Memory and language risk assessment with Wada test in patients candidates for epilepsy surgery. / Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.

AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.

TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.

Differential accumulation of human ß-amyloid and tau from enriched extracts in neuronal and endothelial cells.

While Aß and Tau cellular distribution has been largely studied, the comparative internalization and subcellular accumulation of Tau and Aß isolated from human brain extracts in endothelial and neuronal cells has not yet been unveiled. We have previously demonstrated that controlled enrichment of Aß from human brain extracts constitutes a valuable tool to monitor cellular internalization in vitro and in vivo. Herein, we establish an alternative method to strongly enrich Aß and Tau aggregates from human AD brains, which has allowed us to study and compare the cellular internalization, distribution and toxicity of both proteins within brain barrier endothelial (bEnd.3) and neuronal (Neuro2A) cells. Our findings demonstrate the suitability of human enriched brain extracts to monitor the intracellular distribution of human Aß and Tau, which, once internalized, show dissimilar sorting to different organelles within the cell and differential toxicity, exhibiting higher toxic effects on neuronal cells than on endothelial cells. While tau is strongly concentrated preferentially in mitochondria, Aß is distributed predominantly within the endolysosomal system in endothelial cells, whereas the endoplasmic reticulum was its preferential location in neurons. Altogether, our findings display a picture of the interactions that human Aß and Tau might establish in these cells.

Navigating the Mental Lexicon: Network Structures, Lexical Search and Lexical Retrieval.

This paper examines the implications of the association patterns in our understanding of the mental lexicon. By applying the principles of graph theory to word association data, we intend to explore which measures tap better into lexical knowledge. To that end, we had different groups of English as Foreign language learners complete a lexical fluency task. Based on these empirical data, a study was undertaken on the corresponding lexical availability graph (LAG). It is observed that the aggregation (mentioned through human coding) of all lexical tokens on a given topic allows the emergence of some lexical-semantic patterns. The most important one is the existence of some key terms, featuring both high centrality in the sense of network theory and high availability in the LAG, which define a hub of related terms. These communities of words, each one organized around an anchor term, or most central word, are nicely apprehended by a well-known network metric called modularity. Interestingly enough, each module seems to describe a conceptual class, showing that the collective lexicon, at least as approximated by LA Graphs, is organised and traversed by semantic mechanisms or associations via hyponymy or hiperonymy, for instance. Another empirical observation is that these conceptual hubs can be appended, resulting in high diameters compared to same-sized random graphs; even so it seems that the small-world hypothesis holds in LA Graphs, as in other social and natural networks.

Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain / Mortalidad y riesgo cardiovascular en vasculitis ANCA. Importancia de la hipertension y funcion renal. Experiencia del sur de España

Background: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). Objectives: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. Methods: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). Results: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. Conclusions: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.(AU)

Introducción: La enfermedad cardiovascular (ECV) es una de las principales causas de muerte en las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos (ANCA) (VAA). Objetivos: Evaluar la mortalidad y sus causas, entre ellas la ECV y sus factores de riesgo vascular (FRV) en pacientes con VAA en Andalucía. Métodos: Se estudió una cohorte multicéntrica de 220 pacientes con VAA seguidos desde 1979 hasta junio de 2020 en Andalucía. La información, incluidos los datos sociodemográficos y clínicos, se registró retrospectivamente a través de la revisión de historias clínicas. Los datos se analizaron mediante Chi2, ANOVA y regresión de riesgos proporcionales de Cox de forma uni y multivariante con un intervalo de confianza (IC) del 95%. Resultados: Durante un seguimiento medio y desviación estándar de 96,79 ± 75,83 meses, 51 pacientes fallecieron y 30 presentaron al menos un ECV. Los factores pronósticos independientes de mortalidad fueron la edad (HR 1,083, p=0,001) y la creatinina basal (HR 4,41, p=0,01). Los factores pronósticos independientes de ECV fueron la edad [hazard ratio (HR) 1,042, p=0,005] y la presencia de hipertensión arterial (HTA) seis meses después del diagnóstico (HR 4,641, p=0,01). La prevalencia de HTA, diabetes e insuficiencia renal fue elevada o muy elevada en comparación con la población general emparentada, todos FRCV determinantes para el pronóstico de estos pacientes. Conclusiones: La edad y la función renal basal son predictores de mortalidad y la edad y la HTA de aparición precoz son predictores independientes de tener ECV. Se recomienda el cribado de FRCV en pacientes con vasculitis ANCA.(AU)

Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain.

BACKGROUND: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). OBJECTIVES: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. METHODS: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). RESULTS: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. CONCLUSIONS: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.

Fluctuation Relations to Calculate Protein Redox Potentials from Molecular Dynamics Simulations.

The tunable design of protein redox potentials promises to open a range of applications in biotechnology and catalysis. Here, we introduce a method to calculate redox potential changes by combining fluctuation relations with molecular dynamics simulations. It involves the simulation of reduced and oxidized states, followed by the instantaneous conversion between them. Energy differences introduced by the perturbations are obtained using the Kubo-Onsager approach. Using a detailed fluctuation relation coupled with Bayesian inference, these are postprocessed into estimates for the redox potentials in an efficient manner. This new method, denoted MD + CB, is tested on a de novo four-helix bundle heme protein (the m4D2 "maquette") and five designed mutants, including some mutants characterized experimentally in this work. The MD + CB approach is found to perform reliably, giving redox potential shifts with reasonably good correlation (0.85) to the experimental values for the mutants. The MD + CB approach also compares well with redox potential shift predictions using a continuum electrostatic method. The estimation method employed within the MD + CB approach is straightforwardly transferable to standard equilibrium MD simulations and holds promise for redox protein engineering and design applications.

PERFORMANCE OF SIX SCREENING SCORES FOR OBSTRUCTIVE SLEEP APNOEA IN AN AFRICAN POPULATION.

Introduction: A screening tool for obstructive sleep apnoea (OSA) is useful in low-income countries where it may be difficult to access sleep recordings. The objective of this study was to assess the performance of six screening scores compared with objective sleep recording in an African population sample. Methods: This analysis is based on the "Benin Sleep and Society" (BeSAS) populational study in which respiratory polygraphy (PG) was performed using a type III device and OSA screening questionnaires (STOP, STOP-Bang, Berlin, NOSAS [≥ 8 and ≥ 5), No-Apnea, GOAL) were administered to participants. PG-defined OSA severity categories were defined according to the apnoea-hypopnoea index (AHI): mild (AHI 5 to <15/h), moderate (AHI 15 to <30/h) or severe (AHI≥30/h), and these were compared to score findings. Results: A total of 1810 subjects (mean age 45.4±14.6 years; 57.3% women) were included. For moderate to severe OSA, the area under the receiving operating characteristic (ROC) curve was greatest for GOAL and No-Apnea (0.70), followed by NoSAS5 (0.69). The highest sensitivity values were for NoSAS5 (0.73), No-Apnea (0.72), and GOAL (0.69), while NoSAS8 had the highest specificity (0.91), followed by Berlin (0.88) and GOAL (0.71). All scores performed poorly with respect to the positive predictive value (PPV), which was highest with NoSAS8 (0.38). Conclusion: This study provides the first comparison of the performance of screening scores for OSA in an African population. Although still low, PPV was highest with NoSAS8. Hence, NoSAS8 would be the screening method of choice for OSA in resource-constrained settings where formal sleep recordings are not accessible.

EVALUATION OF A MODIFIED EPWORTH SLEEPINESS SCALE TO RELIABLY ASSESS EXCESSIVE DAYTIME SLEEPINESS IN LOW-INCOME COUNTRIES: RESULTS FROM THE BENIN SOCIETY AND SLEEP (BESAS) STUDY.

Background: The Epworth Sleepiness Scale (ESS) is a tool widely used to assess excessive daytime sleepiness. Unfortunately, it is not reliable in low-income countries where situations such as reading a book, watching TV or driving a car are not common. The aim of this study was thus to assess the performance of a modified version of the Epworth scale in a low-income country. Methods: We used data from the Benin Society and Sleep (BeSAS) study where the ESS and a modified ESS (mESS) were administered to participants. In the mESS, questions four questions over eight were redesigned to reflect common living situations in Benin. The internal coherence of the mESS was assessed using the Cronbach alpha coefficient (CAC). The discriminatory ability of the scale was assessed by comparing the mean scores according to reported sleep quality, insomnia complaints and apnea-hypopnea index (AHI). Results: A total of 2909 participants were recruited, 1129 were male (38.9%) with a mean age (SD) of 44.7 (14.5) y. Overall, 52.4% (1526) completed all the mESS questions while 453 (15.6%) completed the standard ESS. The CAC of the mES was 0.86 showing good internal coherence. Concerning the discriminatory ability, mean scores for mESS were 7.8 for participants with ISI < 8 vs 9.2 for participants with ISI≥8 (p<0.001), 7.8 for participants withPSQI<5 vs 8.3 for participants with PSQI≥5 (p=0.03). No difference was found when comparing the participants participants using different cut-offs of AHI (15 and 30). Conclusion: The mES is more reliable than ES in the Beninese population. mESS shows good internal coherence and differentiates between insomniacs vs non-insomniacs and between good and poor sleepers. Although the mES is not a perfect score, it appears more relevant in the Benin population than the original Epworth scale but needs further validation/improvement in other low-income countries.

“Displasia ósea florida: signos imagenológicos reportados en artículos odontológicos publicados entre el 2012 y 2021” / Florid bone dysplasia: imaging signs reported in dental articles published between 2012 and 2021

Introducción: Identificar los signos imagenológicos característicos de la displasia ósea florida reportados en artículos publicados en revistas odontológicas indexadas en la principal fuente de información de salud (Medline) entre el año 2012 al 2021. Materiales y métodos: Se llevó a cabo un estudio observacional, transversal y retrospectivo evaluando las principales revistas odontológicas encontradas en publicaciones entre los años 2012 al 2021 mediante la búsqueda electrónica en la base de datos de Medline vía PubMed, usando los términos (cemento-osseus displasia) AND (radiology), luego se procedió a depurar la muestra siguiendo los criterios de selección estipulados. Resultados: Se evaluó un total de 7 artículos que cumplieron con los criterios de selección en donde se recopiló la información de 363 casos de displasia ósea florida. Encontrándose en promedio esta lesión a los 51.88 años según la edad con predominio en el sexo femenino, en promedio 49.51 frente a 2.34 para el masculino. Según la ubicación de la lesión, los artículos muestran que es más frecuente en mandíbula con un promedio de 28 casos, seguido de ambos maxilares con 23.29 casos y muy raro en la maxila con 0.57 casos. Imagenológicamente los artículos describen lesiones radiolúcidas o hipodensas en promedio 2.29 casos, mixtas 36.57 casos y radiopacas o hiperdensas en promedio 20.29 casos. Conclusiones: De acuerdo a lo descrito en la literatura, la displasia ósea florida suele presentarse con mayor frecuencia en mujeres adultas, a partir de la quinta década de vida, disminuyendo su incidencia de la sexta década en adelante. Su localización más frecuente es en la mandíbula, en segundo lugar, en ambos maxilares y muy raramente solo en la maxila. Imagenológicamente se presentan con mayor incidencia con un patrón mixto. (AU)

Introduction: Identify the characteristic imaging signs of florid bone dysplasia reported in articles published in dental journals indexed in the main source of health information (Medline) between 2012 and 2021. Materials and methods: An observational, cross-sectional and retrospective study was carried out evaluating the main dental journals found in publications between the years 2012 and 2021 through the electronic search in the Medline database via PubMed. Using the terms (cemento-osseus dysplasia) AND (radiology), we then proceeded to refine the sample following the stipulated selection criteria. Results: A total of 7 articles that met the selection criteria were evaluated, where information from 363 cases of florid bone dysplasia was collected. Finding this lesion on average at 51.88 years according to age, with a predominance in the female sex, on average 49.51 compared to 2.34 for the male. Depending on the location of the lesion, the articles show that it is more frequent in the mandible with an average of 28 cases, followed by both maxillae with 23.29 cases and very rare in the maxilla with 0.57 cases. Imagingly, the articles describe radiolucent or hypodense lesions in an average of 2.29 cases, mixed 36.57 cases, and radiopaque or hyperdense lesions in an average of 20.29 cases. Conclusions: According to what has been described in the literature, florid bone dysplasia tends to occur more frequently in adult women, starting in the fifth decade of life, decreasing its incidence from the sixth decade onwards. Its most frequent location is in the mandible, secondly, in both jaws and very rarely only in the maxilla. Imaging, they present with a higher incidence with a mixed pattern. (AU)

