IISGS - Instituto de Investigación Sanitaria Galicia Sur (Galicia)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16979

El Instituto de Investigación Sanitaria Galicia Sur (IISGS) se crea en el año 2008 mediante la firma de un convenio de colaboración entre la Consellería de Sanidade, el Servicio Galego de Saúde y la Universidade de Vigo. Su creación responde a la estrategia promovida desde el Instituto de Salud Carlos III (ISCIII) para el desarrollo de los Institutos de Investigación Sanitaria como estructuras organizativas de promoción y desarrollo de la Investigación en los hospitales. Con fecha 19 de octubre de 2021, se firma un nuevo convenio de colaboración entre la Consellería de Sanidade, el Servicio Gallego de Salud (Sergas), la Universidad de Vigo y la Fundación Biomédica Galicia Sur, para regular la continuidad y desarrollo del Instituto de Investigación Sanitaria Galicia Sur, que constituye el vínculo jurídico actual del Instituto. El IIS Galicia Sur es un espacio de investigación multidisciplinar en Biomedicina, con sede en el Hospital Álvaro Cunqueiro de Vigo, que aglutina a los grupos de investigación clínicos de las Áreas Sanitarias del Sur de Galicia y a los grupos biomédicos de la Universidad de Vigo, con el objetivo de promover la investigación traslacional y la innovación, garantizando así la aplicación efectiva de los resultados de investigación en términos de beneficios para la salud de los ciudadanos. La Fundación Biomédica Galicia Sur es la entidad gestora del IISGS y se encarga de la gestión integral de los proyectos de investigación, desarrollo e innovación tecnológica que se solicitan y se desarrollan desde todos los grupos de investigación que conforman el Instituto. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2022, 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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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 Mujer
The 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.
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, Luis
Introduction: 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.
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, Rafael
Introduction: 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.
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.
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, Emma
Background: 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.
Analysis of the impact of social determinants and primary care morbidity on population health outcomes by combining big data: A research protocol
(Frontiers Media, 2022-12-16) Couso-Viana, Sabela; Bentué-Martínez, Carmen; Delgado-Martín, María Victoria; Cabeza Irigoyen, Elena; León-Latre, Montserrat; Concheiro-Guisán, Ana; Rodríguez-Álvarez, María Xosé; Roman-Rodriguez, Miguel; Roca-Pardiñas, Javier; Zúñiga-Antón, María; García-Flaquer, Ana; Pericàs Pulido, Pau; Sánchez-Recio, Raquel; González-Álvarez, Beatriz; Rodríguez-Pastoriza, Sara; Gómez-Gómez, Irene; Motrico, Emma; Jiménez-Murillo, José Luís; Rabanaque, Isabel; Clavería, Ana
Background: In recent years, different tools have been developed to facilitate analysis of social determinants of health (SDH) and apply this to health policy. The possibility of generating predictive models of health outcomes which combine a wide range of socioeconomic indicators with health problems is an approach that is receiving increasing attention. Our objectives are twofold: (1) to predict population health outcomes measured as hospital morbidity, taking primary care (PC) morbidity adjusted for SDH as predictors; and (2) to analyze the geographic variability of the impact of SDH-adjusted PC morbidity on hospital morbidity, by combining data sourced from electronic health records and selected operations of the National Statistics Institute (Instituto Nacional de Estadística/INE). Methods: The following will be conducted: a qualitative study to select socio-health indicators using RAND methodology in accordance with SDH frameworks, based on indicators published by the INE in selected operations; and a quantitative study combining two large databases drawn from different Spainﾒs Autonomous Regions (ARs) to enable hospital morbidity to be ascertained, i.e., PC electronic health records and the minimum basic data set (MBDS) for hospital discharges. These will be linked to socioeconomic indicators, previously selected by geographic unit. The outcome variable will be hospital morbidity, and the independent variables will be age, sex, PC morbidity, geographic unit, and socioeconomic indicators. Analysis: To achieve the first objective, predictive models will be used, with a test-and-training technique, fitting multiple logistic regression models. In the analysis of geographic variability, penalized mixed models will be used, with geographic units considered as random effects and independent predictors as fixed effects. Discussion: This study seeks to show the relationship between SDH and population health, and the geographic differences determined by such determinants. The main limitations are posed by the collection of data for healthcare as opposed to research purposes, and the time lag between collection and publication of data, sampling errors and missing data in registries and surveys. The main strength lies in the projectﾒs multidisciplinary nature (family medicine, pediatrics, public health, nursing, psychology, engineering, geography).
Validation and Psychometric Properties of the Spanish Version of the Hopkins Symptom Checklist-25 Scale for Depression Detection in Primary Care.
(2021-07-24) Rodríguez-Barragán, María; Fernández-San-Martín, María Isabel; Clavería-Fontán, Ana; Aldecoa-Landesa, Susana; Casajuana-Closas, Marc; Llobera Cànaves, Joan; Oliván-Blázquez, Bárbara; Peguero-Rodríguez, Eva
Depression constitutes a major public health problem due to its high prevalence and difficulty in diagnosis. The Hopkins Symptom Checklist-25 (HSCL-25) scale has been identified as valid, reproducible, effective, and easy to use in primary care (PC). The purpose of the study was to assess the psychometric properties of the HSCL-25 and validate its Spanish version. A multicenter cross-sectional study was carried out at six PC centers in Spain. Validity and reliability were assessed against the structured Composite International Diagnostic Interview (CIDI). Out of the 790 patients, 769 completed the HSCL-25; 738 answered all the items. Global Cronbach's alpha was 0.92 (0.88 as calculated for the depression dimension and 0.83 for the anxiety one). Confirmatory factor analysis (CFA) showed one global factor and two correlated factors with a correlation of 0.84. Area under the curve (AUC) was 0.89 (CI 95%, 0.86-0.93%). For a 1.75 cutoff point, sensibility was 88.1% (CI 95%, 77.1-95.1%) and specificity was 76.7% (CI 95%, 73.3-79.8%). The Spanish version of the HSCL-25 has a high response percentage, validity, and reliability and is well-accepted by PC patients.
Implementation of the EIRA 3 Intervention by Targeting Primary Health Care Practitioners: Effectiveness in Increasing Physical Activity
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-10-08) Contreras-Martos, Sara; Leiva Rus, Alfonso; Sanchez, Álvaro; Motrico, Emma; Bellón, Juan; Aldecoa Landesa, Susana; Magallón-Botaya, Rosa; Casajuana-Closas, Marc; Zabaleta-Del-Olmo, Edurne; Bol�bar, Bonaventura; Maderuelo, José-Ángel; Llobera Cànaves, Joan
The World Health Organization (WHO) estimated that physical inactivity (PI) is responsible for 20 to 30% of all non-communicable diseases. We aimed to analyze the effectiveness of a multiple health behavior change (MHBC) intervention to increase physical activity (PA) in patients 45 to 75 years old who had at least 2 of 3 unhealthy behaviors (tobacco use, reduced fruit and vegetable consumption, and insufficient PA). The MHBC intervention is based on the Transtheoretical Model and the conceptual framework of the "5 A's" and includes an individually tailored intervention, group sessions, and the use of community resources. We included 3062 participants, 1481 in the intervention group and 1581 in the control group. After 12 months, there were no differences in PA intensity measured by metabolic_equivalent_of_task_minutes/week (adjusted mean difference: 284.093, 95% CI: -298.24, 866.42) nor in the proportion of participants who increased PA levels to moderate or high (OR: 1.02, 95% CI: 0.85, 1.23; p = 0.822), and no differences in blood pressure, weight loss, or waist circumference. We found an increased proportion of patients in the intervention group who followed the WHO recommendations for PA (OR: 1.29; 95% CI: 1.04, 1.60; p = 0.02). We concluded that the intervention did not lead to a significant increase in PA.
Multiple health behaviour change primary care intervention for smoking cessation, physical activity and healthy diet in adults 45 to 75 years old (EIRA study): a hybrid effectiveness-implementation cluster randomised trial
(BioMed Central (BMC), 2021-12-04) Zabaleta-Del-Olmo, Edurne; Casajuana-Closas, Marc; Lopez-Jimenez, Tomas; Pombo, Haizea; Pons-Vigues, Mariona; Pujol-Ribera, Enriqueta; Cabezas-Peña, Carmen; Llobera Cànaves, Joan; Marti-Lluch, Ruth; Vicens, Caterina; Motrico, Emma; Gomez-Gomez, Irene; Maderuelo-Fernandez, Jose-Angel; Recio-Rodriguez, Jose, I; Masluk, Barbara; Contreras-Martos, Sara; Jacques-Aviño, Constanza; Aznar-Lou, Ignacio; Gil-Girbau, Montserrat; Claveria, Ana; Magallon-Botaya, Rosa; Bellon, Juan-Angel; Ramos, Rafael; Sánchez-Pérez, Álvaro; Moreno-Peral, Patricia; Leiva, Alfonso; Gonzalez-Formoso, Clara; Bolibar, Bonaventura
Background: This study aimed to evaluate the effectiveness of a) a Multiple Health Behaviour Change (MHBC) intervention on reducing smoking, increasing physical activity and adherence to a Mediterranean dietary pattern in people aged 45-75 years compared to usual care; and b) an implementation strategy. Methods: A cluster randomised effectiveness-implementation hybrid trial-type 2 with two parallel groups was conducted in 25 Spanish Primary Health Care (PHC) centres (3062 participants): 12 centres (1481 participants) were randomised to the intervention and 13 (1581 participants) to the control group (usual care). The intervention was based on the Transtheoretical Model and focused on all target behaviours using individual, group and community approaches. PHC professionals made it during routine care. The implementation strategy was based on the Consolidated Framework for Implementation Research (CFIR). Data were analysed using generalised linear mixed models, accounting for clustering. A mixed-methods data analysis was used to evaluate implementation outcomes (adoption, acceptability, appropriateness, feasibility and fidelity) and determinants of implementation success. Results: 14.5% of participants in the intervention group and 8.9% in the usual care group showed a positive change in two or all the target behaviours. Intervention was more effective in promoting dietary behaviour change (31.9% vs 21.4%). The overall adoption rate by professionals was 48.7%. Early and final appropriateness were perceived by professionals as moderate. Early acceptability was high, whereas final acceptability was only moderate. Initial and final acceptability as perceived by the participants was high, and appropriateness moderate. Consent and recruitment rates were 82.0% and 65.5%, respectively, intervention uptake was 89.5% and completion rate 74.7%. The global value of the percentage of approaches with fidelity >= 50% was 16.7%. Eight CFIR constructs distinguished between high and low implementation, five corresponding to the Inner Setting domain. Conclusions: Compared to usual care, the EIRA intervention was more effective in promoting MHBC and dietary behaviour change. Implementation outcomes were satisfactory except for the fidelity to the planned intervention, which was low. The organisational and structural contexts of the centres proved to be significant determinants of implementation effectiveness.
External validation of multidimensional prognostic indices (ADO, BODEx and DOSE) in a primary care international cohort (PROEPOC/COPD cohort)
(BioMed Central (BMC), 2016-11-11) Espantoso-Romero, Maite; Roman-Rodriguez, Miguel; Duarte-Perez, Ana; Gonzalvez-Rey, Jaime; Callejas-Cabanillas, Pedro A; Lazic, Durdica Kasuba; Anta-Agudo, Berta; Toran Monserrat, Pere; Magallon-Botaya, Rosa; Kitanovska, Biljana Gerasimovska; Lingner, Heidrun; Assenova, Radost S; Iftode, Claudia; Gude-Sampedro, Francisco; Claveria, Ana; PROEPOC COPD Study Grp
Background: Due to the heterogeneous and systemic nature of the chronic obstructive pulmonary disease ( COPD), the new guidelines are oriented toward individualized attention. Multidimensional scales could facilitate its proper clinical and prognostic assessment, but not all of them were validated in an international primary care cohort, different from the original ones used for model development. Therefore, our main aim is to assess the prognostic capacity of the ADO, BODEx and DOSE indices in primary care for predicting mortality in COPD patients and to validate the models obtained in subgroups of patients, classified by revised Global Initiative for Chronic Obstructive Lung Disease ( 2011) and updated Spanish Guideline ( 2014). Besides, we want to confirm that the prognostic capacity of all indices increases if the number of exacerbations is substituted by the interval between them and to assess the impact on health of the patient's lifestyle, social network and adherence to treatment. Methods: Design: External validation of scales, open and prospective cohort study in primary care. Setting: 36 health centres in 6 European high, medium and low income countries. Subjects: 477 patients diagnosed with COPD, captured in clinical visit by their General Practitioner/Nurse. Predictors: Detailed patient history, exacerbations, lung function test and questionnaires at baseline. Outcomes: Exacerbations, all-cause mortality and specific mortality, within 5 years of recruitment. Analysis: Multivariate logistic regression and Cox regression will be used. Possible non-linear effect of the indices will be studied by using Structured Additive Regression models with penalised splines. Subsequently, we will assess different aspects of the regression models: discrimination, calibration and diagnostic precision. Clinical variables modulated in primary care and the interval between exacerbations will be considered and incorporated into the analysis. Discussion: The Research Agenda for General Practice/Family Medicine highlights that the evidence on predictive values of prognostic indices in primary care is scarce. A prospective cohort like that of PROEPOC/COPD provides good opportunities for research into COPD and make communication easier between family practitioners, nursing staff, pneumologists and other professionals, supporting a multi-disciplinary approach to the treatment of these patients.
Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters
(Elsevier, 2024-01) Corona, Diana; Pérez-Valero, Ignacio; Camacho, Angela; Gutiérrez Liarte, Ángela; Montero-Alonso, Marta; Alemán, María Remedios; Ruiz-Seco, Pilar; Pérez González, Alexandre; Riera, Melchor; Jarrin Vera, Inmaculada; Rivero-Juarez, Antonio; Rivero, Antonio; Gilead Sciences (Spain); Ministerio de Sanidad (España); Plan Nacional de I+D+i (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Instituto de Salud Carlos III; Unión Europea. Comisión Europea. NextGenerationEU; Ministerio de Ciencia e Innovación (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Objectives: The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated. Methods: The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm3 and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm3, at weeks 24 and 48 after initiation of ART. Results: We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG + TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005). Conclusion: Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.
Late presentation of chronic HBV and HCV patients seeking first time specialist care in Spain: a 2-year registry review
(Springer, 2021-12-17) Picchio, Camila A.; Lens, Sabela; Hernandez-Guerra, Manuel; Arenas, Juan; Andrade, Raúl J.; Crespo, Javier; García-Samaniego, Javier; Romero-Gómez, Manuel; Turnes, Juan; Calleja, José Luis; Simón, Miguel Ángel; White, Trenton M.; Riveiro-Barciela, Mar; Pocurull, Anna; Morales-Arraez, Dalia; Gómez, Alexandra; Buti, Maria; Lazarus, Jeffrey V; [Picchio,CA; White,TM; Lazarus,JV] Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain. [Lens,S; Pocurull,A] Liver Unit, Hospital Clinic, Universidad de Barcelona, Barcelona, Spain. [Lens,S; Pocurull,A] IDIBAPS, University of Barcelona, Barcelona, Spain. [Lens,S; Andrade,RJ; García‑Samaniego,J; Calleja,JL; Pocurull,A; Buti,M] CIBER Hepatic and Digestive Diseases (CIBERehd), Instituto Carlos III, Madrid, Spain. [Hernandez-Guerra,M; Morales-Arraez,D] Department of Gastroenterology, University Hospital of the Canary Islands, San Cristóbal de La Laguna, Spain. [Arenas,J; Gomez,A] Biodonostia, Liver Diseases Research Group, Osakidetza Basque Health Service, Donostia University Hospital, San Sebastián, Spain. [Andrade,RJ] Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga‑IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. [Crespo,J] Gastroenterology and Hepatology Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Santander, Spain. [García-Samaniego,J] Liver Unit, Department of Gastroenterology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. [Romero-Gómez,M] UCM Digestive Diseases, Hospital Universitario Virgen del Rocío, Institute of Biomedicine of Seville, Universidad de Sevilla, Seville, Spain. [Turnes,J] Complejo Hospitalario Universitario de Pontevedra, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Pontevedra, Spain. [Calleja,JL] Gastroenterology and Hepatology Department, Hospital Universitario Puerta del Hierro de, Universidad Autónoma de Madrid, Madrid, Spain. [Simón,MA] Department of Digestive Diseases, Hospital Clínico de Zaragoza, Zaragoza, Spain. [Simón,MA] Instituto de Investigación Sanitario Aragón (IIS Aragón), Zaragoza, Spain. [Riveiro-Barciela,M; Buti,M] Liver Unit, Hospital Universitario Vall d’Hebron, Barcelona, Spain.
Chronic viral hepatitis infection affects an estimated 325 million people globally. People who initiate treatment after significant disease progression face increased risk of severe liver complications and death. Data are scarce on the characteristics and risk factors of people who present late to care in Spain and globally. Data were collected from January 2018 to December 2019 to report late presentation (LP) to specialist care at 11 large university hospitals in Spain to assess related risk factors using a multivariable logistic regression model. 2290 (CHB = 505, CHC = 1785) patients were analysed, with 581 (25.2%) presenting late. Hepatitis C patients more frequently reported LP compared to hepatitis B patients (28.1% vs 15.0%; p < 0.001). Older age (p < 0.001), being male (p < 0.001), being Spanish-born (p < 0.001), and having an unknown origin of referral (p = 0.08) were associated with a higher likelihood of LP. Advanced liver disease was identified in 533 (23%) patients and late-stage liver disease in 124 (5.4%). LP, including with irreversible liver damage, to viral hepatitis specialist care is frequent in Spain, despite being a country with unrestricted treatment access. Initiatives to reduce LP should specifically target men, older individuals, foreign-born populations for CHB, and Spanish nationals for CHC.
The Relationship between Adherence to the Mediterranean Diet, Intake of Specific Foods and Depression in an Adult Population (45-75 Years) in Primary Health Care. A Cross-Sectional Descriptive Study.
(2021-08-07) Oliván-Blázquez, Bárbara; Aguilar-Latorre, Alejandra; Motrico, Emma; Gómez-Gómez, Irene; Zabaleta-Del-Olmo, Edurne; Couso-Viana, Sabela; Clavería, Ana; Maderuelo-Fernandez, José A; Recio-Rodríguez, José Ignacio; Moreno-Peral, Patricia; Casajuana-Closas, Marc; López-Jiménez, Tomàs; Bolíbar, Bonaventura; Llobera, Joan; Sarasa-Bosque, Concepción; Sanchez-Perez, Álvaro; Bellón, Juan Ángel; Magallón-Botaya, Rosa
The relationship between the quality of the diet and the adherence to the Mediterranean diet with the presence of persistent or recurrent depressive symptoms have been described. The objective of this study is to analyze the relationship between adherence to the Mediterranean diet and the intake of specific foods in primary care patients aged 45 to 75, having subclinical or major depression. The study also specifically analyzes this relationship in individuals suffering from chronic diseases. A cross-sectional descriptive study was conducted. 3062 subjects met the inclusion criteria from the EIRA study. Sociodemographic variables, clinical morbidity, depression symptomatology (PHQ-9) and adherence to Mediterranean diet (MEDAS) were collected. Being female, younger, with a higher BMI, consuming more than 1 serving of red meat a day and drinking more than one carbonated or sugary drink daily, not consuming 3 servings of nuts a week and not eating 2 vegetables cooked in olive oil a week are predictors of having higher depressive symptomatology. Assessing the type of diet of patients presenting depressive symptoms and promoting adherence to a healthy diet is important, especially in patients with chronic diseases. However, depression is a very complex issue and the relationship between nutrition and depression must be further examined.
Correction to: Complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in primary health care (EIRA study): study protocol for a hybrid trial.
(2018-08-13) Zabaleta-Del-Olmo, Edurne; Pombo, Haizea; Pons-Vigués, Mariona; Casajuana-Closas, Marc; Pujol-Ribera, Enriqueta; López-Jiménez, Tomás; Cabezas-Peña, Carmen; Martín-Borràs, Carme; Serrano-Blanco, Antoni; Rubio-Valera, Maria; Llobera, Joan; Leiva, Alfonso; Vicens, Caterina; Vidal, Clara; Campiñez, Manuel; Martín-Álvarez, Remedios; Maderuelo, José-Ángel; Recio, José-Ignacio; García-Ortiz, Luis; Motrico, Emma; Bellón, Juan-Ángel; Moreno-Peral, Patricia; Martín-Cantera, Carlos; Clavería, Ana; Aldecoa-Landesa, Susana; Magallón-Botaya, Rosa; Bolíbar, Bonaventura
It has been highlighted the original article (1) contained a typesetting mistake in the authorship, and that author Caterine Vicens was omitted.
Complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in primary health care (EIRA study): study protocol for a hybrid trial.
(2018-07-13) Zabaleta-Del-Olmo, Edurne; Pombo, Haizea; Pons-Vigués, Mariona; Casajuana-Closas, Marc; Pujol-Ribera, Enriqueta; López-Jiménez, Tomás; Cabezas-Peña, Carmen; Martín-Borràs, Carme; Serrano-Blanco, Antoni; Rubio-Valera, Maria; Llobera, Joan; Leiva, Alfonso; Vicens, Caterina; Vidal, Clara; Campiñez, Manuel; Martín-Álvarez, Remedios; Maderuelo, José-Ángel; Recio, José-Ignacio; García-Ortiz, Luis; Motrico, Emma; Bellón, Juan-Ángel; Moreno-Peral, Patricia; Martín-Cantera, Carlos; Clavería, Ana; Aldecoa-Landesa, Susana; Magallón-Botaya, Rosa; Bolíbar, Bonaventura
Background: Health promotion is a key process of current health systems. Primary Health Care (PHC) is the ideal setting for health promotion but multifaceted barriers make its integration difficult in the usual care. The majority of the adult population engages two or more risk behaviours, that is why a multiple intervention might be more effective and efficient. The primary objectives are to evaluate the effectiveness, the cost-effectiveness and an implementation strategy of a complex multiple risk intervention to promote healthy behaviours in people between 45 to 75 years attended in PHC. Methods: This study is a cluster randomised controlled hybrid type 2 trial with two parallel groups comparing a complex multiple risk behaviour intervention with usual care. It will be carried out in 26 PHC centres in Spain. The study focuses on people between 45 and 75 years who carry out two or more of the following unhealthy behaviours: tobacco use, low adherence to the Mediterranean dietary pattern or insufficient physical activity level. The intervention is based on the Transtheoretical Model and it will be made by physicians and nurses in the routine care of PHC practices according to the conceptual framework of the 5A's. It will have a maximum duration of 12 months and it will be carried out to three different levels (individual, group and community). Incremental cost per quality-adjusted life year gained measured by the tariffs of the EuroQol-5D questionnaire will be estimated. The implementation strategy is based on the Consolidated Framework for Implementation Research, a set of discrete implementation strategies and an evaluation framework. Discussion: EIRA study will determine the effectiveness and cost-effectiveness of a complex multiple risk intervention and will provide a better understanding of implementation processes of health promotion interventions in PHC setting. It may contribute to increase knowledge about the individual and structural barriers that affect implementation of these interventions and to quantify the contextual factors that moderate the effectiveness of implementation.
Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus.
