https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51237 Wed 28 Feb 2024 16:07:34 AEDT ]]> https://ogma.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.]]> Wed 21 Aug 2024 12:23:27 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43350 Tue 28 Nov 2023 15:50:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21161 Daboia russelii) envenoming in Sri Lanka. All patients received Indian F(ab’)₂ snake antivenom manufactured by VINS Bioproducts Ltd. Antivenom concentrations were measured with sandwich enzyme immunoassays. Timed antivenom concentrations were analysed using MONOLIXvs4.2. One, two and three compartment models with zero order input and first order elimination kinetics were assessed. Models were parameterized with clearance(CL), intercompartmental clearance(Q), central compartment volume(V) and peripheral compartment volume(V_P). Between-subject-variability (BSV) on relative bioavailability (F) was included to account for dose variations. Covariates effects (age, sex, weight, antivenom batch, pre-antivenom concentrations) were explored by visual inspection and in model building. There were 75 patients, median age 57 years (40-70y) and 64 (85%) were male. 411 antivenom concentration data points were analysed. A two compartment model with zero order input, linear elimination kinetics and a combined error model best described the data. Inclusion of BSV on F and weight as a covariate on V improved the model. Inclusion of pre-antivenom concentrations or different batches on BSV of F did not. Final model parameter estimates were CL,0.078 Lh⁻¹, V,2.2L, Q,0.178Lh⁻¹ and V_P,8.33L. The median half-life of distribution was 4.6h (10-90%iles:2.6-7.1h) and half-life of elimination, 140h (10^th-90^th percentilesx:95-223h). Conclusion: Indian F(ab’)₂ snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life.]]> Thu 29 Aug 2024 10:06:52 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28763 Thu 07 May 2020 11:22:50 AEST ]]> https://ogma.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.]]> Mon 26 Aug 2024 08:45:47 AEST ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44173 Mon 10 Oct 2022 10:13:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54106 Mon 05 Feb 2024 09:57:04 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30276 Fri 24 Aug 2018 09:02:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49422 Fri 12 May 2023 15:09:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28762 Fri 06 Apr 2018 11:05:05 AEST ]]>