Cohort Of Australian Patients Research Articles

Describing the ear, nose, and throat symptom burden in a cohort of Australian patients with primary ciliary dyskinesia

Describing the ear, nose, and throat symptom burden in a cohort of Australian patients with primary ciliary dyskinesia

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study.

Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT. To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT. This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing. Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes. Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Describing the burden of disease amongst inpatients with treatment resistant major depressive disorder in Australia.

To describe the quality of life and clinical characteristics of treatment-resistant depression (TRD) patients in an Australian patient cohort recruited cross-sectionally during admission. Inpatients admitted for TRD treatment completed a quality of life questionnaire (AQoL-8D) and a depression severity assessment (HAM-D). A chart review and patient interview occurred for demographic and patient characteristics. Comparisons between the mean AQoL-8D scores of the study population and Australian population norms occurred. 79 TRD inpatients (70.9% female), mean age of 44.8 ± 14.9 years, were recruited, with 78.5% having an anxiety disorder, 48.1% post-traumatic stress disorder, and 30.4% a personality disorder. Adjunctive to antidepressants, 92.4% were taking antipsychotics and 55.7% were taking mood stabilisers. Approximately 42% of patients received transcranial magnetic stimulation, and 35.4% received electroconvulsive therapy. Mean HAM-D score was 20.3 ± 5.2, and AQoL-8D score (120.1 ± 16.5) was significantly higher than Australian population norms (p < .001) indicating reduced quality of life. Personal and clinical characteristics of patients hospitalised for TRD were similar to TRD globally with impaired quality of life relative to the general Australian population. TRD patients on average presented with moderate/severe depression, highlighting the need for greater support for these individuals.

Completion of Pembrolizumab in Advanced Non-Small Cell Lung Cancer—Real World Outcomes After Two Years of Therapy (COPILOT)

BackgroundSeminal trials with first-line pembrolizumab for metastatic non-small cell lung cancer (NSCLC) mandated a maximum two-years treatment. We describe real-world outcomes of a multi-site Australian cohort of patients who completed two-years of pembrolizumab. MethodsRetrospective data were collected from the national AUstralian Registry and biObank of thoRacic cAncers (AURORA). Primary endpoints were progression rate post pembrolizumab discontinuation; and progression free survival (PFS). Local treatment of oligoprogressive disease during pembrolizumab was allowed. ResultsA total of 71 patients from six centers, median age 66.0 years, 49% male and 90% ECOG ≤ 1 were identified. Patients were Caucasian (82%) or Asian (16%); past (66%) or current (24%) smokers with mean 37 pack-years. Histology comprised 73% adenocarcinoma and 16% squamous. 18 patients (25%) had brain metastases at diagnosis. Median PD-L1 tumor proportion score (TPS) was 68%; 12 patients (17%) TPS < 1% and 43 (61%) TPS ≥ 50%. No patients had EGFR/ALK/ROS1 alterations; 29/49 tested (60%) had KRAS mutations.Median follow up was 38.7 months. Objective response rate 78.6%. Median PFS 46.1 months (95% CI 39.5-NR), not reached (46.1-NR) in PD-L1 TPS ≥ 1% versus 28.1 months (16.3-NR) in TPS < 1% (P = .013). 17 patients (24%) received additional local therapy for oligoprogression. Post pembrolizumab discontinuation, 20 patients (28%) had disease progression. Higher rates of progression occurred with TPS < 1% (OR 3.46, P = .06), without complete response (OR 5.06, P = .04), and with treated oligoprogression (OR 3.11, P = .05). 36-month landmark survival was 98.2%. ConclusionPatients completing two-years of pembrolizumab for NSCLC in an Australian cohort had high rates of KRAS mutation and PD-L1 expression; a proportion had brain metastases and treated oligoprogression. Progression post pembrolizumab was higher in PD-L1 TPS < 1% and in those without complete response.

Burden of disease and real-world treatment patterns of patients with systemic lupus erythematosus in the Australian OPAL dataset

ObjectiveTo describe the demographics, disease burden and real-world management of patients with systemic lupus erythematosus (SLE) in Australian community practice.MethodsPatients with a physician diagnosis of SLE and at least 1 visit between 1 January 2009 and 31 March 2021 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 112 Australian rheumatologists. Demographics, basic clinical features and prescribed medications were described, with medication combinations used as a surrogate of disease severity.ResultsOf 5133 patients with a diagnosis of lupus, 4260 (83%) had SLE. Of these SLE patients, almost 90% of patients were female, with a median age of 49 years [IQR 37–61] at first-recorded visit. Of the 2285 SLE patients whose most recent visit was between 1 January 2019 and 31 March 2021, 52.5% had mild disease, 29.9% had moderate-severe disease and 7.4% had very severe disease. Visit frequency increased with disease severity. Most patients (85.8%) were treated with hydroxychloroquine, typically prescribed as first line-of-therapy.ConclusionIn this large real-world Australian cohort of patients with SLE, a substantial burden of disease was identified, with a significant proportion (almost one-third of patients) considered to have moderate to severe disease based on medication use. This study provides a greater understanding of the path from symptom onset to treatment and the heterogeneous presentation of patients with SLE who are treated in community practice in Australia.Key messages• Most published studies describing patients with SLE are derived from specialist lupus centres, typically in the hospital setting, therefore little is known about the characteristics of patients with SLE who are receiving routine care in community clinics.• The OPAL dataset is a large collection of clinical data from the electronic medical records of rheumatologists predominantly practising in private community clinics, which is where the majority (73–80%) of adult rheumatology services are conducted in Australia [1–3] . Since data from community care has not been widely available for SLE research, this study contributes important insight into this large and under-reported patient population.• To improve access to care and effective treatments, and reduce the burden of SLE in Australia, a greater understanding of the characteristics and unmet needs of patients with SLE managed in the community setting is required.

Outcomes of robotic modified Freyer's prostatectomy in an Australian patient cohort.

The study aims to demonstrate the feasibility, safety and efficacy of robotic simple prostatectomy (RSP) using the modified Freyer's approach in an Australian patient cohort. Although RSP is performed in several Australian centres, there is a paucity of published Australian data. We reviewed prospectively collected perioperative and outcomes data for patients who underwent a robotic modified Freyer's prostatectomy (RMFP) from June 2019 to March 2022. Statistics were completed using SPSS statistics v27.0 and reported as mean and range with a p value of <0.05 considered statistically significant. There were 27 patients who underwent RMFP over the study period with a mean age of 67 years and prostate volume of 159.74 cc (100-275). The mean console time was 168 min (122-211), blood loss of 233 ml (50-600) and average length of hospital stay of 3.8days (3-8). The preoperative versus postoperative outcome means were as follows: serum prostate-specific antigen was 9.69 versus 1.2ng/mL, IPPS score was 17.1 versus 1.25, quality of life (QOL) score 3.4 versus 0.4, postvoid residual volume: 223.6 versus 55.9ml, Q-max 7.86 versus 29.6ml/s. These were all statistically significant (p < 0.001). The mean weight of resected tissue was 74 g (43-206) with 25 patients having benign histopathology and two being diagnosed with prostate cancer (Gleason 3 + 3 = 6 and 3 + 4 = 7). No patients returned to theatre or required a blood transfusion. Data from our patient cohort demonstrate the feasibility, safety and efficacy of RMFP for benign prostatic hyperplasia in an Australian patient cohort. Our outcomes compare favourably with published studies on RSP.

Comparative analysis of pre-operative ultrasound and histopathology in small papillary thyroid carcinoma in the era of active surveillance.

Contemporary management of small papillary thyroid carcinomas (PTC) includes active surveillance (AS) as a number of these tumours are indolent. Overseas studies have reported AS in tumours up to 15 mm. This study aims to look at an Australian cohort of patients who have had surgery for non-incidental PTCs and analyse their pre-operative ultrasound and histopathology data to investigate potential issues that might arise in the era of AS. Retrospective review of 82 patients who had surgical removal of PTCs ≤15 mm in diameter. Pre-operative ultrasound imaging was reviewed by an experienced sonologist and histopathology data was obtained from medical records. The AS risk stratification framework by Brito et al. was used to determine those who were feasible for AS based on ultrasound findings. Review of pre-operative ultrasounds demonstrated there were 68 (82.9%) patients who were shown to be either appropriate or ideal for AS. On review of histopathology, 49 (69%) patients had at least one adverse pathological risk factor. This is more than half of the patients that were originally identified as candidates for AS. Our study has revealed a large proportion were suitable for AS but when compared with histopathological guidelines there was a high incidence of adverse pathological features found. This discrepancy indicates that although the guidelines are important, there are unknown pathological variables that need to be considered in patients selected for AS.

Healthcare expenditure and its socio-demographic and clinical predictors in Australians with poorly controlled asthma.

Asthma has substantial and increasing health and economic burden worldwide. This study aimed to estimate healthcare expenditure and determine the factors that increase expenditure in Australians with poorly controlled asthma. Individuals ≥18 years of age with poorly controlled asthma, as determined by a score ≥1.5 on the Asthma Control Questionnaire, were included in the study. Healthcare utilization costs from medical services and medications were estimated over an average follow-up of 12 months from administratively linked data: the Medicare Benefits Schedule and Pharmaceutical Benefits Scheme. A generalized linear model with gamma distribution and log link was used to predict participants' key baseline characteristics associated with variations in healthcare costs. A total of 341 participants recruited through community pharmacies were included. The mean (standard deviation, SD) age of participants was 56.6 (SD 17.6) years, and approximately 71% were females. The adjusted average monthly healthcare expenditure per participant was $AU386 (95% CI: 336, 436). On top of the average monthly costs, an incremental expenditure was found for each year increase in age ($AU4; 95% CI: 0.78, 7), being unemployed ($AU201; 95% CI: 91, 311), one unit change in worsening quality of life ($AU35; 95% CI: 9, 61) and being diagnosed with depression and anxiety ($AU171; 95% CI: 36, 306). In a cohort of Australian patients, characterized by poor asthma control and co-morbidities individuals impose substantial economic burden in terms of Medicare funded medical services and medications. Programs addressing strategies to improve the quality of life and manage co-morbid anxiety and depression and encourage asthma patients' engagement in clinically tolerable jobs, may result in significant cost savings to the health system.

Utility of biomarkers and temporal artery biopsy length for investigating giant cell arteritis in Western Australia.

To explore demographic characteristics, biopsy length, and blood biomarker performance in an Australian cohort of patients who have undergone temporal artery biopsy (TAB) for giant cell arteritis (GCA). We extracted data on biopsies performed for GCA between January 2016 and December 2020 at public hospitals in Perth. Sensitivity, specificity, and area under the curve (AUC) were calculated for blood results. We evaluated the proportion of biopsies with post-fixation length less than 15 mm and explored several length associations. We retrospectively reviewed biopsies of 360 patients (65.8% female, mean age 72.1 years). Biopsy-positive patients were older (6.0 years, P < 0.01), and had higher C-reactive protein (CRP) (44.5mg/L, P < 0.01), erythrocyte sedimentation rate (ESR) (18.9 mm/h, P < 0.01), and platelets (86.8 × 103 /μL, P < 0.01) compared with biopsy-negative patients. CRP and platelets had the highest AUCs at 0.76 and 0.71, respectively. Sensitivities for CRP and ESR were 96.2% and 91.5%, respectively. Specificities were comparatively low at 41.3% for CRP and 37.4% for ESR. The proportion of biopsies with sub-optimal length was 55.9% and this varied significantly by site (P < 0.01). Smaller sites performed worse, with a sub-optimal biopsy rate of 87% amongst the three smallest sites. ESR and CRP are helpful preliminary investigations, especially in identifying low-risk patients, but their specificity is limited. Smaller centers had a higher proportion of biopsies with sub-optimal length. Considering the importance of biopsy length for TAB diagnostic value, reviewing biopsy data may assist services in developing improvement strategies.

Ibrutinib for Steroid Refractory Chronic Graft Vs Host Disease - Real World Experience

Background and aims: Chronic graft vs host disease (cGVHD) is a common complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in 30-70% of recipients receiving T cell replete grafts [1]. While corticosteroids are the backbone of first line therapy for cGVHD, less than 20% of patients achieve a durable partial or complete response with this therapy alone [2]. Despite the advent of novel agents for second line therapy of steroid refractory cGVHD (SR-cGVHD), disease progression is not uncommon highlighting an unmet clinical need. GVHD is believed to be mediated by donor derived alloreactive B and T cells. Ibrutinib is a first in class Bruton tyrosine kinase (BTK) inhibitor, with additional inhibitory effects on other tyrosine kinases such as interleukin-2 inducible kinase (ITK). BTK and ITK play important roles in B and T cell stimulatory signalling pathways respectively. Inhibition of these pathways in alloreactive B and T cell clones may ameliorate cGVHD, and in recent phase 1b/II clinical trials in SR-cGVHD ibrutinib has demonstrated response rates of 60-70% [3]. The outcomes in real world clinical practice may differ from those observed in trials, as patients may have received more lines of cGVHD therapy or have different comorbidities affecting tolerability. We assessed the efficacy and tolerability of ibrutinib given for SR-cGVHD in a real world cohort of Australian patients. Methods: A retrospective review of pharmacy dispensing records was undertaken at six allogeneic bone marrow transplantation centres across Australia between Jan 2018 and Jan 2020 to identify patients treated with ibrutinib on compassionate access for SR-cGVHD. Clinical records of identified patients were reviewed to extract data using standardised case report forms including transplant details, cGVHD manifestations and treatment history, cGVHD response to ibrutinib (as per NIH cGVHD consensus criteria [4]), adverse events, relapse and survival. Results: Demographic details of the 41 eligible patients are outlined in Figure 1. The majority (95%) had extensive cGVHD with a median of 3 lines of systemic therapy (range 2-8) preceding ibrutinib. The median starting dose of ibrutinib was 420mg daily (range 140 - 420mg daily), with an overall response rate of 44%, with a complete response seen in 5% (Figure 2). Corticosteroid dosing information was available for 20 patients, with a mean reduction in dose of 44% during ibrutinib treatment. There were a total of 50 adverse events in 22 patients, of which 48% were infections. After a median follow up of 412 days, 46% of patients were continuing ibrutinib, with the most common reasons for cessation being toxicity (32%) or progressive cGVHD (27%). At last follow up, 32/41 patients were alive, with causes of death being cGVHD (6 patients), infection (2 patients) and secondary malignancy (1 patient). Conclusion: Ibrutinib demonstrates modest activity in a real world setting of heavily pre-treated patients with SR-cGVHD. Toxicities, particularly those related to infections, appear to limit long term use. This study highlights the potential limitations of the use of ibrutinib for SR-cGVHD in a real world context, particularly with reference to tolerability in heavily pre-treated patients.

The first Australian experience with ward-based continuous positive airway pressure for COVID-19 respiratory failure: a retrospective cohort study.

We present the first Australian cohort of patients with COVID‐19 respiratory failure managed with escalating respiratory support including Continuous Positive Airway Pressure (CPAP) on a standard medical ward at a tertiary Sydney hospital during the 2021 COVID‐19 Delta variant outbreak. We demonstrate an equivalent mortality to CPAP delivered in ICU and outline our ward structure and management during the pandemic.This article is protected by copyright. All rights reserved.

Gamma Knife® stereotactic radiosurgery for intracranial cavernous malformations

IntroductionGamma Knife® stereotactic radiosurgery (GKSRS) is a non-invasive alternative to surgical resection for cerebral cavernous malformations (CCMs), especially in eloquent locations. MethodologyA retrospective review was performed on an Australian cohort of patients receiving GKSRS for CCMs at a single institution. All patients exhibited symptoms and/or radiological evidence of haemorrhage before therapy. The minimum follow-up was 1-year post-GKSRS. McNemar’s test was used for differences in matched-pair outcomes pre- and post-GKSRS with an α = 0.05. A systematic review and meta-analysis was additionally performed to synthesise the current published evidence on the clinical efficacy of stereotactic radiosurgery in reducing haemorrhage risk in CCMs using a DerSimonian and Laird random effects model. ResultsThirty-five patients (39 cavernomas) underwent GKSRS. 87.2 % of patients had evidence of at least one haemorrhage before GKSRS and the remainder exhibited seizures. The median dose was 12.5 Gy in a single fraction (IQR 12–13). The median follow-up duration from GKSRS was 809 days (IQR 536–960). There was a significant reduction in matched annual bleed rate from pre-GKSRS (52.1 %) compared to after SRS (12.3 %) (p < 0.001) [OR = 0.07, 95 % 0.008–0.283] There was no statistically significant difference in seizure incidence pre- (30.7 %) versus post-GKSRS (17.9 %) (p = 0.13) [OR = 0.167, 95 %CI 0.004–1.37]. One patient (3 %) with a brainstem lesion experienced long-term treatment-related oedema with persistent ipsilateral weakness and tremors. On meta-analysis of 25 pooled studies, radiosurgery for the treatment of CCMs was associated with a statistically significantly relative risk (RR) reduction in haemorrhage events [random effects RR 0.12 (95 % CI 0.074–0.198), p < 0.001)], with most of the proportionate risk reduction occurring in the initial 2 years following SRS. ConclusionGKSRS significantly reduces the annual rate of haemorrhage for intracranial cavernomas in this cohort and on meta-analysis, particularly in the first 2 years following treatment. The overall risk of treatment-related morbidity is low.

Treatment satisfaction in patients with relapsing-remitting multiple sclerosis initiated on teriflunomide in routine clinical practice: Australian observational data

BackgroundAdherence and persistence are critical to optimising therapeutic benefit from disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). This prospective, open-label, multicentre, observational study (AubPRO), conducted in 13 hospital-based neurology...

Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study

Background and aimsLittle is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population.MethodsWe conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers.ResultsA total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2–15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival.ConclusionIn this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

Diagnostic Performance of CT-Derived Fractional Flow Reserve in Australian Patients Referred for Invasive Coronary Angiography

Non-invasive computed tomography (CT)-derived fractional flow reserve (FFRCT) is computed from standard coronary CT angiography (CTA) datasets and provides accurate vessel-specific ischaemia assessment of coronary artery disease (CAD). To date, the technique and its diagnostic performance has not been verified in the Australian clinical context. The aim of this study was to describe and compare the diagnostic performance of FFRCT and CTA for the detection of vessel-specific ischaemia as determined by invasive fractional flow reserve (FFR) in the Australian patient population. One-hundred-and-nine patients (219 vessels) referred for clinically mandated invasive angiography were retrospectively assessed. Each patient underwent research mandated CTA and FFRCT within 3 months of invasive angiography and invasive FFR assessment. Independent core laboratory assessments were made to determine visual CTA stenosis, FFRCT and invasive FFR values. FFRCT values were matched with the corresponding invasive FFR measurement taken at the given wire position. Visual CTA stenosis ≥50%, FFRCT values ≤0.8 and invasive FFR values ≤0.8 were considered significant for ischaemia. Per vessel accuracy, sensitivity, specificity, positive predictive value and negative predictive value of FFRCT were 80.4%, 80.0%, 80.6%, 64.9% and 90.0% respectively. Corresponding values for CTA were 75.1%, 87.1%, 69.2%, 58.1% and 91.7% respectively. In receiver operating characteristic curve analysis, FFRCT demonstrated superior area under the curve (AUC) compared with CTA in both per vessel (0.87 vs 0.77, p=0.004) and per patient analysis (0.86 vs 0.74, p=0.011). Per vessel AUC of combined CTA and FFRCT was superior to CTA alone (0.89 vs 0.77, p<0.0001). In this cohort of Australian patients, the diagnostic performance of FFRCT was found to be comparable to existing international literature, with demonstrated improvement in performance compared with CTA alone for the detection of vessel-specific ischaemia.

Evaluation of two European risk models for predicting medication harm in an Australian patient cohort.

To externally evaluate the performance of two European risk prediction models, for identifying patients at high-risk of medication harm, in an Australian hospital setting. This was a secondary analysis of a pre-existing cohort study described in a recently published study by Falconer et al. (Br J Clin Pharmacol 87(3):1512-1524, 2021) describing the development of a predictive risk model for inpatient medication harm. We retrospectively extracted relevant variables using the electronic health records of general medical and geriatric patients admitted to a quaternary hospital, in Brisbane, over 6months from July to December 2017. This dataset was used to externally evaluate the two European models, The Brighton Adverse Drug Reaction Risk (BADRI) model by Tangiisuran et al. and a risk model developed by Trivalle et al. The variables were entered into both models and the patients' risk of medication harm was calculated, and compared with actual patient outcomes. Predictive performance was evaluated by measuring area under the receiver operative characteristic (AuROC) curves. The Australian patient cohort included 1982 patients (median age 74years), of which 136 (7%) patients experienced ≥ 1 medication harm event(s). External evaluation of the two European models identified that both the BADRI and the Trivalle models had reduced predictive performance in an Australian patient cohort, compared with their original studies (AuROC of 0.63 [95% CI: 0.58-0.68] and 0.60 [95% CI: 0.55-0.65], respectively). Neither model demonstrated sufficient discrimination to warrant further evaluation in our local setting. This is likely a result of variations between the development and the validation cohorts, and the change in healthcare systems over time, and highlights the need for an up-to-date and context-specific risk prediction model.

Clinical characteristics and prognosis of cardiac amyloidosis defined by mass spectrometry-based proteomics in an Australian cohort.

Cardiac amyloidosis has a very poor prognosis, but it is the nature of the involved precursor protein that ultimately dictates treatment and survival. Definitively characterise the amyloid subtype by mass spectrometry (MS) in an Australian cohort of patients with cardiac amyloidosis. We report the clinical characteristics and survival of 47 cardiac amyloid patients across two Australian centres including 39 patients evaluated for definitive amyloid subtype utilising laser microdissection and tandem mass spectrometry. A quarter (n = 12) of patients were classified as wild-type transthyretin amyloidosis (ATTRwt), 33 patients as light or heavy chain amyloidosis (AL or AH) and two as hereditary mutant transthyretin amyloidosis. Greater left ventricular hypertrophy (interventricular septum 22 vs 15 mm; P = 0.005) and history of cardiac arrhythmia (75% vs 31%; P = 0.016) were significantly associated with ATTRwt patients compared with AL/AH patients. AL patients demonstrated significantly shorter median survival compared with ATTRwt patients (3.5 vs 37 months; P = 0.007). New York Heart Association class III-IV symptoms or plasma cells ≥10% at diagnosis, were the only independent predictors of worse survival in AL patients on multivariate analysis. AL amyloidosis accounted for 68% of our cohort of patients with cardiac amyloidosis while ATTR accounted for 26%. In the era of novel therapies for both AL amyloid and ATTR, identification of the correct amyloid subtype is essential in making therapeutic decisions and providing accurate prognostic information to patients. Laser microdissection and tandem mass spectrometry plays an important role in identifying amyloid subtype, particularly in complex cases.

Determining the Rate of Anti-PF4 Antibody Positive Results in Patients Presenting with Venous Thrombosis but a Normal Platelet Count Following ChAdOx1 Ncov-19 Astrazeneca Vaccination: An Australian Combined State Testing Centre Experience

IntroductionThe CHaDOx1 nCov-19 AstraZeneca (AZ) vaccination has been associated with an antibody-mediated prothrombotic syndrome, termed “Thrombosis with Thrombocytopenia Syndrome” (TTS)[1-3]. The current diagnostic criteria for TTS are thrombosis (venous or arterial) within 4-42 days of AZ vaccine, thrombocytopenia and presence of an antibody to platelet factor 4 (PF4)[4, 5]. TTS commonly presents with cerebral venous sinus thrombosis (CVST) or splanchnic vessel thrombosis (SVT), but outside of TTS, CVST and SVT are uncommon, with an overall incidence of less than 0.5 per 100,000 [5-7]. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are also associated with TTS, however the background incidence of venous thromboembolism (VTE) is much higher, with 1-2 events per 1000 patients per year[7, 8]. Therefore, many patients will present with new VTE and a recent exposure to the AZ vaccine, requiring consideration of investigation for TTS. Recent data suggests that PF4 antibodies can be seen in up to 8% of patients without thrombosis but following AZ vaccination[9]. We hypothesised in patients with recent AZ vaccination, new VTE but with a normal platelet count, that the incidence of a PF4 antibody is similar to this background rate of PF4 positivity. If confirmed, then presence of a normal platelet count despite new VTE and recent vaccination may exclude TTS without the need for PF4 antibody testing. We present our preliminary data on the rates of PF4 antibody positivity amongst patients with VTE, recent AZ vaccination and a normal platelet count at presentation.Aim and MethodsTo assess the incidence of PF4 ELISA positive results in patients with confirmed VTE, recent vaccination (within 4-42 days) with the first dose of AZ vaccine, and platelet count greater than 150x10 9/L.A retrospective audit of cases referred with suspected TTS to Monash Pathology, Melbourne, Victoria, and New South Wales Health Pathology at Royal Prince Alfred Hospital and St George Hospital sites Sydney, New South Wales, Australia, for testing for anti PF4 antibodies from 1 st April to 31 st July 2021.Patient sera were tested for the Anti-PF4 antibody using the STAGO Asserachrom HPIA IgG ELISA (Asnières sur Seine, France). For patients with a positive PF4 antibody test additional testing was sought for either the presence of platelet activating antibodies with a flow cytometry-based assay or the presence of spontaneous serotonin release without heparin in the serotonin release assay.ResultsFrom April 1 st to July 31 st 350 tests were run on 332 patients. 91 patients met our criteria, of whom 51 were female and 40 male, with a median age of 73 years. Median platelet count at presentation was 226x10 9/L, and median D dimer values were 10 times the upper limit of normal. 86 patients had either DVT, PE or both, including 2 with upper limb DVT, and 5 patients had PE with concurrent arterial events (1 axillary artery thrombosis, 3 arterial strokes, 1 coronary artery thrombosis). Further details are presented in table 1. 82 patient samples tested negative for anti-PF4 antibodies by ELISA, 5 were positive, and were 4 weak positive/equivocal (see table 2 for further details). Of the positive results, 3 had functional testing available, of which 2 were negative, and 1 showed discordant results, with a positive SRA but negative flow cytometry. None of the weak positive/equivocal cases had functional testing results available. Of the negative ELISA results, 5 patients had functional testing results available, of which 4 were negative. One of these cases had positive testing by flow cytometry, but negative by SRA (case included in table 2).ConclusionIn our Australian cohort of patients with their first dose of AZ vaccine and new VTE within 4-42days, but a normal platelet count (therefore not fulfilling the clinical criteria of TTS), the incidence of a positive PF4 antibody test was 9/91 (9.9%, 95% CI 3.7-15.9%) and only one had evidence of platelet activating antibodies. This observed rate is similar to that observed in healthy patients without thrombosis who received AZ vaccination as described by Thiele et. al., 2021. Further confirmation in a larger cohort of VTE patients is required, but if confirmed, then PF4 ELISA testing in patients with VTE and normal platelet count post AZ vaccine may not be required, and should give clinicians confidence to institute routine management. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Determinants of Short- and Long-Term Outcomes of an Australian Cohort of Patients Admitted with Alcoholic Hepatitis.

Alcoholic hepatitis is a common condition with high mortality. This study aimed to firstly describe the presentation, treatment, and short- and long-term outcomes of an Australian cohort of patients admitted to hospital with alcoholic hepatitis and secondly to validate existing prognostic models. This is a retrospective study of consecutive patients admitted with alcoholic hepatitis to a major academic liver center in Melbourne, Australia, between January 1, 2010, and December 31, 2019. Cases were identified through appropriate International Classification of Diseases version 10 coding as well as review of non-coded patients with compatible biochemistry. Baseline demographic data, alcohol consumption, laboratory values, treatment, and outcomes at 30days, 90days, and 12months post-diagnosis were collected from electronic medical records. Mortality data were extracted from an independent state government death registry. In total, 126 patients (72 males [57%], median age 51years) were included in the final analysis. Ninety-five (75%) were cirrhotic at diagnosis, 81 (64%) met criteria for severe alcoholic hepatitis, and 41 (33%) had an infection during their index admission. 54% of eligible patients were treated with corticosteroids. 30-day and 12-month mortality rates were 8.7% and 27.1%, respectively, with hepatic encephalopathy (hazard ratio 5.45) and neutrophil-to-lymphocyte ratio (hazard ratio 1.09) independent markers for 12-month mortality on Cox regression analysis. Glasgow alcoholic hepatitis score outperformed other major prognostic models for short-term mortality. The 12-month mortality rate of 27% following alcoholic hepatitis is lower than previously reported studies, with hepatic encephalopathy and neutrophil-to-lymphocyte ratio predictive of long-term outcome.

The impact of antineutrophil cytoplasmic antibody-associated vasculitis on employment and work disability in an Australian population.

Although antineutrophil cytoplasmic antibody-associated vasculitis (AAV) most commonly affects older individuals, many patients develop the disease during their most productive working years. The aim of this study was to examine the effects of AAV on employment and work disability in a cohort of Australian patients of working age. Patients attending a vasculitis clinic located in Melbourne, Australia, completed an employment questionnaire in addition to the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem. The average age of the 47 respondents was 47.8±11.9years (range 22-63years), with a median disease duration of 60months (range 10.2-318.5months). There were 68.1% who were currently employed, but 20.6% of respondents employed at the time of diagnosis were no longer working and 10.6% had experienced a significant reduction in work hours since their diagnosis. There were 12.7% who were dependent on the disability support pension. The rate of work disability was 23.4%. Many participants considered themselves work impaired (41.9%), with 10.1% having missed work in the previous week. Furthermore, 44.7% of respondents reported that their financial stability had been negatively impacted by their vasculitis diagnosis. Fatigue was commonly reported. Work disabled patients were significantly more likely to be obese and less likely to have completed a tertiary education. Work disabled patients tended to be older, myeloperoxidase-antineutrophil cytoplasmic antibody positive, and have renal involvement and lung involvement. A proportion of people living with AAV in Australia experience a decline in employment and an increase in work disability when living with this condition.