Supporting Pharmacovigilance Signal Validation and Prioritization with Analyses of Routinely Collected Health Data: Lessons Learned from an EHDEN Network Study

Introduction: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals. Objective: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process. Methods: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals. Results: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15–60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development. Conclusions: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost–benefit of integrating these analyses at this stage of signal management requires further research

A chromosome-level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex-determining gene in the flatfish Solea senegalensis

Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testisEuropean Union's Horizon 2020 research and innovation programme under grant agreement (AQUA-FAANG). Grant Number: 81792. Junta de Andalucía-FEDER Grant. Grant Number: P20-00938. Spanish Ministry of Economy and Competitiveness, FEDER Grants. Grant Numbers: RTI2018-096847-B-C21, RTI2018-096847-B-C22S

Assessment of Pablo de Olavide University's Alignment with the 2030 Agenda. A Diagnosis from Seville, Spain

Document compiled by staff from Pablo de Olavide University of Seville (UPO), with technical assistance from Periferia Consultoría Social. This project has been funded with support from the European Commission.Versión española del documento en: https://dx.doi.org/10.46661/rio.20230630_1Recognizing the crucial role of universities in implementing the 2030 Agenda, the Pablo de Olavide University (UPO) has conducted a comprehensive assessment to evaluate its alignment and contribution towards achieving the Targets defined within the 17 Sustainable Development Goals (SDGs). The 2030 Agenda presents a dual mandate for universities. Firstly, they are tasked with integrating the SDGs into their educational and research programs. Secondly, they are expected to act as catalysts for societal transformation and promote a governance model in higher education that aligns with the Agenda's objectives. In light of these responsibilities, UPO has recognized the need to equip itself with the necessary tools to effectively assess the fulfillment of these mandates. This accountability is crucial for demonstrating UPO's commitment to the SDGs and for enhancing the effectiveness of its actions within the framework of the Agenda. This document provides a summary of the process undertaken by UPO, in collaboration with Periferia Social Consulting, between November 2022 and May 2023. The objective was to design a set of indicators that can measure UPO's contribution to the 2030 Agenda. The first section describes the methodology and various phases involved in the process. Following that, the document presents the system of indicators developed and provides information on UPO's contribution to the 2030 Agenda for the academic year 2021-2022. In the annexes, two posters are included, displaying the complete set of indicators and the measurements made for the 2021-2022 academic year.Universidad Pablo de Olavid

Diagnóstico sobre alineamiento de la Universidad Pablo de Olavide de Sevilla con la Agenda 2030

Documento elaborado por el Grupo Interno de la UPO, con la asistencia técnica de Periferia Consultoría Social, y la financiación de la Agencia Andaluza de Cooperación Internacional.Versión inglesa del documento en: https://dx.doi.org/10.46661/rio.20230718_1Consciente del papel clave que juegan la universidades en la implementación de la Agenda 2030, la Universidad Pablo de Olavide (UPO) plantea realizar un diagnóstico para conocer el grado de alineamiento y contribución a la consecución de las metas englobadas en los 17 ODS que conforman dicha Agenda. La Agenda 2030 marca un doble mandato a las Universidades; por un lado, incorporar los ODS en el ámbito de la formación y la investigación y por otro, como agente transformador de la sociedad y modelo de gobernanza en Educación Superior. En este sentido, la UPO necesita dotarse de las herramientas necesarias con las que poder determinar cómo se están cumpliendo efectivamente estos mandatos, con la finalidad tanto de rendir cuentas sobre su contribución al cumplimiento de los ODS y de mejorar la eficacia de sus actuaciones en el marco de dicha Agenda. Este documento es un resumen del proceso que desde la UPO con el apoyo de Periferia Consultoría Social se ha llevado a cabo entre los meses de noviembre 2022 y mayo 2023 para la construcción de un Sistema de Indicadores que permite medir la contribución de la UPO a la Agenda 2030. En un primer apartado, se describe la metodología y distintas fases llevadas a cabo; a continuación, se presenta el sistema de indicadores construido y la información sobre la contribución de la UPO a la Agenda 2030 para el curso 2021-2022. En anexos, se pueden encontrar las fichas metodológicas de cada uno de los indicadores que conforman el sistema; así como, dos poster donde visualizar el conjunto de indicadores y la medición realizada para el curso 2021-2022.Universidad Pablo de Olavid

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Caminando en la ruta sentipensante: configuración de experiencias pedagógicas nivel inicial

494 páginasEste texto es realizado en el contexto del Plan de Desarrollo 2016 – 2020, “Bogotá mejor para todos”, en el que se señala: Bogotá es entendida como una ciudad educadora, en la que todos los ciudadanos son agentes educadores y todos los espacios pueden ser escenarios pedagógicos para el aprendizaje. Una ciudad educadora tiene como centro el conocimiento e inspira aprendizaje, formas y lenguajes para reconocernos, para reencontrarnos; los espacios para el aprendizaje son entendidos como espacios para la vida, en los que se posibilita la investigación y la innovación para vivir mejor, para reinventarnos como ciudad, una ciudad mejor para todos. Los dieciocho textos aquí presentados, fruto del acompañamiento pedagógico realizado por el IDEP en 2019, son base y referente para seguir aportando en la configuración y consolidación de comunidades de saber y práctica pedagógica de la ciudad, así como en la conformación de colectivos y redes de maestros. Son la evidencia de un potente trabajo de acompañamiento a experiencias de nivel inicial, caracterizadas por contar con ideas o avances para problematizar, estructurar, fundamentar, elaborar estrategias y un plan de acción

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Artistas sobre outras obras

A pós modernidade encerra a interrogação crítica do homem sobre o homem: a linguagem ameaça o que é significante, o que é corpo. O sujeito é falado, e assim constituído depois da linguagem (Althusser, 1976). O jovem Arthur Rimbaud sintetiza-o, aos dezassete anos, numa carta ao seu professor de retórica Georges Izambard, datada de 13 de maio 1871: «C’est faux de dire: je pense: on devrait dire on me pense. Pardon du jeu de mots. Je est un autre». (Rimbaud, 1999: 237) A identidade resiste à linguagem dos homens. A linguagem é transmitida entre as gerações e com ela transporta os sujeitos, ou, o que é dizer o mesmo, a possível interrogação: quem me fala? É esta também a perplexidade que motivou o tema desta revista Estúdio. Reuniram-se, nesta edição, 22 artigos, provenientes de diferentes autores da Argentina, Brasil, Portugal e Espanha, que se debruçam sobre artistas cuja identidade se mostra e merece ser interrogada: são espaços ‘ex-cêntricos,’ para se descobrir.info:eu-repo/semantics/publishedVersio

Guía de práctica clínica para la prevención, diagnóstico, tratamiento y rehabilitación de la falla cardiaca en población mayor de 18 años, clasificación B, C y D

La falla cardíaca es un síndrome clínico caracterizado por síntomas y signos típicos de insuficiencia cardíaca, adicional a la evidencia objetiva de una anomalía estructural o funcional del corazón. Guía completa 2016. Guía No. 53Población mayor de 18 añosN/