.

57 Sarah Holper Making a long story short: an analysis of abbreviation use in general medical discharge summaries HOLPER S(1), Colman B(1), Barmanray R(1), Smallwood D(1). The Royal Melbourne Hospital

Aim: To determine the frequency and variety of medical abbreviations used in discharge summaries by members of The Royal Melbourne Hospital medical workforce, assessed on a previously unprecedented scale (all 2336 general medical discharge summaries from the year 2015). Background: Abbreviations are common in medical documentation. The tendency to abbreviate is driven by time-saving, avoidance of writing sentences in full, and convenience. As a non-standardised form of communication, abbreviations are ambiguous and may be poorly understood by GPs who are expected to act on discharge summaries. Consequently patient care may be compromised by poor communication. No prior studies have quantified the frequency and range of abbreviations used in discharge summary communication on a large scale. Methods: Researchers designed a computer program (Python) to extract all instances of abbreviations from every general medical discharge summary (2336 total) from the year 2015. Abbreviations were then expanded using medical dictionaries and sense inventories. Researchers manually defined any unmatched abbreviations. The frequency and use of abbreviations was then analysed. Results: Of the 1,551,537 words analysed 161,184 (10.4%) were abbreviations. The most common abbreviation was PO (8.2% of all abbreviations), followed by # (5.5%) and BD (3.5%). The ten most commonly used abbreviations accounted for 28.4% of all abbreviations used, while 2.9% of all words could be accounted for by these same ten abbreviations. Conclusion: Medical abbreviations abound in general medical discharge summaries. With more than 10% of an average discharge summary being abbreviations, further research regarding the mutual understanding of abbreviations is warranted and is being conducted by the investigators.

58 Brent Doolan ARANZ Silhouette Camera: 3D laser use for clinical management of wounds DOOLAN BJ(1), Kern JS(1), Rebbechi A(2), Martyres R(1) & Varigos GA(1) (1) - Department of Dermatology, The Royal Melbourne Hospital, Parkville, VIC 3050; (2) - Department of Medical Illustration, The Royal Melbourne Hospital, Parkville, VIC 3050

Aim: To evaluate the usability, ease of integration and reliability of the hand-held ARANZ Silhouette camera in the management of wounds in a Dermatology Department in patients with chronic ulcers. Background: Chronic wounds are estimated to affect more than 400,000 Australians per year, with an estimated cost of $2.6 billion to the Australian health system, including both inpatient and outpatient public hospital settings. Therefore, it is important that clinicians are able to continually improve wound outcomes and reduce overall burden of disease by adequately assessing and implementing an appropriate plan of care, which is regularly evaluated. Recent publications have shown that documentation of wound assessment and care is frequently poor and can be subjective. Thus, accurate measurement and documentation of chronic wounds would help provide better and objective care. The ARANZ Medical Silhouette is a hand-held wound measurement and documentation system that

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combines a digital camera and structured lighting in the form of three dimensional laser beams to automatically correct for camera location, image scale and skin curvature, allowing rapid and accurate measurements of the wound’s surface area and depth. This technology is currently being evaluated in the Department of Dermatology, Royal Melbourne Hospital to monitor chronic ulcers in patients with epidermolysis bullosa. Methods: A literature review was undertaken: Publications were collated from database citations using key words, including; ‘ARANZ’, ‘3D laser’, ‘Silhouette’, ‘wound’, ‘ulcer’. PubMed database at the National Institutes of Health, MEDLINE, MEDLINE in process, World Health Organization (WHO) online report database, published between March 2005 to March 2017. Results: Use of the ARANZ camera demonstrated improved accuracy and repeatability of wound measurement compared to physical measurement with a tape measure or ruler and acetate tracing in the management of diabetic foot ulcers, pressure ulcers, venous ulcers and patients with chronic, non-healing wounds that attended wound clinics. Inter-operator variability and intra-operator variability were both 1-2% for area and perimeter, and <2% variability for average depth and volume. Minor limitations were noted regarding application cost and training, as well as restriction to wound measurement involving undermining and mild inconsistencies related to alignment of laser to wound. Conclusion: In patients with chronic ulcers, Silhouette data has been shown to be superior compared to standard clinical wound management. This technology may provide a better alternative for outpatient hospital departments that manage chronic ulcers.

59 LOUISE HOBBS A point prevalence survey of hospital acquired pneumonia (HAP) Boreham H1, Phoa P1, Li B1, Ong H1, Edgar S1, Hobbs L2, Richards M2, Ramsay V2,Wynne R 3 Department of Nursing, University of Melbourne1 Department of Infection Prevention and Surveillance Service, Melbourne Health2 Department of Cardiothoracic Surgery, Royal Melbourne Hospital3

Aims: The aim of this study was to determine the prevalence of hospital acquired pneumonia (HAP) not associated with ventilation and to assess nurse sensitive indicators associated with its management. Background: HAP is a clinically defined pneumonia not present on admission that develops during an individual’s stay in hospital. Some point prevalence studies report HAP as accounting for up to 21% of all hospital infections. The mortality rate associated with HAP is reported to be between 20-70%, varying as a consequence of underlying disease processes. Oral care, positioning, mobilisation and airway protection strategies for patients with dysphagia are common nurse sensitive interventions that have the potential to influence HAP development. There is however, scant evidence to underpin best practice or to describe HAP development for patients who have not been ventilated. Methods: A point prevalence survey of RMH inpatients was conducted in December 2016. Following inter-rater reliability tests, patients were assessed by pairs of student nurses under supervision. The presence or absence of HAP was determined according to CDC surveillance criteria. Results: There were 413 in-patients at the time of the survey. Of these patients 190 were excluded based upon the following criteria; 111 (26.9%) hospital for less than 48 hours, 48 (11.6%) were being prepared for discharge, 11 (2.7%) had been mechanically ventilated in the previous 48 hours, 6 (1.5%) had been admitted with community onset pneumonia and 14 (3.4%) were unavailable. There were 2 (0.9%) patients with HAP at the time of this survey and a single patient treated

for HAP who did not meet CDC criteria. Both patients had impaired mobility, and 1 dysphagia. Risk factors focused on nutrition, pain and respiratory therapy were unable to be determined because of inadequate documentation. Documentation to support or refute the implementation of nursing interventions related to HAP was difficult to locate. Conclusion: The prevalence of HAP at the time of this survey was low in contrast to contemporary evidence. Observational studies are needed to identify nursing practice patterns associated with HAP prevention, to benchmark best practice and to establish which interventions warrant testing and validation.

60 LOUISE HOBBS A point prevalence survey of nurse sensitive indicators associated with hospital acquired urinary tract infection (HAUTI) Fenner V1, Tremul E 1, Chirakkaramattathil M1, Gu X1, Ridley S1, Hobbs L2, Demarco C2, Wynne R 3 Department of Nursing, University of Melbourne1 Department of Infection Prevention and Surveillance Service, Melbourne Health2 Department of Cardiothoracic Surgery, Royal Melbourne Hospital3

Aim: To identify the prevalence of hospital and catheter associated urinary tract infection; HAUTI and CAUTI respectively. A secondary aim to identify nurse practice patterns associated with patients who were identified to have a HAUTI or CAUTI. Background: Healthcare associated infections are a common complication of hospitalisation with 30% attributed to urinary tract infections. It has been estimated that 80% of healthcare associated urinary infections (HAUTI) are attributed to the presence of a urinary catheter (CAUTI). To date there has been a number of nurse led protocols to improve catheter care but little progress in developing standardised interventions for patients without catheters. Methods: A point prevalence survey of RMH inpatients was conducted in December 2016 using an adapted pre-existing audit tool. CDC definitions were used to define a HAUTI and CAUTI and nurse practice criteria were collected based upon the findings of a literature review. Following inter-rater reliability tests, patients were assessed by pairs of student nurses under supervision. Results: There were 355 inpatients at the time of the survey, 8 (2.2%) of whom declined to participate. Mean age was 64.1 (SD 19.9) years and 132 (38%) patients were female. The prevalence of HAUTI (non-catheter associated) was 3.5% (n = 12) and CAUTI was 2.6% (n=9). Organisms isolated from specimens (n=3) were Staphylococcus aureus and Citrobacter freudenii. Incontinence was problematic for 43 (12.1%) patients of whom 4 (9.3%) had a HAUTI; 33.3% of total HAUTI (n=4/12). Incontinence pads were in place for 33 (76.7%) incontinent patients with documented pad changes recorded for 19 (44.2%) patients. Indwelling catheters were present in 57 (16.4%) patients, 15 (27.8%) of which were associated with a surgical procedure. Variability in nursing documentation was noted; 61.1% (n = 33) had insertion date, 7.4% (n = 4) and indication for insertion, 11.1% (n = 6) had drainage bag labelled, 33.3% (n = 18) noted hygiene measures, and 5.5% (n = 3) a plan for removal. Patients with CAUTI had evidence of nurse sensitive indicators for infection prevention; no debris at site of catheter (n=8/9), drainage bags off ground (n=7/9), catheter bag below bladder (n=4/9) and no kinks (n=7/9). Conclusion: Nursing documentation of care was poor and very few IUCs had a valid indication for continued insertion. Poor documentation of hygiene, pad changes and toileting could have contributed to HAUTI outcomes. Future research should focus on testing and validating standardised interventions for the prevention of HAUTI.

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61 Kaylene Bastin Compliance with the hospital blood transfusion guidelines: An observational audit and patient survey Aleksandrov D1, Bundy C1, Tovey O1, Cahill L1, Phillips C2, Bastin K2, Wynne R3 (1) Department of Nursing, University of Melbourne (2) Department of Transformation and Quality Service, Melbourne Health (3) School of Nursing & Midwifery, Deakin University

Aim: The aims of this study were to observe blood transfusions at a major metropolitan teaching hospital and determine the extent to which nurses adhere to the Melbourne Health protocol. Background: Blood transfusions are a crucial treatment for patient care and are one of the most common procedures undertaken in hospitals. Every month, Melbourne Health transfuses more than 1000 red cell units, with each transfusion carrying a high risk and involving multiple steps to ensure the right patient received the right blood for the right reason. Methods: An observational audit of blood transfusion procedures was conducted at the Royal Melbourne Hospital between December 2016 and March 2017. Data of adherence to transfusion guidelines, nurses experience, and patient satisfaction were collected. Results: Analysis of the study data will be completed by May 2017. Data reported will describe nurses’ adherence to transfusion guidelines. Insights regarding patients’ level of satisfaction and level of understanding relating to informed consent and blood transfusion will also be gained. In addition, a link between nurses’ experience and adherence to transfusions guidelines will be stressed. Conclusion: Blood transfusions are frequently administered at Melbourne Health and adherence to transfusion guidelines and practices, including the provision of informed patient consent is essential to ensure safe blood transfusion practices. This project provides insight into the blood transfusion practices at Melbourne Health and make recommendations for future practice.

62 Kaylene Bastin Appropriateness of blood transfusions: An observational audit at Royal Melbourne Hospital Jones E1, Al Obaidi G1, Hester M1, Main L1, Sansolis J1, Thompson E1, Bastin K2, Wynne R3 (1) Department of Nursing, University of Melbourne (2) Department of Transformation and Quality Service, Melbourne Health (3) School of Nursing & Midwifery, Deakin University

Aims: The aims of this study are to determine if red blood cells and platelet transfusions were conducted appropriately according to the National Blood Authority (NBA) Patient Blood Management Guidelines and to examine a potential association between the transfusion and patient length of stay in hospital. Background: The Royal Melbourne Hospital conducts an average of 1000 blood product transfusions each month. Due to the adverse outcomes associated with over-transfusion of blood products and the shortage of donated blood in Australia, an assessment of patients requiring blood transfusion is conducted based on the National Blood Authority Patient Blood Management Guidelines to determine the appropriateness of a blood product transfusion. Methods: An audit of 110 platelet and red blood cell transfusions was completed over a two-week period in December 2016. Data were retrospectively collected 24-hours post blood product transfusion from patient medical records and blood transfusion orders. Collected variables were determined as the transfusion indications outlined by the NBA Guidelines. These were collected using an audit tool published by the Victorian State Government Blood Matters Program.

Data were also collected in order to measure an association between appropriateness of blood transfusions and length of hospital stay. Results: Analysis of the study data will examine the prevalence of appropriate and inappropriate transfusions in the sample population and investigate any relationship between this and the length of stay for patients receiving transfusions. Data analysis will be completed by May 2017. Conclusion: Routine auditing of blood product (RBC and platelet) administration can reduce the incidence of unnecessary transfusions. Each transfusion is associated with independent risks contributing to significant patient outcomes, therefore reducing the incidence of inappropriate transfusions can improve patient outcomes and ensure best clinical practice.

63 Shu Su Skin-liver distance and interquartile-median ratio as determinants of inter-operator concordance in Acoustic Radiation Force Impulse (ARFI) imaging Gorelik A(3), Lai J(1), Gibson R(1) (1) Radiology (2) Gastroenterology (3) Melbourne Epicentre, MH

Aim: To use skin-liver distance and interquartile-median ratio to predict the likelihood of inter-operator concordance in acoustic radiation force impulse (ARFI) ultrasound. Background: ARFI ultrasound is used to measure liver stiffness and stage liver fibrosis into grades 0 (normal) to 4 (cirrhotic). The accuracy of ARFI when compared to biopsy is higher when the interquartile range/median-velocity ratio (IMR) is less than 0.3, when there is concordance between two or more operators, and when the skin-liver distance (SLD) is less than 2.5cm. Previous studies from our institution have also found that concordance itself is higher when the SLD is lower, IMR is less than 0.3, and fibrosis grade (F-score) is 0/1 or 4. Hence, we hypothesise that when the first operator ARFI measurement has an F-score of 0/1 or 4, average SLD is less than 2.5cm, or IMR is less than 0.3; then a second operator measurement is not necessary given the high likelihood of inter-operator concordance. Method: The F-score, SLD, and IMR of the first operator, and its concordance with the F-score of the second operator was recorded for 927 consecutive patients. Concordance was defined as F-scores in the same or adjacent grades. Chi-squared tests using SPSS (version 17) were then performed comparing concordance in the following groups: SLD≤2.5cm versus SLD>2.5cm when the first operator F-score was 0/1 or 4, SLD≤2.5cm versus SLD>2.5cm when the first operator F-score was 2 or 3; and IMR <0.3 versus IMR≥0.3 when SLD≤2.5cm, in each of the F-score groups of 0/1, 2, 3 and 4. Results: In general, concordance when SLD was ≤2.5cm, was more than 85%. There was a statistically significant difference between the SLD≤2.5cm and SLD>2.5cm groups when the F-score was 0/1 or 4 (p=0.005), as well as when the F-score was 2 or 3 (p<0.0005). Chi-squared tests for longer skin liver distances were not performed as we know that the correlation to biopsy reduces significantly when SLD is >2.5cm. When SLD was ≤2.5cm, IMR also affected concordance. Although statistical significance varied between groups, concordance fell below 85% when IMR was ≥0.3 in all fibrosis grades except F2. Specifically, the p-values when comparing IMR<0.3 and IMR≥0.3 in the various first operator F-score groups were: p=0.040 for F0/1, p=0.580 for F2, p=0.342 for F3, and p<0.0005 for F4. Conclusion: ARFI measurements from one operator can be considered acceptable when SLD≤2.5cm and IMR<0.3. Otherwise, adding a second operator can improve confidence in the result.

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64 Andrew Talbot Retinal and renal deposits in membranoproliferative glomerulonephritis - Type II TALBOT A (1), Symons A (2,4,5), Finlay M (3,4), Nicholls K (1,4) (1) Department of Nephrology Royal Melbourne Hospital (2) Department of Ophthalmology Royal Melbourne Hospital (3) Department of Anatomical Pathology Royal Melbourne Hospital (4) Department of Medicine, University of Melbourne (5) Department of Surgery, University of Melbourne

Background: Membranoproliferative glomerulonephritis (MPGN) is a rare cause of chronic kidney disease with a highly variable presentation. Injury results from deposition of immune complexes and/or complement factors in the glomerular mesangium. Classification into subgroups is based on electron microscopic findings including glomerular capillary wall thickening, mesangial hypercellularity and synthesis of new glomerular basement membrane. Type II MPGN or “Dense Deposit Disease” is defined by subendothelial electron-dense deposits. Approximately 10% of individuals with MPGN Type II develop retinal complications and visual loss with changes including drusen, pigment epithelial detachment, central serous retinopathy, retinal atrophy and choroidal neovascularisation (CNV). Drusen occur at an early age, frequently detectable in the second decade of life. Distribution of deposits is variable and progress with time, initially having little impact on visual acuity and fields. Case Report: We describe the renal and retinal findings of a 36yo male with MPGN Type 2. He presented at age 21 with deteriorating renal function and increasing proteinuria in the setting of an 8-year history of recurrent upper respiratory tract infections and low complement levels. His renal function continued to decline and he commenced peritoneal dialysis at age 25 before receiving a living related renal transplant 2 years later. At age 28 he developed recurrent disease, with graft failure at age 32, and returned to haemodialysis prior to a deceased donor transplant. Renal biopsies were obtained from the native kidney at initial diagnosis and after each renal transplant. There were characteristic diffuse increases in mesangial matrix with PAS positive intramembranous and paramesangial material. Electron microscopy showed electron dense deposits encroaching from glomerular capillary loops with irregularly thickened basement membranes and diffuse podocyte effacement. At age 35 he described visual disturbance. Colour fundus photographs, red-free photography, infrared reflectance confocal scanning ophthalmoscopy and optical coherence tomography were performed. His right eye showed mild subretinal drusenoid deposits without the typical appearance of pseudoreticular drusen on infrared reflectance. His left eye showed decreased distance between the retinal pigment epithelium and the inner segment ellipsoid zone line on the nasal side suggesting loss of thickness of the photoreceptor outer segments. Infrared reflectance showed some mottled hyper-reflectance centrally in both eyes. Conclusions: We describe severe renal and progressive visual injury in a patient with MPGN Type II. While there is no correlation between disease severity in the kidney and the eye, an ophthalmologic examination at diagnosis and periodic fundoscopy assessments should be part of patient treatment.

65 Andrew Talbot Impact of enzyme replacement therapy on cardiac and renal tissues: A post mortem case series TALBOT A (1), Finlay M (2), Nicholls K (1,3) (1) Department of Nephrology Royal Melbourne Hospital (2) Department of Anatomical Pathology Royal Melbourne Hospital (3) Department of Medicine, University of Melbourne

Aim: Describe post-mortem findings of 3 patients with Fabry disease (FD), 2 men and 1 woman after ≥ 12 years enzyme replacement therapy (ERT) Background: FD is an X-linked lysosomal storage disease, caused by a deficiency in the enzyme α-galactosidase (αGAL), leading to accumulation of globotriaosylceramide predominantly within vascular endothelial cells. ERT has been available for 15years but limited long-term pathology outcome data is available. Methods: Post-mortem cardiac and renal tissue sample were collected. Comparison with tissue collected prior to initiation of ERT was made. Progression in renal function was determined annually by clearance of 51Cr-EDTA while cardiac function assessed by transthoracic echocardiograms. Results: Post-Mortem Demographics Case 1: 65yo Male, C52R Mis-sense mutation, Alpha-galactosidase A level 0.01%, ERT for 13 years; Renal Function: CKD 4, Proteinuria 0.5g/24hr, GFR decline 1.91 ml/min/1.73m2/yr; Cardiac Function: Moderate Diastolic Dysfunction, IVWT/PWT 14mm/12mm pre ERT 10mm/10mm post; Cerebrovascular: Basal Ganglia Infarcts, White Matter Lesions; Cause of Death: Cardiac Arrest - Ventricular Tachycardia; Tissues Biopsied: Cardiac, Renal. Case 2: 45yo Male, M284T Mis-sense mutation, Undetectable Alpha-galactosidase A, ERT 13 years; Renal Function: CKD 5, Renal Transplant x 2; Cardiac Function: Severe Diastolic Dysfunction, IVWT/PWT 10mm/12mm pre ERT 21mm/17mm post; Cerebrovascular: Severe Basilar artery Dolichoectasia, Cerebellar Infarcts; Cause of Death: Cerebellar infarcts, Treatment Withdrawal; Tissues Biopsied: All. Case 3: 68yo Female, delGlu358 Nonsense mutation, Alpha-galactosidase A 0.24nmol/ml/mg, ERT 12 years; Renal Function: CKD 3, Proteinuria 2.5g/24hr, GFR decline 1.77ml/min/1.73m2/yr; Cardiac Function: SevereSystolic Dysfunction, Diastolic Dysfunction, IVWT/PWT 14mm/12mm pre ERT, 14mm/12mm post; Cerebrovascular: Basal Ganglia Infarcts, White Matter Lesions; Cause of Death: Cardiac Arrest, Treatment Withdrawal; Tissues Biopsied: Cardiac, Renal Renal Histology: Male 1: Native kidney biopsies 20 yrs pre-ERT and post-mortem showed similar level of glomerular sclerosis, podocyte vacuolation and interstitial fibrosis; Male 2: Transplant parenchyma preserved, no vacuolation with moderate to severe renovascular disease; Female: Native kidney showed minimal vacuolation of renal parenchyma but moderate interstitial fibrosis and hyaline thickening secondary to renovascular disease. Cardiac Histology: All samples showed hypertrophied cardiomyocytes, intracellular vacuolation and patchy interstitial fibrosis. No glycosphingolipid inclusions in cardiomyocytes on electron microscopy. Conclusion: Initiation of ERT prior to patients reaching CKD5 resulted in stabilisation of function with renal parenchyma remaining viable. Long-term ERT resulted in clearance of globotriaosylceramide from cardiomyocytes but did not prevent cardiac events or occurrence of diastolic dysfunction.

66 Tim Hewitson Histone modifications to H3K9 during renal myofibroblast recruitment HEWITSON TD(1,2), Holt SG(1,2), Wigg B(1), Samuel CS(3), Smith ER (1,2) (1) Department of Nephrology, Royal Melbourne Hospital; (2) Department of Medicine- RMH, University of Melbourne; (3) Department of Pharamacology, Monash University

Aim: In this study we examined the distribution and acquisition of H3K9 modifications in fibrogenesis. Background: Epigenetic regulation of fibroblasts is a key determinant of progression in renal disease. Although DNA

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methylation and miRNA regulation of fibroblasts is reported, the pattern of post-translational histone modifications (marks) and their significance is largely unknown. Epigenetic modification of lysine 9 on histone 3 (H3K9) is of particular interest as it can be both methylated and acetylation. Methods: Confocal microscopy with histone mark specific antisera was used to examine global H3K9 acetylation (H3K9Ac) and tri-methylation (H3K9Me3) after unilateral ureteric obstruction (UUO). Parallel cell culture studies using confocal microscopy and flow cytometry examined the effect of TGF-beta1 on structural arrangement of these marks, and their relationship with kinetics and differentiation. Results: The number of cells carrying each mark were increased 10 days after UUO, with both clearly seen in both proximal tubules (LTL lectin positive cells) and myofibroblasts (alpha smooth muscle actin positive cells). Sub-nuclear localisation in cultured primary rat renal fibroblasts and a proximal tubule cell line (NRK52e) showed that H3K9Ac was co-localised with phosphorylated-Ser2 RNA polymerase II (pRNAPol II), while H3K9Me3 was not, consistent with permissive and repressive effects on gene expression respectively. H3K9Ac was diffusely distributed throughout the nucleus while H3K9Me3 was adjacent to the nuclear membrane. Exogenous TGF-beta1 had no effect on co-localisation with pRNAPol II, but resulted in a redistribution of H3K9Me3 within the fibroblast nucleus. This was unrelated to any change in mitogenesis. Flow cytometry showed that H3K9Me3 but not H3K9Ac was rearranged in myofibroblast differentiation. Conclusions: Myofibroblast differentiation is accompanied by changes in both histone mark arrangement and the acquisition of the repressive H3K9Me3 mark. Future studies will need to identify the genes involved and their ramifications.

67 Michael Cai Calciprotein particle formation in peritoneal dialysis effluent is dependent on dialysate calcium concentration CAI M(1,2), Kent A(3), Smith E(1), Huang L(3,4), Hewitson T(1,2), McMahon L(3,4), Holt S(1,2) 1, Department of Nephrology, The Royal Melbourne Hospital. 2, Department of Medicine (RMH), University of Melbourne. 3, Eastern Health Integrated Renal Services, Eastern Health. 4, Eastern Health Clinical School, Monash University

Background: The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be implicated in driving sterile inflammation and extra osseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unclear whether calcium and glucose concentration, pH and the osmotic agent in PD fluid affect the formation of CPP in vivo. Method: Peritoneal effluents from 12 participants was collected after a 6-hour dwell with 7 different PD fluids (Dianeal® 1.5% glucose PD4, Dianeal® 4.25% glucose PD4, Physioneal® 1.36% glucose, Extraneal® 7.5%, Nutrineal® 1.1%, Dianeal® 1.5% glucose PD2, Dianeal® 1.5% glucose PD. CPP in PD effluent were measured using an optimised flow cytometric method. PD effluent Inflammatory cytokines were measured using the BDTM Cytometric Bead Array Human Inflammatory Cytokines Kit. Results: High inter-subject variability in CPP concentration was observed. PD fluids containing 1.75 mmol/L of calcium (Dianeal 1.5% glucose PD2 and Extraneal 7.5%) enhanced the formation of CPP in vivo, compared with fluids containing 1.25 and 1 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. PD effluent

CPP were not associated with changes in inflammatory cytokines. Conclusion: High calcium containing PD fluid favours intraperitoneal CPP formation. This finding may have relevance for future PD fluid design.

68 Michael Cai Changes in circulating calciprotein particles after renal transplantation CAI M(1,2), Smith E(1), Toussaint N(1,2), Hewitson T(1,2), Holt S(1,2), 1 Department of Nephrology, The Royal Melbourne Hospital, Australia. 2 Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Australia

Background: Kidney transplantation (KTx) is considered the optimal treatment for end stage kidney disease (ESKD). Cardiovascular death following KTx is the most common cause of death with a functional graft in Australia. Calciprotein particles (CPP) have been implicated in cardiovascular disease in CKD. It is unclear whether CPP changes as the result of renal transplantation. The aim of the study is to determine the change in serum CPP before and after KTx. Methods: 10 ESKD patients were recruited at the time of admission for transplantation. Fasting serum samples were collected at the time of transplantation, and at 1, 3 and 6 months after transplantation. Serum CPP were labelled with fluorescent bisphosphonate dye (Osteosense) and quantitatively measured using an optimised flow cytometric method. Results: A total of 7 and 3 recipients of deceased and live donor respectively were recruited to the study. An increase in CPP is seen in 7 patients post KTx with an overall significant increase in CPP across the cohort (One way ANOVA P=0.04). There was no significant change in particle side scatter (P=0.67). The highest increase in CPP post KTx (>4 fold increase) was observed in a patient given calcitriol and high dose oral phosphate supplementation. Conclusion: Despite improvements in renal function, circulating CPP increases post KTx. The effect of oral phosphate and calcitriol on serum CPP requires further investigation.

69 Edward Smith Calciprotein particle ripening induces mitochondrial damage and activates the NLRP3 inflammasome SMITH ER(1), Hewitson TD(1), Holt SG(1) (1) Department of Nephrology, The Royal Melbourne Hospital; (2) Department of Medicine-RMH, University of Melbourne

Background: Mineral nanoparticles may link inflammation and calcification in CKD. Synthetic mineral nanoparticles activate a pro-inflammatory response in the macrophage in vitro, but the effect of endogenous mineral particles or calciprotein particles (CPP) and their ripening from amorphous (CPPI) to crystalline (CPPII) states is unknown. Methods: Uptake and effects on lysosomal/mitochondrial function/cell fate were assessed by flow cytometry. NLRP3 priming/activation was evaluated by qPCR, Western blotting and ELISA in human monocyte-derived macrophage and NLRP3/ASC/Casp1-deficient cell lines. Live-cell imaging and particle localisation were assessed by laser-scanning confocal and super-resolution microscopy. CPPI/II or vehicle were administered to 12 week-old uraemic Wistar rats via tail vein (twice daily for 5 days; n=6 each). Some animals received additional treatment with an NLRP3 inhibitor (MCC950; n=6) via subcutaneous minipump, or a mitochondria-targeted antioxidant (MitoQ10; n=6) via i.p. injection or vehicle controls. Serum was collected after 6 days to assess inflammation/oxidative stress.

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Results: In vitro, CPPI and CPPII were internalised to the endolysosomal compartment via scavenger receptor (SR)-A-/αVβ5 integrin-dependent endocytosis. CPPI failed to prime or activate the NLRP3 inflammasome. In contrast, CPP-II primed inflammatory cytokine synthesis via TLR4/6/NF-κB-signalling. Priming was potentiated by blockade and siRNA silencing of SR-A/αVβ5 receptors. Binding and uptake of CPPII resulted in marked changes in intracellular calcium that were not apparent with CPPI. Intracellular trafficking of CPPII induced lysosomal destabilisation, mitochondrial fission, loss of membrane potential, increased mtROS production and a release of mtDNA. NLRP3 activation, as well as sustained excursions in intracellular calcium, amplified mitochondrial damage via mitochondrial transition pore opening and induced IL-1β secretion. In rats, intravenous administration of CPPII but not CPPI, resulted in marked elevations in IL-1β, IL-6 and oxidative stress over 6 days, which were attenuated by concurrent treatment with MCC950 or MitoQ10 compared to vehicle controls. Conclusions: CPP ripening drives systemic inflammation via NLRP3 activation and effects on mitochondrial function. Targeting these pathways may have therapeutic potential.

70 Joanne Tropea Analgesia use among hip fracture repair patients with dementia compared to patients who are cognitively intact Fatima M (1), LoGiudice D (2,3), TROPEA J (2,3) 1. Barwon Health; 2. Melbourne Health; 3. University of Melbourne

Aim: To investigate use of analgesia following hip fracture repair surgery in people with dementia compared to those who are cognitively intact. Background: People with dementia are at high risk of hip fracture from falls. Hip fracture guidelines recommend use of regional analgesia to improve preoperative pain control and multi-modal postoperative pain management in patients with hip fracture. A small number of studies outside Australia have shown people with dementia do not receive adequate pain management following hip fracture repair. Methods: Retrospective review of records of patients who underwent hip fracture repair surgery at the Royal Melbourne Hospital, Australia between 1st Jan 2015 to 31st Dec 2015. Dementia cases were identified by presence of a dementia code during the admission. Controls were defined as patients without dementia or delirium coded during the admission. Cases and controls were matched based on age, sex and treating unit (a proxy for surgery type). Demographic and clinical data was collected using a structured audit tool. The main outcome of interest was: analgesic use (opiates and paracetamol) in preoperative and 72-hour postoperative periods. Results: Total of 99 patients including 37 patients with dementia and 62 patients without cognitive impairment were reviewed. • Preoperative median (interquartile range) daily dose of opiates (converted to oral morphine equivalent mg/dl) administered was 30mg/dl (15-45) in the dementia group and 52.5mg/dl (30-67.5) in the control group (p<0.001). • On the day of surgery and day 2 postoperative, patients with dementia received significantly lower median daily dose of opiates compared to the cognitively intact group: 15mg/dl (7.5-22.5) compared to 18mg/dl (11.8-33), p=0.022; and 20mg/dl (8-37.5) compared to 30mg/dl (15-45), p=0.029 respectively. • On day 1 and day 3 postoperative, although patients with dementia received less opiates compared to cognitively normal patients, this wasn’t statistically significant. • Significantly fewer patients with dementia received regular paracetamol during the preoperative period, 28 (76%) compared to 58 (94%), p=0.015. There were no differences in paracetamol during the postoperative period.

Conclusion: Preoperative, day of surgery, and day 2 postoperative people with dementia on average received significantly lower daily doses of opiates compared to those who were cognitively intact. Significantly fewer people with dementia received regular paracetamol in the preoperative period.

71 Peter Lange Melatonin for the Treatment of Delirium: Results from a Feasibility Study LANGE PW(1,2), Clayton-Chubb D(1,3), Watson R(1), Maier AB (1,2,4) 1Department of Medicine and Aged Care, The Royal Melbourne Hospital; 2Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, 3 Department of Medicine, Eastern Health, 4 Department of Human Movement Sciences, MOVE Research Institute Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Aim: To determine the feasibility and participants required to test the hypothesis that Melatonin 5mg, administered nightly for 5 nights, reduces the severity of delirium in elderly medical inpatients. Background: Melatonin is a hormone important in regulation of circadian rhythm. Circadian rhythm is often disturbed in delirium. Melatonin levels in serum, CSF and urine are perturbed in delirium. Melatonin 0.5mg and 5mg orally, nightly, are effective for prevention of delirium in elderly inpatients. Melatonin 5mg orally, nightly has not been evaluated for the treatment of established delirium. Methods: A pilot trial was conducted at the Royal Melbourne Hospital, approved by the Ethics Committee. Patients >/=70yrs admitted to general internal medicine units were eligible for inclusion. Melatonin 5mg was administered nightly for 5 days. The primary research outcome was change in the Memorial Delirium Assessment Scale (MDAS) (/30, increasing with severity) assessed daily over days 1-5 (treatment). Results: 154 patients were screened for participation, of whom 74 were eligible to participate. In 29 surrogate decision makers provided consent, and were randomised. The placebo and treatment groups were well matched for age (mean 85 vs 86yrs), gender (male 8/15 vs 6/14 and prevalence of premorbid dementia (8/14 vs 6/14). Age (29/29) and cognitive impairment (14/29) comprised the major predisposing factors to delirium; inflammatory states (15/29), musculoskeletal injury and fracture (9/29) the most frequent precipitating. The MDAS had a mean of -2.15 (SD 4.09) in the placebo group, -1.85 (SD 4.68) in the treatment group. Some patients had a severely decreased arousal on some assessments, making MDAS difficult to administer. There were no adverse events attributed to treatment. Overall 20/29 completed the study; mortality was 5/29. Conclusion: Melatonin is a safe, possible treatment for delirium symptoms. A sample size of 30 patients would have 80% power to detect a clinically significant 3 point reduction in MDAS in elderly general medical inpatients with delirium. Allowing for 27.6% drop-out, 40 participants would be required. This is feasible given the rate of recruitment. The addition of a scale assessing level of arousal as an outcome may be useful.

72 Camilla Tuttle Markers of cellular senescence and chronological age in various human tissues: a systemic review of the literature Waaijer MEC(1), TUTTLE C (2,3), Slee-Valentijn MS(1), Westendorp RGJ(1), Maier AB(1,2,3) 1. VU University Medical Center Amsterdam, 2. University of Melbourne, 3. Melbourne Health

Background: Cellular senescence, a stable growth arrest of cells, is increasingly recognized as a driver of the aging process. Several studies report higher numbers of senescent

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cells in a variety of tissues of older humans when compared to the young. Objective: To systemically describe the literature on the association between markers of cellular senescence and chronological age in different types of tissues. Methods: We searched Pubmed, Web of Science and Embase for articles that reported on senescence markers dependent on age in any human tissue. Out of 3833 unique articles 43 articles reporting on this topic were identified, including 44 cohorts. Data was extracted on the origin of tissue, the type of markers being used, and the age and gender distribution of the donors. A total of 78 associations between senescence markers and age were reported. Outcomes: Cohort sizes ranged from 3 to 176 donors, and varied widely in their age distribution. Out of the 78 associations, 34 were positive and statistically significant associations (p<0.05) between senescence markers and chronological age, six showed positive trends (0.05<p<0.10), 27 associations were inconclusive (p>0.10) and one association showed a negative statistically significant association (p<0.05). A large proportion of the positive associations were based on studies conducted in blood, whereas it was less often the case in kidney and skin. Conclusion: Almost half of the associations between markers of cellular senescence and age show a positive significant association. This can be interpreted as proof of an evident biological phenomenon but it is unclear to what extent publication bias explains for these outcomes.

73 Wendy Bower TANGO, a novel screening tool to identify co-existing causes of Nocturia BOWER WF(1), Goldin J(2), ROSE G(1,2), Ervin CF(1), Whishaw DM(1), Khan F(3) 1.Melbourne Health, Department of Medicine & Community Care, 2. Melbourne Health, Department of Respiratory and Sleep Medicine, 3. Melbourne Health, Department of Rehabilitation

Aim: The aim of this study was to develop a metric to assist in the identification of co-existing causes of nocturia. As we wished to Target Aetiology of Nocturia to Guide optimal Outcomes, the metric was entitled TANGO. Background: The causal pathway of nocturia is multi-factorial and differs between individuals. Optimal management of nocturia requires comprehensive evaluation to identify all potential aetiologies, particularly variables beyond the lower urinary tract. At present, there is no screening tool for multiple and co-existing causes of the symptom. Methods: Individual variables carrying a significant risk association with nocturia of >1/night were identified from a systematic literature review. Validated and reliable measurement tools for these variables were identified and discriminating items extracted and compiled into a self-completed, 57-item questionnaire. Ten pertinent clinical measures were added to generate the TANGO Long Form (LF). 252 patients with nocturia attending a Sleep, Continence, Falls or Rehabilitation service for routine care at a tertiary level hospital completed the TANGO LF. Data analyses, alongside clinical and empirical criteria informed item reduction to produce the 22-item TANGO Short Form (SF). This was subject to test-retest reliability in 40 additional inpatients at the same health service. Data was collected twice, 5 to 10 days apart. Item agreement was analysed using Cohen’s Kappa Statistic. Ethics approval number: LNR/16/MH/22. Results: Univariate analyses of the TANGO LF data revealed 22 items to be significantly associated with nocturia frequency >=2/night (p<0.05). The final regression model for high frequency nocturia explained 68% of the variance and retained 7 variables: fair/ poor health, severe pain, < 3 hours sleep before first nocturia episode (FUST), daily urgency / urgency

incontinence, poor sleep quality and a high depression score. The significant independent predictors were daily urge leakage (OR 2.52), and short FUST (OR 0.40). The TANGO SF was developed from items significantly associated with high frequency nocturia. Patient self-completion required between 30 seconds and 2 minutes. Test-retest reliability of this new metric demonstrated substantial to excellent agreement (Kappa 0.6 to 0.79 and 0.8 to 1.00 respectively). Conclusion: A novel and reliable patient-completed all-cause screening tool has been developed to facilitate identification of clinically relevant co-existing causes of nocturia. TANGO sits alongside bladder diary data and supports clinicians identifying and targeting treatment for nocturnal polyuria, sleep dysfunction, cardiovascular disorders and emotional wellbeing. TANGO has the potential to smooth inequalities associated with current nocturia assessment across health disciplines and services.

74 Emily You What do you see as essential qualities of a community aged care case manager? YOU E (1), Doyle C (2), Ellis K (1), Curran E (1), Dunt D (3) 1.Academic Unit for Psychiatry of Old Age (AUPOA), Department of Psychiatry, The University of Melbourne; 2. School of Nursing, Midwifery and Paramedicine, Australian Catholic University; 3. Centre for Health Policy, Melbourne School of Population and Global Health, University of Melbourne

Background: Community aged care case managers have been playing an important role in coordinating services for community dwelling frail older people. With right qualities, case managers would be able to better perform their role and contribute to improvements in older people’s health and wellbeing. Aim: In this study we aimed to explore essential qualities of case managers working in Australia’s community aged care system from the perspectives of a sample of community aged care case managers. Methods: Thirty-three semi-structured interviews with 47 participants were conducted. The participants were drawn from a list of all case managers that administrated publicly funded community aged care packages (targeting community-dwelling frail older Australians) in Victoria, Australia. Thematic analysis was performed. The competency models were used to organise the reporting of the findings and where applicable the themes were mapped onto the constructs of the models. Results: Four key themes of essential qualities of case managers were identified. The first was knowledge/abilities/skills, including technical knowledge (e.g. knowledge of older people and case management), work management abilities or skills (e.g. ability to build rapport and skills in managing budgets), and interpersonal skills. The second was practice-based learning and improvement (e.g. adequate qualifications and experience). The third quality was professionalism, specifically holistic and person-centred approaches to practising. The last was personal characteristics, encompassing passion for their work, empathy, patience, and a eagerness to learn. Conclusion: These findings may assist with the development of hiring criteria, job descriptions, performance evaluation frameworks, and practice guidelines for case managers. Identification of four themes could also provide a useful guide for self-improvement of case-managers, and provides a framework for future research in which older people’s perception of essential qualities of their case managers is examined.

75 Noleen Bennett The Australian aged care national antimicrobial prescribing survey: An update

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BENNETT N1,2,3, Chen C1,2, Koning S1,2, James R1,4, Bull A3, Worth L3, Buising K1,2,4, Thursky K1,2,4 1 National Centre for Antimicrobial Stewardship, Doherty Institute, 2 Guidance Group, The Royal Melbourne Hospital, 3Victorian Healthcare Associated Infection Surveillance System Coordinating Centre 4 The University of Melbourne

In 2016, Australian Residential Aged Care Facilities (RACFs) were invited to participate in the Aged Care National Antimicrobial Prescribing Survey (acNAPS). This survey built upon findings from the pilot conducted in 2015. This survey was a joint collaboration between the National Centre for Antimicrobial Stewardship and Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. The project team includes one or more Infectious Diseases Physicians, Pharmacists, Infection Control Practitioners, Clinical Microbiologists, Statisticians and Epidemiologists. Prior to 2015, there was no national surveillance program that monitored infections or antimicrobial use in Australian RACFs. Data are collected by nurses, pharmacists and/or Infection Control Practitioners. As of 2016, acNAPS infection and antimicrobial use data can be collected via two different methods: Method 1: A single day prevalence survey only. On the survey day all residents are screened to determine if they: Are prescribed antimicrobial therapy; and/or Have signs and symptoms of a suspected or confirmed infection. Method 2 (Included for 2016 survey): A single day prevalence survey PLUS an additional one month retrospective survey As for Method 1 plus all residents present on the survey day are screened to determine if they were prescribed antimicrobial therapy on any day during the previous month (that were ceased prior to the survey day). There are three data collection forms: The RACF form is completed for each participating RACF and collects summary data about the residents, including gender and age; The Antimicrobial form is completed for those residents who are prescribed antimicrobial therapy (See table below); The Infections form is completed for those residents who have signs and symptoms of a suspected or confirmed infection. Each participating RACF is able to generate a password secure report that in part compares their local, regional and state level results against the national aggregate results. National reports quantify any annual improvement in performance. In the short term, there appears to have already been some improvement in antimicrobial use in Australian RACFs. For example between 2015 and 2016 the percentage of prescriptions with indication not documented fell from 32% to 22% while the number of participating facilities increased from 186 to 251. The percentage of antimicrobials prescribed for greater than 6 months also fell from 31% to 23%. It is likely that over time acNAPS will contribute substantially to resident safety and quality improvement.

76 Frances Batchelor Context-specific falls prevention roadmap using local data F BATCHELOR(1), S Williams(1), R Lewin(2), K Mackenzie(2), L Harvey(2), V Lui(2), P Lange(2), C Said(3,4)* (1)National Ageing Research Institute (2)Royal Melbourne Hospital, (3)Austin Health, (4)University of Melbourne

Aim: To develop and trial a context specific falls prevention roadmap in the Acute Medical Unit (AMU) at Melbourne Health to extract local data and select and implement intervention(s) based on this data. Background: Despite evidence that some falls prevention interventions can work in hospitals, translation of evidence is difficult, possibly due to differences in settings, patient profiles and falls rates; high patient turnover, perception that everything is being done, availability of resources and focus on screening rather than intervention.

Methods: A formal project team as part of the Melbourne Ageing Research Collaboration (MARC) comprised of clinicians and researchers. The approach was trialled at two acute hospitals sites. One site was the Acute Medical Unit (AMU) at Melbourne Health. The approach included 10 weeks collecting information about falls, patient and staff knowledge, perceptions and practices, unit systems and physical environmental issues. Locally-derived data was analysed, findings used to determine the optimal intervention(s) to implement, and presented to falls champions. The falls champions provided education at their site and strategies were implemented by frontline staff, and their impact analysed by a further 10 week data collection period. Results: For the 10 week data collection period in mid-2017, AMU had 21 falls predominantly in patients who were walking or standing and were classified for mobility as independent or supervised. Only 33% of patients who fell had diminished cognition. In 62% of fallers, staff were unable to identify if the patient had been overestimating their ability prior to the fall. Staff identified the need for patient engagement when moving and improved staff risk assessment skills as areas for improvement. Strategies selected to implement were AMU staff performing patient behaviour assessment and appropriate education about falls risk to patients at each shift handover, removal of falls risk signs, increased staff training about falls at an individual patient level and a medical falls risk assessment for all fallers. For 10 weeks in late-2017, AMU at 8 falls. Strategies had addressed the areas of concern. New data highlighted other areas of concern – falls were occurring in non-English speaking patients, those with diminished cognition and early in the admission. Staff are developing strategies to address these concerns. Conclusion: Collaboration between researchers and clinical staff has led to the development of roadmap which will enable different wards/units to select falls prevention interventions appropriate to their local context. *On behalf of members of the Melbourne Ageing Research Collaboration (MARC)

77 Mervyn Kyi Identifying hospitalised patients at risk of adverse glycaemia: a risk stratification model Kyi M (1,2,3), Reid J (1), Gorelik A (4), Kumar S (1), Galligan A (1), Rowan LM (1), Nankervis AJ (1), Marley KA (1), Russell DM (2), Wraight PR (1), Colman PG (1), Fourlanos S (1,2) 1. Diabetes and Endocrinology, RMH. 2. Department of General Medicine, RMH. 3. University of Melbourne, Department of Medicine - RMH. 4. Melbourne EpiCentre, RMH

Background: In hospitalised patients, adverse glycaemia (both extremes of hypo- and hyperglycaemia) are associated with poor outcomes and should be avoided. With the increasing prevalence of diabetes in hospital, there is a need to identify patients at high-risk of developing adverse glycaemia to better direct glycaemic management efforts. In this observational study, we analysed a cohort of inpatients with diabetes and developed a risk-stratification model to predict those at risk of adverse glycaemia. Methods: We recruited 643 consecutive inpatients with diabetes or new onset hyperglycaemia (random capillary blood glucose [BG] ≥ 11.1 mmol/L without known diabetes) with ≥ 2 days length of stay, admitted to a tertiary hospital. Capillary BG measures were collected using networked BG meters and commenced from the time of admission until discharge (or day 14 for long-stayers). Adverse glycaemia was defined as the occurrence of any capillary BG < 4.0 or > 15.0 mmol/L from day 2 onwards after admission. Multivariable logistical regression was performed to analyse the association between adverse glycaemia and patient clinical factors (age, sex, Charlson index, admission

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creatinine, HbA1c, diabetes type, pre-admission diabetes regimen), hospital treatment factors (surgery, glucocorticoid use, duration of hospital stay), and unstable day 1 BG (defined as any BG <4.0, >15.0 or two BG >10.0 mmol/L). A split-sample approach was used where a randomly allocated half of the cohort was used for model construction and the remaining half was used for internal validation. Results: Patient characteristics were: age 70±14 years; HbA1c: 7.6±1.7%; 88% type 2 diabetes; and 33% insulin-treated. Adverse glycaemia occurred in 278 (43%) patients. Factors associated with adverse glycaemia were: Charlson index, HbA1c, duration of hospital stay, sulphonylurea or insulin treatment, and unstable day 1 BG. A risk-stratification model using these five factors had sensitivity 84%, specificity 60%, PPV 64%, NPV 82%. A second model using two practical factors easily available on admission (pre-admission insulin treatment or unstable day 1 BG) predicted the majority of inpatients with adverse glycaemia (sensitivity 83%, specificity 56%, PPV 56%, NPV 83%). Conclusion: In hospitalised patients, factors associated with adverse glycaemia include pre-admission insulin or sulphonylurea treatment, unstable BG on day 1, higher HbA1c and greater comorbidities. These factors should be used to risk-stratify patients for concentration of specialist inpatient diabetes management efforts.

78 Mervyn Kyi Adverse glycemic days in the RAPIDS study: assessing the performance & safety of an inpatient glycemic management program Kyi M (1,2,3), Reid J (1), Galligan A (1), Kumar S (1), Rowan LM (1), Nankervis AJ (1), Gorelik A (4), Marly KA (1), Russell DM (2), Wraight P (1), Colman PG (1), Fourlanos S (1,2) 1. Diabetes & Endocrinology, RMH. 2. Department of General Medicine, RMH. 3. University of Melbourne, Department of Medicine, RMH. 4. Melbourne EpiCentre, RMH.

Aim & Background: We propose the concept of Adverse Glycaemic Day ([AGD]: a patient-day with any capillary blood glucose [BG] <4.0 or >15.0 mmol/L), as a measure of safe diabetes care in hospital, given both hypo- and hyperglycaemia are undesirable. We studied the incidence & associations of AGDs in the 10 week baseline period of the Randomized trial of Proactive Inpatient Diabetes Service (RAPIDS ACTRN12616000265471). Methods: Consecutive inpatients with diabetes or new-onset hyperglycaemia (random BG ≥11.1 mmol/L without known diabetes) were recruited. Connectivity meters were used to record capillary BGs from admission until discharge, or day 14 for long-stayers. Results: We studied 441 patients (87% type 2 diabetes; 29% insulin-treated; A1c: 7.5±1.7%). AGDs occurred in 736 (26%) of 2810 patient-days. Of all AGDs, 83% were due to hyperglycaemia (>15.0 mmol/L), 14% due to hypoglycaemia (<4.0 mmol/L), and 3% due to both. Half (49%) of patients had no AGD while 25% of patients had ≥3 AGDs, accounting for two thirds of all observed AGDs. On multivariable analysis, AGDs were independently associated with multiple clinical factors including insulin-requiring diabetes and higher HbA1c. Conclusion: Adverse glycaemic days were common in inpatients with diabetes and occurred at an approximate rate of 250 per 1000 patient-days. We propose AGD incidence is used to evaluate the performance and safety of hospital glycaemic management programs.

79 John Wentworth Beta-cell function inferred from fasting plasma C-peptide and glucose is a clinically useful measure of disease progression and response to immune therapy in children and young adults with type 1 diabetes.

WENTWORTH JM(1,2,3), Bediaga NG(1,2), Ehlers M(4), Gitelman S(5), Geyer S(6), Evans-Molina C(7), Harrison LC(1,2) on behalf of the Type 1 Diabetes TrialNet and Immune Tolerance Network Study Groups. 1. The Walter and Eliza Hall Institute of Medical Research, 2. Department of Medical Biology, University of Melbourne, 3. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, 4. Clinical Trials Group, Immune Tolerance Network, USA, 5. University of California at San Francisco, USA 6. University of South Florida, USA , 7. Indiana University School of Medicine, USA

Background: Therapies that could preserve beta-cell function in type 1 diabetes (T1D) are being evaluated. Beta-cell function is most commonly assessed as the average C-peptide concentration (CPAVE) during a two-hour meal test. To simplify this assessment we sought to devise a surrogate marker using measures obtained at a single time point. Method: Linear models to approximate CPAVE from fasting biochemical and clinical measures from people aged less than 21 years with recently diagnosed T1D were developed with data from eight clinical trials. These were then tested for their ability to detect loss of beta-cell function and its response to immune therapy. Results: A model based on fasting C-peptide (FCP), fasting glucose (FG), age, HbA1c, disease duration, body mass index and insulin dose most accurately diagnosed loss of beta-cell function (area under ROC 0.89; 95% CI 0.87 to 0.92). The accuracy of a simpler model based on FCP and FG (CPAVE = [0.606 + 1.06xFCPnmol/L - 0.0268xFGmmol/l]2) was similar (AUROC 0.89; 95% CI 0.86 to 0.91) and superior to that of insulin dose-adjusted HbA1c (IDAA1C; AUROC 0.72; 95% CI 0.68 to 0.76). When applied to trials that showed treatment benefit, trial outcomes based on modeled CPAVE were similar to those obtained from CPAVE measure by meal test. One year after T1D diagnosis, Modeled CPAVE had lower variance than actual CPAVE, equating to increased power to detect treatment effects. Conclusion: CPAVE inferred from FCP and FG identifies children and young adults who lose significant beta-cell function over the year after T1D diagnosis. Inferred CPAVE is more accurate than IDAA1C for diagnosing significant loss of beta-cell function and is comparable to actual CPAVE for identifying treatment effects, suggesting it could serve as a simpler primary outcome measure for future trials of disease-modifying therapy in T1D.

80 John Wentworth Cost-effectiveness of gastric band surgery for overweight but not obese adults with type 2 diabetes in the U.S. WENTWORTH JM(1,2,3), Dalziel KM(4), O’Brien PE(1), Burton P(1), Shaba F(4), Clarke PM(4), Laiteerapong N(5), Brown WA (1) 1. Centre for Obesity Research and Education, Monash University, 2. Walter and Eliza Hall Institute, Melbourne University, 3. Royal Melbourne Hospital Department of Medicine, 4. School of Population and Global Health, University of Melbourne, 5. Department of Medicine, University of Chicago, Chicago, IL, USA

Aim: To determine the cost-effectiveness of gastric band surgery in overweight but not obese people who receive standard diabetes care. Method: A microsimulation model (United Kingdom Prospective Diabetes Study outcomes model) was used to project diabetes outcomes and costs from a two-year Australian randomized trial of gastric band (GB) surgery in overweight but not obese people (BMI 25 to 30kg/m2) on to a comparable population of U.S. adults from the National Health and Nutrition Examination Survey (N=254). Estimates of cost-effectiveness were calculated based on the incremental cost-effectiveness ratios (ICERs) for different treatment scenarios. Costs were inflated to 2015 U.S. dollar values and an ICER of less than $50,000 per QALY gained was considered cost-effective.

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Results: The incremental cost-effectiveness ratio for GB surgery at two years exceeded $90,000 per quality-adjusted life year gained but decreased to $52,000, $29,000 and $22,000 when the health benefits of surgery were assumed to endure for 5, 10 and 15 years respectively. The cost-effectiveness of GB surgery was sensitive to utility gained from weight loss and, to a lesser degree, the costs of GB surgery. However, the cost-effectiveness of GB surgery was affected minimally by improvements in HbA1c, systolic blood pressure and cholesterol. Conclusion: GB surgery for overweight but not obese people with T2D appears to be cost-effective in the U.S. setting if weight loss endures for more than five years. Health utility gained from weight loss is a critical input to cost-effectiveness estimates and therefore should be routinely measured in populations undergoing bariatric surgery.

81 Lucy VIvash Optimal injection time for ictal SPECT for the localisation of the epileptogenic zone using subtraction ictal SPECT coregistered to MRI (SISCOM) in patients with focal epilepsy with and without secondary generalisation Hlauschek G(1), Kwan P (1), O’Brien TJ(1), Lichtenstein M(2), Westcott J(2), VIVASH L(1) (1) Melbourne Brain Centre and Departments of Medicine and Neurology, The Royal Melbourne Hospital, The University of Melbourne, (2) Nuclear Medicine, Department of Medical Imaging, The Royal Melbourne Hospital.

Background : Hyperperfusion on ictal SPECT is well established technique for the localisation of the epileptogenic zone (EZ) in patients with focal epilepsy. The accuracy of ictal SPECT can be vastly improved by subtraction of an inter-ictal image, a technique known as subtraction ictal SPECT coregistered to MRI (SISCOM). However, the routine application of ictal SPECT is limited by the necessity for rapid injection of the radiotracer, with poor localisation observed for later injection times (>45 seconds). Conversely secondary generalisation of the seizure has not been shown to affect the likelihood of achieving an accurate ictal scan. More recent studies have investigated the use of an internal control group to improve localisation rates (STATISCOM), finding STATISCOM to be superior to SISCOM. Aim: The purpose of this study is to investigate the optimal tracer injection time from seizure onset and secondary generalisation in ictal-SPECT for localising the EZ . Methods: Retrospective data on all patients who had an ictal SPECT scan whilst within the video-EEG monitoring unit at the Royal Melbourne Hospital was collected (2009-2017). Patient data was evaluated and patients with focal epilepsy with complete imaging (ictal, inter-ictal SPECT and MRI) were included in subsequent analysis. The information collected included age, gender, seizure type (focal seizure with/without secondary generalisation), epilepsy diagnosis (TLE or extra-TLE), injection time of the radiotracer from seizure onset and from generalisation. SISCOM images were created. Thresholding for hyperperfusion was set at 1.0SD, 1.5SD and 2.0SD for each patient. SISCOM images were then reviewed by two blinded reviewers to identify the EZ and extent of abnormality in each image. Images will be stratified according to injection time (<30s, 30-45s, 45-60s, 60-90s, 90<s) and presence or absence of secondary generalisation. Cohen´s kappa score will be used to test interobserver agreement between blinded reviewers. Sensitivity, specificity, positive predictive value and negative predictive value will be calculated in relation to the injection time from seizure onset and generalization. Results: A total of 136 patients had an ictal SPECT. 17 where excluded due to non-focal epilepsy. 50 patients were excluded due to incomplete imaging. This resulted in a evaluable patient

group of 69 patients for whom SISCOM and STATISCOM images have been generated. Expert review of the images is ongoing. Conclusion: This study will provide evidence to improve the clinical utility and optimal image analysis method of ictal SPECT in the VEM unit to improve EZ localisation and ultimately patient outcomes.

82 Withdrawn 83 Varduhi Cahill FDG-PET as an independent predictor of seizure outcomes in epilepsy surgery patients: more than meets the eye Cahill VM(1), Sinclair B(1), Malpas CB(1), McIntosh AM(1,2), Chen Z(1), O'Shea MF(2), Wilson SJ(1), Berlangieri SU(2), Hicks RJ(1,3), Rowe CC(2), Morokoff AP(1), King JA(1), Fabinyi JC(2), Kaye AH(1), Kwan P(1), Berkovic SF(2), O'Brien TJ(1) 1. Departments of Medicine, Neurology and Neurosurgery, The Royal Melbourne Hospital, The University of Melbourne; 2. Epilepsy Research Centre and Department of Medicine, Austin Health, The University of Melbourne; 3. Peter MacCallum Cancer Centre.

Introduction: A significant proportion of patients with mesial temporal lobe epilepsy (mTLE) continue to experience seizures following anterior temporal lobe resection (ATLR). Interictal fluorodeoxyglucose (FDG) PET is commonly employed in the evaluation of surgical candidates and there has been an ongoing quest to identify its predictive value in seizure outcomes. Aims: To investigate the relationship between the extent of resection of the FDG-PET hypometabolism identified preoperatively and seizure outcomes in patients with non-lesional mTLE. Methods: Eighty-two patients who underwent ATLR at the Royal Melbourne or the Austin Hospitals and had ≥2 years of post-operative follow up were studied. FDG-PET and MRI processing was carried out within SPM12. The hypometabolic region in each patient was identified with reference to a healthy control group (p < .005). The resected temporal lobe (TL) volume was calculated from the pre-and post-operative MRIs. The volume of pre-operative FDG-PET hypometabolism was calculated using the SPM software, as well as the proportion of the TL hypometabolism that was actually resected. Results: The brain resection volume was greater (p= 0.034) in patients with excellent seizure outcomes (Engel’s class I) compared to those with less favourable outcomes (class II-IV). The group with excellent seizure outcomes also had a significantly higher proportion of FDG-PET hypometabolism resected (p=0.018) versus those with less favourable outcomes. Conclusions: Both, the size of the ATL resection and the amount of preoperative FDG-PET hypometabolism included in the resection, are predictive of seizure outcome. Computational analysis of PET images could play a role in the pre-surgical planning and prognostication for patients with drug resistant mTLE.

84 Neha Kaul Triheptanoin - a novel dietary therapy for drug-resistant epilepsy KAUL N (1,2), Borges K (3), Germaine J (4), Kwan P (2,4), O'Brien TJ (2,4) 1 Department of Clinical Nutrition, Royal Melbourne Hospital; 2 Department of Medicine, RMH, University of Melbourne; 3 School of Biomedical Sciences, The University of Queensland; 4 Department of Neurology

Aim: To determine if triheptanoin oil is a safe and tolerable add-on treatment for drug-resistant epilepsy. Background: One-third of patients with epilepsy will be resistant to anti-epileptic drug therapies. There are a limited

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number of treatment options available for these patients. Dietary therapy, particularly the high fat, low carbohydrate ketogenic diet, is a well-established treatment for paediatric drug-resistant epilepsy. Its efficacy in adults has not been rigorously investigated, mainly due to concerns of limited adherence to dietary changes long-term. Triheptanoin, the triglyceride of the 7-carbon fatty acid heptanonate, is a synthetic, tasteless oil, which has demonstrated anti-convulsant properties in chronic epilepsy animal models. Methods: Participants experiencing two or more seizures per month were invited to participate in a phase IIa randomised double-blinded placebo control trial. After an 8-week baseline-screening period, participants were randomised to receive either a standard mixed 6/8-carbon medium chain triglyceride (MCT) or triheptanoin oil. The study oil was increased over a three-week uptitration period to a maximum tolerated dose of 35% of total daily caloric intake. The treatment period was 12-weeks, followed by a downtitration period and final follow up visit. Participants completed daily seizures diaries and food diaries prior to each study visit. Results: A total of 55 participants were screened over the recruitment period, 34 met the randomisation criteria. There was an even allocation of 17 participants in both the MCT and triheptanoin groups. There was a similar number of participants completing the full study protocol, n=11 and n=10 in the MCT and triheptanoin groups respectively. The baseline characteristics of the two groups were similar for age, gender, seizure aetiology and tolerated oil dose. There were no serious adverse events reported by participants in either group, however the number of mild adverse events, predominately gastrointestinal symptoms were similar. The mean weight gain was significant over the study period was 1.8kg (p=0.02) for all participants. Five (45%) participants in MCT group and one (11%) in the triheptanoin group experienced >50% reduction in seizure frequency from baseline, however this failed to reach statistical significance (p=0.15). Conclusion: Triheptanoin is a safe and tolerable treatment for patients with drug-resistant epilepsy when compared to standard MCT oil. More targeted advice on calorie and portion control is required to reduce the risk of weight gain. The observed seizure reduction in both groups in patients, particularly those with focal unaware seizures warrants further investigation.

85 Dana Jazayeri Antiepileptic drug use for non epilepsy indications. Report from the Australian Pregnancy Register D JAZAYERI(1), J Graham(2), A Hitchcock(2), TJ O’Brien(2), FJE Vajda(2) 1. The University of Melbourne 2. Royal Melbourne Hospital

Antiepileptic drug use for non epilepsy indications. Report from the Australian Pregnancy Register Aim: Antiepileptic drugs (AEDs), especially valproate are teratogens when taken by women with epilepsy (WWE), but the risk is uncertain when these drugs are taken for indications other than epilepsy, including bipolar disorder, anxiety , neuropathic pain, migraine and multiple sclerosis. These disorders are more common in women in childbearing age. Epilepsy is a less likely cause of malformation than AEDs, and their effects in women with no epilepsy need evaluation. Patients: The Australian Pregnancy Register established in 1998 is a prospective observational study operating with ethical approval and informed written consent for participation.There are currently 2300 women enrolled in the Register, 85 per cent representing WWE. Results: The malformation rates in pregnancies of WWE taking AEDs (5.17%), were higher than in untreated WWE (2.27%). There were, 30 women enrolled taking AEDs for indications other than epilepsy. In this cohort 1/30 of the women had a

malformed child with a cleft palate on a high dose of valproate (VPA, 1700mgper day). Further research with larger numbers of patients is required. Conclusions: These initial findings suggest that women without epilepsy have a similar risk of having a child with a birth defect when exposed to antiepileptic drugs as women with other, non-epileptic conditions. Understanding the role of epilepsy in AED induced birth defects will clarify whether or not the teratogenicity is resulting from AEDs interacting with genetic factors or AEDs interacting with both epilepsy and genetic factors. This is the first attempt to assess at the use of AEDs in a prospective study of women who are pregnant but do not have epilepsy.

86 Frank Vajda Antiepileptic drugs, foetal malformations and spontaneous abortion FRANK VAJDA (!), O'Brien T (1), Graham J (1), Hitchcock A (1), Lander C (2), Eadie M (3) Royal Melbourne Hospital (1), Royal Brisbane Hospital (2), University of Queensland (3)

Aim: To study the foetal complications of antiepileptic drug (AED) exposure. Background: Some recent studies have found an association between foetal malformations in earlier antiepileptic drug exposed pregnancies and an increased hazard of such malformations in subsequent pregnancies. We investigated this matter further, and also considered the possible role of spontaneous abortions in previous pregnancies, in this situation. Methods: Analysis of foetal malformation (FM) data for current and previous pregnancies in women taking AEDs and women with untreated epilepsy in the Australian Pregnancy Register of Antiepileptic Drugs (APR) from 1999 to late 2014. Results: 1223 antiepileptic drug-treated women with either a malformed foetus or a spontaneous abortion in their previous pregnancy had a statistically significant twofold to threefold increased risk of foetal malformation in their next pregnancy, compared with similarly treated women with normal offspring in their previous pregnancy. Foetal malformation rates for all 290 untreated pregnancies was 2.5-3.5%, similar in subsequent pregnancies. In AED exposed pregnancies FM rates were 6.7%v.2.4% RR =2.78, 95% CI 1.30-5.95. The same applied to the valproate exposed subgroup (13.1%v.2.4% RR=5.43 CI 2.50-11.80). In their second pregnancy 121 women were untreated, 590 exposed to AEDs. Third pregnancy involved 53 untreated and 319 AED exposed women. If the first pregnancy outcome was normal (492), the second pregnancy yielded 392 normal, 26 malformed and 63 abortions. If first pregnancy produced a FM (46), second pregnancy was normal (28), malformed (8). In 52 cases of previous spontaneous abortion, 34 produced a normal baby in second pregnancy and 13 spontaneous abortions. On AED treatment, women were more likely to have spontaneous abortions than in previous untreated pregnancies. Conclusion: In assessing the hazard of an AED-treated woman having a malformed foetus, it is important to know both the AEDs being taken and, if there had been a previous pregnancy, whether a foetal malformation or a spontaneous abortion occurred in it.

87 Nanya Hao The influence of ethnic background on participation and pregnancy outcomes in the Australian Pregnancy Register

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Nanya Hao(1,2), Janet Graham(1), Alison Hitchcock(1), Terence O'Brien(1,2), Frank Vajda(1,2) 1 Royal Melbourne Hospital, Department of Neurology, Melbourne, VIC, Australia 2 University of Melbourne, Department of Medicine, Melbourne, VIC, Australia

Purpose: Anti-epileptic Drug (AED) Registers are now well established and have provided important information regarding outcomes of pregnancies exposed to AEDs. Participation by pregnant women in a register may be influenced by the ethnicity of the population, which may influence the applicability of the findings. This issue has received little scientific investigation. Aim of this study is to identify the effects of ethnicity on participation and pregnancy outcomes of the Australian Pregnancy Register (APR). We particularly focused on those of Asian background, as this represents the largest non-European ethic group in Australia. Methods: Since 1999, the APR has recruited 2380 eligible pregnant women with epilepsy, or taking AEDs for another indication. Details about social demography, pregnancy, and epilepsy were obtained. Ethnicities of the participants were defined according to standard classification for sociological research in Australia. Logistic regression analysis is used to examine the association between ethnicity, AEDs, epilepsy and pregnancy outcomes. Results: 856 participants were tentatively identified as being born from outside Australia and were contacted, 458 replied, 49 participants were identified as having Asian ancestry, which was much less than the expected based on general population demographics. Asian-Australians were less likely to have had a convulsive seizure during the first trimester (OR 0.110, CI 0.015-0.803, p 0.03), but more likely to take multiple AEDs during pregnancy (OR 2.126, CI 1.197-3.776, p 0.01). Although no significant differences were found in terms of pregnancy outcome, there was a trend that Asians were less likely to have poor pregnancy outcomes (OR 0.194, CI 0.027-1.417, p 0.106). Conclusion: Ethnicity appears to have a significant influence on participation in voluntary Registers, with reduced participation rate among Asian-Australians in the APR. It is possible that Ethnicity may also influence outcomes of pregnancy exposed to AEDs, and this is an area that warrants further dedicated research.

88 Dana Jazayeri Seizure suppression in a model of genetic absence epilepsy by dietary valproate D JAZAYERI (1), E Braine(2), TJ O’Brien(3), N Jones(2) 1. The University of Melbourne 2. Florey Institute of Neuroscience and Mental Health 3. Royal Melbourne Hospital

The antiepileptic (AED) drug valproate (VPA) is a highly effective anticonvulsant used primarily for treatment of epileptic seizures. Animal models of epilepsy are valuable tools to study effects of new and existing AEDs, particularly with reference to drug efficacy. Conventional methods of AED administration often involve acute injection protocols, and rarely allow for prolonged administration, which is far more relevant to human circumstances. In addition, repeated injections can be stressful for the animal, consequently effecting seizure frequency particularly if delivered intermittently, as well as providing potential risks to the animal and the investigator. This study describes a novel method of VPA administration delivered through the rodent diet to an epileptic strain of rats: Genetic Absence Epilepsy Rats from Strasbourg (GAERs) and studied the efficacy, tolerability, and VPA plasma levels of this mode of delivery. We studied a range of doses of VPA: 0g/kg, 5g/kg (low dose), 10g/kg (medium dose) and 20g/kg (high dose) (VPA per kg of food). The results showed that 20g/kg significantly suppressed seizures by 32% on average and was well tolerated, with no apparent side effects. This dose corresponded to blood levels between 200-300 umol/L. In

addition, we found a linear relationship between dose of drug consumed and plasma blood levels. The results from this study show that administering VPA in the rodent diet is an effective way of chronically exposing rats to VPA with minimal stress on the animal and that doses below 20g/kg are not sufficient to achieve adequate seizure suppression levels.

89 Roxane Dilcher Cognitive differences in patients with epileptic and non-epileptic seizures using a brief cognitive assessment tool Dilcher R(1), Malpas C.B(1,5) Walterfang M(3,4), O’Brien T.J(1,2), Velakoulis D(2,3), VIVASH L(1) (1)Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne. (2)Department of Neurology, Royal Melbourne Hospital. (3)Neuropsychiatry Unit, Royal Melbourne Hospital. (4)Melbourne Neuropsychiatry Centre, University of Melbourne and North Western Mental Health. (5)Melbourne School of Psychological Sciences, University of Melbourne

Background: Patients with epilepsy can have cognitive impairments in different domains. Contributing factors may be the underlying pathophysiology of epilepsy, the effects of seizures, medication or comorbid psychological diseases. Currently there are few reports in the literature, using adequate neuropsychological screening tools for large epilepsy populations. Methods: Retrospective data from patients admitted to the RMH video-electroencephalography monitoring unit was collected. Attention, visuoconstructional, memory, executive and language functioning were assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Patients were classified with respect to seizure etiology (epileptic seizures (ES), psychogenic non-epileptic seizures (PNES), ES and PNES, and other non-epileptic seizures (NES)), to epilepsy syndrome (focal or generalized epilepsy, temporal lobe, extra-temporal lobe epilepsy or uncertain classification), to seizure frequency, to medication treatment and to psychiatric comorbidities (anxiety and/or depression or no psychiatric condition). Repeated measures ANOVA was performed, with log-transformed NUCOG scores as output variable, age as covariate and the different groups as predictors. Results: Eight hundred and ten patients aged 12-77 years were included in the analysis. Patients with NES performed significantly better than patients with epileptic seizures on all NUCOG subscale scores (p = 0.018), except of attention. Bilateral temporal lobe seizure localization resulted in slightly poorer performance compared to right-sided temporal lobe seizure localization (p = 0.040), mainly in attention. Scores did not differ between patients with focal and those with generalized epilepsies, nor between patients with temporal lobe, extra-temporal lobe and unknown classification. NUCOG scores of patients with anxiety and/or depression were lower than those without comorbidities in language functioning. NUCOG performance also differed slightly between patients who had 1-3 seizures a month compared to 4-11 seizures a year in general scores, and in attention and language specifically (p = 0.024). Performance was poorer when patients were treated with medication, mainly with valproic acid (p = 0.000), phenytoin (p = 0.001) and clonazepam (p = 0.008). Conclusion: The study shows that the NUCOG is an adequate measurement for detecting several cognitive profiles in patients with different seizure etiologies. Differences in seizure etiology, temporal lobe laterality, as well as psychiatric comorbidities, seizure frequency and medication are factors that affect cognitive performance.

