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

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Structural health monitoring with 94 GHz radar

Technological developments in low-power mmW radar allow the measurement of deformations in the order of few micrometers and monitoring dynamic processes like structural vibration. This paper presents a fast acquisition FMCW radar operating at 94 GHz and recent experimental results of remote observation of micrometric vibration motion for bridge structural health monitoring. The presented approach offers cost reduction and applicability advantages compared to conventional techniques.Peer ReviewedPostprint (published version

Submillimetric motion detection with a 94 GHz ground based synthetic aperture radar

The paper presents the validation and experimental assessment of a 94 GHz (W-Band) CW-FM Radar that can be configured as a Ground Based SAR for high resolution imaging and interferometry. Several experimental campaigns have been carried out to assess the capability of the system to remotely observe submillimetric deformation and vibration in infrastructures.Peer ReviewedPostprint (published version

Submillimetric motion detection with a 94 GHz ground based synthetic aperture radar

The paper presents the validation and experimental assessment of a 94 GHz (W-Band) CW-FM Radar that can be configured as a Ground Based SAR for high resolution imaging and interferometry. Several experimental campaigns have been carried out to assess the capability of the system to remotely observe submillimetric deformation and vibration in infrastructures.Peer Reviewe

Structural health monitoring with 94 GHz radar

Technological developments in low-power mmW radar allow the measurement of deformations in the order of few micrometers and monitoring dynamic processes like structural vibration. This paper presents a fast acquisition FMCW radar operating at 94 GHz and recent experimental results of remote observation of micrometric vibration motion for bridge structural health monitoring. The presented approach offers cost reduction and applicability advantages compared to conventional techniques.Peer Reviewe

Characteristics Associated to Carbapenem-Resistant <i>Enterobacteriaceae</i> Fecal Carriage by Multivariate Analysis.

<p>OR, odds ratio; CI, confidence interval; HR, hazard ratio; MDRO, multi-drug resistant organism; CRE, carbapenem-resistant <i>Enterobacteriaceae</i>.</p><p>^a p < .05.</p><p>^b p < .01.</p><p>^c p < .001.</p><p>^d Bronchoscopy, digestive tract endoscopy, or invasive mechanical ventilation.</p><p>^e Logistic regression.</p><p>^f Cox proportional hazards regression.</p><p>Characteristics Associated to Carbapenem-Resistant <i>Enterobacteriaceae</i> Fecal Carriage by Multivariate Analysis.</p

Microbiology, Susceptibility Testing, and Molecular Mechanisms of Resistance of Carbapenem-Resistant <i>Enterobacteriaceae</i> Fecal Isolates.

<p>MIC, minimum inhibitory concentration; MIC₅₀, minimum inhibitory concentration for 50% of the given species; MIC₉₀, minimum inhibitory concentration for 90% of the given species.</p><p>Microbiology, Susceptibility Testing, and Molecular Mechanisms of Resistance of Carbapenem-Resistant <i>Enterobacteriaceae</i> Fecal Isolates.</p

Study flowchart.

<p>CRE-fc, Carbapenem-resistant <i>Enterobacteriaceae</i> fecal carriage.</p

Characteristics Associated to Carbapenem-Resistant <i>Enterobacteriaceae</i> Fecal Carriage Incidence.

<p>CRE, carbapenem-resistant <i>Enterobacteriaceae</i>; IQR, interquartile range; MDRO, multi-drug resistant organism.</p><p>Data about hospitalization exposures occurred before the last screening culture.</p><p>^a Systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, vasculitis.</p><p>^b Chronic or acute pancreatitis, inflammatory bowel disease, gastrointestinal hemorrhage, diverticulitis, short bowel syndrome, acute or recurrent cholangitis, benign biliary disease.</p><p>^c Bronchoscopy, digestive tract endoscopy, or invasive mechanical ventilation.</p><p>^d Central venous catheter or urinary catheter (more than 24 hours).</p><p>^e Steroids, azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, hydroxychloroquine, methotrexate, or chemotherapy.</p><p>^f Cox proportional hazards regression.</p><p>Characteristics Associated to Carbapenem-Resistant <i>Enterobacteriaceae</i> Fecal Carriage Incidence.</p