(2018-05-30) Julià, Antonio; López-Longo, Francisco Javier; Pérez Venegas, José J; Bonàs-Guarch, Silvia; Olivé, Àlex; Andreu, José Luís; Aguirre-Zamorano, Mª Ángeles; Vela, Paloma; Nolla, Joan M; de la Fuente, José Luís Marenco; Zea, Antonio; Pego-Reigosa, José María; Freire, Mercedes; Díez, Elvira; Rodríguez-Almaraz, Esther; Carreira, Patricia; Blanco, Ricardo; Taboada, Víctor Martínez; López-Lasanta, María; Corbeto, Mireia López; Mercader, Josep M; Torrents, David; Absher, Devin; Marsal, Sara; Fernández-Nebro, Antonio
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. We identified five new loci associated with SLE at the genome-wide level of significance (p Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci.
miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease
(Sociedad Española de Patología Respiratoria, 2021-07) Matamala, Nerea; Lara, Beatriz; Gomez-Mariano, Gema Maria; Martinez Rodríguez, Selene; Vazquez-Dominguez, Irene; Otero-Sobrino, Álvaro; Muñoz-Callejas, Antonio; Sánchez, Elena; Esquinas, Cristina; Bustamante, Ana; Cadenas, Sergio; Curi, Sergio; Lázaro, Lourdes; Martínez, María Teresa; Rodríguez, Esther; Miravitlles, Marc; Torres-Durán, María; Herrero, Inés; Michel, Francisco Javier; Castillo, Silvia; Hernández-Pérez, José Mª; Blanco, Ignacio; Casas, Francisco; Martinez-Delgado, Beatriz; Instituto de Salud Carlos III; Sociedad Española de Neumología y Cirugía Torácica
Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3'UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease. Methods: Firstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions. Results: Overexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation. Conclusion: Our findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.
New cis-Acting Variants in PI*S Background Produce Null Phenotypes Causing Alpha-1 Antitrypsin Deficiency
(American Thoracic Society (ATS), 2020-10) Matamala, Nerea; Gomez-Mariano, Gema Maria; Perez, Jose Antonio; Baladron-Jimenez, Beatriz Isabel; Torres-Durán, María; Michel, Francisco Javier; Saez, Raquel; Hernández-Pérez, Jose María; Belmonte, Irene; Rodriguez-Frias, Francisco; Blanco, Ignacio; Strnad, Pavel; Janciauskiene, Sabina; Martinez-Delgado, Beatriz; Instituto de Salud Carlos III; Deutsche Forschungsgemeinschaft (Alemania)
Alpha-1 antitrypsin deficiency (AATD) is an inherited condition characterized by reduced levels of serum AAT due to mutations in the SERPINA1 (Serpin family A member 1) gene. The Pi*S (Glu264Val) is one of the most frequent deficient alleles of AATD, showing high incidence in the Iberian Peninsula. Herein, we describe two new alleles carrying an S mutation but producing a null phenotype: QOVigo and QOAachen. The new alleles were identified by sequencing the SERPINA1 gene in three patients who had lower AAT serum levels than expected for the initial genotype. These alleles are the result of combined mutations in cis in a PI*S allele. Sequencing detected the S mutation in cis with Tyr138Cys (S+Tyr138Cys) in two patients, whereas a third one had the S mutation in cis with Pro391Thr variant (S+Pro391Thr). When expressed in a cellular model, these variants caused strong AAT polymerization and very low AAT secretion to almost undetectable levels. The isoelectric focusing method for plasma AAT phenotyping did not show AAT protein encoded by the novel mutant alleles, behaving as null. We called these alleles PI*S-plus because the S variant was phased with another variant conferring more aggressive characteristics to the allele. The current data demonstrate that the clinical variability observed in AATD can be explained by additional genetic variation, such as dual cis-acting variants in the SERPINA1 gene. The possible existence of other unrevealed variants combined in the PI*S alleles should be considered to improve the genetic diagnosis of the patients.
Regional differences in STEMI care in Spain. Data from the ACI-SEC Infarction Code Registry
(Permanyer, 2023) Rodríguez-Leor, Oriol; Cid-Álvarez, Ana Belén; Moreno, Raúl; Rosselló, Xavier; Ojeda, Soledad; Serrador, Ana; López-Palop, Ramón; Martín-Moreiras, Javier; Ramón Rumoroso, José; Cequier, Ángel; Ibáñez, Borja; Cruz-González, Ignacio; Romaguera, Rafael; Raposeiras-Roubín, Sergio; Pérez de Prado, Armando
Introduction and objectives: Geographical and organizational differences between different autonomous communities (AC) can generate differences in care for ST-segment elevation myocardial infarction (STEMI). A total of 17 heart attack code programs have been compared in terms of incidence rate, clinical characteristics, reperfusion therapy, delay to reperfusion, and 30-day mortality. Methods: National prospective observational study (83 centers included in 17 infarction networks). The recruitment period was 3 months (April 1 to June 30, 2019) with clinical follow-up at 30 days. Results: 4366 patients with STEMI were included. The incidence rate was variable between different AC (P < .0001), as was gender (P = .003) and the prevalence of cardiovascular risk factors (P < .0001). Reperfusion treatment was primary angioplasty (range 77.5%-97.8%), fibrinolysis (range 0%-12.9%) or no treatment (range 2.2%- 13.5%). The analysis of the delay to reperfusion showed significant differences (P < .001) for all the intervals analyzed. There were significant differences in 30-days mortality that disappeared after adjusting for clinical and healthcare network characteristics. Conclusions: Large differences in STEMI care have been detected between the different AC, in terms of incidence rate, clinical characteristics, reperfusion treatment, delay until reperfusion, and 30-day mortality. The differences in mortality disappeared after adjusting for the characteristics of the patient and the care network.
GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
(Nature Publishing Group, 2023-05-17) Pairo-Castineira, Erola; Rawlik, Konrad; Bretherick, Andrew D; Qi, Ting; Wu, Yang; Nassiri, Isar; McConkey, Glenn A; Zechner, Marie; Klaric, Lucija; Griffiths, Fiona; Oosthuyzen, Wilna; Kousathanas, Athanasios; Richmond, Anne; Millar, Jonathan; Russell, Clark D; Malinauskas, Tomas; Thwaites, Ryan; Morrice, Kirstie; Keating, Sean; Maslove, David; Nichol, Alistair; Semple, Malcolm G; Knight, Julian; Shankar-Hari, Manu; Summers, Charlotte; Hinds, Charles; Horby, Peter; Ling, Lowell; McAuley, Danny; Montgomery, Hugh; Openshaw, Peter J M; Begg, Colin; Walsh, Timothy; Tenesa, Albert; Flores, Carlos; Riancho, José A; Rojas-Martinez, Augusto; Lapunzina, Pablo; Yang, Jian; Ponting, Chris P; Wilson, James F; Vitart, Veronique; Abedalthagafi, Malak; Luchessi, Andre D; Parra, Esteban J; Cruz, Raquel; Carracedo, Ángel; Fawkes, Angie; Murphy, Lee; Rowan, Kathy; Pereira, Alexandre C; Law, Andy; Fairfax, Benjamin; Hendry, Sara Clohisey; Baillie, J Kenneth; GenOMICC Investigators; SCOURGE Consortium; ISARICC Investigators; The 23andMe COVID-19 Team; Brochado-Kith, Oscar; Ceballos, Francisco C; Fernandez-Rodriguez, Amanda; Jimenez-Sousa, Maria Angeles; Martin-Vicente, Maria; Resino, Salvador; Virseda-Berdices, Ana; Meijome, Xose M; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Fundación Amancio Ortega; Banco Santander; Gobierno de Canarias (España); Fundación Canaria de Investigación Sanitaria; Centro de Supercomputación de Galicia; National Council for Scientific and Technological Development (Brasil); Sepsis Trust NZ; Wellcome Trust; Illumina (Reino Unido); Westlake Educational Foundation; British Heart Foundation; Biotechnology and Biological Sciences Research Council (Reino Unido); UK Research and Innovation; Medical Research Council (Reino Unido); LifeArc; Department of Health and Social Care (Reino Unido)
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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