Guía de práctica clínica para diagnóstico y tratamiento de Hemofilia en el Seguro Social del Perú (EsSalud)

Background: This article summarizes the clinical practice guide (CPG) for diagnosis and treatment of hemophilia in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the diagnosis and treatment of hemophilia in EsSalud. Material and Methods: A guideline development group (GDG) was formed, which included specialist physicians and methodologists, who formulated clinical questions. Systematic searches of systematic reviews were conducted and - when deemed relevant - primary studies in PubMed during 2020 and 2021. Evidence was selected to answer each of the proposed clinical questions. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts before its approval. Results: The CPG addressed 09 clinical questions, divided into 02 topics: diagnosis and treatment. Based on these questions, 05 recommendations were formulated (01 strong and 04 conditional), 51 points of good clinical practice, and 02 flow charts. Conclusion: Evidence-based recommendations were issued for the diagnosis and treatment of persons with hemophilia.Introducción: El presente artículo resume la guía de práctica clínica (GPC) para diagnóstico y tratamiento de hemofilia en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la hemofilia en EsSalud. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y –cuando fue considerado pertinente– estudios primarios en PubMed durante el 2020 y 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicasformuladas. Se evaluó la certeza de la evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos previa a su aprobación. Resultados: La GPC abordó 09 preguntas clínicas de diagnóstico y tratamiento. En base a dichas preguntas se formularon 05 recomendaciones (01 fuerte y 04 condicionales), 51 puntos de buena práctica clínica, y 02 flujogramas. Conclusión: Se emitieron recomendaciones basadas en evidencia para el diagnóstico y tratamiento de personas con hemofilia

ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19

Background: COVID‐19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants of severity but not among some types of symptoms. More importantly, very few studies analysed patients highly exposed to the virus that nonetheless remain uninfected. Methods: We analysed serum levels of ACE2, Angiotensin II and anti-Spike antibodies in 2 different cohorts at high risk of viral exposure, highly exposed but uninfected subjects, either high risk health care workers or persons cohabiting with infected close relatives and seropositive patients with symptoms. We tested the ability of the sera of these subjects to neutralize lentivirus pseudotyped with the Spike-protein. Results: We found that the serum levels of ACE2 are significantly higher in highly exposed but uninfected subjects. Moreover, sera from this seronegative persons can neutralize SARS-CoV-2 infection in cellular assays more strongly that sera from non-exposed negative controls eventhough they do not have anti-CoV-2 IgG antibodies suggesting that high levels of ACE2 in serum may somewhat protect against an active infection without generating a conventional antibody response. Finally, we show that among patients with symptoms, ACE2 levels were significantly higher in infected patients who developed cutaneous as compared with respiratory symptoms and ACE2 was also higher in those with milder symptoms. Conclusions: These findings suggest that soluble ACE2 could be used as a potential biomarker to predict SARS-CoV-2 infection risk and to discriminate COVID-19 disease subtypes.This research was funded by grants from “Ministerio de Ciencia e Innovación” (SAF2013-42850-R, SAF2016-75988-R and PID-2019104760RB-100; FEDER), “Comunidad de Madrid (S2017/BMD-3671. INFLAMUNE-CM; FEDER) to MF, Consejo Superior de Investigaciones Científica, CSIC (CSIC-COV19-108, SGL210235) to MF and UB, CRUE-Supera COVID, the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF), Merck, Sharp & Dohme Investigator Studies Program (code MISP# IIS 60257), and Fondo Supera COVID-19 (2020-001) to SS-V. Institutional grants from “Fundación Ramón Areces” and “Banco de Santander”. This research work was also funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global).Peer reviewe

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Impact of Adding a Rapid PCR-Based Blood Culture Identification Panel to the Antimicrobial Stewardship Program of Patients with Febrile Neutropenia in a Peruvian Referral Hospital

The addition of Biofire® FilmArray® Blood Culture Identification panel 2 (BCID2) to the antimicrobial stewardship program (ASP) could improve outcomes in bloodstream infections (BSI) of patients with febrile neutropenia (FN). A pre- and post-quasi-experimental single-center study was conducted at a reference hospital in Peru. Three groups were considered: patients with BSI before ASP intervention (control group), patients with BSI after ASP intervention (group 1), and patients with BSI after ASP intervention plus BCID2 PCR Panel implementation (group 2). Overall, 93 patients were identified (32 control, 30 group 1, 31 group 2). The median time to effective therapy was significantly shorter in group 2 compared to group 1 and control group, respectively (3.75 vs. 10 h, p = 0.004; 3.75 vs. 19 h, p p < 0.001). In addition to the lack of local studies documenting the microbiological profile of FN episodes, adding syndromic panels-based testing could allow for the consolidation of ASP strategies

Comprensión y Producción de Lenguaje II - HU544 - 202102

Descripción: Comprensión y Producción de Lenguaje 2 es un curso en el que el estudiante desarrolla sus habilidades para la comprensión lectora y la redacción de textos formales argumentativos en situaciones comunicativas determinadas. Para ello, emplea recursos de redacción que le permitirán una organización coherente, un desarrollo sólido y convincente (a partir de la lectura crítica de fuentes diversas), y una escritura respetuosa de la normativa y de la ortografía vigentes. Propósito: Este curso tiene como requisito Comprensión y Producción de Lenguaje 1. Desarrolla, siguiendo la política educativa propuesta por la UPC en SICA, la competencia Comunicación escrita en el nivel de logro 1. El propósito es que el estudiante pueda producir textos argumentativos coherentes y sustentados a partir de una evaluación crítica de la información. Esas habilidades le permitirán comunicarse de manera escrita para convencer acerca de sus propios puntos de vista en los demás cursos de sus carreras. Además, en el mundo laboral, le permitirá sustentar textualmente sus propuestas y proyectos de manera eficiente

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old