المؤلفون: Borobia Pérez, Alberto M., Dapia, Irene, Tong, Hoi Y., Arias, Pedro, Muñoz, Mario, Tenorio, Jair, Hernández, Rafael, García García, Irene, Gordo, Gema, Ramírez García, Elena, Frías Iniesta, Jesús A., Lapunzina, Pablo, Carcas Sansuán, Antonio Javier

المساهمون: UAM. Departamento de Farmacología

مصطلحات موضوعية: individualization, pharmacogenetics, precision medicine, Farmacia

الوصف: In 2014, we established a pharmacogenetics unit with the intention of facilitating the integration of pharmacogenetic testing into clinical practice. This unit was centered around two main ideas: i) individualization of clinical recommendations, and ii) preemptive genotyping in risk populations. Our unit is based on the design and validation of a single nucleotide polymorphism (SNP) microarray, which has allowed testing of 180 SNPs associated with drug response (PharmArray), and clinical consultation regarding the results. Herein, we report our experience in integrating pharmacogenetic testing into our hospital and we present the results of the 2,539 pharmacogenetic consultation requests received over the past 3 years in our unit. The results demonstrate the feasibility of implementing pharmacogenetic testing in clinical practice within a national health system

وصف الملف: application/pdf

العلاقة: Clinical and Translational Science; https://doi.org/10.1111/cts.12526Test; Clinical And Translational Science 11.2 (2018): 189-199; 1752-8054 (print); 1752-8062 (online); http://hdl.handle.net/10486/710583Test; 189; 199; 11

الإتاحة: https://doi.org/10.1111/cts.12526Test
http://hdl.handle.net/10486/710583Test

المؤلفون: Pascual Izquierdo, Cristina, Mingot Castellano, María Eva, Kerguelen Fuentes, Ana E., García-Arroba Peinado, José, Cid, Joan, Moraima Jimenez, Maria, Valcarcel, David, Gómez Seguí, Inés, de la Rubia, Javier, Martin, Paz, Goterris, Rosa, Hernández, Luis, Tallón, Inmaculada, Varea, Sara, Fernández, Marta, García Muñoz, Nadia, Vara, Míriam, Fernández Zarzoso, Miguel, García Candel, Faustino, Paciello, María Liz, García García, Irene, Zalba, Saioa, Campuzano, Verónica, Gala, José María, Vidán Estévez, Julia, Moreno Jiménez, Gemma, López Lorenzo, José Luis, González Arias, Elena, Freiría, Carmen, Solé, María, Ávila Idrovo, Laura Francisca, Hernández Castellet, José Carlos, Cruz, Naylen, Lavilla, Esperanza, Pérez Montaña, Albert, Atucha, Jon Ander, Moreno Beltrán, María Esperanza, Moreno Macías, Juán Ramón, Salinas, Ramón, del Rio Garma, Julio

المصدر: Blood Advances. Vol. 6, nº 24, December 2022, pp. 6219 - 6227

مصطلحات موضوعية: caplacizumab, prednisone, rituximab

الوصف: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX. ; 9 páginas

وصف الملف: application/pdf

العلاقة: http://hdl.handle.net/10498/29789Test

الإتاحة: https://doi.org/10.1182/bloodadvances.2022008028Test
http://hdl.handle.net/10498/29789Test

المؤلفون: Marín-Candón, Alicia, García-García, Irene, Arias, Pedro, Carcas, Antonio J, Díaz-García, Lucía, Feltes Ochoa, Rosa, Hernández Cano, Natalia, Herranz Pinto, Pedro, Jiménez González, María, López -Granados, Eduardo, Martínez-Feito, Ana, Mayor-Ibarguren, Ander, Rosas-Alonso, Rocío, Seco-Meseguer, Enrique, Borobia, Alberto M

مصطلحات موضوعية: Dermatology

الوصف: Introduction There is a need to optimise the management of atopic dermatitis (AD), improving the efficacy of treatments and reducing the toxicity associated with them. Although the efficacy of ciclosporine (CsA) in the treatment of AD has been thoroughly documented in the literature, the optimal dose has not been yet established. The use of multiomic predictive models of treatment response could optimise CsA therapy in AD. Methods and analysis The study is a low-intervention phase 4 trial to optimise the treatment of patients with moderate-severe AD requiring systemic treatment. The primary objectives are to identify biomarkers that could allow for the selection of responders and non-responders to first-line treatment with CsA and to develop a response prediction model to optimise the CsA dose and treatment regimen in responding patients based on these biomarkers. The study is divided into two cohorts: the first comprised of patients starting treatment with CsA (cohort 1), and the second, of patients already receiving or who have received CsA therapy (cohort 2). Ethics and dissemination The study activities began following authorisation by the Spanish Regulatory Agency (AEMPS) and the Clinical Research Ethics Committee of La Paz University Hospital approval. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication. Trial registration of this study can be located at the EU Clinical Trials Register, available from https://euclinicaltrials.eu/search-for-clinical-trials/?lang=enTest . Our clinical trial was registered in the website before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according the WHO. Once our trial was included in a primary and official registry, in order to extend the accessibility to our research, we also registered it retrospectively in clinicaltrials.gov; however, this is not mandatory as per our regulation. Trial registration number NCT05692843 .

وصف الملف: text/html

العلاقة: http://bmjopen.bmj.com/cgi/content/short/13/7/e072350Test; http://dx.doi.org/10.1136/bmjopen-2023-072350Test

الإتاحة: https://doi.org/10.1136/bmjopen-2023-072350Test
http://bmjopen.bmj.com/cgi/content/short/13/7/e072350Test

المؤلفون: Stewart, Stefan, Dodero-Anillo, Jose Manuel, Guijarro-Eguinoa, Javier, Arias, Pedro, Gómez López De Las Huertas, Arturo, Seco-Meseguer, Enrique, García-García, Irene, Ramírez García, Elena, Rodríguez-Antolín, Carlos, Carcas, Antonio J., Rodriguez-Novoa, Sonia, Rosas-Alonso, Rocio, Borobia, Alberto M.

المصدر: Frontiers in Pharmacology ; volume 14 ; ISSN 1663-9812

مصطلحات موضوعية: Pharmacology (medical), Pharmacology

الوصف: The field of pharmacogenetics (PGx) holds great promise in advancing personalized medicine by adapting treatments based on individual genetic profiles. Despite its benefits, there are still economic, ethical and institutional barriers that hinder its implementation in our healthcare environment. A retrospective analysis approach of anonymized data sourced from electronic health records was performed, encompassing a diverse patient population and evaluating key parameters such as prescribing patterns and test results, to assess the impact of pharmacogenetic testing. A head-to-head comparison with previously published activity results within the same pharmacogenetic laboratory was also conducted to contrast the progress made after 10 years. The analysis revealed significant utilization of pharmacogenetic testing in daily clinical practice, with 1,145 pharmacogenetic tests performed over a 1-year period and showing a 35% growth rate increase over time. Of the 17 different medical departments that sought PGx tests, the Oncology department accounted for the highest number, representing 58.47% of all genotyped patients. A total of 1,000 PGx tests were requested for individuals susceptible to receive a dose modification based on genotype, and 76 individuals received a genotype-guided dose adjustment. This study presents a comprehensive descriptive analysis of real-world data obtained from a public tertiary hospital laboratory specialized in pharmacogenetic testing, and presents data that strongly endorse the integration of pharmacogenetic testing into everyday clinical practice.

