Estrategias de uso racional de medicamentos en personas mayores como mejora de la calidad de vida y de promoción del bienestar

El proyecto “Estrategias de uso racional de medicamentos en personas mayores como mejora de la calidad de vida y de promoción del bienestar” se basa en la elaboración y diseño de estrategias de prevención y mejora en torno al cumplimiento terapéutico, el uso racional del medicamento, y la identificación temprana de reacciones adversas a medicamentos, entre otros problemas relacionados con el medicamento. Este proyecto es una continuación del anterior ApS UCM 2019 “Identificación de problemas relacionados con el medicamento y estrategias de mejora en personas mayores”. En esta ocasión, y por la pandemia por COVID-19, este ApS será virtual, desarrollándose diversos talleres en formato de vídeo para dar formación a las personas mayores en materia de medicamento y que se centrarán en el tratamiento de las distintas patologías de la meta 3.4. de los ODS 2030, con el fin de aumentar la calidad de vida y el bienestar social de este colectivo. Esta actividad se integra en la docencia de las asignaturas de Farmacología General, y Farmacología y Farmacoterapia del Grado en Farmacia y del Doble Grado de Farmacia y Nutrición como estrategia de aprendizaje para consolidar y profundizar lo aprendido en estas materias

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score # 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.8 página

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

La memoria de los libros. Estudios sobre la historia del escrito y de la lectura en Europa y América. Vol. I

Numerosos artículos sobre aspectos variados de historia del libro y de la lectura, bibliotecas, manuscritos, iluminación e ilustración, etc

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Implicaciones de las moléculas de adhesión celular neural en los efectos del estrés en procesos de aprendizaje y memoria en la rata

Dado que las glicoproteínas denominadas moléculas de adhesión celular neural (NCAM, su forma polisializada, PSA-NCAM, y LI) desempeñan un papel importante en la consolidación de la memoria, se estudió su expresión en diferentes regiones cerebrales, en ratas entrenadas en el paradigma conductual del condicionamiento del miedo al contexto, bajo diferentes niveles de estrés intrínseco (ligado a la tarea de aprendizaje), y a diferentes tiempos post-entremamiento (12 y 24 horas). También se estudiaron los posibles efectos del estrés crónico sobre la expresión de dichas moléculas de adhesión celular neural en ratas sometidas a inmovilización y/o entrenadas en el condicionamiento del miedo al contexto. Los resultados obtenidos mostraron una diferencial implicación de la polisilaización de NCAM hipocampal en el almacenamiento de información relativa a experiencias que implican diferentes grados de estrés. En conjunto, los resultados mostrados en esta Tesis, apoyan la idea de una modulación de las moléculas de adhesion celular en situaciones de estrés, tanto agudo, como crónico, y sugieren la posibilidad de que los cambios producidos en los niveles de dichas moléculas como consecuencia del estrés participen en los mecanismos neurales implicados en diversas funciones cognitivas. Asimismo, los datos neuroendocrinos y conductuales refuerzan las hipoteizadas acciones de los glucocorticoides sobre los procesos de formación de la memoria, incluidas las memorias traumáticas. Por otro lado, el estrés crónico indujo un descenso de los niveles de NCAM hipocampales, que podría estar implicado en los procesos deletéreos que a nivel sináptico se han descrito en otros estudios a nivel de dicha estructura. Por el contrario, incrementó los niveles de PSA-NCAM y de Ll, moléculas implicadas en el remodelamiento estructural de tipo compensatorio ante el daño neural inducido por el estrés crónico. Además, el estrés crónico también indujo alteraciones en el contenido de dichas moléculas de adhesión en otras regiones cerebrale

The Impact of CXCR4 Blockade on the Survival of Rat Brain Cortical Neurons

Background: Chemokine receptor type 4 (CXCR4) plays a role in neuronal survival/cell repair and also contributes to the progression of cancer and neurodegenerative diseases. Chemokine ligand 12 (CXCL12) binds to CXCR4. In this study, we have investigated whether CXCR4 blockade by AMD3100 (a CXCR4 antagonist, member of bicyclam family) may affect neuronal survival in the absence of insult. Thus, we have measured the mitochondrial membrane potential (MMP), Bax and Bcl-2 protein translocation, and cytochrome c release in AMD3100-treated brain cortical neurons at 7 DIV (days in vitro). Methods: For this aim, AMD3100 (200 nM) was added to cortical neurons for 24 h, and several biomarkers like cell viability, reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release, caspase-3/9 activity, proteins Bax and Bcl-2 translocation, and cytochrome c release were analyzed by immunoblot. Results: CXCR4 blockade by AMD3100 (200 nM, 24 h) induces mitochondrial hyperpolarization and increases caspase-3/9 hyperpolarization without affecting LDH release as compared to untreated controls. AMD3100 also increases cytochrome c release and promotes Bax translocation to the mitochondria, whereas it raises cytosolic Bcl-2 levels in brain cortical neurons. Conclusion: CXCR4 blockade induces cellular death via intrinsic apoptosis in rat brain cortical neurons in absence of insult

Elevated Systemic L-Kynurenine/L-Tryptophan Ratio and Increased IL-1 Beta and Chemokine (CX3CL1, MCP-1) Proinflammatory Mediators in Patients with Long-Term Titanium Dental Implants

Titanium is the mean biocompatible metal found in dental titanium alloys (Ti-6Al-4V). The safety of certain dental biomaterial amalgams has been questioned in patients. The levels of several systemic cytokines (interleukin (IL)-1 beta, IL-4: pg/mL) and chemokines (monocyte chemoattractant protein-1 (MCP-1), soluble fractalkine (CX3CL1: pg/mL) were determined using ELISA and compared between these study groups. The study included 30 controls without dental materials (cont), 57 patients with long-term titanium dental implants plus amalgams (A + I group) as well as 55 patients with long-term dental amalgam alone (A group). All patients (except controls) have had dental titanium implants (Ti-6Al-4V) and/or amalgams for at least 10 years (average: 15 years). We evaluated whether systemic levels of cytokines/chemokines, kyn/L-trp ratio and aromatic amino acid levels (HPLC: mM/L, Phe, L-Trp, His, Treo) could be altered in patients with long-term dental titanium and/or amalgams. These systemic markers were evaluated in 142 patients. The A + I group had higher L-Kynurenine/L-Tryptophan ratios than patients with long-term dental amalgam fillings alone (A). In addition, levels of IL-1 Beta cytokine, CX3CL1 and MCP-1 chemokines were higher in the A + I group than in the A group (A). The increased L-kyn/L-trp ratio and MCP-1 and fractalkine receptor (CX3CR1) elevations could suggest enhanced chemotactic responses by these chemokines in the A + I group

Carob fruit extract-enriched meat improves pancreatic beta-cell dysfunction, hepatic insulin signaling and lipogenesis in late-stage type 2 diabetes mellitus model

The inclusion of functional bioactive compounds of dietary fiber in meat products has been demonstrated to exert a significant impact on human health. Carob fruit extract (CFE) is a dietary fiber rich in proanthocyanidins with known antioxidant, hypolipidemic and hypoglycemic effects. Consumption of CFE-enriched meat (CFE-RM) may provide interesting benefits in late-stage type 2 diabetes mellitus (T2DM). To explore the antidiabetic mechanisms of CFE-RM, we used a model of late-stage T2DM in Wistar rats fed a high-saturated-fat/high-cholesterol diet (Chol-diet) and injected streptozotocin plus nicotinamide (D group). The effects of CFE-RM were tested by incorporating it into the diet as preventive strategy (ED group) or curative treatment (DE group). CFE-RM had a positive effect on glycemia, enhancing hepatic insulin sensitivity and improving pancreatic β-cell regeneration in both ED and DE groups. Western blotting and immunohistochemistry suggested that CFE-RM increased levels of insulin receptor β and phosphatidylinositol-3-kinase, as well as the downstream target phospho-Akt (at Ser473). CFE-RM also up-regulated glucose transporter 2, which improves the insulin-mediated glucose uptake by the liver, and promoted phosphorylation of glycogen synthesis kinase-3βprotein (at ser9), consequently increasing the hepatic glycogen content. In addition, CFE-RM decreased fatty liver by suppressing de novo lipogenesis activation due to down-regulation of liver X receptor-α/β, sterol regulatory element binding protein-1c and carbohydrate-response element-binding protein transcription factors. Our findings suggest that the consumption of CFE-RM included in the diet as a functional food should be considered as a suitable nutritional strategy to prevent or manage late-stage T2DM.Ministerio de Educación, Cultura y Deporte (España)Banco SantanderUniversidad Complutense de MadridDepto. de Farmacología, Farmacognosia y BotánicaFac. de FarmaciaTRUEpu