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

XVI International Congress of Control Electronics and Telecommunications: "Techno-scientific considerations for a post-pandemic world intensive in knowledge, innovation and sustainable local development"

Este título, sugestivo por los impactos durante la situación de la Covid 19 en el mundo, y que en Colombia lastimosamente han sido muy críticos, permiten asumir la obligada superación de tensiones sociales, políticas, y económicas; pero sobre todo científicas y tecnológicas. Inicialmente, esto supone la existencia de una capacidad de la sociedad colombiana por recuperar su estado inicial después de que haya cesado la perturbación a la que fue sometida por la catastrófica pandemia, y superar ese anterior estado de cosas ya que se encontraban -y aún se encuentran- muchos problemas locales mal resueltos, medianamente resueltos, y muchos sin resolver: es decir, habrá que rediseñar y fortalecer una probada resiliencia social existente - producto del prolongado conflicto social colombiano superado parcialmente por un proceso de paz exitoso - desde la tecnociencia local; como lo indicaba Markus Brunnermeier - economista alemán y catedrático de economía de la Universidad de Princeton- en su libro The Resilient Society…La cuestión no es preveerlo todo sino poder reaccionar…aprender a recuperarse rápido.This title, suggestive of the impacts during the Covid 19 situation in the world, and which have unfortunately been very critical in Colombia, allows us to assume the obligatory overcoming of social, political, and economic tensions; but above all scientific and technological. Initially, this supposes the existence of a capacity of Colombian society to recover its initial state after the disturbance to which it was subjected by the catastrophic pandemic has ceased, and to overcome that previous state of affairs since it was found -and still is find - many local problems poorly resolved, moderately resolved, and many unresolved: that is, an existing social resilience test will have to be redesigned and strengthened - product of the prolonged Colombian social conflict partially overcome by a successful peace process - from local technoscience; As Markus Brunnermeier - German economist and professor of economics at Princeton University - indicates in his book The Resilient Society...The question is not to foresee everything but to be able to react...learn to recover quickly.Bogot

Novel assessment of urinary albumin excretion in type 2 diabetes patients by Raman spectroscopy

Urinary albumin excretion remains the key biomarker to detect renal complications in type 2 diabetes. As diabetes epidemy increases, particularly in low-income countries, efficient and low-cost methods to measure urinary albumin are needed. In this pilot study, we evaluated the performance of Raman spectroscopy in the assessment of urinary albumin in patients with type 2 diabetes. The spectral Raman analysis of albumin was performed using artificial urine, at five concentrations of albumin and 24 h collection urine samples from ten patients with Type 2 Diabetes. The spectra were obtained after removing the background fluorescence and fitting Gaussian curves to spectral regions containing features of such metabolites. In the samples from patients with type 2 diabetes, we identified the presence of albumin in the peaks of the spectrum located at 663.07, 993.43, 1021.43, 1235.28, 1429.91 and 1633.91 cm−1. In artificial urine, there was an increase in the intensity of the Raman signal at 1450 cm−1, which corresponds to the increment of the concentrations of albumin. The highest concentration of albumin was located at 1630 cm−1. The capability of Raman spectroscopy for detection of small concentrations of urinary albumin suggests the feasibility of this method for the screening of type 2 diabetes renal complications

Expresión Artística y Espacial - AR287 - 202101

Descripción: El curso de Expresión Artística y Espacial forma al estudiante en el uso del recurso gráfico y su expresividad artística, para que represente sus ideas y resuelva con solvencia los retos que se presenten en su carrera profesional. El estudiante deberá entender y graficar tanto la bidimensionalidad como la tridimensionalidad de las formas y las materializará en sus primeras planimetrías representadas en diversas técnicas gráficas. Este conocimiento será el soporte o andamiaje de los complejos, pero naturales procesos de ideación en las carreras de carácter creativo-productivo Propósito: El curso tiene como propósito permitir al estudiante desarrollar competencias en el uso y la comprensión del lenguaje gráfico tanto tridimensional como bidimensional, desarrollar la creatividad y las capacidades de expresión mediante recursos gráficos. Asimismo, busca contribuir al desarrollo de la competencia específica de Técnica y construcción, (que corresponde a los criterios NAAB : SC1,SC4 y SC6 ) en el nivel 1. Tiene como requisito el Taller de Arquitectura vocacional

Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial

Background: Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. Methods: HERALD is a randomised, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America. By use of an interactive web response system and stratification by country and age group (18–60 years and ≥61 years), adults with no history of virologically confirmed COVID-19 were randomly assigned (1:1) to receive intramuscularly either two 0·6 mL doses of CVnCoV containing 12 μg of mRNA or two 0·6 mL doses of 0·9% NaCl (placebo) on days 1 and 29. The primary efficacy endpoint was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose. For the primary endpoint, the trial was considered successful if the lower limit of the CI was greater than 30%. Key secondary endpoints were the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, severe COVID-19, and COVID-19 of any severity by age group. Primary safety outcomes were solicited local and systemic adverse events within 7 days after each dose and unsolicited adverse events within 28 days after each dose in phase 2b participants, and serious adverse events and adverse events of special interest up to 1 year after the second dose in phase 2b and phase 3 participants. Here, we report data up to June 18, 2021. The study is registered at ClinicalTrials.gov, NCT04652102, and EudraCT, 2020–003998–22, and is ongoing. Findings: Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0–61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (95% CI 42·5–86·1; CVnCoV 12 cases in 1735·29 person-years, placebo 37 cases in 1569·87 person-years). In participants aged 18–60 years, vaccine efficacy against symptomatic disease was 52·5% (95% CI 36·2–64·8; CVnCoV 71 cases in 1591·47 person-years, placebo, 136 cases in 1449·23 person-years). Too few cases occurred in participants aged 61 years or older (CVnCoV 12, placebo nine) to allow meaningful assessment of vaccine efficacy. Solicited adverse events, which were mostly systemic, were more common in CVnCoV recipients (1933 [96·5%] of 2003) than in placebo recipients (1344 [67·9%] of 1978), with 542 (27·1%) CVnCoV recipients and 61 (3·1%) placebo recipients reporting grade 3 solicited adverse events. The most frequently reported local reaction after any dose in the CVnCoV group was injection-site pain (1678 [83·6%] of 2007), with 22 grade 3 reactions, and the most frequently reported systematic reactions were fatigue (1603 [80·0%] of 2003) and headache (1541 [76·9%] of 2003). 82 (0·4%) of 19 783 CVnCoV recipients reported 100 serious adverse events and 66 (0·3%) of 19 746 placebo recipients reported 76 serious adverse events. Eight serious adverse events in five CVnCoV recipients and two serious adverse events in two placebo recipients were considered vaccination-related. None of the fatal serious adverse events reported (eight in the CVnCoV group and six in the placebo group) were considered to be related to study vaccination. Adverse events of special interest were reported for 38 (0·2%) participants in the CVnCoV group and 31 (0·2%) participants in the placebo group. These events were considered to be related to the trial vaccine for 14 (<0·1%) participants in the CVnCoV group and for five (<0·1%) participants in the placebo group. Interpretation: CVnCoV was efficacious in the prevention of COVID-19 of any severity and had an acceptable safety profile. Taking into account the changing environment, including the emergence of SARS-CoV-2 variants, and timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the development of next-generation vaccine candidates. Funding: German Federal Ministry of Education and Research and CureVac

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 (&lt;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

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

Rationale &amp; 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 &amp; 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 (&lt;60, 60-69, and &gt;_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 &amp; 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 &lt;60, 60-69, and &gt;_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

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding