https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51237 Wed 28 Feb 2024 16:07:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:38528 Wed 27 Oct 2021 16:09:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45245 Daboia russelii) venom causes a range of clinical effects in humans. Hypotension is an uncommon but severe complication of Russell’s viper envenoming. The mechanism(s) responsible for this effect are unclear. In this study, we examined the cardiovascular effects of Sri Lankan D. russelii venom in anaesthetised rats and in isolated mesenteric arteries. D. russelii venom (100 µg/kg, i.v.) caused a 45 ± 8% decrease in blood pressure within 10 min of administration in anaesthetised (100 µg/kg ketamine/xylazine 10:1 ratio, i.p.) rats. Venom (1 ng/mL–1 µg/mL) caused concentration-dependent relaxation (EC₅₀ = 145.4 ± 63.6 ng/mL, R_max = 92 ± 2%) in U46619 pre-contracted rat small mesenteric arteries mounted in a myograph. Vasorelaxant potency of venom was unchanged in the presence of the nitric oxide synthase inhibitor, L-NAME (100 µM), or removal of the endothelium. In the presence of high K⁺ (30 mM), the vasorelaxant response to venom was abolished. Similarly, blocking voltage-dependent (K_v: 4-aminopryidine; 1000 µM) and Ca²⁺-activated (K_Ca: tetraethylammonium (TEA; 1000 µM); SK_Ca: apamin (0.1 µM); IK_Ca: TRAM-34 (1 µM); BK_Ca; iberiotoxin (0.1 µM)) K⁺ channels markedly attenuated venom-induced relaxation. Responses were unchanged in the presence of the ATP-sensitive K⁺ channel blocker glibenclamide (10 µM), or H1 receptor antagonist, mepyramine (0.1 µM). Venom-induced vasorelaxtion was also markedly decreased in the presence of the transient receptor potential cation channel subfamily V member 4 (TRPV4) antagonist, RN-1734 (10 µM). In conclusion, D. russelii-venom-induced hypotension in rodents may be due to activation of K_v and K_Ca channels, leading to vasorelaxation predominantly via an endothelium-independent mechanism. Further investigation is required to identify the toxin(s) responsible for this effect.]]> Wed 26 Oct 2022 19:42:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45238 Wed 26 Oct 2022 19:41:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45084 Wed 26 Oct 2022 14:04:08 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50468 Wed 26 Jul 2023 14:52:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47721 1000 U/L). Method: Retrospective review of paracetamol RSTI presentations to two toxicology services over a four-year period. Patients were included if they ingested >4 g per 24 h of paracetamol for a period >8 h, regardless of intent. Data collected included demographics, ingestion history, pathology results, treatments and outcomes. Results: 266 patients were identified with median ingested dose of 9 g per 24 h (IQR: 6–12 g) over a median of 2 days (IQR: 1–5 days). On presentation, paracetamol was detected in 192 (72%), with median concentration of 14 mg/L (IQR: 7–27 mg/L). Median ALT on admission in those developing hepatotoxicity was significantly higher, 1182 U/L (IQR: 598–4251 U/L), compared to 30 U/L (IQR: 18–59 U/L; p < .0001) in those who did not. All 17 who developed hepatotoxicity had an ALT ≥50 U/L on presentation. Five patients presenting with an ALT <50 U/L developed a peak ALT between 50 and 1000 U/L, of which three had a paracetamol concentration <20 mg/L. 139 (52%) received acetylcysteine, of which 64 received an abbreviated course (<20 h), with a median length of infusion of 11 h (IQR: 7–14 h). 127 (48%) patients were not treated with acetylcysteine, none of these patients returned to hospital. Conclusions: Our results confirm that those developing hepatotoxicity from RSTI of paracetamol have an elevated ALT on presentation. Presenting ALT <50 U/L appears to be a safe threshold not to administer acetylcysteine, provided the paracetamol concentration is low.]]> Wed 25 Jan 2023 13:37:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:31074 Wed 24 May 2023 11:57:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43163 Wed 24 May 2023 08:55:31 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:33902 Wed 23 Jan 2019 10:40:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34141 Wed 17 Nov 2021 16:30:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50874 Wed 16 Aug 2023 11:19:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50267 Wed 12 Jul 2023 12:12:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:30917 Wed 11 Apr 2018 13:49:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50852 18y) from the Anuradhapura snakebite cohort were reviewed: Group I had a snakebite during August 2013-October 2014 and was reviewed after 4 years, and group II had a snakebite during May 2017-August 2018, and was reviewed after one year. Patients were invited by telephone, by sending let-ters, or doing home visits, including 199 of 736 patients (27%) discharged alive from group I and 168 of 438 patients (38%) from group II, a total of 367 followed up. Health effects were categorised as musculoskeletal, impact on daily life, and medically unexplained. Health issues were attributed to snakebite in 107/199 patients (54%) from group I and 55/168 patients (33%) from group II, suggesting the proportion with health issues increases with time. Sixteen patients (all viperine bites) had permanent musculoskeletal problems, none with a significant functional disability affecting daily routine. 217/367 reported being more vigilant about snakes while working outdoors, but only 21/367 were using protective foot-wear at review. Of 275 farmers reviewed, only six (2%) had restricted farming activities due to fear of snakebite, and only one stopped farming. 104/199 (52%) of group I and 42/168 (25%) of group II attributed non-specific symptoms (fatigue, body aches, pain, visual impairment) and/or oral cavity-related symptoms (avulsed teeth, loose teeth, receding gums) to the snakebite, which cannot be explained medically. In multivariate logistic regres-sion, farming, type of snake, antivenom administration, and time since snakebite were associated with medically unexplained symptoms. The latter suggests medically unexplained effects increased with time. Based on two groups of snakebite patients reviewed one and four years post-bite, we show that long-term musculoskeletal disabilities are uncommon and not severe in snakebite survivors in rural Sri Lanka. However, a large portion of patients complain of various non-specific general and oral symptoms, not explainable based on the known pathophysiology of snakebite. These perceived effects of snakebite were more common in patients with systemic envenoming, and were more frequent the longer the time post-bite.]]> Wed 09 Aug 2023 09:45:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46919 Wed 07 Dec 2022 10:33:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50169 15 years) patients treated by an Australian state ambulance service with 1.6 mg IM administration of naloxone for respiratory depression (respiratory rate <11 breaths/min and/or oxygen saturation <93% in room air) caused by presumed opioid poisoning. The primary outcome was the proportion of presentations with severe agitation (Sedation Assessment Tool score >1) within 1 hour of naloxone administration. Secondary outcomes were the proportion of presentations with acute opioid withdrawal (tachycardia [pulse rate >100 beats/min], hypertension [systolic >140 mm Hg], vomiting, agitation, seizure, myocardial infarction, arrhythmia, or pulmonary edema), and reversal of respiratory depression (respiratory rate >10 breaths/min and saturation >92% or Glasgow Coma Scale score 15). Results: From October 2019 to July 2021, there were 197 presentations in 171 patients, with a median age of 41 years (range, 18 to 80 years); of the total patients, 119 were men (70%). The most common opioids were heroin (131 [66%]), oxycodone (14 [7%]), and morphine (11 [6%]). Severe agitation occurred in 14 (7% [95% confidence interval {CI} 4% to 12%]) presentations. Opioid withdrawal occurred in 76 presentations (39% [95% CI 32% to 46%]), most commonly in the form of tachycardia (18%), mild agitation/anxiety (18%) and hypertension (14%). Three presentations (1.5%) received chemical sedation for severe agitation within 1 hour of naloxone administration. A single 1.6 mg dose of naloxone reversed respiratory depression in 192 (97% [95% CI: 94% to 99%]) presentations. Conclusion: Severe agitation was uncommon following the administration of 1.6 mg IM naloxone and rarely required chemical sedation.]]> Wed 05 Jul 2023 16:31:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49080 Wed 03 May 2023 16:15:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49047 1%. With results dichotomised as <1.0% or ≥1.0%, our proposed new method versus the ICSH method showed almost perfect agreement [observed agreement 95%, Cohen's kappa (κ)=0.84, SE 0.04, 95% CI 0.76–0.92, p<0.005]. Inter-observer strength of agreement for our method was moderate (Fleiss' κ for comparisons between three non-unique microscopists κ=0.50, SE 0.05, 95% CI 0.41–0.59, p<0.005). Intra-observer reproducibility assessed in two microscopists ranged from substantial (Cohen's κ=0.71, SE 0.08, 95% CI 0.55–0.86, p<0.005) to borderline almost perfect agreement (Cohen's κ=0.81, SE 0.07, 95% CI 0.68–0.93, p<0.005). Schistocyte quantitation using our new method is simpler than the 2012 ICSH method and had almost perfect agreement. Our finding of moderate inter-observer agreement in quantitating helmet, triangle and crescent schistocytes is applicable to both the ICSH and our newly proposed method. This finding underscores the importance of clinicopathological correlation and repeated examinations in the context of a clinically suspected TMA.]]> Wed 03 May 2023 15:40:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45670 Wed 02 Nov 2022 16:06:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46722 Tue 29 Nov 2022 11:20:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46703 Tue 29 Nov 2022 10:10:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43350 Tue 28 Nov 2023 15:50:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44896 98% amino acid sequence similarity with short-chain postsynaptic neurotoxins from other Naja species. When compared to short-chain neurotoxins isolated from cobras in China, α-EPTX-Na1a contained novel residues K47Q (i.e. lysine to glutamine), N48T (i.e. asparagine to threonine) and G49A (i.e. glycine to alanine). In conclusion, α-EPTX-Na1a is a potent, pseudo-irreversible, short-chain neurotoxin. The high prevalence of α-EPTX-Na1a in Chinese N. atra venom is likely to explain the mild neurotoxicity experienced by envenomed patients.]]> Tue 28 Nov 2023 12:09:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43656  17 fold change (p < 0.0001) and receiver operator characteristics area-under-curve (ROC-AUC) > 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.]]> Tue 27 Sep 2022 14:32:55 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:41060 Tue 26 Jul 2022 08:15:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:36181 in silico and in vitro studies have identified factor Xa as an appropriate activating agent, and the phospholipid Actin FS as a cofactor for a Xa clotting time (TenaCT) test. A proof-of-concept study was designed to (1) explore the reproducibility of the TenaCT test and (2) explore factors that could affect the performance of the test. In vitro clotting time tests were carried out using plasma from 20 healthy volunteers. The effect of enoxaparin was determined at concentrations of 0.25, 0.50, and 1.0 IU/mL. Clotting times for the volunteers were significantly prolonged with increasing enoxaparin concentrations. Clotting times were significantly shortened for frozen plasma samples. No significant differences in prolongation of clotting times were observed between male and female volunteers or between the 2 evaluated age groups. The clotting times were consistent between 2 separate occasions. The TenaCT test was able to distinguish between the subtherapeutic and therapeutic concentrations of enoxaparin. Plasma should not be frozen prior to performing the test, without defining a frozen plasma reference range. This stu dy provided proof-of-concept for a Xa-based test that can detect enoxaparin dose effects, but additional studies are needed to further develop the test.]]> Tue 25 Feb 2020 10:13:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:36665 max = 91 ± 1%) in pre-contracted mesenteric arteries. In contrast, E. ocellatus venom (1 μg/ml) only produced a maximum relaxant effect of 27 ± 14%, suggesting that rapid cardiovascular collapse is unlikely to be due to peripheral vasodilation. The prevention of rapid cardiovascular collapse, by 'priming' doses of venom, supports a role for depletable endogenous mediators in this phenomenon.]]> Tue 23 Jun 2020 12:29:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:53796 Tue 16 Jan 2024 14:44:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:41985 Tue 16 Aug 2022 15:55:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46271 Hypnale spp.) bites. Thrombotic microangiopathy (TMA) is increasingly recognized in association with AKI in cases of Hypnale spp envenomation. We investigated AKI in a cohort of cases of Hypnale envenomation, its association with TMA and the early diagnostic value of common biomarkers for AKI occurring. Materials and methods: We conducted a prospective observational study of suspected viper bites and included 103 confirmed cases of Hypnale envenomation, based on venom specific enzyme immunoassay of blood. AKI was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Thrombotic microangiopathy was diagnosed based on thrombocytopenia (platelet count < 150,000 x 10³/μL) and microangiopathic haemolytic anaemia (MAHA). We investigated the diagnostic performance of creatinine, platelet count and INR for AKI within 4 h and 8 h post-bite by area under the receiver operator characteristic curve (AUC-ROC). Results: Ten patients developed AKI: seven AKI stage 1 and three AKI stage 3. Ten patients (10%) developed thrombocytopaenia while 11 (11%) had MAHA. All three AKI stage 3 had thrombocytopaenia and MAHA fulfilling the criteria for TMA. Two of them presented with oliguria/anuria and all three required haemodialysis. Serum creatinine within 4 h post-bite was the best predictor of AKI with AUC-ROC of 0.83 (95% CI: 0.67-0.99) and was no better within 8 h of the bite. Conclusions: We found that AKI is uncommon in Hypnale spp. envenomation, but an important serious complication. Severe AKI was associated with TMA. A creatinine within 4 h post-bite was the best predictor of AKI.]]> Tue 15 Nov 2022 09:04:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43173 Tue 13 Sep 2022 16:03:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43153 Tue 13 Sep 2022 15:28:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51646 Tue 12 Sep 2023 20:13:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:53624 2 years. Information about demographics, bite circumstances, species involved, clinical and laboratory features of envenoming, and treatment is collected and entered into a purpose-built database. Results: Between January 2002 and August 2020, 13 patients with suspected sea snake bite were recruited to ASP, 11 were male; median age was 30 years. Bites occurred in Queensland and Western Australia. All patients were in or around, coastal waters at the time of bite. The species involved was identified in two cases (both Hydrophis zweifeli). Local effects occurred in 9 patients: pain (5), swelling (5), bleeding (2), bruising (1). Envenoming occurred in eight patients and was characterised by non-specific systemic features (6) and myotoxicity (2). Myotoxicity was severe (peak CK 28200 and 48100 U/L) and rapid in onset (time to peak CK 13.5 and 15.1 h) in these two patients. Non-specific systemic features included nausea (6), headache (6), abdominal pain (3), and diaphoresis (2). Leukocytosis, neutrophilia, and lymphopenia occurred in both patients with myotoxicity and was evident on the first blood test. No patients developed neurotoxicity or coagulopathy. Early Seqirus antivenom therapy was associated with a lower peak creatine kinase. Conclusion: While relatively rare, sea snake envenoming is associated with significant morbidity and risk of mortality. Early antivenom appears to have a role in preventing severe myotoxicity and should be a goal of therapy.]]> Tue 12 Dec 2023 15:26:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46899 p = .06), systolic blood pressure of 110 mmHg (range: 65–180) vs 125 mmHg (range: 90–184) (p = .009), respectively. Digoxin concentrations 4.4 nmol/L (range: 3.3–9) vs 4.2 (range: 2–11.2) (p = .42) and potassium concentrations 5.4 mmol/L (range: 3–11) vs 5.1 mmol/L (range: 3.5–8.2) (p = .33) were similar. Median dose of digoxin-Fab used was 1.5 vials (IQR: 1–2). There were 9 (12%) deaths in the Fab group compared to 7 (14%) in those treated with supportive care (risk difference −2.5%; 95% CI: −14 to 9%; p = .68). The median LOS was six days in both groups. Mean changes in potassium concentration [−0.5 ± 0.1 vs. −0.4 ± 0.1 mmol/L; difference −0.1 (95% CI: −.02, 0.4), p = .70] and HR within 4 h [8 ± 1 vs. 7 ± 3 bpm; difference −1.0 (95% CI: −6.7, 4.8), p = 0.74] were similar in the two groups. Conclusions: This study did not appear to show any benefit from the routine use of digoxin-Fab in patients thought to have chronic digoxin poisoning. These patients have multiple co-morbidities that may be contributing to their clinical features, other treatments are often equally effective.are often equally effective.]]> Tue 06 Dec 2022 15:39:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:33780 Tue 03 Sep 2019 18:01:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:40438 14 years who took an overdose of dihydropyridines (amlodipine, felodipine, lercanidipine, nifedipine) were included. Concurrent overdoses with non-dihydropyridine CCBs, alpha-blockers and beta-blockers were excluded. Patient demographics, drugs exposure details, serial vital signs, treatments and outcome were collected. Results: There were 100 patients. 68 took mixed overdoses of dihydropyridines with ARBs/ACEIs and 32 took single overdoses of dihydropyridines without ARBs/ACEIs. The mixed group had lower median nadir mean arterial pressures (62 vs 75 mmHg, p < 0.001), more frequently had hypotension (OR 4.5, 95%CI: 1.7–11.9) or bradycardia (OR 8.8, 95%CI: 1.1–70). Multivariable analysis indicated the mixed overdoses had an 11.5 mmHg (95%CI: 4.9–18.1) lower minimum systolic blood pressure (SBP) compared with the single group; other factors associated with a lower minimum SBP were higher doses [2.3 mmHg (95%CI: 1.1–3.5) lower per 10 defined daily doses] and younger age [2.2 mmHg (95%CI: 0.3–4.2) higher per decade]. A larger proportion of the mixed ingestion group received intravenous fluids (OR 5.7, 95%CI: 1.8–18.6) and antidotes and/or vasopressors (OR 2.9, 95%CI: 1.004–8.6). Conclusion: Combined overdoses of dihydropyridines with ARBs/ACEIs caused more significant hypotension and required more haemodynamic support than overdoses of dihydropyridines alone.]]> Tue 02 Aug 2022 11:11:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:39247 Bungarus multicinctus, the Chinese krait, is a highly venomous elapid snake which causes considerable morbidity and mortality in southern China. B. multicinctus venom contains pre-synaptic PLA2 neurotoxins (i.e., β-bungarotoxins) and post-synaptic neurotoxins (i.e., α-bungarotoxins). We examined the in vitro neurotoxicity of B. multicinctus venom, and the efficacy of specific monovalent Chinese B. multicinctus antivenom, and Australian polyvalent elapid snake antivenom, against venom-induced neurotoxicity. B. multicinctus venom (1–10 μg/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic α-neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese B. multicinctus antivenom (12 U/mL) or Australian polyvalent snake antivenom (15 U/mL), markedly attenuated the neurotoxic actions of B. multicinctus venom (3 μg/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of B. multicinctus antivenom (60 U/mL), or Australian polyvalent snake antivenom (50 U/mL), at the t₉₀ time point after the addition of B. multicinctus venom (3 μg/mL), did not restore the twitch height over 180 min. The earlier addition of B. multicinctus antivenom (60 U/mL), at the t₂₀ or t₅₀ time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t₉₀ values. Repeated washing of the preparation with physiological salt solution, commencing at the t₂₀ time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that B. multicinctus venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by antivenom. This does not appear to be related to antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.]]> Thu 28 Jul 2022 14:45:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50513 Thu 27 Jul 2023 14:20:52 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34308 2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay [LOS], mechanical ventilation) were extracted from a prospective database. Primary outcome was naloxone requirement or ventilation for respiratory depression. Results: From 4488 presentations, 1376 admissions were included with paracetamol alone (929), paracetamol-codeine combinations (346) or paracetamol-codeine-doxylamine combinations (101) without co-ingestants. Median age was 23 years (12-89 years); 1002 (73%) were female. Median dose was 12 g (interquartile range [IQR] : 7.5-20 g). Median LOS was 16 h (IQR: 6.5-27 h) and 564 (41%) were given acetylcysteine. Significantly larger paracetamol doses were ingested and more acetylcysteine given in paracetamol alone versus paracetamol combination overdoses. Seven out of 1376 patients were intubated or received naloxone (0.5%; 95% CI: 0.2-1.1%), three intubated, three given naloxone and one both. Three out of 929 patients ingesting paracetamol alone (0.3%; 95% CI: 0.1-1%) required intubation or naloxone, compared to two out of 346 ingesting paracetamol-codeine combinations (0.6%; 95% CI: 0.1-2.3%; absolute difference, 0.26%; 95% CI: -0.7-1.2%; P = 0.62). Two out of 101 patients ingesting paracetamol-codeine-doxylamine combinations (2%; 95% CI: 0.3-8%) required intubation or naloxone. Four patients were intubated for reasons other than respiratory depression: hepatotoxicity (2), retrieval (1), no data (1). Two out of 929 (0.2%) paracetamol alone overdoses had a Glasgow coma score < 9 compared to three out of 346 (0.9%) in the paracetamol-codeine group. Conclusions: Paracetamol-codeine combination overdoses are rarely associated with severe respiratory depression, with only two given naloxone and none intubated for respiratory depression.]]> Thu 27 Jan 2022 15:58:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:37720 Thu 25 Mar 2021 11:51:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:42585 Thu 25 Aug 2022 15:17:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:42206 Thu 25 Aug 2022 11:54:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51188 Thu 24 Aug 2023 14:39:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51189 Thu 24 Aug 2023 14:38:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51185 Thu 24 Aug 2023 14:37:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45649 1,000 U/L), an adduct concentration ≥1.0 nmol/ml is sensitive and specific for identifying cases secondary to acetaminophen. Our aim was to characterise acetaminophen-protein adduct concentrations in patients following acetaminophen overdose and determine if they predict toxicity. Methods: We performed a multicentre prospective observational study, recruiting patients 14 years of age or older with acetaminophen overdose regardless of intent or formulation. Three serum samples were obtained within the first 24 h of presentation and analysed for acetaminophen-protein adducts. Acetaminophen-protein adduct concentrations were compared to ALT and other indicators of toxicity. Results: Of the 240 patients who participated, 204 (85%) presented following acute ingestions, with a median ingested dose of 20 g (IQR 10–40), and 228 (95%) were treated with intravenous acetylcysteine at a median time of 6 h (IQR 3.5–10.5) post-ingestion. Thirty-six (15%) patients developed hepatotoxicity, of whom 22 had an ALT ≤1,000 U/L at the time of initial acetaminophen-protein adduct measurement. Those who developed hepatotoxicity had a higher initial acetaminophen-protein adduct concentration compared to those who did not, 1.63 nmol/ml (IQR 0.76–2.02, n = 22) vs. 0.26 nmol/ml (IQR 0.15–0.41; n = 204; p <0.0001), respectively. The AUROC for hepatotoxicity was 0.98 (95% CI 0.96–1.00; n = 226; p <0.0001) with acetaminophen-protein adduct concentration and 0.89 (95% CI 0.82–0.96; n = 219; p <0.0001) with ALT. An acetaminophen-protein adduct concentration of 0.58 nmol/ml was 100% sensitive and 91% specific for identifying patients with an initial ALT ≤1,000 U/L who would develop hepatotoxicity. Adding acetaminophen-protein adduct concentrations to risk prediction models improved prediction of hepatotoxicity to a level similar to that obtained by more complex models. Conclusion: Acetaminophen-protein adduct concentration on presentation predicted which patients with acetaminophen overdose subsequently developed hepatotoxicity, regardless of time of ingestion. An adduct threshold of 0.58 nmol/L was required for optimal prediction. Lay summary: Acetaminophen poisoning is one of the most common causes of liver injury. This study examined a new biomarker of acetaminophen toxicity, which measures the amount of toxic metabolite exposure called acetaminophen-protein adduct. We found that those who developed liver injury had a higher initial level of acetaminophen-protein adducts than those who did not. Clinical Trial registration: Australian Toxicology Monitoring (ATOM) Study–Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.]]> Thu 23 Mar 2023 13:56:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:33604 12), 8 strong acids (pH < 2), 29 domestic bleaches, 30 other domestic products, 6 non-domestic products and three unknown. Three patients died in hospital within 24 h (phenol, sodium azide, HCl). Two developed strictures (both strong alkalis): one had complete esophageal destruction; another developed a stricture after 25 d (inpatient grade 2A endoscopy). 24 patients were asymptomatic and discharged without complication. 65 patients were symptomatic (4 catastrophic injuries). 61 reported sore mouth/throat (50), abdominal pain (21), chest pain (17), dysphagia (13); 28 had an abnormal oropharyngeal examination. 25/61 symptomatic patients underwent inpatient endoscopy: normal (3), grade 1 (5), grade 2 (15) and grade 3 (2). Of 88 patients, 12 died (3 inpatients, 9 unrelated), 28 couldn't be contacted and 48 were contacted after 1.7-24 y, including two with strictures. Five couldn't be interviewed (normal endoscopy (1), no dysphagia (3) and stroke (1). 4/41 interviewed reported dysphagia but no objective evidence of stricture. Principal conclusions: All inpatient deaths and severe complications were apparent within hours of ingestion, and occurred with highly corrosive substances. One delayed stricture occurred, not predicted by inpatient endoscopy.]]> Thu 22 Nov 2018 16:43:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:38573 Thu 18 Nov 2021 12:27:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44458 Naja) cause severe local dermonecrosis and myonecrosis, resulting in permanent disabilities. We studied the time scale in which two Indian polyvalent antivenoms, VINS and Bharat, remain capable of preventing or reversing in vitro myotoxicity induced by common cobra (Naja naja) venom from Sri Lanka using the chick biventer cervicis nerve-muscle preparation. VINS fully prevented while Bharat partially prevented (both in manufacturer recommended concentrations) the myotoxicity induced by Naja naja venom (10 μg/mL) when added to the organ baths before the venom. However, both antivenoms were unable to reverse the myotoxicity when added to organ baths 5 and 20 min post-venom. In contrast, physical removal of the venom from the organ baths by washing the preparation 5 and 20 min after the venom resulted in full and partial prevention of the myotoxicity, respectively, indicating the lag period for irreversible cellular injury. This suggests that, although the antivenoms contain antibodies against cytotoxins of the Sri Lankan Naja naja venom, they are either unable to reach the target sites as efficiently as the cytotoxins, unable to bind efficiently with the toxins at the target sites, or the binding with the toxins simply fails to prevent the toxin-target interactions.]]> Thu 13 Oct 2022 15:06:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50904 Thu 10 Aug 2023 13:31:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:31207 E_max model linked to a turnover model for coagulation proteins. In the joint model, an unexpected pharmacodynamic lag was identified and the estimated degradation half-life of VK-dependent coagulation proteins were in agreement with previously published values. The model provided an adequate fit to the observed data. Conclusion: The joint model represents the first work to quantify the influence of warfarin on all six VK-dependent coagulation proteins simultaneously. Future work will expand the model to predict the influence of exogenously administered VK on the time course of clotting factor concentrations after warfarin overdose and during perioperative warfarin reversal procedures.]]> Sat 24 Mar 2018 08:44:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50633 Mon 31 Jul 2023 15:59:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50616 Mon 31 Jul 2023 14:29:01 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:37203 Mon 31 Aug 2020 15:02:09 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46615 Mon 28 Nov 2022 10:44:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44856 Mon 24 Oct 2022 11:02:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44786 2.6 nmol/L (2 µg/L). There were no deaths from acute digoxin toxicity. Conclusions: The new practice of using small, titrated doses of Digoxin-Fab led to a considerable reduction in total usage and major savings. The clinical response to titrated doses was safe and acceptable in acute digoxin poisoning.]]> Mon 24 Oct 2022 09:17:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44777  25% decrease in platelets from the presentation. Patients with TMA were significantly older than non-TMA patients with VICC (53 [35–61] versus 41 [24–55] years, median [IQR], p < 0.0001). AKI developed in 94% (98/104) of TMA patients, with 34% (33/98) requiring dialysis (D-AKI). There were four deaths. In D-AKI TMA cases, eventual dialysis-free survival (DFS) was 97% (32/33). TPE was used in five D-AKI cases, with no significant difference in DFS or time to independence from dialysis. >90-day follow-up for 25 D-AKI cases (130 person-years) showed no end-stage kidney disease but 52% (13/25) had ≥ stage 3 chronic kidney disease (CKD). Conclusion: Our findings support a definition of snakebite-associated TMA as anemia with schistocytosis and either thrombocytopenia or >25% drop in platelet count. AKI occurring with snakebite-associated TMA varied in severity, with most achieving DFS, but with a risk of long-term CKD in half. We found no evidence of benefit for TPE in D-AKI.]]> Mon 24 Oct 2022 09:10:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50379 Mon 24 Jul 2023 13:02:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:32502 4h. Median peak venom concentration in 25 patients with systemic envenoming and a sample available was 8.4ng/L (1-3212 ng/L). No venom was detected in post-antivenom samples, including 20 patients given one vial initially and five patients bitten by inland taipans. Discussion: Australian taipan envenoming is characterised by neurotoxicity, myotoxicity, coagulopathy, acute kidney injury and thrombocytopenia. One vial of antivenom binds all measurable venom and early antivenom was associated with a favourable outcome.]]> Mon 23 Sep 2019 13:46:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:30918 200 μg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records. Results: From 133 admissions for clonidine poisoning (1988–2015), no medical record was available in 14 and 11 took staggered ingestions. Of 108 acute clonidine overdoses (median age 27 years; 14–65 years; 68 females), 40 were clonidine alone ingestions and 68 were clonidine with co-ingestants. Median dose taken was 2100 μg (interquartile range [IQR]: 400–15,000 μg). Median LOS was 21h (IQR: 14–35 h) and there were no deaths. Glasgow coma score [GCS] <15 occurred in 73/108 (68%), and more patients taking co-ingestants (8/68; 12%) had coma (GCS <9) compared to clonidine alone (2/40; 5%). Miosis occurred in 31/108 (29%) cases. Median minimum HR was 48 bpm (IQR: 40–57 bpm), similar between clonidine alone and co-ingestant overdoses. There was a significant association between dose and minimum HR for clonidine alone overdoses (p = 0.02). 82/108 (76%) had bradycardia, median onset 2.5 h post-ingestion (IQR: 1.7–5.5 h) and median duration 20 h (2.5–83 h), similar for clonidine alone and co-ingestant overdoses. There were no arrhythmias. Three patients ingesting 8000–12,000 μg developed early hypertension. Median minimum systolic BP was 96 mmHg (IQR: 90–105 mmHg) and hypotension occurred in 26/108 (24%). 12/108 patients were intubated, but only 2 were clonidine alone cases. Treatments included activated charcoal (24), atropine (8) and naloxone (23). The median total naloxone dose was 2 mg (IQR: 1.2–2.4 mg), but only one patient given naloxone was documented to respond with partial improvement in GCS. Discussion: Clonidine causes persistent but not life-threatening clinical effects. Most patients develop mild central nervous system depression and bradycardia. Naloxone was not associated with improved outcomes.]]> Mon 23 Sep 2019 12:03:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47473 14 years who ingested ≥10 g or 200 mg/kg (whichever is less) of MR paracetamol. Data collected included demographics, ingestion history, pathology results, treatments, and outcomes including hepatotoxicity (ALT >1000 U/L). Results: In total, 116 patients were recruited, 85(73%) were female. The median dose ingested was 32 g (IQR: 20–49 g) and median time to presentation was 3 h (IQR: 2–9 h). 78(67%) had an initial paracetamol concentration above the nomogram line (150 mg/L at 4 h). A further 12(10%) crossed the nomogram after repeat paracetamol measurements, of which five crossed after two non-toxic levels 4 h apart. Six had a double paracetamol peak, in three occurring >24 h post-ingestion. 113(97%) received acetylcysteine of which 67 received prolonged treatment beyond the standard 21 h. This was because of an elevated paracetamol concentration at the completion of acetylcysteine in 39 (median paracetamol concentration 25 mg/L, IQR: 16–62 mg/L). 21 (18%) developed hepatotoxicity, including six treated within 8 h of ingestion. Activated charcoal and double doses of acetylcysteine did not significantly decrease the risk of hepatotoxicity. Conclusions: Drug regulatory authorities are considering restrictions on MR paracetamol preparations. Following an acute MR paracetamol overdose, this study found that many patients had a persistently elevated paracetamol concentrations, many required prolonged treatment and some developed liver injury despite early acetylcysteine treatment. Furthermore, activated charcoal and increased acetylcysteine did not appear to significantly alter the risk of liver injury. Hence, research into better treatment strategies is required.]]> Mon 23 Jan 2023 11:05:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49547 1000 U/L). Snake species was determined by expert identification or venom specific enzyme immunoassay. Analysis included patient demographics, clinical findings, pathology results, treatment and outcomes (length of hospital stay, complications). Results: 1638 patients were recruited January 2003–December 2016, 935 (57%) were envenomed, 148 developed myotoxicity (16%). Snake species most commonly associated with myotoxicity were Notechis spp. (30%), Pseudechis porphyriacus (20%) and Pseudechis australis (13%). Bite site effects occurred in 19 patients. Non-specific systemic symptoms occurred in 135 patients (91%), specific signs and symptoms in 83. In 120 patients with early serial CK results, the median peak CK was 3323 U/L (IQR;1050–785100U/L), the median time to first CK >500 U/L was 11.1 h and median time to peak CK of 34.3 h. White cell count was elevated in 136 patients (93%; median time to elevation, 4.9 h). 37 patients had elevated creatinine, six were dialysed. Two patients died from complications of severe myotoxicity. Antivenom given before the first abnormal CK (>500 U/L) was associated with less severe myotoxicity (2976 versus 7590 U/L). Non-envenomed patients with elevated CK had rapid rise to abnormal CK (median 3.5 h) and less had elevated WCC (32%). Conclusion: Myotoxicity from Australian snakes is relatively common and has systemic effects, with significant associated morbidity and mortality. CK is not a good early biomarker of mytoxicity. Early antivenom may play a role in reducing severity.]]> Mon 22 May 2023 08:45:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:42371 Mon 22 Aug 2022 14:22:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44567 N-acetyl-p-benzoquinone imine in hepatocytes and enhances non-toxic sulphate conjugation. As NAC is the cornerstone of treatment in paracetamol poisoning, trials have mainly focused around optimising dose, duration, rate and route of administration, with the primary aim to decrease rates of adverse events, shorten treatment time and maintain efficacy. NAC use is not just confined to paracetamol and has been utilised for a wide variety of toxins and ingestions. These toxins range from herbicides, mushrooms, hydrocarbons and metals. NAC’s proposed mechanism of action for these toxins is as an antioxidant and/or glutathione replenishing. The evidence for its use in most other toxins is limited to animal studies, case reports and small case series, due to the uncommon occurrence of these toxin exposures. With these toxins NAC is often given in combination with other therapies, making it difficult to determine its utility for many toxins. Because of the relative safety of NAC and the high morbidity associated with many of these ingestions, NAC is often recommended.]]> Mon 17 Oct 2022 11:23:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44536 2 (PLA₂), and L-amino acid oxidase (LAAO) – in the venom of 39 species of Australian elapids (40% of terrestrial species diversity) and used linear parsimony and BayesTraits to investigate any correlation between enzyme activity and phylogeny or diet. Results: PLA₂ activity ranged from 0 to 481 nmol/min/mg of venom, and LAAO activity ranged from 0 to 351 nmol/min/mg. Phylogenetic comparative methods, implemented in BayesTraits showed that enzyme activity was strongly correlated with phylogeny, more so for LAAO activity. For example, LAAO activity was absent in both the Vermicella and Pseudonaja/Oxyuranus clade, supporting previously proposed relationships among these disparate taxa. There was no association between broad dietary categories and either enzyme activity. There was strong evidence for faster initial rates of change over evolutionary time for LAAO (delta parameter mean 0.2), but no such pattern in PLA₂ (delta parameter mean 0.64). There were some exceptions to the phylogenetic patterns of enzyme activity: different PLA₂ activity in the ecologically similar sister-species Denisonia devisi and D. maculata; large interspecific differences in PLA₂ activity in Hoplocephalus and Austrelaps. Conclusions: We have shown that phylogeny is a stronger influence on venom enzyme activity than diet for two of the four major enzyme families present in snake venoms. PLA₂ and LAAO activities had contrasting evolutionary dynamics with the higher delta value for PLA₂ Some species/individuals lacked activity in one protein family suggesting that the loss of single protein family may not incur a significant fitness cost.]]> Mon 17 Oct 2022 09:03:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50978 Mon 14 Aug 2023 15:25:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50970 Mon 14 Aug 2023 15:19:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:54722 Mon 11 Mar 2024 11:58:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:40416 Oxyuranus scutellatus) envenoming causes life-threatening neuromuscular paralysis in humans. We studied the time period during which antivenom remains effective in preventing and arresting in vitro neuromuscular block caused by taipan venom and taipoxin. Venom showed predominant pre-synaptic neurotoxicity at 3 µg/mL and post-synaptic neurotoxicity at 10 µg/mL. Pre-synaptic neurotoxicity was prevented by addition of Australian polyvalent antivenom before the venom and taipoxin and, reversed when antivenom was added 5 min after venom and taipoxin. Antivenom only partially reversed the neurotoxicity when added 15 min after venom and had no significant effect when added 30 min after venom. In contrast, post-synaptic activity was fully reversed when antivenom was added 30 min after venom. The effect of antivenom on pre-synaptic neuromuscular block was reproduced by washing the bath at similar time intervals for 3 µg/mL, but not for 10 µg/mL. We found an approximate 10–15 min time window in which antivenom can prevent pre-synaptic neuromuscular block. This time window is likely to be longer in envenomed patients due to the delay in venom absorption. Similar effectiveness of antivenom and washing with 3 µg/mL venom suggests that antivenom most likely acts by neutralizing pre-synaptic toxins before they interfere with neurotransmission inside the motor nerve terminals.]]> Mon 11 Jul 2022 14:44:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:40389 Oxyuranus scutellatus from four localities on the north-east coast of Australia, spanning a distance of 2000 km. The intra-specific variation in taipan venom was considerably less than the inter-specific variation between it and the other Australian elapids to which it was compared. The electrophoretic venom profile of O. scutellatus was visually different to six other genera of Australian elapids, but not to its congener inland taipan O. microlepidotus. There was minimal geographical variation in taipan venom, as the intra-population variation exceeded the inter-population variation for enzymatic activity, procoagulant activity, and the abundance of neurotoxins. The pre-synaptic neurotoxin (taipoxin) was more abundant than the post-synaptic neurotoxins (3FTx), with a median of 11.0% (interquartile range (IQR): 9.7% to 18.3%; range: 6.7% to 23.6%) vs. a median of 3.4% (IQR: 0.4% to 6.7%; range: 0% to 8.1%). Three taipan individuals almost completely lacked post-synaptic neurotoxins, which was not associated with geography and occurred within two populations. We found no evidence of sexual dimorphism in taipan venom. Our study provides a basis for evaluating the significance of intra-specific venom variation within a phylogenetic context by comparing it to the inter-specific and inter-generic variation. The considerable intra-population variation we observed supports the use of several unpooled individuals from each population when making inter-specific comparisons.]]> Mon 11 Jul 2022 11:21:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44173 Mon 10 Oct 2022 10:13:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51420 Mon 04 Sep 2023 14:58:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51419 120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database. Results: There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25–48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405–1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; p = 0.040), develop coma (16 [9%] vs. none; p = 0.008) and hypotension [systolic BP < 90 mmHg] (15 [8%] vs. one; p = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180–4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3–18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12–31 h; p = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (systolic BP > 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia. Conclusion: Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.]]> Mon 04 Sep 2023 14:57:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:53531 Mon 04 Dec 2023 15:38:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:48602 Mon 01 May 2023 15:45:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:48007 Mon 01 May 2023 15:17:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47198 Fri 30 Jun 2023 10:59:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:41233 Fri 29 Jul 2022 14:02:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45353 1.0% schistocytes on blood film examination, together with absolute thrombocytopenia (<150 x 10⁹ /L) or a relative decrease in platelet count of >25% from baseline. Patients are at risk of long-term chronic kidney disease and long term follow up is recommended.]]> Fri 28 Oct 2022 12:03:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:39807 Fri 24 Jun 2022 08:46:01 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:30276 Fri 24 Aug 2018 09:02:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34253 1000 U/L). Results: Two hundred paracetamol overdoses were analysed, reported median dose ingested was 50 g (interquartile range (IQR): 45-60 g) and median paracetamol ratio 1.9 (IQR: 1.4-2.9, n = 173). One hundred and ninety-three received acetylcysteine at median time of 6.3 h (IQR: 4-9.3 h) post-ingestion. Twenty-eight (14%) developed hepatotoxicity, including six treated within 8 h of ingestion. Activated charcoal was administered to 49(25%), at median of 2 h post-ingestion (IQR:1.5-5 h). Those receiving activated charcoal (within 4 h of ingestion), had significantly lower paracetamol ratio versus those who did not: 1.4 (n = 33, IQR: 1.1-1.6) versus 2.2 (n = 140, IQR: 1.5-3.0) (p < .0001) (paracetamol concentration measured ≥ 1 h after charcoal). Furthermore, they had lower rates of hepatotoxicity [unadjusted OR: 0.12 (95% CI: < 0.001-0.91); adjusted for time to acetylcysteine OR: 0.20 (95%CI: 0.002-1.74)]. Seventy-nine had a paracetamol ratio ≥2, 43 received an increased dose of acetylcysteine in the first 21 h; most commonly a double dose in the last bag (100 to 200 mg/kg/16 h). Those receiving increased acetylcysteine had a significant decrease risk of hepatotoxicity [OR:0.27 (95% CI: 0.08-0.94)] . The OR remained similar after adjustment for time to acetylcysteine and paracetamol ratio. Conclusion: Massive paracetamol overdose can result in hepatotoxicity despite early treatment. Paracetamol concentrations were markedly reduced in those receiving activated charcoal within 4 h. In those with high paracetamol concentrations, treatment with increased acetylcysteine dose within 21 h was associated with a significant reduction in hepatotoxicity.]]> Fri 22 Feb 2019 16:55:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:53857 Fri 19 Jan 2024 12:31:10 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:37583 16 years), who presented with a confirmed snakebite from August 2013 to October 2014 were recruited from Anuradhapura Hospital. Demographic data, information on the circumstances of the bite, first aid, health-seeking behaviour, hospital admission, clinical features, outcomes and antivenom treatment were documented prospectively. There were 742 snakebite patients [median age: 40 years (IQR:27–51; males: 476 (64%)]. One hundred and five (14%) patients intentionally delayed treatment by a median of 45min (IQR:20-120min). Antivenom was administered a median of 230min (IQR:180–360min) post-bite, which didn’t differ between directly admitted and transferred patients; 21 (8%) receiving antivenom within 2h and 141 (55%) within 4h of the bite. However, transferred patients received antivenom sooner after admission to Anuradhapura hospital than those directly admitted (60min [IQR:30-120min] versus 120min [IQR:52-265min; p<0.0001]). A significantly greater proportion of transferred patients had features of systemic envenoming on admission compared to those directly admitted (166/212 [78%] versus 5/43 [12%]; p<0.0001), and had positive clotting tests on admission (123/212 [58%] versus 10/43 [23%]; p<0.0001). Sri Lankan snakebite patients present early to hospital, but there remains a delay until antivenom administration. This delay reflects a delay in the appearance of observable or measurable features of envenoming and a lack of reliable early diagnostic tests. Improved early antivenom treatment will require reliable, rapid diagnostics for systemic envenoming.]]> Fri 19 Feb 2021 15:58:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:30363 Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this.]]> Fri 18 Sep 2020 15:18:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:53167 Fri 17 Nov 2023 11:43:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50090 Fri 14 Jul 2023 11:48:12 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49422 Fri 12 May 2023 15:09:20 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49420 Fri 12 May 2023 15:02:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49393 Fri 12 May 2023 14:34:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:41752 Fri 12 Aug 2022 11:35:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46087 Fri 11 Nov 2022 09:17:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:45713 Fri 04 Nov 2022 10:27:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49785 10,000 U/L)]. The odds of (mild or severe) myotoxicity was lower in patients that received early antivenom (within 6 hours post-bite) compared to those that received late or no antivenom (odd ratio was 0.186; 95% confidence interval, 0.052–0.664). A population pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the relationship between the time course of venom (a mixture of toxins) and effect (elevated CK). In addition, a kinetic-pharmacodynamic (KPD) model was developed to describe the relationship between time course of a theoretical toxin and effect. Model development and parameter estimation was performed using NONMEM v7.3. No single set of parameter values from either the PKPD or KPD models were found that could accurately describe the time course of different levels of severity of myotoxicity. The predicted theoretical toxin half-life from the KPD model was 11 ± 3.9 hours compared to the half-life of venom of 5.3 ± 0.36 hours. This indicates that the putative causative toxin’s concentration-time profile does not parallel that of venom. Conclusion: Early antivenom administration reduces the incidence of myotoxicity. The venom concentration profile does not appear to be the driver for myotoxicity following envenomation. Additional factors that affect the sensitivity of the patient to snake venom/toxins must be explored to understand the relationship with myotoxicity.]]> Fri 02 Jun 2023 17:21:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51341 1.5 (Incomplete VICC = INR>1.5 and complete VICC = ≥3.0). Results: A total of 272 confirmed snakebites (Russell’s viper[76], hump-nosed viper[89], non-venomous snakes[51] and unidentified bites[56]) were recruited (median age: 42 y [interquartile range: 30- 53 y]; 189 males [69%]). On admission, 82 (30%) had incomplete VICC (INR >1.5 and <3) and 77 (28%) had complete VICC (INR ≥3). Sixteen (6%) developed clinically apparent bleeding. The WBCT-15 had the best sensitivity of 47% for detecting VICC and 68% for complete VICC. The sensitivities of the WBCT-20, WBCT-25, CBCT-5 and CBCT-10 was 30–35%. The sensitivities of all tests were better in detecting complete VICC, VICC in Russell’s viper bites and more than 2 h post-bite. The WBCT-15 test had a sensitivity of 76% for VICC in confirmed Russell’s viper bites. For detection of VICC, CBCT-t had an an excellent sensitivity of 97%, but a poor specificity of 35% for an optimal cut-off of >6.25 min. Conclusion: WBCTs are poorly diagnostic for VICC in Russell’s viper and hump-nosed viper envenoming, missing up to two-thirds of patients for some tests. The WBCT-15 was the best test, improving for more severe VICC and greater than 2 h post-bite.]]> Fri 01 Sep 2023 13:35:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:51342 Fri 01 Sep 2023 13:34:38 AEST ]]>