Evidence of the association between increased use of direct oral anticoagulants and a reduction in the rate of atrial fibrillation-related stroke and major bleeding at the population level (2012–2019) / Evidencia a nivel poblacional de la asociación entre el aumento del uso de anticoagulantes orales directos y una reducción de la incidencia de ictus y hemorragias mayores relacionados con fibrilación auricular (2012-2019)

Background: The introduction of direct-acting oral anticoagulants (DOACs) has shown to decrease atrial fibrillation (AF)-related stroke and bleeding rates in clinical studies, but there is no certain evidence about their effects at the population level. Our aim was to assess changes in AF-related stroke and major bleeding rates between 2012 and 2019 in Andalusia (Spain), and the association between DOACs use and events rates at the population level. Methods: All patients with an AF diagnosis from 2012 to 2019 were identified using the Andalusian Health Population Base, that provides clinical information on all Andalusian people. Annual ischemic and hemorrhagic stroke, major bleeding rates, and used antithrombotic treatments were determined. Marginal hazard ratios (HR) were calculated for each treatment. Results: A total of 95,085 patients with an AF diagnosis were identified. Mean age was 76.1±10.2 years (49.7% women). An increase in the use of DOACs was observed throughout the study period in both males and females (p<0.001). The annual rate of ischemic stroke decreased by one third, while that of hemorrhagic stroke and major bleeding decreased 2–3-fold from 2012 to 2019. Marginal HR was lower than 0.50 for DOACs compared to VKA for all ischemic or hemorrhagic events. Conclusions: In this contemporary population-based study using clinical and administrative databases in Andalusia, a significant reduction in the incidence of AF-related ischemic and hemorrhagic stroke and major bleeding was observed between 2012 and 2019. The increased use of DOACs seems to be associated with this reduction.(AU)

Introducción: La introducción de los anticoagulantes orales de acción directa (ACOD) ha demostrado disminuir las tasas de accidentes cerebrovasculares y hemorragias relacionados con fibrilación auricular (FA) en estudios clínicos, pero no hay tanta evidencia sobre sus efectos a nivel poblacional. Nuestro objetivo fue evaluar los cambios en la incidencia de ictus y hemorragias mayores relacionados con FA entre 2012 y 2019 en Andalucía (España), y estudiar la asociación entre el uso de ACOD y estos eventos a nivel poblacional. Métodos: Se incluyeron pacientes con diagnóstico de FA entre los años 2012 y 2019 en la Base de Población Sanitaria de Andalucía, que proporciona información clínica de todos los andaluces. Se determinaron los accidentes cerebrovasculares isquémicos y hemorrágicos anuales, las tasas de sangrado mayor y los tratamientos antitrombóticos utilizados. Se estimaron los hazard ratio para cada tratamiento. Resultados: Se identificaron un total de 95.085 pacientes con diagnóstico de FA. La edad media fue de 76,1±10,2 años (49,7% mujeres). Se observó un aumento en el uso de ACOD a lo largo del período de estudio, tanto en varones como en mujeres (p<0,001). La tasa anual de ictus isquémico disminuyó en un tercio, mientras que la de ictus hemorrágico y hemorragia mayor se redujo de 2 a 3 veces entre 2012 y 2019. Los hazard ratio fueron inferiores a 0,50 para los ACOD en comparación con los antivitamina K para todos los eventos isquémicos o hemorrágicos. Conclusiones: En este estudio poblacional contemporáneo, se observó, utilizando bases de datos clínicas y administrativas de Andalucía, una reducción significativa en la incidencia de ictus isquémico y hemorrágico, y hemorragia mayor relacionados con FA entre los años 2012 y 2019. El mayor uso de ACOD parece estar asociado con esta reducción.(AU)

Evidence of the association between increased use of direct oral anticoagulants and a reduction in the rate of atrial fibrillation-related stroke and major bleeding at the population level (2012-2019).

BACKGROUND: The introduction of direct-acting oral anticoagulants (DOACs) has shown to decrease atrial fibrillation (AF)-related stroke and bleeding rates in clinical studies, but there is no certain evidence about their effects at the population level. Our aim was to assess changes in AF-related stroke and major bleeding rates between 2012 and 2019 in Andalusia (Spain), and the association between DOACs use and events rates at the population level. METHODS: All patients with an AF diagnosis from 2012 to 2019 were identified using the Andalusian Health Population Base, that provides clinical information on all Andalusian people. Annual ischemic and hemorrhagic stroke, major bleeding rates, and used antithrombotic treatments were determined. Marginal hazard ratios (HR) were calculated for each treatment. RESULTS: A total of 95,085 patients with an AF diagnosis were identified. Mean age was 76.1±10.2 years (49.7% women). An increase in the use of DOACs was observed throughout the study period in both males and females (p<0.001). The annual rate of ischemic stroke decreased by one third, while that of hemorrhagic stroke and major bleeding decreased 2-3-fold from 2012 to 2019. Marginal HR was lower than 0.50 for DOACs compared to VKA for all ischemic or hemorrhagic events. CONCLUSIONS: In this contemporary population-based study using clinical and administrative databases in Andalusia, a significant reduction in the incidence of AF-related ischemic and hemorrhagic stroke and major bleeding was observed between 2012 and 2019. The increased use of DOACs seems to be associated with this reduction.

Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments.

PURPOSE: Despite the extensive vaccination campaigns in many countries, COVID-19 is still a major worldwide health problem because of its associated morbidity and mortality. Therefore, finding efficient treatments as fast as possible is a pressing need. Drug repurposing constitutes a convenient alternative when the need for new drugs in an unexpected medical scenario is urgent, as is the case with COVID-19. METHODS: Using data from a central registry of electronic health records (the Andalusian Population Health Database), the effect of prior consumption of drugs for other indications previous to the hospitalization with respect to patient outcomes, including survival and lymphocyte progression, was studied on a retrospective cohort of 15,968 individuals, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. RESULTS: Covariate-adjusted hazard ratios and analysis of lymphocyte progression curves support a significant association between consumption of 21 different drugs and better patient survival. Contrarily, one drug, furosemide, displayed a significant increase in patient mortality. CONCLUSIONS: In this study we have taken advantage of the availability of a regional clinical database to study the effect of drugs, which patients were taking for other indications, on their survival. The large size of the database allowed us to control covariates effectively.

Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival.

OBJECTIVES: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. METHODS: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. RESULTS: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. CONCLUSIONS: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.

Multimorbidity Profiles and Infection Severity in COVID-19 Population Using Network Analysis in the Andalusian Health Population Database.

Identifying the population at risk of COVID-19 infection severity is a priority for clinicians and health systems. Most studies to date have only focused on the effect of specific disorders on infection severity, without considering that patients usually present multiple chronic diseases and that these conditions tend to group together in the form of multimorbidity patterns. In this large-scale epidemiological study, including primary and hospital care information of 166,242 patients with confirmed COVID-19 infection from the Spanish region of Andalusia, we applied network analysis to identify multimorbidity profiles and analyze their impact on the risk of hospitalization and mortality. Our results showed that multimorbidity was a risk factor for COVID-19 severity and that this risk increased with the morbidity burden. Individuals with advanced cardio-metabolic profiles frequently presented the highest infection severity risk in both sexes. The pattern with the highest severity associated in men was present in almost 28.7% of those aged ≥ 80 years and included associations between cardiovascular, respiratory, and metabolic diseases; age-adjusted odds ratio (OR) 95% confidence interval (1.71 (1.44-2.02)). In women, similar patterns were also associated the most with infection severity, in 7% of 65-79-year-olds (1.44 (1.34-1.54)) and in 29% of ≥80-year-olds (1.35 (1.18-1.53)). Patients with mental health patterns also showed one of the highest risks of COVID-19 severity, especially in women. These findings strongly recommend the implementation of personalized approaches to patients with multimorbidity and SARS-CoV-2 infection, especially in the population with high morbidity burden.

Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients.

COVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15-30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan-Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50-0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61-0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57-0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.

La evaluación de impacto en protección de datos en los proyectos de investigación / Impact assessment on data protection in research projects

Los recientes cambios en la normativa europea de protección de datos de carácter personal siguen permitiendo el uso de los datos sanitarios con fines de investigación, pero establecen la evaluación de impacto en protección de datos como instrumento de reflexión y análisis de riesgos en el proceso de tratamiento de datos. La publicación de una guía facilita la realización de esta evaluación de impacto, aunque no es de aplicación directa para los proyectos de investigación. Se detalla la experiencia en un proyecto concreto, y se muestra cómo el contexto del tratamiento toma relevancia respecto a las características de los datos. La realización de una evaluación de impacto es una oportunidad para asegurar el cumplimiento de los principios de la protección de datos en un entorno cada vez más complejo y con mayores desafíos éticos

Recent changes in European regulations for personal data protection still allow the use of health data for research purposes, but they have set the Impact Assessment on Data Protection as an instrument for reflection and risk analysis in the process of data processing. The publication of a guide for facilitates this impact assessment, although it is not directly applicable to research projects. Experience in a specific project is detailed, showing how the context of the treatment becomes relevant with respect to the data characteristics. Carrying out an impact assessment is an opportunity to ensure compliance with the principles of data protection in an increasingly complex environment with greater ethical challenges

Conexión de registros sanitarios: base poblacional de salud de Andalucía / Health record linkage: Andalusian health population database

OBJETIVO: Describir el desarrollo de un sistema de información que conecta datos procedentes de múltiples registros, sanitarios y otros, para su uso con fines asistenciales, de administración, gestión, evaluación, inspección, investigación y salud pública. MÉTODO: Conexión determinística de datos pseudonimizados de una población de 8,5 millones de habitantes, procedentes de Base de datos de usuarios, Historia clínica electrónica DIRAYA, Conjunto mínimo básico de datos (hospitalización, cirugía mayor ambulatoria, urgencias hospitalarias y hospital de día médico) y sistemas de información de salud mental, pruebas de imagen, pruebas analíticas, vacunas, pacientes renales y farmacia. Se utilizó un codificador automático para los diagnósticos clínicos y se definieron 80 enfermedades crónicas para su seguimiento. La arquitectura del sistema de información constó de tres capas: datos (base de datos Oracle 11g), aplicaciones (MicroStrategy BI) y presentación (MicroStrategy Web, librerías JavaScript, HTML 5 y hojas de estilo CSS). Se implantaron medidas para la gobernanza del sistema. RESULTADOS: Se incluyeron datos de 12,5 millones de personas que fueron usuarias entre los años 2001 y 2017, con 435,5 millones de diagnósticos. El 88,7% de estos diagnósticos fueron generados por el codificador automático. Los datos se presentan mediante informes predefinidos o consultas dinámicas, ambos exportables a ficheros CSV para su tratamiento fuera del sistema. Analistas expertos pueden acceder directamente a las bases de datos y realizar extracciones mediante SQL o tratar directamente los datos con herramientas externas. CONCLUSIÓN: El trabajo ha mostrado cómo la conexión de registros sanitarios abre nuevas posibilidades en el análisis de datos

OBJECTIVE: To describe the development of an information system that connects data from multiple health records to improve assistance to patients, health services administration, management, evaluation, and inspection, as well as public health and research. METHOD: Deterministic connection of pseudonymized data from a population of 8.5 million inhabitants provided by: a users database, DIRAYA electronic medical records, minimum basic data sets (inpatients, outpatient mayor surgery, hospital emergencies and medical day hospital), mental health information systems, analytical and image tests, vaccines, renal patients, and pharmacy. An automatic coder was used to code clinical diagnoses and 80 chronic pathologies were identified to follow-up. The architecture of the information system consisted of three layers: data (Oracle Database 11g), applications (MicroStrategy BI) and presentation (MicroStrategy Web, JavaScript libraries, HTML 5 and CSS style sheets). Measures for the governance of the system were implemented. RESULTS: Data from 12.5 million health system users between 2001 and 2017 were gathered, including 435.5 million diagnoses, 88.7% of which were generated by the automatic coder. Data can be accessed through predefined reports or dynamic queries, both exportable to CSV files for processing outside the system. Expert analysts can directly access the databases and perform queries using SQL or directly treat the data with external tools. CONCLUSION: The work has shown that the connection of health records opens new possibilities for data analysis

[Impact assessment on data protection in research projects]. / La evaluación de impacto en protección de datos en los proyectos de investigación.

Recent changes in European regulations for personal data protection still allow the use of health data for research purposes, but they have set the Impact Assessment on Data Protection as an instrument for reflection and risk analysis in the process of data processing. The publication of a guide for facilitates this impact assessment, although it is not directly applicable to research projects. Experience in a specific project is detailed, showing how the context of the treatment becomes relevant with respect to the data characteristics. Carrying out an impact assessment is an opportunity to ensure compliance with the principles of data protection in an increasingly complex environment with greater ethical challenges.

[Health record linkage: Andalusian health population database]. / Conexión de registros sanitarios: base poblacional de salud de Andalucía.

OBJECTIVE: To describe the development of an information system that connects data from multiple health records to improve assistance to patients, health services administration, management, evaluation, and inspection, as well as public health and research. METHOD: Deterministic connection of pseudonymized data from a population of 8.5 million inhabitants provided by: a users database, DIRAYA electronic medical records, minimum basic data sets (inpatients, outpatient mayor surgery, hospital emergencies and medical day hospital), mental health information systems, analytical and image tests, vaccines, renal patients, and pharmacy. An automatic coder was used to code clinical diagnoses and 80 chronic pathologies were identified to follow-up. The architecture of the information system consisted of three layers: data (Oracle Database 11g), applications (MicroStrategy BI) and presentation (MicroStrategy Web, JavaScript libraries, HTML 5 and CSS style sheets). Measures for the governance of the system were implemented. RESULTS: Data from 12.5 million health system users between 2001 and 2017 were gathered, including 435.5 million diagnoses, 88.7% of which were generated by the automatic coder. Data can be accessed through predefined reports or dynamic queries, both exportable to CSV files for processing outside the system. Expert analysts can directly access the databases and perform queries using SQL or directly treat the data with external tools. CONCLUSION: The work has shown that the connection of health records opens new possibilities for data analysis.