Curso de Extensão de Leitura Crítica de Artigos Científicos: relato de experiência

Resumo: objetivou-se relatar a experiência do Curso de Extensão de Leitura Crítica de Artigos Científicos. O relato foi elaborado a partir do projeto de extensão que visou a construção de um espaço para discussão sobre a leitura de artigos científicos. O curso envolveu a participação de estudantes universitários e profissionais da saúde. Foram realizados sete encontros, sendo três presenciais e quatro virtuais. Nos encontros presenciais, oportunizou-se a discussão de um texto, enviado previamente para que os participantes pudessem fazer as leituras. Nos encontros virtuais, foram utilizados disparadores para discussão por meio de um grupo formado em uma rede social

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

2006 GEP-ISFG collaborative exercise on mtDNA: reflections about interpretation, artefacts, and DNA mixtures

We report the results of the seventh edition of the GEP-ISFG mitochondrial DNA (mtDNA) collaborative exercise. The samples submitted to the participant laboratories were blood stains from a maternity case and Simulated forensic samples, including a case of mixture. The success rate for the blood stains was moderate (similar to 77%); even though four inexperienced laboratories concentrated about one-third of the total errors. A similar success was obtained for the analysis of mixed samples (78.8% for a hair-saliva mixture and 69.2% for a saliva-saliva Mixture). Two laboratories also dissected the haplotypes contributing to the saliva-saliva mixture. Most of the errors were due to reading problems and misinterpretation of electropherograms, demonstrating once more that the lack of a solid devised experimental approach is the main cause of error in mtDNA testing. (C) 2007 Elsevier B.V. All rights reserved

