A novel data-driven model for prediction and adaptive control of pH in raceway reactor for microalgae cultivation.

This work proposes a new data-driven model to estimate and predict pH dynamics in freshwater raceway photobioreactors. The resulting model is based purely on data measured from the reactor and divides the pH dynamics into two different behaviors. One behavior is described by the variation of pH due to the photosynthesis phenomena made by microalgae; and the other comes from the effect of CO2 injections into the medium for control purposes. Moreover, it was observed that the model parameters vary throughout the day depending on the weather conditions and reactor status. Thus, a decision tree algorithm is also developed to capture the parameter variation based on measured variables of the system, such as solar radiation, medium temperature, and medium level. The proposed model has been validated for a data set of more than 100 days during 10 months in a semi-industrial raceway reactor, covering a wide range of weather and system scenarios. Additionally, the proposed model was used to design an adaptive control algorithm which was also experimentally tested and compared with a classical fixed parameter control approach.

Chromatin Immunoprecipitation to Investigate H2A.Z Dynamics in Response to Environmental Changes.

DNA methylation and posttranslational modifications of histones instruct gene expression in eukaryotes. Besides canonical histones, histone variants also play a critical role in transcriptional regulation. One of the best studied histone variants in plants is H2A.Z whose removal from gene bodies correlates with increased transcriptional activity. The eviction of H2A.Z is regulated by environmental cues such as increased ambient temperatures, and current models suggest that H2A.Z functions as a transcriptional buffer preventing environmentally responsive genes from undesired activation. To monitor temperature-dependent H2A.Z dynamics, chromatin immunoprecipitation (ChIP) of H2A.Z-occupied DNA can be performed. The following protocol describes a quick and easy ChIP approach to study in vivo H2A.Z occupancy.

What is going on inside of phytochrome B photobodies?

Plants exhibit an enormous phenotypic plasticity to adjust to changing environmental conditions. For this purpose, they have evolved mechanisms to detect and measure biotic and abiotic factors in their surroundings. Phytochrome B exhibits a dual function, since it serves as a photoreceptor for red and far-red light as well as a thermosensor. In 1999, it was first reported that phytochromes not only translocate into the nucleus, but also form subnuclear foci upon irradiation by red light. It took more than 10 years until these phytochrome speckles received their name: These foci were coined photobodies to describe unique phytochrome-containing subnuclear domains that are regulated by light. Since their initial discovery, there has been much speculation about the significance and function of photobodies. Their presumed roles range from pure experimental artifacts to waste deposits or signaling hubs. In this review, we summarize the newest findings about the meaning of phyB photobodies for light and temperature signaling. Recent studies have established that phyB photobodies are formed by liquid-liquid phase separation via multivalent interactions and that they provide diverse functions as biochemical hotspots to regulate gene expression on multiple levels.

Study of pH and Thermodynamic Parameters via Circular Dichroism Spectroscopy of a Recombinant Human Lactoferrin.

The production of human recombinant proteins to be used for therapeutic or nutritional purposes must focus on obtaining a molecule that is as close as possible to the native human protein. This biotechnological tool has been documented in various studies published in recent decades, with lactoferrin being one of those that has generated the most interest, being a promising option for recombinant technology. However, stability studies including thermodynamic parameters have not been reported for recombinant lactoferrin (Lf). The objective of this work was to obtain the human recombinant protein using the yeast Komagataella phaffii to study structural changes modifying pH and temperature using circular dichroism spectroscopy (CD). Thermodynamic parameters such as ΔH, ΔS and Tm were calculated and compared with commercial human lactoferrin. We propose the potential use of CD and thermodynamic parameters as a criterion in the production of recombinant proteins to be used in the production of specialized recombinant proteins.

Modifications of long-term heart rate variability produced in an experimental model of diet-induced metabolic syndrome.

Metabolic syndrome (MetS) has been linked to a higher prevalence of cardiac arrhythmias, the most frequent being atrial fibrillation, but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic nervous system activity, which can be quantified by analysing heart rate variability (HRV). Our aim was to investigate the modifications of long-term HRV in an experimental model of diet-induced MetS to identify the early changes in HRV and the link between autonomic dysregulation and MetS components. NZW rabbits were randomly assigned to control (n = 10) or MetS (n = 10) groups, fed 28 weeks with high-fat, high-sucrose diet. 24-hour recordings were used to analyse HRV at week 28 using time-domain, frequency-domain and nonlinear analyses. Time-domain analysis showed a decrease in RR interval and triangular index (Ti). In the frequency domain, we found a decrease in the low frequency band. Nonlinear analyses showed a decrease in DFA-α1 and DFA-α2 (detrended fluctuations analysis) and maximum multiscale entropy. The strongest association between HRV parameters and markers of MetS was found between Ti and mean arterial pressure, and Ti and left atrial diameter, which could point towards the initial changes induced by the autonomic imbalance in MetS.

Electrical performance enhancement of MHD microgenerators through the longitudinal shaping of the cross-section.

In the present work, the impact that the longitudinal shape of channels has on the current produced in the flow of a magneto-hydrodynamic microgenerator (MHDMG) is studied. The goal is to find the micro-channel geometry via modeling to maximize the current output for low Reynolds and Mach regimes. To carry out this study, a 3D dynamic numerical tool relying on the finite volume method was handled with the open-source software OpenFOAM. It is the base model to study the impact of intricate geometries on the ability to produce energy. An additional steady-state 2D analytical model was also developed to check some basic modeling assumptions. Both models have been experimentally validated on the simplest flow system having a constant square cross-section throughout. The results produced by both models cross-check very well and compare favorably with respect to experimental data. Hence, using the validated numerical tool, three shapes have been further investigated, namely, progressive (linear decrease of the cross-section), arc (parabolic decrease of the cross-section), and wavy (sinusoidal shape). It was found that the arc channel provides the greatest current output for the same volumetric flow. It is therefore the preferred choice for developing high current gain and more efficient MHDMG used in micro-scaled actuators and sensors.

Erratum: Building the foundation for equitable and inclusive research: Seed grant programs to facilitate development of diverse CBPR community-academic research partnerships - CORRIGENDUM.

[This corrects the article DOI: 10.1017/cts.2022.495.].

The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplantation (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were (1) to assess the incidence of severe PGD in an international cohort; (2) to evaluate the performance of the most strongly validated PGD risk tool, the RADIAL score, in a contemporary cohort; and (3) to redefine clinical risk factors for severe PGD in the current era of HT. METHODS: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis, and its calibration was assessed by plotting the percentage of PGD predicted vs that which was observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. RESULTS: A total of 2746 patients have been enrolled in the registry to date, including 2015 (73.4%) from North America, and 731 (26.6%) from Europe; 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (P value for trend by difference sign test = 0.004). The Kaplan-Meier estimate for 1-year survival was 75.7% (95% CI 69.4-80.9%) in patients with severe PGD as compared to 94.4% (95% CI 93.5-95.2%) in those without severe PGD (log-rank P value < 0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD; it had an AUC of 0.53 (95% CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31-4.43), durable left ventricular assist device support (OR 1.77, 95% CI 1.13-2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02-1.41) were associated with an increased risk of severe PGD. CONCLUSIONS: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

An artificial intelligence approach for identification of microalgae cultures.

In this work, a model for the characterization of microalgae cultures based on artificial neural networks has been developed. The characterization of microalgae cultures is essential to guarantee the quality of the biomass, and the objective of this work is to achieve a simple and fast method to address this issue. Data acquisition was performed using FlowCam, a device capable of capturing images of the cells detected in a culture sample, which are used as inputs by the model. The model can distinguish between 6 different genera of microalgae, having been trained with several species of each genus. It was further complemented with a classification threshold to discard unwanted objects while improving the overall accuracy of the model. The model achieved an accuracy of up to 97.27% when classifying a culture. The results demonstrate the effectiveness of the Deep Learning models for the characterization of microalgae cultures, it being a useful tool for the monitoring of microalgae cultures in large-scale production facilities while providing accurate characterization over a wide range of genera.

Evaluación del focus group con farmacéuticos realizado en el proyecto “Igualdad y no discriminación en la atención farmacéutica a personas transexuales en España. Elaboración de un libro blanco” / Evaluation of the focus group with pharmaceuticals carried out in the project “Equality and non-discrimination in the pharmaceutical care of transsexual people in Spain. Preparation of a white paper”

En este artículo se presentan los resultados y la evaluación del focus group con farmacéuticos realizado en el colegio Oficial de Farmacéuticos de Madrid, como parte del proyecto “Igualdad y no discriminación en la atención farmacéutica a personas transexuales en España. Elaboración de un libro blanco”. El focus group ha permitido detectar actitudes, comportamientos y opiniones de los farmacéuticos comunitarios, evidenciándose el desconocimiento de numerosos aspectos relacionados con la realidad transexual, lo que lleva a pensar que se requiere de una formación adecuada del farmacéutico, tanto en los aspectos farmacológicos, como humanos y de comunicación. Sin embargo, no hay ninguna duda de que el farmacéutico comunitario, por su accesibilidad y cercanía, es un elemento de vital importancia para el asesoramiento, acompañamiento y ayuda de las personas transexuales y, en su caso, de sus familiares. (AU)

This article presents the results and the evaluation of the focus group with pharmacists carried out at the Official College of Pharmacists of Madrid, as part of the project “Equality and non-discrimination in pharmaceutical care for transgender people in Spain. Preparation of a white book”. The focus group has made it possible to detect attitudes, behaviors and opinions of community pharmacists, evidencing the ignorance of numerous aspects related to the transsexual reality, which leads to think that adequate training of the pharmacist is required, in both pharmacological aspects, as well as human and communication. However, there is no doubt that the community pharmacist, due to its accessibility and proximity, is an element of vital importance for the advice, accompaniment and help of transsexual people and, where appropriate, their families. (AU)

Transcription Factor Dynamics in Cross-Regulation of Plant Hormone Signaling Pathways.

Cross-regulation between hormone signaling pathways is indispensable for plant growth and development. However, the molecular mechanisms by which multiple hormones interact and co-ordinate activity need to be understood. Here, we generated a cross-regulation network explaining how hormone signals are integrated from multiple pathways in etiolated Arabidopsis (Arabidopsis thaliana) seedlings. To do so we comprehensively characterized transcription factor activity during plant hormone responses and reconstructed dynamic transcriptional regulatory models for six hormones; abscisic acid, brassinosteroid, ethylene, jasmonic acid, salicylic acid and strigolactone/karrikin. These models incorporated target data for hundreds of transcription factors and thousands of protein-protein interactions. Each hormone recruited different combinations of transcription factors, a subset of which were shared between hormones. Hub target genes existed within hormone transcriptional networks, exhibiting transcription factor activity themselves. In addition, a group of MITOGEN-ACTIVATED PROTEIN KINASES (MPKs) were identified as potential key points of cross-regulation between multiple hormones. Accordingly, the loss of function of one of these (MPK6) disrupted the global proteome, phosphoproteome and transcriptome during hormone responses. Lastly, we determined that all hormones drive substantial alternative splicing that has distinct effects on the transcriptome compared with differential gene expression, acting in early hormone responses. These results provide a comprehensive understanding of the common features of plant transcriptional regulatory pathways and how cross-regulation between hormones acts upon gene expression.

Building the foundation for equitable and inclusive research: Seed grant programs to facilitate development of diverse CBPR community-academic research partnerships.

Introduction: The effectiveness of community-based participatory research (CBPR) partnerships to address health inequities is well documented. CBPR integrates knowledge and perspectives of diverse communities throughout the research process, following principles that emphasize trust, power sharing, co-learning, and mutual benefits. However, institutions and funders seldom provide the time and resources needed for the critical stage of equitable partnership formation and development. Methods: Since 2011, the Detroit Urban Research Center, collaborating with other entities, has promoted the development of new community-academic research partnerships through two grant programs that combine seed funding with capacity building support from community and academic instructors/mentors experienced in CBPR. Process and outcomes were evaluated using mixed methods. Results: From 2011 to 2021, 50 partnerships received grants ranging from $2,500 to $30,000, totaling $605,000. Outcomes included equitable partnership infrastructure and processes, innovative pilot research, translation of findings to interventions and policy change, dissemination to multiple audiences, new proposals and projects, and sustained community-academic research partnerships. All partnerships continued beyond the program; over half secured additional funding. Conclusions: Keys to success included participation as community-academic teams, dedicated time for partnership/relationship development, workshops to develop equity-based skills, relationships, and projects, expert community-academic instructor guidance, and connection to additional resources. Findings demonstrate that small amounts of seed funding for newly forming community-academic partnerships, paired with capacity building support, can provide essential time and resources needed to develop diverse, inclusive, equity-focused CBPR partnerships. Building such support into funding initiatives and through academic institutions can enhance impact and sustainability of translational research toward advancing health equity.

Reflexión ética sobre el crecimiento del uso de opioides en España: ¿está fundamentada la limitación de uso del fentanilo de liberación inmediata? / Ethical discussion about the growing use of opioids in Spain: is it fundamented the limination of inmediate release fentanyl use?

El entorno de adicción y mortalidad por opioides (ilegales y de prescripción) en Estados Unidos (lo que comúnmente se ha llamado la epidemia de opioides) ha puesto sobre la mesa la discusión ética sobre la idoneidad de usar o no opioides fuera de indicación, sobre todo en relación al uso del fentanilo de liberación inmediata en pacientes no-oncológicos. En el año 2018 la Agencia Española del Medicamento y Productos Sanitarios (AEMPS) emitió una advertencia en contra de este uso, justificando esta decisión con una serie de argumentos y datos que analizamos en este artículo. Estos medicamentos tienen un papel esencial en el tratamiento del dolor irruptivo, un tipo de dolor que está presente tanto en pacientes con cáncer como en pacientes sin cáncer. Atendiendo a la advertencia regulatoria de la AEMPS, los médicos se enfrentan actualmente al dilema ético de no utilizar estos fármacos en pacientes no-oncológicos, o prescribirlos de forma off-label. (AU)

The current environment of addiction and mortality associated to both illegal and prescription opioids in United States of America (what is commonly called the opioids epidemic) has put on the table the ethical discussion about the use or not of opioids in off-label, especially in relation to the use of immediate release fentanyl in non-cancer patients. In 2018 the Spanish Agency of Medicines issued a warning note about the use of those medicaments supporting this decision in some arguments and data that will be analyzed in this publication. Those drugs have an essential role in the treatment of breakthrough pain, that is present in both cancer and non-cancer patients. Considering the warning of the agency, doctors are facing the ethical dilemma of no use these drugs in no-cancer patients or prescribe them as off-label. (AU)

Evaluación del focus group con personas trans realizado en el proyecto "Igualdad y no discriminación en la atención farmacéutica a personas transexuales en España. Elaboración de un libro blanco" / Evaluation of the focus group with trans people carried out in the project "Equality and non-discrimination in pharmaceutical care for transsexual people in Spain. Preparation of a white paper"

El artículo aborda el análisis de los resultados de la realización de un focus group con personas trans en el contexto del proyecto de investigación “Igualdad y no discriminación en la atención farmacéutica a personas transexuales en España. Elaboración de un libro blanco”. Se establece la metodología empleada, distinguiéndola de otras afines, describiendo su desarrollo y posterior evaluación de su aplicación. Se describe la contribución de los participantes en el focus group, mostrando los resultados más relevantes del focus. Estos resultados se comparan con otro focus group realizado en el contexto del mismo proyecto con farmacéuticos comunitarios en su atención a persona trans. Se concluye que la realización de ambos focus group ha sido una fuente de información y de base de trabajo muy adecuada para intentar dar respuesta a una necesidad no cubierta y dar al farmacéutico comunitario una herramienta que le permita realizar la mejor atención a las personas trans, pudiendo abordar los múltiples aspectos que puedan estar relacionados con sus necesidades y particularidades. (AU)

The article deals with the analysis of the results of the realization of a focus group with trans people in the context of the research project «Equality and non-discrimination in pharmaceutical care for transsexual people in Spain. Preparation of a white paper». The methodology used is established, distinguishing it from other related ones, describing its development and subsequent evaluation of its application. The contribution of the participants in the focus group is described, showing the most relevant results of the focus. These results are compared with another focus group carried out in the context of the same project with community pharmacists in their care for trans people. It is concluded that the realization of both focus groups has been a source of information and a very adequate work base to try to respond to an unmet need and give the community pharmacist a tool that allows him to perform the best care for trans people, being able to address the multiple aspects that may be related to their needs and particularities. (AU)

Análisis secuencial de golpeos finales del punto en pádel mediante árbol decisional / Analysis of Shots Patterns Finishing the Point in Padel through Decision-Tree Analysis

El objetivo de este estudio fue analizar la secuencia de los dos últimos golpeos del punto en pádel, y clasificarlos a través de árbol decisional multivariante. Se analizaron un total de 2110 acciones de juego, siendo las variables analizadas: golpeo, zona de la pista, eficacia, dirección, resultado y lado de juego. Los partidos fueron analizados mediante observación sistemática. Los resultados mostraron que mantener posiciones cercanas a la red aumenta las probabilidades de victoria, observándose que las secuencias de finalización más frecuentes son las de fondo-volea y globo-remate. Las parejas ganadoras realizan mayor número de puntos ganadores en la red y menos errores en el fondo de la pista. Además, utilizar trayectorias cruzadas en el penúltimo golpe aumentará las posibilidades de un error posterior de los rivales. Estos datos tienen aplicación práctica en el entrenamiento perceptivo y decisional del jugador de pádel, y la aplicación de feedbacks por parte del entrenador. (AU)

The main objective was to analyze the sequence of the last two shots of the point in padel and to make a classification through the multivariate decision tree approach. A total of 2110 game actions were analyzed. The variables analyzed were: shot, court zone, efficiency, direction, match outcome and side court. Matches were analyzed through systematic observation. The results determined that maintain net positions during the last two shots would increase the probabilities of victory, observing that the most frequent sequence of the last two shots were groundstroke-volley and lob-smash. In addition, winners make the highest number of winning points on the net and the least number of errors at the baseline. On the other hand, the use of cross-court shots will increase the chances of a opponents’ error. These data have an important practical application in the perceptive and decisional training and the feedback application by the coach. (AU)

Bloqueo bilateral del grupo de nervios pericapsulares (PENG) como analgesia en cirugía de cadera infantil / Bilateral pericapsular nerves group (PENG) block for analgesia in pediatric hip surgery

En la enfermedad quirúrgica de cadera es esencial el manejo y el control efectivo del dolor peri y postoperatorio que minimice el uso de opioides y sus efectos adversos. Una de las dificultades de la analgesia regional eficaz para el control del dolor de cadera es la compleja inervación de la articulación que procede de múltiples nervios. Las técnicas regionales comúnmente realizadas se asocian en ocasiones a complicaciones, entre las que se han descrito la anestesia parcial, la hipotensión o la debilidad de los miembros inferiores. Presentamos el caso de una niña de 5 años con antecedentes de parálisis cerebral infantil que fue intervenida de osteotomía derrotativa y varizante de ambas caderas y tenotomía de los aductores por luxación paralitica a la que se le realizó un bloqueo PENG bilateral asociado al bloqueo del nervio femorocutáneo, por ser una técnica sencilla que no requiere de punciones múltiples para cubrir cada uno de los nervios implicados en la inervación sensitiva de la cápsula articular.(AU)

Effective management and control of peri- and postoperative pain in hip surgery is essential in order to minimize the use of opioids and their adverse effects. Effective regional analgesia for hip pain is made particularly challenging by the complex innervation of the hip joint. Standard regional techniques can be associated with complications, including incomplete anesthesia, hypotension, or lower limb weakness. We present the case of a 5-year-old girl with a history of infantile cerebral palsy who underwent bilateral varus derotation osteotomy and adductor tenotomy due to paralytic dislocation. She received bilateral PENG block and femoral cutaneous nerve block - a simple technique that covers all the nerves involved in the sensory innervation of the joint capsule without the need for multiple injections.(AU)

Leaf endophytic microbiomes of different almond cultivars grafted to the same rootstock.

AIMS: We compared the bacterial endophytic communities of three genetically different almond cultivars that were all grafted on the same type of rootstock, growing side by side within a commercial orchard. METHODS AND RESULTS: We examined the diversity of leaf bacterial endophytes using cultivation-independent techniques and assessed the relative abundance of bacterial families. Two of these three cultivars were dominated by Pseudomonadaceae, while the bacterial composition of the third cultivar consisted mainly of Streptococcaceae. CONCLUSIONS: The experimental set up allowed us to analyse the impact of the shoot cultivar on endophytes, minimizing the influence of rootstock, biogeography, and cultivation status. Our data suggest that the shoot cultivar can shape the leaf endophytic community composition of almond trees. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that the shoot cultivar controls the composition of the foliar bacterial endophytic community of almonds. Overall, our results could provide a first step to develop strategies for a more sustainable almond agriculture.

Bilateral pericapsular nerves group (PENG) block for analgesia in pediatric hip surgery.

Effective management and control of peri- and postoperative pain in hip surgery is essential in order to minimize the use of opioids and their adverse effects. Effective regional analgesia for hip pain is made particularly challenging by the complex innervation of the hip joint. Standard regional techniques can be associated with complications, including incomplete anesthesia, hypotension, or lower limb weakness. We present the case of a 5-year-old girl with a history of infantile cerebral palsy who underwent bilateral varus derotation osteotomy and adductor tenotomy due to paralytic dislocation. She received bilateral PENG block and femoral cutaneous nerve block-a simple technique that covers all the nerves involved in the sensory innervation of the joint capsule without the need for multiple injections.

Complex interactions between nicotine and resveratrol in the Drosophila melanogaster wing spot test.

Nicotine (NIC) and resveratrol (RES) are chemicals in tobacco and wine, respectively, that are widely consumed concurrently worldwide. NIC is an alkaloid known to be toxic, addictive and to produce oxidative stress, while RES is thought of as an antioxidant with putative health benefits. Oxidative stress can induce genotoxic damage, yet few studies have examined whether NIC is genotoxic in vivo. In vitro studies have shown that RES can ameliorate deleterious effects of NIC. However, RES has been reported to have both antioxidant and pro-oxidant effects, and an in vivo study reported that 0.011 mM RES was genotoxic. We used the Drosophila melanogaster wing spot test to determine whether NIC and RES, first individually and then in combination, were genotoxic and/or altered the cell division. We hypothesized that RES would modulate NIC's effects. NIC was genotoxic in the standard (ST) cross in a concentration-independent manner, but not genotoxic in the high bioactivation (HB) cross. RES was not genotoxic in either the ST or HB cross at the concentrations tested. We discovered a complex interaction between NIC and RES. Depending on concentration, RES was protective of NIC's genotoxic damage, RES had no interaction with NIC, or RES had an additive or synergistic effect, increasing NIC's genotoxic damage. Most NIC, RES, and NIC/RES combinations tested altered the cell division in the ST and HB crosses. Because we used the ST and HB crosses, we demonstrated that genotoxicity and cell division alterations were modulated by the xenobiotic metabolism. These results provide evidence of NIC's genotoxicity in vivo at specific concentrations. Moreover, NIC's genotoxicity can be modulated by its interaction with RES in a complex manner, in which their interaction can lead to either increasing NIC's damage or protecting against it.

Epidemiología del ictus cardioembólico y su asociación con la penetración de los ACOD en España: primer estudio poblacional 2005-2018 / Epidemiology of atrial fibrillation-related ischemic stroke and its association with DOAC uptake in Spain: first national population-based study 2005 to 2018

Introducción y objetivos: La prevalencia y la incidencia de la fibrilación auricular (FA), un importante factor de riesgo de ictus cardioembólico, han aumentado sustancialmente en los últimos años. Sin embargo, varios estudios europeos han observado una disminución en la tasa de ictus cardioembólico asociada con un aumento de la penetración de los anticoagulantes orales de acción directa (ACOD). Este estudio ecológico evalúa la asociación entre la penetración de los ACOD y la tasa de incidencia de ictus cardioembólicos en España. Métodos: Los datos se obtuvieron del Registro de Actividad Sanitaria Especializada del Ministerio de Sanidad de España (RAE-CMBD). Los ictus cardioembólicos se identificaron mediante códigos ICD. Las tasas de incidencia se estandarizaron por edad y se ajustaron a la población estándar europea de 2013. Se utilizaron modelos de regresión de Poisson para estimar la asociación entre la penetración de los ACOD y la tasa de ictus cardioembólico en pacientes de 65 o más años. Resultados: La tasa de incidencia ajustada (TI) del ictus cardioembólico aumentó desde 2005 (2,20/100.000 personas/año) hasta 2012 (2,67). A partir de 2012, tras la introducción de los ACOD para la prevención del ictus cardioembólico en España, la TI se ha mantenido constante o ha disminuido ligeramente (en 2018, 2,66). Los resultados del modelo de regresión de Poisson indican que la penetración de los ACOD tiene una influencia estadísticamente significativa en la tasa de ictus cardioembólicos de los mayores de 65 años (RDI=0,995; IC95%, 0,995-0,996). Conclusiones: Los resultados de este estudio muestran una asociación entre la penetración de los ACOD y una menor incidencia de ictus cardioembólicos. A pesar de que esta asociación no implica causalidad, indica que una mayor penetración de los ACOD podría llevar a un mayor beneficio clínico para los pacientes con FA en España (AU)

Introduction and objectives: The incidence and prevalence of atrial fibrillation (AF), a major risk factor for stroke, has increased substantially in the past few years. However, several studies have reported a decline in AF-related stroke rates associated with higher uptake of direct oral anticoagulants (DOACs). This ecological study evaluated the association between DOAC uptake in Spain and the incidence rate (IR) of AF-related ischemic stroke. Methods: Data were obtained from the Registry of Activity of Specialized Healthcare of the Spanish Ministry of Health (RAE-MDS). AF-related ischemic strokes were identified using International Classification of Diseases codes. IR were age-standardized and adjusted to the 2013 European standard population. Poisson regression models were used to identify the association between DOAC uptake and AF-related ischemic stroke in patients aged ≥ 65 years. Results: Before the use of DOACs, the adjusted IR of AF-related ischemic stroke increased steadily from 2005 (IR=2.20 per 100 000 person/y) to 2012 (IR=2.67). Upon DOAC uptake in Spain from 2012 onwards for AF-related ischemic stroke prevention, the IR remained constant or decreased slightly (IR in 2018=2.66). Poisson regression showed that DOAC uptake was a significant predictor for the rate of AF-related ischemic stroke in patients older than 65 years (IRR=0.995; 95%CI, 0.995-0.996). Conclusions: This study shows an association between DOAC use and a reduced incidence of AF-related ischemic stroke. While this association is based on aggregate data and cannot demonstrate causality, these findings suggest that higher DOAC uptake could improve health outcomes in AF patients in Spain (AU)