الإتاحة: https://doi.org/10.3389/fphar.2023.1292416Test

المؤلفون: Pérez-jurado, Luis A., Cáceres, Alejandro, Balagué-dobón, Laura, Esko, Tonu, López de Heredia, Miguel, Quintela, Inés, Cruz, Raquel, Lapunzina, Pablo, Carracedo, Ángel, Abellán, Javier, Acosta-isaac, René, Tavares, Nathali A. C., Carvalho, Maria C. C., Dalmau, David, Dantas-komatsu, Raquel C. S., Darnaude, M. Teresa, De Andrés, Raimundo, De Juan, Carmen, De La Cruz Troca, Juan J., De La Horra, Carmen, De La Hoz, Ana B., Aguado, Jose María, De Martino-rodríguez, Alba, Cruz, Marina S., De Sousa Alves Neri, Julianna Lys, Del Campo-pérez, Victor, Delgado-cuesta, Juan, Diaz De Bustamante, Aranzazu, Díaz-pérez, Anderson, Dietl, Beatriz, Diz-de Almeida, Silvia, Do Monte Alves, Manoella, Aguilar, Carlos, Domínguez-garrido, Elena, Rosa, Lidia S., Luchessi, Andre D., Echave-sustaeta, Jose, Eiros, Rocío, Enciso-olivera, César O., Escudero, Gabriela, España, Pedro Pablo, Estigarribia Sanabria, Gladys, Fariñas, María Carmen, Aguilera-albesa, Sergio, Fernández, Ramón, Fernández-caballero, Lidia, Fernández-cruz, Ana, Fernández-ferrero, Silvia, Fernández Martínez, Yolanda, Fernandez-nestosa, María J., Fernández-robelo, Uxía, Fernández-rodríguez, Amanda, Fernández-sampedro, Marta, Fernández, Ruth, Ahmadi Sabbagh, Abdolah, Fernández-villa, Tania, Fernández-capitán, Carmen, Carioca, Antonio Augusto F., Flores-pérez, Patricia, Fuenmayor-hernández, Lácides, Fuertes-núñez, Marta, Fumadó, Victoria, Gadea, Ignacio, Gagliardi, Lidia, Gago-domínguez, Manuela, Alba, Jorge, Gallego, Natalia, Galoppo, Cristina, García-soidán, Ana, García-cerrada, Carlos, García-de-vicuña, Aitor, Garcia-garcía, Josefina, García-garcía, Irene, García-ibarbia, Carmen, García-montero, Andrés C., García, Leticia, Albu, Sergiu, García, Mercedes, García Torrejón, María Carmen, García, Inés, García-vázquez, Elisa, Garza-frias, Emiliano, Gentile, Angela, Gil-fournier, Belén, De Araújo, Jéssica N. G., Gómez-duque, Mario, Gómez-arrue, Javier, Alcalá-gallardo, Karla A. M., Gómez Carrera, Luis, Gómez García, María, Gómez Sacristán, Ángela, González, Juan R., González-neira, Anna, González Álvarez, Beatriz, González Bernaldo De Quirós, Fernán, González-montelongo, Rafaela, González-peñas, Javier, Gonzalez-sagrado, Manuel, Alcoba-florez, Julia, Gonzalo-benito, Hugo, Gorgojo-galindo, Oscar, Górgolas, Miguel, Guaragna, Florencia, Chaux, Jessica G., Guillén-navarro, Encarna, Guillén-guío, Beatriz, Guisado-vasco, Pablo, Gutiérrez-castañeda, Luz D., Gutiérrez-bautista, Juan F., Alcolea Batres, Sergio, Heili-frades, Sara, Jacomo, Rafael H., Hernández, Estefania, Hernández-moro, Cristina, Hernández-ortega, Luis D., Hernández-pérez, Guillermo, Hernández-vaquero, Rebeca, Herráez, Belén, Herranz, M. Teresa, Herrera, María, Algarin-lara, Holmes Rafael, Herrero, María José, Herrero-gonzález, Antonio, Horcajada, Juan P., Imaz-ayo, Natale, Intxausti-urrutibeaskoa, Maider, Íñigo-campos, Antonio, Íñiguez, María, Jara, Rubén, Jiménez, Ángel, Jiménez-alfaro, Ignacio, Almadana, Virginia, Jiménez, Pilar, Jiménez-sousa, María A., Jordan, Iolanda, Laguna-goya, Rocío, Laorden, Daniel, Lasa-lázaro, María, Lattig, María Claudia, Lauriente, Ailen, Liger Borja, Anabel, Llanos, Lucía, Medeiros, Kelliane A., López-bernús, Amparo, López De Heredia, Miguel, Lopez-garcia, Esther, López-granados, Eduardo, Lopez-rodriguez, Rosario, López-ruz, Miguel A., Lorente, Leonardo, Lorenzo-salazar, José M., Lozano, José E., Lozano-espinosa, María, Almeida, Julia, Mahillo, Ignacio, Mancebo, Esther, Mar, Carmen, Marcelo Calvo, Cristina, Marcos-delgado, Alba, Marcos, Miguel, Marín-candón, Alicia, Mariscal-aguilar, Pablo, Martin-pedraza, Laura, Martin-fernandez, Marta, Almoguera, Berta, Martín-lópez, Caridad, Martín-oterino, José-Ángel, Martín, María Dolores, Martín, Vicente, Martín, María M., Martín-vicente, María, Martinez, Amalia, Martínez-gonzález, Óscar, Martínez, Ricardo, Martinez-paz, Pedro, Alonso, María R., Díaz-caneja, Covadonga M., Martínez-nieto, Óscar, Martínez-lópez, Iciar, Martínez-reséndez, Michel F., Martínez, Silvia, Martínez, Juan José, Martínez-pérez, Ángel, Martínez-ramas, Andrea, Martínez-robles, Violeta, Marzal, Laura, Álvarez, Nuria, Mazzeu, Juliana F., Medrano, Francisco J., Meijome, Xose M., Mejuto-montero, Natalia, Mendes, Ingrid, Duarte, Alice L., Méndez-echevarría, Ana, Mendoza Charris, Humberto, Merayo Macías, Eleuterio, Mercadillo, Fátima, Álvarez-sala Walther, Rodolfo, Mercado-sesma, Arieh R., Mínguez, Pablo, Molina-roldán, Elena, Molina, Antonio J. J., Montoya, Juan José, Pinho, Susana M. T., Moreira-escriche, Patricia, Morelos-arnedo, Xenia, Moreno, Rocío, Moreno Cuerda, Víctor, Álvarez-benítez, Yady, Moreno-docón, Antonio, Moreno-escalante, Junior, Moreno Fernández, Alberto, Muñoz García, Patricia, Neira, Pablo, Nevado, Julián, Nieto-gañán, Israel, Silbiger, Vivian N., Nuñez-torres, Rocío, Obrador-hevia, Antònia, Álvarez-navia, Felipe, Ocejo-vinyals, J. Gonzalo, Olivar, Virginia, Oliveira, Silviene F., Ondo, Lorena, Orfao, Alberto, Ortega-paino, Eva, Ortega, Luis, Ortiz-lópez, Rocío, Ortiz-flores, Fernando, Oteo, José A., Dos Santos, Katiusse A., Pacheco, Manuel, Pacheco-miranda, Fredy Javier, Padilla-conejo, Irene, Panadero-fajardo, Sonia, Parellada, Mara, Pariente-rodríguez, Roberto, Friaza, Vicente, Paz-artal, Estela, Peces-barba, Germán, Pedromingo Kus, Miguel S., Andreu-bernabeu, Álvaro, Perales, Celia, Santos, Ney P. C., Guegel, Genilson P., Pérez, María Jazmín, Pérez, Alexandra, Pérez-matute, Patricia, Pérez, César, Pérez-de-nanclares, Gustavo, Pérez-garcía, Felipe, Pérez, Patricia, Antonijoan, Maria Rosa, Pérez-tomás, M. Elena, Perucho, Teresa, Pichardo, Lisbeth A., Ribeiro, Adriana P., Pinsach-abuin, Mel·lina, Pinzón, Luz Adriana, Medeiros, Jeane F. P., Pita, Guillermo, Pla-juncà, Francesc, Planas-serra, Laura, Martínez-aquino, Eleno, Pompa-mera, Ericka N., Porras-hurtado, Gloria L., Pujol, Aurora, Quevedo-chávez, María Eugenia, Quijada, Maria Angeles, Ramiro-león, Soraya, Rascado Sedes, Pedro, Nunes, Joana F. R., Recalde, Delia, Arana-arri, Eunate, Recio-fernández, Emma, Resino, Salvador, Sousa, Renata R., Rivadeneira-chamorro, Carlos S., Roa-agudelo, Diana, Robelo Pardo, Montserrat, Fernandes, Marianne R., Rodríguez-hernández, María A., Rodriguez-palmero, Agustí, Rodríguez-ruiz, Emilio, Aranda, Carlos, Rodriguez, Marilyn Johanna, Rodríguez-artalejo, Fernando, Rodríguez-ferrer, Marena, Rodríguez-gallego, Carlos, Rodríguez-garcía, José A., Maya, Belén Rodríguez, Rodriguez-nicolas, Antonio, Rodríguez-novoa, German Ezequiel, Rodriguez-urrego, Paula A., Rojo, Federico, Arango, Celso, Romero-coronado, Andrea, Morilla, Rubén, Rondón-garcía, Filomeno, Rosales-castillo, Antonio, Rubio, Cladelis, Olivera, María Rubio, Ruiz-cabello, Francisco, Ruiz-casares, Eva, Ruiz-cubillan, Juan J., Ruiz-hornillos, Javier, Araque, Carolina, Ruiz, Montserrat, Ryan, Pablo, Salamanca, Hector D., Salazar-garcía, Lorena, Salgueiro-origlia, Giorgina Gabriela, Sangil, Anna, Sánchez-pernaute, Olga, Sánchez, Pedro-luis, Sánchez López, Antonio J., Sánchez-pablo, Clara, Araujo, Nathalia K., Sánchez-prados, María Concepción, Sánchez-real, Javier, Sánchez-redondo, Jorge, Sancho-sainz, Cristina, Sande, Esther, Santos, Arnoldo, Schlüter, Agatha, Segovia, Sonia, Serra-llovich, Alex, Sevil-puras, Fernando, Arcanjo, Ana C., Sevilla-porras, Marta, Sicolo, Miguel A., Silván-fuentes, Cristina, Moraes, Vitor M. S., Souza, Vanessa S., Solé-violán, Jordi, Soria, José Manuel, Sorlí, Jose V., Silva, Nayara S., Souto, Juan Carlos, Arnaiz, Ana, Sprockel, John J., Suárez-rama, José Javier, Suárez-zamora, David A., Taboada-fraga, Xiana, Tamayo, Eduardo, Tamayo-velasco, Alvaro, Taracido-fernández, Juan Carlos, Vasconcelos, Romero H. T., Tellería, Carlos, Carratto, Thássia M. T., Arnalich Fernández, Francisco, Tenorio-castaño, Jair Antonio, Teper, Alejandro, Araujo, Izabel M. T., Torres-macho, Juan, Torres-tobar, Lilian, Torres-gutiérrez, Ronald P., Troya, Jesús, Urioste, Miguel, Valencia-ramos, Juan, Valido, Agustín, Arranz, María J., Vargas-gallo, Juan Pablo, Varón, Belén, Vega, Tomas, Velasco-quirce, Santiago, Vélez-santamaría, Valentina, Víctor, Virginia, Vidán-estévez, Julia, Silva, Gabriela V., Vieitez-santiago, Miriam, Vilches, Carlos, Arribas López, José Ramón, Villalobos, Lavinia, Villar, Felipe, Villar-garcia, Judit, Villaverde, Cristina, Villoslada-blanco, Pablo, Virseda-berdices, Ana, Costa, Tatiana X., Yáñez, Zuleima, Zapatero-gaviria, Antonio, Zarate, Ruth, Artiga, Maria-jesús, Zazo, Sandra, Flores, Carlos, Riancho, José A., Rojas-martinez, Augusto, Scourge Cohort Group, Avello-malaver, Yubelly, Ayuso, Carmen, Ballina Martín, Belén, Baptista-rosas, Raúl C., Baldion, Ana María, Barranco-díaz, Andrea, Barreda-sánchez, María, Barrera-penagos, Viviana, Belhassen-garcia, Moncef, Bernal-bello, David, Bernal, Enrique, Bezerra, Joao F., Bezerra, Marcos A. C., Blanca-lópez, Natalia, Blancas, Rafael, Boix-palop, Lucía, Borobia, Alberto, Bravo, Elsa, Brion, María, Brochado-kith, Óscar, Brugada, Ramón, Bustos, Matilde, Cabello, Alfonso, Cáceres-agra, Juan J., Calbo, Esther, Calderón, Enrique J., Camacho, Shirley, Ceballos, Francisco C., Cañadas, Yolanda, Carbonell, Cristina, Cardona-huerta, Servando, Sánchez-carpintero Abad, María, Carpio Segura, Carlos, Carrillo-avila, José Antonio, Campos, Marcela C., Casasnovas, Carlos, Castaño, Luis, Castaño, Carlos F., Castelao, Jose E., Castellano Candalija, Aranzazu, Castillo, María A., Chaves-santiago, Walter G., Chiquillo-gómez, Sylena, Cid-lópez, Marco A., Cienfuegos-jiménez, Óscar, Conde-vicente, Rosa, Cunha, Gabriela C. R., Cordero-lorenzana, M. Lourdes, Corella, Dolores, Corrales, Almudena, Cortés-sánchez, Jose L., Corton, Marta, Souza, Karla S. C., Silva, Fabiola T. C., Cuesta, Luisa

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

الوصف: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality.

وصف الملف: application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.1038/s42003-024-05805-6Test; Communications Biology, 2024, vol. 7, issue. 1; https://doi.org/10.1038/s42003-024-05805-6Test; http://hdl.handle.net/2445/211324Test

الإتاحة: https://doi.org/10.1038/s42003-024-05805-6Test
http://hdl.handle.net/2445/211324Test

المؤلفون: Pascual Izquierdo, Cristina, Mingot Castellano, María Eva, Kerguelen Fuentes, Ana E., García Arroba Peinado, José, Cid Vidal, Joan, Jimenez, Maria Moraima, Valcarcel, David, Gómez Seguí, Inés, Rubia, Javier de la, Martin, Paz, Goterris, Rosa, Hernández, Luis, Tallón, Inmaculada, Varea, Sara, Fernández, Marta, García Muñoz, Nadia, Vara, Míriam, Fernández Zarzoso, Miguel, García Candel, Faustino, Paciello, María Liz, García García, Irene, Zalba, Saioa, Campuzano, Verónica, Gala, José María, Vidán Estévez, Julia, Moreno Jiménez, Gemma, López Lorenzo, José Luis, González Arias, Elena, Freiría, Carmen, Solé, María, Ávila Idrovo, Laura Francisca, Hernández Castellet, José Carlos, Cruz, Naylen, Lavilla, Esperanza, Pérez Montaña, Albert, Atucha, Jon Ander, Moreno Beltrán, María Esperanza, Moreno Macías, Juán Ramón, Salinas, Ramón, Rio Garma, Julio del, Spanish Apheresis Group (GEA), Spanish Thrombotic Thrombocytopenic Purpura Registry (REPTT)

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

مصطلحات موضوعية: Rituximab, Trombosi, Assaigs clínics, Thrombosis, Clinical trials

الوصف: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX.

وصف الملف: 9 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.1182/bloodadvances.2022008028Test; Blood Advances, 2022, vol. 6, num. 24, p. 6219-6227; https://doi.org/10.1182/bloodadvances.2022008028Test; http://hdl.handle.net/2445/196688Test

الإتاحة: https://doi.org/10.1182/bloodadvances.2022008028Test
http://hdl.handle.net/2445/196688Test

المؤلفون: Rodríguez, Amelia, García-García, Irene, Martínez de Soto, Lucía, Gómez López De Las Huertas, Arturo, Borobia, Alberto M., González-Torbay, Andrea, Akatbach-Bousaid, Ibtissam, González-Muñoz, Miguel, Ramírez, Elena

