Predictive Value of Optic Nerve Sheath Diameter for Diagnosis of Intracranial Hypertension in Children With Severe Brain Injury.

Background and Aims: Intracranial Hypertension (ICH) is a life-threatening complication of brain injury. The invasive measurement of intracranial pressure (ICP) remains the gold standard to diagnose ICH. Measurement of Optic Nerve Sheath Diameter (ONSD) using ultrasonography is a non-invasive method for detecting ICH. However, data on paediatric brain injury are scarce. The aim of the study was to determine the performance of the initial ONSD measurement to predict ICH occurring in children with severe brain injury and to describe the ONSD values in a control group. Methods: In this cross-sectional study, ONSD was measured in children aged 2 months-17 years old with invasive ICP monitoring: before placement of ICP probe and within the 60 min after, and then daily during 3 days. ONSD was also measured in a control group. Results: Ninety-nine patients were included, of whom 97 were analysed, with a median (IQR) age of 8.7 [2.3-13.6] years. The median (IQR) PIM 2 score was 6.6 [4.4-9.7] and the median (IQR) PELOD score was 21 [12-22]. Aetiologies of brain injury were trauma (n = 72), infection (n = 17) and stroke (n = 8). ICH occurred in 65 children. The median (IQR) ONSD was 5.58 mm [5.05-5.85]. ONSD performed poorly when it came to predicting ICH occurrence within the first 24 h (area under the curve, 0.58). There was no significant difference between the ONSD of children who presented with ICH within the first 24 h and the other children, with a median (IQR) of 5.6 mm [5.1-5.9] and 5.4 mm [4.9-5.8], respectively. Infants aged less than 2 years had a median (IQR) ONSD of 4.9 mm [4.5-5.2], significantly different from children aged more than 2 years, whose median ONSD was 5.6 mm [5.2-5.9]. Age, aetiology or ICP levels did not change the results. Thirty-one controls were included, with a median age of 3.7 (1.2-8.8) years. The median (IQR) of their ONSD measurement was 4.5 mm [4.1-4.8], significantly lower than the patient group. Conclusion: In a paediatric severe brain injury population, ONSD measurement could not predict the 24 h occurrence of ICH. Severity of patients, timing and conditions of measurements may possibly explain these results.

Do drugs interact together in cardiovascular prevention? A meta-analysis of powerful or factorial randomized controlled trials.

AIM OF THE STUDY: To explore whether preventive cardiovascular drugs (antihypertensive, antiplatelet, lipid lowering and hypoglycemic agents) interact together in cardiovascular prevention. METHODS: We searched PubMed®, Web of science™, Embase and Cochrane library for powerful randomized placebo-controlled trials (>1000 patients). We explored whether drug effect on major vascular events changed according to cross-exposure to other drug classes or to cardiovascular risk factors (hypertension or type 2 diabetes), through a meta-analysis of relative odds ratio computed by trial subgroups. A significant interaction was suggested from confidence intervals of the ratio of odds ratios, when they excluded neutral value of 1. RESULTS: In total, 14 trials with 178,398 patients were included. No significant interaction was observed between co-prescribed drugs or between these medications and type 2 diabetes/hypertension status. CONCLUSIONS: Our meta-analysis is the first one to evaluate drug-drug and drug-hypertension/type 2 diabetes status interactions in terms of cardiovascular risks: we did not observe any significant interaction. This indirectly reinforces the rationale of using several contrasted mechanisms to address cardiovascular prevention; and allows the combination effect prediction by a simple multiplication of their odds ratios. The limited availability of data reported or obtained from authors is a strong argument in favor of data sharing.

Agreement between a regional pharmacovigilance centre and an adjudication committee regarding adverse drug reactions on a cohort of hospitalised children.

BACKGROUND AND PURPOSE: The EREMI project was set up to collect data on adverse drug reactions (ADRs) occurring due to off-label and/or unlicensed drugs prescribed to hospitalised children in France. These events were evaluated by a regional pharmacovigilance centre (RPC) and an adjudication committee (AC). The aim of this study was to assess the agreement between these two different entities on their evaluation of ADRs. EXPERIMENTAL APPROACH: The RPC first validated the ADRs and assessed their causality using the Naranjo scale. The AC assessed then ADRs using all available information, including the RPC evaluation. The agreement on severity and nature of ADRs, role of treatment (suspect or concomitant) and drug causality was calculated using Cohen's nonparametric kappa coefficient (k). KEY RESULTS: Three hundred and eighty-six events were reported in 219 children. The RPC excluded 65 events and validated 321 ADRs. Agreement was very good on nature of ADRs (k=0.85) and role of treatment (k=0.81), moderate on severity of ADRs (k=0.60) and very poor on drug causality (k=0.05). CONCLUSION AND IMPLICATIONS: Agreement between the RPC and the AC was not constant throughout this evaluation. They troubled to agree on severe ADRs and on drug causality.