Pharmacovigilance in children in Camagüey Province, Cuba

Purpose: Our aim was to describe the adverse drug reactions (ADRs) detected following increased education about pharmacovigilance and drug toxicity in children in Camagüey Province, Cuba. Methods: Over a period of 24 months (January 2009 to December 2010), all reports of suspected ADRs in children to the Provincial Pharmacovigilance Centre in Camagüey Province were analysed. ADRs were classified in relation to causality and severity. Results: There were 533 reports involving suspected ADRs in children in the period. Almost one third of the reports received were classified as moderate (155, 29%) or severe (10, 2%). There was one fatality in association with the use of ceftriaxone. Vaccines and antibiotics were responsible for most of the ADR reports (392, 74%) and for all ten severe ADRs. After an intensive educational package, both within the community and the Children’s Hospital, the number of reports increased from 124 in 2008 to 161 in 2009 and 372 in 2010. This was equivalent to a reporting rate of 879 and 2,031 reports per million children per year for 2009 and 2010, respectively. Conclusions: The incidence of ADRs in children Camagüey Province, Cuba, is greater than previously reported. An educational intervention about pharmacovigilance and drug toxicity in children can improve the reporting of ADRs

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4

[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE‐associated discontinuation events occurred in 5.9% and 2.6%. Conclusions. In this large cohort of cirrhotic patients managed in the real‐world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.Instituto de Salud Carlos III; PI15/0015

Activities of Women in Physics group in Spain

In this paper we present the activities of the Spanish Women in Physics group during the past three years. We also describe the relevant equality measures adopted by the Spanish Government and its impact on the status of women in science. The data show an alarming decrease in the number of graduate female students at the universities, although for senior researchers and professors, the percentage of women at the different staff levels remains approximately constant.Peer reviewe

Effectiveness of amino-functionalized sorbents for co2 capture in the presence of Hg

The reduction of CO2 emissions is an urgent need that is acknowledged worldwide. Amino-silica sorbents are one of the most promising adsorbents for capturing CO2 from several gas streams due to their excellent textural properties and reversible reactions with CO2. However, gas streams also contain impurities that can affect the retention of CO2 by such sorbents. This study focuses on the effect of the presence of mercury in the gas stream on a series of amino sorbents developed for CO2 capture. Amino-silica adsorbents were functionalized by grafting with aminopropyl-trimethoxysilane (AP) or trimethoxysilylpropyl-diethylenetriamine (DT) and by impregnation with polyethyleneimine (PEI) or tetraethylenepentamine (TEPA). A double functionalization route that combines grafting and impregnation was also assayed. The effect of mercury on the CO2 adsorption capacity of the sorbents was evaluated in a fixed reactor at 40 °C. The double-functionalized adsorbents showed high CO2 uptakes with CO2 adsorption capacities of 5–6 mmol CO2/g (0.15 bar CO2, 40 °C). In addition, their CO2 adsorption capacity was maintained over several cycles. It was established that the presence of mercury undermined the CO2 adsorption capacity of the adsorbents by just 3–16%, demonstrating in general the good selectivity of these materials for CO2, an essential requirement for avoiding the accumulation of mercury during the regeneration process of the solid sorbent and the consequent environmental and technological problems that might ensue.The authors acknowledge the financial assistance received under project GRUPIN ID2018-000234 and thank the Spanish Ministry of Economy and Competitiveness for awarding a “Ramón y Cajal” postdoctoral contract (RYC-2013-12596) to M.A. López-Antón.Peer reviewe

Leishmanicidal and reversal multidrug resistance constituents from Aeonium lindleyi

