Por... Luis de Proxita, Ferrer, Aragon y Apiano... con... Maria Antonia Ferrer, Proxita, Rocafull, y Albornòs y... Antonio Fernando Puiades Borja, Olim Coloma, Conde de Ana, Sobre la immision en possession de los estados del Condado de Almenara...

Sign.: A-Z2, 2A-D2Port. con grab. xil. representando a la VirgenH. de grab. xil. con un árbol genealógic

Friedrich Hayek and his visits to Chile

F. A. Hayek took two trips to Chile, the first in 1977, the second in 1981. The visits were controversial. On the first trip he met with General Augusto Pinochet, who had led a coup that overthrew Salvador Allende in 1973. During his 1981 visit, Hayek gave interviews that were published in the Chilean newspaper El Mercurio and in which he discussed authoritarian regimes and the problem of unlimited democracy. After each trip, he complained that the western press had painted an unfair picture of the economic situation under the Pinochet regime. Drawing on archival material, interviews, and past research, we provide a full account of this controversial episode in Hayek’s life

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

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

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

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Plaza de toros de Madrid ó Semblanzas de los toreros escriturados en 1845

PC 486; 8 Mb de memoria RAM, recomendado 16 MB; MS-DOS 6.0 y Microsoft Windows 3.1 o superior; Espacio libre en disco local superior a 10 Mb; Monitor VGA, recomendado SVGA, resolución 800x600, 256 colores; Lector de CD-ROM local o en redTít. tomado de la etiquetaBiblioteca Sol y Sombra. Madrid : Ginés Carrión, 1906-1908 Plaza de toros de Madrid ó Semblanzas de los toreros escriturados en 1845 : con un apéndice sobre la reforma de algunos abusos. Madrid : [s. n.] (Establecimiento Tipográfico de D. Francisco de P. Mellado), 1845 ALFONSO CANDELA, José R.: Córdoba taurina : apuntes biográficos de matadores, banderilleros... Málaga : [s. n.] (Imprenta de Enrique Alcalá), [s. d.] BAGÜÉS, Ventura Efemerides taurinas : hoy hace años... Barcelona : Lux, [1915?] DAZA, José: Arte del toreo : manuscrito inédito de 1778 : tomo I. Madrid : Unión de Bibliófilos Taurinos, 1959 FERNÁNDEZ Y GONZALEZ, Manuel: Las glorias del toreo. [S.l.] : [s.n.], [s.d.] GÓMEZ DE BEDOYA, Fernando: Historia del Toreo, y de las principales ganaderías de España. Madrid : [s. n.] (Imprenta de D. Anselmo Sta. Coloma y compañía), 1850 GÓMEZ QUINTANA, Isidro: Apuntes históricos acerca de la fiesta de toros en España : su origen, cambios y vicisitudes... Córdoba [etc.] : R. Molina, 1897 GÓMEZ QUINTANA, Isidro Apuntes necrológico-biográficos de los espadas banderilleros y picadores muertos en las plazas de toros... Madrid [etc.] : Fernando Fé, 1897 MESA, Pablo: Semblanzas de los toreros escriturados en la plaza de Cádiz en la temporada de 1851... Cádiz : [s. n.] (Imprenta de la Sociedad Literaria), 1851 ROJAS Y SOLÍS, Ricardo de Anales de la plaza de toros de Sevilla : 1730-1835. "Sevilla : [s. n.] (Oficina tipográfica de la ""Guia Oficial""), 1917" SÁNCHEZ DE NEIRA, J.: El toreo : gran diccionario tauromáquico : tomo primero. Madrid : [s. n.] (Imprenta y librería de Miguel Guijarro), 1879 SÁNCHEZ DE NEIRA, J.: El toreo : gran diccionario tauromáquico : tomo segundo. Madrid : [s. n.] (Imprenta y librería de Miguel Guijarro), 1879 SÁNCHEZ DE NEIRA, J.: Gran diccionario taurómaco. Madrid : [s. n.] (R. Velasco, impresor), 1896 SÁNCHEZ DE NEIRA, J.: Los toreros de antaño y los de ogaño. Madrid : [s. n.] (Imprenta de Pedro Nuñez), 1884 SANTA COLOMA, José: Apuntes biograficos de los diestros que mas se han distinguido en el arte de torear. Madrid : [s. n.] (Imprenta de J. López), 1872 SERRANO GARCÍA-VAO, Manuel: El año taurino : fiestas taurinas celebradas en la plaza de toros de Madrid en 1898. Madrid : [s. n.] (Imprenta de el Enano), 1898 SERRANO GARCÍA-VAO, Manuel: Toreros, toreritos y torerazos : 303 semblanzas en 303 décimas. Madrid : [s. n.] (Imprenta de Antonio G. Izquierdo), 1902 SERRANO GARCÍA-VAO, Manuel: Toros y toreros en 1904 : detalles y apreciación de la última temporada taurina. Madrid : [s. n.] (Imprenta y estereotipia del Diario Universal), 1904 "SERRANO GARCÍA-VAO, Manuel; AMO, Bruno del: "Las estrellas del toreo : apuntes crítico-biográfico-estadísticos de los cincuenta y cinco matadores de toros que en la actualidad ejercen la profesión. Madrid : [s. n.] (Establecimiento tipográfico de Ginés Carrión), [s. d.] "SERRANO GARCÍA-VAO, Manuel; AMO, Bruno del: "Las estrellas del toreo : apuntes crítico-biográfico-estadísticos de los matadores de toros. Madrid : [s. n.] (Ginés Carrión, impresor), 1915 TIXERA, Josef de la Las fiestas de toros. Madrid : [s. n.] (Oficina de los Hijos de Ducazcal), 1894 VÁZQUEZ Y RODRÍGUEZ, Leopoldo: América taurina. Madrid : Librería de Victoriano Suárez, 1898 VÁZQUEZ Y RODRÍGUEZ, Leopoldo: Biografías de toreros. Madrid : [s. n.] (Establecimiento tipográfico de Ambrosio Pérez y Cía), 1900-1910 VÁZQUEZ Y RODRÍGUEZ, Leopoldo: Efemérides taurinas: recopilacion por meses y dias de los acontecimientos mas notables... Madrid : [s. n.] (Imprenta de la Correspondencia de España), 1880 VÁZQUEZ Y RODRÍGUEZ, Leopoldo: Vocabulario taurómaco ó sea colección de las voces y frases... Madrid : [s. n.] (Imprenta de sucesores de Escribano), 1880 "VÁZQUEZ Y RODRÍGUEZ, Leopoldo; GANDULLO, Luis; LÓPEZ DE SAA, Leopoldo: "La tauromaquia : tomo primero. Madrid : Mariano Núñez Samper, [s. d.] "VÁZQUEZ Y RODRÍGUEZ, Leopoldo; GANDULLO, Luis; LÓPEZ DE SAA, Leopoldo: "La tauromaquia : tomo segundo. Madrid : Mariano Núñez Samper, [s. d.

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

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