ORCID Profile
0000-0002-9341-4792
Current Organisations
University of Southampton
,
Royal Melbourne Hospital Royal Park Campus
,
University of Melbourne
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Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.JDENT.2009.09.002
Abstract: To characterize molar-incisor hypomineralisation (MIH) defects of different severities quantitatively and qualitatively using X-ray microtomography (XMT) and to measure the range of reduction in mineral density (MD) of MIH enamel compared with the normal range. Ten sound teeth and ten MIH teeth were scanned using a commercial XMT system. Four hydroxyapatite phantoms of different densities were used as calibration standards with each scan. A calibration equation derived from the phantoms with each tooth was used for MD calibration. MD was traced from the cementum-enamel junction (CEJ) to the cusp tip and from the dentine-enamel junction (DEJ) to the outer enamel surface. In sound teeth, MD increased from CEJ to cusp/incisal tip, while in MIH teeth MD dropped from the CEJ to the occlusal region, then increased again at the cusp tip. MD was highest midway between DEJ and outer enamel in sound teeth. In MIH, enamel showed normal thickness and MD was highest near the DEJ and then decreased towards the outer enamel. MD of MIH enamel was on average about 19% lower than sound enamel. The MIH defects seemed to follow the incremental lines of enamel formation. MIH defects are hypomineralised defects of different severities that follow the natural incremental lines of enamel formation. Cuspal areas are usually only mildly affected and cervical enamel always appears to be sound.
Publisher: Wiley
Date: 09-06-2017
DOI: 10.1111/JVH.12717
Abstract: While HBV and HCV are risk factors for HCC, uncertainty exists as to whether these viral infections have prognostic significance in HCC. Thus, we compared the overall survival of patients with HBV, HCV and nonviral HCC, and evaluated whether the presence of HBV and HCV predicts patient outcomes. We conducted a multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour characteristics and patient outcomes were obtained from hospital databases, computer records and the Victorian Death Registry. Survival outcomes were compared between HBV, HCV and nonviral hepatitis cases and predictors of survival determined using Cox proportional hazards regression. There were 1436 new HCC cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV 30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On multivariate analysis, independent risk factors for survival included HCC aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and serum creatinine and albumin. After adjusting for these and method of detection, HBV remained an independent predictor of improved overall survival when compared to both nonviral (HR 0.60%, 95% CI 0.35-0.98 P=.03) and HCV-related HCC (HR 0.51%, 95% CI 0.30-0.85 P=.01). In this large multicentre study, HBV is independently associated with improved overall survival compared with HCV and nonviral-related HCC. Further studies are needed to determine the underlying factor(s) responsible.
Publisher: Open Access Pub
Date: 14-11-2017
Publisher: Baishideng Publishing Group Inc.
Date: 2016
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JOCN.2018.10.055
Abstract: Alemtuzumab is a monoclonal antibody used as a disease modifying agent in relapsing and remitting multiple sclerosis. It has not previously been associated with drug induced liver injury. Here we present a case of a 49 year old female developing drug induced liver injury secondary to alemtuzumab, confirmed upon rechallenge. Our patient developed severe hepatitis within two days of starting alemtuzumab, both initially and upon rechallenge. The alanine aminotransferase peaked at 577 units per litre and 426 units per litre after initial dose of alemtuzumab and rechallenge respectively. The patient's liver function tests improved significantly between doses of alemtuzumab and again normalised within three months of the second dose, with no clinical manifestations of acute hepatic failure. A full hepatitis screen ruled out alternative causes of hepatitis, including autoimmune hepatitis and hepatotoxicity relating to other medications. Deliberate rechallenge with a medication thought to be associated with drug induced liver injury is uncommonly performed but provides substantial evidence for causality in the appropriate clinical context. The Roussel Uclaf Causality Assessment Method score was calculated as nine, indicating that drug induced liver injury due to alemtuzumab is highly probable. Drug induced liver injury is a potentially serious condition that should be monitored for during alemtuzumab treatment of relapsing and remitting multiple sclerosis. The role of a rechallenge should be weighed up on a case by case basis.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Springer Science and Business Media LLC
Date: 29-05-2020
DOI: 10.1186/S12885-020-06806-4
Abstract: Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion. Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival. Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2–50.2) from initial TACE. On multivariate analysis greater tumour number ( p = 0.02), higher serum bilirubin ( p = 0.007) post initial TACE, and hepatic decompensation ( p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival ( p = 0.001), compared to patients with serum AFP level that remained 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months ( p = 0.0001) respectively. Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.
Publisher: Springer Science and Business Media LLC
Date: 09-09-2021
DOI: 10.1007/S12029-020-00502-Z
Abstract: Hepatocellular carcinoma (HCC) is responsible for 1% of deaths worldwide, and the incidence continues to increase. Despite surveillance programs, 70% of HCC patients are not suitable for curative options at diagnosis, and therefore, non-curative treatments are essential to modern clinical practice. There are many novel treatments, though their roles are not well defined. This study aimed to contrast Selective Internal Radiation Therapy (SIRT) and Drug Eluting Bead Transarterial Chemoembolisation (DEB-TACE) to further define their roles. This was a retrospective multicentre cohort study. Factors included for analysis were type of HCC treatment, number of lesions, lesion size, multiple disease severity scores, cirrhosis and vascular invasion. The primary endpoint was transplant-free survival. Transplant-free survival was similar between the two cohorts (p = 0.654), despite a variation in median lesion size, SIRT: 54.5 mm, DEB-TACE: 34 mm (p ≤ 0.001). A univariate Cox proportional hazard model utilising treatment modality as the covariate showed no significant difference in survival (DEB-TACE HR 1.4 (95%CI 0.85-2.15 p = 0.207). The size of the largest lesion was the best predictor of 3-year survival (p = 0.035). Lesion size was inversely associated with survival (HR 1.01 (95%CI 1-1.02, p = 0.025)) on multivariate analysis. This study is the first to catalogue the experience of using SIRT in HCC in a real-world Australian population. It has demonstrated no difference in survival outcomes between DEB-TACE and SIRT. Further, it has shown SIRT to be a reasonable alternative to DEB-TACE especially in larger lesions and has demonstrated that DEB-TACE has a role in select patients with advanced disease.
Publisher: Informa UK Limited
Date: 17-10-2020
Publisher: Wiley
Date: 26-04-2022
DOI: 10.1111/LIV.15264
Abstract: Non‐alcoholic fatty liver disease (NAFLD) is predominantly managed by lifestyle intervention, in the absence of effective pharmacotherapies. Mediterranean diet (MedDiet) is the recommended diet, albeit with limited evidence. To compare an ad libitum MedDiet to low‐fat diet (LFD) in patients with NAFLD for reducing intrahepatic lipids (IHL) by proton magnetic resonance spectroscopy ( 1 H‐MRS). Secondary outcomes include insulin resistance by homeostatic model of assessment (HOMA‐IR), visceral fat by bioelectrical impedance analysis (BIA), liver stiffness measurement (LSM) and other metabolic outcomes. In this parallel multicentre RCT, subjects were randomised (1:1) to MedDiet or LFD for 12 weeks. Forty‐two participants (25 females [60%], mean age 52.3 ± 12.6 years) were included, 23 randomised to LFD and 19 to MedDiet. 39 completed the study. Following 12 weeks, there were no between‐group differences. IHL improved significantly within the LFD group (−17% [log scale] p = .02) but not within the MedDiet group (−8%, p = .069). HOMA‐IR reduced in the LFD group (6.5 ± 5.6 to 5.5 ± 5.5, p .01) but not in the MedDiet group (4.4 ± 3.2 to 3.9 ± 2.3, p = .07). No differences were found for LSM (MedDiet 7.8 ± 4.0 to 7.6 ± 5.2, p = .429 LFD 11.8 ± 14.3 to 10.8 ± 10.2 p = .99). Visceral fat reduced significantly in both groups LFD (−76% [log scale], p = .0005), MedDiet (−61%, p = .0005). There were no between‐group differences for hepatic and metabolic outcomes when comparing MedDiet to LFD. LFD improved IHL and insulin resistance. Significant improvements in visceral fat were seen within both groups. This study highlights provision of dietary interventions in free‐living adults with NAFLD is challenging.