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90 Mastura Monif Chronic kidney disease and electroencephalogram (EEG) abnormalities: what factors lead to poor patient prognosis? MASTURA MONIF (1,2,3), Udaya Seneviratne (3) 1.Royal Melbourne Hospital 2.The University of Melbourne 3.Department of Neurosciences, Monash Medical Center

Aim: We report a retrospective analysis of 44 consecutive patients with chronic kidney disease (CKD) referred for an EEG due to altered conscious state. Our aims were to analyse the EEG abnormalities detected in this cohort of patients and to decipher what clinical and biochemical parameters are associated with EEG abnormalities? Background: CKD is a leading cause of morbidity and mortality worldwide. Individuals with CKD are at increased risk of metabolic encephalopathy and seizures. It is unclear if the metabolic derangements (i.e., abnormally high urea and creatinine) are associated with increased seizure risk? Methods: We performed unadjusted logistic regression to test the association of predictors (age at EEG, eGFR, serum urea and EEG category- encephalopathic patterns: type 1; seizure, rhythmic or periodic patterns: type 2) with the outcome. The outcome was defined as ‘favourable’ (discharge to home or rehabilitation) versus ‘unfavourable’ (death, palliation, or discharge to nursing home). Results: The average age of our cohort was 62.06 ±16.3 years (55% male, 45% female). The most common aetiology of CKD was diabetes (56.8%) followed by glomerulonephritis (22.7%). The average creatinine was 500±325.76 umol/L, and average urea of 17.42 ± 8.76 mmol/L. In 65% of individuals the final diagnosis was encephalopathy (n=26), followed by non-convulsive status epilepticus (NCSE) (15%, n=6). Notably, 27% of patients had an ‘unfavourable outcome’. Only age and EEG category were significantly associated with poor outcomes. With increasing age, the odds of unfavourable outcome increased (p=0.027; OR = 1.07, 95% CI 1.01 to 1.15). Type 2 EEG category was associated with increasing odds of an unfavourable outcome (p=0.01; OR 9.5 (1.64-54.99)). Conclusion: Our study reveals that older age and epileptiform/rhythmic/periodic EEG patterns are associated with a poor prognosis irrespective of the degree of renal impairment. Altered conscious state in patients with CKD is due to NCSE in a fair proportion.

91 Shobi Sivathamboo Prolonged cardiorespiratory dysfunction following convulsive seizures SIVATHAMBOO, S(1,2), Perucca, P(1,2), Jones, NC(1), Constantino, TN(3), Chen, Z(1), White, EJ(2), Hollis, C(2), Velakoulis, D(4), Goldin, J(5), Sparks, PB(6), Kwan, P(1,2) and O’Brien, TJ(1,2) (1) Department of Medicine, The University of Melbourne; (2) Department of Neurology, Royal Melbourne Hospital; (3) Monash Centre for Astrophysics, School of Physics and Astronomy, Monash University; (4) Neuropsychiatry Unit, Royal Melbourne Hospital and Melbourne Neuropsychiatry Centre; (5) Department of Respiratory and Sleep Disorders Medicine, Royal Melbourne Hospital; (6) Department of Cardiology, Royal Melbourne Hospital

Aim: To examine cardiorespiratory function during and following convulsive and non-convulsive epileptic seizures. Background: Sudden unexpected death in epilepsy (SUDEP) is a common cause of non-traumatic and non-accidental mortality in epilepsy. SUDEP or near-SUDEP events are often characterized by convulsive seizures in the hours preceding the event. Recent efforts to understand the pathophysiology of SUDEP have demonstrated that there is a rapid, centrally mediated alteration to cardiorespiratory function occurring immediately after a convulsive seizure. Despite its relevance to SUDEP, heart and respiratory function following convulsive seizures has not been adequately described in the literature,

and assessment of continuous cardiac and respiratory function, particularly during and immediately following convulsive seizures, may improve our understanding of the mechanisms leading to SUDEP. Methods: A study to characterize cardiac and respiratory function during seizures was undertaken between February 2012 and March 2017 in patients admitted for video electroencephalogram monitoring (VEEG) with concurrent polysomnography. Both convulsive and non-convulsive seizures were included in this analysis. Heart and respiratory rates, heart rate variability (HRV) and peripheral capillary oxygenation levels were assessed at baseline, before, during and after each seizure. Results: A total of 14 convulsive and 120 non-convulsive seizures were recorded from 50 patients. Significant and persistent tachycardia occurred following all convulsive seizures (P=<0.0001). Significant tachypnea also followed all convulsions (P=<0.0001). Most patients had prolonged tachycardia and tachypnea which persisted for over 30 minutes following convulsive seizure termination. Lastly, we found higher HRV in convulsive seizures with post-ictal generalized electroencephalogram suppression (n=8) compared to those without (n=6; P=<0.05). Conclusion: This study demonstrates clear associations between cardiac and respiratory dysfunction in convulsive seizures that may have substantial implications for the pathophysiology of SUDEP. Sustained cardiorespiratory dysfunction may increase the risk of further convulsive seizures and SUDEP.

92 Lily Vu Prognosis of patients with newly treated epilepsy treated by antiepileptic drugs CHI VU L(1) Chen Z(1) Anderson A(1); Petrovski S(1) Kwan P(1); Berkovic SF(2); Newton MR(2); O’BrienTJ(1) Melbourne Health (1), Austin Health (2)

Aim: To investigate seizure control in patients with newly diagnosed epilepsy treated by antiepileptic drugs (AEDs) in Australia. Background: Approximately one third of patients with epilepsy fail to achieve seizure control when treated with AEDs. It is important to investigate whether this rate applies for Australian patient population. Methods: We conducted an observational study of 469 patients with epilepsy (9 to 90 years old) who were newly treated with AEDs and followed up for at least 1 year (1 to 13 years). All patients were treated by either monotherapy or combined therapy of up to 4 AEDs. Epilepsy was classified as focal, generalised or unclassifiable epileptic syndrome. Seizure freedom is defined to be having no seizure for at least 1 year after institution of treatment. Results: Among the 469 patients, 339 (72%) achieved seizure freedom. The rate of seizure freedom was similar among different epilepsy classifications: 66 (72%) patients with generalised epilepsy, 176 (72%) patients with focal epilepsy and 97 (73%) patients with unclassifiable epilepsy. Moreover, 225 (78%) were seizure free after taking their 1st drug. The rate of seizure freedom decreased in those who had to take multiple AEDs, with 111 (65%) patients who took 2 AEDs, 3 (33%) patients who took 3 AEDs and 0 patients who took 4 AEDs. Conclusion: More than a quarter of Australian newly treated epilepsy patients did not achieve seizure control with AEDs therapy. The likelihood of becoming seizure free diminishes as the number of AEDs required increases. This data is consistent with that from other health care settings.

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93 Shobi Sivathamboo Increased sleep-disordered breathing among epilepsy patients admitted for VEEG monitoring SIVATHAMBOO, S(1,2), Kwan, P(1,2) Perucca, P(1,2), Chen, Z(1), White, EJ(2), Hollis, C(2), Velakoulis, D(3), Jones, NC(1), O’Brien, TJ(1,2) and Goldin, J(4) (1) Department of Medicine, The University of Melbourne; (2) Department of Neurology, The Royal Melbourne Hospital; (3) Neuropsychiatry Unit, The Royal Melbourne Hospital and Melbourne Neuropsychiatry Centre; (4) Department of Respiratory and Sleep Disorders Medicine, The Royal Melbourne Hospital

Aim: To examine the prevalence of sleep disordered breathing in patients admitted for video electroencephalogram monitoring (VEEG) undergoing routine polysomnography. Background: There is emerging evidence that epilepsy patients have an increased prevalence of sleep-disordered breathing (SDB) compared with the general population. This potentially contributes to increased sleepiness, poorer seizure control, and cardiovascular related morbidity and mortality. Chronic sleep-disordered breathing can also result in loss of gray matter and cause deficits to memory and global cognitive function. Despite this, there have been few studies examining sleep-disordered breathing in epilepsy patients. Methods: We retrospectively studied 180 patients admitted for VEEG monitoring who underwent routine polysomnography between February 2012 and March 2017. Results: There was a high prevalence of SDB in patients admitted for VEEG monitoring, with 114 (63.3%) meeting the minimum diagnostic criteria for obstructive sleep apnea (OSA). Of these, 39 (21.6%) had moderate-severe OSA. Conclusion: Routine polysomnography is a useful diagnostic tool in patients admitted for VEEG monitoring. Treatment of OSA may reduce seizure frequency and improve daytime somnolence in patients with epilepsy. Further studies examining the prevalence and severity of OSA and associated hypoxemia, as well as other cardiovascular comorbidities are warranted.

94 Vilija Jokubaitis Identification of genotype-phenotype correlations in relapsing-remitting multiple sclerosis JOKUBAITIS VG (1,2), Kleinova P (3), Izquierdo G (4), Matesanz F (5), Kalincik T (1,2), Kilpatrick TJ (2,6), Lechner-Scott J (7,8), Slee M (9), Manouchehrinia A (10), Patsopoulos N (11),Taylor B (12), Hillert J (10), Horakova D (3), Havrdova E (3), Butzku 1. University of Melbourne, Department of Medicine (RMH), 2. Royal Melbourne Hospital, Department of Neurology 3.Department of Neurology and Center of Clinical Neuroscience Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Czech Republic 4. Hospital Universitario Virgen Macarena, Seville, Spain 5. Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada, Spain 6. Melbourne Neuroscience Institute, University of Melbourne, Melbourne 7. Department of Neurology, John Hunter Hospital, Newcastle 8. School of Medicine and Public Health, University of Newcastle, Newcastle 9. Flinders University and Flinders Medical Centre, Adelaide 10. Karolinska Institutet, Stockholm, Sweden 11. Brigham and Women’s Hospital, Harvard Medical School, MA, USA 12. Menzies Research Institute, University of Tasmania, Hobart 13. Department of Neurology, Box Hill Hospital, Monash University

Background: To-date efforts to identify genetic associations with MS phenotype have been largely unrewarding. One possible explanation for this is that past genotype-phenotype association studies have relied on cross-sectional definitions of disease severity. Despite their limitations, these studies have identified 109 genetic variations putatively associated with disease severity. Objective: To validate putative genetic correlates of disease severity using a robust relapse-onset MS (RMS) disease severity phenotype based on longitudinally acquired outcomes data. Methods: Using data obtained from MSBase, we identified all RMS patients from collaborating centres with minimum disease

duration of 5 years, 5 years minimum prospective follow-up, and minimum 3 expanded disability status scale (EDSS) scores recorded in the absence of a relapse. Area under the EDSS-time curve was calculated for each individual and adjusted for follow-up. Using pre-defined EDSS-time cut-offs we created an algorithm that identified patients at the extremes of RMS outcome. We validated algorithm calls by assessment of an alternate severity scale, the multiple sclerosis severity scale (MSSS). DNA from 1236 consented individuals at the extremes of outcome underwent genotyping using the Ilumina MegaEx platform. The MegaEx platform contains greater than 2 million common single nucleotide polymorphisms (SNPs) including coding variants. Our MegaEx chip further contained custom content to ensure that past suggestive severity associations could be tested. Here we specifically assessed association of previously reported putative severity SNPs in our extremes of phenotype cohort. Results: The mild RMS cohort as selected by our algorithm (25.9% of the total population) had a median symptom duration of 11.6 years (IQR: 8.2, 16.5), 14 EDSS scores assessed (IQR: 8,25), and a median observation follow-up MSSS of 1.50 (IQR: 0.88, 2.25). The severe RMS cohort constituted 18.4% of the total population. Severe RMS cohort characteristics included: median symptom duration of 19.0 years (IQR: 13.5, 25.9), 15 EDSS scores assessed (IQR: 9, 24), and a median observation follow-up MSSS of 7.21 (6.15, 8.27). Here we report that we have successfully validated one of the previously published 109 putative severity associations. Conclusion: We have successfully defined a robust RMS phenotype using longitudinal, prospectively acquired clinical outcomes data validated against the MSSS in which we assessed genotype-phenotype associations. We have validated one of the previously published disease severity variants making this the first replicated genetic variant associated with MS disease severity.

95 Daniel Merlo The feasibility of computerized cognitive monitoring in the clinic and community in people with MS: initial results of the MSReactor study MERLO D (1,2), Van der Walt A(1, 3), Haartsen J(2), Butzkueven H(1,2,3), Darby D(2) (1)Melbourne Health, (2)Eastern Health, (3)University of Melbourne

Aim: Establish the feasibility of a computerized cognitive monitoring tool in the MS clinic and home. Background: Cognitive impairment (CI) affects 40-65% of MS patients. Memory, attention, and processing speed are commonly involved. Mild CI is difficult to detect, even for experienced clinicians. Compared to neuropsychological tests, computerized cognitive batteries (CCB) can be self-administered, have standardized presentations and accurate, automated scoring. Methods: We established a CCB using three cognitive tasks from the uBrainTM system, on a secure, purpose-built website, www.msreactor.com. We implemented msreactor testing in two tertiary MS clinics, screening for processing speed, attention and working memory. Participants confirm the appearance of a ball (Simple Reaction Test, (SRT)), react correctly to the colour of the ball (Choice Reaction Test (CRT)) and detect if consecutive cards are identical (One Back Test (OBT)). Self-administered testing takes under 15 minutes. Scores are immediately uploaded, processed, and graphically displayed. Participants are offered clinic (6 monthly) or home-based testing (1-3 monthly). Clinic-based testing includes electronic versions of the Penn State Worry Questionnaire (PSWQ-15), Patient Health Questionnaire (PHQ-9), and an Acceptability Questionnaire (adapted 10 point Likert scale) and the MusiQol Quality of Life score.

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Results: We recruited 261 patients (n=186 female) with predominantly RRMS (n=257) over 6-months who agreed to clinic and home testing. The median EDSS was 2.64 (Std deviation=1.82) and disease duration 12.8 years (8.7). SRT, CRT and OBT correlated with quality of life (MusiQol) scores (r = -0.24, r = -0.25 and -0.26 respectively). SRT, CRT and OBT correlated with depression (PHQ) scores (r = 0.20, r = 0.23 and r = 0.26 respectively). No correlations were observed (p>0.05) between anxiety (PSWQ) and MSReactor tests. Acceptability was high with 53.3% “not anxious at all” during the test, and 92.7% finding test duration “about right”. Over 50% found tasks “very enjoyable” and 70% of participants would be “very happy” or “happy” to repeat tasks. Interest in the tasks were rated “high” or “about right” in 90% of participants Conclusion: CCBs can fill the cognitive monitoring gap, allowing physicians to detect neurocognitive changes in real-time, potentially informing treatment decisions. The rapid recruitment rate and acceptability of the MSReactor platform demonstrates its feasibility in both clinic and community environments.

96 Emma Foster Assessing the risk of cervical dysplasia in immunosuppressed women using a Victoria-wide data linkage approach FOSTER E(1), Malloy M(2), Jokubaitis V(3), Wrede D(4), Brotherton (2,5), van der Walt A(1,3,5) 1.Department of Neurology, The Royal Melbourne Hospital; 2.Victorian Cervical Cytology Registry, VCS Registries, Melbourne; 3.Melbourne Brain Centre at RMH, Department of Medicine, University of Melbourne; 4.Cervical Dysplasia Service, Royal Women's Hospital; 5. Authors contributed equally.

Background / Aim: Immunosuppressed (ISP) patients have an increased risk of persistent Human papillomavirus (HPV) infection, cervical dysplasia and HPV-related cancers. This risk is important to determine given the planned implementation of the new HPV-based cervical screening program in 2017 and the availability of an effective HPV vaccine. We evaluated and compared the prevalence of cervical dysplasia in the general Victorian population with immunosuppressed cohorts, including those with multiple sclerosis (MS), inflammatory bowel disease (IBD), rheumatological disorders (seropositive rheumatoid arthritis, systemic lupus erythematous, systemic sclerosis), psoriasis, human immunodeficiency virus (HIV) and primary immunodeficiency disorders (PID). Methods: We identified all women aged 18 to 70 with a primary diagnosis coded at hospital separation as an ISP condition, HIV or PID through the Victorian Admitted Episode Database (VAED). The cervical screening history of this cohort was identified using probabilistic data linkage to women who had at least one cervical screening episode between 2009 – 2013 recorded on the Victorian Cervical Cytology Registry (VCCR). Cervical dysplasia outcomes identified were: cytological low- and high-grade abnormalities (LGA, HGA) and histologically confirmed abnormalities (HisA). Results were stratified by age, analysed per disease group, and intergroup comparisons performed. Results: A cohort of 11,447 immunocompromised women was identified, including: IBD (8306), MS (2382), rheumatological disease (772), psoriasis (290), HIV (24) and PID (271). In the combined ISP group, 7.91% had LGA, 2.45% HGA, and 2.04% HisA, compared with 6.84%, 2.46% and 2.31% respectively for all other women. Intergroup comparisons demonstrated similar rates of cytological LGA and HGA in women with MS, IBD, psoriasis and all other women, whereas an increased risk of cytological and histological abnormalities was shown in rheumatological diseases up to the age of 40 years and again after age 60 years. Conclusion: The data demonstrates similar rates of cervical dysplasia for women with MS, IBD and psoriasis to the general

Victorian population, whereas women with rheumatological disorders are at a greater risk for both LGA and HGA. Higher rates of LGA, which are a consequence of active HPV infection, may relate to persistent HPV infection among ISP women. While the results are reassuring, the limitations of de-identified data linkage and inclusion of only patients with a coded hospital admission, may have led to under-matching and under-identification of ISP women. Physicians should remain vigilant and recommend screening, and vaccination, to all ISP patients.

97 Henry Zhao Paramedic validation of an Australian large vessel occlusion triage algorithm for stroke: The ACT-FAST algorithm ZHAO H(1), Pesavento L(1), Coote S(1), Churilov L(2), Smith K(3), Bernard S(3), Yassi N(1), Davis SM(1), Campbell BCV(1) (1)Melbourne Health, Dept of Neurology (2)The Florey Institute of Neuroscience and Mental Health (3)Ambulance Victoria

Aim and Background: Endovascular clot retrieval is now standard treatment for stroke caused by a large vessel occlusion (LVO), but few full-time endovascular centres exist in Australia due to high resource requirements. Most patients with LVO are therefore brought first to non-endovascular centre, and experience significant treatment delay and poorer outcomes due to need for inter-hospital transfer. Examination based tools such as the Spanish Rapid Arterial Occlusion Evaluation Scale (RACE) have been developed to allow paramedics to triage patients with high likelihood of LVO to endovascular centres, but paramedic studies to date show that their usefulness is limited by poor specificity. We aimed to develop an identification algorithm that would provide high accuracy when used by Australian paramedics. Methods: The ACT-FAST algorithm for LVO identification was developed from retrospective review of discriminating clinical features and requires significant unilateral upper limb weakness (arm falls to stretcher <10secs), plus either severe language deficit, or presence of gaze deviation/severe extinction (assessed by response to shoulder tap). Initial retrospective validation was performed in consecutive code stroke patients over a 15-month period at Royal Melbourne and Box Hill Hospitals in Melbourne, followed by prospective paramedic assessment at Royal Melbourne Hospital. Results: Of 565 consecutive patients in the retrospective cohort (82 with LVO), the overall accuracy of ACT-FAST was 87.6%. Four LVO patients with clear endovascular eligibility (4.8% of all LVO) would have been erroneously missed, and 10 smaller infarcts would have been misclassified as LVO (5.7% of all non-LVO infarcts). Prospective use of ACT-FAST by Ambulance Victoria paramedics without additional training in the first 70 patients (13 with LVO) demonstrated 87.9% accuracy, 83.3% sensitivity and 88.9% specificity. No LVOs with clear endovascular eligibility were missed and there were 6 false-positives, of which 5 were intracranial haemorrhages and one was an endovascular-ineligible infarct. All discrimination parameters trended superior to RACE. Conclusion: The new 3-item ACT-FAST algorithm has excellent accuracy for identifying endovascular-eligible LVO and misclassified only a small proportion of non-LVO strokes (mostly intracranial haemorrhage). Implementation of the algorithm in state ambulance services would have significant potential to improve patient outcomes and equality of care through faster treatment access for an otherwise extremely disabling condition.

98 Nawaf Yassi Cortical cerebral microinfarcts on 3T MRI in Alzheimer’s Disease and mild cognitive impairment

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YASSI N (1,2), Hilal S (3), Lim YY (2), Salinas S (1), Kuijf H (4), Xia Y (5), Chen C (3), Salvado O (5), Rowe CC (6,7), Desmond P (1), Masters CL (1,2,7) (1) Royal Melbourne Hospital, University of Melbourne (2) Florey Institute of Neuroscience and Mental Health (3) National University of Singapore (4) University Medical Centre Utrecht (5) Commonwealth Scientific and Industrial Research Organisation (6) Austin Health (7) AIBL Research Group

Aim: We aimed to investigate the prevalence of cortical cerebral microinfarcts (CMI) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls (HC) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL), and to examine their association with vascular risk factors. Background: The prevalence of CMI on neuropathological studies of AD is reported at approximately 40%, and they are associated with cognitive impairment. Recent studies have validated the detection of CMI in-vivo using both 7T and 3T MRI. Methods: Participants were chosen at random from the AIBL database. Baseline imaging and clinical data were assessed in this cross-sectional analysis. CMI were visually graded using 3T MRI by simultaneously viewing 1x1x1mm isotropic T1-weighted and Fluid Attenuated Inversion Recovery (FLAIR) images. They were defined on T1-weighted images as discrete punched out lesions <5mm in diameter and perpendicular to the cortical ribbon. They were either isointense or hyperintense on FLAIR. Results: Baseline images from 97 participants were evaluated (51 female, mean age 73.6 years). The underlying diagnosis was AD in 33%, MCI in 28.9% and HC in 38.1%. The distribution of age and vascular risk factors was similar across the diagnostic categories. Overall, the prevalence of CMI was 8.2%, with 62% of cases being multiple. Only 2.7% of HC had CMI, compared to 14.3% of MCI patients and 9.4% of AD patients, although these trends were non-significant. The presence of CMI was associated with a history of stroke (p=0.014, Fisher’s exact), and cigarette smoking (p=0.029, Chi-square). Conclusions: CMI are detectable in large AD cohorts using standard 3T MRI acquisitions. Our preliminary analysis has demonstrated trends regarding the prevalence of CMI in AD and MCI versus healthy controls as well as associations with vascular risk factors. Important future analyses will explore interactions between CMI and other cerebrovascular disease markers (e.g. lacunes, white-matter hyperintensities), as well as amyloid burden, and longitudinal change in cognition.

99 Mujun Sun Treatment with an interleukin-1 receptor antagonist mitigates neuroinflammation and brain damage after polytrauma SUN M (1), Brady R (1,2), Wright D (3,4), Johnstone M (2), O’Brien T (1), Semple B (1), McDonald S (2), Shultz S (1) 1. Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne; 2. Department of Physiology, Anatomy and Microbiology, La Trobe University; 3. Department of Anatomy and Neuroscience, The University of Melbourne; 4. The Florey Institute of Neuroscience and Mental Health

Aim: To examine the effect of treatment with an interleukin-1 receptor antagonist (IL-1ra) in mice given a TBI and a concomitant tibial fracture (i.e., polytrauma). Background: Traumatic brain injury (TBI) and long bone fracture are common in polytrauma. This injury combination in mice results in elevated levels of the pro-inflammatory cytokine IL-1β and exacerbated neuropathology when compared to isolated-TBI. Method: Adult male C57BL/6 mice were given sham-injuries or polytrauma and treated with saline-vehicle or IL-1ra (100 mg/kg). Treatments were subcutaneously injected at 1, 6, and 24 hours, and then daily for one week post-injury. 7-8

mice/group were euthanized at 48 hours post-injury. 12-16 mice/group underwent behavioral testing at 12 weeks post-injury and MRI at 14 weeks post-injury before being euthanized at 16 weeks post-injury. Results: At 48 hours post-injury, markers for activated microglia and astrocytes, as well as edema, were decreased in polytrauma mice treated with IL-1ra compared to polytrauma mice treated with vehicle. At 14 weeks post-injury, MRI analysis demonstrated that IL-1ra treatment after polytrauma reduced volumetric loss in the injured cortex and mitigated track-weighted MRI markers for axonal injury. Conclusion: IL-1ra treatment is neuroprotective in our polytrauma model, and as IL-1ra (Anakinra) is approved for human use, it may represent a promising therapy in polytrauma cases involving TBI and fracture.

100 Stefanie Bird Activation of the PERK pathway of the unfolded protein response following TBI in mice BIRD S(1), Liu S(1), O'BRIEN T(1), Shultz S(1) Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne

Aim: To investigate whether the PERK pathway of the unfolded protein response is activated in a mouse model of moderate-severe traumatic brain injury. Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Survivors often suffer debilitating and long-lasting neurological consequences. Growing evidence suggests that several different proteins misfold as a result of TBI, and this may contribute to the progressive neurodegeneration that can occur. The unfolded protein response is a biochemical mechanism triggered by the aggregation of misfolded proteins. The unfolded protein response consists of three major components/arms; protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1α (IREα), and activating transcription factor 6 (ATF6). Of these, activation (i.e., phosphorylation) of the PERK pathway can result in the repression of protein synthesis, as well as signalling apoptosis, both of which can be neurotoxic. Prolonged activation of the unfolded protein response is implicated in neurodegenerative conditions with similar proteopathies to brain injury. However, whether activation of the PERK pathway of the unfolded protein response occurs following TBI is not clear. Methods: Mice were randomly assigned to receive either a moderate-severe fluid percussion injury or sham injury. Mice were further randomly assigned for brain tissue collection at 2h, 24h, or 1 week post-injury. Western blots were conducted to assess PERK activation and other downstream mediators involved in the PERK arm of the unfolded protein response. Results: There was a significant increase in phosphorylated-PERK at 2h post-TBI, followed by significant increases in other downstream mediators (e.g., phosphorylated eukaryotic translation initiation factor α; eIF2α) that remained elevated at 1wk post-injury. Conclusion: These findings suggest that persistent activation of the PERK arm of the unfolded protein response occurs following moderate-severe traumatic brain injury.

101 Mary Etty-Leal Osteoporosis therapy initiation post minimal trauma fracture at the Royal Melbourne Hospital ETTY-LEAL M(1), Nguyen V (1), Chan V(2), Kusmanoff L(2), Pearce D(2), Politis A(2), Reynolds L(2), Sepe D(2). Pharmacy Department, Royal Melbourne Hospital, Melbourne VIC, Australia(1), School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia(2)

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Aim: To determine the proportion of patients admitted to the Royal Melbourne Hospital (RMH) aged 50 years and older with a confirmed neck of femur or vertebral minimal trauma fracture, who are commenced on specific anti-osteoporosis therapy by discharge, and to describe the agents prescribed. Background: Osteoporosis is a significant global public health issue that contributes to an increase in morbidity and mortality and has considerable health care costs. Although there are evidence based treatments readily available, treatment rates of osteoporosis post minimal trauma fracture continue to be suboptimal. Method: A retrospective audit of patients admitted to RMH with a minimal trauma fracture of the hip or vertebra between the 1st of January 2016 and 30th of June 2016. Results: A total of 407 patients were audited and 64 patients were included in the study; 37 were admitted for a fractured hip and 27 were admitted for a vertebral fracture. Of these 64 patients, a total of 14 (21.9%) patients were commenced on specific anti-osteoporosis therapy. Denosumab was the most commonly initiated treatment, with it being commenced in 10 of the 14 patients (71.4%). Risedronate was commenced in 3 of the 14 patients (21.4%) and 1 of the 14 patients (7.1%) was commenced on alendronate. Conclusion: The majority of patients presenting to the RMH with a minimal trauma fracture were not commenced on specific anti-osteoporosis therapy in hospital. This is a missed opportunity for intervention that places patients at a higher risk of subsequent fracture; therefore effective strategies should be implemented to address this treatment gap in the future.

102 Adrian Achuthan Role of GM-CSF-induced CCL17 in inflammation ACHUTHAN A, Lee MC, Saleh R, Fleetwood A, Cook A and Hamilton J Dept of Medicine, Royal Melbourne Hospital, The University of Melbourne

GM-CSF plays a key role in rheumatoid arthritis, as evidenced by promising recent clinical trial data targetting GM-CSF or its receptor. However, blockade of its function could lead to undesirable side-effects creating a need to delineate downstream pathways and mediators. We report here that GM-CSF drives CCL17 production via a new interferon regulatory factor 4 (IRF4)-dependent pathway in human monocytes and murine macrophages, as well as in vivo. Moreover, we provide evidence for the first time that GM-CSF controls IRF4 expression via regulating the expression and activity of JMJD3, which demethylases trimethylated-H3K27. Importantly, in arthritis and pain models IRF4-regulated CCL17 formation can mediate the proinflammatory and algesic actions of GM-CSF. Evidence will also presented for new CCL17 functions in inflammatory arthritis and pain. The delineated pathway potentially provides new therapeutic options for the treatment of inflammatory diseases and their associated pain.

103 Gopika Krishnamurthy Inappropriate Medication Prescribing in Oldest Old Patients Admitted to Hospital KRISHNAMURTHY G (1), Manias E (1), Gorelik A (1) The Royal Melbourne Hospital

Aim:To determine the prevalence and patterns of inappropriate prescribing in the oldest old during hospitalisation. Background: Inappropriate prescribing is a common and serious issue. It includes two kinds of medications: (i) potentially inappropriate medications that are likely to be harmful and need to be stopped and (ii) potential prescribing omissions which are medications that could be beneficial but are not prescribed. Older people, especially the oldest old (defined as individuals aged ≥85 years) are at an increased risk of adverse events from medications due to changes in

body composition associated with ageing. The Screening Tool of Older Persons’ Prescriptions and the Screening Tool to Alert doctors to the Right Treatment are a set of criteria to identify inappropriate prescribing. Methods: A retrospective clinical audit was conducted at the Royal Melbourne Hospital on a random sample of patients satisfying the following criteria: patients admitted to the hospital aged ≥85 years, who presented to the Emergency Department from January 2016 to December 2016, with at least one medication on presentation. Patients admitted to Intensive Care Unit were excluded. The tools were applied to each patient for medications at four different time points: (i) on presentation to the Emergency Department, (ii) on admission to acute wards (iii) on admission to sub-acute wards and (iv) on hospital discharge. Results: The median age of the 246 patients included in the study was 88.5 years with 152 (61.8%) patients being female. The total number of potentially inappropriate medications at each time point was 224, 143, 65 and 131. The total number of potential prescribing omissions at each time point was 164, 161, 68 and 130. The prevalence of patients having at least 1 potentially inappropriate medication at each time point was 57.7%, 44.3%, 49% and 43.1%. The prevalence of patients having at least 1 potential prescribing omission at each time point was 45.9%, 45.9%, 43.5% and 39%. Conclusion: The prevalence of inappropriate prescribing is high in the oldest old and is similar to rates previously reported in the literature for the younger old (≥65 years). There is an overall trend towards a decrease in inappropriate prescribing with hospitalisation.

104 Edward Carson Disparity of age-specific Indigenous mortality in Australia by residential remoteness CARSON E(1), Sharmin S(2), Robertson Y(2), Maier AB(1,3), Meij HJ(2) 1. University of Melbourne, Royal Melbourne Hospital, Melbourne, Vic, Australia. 2. Melbourne Academic Centre of Health, Melbourne, Vic, Australia. 3. Department of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, The Netherlands.

Aim: To identify if Indigenous mortality varies between remoteness areas for each age. Background: Australia has experienced no improvement in Indigenous mortality over the past decade. There have been observed differences in Indigenous mortality between urban, rural and very remote areas but it remains uncertain how different ages are affected. Methods: This cross-sectional study assesses Indigenous mortality in New South Wales, South Australia, Queensland, Western Australia and the Northern Territory between the years 2008 to 2012. Mortality and population data was provided by the Australian Institute of Health and Welfare, and Australian Bureau of Statistics respectively. Remoteness was based on the Accessibility/Remoteness Index of Australia. Age groups were based on 5-year increments from 0 years to 85 years and older. Mean differences in Indigenous mortality between states, stratified for age groups were measured using one-way analysis of variance (ANOVA). Results: This study included an average annual Indigenous population of 580,741 people and 2322 (0.4%) annual deaths. Statistically significant higher mortality was observed for ages 0-4 years in the Northern Territory, Western Australia and Queensland compared to New South Wales. For ages 10-79 years, mortality was significantly higher in the Northern Territory followed by Western Australia. However, in the ages 85 years and older, mortality in Northern Territory, Western Australia and Queensland showed no significant difference to New South Wales, while South Australia experienced significantly lower mortality.

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Conclusion: Because of greater access to health services, it is expected to be beneficial to live in an urban area compared to a rural or very remote area. For Indigenous children and young adults, where mortality is commonly caused by trauma or mental illness, there is a benefit to living in an urban area. Likewise, adults aged 35-79 years who are more affected by chronic diseases, living within close proximity to health services appears to also be advantageous. This is in contrast to Indigenous aged 85 years and older who gain no clear benefit from urbanisation. Lower mortality in very remote areas may be attributed to selection of healthy individuals who are less reliant on the health care system compared to their urban counterparts.

105 Richard Toh An audit of ketamine use for acute postoperative pain in adult surgical patients at the Royal Melbourne Hospital in 2016. Toh R, Leslie K. Royal Melbourne Hospital

Aims: To understand and identify prescribing patterns of ketamine for acute postoperative pain in adult surgical patients at the Royal Melbourne Hospital in 2016, and report the occurrence of adverse events related to the use of ketamine. Introduction: Intravenous ketamine is widely used in low doses for acute postoperative pain in surgical patients, and is under investigation as a preventive agent for persistent postoperative pain. However exact prescribing patterns at the Royal Melbourne Hospital have not been determined. Furthermore, our incidence of ketamine-induced side effects is unknown. Therefore, an audit of patients who were admitted to the Acute Pain Service (APS) for acute postoperative pain in 2016 was conducted, to determine their demographics, surgery type, and how much postoperative ketamine did they receive. Methods: A retrospective audit of 3066 scanned patient records was conducted over a 2-month period in 2017. These patients were seen by APS and were recorded in the APS database, and they were subsequently identified through a search of the same database. Demographic patient characteristics, intraoperative data, PACU data, and postoperative treatment with ketamine were identified and recorded in a spreadsheet for data analysis. Categorical data was summarised with the number and percent, whilst continuous data was summarised with median (range, IQR) as it mostly had a skewed distribution. Wilcoxon rank-sum tests (continuous data), and chi-squared or Fisher's exact tests (categorical data) were used to analyse the data. P <0.05 will be considered statistically significant. Results: Of the audited patients, 564 unique admissions fit the study inclusion criteria of having had a procedure with a surgical incision and an infusion of ketamine as part of their postoperative analgesia regimen. Data collection and statistical analyses are ongoing. Conclusion: Findings from this study will not only be used for improving prescribing practices at the Royal Melbourne Hospital, but will also provide information that will support recruitment to the ROCKet trial. This multicentre, double-blind, placebo controlled, randomised control trial (commencing in 2017) will randomise patients to ketamine or placebo to prevent the development of chronic post-surgical pain.

106 Amelia Steel The Role of Focused Echocardiography in Beachchair Surgery STEEL A (1), Soeding P (1,2), Hoy G (3), Wong J (2) The University of Melbourne, The Royal Melbourne Hospital, The Avenue Hospital

Background: The beachchair position (BCP), commonly used in shoulder surgery, is associated with hypotension and risk of cerebral ischaemia. This upright posture significantly decreases intrathoracic blood volume, preload and cardiac output. Patients with chronic hypertension may be at increased risk due to the presence of left-ventricular hypertrophy (LVH), alteration of chamber size and geometry. Aim: This study investigated the role of transthoracic echocardiography (TTE) in identifying cardiac features that may predispose patients to beachchair hypotension. Methods: Prior to surgery a limited echocardiographic examination was performed (5–1 MHz phased array transducer (P21x) M-turbo, Sonosite, Sydney, Australia), involving parasternal long-axis (PLAX), short-axis (SAX) and apical 5-chamber (5C) views. Surgery was performed using combined interscalene and general anaesthesia without muscle paralysis. Echocardiographic examination was repeated after beachchair placement. During anaesthesia mean arterial pressure (MAP) and cerebral oxygen saturation (ScO2) were continuously monitored. Results: Of 26 patients, preoperative TTE showed 5 had significant valvular regurgitation and one with dilated LV hypokinesis was withdrawn. Cardiac LV mass index (LVMI) was increased in both hypertensive patients and endurance athletes, with chamber size (LVIDD) and LV outflow diameter (LVOT) smaller in the hypertensive group. In control patients BCP resulted in MAP and ScO2 decreasing by 9 (16) mmHg and 5(5) % respectively, and associated with a decrease in chamber size LVIDD (20 (13) %) and cardiac output CO (34(12) %). Similar changes occurred in patients with hypertension and in these patients no flow convergence or LVOT obstruction was evident on BCP placement. Athletes compensated for BCP by maintaining MAP with greater increases in LV contractile force, heart rate and systemic vascular resistance (SVR). Conclusion: In hypertensive patients, preoperative TTE identified morphological features present known to correlate with LV outflow obstruction. Further with BCP, intraoperative TTE enabled direct correlation of cardiac function with haemodynamic and cerebral oxygen saturation measurement.

107 Chun-Yiu Tseng The use of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange for pre-oxygenation in neurosurgical patients: a randomised controlled trial Tseng C Background: Pre-oxygenation is a technique that increases body oxygen reserve to delay the onset of desaturation associated with endotracheal intubation. Optiflow Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) is a device that delivers humidified and heated oxygen up to 70L/min through nasal prongs. Its potential benefits for pre-oxygenation and intubation includes providing 1) high FiO2, 2) positive end expiratory pressure, and 3) apnoeic oxygenation. Aim: This study aims to investigate the role of THRIVE for pre-oxygenation and intubation. We hypothesise that THRIVE can significantly increase PaO2 after pre-oxygenation when compared to standard facemask. Method: This was a single centre, randomised controlled trial conducted at the Royal Melbourne Hospital. The study recruited patients who underwent neurosurgical operations requiring asleep oro-tracheal intubation and indwelling arterial catheter. The recruited patients were randomly assigned to Facemask group or THRIVE group. Both groups received 5-minutes of pre-oxygenation with the allocated device and induction commenced after pre-oxygenation. After induction, subjects in the Facemask group received bag-mask ventilation whereas subjects in the THRIVE group received apnoeic

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oxygenation. Intubation commenced when nerve stimulator equalled to zero. Arterial blood gas samples were collected at: 1) baseline, 2) after pre-oxygenation, 3) pre-intubation, and 4) post-intubation. The primary outcome was PaO2 after 5-min of pre-oxygenation. Secondary outcomes included PaO2 and PaCO2 over the timepoints as stated above, satisfaction scores and adverse events. Results: 34 patients were recruited for the study (n=17 in each group). One patient was excluded from analysis because of intolerance to THRIVE device. The median PaO2 after 5-minutes of pre-oxygenation was significantly higher in the THRIVE group than the control group [471 (404-521) vs 359 (334-450) mmHg, p=0.03]. However, PaO2 at pre-intubation was significantly lower in the THRIVE group than the control group [359 (165-466) vs 468 (376-505) mmHg, p=0.03]. PaCO2 was significantly higher in the THRIVE group than the control group at pre-intubation [52 (49-54) vs 42 (39-46) mmHg, p<0.01] and post-intubation [53 (50-57) vs 45 (41-47), p<0.01). There was no statistical significant difference in satisfaction scores and complications. Conclusion: OptiflowTM THRIVE appears to be a better method for pre-oxygenation as it provides a significantly higher PaO2 after pre-oxygenation than standard facemask. However, its use after induction is questionable as PaO2 decreases and PaCO2 increases during apnoeic oxygenation. Lack of feedback of upper airway patency could be one of the reasons. Routine use of airway adjunct during apnoeic oxygenation could potentially be beneficial.

108 Kelsey Turner & Samuel Thorburn Community opioids following acute surgical care at The Royal Melbourne Hospital TURNER K (1), THORBURN S (1) The University of Melbourne (1)

Aim: This study will aim to determine if there is a community reservoir of unused opioid medication following surgical care at The Royal Melbourne Hospital. Background: Opioid-based analgesic preparations have a fundamental role in the management of surgical pain. There is rising concern that over-prescription of opioids in surgical patients at hospital discharge has led to a community reservoir of unused medication. These medications are often stored in non-secure locations representing a source of pharmaceutical diversion and harm. To improve community safety it is important to identify how we as healthcare professionals are contributing to excess opioids in the community. Methods: Over an 8-week period, we approached every patient who underwent surgery at The Royal Melbourne Hospital and stayed at least 1 night post-operatively. To be eligible for study inclusion, patients had to be adult (>18y), English speaking, available for telephone follow-up at 2-weeks post-discharge, cognitively intact and able to provide informed consent. Demographic data was collected from medical record review. Electronic pharmacy records were utilised to determine if opioids had been dispensed on discharge. Participants who received an opioid at discharge were then administered a telephone based questionnaire to determine subjective pain experience, opioid medication usage, storage, and disposal. Data was entered into a de-identified electronic database and checked for accuracy in transcription. Descriptive statistics and exploratory analysis of predictive factors were performed using Chi squared testing, rank sum statistics and logistic regression as appropriate. Results: 1086 surgical patients were screened for eligibility. Of the 797 who fulfilled the inclusion criteria, 81.8% consented to telephone follow-up. At 2-weeks post-discharge we successfully contacted 307 (78.9%) participants, with 82 (20.1%) lost to follow-up. 68.2% of respondents had left-over opioids, with 50.5% reporting using less than or equal to half of

their dispensed opioids. Of the patients with left-over medication, 94.5% were storing it at home, with 86% stored in a non-secure location. Only 13.1% of patients received instructions on how to dispose of medication. Conclusion: Our findings suggest that the majority of patients who receive surgical care at The Royal Melbourne Hospital are being dispensed ‘too many’ opioids at discharge relative to analgesic requirements. Worryingly, an overwhelming proportion of patients are not receiving medication safety instructions. We hope to develop an intervention to target excessive opioid prescribing and to better educate patients on the safe storage, and disposal of opioid medication.

109 Joel Loth Frailty and Health Assets in Elderly Emergency Surgical Patients LOTH J(1,2), Darvall J(1,2), Greentree K(1,2), Bose T(1,2) Royal Melbourne Hospital, University of Melbourne

Aim: To assess predictive accuracy of pre-existing frailty tools in an emergency surgery cohort and to provide a foundation on which future observational and interventional trials may build. Background: Frailty is a multifactorial state, increasing mortality, postoperative complications, LOS and rates of institutionalisation in elderly surgical patients. Accurate, timely determination of frailty is essential for improving postoperative outcomes in elderly surgical patients. Limited work has been done in assessing frailty in emergency surgical compared with elective surgical cohorts. Additionally, health assets (protective patient factors) have been identified which may serve to reduce the effects of frailty. This study aims to assess the impact of frailty and health assets on postoperative outcomes in an emergency surgery cohort, and the accuracy of individual pre-validated frailty scoring systems in predicting outcomes within this population. Methods: We prospectively measured frailty and health assets in a convenience sample of 90 patients (aged 65 years or older) presenting to The Royal Melbourne Hospital (RMH) for emergency surgery from February to June 2017. Frailty was assessed using three validated frailty scales and a Health Assets Index was utilised. Other risk assessment scores (POSSUM and Charlson Comorbidity Index) were used alongside several validated wellbeing and functional independence scores. Main outcomes assessed were 30 day mortality, postoperative complications, length of stay and discharge destination. Results: Poor correlation was seen between the Clinical Frailty Scale (one of our three validated frailty scales) and our primary outcomes. There was significant correlation between frailty, decreased self-reported health and functional dependence. Evaluation of the correlation of our other frailty tools with outcomes is ongoing. Conclusion: The initial lack of correlation between a simple frailty scale, validated in other surgical cohorts, and outcomes following emergency surgery suggests it may be necessary to develop new measurements of frailty in these patients. A loss of subjective wellbeing and functional independence in frailer individuals are significant factors to take into account in patient assessment and future studies. Further trials with higher recruitment and outcome numbers are required to draw more powerful conclusions in regards to elderly emergency surgical patients.

110 Alexandra La Hood Associations between Type 1 diabetes mellitus, musculoskeletal health and body composition in young women

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LA HOOD A(1), Nankervis A(2), Price S(2), Subasinghe A(3), Garland SM(4), Callegari ET(1), Gorelik A(5), Clifford V(6), Wark JD(7) 1: University of Melbourne, Parkville, Australia. 2: Royal Melbourne Hospital, Department of Endocrinology, Parkville, Australia. 3: Murdoch Children’s Research Institute, Infection and Immunity Theme, Parkville, Australia. 4: Royal Women’s Hospital, Department of Microbiology and Infectious Diseases, Parkville, Australia. 5: Melbourne Epicentre, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia. 6: Department of Microbiology and General Medicine, Royal Children's Hospital, Parkville, Australia. 7: Royal Melbourne Hospital, Department of Bone and Mineral Medicine, University of Melbourne, Parkville, Australia.

Aim: To explore whether musculoskeletal and body composition parameters differ between those with diabetes and healthy controls of the same age. Background: There is evidence that Type 1 diabetes mellitus (T1DM) exerts a negative influence on musculoskeletal health in women. However, there is a paucity of evidence for the impact of T1DM on body composition, bone and muscle health in younger women. Methods: T1DM participants aged 16-25 years were recruited mainly from social media and the Royal Melbourne Hospital Young Adults with Diabetes clinic and controls were sourced from the Young Female Health Initiative (YFHI) and Safe-D studies. Anthropometric measures, serum calcium, bone turnover markers, renal, liver and thyroid function, lipids and HbA1c were assessed. Bone mineral density (BMD) and bone mineral content (BMC) were measured using dual energy X-ray absorptiometry at the whole body, lumbar spine, total hip and femoral neck. Body composition measures were taken. Peripheral quantitative computed tomography was performed at the tibia. Leonardo mechanography was used to measure muscle power and force, and balance. Statistical analysis was performed using SPSS version 24. Results: Data were available for 19 participants with T1DM and 688 participants from YFHI and Safe-D (median age 22 years old [Quartile 1 – Quartile 3; 20-24] in the comparator group and 23 years old [21-24] in group with T1DM). Abdominal visceral fat was 42% greater in the group with T1DM (median 2.28 kg [1.61-3.67] vs 1.61 kg [1.21-2.31] in the comparator group, p=0.004). Beta-Crosslaps was significantly lower in the T1DM group (median 0.39 ng/mL [0.31-0.53] vs 0.51 ng/mL [0.37-0.69] in the comparator group, p=0.023). Total serum cholesterol level was significantly higher in participants with T1DM (5 mmol/L [4.4-5.5] vs 4.6 mmol/L [4-5.2] in the comparator group, p=0.035) Other measures, including BMD at all measured sites, BMC less head, trabecular and cortical density, procollagen type 1 N propeptide, vitamin D status and mechanography variables, did not differ between groups. Body composition measures including total fat mass (p=0.014), body fat percentage (p<0.001) were positively correlated with insulin and HbA1c. Conclusion: These preliminary findings suggest associations between musculoskeletal health, body composition and T1DM in young women. These associations may have important implications for the future health of young women with T1DM. Future investigation into these parameters is required to consider population-specific early prevention and treatment strategies.

111 Yeung-Ae Park Associations between serum sodium concentration and indices of bone health in individuals who use antiepileptic drugs PARK YA(1), Subasinghe A(2,3), Chiang C(4), Gorelik A(5), Garland SM(2,3,6), Clifford V(7), Wark JD(1,8) 1 University of Melbourne Department of Medicine, Royal Melbourne Hospital, Parkville, Australia 2 Royal Women's Hospital, Department of Microbiology and Infectious Diseases, Parkville, Australia 3 Murdoch Childrens Research Institute, Infection and Immunity Theme, Parkville, Australia 4 Department of Pathology, Royal Melbourne Hospital, Parkville, Australia 5 Melbourne EpiCentre, Royal Melbourne Hospital, University of

Melbourne 6 University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women’s Hospital Parkville, Australia 7 Infectious Diseases, Royal Children’s Hospital 8 Bone and Mineral Medicine, Royal Melbourne Hospital, Parkville, Australia

Aim: To evaluate associations between serum sodium concentrations, bone mineral density (BMD), fractures and antiepileptic drugs (AEDs). Background: Hyponatraemia ([Na+]<135mmol/L) is associated with increased risk of osteoporosis and fractures. One of the common causes of drug-induced hyponatraemia is AEDs, which is also independently associated with increased risk of osteoporosis and fractures. However, the mechanism of the association remains uncertain. The association between hyponatraemia and bone health in patients using AEDs has not been explored and could help explain how AEDs affect bone health. Methods: This cross-sectional study comprised 72 patients, aged 18-75 years, who had been treated with AEDs for more than one year. These patients had BMD scans between January 2005 - March 2017 and serum sodium levels recorded for 5-10 years prior to their BMD scan at the Royal Melbourne Hospital and its affiliated sites. Demographic and clinical data were obtained by questionnaires including fracture history, AEDs use and duration. Statistical analysis was performed using SPSS version 24. Statistical significance was set at p≤0.05. Results: Prevalence of hyponatraemia in the cohort was 6.9%. Duration of oxcarbazepine use was negatively correlated with total hip BMD independent of serum sodium concentrations (Rho=-0.949, p=0.05), whilst a weak positive correlation was detected between duration of sodium valproate use and lumbar spine BMD (Rho=0.377, p=0.03). Reported history of fracture was significantly greater with the enzyme-inducing AEDs (EIAEDs) and non-enzyme-inducing AEDs (NEIAEDs) polytherapy compared to those using EIAEDs or NEIAEDs alone (p=0.038). Those who reported a history of fracture had longer durations of sodium valproate use (p=0.036) and NEIAEDs use (p=0.02) than those who did not report a history of fracture. No statistically significant associations were found between i) serum sodium concentration and BMD or fractures, and ii) serum sodium concentrations and AEDs regimens. Conclusion: This retrospective pilot study did not suggest serum sodium concentration to be an explanatory mechanism for poor bone health associated with AEDs. Oxcarbazepine, well-known for inducing hyponatraemia, was associated with lower total hip BMD independent of serum sodium concentrations. The significant association between reported history of fracture and EIAEDs and NEIAEDs polytherapy may influence clinical decision-making in prescription of AEDs. Further studies with a larger sample size, better documentation of AEDs use, BMD and serum biochemistry are required to investigate the association between serum sodium concentrations and bone health in individuals who use AEDs and the effects of its reversibility for better prevention and management of bone health.

112 Nally Ieong Association between chronic back pain and depression in young women aged between 16-25 years old IEONG N (1), Subasinghe A (2), Garland S (2), Gorelik A (3), Clifford V (4), Slater H (5), Briggs A (5), Wark J (3) University of Melbourne (1), Royal Women's Hospital (2), Royal Melbourne's Hospital (3), Royal Children's Hospital (4), Curtin University (5)

Aim: To study the association between CBP and depression in young women. Background: Evidence demonstrates chronic back pain (CBP) that begins during adolescence and young adulthood is likely to persist into adulthood leading to long term disability. Young females are at a greater risk of both CBP and depression

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compared to males, yet they are still an under-researched population. Methods: Young Victorian females (16-25 years) were recruited via Facebook between 2012 and 2015 into the Young Female Health Initiative (YFHI) and Safe-D studies. Participants completed five comprehensive online modules that captured demographic factors, physical activity levels, mental wellbeing (PHQ-9, GAD-7, K10, SF-12 MCS), social factors and family history of mental disorders and CBP. CBP was defined as having persistent back pain lasting for at least 6-months. Depression was defined by self-reported lifetime diagnosis of depression. A longitudinal follow up survey was sent in 2017 to 600/687 of the original participants, which explored their engagement with the healthcare system and back pain related using the Orebro Musculoskeletal Pain Questionnaire (OMPQ). Results: In the cross sectional study (N=652), approximately 57% of the cohort reported CBP only. There was a significantly higher proportion of depression in CBP group compared to healthy group (37% vs 21%, p<0.001). There were statistically significant differences between the two groups in terms of demographic and biopsychosocial factors. There was a significantly higher proportion of overweight (p=0.001), sedentary behaviour (p<0.001) and history of childhood sexual abuse (0.007) in the CBP group compared to the healthy group. CBP participants reported more severe depressive symptoms (PHQ9) (p=0.02), anxiety (GAD7) (p=0.01) and psychological distress (K10) (p=0.001) compared to healthy participants. Multivariable regression analysis demonstrated participants with depression have more than twice the risk of CBP (OR=2.16 (1.1304.14), p=0.02) compared to those without depression. Results from supplementary survey (response rate 238/600=40%) revealed cost and time were the most common reasons that prevented young women with CBP to seek healthcare assistance. Furthermore, 25% were at a high risk of future work disability (OMPQ score >50). Conclusion: CBP is a highly prevalent condition (57%) among young females. Similar to previous findings, we found that CBP is associated with depression. We also identified certain biopsychosocial factors that were more prevalent in those with CBP. These findings emphasise the need to address mental wellbeing in young women with CBP.

113 Steven Megaloudis Immunophenotyping as Subclassification Strategy of Primary Immunodeficiencies MEGALOUDIS S(1,2), Tempany J(2,3), Slade C(2,3,4), Douglass J(4,5), Bryant V(2,3,4) (1)University of Melbourne, Australia (2)Immunogenetics Research Team, Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia (3)Department of Medical Biology, University of Melbourne, Australia (4)Department of Immunology and Allergy, The Royal Melbourne Hospital, Parkville, Australia (5)Department of Medicine, University of Melbourne, Australia

Aim: To immunophenotype a cohort of Victorian antibody-deficient patients and identify specific defects in immune cell populations, thereby identifying relationships between immunophenotype, clinical features and genotype. Background: Common Variable Immunodeficiency (CVID) is a heterogeneous collection of Primary Immunodeficiencies, characterised by hypogammaglobulinaemia, and associated with a number of comorbidities, including autoimmunity. The aetiology of most cases remains elusive, and although stratification of patient cohorts by immunological phenotyping has elucidated subgroups with some common clinical features, these strategies do not adequately represent the many features of immune dysfunction known to occur in CVID.

Methods: We performed flow cytometric phenotyping of 46 immune cell subsets in 19 CVID patients from the Royal Melbourne Hospital, 4 unaffected family members and 37 unrelated healthy controls. Cells from each donor were stained using three (12-colour) monoclonal antibody panels and proportions of T and B lymphocytes, natural killer cells and monocytes, and their subsets, were analysed by flow cytometry. Clinical and, where possible, genetic data were collected for each patient and the cohort was stratified based on clinical features and known genotypes. Statistical comparisons were made using the Mann-Whitney U-test. Results: We observed reduced frequencies of several lymphocyte populations in the CVID cohort, compared to healthy controls, in memory B- and naïve CD4+ T cell subsets, non-classical monocytes and myeloid dendritic cells. In contrast, significantly increased frequencies of T-follicular helper and activated effector memory T-cell subsets were observed in CVID patients, overall. Reduced proportions of regulatory T cells, but increased proportions of naïve CD4+ T cells, monocytes and myeloid dendritic cells, were observed in CVID patients with NFKB2 mutations, when compared to other CVID patients. When segregated by clinical phenotype, patients with autoimmune manifestations showed fewer regulatory T cells, IgG+ memory B-cells and plasmacytoid dendritic cells, but increased populations of activated CD4+ T cells. Similarly, a higher proportion of total and activated CD4 T cell effector memory cells, but significantly fewer plasmablasts and CD21lo transitional B cells were observed in CVID patients with enteropathy, compared to healthy controls. Conclusion: This study investigated specific immune cell defects of a Victorian CVID cohort, stratified according to clinical phenotype and genotype. Here we revealed immunophenotypic signatures of subsets of patients with defects in NFκB signalling pathways, autoimmunity and enteropathies. This data will contribute to better diagnostic and prognostic testing of CVID patients and uncover new immunological mechanisms of disease that explain its diverse array of presentations.

114 Julian Daniell Peutz-Jeghers Syndrome and STK11: Analysis of the association between variants and malignancy DANIELL JM(1,2), JP Plazzer (2), A Perera (1), Macrae FA(1,2), 1 - The University of Melbourne; 2 - Royal Melbourne Hospital

Introduction: Peutz-Jeghers Syndrome is characterised my hamartomatous polyps, mucocutaneous pigmentation and an increased predisposition towards developing malignancy. It is inherited in an autosomal dominant manner secondary to germline mutations in STK11. STK11 is a tumour suppressor gene, comprised of 433 amino acids across nine coding exons, located on Chromosome 19. Aim: To determine any potential associations between STK11 variants, their location and type, and Peutz-Jeghers phenotype, especially the development of malignancy. Methods: Data on PJS patients and STK11 were sourced from the literature between 1995 and January 2017 and entered into a Leiden Open Variation Database (LOVD) platform. Inclusion criteria required reporting of genetic testing and clear proband phenotype. International Society for Gastrointestinal Hereditary Tumors (InSiGHT) members were also invited to directly submit personally accrued data. 1,362 patients were included in the study. Chi-square tests were performed on the data and where appropriate Fisher’s exact test was used. Results: Nine-hundred and eighty-five variants were detected in unrelated PJS probands. Of this 985, 447 were unique. These 447 unique variants were non-randomly distributed across all nine exons. Five variants were discovered to occur at a greater frequency than other variants in unrelated individuals. These were at codon 60, codon 194, codon 304 and large deletions of exon 1, and the whole gene. There was no statistical significance in the different rates of malignancy

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when the variants were categorised via their type (p=0.138) or location (p=0.58). However, a trend towards truncating mutations being more pathogenic than non-truncating mutations was seen. A total of 242 malignancies were identified in 155 individuals, with gastrointestinal cancers accounting for 109 of the 242. Variants in Functional Domain XI had the greatest proportion of malignancies (32.47%). Conclusion: This study represents the largest database of STK11 variants. Future studies could undertake a more thorough exploration into the ‘hot spots’ identified here or could explore another marker of phenotype severity, other than the development of malignancy. Abbreviations: PJS = Peutz-Jeghers Syndrome STK11 = Serine-Threonine Kinase 11 LOVD = Leiden Open Variation Database InSiGHT = International Society for Gastrointestinal Hereditary Tumors Key words: ‘Peutz-Jeghers Syndrome’; ‘STK11’; ‘hereditary gastrointestinal cancer’

115 Nicholas Lord Impact of TNF-alpha Antagonists on Cervical Dysplasia Incidence: An Inflammatory Bowel Disease Cohort Lord N(1), Macrae F(2), Turner M(3), Brotherton J(4), Viney B(2), Gorelik A(2) University of Melbourne (1), The Royal Melbourne Hospital (2), BioGrid (3), Victorian Cervical Cytology Registry (4)

Introduction: Women who are immunosuppressed, either from a disease entity (Human Immunodeficiency Virus) or iatrogenic treatment (immunomodulatory medication) have been shown to be at greater risk of developing cervical dysplasia. Autoimmune diseases have also been tentatively linked with increasing the incidence of cervical dysplasia. The purpose of this study is to ascertain whether women diagnosed with and treated for Inflammatory Bowel Disease have a higher risk of developing abnormal cervical cytology, and if such a risk exists, what additional cervical cancer screening interventions should be put in place to mitigate the risk. Methods: This case control study will identify inpatients treated for Inflammatory Bowel Disease at the Royal Melbourne Hospital through the hospital coding system. Relevant surgeries and procedures that act as markers of disease severity will also be recorded, in addition to TNF-alpha antagonist use. Data linkage will then be undertaken by BioGrid, through which patient pap smear and histological data from the Victorian Cervical Cytology Registry will be obtained. Three controls per patient will be randomly generated by the Victorian Cervical Cytology Registry, matched for age and postcode. To determine what additional cervical cancer screening interventions would be most appropriate to implement for Inflammatory Bowel Disease patients, a survey containing 10 screening interventions will be sent to 81 members of the Australian Society of Gynaecological Oncologists, who will be asked to ascribe each intervention a relative risk which justifies a specific recommendation. Results: Data collection is underway, with all results expected to be compiled before the end of June 2017. Upon completion of analysis, the study will have determined the relative risk of cervical dysplasia in Inflammatory Bowel Disease patients when compared to controls, the participation rates in cervical cancer screening of these patients, and what screening interventions are justified at the established relative risk. Conclusion: This study will provide data about the relative risk of Inflammatory Bowel Disease patients of developing abnormal cervical cytology, which in conjunction with the

survey findings, will facilitate the implementation of effective, focused healthcare for these women.

116 George Yang Retrospective analysis of the impact of human herpes viruses on pemphigus vulgaris patients at the Royal Melbourne Hospital. YANG G(1), YAP T(1), SCARDAMAGLIA L(1), BRAUE A(1), MARTYRES R(1), VARIGOS G(1) 1. Department of Dermatology, Royal Melbourne Hospital.

Introduction: Pemphigus vulgaris (PV) is a rare autoimmune bullous condition, affecting 0.1 - 0.5 per 100,000 people, characterised by blistering of the skin and mucosa, particularly the oral mucosa. Although the aetiology of PV is not well understood, it is known that the presence of autoantibodies leads to the destruction of cell adhesion molecules. The use of systemic corticosteroids and steroid-sparing agents, particularly, mycophenolate mofetil are now a mainstay for management of the disease. Human herpesviruses (HHV) such as HSV and CMV have been implicated in both the pathogenesis of PV but may also contribute exacerbation of disease, which is often difficult to distinguish clinically from refractory disease. Thus, it is important to investigate the circumstances in which herpesvirus infection occurs and its relationship with PV. Methods: Longitudinal data was collected from the medical records of 27 PV patients seen in the Dermatology Unit at the Royal Melbourne Hospital, Victoria. Details included demographic data, clinical assessment of disease severity, medical management, serological markers and HHV detection by flocked swab and PCR. The temporal relationships of disease and management variables and HHV detection were inspected. Descriptive statistics were prepared to compare subgroups. Results: The cohort consisted of 41% (11/27) male and 59% (16/27) female patients with a median age at presentation of 47.4 years (33.2-75.5). Clinical data spanned from 1.6 months to 18.0 years. 33% (9/27) of patients achieved a complete remission by 12 months. 100% of patients treated over 12 months had at RMH reached clinical remission although 71% (17/24) experienced a relapse. 13 patients were swabbed for the presence of oral herpesviruses during their management at the hospital. 38% (5/13) had at least one positive viral swab, of which 50% (5/10) were on a maximal dose of mycophenolate mofetil. Further results are pending. Discussion: Clinical trends including the temporal relationship of clinical and laboratory disease findings are important in rare diseases such as pemphigus. Here we present the findings from the largest Pemphigus Vulgaris cohort in Australasia.

117 Melanie Eden Combined modality endoscopic treatment of dysplasia and early oesophageal adenocarcinoma in Barrett’s oesophagus EDEN M, Macrae F, Metz A Royal Melbourne Hospital

Aim: The aim of this study is to audit outcomes and processes to ensure quality against international standards of care. Furthermore, there is limited data from Australian centres on the efficacy and durability of radiofrequency ablation in the treatment of dysplastic Barrett's oesophagus, so this study aims to address this gap in the literature. Finally, this study aims to identify the relationship between treatment failure and age, sex, length of Barrett's oesophagus and presence of hiatal hernia. Introduction: Historically, Barrett’s oesophagus with high-grade dysplasia or adenocarcinoma has been treated with oesophagectomy, but in the past 15 years there have been

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developments in minimally invasive endoscopic treatment modalities. Radiofrequency ablation with endoscopic mucosal resection for visible lesions has been utilised at The Royal Melbourne Hospital for the past 10 years. Methods: This study involves retrospective collection of endoscopy and histopathology reports of patients with Barrett’s oesophagus at The Royal Melbourne Hospital identified by searches of “Barrett’s” and “intestinal metaplasia” on endoscopy, histopathology and waiting list databases in the past 10 years. Results: Patients will be divided into dysplastic and non-dysplastic groups on initial endoscopy. The rate of neoplastic progression, number of radiofrequency ablation procedures to remission in those with dysplasia, and length of Barrett’s oesophagus will be of interest. In addition, those who failed ablative therapy will be compared to where ablative treatment was successful in terms of sex, age, Prague criteria and presence of hiatal hernia. Conclusion: Findings of this study will be considered in relation to international standards. In addition, indicators of treatment failure will be identified.

118 Logan Denny Medical emergency calls in the Intensive Care Unit DENNY L(1), Deane A(2), Morley P(1,2) 1.The University of Melbourne; 2.The Royal Melbourne Hospital

Aim: To determine the nature of emergency calls occurring in the Royal Melbourne Hospital (RMH) Intensive Care Unit (ICU), including the events during, outcomes, and antecedents. Background: Unlike Medical Emergency Team calls occurring in the wider hospital setting, medical emergency calls in the ICU have been subjected to little scrutiny in the medical literature. At RMH, ICU medical emergency calls occur when clinicians at the patient bedside require urgent assistance as a patient rapidly deteriorates. During the six months from 01/07/2016 to 31/12/2016, there were a total of 242 undifferentiated emergency calls in the RMH ICU. This study sets out to describe in greater detail the events, antecedents, and outcomes of these calls. Methods: This is a prospective study covering the period from 01/01/2017 to 31/05/2017, reviewing data routinely collected as a part of normal RMH ICU patient care. Medical emergency calls were identified from the RMH ICU's Merlon Nurse Call system database. These were then matched to the relevant patient using the inpatient management software iPM. Patient progress notes, observation charts, and other documentation were then examined to gather the required information. Results: The data presented here represents preliminary results, as data collection is yet to be finalised. From 01/01/2017 to 31/05/2017, there were a total of 122 recorded emergency buzzer calls. 81 of these calls have been determined to be legitimate emergency calls, including Code Grey calls. There are another 13 calls which are yet to have data collection completed. Data analysis has been completed for 29 of these legitimate calls. This represents a total of 24 patients, 16 of which were male. Of the 24 patients seven died in-ICU (30.4%), with three dying at the time of the emergency call, and four dying post-call. 21 of these calls occurred out of hours (outside the times between 7am to 7pm, Monday to Friday), and 18 occurred within 24 hours of ICU admission. Conclusion: Preliminary data from this study shows that there was a greater prevalence of males, more episodes occurring out of hours, and an in-ICU mortality rate of 30.4%.

119 Kate Greentree Effect of Frailty and Health Assets on Critically Ill Patient Outcomes: Feasibility Study

Darvall JN(1,2), GREENTREE K(1), Loth J(1), Bose T(1) (1) University of Melbourne, (2) Melbourne Health

Aim: The aim of this study is to determine the feasibility of frailty measurement in critically ill Australian patients; and the effect of frailty and health assets on patient outcomes after intensive care admission. Background: Frailty is a multidimensional syndrome shown to confer poorer outcomes in older critically ill adults. Identification of frailty and its relation to patient outcomes has been studied in international populations however, there is a lack of data in critically ill Australian populations. Recent interest has emerged in health assets, protective patient factors, as a modifier of outcomes for frail older hospitalised patients, however their role in critically ill patients is not defined. Methods: We conducted a single-center prospective study in the Intensive Care Unit at the Royal Melbourne Hospital. A convenience sample of patients aged 50yrs and over admitted between February and June 2017 were recruited. Frailty was determined by the Reported Edmonton Frailty Scale (REFS), Clinical Frailty Scale (CFS) and a Frailty Index (FI). Frailty was defined as REFS >7, CFS >4 and FI >0.25. The primary outcome was all-cause mortality, with secondary outcomes including discharge destination and length of stay. Clinical interviews and chart review performed by final year medical student. Results: Of the 379 patients screened, 121 patients recruited to the study. Next of kin derived assessments were performed for 31% of patients. Using the CFS, EFS and FI, 32.2%, 37.2% and 21.5% of patients respectively were classified as frail. Frail patients (CFS >4) were older (median age 72 (67-79) vs. 69 (61-75), p=0.025) and had lower levels of pre-morbid functional independence (Katz index: median (IQR), frail: 5(4-6), non-frail 6(6-6), p=0.000). A total of 15 patients died, 66.6% of them frail (CFS>4) pre-morbidly. Frail patients had greater lengths of stay in hospital (median days (IQR), frail:14.2 (10.2-21.8), non-frail: 10.0 (7.2-16.9), p=0.010) and were more likely to be discharged to a rehabilitation program (48% of frail group vs. 17% of non-frail group, p=0.013). The frail group also had fewer health assets (frail: 10 (8.5-11), non-frail: 11.5 (10-12.5), p=0.001). Conclusions: Premorbid frailty in older intensive care patients is feasibly assessed by interview of either the patient or their NOK. Frail critically ill older adults have poorer outcomes than their non-frail counterparts. Frail older adults have less protective factors (health assets) than non-frail older adults, however the clinical significance of this is unknown.

120 Rachel Cheong Cardiopulmonary Resuscitation (CPR) in a Quaternary teaching Hospital: Performance Component Quality and Impact on Patient Outcomes. An observational study. CHEONG R(1), Burke J(2), Deane A(2), Morley P(2) Aim: To determine the quality of multiple technical parameters of CPR, as practiced at the RMH, and to correlate CPR quality components and patient-related factors with in-hospital cardiac arrest (IHCA) patient outcomes. Background: High-quality CPR had been shown to relate to successful cardiac arrest resuscitation. However, optimal targets of CPR quality components had been difficult to define. Advances in defibrillator technology had made objective measurements of CPR a possibility. At the Royal Melbourne Hospital (RMH), objective CPR quality had not been previously measured. Methods: Consecutive patients requiring CPR with ZOLL defibrillator with novel real-time sensors attached from 1 July 2016 to 31 December 2017 are being recruited. Technical parameters of CPR including detailed components of chest

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compression, ventilation and pauses are statistically analysed by ZOLL software. Patient demographics, arrest characteristics, and the key outcomes of return of spontaneous circulation (ROSC), survival to hospital discharge (STHD) and discharge destination are extracted from patient records. Results: At this stage, fifteen (15) events have had a preliminarily analysis. 3/15 (20%) had a shockable initial arrest rhythm. 6/15 (40%) and 4/15 (26.7%) had compressions within guideline-recommended targets for rate and depth respectively. 3/15 (20%) achieved guideline-recommended chest compression fraction of >0.8. General trends for ventilation and compression pauses do not appear to reflect adherence to national guidelines. 13/15 (86.7%) achieved ROSC, 9/15 (60%) achieved 24-hour survival while only 1/15 (6.7%) STHD. Association of CPR quality components with patient-related factors is being evaluated. Conclusion: Preliminary analysis suggests that the measured CPR parameters do not conform to guideline recommendations. Continued recruitment of patients is necessary to identify correlation between CPR quality parameters and patient outcomes. A larger prospective trial with routine CPR measurement, monitoring and feedback during actual resuscitation episode is necessary to validate the effects of particular CPR quality components on overall patient outcomes in our setting.

121 Apayandth Balachandra Postoperative Delirium: Exploring the risk factors through a retrospective case-control study BALACHANDRAA(1), TROPEAJ(1), LOGIUDICED(1, 2) 1. Royal Melbourne Hospital (city campus) 2 Royal Melbourne Hospital (Royal Park campus)

Background: Postoperative delirium is a significant complication following major surgical procedures due to the increased risk of mortality of patients and increasing overall length of stay in hospitals, placing greater burden on the healthcare system. Figures quoted by American Geriatrics Society states that incidence can vary anywhere between 5-50% among older patients undergoing surgery. The aim of this research is to explore the risk factors that predispose to postoperative delirium after major surgical procedure. Methods: We conducted a retrospective case-control study where the data was retrieved from iPM at Royal Melbourne Hospital for patients undergoing major surgical procedures between the periods of November 2015 – January 2017. From here, we were able to use the unique UR numbers to extract data from online medical records (ECM). Our patient population includes those who are >65 years who have undergone a major surgical procedure, with our outcome of interest as postoperative delirium. The cases were matched to controls based on age, sex and procedure type. We determined the risk factors of interest through review of multiple online literature and categorised them into predisposing and precipitating factors. The predisposing risk factors include; medical comorbidities, number of preoperative medications, ASA score and precipitating risk factors include; fluids administered, intraoperative benzodiazepine and length of anaesthetic time. Results: In total, we included 126 patients, of which 45 had postoperative delirium. We looked at both pre-operative and intra-operative risk factors. If the estimated p-value from univariate analysis is <0.2, we will include this variable in multivariate logistic regression model analysis to identify risk factors associated with the development of delirium. Results will be presented as odds ratios (with 95% confidence intervals). Statistical significance will be considered if the p-value is less than 0.05. SPSS will be used to conduct the statistical analysis.

122 Alvin Shae Survey assessing environmental exposure in multiple sclerosis SHAE A(1), Kalincik T(1,2), Butzkueven(1,2,3), Jokubaitis V(1,2) 1) Department of Medicine, University of Melbourne; 2) Department of Neurology, Royal Melbourne Hospital; 3) Department of Neurology, Box Hill Hospital, Monash University

Aim: We created a standardized, environmental exposure questionnaire for integration with MSBase, a large, prospective, longitudinal multiple sclerosis outcomes registry. Introduction: Multiple sclerosis is an immune-mediated, demyelinating disease of the central nervous system. It globally affects an estimated 2.3 million people. The etiology of multiple sclerosis is complex. Genetic predispositions are well known, but a growing pool of epidemiological evidence suggests that environmental factors strongly influence risk and exacerbation of multiple sclerosis. Factors that increase multiple sclerosis risk include both smoking and infection with Epstein-Barr Virus. In contrast, sunlight exposure, vitamin D supplementation, and alcohol intake appear protective. Furthermore, these factors may interact together or with genetics to increase risk up to 8-fold. However, a clear causal relationship between exposure and disease has yet to be established. This is due largely to methodological limitations. Perhaps because of the impractical costs inherent in large-scale serum investigations, most studies assess environmental exposures through a wide variety of questionnaires. These questionnaires are mostly applied to retrospective study designs, and risk of bias is high. As a result, studies are generally small in sample size and difficult to compare. Method: We systematically reviewed the literature for specific questions implemented to assess putative environmental factors in the context of multiple sclerosis risk and progression. We qualitatively analyzed our results along with questionnaires from other epidemiological fields to determine which questions could robustly characterize environmental exposure in a clinical setting. From this, we created a digital survey wireframe using Balsamiq. Results: Our search terms produced 1,406 studies, from which 70 studies were included in our review. The most effective metrics include recall of infectious mononucleosis, yes / no response for vitamin D supplementation, daily duration-in-sun, cigarette pack-years, smoke-free duration for ex-smokers, duration of passive smoking, and quantity / frequency of alcohol intake within the last 12 months. Conclusion: We developed a survey that characterizes environmental exposures that are relevant to multiple sclerosis. International implementation of this survey into MSBase will prospectively characterize environmental exposure across more than 50,000 patients. This could greatly benefit future epidemiological studies, contribute to risk assessment for disease susceptibility, and improve clinical management.

123 Jake Jun Disease Modifying Therapy Affects the Phenotype, Severity and Recovery of Multiple Sclerosis Relapses JUN J(1,2) Melbourne Brain Centre, University of Melbourne

Aim: The objective was to analyse the effect of disease modifying therapies (DMTs) on the probability of relapse phenotype occurrence in multiple sclerosis (MS) and also assess their effect on relapse severity and recovery post-relapse. Background: MS is an autoimmune, inflammatory, demyelinating disease of the central nervous system (CNS). MS relapses can exhibit up to seven phenotypes with pyramidal, sphincteric and cerebellar relapses shown to be associated with greatest effect on long term disability. DMTs

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have been shown to be highly efficacious in the treatment of MS however, their effect on relapse phenotype, severity and recovery has not yet been investigated. Methods: Data was collected from MSBase, an international observational registry of 119 MS centres in 35 countries. Associations between DMTs and relapse phenotype occurence, severity and recovery were tested with mixed effects, multivariable, logistic regression models. These models were adjusted for patient and disease characteristics known to affect relapse phenotype. Results: Among the 30,840 eligible patients (204,440 follow-up years), there were 46,813 recorded relapses with phenotypic data. Dimethyl Fumarate was positively associated with pyramidal relapses and negatively associated with visual relapses. Fingolimod was positively associated with pyramidal, cerebellar and cognitive relapses and negatively associated with visual and sensory relapses. Glatiramer Acetate was positively associated with pyramidal and cognitive relapses and negatively associated with visual, brainstem and sensory relapses. Interferon-β was positively associated with pyramidal and cognitive relapses and negatively associated with sphincteric, visual and brainstem relapses. Mitoxantrone was positively associated with cerebellar relapses and negatively associated with brainstem and sensory relapses. Natalizumab was positively associated with pyramidal and cognitive relapses and negatively associated with visual and sensory relapses. Rituximab was positively associated with sphincteric relapses. Finally, Teriflunomide was negatively associated with visual relapses. Relapses on Fingolimod were less likely to experience complete recovery relative to relapses on no treatment (OR=0.82, p=0.04). Relapses on Interferon-β had higher probability of being mild (OR=0.87, p=0.0002) while those on Mitoxantrone had higher probability of being moderate/severe relative to relapses on no treatment (OR=2.02, p=0.003). Conclusion: DMTs were associated with relapse phenotype as well as relapse severity and likelihood of complete recovery.

124 Niveshan Sivathamboo The effect of antidepressants on the incidence of congenital malformations and occurrence of seizures in pregnant women with epilepsy. SIVATHAMBOO N(1,2), Hitchcock A (1,2), Graham J (1,2), Chen Z (1), O'Brien TJ (1,2), Vajda FJE (1,2) (1) Department of Medicine (RMH), The University of Melbourne (2) Department of Neurology, The Royal Melbourne Hospital

Background: Up to 0.7% of all pregnancies are in women with epilepsy (WWE). Although some WWE can discontinue antiepileptic drugs (AED) prior to conception, most require long term AED treatment to control seizures. First-trimester exposure to AEDs increase the risk of congenital malformations (CM) from the background risk. A third of patients diagnosed with epilepsy have a concomitant psychiatric illness. Depression is the most common, with many population-based studies reporting prevalence over 20%. Antidepressant (ADD) medication throughout pregnancy has been steadily increasing over the last twenty years, despite being questioned for increasing the risk of CMs. The combined foetal risk of medicating with both AEDs and ADDs in WWE is unanswered in the scientific literature. Methods. A retrospective, observational, community-based cohort study was performed comparing the rate of CMs. The APR is a voluntary, Australia-wide, telephone-interview-based register enrolling WWE taking AEDs and not taking AEDs from 1999 to 2016. Four interviews were taken: (1) On recruitment, usually in the first or second trimester, (2) 7 months of pregnancy, (3) in the post-natal month and (4) at the end of the post-natal year.

Results: A total of 2081 pregnancies had been completed, with 43 sets of twins, for a total of 2124 pregnancy outcomes. 1954 outcomes were exposed to AEDs in utero, whilst 170 were unexposed. Further comparisons were made among three exposure types: (1) pregnancy outcomes with first-trimester exposure to ADDs (n=88), (2) those with mothers diagnosed with depression and/or anxiety but were not medicating with an ADD (n=65) and (3) those with mothers who were not diagnosed with depression and/or anxiety and were not medicating with ADD (n=1801). The prevalence of malformations in infants who were exposed to both AEDs and ADDs was 10.2%, compared to non-medicated depression/anxiety which was 7.7% and 6.9% for the not depressed/anxious group. These results are not statistically different (P=0.448). The malformation rate in pregnancy outcomes unexposed to AEDs were insignificant (P=0.266). In regards to seizure control, 4.6% of WWE medicated with AEDs and ADDs had convulsive seizures throughout pregnancy and 10.3% had non-convulsive seizures. These rates were statistically akin to the comparison groups (P=0.784 and P=0.450 respectively). Conclusion: Co-medicating with ADDs in WWE taking AEDs does not appear to confer an added teratogenic risk nor does it affect seizure control. This data should be helpful for clinicians treating WWE who have depression or anxiety in which an ADD may be indicated.

125 Jordana Hughes Contribution of inflammation to disability accrual in primary progressive multiple sclerosis HUGHES J (1), Jokubaitis V (2,3), Spelman T (2,3), Van der Walt A (2,3), Butzkueven H (2, 3, 4), Kalincik T (1,3); on behalf of the MSBase Study Group 1. CORe Unit, Department of Medicine, University of Melbourne; 2. Department of Medicine, University of Melbourne; 3. Department of Neurology, Royal Melbourne Hospital; 4. Department of Neurology, Box Hill Hospital, Monash University

Aim: To examine the effect of superimposed relapses in progressive-onset MS on disease outcomes. Background: Primary progressive multiple sclerosis (MS) may present with or without superimposed relapses. The role these relapses play in disability accumulation remains contested. Methods: 1427 patients with progressive-onset MS from MSBase, an international prospective cohort, were analyzed. Inclusion criteria consisted of primary progressive MS (with or without relapses), adult-onset disease, at least three visits with Expanded Disability Status Scale (EDSS) recorded, first and last visit a minimum of 3 months apart and availability of minimum dataset. Multivariable regression models were used to compare effect of superimposed relapses on cumulative hazard of 3-month confirmed EDSS progression events and EDSS score 4, 6 and 8. Three sensitivity analyses for data from high quality centres, 12-month relapse-free EDSS progression and exclusion of bout-onset progressive MS were performed. Results: 1427 eligible patients were identified for the analysis of the cumulative hazard of confirmed EDSS progression events. Progressive onset patients with recorded relapses were younger at disease onset (median 39 vs. 43 years) and baseline visit (median 46 vs. 51 years), and demonstrated a lower baseline EDSS (median 4.0 vs. 4.5 years) compared to those without relapses, respectively. The likelihood of confirmed disability progression was lower in patients with superimposed relapses (HR: 0.83, p<0.01). In the cohort with active progressive MS, we observed an association between the proportion of the follow-up time spent on immunotherapy and the hazard of confirmed disability progression events (HR: 0.996, p=0.01). This association was not seen in the progressive MS without relapses (HR: 1.00, p=0.21). Three subcohorts were analyzed for cumulative hazard of EDSS 4

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(n=504), 6 (n=965) and 8 (n=1399). Likelihood of reaching EDSS 4 (HR: 0.78, p=0.07), 6 (HR: 0.81, p=0.07) and 8 (HR: 0.64, p=0.06) was not significantly associated with superimposed relapses. Conclusion: In patients with primary progressive MS, superimposed relapses are associated with a lower risk of confirmed disability progression. This is most likely attributed to the preventative effect of immunotherapy on disability accrual in patients with active primary progressive disease. The findings of this study suggest that disease-activity is an important modifier of disability in primary progressive disease.

126 Laura Tu Antiepileptic drug-related cognitive symptoms in newly treated epilepsy patients: a prospective cohort study. TU L (2), Chen Z (1, 2), Perucca P (1), O'Brien TJ (1, 2), Kwan P (1, 2) 1) Department of Neurology, The Royal Melbourne Hospital; 2) The University of Melbourne

Aim: To identify potential predictive factors for subjective cognitive complaints in newly treated epilepsy patients, and to determine whether cognitive symptoms were associated with different antiepileptic drugs as monotherapy. Background: Antiepileptic drug therapy remains the current mainstay treatment for epilepsy with 60-70% of newly diagnosed patients achieving seizure control after commencing treatment. However, antiepileptic drugs are associated with a range of cognitive adverse effects which are a major determinant of treatment adherence and health-related quality of life. There is a general perception that the newer antiepileptic drugs are less likely to affect cognitive function. Methods: Patients newly treated for epilepsy were recruited from the Royal Melbourne Hospital and Austin Hospital (n=448). Cognitive complaints were measured by the A-B Neuropsychological Assessment Scale (ABNAS) upon recruitment. Patients were prospectively followed up for two years to record changes in medication, seizure control, drug-related side effects, and ABNAS score. Results: Four hundred and forty patients completed baseline and follow-up ABNAS. No significant change in ABNAS score was observed at the next available follow-up (p=0.20). Among them, 341 patients remained on the initial monotherapy drug at the next available follow-up. In univariate analyses, patients with focal epilepsy (n=182) reported significantly greater cognitive decline after commencing antiepileptic treatment than those with unclassified epilepsy (n=90; p=0.045). Patients with self-reported cognitive difficulties had a lower change in ABNAS score (p=0.014) during follow-up than those without. These two factors remained significant in the multivariable regression model (p=0.008 and p=0.037, respectively). The most commonly prescribed monotherapies were Carbamazepine, Sodium Valproate, Levetiracetam, Lamotrigine, and Phenytoin. Among patients who remained on initial monotherapy (n=341) there was no significant difference in change in ABNAS score during follow-up between different drugs (p=0.67). Conclusion: Patient- and disease-related factors may play a greater role than antiepileptic drugs in the extent of cognitive symptoms experienced by patients with newly diagnosed epilepsy. These findings will help inform evidence-based counselling of patients when commencing antiepileptic drug therapy.

127 Simon Li Identification of occult anterograde flow using dynamic CT angiography derived from CT perfusion LI SJ(1), Rodrigues E(1), Sharma G(1), Campbell B(1)

Department of Neurology, Royal Melbourne Hopsital

Aim: To examine the prevalence of occult anterograde flow using dynamic CT angiography in stroke patients with proven vessel occlusion. Background: The effectiveness of stroke thrombolysis decreases with time. Previous studies have suggested that occult anterograde flow (OAF) is associated with early recanalisation after intravenous alteplase. Methods: Thin (1-1.5mm) slice axial reformats of CT perfusion (CTP) data were prospectively collected in consecutive patients admitted to the Royal Melbourne Hospital Stroke Unit (05/01/13-09/01/17). Patients with large vessel occlusion on single phase CTA were identified and the CTP data visualized as 4D (time resolved) dynamic angiograms using custom-built software. Occult anterograde flow was determined by visual assessment by two neurologists and the association with time from symptom onset and functional outcome assessed. Results: Of 50 patients with acute intracranial large vessel occlusion examined to date, 11 were excluded due to incomplete coverage of the relevant arterial segment. Occult anterograde flow was detected in 9/39(23.1%) patients. Time from last known well to CTP was 6.62±6.28hr in patients with OAF compared to 3.23±3.15hr in those without OAF. CTP ischemic core volume was 38±36ml in those with OAF and 58±42ml in those without OAF. In patients with OAF, 4/8(50.0%) had a good outcome (90 day mRS≤2) versus 7/26(26.9%) in patients without OAF. Conclusion: A substantial proportion of patients with complete occlusion on single phase CTA had occult anterograde flow on dynamic CTA. This may identify patients with greater likelihood of successful reperfusion with thrombolysis. Results in a larger dataset will be presented at the conference.

128 Laura Tu Baseline cognitive symptoms predicts seizure outcome in newly treated epilepsy patients: a prospective cohort study. TU L (2), Chen Z (1, 2), Perucca P (1), O'Brien TJ (1, 2), Kwan P (1, 2) 1) Department of Neurology, The Royal Melbourne Hospital ; 2) The University of Melbourne

Aim: To investigate whether baseline cognitive symptoms are associated with antiepileptic drug treatment response, and to identify clinically useful predictors of seizure control in patients newly treated for epilepsy. Background: Bidirectional relationship between cognition and epilepsy is a topic of increasing interest. Cognitive complaints often exist from onset of the disease, if not before. They are often a manifestation of the underlying aetiology, and therefore, may potentially confer prognostic information on the outcome of epilepsy and its treatment. Methods: Patients newly treated for epilepsy were recruited from the Royal Melbourne Hospital and Austin Hospital (n=448). Cognitive complaints were measured by the A-B Neuropsychological Assessment Scale (ABNAS) upon recruitment. Patients were prospectively followed up for two years to record changes in medication, seizure control, drug-related side effects, and ABNAS score. Patients were classified as nonresponsive if they had at least 1 unprovoked seizure by the 1-year follow-up, with or without subsequent changes to treatment regimen. Results: Drug response phenotype was able to be determined in 396 patients who had either 1-year or 2-year follow-up, and had continuous antiepileptic drug therapy in the initial 12-months. One third of the patients (n=119) failed to respond to treatment, while the remaining 70% of patients (n=277) achieved seizure freedom. A positive relationship was found between increasing baseline ABNAS scores and non-

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responders (odds ratio [OR]=1.11, 95% confidence interval [CI]: 1.03-1.21). Presence of epileptiform discharges on EEG was associated with higher risk of seizure recurrence (OR=1.67, 95% CI: 1.08-2.59). Pretreatment seizure number also seemed to predict seizure control (p<0.001). Patients who experienced more than 5 seizures before commencing treatment had 3.13 times the odds of having refractory seizure than those who experienced ≤2 seizures (95% CI: 1.89-5.25). Presence of epileptogenic lesion on MRI adjusted for interaction with ABNAS scores was found to be significant for poor drug response (p<0.001). In the multivariable regression model, baseline ABNAS scores, presence of epileptogenic lesion on MRI, demonstration of epileptiform on EEG, and having >5 pretreatment seizures, were found to be independent predictors of non-responsiveness at 12-months (p=0.005; p=0.005; p <0.026; and p<0.001 respectively). Conclusion: Self-reported cognitive symptoms provide prognostic information regarding treatment response in patients newly treated with antiepileptic drugs. Furthermore, epilepsy-related factors such as epilepsy classification, presence of epileptogenic lesion on MRI, demonstration of epileptiform on EEG, and pretreatment seizure numbers provide additional information in predicting treatment response.

129 Jack Watson Using Voltage Sensitive Dyes to Investigate Neuronal Firing Properties and Neuronal Network Activity WATSON J(1), French C(2) University of Melbourne, Royal Melbourne Hospital, Melbourne Brain Centre

Aims: In this study, we aimed to investigate neuronal firing patterns and membrane voltage changes in hippocampal brain slices using indocyanine green (ICG), the dye which was recently discovered to have voltage sensitive properties. This required a significant amount of set up and calibration as the experiments required both fast and sensitive recording equipment to capture the subtle changes that occur following stimulation. Background: In order to understand the fundamental workings of the brain we need a way to observe and analyze neural circuits in action. Traditionally, research regarding membrane potential recording involved the use of patch clamping or calcium imaging techniques which are generally restricted as they cannot provide detailed information about whole circuit activity in real time. One way to overcome these issues is by using a voltage sensitive dye. These dyes were previously thought to be too toxic for use in humans however a recent study has shown that ICG, a dye commonly used in humans also has voltage sensitive properties. Methods: Experiments were performed in acute rat hippocampal brain slices, organotypic brain slice cultures, and HEK293 cell cultures. Initial experiments used epifluorescence microscopy and the calcium flurophore Fluo-2 to set up the equipment for recording. Following this we were able to use the established VSD Di-8-ANEPPS and finally ICG. Organotypic brain slice cultures were used to supplement in vivo experiments and as a starting point for ICG experiments as ICG has previously been established to have voltage sensitive properties in this tissue preparation. The electrophysiology setup required calibration of the PointGrey Grasshopper3 camera with a computer running FlyCapture. Image analysis was performed using ImageJ. Results: Results from these experiments have shown that we were able to record membrane voltage changes in both HEK cells and rat hippocampal brain slices using the VSDs Di-8-ANEPPs and ICG with the above set up. We were able to show that with sufficient preparation it was possible to record neuronal firing patterns and membrane voltage changes in hippocampal brain slices following electrical stimulation using

ICG. This allowed us to record fluorescence changes of ICG associated with epileptiform activity in acute brain slices. Conclusions: This study is a preliminary one which provides the foundation for future experiments to further investigate the voltage sensitive properties of ICG and indicates that ICG could have a novel use in both lab based as well as clinical research.

130 Hannah Meiklejohn Peripheral expression of UBE2K as a marker of treatment-resistant schizophrenia MEIKLEJOHN H, Mostaid M, Luza S, Mancuso S, Kang S, Cropley V, Weickert C, Opazo C, Pantelis C, Bush A, Everall I, Bousman C Schizophrenia is a chronic and debilitating psychiatric condition with a lifetime risk of up to 1%. Although the underlying aetiology of schizophrenia remains unclear, emerging evidence suggests that it may be better understood as a “pathway” disorder, in which dysregulation of one of a number of possible genes in a complex biological pathway interacts with environmental and developmental factors to produce the disease phenotype. UBE2K is a ubiquitin conjugating enzyme which plays an essential role in protein degradation and turnover as part of the larger ubiquitin proteasome system (UPS). It has been identified as a candidate marker of severity in psychosis, with a previous study demonstrating a positive association between UBE2K expression and positive symptom severity in peripheral blood of patients with psychotic disorders. This study utilised cross-sectional clinical and biological data from 71 patients with treatment-resistant schizophrenia (TRS) and 57 control subjects to compare gene and protein expression of UBE2K in peripheral blood mononuclear cells (PBMC). Preliminary findings show increased expression of UBE2K in patients with TRS compared with controls, suggesting a possible underlying role of the UPS, and UBE2K more specifically, in schizophrenia.

131 Haiying Chen Optical coherence tomography analysis of patients with untreated diabetic macular edema Haiying Chen (1,3), Symons RCA (2,3) 1. The University of Melbourne; 2. Department of Surgery, The University of Melbourne; 3. Department of Ophthalmology, The Royal Melbourne Hospital

Aim: This study aimed to investigate the natural history of diabetic macular edema. Specifically, it would determine the proportion of untreated eyes that had worsening diabetic macular edema over a period of six to twelve months. It would study the predictive values of a number of medical and ophthalmic factors. Background: Diabetic macular edema is an ophthalmic complication of diabetes. It is abnormal thickening of the macula from accumulation of fluid and lipid exudates. Diabetic macular edema is the major cause of loss of central vision in people with diabetes. An improved understanding of the natural course of diabetic macular edema may guide more cost-effective management. Method: Optical coherence tomography scans of a cohort of patients with diabetes at The Royal Melbourne Hospital were assessed. The first scan of an eye that demonstrated the presence of diabetic macular edema was compared with a subsequent scan six to twelve months following the initial scan. Only eyes that received no treatment for a specified period prior to the first scan and no treatment between the two studied scans were included. Medical and ophthalmic data of the patients/eyes were collected from clinical notes. One eye from each of the 97 eligible patients was randomly selected for analysis. Results: There was no significant change in central subfield thickness, visual acuity or macular volume over a median period of eight months. The numbers of eyes that had

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increased (greater than 25 microns), decreased (greater than 25 microns), and stable (change between -25 to 25 microns) central subfield thicknesses on optical coherence tomography scans were 16 (16.5%), 6 (6.2%), 75 (77.3%), respectively. These three groups of patients/eyes will be compared with respect to baseline central subfield thicknesses, duration of diabetes, and haemoglobin A1c. Conclusion: The preliminary result from this study suggests that in most patients central retinal thickness and visual acuity in eyes with diabetic macular edema identified on optical coherence tomography scans remain stable without treatment over a median period of eight months. This study will present further results in relation to the predictive values of medical and ophthalmic factors on the natural history of diabetic macular edema.

132 Callum Umstad The Rate of Progression of Diabetic Retinopathy in Psoriasis Patients on TNFa, IL-17 and IL-12/23 Inhibitors: A Protocol Development UMSTAD C(1, 2), Vu M(2), Martyres R(2), Phemister A(2), Braue A(2), Guest D(3), Foley P(4), Symons RCA, Varigos, G(2) 1. Dept of Ophthalmology, Royal Melbourne Hospital; 2. Dept of Dermatology, Royal Melbourne Hospital; 3. Dept of Vision Sciences, The University of Melbourne; 4. Skin and Cancer Foundation

Introduction: Diabetes is a leading cause of blindness, with major vision-threatening complications including diabetic retinopathy, macular oedema and neovascular glaucoma. Diabetic retinopathy is known to share some underlying inflammatory foundations with psoriasis, a chronic inflammatory skin condition affecting 1-2% of Australians. Recent advancements in the management of psoriasis include systemic treatment with 'biologic agents' targeting specific pathways: TNFa, IL-17 and IL-12/23. The effect of inhibiting these pathways on the rate of progression of diabetic retinopathy is unknown although the literature suggests patients with psoriasis are subject to greater risk of developing type II diabetes and are subject to accelerated progression of diabetic retinopathy. Methods: This prospective study involves recruitment of psoriasis patients with diabetes. Two arms, with 60 participants in each, will be recruited: patients with psoriasis commencing biologic therapy will be compared with patients stable on non-biologic maintenance therapies for their psoriasis (such as methotrexate or topical steroid alone). Prior to commencement of their first biologic injection, participants will undergo a complete ophthalmic examination to establish the degree of diabetic retinopathy present. Repeat examinations will take place at 1, 3 and 12 months following the initial assessment. Results will also be correlated with psoriasis area and severity index (PASI) scores and glycaemic control (HbA1c) throughout the 12-month follow-up. Results: As of May 2017, there is insufficient data available for analysis. A number of issues have impacted patient recruitment, and thus data analysis, including inaccurate estimation of patient numbers, poor participant uptake and failure to meet inclusion criteria despite dual diagnosis of psoriasis and diabetes. A protocol amendment to add the Skin and Cancer Foundation as a second site of recruitment, as well as widening of inclusion criteria, is in the process of being submitted in order to increase the potential number of participants. Discussion: The study aim is to establish whether certain biologic agents for psoriasis provide an additional benefit in slowing the rate of diabetic retinopathy progression. This evidence may then potentiate the use of specific biologic agents as dual therapies in patients with both psoriasis and diabetes. Data collection continues and expected completion is in February 2019.

133 David See Comparing symptom burden between patients with malignant and non-malignant disease SEE D (1,2), Le B (2,3), Eastman P (2,4), Gorelik A (1,2) 1. University of Melbourne, 2. Royal Melbourne Hospital, 3. Victorian Comprehensive Cancer Centre, 4. Barwon Health

AIM: To investigate differences in symptom burden between patients with cancer and non-malignant conditions admitted to a palliative care unit. BACKGROUND: Much focus in palliative care is directed at patients with cancer, however there is increasing recognition that patients with non-malignant disease are likely to have comparable physical and psycho-social symptom burden. There is currently limited data directly comparing symptom burden between patients with malignant and non-malignant diseases. METHOD: A retrospective cohort study involving 200 consecutive palliative care inpatient admissions was undertaken. Patients were dichotomised on the basis of malignant or non-malignant disease. Demographic and clinical data were collected and analysed. Symptom burden at admission was assessed using the Symptom Assessment Scale and Palliative Care Problem Severity Score. Group differences in symptoms were analysed using univariate and multi-variate analyses. RESULTS: One hundred and nine admissions (54.5%) were for cancer with upper gastrointestinal the commonest cancer type (18.3%). Amongst the 91 admissions for non-malignant disease, neurological and respiratory conditions were most prevalent (38.5% and 18.7% respectively). In comparison to cancer, admissions for non-malignant disease were older (median age 83 vs 73, p < 0.001), were more likely to have a lower performance status (p<0.001) and more dependent for activities of daily living (p<0.001). No other differences in demographics between groups were observed. Regression analysis found that patients admitted with cancer were more likely to have pain (OR 2.31, 95% Confidence Interval [CI] 1.17-4.56) and fatigue (OR 2.83, 95%CI 1.13-7.1). No other differences in symptoms were observed between groups. CONCLUSION: There is a difference in symptoms between malignant and non-malignant patients at admission to a palliative care unit. These differences were seen in severity of pain and fatigue, however there were no differences seen in other symptoms suggesting that although less symptomatic there is still a need for symptom management in non-malignant patients. Further exploration of the utility of palliative care interventions in non-malignant settings is an important area for further research.

134 James May Managing expectations of donor-site morbidity in free flap surgery MAY JS(1,2), Linklater N(2), Barton RJ(2), Ramakrishnan A(2) (1) University of Melbourne, (2) The Royal Melbourne Hospital

We present a prospective pilot study on the benefits of pre-operative consent using clinical photographs of expected donor-site aesthetics to improve patient perceived outcomes in free flap surgery. Background: Since first described in the 1970’s and 1980’s, advances in free flap surgery have focused on preserving the viability of flaps at the recipient site. Improved perioperative techniques and advances in microsurgery have greatly reduced rates of flap loss. Other aspects of the surgery now gain focus, notably the postoperative function and appearance of the donor-site, as donor-site morbidity is important in the choice of free flap when more than a single potential donor-site is appropriate for a given indication.

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Managing patient expectations towards the appearance and functional outcomes of the flap and donor-site can have a significant impact on overall patient satisfaction with their surgery. Studies comparing preoperative expectations of donor-site appearance with postoperative satisfaction are limited. Some authors recommend using serial photographs of wound healing to encourage more realistic expectations. This concept has not previously been applied during preoperative consent for free flap surgery regarding the donor-site. This prospective study examines the effect of clinical photography in informed consent for free flap surgery. Primary objectives: To examine the impact of pre-operative counselling on patient satisfaction with donor-site aesthetics and function in free flap surgery using non-standardised Likert scales. Secondary objective: To examine the impact of donor-site morbidity in free flap surgery on overall quality of life as measured using the standardised Short-Form 12 Quality of Life Surv. Methods: A consecutive series of patients undergoing free flap surgery at the Royal Melbourne Hospital were consented before reconstruction using clinical photographs of their planned donor-site at one and six weeks post-surgery and a brochure with basic information about free flap surgery. Patients were reviewed after six weeks with a survey containing non-standardised Likert scales and the Short-Form 12 Quality of Life Survey. This was compared to patients completing the survey after six weeks who were not shown photographs of donor-sites.

135 Jason K. Hsu The effectiveness of a sleep clinical pathway in an inpatient rehabilitation setting: a randomised controlled trial HSU J(1,2), Ng L(1,2) 1. The Royal Melbourne Hospital, 2. The University of Melbourne

Aim: To assess the effectiveness of a sleep clinical pathway in improving objective and subjective sleep quality in an inpatient rehabilitation setting. To determine if improvements in sleep quality improve rehabilitation outcomes and patient engagement. Background: Sleep is important for health, quality of life and general well-being yet sleep in rehabilitation patients is poorly studied and efficacious treatments are lacking. Poor sleep in hospitalized patients is common and can affect recovery, engagement, and prolong hospital stay. Methods: Musculoskeletal inpatient rehabilitation participants were recruited over four months and randomized into “usual care”, and “clinical pathway” groups. Outcome assessors were blinded to which arm the patient was allocated. Outcome measures include: Pittsburgh Sleep Quality Index (PSQI), Hopkins Rehabilitation Engagement Rating Scale (HRERS), Fatigue Severity Scale (FSS), Self-Rated Sleep Quality (SRSQ), and Actigraphy. Outcome measures and actigraphy were conducted within 72 hours of admission and again within 72 hours of discharge from the ward. Actigraphy was donned for 72 hours both after initial and final assessments as objective measures of sleep/wake status. Results: A total of 51 patients underwent randomisation, 29 to control, and 22 to intervention. The mean age for the control and intervention groups was 61.7±17.2 and 63.4±13.8 respectively. No significant differences between groups in any of the outcome measures except for less "Hours Spent in Bed" in the intervention group at -0.43 (95% confident interval [CI]; 0.24-2.99; P=0.022). As a cohort there were significant differences from admission to discharge both statistically and clinically in six of the outcome measures. PSQI (-2.31; 95% CI -3.33 to -1.30 P=<0.001), FSS (-8.75; 95% CI -13.15 to –4.34;

P=<0.001), HRERS-Physiotherapists (PT) (+1.37; 95% CI 0.51-3.17; P=0.037), HRERS-Occupational Therapists (OT) (+1.84; 95% CI 0.089-2.65; P=0.008), Hours Asleep (+0.833; 95% CI 0.098-1.57; P=0.05), and SRSQ (+0.824; 95% CI 0.35-1.30; P=0.001). Actigraphy results pending. Conclusion: Though there was no statistically significant difference between groups, the cohort as a whole improved both statistically and clinically. Participation in the study may have raised awareness regarding sleep variables and types of disturbances which may have contributed to the cohort improvements. Larger studies are needed to confirm these findings.

136 Zachary Smith Patient preferences for management of solitary pulmonary nodules with intermediate probability of malignancy SMITH Z, Gorelik A, Manser R The Royal Melbourne Hospital

Aim: To determine patient preferences for management of solitary pulmonary nodules with intermediate probability of malignancy and identify which patient factors influence these preferences. Background: Solitary pulmonary nodules are common radiological findings with a variety of benign and malignant aetiologies. Potential management options include surveillance imaging, minimally-invasive biopsy techniques or surgical resection, each of which entails differing risks and benefits. Current guidelines recommend that strategy selection incorporates patient preferences. Low-dose computed tomography screening programs for lung cancer, if introduced, would significantly increase indeterminate nodule detection rates. An improved understanding of patient preferences for pulmonary nodule management may contribute to evaluation of such screening programs and assist in clinical decision making. We therefore aimed to elicit patient preferences for management of intermediate-risk nodules and identify patient factors contributing to these preferences. Methods: We constructed a questionnaire to elicit patient preferences with input from relevant fields including respiratory, cardiothoracic surgery and radiology. This questionnaire was conducted using a trained interviewer format. Patients were recruited from Royal Melbourne Hospital inpatients and respiratory and sleep clinics. Secondarily, demographic information was collected from these patients to examine their influence on preferences. Data was analysed using SPSS version 23. Results: We interviewed 100 patients with an average age of 62.0 year. The majority (53.5%) prefer surgical management for nodules with 30% risk of malignancy, increasing to 77.7% at 50% risk of malignancy and 86.2% at 70% risk of malignancy. Even at 10% risk of malignancy, a significant proportion (21.2%) of patients still preferred surgical management. We found that these preferences may be influenced by gender, English speaking background and educational attainment. Age, gender, previous nodule status and smoking history were not significantly associated with varying preferences. Preferences were also influenced by the diagnostic yield for minimally-invasive biopsy. Conclusion: Our results indicate that many patients have a low threshold for preferring surgical management of indeterminate lung nodules with intermediate risk of malignancy. As well as informing clinicians of patient attitudes, this research may have impacts on healthcare development. If lung cancer screening programs are enacted in patient-centred clinical environments, excess morbidity and mortality caused by resection of benign nodules may partially offset the observed benefits of lung cancer screening program. Efforts will be needed to balance patient-centred care against an acceptable rate of benign

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resections. Although some demographic factors proved significant to patient preferences, further study is necessary to determine how various factors influence patient preferences.

137 Bridget King The accuracy of Lung cancer risk self-perception amongst patients who are current/previous smokers KING B(1), Steinfort D(1), See K(1). Aim: To determine the accuracy of lung cancer risk perception amongst patients who are current/previous smokers. Background: Lung cancer is leading cause of cancer mortality in Australia and has a low survival rate, primarily due to it frequently being diagnosed in the advanced stages. This creates a strong potential for a lung cancer-screening program with lose dose-computed tomography (CT). In order for screening to be effective, high-risk patients must be screened. However, those at high risk and therefore eligible for screening need to recognise this risk and present for voluntary screening. This study investigated the correlation between calculated lung cancer risk (and therefore eligibility for screening) and patient self-perceived lung cancer risk. Methods: A written questionnaire was administered to 88 past or current smokers aged 55-80, who had never been diagnosed with lung cancer. Participants were patients at The Royal Melbourne hospital from the General Respiratory clinic and the Monday (non-malignant) bronchoscopy list. Lung cancer risk was calculated according to the PLCOm2012 criteria and self-perceived risk was calculated according to 4 specific questions embedded in the questionnaire about the patient’s perceived risk. Results: It was found that 55.3% of patients who were eligible for screening considered themselves to be at increased risk for lung cancer, while 44.7% of patients who were eligible for screening did not recognise their elevated risk. 46.0% of patients who were not eligible for screening still considered themselves to be at increased risk for lung cancer, while 54.0% of patients who were not eligible for screening recognised their low risk. Overall, there was no statistically significant correlation between a patient's calculated lung cancer risk and their perceived lung cancer risk. Conclusion: While further investigation with a greater sample size is required in this area, the results indicate that there are a proportion of previous/current smokers who are at high-risk for lung cancer who fail to recognise this risk. If a lung cancer-screening program were to be implemented, there would be a need to target these patients to improve knowledge in regards to risk perception, in order to motivate them to present for screening.

138 Starling Sim Viral respiratory tract infections in allogeneic haematopoietic stem cell transplant recipients SIM SA(1,4), Leung V(1), Ritchie D(2), Teh BW(3), Sullivan S(1,4) (1) WHO Collaborating Centre for Reference and Research on Influenza, Victoria, Australia (2) Department of Haematology, Melbourne Health, (3) National Centre for Infections in Cancer, Victoria, Australia (4) University of Melbourne

Aim: The objectives of this study were to assess the epidemiological characteristics, risk factors, and outcomes of vRTI in allogeneic haematopoietic stem cell transplantation (alloHSCT) in the era of molecular testing. Background: Viral respiratory tract infections (vRTI) are a significant cause of morbidity and mortality in immunocompromised patients, especially patients undergoing alloHSCT. The diagnosis of respiratory viruses, especially in older studies was mainly dependent on non-molecular diagnostic methods which are limited by poor sensitivity and high false negative results. Molecular testing by multiplex

polymerase chain reaction (PCR) is now the current standard of practice in clinical settings. Methods: This study was a cross-sectional study, which involved a retrospective medical record review of adult patients admitted for alloHSCT at Royal Melbourne Hospital from January 2010 to December 2015. Uniform data were collected including: underlying disease, conditioning therapy, type of transplant, previous therapy, clinical presentation, and outcomes (intensive care unit [ICU] admission, death) for first 100 days post-transplant. Viruses included in the multiplex PCR were respiratory syncytial virus (RSV), influenza type A and B, and rhinovirus. Logistic regression was used to identify risk factors for vRTI. The risk of death or ICU admission by vRTI status was estimated using Kaplan-Meier analysis. Results: 387 alloHSCT patients were included in this study. There were 65 episodes of vRTI identified in 56 patients (14.5%). Rhinovirus accounted for the majority of infections (70.8%), followed by RSV (15.4%) influenza type A (10.8%) and B (3.1%). A majority of episodes presented initially with upper respiratory tract infections (58.5%). 11 episodes (16.9%) resulted in ICU admission. Five patients died within 100 days post rhinovirus infection but no deaths were attributable to infection. On univariable and multivariable analysis, only previous autologous haematopoietic stem cell transplant increased the risk for vRTI (OR=2.1, 95% CI=1.0-4.2). The risk of death (p=0.4) or ICU admission (p=0.7) 100 days post-transplant was not significantly different by vRTI status. Conclusion: vRTI is common in the first 100 days post-alloHSCT but its impact on mortality appears limited.

139 Robert McCubbin Implementation and evaluation of a new whole of hospital sepsis pathway at the Royal Melbourne Hospital MCCUBBIN R(1), Gasparini D(1), Sykes K(2), Vasquez T(2), Smallwood D(2), Thursky K(3,4), together with the RMH sepsis working party 1 - University of Melbourne, 2 - Royal Melbourne Hospital, 3 - Doherty Institute, 4 - Peter MacCallum Cancer Centre

Introduction: Sepsis is a life-threatening dysregulated response to infection resulting in organ dysfunction. Globally, 31.5 million cases of sepsis and 5.3 million deaths from sepsis are estimated to occur annually. Best practice care for patients requires early recognition and assessment, and prompt management. A clinical pathway for sepsis diagnosis and management was implemented as a whole of hospital pathway at Royal Melbourne Hospital. This project aims to evaluate the impact of the pathway. Methods: The pathway was introduced in the cancer wards in 2015 but was modified for ED and general inpatient ward use. It was piloted in three inpatient wards between November 2016 and January 2017, before a phased rolled out to all hospital wards between 31st Jan and end of March 2017 (except ICU). The clinical pathway consists of a paper medical record form with criteria to alert nursing and medical staff to possible sepsis and a standardised management protocol. Implementation was supported by, education and discussion sessions for all medical and nursing staff, department heads and a hospital awareness campaign. The results of the clinical pathway implementation has been compared to historical data collected in ED in 2016, although detailed pre and post interventions data collection is underway Results: Between 30 January 2017 and 24 May 2017, 506 patients (83% from ED) received care guided by the clinical pathway for sepsis. For these patients 91.7% (n=484) had lactate collected and 83.8% had two or more blood cultures collected (n=462). Median time to antibiotics in ED for patients managed with the pathway was 62.5 minutes (n=312) compared to 122 minutes (n=156) in historical controls,

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representing a 48.8% reduction. Final statistical analysis will occur following termination of data collection on 1 June 2017. Conclusions: The early results demonstrate a trend of improved appropriateness of care for patients managed with the sepsis pathway. Further statistical analysis is needed to accurately assess the impact of the clinical pathway. The results of this study indicate that a multidisciplinary approach to the management of sepsis is important in achieving results, but that a sustainable model of care needs to be established.

140 Dominic Gasparini Implementation and evaluation of a clinical pathway for sepsis GASPARINI D(1), McCubbin R(1), Sykes K(1), Smallwood D(1), Vasquez T(1), Thursky K(1,2) (1) Melbourne Health, (2) Peter MacCallum Cancer Centre

Aim: To describe the implementation of a clinical pathway for sepsis and evaluate its impact on patient outcomes. Background: Sepsis is a life-threatening dysregulated response to infection resulting in organ dysfunction. Globally, 19.4 million cases of sepsis and 5.3 million deaths from sepsis are estimated to occur annually. Early and appropriate management can reduce the risk of death and morbidity from sepsis. In 2017, a whole-of-hospital clinical pathway for sepsis diagnosis and management was implemented at Melbourne Health. Methods: The pathway was introduced in the haematology and oncology wards in 2015 and was modified for use in other hospital departments. It was piloted in three inpatient wards between 7 November 2016 and 29 January 2017, before a phased rolled out to all hospital wards except the intensive care unit (ICU) between 30 January and 20 March 2017. The clinical pathway consists of a paper medical record form with criteria to alert nursing and medical staff to possible sepsis and a standardised management protocol. Implementation was supported by education and discussion sessions for all medical and nursing staff, department heads and a hospital awareness campaign. Preliminary comparisons on the impact of the program have been made using coding data and historical audit data from 2016, although detailed data collection is underway. Results: Between 30 January 2017 and 24 May 2017, 506 patients received care that was guided by the sepsis pathway. Eighty-three percent of patients were in ED. The mortality rate for patients managed with the sepsis pathway was 8.7% (n=361) compared with 13.6% in historical controls. Average length of hospital stay was reduced in patients managed with the sepsis pathway (6.6 days [n=330] vs 8.8 days) and the percentage of patients with sepsis admitted to the ICU was lower in patients managed with the pathway (8.0% [n=330] vs 12.1%). Further data collection and statistical analysis are ongoing. Conclusions: The early results demonstrate a trend of improved patient outcomes for patients managed with the sepsis pathway. Further data collection and statistical analysis are needed to accurately assess the impact of the clinical pathway. The results of this study support a multidisciplinary approach to the management of sepsis.

141 Tim Shaw Gene Control to Major TOM: “Your circuit’s dead, something’s wrong: the CAT’s is out and ROS turned on.” SHAW T(1,3), Peel A (2,3) Victorian Infectious Diseases Reference Laboratory (1); Scram Software(2); NucleopharmGT(3)

Background: As similarities between evolved (genetic) and engineered (computational) control networks become

increasingly evident, the idea that multicellular eukaryotes behave like super-efficient computer networks is becoming generally accepted. Complex computational networks need integrated power supplies that satisfy the opposing demands of stability and rapid adaptability. Mitochondria, the cytoplasmic organelles that power most eukaryotic cells by supplying ATP generated by oxidative phosphorylation, sense energy demand by integrating signals from multiple metabolic inputs and respond by modulating their numerous outputs accordingly. Most mitochondrial genes have been transferred to the nucleus during billions of years of evolution of mitochondria from bacterial endosymbionts. These genes must be expressed in correct temporal sequences and their processed transcripts must be translated by cellular ribosomes. A large majority their promoter sequences are contained within GC-rich ("Gene Control") islands, allowing combinatorial control of their expression by reversible epigenetic modifications which include methylation, deamination and, (most significantly), oxidation. Newly synthesised proteins are imported into mitochondria via an evolutionarily conserved protein complex called the major translocator of the outer mitochondrial outer membrane (Major TOM). Mitochondrial respiration produces the highly reactive and potentially harmful superoxide anion as a by-product. The enzyme superoxide dismutase (SOD) detoxifies superoxide, producing hydrogen peroxide, an essential signalling molecule which is also potentially damaging, since in the presence of iron ions, it may be used to generate a variety of reactive oxygen species (ROS) via the Fenton reaction. Excess hydrogen peroxide induces the expression of catalase (CAT), which reduces it to water. The concerted activities SOD, CAT and associated antioxidants normally operate as a dynamic self-organising network that acts via redox-sensitive transcription factors to ensure that mitochondria are supplied with essential proteins. Highly Optimised Tolerance (HOT) describes the operation of complex networks of this type. Aim and Methods: To produce a metabolic flux model of the mitochondrial HOT-TOM-CAT circuitry using published biochemical and genetic data and to design testable electronic and mathematical analogues of this model. Results and Conclusion: Models that have the potential to be tested theoretically by computer simulation and experimentally using hard-wired circuitry were constructed. Consistent with experimental observations, they predict that mitochondrial power generation is rapidly adaptable and robust (HOT) except when demand exceeds normal by a very large factor and/or for prolonged times. Under these conditions the network will shut down or fail completely. Catalase activity and the ironic Fenton reaction are predicted to play opposing roles in the shutdown “decision” process.

142 Tim Shaw The innate natural gen(e)ius of the acytota: An obverse C-Value paradox SHAW T(1,3), Peel A (2,3) Victorian Infectious Diseases Reference Laboratory (1); Scram Software(2); NucleopharmGT(3)

Background: Parallels between evolved (genetic) and engineered (computational) control networks have become increasingly evident and most computer scientists are acutely aware of the superiority of evolved control systems, which are capable of amazingly stable and robust performance even in extreme environments. Synthetic biology, which is devoted to the study of complex biological control systems, aims to design engineered systems that can emulate them and conversely, to engineer genetic control systems that can control the biota. In this context, an intriguing biological problem that is often overlooked is the C-value paradox: the lack of correlation between genome size and organismal complexity. Although,

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with the advent of whole genome sequencing, some non-coding “junk” DNA has been shown to be involved in sophisticated genetic control networks – why is there so much of it in most genomes? The genomes of the Acytota (the domain of cell-free replicons, including viruses, plasmids, bacteriophages, viroids and virusoids) pose the opposite problem. Although only “alive” when provided with a suitable cellular environment, they comprise an overwhelming majority of the biosphere’s genetic reserve and have vastly greater influence on biological processes than expected from their minimal coding capacity. Aims and Methods: The structure and behaviour of the smallest genome known to be capable of semi-autonomous replication - the Rice Yellow Mottle Virus Satellite (RYMVS) was examined in detail from a control systems perspective, with the aim of developing the simplest possible model of a biological nano-computer. Results and Conclusion: Modelling using a variety of computational resources shows that RYMVS can respond in an “intelligent” way to its micro-environment, as we show by hierarchical decision chart. The genome structure is predicted to be sensitive to redox potential, pH and ionic strength such that the rate of change of these parameters determines whether it will replicate, transcribe or translate. Similarly, the translated peptide product is predicted to be responsive to its micro-environment, which will determine whether it behaves like a transcription factor to promote or suppress RNA-dependent RNA polymerase activity, to inhibit or promote RYMV's ribozyme activity, or to insert into membranes where it may aggregate to form transmembrane ion channels. The passage of ions through these channels is predicted to modulate RYMV directed activities by altering its genome structure. Although viroids and virusoids are thought to be exclusively botanical phenomena, these observations also have relevance to control mechanisms in animal cells, particularly neurons, which harbour a multitude of small circular RNAs.

143 Blake Smith Development of mouse models for Dominant Dystrophic Epidermolysis Bullosa Smith, BRC(1), Kern JS(2), Varigos GA(2), Pang KC (1) 1 Murdoch Childrens Research Institute, Royal Children's Hospital and University of Melbourne; 2 Dept of Dermatology, Royal Melbourne Hospital

Background: Epidermolysis Bullosa (EB) is a group of genetic conditions that affect anchoring proteins within skin. Mutations in the collagen VII (Col7a1) gene lead to some of the more severe forms of EB known as Dystrophic Epidermolysis Bullosa (DEB), which can be inherited in either a dominant (DDEB) or recessive manner. For DDEB, mutations commonly involve glycine substitutions within the collagen VII triple helical domain, which leads to problems with anchoring fibril assembly, reduced triple helix stability, and ultimately increased skin fragility and blistering that can be life-long. Having a mouse model that successfully recapitulates DDEB would greatly facilitate the development of novel therapies for this disorder, but currently there are no such models for DDEB. Aim: To create mouse models of DDEB. Methods: Traditionally, generating a new mouse model for a human disease presents many challenges, since it requires significant investment of time, effort, and money with no guarantee of phencopying the intended disease. Recently, the ease of generating genetically-modified mice has dramatically increased with the advent of a new technology, known as CRISPR-mediated genome editing. Using an online database of human DDEB mutations, we identified the two most common Col7a1 mutations responsible for DDEB, and then used CRISPR technology to introduce these mutations into the genomes of early stage mouse embryos.

Results: From the resultant mice, we simultaneously generated several new mouse strains that appear to directly model DDEB. As planned, we created two strains, each of which carries a mutation within the tropical helical domain that is directly analogous to the most frequently occurring Col7a1 human mutations responsible for DDEB. Both strains show a dominantly inherited blistering phenotype that is evident from birth, thus mimicking humans with the same mutations. By serendipity, a number of other Col7a1 mutant strains were generated as by-products of the CRISPR-mediated genome editing process and were subsequently found to contain small in-frame deletions within Col7a1. Observations of these mice also revealed a dominantly inherited blistering phenotype. Conclusion: Based on the genomic data of DDEB patients, we have created new mouse models of DDEB. These models phenocopy the human disease and should aid in the development of new therapies for the condition.

144 Catherine Beard Neurofibromatosis Type 1: The nexus between general and cancer genetic counselling BEARD C(1), Winship I(1,2) (1) Genomic Medicine and Familial Cancer Centre, Royal Melbourne Hospital; (2) Office for Research, Royal Melbourne Hospital

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition, with an incidence of around 1 in 5,000. Features of NF1 can include multiple neurofibromas visible on the skin, café au lait macules, scoliosis, mild learning disability, high blood pressure, as well as optic nerve pathway and brainstem gliomas, breast cancer and phaeochromocytoma. While NF1 is highly penetrant, it displays variable expression. Around 50% of NF1 cases are the result of a de novo mutation. Because NF1 can present with benign and cancerous tumours, as well as features affecting an individual’s quality of life, genetic counselling for NF1 requires counselling skills utilised in both general and cancer genetic settings. The genetic counselling challenges encountered in NF1 cases are compounded by the condition’s variable expression, with some families experiencing an unusually heightened penetrance of cancer, compared with mutation positive individuals who don’t meet clinical criteria for a diagnosis of NF1. We have used three NF1 cases to highlight these genetic counselling challenges, which include grief and loss, the emotionally charged question ‘why me?’, cancer anxiety, guilt over the limited expression of NF1 in a mother compared to her more severely affected children, the experience of a diagnostic odyssey and the impact of NF1 on quality of life.

145 Charlotte Slade Primary antibody deficiencies in Victorian adults: Past experience, current Insights and a vision for the future Slade CA(1,2,3*), Bosco JJ(4*), Binh Giang T(1,2), Kruse E(2,3), Stirling RG(4), Hore-Lacy F(4), Cameron PU(5), Sutherland MF(6), Barnes SL(7), Holdsworth SR(7), Unglik GA(1), De Luca J(1), Patel M(1), Spriggs K(1), Tran Y(1), Au Yeung P(1), Nicholls 1. Department of Clinical Immunology and Allergy, The Royal Melbourne Hospital 2. Immunology Division, The Walter and Eliza Hall Institute for Medical Research 3. Department of Medical Biology, The University of Melbourne 4. Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital 5. Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne 6. Department of Respiratory and Sleep Medicine, The Austin Hospital 7. Departments of Medicine, and Allergy and Immunology, Monash Medical Centre 8. School of Medicine, The University of Melbourne 9. Department of Immunology and Pathology, Central Clinical School, Monash University * These authors contributed equally to this work.

Aim: To describe the clinical features of adult patients in Victoria with Primary antibody deficiency disorders (PADs). Background: Primary immunodeficiencies (PIDs) are complex disorders with heterogenous clinical phenotypes. Primary antibody deficiencies (PADs) are the most common PID type in adult cohorts worldwide and are often under-recognised

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leading to delayed diagnosis and potentially end-organ damage such as bronchiectasis. In addition, these conditions are frequently accompanied by comorbid autoimmune disease, and increased risk of malignancy. Methods: We identified adult patients with a diagnosis of PAD at four major Victorian hospitals, and retrospectively characterised the clinical and diagnostic features, and where possible, implemented therapies. Results: 153 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre, consented to review of their clinical records. Of the cohort, 81(53%) were female, and their current ages ranged from 15-87 years, with a median of 45 years. The most frequent antibody deficiencies were Common Variable Immunodeficiency (CVID) in 109 (71.2%) and X-linked agammaglobulinaemia (XLA) in 15 (9.8%). 10 had specific antibody deficiency (6.5%) and another 10 were diagnosed with hypogammaglobulinaemia without further classification. Other diagnoses were combined immunodeficiency, in 7 patients, including 4 patients with Good Syndrome, and disorders of immune dysregulation in 3. The IgG at diagnosis for CVID compared to unspecificied hypogammaglobulinemic patients was not significantly different (4.45±3.4 g/L versus 5.25±0.92 g/L) while the IgA levels were significantly different (0.32±0.36 versus 0.89±1.07 g/L, p=0.002). Overall, diagnosis was later in females with a median age at diagnosis of 38.5 years, compared with a median age of 20 in males, 30 when XLA was excluded from analysis). The median diagnostic delay was 8 years for females and 6 years for males, with no sex difference when XLA was excluded. Patients with a molecular diagnosis experienced a shorter median diagnostic delay of 5 years. Respiratory tract infections were the most common clinical manifestation (144 of 153 patients). Radiological bronchiectasis was detectable in 40 patients. Of those patients in whom the clinical phenotype was well-defined, 60 of 103 (58.3%) had features of immune dysregulation. Conclusions: Our data are consistent with the experience of other centres internationally, however there is a longer diagnostic delay and higher proportion of immune dysregulation, which is particularly challenging both diagnostically and therapeutically. It is likely that these challenges will be in part overcome by continued advances in diagnosis of genetic causes of PADs, and with that opportunities for personalised medicine.

146 Mi Vu Brooke-Spiegler Syndrome: the impact of rare disease VU M(1), Duong B(2), Walsh M(2), Winship I(2,3) 1. Dermatology Department, The Royal Melbourne Hospital. 2. Clinical Genetics, The Royal Melbourne Hospital. 3.Department of Medicine, The University of Melbourne, The Royal Melbourne Hospital

Brooke-Spiegler syndrome is a rare inherited disorder characterised by combination of multiple benign adnexal neoplasms including trichoepitheliomas, cylindromas and spiroadenomas. The assessment, diagnosis and management of patients with BSS is often complex requiring a multidisciplinary team approach. We report two cases of BSS with novel CYLD mutations. A 24-year-old male Somalian refugee presented with extensive centro-facial lesions with no family history of similar lesions. Histology confirmed the clinical diagnosis of a benign trichoepithelioma. CYLD testing was requested with sequencing of exons 9-15 which identified a novel truncating CYLD variant (NM_015247.2:c.1599dupT, p.Val534Cysfs*9). A 41-year-old Caucasian female presented for evaluation of multiple facial papules and nodules on the scalp and trunk. There was a family history of similar lesions. Ten core biopsies

of the face were previously taken with histology confirming nine as cylindromas and one as a trichofolliculoma. Sequencing and copy number analysis of CYLD was requested which showed the patient carried a novel heterozygous deletion of CYLD (NM_015247.2) exon 15. Despite varying phenotypic load, owing to the visible disfigurement both patients faced discrimination with considerable impact on their self-esteem and quality of life. Timely diagnosis of BSS may improve the therapeutic management to minimise complications and monitor for malignant transformation.

147 Gita Soraya An impedance sensor for sensitive and label-free detection of PfHRP2 in saliva: implications for point-of-care use in malaria elimination SORAYA, GV (1,5), Abeyrathne CD (2,3), Buffet C (1,4), Hyunh DH (2,3), Chan J (1), Skafidas E(2,3), Kwan P (1,3), Rogerson S (1,4) (1) Department of Medicine (RMH), The University of Melbourne (2) Centre for Neural Engineering, The University of Melbourne (3) Department of Electrical and Electronic Engineering, Melbourne School of Engineering, The University of Melbourne (4) The Peter Doherty Institute for Infection and Immunity (5) Faculty of Medicine, Hasanuddin University, South Sulawesi,Indonesia

Background and Aim: Detection of very low-density malaria infection is essential for malaria elimination, but current diagnostics are insensitive and/or costly. We aim to develop a point-of-care, impedance based sensing platform for detection of plasmodium falciparum histidine-rich protein 2 (PfHRP2) at subclinical levels for applications in malaria elimination. To do this we aim to detect the target protein at levels three logs lower than conventional malaria rapid diagnostic tests (RDTs), and two logs lower than next generation IDTs (Infection Detection Tests). Methods: Planar interdigitated microelectrodes (IDEs) were fabricated using UV-lithography with additional SiO2 deposition, and surface modification was achieved through APTES-Glutaraldehyde functionalization. PfHRP2 capture was performed through solid-state binding of the target to surface immobilized Anti-PfHRP2 IgG. Electrical measurements were performed before and after 1-2 hour incubation of the sample, using a signal generator and lock-in-amplifier setup. Frequency-dependent changes in output voltage and phase obtained through the setup were used to extract the electrical impedance parameters occurring during the detection process. Protocol optimization, platform sensitivity and specificity were first assessed using recombinant PfHRP2 in PBS, and then adapted for use in PfHRP2 spiked saliva samples. Results: The optimal IDE gap size for the PfHRP2 detection is 8 μm, with optimal detection frequency in the range of 20-50 Khz. The lower limit of detection of the platform is 2.5 pg/mL PBS with 1-hour incubation. This protocol was then tested on crude saliva samples spiked with 2.5 pg/mL of PfHRP2. Using only filtering as pretreatment of the saliva samples, the platform can distinguish between 2.5 pg/mL PfHRP2 in saliva with negative saliva samples. For this purpose, the most dominant parameter of distinction is change in the impedance magnitude (%∆Z) of the sensor (p=0.0022, Mann-Whitney U Test, n=6 sensors per group) and change in resistance (%∆Rs) of the sensor (p=0.0022, Mann-Whitney U Test, n-6 sensors per group). A 2-hour incubation period was required for detection of PfHRP2 in saliva. Conclusions: The impedance based IDE sensing platform shows sensitivity suitable for the detection of PfHRP2 at subclinical levels of 2.5 pg/mL otherwise undetectable using RDTs. In addition, sensitivity is not compromised when detection is performed in crude saliva samples. The low cost and ultrasensitive nature of the platform in addition to the non-invasive premise of PfHRP2 detection in saliva shows potential for implementation in malaria elimination settings. Further

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development is required to integrate the sensing platform into a point-of-care device.

148 Vivian Leung Antibody response and influenza-like illness among healthcare workers after influenza vaccination LEUNG V(1), Aban A(1), Carolan L(1), Laurie K(1), Druce J(2), Slavin M(3), Marshall C(3,4), Sullivan S(1,5,6) 1 WHO Collaborating Centre for Reference and Research on Influenza; 2 Victorian Infectious Disease Reference Laboratory; 3 Victorian Infectious Disease Service, Royal Melbourne Hospital; 4 Infection Prevention and Surveillance Service, Royal Melbourne Hospital; 5 Department of Epidemiology, University of California, Los Angeles, USA; 6 School of Population and Global Health, University of Melbourne

Aim: To compare antibody response and the frequency of influenza-like illness (ILI) among HCWs by vaccination history. Background: Annual seasonal influenza vaccination is recommended for health care workers (HCW). However, recent studies of vaccine effectiveness have reported a reduction in serological response among repeat vaccinees. Methods: A prospective serosurvey was performed at the Royal Melbourne Hospital in Victoria, Australia. Influenza antibody titres were measured pre-vaccination, post-vaccination and post-season. HCWs were monitored weekly for the development of ILI during the influenza season. Estimated geometric mean titres (GMTs) and geometric mean fold ratios (GMRs) by the number of vaccinations received in the past 5 years were calculated. Results: Of the 190 HCWs enrolled, 157 completed the study. All HCWs demonstrated an increase in post-vaccination GMTs against the four vaccine strains. The rise in titres for all vaccine strains among vaccine-naïve HCWs were significantly greater than increases observed for HCWs who received between 1 and 5 prior vaccinations (p<0.001, respectively). The largest post-vaccination rise was observed among vaccine-naïve HCWs against A/H1N1pdm09 (GMR 16.5, p<0.001). Post-season GMTs were maintained for A/ H1N1pdm09 and A/H3N2. However, there was a significant decline in GMTs post-season for both B lineages. Sixty five (41%) HCWs reported at least one ILI episode, with 6 (4%) identified A/H3N2-positive. Conclusion: All HCWs in our study demonstrated protective antibody titres post-vaccination. There were no clear trends between the number of prior vaccinations and post-vaccination response. However, these preliminary findings suggest greater post-vaccination responses among vaccine-naïve HCWs.

149 Michael Richards Improving uptake of national guidelines for antibiotic prophylaxis in Australia: impact of performance feedback on surgical site infection rates Bull A1, Worth L1,2, Spelman T1, RICHARDS R1 1 Victorian Healthcare Associated Infection Surveillance Coordinating Centre, Doherty Institute 2 Department of Medicine, University of Melbourne

Surgical antibiotic prophylaxis (SAP) has been demonstrated as an effective intervention to reduce surgical site infections (SSI) following a broad range of surgical procedures. SAP data have been collated since 2003 as part of routine surveillance for SSIs in Victoria, Australia. Compliance with SAP measures is assessed against national guidelines and fed back to participating hospitals for local quality improvement alongside infection rates via a secure online portal. Routinely captured SAP and SSI surveillance data for the period 1 January 2003 to 31 December 2015 were retrospectively analysed. Compliance assessment: Antibiotic choice – assessed as optimal (concordant with guidelines) or adequate (not exactly concordant but will cover the expected range of pathogens) Antibiotic timing - timing of administration (first dose) was assessed as concordant with guidelines if administered within

60 minutes prior to surgical incision (except for vancomycin). Vancomycin was considered concordant if the infusion started at least 30 minutes prior to the procedure. Duration – Duration was considered concordant if all prophylaxis ceased within 24 hours of the procedure. Note: If more than one antibiotic was given, the assessment for each measure was only considered concordant if each antibiotic was administered correctly. Association of risk for SSI with non-compliance for antibiotic prophylaxis was assessed using logistic regression clustered on the patient using SSI (all infections meeting definition of superficial, deep or organ space infection) as the outcome variable. A total of 144,075 procedures were analysed. Significant annual improvement was demonstrated in both optimal and adequate categories for antibiotic choice for all procedure groups analysed: major cardiac surgery, colorectal surgery, hip/knee arthroplasty, cholecystectomy and hysterectomy. The annual Odds Ratio (OR) for receiving optimal choice of prophylaxis (all procedures) was 1.13 (95% CI 1.12-1.13, p value <0.001). There was an annual increase in the OR for all groups when tested individually and in each case the p value was highly significant. An increased risk of SSI was demonstrated where antibiotic choice was inadequate and timing was not compliant with guidelines (OR 1.33, 95% CI 1.24 – 1.43) when all procedures were analysed together. Analysed separately, SSI risk was higher for all groups except cardiac (no association). The trend was not statistically significant for hysterectomy and cholecystectomy. We demonstrated sustained improvements in compliance with national guidelines for SAP following routine data collation and feedback of results. We also demonstrated inadequate antibiotic selection and non-compliant timing of administration was associated with an increased risk of infection.

150 Matthew Richards Resolution of a vanA VRE outbreak with no change in vanB VRE RICHARDS M(1), Williams K(1), Hobbs L(1), Marshall C(1) (1) Melbourne Health

Introduction: During an outbreak of vanA vancomycin-resistant enterococcus (VRE) in our intensive care unit (ICU) and cardiothoracic surgery ward (CTW), multiple infection control interventions were put in place resulting in resolution of the outbreak, yet we continued to have high rates of vanB VRE despite these measures. Method: A multi-faceted approach to containing this outbreak included: reinforcement of transmission based precautions, hand hygiene and compliance with cleaning. Additionally other strategies were introduced such as chlorhexidine body washes. Admission, discharge and weekly rectal swabs for VRE screening were commenced in ICU and CTW and from which vanA and vanB VRE incidence and prevalence were determined. Results: Between June 1 2015 and May 31 2016, 1452 VRE screening swabs were obtained. Of these, 81 (5.6%) were vanA VRE positive and 207 (14.3%) vanB VRE positive. There was no significant change in the incidence of vanB VRE whereas vanA VRE incidence peaked in October 2015 at 21 (11.3%) and then dropped to zero within the same timeframe. Conclusion: Despite there being uniform management strategies implemented, there were distinct differences in the way in which each VRE type responded. This suggests that vanA VRE was amenable to control interventions and whereas vanB VRE was not.

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151 Mary Qian Utility of individualised patient breathlessness plans for refractory dyspnoea due to advanced chronic obstructive pulmonary disease – qualitative review of patients’ perceptions QIAN MYY(1), Politis J(1), Thompson M(1), Le B(2), Irving L(1), Smallwood N(1) (1) Department of Respiratory Medicine, Royal Melbourne Hospital; (2) Department of Palliative Care, Royal Melbourne Hospital

Background: Up to 98% of patients with advanced chronic obstructive pulmonary disease (COPD) experience distressing breathlessness. As the management of refractory breathlessness is complex, written individualised patient breathlessness plans (PBP) may improve compliance and thus reduce episodes of dyspnoea crisis. Aim: To assess the efficacy of, and COPD patients’ views towards, individualised patient breathlessness plans. Here we report the findings regarding patients’ perceptions. Methods: An individualised PBP, dyspnoea education from a respiratory physician and a handheld fan were offered to patients with severe COPD and refractory breathlessness attending the Advanced Lung Disease Clinic at The Royal Melbourne Hospital. Efficacy of and patients’ perceptions regarding the PBP were assessed after six weeks. A standardised, semi-structured telephone interview script was used to record patient perceptions. Results: Thirty-two patients participated, with mean age 74.3 years and 20 (62.5%) female. Mean FEV1 was 0.7L (37% predicted), DLCO 33% predicted and 25 (78%) patients used domiciliary oxygen therapy. Mean MMRC breathlessness score was 3.6 and 17 (53%) patients were on opioids for breathlessness. The mean number of hospital admissions in the preceding 12 months was 2.2. Overall there was a significant improvement in subjective breathlessness scores. Nine of the 32 patients completed qualitative interviews. All patients found the initial clinical contact and written resources useful, and valued the intervention. Eight of the 9 patients had previously completed pulmonary rehabilitation, however for most patients the breathlessness management information was new. Respondents reported utilising the self-management information to adopt new practices and change daily routines, with the use of a handheld fan and regular practice of breathing training exercises both perceived as being highly beneficial. The need for short (under 30 minutes), repetitive breathlessness education sessions, with specific reinforcement of coping strategies, was highlighted by respondents as being important for translating education into routine practice and to overcome dyspnoea crises. Conclusion: This pilot study of individualised breathlessness plans in patients with severe COPD, refractory breathlessness and multiple admissions despite previously optimised treatment, is the first study to demonstrate reduced dyspnoea scores, behavioural change and high levels of patient satisfaction.

152 Sandeep Prabhu A comparison of the electrophysiologic and electroanatomic characteristics between the right and left atrium in persistent atrial fibrillation: Is the right atrium a window into the left? PRABHU S(1,2,3,4), Voskoboinik A(1,2,3,4), McLellan AJA(2,3), Peck KY (2) Pathik B (1,4), Nalliah CJ (1,4), Wong GR(1,4), Azzopardi SM(2,3), Lee G(1), Mariani JA (2,3), Ling LH (2,4), Taylor AJ(2,3) Kalman JM(1,4), and Kistler PM(1,2,4) 1. Melbourne Health, 2. Alfred Health, 3. Baker Heart and Diabetes Institute, 4. University of Melbourne

Aim: To determine the extent to which the electrical structural remodelling associated with persistent AF occurring in the right atrium (RA) is representative of changes occurring in the left atrium (LA). Background: The RA is readily accessible however it is unclear whether changes in the RA are representative of the LA, accessible only via transseptal. We performed detailed bi-atrial electro-anatomic mapping to determine the electrophysiological relationship between the atria Methods: Consecutive patients with persistent AF underwent detailed high density bi-atrial electro-anatomical mapping with a contact force catheter acquiring points with >10g prior to ablation. Points were analysed offline for tissue voltage (bipolar and unipolar), complex electrograms, low voltage (bipolar<0.5mV), scar (bipolar<0.05mV) and conduction velocity (CV). Results: 40 patients (mean age 59 ± 9.2yrs, AF duration 12.9 ± 9.2 months, LA area: 28 ± 5.2, RA area: 25 ± 6.4mm2, LVEF: 44 ± 15%) underwent mapping (number of points: LA 220 ± 66 vs RA 216 ± 54, p=0.76) during CS pacing. Bipolar voltage (R=0.57, p<0.001), unipolar voltage (R=0.68, p<0.001), low voltage (R=0.48, p=0.002), fractionation (R=0.73, p<0.001) and CV (R=0.49, p=0.001) correlated well between the atria. No difference existed in bipolar voltage (LA 1.89 ± 0.77 vs RA 1.77 ± 0.57 mV, p=0.57); complex electrograms (LA 20% vs RA 20%, p=0.99) or low voltage (LA 15% vs RA 16%, p=0.84). Unipolar voltage was higher in the LA compared the RA (2.95 ± 1.14 vs 2.28 ± 0.65 mV, p=0.002) and CV significantly slower in the RA compared the LA (0.93 ± 0.15ms-1 vs 11.01 ± 0.19ms-1, p=0.001). Conclusions: AF is associated with remodeling processes affecting both atria. The more accessible RA provides a window into the bi-atrial remodeling associated with AF in various disease states without transseptal access.

153 Sandeep Prabhu Systolic heart failure is associated with more advanced bi-atrial substrate and electrical remodelling independent of AF duration in persistent AF PRABHU S(1,2,3,4), Voskoboinik A(1,2,3,4), McLellan AJA(2,3), Peck KY (2) Pathik B (1,4), Nalliah CJ (1,4), Wong GR(1,4), Azzopardi SM(2,3), Lee G(1), Mariani JA (2,3), Ling LH (2,4), Taylor AJ(2,3) Kalman JM(1,4), and Kistler PM(1,2,4) 1. Melbourne Health, 2. Alfred Health, 3. Baker Heart and Diabetes Institute, 4. University of Melbourne

Aim: To determine the impact of systolic heart failure upon the atrial substrate, in the setting of persistent AF and heart failure (HF). Background: AF and heart failure (HF) frequently coexist however, the contribution of HF to the biatrial substrate in persistent AF (PeAF) is yet to be determined. We aimed to characterise the bi-atrial substrate in HF and PeAF Methods: Consecutive patients with PeAF and either normal LV (NLV) function (LVEF>55%) or idiopathic cardiomyopathy (LVEF≤45%) undergoing AF ablation were enrolled. In AF, pulmonary vein cycle length (PVCL) was measured in each PV for 100 consecutive cycles. Following DCR and prior to ablation, high-density bi-atrial electro-anatomic (EA) mapping was performed during CS pacing with a contact force enabled catheter (CARTO), including the pulmonary venous antrum in the LA. Complex electrograms, voltage, scarring and conduction velocity were assessed. Results: (See table) 40 patients, 20 patients with HF (mean age: 59±7 yrs, AF duration 14±11 months and LVEF: 32 ± 7.3%) and 20 with NLV (mean age: 57±10 yrs, AF duration 14±9 months, p=0.97 and mean LVEF: 60±4%, p<0.001) underwent bi-atrial EA mapping. HF was associated with a significant reduction in tissue voltage in the right (Bipolar, HF vs NLV: 1.49 ± 0.39 vs 2.13 ± 0.75, p=0.002; Unipolar, 1.93 ±

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0.50 vs 2.67 ± 0.84, p=0.003) and left atrium (Bipolar, HF vs NLV: 1.54 ± 0.68 vs 2.28 ± 0.75, p=0.001; Unipolar, 2.36 ± 0.92 vs 3.58 ± 1.07, p<0.001) with greater bipolar voltage variability (co-efficient of variation [CV] SD/mean) (RA: 0.79 ± 0.11 vs 0.70 ± 0.11, p=0.013; LA 0.75 ± 0.15 vs 0.61 ± 0.07, p<0.001). HF was also associated with significantly more fractionation (LA: 29% vs 9%, p<0.001, RA: 28% vs 11%, p<0.001) and low voltage (<0.5mV) (LA: 23% vs 6%, p=0.002; RA: 20% vs 11%, p=0.006) in both atria, and scarring (<0.05mV) in the LA (p=0.01). Remodelling in HF was worse the posterior and PV antral regions with respect to tissue voltage (p<0.001), complex electrograms (p<0.001), low voltage (p<0.001, p=0.012 respectively) and the presence of scar (p=0.005, p=0.006 respectively). HF was associated with a slower average PVCL (185 vs 164ms, p=0.016), which correlated significantly with PV antral bipolar voltage (R=-0.62, p<0.001) and fractionation (R=0.46, p=0.001). Conclusion: HF is associated with more advanced bi-atrial remodelling in persistent AF. These findings may have implications for ablation strategies to improve outcomes in patients with AF and HF

154 Sandeep Prabhu Rapid pulmonary vein firing does not predict AF ablation outcome in persistent AF PRABHU S(1,2,3,4), Voskoboinik A(1,2,3,4), McLellan AJA(2,3), Peck KY (2) Pathik B (1,4), Nalliah CJ (1,4), Wong GR(1,4), Azzopardi SM(2,3), Lee G(1), Mariani JA (2,3), Ling LH (2,4), Taylor AJ(2,3) Kalman JM(1,4), and Kistler PM(1,2,4) 1. Melbourne Health, 2. Alfred Health, 3. Baker Heart and Diabetes Institute, 4. University of Melbourne

Variability of pulmonary vein firing rather than rate is predictive of long term outcome following catheter ablation for persistent AF. Aim: To determine the extent to which the rapidity of pulmonary vein activity in AF was predictive of outcome in patients with persistent AF. Background: PVI remains the cornerstone of catheter ablation (CA) in persistent AF (PeAF) although less successful than for PAF. Rapid PV firing may identify PeAF patients more likely to benefit from a PV based approach. We sought to evaluate the relationship between PVCL and outcome following CA for PeAF. Methods: Prior to ablation for PeAF, PV cycle length (PVCL) was recorded with a multipolar catheter in each PV and the left atrial appendage (LAA) for 100 consecutive cycles. For each patient, the average PVCL of all 4 veins (PV4Vaverage), the fastest PV average (PVFVaverage) and the fastest PVCL (PVfast) both individually and relative to the average LAA cycle length (LAAaverage), was calculated. The co-efficient of variation (CoV) for PV4Vaverage was also determined (SD/mean). Ablation strategy included PVI and posterior wall isolation with a minimum 12 months follow up with either six monthly holter monitoring or device (dual lead pacemaker or ICD or implantable loop recorder interrogation). Results: 123 patients underwent index CA (age 62±9.1yrs; 42% hypertensive; average CHADS2 score = 0.9±0.8; LVEF = 48±13%; LA area 31±8.7cm2; AF duration 16±17 months). PVI was achieved in 100%. Single procedure success (freedom from AF of atrial tachycardia >30 seconds) was achieved in 67% at 16±8.6 months. There was no significant difference in absolute PV4Vaverage (recurrence vs no recurrence: 175±27 vs 178±24ms, p=0.46), PVFVaverage (162±27 vs 188±24ms, p=0.24) or PVfast (101±24 vs 101±36ms) or as ratio relative to average LAA CL (1.02±0.11 vs 1.07±0.22, p=0.08) or AF within a PV (38% vs 46%, p=0.38) in patients with or without AF recurrence. Pulmonary vein activity was significantly more variable in those with recurrence compared to those free from

recurrence (CoV (SD/mean): 0.14±0.04 vs 0.12±0.02, p=0.009). Conclusion: Regularity of PV firing rather than rate (average PVCL) was a determinant of single procedure success following CA of persistent AF.

155 William Cranwell The effect of immunosuppression with mammalian target of rapamycin inhibitors on nonmelanoma skin cancers in renal transplant recipients Angputra M(1)(2), CRANWELL W(2), Martyres R(2), Upjohn E(2), Hughes P(3), Varigos G(2). 1.The University of Melbourne; 2.Dept of Dermatology, Royal Melbourne Hospital; 3. Dept of Nephrology, The Royal Melbourne Hospital

Aims: We aim to determine the incidence of non-melanoma skin cancer (NMSC) in a cohort of renal transplant recipients treated with mTOR inhibitor immunosuppression. We hope to determine whether mTOR inhibitor use affects the type and histological staging of NMSC, and determine what clinical risk factors contribute to an increased risk of NMSC. Background: Organ transplant recipients are approximately 65 to 250 times more likely to develop a NMSC. These skin cancers, particularly squamous cell carcinomas, are more aggressive and are associated with significantly higher rates of mortality than those in the general population. The long-term immunosuppression required to maintain host tolerance following solid organ transplantation contributes to the increased risk of developing malignancy in transplant recipients. A number of studies have suggested a benefit from mTOR inhibitors for delaying and preventing NMSC post-transplant. However, these studies have not determined which clinical situations immunosuppression with mTOR inhibitors is of greatest benefit for reducing NMSC in renal transplant patients. Methods: A retrospective study was performed on adult renal transplant recipients exposed to an mTOR inhibitor and receiving follow up at the Royal Melbourne Hospital Nephrology Unit. The Nephrology Data Systems Coordinator retrieved clinical information from the Nephworks Database. Data included demographics, medical history, transplant information, and follow-up. NMSC details were retrieved via the Melbourne Health web-based histopathology viewing system. Results: We collected data for 115 renal transplant recipients who received mTOR inhibitor immunosuppression. The mean age at transplant was 44 ± 16 years. Eighty-six patients (75%) were male. In total, 35 individual patients (30%) developed NMSC.112 basal cell carcinomas were found in 26 (22%) patients and 149 squamous cell carcinomas were found in 29 (25%) patients. Discussion: This presents the initial results of our study, demonstrating a relatively high incidence of NMSC in renal transplant recipients exposed to mTOR inhibitor immunosuppression. This may be attributed to a long period of follow-up or a cohort of high-risk patients.

156 Ahmad Azri Zulkifli Overcoming tumor resistance to epidermal growth factor receptor targeted therapy ZULKIFLI AA(1), Tan FH(1), Stylli SS(1,2), Luwor RB(1). (1) Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital; (2) Department of Neurosurgery, The Royal Melbourne Hospital

Activation of the Epidermal Growth Factor Receptor (EGFR) trigger multiple pathways including RAS-RAF-MEK-ERK1/2 pathways, PI3K-AKT-mTOR pathway and Src-Signal Transducer and Activator of Transcription (STAT) pathway that involve in maintaining cellular activities. Aberrations in these pathways often lead to uncontrolled growth of tumor. Therefore, therapies targeting the EGFR have been developed

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such as Cetuximab and Panitumumab. However, tumors often develop resistance towards these treatments. One of the implicated pathways that confer the resistance is the STAT3 signaling pathway. The main aim of this study is to evaluate the role of STAT3 in driving cancer resistance to anti-EGFR therapy. STAT3 is a transcription factors which is a key regulator in oncogenic development that mediates cellular functions such as proliferation, cell differentiation, angiogenesis and metastasis. It can be activated by several pathways including EGFR and IL-6 pathways. To study STAT3 signaling, we used colorectal cancer cell lines and have developed three Cetuximab-resistance cell lines denoted as LIM1215 C225, SW48 C225 and CACO2 C225. Using Western Blots, we determined the basal level of activated STAT3 in both sensitive and resistance cell lines. All resistance cell lines showed increase in activated STAT3 compared to sensitive cell lines suggesting it could have an increase in growth rate. Resistance cells grow much faster in scratch assay with the wound closing in 3 days compared to sensitive cell lines over the treatment period of 5 days. These results have shown that the resistant cell lines have enhanced growth rate and possibly due to elevated STAT3 activity. However, more studies need to be done to further confirm the role of STAT3 in driving the resistance to anti-EGFR therapy.

157 Zammam Areeb Overcoming treatment resistance in Glioblastoma using microRNA expression analysis and autophagy inhibition AREEB Z1,2, Luwor R2, Stylli S2,3, Kaye A2,3, Koldej R4 Glioblastoma (GBM) is an aggressive and the most common type of glioma, accounting for approximately half of gliomas. Currently, the therapeutic regimen consisting of surgery, irradiation and temozolomide only results in a mean survival time of 7-12 months. Furthermore, GBM patients have a high rate of recurrence due to the highly resistant nature of the glioma. Clearly, there is a need to identify key and clinically relevant mechanisms that result in treatment resistance. This project focusses on understanding the critical events that leads to resistant and recurrent GBM. First, we aimed to determine the key signalling molecules that are essential to treatment resistance, and eventually recurrence, in our primary GBM cell lines. Surprisingly, after treating GBM cell lines with irradiation and temozolomide, an RTK array showed that the treatment resistant population had down-regulated receptor tyrosine kinase levels. Additionally, expression levels of some downstream signalling molecules were also suppressed in human GBM cell lines. This finding made us look into autophagy as a potential resistant mechanism in irradiation and temozolomide-treated GBM. Initial results indicate that LC3 levels, a key autophagy marker, were up-regulated in treated GBM cells. We are now in the process of generating stable GBM cell lines expressing GFP-LC3 constructs in order to establish whether autophagy is a resistant mechanism. This will be followed by studying possible links between RTK suppression and autophagy influenced treatment resistant GBM. Lastly, using Nanostring technology, we obtained the expression data for 800 microRNAs after GBM cell lines were treated with irradiation and temozolomide. The results from the miRNA screen will be used to produce a miRNA signature which will be able to predict treatment resistance and patient survival. Also, the miRNA data will be utilised to elucidate the relationship between the expression levels of certain miRNAs and GBM resistance associated signalling molecules and autophagy.

158 Gita Soraya Label-free, quantitative fecal hemoglobin detection platform for colorectal cancer screening

SORAYA GV (1,5), Nguyen TC (2,3), Abeyrathne CD (2,3), Hyunh DH (2,3), Chan J (1), Phuong DN (2,3), Nasr B (2,3), Chana G (2,4), Skafidas E(2,3), Kwan P (1,3) 1.Department of Medicine, Royal Melbourne Hospital, The University of Melbourne; 2.Centre for Neural Engineering, The University of Melbourne; 3.Department of Electrical and Electronic Engineering, Melbourne School of Engineering, The University of Melbourne; 4.Department of Psychiatry, Royal Melbourne Hospital, The University of Melbourne; 5.Faculty of Medicine, Hasanuddin University, South Sulawesi, Indonesia

Background and Aim: The early detection of colorectal cancer (CRC) is vital for disease management and patient survival. Fecal hemoglobin detection is a widely adopted method for screening and early diagnosis. Fecal Immunochemical Test (FIT) is favored over the older generation chemical based Fecal Occult Blood Test (FOBT) as it does not require dietary or drug restrictions, and is specific to human blood from the lower digestive tract. To date no quantitative FIT platforms are available for use in the point-of-care setting. Here, we aim to generate proof of principle data of a novel low cost quantitative fecal immunochemical-based biosensor platform that may be further developed into a point-of-care test in low-resource settings. Methods: Interdigitated microelectrodes (IDEs) were fabricated using laser ablation, and surface functionalized using APTES-Glutaraldehyde protocols. Antibodies to human hemoglobin were immobilized on the sensor surface and detection was performed in solid-state using 20µl of the hemoglobin spiked fecal samples. Electrical measurement was performed before and after 1 hour of target binding and wash. Frequency dependent changes in output voltage (∆V0) and phase (∆θ0) obtained through the setup were used to extract the electrical impedance parameters occurring during the detection process. Results: Optimal applied frequency for quantitative distinction of various concentrations of faecal hemoglobin was 1 Khz (p=0.0205 for ∆V0, p=0.0014 for ∆θ0, Kruskal-Wallis ANOVA, n=3 per concentration) and 100 Hz (p=0.0028 for ∆V0, p=0.0328 for ∆θ0, Kruskal-Wallis ANOVA, n=3 per concentration). At 1 Khz frequency, ∆V0 increased monotonically with the increasing hemoglobin concentration. At concentrations of 0.01 mg, 4 mg, and 40 mg of hemoglobin per gram feces, the average difference compared with control samples is 2 mV, 3.19 mV and 6.27 mV. The change in resistance and capacitance was also highly dependent on the applied frequency, with the optimal being 100 Hz and 1 Khz. Conclusions: The proposed sensors can detect the sample to a minimum concentration of 10 µg Hb/g feces, which is comparable to currently used bench-top quantitative FIT detection, within 1 hour. Differentiation between various hemoglobin concentrations in human fecal samples can be performed either directly through amplitude and phase characterization, as well as indirectly by extracting equivalent values of capacitance and resistance. All parameters can be detected optimally at a single frequency of 1 Khz. The results provide proof-of-principle data that demonstrates the feasibility to quantitatively measure hemoglobin concentration in fecal sample using impedance spectroscopy technology without labelling, applicable for CRC screening.

159 Alice West Evaluation of the role of a panel of FDA approved agents on recurrent glioblastoma WEST AJ(1), Stylli SS(1,2), Paradiso L(1), Morokoff AP(1,2), Luwor RB(1) (1) Dept of Surgery, The University of Melbourne, The Royal Melbourne Hospital. (2) Dept of Neurosurgery, The Royal Melbourne Hospital

INTRODUCTION: Glioblastoma is a World Health Organisation Grade IV astrocytoma with a 5-year survival rate for treated patients of less than 5%. The inevitable fatality of glioblastoma is due to recurrence of the tumour and resistance to current standard therapies, including use of temozolomide (TMZ) and radiotherapy. By evaluating F.D.A approved agents

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that target known overexpressed signalling pathways of recurrent glioblastoma, alternatives to the current standard therapies may become used within recurrent glioblastoma as targeted therapy without having to develop new agents. Methods: Glioblastoma cell lines generated from patients with recurrent tumours (#28 and #35) alongside cell lines that have been developed to be resistant to TMZ and radiotherapy have been used in experiments with an original panel of 38 F.D.A. approved agents to determine efficacy. Experiments thus far have used Western Blots, luciferase and cell viability assays, qPCR and immunofluorescence. Results: Thus far, out of the 38 agents originally panelled, those that were known to inhibit overexpressed in the signal transducer and activator 3 and Janus kinase (STAT3/JAK) signalling pathway have had the greatest effect at reducing viability of the cells, and phosphorylation of proteins associated with the STAT3/JAK signalling pathway. Specifically, Ruxolitinib (a JAK2 inhibitor), Ibrutinib (a Src inhibitor) and Lenalidomide (a tumour necrosis factor α inhibitor) have proven most effective at minimising cell viability. Lenalidomide at 0.01µM was able to reduce cell viability by 92.3% (p<0.001), Ruxolitinib and Ibrutinib at 0.01µM reduced cell viability by 86.9% and 99% respectively (p<0.002 and p<0.001 respectively) for cell line #35, which was less responsive to the three agents compared to cell line #28. Current experiments are evaluating the efficacy of these agents in the cell lines made resistant to TMZ and radiotherapy. Conclusion: Collectively, the data so far demonstrates the importance of the STAT3/JAK signalling pathway in recurrent glioblastoma, and it has shown the efficacy of Ruxolitinib, Ibrutinib and Lenalidomide as potential therapeutic agents against recurrent glioblastoma.

160 Fiona Tan Ponatinib Inhibits Interleukin-11 mediated STAT3 signalling in colon cancer and reduces tumour growth TAN F(1), Putoczki T (1,2,3), Stylli S (1,4) and Luwor R (1) (1)Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital; (2)Inflammation Division, Walter and Eliza Hall Institute; (3)Department of Medical Biology, The University of Melbourne; (4)Department of Neurosurgery, The Royal Melbourne Hospital

Colorectal cancer is the 4th most common cancer globally and the 2nd most common cancer in Australia. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) has been observed in over 50% of human colorectal carcinomas and its role in tumour progression has been confirmed in numerous mouse models and clinically in human samples. Previous data suggests the hyper-activation of upstream molecules notably, Epidermal Growth Factor Receptor (EGFR) and the Interleukin (IL)-6-gp130 family of cytokines, contributes to enhanced STAT3 activation and tumourigenesis. With the aim of overcoming STAT3-driven tumorigenicity, we evaluated a panel of 1167 FDA approved agents for their ability to inhibit STAT3 activity. In this initial drug screen, human colorectal cancer cell lines were assessed by the adenoviral STAT3 luciferase reporter assay. In the presence of inhibitors, cells were also stimulated with EGF and IL-6 allowing enhanced STAT3 activity at 10µM. We identified 51 FDA approved agents to have reduced STAT3 activity by ≥50%. Our secondary drug screen further evaluated inhibitors by EGF and IL-6 mediated STAT3 activity by western blot and resulted with 9 inhibitors to have shown successive reduction at 1µM. It has been recently shown that IL-11, a closely related IL-6 family member has a more prominent role than IL-6 during the progression of gastrointestinal cancers, including colorectal tumours, and therefore in our tertiary screen we further evaluated agents that could inhibit IL-11, IL-6 and EGF

mediated STAT3 phosphorylation by western blot analyses. As a result, Ponatinib (AP24534) markedly reduced EGF, IL-6 and IL-11 driven STAT3 activation. Ponatinib is a multi-targeted tyrosine kinase inhibitor and is currently approved for the treatment of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia. With further in-vitro and in-vivo analyses performed, Ponatinib also reduced transcriptional gene expression of STAT3 regulated genes, cell viability, migration and tumour growth. While the effectiveness of Ponatinib requires additional investigation, our findings both in-vitro and in-vivo offer proof-of-principle evidence for the potential use of Ponatinib for the treatment of STAT3 driven colorectal cancers.

161 Rachel Cooke Progression from newly diagnosed multiple myeloma to relapsed refractory multiple myeloma is associated with significant alterations in the CD4+ Treg population phenotype COOKE RE (1,3), Quach H(2,3), Harrison S(2, 3), Prince M(2, 3), Koldej R(1, 3), Ritchie D(1, 2, 3) 1. Australian Cancer Research Foundation Laboratory, Royal Melbourne Hospital; 2. Peter MacCallum Cancer Centre;3. Department of Medicine, University of Melbourne

Introduction: Immune compromise is a complication of multiple myeloma (MM), aging and anti-MM therapies used throughout disease course. Our group have previously reported that patients with relapsed/refractory MM (RRMM) have marked CD4+ T lymphopenia that is not present in newly diagnosed MM (NDMM) and does not recover with successive cycles of lenalidomide and dexamethasone (len/dex). However, the proportion of Tregs within the CD4+ T cell population increased with treatment and approached normal range by cycle 9. We hypothesised that this represented homeostatic proliferation of peripherally-derived Tregs (pTreg) as opposed to thymic production of naturally-derived Tregs (nTreg), which can be differentiated by methylation status of the T-cell specific demethylation region (TSDR) found in intron 1 of the Foxp3 gene. Methods: We sought to establish when this change occurred by analysing 5 paired samples from patients with NDMM and RRMM, and comparing with 5 age-matched normal donors. In the NDMM cohort, we examined Tregs from samples at baseline, after 4 cycles of len/dex, and after autologous stem cell transplant (ASCT); and in the RRMM cohort samples from baseline and after 9 cycles of len/dex. Tregs (defined as CD4+CD127-CD25+) were FACS sorted from each sample and DNA was extracted and bisulfite converted. The TSDR was PCR amplified, and transformed into chemically competent E.coli. Individual colonies were picked and DNA plasmids were sequenced. Cytosine matches/mismatches at CpG sites in the TSDR were identified and % methylation calculated. Results: (1) The TSDR methylation status of Tregs from baseline NDMM patient samples is largely unmethylated and similar to age-matched controls, i.e. predominantly nTregs. (2) The TSDR methylation status of Tregs from baseline RRMM patient samples is largely methylated, i.e. predominantly pTregs. (3) Len/dex treatment in both NDMM and RRMM patient did not alter the respective phenotypes. (4) After ASCT, 2 of the 5 NDMM patient samples analysed had changed to a “pTreg phenotype”. Both these patients subsequently relapsed from complete remission, compared to 2 of 3 of the patients with an “nTreg phenotype” maintaining CR 8-9 years later. Conclusions: This study adds evidence that the character of the CD4+ T cell population is radically altered in RRMM, compared with NDMM and age-matched controls. It is likely that thymic involution is a contributor to this, which is not only a normal occurrence with immunosenescence, but may be

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accelerated with ASCT in some patients. Methylation status of the TSDR could potentially represent a biomarker for poorer prognosis.

162 Abby Douglas A novel assay to assess immune compromise and risk of infection post haematopoietic stem cell transplantation DOUGLAS AP(1,4,5), Yu J(2,4), Szer J(3,4), Ritchie D(3,4), Slavin MA(1,4,5), Sasadeusz J(1,4), Visvanathan K(2,4) 1.Victorian Infectious Diseases Service, Royal Melbourne Hospital; 2.Immunology Research Centre, St Vincent’s Hospital; 3.Dept of Clinical Haematology and Bone Marrow Transplant Service, Royal Melbourne Hospital; 4.University of Melbourne; 5. Peter MacCallum Cancer Centre

Aim: To monitor IFN-γ levels in stimulated blood in allogeneic haematopoietic stem cell transplantation (alloHSCT) patients over the transplant course using the QuantiFERON Monitor® (QFM) assay, to describe immune recovery post-transplant, and to correlate the QFM assay with episodes of infection and GVHD. Background: Managing immunosuppression in patients post alloHSCT is challenging. Excessive immunosuppression can be complicated by infection, while inadequate immunosuppression can result in graft versus host disease (GVHD). An accurate method to assess immune status in the setting of HSCT is lacking. Unlike other commercially available assays which assess the adaptive immune response alone, QuantiFERON Monitor® (QFM) measures interferon-gamma (IFN-γ) release from whole blood following incubation with both innate (Toll like receptors 7/8 ligands) and adaptive (CD3 antibody) immune stimulants. Methods: Whole blood samples were prospectively collected from alloHSCTs at baseline, pre-conditioning and days 10, 30, 60, 90, 120 and 180 post alloHSCT and assayed by the QFM test. IFN-γ levels were plotted against time post alloHSCT and correlated to episodes of infection and GVHD. Results: 40 patients were enrolled in the study (68% male; median age 47 years; 33% myeloablative, 67% reduced intensity conditioning). IFN-γ levels rose steadily post transplantation, however they did not reach baseline by 180 days. On average, younger recipients had higher IFN-γ levels than older recipients at any time point. There were 63 episodes of clinical suspected and/or microbiologically confirmed infection in 38 patients, with 60 identified organisms (18 viral, 39 bacterial and 3 possible fungal infections) and 11 culture negative episodes. IFN-γ levels were statistically significantly lower in those with active infection compared to those without (p<0.001 using logistic regression with IFN-γ as a continuous variable). There was no statistically significant association between acute or chronic GVHD and IFN-γ levels, although numbers were small. Conclusion: Immune function, as measured by the QFM assay, appears to steadily increase over the first 180 days post alloHSCT. Lower IFN-γ levels correlated with risk of infection. This assay is promising as a means to monitor immune recovery and predict risk of infection and hence tailor immunosuppression and prophylaxis accordingly.

163 Chia Sharpe Comparison of innate immunity changes following novel therapies for the treatment of relapsed Chronic Lymphocytic Leukaemia patients Sharpe, C (1,2), Davis, J (1,2), Mason, K (1,2,3), Koldej, R (1,2), Tam, C (4,5,6), Ritchie, D (1,2,3). 1. ACRF Translational Research Laboratory. The Department of Research, The Royal Melbourne Hospital; 2. Department of Medicine, University of Melbourne; 3. Clinical Haematology and Bone Marrow Transplantation Service, Department of Clinical Oncology and Haematology, The Royal Melbourne Hospital; 4. Sir Peter MacCallum Department of Oncology,

University of Melbourne; 5. Department of Haematology, Peter MacCallum Cancer Centre; 6. Department of Haematology, St Vincent’s Hospital

Aim: This project aims to understand the effect that long term use of emerging therapies for Chronic Lymphocytic Leukaemia (CLL) have on the immune system of patients. Background: CLL is associated with profound immunodeficiency, which perturbs the ability of the immune system to properly respond to cancer cells or infections. Innate immune cells such as NK cells and monocytes play important roles in CLL, both to the anti-tumour immune response and as components of the CLL supportive microenvironment. Targeted small molecule inhibitors, including the BTK inhibitor Ibrutinib and the Bcl-2 inhibitor Venetoclax, are revolutionising the way CLL is treated. However, little is known about the effects that long-term treatment has on immune system. Methods: Multi-parametric flow cytometry was used to identify the immunological changes caused by long-term treatment with small molecule inhibitors mononuclear cells were isolated from the peripheral blood of patients enrolled on ethically approved studies of immune function. They received either Ibrutinib (n=12) or Venetoclax (n=6) on phase I–III studies of these agents, or as best standard of care. Samples were obtained immediately prior to and after 1 year of therapy. PBMC from 10 age-matched healthy donors were obtained from the Australian Red Cross Blood Service. The relative frequencies and absolute count of immune subsets were calculated. Results: Following Ibrutinib treatment, patients showed a significant increase in the frequency and absolute number of monocytes. Furthermore, the frequency of monocytes in Venetoclax treated patients exceeded the frequency observed in healthy donors. Myeloid derived suppressor cells also increased in frequency in treated patients but did not exceed that observed in healthy donors. In both Ibrutinib and Venetoclax treated patients there was a significant increase in the frequency of NK cells but only in Venetoclax treated patients did the NK cells proportion return to that observed in healthy donors. Furthermore, in both Ibrutinib and Venetoclax treated patients there was a significant increase in the frequency of γδT cells. Finally, there was no change in the absolute numbers of T cells or to the CD4:CD8 ratio, which remained significantly lower than seen in age-matched healthy donors. Conclusion: BTK and Bcl-2 inhibitors have different effects on innate immune subsets. Our results show that while there are improvements in the immunological profile of patients treated with targeted therapies, these seemed to be greatest in those treated with Venetoclax. This provides an opportunity for the potential introduction of immunotherapies to promote anti-CLL immunity.

164 Mervyn Kyi The management of unstable diabetes in a cancer population – a retrospective audit QIAN S(1), Parlapiano C(1), Marley KA(1), Kyi M(1,2), Fourlanos S(1,2), Colman PG(1) 1. Diabetes and Endocrinology, RMH. 2. Dept of General Medicine, RMH

Background: In patients with cancer, diabetes is prevalent and associated with poorer prognosis. Surgery, chemotherapy and glucocorticoids significantly affect glycaemic control. We undertook an audit in this group as baseline study to determine the benefit of future management initiatives. Methods: All patient admissions coded with cancer and unstable diabetes from Oct 2014 to Oct 2015, were identified. Histories and pathology were reviewed. Hyperglycaemia was defined as preprandial blood glucose (BG) >8.0 mmol/L, hypoglycaemia was defined as BG <4.0 mmol/L. The aim was to determine current management of unstable diabetes in cancer patients.

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Results: There were 108 admissions identified, with 96 admissions available for review. Median age was 69yr (range 43-89); 53 (55%) were male. A majority of patients had type 2 diabetes (n=92) and were insulin-requiring (n=50). Solid organ malignancies were present in 68 (71%) patients and haematological malignancies in 28 (29%). Chemotherapy was required for 19 (20%) patients and surgery in 35 (36%). Notably, 16 (17%) patients received end-of-life care. Glycaemic emergencies were the reason for admission in 3 cases (HHS, severe hyperglycaemia and hypoglycaemia). During admission, diabetes control issues were hyperglycaemia (n=64, 67%), hypoglycaemia (n=8, 8%) and both hyperglycaemia/hypoglycaemia (n=24, 25%). Significant factors in hyperglycaemia cases included glucocorticoid use (n=42) and infection (n=27). Blood glucose readings were recorded in 92 (96%) patients; 55 (57%) had biochemical blood glucose measurements and 20 (20%) had HbA1c tested. Management was largely conducted by the parent unit, with endocrinology consultation occurring in 21 (22%) cases and diabetes nurse educators involvement in 14 (15%) cases. Eighteen (19%) patients died during admission, no deaths were due to diabetes-related complications. Conclusion: This audit characterises clinical features of patients with cancer and unstable diabetes. The development of a standardised approach to the management of diabetes in this population, taking into account overall prognosis, may reduce the incidence of glycaemic and other adverse events.

165 Katie Marley Diabetes management in cancer patients: Changes in nursing practice MARLEY K, Rosenthal M, Grant C, Bacon L, Enright L, Nanayakkara N, Kumar S, Paldus B, Galligan A, Sandison A, Dawson W, Tsan J, Rowan L, Thien C, Urban E, Comer R, Parlapiano C, WCMICS Steering Committee (1,2,3), Colman P 1. St. Vincents Hospital Melbourne, 2. Peter MacCallum Cancer Centre, 3. Western & Central Melbourne Integrated Cancer Service

Background and Aim: Chemotherapy regimens can have a significant impact on blood glucose levels (BGL’s) in patients with or without diabetes. Identifying and managing these patients, who are often treated in day chemotherapy wards is a challenge. Historically, BGL’s were not monitored in the Day Oncology Centre. The Western and Central Melbourne Integrated Cancer Services’ (WCMICS) Diabetes and Cancer project developed guidelines for detecting and managing diabetes during chemotherapy treatment. We report their implementation in the Day Oncology Centre. Methods: Extensive education and support was provided to the day oncology staff and a ‘Diabetes and Oncology’ information sheet was developed for patients attending pre-chemotherapy education. New nursing care plans mandated a finger prick or venous BGL and HbA1c on all patients. Loan blood glucose meters were available to patients without diabetes. Staff were to refer patients commencing on steroids or with BGL’s <4 or >12mmol/l to the Diabetes Team. Results: Fifty three patients were identified with or at risk of developing diabetes/ unstable BGLs as a result of their chemotherapy regimen. 27 (51%) patients were identified through the pre-chemo assessment and 9 were referred by concerned staff. 39 (73%) of the 53 patients identified received steroids as part of their regimen. 34 (64%) had their BGL checked during treatment and 28 (53%) had a HbA1c. Of the 34 patients, 12 (35%) had levels below 4mmol/l or above 12mmol/l; 8 were referred to Diabetes Education and Endocrinology. The day oncology staff engaged and worked extremely well with the Diabetes Team. Conclusion: Through increased education, support and awareness about diabetes, we changed standard practice to

include random BGL and HbA1c testing. We increased vigilance and referral of cancer patients with unstable BGL’s in the Day Oncology Centre. We expect this initiative will improve outcomes for patients by reducing risk of adverse glycaemic outcomes.

166 Renate Schwab Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells SCHWAB RHM 1, Flanagan DJ 1, Amin N 1, Phesse TJ 1,2, Vincan E 1,3. 1 Molecular Oncology Laboratory, University of Melbourne and the Victorian Infectious Diseases Reference Laboratory, Doherty Institute of Infection and Immunity; 2 European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Wales, UK. 3 School of Biomedical Sciences, Curtin University

Aim: Investigate which Wnts interact with Fzd7 during the mesenchymal to epithelial transition in colorectal cancer cells Background: Wnt/beta-catenin signalling has multiple functions throughout gut development and homeostatic control of the intestinal epithelium. Aberrant activation of the Wnt pathway is observed in over 90% of human colorectal cancers (CRC) and it is now evident that this aberrant activation plays pivotal roles in the initiation, growth and progression of CRC. Our findings implicate that FZD7 transmits Wnt signals in both normal intestinal epithelium and in CRC. Investigating the latter, we established a unique in vitro 3D CRC morphogenesis model (LIM1863-Mph) that forms multicellular organoids resembling enclosed carcinoma tubules. The LIM1863-Mph organoids contain several intestinal epithelium cell types; including goblet cells, enterocytes and LGR5+ undifferentiated cells. They also recapitulate many features of the phenotypic transitions that underlie tumour morphogenesis, invasion and metastasis. We previously showed that FZD7 is required for tubular patterning of the LIM1863-Mph organoids. As Wnt signalling is activated via the binding of an extracellular Wnt to the Fzd receptor, our next question was which Wnts interact with Fzd7 during tubular patterning. Methods: We conducted superarray analysis of transcript levels in organoid and monolayer cells of various Wnts. The results revealed increases in Wnt2b and Wnt3 levels in the organoids, thereby implicating these Wnts in tubular patterning. To investigate their role in tubular patterning of the organoids, we employed the small molecule inhibitor IWP2. IWP2 is a Porcupine (PORC) inhibitor that prevents the secretion of all Wnts, as PORC is required for the palmitoylation of the Wnt proteins before secretion. Following treatment of the LIM1863-Mph monolayer cultures with IWP2, recombinant Wnts were reintroduced to the cells and their effect monitored. Results: The phenotypes we observe are consistent with Wnt2b and Wnt3 co-operating with FZD7 in establishing the architecture of the organoids. It is already known that Wnt3 binds FZD7; via co-immunoprecipitation we show an interaction between Wnt2b and FZD7 as well. Conclusion: This study shows that both Wnt2b and Wnt3 co-operate with Fzd7 to mediate tubular patterning in colorectal cancer. Insight into the functioning roles of Wnts and FZDs in CRC can offer novel avenues in treatments to target key events during tumour growth and progression.

167 Elizabeth VINCAN Mini-liver organoids, an innovative tool to understand oncogenic Wnt signalling and HBV infection Tran BM (1), Flanagan DJ (1), Fifis T (2), Christophi C (2), Phesse TJ (1, 3), VINCAN E (1,4) 1. Molecular oncology Laboratory, University of Melbourne and Victorian Infectious Diseases Reference Laboratory, Doherty Institute; 2. University of Melbourne Department of Surgery, Austin Hospital; 3. European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, UK; 4. Medical School, Curtin University

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Aim: Understand the oncogenic interplay between Wnt signalling and HBV infection Background: Infection of liver cells with the Hepatitis B virus (HBV) can ultimately lead to liver cancer. The vast majority of HBV related liver cancers also harbour active Wnt signalling. However, our understanding of the interplay between these two oncogenic drivers of liver cancer is not well-understood. This is primarily because HBV is a hepatotropic virus that mainly or exclusively infects human liver cells (hepatocytes). Thus, the study of HBV entry into, and natural infection of, human hepatocytes has been hampered by a lack of suitable models. Continuous human liver cancer cell lines are refractory to natural HBV infection. Even when these cells are genetically modified to stably express putative cells surface receptors for HBV, the cells remain relatively refractory despite the use of concentrated (high-titre) viral particles, spin-inoculation and various other tricks that work with other viral particles. HBV does efficiently infect cultured primary liver cells but this has limited experimental application as these cultures are short-lived and do not recapitulate the normal liver because the cells adapt to in-vitro culture once removed from the body. Methods: To overcome these obstacles, we recently established an in vitro mini-liver organoid culture system that faithfully recapitulates the intact liver, both phenotypically and functionally. The liver organoids support infection with HBV and allow us to study natural HBV infection of human hepatocytes in a tissue culture setting. Results: Using a Wnt-reporter assay in continuous liver cancer cell lines, we have identified a HBV viral protein that potently activates oncogenic Wnt signalling. We have performed proof-of-principle studies using mouse liver and show that mouse liver organoids can be expanded in vitro, frozen and thawed, and differentiated to functional hepatocytes. Recently we gained access to human liver resected tissues and are now investigating the impact of HBV proteins on Wnt signalling during natural infection of human hepatocytes using our novel mini-liver organoid cultures. Conclusion: Liver organoids grown in tissue culture retain features of normal adult hepatocytes and support natural infection. Furthermore, we have established patient-derived liver cancer organoids to assess the response of liver cancer cells to modulators of Wnt signalling.

168 Virginia Pilcher The development of vitiligo while receiving ustekinumab therapy for psoriasis - a case series of two and review of the literature PILCHER V, Dolianitis C, Nicolopoulos J, Varigos G Department of Dermatology, The Royal Melbourne Hospital

169 Lucy Sharrock A pristine interaction: Raising awareness of the potential significance of pristinamycin CYP3A4 inhibition SHARROCK L, Hill L, Nalder M Pharmacy Department, Royal Melbourne Hospital

Objective: To report a clinically significant drug interaction between pristinamycin and tacrolimus. A literature review performed at the time suggested that pristinamycin was a CYP3A4 inhibitor, however there were few specific reports on the interaction between these two drugs, and none which indicated the degree of inhibition that occurred in this case. Clinical Features: A 45 year old female with an indwelling catheter, multiple drug allergies and a history of multiple drug resistant urinary tract infections (UTIs) presented to hospital with Klebsiella pneumoniae Extended Spectrum Beta Lactamase bacteraemia (ESBL) and a Van A Vancomycin Resistant Enterococci (VRE) UTI. Due to end stage renal

disease, she had received a kidney transplant seven weeks prior and was receiving tacrolimus (target trough 5 – 8microg/L), mycophenolate and prednisolone. Interventions, Case Progress and Outcomes: The patient was initially commenced on meropenem for the Klebsiella pneumoniae ESBL and daptomycin for the Van A VRE UTI. Following clinical improvement the infectious diseases team recommended de-escalating the daptomycin to pristinamycin 1g three times a day. Pristinamycin is a mixture of two synergistic components, pristinamycin I (a macrolide), and pristinamycin II (a depsipeptide). A literature review suggested that pristinamycin inhibited cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, with the degree of inhibition being similar to erythromycin. Tacrolimus is a CYP3A4 and p-glycoprotein substrate leading the pharmacist to suspect that a clinically significant drug interaction was likely and that close monitoring of tacrolimus levels would be required. Prior to commencing pristinamycin the tacrolimus dose was 1.5mg twice daily and trough level 7.4microg/L. A fourfold increase to 29microg/L was detected after three doses of pristinamycin. Tacrolimus was withheld and restarted at 500mg twice daily three days later. Following cessation of pristinamycin, tacrolimus levels were subtherapeutic within 60 hours, necessitating a tacrolimus dose increase. In the following days multiple dose adjustments of tacrolimus were required to maintain desired levels. Conclusions: This case highlights the significance of the interaction between tacrolimus and pristinamycin. A pre-emptive dose reduction of tacrolimus should be considered when starting pristinamycin, in addition to close monitoring of tacrolimus levels.

170 Adrienne Sexton Australian male breast cancer survivors: A needs assessment Hoskins, C(1,2), SEXTON A(1,3), Steel E(1), Keogh L(1), TRAINER A(3,4) (1)University of Melbourne (2)Murdoch Childrens Research Institute (3)The Royal Melbourne Hospital (4)Peter MacCallum Cancer Institute

Background: In contrast to the widespread awareness, support and research on breast cancer in women, little is known about male breast cancer and how the condition affects men psychologically, physically and socially. Aim: This study aimed to explore the experiences of a sample of Australian male breast cancer survivors. Methods: A mixed-methods approach using a sequential explanatory model, integrating data from both quantitative and qualitative collection phases. Phase 1: Participants completed a self-reporting questionnaire in order to investigate experiences and perceptions. Phase 2: To further explore and elaborate on domains identified from the questionnaire responses, semi-structured interviews were conducted with a purposive sample of respondents. Results: Data from 38 questionnaires and 5 interviews revealed a wide range of experiences and perceptions, with various pathways leading up to diagnosis. Participants identified a lack of relevant and accurate information in relation to male breast cancer, and a need for gender-specific peer support resources. Conclusions: This study is the first Australian investigation into the experiences of male breast cancer survivors and reveals that compared to reports from other countries, Australian men were more open about their diagnosis. Findings indicate that an increase in awareness of male breast cancer could contribute to the improvement of outcomes and experiences for Australian men diagnosed with the disease in the future.

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171 Melinda Pattanasri Uptake of adjuvant breast cancer treatments recommended by multi-disciplinary meetings PATTANASRI M (1), Elder K (1), Mann GB (1) Nickson C (2) (1) Royal Melbourne Hospital (2) University of Melbourne

Purpose: Adjuvant therapy for breast cancer is routinely discussed and recommended in multidisciplinary meetings (MDMs). Current literature explores how treatments received by patients differ from national guidelines. Treatment received is a combination of MDM treatment recommendations and how clinicians and patients follow them. The latter aspect has received little attention. Methods: A retrospective cohort study of patients with breast cancer presented at The Royal Melbourne Hospital MDM in 2010 and 2014 to investigate the concordance between MDM recommendations and treatment received. Results: The study group comprised 477 patients (191 from 2010 and 286 from 2014). A total of 374 patients were included in the analyses. Overall, concordance between recommended and received treatment was 92% ranging from 89% to 93% for adjuvant endocrine therapy, radiotherapy and chemotherapy. We found no significant relationships between tumour characteristics at diagnosis (invasive/DCIS, node positive/negative) and chemotherapy or radiotherapy. However, for endocrine therapy, patients diagnosed with invasive cancers had significantly higher concordance rates to endocrine therapy as compared to those with DCIS (97% vs 81% CI, p<0.001), as was found for those with positive as compared to negative nodal status (98% vs 92%, p = 0.032). Conclusions: Uptake of MDM-recommended treatments is high. There is a minority of patients in whom MDM recommendations are not followed, highlighting that there are extra steps between treatment recommendations at an MDM and treatment decisions. More attention to this group is appropriate, and the reasons for non-concordance warrant further study.

172 David Glenister Capturing religious identity during hospital admission: a valid practice in our increasingly secular society? GLENISTER D Aim: Most major Victorian hospitals include religious identity in routine admission demographic questions. However, approximately 20% of admissions do not have their religious identity recorded. At Royal Melbourne Hospital this missing 20% was surveyed throughout 2014-15 for two reasons: 1) to enable patient care and 2) to provide an insight into the significance of religious identity for patients. Background: There is scarce literature on this subject, so this mixed methods study, including a qualitative component, will begin to bridge the gap. This mixed methods study approaches the issue from the patient perspective, via a spiritual screening survey which included a qualitative component, so will begin to bridge a gap in knowledge. METHODOLOGY: All the patients surveyed were listed on the inpatient management system as “Not-Specified” religion, and were from all care areas. These patients were asked (within sensitive spiritual screening) if they identified with a particular faith tradition (including Atheist) or No Religion, or preferred to remain Not-Specified. Consequently, they were asked their choice of follow up service, or not, and these choices were recorded and entered with their basic demographics (age, gender, cultural background, clinical unit) under one of six categories. Results: The quantitative component of the study found that Religious Identity was important for a significant proportion of our diverse populations, and that in general demographics

were congruent with ABS census figures. The qualitative component also revealed significant complexity behind religious identity labels, which the census is unable to capture, providing an insight into the requirements of our growing multicultural population. What are the implications for practitioners? Improved understanding of the complexity of our multicultural populations’ spiritual needs, and commensurate emphasis on necessity of individual screening and assessment

173 Jacqueline Kay Identifying and addressing barriers to safe and effective care of bariatric patients in a tertiary trauma hospital KAY J(1), Becker F (2), Begg F (2), Finnigan K (2), Cosgriff C(2) (1)Royal Melbourne Hospital Physiotherapy Department (2)Royal Melbourne Hospital

Aim: To improve the outcomes and experiences, of bariatric patients admitted to Royal Melbourne Hospital (RMH), by determining the barriers to safe and effective care. Background: The Royal Melbourne Hospital (RMH) has experienced an increase in the number of bariatric patients needing care, creating issues with equipment provision and staffing. A project was then commissioned to explore the barriers and determine plausible solutions. Method: The project team consisted of representatives from the following RMH Departments: Quality and Safety, Manual Handling, Nursing, Allied Health, and Human Resources. The team used the lean six sigma methodology to determine the main barriers to care and determine cost effective strategies to address the issues. Staff engagement, from all levels, occurred from the beginning. Bariatric patients and their carer’s were also interviewed to ensure the project would address their concerns and needs. The project team also undertook an extensive bariatric readiness audit of the hospital to identify the physical barriers to access to each ward and procedural area. Results: The barriers identified fell into three main categories: 1) Physical space; 2) Staff awareness and attitudes to bariatric patient management and complications; 3) Access to equipment. These barriers had resulted in bariatric patients being unable to access specialist wards, investigative and procedural services (Theatre, Radiology), poor patient outcomes and increased in length of stay. The bariatric readiness audit provided the project team with a road map for better care of bariatric patients, and has guided the development of Bariatric ‘Kits’ with specific equipment, a Bariatric Management Procedure, and the allocation of bariatric patients to the most appropriate room on the specialist ward. Conclusion: The project team was able to make a significant, low-cost implementation as a result of an organisation-wide assessment to improve the care and outcomes for bariatric patients throughout their journey at RMH. Full evaluation of the impact of the Bariatric ‘Kits’ is to be completed.

174 Anita Goh Predictors of workplace disability in premanifest Huntington's disease GOH AMY(1,2,5), You E(1), Perin S(1), Clay FJ(3), Loi S(1,2), Ellis K(1), Chong T(1), Ames D(1,4), Lautenschlager N(1,5) 1 Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne 2 Neuropsychiatry Unit, Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital 3 Department of Psychiatry, University of Melbourne 4 National Ageing Research Institute, Parkville, Australia 5 NorthWestern Mental Health, Melbourne Health

Aim: The aim of this study was to explore the predictors of work impairment and disability in a cohort of employed, premanifest Huntington's disease individuals.

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Background: Huntington’s disease (HD) is an inherited neurodegenerative disease involving motor, cognitive and psychiatric/behavioural impairments that will eventually affect work role functioning. Few objective data exist regarding predictors of workplace disability in HD. Methods:This study explored the predictors of work impairment and disability in a cross-sectional cohort of 656 employed, premanifest HD (preHD) individuals. Results: In this cohort, the majority of whom were female, urban dwelling, married/partnered, and working full time, with minimal cognitive impairment, good function, minimal motor abnormality, and no indication of significant mental health issues, the number of participants who reported that they had missed work due to HD was low (2.4%). However, 12% of the study sample reported experiencing impairment whilst working due to preHD, 12.2% reported work-related activity impairment due to preHD, and 12.7% reported impairment in their overall work ability. Higher numbers of CAG repeats on the mutant allele and having more motor symptoms were associated with significantly higher odds of experiencing workplace impairment. Importantly, several modifiable factors were also found to predict workplace disability. Specifically, higher levels of anxiety symptoms were associated with significantly higher odds of experiencing workplace impairment. Good mental and physical health served as protective factors, where good physical health was associated with 6% less odds to experience impairment or to miss work time, and good mental health associated with 10-12% less odds. Conclusion: Results provide important new knowledge for the development of future targeted intervention trials to support preHD individuals to maintain their work roles as long as possible. This study identifies a number of key predictors of work disability-related outcomes due to preHD. Several of these key predictors are modifiable and are potentially responsive to interventions. For example, there exist effective pharmacological and non-pharmacological treatments for mental health disorders, particularly for depression and anxiety. Promotion of social support and engagement is now a target for workplace health interventions. Physical functioning, accomplishments, limitations of physical roles, extent of bodily pain, and general health can be boosted via lifestyle interventions, and asymptomatic preHD participants should focus on keeping physically healthy, ideally collaboratively with their healthcare providers. Supporting mental health and physical health, and the effective prevention and treatment of depression and anxiety can be strategically targeted to help maintain preHD individuals in work roles.

175 Katherine Bray Default mode network resting-state functional connectivity and depressive symptoms in middle/late childhood BRAY K (1,2), Pantelis C (2), Anderson V (1,3), Whittle S (1,2) 1. Melbourne School of Psychological Sciences, University of Melbourne; 2. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne; 3. Murdoch Childrens Research Institute

Background: Depression is the most common mental health problem, affecting millions of people worldwide. There is strong evidence for alterations in connectivity within the Default Mode Network (DMN, a neural network underlying self-reflective and social functions) in adults with depressive disorders. The majority of adults with depression experience sub-clinical levels of symptoms during childhood. The examination of DMN connectivity relating to depressive symptoms in children thus has the ability to shed light on the development of depression. Only a few studies have examined resting-state functional connectivity in the DMN in children, with inconsistent findings. These studies have examined children

“at-risk” (based on family history or remitted disorder) for depression, but not current symptom levels. Aim: The current study investigated functional connectivity during resting state in a community sample of 65 children aged 9-10 years. Methods: Children completed a resting state functional Magnetic Resonance Imaging scan and completed the Children’s Depression Inventory (CDI-2). Analyses investigated the association between CDI scores and resting state connectivity of the posterior cingulate cortex (PCC), the primary hub within the DMN. Results: For female children, higher depressive symptoms were related to increased connectivity between the PCC seed and the left medial/inferior temporal lobe. When the subscales of the CDI-2 were examined, it was found that this effect was primarily driven by the negative mood and physical symptoms subscale. Scores on this subscale were also associated with PCC connectivity with the right medial/inferior temporal lobe and the right superior/middle occipital gyrus. For males there was no relationship between depressive symptoms and PCC connectivity. This finding was in the absence of gender differences in depressive symptoms, and gender differences in overall PCC connectivity. Conclusion: Evidence of altered DMN connectivity in children with elevated depressive symptoms may suggest that such alterations represent vulnerability to the development of depressive disorder. The female-specific results may demonstrate that gender differences in the underlying neural mechanisms of depressive symptoms begin to emerge as early as 9 or 10 years old. Knowledge of ‘vulnerable’ connectivity patterns could assist with early detection of risk for depression, or may be a useful tool in monitoring treatment effectiveness.

176 Samantha Loi Investigating socially assistive robots in people under 65 and the staff who work with them LOI SM (1,2), Bennett A (1), Pearce M (1), Nguyen K (3), Lautenschlager NT (1,2), Khosla R (3), Velakoulis D (1,2) 1 NorthWestern Mental Health, Melbourne Health; 2 Department of Psychiatry, University of Melbourne; 3 RECCSI, Latrobe University

Aim: This project investigated the utility of socially assistive robots in people who were younger than 65 years old, specifically in terms of the types of services provided and the acceptability of the robot by these patients and the staff who work with them. Background: Socially assistive robots, like Betty, are unique in that they have the ability to provide reciprocal interactions and hence potentially increased engagement with people. Betty is 39cm tall, weighs about 6kg, can converse in a few languages and can connect to the internet. She and her siblings can be programmed with music, books and quizzes which can be personalised to each individual. A touchpad or voice control is used to interact with Betty. Betty has been introduced to aged care facilities (ACFs) and found to be acceptable and enjoyable by the older residents and their staff, but has not yet been investigated in people younger than 65 years old. Methods: Betty was piloted in two settings, the Neuropsychiatry Unit (NPU) and Cyril Jewell House (CJH). The NPU is an 8 bed unit which admits mostly younger patients with a range of neuropsychiatric conditions such as younger-onset dementia (YOD), schizophrenia and depression. CJH is a residential facility which accommodates younger people who require high level care, with conditions such as multiple sclerosis and YOD. Pre and post-questionnaires were administered to the staff and consenting participants to assess acceptability. In order to record the types of services utilised, Betty has the ability to record this information (duration, frequency and type of

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services). Qualitative feedback from the staff was also obtained. Statistical analyses: Descriptive statistics were used to analyse demographics. Chi square were used to analyse proportional changes in Likert scores between pre- and post-questionnaire. Results: Between both settings, 40 and 20 staff completed the pre- and post-questionnaires respectively. Generally there was positive feedback but this was only significant in CYH. The types of services utilised included most frequently music, mindfulness and the news. Qualitative feedback revealed two major themes - Betty had much potential, but these were limited by technological difficulties such as Wifi connectivity issues and speed of Betty's responses. Conclusion: Betty was found to be acceptable by the staff and younger people and there was scope for alternative uses. Further study would include larger sample sizes, refinement of Betty and the services she provided, and ongoing support for the staff.

177 Meghan Bowtell Clinical and demographic predictors of continuing remission or relapse following discontinuation of antipsychotic medication after a first episode of psychosis. A systematic review BOWTELL M (1-2), Ratheesh A (1-3), McGorry P (1-2), Killackey E (1-2), O’Donoghue B (1-3). 1. Orygen, the National Centre of Excellence in Youth Mental Health 2. Centre for Youth Mental Health, University of Melbourne, 3. Orygen Youth Health

Background: The necessity of long-term antipsychotic maintenance therapy after a first episode of psychosis (FEP) is controversial. Clinical guidelines recommend maintenance treatment with antipsychotic medication for one to two years following remission of symptoms after a FEP. However, recent research has suggested that this length of treatment may not be necessary. Consistent predictors of outcome after discontinuation would be beneficial to guide clinicians. Aim: This study reviews the literature with the aim of identifying demographic and clinical predictors of either relapse or continued remission in those with a FEP following discontinuation of antipsychotic medication. Methods: Data Sources: A systematic search of PubMed, CINAHL, and PsychInfo databases was performed. Eligibility Criteria: Cohort, case-control and clinical trials studies that were published in English, included participants with a FEP, and examined clinical and demographic predictors of relapse or continued remission after antipsychotic discontinuation. Results: Eight studies fulfilled the inclusion criteria. Predictors of continuing remission following discontinuation were more years of education and better subjective clinician rated prognosis at baseline. Predictors of relapse were: male sex, unemployment, not in education or training, a diagnosis of schizophrenia, less severe positive symptoms after acute treatment, more severe negative symptoms, poorer functioning, substance misuse, poorer premorbid adjustment and schizoid-schizotypal traits and a greater number of prior psychiatric hospital admissions. Variables found not to be associated with either relapse or continued remission: age at presentation and illness onset, duration of antipsychotic treatment, DUP, depressive symptoms and insight. No predictive findings were replicated between studies. Conclusion: While a number of predictors of continued remission and relapse following discontinuation were identified, further studies are required to replicate these findings.

178 Md Shaki Mostaid Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients MOSTAID MS(1,4), Lee T(2), Chana G(2,3,11), Sundram S(3,5,6), Weickert CS(8,9,10), Pantelis C(1,2,3,4,5), Everall IP(1,2,3,4,5), Bousman C(1,3,4,7) 1.Melbourne Neuropsychiatry Centre, University of Melbourne; 2.Centre for Neural Engineering, University of Melbourne; 3.Florey Institute of Neuroscience and Mental Health, University of Melbourne; 4.The Cooperative Research Centre for Mental Health; 5.Northwestern Mental Health;6.Department of Psychiatry, Monash University; 7.Department of General Practice, University of Melbourne; 8.Schizophrenia Research Institute; 9.Schizophrenia Research Laboratory, Neuroscience Research Australia; 10.School of Psychiatry, Faculty of Medicine, UNSW; 11.Department of Medicine, Royal Melbourne Hospital

Aim: Exploration of the Neuregulin-1 (NRG1) pathway for peripheral biomarkers of clozapine-treated schizophrenia. Background: Differential expression of neuregulin-1 (NRG1) mRNA isoforms and proteins has been reported in schizophrenia, primarily in post-mortem brain tissue. Although peripheral blood studies exist, the mRNA isoforms and proteins examined have varied and the impact of genetic variation, medication, lifestyle (e.g. smoking), and/or symptom severity have on NRG1 mRNA and protein expression has not been examined. Methods: In this study we examined 14 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I(Ig2), type II, type III, type IV, EGFα, EGFβ, pan-NRG1) in whole blood and NRG1-β1 protein in serum of clozapine-treated schizophrenia patients (N=71) and healthy controls (N=57). In addition, using cultured peripheral blood mononuclear cells from 15 healthy individuals, we examined in vitro the effect of clozapine exposure on NRG1 mRNA isoform and protein expression at two time-points (24 hours and 7 days). Results: We found elevated mRNA expression of EGFα (P=0.0175), EGFβ (P=0.002) and typeI(Ig2)(P=0.023) and lower NRG1-β1 serum protein levels (p= 0.019) in schizophrenia patients compared to healthy controls. However, adjusting for smoking status attenuated the difference in NRG1-β1 serum levels (p=0.050). We found no evidence that NRG1 mRNA isoform or protein expression was associated with NRG1 genetic variation, symptom severity, clozapine plasma levels or chlorpromazine equivalent antipsychotic exposure, which was further corroborated by our in vitro analysis. Conclusion: Our findings suggest a unique peripheral expression profile of NRG1 isoforms in schizophrenia and support further investigation of the clinical correlates of dyregulated peripheral NRG1 transcription among those with schizophrenia.

179 Suriati Mohamed Saini Meta-analysis supports GWAS implicated link between GRM3 and schizophrenia risk SURIATI MS (1,2), Mancuso SG (1), Mostaid MS (1), Liu C (1), Pantelis C (1,3,4), Everall IP (1,3,4)*, Bousman CA (1,3,6)* 1. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne; 2. UKM Medical Center, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia; 3. Florey Institute of Neuroscience and Mental Health, The University of Melbourne; 4. Department of Psychiatry, School of Clinical Sciences, Monash University and Monash Health; 5. North Western Mental Health; 6. Department of General Practice, The University of Melbourne. *contributed equally

Aims: To provide an updated and comprehensive meta-analysis of the association between GRM3 genetic variation and schizophrenia as well as an exploration of potential population stratification. Background: Genome-wide association study (GWAS) evidence has identified the metabotropic glutamate receptor 3

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(GRM3) gene as a potential harbour for schizophrenia risk variants. However, previous meta-analyses have refuted the association between GRM3 single-nucleotide polymorphisms (SNPs) and schizophrenia risk. Methods: We conducted the largest and most comprehensive meta-analysis of 14 SNPs in GRM3 from a total of 9,797 schizophrenia cases, 12,349 controls, and 486 parent-proband trios obtained from a systematic search of databases. Results: We found significant associations for three SNPs (rs2237562, rs13242038, rs917071). Two of these SNPs (rs2237562, rs917071) were in strong to moderate linkage disequilibrium with the top GRM3 GWAS significant SNP (rs12704290) reported by the Schizophrenia Working Group of the Psychiatric Genomics Consortium. We also found evidence for population stratification related to rs2237562 in that the ‘risk’ allele was dependent on the population under study. Conclusion: Our findings support the GWAS implicated link between GRM3 genetic variation and schizophrenia risk as well as support the notion that alleles conferring this risk may be populations specific.

180 Eleni Ganella Risk and resilience brain networks in treatment-resistant schizophrenia Ganella E(1,2,3,4,5), Seguin C(1,2), Cali F. Bartholomeusz C(1,3,4), Sarah Whittle S(1,2), Bousman C(1,2,5,7,10,11), Wannan C(1,2,3,4,5), Di Biase M(1,2), Everall E(2,5,6,7,8), Pantelis C(1,2,5,6,7,8), Zalesky A(1,2,8) 1.Melbourne Neuropsychiatry Centre, Department of Psychiatry, the University of Melbourne and Melbourne Health. 2. Department of Psychiatry, the University of Melbourne. 3. Orygen, the National Centre of Excellence in Youth Mental Health. 4. The Centre for Youth Mental Health, the University of Melbourne. 5. The Cooperative Research Centre for Mental Health 6. North Western Mental Health, Melbourne Health. 7. Florey Institute for Neurosciences and Mental Health. 8. Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne. 9. Melbourne School of Engineering, The University of Melbourne.10. Swinburne University of Technology, Centre for Human Psychopharmacology

Aim: To characterize functional network markers of risk and resilience in schizophrenia. Background: Genes, molecules and neural circuits that are associated with, or confer risk to developing schizophrenia have been studied and mapped. It is hypothesized that certain neural systems may counterbalance familial risk of schizophrenia, and thus confer resilience to developing the disorder. This study sought to identify resting-state functional brain connectivity (rs-FC) representing putative risk or resilience endophenotypes in schizophrenia. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed in 42 individuals with treatment resistant schizophrenia (TRS), 16 unaffected first-degree family members (UFM) and 42 healthy controls. Whole-brain rs-FC networks were mapped for each individual and analysed graph theoretically to identify network markers associated with schizophrenia risk or resilience. Results: The ~900 functional connections showing significant between-group differences were operationalized as conferring: i) resilience, ii) risk, or iii) precipitating risk and/or illness effects. Approximately 95% of connections belonged to the latter two categories, with substantially fewer connections associated with resilience. Schizophrenia risk primarily involved reduced frontal and occipital rs-FC, with patients showing additional reduced frontal and temporal rs-FC. Functional brain networks were charecterized by greater local efficiency in UFM, compared to TRS and controls. Conclusions: TRS and UFM share frontal and occipital rs-FC deficits, representing a ‘risk’ endophenotype. Additional reductions in frontal and temporal rs-FC appear to be associated with risk that precipitates psychosis in vulnerable individuals, pathophysiological changes throughout the course

of illness or be due to other illness-related effects, such as medication effects. Functional brain networks are more topologically resilient in UFM compared to TRS, which may protect UFM from psychosis onset despite familial liability.

181 Cassandra Wannan Structural connectivity predicts location of regional cortical thinning in treatment-resistant schizophrenia WANNAN C (1,2,3,4,5), Bartholomeusz C (1,2,3), Cropley V (1,6), Bousman C (1,4,7,10,11), Ganella E (1,2,3,4,5), Di Biase M (1), Phassouliotis C (1), Everall I (4,5,7,8,9), Pantelis C (1,4,5,7,8,9), Zalesky A (1,9) (1) Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health. (2) Orygen, The National Centre of Excellence in Youth Mental Health. (3) The Centre for Youth Mental Health, The University of Melbourne. (4) The Cooperative Research Centre for Mental Health (5) North Western Mental Health, Melbourne Health. (6) Brain and Psychological Sciences Research Centre, Faculty Healthy, Arts, and Design, Swinburne University. (7) Florey Institute for Neurosciences and Mental Health. (8) Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne. (9) Melbourne School of Engineering, The University of Melbourne. (10) Swinburne University of Technology, Centre for Human Psychopharmacology. (11) The University of Melbourne, Department of General Practice

Background: Evidence suggests that cortical thinning in schizophrenia occurs across disparate brain regions that are structurally connected to each other. Aims: The current study aimed to: (i) characterise cortical thinning in individuals with treatment-resistant schizophrenia (TRS), (ii) examine whether the strength of corticocortical connections was greater between brain regions showing significant cortical thinning in individuals with TRS and, (iii) compare brain network properties between TRS patients and healthy controls. Methods: Cortical thickness was compared in 148 cortical regions between 47 individuals with TRS and 54 healthy controls to identify regions with significant thinning in TRS patients. Corticocortical connectivity between each pair of regions was quantified by the covariance in cortical thickness across subjects, controlling for age. Covariance in cortical thickness was determined separately for patient and control groups, resulting in a 148 × 148 connectivity matrix for both groups. The average structural connectivity strength between pairs of regions with significant cortical thinning in patients was computed. To test the hypothesis that cortical thinning is circumscribed to a sub-network of strongly connected regions, this average value was compared with the average structural connectivity in 5000 groups of randomly chosen regions. A p-value was computed as the proportion of the 5000 random groups with average connectivity equal to or exceeding the average connectivity in the group of regions with cortical thinning. This was repeated for the set of n regions with the most significant reduction in thickness, where n = 2,…i, and a p-value was similarly determined for each value of n. Each random set comprised the same number of regions as the observed number of regions with reduced thickness. Corticocortical connectivity in regions of reduced thickness was then compared between groups. Results: Significant thinning was observed in 107 of the 148 cortical regions in the TRS group relative to controls (false discovery rate corrected < 0.05). Both TRS patients and controls showed significantly greater structural covariance in cortical regions associated with thinning in TRS patients (p<0.001). However, the strength of the cortical thickness correlations was greater in TRS individuals than healthy controls (p<.001). Conclusions: Structural connectivity is a significant predictor of regional cortical thinning in schizophrenia, with regions of reduced thickness demonstrating greater structural connectivity not only in TRS individuals, but also in healthy people. Our findings suggest that cortical thinning is closely linked with

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brain connectivity, possibly due to disconnection, loss of signalling, postsynaptic dendrite retraction or transneuronal degeneration.

182 Oneil Bhalala Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue BHALALA OG(1,2), Nath AP(2,3), UK Brain Expression Consortium, Inouye M (2,4), Sibley CR(2,5,6). (1) The Royal Melbourne Hospital, Melbourne Health; (2) Centre for Systems Genomics, School of BioSciences, The University of Melbourne; (3) Department of Microbiology and Immunology, The University of Melbourne; (4) Department of Pathology, The University of Melbourne; (5) Department of Molecular Neuroscience, University College London Institute of Neurology, Russell Square House, London, UK; (6) Department of Medicine, Division of Brain Sciences, Imperial College London, UK.

Schizophrenia and the affective disorders, here comprising bipolar disorder and major depressive disorder, are psychiatric illnesses that lead to significant morbidity and mortality worldwide. Whilst understanding of their pathobiology remains limited, large case-control studies have recently identified single nucleotide polymorphisms (SNPs) associated with these disorders. However, discerning the functional effects of these SNPs has been difficult as the associated causal genes are unknown. Here we evaluated whether schizophrenia and affective disorder associated-SNPs are correlated with gene expression within human brain tissue. Specifically, to identify expression quantitative trait loci (eQTLs), we leveraged disorder-associated SNPs identified from ten genome-wide association studies with gene expression levels in post-mortem, neurologically-normal tissue from two independent human brain tissue expression datasets (UK Brain Expression Consortium (UKBEC) and Genotype-Tissue Expression (GTEx)). We identified 8,169 and 22,196 cis-acting SNPs (p < 5x10-8) in UKBEC and GTEx datasets, respectively. 1,485 cis-eQTLs associated with expression of 21 genes, including five non-coding RNAs, were significant in a meta-analysis leveraging overlapping brain regions. One cis-eQTL, rs16969968, results in a functionally disruptive missense mutation in CHRNA5, a schizophrenia-implicated gene. Importantly, comparing across tissues, we find that blood eQTLs capture < 10% of brain cis-eQTLs. Contrastingly, > 30% of brain-associated eQTLs are significant in tibial nerve. This study identifies putatively causal genes whose expression in region-specific tissue may contribute to the risk of schizophrenia and affective disorders.

183 Carolina Barbosa The role of parenting and adrenarcheal timing on affective brain function and mental health – a cross-sectional study during late childhood BARBOSA C (1), Simmons S (1), Patton G (1), Mundy L (1), Dudgeon P (1), Allen N (2), Whittle S (1) 1. The University of Melbourne; 2. University of Oregon

Internalising and externalising symptoms increase in frequency and severity from childhood to adolescence. Aspects of the pubertal transition, such as pubertal timing, have consistently been shown to play a key role in this process. However, most extant literature has focused exclusively on gonadarche, thereby neglecting potential effects of adrenarche. This earlier pubertal stage is driven by a rise in adrenal hormones, thought to affect brain function. Despite this, the role of brain function on the relationship between adrenarche and mental health has seldom been explored. Furthermore, important environmental risk factors for mental illness in childhood/adolescence, such as parenting behaviours, have rarely been considered in the context of puberty and brain function. Research integrating these neurobiological and environmental risk factors is therefore needed.

The current study aimed to investigate the role of adrenarcheal timing and parenting behaviours on affective brain function and mental health in late childhood (N=79, 39 males, 40 females, M age 9.6, s.d. 0.35). Participants were selected from a larger cohort study based on salivary measures of pubertal hormones, and were grouped into either a relatively ‘early’ or ‘late’ timing group. Participants completed a passive affective face fMRI task, and the CDI to assess depressive symptoms. Parents completed the APQ measuring parenting behaviors, and CBCL reporting on their child’s mental health. Results showed that for ‘happy’ faces higher levels of negative parenting, in particular ‘poor monitoring and supervision’ (PMSU), interacted with adrenarcheal timing to predict activity in the left superior frontal gyrus. For negative faces, PMSU interacted with 1) gender to predict activity in the right middle orbito-frontal gyrus; and 2) gender and adrenarcheal timing to predict activity in the right inferior frontal and right superior frontal gyrus. Furthermore, within the ‘early’ timing group, activity in the left superior frontal gyrus correlated with CBCL aggressive behaviour, and activity in the right inferior frontal gyrus correlated with CDI scores. These results suggest that adrenarcheal timing and parenting behaviours interact to predict affective brain function, and this may be an important mechanism for the emergence of psychopathology. Next steps in this study will include mediation analyses further exploring this hypothesis.

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