EAP viewpoint on unpublished data from paediatric clinical trials.

European children and paediatricians rely heavily on the fair, complete and timely publication of data obtained from paediatric randomised controlled trials (RCTs). Selective publication and reporting of paediatric RCTs is common practice. Industry-sponsored trials are more likely to remain unpublished, and take longer to get published compared with trials sponsored by others. However, also academic sponsors contribute to inefficiencies in publishing clinical data. Publication bias violates the ethical obligation that investigators have towards study participants, leads to considerable inefficiencies in research and a waste of financial and human resources, and has the potential to distort evidence for treatment approaches. CONCLUSION: The European Academy of Paediatrics (EAP) therefore actively supports initiatives that increase the public dissemination of paediatric clinical trial data. The EAP will raise awareness about the guidelines for Good Publication Practice among European paediatricians and subspecialty societies.

Determination of methylphenidate in plasma and saliva by liquid chromatography/tandem mass spectrometry.

Methylphenidate (MPH) is a phenethylamine derivative used in the treatment of attention-deficit hyperactivity disorder (ADHD). In adults, clinical monitoring of MPH therapy is usually performed by measuring plasma MPH concentrations. In children blood sampling is however undesirable. Saliva may be an alternative matrix for monitoring MPH concentrations with the advantage that it can be obtained non-invasively. Therefore, we developed an analytical method for the quantification of MPH in both plasma and saliva. We present the validation of a liquid chromatography-tandem mass spectrometric method using a hydrophilic interaction liquid chromatography column (HILIC). In 100 µL sample, proteins were precipitated with 750 µL acetonitrile/methanol 84/16 (v/v) containing d9-methylphenidate as the internal standard. Standard curves were prepared over the MPH concentration range of 0.5-100.0 µg/L. The total analysis time was 45 s. Accuracy and within- and between-run imprecision were in the range of 98-108% and less than 7.0%, respectively. Matrix effects were greater for plasma than saliva with 46% and 8% ionization suppression. The matrix effects were adequately compensated by the use of deuterated MPH as internal standard. MPH significantly degraded in plasma and saliva at room temperature and 5°C. Samples were stable at -20°C for at least 4 weeks. The method was successfully applied for the determination of MPH concentrations in plasma and saliva samples from an adult healthy volunteer. Using protein precipitation and hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry, this method allows fast, accurate and precise quantification of MPH in both plasma and saliva.

Evaluation of the EndoPAT as a Tool to Assess Endothelial Function.

Endothelial dysfunction is a potential target for (pharmaceutical) intervention of several systemic pathological conditions. We investigated the feasibility of the EndoPAT to evaluate acute changes in endothelial function with repeated noninvasive measurements and assessed its discriminating power in different populations. Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%). Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9 ± 1.4 and 1.8 ± 0.3, resp., versus 1.8 ± 0.5, P > 0.05). The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline 0.08 ± 0.50, 95% confidence interval -0.44 to 0.60; smoking: change from baseline 0.49 ± 0.92, 95% confidence interval -0.47 to 1.46). This suggests that at present the EndoPAT might not be suitable to assess (changes in) endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice.

Evaluation of decompression tables by Doppler technique in caisson work in The Netherlands.

INTRODUCTION: Hyperbaric work was conducted for constructing an underground tramway in the Netherlands. A total of 11,647 exposures were conducted in 41,957 hours. For these working conditions specifically developed oxygen decompression tables were used. METHODS: Fifteen workers were submitted to Doppler monitoring after caisson work at a depth at 12 msw. Measurements were done according to the Canadian DCIEM protocol. For bubble grading the Kisman-Masurel 12-points ordinal scale (0-IV) was used. RESULTS: Bubbles were detected in 17 of the 38 examinations. The highest grade (III-) was found in four measurements. At rest the grading was never higher than I+. Two hours after decompression the grading was remarkably higher than after one hour. CONCLUSIONS: Bubble scores were relatively low, although the maximum grading probably is not reached within two hours after decompression. It may be concluded that the oxygen decompression tables used, were reliable under these heavy working conditions. At group level, decompression stress can be evaluated by Doppler monitoring. In order to reduce health hazard of employees, use of oxygen during decompression in caisson work should be embodied in the occupational standard.