المصدر: Frontiers in Pharmacology ; volume 13 ; ISSN 1663-9812

مصطلحات موضوعية: Pharmacology (medical), Pharmacology

الوصف: Background: The Roussel Uclaf Causality Assessment Method (RUCAM) is a validated tool for assessing causality in cases of suspected drug-induced liver injury (DILI). However, RUCAM cannot discriminate between concomitant hepatotoxic drugs with the same temporal sequence. Objective: To analyse the utility of the lymphocyte transformation test (LTT) for assisting updated RUCAM in 45 patients and 40 controls with a clinical diagnosis of DILI. Methods: Suspected DILI cases were detected through the Prospective Pharmacovigilance Program from Laboratory Signals in Hospital (PPLSH) or by consultations. The controls completed the drug therapy with no adverse reactions during the study period. A receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value for the stimulation index (SI), corresponding to the largest sum for the specificity and sensitivity values of LTT for true DILI cases. Results: Out of 45 patients diagnosed with DILI, 42 cases were detected by the PPLSH, two cases by consultation and one case by both methods. Most DILI cases (64.4%) arose during hospitalization. According to the biochemical parameters, 24 cases (53.3%) had the hepatocellular phenotype, 14 (31.1%) had the cholestatic phenotype, and 7 cases (15.6%) had the mixed phenotype. Considering the severity criteria, 7 (15.5%) cases were classified as moderate DILI, and 4 (8.9%) were severe DILI; there were no fatal cases. A total of 149 drugs (median/case, 3; IQR, 2–5) were suspected to be involved in the DILI cases (RUCAM score ≥3). In 8 cases, only one drug was suspected, and polypharmacy (≥5 drugs) was identified in 29% of the cases. Of all DILI cases, 46 (30.9%) of the 149 suspected drugs produced positive LTT results, and the LTT was positive in 34 (75.5%) of the 45 patients. No exposed controls produced positive LTT results. The optimal cut-off of 1.95 for the SI was obtained with a sensitivity of 77% and specificity of 100% (area under the curve, 0.91; 95% asymptotic confidence interval ...

الإتاحة: https://doi.org/10.3389/fphar.2022.819589Test

المؤلفون: Manjón Herrera, José Vicente, Universitat Politècnica de València. Departamento de Física Aplicada - Departament de Física Aplicada, Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials, García García, Irene Estela

الوصول الحر: https://www.europeana.eu/item/355/https___hispana_mcu_es_lod_oai_riunet_upv_es_10251____156294_ent0?utm_source=api&utm_medium=api&utm_campaign=YuvuWBeCaTest

المؤلفون: García-García, Irene, Seco-Meseguer, Enrique, Borobia, Alberto M, Carcas-Sansuán, Antonio J

المصدر: Expert Review of Clinical Pharmacology; Jan2024, Vol. 17 Issue 1, p1-10, 10p

مصطلحات موضوعية: CLINICAL trials, PHARMACOGENOMICS, LITERATURE reviews, DATA privacy, MEDICAL ethics committees, PLANT protection

مستخلص: The implementation of pharmacogenetic analysis within clinical trials faces methodological, ethical, and regulatory challenges, as well as tackling the difficulty in obtaining actionable information with a sufficient level of evidence to enable its integration into routine clinical practice. We discuss the current status of pharmacogenetics integration in clinical trials, underscore the associated challenges, and make some suggestions on the aspects to address in any clinical trial including a pharmacogenetic evaluation. We conducted a literature review, thoroughly reviewed the applicable regulations and available guidelines, and assessed the application dossiers submitted for evaluation to the Ethics committee of Hospital La Paz (Madrid, Spain) to extract information related to inclusion of pharmacogenetics evaluations. The integration of pharmacogenetics into clinical trials is becoming increasingly common. However, several regulatory, methodological and ethical aspects involved are insufficiently addressed. There is a need for specific and transparent guidelines that establish unified and compliant criteria for methodology, proper handling of samples in compliance with regulations, and the protection of data privacy and confidentiality. Participants should receive complete and appropriate information regarding the purpose, handling, storage, and transfer of their samples and data, and should have the right to decide about their processing. [ABSTRACT FROM AUTHOR]

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المؤلفون: García-Alfonso, Pilar, Saiz-Rodríguez, M., Mondéjar, R., Salazar, Juliana, Páez, David, Borobia, Alberto M, Safont, M. J., García-García, Irene, Colomer, Ramon, García-González, Xandra, Herrero Cervera, María José, López-Fernández, L. A., Abad-Santos, Francisco, Universitat Autònoma de Barcelona

مصطلحات موضوعية: 5-fluorouracil, Capecitabine, Dihydropyrimidine dehydrogenase, Genotypes, Pharmacogenetics, Toxicity

الوصف: 5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.

وصف الملف: application/pdf

العلاقة: Clinical & Translational Oncology; Vol. 24 (november 2021), p. 483-494; https://ddd.uab.cat/record/258969Test; urn:10.1007/s12094-021-02708-4; urn:oai:ddd.uab.cat:258969; urn:pmcid:PMC8885558; urn:pmc-uid:8885558; urn:pmid:34773566; urn:oai:pubmedcentral.nih.gov:8885558; urn:articleid:16993055v24p483

الإتاحة: https://ddd.uab.cat/record/258969Test