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

Aportes a la investigación, fortalecimiento de capacidades y formulación de políticas para el sector cafetalero en 20 años de ensayos de sistemas agroforestales con café

A finales de los años 1990 el CATIE, con apoyo de varias ins tituciones, inició una red de ensayos de largo plazo en sistemas agroforestales con café. Los vacíos de información sobre las inte racciones agroecológicas en sistemas con diferentes enfoques de producción a largo plazo, sumados a la urgente necesidad de ase gurar sostenibilidad y restauración ecológica, fueron las principales motivaciones. Se presenta una reseña general de los primeros 20 años de estudios continuos en el CATIE, Turrialba, Costa Rica, a partir de un proceso interinstitucional e interdisciplinario. La idea base era generar conocimientos sobre las complejas interacciones entre clima, suelo, sombra, niveles y tipos de insumos y variedades de café que posibilitara el desarrollo de estrategias de diseño y manejo de sistemas agroforestales con potencial de sostener nive les de productividad aceptables y, a la vez, garantizar sinergismos ecológicos para la mejora del suelo, la biodiversidad y los servicios ambientales. El ensayo fue diseñado con seis tipos de sombra con la especie de servicio Erythrina poepiggiana y los maderables Terminalia amazonia (no fijador de nitrógeno) y Chloroleucon eurycyclum (fijador de nitrógeno), solos y en combinación, en contraste con el testigo a pleno sol. Como sub-tratamientos se definieron dos tipos de manejo (orgánico y convencional) en cuatro niveles: alto convencional (AC), moderado convencional (MC), orgánico intensivo (MO) y bajo orgánico (BO). La variedad principal de estudio fue la Caturra; además, se establecieron en algunos sistemas microparcelas con Costa Rica 95 y los híbridos Centroamericano y Milenio, L2A11, L3A17, L3A12 y L3A15. Luego de superar la fase crítica de establecimiento (primeros dos años), la plataforma de investigación se consolidó generando una invaluable base de datos y estudios a lo largo del tiempo. Con la colaboración de 22 universidades e instituciones de diversas partes del mundo, se desarrollaron 41 tesis de grado y posgrado, 23 artículos científicos en revistas internacionales y 22 documen tos técnicos para diferentes públicos. Los resultados, usando una síntesis matricial sobre los estudios de los sistemas evaluados, indican elementos claves sobre las interacciones agroecológicas y sus vínculos con la sostenibilidad productiva y sinergias ecológicas. Los sistemas de producción con la variedad Caturra a pleno sol y/o con dos podas drásticas anuales de los árboles de sombra (bajo aporte de biomasa y mucha entrada de luz) con manejos AC y MC, aun con altos niveles de productividad, impactaron negativamente en variables biofísicas y en servicios ambientales. Los SAF con Terminalia y Caturra con manejo BO perdieron viabilidad en los primeros 10 años. Los SAF, en su conjunto, mejoraron el micro clima. En particular los SAF con presencia de Erythrina mejoraron el desempeño productivo y los servicios ambientales. Todos los SAF presentaron mejor valoración de servicios ambientales que los sistemas a pleno sol. Los SAF que se destacaron en producti vidad y servicios ambientales fueron Erythrina en manejo MO y MC. Los sistemas Erythrina y Erythrina más Chloroleucon, ambos en manejo BO, han presentado buena rentabilidad, con bajos costos y buena valoración en servicios ambientales. Respecto a la comparación productiva entre diferentes variedades, los híbridos F1 Milenio y Centroamericano, produjeron más del doble (14 212,5 y 13 368,75 kg/ha respectivamente en valores promedio), que Caturra con el promedio más bajo (5230,62 kg/ha), y también superado por Costa Rica 95 (con promedio de 9823,75 kg/ha). Tanto los enfoques metodológicos, como las innovaciones generadas, han sido sociali zadas ampliamente en procesos de fortalecimiento de capacidades en los países productores de café en las Américas (capacitación a más de 42 041 productores). Se ha dado soporte al diseño e imple mentación de políticas cafetaleras orientadas a la sostenibilidad productiva, económica, social y ambiental. Para este logro fue determinante la colaboración con PROMECAFE, los Institutos de Café en Centroamérica, RECIPROCAFE y la Alianza de Mujeres en Café. En los últimos cuatro años, el Programa Regional de Gestión Integral de la Roya (PROCAGICA-IICA-UE), ha faci litado vínculos entre la agenda de investigación/validación en el ensayo propiamente y los protocolos de validación de innovaciones en la red de fincas de referencia en cinco países de América Central (Guatemala, Honduras, El Salvador, Nicaragua y Costa Rica). Dada su relevancia, aun con la meta inicial de 20 años ya cumplida, la idea es seguir operando en el ensayo de largo plazo de SAF con café en CATIE. Las experiencias pioneras desarrolladas han sido fuente para otras experiencias en diferentes países, lo cual permitió ampliar la red de ensayos agroforestales para estudios de largo plazo. En este ámbito, destaca el ensayo de SAF cítricos orgánicos (Hacienda de la Toca, São Paulo, Brasil); los ensayos de café, cacao y naranjilla (INIAP-Estación Central de la Amazonia, Ecuador); el ensayo SAF café (EARTH, Caribe, Costa Rica) y más recientemente, los ensayos de largo plazo con cacao y pasturas establecidos en CATI

First scientific observations with MEGARA at GTC

On June 25th 2017, the new intermediate-resolution optical IFU and MOS of the 10.4-m GTC had its first light. As part of the tests carried out to verify the performance of the instrument in its two modes (IFU and MOS) and 18 spectral setups (identical number of VPHs with resolutions R=6000-20000 from 0.36 to 1 micron) a number of astronomical objects were observed. These observations show that MEGARA@GTC is called to fill a niche of high-throughput, intermediateresolution IFU and MOS observations of extremely-faint narrow-lined objects. Lyman-α absorbers, star-forming dwarfs or even weak absorptions in stellar spectra in our Galaxy or in the Local Group can now be explored to a new level. Thus, the versatility of MEGARA in terms of observing modes and spectral resolution and coverage will allow GTC to go beyond current observational limits in either depth or precision for all these objects. The results to be presented in this talk clearly demonstrate the potential of MEGARA in this regard

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien\u2013Dindo Grades III\u2013V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49\u20132.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46\u20130.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease

Delaying surgery for patients with a previous SARS-CoV-2 infection

Not availabl