First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Bonfa, Eloisa. Universidade de Sao Paulo; BrasilFil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; MéxicoFil: Izcovich, Ariel. Hospital Alemán; ArgentinaFil: Popoff, Federico. Hospital Aleman; ArgentinaFil: Criniti, Juan M.. Hospital Alemán; ArgentinaFil: Vásquez, Gloria. Universidad de Antioquia; ColombiaFil: Massardo, Loreto. Universidad San Sebastián; ChileFil: Duarte, Margarita. Hospital de Clínicas; ParaguayFil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; MéxicoFil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amigo, Mary Carmen. Centro Médico Abc; MéxicoFil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; BrasilFil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; PerúFil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; VenezuelaFil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; EcuadorFil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; ColombiaFil: Molina, José Fernando. Centro Integral de Reumatología; ColombiaFil: Neira, Oscar. Universidad de Chile; ChileFil: Silva, Clóvis A.. Universidade de Sao Paulo; BrasilFil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; UruguayFil: Gómez Puerta, José A.. Hospital Clinic Barcelona; EspañaFil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; ArgentinaFil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; BrasilFil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Drenkard, Cristina. University of Emory; Estados UnidosFil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cavalcanti, André. Universidade Federal de Pernambuco; BrasilFil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; UruguayFil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; VenezuelaFil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; BrasilFil: Eraso Garnica, Ruth M.. Universidad de Antioquia; ColombiaFil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; ColombiaFil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Robaina Sevrini, Ricardo. Universidad de la República; UruguayFil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rosario, Violeta. Hospital Docente Padre Billini; República DominicanaFil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; ArgentinaFil: Appenzeller, Simone. Universidade Estadual de Campinas; BrasilFil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; BrasilFil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Naranjo, Luis A.. Universidad de Antioquia; ColombiaFil: González Bello, Yelitza C.. Ceibac; MéxicoFil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Cairoli, Ernesto. Universidad de la República; UruguayFil: Conti, Silvana M.. Hospital Provincial de Rosario; ArgentinaFil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Borba, Eduardo F.. Universidade de Sao Paulo; BrasilFil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; ArgentinaFil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; BrasilFil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; BrasilFil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; BrasilFil: Da Silva, Nilzio A.. Universidade Federal de Goiás; BrasilFil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; BrasilFil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; BrasilFil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; BrasilFil: Llanos, Carolina. Universidad Católica de Chile; ChileFil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El SalvadorFil: Garcia De La Torre, Ignacio. Hospital General de Occidente; MéxicoFil: Pineda, Carlos. Instituto Nacional de Rehabilitación; MéxicoFil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Danza, Alvaro. Hospital Pasteur Montevideo; UruguayFil: Guibert Toledano, Marlene. Medical-surgical Research Center; CubaFil: Reyes, Gil Llerena. Medical-surgical Research Center; CubaFil: Acosta Colman, Maria Isabel. Hospital de Clínicas; ParaguayFil: Aquino, Alicia M.. Hospital de Clínicas; ParaguayFil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República DominicanaFil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; MéxicoFil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; ChileFil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unido

The Research Journey as a Challenge Towards New Trends

The academic community of the department of Risaralda, in its permanent interest in evidencing the results of the research processes that are carried out from the Higher Education Institutions and as a product of the VI meeting of researchers of the department of Risaralda held in November 2021 presents its work: “The journey of research as a challenge towards new trends”, which reflects the result of the latest research and advances in different lines of knowledge in Agricultural Sciences, Health Sciences, Social Sciences and Technology and Information Sciences, which seek to solve and meet the demands of the different sectors. This work would not have been possible without the help of each of the teachers, researchers and authors who presented their articles that make up each of the chapters of the book, to them our gratitude for their commitment, dedication and commitment, since their sole purpose is to contribute from the academy and science to scientific and technological development in the search for the solution of problems and thus contribute to transform the reality of our society and communities. We also wish to extend our gratitude to the institutions of the Network that made this publication possible: UTP, UCP, UNAD, UNIREMINGTON; UNISARC, CIAF, Universidad Libre, Uniclaretiana, Fundación Universitaria Comfamiliar and UNIMINUTO, institutions that in one way or another allowed this work to become a reality, which we hope will be of interest to you.Preface............................................................................................................................7 Chapter 1. Technologies and Engineering Towards a humanization in Engineering using soft skills in training in Engineers.............................................................................................................11 Omar Iván Trejos Buriticá1, Luis Eduardo Muñoz Guerrero Innovative materials in construction: review from a bibliometric analysis....................................................................................................................27 Cristian Osorio Gómez, Daniel Aristizábal Torres, Alejandro Alzate Buitrago, Cristhian Camilo Amariles López Bibliometric review of disaster risk management: progress, trends, and challenges.........................................................................................................51 Alejandro Alzate Buitrago, Gloria Milena Molina Vinasco. Incidence of land coverage and geology, in the unstability of lands of the micro-basin of the Combia creek, Pereira, Risaralda....................................73 Alejandro Alzate Buitrago, Daniel Aristizábal Torres. Chapter 2. Arts, Humanities, and Social Sciences Training experience with teachers teaching mathematics using the inquiry methodology ...............................................................................................95 Vivian Libeth Uzuriaga López, Héctor Gerardo Sánchez Bedoya. Interpretation of the multiple representations of the fears associated to the boarding of limited visual patients in the elective I students’ written productions and low vision ...................................................................................113 Eliana Bermúdez Cardona, Ana María Agudelo Guevara, Caterine Villamarín Acosta. The relevance of local knowledge in social sciences............................................131 Alberto Antonio Berón Ospina, Isabel Cristina Castillo Quintero. Basic education students’ conceptions of conflict a view from the peace for the education....................................................................................................143 Astrid Milena Calderón Cárdenas,Carolina Aguirre Arias, Carolina Franco Ossa, Martha Cecilia Gutiérrez Giraldo, Orfa Buitrago. Comprehensive risk prevention in educational settings: an interdisciplinary and socio-educational approach ............................................................................163 Olga María Henao Trujillo, Claudia María López Ortiz. Chapter 3. Natural and Agricultural Sciences Physicochemical characterization of three substrates used in the deep bedding system in swine .......................................................................................175 Juan Manuel Sánchez Rubio, Andrés Felipe Arias Roldan, Jesús Arturo Rincón Sanz, Jaime Andrés Betancourt Vásquez. Periodic solutions in AFM models........................................................................187 Daniel Cortés Zapata, Alexander Gutiérrez Gutiérrez. Phenology in flower and fruit of Rubus glaucus benth. Cv. Thornless in Risaralda: elements for phytosanitary management .........................................199 Shirley Palacios Castro, Andrés Alfonso Patiño Martínez, James Montoya Lerma, Ricardo Flórez, Harry Josué Pérez. Socio-economic and technical characterization of the cultivation of avocado (Persea americana) in Risaralda..............................................................217 Andrés Alfonso Patiño Martínez, Kelly Saudith Castañez Poveda, Eliana Gómez Correa. Biosecurity management in backyard systems in Santa Rosa de Cabal, Risaralda................................................................................................................227 Julia Victoria Arredondo Botero, Jaiver Estiben Ocampo Jaramillo, Juan Sebastián Mera Vallejo, Álvaro de Jesús Aranzazu Hernández. CONTENTS Physical-chemical diagnosis of soils in hillside areas with predominance of Lulo CV. La Selva production system in the department of Risaralda.............241 Adriana Patricia Restrepo Gallón, María Paula Landinez Montes, Jimena Tobón López. Digestibility of three concentrates used in canine feeding....................................271 María Fernanda Mejía Silva, Valentina Noreña Sánchez, Gastón Adolfo Castaño Jiménez. Chapter 4. Economic, Administrative, and Accounting Sciences Financial inclusion in households from socioeconomic strata 1 and 2 in the city of Pereira ..................................................................................................285 Lindy Neth Perea Mosquera, Marlen Isabel Redondo Ramírez, Angélica Viviana Morales. Internal marketing strategies as a competitive advantage for the company Mobilautos SAS de Dosquebradas........................................................................303 Inés Montoya Sánchez, Sandra Patricia Viana Bolaños, Ana María Barrera Rodríguez. Uses of tourist marketing in the tourist sector of the municipality of Belén de Umbría, Risaralda.............................................................................................319 Ana María Barrera Rodríguez, Paola Andrea Echeverri Gutiérrez, María Camila Parra Buitrago, Paola Andrea Martín Muñoz, Angy Paola Ángel Vélez, Luisa Natalia Trejos Ospina. Territorial prospective of Risaralda department (Colombia), based on the SDGS...............................................................................................................333 Juan Guillermo Gil García, Samanta Londoño Velásquez. Chapter 5. Health and Sports Sciences Performance evaluation in times of pandemic. What do medical students think?.......................................................................................................353 Samuel Eduardo Trujillo Henao, Rodolfo A. Cabrales Vega, Germán Alberto Moreno Gómez. The relevance of the therapist’s self and self-reference in the training of psychologists.....................................................................................................371 Maria Paula Marmolejo Lozano, Mireya Ospina Botero. Habits related to oral health which influence lifestyle of elder people in a wellness center for the elderly in Pereira 2020. .............................................387 Isadora Blanco Pérez, Olga Patricia Ramírez Rodríguez, Ángela María Rincón Hurtado. Analysis of the suicide trend in the Coffee Region in Colombia during the years 2012-2018 ..............................................................................................405 Germán Alberto Moreno Gómez, Jennifer Nessim Salazar, Jairo Franco Londoño, Juan Carlos Medina Osorio. Hind limb long bone fractures in canines and felines...........................................419 María Camila Cruz Vélez, Valentina Herrera Morales, Alba Nydia Restrepo Jiménez, Lina Marcela Palomino, Gabriel Rodolfo Izquierdo Bravo. Prevalence of overweight and obesity in children in the rural and urban area of Risaralda....................................................................................................439 Angela María Álvarez López, Angela Liceth Pérez Rendón, Alejandro Gómez Rodas, Luis Enrique Isaza Velásquez. Chapter 6. Architecture, Design and Advertising The artisan crafts of Risaralda, characteristics, importance, and risks within the Colombian Coffee Cultural Landscape, CCCL....................................457 Yaffa Nahir Ivette Gómez Barrera, Javier Alfonso López Morales

Ítacas: sentidos, territorios y experiencias investigativas en Comunicación Social.

El programa de Comunicación Social de UNIMINUTO produce nuevo conocimiento desde enfoques multidisciplinares en las líneas de Educación, transformación social e innovación; Desarrollo humano y comunicación; Innovaciones sociales y productivas; y Gestión social, participación y desarrollo comunitario, las cuales aportan y fortalecen el perfil profesional e investigador de docentes y estudiantes del programa. Los resultados de las reflexiones que realizan los profesores y estudiantes se plantean como ejercicios introspectivos desde la investigación en comunicación social. Esta publicación busca divulgar el trabajo investigativo de profesores y estudiantes, especialmente este primer número representa el inicio de un camino que esperamos derive en la formación posgradual en niveles superiores de nuestros investigadores y aporte a la comprensión de la comunicación digital en este mundo globalizado. Desde una perspectiva amplia de la producción académica, la investigación se entiende como una mixtura de enfoques (cualitativo y cuantitativo), incluyendo los emergentes, además de variadas estrategias de recolección de información que resultan coherentes con los intereses investigativos del programa y los objetivos propuestos en la ruta de fortalecimento académico, para la articulación adecuada entre la formación y el desarrollo de propuestas científicas. Es así como el grupo de investigación Comunicación, Convergencia y Desarrollo asume la responsabilidad de conducir cada proyecto de investigación propuesto, de acuerdo con los propósitos de formación y la amplia comprensión del campo de la comunicación

Ítacas: sentidos, territorios y experiencias investigativas en Comunicación Social.

El programa de Comunicación Social de UNIMINUTO produce nuevo conocimiento desde enfoques multidisciplinares en las líneas de Educación, transformación social e innovación; Desarrollo humano y comunicación; Innovaciones sociales y productivas; y Gestión social, participación y desarrollo comunitario, las cuales aportan y fortalecen el perfil profesional e investigador de docentes y estudiantes del programa. Los resultados de las reflexiones que realizan los profesores y estudiantes se plantean como ejercicios introspectivos desde la investigación en comunicación social. Esta publicación busca divulgar el trabajo investigativo de profesores y estudiantes, especialmente este primer número representa el inicio de un camino que esperamos derive en la formación posgradual en niveles superiores de nuestros investigadores y aporte a la comprensión de la comunicación digital en este mundo globalizado. Desde una perspectiva amplia de la producción académica, la investigación se entiende como una mixtura de enfoques (cualitativo y cuantitativo), incluyendo los emergentes, además de variadas estrategias de recolección de información que resultan coherentes con los intereses investigativos del programa y los objetivos propuestos en la ruta de fortalecimento académico, para la articulación adecuada entre la formación y el desarrollo de propuestas científicas. Es así como el grupo de investigación Comunicación, Convergencia y Desarrollo asume la responsabilidad de conducir cada proyecto de investigación propuesto, de acuerdo con los propósitos de formación y la amplia comprensión del campo de la comunicación

Experiencias en el aula: tercer encuentro de prácticas pedagógicas innovadoras.

Experiencias de profesores en su quehacer en los distintos ambientes de aprendizaje presenciales y a distancia.Para el Centro de Excelencia Docente aeiou constituye un honor presentar la publicación del Tercer Encuentro de Prácticas Pedagógicas Innovadoras en el que se destacan cuarenta trabajos de profesores de UNIMINUTO provenientes de diferentes sedes. Con este encuentro son ya tres que bajo la dirección de aeiou los profesores han compartido su quehacer en los distintos ambientes de aprendizaje presenciales y a distancia. Cada año el Centro de Excelencia Docente invita a los profesores a participar en este evento, para el 2108 además de la inscripción voluntaria por parte de cada profesor, se invitó al estudiantado a que postularan a sus profesores que consideraban eran innovadores y creativos en el cumplimiento de su función docente y se obtuvo una respuesta importante por parte de los estudiantes, que para algunos profesores resultó sorpresiva porque quizás no habían considerado que el trabajo que hacían en su ambiente de aprendizaje era diferente, fuera de lo común. Luego de una evaluación de jurados nacionales e internacionales de las prácticas presentadas y de la realización del evento, que tuvo como novedad hacerlo de forma simultánea en cuatro sedes donde UNIMINUTO tiene presencia: Buga, Ibagué, Pereira y Bogotá, se comparte la presente publicación para tener como referencia y evidencia el trabajo que los profesores hacen a diario

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB