https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50481  1,000 U/L). The Australian Toxicology Monitoring (ATOM) study is a prospective observational study, recruiting via two poison information centers and four toxicology units. Patients following an acute APAP ingestion presenting < 24 hours post-ingestion were recruited. Initial samples were analyzed for APAP metabolites, those measured were the nontoxic glucuronide (APAP-Glu) and sulfate (APAP-Sul) conjugates and NAPQI (toxic metabolite) conjugates APAP-cysteine (APAP-Cys) and APAP-mercapturate (APAP-Mer). The primary outcome was hepatotoxicity. In this study, 200 patients were included, with a median ingested dose of 20 g, 191 received acetylcysteine at median time of 5.8 hours post-ingestion. Twenty-six patients developed hepatotoxicity, one had hepatotoxicity on arrival (excluded from analysis). Those who developed hepatotoxicity had significantly higher total CYP metabolite concentrations: (36.8 μmol/L interquartile range (IQR): 27.8-51.7 vs. 10.8 μmol/L IQR: 6.9-19.5) and these were a greater proportion of total metabolites (5.4%, IQR: 3.8-7.7) vs. 1.7%, IQR: 1.3-2.6, P < 0.001)]. Furthermore, those who developed hepatotoxicity had lower APAP-Sul concentrations (49.1 μmol/L, IQR: 24.7-72.2 vs. 78.7 μmol/L, IQR: 53.6-116.4) and lower percentage of APAP-Sul (6.3%, IQR: 4.6-10.9 vs. 13.1%, IQR, 9.1-20.8, P < 0.001)]. This study found that those who developed hepatotoxicity had higher APAP metabolites derived from CYP pathway and lower sulfation metabolite on presentation. APAP metabolites may be utilized in the future to identify patients who could benefit from increased acetylcysteine or newer adjunct or research therapies.]]> Wed 26 Jul 2023 18:22:28 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47712 HLA ‐B*57:01 is an established genetic risk factor for flucloxacillin DILI . To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single‐nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA ‐B*57:01 was the major risk factor (allelic odds ratio (OR ) = 36.62; P = 2.67 x 10⁻⁹⁷). HLA ‐B*57:03 also showed an association (OR = 79.21; P = 1.2 x 10⁻⁶). Within the HLA ‐B protein sequence, imputation showed valine⁹⁷, common to HLA ‐B*57:01 and HLA ‐B*57:03, had the largest effect (OR = 38.1; P = 9.7 x 10⁻⁹⁷). We found no HLA ‐B*57 association with DILI due to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no significant non‐HLA signals for any penicillin‐related DILI.]]> Tue 21 Mar 2023 18:39:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7558 Sat 24 Mar 2018 08:42:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7163 Sat 24 Mar 2018 08:34:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14378 1 Despite the availability of numerous methods for assessing the risk of TdP on the basis of the presence of QT prolongation,^2-5few studies have investigated the direct relationship between the magnitude of QT prolongation and the risk of TdP. Previous studies have generally considered the presence or absence of QT prolongation as a marker of the potential risk for TdP. In addition, they investigated data arising from a range of different drugs, with differing intrinsic cardiotoxic effects. This carries the potential for confounding of the relationship between the magnitude of prolongation of the QT interval and the inherent cardiotoxicity of the drug. Amisulpride is an atypical antipsychotic drug used to treat both the positive and negative symptoms of schizophrenia. It has affinity for limbic D₂ and D₃ receptors and only slight affinity for serotonergic, cholinergic, adrenergic, and histaminergic receptors.⁶ An overdose of the drug has been reported to cause QT prolongation and TdP.⁷ The aim of this study was to investigate whether the magnitude of QT prolongation is a better predictor of TdP than either the occurrence of QT prolongation per se or the dose of the drug. This was investigated in a case series of drug overdose events involving amisulpride.]]> Sat 24 Mar 2018 08:23:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51568 Mon 11 Sep 2023 14:22:09 AEST ]]>