Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

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

Externado de Ginecología y Obstetricia - ME215 - 202102

Curso de la carrera de medicina, de carácter teórico-práctico del ciclo 10, en el que los estudiantes presentan una historia clínica con su respectivo plan diagnóstico, terapéutico y procedimientos en un paciente con una condición ginecológica u obstétrica, a través de la realización de actividades de simulación y metodología activa en aula. El curso del externado de ginecología y obstetricia, busca desarrollar las competencias específicas de profesionalismo-sentido ético y legal y responsabilidad profesional(nivel 3). El externado de ginecología y obstetricia, le permitirá al estudiante plantear un adecuado tratamiento y plan de trabajo según el diagnóstico de los principales problemas ginecológicos y obstétricos que le servirán en su vida futura profesional

Comprensión y Producción de Lenguaje I - HU543 - 202102

Descripción: Comprensión y Producción de Lenguaje 1 es un curso de primer ciclo, que busca desarrollar las habilidades vinculadas con la comprensión lectora y la redacción de textos escritos formales y adecuados a una situación comunicativa determinada. Por ello, durante el curso, las actividades posibilitarán que el estudiante reflexione sobre cómo el lenguaje es una herramienta que nos permite entender la realidad (comprensión) y comunicar adecuadamente nuestras ideas sobre ella (producción). Esta reflexión se realizará con énfasis en el uso del lenguaje en las redes sociales, espacio que se ha constituido como un nuevo lugar para la divulgación de asuntos diversos: desde temas de ocio o entretenimiento hasta temas académicos, científicos y políticos. En ese sentido, este curso propone que el alumno asuma el rol de un ciudadano crítico, es decir, aquella persona que no solo consume información, sino que produce contenido a partir de una investigación en fuentes confiables. Considerando lo explicado, nuestros alumnos no solo serán capaces de redactar un texto escrito formal de acuerdo con las necesidades comunicativas del ámbito universitario y de la sociedad actual, sino que podrán transformarlo en un texto multimodal (el cual involucra diferentes medios de comunicación: visual, auditivo, imagen, texto, entre otros) que tenga sentido en las redes sociales, lugar de interacción real con sus lectores. Estos productos comunicativos deberán presentar una organización conveniente, un desarrollo sólido y suficiente (lo que implica una lectura crítica de las fuentes de información), y una escritura acorde con la normativa vigente. Propósito: El curso desarrolla la competencia de comunicación escrita, en el nivel 1; es decir, el estudiante es capaz de construir mensajes coherentes y sólidos que se adecúan a la situación y propósito comunicativo. Este desarrollo le permite la generación y construcción de nuevas ideas, lo cual es relevante para su vida académica y profesional. La actual sociedad de la información y el conocimiento, caracterizada por la disrupción, la innovación y la complejidad en las formas de comunicación mediadas por la tecnología, enfrenta al estudiante y al profesional a nuevos retos en las maneras de comunicar aquello que conoce y que construye. En este escenario, la competencia comunicativa escrita adquiere protagonismo como herramienta para transmitir el conocimiento creado. El curso se alinea con esta exigencia, pues contribuye a que el estudiante responda exitosamente a las demandas comunicativas del contexto académico, y a que el egresado pueda desenvolverse idóneamente en el campo profesional y laboral

Externado de Medicina Interna - ME212 - 202101

Curso de la carrera de medicina, de carácter teórico-práctico del ciclo 9, en el que los estudiantes presentan una historia clínica con su respectivo plan diagnóstico, terapéutico y de procedimientos en un paciente con una condición médica, a través de la realización de actividades de simulación y metodología activa. El curso del externado de medicina interna busca desarrollar la competencia general de comunicación escrita (nivel 3) y las competencias específicas de práctica clínica-diagnóstico(nivel 3) y profesionalismo-sentido ético y legal y responsabilidad profesional(nivel 3). El externado de medicina al estudiante le permitirá plantear un adecuado tratamiento y plan de trabajo según el diagnóstico de los principales problemas médicos que le servirá en su futura vida profesional

Clínica Integrada - ME210 - 202101

Curso de especialidad, de la carrera de medicina, de carácter teórico- práctico del ciclo 7, en el que los estudiantes integran conocimientos previos con la anamnesis, el examen físico y establecen el diagnostico por síndromes o problemas y el plan de trabajo. El curso de Clínica integrada busca desarrollar las competencias generales de comunicación escrita y comunicación oral(nivel 2) y las competencias específicas de práctica clínica-diagnóstico (nivel 2) y profesionalismo-sentido ético y legal y responsabilidad profesional(nivel 2). La integración de conocimientos en la historia clínica, permitirá al estudiante, plantear un adecuado diagnóstico, plan de trabajo para la atención de su futuro paciente

Global and regional molecular epidemiology of HIV-1, 1990–2015: a systematic review, global survey, and trend analysis

International audienceGlobal genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990–2015.We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990–2015. We grouped countries into 14 regions and analysed data for four time periods (1990–99, 2000–04, 2005–09, and 2010–15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164.This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990–2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010–15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005–15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time.Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines

Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis

BACKGROUND: Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015. METHODS: We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. FINDINGS: This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. INTERPRETATION: Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. FUNDING: None.status: publishe