Validación externa del algoritmo InShape II para la exclusión de la enfermedad tromboembólica crónica en los pacientes con tromboembolismo pulmonar / External validation of the InShape II study algorithm for exclusion of chronic thromboembolic pulmonary hypertension in patients with pulmonary thromboembolism

Antecedentes y objetivo La complicación a largo plazo más grave del embolismo pulmonar (EP) es la hipertensión pulmonar tromboembólica crónica (HPTEC), cuyo diagnóstico precoz implica la realización de un gran número pruebas. El estudio InShape II propone un algoritmo de cribado precoz que pretende disminuir el número de estudios ecocardiográficos. El objetivo de nuestro estudio es validar este algoritmo en nuestra cohorte de pacientes. Material y métodos Se analizaron retrospectivamente los pacientes ingresados con diagnóstico de EP por angio-TC, en el Hospital Rey Juan Carlos entre noviembre del 2017 y febrero del 2020, seguidos durante al menos un año. Se recogieron datos clínicos, analíticos, y pruebas complementarias a los 3 meses y al año. Se aplicó a estos pacientes el algoritmo del estudio InShape II para validar sus resultados. Resultados En el periodo de estudio fueron diagnosticados de EP 236 pacientes, de los cuales 137 fueron excluidos. Se validó el algoritmo en 99 pacientes. Aplicando el score del InShape II hubiéramos realizado 19 ecocardiogramas (3 de ellos con probabilidad intermedia/alta de HPTEC) y no se hubieran hecho en 80 (2 de ellos con probabilidad intermedia/alta), por lo que se estableció una sensibilidad del score de un 60%, con una especificidad de un 83%, y un área bajo la curva (AUC) de 0,715 (IC 95%: 0,472-0,958). Conclusiones Nuestros resultados apoyan que el algoritmo del estudio InShape II podría ser una herramienta útil en el cribado inicial del estudio de HPTEC en entornos de baja incidencia, ya que evitaría la realización de ecocardiogramas que no aportan valor (AU)

Background and aim The most severe long-term complication of pulmonary embolism (PE) is chronic thromboembolic pulmonary hypertension (CTEPH), and its early diagnosis often requires numerous diagnostic tests. The InShape II study proposes an early screening algorithm that aims to reduce the number of echocardiographic studies. The objective of our study is to validate this algorithm in our patient cohort. Materials and methods We retrospectively analyzed patients admitted to Hospital Rey Juan Carlos between November 2017 and February 2020, who were diagnosed with PE based on computed tomography angiography (CTA). Patients were followed for at least one year, and clinical, laboratory, and complementary test data were collected at three months and one year. The InShape II algorithm was applied to these patients to validate its results. Results During the study period, 236 patients were diagnosed with PE, of which 137 were excluded. The algorithm was validated in 99 patients. Applying the InShape II score, 19 echocardiograms would have been performed (three of them with intermediate-high probability of CTEPH), while 80 echocardiograms would have been avoided (two of them with intermediate-high probability). This yielded a sensitivity of 60% and a specificity of 83% for the score, with an area under the curve (AUC) of 0.715 (95% CI: 0.472-0.958). Conclusions Our results support the notion that the InShape II algorithm could be a useful tool for initial screening of CTEPH in low-incidence settings, as it would avoid unnecessary echocardiograms that do not provide additional value (AU)

External validation of the InShape II study algorithm for exclusion of chronic thromboembolic pulmonary hypertension in patients with pulmonary thromboembolism.

BACKGROUND AND AIM: The most severe long-term complication of pulmonary embolism (PE) is chronic thromboembolic pulmonary hypertension (CTEPH), and its early diagnosis often requires numerous diagnostic tests. The InShape II study proposes an early screening algorithm that aims to reduce the number of echocardiographic studies. The objective of our study is to validate this algorithm in our patient cohort. MATERIALS AND METHODS: We retrospectively analyzed patients admitted to Hospital Rey Juan Carlos between November 2017 and February 2020, who were diagnosed with PE based on computed tomography angiography (CTA). Patients were followed for at least one year, and clinical, laboratory, and complementary test data were collected at three months and one year. The InShape II algorithm was applied to these patients to validate its results. RESULTS: During the study period, 236 patients were diagnosed with PE, of which 137 were excluded. The algorithm was validated in 99 patients. Applying the InShape II score, 19 echocardiograms would have been performed (three of them with intermediate-high probability of CTEPH), while 80 echocardiograms would have been avoided (two of them with intermediate-high probability). This yielded a sensitivity of 60% and a specificity of 83% for the score, with an area under the curve (AUC) of 0.715 (95% CI: 0.472-0.958). CONCLUSIONS: Our results support the notion that the InShape II algorithm could be a useful tool for initial screening of CTEPH in low-incidence settings, as it would avoid unnecessary echocardiograms that do not provide additional value.

Analysis of the characteristics of the smash in padel: validation of the OASP instrument / Análisis de las características del remate en pádel: validación del instrumento OASP

The purpose of this study was to design and validate an observation instrument for the analysis of the performance parameters related to the smash in padel. Eleven experts, who had to meet four of the five inclusion criteria, participated in the process. Aiken's V coefficient and confidence intervals were used to calculate content validity and Cronbach's α coefficient to analyze reliability. The adequacy and writing of the eighteen items initially designed were evaluated. Four variables were eliminated due to obtaining values ​​<.87 in Aiken's V coefficient for adequacy. The rest of the variables were modified in their wording, according to the qualitative evaluations of the experts, or were considered correct. The reliability of the instrument was acceptable, (α=.82). The OASP instrument is very new, as it is of interest for analyzing the use and effectiveness of the padel smash. (AU)

El propósito de este estudio fue diseñar y validar un instrumento de observación para el análisis de las características del remate relacionadas con el rendimiento en pádel. En el proceso participaron once expertos, los cuales debían cumplir cuatro de los cinco criterios de inclusión. El coeficiente V de Aikene intervalos de confianza se utilizaron para calcular la validez de contenido y el coeficiente 𝛼de Cronbach para analizar la fiabilidad. Se evaluó la adecuación y redacción de los dieciocho ítems diseñados inicialmente. Se eliminaron cuatro variables por obtener valores <.87 en el coeficiente V de Aikenen la adecuación. El resto de las variables fueron modificadas en su redacción, según las valoraciones cualitativas de los expertos, o se consideraron correctas. La fiabilidad del instrumento fue aceptable, (𝛼=.82). El instrumento OASP es muy novedoso, pues resulta de interés para analizar el uso y la eficacia del remate en pádel. (AU)

Controlled Ovarian Stimulation Initiated at Different Phases of the Menstrual Cycle for Fertility Preservation in Oncological Patients: a Retrospective Study.

The purpose of this study is to compare conventional start in early follicular phase (EFP) with late follicular phase (LFP) and luteal phase (LP) in controlled ovarian stimulation (COS) for fertility preservation (FP) to assess differences in clinical outcomes. Retrospective study of the first cycles of COS for FP in oncological patients between 2012 and 2020 in a tertiary hospital. Two-hundred forty-eight cycles were classified into 3 groups: 176 cycles in EFP, 8 cycles in LFP, and 52 cycles in LP. Comparing LFP to EFP, there were no differences in number of oocytes (10.0 [6.3-16.0] vs 12.0 [8.0-18.0]; p = 0.253) or number of metaphase II (MII) obtained (7.0 [2.3-13.3] vs 9.0 [6.0-13.0]; p = 0.229). Total number of days needed was higher in LFP (14.5 [12.5-16.0] vs 3.0 vs 10.0 [8.3-11.0 p = 0.000) but without significant differences in number of days of usage of gonadotropins (11.5 [8.3-12.8] vs 10.0 [8.3-11.0] p = 0.308). No differences were found between LP and EFP in number of oocytes (14.5 [9.0-20.0] p = 0.151) or MII (11.5 [7.0-16.0] p = 0.084). Number of days of gonadotropins (11.0 [10.0-12.0] p = 0.00) and total dosing (3000.0 [2475.0-3600.0] p = 0.013) were significantly higher in LP. FORT and FOI were similar in all groups. COS with a random start in fertility preservation has similar outcomes to EFP start. Therefore, we can initiate COS at any phase of the menstrual cycle with optimal results. However, LP may need more days of stimulation.

Conducting Action Research to Improve Operational Efficiency in Manufacturing: The Case of a First-Tier Automotive Supplier.

Optimising available resources and minimising production costs and throughput time is vital for first-tier suppliers in the worldwide automotive sector. To develop this type of optimisation and efficiency, MAHLE applied Action Research (AR) in one of its factories located in Spain. A multidisciplinary collaborative work team was created with the aim of deploying the AR initiative in combination with Lean Manufacturing and Six Sigma tools. Four improvement and learning cycles were deployed and key performance metrics were defined to collect and measure data in order to analyse the improvements achieved. The application of the AR initiative in the production line of a power filter device enabled improvements in both production times and quality indicators in the manufacturing process. The most outstanding results were the improvements made in the decrease in initial throughput time (34.78%) and in average daily rejections (73.53%). In addition, the AR initiative generated practical and theoretical contributions for business and academia, allowing the AR initiative to be applied in other areas of the company, and contributing to the current state of the art in the industrial application of this methodology.

Evaluación de los comparadores empleados en los estudios pivotales de nuevos medicamentos e indicaciones / Assessment of comparators used in pivotal studies of new medicines and indications

Objetivo: En algunos casos, los estudios pivotales para aprobar nuevos medicamentos no emplean el comparador más adecuado. El objetivo es cuantificar este problema analizando los Informes de Posicionamiento Terapéutico (IPT) publicados por el Ministerio de Sanidad español.Métodos: El comparador se clasificó en seis categorías según la adecuación del tratamiento, es decir, si coincidía con el estándar de tratamiento al ser autorizado: A-“inicialmente adecuado”, B-“sin comparador por causa ética”, C-“sin comparador excluyendo los clasificados en B”, D-“inadecuado” y E-“parcialmente subóptimo” (cuando era estándar solo para parte de los pacientes).La variable principal fue la proporción de nuevos fármacos/indicaciones con comparación suficiente (categorías A, B y C) o deficiente (el resto). La información sobre comparadores y tratamiento estándar se extrajo del IPT. Resultados: Se analizaron aleatoriamente 186 IPT con nuevos medicamentos/indicaciones, publicados entre 2013 y 2022. La comparación se consideró suficiente en un 73,7% (IC95 66,9-79,5) de los casos. El 26,3% restante (IC95 20,5-33,1) presentaba comparaciones deficientes en el ensayo pivotal, ya fuera por comparador inadecuado (11,3%), parcialmente subóptimo (5,4%) o ausencia de un estudio comparativo (9,7%). No hubo diferencias en relación con el año de aprobación.Conclusiones: Aproximadamente uno de cada cuatro nuevos medicamentos o indicaciones carece de una comparación suficiente en el momento de empezar a ser utilizado en la práctica clínica. La proporción no mejora a lo largo de los últimos 10 años. Las agencias reguladoras deben ser más exigentes en la selección del comparador para los ensayos clínicos pivotales, por cuestiones éticas y sanitarias. (AU)

Objective: Pivotal studies to approve new medicines often do not use the most appropriate comparator. The objective is to quantify this problem by analysing the Therapeutic Positioning Reports (IPT for its acronym in Spanish) published by the Spanish Health Ministry.Methods: The comparator was classified into six categories, based on the appropriateness of the treatment, i.e. whether it matched the standard of treatment when authorised: A-«initially adequate» (at the start of the study), B-«no comparator for ethical reasons», C-«no comparator -excluding B-«, D-«inadequate» and E-«partially suboptimal» (when it was standard for part of the included patients but not for all of them).The primary endpoint was the proportion of new drugs/indications with sufficient (categories A, B and C) or poor comparator (the rest). Information on comparators and standard treatment was extracted from the IPT. Results: We randomly analysed 186 IPTs with new drugs or indications, published between 2013 and March 2022. Comparability was assessed as sufficient in 73.7% (95%CI 66.9-79.5) of cases. The remaining 26.3% (95%CI 20.5-33.1) had poor comparisons in the pivotal trial, either due to inadequate comparator (11.3%), partially suboptimal (5.4%) or absence of a comparative study excluding ethical justification (9.7%). Conclusions: Approximately one in four new medicines or indications lacks sufficient comparability at the time of entry into clinical practice. The proportion has not improved over the last 10 years. Regulatory agencies need to be more stringent in comparator selection for pivotal clinical trials, for ethical and health reasons. (AU)

Protocolo de optimización de uso de medicamentos biológicos en enfermedades inflamatorias inmunomediadas / Protocol for optimization of the use of biological drugs in immune-mediated inflammatory diseases

Objetivo: La artritis reumatoide (AR), espondilitis anquilosante, psoriasis (Ps), artritis psoriásica (APs) están mediadas por factor de necrosis tumoral (TNF). El objetivo es el diseño multidisciplinar de un protocolo personalizado de agentes biológicos en enfermedades reumáticas y dermatológicas. Métodos: Se seleccionaron pacientes con AR, APs, espondiloartritis y Ps que recibían etanercept o adalimumab durante al menos 6 meses ininterrumpidamente. La monitorización terapéutica consideró criterios bioquímicos y criterios clínicos. Rangos terapéuticos óptimos de adalimumab: 5-8 μg/mL para AR y APs, 3.2-7 μg/mL para Ps y 4.6-12 μg/mL para espondiloartritis. Rangos óptimos de etanercept fueron: 2-3 μg/mL para AR y espondiloartritis, y 2-7 μg/mL para Ps y APs. Resultados: Se realizaron propuestas de optimización del tratamiento en pacientes con adecuada respuesta clínica y niveles de fármaco biológico superiores al rango terapéutico óptimo. Si la propuesta de optimización fue aceptada por facultativo, se valoró percepción de la enfermedad del paciente al primer y tercer mes. Los pacientes con niveles plasmáticos de fármaco inferiores al rango terapéutico óptimo, ausencia de anticuerpos anti-fármaco y adecuada respuesta clínica fueron propuestos a optimización de tratamiento mediante discontinuación o espaciamiento de administración. Los pacientes con niveles plasmáticos de fármaco inferiores al rango óptimo y anticuerpos anti-fármaco fueron propuestos a cambio de tratamiento o discontinuación, si se pudiera alcanzar control de enfermedad. Conclusiones: Este protocolo permite la personalización terapéutica de etanercept y adalimumab para enfermedades inflamatorias inmunomediadas en áreas de dermatología y reumatología. La implantación del protocolo podría mejorar la eficacia, seguridad, conveniencia y eficiencia de etanercept y adalimumab. (AU)

Objective: Rheumatoid arthritis (RA), ankylosing spondylitis, psoriasis (Ps), psoriatic arthritis (PAs) are mediated by tumor necrosis factor (TNF). The objective is the multidisciplinary design of a personalized protocol of biological agents in rheumatic and dermatological diseases. Methods: Patients with RA, PAs, spondyloarthritis and Ps receiving etanercept or adalimumab for at least 6 months uninterruptedly were selected. Therapeutic monitoring considered biochemical criteria and clinical criteria. Optimal therapeutic ranges of adalimumab were: 5-8 μg/mL for RA and APs, 3.2-7 μg/mL for Ps and 4.6-12 μg/mL for spondyloarthritis. Optimal ranges of etanercept were: 2-3 μg/mL for RA and spondyloarthritis, and 2-7 μg/mL for Ps and APs. Results: Proposals were elaborated to optimize treatment in patients with adequate clinical response and levels of biological drug higher than the optimal therapeutic range. If the optimization proposal was accepted by the physician, the patient’s perception of disease was evaluated at the first and third months. Patients with plasma drug levels below the optimal therapeutic range, absence of anti-drug antibodies and adequate clinical response were proposed for treatment optimization by discontinuation or spacing of administration. Patients with plasma drug levels below the optimal range and anti-drug antibodies were proposed in exchange for treatment or discontinuation -if disease control could be achieved-. Conclusions: This protocol allows the therapeutic personalization of etanercept and adalimumab for immune-mediated inflammatory diseases in areas of dermatology and rheumatology. Implementation of the protocol could improve the efficacy, safety, convenience and efficiency of etanercept and adalimumab. (AU)