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

La comprensión simbólica de imágenes digitales que representan acciones dirigidas hacia un fin

Electronic devices are increasingly present in our everyday lives. These devices are starting to be used in communication and learning at very early ages. Although parents and educators suppose that small children understand the symbolic function of their images, incipient but growing research in the area has not yet produced clear results. The aim of this study was to investigate whether young children understand that the images provided by a tablet represent actions that can occur in reality. We presented to 24-, 30- and 36-month-old children sequences of images of everyday actions without showing the results of those actions. Then the children had to choose real objects that exhibit the result of the action that had been presented. We found that 30-month and 36-month-old, but not 24-month-old children, understood not only the actions themselves but that the images they saw represented real actions, correctly choosing the objects that showed the results of the actions presented. The results of the study are discussed with respect to the comprehension of goal-directed actions and regarding the symbolic comprehension of the images representing such actions.Os dispositivos digitais estão cada vez mais presentes na vida cotidiana e têm começado a se utilizar na comunicação e na aprendizagem a idades muito prematura. Ainda que pais e educadores supõem que os pequenos compreendem a função simbólica das suas imagens enquanto representações da realidade, a incipiente, mas crescente pesquisa na área não tem mostrado resultados claros ao respeito. O objetivo do presente estudo foi indagar se as crianças pequenas compreendem que as imagens providas por uma tablet representam ações que ocorrem na realidade. Apresentamos a crianças de 24, 30 e 36 meses de idade sequencias de imagens de ações cotidianas sem mostrar o resultado da ação. Após observar a sequência as crianças deviam escolher um objeto real que ostentava o resultado da ação. Encontramos que aos 30 e 36 meses as crianças compreendem não só a ação em si mesma, senão que as imagens da tablet representam a uma ação real, devido a que escolheram o objeto que mostrava o resultado da ação. Os resultados discutem-se em torno tanto à compreensão de ações dirigidas a um fim, quanto à compreensão simbólica das imagens que as representam.Los dispositivos digitales están cada vez más presentes en la vida cotidiana y han comenzado a utilizarse en la comunicación y el aprendizaje a edades muy tempranas. Aunque padres y educadores suponen que los pequeños comprenden la función simbólica de sus imágenes, la incipiente pero creciente investigación en el área no ha arrojado resultados claros al respecto. El objetivo del presente estudio fue indagar si los niños pequeños comprenden que las imágenes provistas por una tablet representan acciones que pueden ocurrir en la realidad. Presentamos a niños de 24, 30 y 36 meses de edad imágenes de acciones cotidianas en secuencias que no mostraban el resultado de la acción. Luego, los niños debían escoger un objeto real que ostentaba el resultado de la acción. Encontramos que a los 30 y 36 meses, pero no a los 24, los niños comprenden que las imágenes representan una acción que puede ocurrir en la realidad. Los resultados se discuten en torno a la comprensión simbólica de imágenes y a la comprensión de acciones intencionales cuyo fin los niños deben imaginar

Infancia y aprendizaje

Resumen tomado de la publicaciónSe estudia el impacto de la instrucción en la comprensión temprana de un objeto simbólico. Se investiga si y cuando la enseñanza del adulto afecta la comprensión y el uso del mapa sencillo por parte de niños pequeños (30, 36, 42 y 46 meses de edad). Se empleo una tarea de búsqueda en la que los niños debían encontrar un juguete valiéndose de un mapa como fuente de información. Los resultados muestran que antes de los 42 meses los niños no la comprenden todos. Y a partir de los 46 meses los niños comprenden espontáneamente la función representacional del mapa. Se estudio si es posible enseñar esa función y los niños de 36 meses logran comprenderlo pero no así los niños de 30 meses. Los resultados muestran que la comprensión de un objeto simbólico depende de la edad y la enseñanza del adulto en algunos casos .MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

La construcción de producciones orales en la infancia a partir de imágenes realistas y no realistas

El objetivo de este trabajo fue examinar la construcción de narrativas de ficción por parte de niños/as de 5 y 6 años de edad a partir de imágenes con distinto nivel de realismo. Analizamos 49 relatos, 24 realizados a partir de imágenes realistas y 25 a partir de imágenes no realistas. Primero clasificamos las producciones en narraciones, descripciones y otras producciones, y analizamos el ordenamiento de las imágenes. La mayoría de los niños/as que participaron en la condición no-realista construyeron narraciones e identificaron una imagen para el comienzo y otra para el cierre; mientras que los que observaron imágenes realistas construyeron mayormente descripciones y no las organizaron en secuencias. Luego realizamos un análisis de datos textuales consignando: recuento de palabras y segmentos, y recuento de tipos de palabras y segmentos; glosario de palabras y segmentos ordenados según su frecuencia; y respuesta característica (la más significativa de cada grupo). No se encontraron diferencias en el número de palabras y la cantidad de tipos de palabras utilizadas en cada producción, pero sí en las palabras características y en las respuestas que caracterizaron a cada grupo. En las descripciones se utilizaron más sustantivos, mientras que en las narraciones se utilizaron verbos y conectores causales. La respuesta característica de la descripción consistió en una exposición acerca de cada una de las imágenes por separado. La narración presentó un conflicto o estado emocional, una resolución y un cierre. Los resultados muestran que los niños/as construyeron distintas producciones (narraciones o descripciones) según el tipo de imágenes presentadas

¿Muestran empatía los niños hacia un perro?: Un estudio empírico sobre conductas de ayuda en niños pequeños

The study of the empathic behaviors of children towards animals is of utmost importance since it could contribute to the design of intervention strategies against violence towards animals and, by extension, towards people. However, this topic has been little studied. The objective of this study was to explore whether young children show empathetic behaviors (helping behaviors) towards animals, specifically towards domestic dogs. To this end, children were presented with a task in which they observed a dog facing a problem; the dog could not access the food that was inside a box. The behavior of the child in such situation was recorded. Twenty children between 18 and 38-months-of-age participated. The results showed that when children observed the animal facing a problem, they helped the animal to achieve its objectives, that is, children acted empathetically.   El estudio de las conductas empáticas de los niños hacia los animales resulta de suma importancia, ya que podría contribuir al diseño de estrategias de intervención contra la violencia hacia los animales y, por extensión, hacia las personas. Sin embargo, esta temática ha sido poco estudiada. La presente investigación tuvo por objetivo explorar si los niños pequeños muestran conductas empáticas (conductas de ayuda) hacia los animales, específicamente hacia los perros domésticos. Para tal fin, se presentó a un grupo de niños de entre 18 a 38 meses de edad una situación en la que observaba a un perro que no podía acceder al alimento que se encontraba dentro de una caja. Se registraba el comportamiento del niño ante tal situación. Los resultados muestran que cuando observaron al animal ante un problema, los niños se comportaron de manera empática ayudándolo a lograr sus objetivos

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791