IIS Aragón - Instituto de Investigación Sanitaria Aragón (Aragón)
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16973
El IIS Aragón es el Instituto de Investigación Sanitaria del Complejo Hospitalario formado por los Hospitales Universitarios “Hospital Clínico Universitario Lozano Blesa” y “Hospital Universitario Miguel Servet” y Atención Primaria de Salud. El IIS Aragón es el Instituto de Investigación Sanitaria formado por los Hospitales Universitarios “Lozano Blesa” y “Miguel Servet”, la Atención Primaria de Salud, la Universidad de Zaragoza y el Instituto Aragonés de Ciencias de la Salud. Los fines del IIS Aragón son: Aproximar la investigación básica y aplicada, clínica y de servicios sanitarios. Crear un entorno investigador, asistencial y docente de calidad que integre a los Profesionales sanitarios, los especialistas en formación, los alumnos de postgrado, y grado. Constituir el lugar idóneo para la captación de talento y la ubicación de las grandes instalaciones científico-tecnológicas. Conforme a lo establecido en el Real Decreto 339/2004, se constituye la Fundación Instituto de Investigación Sanitaria Aragón para la gobernanza y gestión del IIS Aragón. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2015, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.
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Publication Patient and Public Involvement in Malnutrition Disorders Health Research: A Methodological Systematic Review Protocol(Multidisciplinary Digital Publishing Institute (MDPI), 2025-04-07) Garcia-Garcia, Arturo; Carretero-Randez, Cristina; Camacho-Bejarano, Rafaela; Roldán-Chicano, María Teresa; Castellano-Santana, Pedro Raúl; Camacho-Montaño, Lucia; Montero-Marco, Jesica; Charlo-Bernardos, Marta; Orts-Cortes, Maria IsabelBackground/Objectives: Older adults are particularly susceptible to undernutrition and conditions that can aggravate it, such as frailty and conditions associated with swallowing difficulties or dysphagia. To address these challenges, it is important to consider the perspectives of older adults and their caregivers, especially those with conditions such as frailty or cognitive impairment, as they can provide valuable insights on supporting nutrition in these vulnerable populations. This participatory approach requires structures formed by scientific research committees working together with other stakeholders, involving various actors at all stages of the research process. The aim of this study is to analyze the methodology for involving patients aged 65 and older with malnutrition or at risk of malnutrition as co-investigators in research. Methods: This protocol has been developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) checklist. A literature search will be carried out in the following electronic databases: PubMed/MEDLINE, EMBASE and CINAHL. Through the COVIDENCE program, the research team will independently review the different screening phases of the identified studies for possible inclusion or exclusion. Expected Results: This systematic review will provide up-to-date evidence on the use of non-scientific actors at different stages of research. The main limitation stems from the use of non-scientific agents in a topic as specific as adults with or at risk of undernutrition, which may make it difficult to extrapolate the results to other settings. The registration number in PROSPERO is CRD42024444374.Publication Novel risk loci for COVID-19 hospitalization among admixed American populations(eLife Sciences Publications, 2024-10-03) Diz-de Almeida, Silvia; Cruz, Raquel; Luchessi, Andre D; Lorenzo-Salazar, José M; López de Heredia, Miguel; Quintela, Inés; González-Montelongo, Rafaela; Nogueira Silbiger, Vivian; Porras, Marta Sevilla; Tenorio Castaño, Jair Antonio; Nevado, Julián; Aguado, José María; Aguilar, Carlos; Aguilera-Albesa, Sergio; Almadana, Virginia; Almoguera, Berta; Alvarez, Nuria; Andreu-Bernabeu, Álvaro; Arana-Arri, Eunate; Arango, Celso; Arranz, María J; Artiga, Maria-Jesus; Baptista-Rosas, Raúl C; Barreda-Sánchez, María; Belhassen-García, Moncef; Bezerra, Joao F; Bezerra, Marcos A C; Boix-Palop, Lucía; Brion, María; Brugada, Ramón; Bustos, Matilde; Calderón, Enrique J; Carbonell, Cristina; Castano, Luis; Castelao, Jose E; Conde-Vicente, Rosa; Cordero-Lorenzana, M Lourdes; Cortes-Sanchez, Jose L; Corton, Marta; Darnaude, M Teresa; De Martino-Rodríguez, Alba; Del Campo-Pérez, Victor; Diaz de Bustamante, Aranzazu; Domínguez-Garrido, Elena; Eirós, Rocío; Fariñas, María Carmen; Fernandez-Nestosa, María J; Fernández-Robelo, Uxía; Fernandez-Rodriguez, Amanda; Fernández-Villa, Tania; Gago-Dominguez, Manuela; Gil-Fournier, Belén; Gómez-Arrue, Javier; González Álvarez, Beatriz; González Bernaldo de Quirós, Fernan; González-Neira, Anna; González-Peñas, Javier; Gutiérrez-Bautista, Juan F; Herrero, María José; Herrero-Gonzalez, Antonio; Jimenez-Sousa, Maria Angeles; Lattig, María Claudia; Liger Borja, Anabel; Lopez-Rodriguez, Rosario; Mancebo, Esther; Martín-López, Caridad; Martín, Vicente; Martinez-Nieto, Oscar; Martinez-Lopez, Iciar; Martinez-Resendez, Michel F; Martinez-Perez, Angel; Mazzeu, Juliana F; Merayo Macías, Eleuterio; Minguez, Pablo; Moreno Cuerda, Victor; Oliveira, Silviene F; Ortega-Paino, Eva; Pompa-Mera, Ericka N; Parellada, Mara; Paz-Artal, Estela; Santos, Ney PC; Pérez-Matute, Patricia; Perez, Patricia; Pérez-Tomás, M Elena; Perucho, Teresa; Pinsach-Abuin, Mel·lina; Pita, Guillermo; Porras-Hurtado, Gloria L; Pujol, Aurora; Ramiro León, Soraya; Resino, Salvador; Fernandes, Marianne R; Rodríguez-Ruiz, Emilio; Rodríguez-Artalejo, Fernando; Rodriguez-Garcia, José A; Ruiz-Cabello, Francisco; Ruiz-Hornillos, Javier; Ryan, Pablo; Soria, José Manuel; Souto, Juan Carlos; Tamayo, Eduardo; Tamayo-Velasco, Álvaro; Taracido-Fernandez, Juan Carlos; Teper, Alejandro; Torres-Tobar, Lilian; Urioste, Miguel; Valencia-Ramos, Juan; Yáñez, Zuleima; Zarate, Ruth; de Rojas, Itziar; Ruiz, Agustín; Sánchez, Pascual; Real, Luis Miguel; SCOURGE Cohort Group; Guillén-Navarro, Encarna; Ayuso, Carmen; Parra, Esteban; Riancho, José A; Rojas-Martinez, Augusto; Flores, Carlos; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Banco Santander; Fundación La Caixa; Agencia Estatal de Investigación (España); Gobierno de Canarias (España); Fundación Canaria de Investigación Sanitaria; Xunta de Galicia (España); Fundación Amancio Ortega; Estrella de Levante; Colabora MujerThe genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations ( and ). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in . Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.Publication Extracellular Vesicles-Mediated Bio-Orthogonal Catalysis in Growing Tumors(Multidisciplinary Digital Publishing Institute (MDPI), 2024-04-16) Sancho-Albero, Maria; Sebastián, Víctor; Perez-Lopez, Ana M; Martin-Duque, Pilar; Unciti-Broceta, Asier; Santamaria, Jesus; Unión Europea. Comisión Europea. European Research Council (ERC); Asociación Española Contra el Cáncer; Fundación Ramón Areces; Fundación BBVA; Engineering and Physical Sciences Research Council (Reino Unido)Several studies have reported the successful use of bio-orthogonal catalyst nanoparticles (NPs) for cancer therapy. However, the delivery of the catalysts to the target tissues in vivo remains an unsolved challenge. The combination of catalytic NPs with extracellular vesicles (EVs) has been proposed as a promising approach to improve the delivery of therapeutic nanomaterials to the desired organs. In this study, we have developed a nanoscale bio-hybrid vector using a CO-mediated reduction at low temperature to generate ultrathin catalytic Pd nanosheets (PdNSs) as catalysts directly inside cancer-derived EVs. We have also compared their biodistribution with that of PEGylated PdNSs delivered by the EPR effect. Our results indicate that the accumulation of PdNSs in the tumour tissue was significantly higher when they were administered within the EVs compared to the PEGylated PdNSs. Conversely, the amount of Pd found in non-target organs (i.e., liver) was lowered. Once the Pd-based catalytic EVs were accumulated in the tumours, they enabled the activation of a paclitaxel prodrug demonstrating their ability to carry out bio-orthogonal uncaging chemistries in vivo for cancer therapy.Publication Severity Patterns in COVID-19 Hospitalised Patients in Spain: I-MOVE-COVID-19 Study.(Multidisciplinary Digital Publishing Institute (MDPI), 2024-10-30) Latorre-Millán, Miriam; Rodríguez Del Águila, María Mar; Clusa, Laura; Mazagatos, Clara; Larrauri, Amparo; Fernández, María Amelia; Rezusta, Antonio; Milagro, Ana María; Unión Europea. Comisión Europea. H2020In the frame of the I-MOVE-COVID-19 project, a cohort of 2050 patients admitted in two Spanish reference hospitals between March 2020 and December 2021 was selected and a range of clinical factor data were collected at admission to assess their impact on the risk COVID-19 severity outcomes through a multivariate adjusted analysis and nomograms. The need for ventilation and intensive care unit (ICU) admission were found to be directly associated with a higher death risk (OR 6.9 and 3.2, respectively). The clinical predictors of death were the need for ventilation and ICU, advanced age, neuromuscular disorders, thrombocytopenia, hypoalbuminemia, dementia, cancer, elevated creatin phosphokinase (CPK), and neutrophilia (OR between 1.8 and 3.5), whilst the presence of vomiting, sore throat, and cough diminished the risk of death (OR 0.5, 0.2, and 0.1, respectively). Admission to ICU was predicted by the need for ventilation, abdominal pain, and elevated lactate dehydrogenase (LDH) (OR 371.0, 3.6, and 2.2, respectively) as risk factors; otherwise, it was prevented by advanced age (OR 0.5). In turn, the need for ventilation was predicted by low oxygen saturation, elevated LDH and CPK, diabetes, neutrophilia, obesity, and elevated GGT (OR between 1.7 and 5.2), whilst it was prevented by hypertension (OR 0.5). These findings could enhance patient management and strategic interventions to combat COVID-19.Publication Characterization model of the post COVID-19 condition based on immunological, biochemical, and cytokine markers(Elsevier, 2024-09-20) Oliván-Blázquez, Bárbara; Bona-Otal, Marta; Méndez-López, Fátima; Lerma-Irureta, David; García-Izuel, Paula; Ibáñez-Ruiz, Jesús; Montolío, Alberto; Ruiz-Herreros, María; Godino, Javier; Jimeno-Beltran, Beatriz; Encabo-Berzosa, María Del Mar; Arenaz, Izaskun; Medel-Martínez, Ana; Casado-Vicente, Verónica; Coiras, Mayte; Tellería-Orriols, Carlos; Schoorlemmer, Jon; Magallón-Botaya, Rosa; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Comisión Europea. Horizonte Europa; Gobierno de Aragón (España); Instituto de Investigación Sanitaria Aragón; Instituto Aragonés de Ciencias de la SaludPost-coronavirus disease condition (PCC) continues to affect many people globally, yet there remains a lack of diagnostic biomarkers to distinguish PCC from those recovered from acute COVID-19. This study compared biomarkers between two age- and gender-matched groups: PCC individuals and those recovered within three months of acute COVID-19 in 2020 ( = 85 each). Biomarkers were assessed 12-24 months after initial diagnosis, examining biochemical profiles, blood cell counts, coagulation status, antibody serology, lymphocyte populations, and cytokine levels. PCC individuals exhibited significant alterations in 49 of 167 markers, including K+ levels, αGAD antibodies, antithrombin III, insulin-like growth factor-binding protein 3 (IGFBP3), and interleukin-10 (IL-10). A panel of αGAD, IL-10, potassium levels, and CD16CD56 cell presence distinguished PCC individuals from recovered patients with >88% accuracy and <92% precision.Publication Executive Summary of the Consensus Statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Association of Surgeons (AEC), the Spanish Society of Pneumology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Vascular and Interventional Radiology (SERVEI), and the Spanish Society of Paediatric Infectious Diseases (SEIP), on the Management of Cystic Echinococcosis(Elsevier, 2020) Belhassen-García, Moncef; Balboa Arregui, Óscar; Calabuig-Muñoz, Eva; Carmena, David; Esteban Velasco, Maria Del Carmen; Fuentes Gago, Marta; Fumado Pérez, Victoria; García Alonso, Jesús; García López Hortelano, Milagros; González Fernández, Luis Miguel; Herrero Martínez, Juan María; Iglesias Iglesias, Manuel José; Jiménez López, Marcelo; López-Vélez, Rogelio; Muñoz-Bellvis, Luis; Muro, Antonio; Pardo-Lledías, Javier; Peñaranda-Vera, Maria; Perteguer-Prieto, Maria Jesus; Picado, Albert; Quiñones Sampedro, Jose Edecio; Rodríguez-Guardado, Azucena; Royo Crespo, Íñigo; Salvador, Fernando; Sánchez-Montalvá, Adrián; Torrús-Tendero, Diego; Velasco Pelayo, Luis; Sociedad Española de Medicina Tropical y Salud Internacional[EN] The Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Tropical Medicine and International Health (SEMTSI), the Spanish Association of Surgeons (AEC), the Spanish Society of Pneumology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Vascular and Interventional Radiology (SERVEI), and the Spanish Society of Paediatric Infectious Diseases (SEIP) considered it pertinent to issue a consensus statement on the management of cystic echinococcosis (CE) to guide healthcare professionals in the care of patients with CE. Specialists from several fields (clinicians, surgeons, radiologists, microbiologists, and parasitologists) identified the most clinically relevant questions and developed this Consensus Statement, evaluating the available evidence-based data to propose a series of recommendations on the management of this disease. This Consensus Statement is accompanied by the corresponding references on which these recommendations are based. Prior to publication, the manuscript was open for comments and suggestions from the members of the SEIMC and the scientific committees and boards of the various societies involved. [ES] La Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), la Sociedad Española de Medicina Tropical y Salud Internacional (SEMTSI), la Asociación Española de Cirujanos (AEC), la Sociedad Española de Neumología y Cirugía Torácica (SEPAR), la Sociedad Española de Cirugía Torácica (SECT), la Sociedad Española de Radiología Vascular e Intervencionista (SERVEI) y la Sociedad Española de Infectología Pediátrica (SEIP) han considerado pertinente la elaboración de una declaración de consenso sobre el tratamiento de la equinococosis quística (EQ) que sirva de ayuda al personal sanitario en la atención de pacientes con EQ. Varios tipos de profesionales (médicos, cirujanos, radiólogos, microbiólogos y parasitólogos) han seleccionado las preguntas más clínicamente relevantes y han desarrollado esta Declaración de consenso, en la que evalúan los datos basados en la evidencia disponibles para proponer una serie de recomendaciones sobre el tratamiento de esta enfermedad. Esta Declaración de consenso se acompaña de la bibliografía correspondiente que fundamenta estas recomendaciones. Antes de su publicación, el manuscrito estuvo abierto a comentarios y sugerencias de los miembros de la SEIMC y de los comités científicos y juntas directivas de las diferentes sociedades implicadas.Publication Isolation and Characterization of Milk Exosomes for Use in Advanced Therapies(Multidisciplinary Digital Publishing Institute (MDPI), 2024-07-08) Medel-Martínez, Ana; Redrado-Osta, Ana; Crespo-Barreda, Alejandra; Sancho-Albero, Maria; Sánchez, Lourdes; Sebastián, Víctor; Pardo, María; De la Vieja, Antonio; Martin-Duque, Pilar; Instituto de Salud Carlos III; Asociación de Padres de Niños Oncológicos de Aragón; Asociación Española Contra el Cáncer; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Ciencia e Innovación (España); Fundación Ramón ArecesExosomes are cell-derived extracellular vesicles (EVs) with diameters between 30 and 120 nm. In recent years, several studies have evaluated the therapeutic potential of exosomes derived from different fluids due to their low immunogenicity and high biocompatibility. However, producing exosomes on a large scale is still challenging. One of the fluids from which they could be isolated in large quantities is milk. Moreover, regeneration is a well-known property of milk. The present work seeks to optimize a method for isolating exosomes from bovine and human milk, comparing different storage conditions and different extraction protocols. We found differences in the yield extraction associated with pre-storage milk conditions and observed some differences according to the processing agent. When we removed milk fat globules and added rennet before freezing, we obtained a cleaner final fraction. In summary, we attempted to optimize a rennet-based new milk-exosome isolation method and concluded that pre-treatment, followed by freezing of samples, yielded the best exosome population.Publication Broad Protection against Invasive Fungal Disease from a Nanobody Targeting the Active Site of Fungal β-1,3-Glucanosyltransferases(Wiley, 2024-08-19) Redrado-Hernández, Sergio; Macías-León, Javier; Castro-López, Jorge; Belén Sanz, Ana; Dolader, Elena; Arias, Maykel; González-Ramírez, Andrés Manuel; Sánchez-Navarro, David; Petryk, Yuliya; Farkaš, Vladimír; Vincke, Cécile; Muyldermans, Serge; Garcia-Barbazan, Irene; Del Agua, Celia; Zaragoza, Oscar; Arroyo, Javier; Pardo, Julián; Gálvez, Eva M; Hurtado-Guerrero, Ramon; Redrado-Hernández, Sergio; Macías-León, Javier; Castro-López, Jorge; Belén Sanz, Ana; Dolader, Elena; Arias, Maykel; González-Ramírez, Andrés Manuel; Sánchez-Navarro, David; Petryk, Yuliya; Farkaš, Vladimír; Vincke, Cécile; Muyldermans, Serge; Del Agua, Celia; Zaragoza, Oscar; Arroyo, Javier; Pardo, Julián; Gálvez, Eva M; Hurtado-Guerrero, Ramon; Fundación Agencia Aragonesa para la Investigación y el Desarrollo; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Instituto de Salud Carlos III; Ministry of Education, Youth and Sports (República Checa); Ministerio de Ciencia, Innovación y Universidades (España); Comunidad de Madrid (España); Asociación de Padres de Niños Oncológicos de Aragón; Gobierno de Aragón (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Unión Europea. Comisión Europea. 7 Programa Marco; Ministerio de Ciencia e Innovación (España); Agencia Estatal de Investigación (España)Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal β-1,3-glucanosyltransferases (Gel) involved in β-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for β-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of β-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.Publication Delving into public-expenditure elasticity: Evidence from a National Health Service acute-care hospital network(Public Library of Science (PLOS), 2024) Comendeiro-Maaløe, Micaela; Ridao-Lopez, Manuel; Bernal-Delgado, Enrique; Sansó-Rosselló, AndreuIntroduction: The sustainability of public hospital financing in Spain is a recurring issue, given its representativeness in annual public healthcare budgets which must adapt to the macroeconomic challenges that influence the evolution of spending. Knowing whether the responsiveness of hospital expenditure to its determinants (need, utilisation, and quasi-prices) varies according to the type of hospital could help better design strategies aimed at optimising performance. Methods: Using SARIMAX models, we dynamically assess unique nationwide monthly activity data over a 14-year period from 274 acute-care hospitals in the Spanish National Health Service network, clustering these providers according to the average severity of the episodes treated. Results: All groups showed seasonal patterns and increasing trends in the evolution of expenditure. The fourth quartile of hospitals, treating the most severe episodes and accounting for more than 50% of expenditure, is the most sensitive to quasi-price factors, particularly the number of beds per hospital. Meanwhile, the first quartile of hospitals, which treat the least severe episodes and account for 10% of expenditure, is most sensitive to quantity factors, for which expenditure showed an elasticity above one, while factors of production were not affected. Conclusions: Belonging to one or another cluster of hospitals means that the determinants of expenditure have a different impact and intensity. The system should focus on these differences in order to optimally modulate expenditure not only according to the needs of the population, but also according to the macroeconomic situation, while leaving hospitals room for manoeuvre in case of unforeseen events. The findings suggest strengthening a network of smaller hospitals (Group 1)-closer to their reference population, focused on managing and responding to chronicity and stabilising acute events-prior to transfer to tertiary hospitals (Group 4)-larger but appropriately sized, specialising in solving acute and complex health problems-when needed.Publication The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018)(Frontiers Media, 2023) Gracia-Ahufinger, Irene; López-González, Laura; Vasallo, Francisco José; Galar, Alicia; Siller, María; Pitart, Cristina; Bloise, Iván; Torrecillas, Miriam; Gijón-Cordero, Desirée; Viñado, Belén; Castillo-García, Javier; Campo, Rainer; Mulet, Xavier; Madueño-Alonso, Ana; Chamizo-López, Francisco Javier; Arrastia-Erviti, Maitane; Galán-Sánchez, Fátima; Fernández-Quejo, Melisa; Rodríguez-Díaz, Juan Carlos; Gutiérrez-Zufiaurre, María Nieves; Rodríguez-Maresca, Manuel Angel; Ortega-Lafont, María Del Pilar; Yague-Guirao, Genoveva; Chaves-Blanco, Lucía; Colomina-Rodríguez, Javier; Vidal-Acuña, María Reyes; Portillo, María Eugenia; Franco-Álvarez de Luna, Francisco; Centelles-Serrano, María José; Azcona-Gutiérrez, José Manuel; Delgado-Iribarren García Campero, Alberto; Rey-Cao, Sonia; Muñoz, Patricia; Calvo-Montes, Jorge; Zboromyrska, Yuliya; Grandioso, David; Càmara, Jordi; Cantón, Rafael; Larrosa-Escartín, Nieves; Díaz-Regañón, Jazmín; Martínez-Martínez, LuisIntroduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.Publication Role of personal aptitudes as determinants of incident morbidity, lifestyles, quality of life, use of health services, and mortality (DESVELA cohort): quantitative study protocol for a prospective cohort study in a hybrid analysis(Frontiers Media, 2023) Martí-Lluch, Ruth; Bolíbar, Bonaventura; Llobera Cànaves, Joan; Maderuelo-Fernández, José A; Magallón-Botaya, Rosa; Sánchez-Pérez, Álvaro; Fernández-Domínguez, Maria José; Motrico, Emma; Vicens-Pons, Enric; Notario-Pacheco, Blanca; Alves-Cabratosa, Lia; Ramos, RafaelIntroduction: The healthcare and well-being of the population depend on multiple factors and should adapt to societal changes. The opposite is also occurring; society has evolved concerning the individuals' approach to their care, which includes participation in decision-making processes. In this scenario, health promotion and prevention become crucial to provide an integrated perspective in the organization and management of the health systems.Health status and well-being depend on many aspects, determinants of health, which in turn may be modulated by individual behavior. Certain models and frameworks try to study the determinants of health and individual human behaviors, separately. However, the interrelation between these two aspects has not been examined in our population.Our main objective is to analyze whether personal aptitudes related to behaviors are independently associated with the incidence of morbidity. A secondary objective will enquire whether these personal aptitudes are independently associated with lower all-cause mortality, enhanced adoption of healthy lifestyles, higher quality of life, and lower utilization of health services during follow-up. Methods: This protocol addresses the quantitative branch of a multicenter project (10 teams) for the creation of a cohort of at least 3,083 persons aged 35 to 74 years from 9 Autonomous Communities (AACC). The personal variables to evaluate are self-efficacy, activation, health literacy, resilience, locus of control, and personality traits. Socio-demographic covariates and social capital will be recorded. A physical examination, blood analysis, and cognitive evaluation will be carried out.Several sets of six Cox models (one for each independent variable) will analyze the incidence of morbidity (objective 1); all-cause mortality and the rest of the dependent variables (objective 2). The models will be adjusted for the indicated covariates, and random effects will estimate Potential heterogeneity between AACC. Discussion: The analysis of the association of certain behavioral patterns and determinants of health is essential and will contribute to improving health promotion and prevention strategies. The description of the individual elements and interrelated aspects that modulate the onset and persistence of diseases will allow the evaluation of their role as prognostic factors and contribute to the development of patient-tailored preventive measures and healthcare.Clinical Trial Registration: ClinicalTrials.gov, NCT04386135. Registered on April 30, 2020.Publication Mindfulness skills and experiential avoidance as therapeutic mechanisms for treatment-resistant depression through mindfulness-based cognitive therapy and lifestyle modification(Frontiers Media, 2023) Garcia Toro, Mauro; Aguilar-Latorre, Alejandra; Garcia, Aurora; Navarro-Guzmán, Capilla; Gervilla Garcia, Elena; Seguí, Andrea; Gazquez, Francisco; Marino, Jose Antonio; Gomez-Juanes, Rocío; Serrano-Ripoll, Maria Jesus; Oliván-Blázquez, Bárbara; Garcia-Campayo, Javier; Maloney, Shannon; Montero-Marin, JesúsBackground/objective: The COVID-19 pandemic and consequent physical distancing has made it difficult to provide care for those with Treatment-Resistant Depression (TRD). As a secondary analysis of a clinical trial, the aim of this study was to explore potential mechanisms through which three online-delivered approaches, added to treatment as usual, improve depressive symptoms in TRD patients. Methods: The three approaches included (a) Minimal Lifestyle Intervention (MLI), (b) Mindfulness-Based Cognitive Therapy (MBCT), and (c) Lifestyle Modification Program (LMP). Sixty-six participants with TRD completed assessments pre-post intervention (mindfulness skills [FFMQ]; self-compassion [SCS]; and experiential avoidance [AAQ-II]) and pre-intervention to follow-up (depressive symptoms [BDI-II]). Data were analyzed using within-subjects regression models to test mediation. Results: Mindfulness skills mediated the effect of MBCT on depressive symptoms (ab = -4.69, 95% CI = -12.93 to-0.32), whereas the lack of experiential avoidance mediated the effect of LMP on depressive symptoms (ab = -3.22, 95% CI = -7.03 to-0.14). Conclusion: Strengthening mindfulness skills and decreasing experiential avoidance may promote recovery in patients with TRD, MBCT, and LMP have demonstrated that they may help increase mindfulness skills and decrease experiential avoidance, respectively. Future work will need to unpick the components of these interventions to help isolate active ingredients and increase optimization.Publication La Red de Investigación en Actividades Preventivas y Promoción de la Salud (redIAPP): una red de referencia e impulsora de la investigación en atención primaria(Elsevier, 2023-07-21) Bolibar Ribas, Bonaventura; Llobera Cànaves, Joan; García-Ortiz, Luis; Bellón, Juan-Ángel; Ramos, Rafel; García-Campayo, Javier; Sánchez-Pérez, Álvaro; Claveria, Ana; Martínez, Vicente; Vicens, Enric; Minué, César; Gil-Guillen, Vicente; Berenguera, Anna; Moleras-Serra, Anna[ES] La Red de Investigación en Actividades Preventivas y Promoción de la Salud (redIAPP), una red de referencia e impulsora de la investigación en atención primaria fue creada en 2003 gracias al programa Redes Temáticas de Investigación Cooperativa en Salud (RETICS) del Instituto de Salud Carlos III (ISCIII). Su creación ha supuesto un cambio radical en la situación de la investigación en atención primaria. A lo largo de sus 19 años (2003-2021) han participado distintos grupos de investigación y comunidades autónomas, y se han desarrollado distintas líneas de investigación con numerosos proyectos y publicaciones. A pesar de las dificultades sufridas, ha creado una experiencia de investigación colaborativa entre distintas comunidades autónomas con gran vitalidad y con importantes resultados para la atención primaria. La redIAPP, por tanto, ha sido un gran referente para la investigación en atención primaria y para la profundización de su área de conocimiento. Se sugieren varias líneas de mejora para el futuro de la investigación en atención primaria. [EN] The Research Network on Preventive Activities and Health Promotion (redIAPP), a reference network and promoter of primary care research was created in 2003 thanks to the program Thematic Networks for Cooperative Research in Health (RETICS) of the Instituto de Salud Carlos III (ISCIII). Its creation has meant a radical change in the situation of research in primary care. Throughout its 19 years (2003-2021), different research groups and autonomous communities have participated, and different lines of research have been developed with numerous projects and publications. Despite the difficulties suffered, it has created a collaborative research experience between different autonomous communities with great vitality and with important results for primary care. The redIAPP, therefore, has been a great reference for research in primary care and for the deepening of its area of knowledge. Several lines of improvement are suggested for the future of primary care research.Publication Efficacy of an adjuvant non-face-to-face multimodal lifestyle modification program for patients with treatment-resistant major depression: A randomized controlled trial(2023-01) Garcia, Aurora; Yáñez, Aina M; Bennasar-Veny, Miquel; Navarro, Capilla; Salva, Joan; Ibarra, Olga; Gomez-Juanes, Rocío; Serrano-Ripoll, Maria Jesus; Oliván, Bárbara; Gili, Margalida; Roca, Miquel; Riera-Serra, Pau; Aguilar-Latorre, Alejandra; Montero-Marin, Jesús; Garcia Toro, MauroBackground: The high prevalence of depression is partly attributable to the poor response of patients to first-line antidepressants. Multimodal programs that promote a healthy lifestyle are successful in treating depression when used as a complementary therapy, but their medium- and long-term benefits have not been demonstrated for patients with treatment-resistant depression (TRD). The main aim of this study was to compare the effectiveness of a lifestyle modification program (LMP) with mindfulness-based cognitive therapy (MBCT) and a placebo-control (written suggestions for lifestyle changes) in Spanish patients with TRD. Methods: This controlled clinical trial randomized 94 patients with TRD into 3 arms. The primary outcome was the Beck Depression Inventory-II (BDI-II) score at baseline, 2, 6 and 12 months. The secondary outcomes were changes in scores that evaluated quality-of-life, adherence to the Mediterranean diet, physical activity, and social support. Results: Relative to the placebo group, the LMP and MBCT groups had significantly better quality of life (p = 0.017; p = 0.027), and the LMP group had significantly better adherence to the Mediterranean diet (p<0.001) and reduced use of antidepressants (p = 0.036). However, the three groups showed no significant differences in BDI-II score. Limitations: Only about half of the planned 180 patients were recruited, in part due to the COVID-19 pandemic. Conclusions: There was no evidence that the LMP treatment significantly reduced symptoms of depression relative to the other groups during the COVID-19 lockdown.Publication A multiple health behaviour change intervention to prevent depression: A randomized controlled trial(Elsevier, 2023) Gómez-Gómez, Irene; Motrico, Emma; Moreno-Peral, Patricia; Casajuana-Closas, Marc; López-Jiménez, Tomàs; Zabaleta-Del-Olmo, Edurne; Clavería, Ana; Llobera Cànaves, Joan; Martí-Lluch, Ruth; Ramos, Rafael; Maderuelo-Fernández, José-Ángel; Vicens-Caldentey, Caterina; Domínguez-García, Marta; Bartolomé-Moreno, Cruz; Recio-Rodriguez, Jose I; Bellón, Juan ÁObjective: To examine the effectiveness of a 12-month MHBC intervention in the prevention of onset depression in primary health care (PHC). Methods: Twenty-two PHC centres took part in the cluster-randomized controlled trial. Patients were randomized to receive either usual care or an MHBC intervention. The endpoints were onset of major depression and reduction of depressive symptoms in participants without baseline depression at a 12-month follow-up. Results: 2531 patients agreed and were eligible to participate. At baseline, around 43% were smokers, 82% were non-adherent to the Mediterranean diet and 55% did not perform enough physical activity. The intervention group exhibited a greater positive change in two or more behaviours (OR 1.75 [95%CI: 1.17 to 2.62]; p = 0.006); any behaviour (OR 1.58 [95%CI: 1.13 to 2.20]; p = 0.007); and adherence to the Mediterranean diet (OR 1.94 [95%CI: 1.29 to 2.94]; p = 0.002), while this increase was not statistically significant for smoking and physical activity. The intervention was not effective in preventing major depression (OR 1.17; [95% CI 0.53 to 2.59)]; p = 0.690) or reducing depressive symptoms (Mean difference: 0.30; [95% CI -0.77 to 1.36]; p = 0.726) during follow-up. Conclusions: As compared to usual care, the MHBC intervention provided a non-significant reduction in the incidence of major depression. Trial registration: ClinicalTrials.gov, NCT03136211.Publication Utility of PHQ-2, PHQ-8 and PHQ-9 for detecting major depression in primary health care: a validation study in Spain(Cambridge University Press, 2022-10-19) Gómez-Gómez, Irene; Benítez, Isabel; Bellón, Juan; Moreno-Peral, Patricia; Oliván-Blázquez, Bárbara; Clavería, Ana; Zabaleta-Del-Olmo, Edurne; Llobera Cànaves, Joan; Serrano-Ripoll, Maria Jesus; Tamayo-Morales, Olaya; Motrico, EmmaBackground: Primary health care (PHC) professionals may play a crucial role in improving early diagnosis of depressive disorders. However, only 50% of cases are detected in PHC. The most widely used screening instrument for major depression is the Patient Health Questionnaire (PHQ), including the two-, eight- and nine-item versions. Surprisingly, there is neither enough evidence about the validity of PHQ in PHC patients in Spain nor indications about how to interpret the total scores. This study aimed to gather validity evidence to support the use of the three PHQ versions to screen for major depression in PHC in Spain. Additionally, the present study provided information for helping professionals to choose the best PHQ version according to the context. Methods: The sample was composed of 2579 participants from 22 Spanish PHC centers participating in the EIRA-3 study. The reliability and validity of the three PHQ versions for Spanish PHC patients were assessed based on responses to the questionnaire. Results: The PHQ-8 and PHQ-9 showed high internal consistency. The results obtained confirm the theoretically expected relationship between PHQ results and anxiety, social support and health-related QoL. A single-factor solution was confirmed. Regarding to the level of agreement with the CIDI interview (used as the criterion), our results indicate that the PHQ has a good discrimination power. The optimal cut-off values were: ⩾2 for PHQ-2, ⩾7 for PHQ-8 and ⩾8 for PHQ-9. Conclusions: PHQ is a good and valuable tool for detecting major depression in PHC patients in Spain.Publication Relationship between time from symptom's onset to diagnosis and prognosis in patients with symptomatic colorectal cancer(BioMed Central (BMC), 2022-08-22) Esteva Cantó, Magdalena; Leiva, Alfonso; Ramos Monserrat, Maria; Espí, Alejandro; González-Luján, Luis; Macià, Francesc; Murta-Nascimento, Cristiane; Sanchez-Calavera, Maria Antonia; Magallón, Rosa; Balboa-Barreiro, Vanesa; Seoane-Pillado, Teresa; Pertega-Díaz, SoniaBackground: Controversy exists regarding the relationship of the outcome of patients with colorectal cancer (CRC) with the time from symptom onset to diagnosis. The aim of this study is to investigate this association, with the assumption that this relationship was nonlinear and with adjustment for multiple confounders, such as tumor grade, symptoms, or admission to an emergency department. Methods: This multicenter study with prospective follow-up was performed in five regions of Spain from 2010 to 2012. Symptomatic cases of incident CRC from a previous study were examined. At the time of diagnosis, each patient was interviewed, and the associated hospital and clinical records were reviewed. During follow-up, the clinical records were reviewed again to assess survival. Cox survival analysis with a restricted cubic spline was used to model overall and CRC-specific survival, with adjustment for variables related to the patient, health service, and tumor. Results: A total of 795 patients had symptomatic CRC and 769 of them had complete data on diagnostic delay and survival. Univariate analysis indicated a lower HR for death in patients who had diagnostic intervals less than 4.2 months. However, after adjustment for variables related to the patient, tumor, and utilized health service, there was no relationship of the diagnostic delay with survival of patients with colon and rectal cancer, colon cancer alone, or rectal cancer alone. Cubic spline analysis indicated an inverse association of the diagnostic delay with 5-year survival. However, this association was not statistically significant. Conclusions: Our results indicated that the duration of diagnostic delay had no significant effect on the outcome of patients with CRC. We suggest that the most important determinant of the duration of diagnostic delay is the biological profile of the tumor. However, it remains the responsibility of community health centers and authorities to minimize diagnostic delays in patients with CRC and to implement initiatives that improve early diagnosis and provide better outcomes.Publication Position guidelines and evidence base concerning determinants of childhood obesity with a European perspective(Wiley, 2022-01) Alfredo Martinez, J; Sassi, Franco; Moreno, Luis A; Tur, Josep AChildhood obesity is one of the most pressing global public health issues, with rates increasing fastest in countries at low levels of income. Obesity occurring during childhood is likely to persist throughout the life course, and it is a cause of increased disease risk from the early years of life. This supplement is the result of collaborations involving a large and multidisciplinary group of researchers that were established in the context of the ongoing European Horizon 2020 project Science and Technology in childhood Obesity Policy (STOP). The aim, as in the entire STOP project, is to generate evidence that can support better policies to tackle the problem of childhood obesity in Europe and elsewhere. Quality of life and health well-being concerning children needs to consider personalized, population, and planetary facets to tackle childhood obesity at early stages of life, for in-deep phenotyping, integrating personalized medicine and precision public health interventions at global levels. This supplement contributes to this aim.Publication Long-term Effectiveness of a Smartphone App Combined With a Smart Band on Weight Loss, Physical Activity, and Caloric Intake in a Population With Overweight and Obesity (Evident 3 Study): Randomized Controlled Trial(JMIR Publications, 2022-02-01) Lugones-Sanchez, Cristina; Recio-Rodriguez, Jose I; Agudo-Conde, Cristina; Repiso-Gento, Irene; Adalia, Esther G; Ramírez-Manent, José Ignacio; Sanchez-Calavera, Maria Antonia; Rodriguez-Sanchez, Emiliano; Gomez-Marcos, Manuel A; Garcia-Ortiz, LuisBackground: Multicomponent mobile health approaches can improve lifestyle intervention results, although little is known about their long-term effectiveness. Objective: This study aims to evaluate the long-term effectiveness (12 months) of a multicomponent mobile health intervention-combining a smartphone app, an activity tracker wristband, and brief counseling, compared with a brief counseling group only-on weight loss and improving body composition, physical activity, and caloric intake in Spanish sedentary adults with overweight or obesity. Methods: We conducted a randomized controlled, multicenter clinical trial (Evident 3). A total of 650 participants were recruited from 5 primary care centers, with 318 participants in the intervention group (IG) and 332 in the control group (CG). All participants were briefly counseled about a healthy diet and physical activity at the baseline visit. For the 3-month intervention period, the IG received training to use the app to promote healthy lifestyles and the smart band (Mi Band 2, Xiaomi). All measurements were performed at baseline and at 3 and 12 months. Physical activity was measured using the International Physical Activity Questionnaire-Short Form. Nutritional habits were assessed using the Food Frequency Questionnaire and Adherence to Mediterranean diet questionnaire. Results: Of the 650 participants included, 563 (86.6%) completed the 3-month visit and 443 (68.2%) completed the 12-month visit. After 12 months, the IG showed net differences in weight (-0.26, 95% CI -1.21 to 0.70 kg; P=.02), BMI (-0.06, 95% CI -0.41 to 0.28 points; P=.01), waist-height ratio (-0.25, 95% CI -0.94 to 0.44; P=.03), body adiposity index (-0.33, 95% CI -0.77 to 0.11; P=.03), waist circumference (-0.48, 95% CI -1.62 to 0.66 cm, P=.04) and hip circumference (-0.69, 95% CI -1.62 to 0.25 cm; P=.03). Both groups lowered daily caloric intake and increased adherence to the Mediterranean diet, with no differences between the groups. The IG increased light physical activity time (32.6, 95% CI -30.3 to 95.04 min/week; P=.02) compared with the CG. Analyses by subgroup showed changes in body composition variables in women, people aged >50 years, and married people. Conclusions: The low-intensity intervention of the Evident 3 study showed, in the IG, benefits in weight loss, some body composition variables, and time spent in light physical activity compared with the CG at 3 months, but once the devices were collected, the downward trend was not maintained at the 12-month follow-up. No differences in nutritional outcomes were observed between the groups. Trial registration: ClinicalTrials.gov NCT03175614; https://clinicaltrials.gov/ct2/show/NCT03175614. International registered report identifier (irrid): RR2-10.1097/MD.0000000000009633.Publication Long-Term Effectiveness of a Smartphone App and a Smart Band on Arterial Stiffness and Central Hemodynamic Parameters in a Population with Overweight and Obesity (Evident 3 Study): Randomised Controlled Trial(Multidisciplinary Digital Publishing Institute (MDPI), 2022-11-10) Gómez-Sánchez, Leticia; Gómez-Sánchez, Marta; Lugones-Sánchez, Cristina; Rodríguez-Sánchez, Emiliano; Tamayo-Morales, Olaya; Gonzalez-Sánchez, Susana; Magallón-Botaya, Rosa; Ramírez-Manent, José Ignacio; Recio-Rodriguez, Jose I; Agudo-Conde, Cristina; García-Ortiz, Luis; Gómez-Marcos, Manuel AmHealth technologies could help to improve cardiovascular health; however, their effect on arterial stiffness and hemodynamic parameters has not been explored to date. To evaluate the effect of a mHealth intervention, at 3 and 12 months, on arterial stiffness and central hemodynamic parameters in a sedentary population with overweight and obesity. Randomised controlled clinical trial (Evident 3 study). 253 subjects were included: 127 in the intervention group (IG) and 126 in the control group (CG). The IG subjects were briefed on the use of the Evident 3 app and a smart band (Mi Band 2, Xiaomi) for 3 months to promote healthy lifestyles. All measurements were recorded in the baseline visit and at 3 and 12 months. The carotid-femoral pulse wave velocity (cfPWV) and the central hemodynamic parameters were measured using a SphigmoCor Systemﾮ device, whereas the brachial-ankle pulse wave velocity (baPWV) and the Cardio Ankle Vascular Index (CAVI) were measured using a VaSera VS-2000ﾮ device. Of the 253 subjects who attended the initial visit, 237 (93.7%) completed the visit at 3 months of the intervention, and 217 (85.3%) completed the visit at 12 months of the intervention. At 12 months, IG showed a decrease in peripheral augmentation index (PAIx) (-3.60; 95% CI -7.22 to -0.00) and ejection duration (ED) (-0.82; 95% CI -1.36 to -0.27), and an increase in subendocardial viability ratio (SEVR) (5.31; 95% CI 1.18 to 9.44). In CG, cfPWV decreased at 3 months (-0.28 m/s; 95% CI -0.54 to -0.02) and at 12 months (-0.30 m/s, 95% CI -0.54 to -0.05), central diastolic pressure (cDBP) decreased at 12 months (-1.64 mm/Hg; 95% CI -3.19 to -0.10). When comparing the groups we found no differences between any variables analyzed. In sedentary adults with overweight or obesity, the multicomponent intervention (Smartphone app and an activity-tracking band) for 3 months did not modify arterial stiffness or the central hemodynamic parameters, with respect to the control group. However, at 12 months, CG presented a decrease of cfPWV and cDBP, whereas IG showed a decrease of PAIx and ED and an increase of SEVR.