Clinical pharmacology facing the real-world setting: Pharmacovigilance, pharmacoepidemiology and the economic evaluation of drugs

Adverse drug reaction; Effectiveness; PharmacoeconomicsReacció adversa als fàrmacs; Eficàcia; FarmacoeconomiaReacción adversa a medicamentos; Eficacia; FarmacoeconomíaTraditionally, clinical pharmacology has focused its activities on drug-organism interaction, from an individual or collective perspective. Drug efficacy assessment by performing randomized clinical trials and analysis of drug use in clinical practice by carrying out drug utilization studies have also been other areas of interest. From now on, Clinical pharmacology should move from the analysis of the drug-individual interaction to the analysis of the drug-individual-society interaction. It should also analyze the clinical and economic consequences of the use of drugs in the conditions of normal clinical practice, beyond clinical trials. The current exponential technological development that facilitates the analysis of real-life data offers us a golden opportunity to move to all these other areas of interest. This review describes the role that clinical pharmacology has played at the beginning and during the evolution of pharmacovigilance, pharmacoepidemiology and economic drug evaluations in Spain. In addition, the challenges that clinical pharmacology is going to face in the following years in these three areas are going to be outlined too

Hepatoid adenocarcinoma of the stomach – a different histology for not so different gastric adenocarcinoma: a case report

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects

Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting

26 p.-6 fig.-1 tab.-1 graph. abst.There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)—the principal methyl donor—acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.M.V.-R. is supported by Proyecto PID2020-119486RB-100 (funded by MCIN/AEI/10.13039/501100011033), Gilead Sciences International Research Scholars Program in Liver Disease, Acción Estratégica Ciberehd Emergentes 2018 (ISCIII), Fundación BBVA, HORIZON-TMA-MSCA-Doctoral Networks 2021 (101073094), and Redes de Investigación 2022 (RED2022-134485-T). M.L.M.-C. is supported by La CAIXA Foundation (LCF/PR/HP17/52190004), Proyecto PID2020-117116RB-I00 (funded by MCIN/AEI/10.13039/501100011033), Ayudas Fundación BBVA a equipos de investigación científica (Umbrella 2018), and AECC Scientific Foundation (Rare Cancers 2017). A.W. is supported by RTI2018-097503-B-I00 and PID2021-127169OB-I00, (funded by MCIN/AEI/10.13039/501100011033) and by “ERDF A way of making Europe,” Xunta de Galicia (Ayudas PRO-ERC), Fundación Mutua Madrileña, and European Community’s H2020 Framework Programme (ERC Consolidator grant no. 865157 and MSCA Doctoral Networks 2021 no. 101073094). C.M. is supported by CIBERNED. P.A. is supported by Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT1476-22), PID2021-124425OB-I00 (funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe,” MCI/UE/ISCiii [PMP21/00080], and UPV/EHU [COLAB20/01]). M.F. and M.G.B. are supported by PID2019-105739GB-I00 and PID2020-115472GB-I00, respectively (funded by MCIN/AEI/10.13039/501100011033). M.G.B. is supported by Xunta de Galicia (ED431C 2019/013). C.A., T.L.-D., and J.B.-V. are recipients of pre-doctoral fellowships from Xunta de Galicia (ED481A-2020/046, ED481A-2018/042, and ED481A 2021/244, respectively). T.C.D. is supported by Fundación Científica AECC. A.T.-R. is a recipient of a pre-doctoral fellowship from Fundación Científica AECC. S.V.A. and C.R. are recipients of Margarita Salas postdoc grants under the “Plan de Recuperación Transformación” program funded by the Spanish Ministry of Universities with European Union’s NextGeneration EU funds (2021/PER/00020 and MU-21-UP2021-03071902373A, respectively). T.C.D., A.S.-R., and M.T.-C. are recipients of Ayuda RYC2020-029316-I, PRE2019/088960, and BES-2016/078493, respectively, supported by MCIN/AEI/10.13039/501100011033 and by El FSE invierte en tu futuro. S.L.-O. is a recipient of a pre-doctoral fellowship from the Departamento de Educación del Gobierno Vasco (PRE_2018_1_0372). P.A.-G. is recipient of a FPU pre-doctoral fellowship from the Ministry of Education (FPU19/02704). CIC bioGUNE is supported by Ayuda CEX2021-001136-S financiada por MCIN/AEI/10.13039/501100011033. A.B.-C. was funded by predoctoral contract PFIS (FI19/00240) from Instituto de Salud Carlos III (ISCIII) co-funded by Fondo Social Europeo (FSE), and A.D.-L. was funded by contract Juan Rodés (JR17/00016) from ISCIII. A.B.-C. is a Miguel Servet researcher (CPII22/00008) from ISCIII.Peer reviewe

One-year changes in fruit and vegetable variety intake and cardiometabolic risk factors changes in a middle-aged Mediterranean population at high cardiovascular risk

Background and aims Previous studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome. Methods a one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (β-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors. Results Two points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (−0.33 mg/dL (0.58, −0.07)), body weight (−0.07 kg (−0.13, −0.02)) and waist circumference (WC) (−0.08 cm (−0.16, −10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (−0.50 mg/dL (−0.93, −0.08)), glucose (−0.21 mg/dL (−0.32, −0.11)), body weight (−0.11 kg (−0.15, −0.07)) and WC (−0.10 cm (−0.14, −0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (−1.26 mg/dL (−2.09, −0.43)), body weight (−0.40 kg (−0.58, −0.23)) and WC (−0.50 cm (−0.73, −0.28)). Conclusion Greater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk

Treatment of EVA with corona discharge to improve its adhesion to polychloroprene adhesive

Ethylene vinyl acetate (EVA) material containing 20 wt% vinyl acetate (EVA20) was treated with corona discharge to improve its adhesion to polychloroprene adhesive. Several experimental variables in the corona discharge treatment of EVA20 were considered: corona energy, type of electrode, and number of consecutive treatments. Advancing contact angle measurements (water, 25±C) showed an increase in the wettability of EVA20 after treatment with corona discharge, which corresponds to an increase in the O/C ratio on the treated surface. The higher the corona energy (i.e. the higher discharge power and longer treatment times), the greater the degree of surface oxidation. Peel strength values of the joints produced with EVA20 using a polychloroprene adhesive containing 5 wt% isocyanate increased from 1.5 kN/m (as-received EVA20) to 4.3 kN/m (corona-treated EVA20). A mixed (adhesional C cohesive in EVA20) locus of failure was obtained in all adhesive joints produced with corona discharge-treatedEVA20. Finally, the number of consecutive corona discharge treatments and the surface area of the electrode (spherical versus hook-shaped electrode) did not greatly influence the adhesion of EVA20 to polychloroprene adhesive

Experiencias en la realización y evaluación de trabajo colaborativo en asignaturas de la Licenciatura en Química, para su adaptación al nuevo Grado en Química

Póster presentado en las IX Jornadas de Redes de Investigación en Docencia Universitaria, Alicante, 16-17 junio 2011.En el nuevo Grado en Química, la asignatura Introducción a la Ciencia de los Materiales prestará la mayor parte de sus contenidos a la asignatura del segundo curso Sólidos Inorgánicos. El trabajo colaborativo es una metodología docente que permite al alumnado aprender no solo contenidos relacionados con las asignaturas, sino también desarrollar habilidades y capacidades contempladas en las competencias Genéricas del Grado en Química, como GCG1, CG3, CG6 y Genéricas de la UA, como CGUA2 y CGUA3. El trabajo no presencial del alumno requiere el uso de herramientas no presenciales que puedan facilitar el aprendizaje colaborativo, como las que se incluyen en sistema de gestión del aprendizaje (LMS), en nuestro caso Campus Virtual y Moodle. Para facilitar la realización del trabajo por parte de los grupos, se debe elaborar el conjunto de parámetros que utilizará el profesorado para realizar la evaluación, que servirán de guía para que el alumnado consiga llegar a alcanzar los objetivos formativos y transversales de los trabajos. Dicho conjunto se denomina en la bibliografía anglosajona “rubric”, pudiendo encontrar en la web un enorme abanico de instrucciones para su definición

Lab-On-A-Screen 2.0: Ludificación e Inmersión en Experimentos de Química Inorgánica

La experiencia docente desarrollada a lo largo de este proyecto de investigación docente está centrada en profundizar sobre los objetivos desarrollados en la red anterior (Lab-on-a-Screen) mediante (1) la mejora y expansión de una herramienta online gracias a la cual el alumnado pueda, de forma lúdica, adquirir conocimientos y destrezas sobre el material de laboratorio y su clasificación, así como de algunas operaciones básicas de laboratorio de Química Inorgánica mediante “e-learning” y (2) posibilitar la inmersión del alumnado en el entorno de laboratorio para mejorar su comprensión y manejo del mismo mediante la grabación de videos didácticos y la construcción de entornos de realidad virtual. La aplicación está vinculada al Campus Virtual de la Universidad de Alicante y cuenta con cuatro actividades principales, que recogen tres experiencias básicas de laboratorio de Química Inorgánica (i.e. destilación, calentamiento a reflujo y destilación a vacío) y una cuarta actividad de carácter más general, que consiste en identificar correctamente material de laboratorio