Clinical and Immunological Factors That Distinguish COVID-19 From Pandemic Influenza A(H1N1)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Habitabilidad y política de vivienda

En esta obra, en la que participan destacados investigadores y profesores, dedicados al estudio de la problemática habitacional se presentan diferentes análisis que permiten conocer cuales son las condiciones de habitabilidad y las características de la actual política de vivienda de México. En sus capítulos se abordan los principales desafíos que enfrentan las familias mexicanas para acceder a una vivienda digna y decorosa y cuales son los retos económicos, políticos, territoriales, arquitectónicos, ambientales, financieros y culturales de las formas de producción habitacional en México y en otros países, en el marco de una sociedad global

Perspectivas feministas para fortalecer los liderazgos de mujeres jóvenes

Las elaboraciones conceptuales feministas en torno al poder, la política, la conformación del Estado, la democracia y la gobernabilidad democrática forman parte de una compleja y novedosa teorización relativa a la formación de la ciudadanía femenina y de la relación de las mujeres con el Estado. Este libro aborda estos temas, desde la perspectiva de género feminista, en la cual, un elemento constante es la contextualización de cada una de las reflexiones compartidas, así como el vincular las posibilidades de participación política de las mujeres y las oportunidades de fortalecimiento de las distintas expresiones de los liderazgos. Destacan en particular las referencias a la globalización, el neoliberalismo y la construcción de los derechos humanos de las mujeres , para erradicar el conjunto de condiciones sociales que subyace a la continuidad de su desigualdad, dominación y exclusión en prácticamente en todas las condiciones de la vida

The global challenges of the long COVID-19 in adults and children

Institución Universitaria Visión de las Américas. Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Risaralda, Colombia / Universidad Científica del Sur. Faculty of Health Sciences. Lima, Peru / Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia.Universidad Científica del Sur. Faculty of Health Sciences. Lima, Peru.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Lebanese American University. Gilbert and Rose-Marie Chagoury School of Medicine. Beirut, Lebanon.Municipal Autonomous Government of Cochabamba. Municipal Secretary of Health. Direction of First Level. Cochabamba, Bolivia.Franz Tamayo University. National Research Coordination. La Paz, Bolivia.Universidad Continental. Research Unit. Huancayo, Peru.Universidad Nacional de Colombia. Department of Pediatrics. Bogotá, DC, Colombia / Fundación HOMI. Hospital Pediátrico La Misericordia. Division of Infectious Diseases. Bogotá, DC, Colombia / Fundación Hospital Infantil Universitario de San José. Bogotá, DC, Colombia.Hemera Unidad de Infectología IPS SAS. Bogota, Colombia.Hospital San Vicente Fundación. Rionegro, Antioquia, Colombia.Clinica Imbanaco Grupo Quironsalud. Cali, Colombia / Universidad Santiago de Cali. Cali, Colombia / Clinica de Occidente. Cali, Colombia / Clinica Sebastián de Belalcazar. Valle del Cauca, Colombia.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina.Universidade Estadual Paulista Júlio de Mesquita Filho. Botucatu Medical School. Infectious Diseases Department. São Paulo, SP, Brazil / Brazilian Society for Infectious Diseases. São Paulo, SP, Brazil.Institute of Infectious Diseases Emilio Ribas. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Pará. Faculdade de Medicina. Belém, PA, Brazil.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muñiz. Buenos Aires, Argentina.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muñiz. Buenos Aires, Argentina.Centro de Referencia de Salud Dr. Salvador Allende Gossens. Policlínico Neurología. Unidad Procedimientos. Santiago de Chile, Chile.Hospital Salvador Bienvenido Gautier. Santo Domingo, Dominican Republic.Universidad Central del Ecuador. Jefatura de Cátedra de Enfermedades Infecciosas. Quito, Ecuador.Universidad Autónoma de Santo Domingo. Santo Domingo, Dominican Republic.Hospital Roosevelt. Guatemala City, GuatemalaNational Autonomous University of Honduras. Institute for Research in Medical Sciences and Right to Health. Tegucigalpa, Honduras.National Clinical Coordinator COVID-19-WHO Studies. Colombia / Universidad Nacional de Colombia. Facultad de Medicina. Clinica Colsanitas. Clinica Universitaria Colombia. Colombia.Think Vaccines LLC. Houston, Texas, USA.Universidad Simón Bolívar. Centro de Investigación en Ciencias de la Vida. Barranquilla, Colombia / Grupo de Expertos Clínicos Secretaria de Salud de Barranquilla. Barranquilla, Colombia.Universidad San Ignacio de Loyola. Vicerrectorado de Investigación. Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud. Lima, Peru.Hospital Evangélico de Montevideo. Montevideo, Uruguay.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Colombia / University of California. School of Public Health. Division of Infectious Diseases and Vaccinology. Berkeley, CA, USA.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela / Biomedical Research and Therapeutic Vaccines Institute. Ciudad Bolivar, Venezuela.University of Colorado Anschutz Medical Campus. School of Medicine. Division of Infectious Diseases. Aurora, CO, USA.Tribhuvan University Teaching Hospital. Institute of Medicine. Kathmandu, Nepal / Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth. Dr. D. Y. Patil Medical College. Department of Microbiology. Pune, Maharashtra, India / Dr. D.Y. Patil Dental College and Hospital. Department of Public Health Dentistry. Dr. D.Y. Patil Vidyapeeth, Maharashtra, India.Universidad Cesar Vallejo. Escuela de Medicina. Trujillo, Peru.Universidad de San Martín de Porres. Facultad de Medicina Humana. Chiclayo, Peru.Friedrich Schiller University Jena. Institute of Microbiology. Beutenbergstraße, Jena, Germany / Pontificia Universidad Católica del Ecuador. School of Medicine. Postgraduate Program in Infectious Diseases. Quito, Ecuador.Universidad Simón Bolivar. Faculty of Health Sciences. Barranquilla, Colombia.Johns Hopkins Aramco Healthcare. Specialty Internal Medicine and Quality Department. Dhahran, Saudi Arabia / Indiana University School of Medicine. Department of Medicine. Infectious Disease Division. Indianapolis, IN, USA / Johns Hopkins University School of Medicine. Department of Medicine. Infectious Disease Division. Baltimore, MD, USA.Johns Hopkins Aramco Healthcare. Molecular Diagnostic Laboratory. Dhahran, Saudi Arabia / Alfaisal University. College of Medicine. Riyadh, Saudi Arabia / The University of Haripur. Department of Public Health and Nutrition. Haripur, Pakistan.VM Medicalpark Samsun Hospital. Department of Infectious Diseases. Samsun, Turkey.University of Miami. Miller School of Medicine. Department of Medicine. Division of Infectious Diseases. Miami, FL, USA.Caja Costarricense de Seguro Social. Centro de Ciencias Médicas. Hospital Nacional de Niños Dr. Carlos Sáenz Herrera. Servicio de Infectología Pediátrica. San José, Costa Rica / Instituto de Investigación en Ciencias Médicas. San José, Costa Rica / Universidad de Ciencias Médicas. Facultad de Medicina. Cátedra de Pediatría. San José, Costa Rica

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis