Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection : A Spanish, Multicenter, Cohort Study

We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality. We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed. During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094). These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results. European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415 The online version of this article (10.1007/s40121-020-00373-8) contains supplementary material, which is available to authorized users

Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study)

Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. Methods: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. Results: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. Conclusion: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics

Prescripción de inhibidores de acetilcolinesterasa y memantina en Canarias: comparación con la población española

Fundamentos: En Canarias las recetas facturadas al Sistema Nacional de Salud están registradas en una base de datos (FarmaCanarias). El objetivo principal de este estudio fue calcular el consumo de inhibidores de la acetilcolinesterasa (IACE) y memantina en Canarias y compararlo con una muestra representativa de la población española procedente de la Base de Investigación Farmacoepidemiológica en Atención Primaria (BIFAP). Como objetivo secundario determinamos el porcentaje de casos tratados en la muestra española. Métodos: Las prescripciones de IACE y/o memantina se calcularon como Dosis Diarias Definidas por 100 habitantes (DHD) en FarmaCanarias y en BIFAP. Se calcularon los resultados por isla y también se compararon por grupos de edad. Los casos tratados se calcularon como porcentaje sobre los casos con demencia totales en BIFAP. Todas las comparaciones fueron efectuadas con la χ2 de Pearson. Resultados: El consumo de IACE y Memantina fue de 3,042% (IC 95%; 3,039-3,045) y 1,584% (IC 95%; 1,582-1,587) en Canarias, respectivamente y de 2,545% (IC 95%; 2,518-2,572) y 0,922% (IC 95%; 0,906-0,938), en BIFAP (p<0,001). Las DHD entre islas fueron diferentes, salvo en dos (p<0,001). La distribución por grupos de edad entre FarmaCanarias y BIFAP fue heterogénea (p<0,001). El porcentaje de casos tratados en BIFAP fue: 45,51% (IC 95%; 45,186-45,838). Conclusiones: La prescripción de IACE y Memantina fue mayor en Canarias lo que, añadido a la diferencia por grupos de edad, sugiere diferencias epidemiológicas en demencia frente al resto de España. Existe heterogeneidad entre islas que podría deberse a factores epidemiológicos, de proveedor o del Servicio Público de Salud

Generation of the antioxidant hydroxytyrosol from tyrosol present in beer and red wine in a randomized clinical trial

Beer and wine contains the simple phenol tyrosol (TYR) which is endogenously converted into hydroxytyrosol (HT), one of the strongest dietary antioxidants, by CYP2A6 and CYP2D6 polymorphic enzymes. We investigated in humans the rate of this bioconversion after beer and red wine (RW) intake. In a single blind, randomized, crossover, controlled clinical trial (n = 20 healthy subjects), we evaluated TYR absorption and biotransformation into HT following a single dose of (i) RW, (ii) Indian pale ale beer (IPA), (iii) blonde beer, and (iv) non-alcoholic beer (free). Individuals were genotyped for CYP2A6 and CYP2D6, and a polygenic activity score (PAS) was derived. RW triggered the highest increase in total TYR recovered, followed by IPA, blonde, and free beers. Although the HT content in beer was minimal, an increase in HT production was observed in all beers following TYR in a dose-response manner, confirming TYR to HT biotransformation. Sex differences were identified in the rate of the conversion following RW. PAS scores correlated linearly with the recoveries of HT (HT:TYR ratios) after RW intake. In conclusion, after beer and RW consumption, TYR is absorbed and endogenously biotransformed into HT. This mechanism could be modulated by sex, genetics, and matrix components

Study Design and Rationale of “A Multicenter, Open-Labeled, Randomized Controlled Trial Comparing MIdazolam Versus Morphine in Acute Pulmonary Edema”: MIMO Trial

Purpose: Morphine has been used for several decades in cases of acute pulmonary edema (APE) due to the anxiolytic and vasodilatory properties of the drug. The non-specific depression of the central nervous system is probably the most significant factor for the changes in hemodynamics in APE. Retrospective studies have shown both negative and neutral effects in patients with APE and therefore some authors have suggested benzodiazepines as an alternative treatment. The use of intravenous morphine in the treatment of APE remains controversial. Methods: The MIdazolan versus MOrphine in APE trial (MIMO) is a multicenter, prospective, open-label, randomized study designed to evaluate the efficacy and safety of morphine in patients with APE. The MIMO trial will evaluate as a primary endpoint whether intravenous morphine administration improves clinical outcomes defined as in-hospital mortality. Secondary endpoint evaluation will be mechanical ventilation, cardiopulmonary resuscitation, intensive care unit admission rate, intensive care unit length of stay, and hospitalization length. Conclusions: In the emergency department, morphine is still used for APE in spite of poor scientific background data. The data from the MIMO trial will establish the effect—and especially the risk—when using morphine for APE.Sin financiación2.771 JCR (2017) Q2, 56/128 Cardiac and Cardiovascular Systems, 111/261 Pharmacology and PharmacyUE

Cardioprotection with melatonin in the acute myocardial infarction: Awaiting results of MARIA trial?

Sin financiación4.638 JCR (2015) Q1, 20/124 Cardiac and Cardiovascular SystemsUE