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

The impact of daydreaming on creative exploration and personal connection with English literary texts

The concept of daydreaming has recently been praised as a necessary tool to access imagination and creative thought. English literature is a subject that requires analytical skills and writing mechanics, but it also necessitates creative thinking to be able to explore, understand and empathise with the narratives and themes that are discussed. Such creative thinking is sometimes difficult to foster, particularly in an exam-based culture where time is short and ploughing through content is prioritised. This study aims to see how daydreaming— a term used to highlight the sometimes unpredictable and surprising nature of thought—could aid students in deepening their exploration of a literary text and forming personal connections—with the hope that a love and enjoyment of literature develops as a result. The study concludes that unfacilitated daydreaming could benefit students by allowing them to form reflective, personal connections between the literary texts and wider philosophical ideas and experiences. Facilitated daydreaming was found to offer students a space to hone their arguments and ideas which resulted in more detailed, definitive language; this led to the creation of higher-level thesis statements with a focus on authorial intention. It also produced further links between the literary text and more intentional historical context, cultural context and allusions. Wider implications of the study are that learning and progress extend beyond the classroom, and that time and space for personal connections and philosophical contemplation are recognised and encouraged. This challenges the reductive concepts of teaching and learning that seem to dominate contemporary discourses of education

Lower Extremity Injury Prevention in Taekwondo Poomsae Athletes: An Educational Intervention

Poomsae is a non-contact form of taekwondo that involves physical exertion, technique, skills, and art. It combines kicks, blocks, stances, strikes, and punches demonstrated with an imaginary opponent. It is practice for self-defense, belt promotion, and action preparation for contact sparring. Chronic Overuse injuries are common in taekwondo Poomsae athletes as they participate in repetitive stress to attain mastery of forms used in competitions. The goal is to provide deep understanding and knowledge essential for training and optimal performance in sports to athletes and coaches. Educational intervention is deployed as a free webinar session consisting of 221 participants attended. The data are collected through a qualitative reflective feedback form consisting of questions targeting knowledge acquired and application of the information towards their practice as a coach and athlete. The result showed common reflective feedback towards the injury prevention strategy in Poomsae from the webinar: 1) Discovering strength and weakness, 2) Reason for strength and conditioning, 3) Prevention and management of injury

Comparing natural language documents: a DL based approach

We propose a method to compare semantically two natural language texts. The process is realized in two steps, the first translates the texts into description logics terminologies. The second computes the difference between the terminologies obtained. We show how the best covering problem can be used to compute the difference between two terminologies and propose a method to calculate this difference. 1 Introduction an

Planning Problems in Arc Routing

Planning problems over multi-period horizons occur in arc routing but are neglected by OR researchers. This paper presents these new problems, a classification and a hybrid GA able to tackle the planning and scheduling levels simultaneously