Simposio Internacional de Investigación Educativa y Pedagógica

El 4º. Simposio Internacional de Investigación Educativa y Pedagógica de la Red SUE Caribe, es un encuentro que reúne periódicamente a académicos nacionales y extranjeros de reconocida presencia y trayectoria, a estudiantes de maestría y doctorado y a maestros investigadores, que se concentran durante las jornadas agendadas del evento. Se constituye así un escenario propicio para la socialización de resultados de investigación, la reflexión y el debate alrededor de asuntos actuales en educación, pedagogía, psicología del aprendizaje, sobre las didácticas emergentes tecnología aplicada a la gestión de la enseñanza y el aprendizaje y en relación con el desarrollo humano y social.Presentación 12Líneas temáticas por mesas de trabajo 14Mesa 1. Didáctica, Mediación pedagógica y tecnologías en contextos vulnerables 15Percepciones sobre la influencia de un programa apoyado en TIC en relación con las prácticas de actividad física y deportiva de estudiantes de la Institución Educativa Rancho Grande de Montería. María Julia Caldera Quintero - Yina Paola Pérez Siyag 16Aplicación de estrategias cognitivas y metacognitivas en el uso del castellano escrito en estudiantes con discapacidad auditiva. Mercedes del Carmen Pico Aycardi 18Aprendizaje colaborativo con ambientes de liderazgo en el desarrollo del componente geométrico métrico. Lenis Judith Sierra Llorente – Juana Raquel Robles González 20Escenario de construcción conjunta del conocimiento mediado por las TIC en el área de filosofía en la Institución Educativa Normal Superior de Sahagún-Córdoba. Dayro Ruiz Araujo - Andrés Mercado Herazo 22Programa de formación docente para el mejoramiento de la lectura crítica de estudiantes de pregrado: una intervención formativa con docentes de la Universidad de Córdoba. Ibeth Morales Escobar – Arnaldo Peinado Méndez - Sonia Jerez Rodríguez 24Las prácticas de enseñanza. Un estudio interpretativo en las instituciones de la subregión sabanas del Departamento de Sucre, Colombia. Edy Luz Castro De Rodríguez 26Modelos pedagógicos y factores identitarios en las prácticas de enseñanza en contextos emergentes. Adriana Cristina Pérez Aguilar 28Rol del tutor durante los diálogos de reflexión desarrollados con futuros docentes mediatizados con video. Ceferina Cabrera Félix - Jesús Salcedo –Martha Serrata Taveras 30Desarrollo del pensamiento aleatorio a través de la utilización de un entorno virtual de aprendizaje en estudiantes de básica secundaria. Anny Leidys Valero Peña – Francisco Antonio Avilez Aguas – Juana Raquel Robles González 32Efectos de un programa de géneros textuales y la incidencia de factores sociodemográficos en los desempeños de lectura crítica. Diana Arroyo -Tatiana Becerra Posada – Antonio Oviedo Acosta 34El conocimiento glocal para alentar la confianza al hablar inglés: investigación-acción en una secundaria de Cartagena. Maryuris Vanessa Pérez Salcedo 36Los textos multimodales una estrategia didáctica para la inclusión educativa. Maura Paola Hoyos Carvajal - María Fernanda Martínez Garcés - Ludwig Isabel Segura Bermúdez 38Didáctica Ecoformadora para el desarrollo de la comprensión lectora de una lengua extranjera. Zaily Patricia Del Toro García 40Desarrollo de la competencia científica “indagación” a partir de la vivencia filosófica en los educandos de Básica Primaria. Un análisis desde sus fundamentos teóricos. Dina Villar Ortega - Nataly López Conde 42La estrategia metacognitiva y didáctica “Bitácora MAP” para el desarrollo del aprendizaje significativo en ciencias naturales en estudiantes del Alto San Jorge- Córdoba. Diana Sofía Blanquicet Arrieta - José Pantaleón Barrera Sierra 44Las concepciones del currículo y las prácticas curriculares de los docentes. Una revisión sistemática de literatura. Brianda Isabel Vergara Ibarra - Yisenia Lucía Vergara Vergara 46Implementación de metodologías activas en el fortalecimiento de competencias comunicativas en escenarios vulnerables. Liana Álvarez Cantero – José Antonio Sánchez Sánchez 48Estrategia pedagógica discursiva interactiva para el mejoramiento de la comprensión textual de estudiantes de básica primaria. Osvaldo Enrique Manjarrez Villalba - Ibeth Del Rosario Morales Escobar 50Proyecto pedagógico para mejorar la lectoescritura en los estudiantes de grado 5º aula multigrado. Miriam Albán Villarreal – María Dorila Díaz Valentierra 52La Oratoria como escenario pedagógico para el desarrollo de habilidades de pensamiento crítico: una apuesta en la virtualidad. María Andrea Baquero Escobar – Rudy Doria Correa 54Mesa 2. Pedagogía social, ética y desarrollo humano 56Prácticas discursivas en torno a la enseñanza de la Educación Religiosa: una perspectiva desde el educando. Cetty Carlos Benjumea Loaiza - Jesús Andrés Vélez Vélez 57Transversalidad de la formación en valores en las prácticas de enseñanza de docentes de básica secundaria en la institución etnoeducativa Los Córdobas. Emilio Elis Cogollo – Ezequías Balaguera Ortiz 59Mediaciones pedagógicas para el fortalecimiento