Introduction: CYP2C19 is a highly polymorphic gene responsible for metabolizing commonly used drugs. CYP2C19*2,*3 (loss of activity alleles) and *17 (increased activity allele) are the principal alleles included in clinical guidelines, however their prevalence varies among different ethnicities. Ecuadorian population is formed by Mestizos, Afrodescendants and Native Americans and frequency of CYP2C19 alleles could be different among them. The objective of this study was to establish the frequency of these variants in the different populations of Ecuador and to compare them with other populations. Materials and methods: DNA from 105 Afrodescendants, 75 Native Americans of the Kichwa ethnicity, and 33 Mestizos Ecuadorians was analyzed by nested-PCR to identify CYP2C19*17 carriers. CYP2C19*2 allele was analyzed in DNA from 78 Afrodescendants, 29 Native Americans of the Kichwa, and 16 Mestizos by TaqMan Allelic Discrimination Assay. CYP2C19*3 was analyzed in 33 Afrodescendants by nested-PCR. Results: The global frequencies of the alternate alleles were 14.22% (CYP2C19*2) and 2.10% (CYP2C19*17). No differences (p > 0.05) were observed among the subgroups. No CYP2C19*3 carrier was identified. CYP2C19*2 frequencies in Ecuador were similar to the ones reported in Europe, Africa and Middle East countries and to some American populations. Low CYP2C19*17 frequencies, like the ones in our population, were also observed in East and South Asia and in Native American groups. Discussion: Absence of differences in the ethnic groups in Ecuador for CYP2C19*2 and *17 could be due to either a bias in sample selection (ethnic group was assed by self-identification) or to a high interethnic admixture in the Ecuadorian population that would had diluted genetic differences. In addition, CYP2C19*2, *3, and *17 alleles frequencies in our study suggest that Ecuadorians ancestry is mostly of Native American origin.
Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate-severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy.
This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.
Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer's disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis.
Self-inflicted violence is a major and growing public health problem and its prediction and prevention is challenging for healthcare systems worldwide. Our aim was to identify prescribed drugs associated with self-directed violent behaviors in Spain. A descriptive, longitudinal and retrospective study of spontaneous reports of adverse drug reactions corresponding to self-directed violence was recorded in the Spanish Pharmacovigilance Database (FEDRA®) from 1984 to 31 March 2021. A total of 710 cases were reported in the study period. The mean age was 45.52 years (range 1-94). There were no gender differences except in children, where most reports were of male children. The main therapeutic groups that were involved included drugs for the nervous system (64.5%) and anti-infectives for systemic use (13.2%). The most commonly reported drugs were varenicline, fluoxetine, lorazepam, escitalopram, venlafaxine, veralipride, pregabalin, roflumilast and bupropion. There were reports of montelukast, hydroxychloroquine, isotretinoin, methylphenidate, infliximab, natalizumab, ribavirin and efavirenz, which were less known to be involved in self-directed violence. This study shows that self-directed violence is a rare adverse drug reaction, and can be related to the use of some medicines. It is important for healthcare professionals to consider this risk in their clinical praxis, implementing person-centred approaches. Further studies are needed, considering comorbidities and potential interactions.
