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Aim: To characterise usage and monitoring of intravenous tobramycin in cystic fibrosis ( CF) patients in Australia and the UK. Methods: An anonymous, online survey of healthcare professionals caring for CF patients was conducted. Survey questions were designed to obtain information on tobramycin dosing, therapeutic drug monitoring and toxicity monitoring. Results: The survey was sent to pharmacists and clinicians in 73 CF centres. Responses were received from 32 and 40 healthcare professionals, from Australia and the UK, respectively. Once-daily dosing of tobramycin was the preferred administration regimen for 93.8 and 67.5% of participants in Australia and the UK, respectively. Among them 68.8% of Australian and 55% of UK participants initiated tobramycin therapy at a dose of 10 mg/kg/day or greater. Australian participants most commonly adjusted tobramycin dosage using log-linear regression analysis (40.6%) or trough measurements (28.1%). UK participants most commonly adjusted tobramycin dosage using trough (55%) or peak and trough measurements (37.5%). In 90.6% of Australian and 95% of UK participants practices, serum creatinine was routinely monitored during admission. Standard pure tone audiometry was performed by 15.6% of Australian and 17.5% of UK participants and high-frequency pure tone audiometry was performed by 15.6% of Australian and 10% of UK participants, once or twice a year. Conclusions: Many discrepancies exist between Australia and the UK and within each country with respect to monitoring of intravenous tobramycin in CF patients. Greater ototoxicity monitoring is likely necessary in both countries. Further education of health professionals about the existence of national guidelines and guidance on how they can be applied in practice is likely required. [ABSTRACT FROM AUTHOR]

The objective was to study the population pharmacokinetics of bound and unbound phenytoin in critically ill children, including influences on the protein binding profile. A population pharmacokinetic approach was used to analyze paired protein-unbound and total phenytoin plasma concentrations (n = 146 each) from 32 critically ill children (0.08-17 years of age) who were admitted to a pediatric hospital, primarily intensive care unit. The pharmacokinetics of unbound and bound phenytoin and the influence of possible influential covariates were modeled and evaluated using visual predictive checks and bootstrapping. The pharmacokinetics of protein-unbound phenytoin was described satisfactorily by a 1-compartment model with first-order absorption in conjunction with a linear partition coefficient parameter to describe the binding of phenytoin to albumin. The partitioning coefficient describing protein binding and distribution to bound phenytoin was estimated to be 8.22. Nonlinear elimination of unbound phenytoin was not supported in this patient group. Weight, allometrically scaled for clearance and volume of distribution for the unbound and bound compartments, and albumin concentration significantly influenced the partition coefficient for protein binding of phenytoin. The population model can be applied to estimate the fraction of unbound phenytoin in critically ill children given an individual's albumin concentration. [ABSTRACT FROM AUTHOR]

Introduction: Antenatal maternal magnesium sulfate (MgSO 4 ) administration is a proven efficacious neuroprotective treatment reducing the risk of cerebral palsy (CP) among infants born preterm. Identification of the neuroprotective component with target plasma concentrations could lead to neonatal treatment with greater efficacy and accessibility., Methods and Analysis: This is a prospective observational cohort study, in three tertiary Australian centres. Participants are preterm infants, irrespective of antenatal MgSO 4 exposure, born in 2013-2020 at 24 +0 to 31 +6 weeks gestation, and followed up to 2 years corrected age (CA) (to September 2023). 1595 participants are required (allowing for 17% deaths/loss to follow-up) to detect a clinically significant reduction (30% relative risk reduction) in CP when sulfate concentration at 7 days of age is 1 SD above the mean.A blood sample is collected on day 7 of age for plasma sulfate and magnesium measurement. In a subset of participants multiple blood and urine samples are collected for pharmacokinetic studies, between days 1-28, and in a further subset mother/infant blood is screened for genetic variants of sulfate transporter genes.The primary outcome is CP. Surviving infants are assessed for high risk of CP at 12-14 weeks CA according to Prechtl's Method to assess General Movements. Follow-up at 2 years CA includes assessments for CP, cognitive, language and motor development, and social/behavioural difficulties.Multivariate analyses will examine the association between day 7 plasma sulfate/magnesium concentrations with adverse neurodevelopmental outcomes. A population pharmacokinetic model for sulfate in the preterm infant will be created using non-linear mixed-effects modelling., Ethics and Dissemination: The study has been approved by Mater Misericordiae Ltd Human Research Ethics Committee (HREC/14/MHS/188). Results will be disseminated in peer-reviewed journal publications, and provided to the funding bodies. Using consumer input, a summary will be prepared for participants and consumer groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Aims: To evaluate 3 Bayesian forecasting (BF) programs-TDMx, InsightRx and DoseMe-on their user-friendliness and common liked and disliked features through a survey of hospital pharmacists., Methods: Clinical pharmacists across 3 Australian hospitals that did not use a BF program were invited to a BF workshop and complete a survey on programs they trialled. Participants were given 4 case scenarios to work through and asked to complete a 5-point Likert scale survey evaluating the program's user-friendliness. Liked and disliked features of each program were ascertained through written responses to open-ended questions. Survey results were compared using a χ 2 test of equal or given proportions to identify significant differences in response., Results: Twenty-seven pharmacists, from hospitals, participated. BF programs were rated overall as user-friendly with 70%, 41% and 37% (P = .02) of participants recording a Likert score of 4 or 5 for DoseMe, TDMx and InsightRx, respectively. Participants found it easy to access all required information to use the programs, understood dosing recommendations and visualisations given by each program, and thought programs supported decision-making with >50% of participants scoring a 4 or 5 across the programs in these categories. Common liked features across all programs were the graphical displays and ease of data entry, while common disliked features were related to the units, layout and information display., Conclusion: Although differences exist between programs, all 3 programs were most commonly rated as user-friendly across all themes evaluated, which provides useful information for healthcare facilities wanting to implement a BF program., (© 2019 The British Pharmacological Society.)

Background: The impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain., Aims: To determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung injury at age 5 years; (2) accelerated lung function decline between ages 5 years and 14 years and (3) to identify explanatory variables., Methods: A cross-sectional analysis of association between Aspergillus positive bronchoalveolar lavage (BAL) cultures and chest high-resolution CT (HRCT) scan findings at age 5 years in subjects from the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study was performed. A non-linear mixed-effects disease progression model was developed using FEV 1 % predicted measurements at age 5 years from the ACFBAL study and at ages 6-14 years for these subjects from the Australian Cystic Fibrosis Data Registry., Results: Positive Aspergillus BAL cultures at age 5 years were significantly associated with increased HRCT scores for air trapping (OR 5.53, 95% CI 2.35 to 10.82). However, positive Aspergillus cultures were not associated with either FEV 1 % predicted at age 5 years or FEV 1 % predicted by age following adjustment for body mass index z-score and hospitalisation secondary to pulmonary exacerbations. Lung function demonstrated a non-linear decline in this population., Conclusion: In children with cystic fibrosis, positive Aspergillus BAL cultures at age 5 years were associated contemporaneously with air trapping but not bronchiectasis. However, no association was observed between positive Aspergillus BAL cultures on FEV 1 % predicted at age 5 years or with lung function decline between ages 5 years and 14 years., Competing Interests: Competing interests: CW reports grants from Australian National Health and Medical Research Council and non-financial support from Pathogenesis, then Chiron, and then Novartis during the conduct of the ACFBAL study, reports income on a per-patient basis derived from Pharmaceutical Studies – Vertex Pharmaceuticals Inc, Boehringer-Ingelheim and Ablynx NV. Epidemiological research support from GlaxoSmithKline – Analysis of Bronchoalveolar lavage (BAL) fluid from children with respiratory disorders; 2010–2012 Research Grant from Novo Nordisk Pharmaceuticals P/L- CF-IDEA Study; 2012–2013 Other Reimbursement: Vertex Pharmaceuticals Inc. – Consultant on the Vertex Physician Pediatric CF Advisory Board and the Vertex Innovation Awards (VIA) Grants Committee Gilead Sciences, Inc. – AZLI Advisory Board Honorarium 2010 Medscape – Consultation interview regarding CF Studies 2012 Vertex Pharmaceuticals 2013 San Francisco return flight and accommodation as Investigator in Lumacaftor study (104) Vertex Pharmaceuticals 2014 return flight and accommodation + honorarium as invited speaker at European CF Conference, Gothenburg, Sweden Vertex Pharmaceuticals (Australia) 2015 honorarium as speaker at a Vertex sponsored educational meeting series Vertex Pharmaceuticals 2015 Chicago return flight and accommodation as Investigator in Lumacaftor study (109) Vertex Pharmaceuticals (Australia) 2015 honorarium for attendance at Advisory Board meeting at Australasian CF Conference held in Sydney in August; Vertex Pharmaceuticals P/L honorarium to attend the Vertex Steering Committee Meetings re VX15-770-123 Study and to attend the Global Medical Advisory Board Meeting in March 2016. Novartis Pharmaceuticals 2013 return travel and accommodation to give a symposium at European CF Conference in Lisbon Novartis Pharmaceuticals Australia P/L 2013 honorarium to present symposium at Australasian CF Conference in Auckland Novartis Pharmaceuticals 2014 return flight and accommodation + honorarium as invited speaker at National Pediatric Congress in Lebanon Novartis Pharmaceuticals Australia P/L 2015 honorarium to present symposium at Australasian CF Conference in Sydney in August; The University of Miami honorarium for meeting attendance. Thorax honorarium for associate editor duties Q3/Q4 2015 and BMJ honorarium for consulting work in April 2016. Current Board Positions – Thoracic Society Australia and New Zealand; and International Advisory Board Vertex Pharmaceuticals P/L. (N.B. Payments for all items listed above have been made into an institutional consultancy fund account). KG reports grants from Australian National Health and Medical Research Council and non-financial support from Pathogenesis, then Chiron, and then Novartis during the conduct of the ACFBAL study., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)