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 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 m 2), 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

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 &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;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 &lt;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&lt;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&lt;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

Avatares de la digitalización en la formación universitaria

El objetivo de este libro es adentrarse a las diferentes experiencias y prácticas que llevan a cabo diversos colectivos docentes de Instituciones de Educación Superior (IES) en Iberoamérica. Se presenta un acercamiento a los modelos educativos, a las diversas herramientas utilizadas en el proceso de enseñanza aprendizaje que son producto de innovación educativa, que han creado metodologías exitosas a fin de poder replicarlas en otros entornos. Se trata de narrativas que dan cuenta de los avatares que enfrenta la formación universitaria en el contexto de la transformación digital de las Universidades e Instituciones de Educación Superior. En el primer capítulo, la propuesta destaca la claridad jurídica de su exposición como eje simbiótico entre dos complejos mundos de la realidad actual que tienen impacto en la educación: el avance en los derechos humanos y su relación con el avance tecnocientífico. En el segundo capítulo se abordan las formas en las que el paradigma tecnocientífico ha impuesto nuevos desafíos a la formación universitaria, lo que obliga un proceso de transformación y renovación de las Universidades y de las IES. En el tercer capítulo se detalla una experiencia de colaboración entre dos facultades que busca fortalecer los procesos formativos mediante el uso de la metodología de simulación. Se trata de un proyecto piloto relevante que integra dos disciplinas, en apariencia, lejanas: ciencias de la salud y ciencias administrativas. En el capítulo cuatro se expone la metodología que se ha implementado en la formación de habilidades directivas a partir de la integración de los métodos de simulación de negocio con base tecnológica. El capítulo cinco destaca la importancia del trabajo final en la formación universitaria. En el capítulo seis se aportan los resultados preliminares de una investigación en curso respecto a la integración de simuladores de negocio como una herramienta que fortalezca el proceso de aprendizaje y los conocimientos en alumnos de administración. Se continua con el capítulo siete, el cual resalta por su enfoque holístico a partir de una innovadora integración de la gamificación en una experiencia de aprendizaje. El capítulo ocho presenta los resultados de una investigación de orden cuantitativo sobre el impacto del foro asíncrono en alumnos universitarios de recién ingreso. Se confrontan dos momentos, la pre-prueba y post-prueba con el fin de buscar una relación causal sobre la pertinencia del foro de discusión asíncrona para la comprensión de temas específicos. En el penúltimo capítulo, se señala que la selección de una herramienta tecnológica para la educación no es un camino sencillo. Una de las etapas de mayor cuidado reside en el diseño de la metodología que debe implementar el docente para la integración de ambientes de inmersión en algunas temáticas que resultan poco atractivas para los alumnos. Finalmente, el capítulo diez resalta por una cuestión fundamental, el teléfono inteligente que ha pasado de ser una simple tecnología para comunicar a ser un objeto cultural presente en gran parte de la vida social de las personas, en donde se incluye la educación

E-readiness in construction: an incongruous paradigm of variables

The construction industry has witnessed unprecedented levels of technological change over the last 10 years in particular, the corollary of which has required key decision makers to fundamentally re-think the way they: (a) have undertaken business in the past; (b) are currently doing business at the moment; and, (c) will need to change their business practices in order to compete in the future. This research attempts to understand this trichotomy, with a specific emphasis on understanding key decision makers' perception of e-readiness within the context of the construction industry. Research findings highlighted the importance of People, Process and Technology, along with five core enablers that are deemed priority areas for operationalisation. The rubrics for managing these dependences are also discussed in the context of future leveraging opportunities. This research reports the significant importance of ICT to capture, store and reuse knowledge in the organisational and demonstrates the need for the organisation to be e-ready

Evolocumab and clinical outcomes in patients with cardiovascular disease

peer reviewedBACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. © 2017 Massachusetts Medical Society

Cytoprotection by Melatonin: The Metabolic Syndrome as an Example

Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, in part because of its function as a metabolic regulator and mitochondrial protector. As a chronobiotic/cytoprotective agent, melatonin may occupy a special place in the prevention and treatment of metabolic syndrome.Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vigo, Daniel Eduardo. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin