Noel Cranswick

Atopic eczema or atopic dermatitis is a chronic inflammatory skin disease. Current conventional medical treatment for moderate and severe atopic eczema is not satisfactory. There is promising evidence derived from randomised clinical trials to support the clinical use of Chinese herbal medicine in the management of atopic eczema. However, the available evidence is compromised by the high risk of bias associated with most of the included trials. Therefore, well-designed and adequately powered randomised clinical trials are needed. The primary aim of this trial is to evaluate the efficacy and safety of oral ingestion of an oral Chinese herbal formula (Pei Tu Qing Xin granules; PTQX) in children aged between 6 and 16 years with moderate to severe atopic eczema. We have designed a randomised, double-blind, placebo-controlled, two-arm, parallel clinical trial with 12 weeks of treatment and a 4-week follow-up period. A pilot study with 30 participants will be conducted at the RMIT University in Australia to determine the feasibility of the full-scale randomised clinical trial (N = 124). Eczema Area and Severity Index score will be the primary outcome. Secondary outcome measures include change in symptoms using the Patient-Oriented Eczema Measure, the Children’s Dermatology Life Quality Index and the use of concomitant medicines. Safety parameters include report of adverse events and pathology tests during the trial period. Key elements for conducting a high-quality randomised clinical trial have been addressed in this protocol. Findings from the proposed trial will provide critical evidence regarding Chinese herbal medicine treatment for atopic eczema. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614001172695 . Date of Registration: 7 November 2014.

There are a number of challenges to using anti-infective agents in children and pregnant women. There is limited understanding of the altered pharmacokinetics of anti-infectives in these populations and as a result, optimized dosing regimens are yet to be established. The potential adverse effects of the drug on pregnancy outcome and the developing foetus is a major consideration, and the long term implications of drug side effects must be taken into account when drug exposure occurs early in life. These factors hinder research and licensing of new anti-infective drugs in these populations. We describe the current deficiencies and future challenges of anti-infective use in children and pregnant women, providing specific examples.

The ACTION study (Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study. Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo. The methodology for the ACTION study has been detailed. The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment. Australian and New Zealand Clinical Trials Registry ACTRN12607000535471 .

Aim:  Once‐daily tobramycin in patients with cystic fibrosis (CF) is a more convenient dosing regimen than thrice daily dosing. There are limited data on the pharmacokinetic (PK) profile for once‐daily tobramycin in patients with CF. The aim of this study was to define the PK parameters for once‐daily tobramycin in children with CF and develop an algorithm for therapeutic drug monitoring dosing.Methods:  CF patients admitted to hospital were commenced on once‐daily intravenous tobramycin (12 mg/kg/day) and ticarcillin/clavulinic acid. Serum tobramycin levels were taken at 30 min, 2–4 h and 12 h post dose. Data points for the PK model included: age, sex, weight, tobramycin dose, time of tobramycin doses and levels, tobramycin levels. WinNonMix was used to obtain the PK parameters.Results:  Forty‐four children with 86 admissions who were aged 9 months−20 years were included. A one‐compartment intravenous infusion model with first order elimination kinetics produced the best model. Population parameters were: volume of distribution (V_d) = 0.267 L/kg (95% confidence interval (CL) 0.260–0.272), clearance (CL) 0.103 L/kg/h (95% CI 0.098–0.107) and half‐life (t_1/2) 1.82 (95% CI 1.77–1.88) h. Once the population model was established post hoc analysis was used to calculate individual subject predictions. Plots of individual prediction curves agreed well with observed values.Conclusion:  This study has established an algorithm for routine monitoring of once‐daily tobramycin in children with CF. Satisfactory serum levels of tobramycin were obtained with a dose of 12 mg/kg/day and a regimen algorithm that uses only one measurement to monitor the plasma concentration is suggested.

Background: The use of tramadol at The Royal Children's Hospital, Melbourne has dramatically increased. This has coincided with the emergence of adverse drug reactions (ADRs).Aim: To investigate potential adverse reactions to tramadol in children and adolescents as compared with adults.Method: The ADR program at the hospital detects both spontaneously reported ADRs and those identified by medical records coding reports. For this study, reported reactions to tramadol were retrieved from the hospital's ADR database. Comparison with reports from the Australian Adverse Drug Reaction Advisory Committee and the literature was made.Results: 8 ADR reports implicating tramadol in patients aged from 14 months to 22 years were identified.Conclusion: Some insight was gained into the possible adverse effects of tramadol in children and adolescents, which are similar to the reported profile of adverse reactions in adults. Further pharmacovigilance studies are required to expand on these findings and provide direction to ensure the safe use of tramadol in this age group.

Objectives:  To identify cases of clonidine poisoning presenting to a tertiary paediatric hospital and to investigate trends in presentation, outcome and prevention. Furthermore, any public health implications of the use of clonidine in children are to be explored.Methods:  Cases of clonidine poisoning presenting to Royal Children's Hospital were reviewed over the period from 1997 to 2001 (inclusive), with significant data obtained from coded medical records.Results: Twenty‐four cases of clonidine poisoning were identified over the 5‐year period. Nine patients ingested their own medication, which was prescribed for attention‐deficit hyperactivity disorder. Clonidine was prescribed for a child in 16 cases (67%). Impaired conscious state and bradycardia were the most common presenting features. Activated charcoal was given in 14 cases and volume expansion in six. There were 12 children (50%) who required admission to intensive care for monitoring, including three who received mechanical ventilation. The average length of stay was 25.7 h with no long‐term complications.Conclusions:  This is the largest series of clonidine poisoning in children recorded in Australia, with morbidity considerable. Emphasis needs to be placed on educating parents of clonidine's dangers in overdose to their own children as well as others.