Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailableDiscontinuation of nucleot(s)ide analogue therapy in HBeAg-negative chronic hepatitis B: a meta-analysis(BMJ PUBLISHING GROUP, 2022-08)BACKGROUND AND AIMS: Sustained virological suppression and hepatitis B surface antigen (HBsAg) loss have been described after nucleot(s)ide analogue (NA) discontinuation for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We performed a meta-analysis of the clinical outcomes after NA discontinuation for HBeAg-negative CHB. METHODS: Studies involving NA cessation in HBeAg-negative CHB individuals with a median follow-up of ≥12 months were included. Participants were HBeAg-negative at the time of NA initiation. Random effects meta-analyses were performed for the following clinical outcomes: (1) virological relapse (VR) at 6 and 12 months; (2) clinical relapse (CR) at 6 and 12 months and (3) HBsAg loss. Effect of other variables was estimated using subgroup analysis and meta-regression. Studies including patients stopping entecavir (ETV) and/or tenofovir disoproxil fumarate (TDF) were considered separately to studies including patients stopping older generation NA. RESULTS: N=37 studies met inclusion criteria. Cumulative incidence of VR and CR after stopping ETV/TDF was 44% and 17% at 6 months and 63% and 35% at 12 months. Similar relapse rates were observed after stopping older NAs. Among patients stopping ETV/TDF, TDF cessation was associated with increased CR rates at 6 months versus ETV. There was an association between follow-up ≥4 years and HBsAg loss rates when stopping older NAs. Hepatic decompensation and hepatocellular carcinoma were rare but occurred more frequently in studies including cirrhotic individuals. CONCLUSION: VR is common after NA discontinuation, however, CR was only seen in one-third of patients at 12 months. Stopping NA therapy can be followed by HBsAg clearance, and rates are higher with longer follow-up.
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ItemNo Preview AvailableDamage Trajectories in Systemic Sclerosis Using Group-Based Trajectory Modeling(WILEY, 2022-11-15)OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive organ damage, which can be measured using the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). We aimed to identify whether distinct trajectories of damage accrual exist and to determine which variables are associated with different trajectory groups. METHODS: Incident cases of SSc (<2 years) were identified in the Australian Scleroderma Interest Group and Canadian Scleroderma Research Group prospective registries. Group-based trajectory modeling was used to identify SCTC-DI trajectories over the cohort's first 5 annual visits. Baseline variables associated with trajectory membership in a univariate analysis were examined in multivariable models. RESULTS: A total of 410 patients were included. Three trajectory groups were identified: low (54.6%), medium (36.2%), and high (10.3%) damage. Patients with faster damage accrual had higher baseline SCTC-DI scores. Older age (odds ratio [OR] 1.57 [95% confidence interval (95% CI) 1.18-2.10]), male sex (OR 2.55 [95% CI 1.10-5.88]), diffuse disease (OR 6.7 [95% CI 2.57-17.48]), tendon friction rubs (OR 5.4 [95% CI 1.86-15.66]), and elevated C-reactive protein level (OR 1.98 [95% CI 1.49-2.63]) increased the odds of being in the high-damage group versus the reference (low damage), whereas White ethnicity (OR 0.31 [95% CI 0.12-0.75]) and anticentromere antibodies (OR 0.24 [95% CI 0.07-0.77]) decreased the odds. CONCLUSION: We identified 3 trajectories of damage accrual in a combined incident SSc cohort. Several characteristics increased the odds of belonging to worse trajectories. These findings may be helpful in recognizing patients in whom early aggressive treatment is necessary.
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ItemNo Preview AvailableIS QUALITY OF LIFE RECOVERY ASSOCIATED WITH LOWER MORTALITY 5 YEARS POST-FRACTURE IN COMMUNITY-DWELLING OLDER ADULTS?(SPRINGER LONDON LTD, 2022-04-01)
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ItemChildhood antibiotics as a risk factor for Crohn's disease: The ENIGMA International Cohort Study(WILEY, 2022-06-01)BACKGROUND AND AIM: Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations. METHODS: This case-control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at-risk individuals including non-affected first-degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self-developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development. RESULTS: From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98 ± 13.76 years; 58.3% male), 73 FDR (mean age: 49.35 ± 13.28 years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50 ± 13.25 years; 47.5% male), and 78 HC (mean age: 45.57 ± 11.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18 years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38-8.69; P = 0.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use <18 years old was a risk factor for CD development in the Chinese (adjusted OR 4.80, 95% CI 1.62-12.24; P = 0.005) but not in Australian populations (OR 1.80, 95% CI 0.33-9.95; P = 0.498). CONCLUSION: Use of antibiotics <18 years was a risk factor for CD development. Attention should be paid to identifying modifiable environmental risk factors in early childhood, especially in at-risk families.
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ItemINFERRING PATIENT-SPECIFIC PHYSIOLOGICAL PARAMETERS FROM INTRACRANIAL EEG: APPLICATION TO CLINICAL DATA(WILEY-BLACKWELL, 2012-09-01)Purpose: Intracranial EEG (iEEG) provides information regarding where and when seizures occur, whilst the underlying mechanisms are hidden. However physiologically plausible mechanisms for seizure generation and termination are explained by neural mass models, which describe the macroscopic neural dynamics. Fusion of models with patient-specific data allows estimation and tracking of the normally hidden physiological parameters. By monitoring changes in physiology, a new understanding of seizures can be achieved. This work addresses model-data fusion for iEEG for application in a clinical setting. Method: Data was recorded from three patients undergoing evaluation for epilepsy-related surgery at St. Vincent's Hospital, Melbourne. Using this data, we created patient-specific neural mass mathematical models based on the formulation of Jansen and Rit (1995). The parameters that were estimated include the synaptic gains, time constants, and the firing threshold. The estimation algorithm utilized the Unscented Kalman Filter (Julier and Uhlmann, 1997). Result: We demonstrate how parameters changed in relation to seizure initiation, evolution and termination. We also show within-patient (across different seizures) and between-patient specificity of the parameter estimates. Conclusion: The fusion of clinical data and mathematical models can be used to infer valuable information about the underlying mechanisms of epileptic seizure generation. This information could be used to develop novel therapeutic strategies
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ItemINFERRING PATIENT-SPECIFIC PHYSIOLOGICAL PARAMETERS FROM INTRACRANIAL EEG: THEORETICAL STUDIES(WILEY-BLACKWELL, 2012-09-01)
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ItemIdentification of a Neural Mass Model of Burst Suppression(IEEE, 2019)Burst suppression includes alternating patterns of silent and fast spike activities in neuronal activities observable in micro to macro scale recordings. Biological models of burst suppression are given as dynamical systems with slow and fast states. The aim of this paper is to give a method to identify parameters of a mesoscopic model of burst suppression that can provide insights into study underlying generators of intracranial electroencephalogram (iEEG) data. An optimisation technique based upon a genetic algorithm (GA) is employed to find feasible model parameters to replicate burst patterns in the iEEG data with paroxysmal transitions. Then, a continuous discrete unscented Kalman filter (CD-UKF) is used to infer hidden states of the model and to enhance the identification results from the GA. The results show promise in finding the model parameters of a partially observed mesoscopic model of burst suppression.
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ItemNo Preview AvailableEndoscopic features of buried Barrett's mucosa: visible to the trained eye?(Wiley, 2019-12-01)
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ItemPhase 2 Study of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer Follow-Up(National Society for Cutaneous Medicine, 2020-10-27)Abstract not available.
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ItemCemiplimab Improves Health-Related Quality of Life (HRQoL) and Reduces Pain in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Results from a Post Hoc Exploratory Analysis of a Phase 2 Clinical Trial(National Society for Cutaneous Medicine, 2021-01-01)Abstract not available.