de la convivencia escolar entre estudiantes, una revisión en el contexto educativo hispano parlante. Jesús Alberto Peñaranda Bastidas – José Tomas Fragozo Soto – Miladys Paola Redondo Marin 61La mediación como estrategia de convivencia escolar en la Institución Educativa Técnica Agropecuaria La Buena Esperanza del municipio de Turbaco – Bolívar. Cinthya Inés Martínez Mendoza 63Formación de maestros educadores para la paz desde la didáctica del conflicto para la inclusión educativa. Dilia Elena Mejía Rodríguez – Liris Múnera Cavadía 65Educación en derechos humanos desde el reconocimiento y humanismo del otro. Ledys Alcira Arrieta Perez – María Alejandra Taborda Caro 67Educación para la convivencia y la paz: Una mirada crítica desde la intervención docente. Decired Ojeda Pertuz 69El clima escolar en el diseño curricular: Una perspectiva que favorece la enseñanza - aprendizaje en instituciones educativas rurales de Cartagena de Indias, Colombia. Neisa del Carmen Gómez Diaz - Alexander Javier Montes Miranda 71La danza folclórica cómo satisfactor sinérgico de necesidades humanas en los estudiantes del grupo de danzas folclóricas sede Montería de la Universidad de Córdoba. Elaine Patricia Parra Martínez - Fernando De La Espriella Arenas 73La música, una estrategia didáctica para el fortalecimiento de las competencias ciudadanas. Marta Guerra Muñoz – Rosa Beatriz Gómez -Yamira Rodríguez 74Convivencia escolar desde la pedagogía de paz: estrategia didáctica a través de la lúdica. Hna. Olga Lucia Canchila Salcedo - Martha Pacheco Lora 76Mesa 3. Innovación educativa y pedagógica 78Mesa 3. Innovación educativa y pedagógica 78Objetos virtuales de aprendizaje para la formación profesional: una mirada desde los estudiantes de la Universidad del Atlántico. Mirna Patricia Bernal Martínez - Roberto Enrique Figueroa Molina - Melba Rosa Cuadrado Galán 80Las apuestas investigativas y el desarrollo profesional de los egresados de la Maestría en Educación SUE Caribe Universidad de Cartagena. Nadia Mallarino Miranda – Katia Martínez Morad 82Investigación y desarrollo profesional de los egresados de la Maestría en Educación SUE Caribe. Universidad de Cartagena, 2006-2018. Clara Inés Sagre Hernández 84Aprendizaje Invertido: autoinstrucción, evaluación formativa y desempeños de comprensión. Esteban Rodríguez Garrido 86Transformación de la praxis docente durante un programa de formación en Pedagogía de Géneros Textuales para la enseñanza de la lectura crítica. José David Herazo Rivera – Paula García Montes - Pedro Guerra Meza 88Estrategias didácticas basadas en laboratorios virtuales y presenciales en el aprendizaje de las leyes de Newton. Alberto Iriarte Pupo – Yessica Ortega Pérez - Lizeth Estrada Soto 90Impacto del uso de la estrategia "Leo y argumento" para el desarrollo de las habilidades del pensamiento crítico. Dairo de Jesus Bustamante de Hoyos – Paulo Emilio Fúnez Chávez 92Impacto de la mediación pedagógica virtual como contingencia ante situación de pandemia Covid-19 en la Institución de Educación Superior ITFIP. Mauren Andrés Guayara Ramírez - Luis Antonio Herrán Cardoso -Jimmy Alexander Vergara Rodríguez 94Origem da Escola Doméstica Dona Júlia e a influência do Grêmio Literário Júlia Lopes De Almeida no proceso implementação da instituição em Cuiabá/MT (1946-1947). Gabriella Moura da Silva – Nilce Vieira Campos Ferreira 96Uso de Tecnologías de la Información y la Comunicación (TIC) por docentes de educación primaria en atención a estudiantes en confinamiento por pandemia. Leida de la Rosa Rosa 98Resignificación de la praxis educativa para favorecer la competencia lectora desde la sistematización de experiencias docentes. Elia Marina Santuario Rada - Jorge Carlos Peinado Ballesteros 100Relación entre competencias mediáticas y saberes digitales en la formación de maestros. Claudia Saavedra - Dijibath Matallana Rodríguez – Karen Medina Jaime 102Las concepciones de evaluación de los docentes de ciencias naturales. Gina Violeta Verbel González 104Estrategias para la mejora del aprendizaje autónomo del alumnado de la Licenciatura en Educación Física. Sandy Portorreal - Atlas Osiris Sosa - Rudy Gilberto López 106Escuelas Normales: Instituciones formadoras de profesoras rurales en Cundinamarca 1950-1970. Nataly Rojas - Nilce Vieira Campos Ferreira 108Perspectivas teóricas del liderazgo escolar: una resignificación pedagógica del liderazgo transformacional y su contribución a la calidad educativa. Amalfi Rosales - Alexander Montes - Vladimir Figueroa Gutiérrez 110Gestión de prácticas educativas innovadoras desde un enfoque educativo STEM+A. Arnovis Alemán - Rainer Villarreal Contreras – Daniel Salas Álvarez 112La investigación, un camino para la transformación de las prácticas pedagógicas. Belkis Vergara Pérez 113Processo Histórico De Denominação Da Escola Estadual Da Polícia Militar “Tiradentes”. Junior Cézar Lopes dos Santos – Nilce Vieira Campos Ferreira 115Modelos de mediación para el análisis de datos educativos: Más allá de los modelos cuantitativos típicamente usados en las tesis de postgrado en Educación en Colombia. Claudia Patricia Ovalle Ramirez 117Mesa 4. Perspectivas neurocientíficas y abordajes psicosociales contemporáneos en educación 119Análisis de la relación entre inteligencia emocional y estrategias de afrontamiento en situaciones de acoso y cyberbullyng en universitarios. María Fernanda Méndez Losada - Isabel Alicia Sierra Pineda 121Emoción y academia: historias no contadas de las estancias doctorales. Harold Castañeda Peña - Pilar Méndez - Carmen Helena Guerrero 123La conciencia fonológica en la enseñanza de la lectura en estudiantes de grado primero de la Institución Educativa Santa María Goretti en Montería. María Victoria González Zapa 125Estrategias educativas para promover competencias socioemocionales en los estudiantes articulando procesos pedagógicos y evaluativos. Becky Román Pérez 127La competencia docente de análisis de idoneidad didáctica en futuros profesores de matemáticas al planificar la enseñanza. Juan Alberto Barboza Rodríguez - Walter Fernando Castro Gordillo 129Pensamiento pedagógico en la Educación Superior del departamento de Córdoba 1951-2019. Carolina Castellanos Ramos 131Concepciones y Creencias de futuros profesores de matemáticas sobre la enseñanza y evaluación al planificar clases en el componente geométrico métrico. José Luis Acosta Pérez - Juan Alberto Barboza Rodríguez 133Comprensión de la incidencia formativa de un grupo de maestros de Ciencias Sociales a través de narrativas biográficas en el departamento de Córdoba. María Andrea Acosta García - Daniel David Chimá Arroyo 135Percepciones de los docentes de una institución privada de Montería, sobre la implementación del modelo pedagógico institucional, incluyendo sus prácticas de aula. Keila Paola Ramos Buelvas 137Indagación narrativa de la identidad profesional del docente de Tecnología e Informática: Tensiones y reflexiones en la construcción cotidiana del currículo. Atahualpa Villadiego Alvarez 139Autopercepción de los docentes sobre neurociencia y transferencia a la didáctica de las ciencias: un estudio fenomenográfico. Claudia Patricia Mercado Aguado - Isabel Alicia Sierra Pineda 140Mesa 5. Multiculturalidad, diversidad y educación inclusiva 142Formación inclusiva: concepciones y prácticas pedagógicas en docentes de educación superior. Roberto Figueroa Molina – Mirna Patricia Bernal Martínez - Roberto Thorné Torné 144La Escuela: Un lugar en la cartografía y en los imaginarios de las Ciencias Sociales. Daniel Antonio Pérez Cerro – Luis Alfredo González Monroy – Iván Manuel Sánchez Fontalvo 146Lineamientos para incorporar la política de inclusión social en los planes de acción del plan de desarrollo en el municipio de El Charco de Nariño. Aura Pérez Caicedo - Delia De la Hoz – Robinson Rafael Peña Almeida 148Inclusión de estudiantes en situación de discapacidad en una Institución Educativa: visiones desde la ruralidad. Leidy Sofía Peñata Doria 150Percepciones sobre la discapacidad física en las clases de educación física en Montería. Heider Ramiro Díaz Better - Cleiber Eusse López 152Framework basado en gestión de conocimiento para la salvaguarda de la lengua embera. Ernesto Llerena García – Manuel Caro Piñeres 154Educación inclusiva: una oportunidad para la transformación de la escuela rural. Liliana María Escobar Guerra - Isabel Hernández Arteaga – Henry David Uribe Londoño 156Ciudadanía Planetaria. Una mirada desde la multiculturalidad y la interculturalidad. Milton Fabián Badel Gómez 158Nivel de apropiación de la Competencia Tic e Intercultural en docentes de básica primaria del departamento del Atlántico. Nathaly Sofía Daza Morales 160El sistema pictográfico como medio para fomentar la comunicación de estudiantes con Síndrome de Down en el entorno escolar. Evis Danith Ariza Jiménez 162Literatura infantil y deporte inclusivo: estrategias didácticas para fomentar la inclusión, el respeto a la diferencia y a la diversidad en la educación infantil. Jesús Kerguelén - Luisa Fernanda Llorente Vergara - Luis Pacheco Lora 164Modelos de enseñanza de los docentes de música Vallenata en la Facultad de Bella Artes, Universidad Popular del Cesar. Juan De La Rosa López – Camilo Andrés Andrade Guerra – Martha Guerra Muñoz 166Enseñando fracciones desde un aula inclusiva: fracciones para no fraccionarnos. Silvia Madera - Nasly Ruíz – Ángel Viloria - Heidy Esperanza Gordillo 168Escenarios para la apropiación patrimonial con tecnologías digitales en Santa Cruz de Lorica. Jacob Vargas Arteaga 1701 Edició

Make EU trade with Brazil sustainable

Brazil, home to one of the planet's last great forests, is currently in trade negotiations with its second largest trading partner, the European Union (EU). We urge the EU to seize this critical opportunity to ensure that Brazil protects human rights and the environment

Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

© 2020 Elsevier Ltd. All rights reserved.Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.info:eu-repo/semantics/publishedVersio

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable