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Background and Aim: Current guidelines recommend indefinite nucleot( s)ide analog (NA) therapy for patients with HBeAg-negative chronic hepatitis B virus (HBV). However, sustained virological response (SVR) has been described in patients after discontinuation of long-term NA therapy. The HBV-STOP study is a prospective multicenter study of NA discontinuation in patients who have achieved long-term virological suppression on treatment. In addition to previously describing clinical outcomes after treatment discontinuation, we also aim to detail the immunological response in this scenario, especially that of the innate immune system. Method(s): Stimulation study: To gauge the potential innate activation of the peripheral blood cells by the flare, we stimulated peripheral blood mononuclear cell (PBMC) samples of HBV-STOP study patients by toll-like receptor (TLR)-specific ligands (TLR-2, TLR-3, TLR-4, TLR-7/8, and TLR-9) ex vivo. These patients either had a large biochemical flare (alanine aminotransferase [ALT] level > 10 x ULN) or did not have a biochemical flare (ALT < ULN). PBMCs were tested at baseline and peak ALT level time points, and matched non-flare samples were used as controls. Cytokine levels (IL-6, IL-8, IL-10, TNF, CCL-2, and CXCL-10) were measured after PBMC stimulation. Flow cytometry study: Additionally, we performed flow cytometry on PBMC samples of HBV-STOP study patients who either had a large biochemical flare (ALT > 10 x ULN) or did not have a biochemical flare. We did these studies at baseline and peak ALT level time points. Non-flare samples were matched to the closest respective week. Flow cytometry was used to isolate specific natural killer (NK) cell and monocyte populations using CD 56, CD 3, CD 16, and CD 14 cell surface markers. Expression of various immune markers was assessed in each cell population, including NKP46, NKG2D, TLR2, TLR4, and TREM1. Result(s): The stimulation study cohort consisted of 13 patients with flares and 12 patient

Background and Aim: Current guidelines recommend indefinite nucleot(-s)ide analog (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB) infection. However, sustained virological response (SVR) has been described in patients after discontinuation of long-term NA therapy, as well as HBsAg loss. The HBV-STOP study is a prospective multicenter study of NA discontinuation in patients who have achieved long-term virological suppression of hepatitis B virus (HBV) on treatment. The study describes clinical outcomes after treatment discontinuation, with the aim of identifying determinants of SVR. Method(s): We performed an interim narrative analysis of outcomes at Week 48 after NA discontinuation. Outcomes at Week 96 are the primary endpoint for the study. Inclusion criteria for the study were HBeAg-negative, non-cirrhotic, and virological suppression for > 18 months on NA therapy uninterrupted for > 2 years. Criteria for recommencing NA therapy were HBV DNA > 2000 IU/mL with either alanine aminotransferase (ALT) > 5x ULN for > 16 weeks or ALT > 10x ULN for > 8 weeks, international normalized ratio > 1.5, bilirubin level > 2x ULN, ascites, hepatic encephalopathy, and investigator discretion. Result(s): The cohort is fully enrolled, and data are currently available for 111 patients. At baseline, median patient age was 56 years, 64% were male, and 85% were Asian. The median HBsAg level was 705 IU/mL (214-2325). All patients were non-cirrhotic. Virological reactivation occurred in all, with a median time to detection of 8 weeks (4-12). Patients stopping tenofovir (TDF) experienced virological and biochemical relapse earlier than patients stopping entecavir (ETV) (Fig. 1; P < 0.001). Twenty-three patients (21%) have experienced an ALT flare > 10x ULN; there was no significant difference in the rate of ALT flare > 10x ULN after stopping TDF versus ETV. Two patterns of ALT flare were observed: beneficial flares that were associated with reductions in HBV DNA and

Background and Aim: The most commonly used diagnostic instrument to detect inflammation of an ileal pouch-anal anastomosis (IPAA) is the 18-point Pouchitis Disease Activity Index (PDAI). A total PDAI score of >= 7 or a modified PDAI (mPDAI) score of >= 5 is considered diagnostic for pouchitis. The consistency of scoring between endoscopists using the PDAI is poor, likely owing to the variable interrater reliability of the endoscopic components of the score; therefore, alternative scoring systems have been proposed.We aimed to assess the interrater reliability of endoscopic findings and compare the diagnostic utility of a simpler version of the PDAI. Method(s): We conducted a prospective, observational study at a single tertiary center. Consecutive patients with an IPAA were recruited. Clinical, endoscopic, and histological data were collected. Pouchoscopies occurred a median of 37 days after clinical review and were reviewed by two experienced gastroenterologists, while biopsies were reviewed by a single pathologist, all of whom were blinded to the clinical history. We assessed the interrater reliability and diagnostic performance of three disease activity scores: the traditional PDAI; a proposed alternative score combined with clinical PDAI; and a simplified PDAI (sPDAI), which uses only PDAI endoscopy items with at least high-moderate interrater reliability (Cohen's kappa >= 0.5). Interrater reliability was assessed by calculating observed agreement and Cohen's kappa coefficient. Diagnostic performance was analyzed using receiver operator characteristic (ROC) analysis. Result(s): A total of 35 patients (mean age, 52 years; 72% male) underwent a pouchoscopy. All had a J pouch. The mean age of the pouches was 12.8 years (1-27). Seven patients had a normal pouch, 13 had antibiotic-responsive pouchitis, eight had antibiotic-dependent pouchitis, three had antibiotic-refractory pouchitis, and three had Crohn's disease of the pouch. Of the PDAI endoscopic components, onl

Introduction/Aim. Virus infections in patients with pre-existing lung conditions such as asthma and chronic obstructive pulmonary disease often have devastating consequences. Transforming growth factor beta (TGFB) is upregulated in these diseases and its immune-suppressive actions may be pertinent to the vulnerability of patients to damaging infections. We explored influenza A virus (IAV) infection in models of acute and chronic TGFB over-expression and evaluated benefits of pirfenidone, a TGFB antagonist in clinical use for lung fibrosis. Methods. We utilised a transgenic mouse model of TGFB overexpression in the lung. Following IAV infection, tissue and bronchoalveolar lavage (BAL) fluid were assessed for IAV replication, disease severity, inflammation and immune responses. Treatment with pirfenidone was given by gavage and responses compared. Results. In both acute and chronic models mice with elevated TGFB developed more severe bronchitis and pneumonia (P < 0.05). IAV replication was increased (P < 0.001), the result of blunted innate immune responses (P < 0.001). TGFB also mediated significant elevations of inflammatory cytokines, chemokines and inflammatory cell populations in BAL. Administration of pirfenidone during infection reduced disease severity by dampening inflammatory responses and reducing IAV replication. Conclusion. Our findings demonstrate profound immune suppression mediated by TGFB leading to amplified virus infection and intensified lung inflammation. Pirfenidone opposed the detrimental effects of TGFB by reducing inflammation, thus diminishing the extent of infection. Collectively, these data reveal the damaging activities of TGFB during virus infections in lung diseases characterised by TGFB over-production. We further provide proof-of-concept evidence that repurposing pirfenidone can oppose TGFB activities and attenuate virus infections in a susceptible patient population.

Aim: To investigate the effect of latent cytomegalovirus (CMV) infection on experimental anti-myeloperoxidase (MPO) autoimmunity and glomerulonephritis (GN). Background(s): Autoimmunity to MPO results in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and GN. CMV is present, lifelong, in a latent state after primary infection. Latent CMV infection causes increased peripheral blood CD28- T cells that contribute to mortality in AAV, but this is mechanistically unclear. Method(s): Mice were infected with mouse CMV (K181delm157). Seven weeks later, when viral latency was established (by organ CMV plaque assay, including kidneys), mice were immunised with MPO and autoimmunity assessed 10- and 28-days after immunization. Anti-MPO GN was induced by immunising mice with MPO, GN was triggered by low dose anti-mouse basement membrane globulin, and disease assessed 4 days post trigger (day 21). Result(s): Latent CMV infection induced heightened anti-MPO autoimmunity with increased lymph node MPO-stimulated IL-17A and IFNgamma production (ELISPOT day 10, sustained at day 21 in anti-MPO GN). Latent CMV infection did not significantly increase MPO-ANCA titres, but autoreactive B cell numbers were increased. In mice with GN, latent infection resulted in increased intrarenal macrophages, CD4 + and CD8+ T cells. Intrarenal CMVspecific CD8+ T cells were detected in CMV infected mice with GN by MHCIpeptide tetramer staining. CD28-CD4 + and CD8 + populations were expanded, while intrarenal CD4+ and CD8+ T cells in CMV infected mice with GN exhibited heightened TNF and IFNgamma production as well as increased cytotoxic potential, measured by surface CD107a expression. CMV infected mice with GN developed increased proteinuria, though short-term histological glomerular injury was similar. Conclusion(s): Experimentally, latent CMV infection results in heightened anti-MPO autoimmunity and renal inflammation; and may directly influence the course of MPO-AAV in humans.

Introduction/Aim. Clinical guidelines on obstructive lung disease contain few recommendations on household air pollution (HAP), although it is known to cause oxidative stress, which is associated with pathogenesis of obstructive lung disease. Associations between HAP and obstructive lung disease may be modified by Glutathione S-Transferase (GST) gene polymorphisms and home ventilation. We aimed to identify longitudinal HAP profiles associated with asthma risk and lung function decline in middle-aged adults and whether these associations were modified by GST gene variants and home ventilation. Methods. We used measurements of HAP exposures (emission sources for heating/cooking, mould, smoking) asthma, and housing characteristics collected for the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n = 3314). Latent class analysis was used to characterize longitudinal exposure patterns. A sub group had data on lung function (n = 897) and GST polymorphisms (GSTM1, GSTT1 and GSTP1) (n = 928). Regression models assessed associations and interactions. Results. We identified seven longitudinal HAP profiles. Four of these ("wood heating", "all gas", "wood heating/smoking" and "wood heating/gas cooking") were associated with persistent asthma, greater lung function decline and greater bronchodilator reversibility (BDR) by age 53 years. Exposed participants with GSTP1 Ile/Ile and GSTM1 null genotypes were at higher risk of asthma or greater lung function decline compared to other genotypes. Home ventilation modified these adverse effects; participants not using cooking exhaust fans or living in newer, better sealed, buildings had increased risk of asthma. Conclusion. Longitudinal exposure to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risk of persistent asthma, lung function decline and increased BDR. There was evidence of effect modification by GST genotypes and home ventilation. These findings inform the developm

Introduction. Whether systemic and airway inflammation persist in remitted asthma and whether such inflammation is associated with adverse long-term respiratory outcomes remains unclear. Objective. To determine the prevalence of systemic and airway inflammation in adults with remitted asthma, and to examine their associations with asthma relapse and lung function decline. Methods. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort first studied in 1968 (n = 8,583). In 2004 (age 44), biomarkers of systemic inflammation (serum IL-4, IL-5, IL-6, IL-8, IL10, TNF-) were measured in a subgroup (n = 1,389) and categorised into cytokine profiles using latent profile analysis (LPA). In 2010 (age 50), markers of airway inflammation, methacholine challenge tests (n = 836) and total nitric oxide products in exhaled breath condensate (EBC NOx), were measured. Asthma relapse and lung function decline were assessed at follow-up in 2014. Multivariable linear and Poisson regression were used to examine relevant associations. Results. Of adults with remitted asthma at age 50 years, 20.8% [95% CI 15.9, 26.7] had bronchial hyperresponsiveness (BHR) and 7.1% [95% CI 4.2 ,11.9] had an elevated EBC NOx (>5.05 mumol/L). Asthma relapse was associated with BHR (RR 2.25 [95%CI 1.52, 3.32]), but not with elevated EBC NOx. Three distinct cytokine profiles were identified via LPA: A reference anormala cytokine profile, a aTh2-higha profile associated with accelerated post-BD FEV1/FVC decline (MD-0.18% predicted/year [-0.33,-0.02]), and a aTh2-lowa profile associated with accelerated postBD FEV1 (MD-0.41% predicted/year [-0.75,-0.06]) and post-BD FVC decline (MD-0.31% predicted/year [-0.62, 0.01]). Conclusion. BHR and elevated biomarkers of asthma activity have prognostic value in adults with remitted asthma. At-risk individuals may benefit from closer follow-up, repeat spirometry and potentially antiinflammatory agents.

Aim: To investigate whether recombinant follistatin can suppress renal interstitial fibrosis in a mouse model of folic acid nephropathy (FAN). Background(s): Renal interstitial fibrosis is a common pathologic feature in progressive kidney disease, but we lack effective anti-fibrotic therapies. Activin A, a member of the transforming growth factor beta superfamily of cytokines, is upregulated in animal models of renal fibrosis including unilateral ureter obstruction and diabetic kidney disease. Follistatin is a secreted protein that binds to and inhibits the function of Activin A. We evaluated the therapeutic potential of recombinant follistatin (FST288) in the FAN model. Method(s): Male C57BL/6 mice (n = 8/9 group) were administered 250 mg/ kg folic acid. Urine was collected on day 3. Mice were treated once daily with 2 mg/kg FST288 (Paranta Biosciences) or vehicle by intraperitoneal injection from day 6 until being killed on day 14. Normal mice were controls. Renal function, inflammation and fibrosis were assayed. Result(s): Vehicle-treated animals developed renal function impairment (12.1 +/- 2.4 vs 7.2 +/- 1.7 mumol/L plasma creatinine in normals; P < 0.01), with focal areas of the cortex exhibiting tubular damage, macrophage and myofibroblast infiltration and collagen IV deposition. RT-PCR analysis of kidney tissue showed increased levels of Collagen I, CD68, alpha-SMA and Activin A mRNA. Treatment with FST288 did not affect renal dysfunction (10.5 +/- 1.8 mumol/L plasma creatinine; P=NS). Similarly, FST288 treatment did not affect histologic damage or reduce mRNA levels of collagen I, CD68, alpha-SMA or ActA (all P=NS). The day 3 urine KIM-1 to creatinine ratio was not different between FST288 and vehicle treated groups, confirming an equivalent induction of acute kidney injury. Conclusion(s): FST288 treatment did not provide protection against renal interstitial inflammation or fibrosis in the FAN model.

Introduction/Aim. Clinical guidelines recommend people with bronchiectasis undertake exercise training and physical activity as part of their disease management. This systematic review aimed to determine the effects of exercise training compared to usual care on exercise tolerance and health-related quality of life (HRQoL) in people with bronchiectasis. Methods. Randomised controlled trials (RCTs) involving structured exercise training programs of >=4 weeks duration which targeted improvements in physical function +/- exercise tolerance were identified from the Cochrane Airways Specialist Register (up to June 2019). Co-interventions such as airway clearance therapy or respiratory muscle training were permitted. Two review authors independently assessed studies for inclusion, data extraction and risk of bias. Outcomes included incremental shuttlewalk test distance (ISWD), 6-minute walk distance (6MWD), St Georgeas Respiratory Questionnaire (SGRQ) total score and Leicester Cough Questionnaire (LCQ) total score, at end intervention. Results. Six RCTs involving 275 participants were included. When applied for people with stable bronchiectasis (n = 5 studies), exercise training was associated with greater improvements in ISWD (standardised mean difference 0.97 [95%CI 0.64 to 1.31]) and SGRQ total score (mean difference [MD]-9.21[-12.65 to-5.77] units), but not LCQ total score (MD 0.01 [95%CI-0.76 to 0.78] units) compared to usual care. No discernible difference between exercise training and usual care was evident in 6MWD (MD 11 m [95%CI-27 to 49 m]) or LCQ total score (MD-0.08 [95% CI-0.94 to 0.78] units) when applied after an acute exacerbation (n = 1 study). Risk of selection, detection and reporting bias was generally low or unclear. Conclusions. Exercise training improves exercise tolerance, diseasespecific and cough-related QOL in people with stable bronchiectasis, but may offer limited value in the period after a recent exacerbation., A. Lee, Monash University, CONFERENCE ABSTRACT

Background and Aim: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis, with no established clinical guidelines.We sought to define the clinical outcomes of patients presenting with HH and managed with current standards of care. Method(s): ICD-10 codes identified cirrhotic patients with HH presenting to three tertiary centers in Melbourne, Australia, from 2010 to 2018. HH was defined as pleural effusion in the absence of cardiopulmonary disease. Medical records were reviewed to determine baseline characteristics and survival. The primary outcome was 12-month mortality. The Kaplan- Meier method was used to calculate survival probability. Result(s): A total of 82 patients were included (median age, 59 years [IQR, 54-63]; 56% male; median Model for End-Stage Liver Disease score, 29 [IQR, 25-33]). Common causes of cirrhosis were viral (33%), non-alcoholic fatty liver disease (19%), and alcohol (16%); 29% of patients had hepatocellular carcinoma. Pleural effusions were typically right-sided (85%), and 73% had concurrent ascites. There were 169 hospital admissions for HH during the study period. Mean length of stay was 12 days, and 27% required intensive care unit admission. At presentation, 89% and 7% of patients were prescribed diuretics and non-selective betablockers, respectively. Diuretic therapy alone was commenced in 13 presentations (8%), while 120 patients (71%) received diuresis and pleurocentesis (median, 3 L drained); 25% required blood products to facilitate pleurocentesis. Twenty-three patients received intercostal drain insertion, one had pleurodesis, and 10 proceeded to transjugular intrahepatic portosystemic shunt insertion. There were 24 patients (29%) who underwent orthotopic liver transplantation (OLT). Significant complications were observed in 46% of admissions, including acute kidney injury (n = 54), infection (n = 28), hepatic encephalopathy (n = 21), and pneumothorax (n = 11). Overall, 83% of patients require

Background and Aim: Patients with ileal pouch-anal anastomosis (IPAA) often require a pouchoscopy to investigate symptoms of increased frequency, urgency, and abdominal cramps, which are not specific to pouchitis. Fecal calprotectin (FC) testing has the potential to be an alternative non-invasive tool for the assessment of pouch activity.We aimed to assess the utility of FC testing in the assessment of inflammatory complications of the pouch. Method(s): We conducted a prospective observational study at a single center between October 2018 and November 2019. Consecutive symptomatic patients with IPAA referred from clinic were recruited. At recruitment, clinical data, as well as FC and serum C-reactive protein (CRP) levels, were measured. Pouchoscopy was performed after a median of 35 days. Histopathological examination of biopsies of the pre-pouch ileum, pouch body, and cuff was performed by a single pathologist blinded to the clinical history. A diagnosis of pouchitis was defined as Pouchitis Disease Activity Index (PDAI) score >= 7. Associations were assessed by correlation and regression analyses, and area under the curve (AUC) for receiver operator characteristic analysis was used to analyze diagnostic performance of CRP and FC. Result(s): Of 40 patients, 34 had complete data (mean age, 52.4 years; 72% male). Seven had a normal pouch, 13 had antibiotic-responsive pouchitis, eight had antibiotic-dependent pouchitis, three had antibiotic-refractory pouchitis, and three had Crohn's disease of the pouch. Two-thirds had active pouchitis. Median FC level was higher in 20 patients with pouchitis (442 mug/g; interquartile range [IQR], 345- 590) compared with 11 with isolated cuffitis and/or pre-pouch ileitis without pouchitis (167 mug/g; IQR, 75-320; P = 0.03) and nine without pouchitis or cuffitis/pre-pouch ileitis (66 mug/g; IQR, 44-120; P < 0.001). No patients had isolated pouchitis without cuffitis or ileitis. After multivariate adjustment for presence of cuffitis (n

Introduction: Lower gastrointestinal haemorrhage (LGIH) is a challenging phenomenon in a comorbid, elderly population. CT mesenteric angiography (CTMA) allows localisation of the site of haemorrhage, and provides a target for interventional techniques, but the intermittent nature of LGIH makes it challenging to reliably demonstrate extravasation. This study aimed to identify objective factors that may predict scan outcomes. Method(s): In this retrospective cohort study, all patients undergoing CTMA for LGIH at Monash Health from January 2011 to December 2019 (n = 854) were included. Baseline patient characteristics included age, bowel resection/endoscopic intervention within the past 14 days, known bowel malignancy, anticoagulant/antiplatelet use, duration of symptoms, vital signs, transfusion requirements in the past 24 h and investigation results (recent haemoglobin levels, platelet count, international normalised ratio and creatinine levels). Univariate analysis was performed, and significant factors were entered into a multivariate model. Result(s): The final multivariate model was statistically significant (P < 0.001) and consisted of bowel resection/endoscopic intervention within the past 14 days (OR = 2.15), use of antiplatelet agents (OR = 2.03), blood transfusion requirement greater than 3 units per 24 h (OR = 1.79), systolic blood pressure less than 100 mmHg (OR = 1.56) and heart rate greater than 100 beats per minute (OR = 1.52). Conclusion(s): The factors identified above are objective, independently associated with positive scan outcomes, readily available to radiologists and are useful for more judicious patient selection.Copyright © 2021 The Royal Australian and New Zealand College of Radiologists

Background and Aim: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with limited effective medical therapies and a paucity of epidemiological and outcome-based data in Australia. We aimed to retrospectively evaluate the demographics and outcomes of an Australian cohort of patients with PSC. Method(s): We performed a retrospective cohort study of patients with PSC at six tertiary health services, including two liver transplant units. Patients were identified by a computerized search of radiological reports. Predictors of transplant-free survival (need for liver transplantation or death from any cause) were analyzed. Result(s): We identified 405 patients with PSC, of whom 261 patients (64.4%) were known to a liver transplant unit. The median age at diagnosis was 36.2 years (IQR, 23.4-50.9), and 261 patients (64.4%) were male. The median alkaline phosphatase (ALP) level at diagnosis was 251 U/L (IQR, 156-436). During a median follow-up of 7.0 years (IQR, 3.3-12.0), the median ALP level improved to 143 U/L (IQR, 92-278) (P < 0.01). Most patients (247, 61%) were prescribed ursodeoxycholic acid (UDCA) at a median dose of 1000 mg (IQR, 750-1000). Of those treated with UDCA, 91 (36.8%) achieved a > 50% reduction in baseline ALP level during follow-up. An overlap syndrome was identified in 47 patients (15.2%), and a dominant stricture (DS) developed in 122 (30.1%). A total of 191 patients (47.3%) developed cirrhosis, of whom 87 (45.6%) had a decompensation episode. There were 282 patients (71.6%) with concomitant inflammatory bowel disease (IBD): ulcerative colitis (54%), Crohn's disease (16%), or IBD unspecified (2%). One hundred patients (24.7%) underwent liver transplantation, and 51 (12.6%) died (82.3% liver-related death). Gastrointestinal malignancies included cholangiocarcinoma (CCA) (26, 6.4%), hepatocellular carcinoma (HCC) (12, 3.0%), and colorectal cancer (15, 3.8%). The proportion of transplant-free survival was 88.5% at 5 years, 73.8%

Background and Aim: Transient elastography with liver stiffness measurement (LSM) is known to correlate with liver fibrosis and liver-related outcomes. 4AGP is a new algorithm that uses indirect biomarkers to determine those who are at risk of elevated LSM (> 12.5 kPa). It is calculated using alpha-fetoprotein, albumin, aspartate aminotransferase, age, sex (gender), and platelet count. Although 4AGP correlates with elevated LSM in patients with chronic hepatitis C (CHC) virus infection, it is unknown whether it also predicts liver-related outcomes. We aimed to determine whether LSM or 4AGP, or other indirect biomarkers such as aspartate aminotransferase to platelet ratio index (APRI), Fibrosis-4 (FIB-4), or Forns index, can best predict liver-related outcomes in a cohort of patients with CHC. Method(s): The Community Approach Targeting Cirrhosis and Hepatocellular Carcinoma (CATCH) study is a prospective study that recruited patient with CHC. Baseline LSM and indirect biomarkers were assessed (all were before treatment), along with outcomes (hepatocellular carcinoma [HCC], decompensation, or liver-related death). Survival curves were analyzed using a log-rank test, along with receiver operator characteristic (ROC) curves and Cox proportional hazard ratios. Optimal cut-off points were calculated, accounting for sensitivity, specificity, false positives and negatives, as well as the area under the ROC curve (AUROC). Result(s): A total of 1049 patients with CHC were recruited between October 2014 and June 2018. Mean follow-up was 3.4 +/- 0.7 years, indicating 3631 patient-years. Patients' mean age was 45.1 years (19-82), and 31.3% were female. Seven patients developed HCC; the best predictors of HCC development were, in order, 4AGP, Forns index, FIB-4, LSM, and APRI (Fig. 1a). An LSM of 21.3 kPa was the optimal cut-off point for predicting HCC, with a sensitivity of 85.7%, specificity of 92.2%, and a hazard ratio (HR) of 30 (95% CI, 5.7-150). A 4AGP value of -2.81 had

Background and Aim: Peroral endoscopic myotomy (POEM) is an emerging minimally invasive technique for the management of achalasia. Previously, treatment options consisted of endoscopic pneumatic dilatation or laparoscopic Heller myotomy with Dor fundoplication (LHM). We aimed to compare differences in length of stay, costs incurred, and clinical outcomes among patients with achalasia who underwent a POEM or LHM in a single tertiary center. Method(s): We performed a retrospective audit of all patients who underwent POEM or LHM for diagnosed achalasia at our center between July 2016 and June 2020. All patients had data on their demographics, length of inpatient admission, cost of inpatient admission, theater costs, theater time, and weighted inlier equivalent separation (WIES) funding recorded. The two-sample Wilcoxon rank-sum (Mann-Whitney) test and Shapiro-Wilk W test were used to compare patient demographics and procedural characteristics between the two groups. Costs were in Australian dollars. Clinical success was defined as no need for further intervention, either endoscopic or surgical. Given the small sample sizes, statisticalsignificance was based on the calculation of exact P values. Statistics were calculated using Stata (StataCorp). Result(s): During the period of July 2016 to June 2020, 18 patients underwent POEM, and 14 patients underwent LHM. The average age of patients overall was 55.1 years (POEM, 63.1 years; LHM, 45 years). There were eight men and 10 women who underwent POEM, and nine women and five men who underwent LHM. The mean follow-up time was 7.97 months (SD, 5.23) for POEM patients and 9.14 months (SD 8.84) for LHM patients. Mean length of stay for POEM was 1.72 days (SD, 1.07), compared with 3.29 days (SD, 1.64) days for LHM (P = 0.0009). The median total cost of admission for LHM was $8363.02 (IQR, $7354.64 to $9803.32), compared with $10 472.12 (IQR, $8950.29 to $14 167.95) for POEM (P = 0.0229). Mean total costs less theater consumables

Aim: To investigate the relationship between ANCA-associated vasculitis (AAV), work disability, and employment in a cohort of Australian patients of working age. Background(s): AAV may impact individuals of working age. Those affected frequently experience ongoing morbidity and reduced quality of life due to low-grade disease activity, disease relapses, fatigue, psychosocial factors, immunosuppressant toxicity, and irreversible end-organ damage. These effects can impact on the ability of an individual to work. Method(s): Patients completed an employment questionnaire in addition to a Work Productivity and Activity Impairment Questionnaire: Specific Health Problem at the time of their Vasculitis Clinic appointment. Result(s): 47 respondents were included in the study. They had an average age of 47.8 +/- 11.9 years (range 22-63 years) and a median disease duration of 60 months (range 10.2-318.5 months). 68.1% of the respondents were currently employed. 20.6% of those employed at the time of diagnosis were no longer working and 10.6% had experienced a significant reduction in work hours since their diagnosis. 23.4% of participants were work disabled, including 12.7% dependent on the disability support pension. 41.9% considered themselves work impaired and 44.7% reported that their financial stability had been adversely impacted by their vasculitis diagnosis. Fatigue was a commonly reported complaint impacting on work and productivity. Work disabled patients were significantly more likely to be obese and less likely to have completed tertiary education. Work disabled patients tended to be older, MPO-ANCA positive, and have renal involvement and lung involvement. Conclusion(s): Work disability is common in Australians with AAV. The potentially modifiable factors of fatigue and obesity are at least associated with, and likely contribute to work disability.

Objective: Misuse of prescription opioids is a significant public health issue in Australia. There has been a rapid rise in prescription opioid use, with an associated increase in overdose and death. The over-prescribing of oral opioids, especially oxycodone, in the ED has been identified as a contributor to this problem overseas. It is unclear if similar practice occurs in the Australian ED. The primary aim of our study was to identify the incidence of oral oxycodone administration to patients within the ED. The secondary outcome was to identify the incidence of oxycodone prescribed to patients on discharge from the ED into the community. Method(s): Our study was designed as an observational, retrospective data analysis of the incidence of oxycodone prescribed within the three EDs of a large Australian public health service. All immediate-release (IR) and slow-release (SR) oral oxycodone prescribed over a 4-year period (2015-2018) was included. Result(s): There were 890 557 presentations to the three EDs during the period, which resulted in 288 242 episodes of oxycodone administration within department, equivalent to 324 administrations per 1000 presentations. There were 39 381 prescriptions for oxycodone provided on discharge, resulting in an incidence of 44 prescriptions per 1000 discharged. The most frequently prescribed opioid medication in the ED was oxycodone IR 5 mg, 78.6% of discharge prescriptions generated provided a maximum quantity (20 for IR formulation or 28 for SR) of tablets allowable under the pharmaceutical benefits scheme. Conclusion(s): There is a higher incidence of oxycodone prescribing in the Australian ED than previously recognised. An overuse of oxycodone may be contributing to adverse patient outcomes and a public health crisis. Hospitals should consider appropriate steps to reduce the incidence of opioid prescribing and the supply of these medications into the community.Copyright © 2020 Australasian College for Emergency Medicine

Introduction/Aim. Aortic stiffness is a key determinant of cardiovascular morbidity and mortality. Acute Exacerbations of COPD (AECOPD) are accompanied by a spike in systemic stiffness. We investigated an important constituent of systemic stiffness, aortic strain (AS), in a prospective observational cohort study of patients admitted to our tertiary centre with doctor-diagnosed AECOPD. The primary hypothesis was that AS would be increased at exacerbation in comparison to recovery, and the secondary hypothesis was that AS would be associated with clinical and biochemical parameters. Methods. 67 individuals underwent dynamic ECG-gated 256-multidetector CT both during hospitalisation for AECOPD and following discharge and clinical recovery. Ascending aortic cross-sectional area was measured at 10% ECG R-R intervals at the ascending aorta midpoint (mid-way between aortic valve and brachiocephalic trunk). AS was calculated as (maximum area a- minimum area)/minimum area. Paired ttests and Pearson correlations were used for analysis. Results. AS was lower at recovery compared to AECOPD (10.2 +/- 6.4 vs 8.3 +/- 4.2, mean +/- SD, P = 0.01) and it was negatively correlated with age (r = -0.434, P < 0.001). AI was not associated with FEV1, diffusing capacity, emphysema index, left ventricular ejection fraction, coronary artery calcium score, troponin, b-type natriuretic peptide, length of stay, baseline modified Medical Research Council dyspnoea score, Charlson Comorbidity Index or COPD Assessment Test. Conclusion. AS is higher during AECOPD than at recovery. However, it was not associated with other measures of disease and comorbidities beyond that of older age. Our findings suggest that complex mechanisms govern vascular stiffness in COPD; processes that are amplified during AECOPD.

Background and Aim: Hepatitis C virus (HCV) is now a highly treatable condition. HCV is overrepresented in people with serious mental illness, largely as a consequence of substance misuse. People with serious mental illness are marginalized in terms of access to care. Strengthened community engagement to optimize population HCV management could feasibly reduce overall HCV seroprevalence, while likely reducing disease incidence. As such, we aimed to investigate the prevalence of HCVin a tertiary mental health service and, hence, identify barriers to care and opportunities to optimize community-based HCV management. Method(s): We retrospectively analyzed 4492 people admitted to a multisite mental health service between January 2017 and December 2018. We appraised patterns and rates of HCV screening using medical records, electronic pathology, and ICD-10 coding. Referral pathways were analyzed for people with serious mental illness and potentially treatable HCV. Intensified access to HCV care was prospectively provided to eligible, untreated people within community mental health services. Result(s): HCV seroprevalence was 6.2%, based on pooled serology together with HCV ICD-10 coding. In a sensitivity analysis, 19.1% (35/ 183) of those with identified HCV risk factors remained unscreened. We identified 209 people who required additional HCV work-up or treatment. Multiple opportunity losses were manifest in the care cascade, particularly through lack of referral to treatment (89, 42.6%) and failure to attend specialist outpatient clinics (52, 25.8%). Given this attrition, we identified 48 community-managed patients who were untreated or incompletely worked up for HCV. Of these, 10 people (20.8%) with longstanding mental health service integration achieved a sustained virological response at 12 weeks through bolstered community support. However, 22 people (45.8%) could not be engaged (Fig. 1). Conclusion(s): HCV screening and treatment should be prioritized in people wit

Background and Aim: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with limited effective medical therapies and a paucity of epidemiological and outcome-based data in Australia. We aimed to retrospectively evaluate the demographics and outcomes of an Australian cohort of patients with PSC. Method(s): We performed a retrospective cohort study of patients with PSC at six tertiary health services, including two liver transplant units. Patients were identified by a computerized search of radiological reports. Predictors of transplant-free survival (need for liver transplantation or death from any cause) were analyzed. Result(s): We identified 405 patients with PSC, of whom 261 patients (64.4%) were known to a liver transplant unit. The median age at diagnosis was 36.2 years (IQR, 23.4-50.9), and 261 patients (64.4%) were male. The median alkaline phosphatase (ALP) level at diagnosis was 251 U/L (IQR, 156-436). During a median follow-up of 7.0 years (IQR, 3.3-12.0), the median ALP level improved to 143 U/L (IQR, 92-278) (P < 0.01). Most patients (247, 61%) were prescribed ursodeoxycholic acid (UDCA) at a median dose of 1000 mg (IQR, 750-1000). Of those treated with UDCA, 91 (36.8%) achieved a > 50% reduction in baseline ALP level during follow-up. An overlap syndrome was identified in 47 patients (15.2%), and a dominant stricture (DS) developed in 122 (30.1%). A total of 191 patients (47.3%) developed cirrhosis, of whom 87 (45.6%) had a decompensation episode. There were 282 patients (71.6%) with concomitant inflammatory bowel disease (IBD): ulcerative colitis (54%), Crohn's disease (16%), or IBD unspecified (2%). One hundred patients (24.7%) underwent liver transplantation, and 51 (12.6%) died (82.3% liver-related death). Gastrointestinal malignancies included cholangiocarcinoma (CCA) (26, 6.4%), hepatocellular carcinoma (HCC) (12, 3.0%), and colorectal cancer (15, 3.8%). The proportion of transplant-free survival was 88.5% at 5 years, 73.8%

Introduction/Aim. The Australian Bronchiectasis Registry (ABR), established in 2015, is a common nation-wide research platform to improve longitudinal data collection in children and adults with bronchiectasis unrelated to cystic fibrosis. Current descriptions of paediatric cohorts with bronchiectasis are largely unicentric and ABR is thus the leading paediatric cohort in Australia. Using ABR, we described the baseline characteristics of paediatric participants and sought to determine regional variations in this cohort. Methods. We analysed the baseline data of paediatric patients (<18 years) with radiologically confirmed bronchiectasis using ABRas centralised database. Results. From March 2016-August 2019, 496 children [222 females; 321 Indigenous; median age = 8 years (IQR 6-11)] were enrolled from 4 Australian sites. The aetiology was considered post-infectious in 70% of children, with 40% having had bronchiectasis for >5 years. Asthma (24%) was the most common reported co-morbidity and non-respiratory comorbidities were uncommon. Spirometry was available only in 21% of the cohort, with median FEV1 = 59.1% predicted (IQR 50.8-69.48), FVC = 66% (58.56-74.6). On CT chest, left (80%) and right (78%) lower lobes were the most common lobes affected, majority with cylindrical bronchiectasis, 6 children had cystic bronchiectasis. 6% children isolated Pseudomonas aeruginosa (PsA) from the lower airways, significantly higher proportion of these had Primary Ciliary Dyskinesia (PCD, 13.3% vs 2.1% in nonPsA; P < 0.001). Macrolide therapy was used in 43.5% of the cohort, with nearly a quarter of the group on short acting bronchodilator therapy. 244/488 (50%) children had at least 1 exacerbation requiring hospital an admission in the last 12 months, with exacerbations in 6.5% of the cohort treated with outpatient intra-venous antibiotic therapy. Conclusion. The largest cohort of Australian children with bronchiectasis has been described. Some regional differences exist in the

Background and Aim: Current guidelines recommend indefinite nucleot(-s)ide analog (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB) infection. However, sustained virological response (SVR) has been described in patients after discontinuation of long-term NA therapy, as well as HBsAg loss. The HBV-STOP study is a prospective multicenter study of NA discontinuation in patients who have achieved long-term virological suppression of hepatitis B virus (HBV) on treatment. The study describes clinical outcomes after treatment discontinuation, with the aim of identifying determinants of SVR. Method(s): We performed an interim narrative analysis of outcomes at Week 48 after NA discontinuation. Outcomes at Week 96 are the primary endpoint for the study. Inclusion criteria for the study were HBeAg-negative, non-cirrhotic, and virological suppression for > 18 months on NA therapy uninterrupted for > 2 years. Criteria for recommencing NA therapy were HBV DNA > 2000 IU/mL with either alanine aminotransferase (ALT) > 5x ULN for > 16 weeks or ALT > 10x ULN for > 8 weeks, international normalized ratio > 1.5, bilirubin level > 2x ULN, ascites, hepatic encephalopathy, and investigator discretion. Result(s): The cohort is fully enrolled, and data are currently available for 111 patients. At baseline, median patient age was 56 years, 64% were male, and 85% were Asian. The median HBsAg level was 705 IU/mL (214-2325). All patients were non-cirrhotic. Virological reactivation occurred in all, with a median time to detection of 8 weeks (4-12). Patients stopping tenofovir (TDF) experienced virological and biochemical relapse earlier than patients stopping entecavir (ETV) (Fig. 1; P < 0.001). Twenty-three patients (21%) have experienced an ALT flare > 10x ULN; there was no significant difference in the rate of ALT flare > 10x ULN after stopping TDF versus ETV. Two patterns of ALT flare were observed: beneficial flares that were associated with reductions in HBV DNA and

Introduction. Whether systemic and airway inflammation persist in remitted asthma and whether such inflammation is associated with adverse long-term respiratory outcomes remains unclear. Objective. To determine the prevalence of systemic and airway inflammation in adults with remitted asthma, and to examine their associations with asthma relapse and lung function decline. Methods. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort first studied in 1968 (n = 8,583). In 2004 (age 44), biomarkers of systemic inflammation (serum IL-4, IL-5, IL-6, IL-8, IL10, TNF-) were measured in a subgroup (n = 1,389) and categorised into cytokine profiles using latent profile analysis (LPA). In 2010 (age 50), markers of airway inflammation, methacholine challenge tests (n = 836) and total nitric oxide products in exhaled breath condensate (EBC NOx), were measured. Asthma relapse and lung function decline were assessed at follow-up in 2014. Multivariable linear and Poisson regression were used to examine relevant associations. Results. Of adults with remitted asthma at age 50 years, 20.8% [95% CI 15.9, 26.7] had bronchial hyperresponsiveness (BHR) and 7.1% [95% CI 4.2 ,11.9] had an elevated EBC NOx (>5.05 mumol/L). Asthma relapse was associated with BHR (RR 2.25 [95%CI 1.52, 3.32]), but not with elevated EBC NOx. Three distinct cytokine profiles were identified via LPA: A reference anormala cytokine profile, a aTh2-higha profile associated with accelerated post-BD FEV1/FVC decline (MD-0.18% predicted/year [-0.33,-0.02]), and a aTh2-lowa profile associated with accelerated postBD FEV1 (MD-0.41% predicted/year [-0.75,-0.06]) and post-BD FVC decline (MD-0.31% predicted/year [-0.62, 0.01]). Conclusion. BHR and elevated biomarkers of asthma activity have prognostic value in adults with remitted asthma. At-risk individuals may benefit from closer follow-up, repeat spirometry and potentially antiinflammatory agents.

Aim: To assess computerised tomography (CT) use and the risk of intracranial haemorrhage (ICH) in children with bleeding disorders following a head trauma. Method(s): Design: Multicentre prospective observational study. Setting(s): 10 paediatric emergency departments (ED) in Australia and New Zealand. Patient(s): Children <18 years with and without bleeding disorders assessed in ED following head trauma between April 2011 and November 2014. Intervention(s): Data collection of patient characteristics, management and outcomes. Main Outcome Measure(s): Rate of CT use and frequency of ICH on CT. Result(s): Of 20 137 patients overall, 103 (0.5%) had a congenital or acquired bleeding disorder. CT use was higher in these patients compared with children without bleeding disorders (30.1 vs. 10.4%; rate ratio 2.91 95% CI 2.16-3.91). Only one of 31 (3.2%) children who underwent CT in the ED had an ICH. This patient rapidly deteriorated in the ED on arrival and required neurosurgery. None of the patients with bleeding disorders who did not have a CT obtained in the ED or had an initial negative CT had evidence of ICH on follow up. Conclusion(s): Although children with a bleeding disorder and a head trauma more often received a CT scan in the ED, their risk of ICH seemed low and appeared associated with post-traumatic clinical findings. Selective CT use combined with observation may be cautiously considered in these children based on clinical presentation and severity of bleeding disorder.Copyright © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians)

Introduction/Aim. Recent evidence suggest that effects of adverse exposures before conception can be transferred across generations to increase the risk of asthma in offspring. Our aim was to investigate the association between preconception Body Mass Index (BMI) trajectories of parents and risk of asthma in their offspring. Methods. We analysed data collected from the Tasmanian Longitudinal Health Study (TAHS). In 1961, TAHS recruited 8583, 7-year-old children attending schools in Tasmania. Age, height and weight of these participants were extracted from their school medical records from ages 4 a- 15 years. Calculated BMI was standardized according to UK reference growth charts. At the age of 53 years, TAHS original participants (hereafter referred to as parents) were asked about their offspringas asthma. Group-based trajectory modelling was used to identify parentsa distinct BMI trajectories. Multinomial regression models adjusted for potential confounders were employed to estimate the association between parentsa BMI trajectories and risk of asthma phenotypes in their offspring. Results. Information on BMI were available for 2011 parents, who had 4670 offspring. Four BMI trajectories were identified as the best fit model: 1) Low BMI (8.8%), 2) Normal BMI (44.1%), 3) In-between normal and high BMI (40.2%), and 4) High BMI (7.0%). Paternal "High BMI" trajectory was associated with increased risk of allergic asthma before the age of 10 years (OR 1.72 (95%CI 0.97, 3.05)) and after 10 years (OR 3.96 (95% CI 1.11, 14.1)) in offspring. Similarly, paternal "High BMI" trajectory was associated with increased risk of allergic ever asthma in offspring, OR 1.99 (95%CI 1.13, 3.50). No associations were observed for maternal BMI trajectories. Conclusion. This cohort study over six decades of life and across two generations provides evidence that a high BMI trajectory in fathers, well before conception, may increase the risk of diagnosed asthma in their offspring. Such a risk s

Introduction: Diabetes and bone health are closely related. We examined the incidence and risk factors of hip fractures in Chinese patients with type 2 diabetes (T2D). Material(s) and Method(s): In this prospective cohort, we consecutively enrolled 22,325 adults with T2D above the age of 40 years in the Hong Kong Diabetes Register between 1994 and 2015 with crude hip fracture incidence rate censored in 2017. Result(s): At baseline, the mean age of this cohort was 60.9 +/- 10.5 years (mean duration of diabetes 6 years, 52.4% male). During a mean +/- standard deviation (SD) follow-up period of 8.7 +/- 5.2 years with 193,553 person-years, 603 patients were hospitalized due to hip fractures with an incidence (95% confidence interval, CI) of 315.1 (290.4-341.3) per 100,000 person-years. On multivariable analysis with competing death risk adjusted, the independent hazard ratios (95% CI) for hip fractures in T2D were 2.01 (1.61-2.51) for female sex, 1.08 (1.07-1.09) for age, 0.93 (0.90-0.95) for body mass index, 1.52 (1.25-1.85) for albuminuria and 1.12 (1.02-1.23) for low density lipoprotein-cholesterol. In men, the 30-day, 1-year and 5-year post-hip fracture mortality rate (95% CI) were 5.8 (2.4-9.1) %, 29.2 (22.3-35.5) % and 65.9 (57.3-72.8) % respectively. The corresponding rates in women were 3.4 (1.6-5.1) %, 18.6 (14.7-22.4) %, and 46.8 (40.9-52.1) %. Conclusion(s): Southern Chinese patients with T2D have a high risk of hip fracture associated with suboptimal cardiometabolic-renal risk factors and a high post-fracture mortality rate. The effects of improving modifiable risk factors on bone health warrants further evaluation.Copyright © 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd

Introduction: To evaluate the adoption of hypofractionated radiotherapy (HFRT) for breast cancer (BC) in Victoria, Australia. Method(s): This is a population-based cohort of women with BC who had breast RT as captured in the Victorian Radiotherapy Minimum Data Set between 2012 and 2017. We defined HFRT as < 25 fractions of RT. The pattern of HFRT use over time was evaluated with the Cochrane-Armitage test for trend. Factors associated with HFRT were identified using multivariable logistic regression. Result(s): 12,717 women were included in the study. Overall, 6,653 (52%) patients had HFRT. HFRT use increased from 35% in 2012 to 66% in 2017 (P-trend < 0.001). Older women were more likely to have HFRT (74% for women aged >= 70 years vs. 27% for women aged < 50 years; P < 0.001). Women who had nodal irradiation were less likely to have HFRT compared with those who did not (13% vs. 57%; P < 0.001). HFRT use was more common in public than private institutions (57% vs. 46%, P < 0.001), and in metropolitan than regional centres (54% vs. 46%, P < 0.001). In multivariable analyses, the progressive increase in HFRT use over time was independent of other covariates - women treated in 2017 were 7.3 times (95% CI = 6.3-8.6, P < 0.001) more likely to be treated with HFRT than in 2012. Age at RT, nodal irradiation, area of residence and institutional type and locations were all independently associated with HFRT use. Conclusion(s): This large Australian contemporary population-based study demonstrates increasing use of HFRT for BC. However, large sociodemographic and institutional provider-related variations in practice still exist.Copyright © 2021 The Royal Australian and New Zealand College of Radiologists

Introduction/Aim. Nasal high flow (NHF) may improve symptoms of dyspnoea in both stable and acutely exacerbating chronic obstructive lung disease (COPD). This may reduced symptoms are readmission rate. Method(s): This was a feasibility study prospectively recruiting subjects admitted to hospital for acute uncomplicated exacerbations of COPD.Consenting subjects were commenced on NHF and discharged when clinically stable determined by the clinical team who were not part of the study. NHF was maintained for minimum of 6 hours per day in the home setting for 30 days under supervision of HITH. Outcome measures were compared to matched retrospective controls Conclusion. The addition of NHF to the discharge plan supported by HITH was not associated with reduced LOS but was associated with low 30 day readmission rate.

Introduction/Aim. An increased ratio of pulmonary artery (PA) to aortic diameter (PA:A) on computed tomography (CT) correlates with increased pulmonary artery pressure [1]. PA:A > 1 identifies pulmonary hypertension and in COPD is associated with increased risk of hospitalised exacerbations [2]. Conventional CT has been used in previous studies investigating PA:A, however only samples a single asnapshota at a random point in the cardiac cycle. We hypothesised that ECG-gated, dynamic 256-multidetector CT (256-MDCT) would demonstrate variability in PA:A throughout the cardiac cycle, not identifiable with conventional CT [3]. We further hypothesised that PA:A would be higher at exacerbation versus recovery. Methods. Paired dynamic 256-MDCT were performed both during acute exacerbation and following exacerbation recovery. PA:A was based on the maximal PA and aortic diameter at 10% R-R intervals. The primary outcome was to assess the number of cases where the PA:A ratio crossed 1 at any point in the cardiac cycle. The secondary outcome was the change in PA:A ratio from acute scan to recovery scan. Results. Pairs of CT scans were compared in 63 cases admitted to our hospital with a COPD exacerbation. PA:A was variable throughout the cardiac cycle (highest in systole and lowest in diastole). In 12/63 (19.0%) of acute scans and 14/63 (22.2%) of recovery scans, PA:A crossed the threshold of 1. Figure 1 illustrates the variability in PA:A in the overall population during the cardiac cycle at acute exacerbation and at recovery. There was a reduction in mean PA:A ratio between the acute and recovery scans of 0.0159 (P < 0.0001). Maximal PA diameter was increased in the acute scan cohort by a mean of 0.22 mm in comparison to recovery (P = 0.0031). Conclusion. In patients with COPD, PA:A varies throughout the cardiac cycle and the timing of scan acquisition impacts this measurement. Dynamic CT allows better characterisation of PA:A assessment compared to conventional CT. PA:A inc

Introduction/Aim. Clinical guidelines recommend people with bronchiectasis undertake exercise training and physical activity as part of their disease management. This systematic review aimed to determine the effects of exercise training compared to usual care on exercise tolerance and health-related quality of life (HRQoL) in people with bronchiectasis. Methods. Randomised controlled trials (RCTs) involving structured exercise training programs of >=4 weeks duration which targeted improvements in physical function +/- exercise tolerance were identified from the Cochrane Airways Specialist Register (up to June 2019). Co-interventions such as airway clearance therapy or respiratory muscle training were permitted. Two review authors independently assessed studies for inclusion, data extraction and risk of bias. Outcomes included incremental shuttlewalk test distance (ISWD), 6-minute walk distance (6MWD), St Georgeas Respiratory Questionnaire (SGRQ) total score and Leicester Cough Questionnaire (LCQ) total score, at end intervention. Results. Six RCTs involving 275 participants were included. When applied for people with stable bronchiectasis (n = 5 studies), exercise training was associated with greater improvements in ISWD (standardised mean difference 0.97 [95%CI 0.64 to 1.31]) and SGRQ total score (mean difference [MD]-9.21[-12.65 to-5.77] units), but not LCQ total score (MD 0.01 [95%CI-0.76 to 0.78] units) compared to usual care. No discernible difference between exercise training and usual care was evident in 6MWD (MD 11 m [95%CI-27 to 49 m]) or LCQ total score (MD-0.08 [95% CI-0.94 to 0.78] units) when applied after an acute exacerbation (n = 1 study). Risk of selection, detection and reporting bias was generally low or unclear. Conclusions. Exercise training improves exercise tolerance, diseasespecific and cough-related QOL in people with stable bronchiectasis, but may offer limited value in the period after a recent exacerbation.

Background and Aim: The most commonly used diagnostic instrument to detect inflammation of an ileal pouch-anal anastomosis (IPAA) is the 18-point Pouchitis Disease Activity Index (PDAI). A total PDAI score of >= 7 or a modified PDAI (mPDAI) score of >= 5 is considered diagnostic for pouchitis. The consistency of scoring between endoscopists using the PDAI is poor, likely owing to the variable interrater reliability of the endoscopic components of the score; therefore, alternative scoring systems have been proposed.We aimed to assess the interrater reliability of endoscopic findings and compare the diagnostic utility of a simpler version of the PDAI. Method(s): We conducted a prospective, observational study at a single tertiary center. Consecutive patients with an IPAA were recruited. Clinical, endoscopic, and histological data were collected. Pouchoscopies occurred a median of 37 days after clinical review and were reviewed by two experienced gastroenterologists, while biopsies were reviewed by a single pathologist, all of whom were blinded to the clinical history. We assessed the interrater reliability and diagnostic performance of three disease activity scores: the traditional PDAI; a proposed alternative score combined with clinical PDAI; and a simplified PDAI (sPDAI), which uses only PDAI endoscopy items with at least high-moderate interrater reliability (Cohen's kappa >= 0.5). Interrater reliability was assessed by calculating observed agreement and Cohen's kappa coefficient. Diagnostic performance was analyzed using receiver operator characteristic (ROC) analysis. Result(s): A total of 35 patients (mean age, 52 years; 72% male) underwent a pouchoscopy. All had a J pouch. The mean age of the pouches was 12.8 years (1-27). Seven patients had a normal pouch, 13 had antibiotic-responsive pouchitis, eight had antibiotic-dependent pouchitis, three had antibiotic-refractory pouchitis, and three had Crohn's disease of the pouch. Of the PDAI endoscopic components, onl

Background and Aim: The rapid transition from adolescence to adulthood challenges many young patients with chronic conditions, such as inflammatory bowel disease (IBD), to suddenly adapt to a more independent model of care. Up to 25% of IBD diagnoses in Australia are now being made in the pre-adulthood period.1 The Young Adult (YA) IBD Clinic is a newly developed clinic aimed primarily at smoothing the transition from pediatric to adult services. We aimed to demonstrate the impact of this clinic on improving IBD clinical outcomes and patient satisfaction. Method(s): All patients who attended the YA IBD clinic between November 2016 and June 2018 were identified. For comparison, young patients from the Adult IBD clinic were also recruited. To assess clinical outcomes, we compared IBD-related emergency department (ED) presentations from each group before and after their first respective IBD clinic attendance, using a search of electronic medical records. To assess patient satisfaction, a subset of patients from the YA IBD clinic and all patients from the Adult IBD clinic were recruited to complete our IBD-Patient Satisfaction Questionnaire (IBD-PSQ), a tool developed for this project. On the IBD-PSQ, participants from each group expressed their satisfaction with their respective clinic by answering 27 questions in seven different clinical domains using a 5-point Likert scale, with a response scoring 4 or greater indicating satisfactory performance in that domain. Result(s): We recruited 64 and 33 patients from the YA and Adult IBD Clinics, respectively. Average ages of the YA and Adult IBD Clinic groups were 18.9 and 20.0 years, respectively. Patients in the YA Clinic group had a total of 21 ED presentations before their first clinic attendance, with an average of 0.63 ED presentations per person. After attending the clinic, there were a total of 11 ED presentations during the study period, with an average of 0.25 ED presentations per person, showing a 47.6% reduction

Aim: To describe the impact of initial steroid sensitivity on risk of disease recurrence and transplant failure for children following kidney transplantation for steroid resistant nephrotic syndrome (SRNS). Background(s): Scarce prior data suggest that children transplanted for SRNS who were steroid responsive at their initial presentation have an increased risk of recurrence post transplantation. There are no data informing the impact of initial steroid sensitivity on transplant survival. Method(s): Children who received a kidney transplant between 2000 and 2019 for SRNS in 7 paediatric centres were included. Clinical data were gathered from chart reviews and transplant data were provided from ANZDATA following ethics approval. Transplant survival was estimated using the Kaplan-Meier estimator, and the association between variables and graft survival estimated by Cox modelling. Result(s): There were 56 children, 32 (57%) male, average age at transplant 11 years (SD 4) and 36 (65%) Caucasian. At presentation, 19/56 (34%) were steroid sensitive before developing SRNS. Of those steroid sensitive initially, 18/19 (95%) had recurrence post-transplant, 9/18 (50%) achieved full remission, although 3 of these had further recurrences. In those not steroid sensitive initially, 14/37 (38%) had recurrence post-transplant, 7/14 (50%) achieved full remission although one had further recurrences. Overall, 5-year transplant survival was 72% (95%CI = 60-86%) and initial steroid sensitivity was not significantly associated with transplant loss (p = 0.07). Conclusion(s): Initial steroid sensitivity is strongly associated with SRNS recurrence. Transplant survival for children with SRNS is poor. Further research in other cohorts is needed to assess if initial steroid sensitivity is associated with poorer graft outcomes.

Background: Melasma is an acquired cutaneous disorder characterised by prominent hyperpigmentation which presents with brown macules or patches on photo-exposed areas. Current first-line treatments for melasma include non-pharmacological measures as photoprotection, cosmetic camouflage and topical therapies such as hydroquinone. 1 Although hydroquinone remains as the gold standard treatment for melasma, its actions are limited by side effects and potential relapses.1 More recently cysteamine cream has been trialled as an alternative therapy for melasma and an early trial has shown benefits compared to placebo.2 There have been no direct comparisons between cysteamine cream and hydroquinone cream. Objective(s): Our study aims to determine the efficacy of cysteamine cream compared to hydroquinone cream in the treatment of melasma. Method(s): Female patients, 18 years and older, with at least three months history of moderate to severe melasma and satisfied the exclusion criteria were included in the study. Patients were randomised to the two study arms; the control was advised to apply hydroquinone daily for 16 weeks and the treatment group was advised to apply cysteamine cream daily for 16 weeks. Both groups were advised on regular sunscreen application. The primary endpoint measurement was the modified Melasma Area and Severity Index (mMASI) score. Result(s): 20 patients have satisfied the inclusion/exclusion criteria and are enrolled in the study. Results to be updated prior to the conference. Conclusion(s): This randomised control study will evaluate the efficacy of cysteamine cream for the treatment of melasma and whether it may be superior compared to the current gold standard treatment hydroquinone.

Background and Aim: Diagnosis and management of inflammatory bowel disease (IBD) requires a clinical approach, combining information from histology and other modalities for clinical decision making. However, histology is costly due to specimen processing, and intra- and interobservational variation and the significance of subtle findings remain unclear when translating into clinical practice. Biospectroscopy involves combining microscopy with spectroscopy and provides chemical and imaging identification for complex biological specimens, which, as an advantage, do not require any chemical processing techniques or staining. Briefly, infrared (IR) or laser energies vibrate biochemical bonds in biospecimens (fluids or tissue), which are then recorded as absorbance intensities in large hyperspectral datasets. Regression and classification algorithms used in multivariate analysis for machine learning are then applied for modeling and predictive capacity. To date, there has been little published research using this technology for assessing IBD. We aimed to undertake an explorative analysis of intestinal inflammation using Fourier-transform infrared microspectroscopy, develop a model for assessing severity of colitis, and identify potential spectral biomarkers for colitis. This study was a proof-of-concept study using a gold-standard murine colitis model to inform further research in human work. Method(s): We used formalin-fixed paraffin-embedded intestinal sections from C57/BL6 mice (30 mice, three sections per mouse) with chronic colitis induced by 3% oral dextran sodium sulfate (n = 27), of which a subset (n = 14) were treated with intravenous human amnion epithelial cells and showed a reduction in histological severity of inflammation. Tissue sections were placed on a reflective slide, and an adjacent 5 mum section was stained with hematoxylin and eosin for comparison. Background scans and regions of interest from the intestinal mucosa were imaged using the Agilent Cary

Background and Aim: Despite many years since the registry trial of infliximab in Crohn's disease, the strategy of top-down treatment remains controversial for both adults and children. We aimed to compare clinical outcomes and costs for a retrospective pediatric Crohn's disease (pCD) cohort treated with early-use infliximab (EUI) within 12 months, compared with later-use infliximab (LUI). Method(s): We undertook a retrospective review of all children with pCD who commenced infliximab in a tertiary Australian pediatric center. Result(s): We identified pCD progressing to infliximab in 70 children: 38 (54%) in the EUI cohort and 32 (46%) in the LUI cohort. Intestinal surgery had a lower risk of occurring in the EUI group compared with the LUI group (2 [5%] vs 9 [28%]; hazard ratio, 5.67; 95% confidence interval, 1.21-26.38; P = 0.027). No patients in the EUI group underwent intestinal surgery after infliximab commencement, compared with three (9%) in the LUI group (P = 0.09). Escalation of infliximab in luminal Crohn's disease was not significantly different in the EUI group compared with the LUI group (3 [10.3%] vs 9 [39.1%]; P = 0.1). EUI was more frequently used than LUI in 2015-2018 (27 [71%] vs 14 [44%]; P = 0.029), with the inverse occurring in 2010-2014 (11 [29%] vs 18 [56%]). Hospital admissions per person per year in the EUI and LUI groups were 43 (0.23 visits/person/year) and 84 (0.67 visits/person/year), respectively (incidence rate ratio, 2.51; 95% confidence interval, 0.9- 7.01; P = 0.078). Health costs were not significantly different between the cohorts. Conclusion(s): EUI in pCD is associated with an increased likelihood of being diagnosed in more recent years, less intestinal surgery, and a trend towards decreased hospital admissions, compared with LUI.

Background: Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular morbidity and mortality compared to the healthy populous. The mechanisms are complex but involve cardiac fibrosis (CFib) and related dysfunction. Cardiac magnetic resonance imaging (cMRI) allows evaluation of both, and we explored CFib in patients with CKD compared to healthy volunteers (HV) with normal kidney function. Method(s): Cardiac function, morphology and tissue characterization were compared between 10 patients with CKD Stages 3-5, 12 patients on maintenance haemodialysis (HD) and 26 HV. Cardiac function and native T1 mapping time (nT1mt), using saturation recovery single-shot acquisition (SASHA) and shortened modified look-locker inversion recovery (ShMOLLI) to measure CFib, were compared across groups using analysis of variance (ANOVA) and post-hoc comparison. Result(s): Left ventricular (LV) ejection fraction was 62 +/- 5%, 62 +/- 8%, and 64 +/- 10% (p = 0.692), and LV mass was 111 +/- 34 g/m2, 136 +/- 32 g/m2, and 137 +/- 34 g/m2 (p = 0.056) in HV, CKD and HD groups, respectively. The nT1mt (SASHA) were 1485 +/- 42 ms, 1547 +/- 45 ms and 1600 +/- 105 ms (p < 0.001), and (ShMOLLI) 1157 +/- 63 ms, 1186 +/- 36 ms and 1219 +/- 47 ms (p < 0.001), respectively. In post hoc comparisons, nT1mt were significantly lower in HV than CKD (p = 0.034 for SASHA, p < 0.01 for ShMOLLI) or HD (p < 0.01 for both), but not different between CKD and HD (p = 0.152 for SASHA, p = 0.255 for ShMOLLI). Conclusion(s): Despite similar LV ejection fraction and LV mass, cMRI detected increased CFib in patients with CKD and HD. Thus, CFib appears early in CKD and may help identify CKD patients at higher risk of adverse cardiac outcomes.

To date, 18 living recommendations for the clinical care of pregnant and postpartum women with COVID-19 have been issued by the National COVID-19 Clinical Evidence Taskforce. This includes recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids, angiotensin-converting enzyme inhibitors, disease-modifying treatments (including dexamethasone, remdesivir and hydroxychloroquine), venous thromboembolism prophylaxis and advanced respiratory support interventions (prone positioning and extracorporeal membrane oxygenation). Through continuous evidence surveillance, these living recommendations are updated in near real-time to ensure clinicians in Australia have reliable, evidence-based guidelines for clinical decision-making. Please visit https://covid19evidence.net.au/ for the latest recommendation updates.Copyright © 2020 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Vitiligo is a depigmenting condition which presents with white patches of the skin and is estimated to affect 1% of the population worldwide.1 As vitiligo can involve visible areas such as the face, neck, hands and feet, individuals with vitiligo experience significant psychological and social impacts. Current medical treatment includes topical or systemic immunosuppressants, phototherapy or surgical grafting, though results are often delayed or unsatisfactory. Camouflaging therapy involves the use of pigments and dyes to temporary conceal vitiligo and has been recognised to improve self-esteem and quality of life in adults and children with vitiligo2,3. Despite this, there is limited information regarding camouflaging products for vitiligo and its general use by dermatologists and patients with vitiligo. We will present the results from a global survey completed by patients and dermatologists regarding the use of camouflage therapy in vitiligo. The aim of the survey is to investigate the current awareness, usage, barriers and accessibility regarding camouflage products for vitiligo. Implications of this survey will allow a better understanding of the use of camouflage products for vitiligo and any barriers that could be addressed. Results from the survey may also highlight any discrepancies between patients' interest in camouflage products compared to the frequency of recommendation by dermatologists.

Background and Aim: Patients with ileal pouch-anal anastomosis (IPAA) often require a pouchoscopy to investigate symptoms of increased frequency, urgency, and abdominal cramps, which are not specific to pouchitis. Fecal calprotectin (FC) testing has the potential to be an alternative non-invasive tool for the assessment of pouch activity.We aimed to assess the utility of FC testing in the assessment of inflammatory complications of the pouch. Method(s): We conducted a prospective observational study at a single center between October 2018 and November 2019. Consecutive symptomatic patients with IPAA referred from clinic were recruited. At recruitment, clinical data, as well as FC and serum C-reactive protein (CRP) levels, were measured. Pouchoscopy was performed after a median of 35 days. Histopathological examination of biopsies of the pre-pouch ileum, pouch body, and cuff was performed by a single pathologist blinded to the clinical history. A diagnosis of pouchitis was defined as Pouchitis Disease Activity Index (PDAI) score >= 7. Associations were assessed by correlation and regression analyses, and area under the curve (AUC) for receiver operator characteristic analysis was used to analyze diagnostic performance of CRP and FC. Result(s): Of 40 patients, 34 had complete data (mean age, 52.4 years; 72% male). Seven had a normal pouch, 13 had antibiotic-responsive pouchitis, eight had antibiotic-dependent pouchitis, three had antibiotic-refractory pouchitis, and three had Crohn's disease of the pouch. Two-thirds had active pouchitis. Median FC level was higher in 20 patients with pouchitis (442 mug/g; interquartile range [IQR], 345- 590) compared with 11 with isolated cuffitis and/or pre-pouch ileitis without pouchitis (167 mug/g; IQR, 75-320; P = 0.03) and nine without pouchitis or cuffitis/pre-pouch ileitis (66 mug/g; IQR, 44-120; P < 0.001). No patients had isolated pouchitis without cuffitis or ileitis. After multivariate adjustment for presence of cuffitis (n

Aim: To investigate the role of spleen tyrosine kinase (SKY) in inflammatory cell signalling pathways in macrophages. Background(s): SKY is expressed in B-lymphocytes and myeloid cells. Inhibition of SKY has been shown to prevent or reduce disease severity in animal models of inflammatory kidney disease, including LPS-induced acute kidney injury. This protection is associated with reduced expression of monocyte chemo attractant protein-1 (MCP-1), an important chemokine recruiting macrophages to sites of inflammation. Method(s): LPS stimulation assay was performed in cultured primary mouse bone marrow-derived macrophages (Baca) and RAW264.7 murine macrophage cells. SKY inhibition was achieved using an SKY inhibitor (SYKi), GS-492429, and Sykf/f Csf1rCre mice with selective Syk gene knockout in myeloid cells. RNA expression of inflammatory markers was examined by RT-PCR and protein secretion over 24 hours into culture media was examined by ELISA. Result(s): MCP-1 mRNA expression was significantly upregulated 6 hours after LPS stimulation, and this was reduced by 33% by SYKi in RAW264.7 cells (p < 0.01). SYKi reduced LPS-induced MCP-1 secretion by 74% (p < 0.01) in RAW264.7 cells over 24 hours. This finding was confirmed using BMMacs in which Syk knockout reduced LPS-induced MCP-1 secretion by 48% (p = 0.01). Interestingly, SYKi treatment did not affect NFkappaB activation (IkappaBalpha degradation by Western blot) or up-regulation of TNF mRNA levels at 1 hour post-LPS. Finally, delaying SYKi addition until 1 hour after LPS stimulation still inhibited MCP-1 secretion by 60% (p < 0.01) in RAW264.7 cells. Conclusion(s): SKY inhibition reduces MCP-1 expression and release from macrophages after LPS stimulation. This appears to be independent of NFkB activation. These new findings highlight the potential role of SKY in inflammatory kidney disease.

Background and Aim: Vitamin D has been shown to play a role in inflammation in multiple conditions, including inflammatory bowel disease (IBD). Low vitamin D levels have been shown to be associated with active IBD in retrospective studies. Some evidence of an inverse correlation with disease activity and inflammatory markers exists. The current gold-standard inflammatory marker is fecal calprotectin (FC); however, FC testing is not reimbursed in Australia, and sample collection is not as simple as blood testing. We aimed to assess whether serum vitamin D level is useful as a biomarker in real time. Method(s): Quality assurance ethical approval was obtained from the hospital ethics committee. We collected retrospective data via a chart review of the hospital pathology system and medical records. Patients were initially identified using the pathology database to find those who had FC measured in 2019; then, a subset of patients with IBD with both FC and blood tests within 3 months was selected. Demographic data, IBD type, inflammatory markers, and vitamin D levels were obtained from patient records. The vitamin D levels were compared with levels of FC (with a positive FC level being set at 150 mug/g), C-reactive protein (CRP), albumin, hemoglobin, and platelets. Non-parametric tests were used for comparison. Result(s): We identified 616 patients from the initial cohort with FC tests. There were 328 patient episodes with matched FC and blood tests, including vitamin D, CRP, albumin, hemoglobin, and platelets. This subset comprised 101 patients with Crohn's disease (CD) with 198 time points of matched data and 68 patients with ulcerative colitis (UC) with 116 time points of matched data. There were 14 IBD-unspecified episodes. Of the patients with CD, 46% were male, and of the patients with UC, 43% were male. Median disease duration was 8 years (interquartile range, 4-13.5 years) for those with CD and 5.5 years (interquartile range, 3-12.5 years) for those with UC. Over

Aim: To determine if a Comprehensive Geriatric Assessment (CGA) will allow frail older patients with chronic kidney disease (CKD) to better attain their treatment goals and improve their frailty and quality of life, while being cost-effective. Background(s): There is an increasing number of frail older patients with CKD. Many of them face deteriorating health and functional status, which adversely affects their quality of life. CGA is an effective intervention to improve survival and independence of older people but its effect in people with CKD remains unknown. Method(s): GOAL is a NHMRC-funded cluster randomized controlled trial developed by consumers, clinicians and researchers. It will recruit patients from January 2021 aged >=65 with CKD stage 3-5/5D and a Frailty Index >0.25. The intervention clusters will receive a CGA by a geriatrician to identify medical, social and functional needs, optimize medication prescribing and arrange multidisciplinary referral if required. The primary outcome is attainment of patient determined goals assessed by standardized Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS scores at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost effectiveness and safety (causespecific hospitalizations, mortality) at 12 months. Result(s): A two-arm design of 16 clusters with 1:1 allocation (~500 participants) has 90% power to detect a clinically meaningful mean difference in GAS score of 10 units. Conclusion(s): The GOAL trial addresses patient-prioritized outcomes and will be conducted, disseminated and implemented in partnership with patients and their caregivers. This is the first study, internationally, to evaluate the clinical and cost effectiveness of CGA in improving patient-important health outcomes in frail older people with CKD.

Aim: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected GKD. Background(s): Genetic kidney disease (GKD) is increasingly recognized as an important cause of CKD and can be difficult to accurately diagnose using traditional diagnostic strategies. There is a paucity of data on the clinical utility of genomic testing in kidney disease patients. Method(s): We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Result(s): ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis following ES. A diagnosis on ES was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%) and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion(s): In this pragmatic paediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

Introduction/Aim. To estimate the burden of oral corticosteroid (OCS) use for asthma in Australia, referenced to potentially toxic cumulative thresholds (>=1000 mg prednisolone-equivalent). Methods. This retrospective cohort study used a 10% random sample of the Australian Pharmaceutical Benefits Scheme to identify asthma patients aged >=12 years based on inhaled controller medication dispensing. The primary outcome was cumulative OCS dispensing for asthma over five years. The association between overall dispensing of OCS, with that of diabetes and osteoporosis medication, was examined. The secondary outcome was >=1000 mg prednisolone-equivalent dose dispensing over 12 months, stratified by inhaled controller therapy dose and usage. Results. The national OCS burden can be estimated by multiplying study results by ten. Over five years, 34,580 individuals (27.9%) of the study asthma population were dispensed cumulative prednisoloneequivalent doses of >=1000 mg, and a further 29,532 (23.8%) dispensed doses <1000 mg. Patients on any inhaler accounted for 49.3% of all cumulative dispensing >=1000 mg in the 10% PBS sample. Overall, patients dispensed >=1000 mg prednisolone-equivalent also had higher dispensing rates of diabetes and osteoporosis medication. Over 12 months, 4,633 patients with asthma on high-dose controllers were dispensed >=1000 mg prednisolone-equivalent, more than half of whom had inadequate (<50%) controller therapy usage. Conclusion. Cumulative exposure to OCS in Australia reaches levels associated with toxicity in a quarter of asthma patients on inhaled controller therapy. Potentially toxic OCS use often occurs in patients taking insufficient inhaled controller medication. Better approaches are needed to improve asthma outcomes whilst minimising OCS burden and toxicity.

Introduction/Aim. Virus infections in patients with pre-existing lung conditions such as asthma and chronic obstructive pulmonary disease often have devastating consequences. Transforming growth factor beta (TGFB) is upregulated in these diseases and its immune-suppressive actions may be pertinent to the vulnerability of patients to damaging infections. We explored influenza A virus (IAV) infection in models of acute and chronic TGFB over-expression and evaluated benefits of pirfenidone, a TGFB antagonist in clinical use for lung fibrosis. Methods. We utilised a transgenic mouse model of TGFB overexpression in the lung. Following IAV infection, tissue and bronchoalveolar lavage (BAL) fluid were assessed for IAV replication, disease severity, inflammation and immune responses. Treatment with pirfenidone was given by gavage and responses compared. Results. In both acute and chronic models mice with elevated TGFB developed more severe bronchitis and pneumonia (P < 0.05). IAV replication was increased (P < 0.001), the result of blunted innate immune responses (P < 0.001). TGFB also mediated significant elevations of inflammatory cytokines, chemokines and inflammatory cell populations in BAL. Administration of pirfenidone during infection reduced disease severity by dampening inflammatory responses and reducing IAV replication. Conclusion. Our findings demonstrate profound immune suppression mediated by TGFB leading to amplified virus infection and intensified lung inflammation. Pirfenidone opposed the detrimental effects of TGFB by reducing inflammation, thus diminishing the extent of infection. Collectively, these data reveal the damaging activities of TGFB during virus infections in lung diseases characterised by TGFB over-production. We further provide proof-of-concept evidence that repurposing pirfenidone can oppose TGFB activities and attenuate virus infections in a susceptible patient population.

Introduction/Aim. The leading cause of cancer mortality is lung cancer and it is the fifth most common diagnosed cancer in Australia. Endobronchial ultrasound (EBUS) is a bronchoscopic technique that utilizes ultrasound to identify masses and nodes within the thorax. This allows for the diagnosis and staging in patients with suspected or proven lung cancers. Our aim was to investigate the trend of lung oncology, nodule and cancer clinic consultations and the relationship with the number of EBUS procedures performed. Methods. Retrospective audit of the numbers of cases discussed at lung multidisciplinary meeting, lung oncology, lung nodule clinic consultations and EBUS procedures performed in a single Melbourne tertiary hospital between Feb 2017 to Sept 2019. The results were analyzed by yearly quartile (3 monthly). Results. 1352 patients were discussed in Lung MDM, Median (quartile) = 129 (122 a- 139), 786 patients were seen in Lung Oncology Clinic, 80 (68 a- 89), 492 patients were seen in Lung nodule clinic. 50 (30 a- 65) and 621 EBUS procedures were performed. 60 (55 a- 65). The number of EBUS performed increased significantly with rising lung oncology attendances (P value = 0.04) using repeated measures ANOVA. Over the past 2 years, there was a 12% increase and 10% increase in the attendees to lung oncology outpatient, and increase of 25% and 12% of EBUS performed in the 2nd and 3rd quartile respectively. Conclusion. EBUS is a vital tool in the diagnosis and staging of lung cancer. Increasing lung oncology clinic attendances have been paralleled by the number of EBUS procedures performed. This may be an important factor when considering resource allocation and planning in the future of lung cancer management.

Aim: To determine predictors and outcomes of extubation failure in extremely preterm (EP) infants born <28 weeks' gestational age (GA). Method(s): Retrospective clinical audit across two tertiary-level neonatal intensive care units in Melbourne, Australia. Two-hundred and four EP infants who survived to their first extubation from mechanical ventilation. Extubation failure (re-intubation) within 7 days after the first extubation. Result(s): Lower GA (odds ratio [OR] 0.71, 95% confidence interval (CI), 0.61-0.89, P < 0.001) and higher pre-extubation measured mean airway pressure (MAP) on the mechanical ventilator (OR 1.9 [95% CI 1.41-2.51], P < 0.001) predicted extubation failure. The area under a receiver operating characteristic curve for GA and MAP was 0.77 (95% CI 0.70-0.82). After adjustment for GA, infants who experienced extubation failure had higher rates of bronchopulmonary dysplasia (P < 0.001), post-natal systemic corticosteroid treatment (P < 0.001), airway trauma (P < 0.003), longer durations of treatment with mechanical ventilation (P < 0.001), non-invasive respiratory support (P < 0.001), supplemental oxygen therapy (P = 0.05) and longer hospitalisation (P = 0.025). Conclusion(s): Lower GA and higher pre-extubation measured MAP were predictive of extubation failure within 7 days in extremely preterm infants. Extubation failure was associated with increased morbidity and extended periods of respiratory support and hospitalisation.Copyright © 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians)

Aim: We developed a risk prediction score for overall graft survival in adult recipients of a living kidney donor transplant in an Australian and New Zealand population. Background(s): Risk scores may aid risk quantification and decision-making in kidney transplantation. The Living Kidney Donor Profile Index (LKDPI) was developed to choose between living donors. The original LKDPI is not discriminatory (C = 0.59, 95% CI 0.55-0.62) or well calibrated in Australia/New Zealand. Method(s): Using data from the Australia and New Zealand Dialysis and Transplant Registry, we included adult recipients of living kidney donor transplants over 2004-2018. We constructed Cox models for overall graft survival. We refit the original USA variables and constructed a new model considering all available potential covariates. Model performance was examined by partial validation, bootstrapping, Harrell's C-statistic (C) and Akaike information criterion (AIC). Result(s): 4049 living donors were included; 58.2% were female, 10.4% had hypertension and 18.7% were obese. For the original USA LKDPI the variables of both male and donor: recipient weight ratio were mis-specified. The C-statistic for the re-fit model was 0.57 (95%CI 0.54-0.59). When remodelling the score, the new variables included were history of hypertension and HLA-A mismatches. Variables excluded were donor: recipient weight ratio, HLA-B, both male, and ABO incompatibility. The Aus/NZ LKDPIC-statistic was 0.56 (95%CI 0.54-0.58). Calibration was similar but the Aus/NZ LKDPI had better model fit (AIC: 10402 vs. 11 023). Conclusion(s): The Aus/NZ LKDPI had similar discrimination to the original LKDPI and the LKDPI with adjusted coefficients. The discrimination was low for both scores and so should be used with caution to decide between donors. The new score is better calibrated for our population so could be used to predict graft prognosis.