Comunicação de notícias difíceis em um hospital universitário : desafios e possibilidades na formação médica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Psicologia, Programa de Pós-Graduação em Psicologia Clínica e Cultura, 2020.Notícias difíceis são quaisquer informações que afetem seriamente e de forma adversa a visão de um indivíduo sobre o seu futuro. Na saúde, elas são hipóteses diagnósticas de condições clínicas (agudas ou crônicas), com prognóstico limitado, terapia desfavorável de quadros irreversíveis (sequelas) ou sem tratamento modificador do curso da doença, (assistência paliativa, óbito). Aos médicos é atribuída a competência de comunicá-las, mas nem sempre eles se sentem preparados e motivados a fazê-la. Assim, realizou-se uma pesquisa descritiva-exploratória, de caráter qualitativo, com objetivo de compreender como ocorre a preparação de médicos residentes para comunicar notícias difíceis em um hospital universitário do Distrito Federal. Participaram 19 médicos dos programas de residência em Cirurgia Geral, Clínica Médica, Ginecologia e Obstetrícia e Pediatria, dentre staffs, R1, R2 e R3, que responderam a uma entrevista semiestruturada com 10 perguntas. Compôs a coleta dos dados uma pesquisa documental dos projetos pedagógicos dessas residências, analisando carga horária, objetivos associados à comunicação de notícias difíceis, cenários de atuação hospitalar e disciplina sobre comunicação de notícias difíceis, assim como os registros vivenciais da pesquisadora em campo. A análise das entrevistas usou como método o discurso do sujeito coletivo (DSC). Os participantes relataram etapas preparatórias dos protocolos SPIKES e P-A-C-I-E-N-TE. A falta de espaço privativo para conversar, a reação comportamental do paciente ou da família, as barreiras de comunicação e as interferências familiares foram as dificuldades mais apontadas. A tentativa de providenciar um ambiente adequado, checar com o paciente o que ele já sabe, o apoio familiar, o apoio da equipe multiprofissional e o linguajar acessível foram as estratégias mais citadas. Para aprimoramento dos programas, os residentes apontaram a necessidade de treinamento médico, o suporte da equipe multiprofissional, a realização de grupos de apoio e discussão com apoio matricial, enquanto os staffs sinalizaram a possibilidade de aulas com a Psicologia para orientação teórica e técnica quanto a abordagem dessas notícias. Por fim, a educação interprofissional em saúde surgiu como fator relevante para a abordagem e prática dessas comunicações.Difficult news are any information that seriously and adversely affect an individual's view of their future. In health, they are diagnostic hypotheses of clinical conditions (acute or chronic), with limited prognosis, unfavorable therapy for irreversible conditions (sequelae) or without treatment that changes the course of the disease (palliative care, death). Physicians are empowered to communicate them, but they are not always prepared and motivated to do so. Thus, a qualitative descriptive-exploratory research was carried out with the objective of understanding how the preparation of resident doctors to communicate difficult news occurs in a university hospital in the Federal District. Nineteen physicians from the residency programs in General Surgery, Internal Medicine, Gynecology and Obstetrics and Pediatrics participated, among staffs, R1, R2 and R3, who answered a semi-structured interview with 10 questions. The data collection comprised a documentary research of the pedagogical projects of these residences, analyzing the workload, objectives associated with the communication of difficult news, scenarios of hospital activities and discipline on communication of difficult news, as well as the experimental records of the researcher in field. The analysis of the interviews used the collective subject discourse (CSD) as a method. Participants reported preparatory steps for the SPIKES and P-A-C-I-E-N-TE protocols. The lack of private space to talk, the patient's or family's behavioral reaction, communication barriers and family interference were the most pointed difficulties. The attempt to provide an adequate environment, check with the patient what he already knows, family support, support from the multidisciplinary team and accessible language were the most cited strategies. To improve the programs, the residents pointed out the need for medical training, the support of the multidisciplinary team, the holding of support groups and discussion with matrix support, while the staffs signaled the possibility of classes with Psychology for theoretical and technical guidance regarding approach to these news. Finally, interprofessional health education emerged as a relevant factor for the approach and practice of these communications

