ORCID Profile
0000-0003-4478-5308
Current Organisations
Royal Children's Hospital
,
Monash Health
,
Deakin University
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
Publisher: Wiley
Date: 30-09-2014
DOI: 10.1111/JPC.12734
Abstract: Childhood nephrotic syndrome is a condition managed by general paediatricians and paediatric nephrologists. Whether treating a first presentation or a relapse, the clinician requires expertise in order to minimise the risk of serious complications and optimise long-term care. Indeed, many children suffer a difficult relapsing course in their disease, warranting consideration of second-line therapies. The last two decades have witnessed a growing knowledge of the condition and increased complexity of diagnostic and therapeutic options, which poses a challenge for the general paediatrician, given the condition's relative rarity in daily practice. This review aims to familiarise the reader with some of the most important recent developments and particularly to provide an insight into what management options are available and when it may be appropriate to seek advice from a nephrologist.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2014
Publisher: Wiley
Date: 07-2020
DOI: 10.1111/BCP.14434
Abstract: Twenty years ago, target concentration intervention (TCI) was distinguished from therapeutic drug monitoring (TDM). It was proposed that TCI would bring more clinical benefit because of the precision of the approach and the ability to link TCI to principles of pharmacokinetics and pharmacodynamics to predict the dose required by an in idual (1). We examine the theory and clinical trial evidence supporting the benefits of TCI over TDM and conclude that in the digital age TDM should be abandoned and replaced by TCI.
Publisher: Informa UK Limited
Date: 2017
Publisher: Wiley
Date: 29-06-2022
DOI: 10.1111/NEP.14080
Abstract: To examine whether differences in tacrolimus and mycophenolic acid (MPA) pharmacokinetics contribute to the poorer kidney transplant outcomes experienced by Aboriginal Australians. Concentration‐time profiles for tacrolimus and MPA were prospectively collected from 43 kidney transplant recipients: 27 Aboriginal and 16 Caucasian. Apparent clearance (CL/F) and distribution volume (V/F) for each in idual were derived from concentration‐time profiles combined with population pharmacokinetic priors, with subsequent assessment for between‐group difference in pharmacokinetics. In addition, population pharmacokinetic models were developed using the prospective dataset supplemented by previously developed structural models for tacrolimus and MPA. The change in NONMEM objective function was used to assess improvement in goodness of model fit. No differences were found between Aboriginal and Caucasian groups or empirical Bayes estimates, for CL/F or V/F of MPA or tacrolimus. However, a higher prevalence of CYP3A5 expressers (26% compared with 0%) and wider between‐subject variability in tacrolimus CL/F (SD = 5.00 compared with 3.25 L/h/70 kg) were observed in the Aboriginal group, though these differences failed to reach statistical significance ( p = .07 and p = .08). There were no differences in typical tacrolimus or MPA pharmacokinetics between Aboriginal and Caucasian kidney transplant recipients. This means that Bayesian dosing tools developed to optimise tacrolimus and MPA dosing in Caucasian recipients may be applied to Aboriginal recipients. In turn, this may improve drug exposure and thereby transplant outcomes in this group. Aboriginal recipients appeared to have greater between‐subject variability in tacrolimus CL/F and a higher prevalence of CYP3A5 expressers, attributes that have been linked with inferior outcomes.
Publisher: Informa UK Limited
Date: 19-02-2023
Publisher: Frontiers Media SA
Date: 27-10-2022
DOI: 10.3389/FIMMU.2022.1022104
Abstract: Bronchopulmonary dysplasia (BPD), its complication pulmonary hypertension (BPD-PH) and preterm brain and gut injury lead to significant morbidity and mortality in infants born extremely prematurely. There is extensive evidence that the pro-inflammatory cytokine interleukin 1 (IL-1) plays a key role in the pathophysiology of these illnesses. Two decades of clinical use in paediatric and adult medicine have established an excellent safety and efficacy record for IL-1 blockade with IL-1 receptor antagonist (IL-1Ra, medication name anakinra). Building on robust pre-clinical evidence, the Anakinra Pilot trial aims to demonstrate safety and feasibility of administering anakinra to preterm infants, and to establish pharmacokinetics in this population. Its ultimate goal is to facilitate large studies that will test whether anakinra can ameliorate early-life inflammation, thus alleviating multiple complications of prematurity. Anakinra Pilot is an investigator-initiated, single arm, safety and feasibility dose-escalation trial in extremely preterm infants born between 24 weeks 0 days (24 0 ) and 27 6 weeks of gestational age (GA). Enrolled infants will receive anakinra intravenously over the first 21 days after birth, starting in the first 24 h after birth. In the first phase, dosing is 1 mg/kg every 48 h, and dosage will increase to 1.5 mg/kg every 24 h in the second phase. Initial anakinra dosing was determined through population pharmacokinetic model simulations. During the study, there will be a interim analysis to confirm predictions before undertaking dose assessment. Anakinra therapy will be considered safe if the frequency of adverse outcomes/events does not exceed that expected in infants born at 24 0 -27 6 weeks GA. clinicaltrials.gov/ , identifier NCT05280340.
Start Date: 2016
End Date: 2018
Funder: Royal Children’s Hospital Foundation
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