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.

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.

Impact of COVID-19 on the Health of the General and More Vulnerable Population and Its Determinants: Health Care and Social Survey-ESSOC, Study Protocol.

This manuscript describes the rationale and protocol of a real-world data (RWD) study entitled Health Care and Social Survey (ESSOC, Encuesta Sanitaria y Social). The study's objective is to determine the magnitude, characteristics, and evolution of the COVID-19 impact on overall health as well as the socioeconomic, psychosocial, behavioural, occupational, environmental, and clinical determinants of both the general and more vulnerable population. The study integrates observational data collected through a survey using a probabilistic, overlapping panel design, and data from clinical, epidemiological, demographic, and environmental registries. The data will be analysed using advanced statistical, sampling, and machine learning techniques. The study is based on several measurements obtained from three random samples of the Andalusian (Spain) population: general population aged 16 years and over, residents in disadvantaged areas, and people over the age of 55. Given the current characteristics of this pandemic and its future repercussions, this project will generate relevant information on a regular basis, commencing from the beginning of the State of Alarm. It will also establish institutional alliances of great social value, explore and apply powerful and novel methodologies, and produce large, integrated, high-quality and open-access databases. The information described here will be vital for health systems in order to design tailor-made interventions aimed at improving the health care, health, and quality of life of the populations most affected by the COVID-19 pandemic.

A Clinical Decision Support System (KNOWBED) to Integrate Scientific Knowledge at the Bedside: Development and Evaluation Study.

BACKGROUND: The evidence-based medicine (EBM) paradigm requires the development of health care professionals' skills in the efficient search of evidence in the literature, and in the application of formal rules to evaluate this evidence. Incorporating this methodology into the decision-making routine of clinical practice will improve the patients' health care, increase patient safety, and optimize resources use. OBJECTIVE: The aim of this study is to develop and evaluate a new tool (KNOWBED system) as a clinical decision support system to support scientific knowledge, enabling health care professionals to quickly carry out decision-making processes based on EBM during their routine clinical practice. METHODS: Two components integrate the KNOWBED system: a web-based knowledge station and a mobile app. A use case (bronchiolitis pathology) was selected to validate the KNOWBED system in the context of the Paediatrics Unit of the Virgen Macarena University Hospital (Seville, Spain). The validation was covered in a 3-month pilot using 2 indicators: usability and efficacy. RESULTS: The KNOWBED system has been designed, developed, and validated to support clinical decision making in mobility based on standards that have been incorporated into the routine clinical practice of health care professionals. Using this tool, health care professionals can consult existing scientific knowledge at the bedside, and access recommendations of clinical protocols established based on EBM. During the pilot project, 15 health care professionals participated and accessed the system for a total of 59 times. CONCLUSIONS: The KNOWBED system is a useful and innovative tool for health care professionals. The usability surveys filled in by the system users highlight that it is easy to access the knowledge base. This paper also sets out some improvements to be made in the future.

Ecografía 4D para el diagnóstico de malformaciones congénitas / Analysis of the relationship between maternal anxiety and pregnancy

Objetivo. Evaluar el nivel de ansiedad materna en el tercer trimestre del embarazo según el riesgo gestacional: bajo riesgo, riesgo intermedio y alto/muy alto riesgo. Pacientes y métodos. Estudio observacional, analítico y transversal que evalúa el nivel de ansiedad en 174 gestantes controladas en nuestro hospital. Se valoran tanto los niveles de ansiedad estado, como los de ansiedad rasgo en los tres grupos de gestantes. Resultados. De las 174 participantes en el estudio 98 (56,3%) presentaban embarazos de bajo riesgo, 40 (23%) gestantes de riesgo medio y 36 (20,7%) mujeres presentaban riesgo gestacional alto o muy alto. Se obtuvo una media de 32,8 puntos para la ansiedad estado y de 27,3 para la variable ansiedad rasgo. La media de ansiedad de las gestantes de alto/muy alto riesgo se situó en 44,1 puntos, en las de riesgo medio en 33 puntos y en las de bajo riesgo en 28,5 puntos; estas diferencias fueron estadísticamente significativas (p=0,0001 para las de alto riesgo y p=0,038 para las de riesgo intermedio). Se encontró una correlación estadísticamente significativa entre la ansiedad rasgo y la ansiedad estado (p=0,00001). Se encontraron diferencias estadísticamente significativas en la variable ansiedad relacionada con el número de hijos (p=0,0001). Conclusiones. La ansiedad en las gestantes estudiadas se sitúa por encima de la media poblacional. Los valores de ansiedad aumentan conforme lo hace el riesgo gestacional. El nivel de ansiedad disminuye conforme aumenta la paridad de la gestante (AU)

Objective. To evaluate levels of maternal anxiety in third trimester pregnancies according to pregnancy risk, classified as low, medium and high-risk/very high-risk. Patients and methods. We performed an observational, analytical and cross-sectional study of anxiety levels in 174 pregnant women followed-up in our hospital. Levels of both state anxiety and trait anxiety were evaluated in the three groups of pregnant women. Results. Of the 174 participants in the study, 98 (56.3%) had low risk pregnancies, 40 showed medium risk (23%) and 36 (20.7%) had high risk or very high risk pregnancies. We obtained a mean of 32.8 points for state anxiety and of 27.3 points for trait anxiety. Mean anxiety levels scores were 44.1 points in the high/very high risk group, 33 points in the medium risk group, and 28.5 points in the low risk group, with statistically significant differences (P=.0001 for the high risk group and P=.038 for the medium risk pregnancies). A significant correlation was found between trait anxiety and state anxiety (P=.0001). Statistically significant differences were observed in anxiety related to the number of children (P=.0001). Conclusions. In pregnant women, anxiety levels were higher than average levels in the general population. Anxiety levels increased in accordance with greater risk in the pregnancy. The greater the number of children the mother already had the lower her anxiety level (AU)

Systematic review of HER2 breast cancer testing.

HER2 status is of great clinical value in breast tumors for the identification of those patients who are eligible for trastuzumab therapy. There is a debate about the advantages and disadvantages of immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and where, when, how, and who would perform HER2 testing. The purpose of this study was to analyze clinical and analytic validity and clinical utility for HER2 testing (IHC and FISH) for the appropriate selection of breast cancer patients who were suitable for trastuzumab therapy. A systematic review of the literature was carried out using online databases (MedLine, Embase, Centre for Reviews and Dissemination and the Cochrane Library). It brings up to date the cost-effectiveness analysis published by Technology Assessment Unit of the McGill University Health Centre (MUHC). The articles that were selected according to the following inclusion criteria: (1) included breast cancer patients, (2) used IHC and FISH assays, (3) reported the sensibility, specificity, reliability of IHC and FISH, or concordance between both techniques, and (4) were published in any language. A critical appraisal was performed using an ad hoc scale based on CASPe (Critical Appraisal Skills Programme Spanish) criteria. Literature search generated 17 studies that satisfied the inclusion criteria. Most articles evaluated the HercepTest and PathVysion assays. FISH was considered the gold standard test. We calculated the FISH positivity rate in each IHC score category. The percentage of FISH positive results (median) was estimated as 3.5 for IHC0, 5.8 for IHC1+, 17 for IHC2+, and 83.5 for IHC3+. Our findings have shown high concordance rates between IHC and FISH in tumors IHC0 and IHC1+, and discordance rates among cases with IHC2+ and IHC3+. In these cases, FISH is considered gold standard for confirming or excluding HER2 amplification.

Células progenitoras en pacientes con cardiopatía / Stem cells treatment for patients with heart diseases

No disponible

Genotipado de pacientes psiquiátricos mediante micromatrices de oligonucleótidos / Genotyping of psychiatric patients through oligonucleotide microarrays

La farmacogenética ofrece un potencial enorme para proveer beneficios clínicos a los pacientes (medicina personalizada), así como beneficios económicos a los sistemas sanitarios. Teóricamente, las pruebas de genotipado deben identificar la mayoría de las variantes genéticas que desempeñen un papel importante en la expresión o función de las enzimas metabolizadoras y transportadoras, como de sus receptoras de fármacos. La superfamilia de enzimas del citcromo P450, cuyo papel es esencial en el metabolismo de los fármacos, representa uno de los ejemplos de variación farmacogenética mejor estudiados. De entre las variantes alélicas del citocromo P450, que identifican cuatro niveles de actividad enzimática o fenotipos diferentes (lentos, intermedios, normales o rápidos y ultrarrápidos), destacan las que definen los metabolizadores lentos, relacionados con una incidencia mayor de reacciones adversas medicamentosas y tratamientos más costosos que requieren largas hospitalizaciones. AmpliChip CYP450® se presenta como uno de los métodos más prácticos y eficientes para analizar un número elevado de variantes genéticas de los genes CYP2D6 y CYP2C19 e identificar los perfiles farmacogenéticos en pacientes psiquiátricos. Sin embargo, importantes cuestiones logísticas, éticas, jurídicas y económicas aun hoy deben ser resueltas antes de aplicarse a la práctica clínica diaria (AU)

Pharmacogenetics has enormous potential to benefit patients (personalized medicine) and reduce health costs. Theoretically, genotyping tests should identify most of genetic variants that play a major role in the expression or function of drug metabolizing enzymes, receptors, and transporters. The cytochrome P450 superfamily, which plays an essential role in drug metabolism, is one of the best studied examples of pharmacogenetic variation. Among the allele variations of cytochrome P450, four different levels of enzymatic activity or phenotypes can be distinguished: poor, intermediate, extensive and ultrarapid metabolizers. Notable are the poor metabolizers, since they may be associated with a higher incidence of adverse drug reactions and more expensive treatments requiring longer hospital stays. AmpliChip CYP450® seems to be one of the most efficient and complete tests to study multiple CYP2D6 and CYP2C19 alleles in a single assay, establishing pharmacogenetic profiling in psychiatric patients. However, there are important logistic, ethical, legal and economic issues that need to be resolved before this test can be applied in daily clinical practice (AU)

Evaluación de la implantación de una guía de incorporación de nuevos medicamentos en un hospital / Evaluation of a guide for the introduction of new drugs in a hospital

Objetivo: La incorporación de nuevos fármacos en los hospitales tiene una gran repercusión en el uso racional de medicamentos del Sistema Nacional de Salud, aunque existe un apreciable grado de variabilidad entre diferentes centros, lo que genera problemas de equidad y accesibilidad. Para dar respuesta a estos problemas, en Andalucía se elaboró la Guía de Incorporación de Nuevos Fármacos (GINF) que propone un procedimiento estructurado de toma de decisiones, fundamentado en la evaluación de la evidencia disponible. Material y métodos: Se evalúan todas las solicitudes recibidas en la Comisión de Farmacia y Terapéutica del Hospital Virgen del Rocío de Sevilla, con la metodología propuesta en la guía GINF, desde enero de 2002 a julio de 2003. Se realiza un estudio descriptivo sobre las características de los fármacos, los solicitantes, la actividad de la Comisión, indicadores de calidad de las solicitudes, el proceso seguido y las decisiones. Resultados: Se evaluó el total de las 32 solicitudes recibidas, correspondientes a 26 fármacos. Se aprobaron 19 (73 por ciento), aunque, de éstos, 14 lo fueron de forma restringida o con un protocolo específico de utilización, 4 como equivalentes terapéuticos y sólo 1 sin ninguna restricción. El 72 por ciento de los solicitantes aportó los ensayos clínicos pertinentes, mientras que las estimaciones sobre el número de pacientes/año y otros datos para la evaluación económica fueron mucho más escasas. Conclusiones: Es posible mejorar el proceso de introducción de fármacos en los hospitales mediante una guía que facilite a los profesionales y las comisiones de Farmacia criterios explícitos y transparentes (AU)