Comunicação de notícias difíceis: o papel da relação dos médicos com a família

O processo de comunicar más notícias a familiares constitui-se como um desafio para profissionais da saúde. Assim, este trabalho teve como objetivo apresentar os relatos de médicos em relação ao processo de comunicar notícias difíceis às famílias e envolveu uma amostra de 19 médicos dos programas de residência do Hospital Universitário de Brasília (HUB), entre eles 15 residentes e 4 staffs das áreas de Cirurgia Geral, Clínica Médica, Ginecologia e Obstetrícia e Pediatria. Os dados foram coletados a partir de entrevistas semiestruturadas e posteriormente analisados com o método do Discurso do Sujeito Coletivo. Os resultados apontam dificuldades em comunicar notícias difíceis aos familiares e em manejar suas reações, sendo a atenção e o cuidado com a singularidade de cada família uma estratégia importante. A partir disso, é possível concluir a necessidade de implementação, na formação médica, o preparo para comunicar notícias difíceis a pacientes e familiares

I Congresso Ibero-Americano de Bibliotecas Escolares

Actas de la primera edición del I Congreso Iberoamericano de Bibliotecas Escolares, CIBES 2015, organizado por la Universidad Carlos III de Madrid (España), la Universidad Estatal Paulista (Brasil) y el Ayuntamiento de Getafe (España). Celebrado: 21 - 23 de octubre de 2015 en la Universidad Estatal Paulista (Marília) y 26 - 28 de octubre de 2015 en la Universidad Carlos III de Madrid (Getafe)Universidad Carlos III de Madrid (España)Universidad Estatal Paulista (Brasil)Ayuntamiento de Getafe (España)Dimensiones y visiones de la biblioteca escolar en una Educación por competencias: la necesidad de una política estratégica / Miguel Ángel Marzal. -- Getafe ciudad educadora, lectora y escritora: Bibliotecas escolares / Lourdes Muñoz Santiuste. -- Presente y futuro: biblioteca escolar-CREA y proyectos interdisciplinares / Rosa Piquín. -- Cultura en información: un reto esencial de la biblioteca escolar / Mónica Baró. -- Bibliotecas escolares de Galicia: un mundo de oportunidades a favor de la Educación / Cristina Novoa. -- 10 años de la Red de Bibliotecas Escolares de Extremadura (REBEX) / Casildo Macías Pereira. -- Biblioteca Escolar y uso ético de la información para una Cultura de Paz / Ana Barrero Tíscar. -- Dinamización de la Biblioteca Escolar Plumita durante el curso escolar 2014/15 / María Antonia Cano Cañada. -- Experiencia de la creación de una biblioteca escolar / Susana Santos Martín. -- Grupo cooperativo Bibliotecas escolares en Red-Albacete / José Manuel Garrido Argandoña y Eva Leal Scasso. -- La BCREA "Juan Leiva". El fomento de la lectura desde la web social / Andrés Pulido Villar. -- Proceso de implantación de una herramienta de autoevaluación en la red de bibliotecas escolares de Extremadura (REBEX) / Casildo Macías Pereira. -- La biblioteca escolar: abriendo fronteras / Lorena Verónica Cabrera Orellana. -- O programa RBE e a avaliaçao das bibliotecas escolares: melhoria, desenvolvimiento e innovaçao / Elsa Conde. -- Profesional de Biblioteconomía y Documentación: esencial en la plantilla de la escuela / Pilar del Campo Puerta. -- Una mirada activa al proceso educativo desde la biblioteca escolar / María Jesús Fontela Fernández . -- Con otra mirada "La ilustración como vehículo de comunicación y aprendizaje en las bibliotecas escolares" / Pablo Jurado Sánchez-Galán. -- Fingertips. Recriar a biblioteca escolar na sala de aula / Rui Alfonso Mateus. -- Hablemos de libros. Cómo transformar una clase de literatura en una comunidad de interpretación de textos / Francisco César Díaz Rey. -- Inclusión social de familias inmigrantes a través de un programa de aprendizaje de la lengua castellana / Ana Carmen Tolino Fernández-Henarejos. -- O desenvolvimento de atividades de mediação de leitura em biblioteca escolar: o caso da biblioteca da Escola Sesc de Ensino Médio / Vagner Amaro. -- La biblioteca escolar. Proceso de enseñanza-aprendizaje de padres a hijos / Ana Carmen Tolino Fernández- Henarejos. -- Leo con y para los demás / Ismael Fernández Fernández, Ana María Moreno Vicente y Ana Beatriz Vicente Pérez. -- Nanas y arrullo. Poesía a la deriva / Bernardo Fuentes Navarrete y Carlos García-Romeral Pérez. -- Gestión y evaluación de servicios bibliotecarios para personas con dislexia: una biblioteca escolar inclusiva desde una perspectiva internacional / Carmen Jorge García-Reyes. -- Sueños lectores compartidos hechos realidad: la biblioteca escolar del C.E.I.P-S.E.S-A.A “LA PAZ” de Albacete / Ana Rosa Cabañero Tobarra, Juan Manuel Herráez, Eva Leal Scasso, María Marín Sánchez, Ana Belén Medrano Martínez y María José Nortes Ruipérez. -- El programa biblioteca escuela en Civican. La literatura como elemento motivador para la alfabetización informacional / Villar Arellano Yanguas. -- La competencia digital en el diseño curricular: desde la biblioteca al aula / Felicidad Campal García. -- O deselvomimento da pesquisa escolar por meio da competência em informaçao / Luciane de Fátima Cavalcante Beckman y Marta Leandro da Mata. -- Proyecto escolar de investigación documental "Te pillé leyendo" / José Manuel Garrido Argandoña. -- Aprender com a Biblioteca Escolar: formar para as literacias / Paula Correia y Isabel Mendinhos. -- Sucedió en el siglo XX / María Antonia Becerra Montalbán, Ángel Bernabé Muñoz y Sofía Vaz Romero. -- El Club de lectura en la nube / Belén Benito Blázquez y Ana Ordás García. -- Promover a leitura e a escrita na era digital: prácticas nas bibliotecas escolares / María Raquel Ramos. -- A biblioteca escolar e o desafío da interculturalidade: o projeto Ser + cidadao / María da Conceição Tomé. -- Cuando la competencia digital encontró a la alfabetización informacional o Mucho ruido y pocas nueces / Felicidad Campal García. -- Hora de ler, un programa para el fomento de la lectura en contexto educativo / Cristina Novoa. -- Hábitos de lectura para las competencias en información y alfabetización en información en bibliotecas escolares de Puerto Rico / Karen Denise Centeno Casillas. -- Repositorios digitales en las bibliotecas escolares andaluzas: situación, modelos y herramientas para su creación / Dolores Olmos Olmos y Andrés Pulido Villar. -- Trabajando las competencias clave con las aventuras de Mozarito en Extremadura / María Teresa Carballosa González y María Esther Nieto Vidal. -- Análisis de modelos de evaluación de la web de la biblioteca escolar / Raúl Cremades García. -- Emociónate con las historias: El bosque de las emociones e historias con mucho teatro / Esther Luis Pérez y Ana María Peromingo Fernández. -- Biblioteca escolar de innovación y continuación / E. María Guerrero Palacios y Silvia Mora Ramírez. -- Uso de estándares y licencias para la creación y difusión de contenidos en las bibliotecas escolares / José Luis Barreiro Cebey. -- La biblioteca escolar digital móvil / Javier Fernández Delgado. -- Uso de aplicaciones móviles para el desarrollo de la competencia lingüística. Proyecto Hansel App Gretel / Dolores Olmos Olmos. -- A memória e a mediação segundo Vigotski / Leda Maria Araújo, Patricia Celia Santana, Sueli Bortolin y Leticia Gorri Molina. -- Bibliotecas escolares como tema de estudo dos alunos de graduação em blioteconomia do Instituto de Ensino Superior da FUNLEC: estado da arte / Tiago Pereira Nocera y Rodrigo Pereira. -- Ações de mediação da leitura e da informação em bibliotecas escolares: um olhar sobre as bibliotecas dos Colégios de Aplicação / Tatyanne Christina Gonçalves Ferreira Valdez y Alberto Calil Júnior. -- Mediação pedagógica numa biblioteca de escola pública em Londrina / Rovilson José da Silva, Teba Silva Yllana y Sueli Bortolin. -- Utilização de categorias por cores em sistema de biblioteca voltado ao público infanto-juvenil / Liliana Giusti Serra. -- Atividades de ensino dos atos de leitura com crianças em risco social / Adriana Naomi Fukushima da Silva y Dagoberto Buim Arena. -- Biblioteca escolar: espaço de significados entre alunos, professores e bibliotecários / Rodrigo Barbosa Paulo, Marisa Xavier, Helen Castro Casarin y Creuza Barbaroto. -- A Biblioteca Escolar no Contexto da Legislação e do Processo Educativo / Eliane Lourdes da Silva Moro, Francisca Rosaline Leite Mota y Raimundo Martins de Lima. -- O jornal impresso como fonte de informação: a importância da formação de leitores críticos / Mariana Pícaro Cerigatto. -- Bibliotecas escolares no estado do Rio Grande do Sul: a trajetória de realização dos fóruns gaúchos pela melhoria das bibliotecas escolares / Eliane Lourdes da Silva Moro y Lizandra Brasil Estabel. -- O acesso à informação dos usuários surdos na biblioteca escolar / André Luís Onório Coneglian y Mayara Melo Santana. -- Aprendizagem coletiva de bibliotecários e a competência de pesquisa dos docentes: o caso do Instituto Federal do Espírito Santo / Maristela Almeida Mercandeli Rodrigues y Beatriz Quiroz Villardi. -- Biblioteca escolar: atores, parâmetros e competências / Mavi Galante Mancera Dall´Acqua Carvalho y Claudio Marcondes de Castro Filho. -- Estratégias de aprendizagem de escrita no Ensino Fundamental II / Érika Christina Kohle. -- Bebês e livros: leitura nas bebetecas. Kenia Adriana de Aquino Modesto Silva, Juliane Francischeti Martins Motoyama y Renata Junqueira de Souza. -- Práticas alternativas para organização de acervos nos espaços de leitura em ambientes escolares / Luciana Souza Gracioso, Ariovaldo Alves, Débora Nascimento, Suelen Redondo, Tainara Torika Kiri de Castro, Elizabete Angelon y Eduardo Barbosa. -- Reflexões sobre a modelagem e criação de uma Rede Virtual de Leitores para Bibliotecas Escolares / Carla Floriana Martins y Raoni Guerra Rajão. -- Biblioteca escolar: espaço de formação leitora? / Silvana Ferreira de Souza Balsan y Renata Junqueira de Souza. -- “Se a Biblioteca Escolar é minha mãe, o Google é meu pai”: representações da relação entre Biblioteca Escolar e Google no imaginário de alunos do ensino técnico / Adriana Bogliolo Sirihal-Duarte, Maria L. Amorim Antunes y Raquel Miranda Vilela Paiva. -- Desafios e propostas para a universalização das bibliotecas escolares no Brasil e na Espanha / Rodrigo Pereira, Daniela Spudeit y Fernanda de Sales. -- Bibliotecário educador: possibilidades de atuação no contexto da biblioteca escolar / André Carlos da Silva, Valéria Martin Valls y Mariana de Paula Silva. -- Uma ONG para Bibliotecas Escolares : estratégia para ampliar a igualdade e capacidade de acesso e uso da informação e educação escolar de qualidade / Suelen Camilo Ferreira y Luciana de Souza Gracioso. -- O aluno com deficência: o papel do bibliotecário na disponibilidade de recursos acessíveis na biblioteca escolar / Adriano de Sales Coelho, Rosilene de Melo Oliveira y Marcos Pastana Santos. -- Biblioteca digital virtual e o uso do tablete: uma possibilidade de construção de novas práticas de leitura na escola / Barbara Cibelli da Silva Monteagudo y Dagoberto Buim Arena. -- A importância da biblioteca na educação de crianças de 0 a 3 anos / Yngrid Karolline Mendonça Costa y Cyntia Graziella Guizelim Simões Girotto. -- Comportamento Informacional de adolescentes: a relação com bibliotecas e escolas / Nelson Sebastian Silva-Jerez y Helen de Castro S. Casarin

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Comunicação de notícias difíceis: o papel da relação dos médicos com a família

O processo de comunicar más notícias a familiares constitui-se como um desafio para profissionais da saúde. Assim, este trabalho teve como objetivo apresentar os relatos de médicos em relação ao processo de comunicar notícias difíceis às famílias e envolveu uma amostra de 19 médicos dos programas de residência do Hospital Universitário de Brasília (HUB), entre eles 15 residentes e 4 staffs das áreas de Cirurgia Geral, Clínica Médica, Ginecologia e Obstetrícia e Pediatria. Os dados foram coletados a partir de entrevistas semiestruturadas e posteriormente analisados com o método do Discurso do Sujeito Coletivo. Os resultados apontam dificuldades em comunicar notícias difíceis aos familiares e em manejar suas reações, sendo a atenção e o cuidado com a singularidade de cada família uma estratégia importante. A partir disso, é possível concluir a necessidade de implementação, na formação médica, o preparo para comunicar notícias difíceis a pacientes e familiares

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

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics

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

Background Sparsentan, 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. Methods PROTECT, 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. Findings Between 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. Interpretation Over 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.</p

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status