Publisher: Wiley
Date: 03-04-2023
DOI: 10.1111/IMJ.16053
Abstract: Hepatic encephalopathy is a confusional state associated with cirrhosis. Serum ammonia levels are neither sensitive nor specific for the diagnosis. We audited the ordering location and hospital unit whilst assessing the impact on management at a major Australian tertiary centre. We conducted a single‐centre retrospective chart review of the ordering of serum ammonia levels between 1 March 2019 and 29 February 2020 at The Royal Melbourne Hospital, a tertiary‐referral centre in Melbourne, Victoria. Demographic, medication and pathology results, including serum ammonia measurements, were collected. The main outcomes assessed were ordering location, sensitivity, specificity and impact on management. A total of 1007 serum ammonia tests were ordered in 425 patients. Nearly all ammonia ordering was by non‐gastroenterologists, 24.2% by the intensive care unit, 23.1% by general medicine and 19.5% by the emergency department (ED). Only 21.6% of patients had a history of cirrhosis, with hepatic encephalopathy diagnosed in 13.6%. On subgroup analysis, 217 ammonia tests were performed in 92 patients with cirrhosis. Cirrhotic patients were older (64 vs 59 years, P = 0.012) and had higher median ammonia levels (64.46 vs 59 μmol/L, P 0.001) compared with non‐cirrhotic patients. In cirrhotic patients, the sensitivity and specificity for serum ammonia and diagnosis of hepatic encephalopathy were 75% and 52.3% respectively. We affirm the poor utility of serum ammonia levels for guiding management of hepatic encephalopathy within the Australian context. ED and general medical units account for the majority of test ordering within the hospital. Understanding where ordering occurs provides a target for targeted education.
Publisher: Elsevier BV
Date: 02-2018
Publisher: Baishideng Publishing Group Inc.
Date: 2014
DOI: 10.5500/WJT.V4.I1.30
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2003
Publisher: Wiley
Date: 04-2021
DOI: 10.1111/IMJ.15267
Publisher: Wiley
Date: 28-12-2020
DOI: 10.1111/JGH.14924
Abstract: The prevalence of primary biliary cholangitis (PBC) reported in different countries varies significantly and in some parts of the world appears to be increasing. The aim of this study was to determine the 2013 prevalence of PBC in Victoria, Australia, and to determine the time trend by comparing it with previous studies undertaken in 1991 and 2002. Four case-finding methods were used to identify cases of PBC in Victoria: (1) physicians' survey (2) tertiary hospital search (3) liver transplant database search and (4) private pathology antimitochondrial antibody search. The prevalence of PBC in Victoria, Australia, is 189.0 per million using all four methods. The average annual increase in prevalence from 1991 to 2013 was 7.7 per million per year. Using the same case-finding methods as the 1991 Victorian prevalence study (methods 1 and 2), the prevalence of PBC increased from 19.1 per million in 1991 to 49.4 per million in 2002 (P < 0.001) and to 80.7 per million in 2013 (P < 0.001). The current prevalence of PBC in Victoria is significantly higher than previously reported. The use of private pathology-based case-finding methods is important in identifying the maximum number of PBC cases.
Publisher: Elsevier BV
Date: 08-2004
DOI: 10.1053/J.GASTRO.2004.04.064
Abstract: The prevalence of primary biliary cirrhosis (PBC) reported in different countries varies widely, indicating that genetic or environmental factors may be important in the etiology of the disease. The aim of this study was to examine this issue further by determining the overall prevalence of PBC in one state in Australia and to examine the prevalence among different migrant groups within this population. Thorough case-finding methods were used to identify all cases of PBC in Victoria, Australia. Age-adjusted prevalence rates among different migrant groups were examined. A total of 249 cases were identified, giving a prevalence of 51 cases per million. This is significantly higher than the rate documented in a 1991 Victorian study. Prevalence in the 3 largest migrant groups was greater than that of Victoria as a whole (141, 200, and 208 cases per million in British, Italian, and Greek migrants, respectively). In women older than 40 years, previous studies have documented a prevalence of 940 cases per million in women in the United Kingdom however, the prevalence was 344 cases per million in British-born immigrants to Victoria and 160 cases per million in Australian-born women. The current prevalence of PBC in Victoria is higher than previously reported, but the age-adjusted prevalence in those born in Victoria remains significantly lower than in the United Kingdom and is less than in migrant communities. These findings suggest that Victorians may be relatively protected from developing the disease and add further weight to the suggestion that environmental factors may play a role in the etiology of PBC.
Publisher: OAE Publishing Inc.
Date: 2021
Publisher: Medknow
Date: 2019
Publisher: Wiley
Date: 19-06-2018
DOI: 10.1111/TID.12934
Abstract: Although antiviral prophylaxis is effective in preventing early cytomegalovirus (CMV) reactivation following liver transplantation (OLT), it predisposes patients to late CMV after prophylaxis has ceased. QuantiFERON-CMV (QFN-CMV, Qiagen, The Netherlands) measures an in idual's viral-specific immune response. Fifty-nine OLT recipients were prospectively monitored post-OLT in an observational cohort study. QFN-CMV was performed at regular time-points. An absolute QFN-CMV 90% already express viral-specific immunity as early as 3 months. Conceivably, antiviral prophylaxis could be discontinued early in these patients.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Frontiers Media SA
Date: 12-11-2012
DOI: 10.1111/TRI.12011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-03-2017
DOI: 10.1002/LT.24730
Abstract: Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study 55/75 (73.3%) patients experienced a total of 89 clinical events. Most events occurred within the first month. Low week 1 results were significantly associated with risk of early infection (area under the receiver operating characteristic curve [AUROC], 0.74 P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93 sensitivity, 71.4% specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77 P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection ( P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow in idualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487–497 2017 AASLD.
Publisher: Wiley
Date: 29-09-2017
DOI: 10.1002/JUM.14375
Abstract: A new 2-dimensional (2D) shear wave elastographic (SWE) device has been developed for the noninvasive assessment of liver fibrosis. Guidelines on measurement acquisition parameters are not yet well established for this technique. Our study aimed to assess 2D SWE measurement variability and to determine the number of measurements required per patient to reliably assess liver stiffness. Two-dimensional SWE was assessed in 55 patients with mixed-etiology chronic liver disease on an Aplio 500 ultrasound system (Toshiba Medical Systems Corporation, Tochigi, Japan). Ten measurements were obtained per patient by an operator blinded to all preceding readings. Results were analyzed with clinical information obtained from medical records. The median interquartile range/median ratio for 2D SWE was 0.131 (quartiles 1-3, 0.089-0.174). Five readings provided an approximation within 0.11 m/s, or 4.2% of the median velocity of 10 measurements. Factors associated with increased measurement variability included body mass index (ρ = 0.388 P = .01), increased skin-to-liver capsule distance (ρ = 0.426 P = .002), and measurements taken within 1.5 cm of the liver capsule (P 0.15) showed greater deviation from the set's median velocity than those with an ROI SD/speed ratio of 0.15 or lower (0.42 versus 0.22 m/s P = .001). Two-dimensional SWE showed low overall measurement variability, with a minimum of 5 readings providing equivalent precision to the existing method using 10 s les. Obesity, increasing abdominal wall thickness, subcapsular measurements and an ROI SD/speed ratio of greater than 0.15 were all associated with increased measurement variability. The ROI SD/speed ratio warrants further evaluation as a quality assessment metric, to allow objective operator assessment of in idual 2D SWE measurement reliability in real time.