A new bicyclic diterpene with a labdane skeleton, 7-oxo-labd-8-en-15-ol (1), along with two known diterpenes and ten flavonoids were isolated from the leaves of Aeonium lindleyi (Crassulaceae). Their structures were elucidated on the basis of spectroscopic data, including 1D and 2D NMR experiments, and comparison with spectroscopic data reported in the literature. Labdan-8α,15-diol (2) and labd-8(17)-en-3β,15-diol (3) showed leishmanicidal activity against Leishmania tropica (IC50 = 77.0 μ M) and Leishmania braziliensis (IC50 = 68.0 μ M) similar to ketoconazole used as positive control. 5,3-Dihydroxy-3,7,4,5-tetramethoxyflavone (8) and combretol (9) showed moderate activity (growth inhibition 87.3 and 73.0 %, respectively, at 50 μ M) against a multidrug-resistant L. tropica line. © Georg Thieme Verlag KG Stuttgart - New York.Peer Reviewe

Discovery of amoebicidal compounds by combining computational and experimental approaches

36 p.-6 fig.-4 tab.Pathogenic and opportunistic free-living amoebae such as Acanthamoeba spp. can cause keratitis (Acanthamoeba keratitis [AK]), which may ultimately lead to permanent visual impairment or blindness. Acanthamoeba can also cause rare but usually fatal granulomatous amoebic encephalitis (GAE). Current therapeutic options for AK require a lengthy treatment with nonspecific drugs that are often associated with adverse effects. Recent developments in the field led us to target cAMP pathways, specifically phosphodiesterase. Guided by computational tools, we targeted the Acanthamoeba phosphodiesterase RegA. Computational studies led to the construction and validation of a homology model followed by a virtual screening protocol guided by induced-fit docking and chemical scaffold analysis using our medicinal and biological chemistry (MBC) chemical library. Subsequently, 18 virtual screening hits were prioritized for further testing in vitro against Acanthamoeba castellanii, identifying amoebicidal hits containing piperidine and urea imidazole cores. Promising activities were confirmed in the resistant cyst form of the amoeba and in additional clinical Acanthamoeba strains, increasing their therapeutic potential. Mechanism-of-action studies revealed that these compounds produce apoptosis through reactive oxygen species (ROS)-mediated mitochondrial damage. These chemical families show promise for further optimization to produce effective antiacanthamoebal drugs.Funding from RICET (RD16/0027/0010) and (RD16/0027/0001), FEDER funds (PI18/01380), MECD (Grant FPU15/1465 to V. S.-P.) is acknowledged, M. R. B. was also funded by RICET and I. S. was funded by Agustin de Betancourt Programme.Peer reviewe

Therapeutic Potential of a Combination of Two Gene-Specific Small Interfering RNAs against Clinical Strains of Acanthamoeba▿

Pathogenic strains of the genus Acanthamoeba are causative agents of severe infections, such as fatal encephalitis and a sight-threatening amoebic keratitis. Antimicrobial therapy for these infections is generally empirical, and patient recovery is often problematic, due to the existence of a highly resistant cyst stage in these amoebae. In previous studies, small interfering RNAs (siRNAs) against the catalytic domains of extracellular serine proteases and glycogen phosphorylase from Acanthamoeba were designed and evaluated for future therapeutic use. The silencing of proteases resulted in Acanthamoeba failing to degrade human corneal cells, and silencing of glycogen phosphorylase caused amoebae to be unable to form mature cysts. After the siRNA design and concentration were optimized in order to avoid toxicity problems, cultures of Acanthamoeba were treated with a combination of both siRNAs, and cells were evaluated under an inverted microscope. This siRNA-based treatment dramatically affected the growth rate and cellular survival of the amoebae. These results were observed less than 48 h after the initiation of the treatment. In order to check possible toxic effects of the siRNA combination, three eukaryotic cell lines (HeLa, murine macrophages, and osteosarcoma cells) were treated with the same molecules, and cytotoxicity was examined by measuring lactate dehydrogenase release. The future use of the combination of these siRNAs is proposed as a potential therapeutic approach against pathogenic strains of Acanthamoeba

Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predni(so)lone administration

In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options.This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047).In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.Copyright © 2023 American Association for the Study of Liver Diseases