Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

The impact of maternal morbidity on cesarean section rates: exploring a Latin American network of sentinel facilities using the Robson’s Ten Group Classification System

Abstract Background Latin America has the highest Cesarean Section Rates (CSR) in the world. Robson’s Ten Group Classification System (RTGCS) was developed to enable understanding the CSR in different groups of women, classified according to obstetric characteristics into one of ten groups. The size of each CS group may provide helpful data on quality of care in a determined region or setting. Data can potentially be used to compare the impact of conditions such as maternal morbidity on CSR. The objective of this study is to understand the impact of Severe Maternal Morbidity (SMM) on CSR in ten different groups of RTGCS. Methods Secondary analysis of childbirth information from 2018 to 2021, including 8 health facilities from 5 Latin American and Caribbean countries (Bolivia, Guatemala, Honduras, Nicaragua, and the Dominican Republic), using a surveillance database (SIP-Perinatal Information System, in Spanish) implemented in different settings across Latin America. Women were classified into one of RTGCS. The frequency of each group and its respective CSR were described. Furthermore, the sample was divided into two groups, according to maternal outcomes: women without SMM and those who experienced SMM, considering Potentially Life-threatening Conditions, Maternal Near Miss and Maternal Death as the continuum of morbidity. Results Available data were obtained from 92,688 deliveries using the Robson Classification. Overall CSR was around 38%. Group 5 was responsible for almost one-third of cesarean sections. SMM occurred in 6.7% of cases. Among these cases, the overall CSR was almost 70% in this group. Group 10 had a major role (preterm deliveries). Group 5 (previous Cesarean section) had a very high CSR within the group, regardless of the occurrence of maternal morbidity (over 80%). Conclusion Cesarean section rate was higher in women experiencing SMM than in those without SMM in Latin America. SMM was associated with higher Cesarean section rates, especially in groups 1 and 3. Nevertheless, group 5 was the major contributor to the overall CSR

Neonatal outcomes according to different degrees of maternal morbidity: cross-sectional evidence from the Perinatal Information System (SIP) of the CLAP network

Background The burden of maternal morbidity in neonatal outcomes can vary with the adequacy of healthcare provision and tool implementation to improve monitoring. Such information is lacking in Latin American countries, where the decrease in severe maternal morbidity and maternal death remains challenging. Objectives To determine neonatal outcomes according to maternal characteristics, including different degrees of maternal morbidity in Latin American health facilities. Methods This is a secondary cross-sectional analysis of the Perinatal Information System (SIP) database from eight health facilities in five Latin American and Caribbean countries. Participants were all women delivering from August 2018 to June 2021, excluding cases of abortion, multiple pregnancies and missing information on perinatal outcomes. As primary and secondary outcome measures, neonatal near miss and neonatal death were measured according to maternal/pregnancy characteristics and degrees of maternal morbidity. Estimated adjusted prevalence ratios (PRadj) with their respective 95% CIs were reported. Results In total 85,863 live births were included, with 1,250 neonatal near miss (NNM) cases and 695 identified neonatal deaths. NNM and neonatal mortality ratios were 14.6 and 8.1 per 1,000 live births, respectively. Conditions independently associated with a NNM or neonatal death were the need for neonatal resuscitation (PRadj 16.73, 95% CI [13.29–21.05]), being single (PRadj 1.45, 95% CI [1.32–1.59]), maternal near miss or death (PRadj 1.64, 95% CI [1.14–2.37]), preeclampsia (PRadj 3.02, 95% CI [1.70–5.35]), eclampsia/HELPP (PRadj 1.50, 95% CI [1.16–1.94]), maternal age (years) (PRadj 1.01, 95% CI [<1.01–1.02]), major congenital anomalies (PRadj 3.21, 95% CI [1.43–7.23]), diabetes (PRadj 1.49, 95% CI [1.11–1.98]) and cardiac disease (PRadj 1.65, 95% CI [1.14–2.37]). Conclusion Maternal morbidity leads to worse neonatal outcomes, especially in women suffering maternal near miss or death. Based on SIP/PAHO database all these indicators may be helpful for routine situation monitoring in Latin America with the purpose of policy changes and improvement of maternal and neonatal health

The burden of stillbirths in low resource settings in Latin America: Evidence from a network using an electronic surveillance system.