Publisher: Informa UK Limited
Date: 02-11-2018
DOI: 10.1080/00365521.2018.1517277
Abstract: The objectives of our study were firstly to characterize the treatment stage migration phenomenon in early (Barcelona Clinic Liver Cancer [BCLC]-0/A) stage hepatocellular carcinoma (HCC) by comparing the efficacy of curative therapies with trans-arterial chemoembolization [TACE] and secondly, determining baseline and on-treatment predictors of survival. All patients within BCLC-0/A stage from six tertiary hospitals who received curative therapy with either resection, transplantation, or ablation or TACE as first-line treatment were included in the analyses. The primary endpoint was overall survival secondary end-points were transplant-free survival and recurrence-free survival. Between January 2000 and December 2013, we identified 253 BCLC-0/A HCC patients of whom 148 (58.5%) received curative therapy and 105 (41.5%) migrated to TACE. Patients undergoing TACE had lower median survival (2.7 vs. 6.7 years p < .0001), transplant-free survival (2.6 vs. 4.8 years p < .0001) and recurrence-free survival (1.3 vs. 2.7 years p < .001). On multivariate analysis treatment allocation to TACE was an independent prognostic predictor for both lower overall survival (HR 1.70, p = .04) and for HCC recurrence (HR 2.25, p < .001). The main prognostic determinant for each target outcome was Child-Pugh score. Our study confirms that curative treatments should always be preferred when applicable in early-stage HCC, but that in cases where this is not possible, TACE is a reasonable albeit inferior treatment option. In addition, it provides unique prognostic information on a significant proportion of patients with early-stage disease in whom curative therapy is not applicable.
Publisher: Symbiosis Group
Date: 2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-11-2015
DOI: 10.1002/LT.24216
Abstract: Cytomegalovirus (CMV) can reactivate following liver transplantation. Management of patients currently considered low risk based on pretransplant serology remains contentious, with universal prophylaxis and preemptive strategies suffering from significant deficiencies. We hypothesized that a CMV‐specific T cell assay performed early after transplant as part of a preemptive strategy could better stratify “low‐risk” (recipient seropositive) patients. We conducted a prospective, blinded, observational study in 75 adult recipients. QuantiFERON‐cytomegalovirus was performed both before and at multiple times after transplant. Low‐risk patients (n = 58) were monitored as per unit protocol and treatment was commenced if CMV 1000 copies/mL (DNAemia). Twenty patients needed antiviral treatment for other reasons and were censored (mainly for rejection or herpes simplex virus infection) 19/38 (50%) of the remaining low‐risk patients developed DNAemia at mean 34.6 days after transplant. A week 2 result of .1 IU/mL was significantly associated with risk of subsequent DNAemia (hazard ratio [HR], 6.9 P = 0.002). The positive predictive value of 80% suggests these patients are inappropriately labeled low risk and are actually at high likelihood of CMV reactivation. A secondary cutoff of .2 IU/mL was associated with moderate risk (HR, 2.8 P = 0.01). In conclusion, a protocol based on a single early CMV‐specific T cell based assay would offer improved risk stratification and in idualization of patient management after transplant. This could offer improved drug and service utilization and potentially result in significant improvements over both currently used protocols to manage supposedly low‐risk patients. Liver Transpl 21:1478‐1485, 2015 . © 2015 AASLD.
Publisher: Termedia Sp. z.o.o.
Date: 2020
Publisher: Wiley
Date: 21-06-2016
Abstract: The accuracy of Acoustic Radiation Force Impulse (ARFI) imaging has been validated in the setting of hepatitis C, however, the accuracy in the setting of fatty liver disease (FLD) has been less well-established. The aim of this study was to assess the accuracy of ARFI in the setting of hepatic steatosis. Patients with biopsy proven or sonographically diagnosed liver steatosis were assessed for ARFI trends including: inter-operator concordance, interquartile range, ARFI failure rate, relationship between ARFI velocity and steatosis severity, and concordance between biopsy and ARFI fibrosis scores. Three hundred and forty-nine patients were assessed (53 'biopsy' cohort and 296 'ultrasound' cohort), with 28 patients having biopsy on the same day as ARFI. Low stages of fibrosis (F0/1) were over-estimated by ARFI in 62% of cases with biopsy correlation (n = 16, P < 0.001), with ARFI offering increased accuracy in regard to higher-stage fibrosis (14/15 cases, 93%). In both the biopsy and ultrasound cohorts the failure rate and median inter-quartile range increased with increasing steatosis, and the inter-operator concordance remained good across all liver steatosis severities. In the setting of steatosis, ARFI is very sensitive in detecting, and accurate in diagnosing, higher stages of fibrosis regardless of steatosis severity. It tends to overestimate the fibrosis category in lower stages of fibrosis. The present study does not show conclusively if the presence of steatosis or its severity independently alters ARFI measurements.
Publisher: Wiley
Date: 11-04-2019
DOI: 10.1111/APT.15248
Abstract: Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre-treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JHEP.2018.04.013
Abstract: As many as 70% of in iduals with chronic hepatitis C (CHC) are managed solely in primary care. The aims of this study were to determine the prevalence of elevated liver stiffness measurement (LSM) in a cohort of community managed patients with CHC and to evaluate predictors of advanced liver disease and liver-related events. A prospective cohort of adult patients with CHC were recruited from 21 primary care practices throughout Victoria, Australia. Inclusion criteria included the presence of CHC for >6 months, no recent (<18 months) specialist input and no history of hepatocellular carcinoma. Clinical assessment, LSM and phlebotomy were carried out in primary care. A hospital cohort was recruited for comparison. Participants were followed longitudinally and monitored for liver-related events. Over 26 months, 780 community patients were recruited and included in the analysis. The median LSM was 6.9 kPa in the community, with 16.5% of patients at risk of advanced fibrosis (LSM ≥12.5 kPa) of these 8.5% had no laboratory features of advanced liver disease. The proportion at risk of cirrhosis was no different between the community and hospital cohorts (p = 0.169). At-risk alcohol consumption, advancing age, elevated body mass index and alanine aminotransferase were independent predictors of elevated LSM. Over a median follow-up of 15.2 months, liver-related events occurred in 9.3% of those with an LSM ≥12.5 kPa. An LSM of 24 kPa had the highest predictive power for liver-related events (hazard ratio152 p <0.001). The prevalence of advanced fibrosis, as determined by LSM, in primary care managed CHC is significant and comparable to a hospital cohort. Furthermore, this study supports the use of LSM as a community screening tool in a CHC population and indicates a possible role in predicting liver-related events. The prevalence of advanced liver disease in primary care managed hepatitis C is unknown. Our data suggests that rates of advanced fibrosis in the community are significant (16.5%), often underdiagnosed and comparable to rates seen in specialist referral centres. Liver stiffness measurement is a feasible community screening tool prior to hepatitis C therapy and can predict liver-related adverse events.
Publisher: Wiley
Date: 06-2017
DOI: 10.1111/IMJ.13435
Publisher: Wiley
Date: 03-09-2021
DOI: 10.1111/LIV.15036
Abstract: IgG4 sclerosing cholangitis (IgG4‐SC) is the biliary component of the multisystem IgG4‐related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4‐SC in a large Australian cohort. We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA‐CRN). 39 sites were invited to participate. IgG4‐SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09‐67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. Our study confirms the preponderance of IgG4‐SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.
Publisher: Wiley
Date: 27-03-2019
DOI: 10.1111/AJD.13033
Publisher: Elsevier BV
Date: 2018
Publisher: Therapeutic Guidelines Limited
Date: 08-2013
Publisher: Elsevier BV
Date: 2020
Publisher: AMPCo
Date: 04-2020
DOI: 10.5694/MJA2.50483
Publisher: Oxford University Press (OUP)
Date: 05-09-2020
DOI: 10.1093/CID/CIAA1318
Abstract: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of & % in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most however, serious AEs can occur in those with advanced liver disease.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.HLC.2019.09.010
Abstract: The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as in iduals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. KEYPOINTS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-04-2014
Publisher: Wiley
Date: 22-07-2013
DOI: 10.1111/JGH.12196
Abstract: Paracetamol is the most frequently used analgesic in Australia and can be purchased without a prescription. We aimed to investigate the epidemiology and outcome of paracetamol overdoses occurring in Victoria, Australia. The Victorian admitted episode dataset was examined for all patients who had a diagnosis of paracetamol poisoning (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification [ICD-10-AM]: T39.1) or paracetamol adverse effect in therapeutic use (Y45.5) from July 1, 2000 to June 30, 2007. Data extracted included all ICD-10 codes related to their admissions, gender, age range, date of admission, and cause of death (if applicable). Over 7 years, there was a total of 14,662 hospital admissions for paracetamol overdose with a mean of 2095 cases per year. Accidental overdoses comprised 15% (n = 2149) of cases. The overdose rate fell from 46 cases per 100,000 in 2001 to 39 cases per 100,000 in 2006 (P < 0.001). Most overdoses occurred in women (71%), and patients between 15 and 50 years old comprised 78% of all cases. Complications and mortality were relatively uncommon, with only 26 deaths directly attributable to paracetamol overdose over the 7 years. No child under 15 years old died from their overdose. Admission to Victorian hospitals with paracetamol overdose presents an enormous and in many cases preventable health-care burden. Fortunately, there has been a gradual fall in admissions, and most cases appear relatively benign. Further reductions in overdose could be achieved with increased awareness by physicians and the general public regarding the potential for accidental overdose, and increasing funding for mental health initiatives.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-12-2020
Publisher: Elsevier BV
Date: 04-2023
Publisher: Emerald
Date: 11-09-2017
Abstract: The purpose of this paper is to identify the arbitrage opportunities between US industry-level credit and stock markets with a focus on dynamic lead-lag relationships given that these markets involve heterogeneous agents operating over various time horizons. The authors use daily data of 11 US industries stock markets and their credit counterparts to model the dynamic dependence and casual nexuses using time-frequency approach, namely, wavelet squared coherence (WTC). The WTC estimation results show that credit and stock markets are out of phase (counter cyclical) and stock markets lead their credit counterparts. The coherence between two markets increases during financial crises. The banks (utilities) industry credit and stock markets have relatively high (low) dependence. The casual nexuses between stock and credit markets have multilateral dimensions. Greater interest in examining the relationship between stock markets and credit default swap (CDS) spreads emerged as an important albeit a complex area of research, and gained prominence especially at the onset and following the global financial crises of 2007-2008 which clearly showed that the positive views of CDSs contribution in creating a resilient and efficient financial sector was nothing further from the truth. The arbitrage and hedging opportunities between stock and credit markets are industry dependent and vary over investment time horizons. The utilities industry seems attractive for the investment with the objective to exploit arbitrage, but not for hedging. The paper, for the first time, employs time-frequency approach to assess the arbitrage opportunities between US industry-level credit and stock markets.
Publisher: Massachusetts Medical Society
Date: 23-11-2017
DOI: 10.1056/NEJMC1712682
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Siddharth Sood.