DelIrium VULnerability in GEriatrics (DIVULGE) study: a protocol for a prospective observational study of electroencephalogram associations with incident postoperative delirium

IntroductionDelirium is a neurocognitive disorder common in older adults in acute care settings. Those who develop delirium are at an increased risk of dementia, cognitive decline and death. Electroencephalography (EEG) during delirium in older adults is characterised by slowing and reduced functional connectivity, but markers of vulnerability are poorly described. We aim to identify EEG spectral power and event-related potential (ERP) markers of incident delirium in older adults to understand neural mechanisms of delirium vulnerability. Characterising delirium vulnerability will provide substantial theoretical advances and outcomes have the potential to be translated into delirium risk assessment tools.Methods and analysisWe will record EEG in 90 participants over 65 years of age prior to elective coronary artery bypass grafting (CABG) or transcatheter aortic valve implantation (TAVI). We will record 4-minutes of resting state (eyes open and eyes closed) and a 5-minute frequency auditory oddball paradigm. Outcome measures will include frequency band power, 1/f offset and slope, and ERP amplitude measures. Participants will undergo cognitive and EEG testing before their elective procedures and daily postoperative delirium assessments. Group allocation will be done retrospectively by linking preoperative EEG data according to postoperative delirium status (presence, severity, duration and subtype).Ethics and disseminationThis study is approved by the Human Research Ethics Committee of the Royal Adelaide Hospital, Central Adelaide Local Health Network and the University of South Australia Human Ethics Committee. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences.Trial registration numberACTRN12618001114235 and ACTRN12618000799257.

South Australian facial trauma: a population analysis of social economic deprivation and facial fractures

Background: Trauma remains a leading cause of morbidity and mortality in Australia. The objective of this South Australian study was to analyse epidemiological trends in facial fractures and assess the relationship between socioeconomic disadvantage and clinical outcomes. Part one of this paper includes methods and results; part two includes discussion and conclusion. The two papers should be read together. Method: A retrospective analysis of the relationship was conducted between socioeconomic disadvantage and facial fractures. All paediatric and adult patients with facial fractures who attended the Royal Adelaide Hospital and the Women’s and Children’s Hospital Adelaide between January 2012 and January 2017 either as in- or outpatients. The medical records, progress notes, imaging and operative notes from plastics, craniofacial and oral maxillofacial surgery teams were retrospectively collated into a registry and reviewed. Ethics approval was granted from the RAH Human Research and Ethics Committee [HREC/17/RAH/402]. Results: A total of 2559 patients, 1976 males (77.2%) and 583 females (22.8%), sustained a facial fracture. The most disadvantaged group had the highest proportion of facial fractures (36.9%), with the highest incidence in the 25–34 age group (22.4%). Assaults were the most common injury with decreasing odds as socioeconomic advantage increased (p<0.05). Orbitozygomatic fractures were the most common type of facial fracture (27.7%). Indigenous patients were more likely (OR=2.8) to have surgery compared to non–indigenous patients (p<0.05). There were no significant differences in length of stay between socioeconomic groups (F(4,964.387)=2.091, p = 0.080). Conclusion: Socioeconomic status strongly influences the mechanisms on injury, types of fracture and likelihood of surgery with the most disadvantaged having higher rates compared to the least disadvantaged.

South Australian facial trauma: a population analysis of social economic deprivation and facial fractures

Background: Trauma remains a leading cause of morbidity and mortality in Australia. The objective of this South Australian study was to analyse epidemiological trends in facial fractures and assess the relationship between socioeconomic disadvantage and clinical outcomes. Part one of this paper includes methods and results; part two includes discussion and conclusion. The two papers should be read together. Method: A retrospective analysis of the relationship was conducted between socioeconomic disadvantage and facial fractures. All paediatric and adult patients with facial fractures who attended the Royal Adelaide Hospital and the Women’s and Children’s Hospital Adelaide between January 2012 and January 2017 either as in- or outpatients. The medical records, progress notes, imaging and operative notes from plastics, craniofacial and oral maxillofacial surgery teams were retrospectively collated into a registry and reviewed. Ethics approval was granted from the RAH Human Research and Ethics Committee [HREC/17/RAH/402]. Results: A total of 2559 patients, 1976 males (77.2%) and 583 females (22.8%), sustained a facial fracture. The most disadvantaged group had the highest proportion of facial fractures (36.9%), with the highest incidence in the 25–34 age group (22.4%). Assaults were the most common injury with decreasing odds as socioeconomic advantage increased (p<0.05). Orbitozygomatic fractures were the most common type of facial fracture (27.7%). Indigenous patients were more likely (OR=2.8) to have surgery compared to non–indigenous patients (p<0.05). There were no significant differences in length of stay between socioeconomic groups (F(4,964.387)=2.091, p = 0.080). Conclusion: Socioeconomic status strongly influences the mechanisms on injury, types of fracture and likelihood of surgery with the most disadvantaged having higher rates compared to the least disadvantaged.

A Novel TPS Toolkit to Assess Correlation Between Transit Fluence Dosimetry and DVH Metrics for Adaptive Head and Neck Radiotherapy

Inter-fractional anatomical variations in head and neck (H&N) cancer patients can lead to clinically significant dosimetric changes. Adaptive re-planning should thus commence to negate any potential over-dosage to organs-at-risk (OAR), as well as potential under-dosage to target lesions. The aim of this study is to explore the correlation between transit fluence, as measured at an electronic portal imaging device (EPID), and dose volume histogram (DVH) metrics to target and OAR structures in a simulated environment. Planning data of 8 patients that have previously undergone adaptive radiotherapy for head and neck cancer using volumetric modulated arc therapy (VMAT) at the Royal Adelaide Hospital were selected for this study. Through delivering the original treatment plan to both the planning and rescan CTs of these 8 patients, predicted electronic portal images (EPIs) and DVH metrics corresponding to each data set were extracted using a novel RayStation script. A weighted projection mask was developed for target and OAR structures through considering the intra-angle overlap between fluence and structure contours projected onto the EPIs. The correlation between change in transit fluence and planning target volume (PTV) D98 and spinal cord D0.03cc with and without the weighting mask applied was investigated. PTV D98 was strongly correlated with mean fluence percentage difference both with and without the weighting mask applied (RMask = 0.69, RNo Mask = 0.79, N = 14, p < 0.05), where spinal cord D0.03cc exhibited a weak correlation (RMask = 0.35, RNo Mask = 0.53, N = 7, p > 0.05) however this result was not statistically significant. The simulation toolkit developed in this work provided a useful means to investigate the relationship between change in transit fluence and change in key dosimetric parameters for head and neck cancer patients.

POS0883 DETECTION OF AUTOANTIBODIES AGAINST MUSCLE-SPECIFIC FOUR-AND-A-HALF-LIM DOMAIN 1 (FHL1) IN INFLAMMATORY MYOPATHIES: RESULTS FROM A SINGLE-CENTER COHORT

Background:Autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), have been previously identified in patients with idiopathic inflammatory myopathies (IIM) (1).Objectives:The aim of this project was to determine the prevalence and associations of anti-FHL antibody in South Australian patients with histologically-confirmed IIM and in an autoimmune disease control (systemic sclerosis (SSc)).Methods:Sera from patients with IIM (n=267) from the South Australian Myositis Database (SAMD), and SSc (n=174) from the Australian Scleroderma Cohort Study (ASCS) followed at the Royal Adelaide Hospital, and healthy controls (HC, n=100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Clinical, serological and histological details were retrieved from the SAMD and the ASCS.Results:Autoantibodies to FHL1 were more frequent in patients with IIM (55/267, 20.5%) compared with SSc (18/174, 10%) (p<0.001) and HC (4/100, 4%) (p<0.001). Muscular vessel inflammation and atrophy were seen more frequently in IIM anti-FHL1+ patients compared with anti-FHL1- (p<0.01 and p<0.05). Dysphagia, marked muscle atrophy, and high CK levels were frequent in anti-FHL1+ patients with inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). In 35/54 anti-FHL1+ patients, there were no other myositis-specific autoantibodies present. Anti-FHL1 autoantibodies in patients with SSc were associated with gastric antral vascular ectasia.Conclusion:Anti-FHL1 autoantibodies were detected in 20.5% of IIM patients. In IBM and IMNM, the presence of anti-FHL1-autoantibodies was associated with a severe myopathy as suggested by presence of dysphagia and muscle atrophy.References:[1]Albrecht I, Wick C, Hallgren A, Tjarnlund A, Nagaraju K, Andrade F, et al. Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. J Clin Invest. 2015;125(12):4612-24.Disclosure of Interests:Angeles Shunashy Galindo-Feria: None declared, Begum Horuluoglu: None declared, Jessica Day: None declared, Catia Cerqueira: None declared, Susanna Proudman: None declared, Ingrid E. Lundberg Consultant of: Consulting fees from Corbus Pharmaceuticals, Inc, Grant/research support from: Research grants from Bristol Myers Squibb and Astra Zeneca, Vidya Limaye Consultant of: Scientific adviser for Actelion and Boehringer-Ingelheim, Grant/research support from: PI for clinical trials for Bayer, Boehringer-Ingelheim, Corbus, and CSL

Combined chemotherapy and EUS-guided intra-tumoral 32-P implantation for locally advanced pancreatic ductal adenocarcinoma: a pilot study

Aim: This study evaluated clinical outcomes of combined chemotherapy and Endoscopic Ultrasound (EUS) guided intra-tumoral radioactive phosphorus-32 (32P OncoSil) implantation in locally advanced pancreatic adenocarcinoma (LAPC). Methods: Consecutive patients with a new histological diagnosis of LAPC were recruited over 20 months. Baseline CT and 18FDG PET-CT were performed and repeated after 12 weeks to assess response to treatment. Following 2 cycles of conventional chemotherapy, patients underwent EUS-guided 32P OncoSil implantation followed by a further six cycles of chemotherapy. Results: Twelve patients with LAPC (8M:4F; median age 69 years, IQR 61.5-73.3) completed the treatment. Technical success was 100% and no procedural complications were reported. At 12 weeks, there was a median reduction of 8.2cm3 (95% CI 4.95-10.85; p=0.003) in tumour volume, with minimal or no 18FDG uptake in 9 (75%) patients. Tumour downstaging was achieved in 6 (50%) patients, leading to successful resection in 5 (42%) patients, of which 4 patients (80%) had clear (R0) resection margins. Conclusions: EUS guided 32P OncoSil implantation is feasible and well tolerated and was associated with a 42% rate of surgical resection in our cohort. However, further evaluation in a larger randomized multicenter trial is warranted. (32P funded by OncoSil Medical Ltd, equipment and staff funded by the Royal Adelaide Hospital, ClinicalTrials.gov number, NCT03003078).

Coronary artery echo-attenuated plaques in acute coronary syndromes: a serial intravascular ultrasound imaging study

Background Echo attenuation of atherosclerotic plaque (EAP) identified with intravascular ultrasound (IVUS) has been shown to correlate with vulnerable plaque morphologies and their presence is predictive of future cardiovascular events. EAP have predominantly been assessed at a single time point and their natural history in the immediate post acute coronary syndrome (ACS) period remains unknown. We aimed to assess this and whether their presence correlated with a more modifiable plaque composition in the immediate post-ACS setting. Methods Serial IVUS imaging was performed in non-culprit vessels of 270 patients undergoing angiogram for ACS and at 3 month follow up. IVUS analysis of plaque burden and EAP was performed. Results Baseline characteristics are described in Table 1. EAP were present at baseline in 62 patients (23%) with these patients more likely to be male (89.1% vs. 76.7%, p=0.03) but no differences in other atherosclerotic risk factors. There was no difference in baseline plaque burden between patients with EAP and those without (Percent atheroma volume [PAV] 38.9% vs. 37.8%, p=0.32). At follow up IVUS change in PAV was not statistically significantly different between patients with baseline EAP and those without (ΔPAV 0.09% vs. −0.36%, p=0.43), and neither was there a difference in the frequency of plaque regressors (42.7% vs 50%, p=0.31). EAP had resolved in 25 patients (40%) within 3 months at the follow up IVUS. Despite contemporary post-ACS therapy 18 patients who had not had EAP present at baseline (9%) developed new EAP at the follow up IVUS. Conclusion EAP were present in a quarter of ACS patients and were not associated with baseline plaque burden or a more modifiable plaque phenotype. In the setting of contemporary ACS treatments the natural history of high risk IVUS plaque characteristics such as EAP is dynamic with significant change even over a 3 month period in the post ACS setting. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Royal Adelaide Hospital Research Fund AR Clarkson Scholarship

Outcomes following grade V subarachnoid haemorrhage: A single-centre retrospective study

Summary Grade V subarachnoid haemorrhage is associated with high mortality and morbidity, yet there are few contemporary reports on the treatment provided and outcomes of these patients. In this single-centre retrospective cohort study, we primarily sought to determine the 12-month mortality of patients admitted to the Royal Adelaide Hospital intensive care unit between 2006 and 2016 with grade V subarachnoid haemorrhage. Secondary objectives were to describe treatments provided, patient destination following hospital discharge, organ donation and hospital financial costs. Over the 11-year study period, there were 139 patients admitted with grade V subarachnoid haemorrhage. The annual number of admissions did not change over time. The median age was 56 (interquartile range 48–70) years, 88 (63%) were female and 77 (55%) had a procedure to isolate an aneurysm. There were 77 (55%) patients who died in the intensive care unit, 87 (63%) died in hospital and 89 (64%) had died at 12 months. Of the 52 patients who survived to hospital discharge, 33 (63%) were transferred to a rehabilitation facility, 17 (33%) to another acute care hospital and two (4%) were discharged. Of the 87 patients who died in hospital, 45 (52%) donated organs. The total hospital cost of managing this cohort was A$8.3 million, with a median cost of A$41,824 (interquartile range A$9,933–A$97,332) per patient. Grade V subarachnoid haemorrhage has a high mortality rate, with one-third of patients alive after one year.

70Autonomic dysfunction in atrial fibrillation (AF) patients: absent vasomotor reflex to decreased cardiac venous return during af in comparison to sinus rhythm; implications for earlier rhythm control

Funding Acknowledgements Dr Malik is supported by an Australian Postgraduate Award Scholarship from the University of Adelaide. OnBehalf Centre for Heart Rhythm Disorders, University of Adelaide & Royal Adelaide Hospital Background A bi-directional relationship exists between AF and the autonomic nervous system (ANS). Patients with AF studied in sinus rhythm (SR) have impaired vasomotor responses to decreased cardiac volume. Whether autonomic dysfunction worsens during AF itself, is unknown. Purpose We examined haemodynamic responses to lower body negative pressure (LBNP) in patients with persistent AF compared to AF studied in SR. LBNP decreases cardiac volume, deactivates atrial stretch receptors and induces a reflex to maintain blood pressure by increasing systemic vascular resistance (SVR). Methods 21 consecutive patients with paroxysmal or persistent AF were studied; during AF (n = 8) or SR (n = 13). Anti-arrhythmic and anti-hypertensives were withheld for 5 half-lives. Patients underwent LBNP using a custom-made chamber sealing both lower limbs. Negative pressure at sham (-0 mmHg), low (-20 mmHg) and high level (-40 mmHg) was applied for 5 minutes each. Finger photo plethysmography was used for beat-beat-blood pressure. Computation of SVR during AF is not feasible with this method. Therefore, the right forearm was used to perform venous occlusion plethysmography (VOP); non-invasive, well validated with LBNP and impervious to AF: to estimate forearm blood flow (FBF) and SVR (inversely proportional). Results Baseline characteristics and responses to LBNP are presented in Table 1. MAP was maintained, and HR rose slightly, in the SR group. MAP and HR decreased in the AF group. VOP demonstrates a reduction in FBF in the SR group (vasoconstriction); whereas the vasomotor response to LBNP was absent during AF. Figure 1 (Panels A-C). Conclusion The presence of AF is associated with autonomic dysfunction from impaired cardiac volume regulation. This novel finding may contribute to the known risk of falls and syncope due to AF. Further studies are needed to evaluate whether abnormal cardiac reflexes are involved in atrial remodelling and AF progression. Table 1 Baseline Characteristics During AF During SR P Value Age 65 ± 5 59 ± 3 0.4 AAD & Anti-HTN medications withheld (%) 75 85 0.6 Resting mean arterial pressure (MAP) 109 ± 9 93 ± 6 0.1 Resting heart rate (HR) 94 ± 6 60 ± 4 0.0001* Haemodynamic response to LBNP % Δ MAP due to LBNP -9 ± 5 +0.5 ± 3 0.2 % Δ HR due to LBNP -6 ± 3 +5 ± 3 0.03* % Δ FBF due to LBNP +75 ± 59 -27 ± 8 0.02* AAD Anti-arrhthmic. HTN: Hypertension. Mean +/- SEM. Abstract Figure. Vasomotor response to LBNP: in AF vs SR