bioRxiv ScienceSearch

bioRxiv · 10.1101/463240

Drug prescription pattern in European neonatal units

Abstract

BackgroundHospitalized neonates receive the highest number of drugs compared to all other age groups, but consumption rates vary between studies depending on patient characteristics and local practices. There are no large scale international studies on drug use in neonatal units. We aimed to describe drug use in European neonatal units and characterize its associations with geographic region and gestational age (GA).\n\nMethodsA one-day point prevalence study (PPS) was performed as part of the European Study of Neonatal Exposure to Excipients (ESNEE) from January to June 2012. All neonatal prescriptions and demographic data were registered in a web-based database. The impact of GA and region on prescription rate were analyzed with logistic regression.\n\nResultsIn total, 21 European countries with 89 neonatal units participated. Altogether 2173 prescriptions given to 726 neonates were registered. The 10 drugs with the highest prescription rate were multivitamins, vitamin D, caffeine, gentamicin, amino acids for parenteral nutrition, phytomenadione, ampicillin, benzylpenicillin, fat emulsion for parenteral nutrition and probiotics. The six most commonly prescribed ATC groups (alimentary tract and metabolism, blood and blood-forming organs, systemic anti-infectives, nervous, respiratory and cardiovascular system) covered 98% of prescriptions. GA significantly affected the use of all commonly used drug groups. Geographic region influenced the use of alimentary tract and metabolism, blood and blood-forming organs, systemic anti-infectives, nervous and respiratory system drugs.\n\nConclusionsWhile GA-dependent differences in neonatal drug use were expected, regional variations (except for systemic anti-infectives) indicate a need for cooperation in developing harmonized evidence-based guidelines and suggest priorities for collaborative work.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mesek, I., Nellis, G., Lass, J., Metsvaht, T., Varendi, H., Visk, H., Turner, M. A., Nunn, A. J., Duncan, J., Lutsar, I.. 2018-11-05. Drug prescription pattern in European neonatal units. https://doi.org/10.1101/463240

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Lipid-ASO therapeutics exhibit differential tissue targeted delivery upon systemic or local CNS administration

Antisense oligonucleotides (ASOs) are a powerful therapeutic modality, but their full potential is hindered by pharmacokinetic properties that affect tissue and cellular delivery. Lipid conjugation is increasingly used to modulate ASO's biodistribution and promote extrahepatic activity, yet lipid dependent effects on in vivo functional delivery, particularly in the central nervous system (CNS), remain less explored. Here, we performed a side by side in vivo comparison of cholesterol, palmitic acid (C16:0), docosanoic acid (C22:0), and eicosapentaenoic acid (C20:5) conjugated to a fully phosphorothioated 3 10 3 LNA gapmer ASO targeting the Malat1 long non coding RNA. Lipid-ASO conjugates were administered systemically or locally in the brain of mice and evaluated for tissue level and cellular level distribution by imaging, qPCR and single-cell RNA sequencing, simultaneously annotating cell origin and global transcriptional changes within the cell. Following systemic administration in mice, lipid conjugation improved overall multi organ efficacy compared to unconjugated ASO, but with pronounced tissue specific differences. Single cell sequencing of liver and heart transcriptomes revealed lipid dependent cellular uptake patterns and transcriptional responses distinct from administration of unconjugated ASO. After intracerebroventricular administration, selected fatty acid conjugates enhanced silencing in deep brain regions such as the striatum, whereas cholesterol conjugation impaired functional delivery despite increased CNS retention. Light-sheet microscopy showed restricted parenchymal penetration of cholesterol ASOs compared with broader but heterogeneous distribution of palmitic acid conjugate. Together, these findings demonstrate that lipid identity critically determines ASO efficacy, productive cellular uptake, and regional CNS engagement, emphasizing the need for context specific lipid design in ASO therapeutic development.

pharmacology and toxicology

Novel Dissymmetric Ionizable Lipid-Assembled Lipid Nanoparticles for Delivery of Ferroptosis-Related siRNA in Diabetic Treatment

Small interfering RNA (siRNA) enables precise post-transcriptional gene silencing for refractory diseases, yet its clinical translation remains limited by the lack of safe and efficient delivery vectors. Inspired by the dissymmetric alkyl chain architecture of natural membrane phospholipids, we designed and synthesized 34 novel ionizable lipids with dissymmetric hydrophobic tails and formulated them into lipid nanoparticles (LNPs). Through systematic physicochemical and biological assessments, we established clear structure-activity relationships and identified two lead LNPs (O14-LNP, H18a-LNP) with superior endosomal escape capacity, enhanced in vivo gene silencing potency, and favorable biosafety relative to the clinical benchmark MC3-LNP. In both streptozotocin-induced and spontaneous db/db type 2 diabetes (T2D) mouse models, lead LNPs delivering ferroptosis-related siRNAs effectively ameliorated glucose and lipid metabolic disorders, restored islet function, and alleviated hepatic steatosis. This study not only lays a theoretical foundation for the rational design of novel ionizable lipids, but also validates the therapeutic potential of siRNA therapy targeting ferroptosis, providing a versatile delivery platform and targeted therapeutic strategy for the treatment of T2D.

pharmacology and toxicology

Antimalarial drug mefloquine kills both trophozoite and cyst stages of Entamoeba

Entamoeba histolytica is a protozoan parasite which infects approximately 50 million people worldwide, resulting in an estimated 70,000 deaths every year. Since the 1960s E. histolytica infection has been successfully treated with metronidazole. However, drawbacks to metronidazole therapy exist, including adverse effects, length of treatment, and the need for additional drugs to prevent transmission. All of these may decrease patient compliance and hence increase disease severity and spread of infection. In this study we identified the antimalarial drug mefloquine as possessing more potent, rapid, amoebicidal in vitro activity against E. histolytica trophozoites than metronidazole. We also showed that mefloquine could kill the cysts of a closely related reptilian parasite Entamoeba invadens unlike metronidazole. Additionally, mefloquine is known to possess a much longer half-life in human patients than metronidazole. This property, along with mefloquines rapid and broad action against E. histolytica position it as a promising new drug candidate against this widespread and devastating disease.\n\nAuthor SummaryEvery year, around 70,000 people worldwide die from infection by the intestinal parasite Entamoeba histolytica, despite the widespread availability of the drug metronidazole as a treatment. Part of the reason for this may be due to issues with patients failing to comply with the full course of treatment for the drug, due either to unpleasant side-effects, to the somewhat long treatment period, or the need for a secondary drug to kill the transmissible life stage of the parasite. In this report we discovered that the antimalarial drug mefloquine killed E. histolytica more potently and more rapidly than metronidazole, and, importantly, also killed the transmissible cyst stage of another Entamoeba species used as a model system. These findings make mefloquine an excellent candidate for an alternative drug to the current standard, with a simpler course of treatment and a more effective strategy to reduce the spread of this disease.

pharmacology and toxicology