Unidad de Investigación en Salud Digital (UITeS)
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/19619
La Unidad Investigación en Salud Digital (UITeS) tiene como misión promover y desarrollar actividades de Investigación y Desarrollo e Innovación en el campo de las Tecnologías de la Información y las Comunicaciones (TIC) aplicadas a la Salud. Sus líneas de trabajo siguen las prioridades del Programa Nacional de I+D+i, del Programa Marco de la UE en TIC para la Salud y de Salud Pública y Medio Ambiente. Las áreas temáticas se centran fundamentalmente en las de la Salud Digital: telemedicina, e-Salud, sistemas móviles, plataformas de servicios en red, instrumentación biomédica, redes inalámbricas, gestión de la información clínica, extracción de conocimiento, salud personalizada, seguridad y compatibilidad electromagnética así como aplicaciones para soporte a la asistencia de las personas con dolencias crónicas y la prevención de la dependencia. Los campos de actividad cubren la Investigación científica y tecnológica y la promoción de la innovación en el SNS realizando pilotos, demostradores y ensayos clínicos en colaboración con otros grupos de investigación, instituciones sanitarias y la industria relacionada.
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Publication Effects of 700 and 3500 MHz 5G radiofrequency exposure on developing zebrafish embryos.(Elsevier, 2024-03-10) Torres-Ruiz, Mónica; Suárez, Oscar J; López-Alonso, Victoria; Marina-Boillos, Pablo; Sanchis Otero, Aranzazu; Liste-Noya, Isabel; De Alba-González, Mercedes; Ramos-Gonzalez, Maria VictoriaTelecommunications industries are rapidly deploying the fifth generation (5G) spectrum and there is public concern about the safety and health impacts of this type of Radio Frequency Radiation (RFR), in part because of the lack of comparable scientific evidence. In this study we have used a validated commercially available setting producing a uniform field to expose zebrafish embryos (ZFe) to unmodulated 700 and 3500 MHz frequencies. We have combined a battery of toxicity, developmental and behavioral assays to further explore potential RFR effects. Our neurobehavioral profiles include a tail coiling assay, a light/dark activity assay, two thigmotaxis anxiety assays (auditory and visual stimuli), and a startle response - habituation assay in response to auditory stimuli. ZFe were exposed for 1 and 4 h during the blastula period of development and endpoints evaluated up to 120 hours post fertilization (hpf). Our results show no effects on mortality, hatching or body length. However, we have demonstrated specific organ morphological effects, and behavioral effects in activity, anxiety-like behavior, and habituation that lasted in larvae exposed during the early embryonic period. A decrease in acetylcholinesterase activity was also observed and could explain some of the observed behavioral alterations. Interestingly, effects were more pronounced in ZFe exposed to the 700 MHz frequency, and especially for the 4 h exposure period. In addition, we have demonstrated that our exposure setup is robust, flexible with regard to frequency and power testing, and highly comparable. Future work will include exposure of ZFe to 5G modulated signals for different time periods to better understand the potential health effects of novel 5G RFR.Publication Heart failure in the family practice: a study of the prevalence and co-morbidity.(Oxford University Press, 2011-04) Carmona, Montserrat; García-Olmos, Luis M; Alberquilla, Angel; Muñoz Carrero, Adolfo; García-Sagredo, Pilar; Somolinos, Roberto; Pascual-Carrasco, Mario; Salvador, Carlos H; Monteagudo, Jose Luis; Centro para el Desarrollo Tecnológico Industrial (España); Instituto de Salud Carlos III; Fundación Vodafone EspañaBackground: Heart failure (HF) is a health problem that particularly affects the elderly population. Its onset is associated with other chronic diseases, a circumstance that makes it a challenge for health care services. The aim of this study is to quantify the prevalence of HF in family medicine offices and describe the chronic co-morbidity associated with it. Methods: A cross-sectional, observational descriptive study set in a health area of the Community of Madrid, Spain. The study was carried out in a population of 198,670 individuals over 14 years of age, attended to by 129 specialists in family medicine. The patient was considered to have HF when this diagnosis (ICPC code K77) appeared in his or her electronic medical record. The prevalence of HF was quantified and its association with another 25 chronic diseases was analysed. Results: The prevalence of HF was 6.9‰, 7.9‰ among women and 5.9‰ among men. Patients with HF had a high rate of chronic co-morbidity, with an average of 5.2 + 2.1 chronic diseases. Only 3% of the patients present with isolated HF and >60% have four or more additional chronic problems. Hypertension, cardiac arrhythmias, hyperlipidaemia, obesity and diabetes mellitus are the chronic diseases most frequently detected in HF patients. Conclusion: Patients with HF frequently visit the offices of family physicians, presenting with a high rate of cardiac and non-cardiac co-morbidity that proves to be a challenge on the clinical level and in terms of the organization of health care services.Publication ICF disability measured by WHO-DAS II in three community diagnostic groups in Madrid, Spain.(Elsevier, 2011-12) Pedro-Cuesta, Jesus de; Alberquilla, Ángel; Virues-Ortega, Javier; Carmona, Montserrat; Alcalde-Cabero, Enrique; Bosca, Graciela; López Rodríguez, Fernando; Garcia-Sagredo, Pilar; García-Olmos, Luis; Salvador, Carlos H; Monteagudo, Jose Luis; Centro para el Desarrollo Tecnológico Industrial (España); Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)Objective: The planning, provision and monitoring of medical and support services for patient groups with chronic ailments may require disability assessment and registration. The purpose of this study was to assess disability in three groups of patients with chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) or stroke. Methods: Convenience samples of consecutive patients diagnosed with COPD (102), CHF (99), and stroke (99) were taken from 1,053 primary care users in the southern area of the autonomous region of Madrid. The patients were informed of the study and were assessed in their homes by trained field workers using the World Health Organization Disability Assessment Schedule II (WHO-DAS II). Results: None of the groups had patients with extreme disability on their global WHO-DAS II scores. The prevalence of severe disability differed among the groups and was highest for stroke and CHF (33.33% and 29.29%, respectively) and lowest for COPD (14.71%). The three groups shared two similar traits, namely, a higher prevalence of disability among women than men, and a specific pattern by domain, with the highest prevalence of severe/extreme limitations being found in household life activities and mobility. Severe restrictions in Social Participation were more frequent in patients with stroke and CHF. The group with moderate disability according to the global WHODAS II score (n=94) showed a high prevalence of severe limitations in mobility, life activities and self-care. Conclusions: Disability among non-institutionalized persons with COPD, CHF and stroke is frequent and shows gender- and domain-related patterns similar to those described in a population-based study performed using the WHO-DAS II in elderly persons in Spain. ICF-validated disability categories could be useful in epidemiological surveys, individual assessments and primary care data monitoring systems.Publication Evaluation of a telemedicine service for the secondary prevention of coronary artery disease.(Lippincott Williams & Wilkins (LWW), 2012) Blasco, Ana; Carmona, Montserrat; Fernández-Lozano, Ignacio; Salvador, Carlos H; Pascual-Carrasco, Mario; Sagredo, Pilar G; Somolinos, Roberto; Muñoz Carrero, Adolfo; Garcia Lopez, Fernando Jose; Escudier, Juan M; Mingo, Susana; Toquero, Jorge; Moñivas, Vanessa; González, Miguel A; Fragua, Juan A; López-Rodríguez, Fernando; Monteagudo, Jose Luis; Alonso-Pulpón, Luis; Ministerio de Sanidad y Consumo (España); Fundación Vodafone EspañaPurpose: Efficient ways are needed to implement the secondary prevention (SP) of coronary heart disease. Because few studies have investigated Web-based SP programs, our aim was to determine the usefulness of a new Web-based telemonitoring system, connecting patients provided with self-measurement devices and care managers via mobile phone text messages, as a tool for SP. Methods: A single-blind, randomized controlled, clinical trial of 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. All patients received lifestyle counseling and usual-care treatment. Patients in the telemonitoring group (TMG) sent, through mobile phones, weight, heart rate, and blood pressure (BP) weekly, and capillary plasma lipid profile and glucose monthly. A cardiologist accessed these data through a Web interface and sent recommendations via short message service. Main outcome measures were BP, body mass index (BMI), smoking status, low-density lipoprotein-cholesterol (LDL-c), and glycated hemoglobin A₁c (HbA₁c). Results: At 12-month followup, TMG patients were more likely (RR = 1.4; 95% CI = 1.1-1.7) to experience improvement in cardiovascular risk factors profile than control patients (69.6% vs 50.5%, P = .010). More TMG patients achieved treatment goals for BP (62.1% vs 42.9%, P = .012) and HbA₁c (86.4% vs 54.2%, P = .018), with no differences in smoking cessation or LDL-c. Body mass index was significantly lower in TMG (-0.77 kg/m² vs +0.29 kg/m², P = .005). Conclusions: A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention, especially for overweight patients.Publication A Methodology to Extract Knowledge from Datasets Using ML(Multidisciplinary Digital Publishing Institute (MDPI), 2025-05-28) Sánchez-de-Madariaga, Ricardo; Pascual-Carrasco, Mario; Muñoz Carrero, AdolfoThis study aims to verify whether there is any relationship between the different classification outputs produced by distinct ML algorithms and the relevance of the data they classify, to address the problem of knowledge extraction (KE) from datasets. If such a relationship exists, the main objective of this research is to use it in order to improve performance in the important task of KE from datasets. A new dataset generation and a new ML classification measurement methodology were developed to determine whether the feature subsets (FSs) best classified by a specific ML algorithm corresponded to the most KE-relevant combinations of features. Medical expertise was extracted to determine the knowledge relevance using two LLMs, namely, chat GPT-4o and Google Gemini 2.5. Some specific ML algorithms fit much better than others for a working dataset extracted from a given probability distribution. They best classify FSs that contain combinations of features that are particularly knowledge-relevant. This implies that, by using a specific ML algorithm, we can indeed extract useful scientific knowledge. The best-fitting ML algorithm is not known a priori. However, we can bootstrap its identity using a small amount of medical expertise, and we have a powerful tool for extracting (medical) knowledge from datasets using ML.Publication Interoperabilidad semántica en usos secundarios de datos de salud. Caso de uso: repositorio de datos MePRAM(2025-05-29) Pascual-Carrasco, MarioEn este seminario, Mario Pascual, explica qué es y para sirve la interoperabilidad semántica y su aplicación en el repositorio MePRAM. La interoperabilidad semántica es la capacidad que emerge en ecosistemas integrados por datos estructurados, enriquecidos con semántica explícita, y por herramientas tecnológicas capaces de interpretar, procesar, y compartir esos datos, preservando su significado original, utilizando conceptos consensuados, conocimiento contextual y representaciones formales. Los llamados hechos de salud, o procesos de salud, se componen de observaciones, evaluaciones, instrucciones y acciones. Cada una de estas 4 partes tiene una terminología especifica que hay que controlar y una superior (SNOMED-CT) que une a todas las demás. Para poder conseguir la interoperabilidad semántica hay que normalizar los hechos de salud y estandarizar la terminología, consiguiendo así un ecosistema de servicios y herramientas útiles que nos permitan implementarlo y utilizarlo. El repositorio MePRAM (medicina de precisión contra la resistencia a antimicrobianos) tiene como objetivo el desarrollo de acciones metodológicas y tecnológicas en ámbito clínico para potenciar la atención al ciudadano a través de la prevención, diagnóstico de precisión y tratamiento personalizado de infecciones ocasionadas por patógenos multirresistentes.Publication Phase IV adaptive randomised clinical trials evaluating efficacy and cost-efficacy of pre-emptive pharmacogenetic genotyping strategies in the Spanish National Health System: iPHARMGx Master Protocol and PREVESTATGx nested clinical trial(BMJ Publishing Group, 2024-11-07) Stewart, Stefan; Seco-Meseguer, Enrique; Diago-Sempere, Elena; Marín-Candón, Alicia; Carmona, Montserrat; Estébanez, Miriam; López-Fernández, Luis A; Imaz-Iglesia, Iñaki; Del Mar García Saiz, María; Laserna-Mendieta, Emilio J; Peiró, Ana M; Farré, Magí; Rodriguez-Jimenez, Consuelo; Saiz-Rodriguez, Miriam; Sanabria-Cabrera, Judith; Rosas-Alonso, Rocío; Abad-Santos, Francisco; Pedrosa-Pérez, Lucía; Carcas, Antonio J; García García, Irene; Borobia, Alberto M; iPHARMGx study group; Instituto de Salud Carlos III; Unión Europea. Comisión Europea. NextGenerationEUIntroduction: Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as statins, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policy-makers. The Spanish Consortium for the Implementation of Pharmacogenetics (iPHARMGx Consortium) addresses this by developing a clinical trial master protocol that will govern multiple nested adaptive clinical trials that compare genotype-guided treatments to standard care in specific drug-gene-population triads, asses their cost-efficacy and identify novel biomarkers through advanced sequencing techniques. The first of these studies aims to assess whether a pre-emptive statin therapy genotyping scheme reduces the incidence of statin-associated muscle symptoms (SAMS) in a population at risk of cardiovascular disease susceptible of receiving high-intensity or moderate-intensity doses of statins: The PREVESTATGx trial. Methods and analysis: the PREVESTATGX trial is a multicentre, adaptive randomised controlled pragmatic phase IV clinical trial nested to the iPHARMGx master protocol with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial and genotyping has been performed, subjects will be randomly allocated to experimental group (pharmacogenetic genotype-guided statin prescription) or standard-of-care statin prescription (as deemed by attending physician). The main objective is to assess the efficacy of a statin pre-emptive genotyping strategy in reducing the incidence of SAMS. A total of 225 subjects will be recruited among the 10 participating centres if no futility/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period and subjects will be followed for a 9-month period. Ethics and dissemination: The PREVESTATGx trial received ethical approval on 24 April 2024. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open-access peer-reviewed medical speciality-specific publication. Trial registration number: EU CT number: 2023-509418-12-00/Clinical trial Identifier (ClinicalTrials.gov): NCT06262685. Protocol version 1.2 12 April 2024 (includes non-substantial modification number 14 June 2024). Trial registration of this study can be located at both the EU Clinical Trials Register available from https:// euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov. Registration on both websites was done before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according to the WHO.Publication Background levels and brain organoid impact of RF field exposure in a healthcare environment(Frontiers Media, 2024-03) Hernández, José A.; Rosca, Andreea; Suárez, Samuel; Coronel Lopez, Raquel; Suarez, Oscar J; Perán-Ramos, Paula; Marina-Boillos, Pablo; Rabassa, Luis E.; Mateos-Martínez, Patricia; Liste-Noya, Isabel; López-Alonso, Victoria; Torres-Ruiz, Mónica; Febles, Víctor M; Ramos-Gonzalez, Maria Victoria; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Agencia Estatal de Investigación (España)Introduction: This study is an introduction to the empirical and impact evaluation of radiofrequency electromagnetic field (RF-EMF) radiation exposure in a healthcare environment, focusing on an indoor microenvironment. It explores the expression of various genes associated with cellular responses, cell proliferation, senescence, and apoptotic cell death. The assessment analyzes current personal mobile communications (2G-5G FR1), providing a clear understanding of RF-EMF exposure and compliance with regulatory limits. Methods: The signals from different wireless communication systems at Hospital Universitario de Canarias (HUC) in Tenerife, Canary Islands, Spain, were examined in 11 locations. Four measurement campaigns were performed with frequencyselective exposimeters (PEMs) and an EME Spy 200 MVG, and experimental electric field values were compared as a long-term exposition. The frequency with the highest contribution (2.174 V/m) observed (1840 MHz) in UMTS was selected for biological effects evaluation. Results: The study focuses on four locations with the highest exposure to communication systems (downlinks), analyzing the results to verify compliance with regulations that ensure the safety of patients, the general public, and healthcare workers. LTE B20 (DL), GSM+UMTS 900 (DL), GSM 1800 (DL), UMTS 2100 (DL), and LTE B7 (DL) exhibited relatively higher E/m values throughout the campaigns, and these values consistently remained below the ICNIRP reference levels, signifying a consistently low level of exposure. In addition, this work presents the biological effects on neural stem cells (NSCs) using 3D brain organoids (BOs) exposed to RF signals in a validated and commercial experimental setting: the Gigahertz Transverse Electromagnetic cell (GTEM). The GTEM allows for the creation of homogeneous field electromagnetic fields in a small, enclosed setting and guarantees exposure conditions in a wide range of frequencies. BOs are an in vitro 3D cell-culture technology that reproduces the cellular composition and structure of the developing brain. Analyzing the expression of several genes associated with cellular responses, cell proliferation, senescence, and apoptotic cell death,wefound that exposure of BOs at 1840MHzdid not affectmRNAexpression in brain genes related to apoptosis or senescence. However, a decrease in gene expression for cell proliferation and cell activity markers was observed during the differentiation stage of BOs. Discussion: The discussion emphasizes the coexistence and evolution of various heterogeneous networks and services throughout the four measurement campaigns. Across all measured results, the levels of the obtained E-field were consistently well below the exposure limits set by internationally accepted standards and guidelines. These obtained values have been established in order to consider their potential effects on cell proliferation and cell activity, especially in differentiating biological organisms. Consequently, the results obtained and the methodology presented could serve as a foundational framework for establishing the basis of RF-EMF assessment in future heterogeneous 5G developments, particularly in the millimeter wave (mmWave) frequency range, where the forecast is for massive high-node density networks.Publication Can OpenEHR, ISO 13606, and HL7 FHIR Work Together? An Agnostic Approach for the Selection and Application of Electronic Health Record Standards to the Next-Generation Health Data Spaces(JMIR Publications, 2023-12-28) Pedrera-Jiménez, Miguel; García-Barrio, Noelia; Frid, Santiago; Moner, David; Boscá-Tomás, Diego; Lozano-Rubí, Raimundo; Kalra, Dipak; Beale, Thomas; Muñoz Carrero, Adolfo; Serrano-Balazote, Pablo; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Comunidad de Madrid (España)In order to maximize the value of electronic health records (EHRs) for both health care and secondary use, it is necessary for the data to be interoperable and reusable without loss of the original meaning and context, in accordance with the findable, accessible, interoperable, and reusable (FAIR) principles. To achieve this, it is essential for health data platforms to incorporate standards that facilitate addressing needs such as formal modeling of clinical knowledge (health domain concepts) as well as the harmonized persistence, query, and exchange of data across different information systems and organizations. However, the selection of these specifications has not been consistent across the different health data initiatives, often applying standards to address needs for which they were not originally designed. This issue is essential in the current scenario of implementing the European Health Data Space, which advocates harmonization, interoperability, and reuse of data without regulating the specific standards to be applied for this purpose. Therefore, this viewpoint aims to establish a coherent, agnostic, and homogeneous framework for the use of the most impactful EHR standards in the new-generation health data spaces: OpenEHR, International Organization for Standardization (ISO) 13606, and Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR). Thus, a panel of EHR standards experts has discussed several critical points to reach a consensus that will serve decision-making teams in health data platform projects who may not be experts in these EHR standards. It was concluded that these specifications possess different capabilities related to modeling, flexibility, and implementation resources. Because of this, in the design of future data platforms, these standards must be applied based on the specific needs they were designed for, being likewise fully compatible with their combined functional and technical implementation.Publication An Ontology-Based Approach for Consolidating Patient Data Standardized With European Norm/International Organization for Standardization 13606 (EN/ISO 13606) Into Joint Observational Medical Outcomes Partnership (OMOP) Repositories: Description of a Methodology(JMIR Publications, 2023-03-08) Frid, Santiago; Pastor Duran, Xavier; Bracons Cucó, Guillem; Pedrera-Jiménez, Miguel; Serrano-Balazote, Pablo; Muñoz Carrero, Adolfo; Lozano-Rubí, Raimundo; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Background: To discover new knowledge from data, they must be correct and in a consistent format. OntoCR, a clinical repository developed at Hospital Clínic de Barcelona, uses ontologies to represent clinical knowledge and map locally defined variables to health information standards and common data models. Objective: The aim of the study is to design and implement a scalable methodology based on the dual-model paradigm and the use of ontologies to consolidate clinical data from different organizations in a standardized repository for research purposes without loss of meaning. Methods: First, the relevant clinical variables are defined, and the corresponding European Norm/International Organization for Standardization (EN/ISO) 13606 archetypes are created. Data sources are then identified, and an extract, transform, and load process is carried out. Once the final data set is obtained, the data are transformed to create EN/ISO 13606-normalized electronic health record (EHR) extracts. Afterward, ontologies that represent archetyped concepts and map them to EN/ISO 13606 and Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) standards are created and uploaded to OntoCR. Data stored in the extracts are inserted into its corresponding place in the ontology, thus obtaining instantiated patient data in the ontology-based repository. Finally, data can be extracted via SPARQL queries as OMOP CDM-compliant tables. Results: Using this methodology, EN/ISO 13606-standardized archetypes that allow for the reuse of clinical information were created, and the knowledge representation of our clinical repository by modeling and mapping ontologies was extended. Furthermore, EN/ISO 13606-compliant EHR extracts of patients (6803), episodes (13,938), diagnosis (190,878), administered medication (222,225), cumulative drug dose (222,225), prescribed medication (351,247), movements between units (47,817), clinical observations (6,736,745), laboratory observations (3,392,873), limitation of life-sustaining treatment (1,298), and procedures (19,861) were created. Since the creation of the application that inserts data from extracts into the ontologies is not yet finished, the queries were tested and the methodology was validated by importing data from a random subset of patients into the ontologies using a locally developed Protégé plugin ("OntoLoad"). In total, 10 OMOP CDM-compliant tables ("Condition_occurrence," 864 records; "Death," 110; "Device_exposure," 56; "Drug_exposure," 5609; "Measurement," 2091; "Observation," 195; "Observation_period," 897; "Person," 922; "Visit_detail," 772; and "Visit_occurrence," 971) were successfully created and populated. Conclusions: This study proposes a methodology for standardizing clinical data, thus allowing its reuse without any changes in the meaning of the modeled concepts. Although this paper focuses on health research, our methodology suggests that the data be initially standardized per EN/ISO 13606 to obtain EHR extracts with a high level of granularity that can be used for any purpose. Ontologies constitute a valuable approach for knowledge representation and standardization of health information in a standard-agnostic manner. With the proposed methodology, institutions can go from local raw data to standardized, semantically interoperable EN/ISO 13606 and OMOP repositories.Publication MODULEN: modelo predictivo en procesos de fragilización basado en actividades cotidianas(Sociedad Española de Informática de la Salud, 2020-03-03) Sánchez-de-Madariaga, Ricardo; Pascual-Carrasco, Mario; López Rodríguez, Fernando; Casado-Ramirez, Elvira; Texeira-Santos, L; Bonmatí-Carrión, María-Ángeles; Muñoz Carrero, Adolfo; Moreno-Casbas, Teresa; RETICS-Servicios de Salud Orientados a Enfermedades Crónicas (REDISSEC-ISCIII) (España); Fundación General (CSIC); Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERFES (Fragilidad y Envejecimiento Saludable); RETICS-Servicios de Salud Orientados a Enfermedades Crónicas (REDISSEC-ISCIII) (España); Red de Investigación Cooperativa en Investigación en Sida (España); Ministerio de Ciencia, Innovación y Universidades (España); Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de MurciaLa expectativa de vida libre de discapacidad (HLY) está condicionada principalmente por el deterioro en el desempeño de actividades de la vida diaria (AVD), y se asocia con la fragilidad. Incrementar HLY requiere implementar estrategias innovadoras de gestión de la fragilidad preventivas, objetivas y proactivas [1] que deben afrontar diversos retos. El objetivo del proyecto es el desarrollo de un modelo predictivo para la detección precoz de procesos de fragilización a partir de la monitorización y análisis a través de algoritmos de aprendizaje máquina (ML), de parámetros relacionados con las actividades cotidianas en entornos de vida habitual.Publication EDUCA: App para el soporte de planes formativos personalizados en receptores de transplante pulmonar(Sociedad Española de Informática de la Salud, 2020-03-03) Burgos Llamo, Alfredo; Pérez de la Cámara, Santiago; Pascual-Carrasco, Mario; López Rodríguez, Fernando; Muñoz Carrero, Adolfo; Sanabrias Fernández de Sevlla, Raquel; Calvo Salvador, M; Ussetti Gil, Piedad; RETICS-Servicios de Salud Orientados a Enfermedades Crónicas (REDISSEC-ISCIII) (España); Instituto de Salud Carlos IIILa mejora de la función respiratoria y calidad de vida del paciente receptor de trasplante pulmonar se acompaña de la necesidad de asumir indefinidamente un tratamiento complejo con efectos adversos, y seguir estrictas normas de control de la función pulmonar y nuevos hábitos higiénico-dietéticos. El objetivo de este trabajo es: (1) presentar la app EDUCA que se ha implementado para dar soporte a un programa educativo multimedia, multidisciplinar y personalizado para el empoderamiento del paciente trasplantado pulmonar; y (2) presentar la metodología de evaluación de la eficacia de este programa educativo suministrado a través de la app EDUCA, respecto a la vía habitual de provisión de actuaciones formativas (presencial en el hospital).Publication CAREVID+: Plataforma web para la evaluación de la implantación de buenas prácticas en cuidados(Sociedad Española de Informática de la Salud, 2020) Burgos Llamo, Alfredo; Pérez de la Cámara, Santiago; Pascual-Carrasco, Mario; López Rodríguez, Fernando; Muñoz Carrero, Adolfo; Albornos-Muñoz, Laura; González María, Esther; Moreno-Casbas, Teresa; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERFES (Fragilidad y Envejecimiento Saludable); RETICS-Servicios de Salud Orientados a Enfermedades Crónicas (REDISSEC-ISCIII) (España)El objetivo de este trabajo es presentar la plataforma web CAREVID+, como una herramienta para el soporte de: (1) la implantación de guías de e buenas prácticas (BBPP) en aquellas entidades sanitarias adheridas al Programa de Implantación de Guías de Buenas Prácticas en Centros Comprometidos con la Excelencia en Cuidados (CCEC®); y (2) la evaluación continuada del proceso de implantación de las guías de BBPP, a través del análisis de una serie de indicadores definidos en cada guía.Publication Effects of 700 and 3500 MHz 5G radiofrequency exposure on developing zebrafish embryos [Dataset](Instituto de Salud Carlos III (ISCIII), 2023-05) Torres-Ruiz, Mónica; Suarez, Oscar J; López-Alonso, Victoria; Marina-Boillos, Pablo; Sanchis Otero, Aranzazu; Liste-Noya, Isabel; De Alba-González, Mercedes; Ramos-Gonzalez, Maria Victoria; Instituto de Salud Carlos IIIEn este estudio, hemos utilizado una configuración disponible comercialmente validada que produce un campo uniforme para exponer embriones de pez cebra (ZFe) a frecuencias no moduladas de 700 y 3500 MHz. Hemos combinado una batería de ensayos de toxicidad, desarrollo y comportamiento para explorar más a fondo los posibles efectos de las radiaciones de radiofrecuencia (RFR). Nuestros perfiles neuroconductuales incluyen un ensayo de enrollamiento de la cola, un ensayo de actividad de luz/oscuridad, dos ensayos de ansiedad de tigmotaxis (estímulos auditivos y visuales) y una respuesta de sobresalto: ensayo de habituación en respuesta a estímulos auditivos. Se expusieron ZFe durante 1 y 4 h durante el período de desarrollo de la blástula y se evaluaron los puntos finales hasta 120 horas después de la fertilización (hpf). Nuestros resultados no muestran efectos sobre la mortalidad, la eclosión o la longitud corporal. Sin embargo, hemos demostrado efectos morfológicos de órganos específicos y efectos conductuales en la actividad, el comportamiento similar a la ansiedad y la habituación que perduraron en las larvas expuestas durante el período embrionario temprano. También se observó una disminución de la actividad de la acetilcolinesterasa, lo que podría explicar algunas de las alteraciones conductuales observadas. Curiosamente, los efectos fueron más pronunciados en ZFe expuesto a la frecuencia de 700 MHz, y especialmente durante el período de exposición de 4 h. Además, hemos demostrado que nuestra configuración de exposición es robusta, flexible con respecto a las pruebas de frecuencia y potencia, y altamente comparable. El trabajo futuro incluirá la exposición de ZFe a señales moduladas de 5G durante diferentes períodos de tiempo para comprender mejor los posibles efectos en la salud de la nueva RFR de 5G.Publication HAZLO: Plataforma de telesalud basada en tecnologías mhealth para el despliegue de programas personalizados de rehabilitación cardiaca fase II(Sociedad Española de Ingeniería Biomédica, 2015-11-04) Pérez de la Cámara, Santiago; Carmona, Montserrat; Tena-Davila, Maria José de; López Rodríguez, Fernando; Pozo Peralta, Alejandro; García Pacheco, José Luis; Velasco, Elisa; Portabales, Laura; Garcia-Sagredo, Pilar; Muñoz Carrero, Adolfo; de Pablo Zarzosa, Carmen; Pascual-Carrasco, Mario; Instituto de Salud Carlos IIIActualmente, los Programas de Rehabilitación Cardiaca, tanto en provisión presencial como domiciliaria, afrontan la necesidad de incrementar sus tasas de adopción y adherencia, y en estos retos, los servicios de telesalud basados en mhealth comienzan a jugar un papel relevante, aunque la evidencia es fragmentada y de baja calidad. Se ha implementado un servicio de telesalud que despliega un programa basado en actividades terapéuticas de rehabilitación física (marcha) y psicológica (relajación), contenidos educativos para la autogestión, y herramientas para la interacción virtual (mensajería, videollamada y foros). Se presenta en este trabajo la descripción del servicio y los resultados del pilotaje (41 pacientes, 5 meses), para evaluar la viabilidad en términos de operatividad-funcionalidad en cada uno de sus componentes y adherencia a los protocolos por parte de los pacientes. Se ha iniciado un ensayo aleatorizado controlado (128+128 pacientes) para estudiar la no inferioridad en resultados clínicos del modelo de provisión basado en telesalud frente al tradicional; adicionalmente, se estudiarán la mejora en calidad de vida, satisfacción y usabilidad.Publication Co-creation Initiatives in Healthcare in Small Communities(Galvin Publishers, 2022-08) Ramos-Gonzalez, Maria Victoria; San Pedro-Botas, Iris de; Casado-Ramirez, Elvira; Tena-Davila, Maria José de; Burgos Llamo, Alfredo; Pérez de la Cámara, Santiago; Marina-Boillos, Pablo; Pascual-Carrasco, Mario; Dochao, Andres; Caeiro, Anabela; D’Amico, Roberto; Duta, Greghory; Santacruz, Esmeralda; Hernández, Coral; Alcoceda, Jose Antonio; Unión Europea. Comisión Europea. H2020The uses of technology in public spaces are not new, but now we find new forms of social interactions and practices, socio-spatial representations and relationships. The close relationship between real and virtual worlds also opens up new ways of advancing knowledge. In order to facilitate the implementation of Open Science, we explore different co-creation methods with multiple stakeholders. All groups are involved and have influence throughout the project lifecycle: from the beginning, to planning, to implementation, to dissemination. Research activities should involve a wide variety of stakeholders interested, including government, educators, nurses, charities, civil societies, patient groups and the publics, based in a way to (1) obtaining contributions by customers, (2) selecting the best of these contributions, and (3) incorporating these selected contributions into products, processes, or services. Interactions between Information and Communication Technologies (ICT), public spaces, and healthcare are considered as s a tool for connecting people in small communities (enhancing participation). A Platform (DXP - Digital eXperience Platform) through “headless” technologies may provide content management capabilities and easy integration with devices and various sources, driven by user needs and developed with the concept of “Community in mind” in order to create strong and active communities and transform our small communities into more human environments, rather than just more high-tech places, and to understand that “smartness” should be people-friendly. It was applies the Responsible Research and Innovation (RRI) principles on the scientific process and governance, identify drivers and barriers, interests and values for current and future societal challenges.Publication A substrate-induced gating mechanism is conserved among Gram-positive IgA1 metalloproteases(Nature Publishing Group, 2022-11-07) Redzic, Jasmina S; Rahkola, Jeremy; Tran, Norman; Holyoak, Todd; Lee, Eunjeong; Martin-Galiano, Antonio Javier; Meyer, Nancy; Zheng, Hongjin; Eisenmesser, Elan; National Institutes of Health (Estados Unidos)The mucosal adaptive immune response is dependent on the production of IgA antibodies and particularly IgA1, yet opportunistic bacteria have evolved mechanisms to specifically block this response by producing IgA1 proteases (IgA1Ps). Our lab was the first to describe the structures of a metal-dependent IgA1P (metallo-IgA1P) produced from Gram-positive Streptococcus pneumoniae both in the absence and presence of its IgA1 substrate through cryo-EM single particle reconstructions. This prior study revealed an active-site gating mechanism reliant on substrate-induced conformational changes to the enzyme that begged the question of whether such a mechanism is conserved among the wider Gram-positive metallo-IgA1P subfamily of virulence factors. Here, we used cryo-EM to characterize the metallo-IgA1P of a more distantly related family member from Gemella haemolysans, an emerging opportunistic pathogen implicated in meningitis, endocarditis, and more recently bacteremia in the elderly. While the substrate-free structures of these two metallo-IgA1Ps exhibit differences in the relative starting positions of the domain responsible for gating substrate, the enzymes have similar domain orientations when bound to IgA1. Together with biochemical studies that indicate these metallo-IgA1Ps have similar binding affinities and activities, these data indicate that metallo-IgA1P binding requires the specific IgA1 substrate to open the enzymes for access to their active site and thus, largely conform to an "induced fit" model.Publication Discovering HIV related information by means of association rules and machine learning(Nature Publishing Group, 2022-10-28) Araujo, Lourdes; Martinez-Romo, Juan; Bisbal, Otilia; Sánchez-de-Madariaga, Ricardo; Cohort of the Spanish HIV/AIDS Research Network (CoRIS); Ministerio de Ciencia e Innovación (España); Instituto de Salud Carlos III; Red de Investigación Cooperativa en Investigación en Sida (España); Plan Nacional de I+D+i (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts.Publication TransformEHRs: a flexible methodology for building transparent ETL processes for EHR reuse(Thieme Medical Publishers, 2022-12) Pedrera-Jiménez, Miguel; García-Barrio, Noelia; Rubio-Mayo, Paula; Tato-Gómez, Alberto; Cruz-Bermúdez, Juan Luis; Bernal-Sobrino, José Luis; Muñoz Carrero, Adolfo; Serrano-Balazote, Pablo; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos IIIBackground: During the COVID-19 pandemic, several methodologies were designed for obtaining electronic health record (EHR)-derived datasets for research. These processes are often based on black boxes, on which clinical researchers are unaware of how the data were recorded, extracted, and transformed. In order to solve this, it is essential that extract, transform, and load (ETL) processes are based on transparent, homogeneous, and formal methodologies, making them understandable, reproducible, and auditable. Objectives: This study aims to design and implement a methodology, according with FAIR Principles, for building ETL processes (focused on data extraction, selection, and transformation) for EHR reuse in a transparent and flexible manner, applicable to any clinical condition and health care organization. Methods: The proposed methodology comprises four stages: (1) analysis of secondary use models and identification of data operations, based on internationally used clinical repositories, case report forms, and aggregated datasets; (2) modeling and formalization of data operations, through the paradigm of the Detailed Clinical Models; (3) agnostic development of data operations, selecting SQL and R as programming languages; and (4) automation of the ETL instantiation, building a formal configuration file with XML. Results: First, four international projects were analyzed to identify 17 operations, necessary to obtain datasets according to the specifications of these projects from the EHR. With this, each of the data operations was formalized, using the ISO 13606 reference model, specifying the valid data types as arguments, inputs and outputs, and their cardinality. Then, an agnostic catalog of data was developed through data-oriented programming languages previously selected. Finally, an automated ETL instantiation process was built from an ETL configuration file formally defined. Conclusions: This study has provided a transparent and flexible solution to the difficulty of making the processes for obtaining EHR-derived data for secondary use understandable, auditable, and reproducible. Moreover, the abstraction carried out in this study means that any previous EHR reuse methodology can incorporate these results into them.Publication Lung Adenocarcinoma Cell Sensitivity to Chemotherapies: A Spotlight on Lipid Droplets and SREBF1 Gene(Multidisciplinary Digital Publishing Institute (MDPI), 2022-09-14) Gründing, Anna Ricarda; Schneider, Marc A; Richtmann, Sarah; Kriegsmann, Mark; Winter, Hauke; Martinez-Delgado, Beatriz; Varona Fernandez, Sarai; Liu, Bin; DeLuca, David S; Held, Julia; Wrenger, Sabine; Muley, Thomas; Meister, Michael; Welte, Tobias; Janciauskiene, Sabina; German Center for Lung Research (Alemania)To explore the relationship between cancer cell SREBF1 expression, lipid droplets (LDs) formation, and the sensitivity to chemotherapies, we cultured lung adenocarcinoma cells H1299 (with LD) and H1563 (without LD) in a serum-free basal medium (BM) or neutrophil degranulation products containing medium (NDM), and tested cell responses to cisplatin and etoposide. By using the DESeq2 Bioconductor package, we detected 674 differentially expressed genes (DEGs) associated with NDM/BM differences between two cell lines, many of these genes were associated with the regulation of sterol and cholesterol biosynthesis processes. Specifically, SREBF1 markedly declined in both cell lines cultured in NDM or when treated with chemotherapeutics. Despite the latter, H1563 exhibited LD formation and resistance to etoposide, but not to cisplatin. Although H1299 cells preserved LDs, these cells were similarly sensitive to both drugs. In a cohort of 292 patients with non-small-cell lung cancer, a lower SREBF1 expression in tumors than in adjacent nontumor tissue correlated with overall better survival, specifically in patients with adenocarcinoma at stage I. Our findings imply that a direct correlation between SREBF1 and LD accumulation can be lost due to the changes in cancer cell environment and/or chemotherapy. The role of LDs in lung cancer development and response to therapies remains to be examined in more detail.


