Utilization of psychotropic medicines in Romania during 1998–2018

Background: Mental disorders can have a significant impact on patients’ life, including economic, social and individual consequences, and psychotropic medication is essential to treat these conditions. Psychotropic drug utilization studies contribute to a clearer picture of the management of these conditions. Data published from Romania on this topic is limited. The present study aims to characterize the utilization patterns of anxiolytics, antidepressants (ADs), and antipsychotics (APs) in Romania during 1998–2018.Methods: Drug utilization data were provided by Management Center for Documentation, Information and Marketing (CEGEDIM) Romania and quantitative data for each psychotropic medicine were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The total use of medicines in DDD/TID was computed in order to obtain the drug utilization 90% (DU90%) segment.Results: An increasing trend in total utilization of psychotropic medicines in Romania started in 2004. Anxiolytics use was predominant until 2013 and the yearly anxiolytic use over the entire study period remained between 10 and 15 DDD/TID. Diazepam lost popularity over time in detriment of the utilization of other anxiolytic benzodiazepines, such as alprazolam and lorazepam. ADs utilization markedly increased during the study period (the average annual growth rate was 13.66% starting 1999). Selective serotonin reuptake inhibitors (SSRIs) became present on the 2008 DU90% and was the dominant class of ADs, with sertraline being the most prescribed, followed by escitalopram and paroxetine. APs utilization showed an increasing trend from 2003 until 2018. Atypical APs became present on the 2008 DU90%, while typical APs were no longer included in the 2018 DU90%. Among atypical APs, olanzapine was the main agent prescribed, and starting 2010 was followed by quetiapine and risperidone. The uptake of APs long-acting formulations became more evident during the last analyzed years (2015–2018).Conclusion: We observed an increasing utilization of APs and a more prominent increase in ADs utilization in Romania during 1998–2018. The anxiolytic prescribing remained nearly stable during this time. Further research can bring more information on the various factors influencing psychotropic utilization in Romania

Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research

Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1–Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism

A VigiBase Descriptive Study of Fluoroquinolone-Associated Peripheral Nervous System Disorders

Background: Recent drug safety concerns described fluoroquinolone (FQ)-induced peripheral nervous system reactions. The objective of this study was to characterize such reports from VigiBase. Methods: The analysis included FQ-induced peripheral nervous system disorder adverse drug reaction (ADR) reports (up to July 2019). We looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values, and descriptive analysis was performed for FQ-ADRs positive associations (ADRs, suspected FQs, potential risk factors, such as associated therapy and underlying disease). Results: Disproportionality analysis revealed 4374 reports (3531 serious) with peripheral nervous system ADRs associated with at least three FQs (neuropathy peripheral, 5492; neuralgia, 481; polyneuropathy, 220; sensory loss, 99; peripheral sensorimotor neuropathy, 39). Among these, both time-to-onset and duration of reaction were mostly between 1–7 days and ≥30 days. Most of the ADRs were not recovered/resolved at the time of reporting. Conclusion: The results augment the existing data on FQ safety concerns, specifically their potential effect on the nervous system

Safety of COVID-19 Vaccines Among the Paediatric Population: Analysis of the European Surveillance Systems and Pivotal Clinical Trials

Background and objectives: The European Medicine Agency extended the use of Comirnaty, Spikevax, and Nuvaxovid in paediatrics; thus, these vaccines require additional real-world safety evidence. Herein, we aimed to monitor the safety of COVID-19 vaccines through Covid-19 Vaccine Monitor (CVM) and EudraVigilance surveillance systems and the published pivotal clinical trials. Methods: In a prospective cohort of vaccinees aged between 5 and 17 years, we measured the frequency of commonly reported (local/systemic solicited) and serious adverse drug events (ADRs) following the first and second doses of COVID-19 vaccines in Europe using data from the CVM cohort until April 2022. The results of previous pivotal clinical trials and data in the EudraVigilance were also analysed. Results: The CVM study enrolled 658 first-dose vaccinees (children aged 5-11 years; n = 250 and adolescents aged 12-17 years; n = 408). Local/systemic solicited ADRs were common, whereas serious ADRs were uncommon. Among Comirnaty first and second dose recipients, 28.8% and 17.1% of children and 54.2% and 52.2% of adolescents experienced at least one ADR, respectively; injection-site pain (29.2% and 20.7%), fatigue (16.1% and 12.8%), and headache (22.1% and 19.3%) were the most frequent local and systemic ADRs. Results were consistent but slightly lower than in pivotal clinical trials. Reporting rates in Eudravigilance were lower by a factor of 1000. Conclusions: The CVM study showed high frequencies of local solicited reactions after vaccination but lower rates than in pivotal clinical trials. Injection-site pain, fatigue, and headache were the most commonly reported ADRs for clinical trials, but higher than spontaneously reported data