Background: As the world becomes increasingly digital, advances in technology have changed how students access evidence-based information. Research suggests that students overestimate their ability to locate quality online research and lack the skills needed to evaluate the scientific literature. Clinical nurses report relying on personal experience to answer clinical questions rather than searching evidence-based sources. To address the problem, a web-based, evidence-based research (EBR) tool that is usable from a computer, smartphone, or iPad was developed and tested. The purpose of the EBR tool is to guide students through the basic steps needed to locate and critically appraise the online scientific literature while linking users to quality electronic resources to support evidence-based practice (EBP).

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Amyotrophic lateral sclerosis is a neurodegenerative fatal disease. The only drug recognized to increase the survival time is riluzole(RLZ). In animal models, minocycline (MNC) delayed the onset of the disease and increased the survival time (in combination with RLZ). The objective of our work was to study the interactions between RLZ, MNC and the efflux pump p-glycoprotein (p-gp) at the blood-brain barrier. We investigated these two drugs as: (i) p-gp substrates by comparing their brain uptake in CF1 mdr1a ()/)) and mdr1a (+/+) mice, (ii) p-gp modulators by studying their effect on the cerebral uptake of digoxin. mdr1a ()/)) mice showed higher brain uptake of MNC and RLZ than mdr1a (+/+) (in a 1.6-and 1.4-fold, respectively); and in mdr1a (+/+) mice pre-treated with repeated doses of MNC, brain uptake of digoxin was increased. When both drugs were administrated to mdr1a (+/+) mice, MNC increased the brain uptake of RLZ in a 2.1-fold. In conclusion, MNC and RLZ are both p-gp substrates. MNC is also a p-gp inhibitor and increases the brain diffusion of RLZ. In vitro experiments with the GPNT cell line confirmed these results. These interactions should be taken into account in the design of future clinical trials.

-Purpose. Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by the loss of motorneurons. The only drug approved is riluzole. Minocycline is an antibiotic with numerous neuroprotective properties. riluzole and minocycline were given to an animal model of ALS and had beneficial effect on the disease. The combination was then tested in humans in phase II and phase III studies with less beneficial effects and a faster decline of the disease in the group treated with minocycline. In a previous study, we showed that riluzole is transported out of the brain by the P-glycoprotein at the bloodbrain barrier level. In this work, we tested the hypothesis of a drug-drug interaction between riluzole and minocycline. Methods. We studied in CF1 mice, the plasma and brain pharmacokinetics of riluzole combined or not with minocycline. Results. Our results showed that riluzole pharmacokinetics are not linear with dose, but that brain AUC 0-t increase proportionally with plasma AUC 0-t . At the dose of 10 mg/kg, the brain AUC0-t /plasma AUC0-t ratio was 4.6 in mdr1a (-/-) mice and 2.4 in mdr1a (+/+) mice. The combination of minocycline (170 mg/kg) and riluzole (10 mg/kg) induced a 2 fold increase in the brain AUC0-t of riluzole and induced a neuromuscular toxicity in mice. This effect of minocycline was not found at low concentration (10 mg/kg of minocycline). Conclusions. If our results are confirmed in humans, riluzole brain concentrations could be predicted by plasma concentrations. Furthermore, the combination of high doses of minocycline with riluzole could induce neurological toxicity that lead to deceiving results in ALS clinical studies. Hence, a dose-range of minocycline combined with riluzole should be tested in further clinical studies.