ObjectiveTo determine stillbirth ratio and its association with maternal, perinatal, and delivery characteristics, as well as geographic differences in Latin American countries (LAC).MethodsWe analysed data from the Perinatal Information System of the Latin American Center for Perinatology and Human Development (CLAP) between January 2018 and June 2021 in 8 health facilities from five LAC countries (Bolivia, Guatemala, Honduras, Nicaragua, and the Dominican Republic). Maternal, pregnancy, and delivery characteristics, in addition to pregnancy outcomes were reported. Estimates of association were tested using chi-square tests, and P ResultsIn total, 101,852 childbirths comprised the SIP database. For this analysis, we included 99,712 childbirths. There were 762 stillbirths during the study period; the Stillbirth ratio of 7.7/1,000 live births (ranged from 3.8 to 18.2/1,000 live births across the different maternities); 586 (76.9%) were antepartum stillbirths, 150 (19.7%) were intrapartum stillbirths and 26 (3.4%) with an ignored time of death. Stillbirth was significantly associated with women with diabetes (PRadj 2.36; 95%CI [1.25-4.46]), preeclampsia (PRadj 2.01; 95%CI [1.26-3.19]), maternal age (PRadj 1.04; 95%CI [1.02-1.05]), any medical condition (PRadj 1.48; 95%CI [1.24-1.76, and severe maternal outcome (PRadj 3.27; 95%CI [3.27-11.66]).ConclusionsPregnancy complications and maternal morbidity were significantly associated with stillbirths. The stillbirth ratios varied across the maternity hospitals, which highlights the importance for individual surveillance. Specialized antenatal and intrapartum care remains a priority, particularly for women who are at a higher risk of stillbirth

El Derecho Argentino frente a la pandemia y post-pandemia COVID-19. TOMO III

La Facultad de Derecho de la Universidad Nacional de Córdoba no podía permanecer indolente frente a la conmoción que, durante este año 2020, ha provocado en el mundo la pandemia de COVID-19. Como comunidad educativa advertíamos que la prioridad máxima era lograr la continuidad de la labor de nuestra Casa de Estudios, para garantizar a nuestros alumnos del grado y del posgrado, el ejercicio de su derecho a estudiar, continuando y en algunos casos iniciando sus estudios, a pesar de las condiciones adversas que se vivían. Con esa finalidad convocamos a los profesores titulares de todas las cátedras y eméritos y consultos que quisieran hacerlo, a sumarse con sus aportes a esta construcción colectiva, que aborda los temas que nos ocupan desde las diversas perspectivas de las distintas áreas del mundo jurídico. Y la desinteresada respuesta positiva no se hizo esperar. Prueba de ello es este libro cuyas dimensiones, tanto en lo cuantitativo como en lo cualitativo, superaron las expectativas iniciales. La jerarquía de los autores que generosamente han participado con sus contribuciones, en algunos casos en forma individual y en otros acompañados por sus equipos de colaboradores, permiten prever que esta obra ha de brindar elementos de juicio de gran utilidad para continuar construyendo el mundo jurídico, dentro de la pandemia y después de ella.ÍNDICE GENERAL. TOMO III. DERECHO DE LOS RECURSOS NATURALES Y AMBIENTAL. "El Derecho Ambiental frente a la pandemia y post pandemia COVID-19 algunas perspectivas" por Aldo Novak. "Sustentabilidad y extractivismo: análisis crítico en contexto de pandemia" por Darío Ávila, María Laura Foradori y Soledad Graupera. II. "Género y ambiente: su inclusión en la agenda pública a partir del COVID-19" por Graciela Tronca María Cecilia Tello Roldán, María Eugenia Villalba y Candela González. DERECHO DE LA NAVEGACIÓN, TRANSPORTE Y COMUNICACIONES. "Derecho Aduanero. Derecho del turismo" por Giselle Javurek. Profesores: M. Soledad Pesqueira Nozikovsky, Ernesto Frontera Villamil, Juan Marcelo Cinalli y Hugo Rivarola. Adscriptos: Nelly Baigorria, Diego Cevallos, Victoria Ferronato, Maricel Freijo, M. Victoria Giubergia, Paula González Boarini,Guadalupe Hidalgo, Ignacio Latini Marramá, Iván Luna, Noelia I Mana, Dante Ariel Nuñez, Lucía Olivier y Erika Saimandi. DERECHO PROCESAL. "La justicia y el proceso judicial frente a la pandemia y post pandemia COVID-19" por Rosa A. Avila Paz de Robledo. Profesores: Mario R. Lescano, Mariano G. Lescano, Mariela Roldán, Carolina Vallania, Roxana Garay, y Santiago Molina Sandoval. "La Justicia y las personas en condiciones de vulnerabilidad frente a la Pandemia y Post Pandemia COVID-19" por Rosa A. Avila Paz de Robledo Federico M. Arce, Víctor Luna Cáceres, Horacio L. Cabanillas, Miriam Mabel Marchetti, Daniela Moyano Escalera, Eric A. Opl. "Acceso a la justicia en el COVID-19. Caso fortuito y la reforma procesal" por Cristina González de la Vega. "Nuevas tecnologías en la justicia civil de Córdoba en tiempos de pandemia COVID-19" por Leonardo González Zamar. "El proceso judicial en la época de la pandemia COVID-19. El Ministerio Público Fiscal en la oralidad" por Silvia Elena Rodríguez y Ariel Ksen. "Garantías judiciales en el COVID-19 desde la perspectiva del Sistema Interamericano de Derechos Humanos y del sistema jurídico argentino" por Diego Robledo. "La protección de datos personales en la nueva normalidad: salud pública y vigilancia digital" por María Cecilia Tello Roldan. "La emergencia sanitaria COVID-19 y la tecnología en los procesos de familia en la provincia de Córdoba" por Mariela Denise Antun y Sonia Elizabeth Cabral. "Justicia y pandemia: medidas implementadas en la justicia federal y provincial en el marco del COVID-19" por Adriana De Cicco, Ramón Agustín Ferrer Guillamondegui,Natalia Luna Jabase y Mauricio Zambiazzo. "La pandemia c 19 y el proceso judicial en Córdoba. Algunas reflexiones y las audiencias en el proceso penal" por Emilio Albarenga y Rodolfo Gaspar Lingua Rostagno. TEORÍAS DEL CONFLICTO Y DE LA DECISIÓN. MÉTODOS DERESOLUCIÓN DE CONFLICTOS. "Pensando con Morin en tiempos de incertidumbre. La noción de sujeto y la organización de los conocimientos" por Elena Garcia Cima de Esteve y Noemi G. Tamashiro de Higa. "El derecho argentino frente a la pandemia: los aportes desde la teoría del conflicto y los rad" por Daniel Gay Barbosa. "Estragos vs. orden jurídico: consenso superador para la protección de los derechos" por María Cristina Di Pietro. "El aislamiento y la resolución de conflictos. Raúl Álvarez" por Sergio Cattaneo. "El rol de mediador. Del amor en los tiempos del coronavirus" por Carla Saad y Leonardo Colazo. DERECHO POLITICO. "Pandemia. Decretos de necesidad y urgencia y constitución" por Jorge Edmundo Barbará. "La reformulación estatal en un escenario de globalización y pandemia" por Carlos Juárez Centeno. ECONOMIA. "Resolución de la CIDH 1/2020 “pandemia y derechos humanos en las Américas”. Una aproximación integral al documento emitido por la Comisión Interamericana de Derechos Humanos de la OEA" por Daniel Gattás. EDUCACION Y PANDEMIA. "Educación y pandemia. Introducción" por Graciela Ríos. "La política y el derecho educacional argentinos en tiempos de pandemia" por Claudia Giacobbe y María Florencia Blanco Pighi. "“Educar” en pandemia el acceso a la educación digital vs la desigualdad en tiempos de pandemia" por Noelia Nieva, Rosa Carnero, Florencia Pereyra y Lucas Cajeao. "Digitalización e igualdad educativa. ¿un equilibrio inestable? Un análisis de los espacios virtuales, las TIC y su necesidad en la educación básica a partir de la experiencia de emergencia sanitaria y confinamiento social" por Matías Parmigiani y Paula Gastaldi. ETICA Y DERECHO. "La pandemia como remedio de la política" por Hugo Omar Seleme. SOCIOLOGIA JURIDICA. "Pandemia COVID-19. Biopolítica y estado de excepción" por Martha Díaz de Landa.Fil: Novak, Aldo. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Ávila, Darío. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Foradori, María Laura. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Graupera, Soledad. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Tronca, Graciela. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Tello Roldán, María Cecilia. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Villalba, María Eugenia. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: González, Candela. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Javurek, Giselle. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Pesqueira Nozikovsky, M. Soledad. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Frontera Villamil, Ernesto. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit