Number needed to treat and associated cost analysis of cenobamate versus third-generation anti-seizure medications for the treatment of focal-onset seizures in patients with drug-resistant epilepsy in Spain

Medicamentos anticonvulsivos; Cenobamato; EficienciaMedicaments anticonvulsius; Cenobamat; EficiènciaAnti-seizure medications; Cenobamate; EfficiencyIntroduction Epilepsy is a serious neurological disease, ranking high in the top causes of disability. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, approximately 40% of patients suffer from Drug-Resistant Epilepsy (DRE) despite the availability of the latest options called third-generation Anti-Seizure Medications(ASMs). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. The introduction of a new drug increases the number of therapeutic options available, making it important to compare it with existing alternatives in terms of clinical benefit and efficiency. Purpose This study aimed to compare the clinical benefit, in terms of the Number Needed to Treat (NNT), and the efficiency, in terms of Cost per NNT (CNT), associated with cenobamate versus third-generation ASMs used in Spain for the adjunctive treatment of FOS in patients with DRE. Methods The Number Needed to Treat data was calculated based on the ≥50% responder rate and seizure freedom endpoints (defined as the percentage of patients achieving 50% and 100% reduction in seizure frequency, respectively), obtained from pivotal clinical trials performed with cenobamate, brivaracetam, perampanel, lacosamide, and eslicarbazepine acetate. The NNT was established as the inverse of the treatment responder rate minus the placebo responder rate and was calculated based on the minimum, mid-range Daily Defined Dose (DDD), and maximum doses studied in the pivotal clinical trials of each ASM. CNT was calculated by multiplying the annual treatment cost by NNT values for each treatment option. Results In terms of NNT, cenobamate was the ASM associated with the lowest values at all doses for both ≥50% responder rate and seizure freedom compared with the alternatives. In terms of CNT, for ≥50% responder rate, cenobamate was the ASM associated with the lowest CNT values at DDD and lacosamide and eslicarbazepine acetate at the minimum and maximum dose, respectively. For seizure freedom, cenobamate was associated with the lowest CNT value at DDD and the maximum dose and lacosamide at the minimum dose. Conclusions Cenobamate could represent the most effective ASM in all doses studied compared to the third-generation ASMs and the most efficient option at DDD for both ≥50% responder rate and seizure freedom. This study could represent an important contribution towards informed decision-making regarding the selection of the most appropriate therapy for FOS in adult patients with DRE from a clinical and economical perspective in Spain.This study was sponsored by Angelini Pharma España, S.L.U

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient's own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL

Transmission of Beauveria bassiana from male to female Aedes aegypti mosquitoes

<p>Abstract</p> <p>Background</p> <p>Resistance to chemical insecticides plus high morbidity rates have lead to rising interest in fungi as candidates for biocontrol agents of mosquito vectors. In most studies fungal infections have been induced by exposure of mosquitoes to various surfaces treated with conidia. In the present study eight Mexican strains of <it>Beauveria bassiana </it>were assessed against <it>Aedes aegypti </it>by direct exposure of females to 6 × 10⁸conidia ml ^-1on a filter paper, afterwards, the transmission of the least and most virulent isolates was evaluated by mating behavior from virgin, fungus-contaminated male to females, to examine this ethological pattern as a new approach to deliver conidia against the dengue vector.</p> <p>Methods</p> <p>In an exposure chamber with a filter paper impregnated with 6 × 10⁸conidia ml ^-1of the least and most virulent strains of <it>B. bassiana</it>, 6-8 day old males of <it>A. aegypti </it>were exposed for 48 hours, and then transferred individually (each one was a replicate) to another chamber and confined with twenty healthy females of the same age. Clean males were used in controls. Survival, infection by true mating (insemination) or by mating attempts (no insemination) and fecundity were daily registered until the death of last female. Data analysis was conducted with proc glm for unbalanced experiments and means were separated with the Ryan test with SAS.</p> <p>Results</p> <p>All strains were highly virulent with LT₅₀ranging from 2.70 (± 0.29) to 5.33 (± 0.53) days. However the most (Bb-CBG2) and least virulent (Bb-CBG4) isolates were also transmitted by mating behavior; both killed 78-90% of females in 15 days after being confined with males that had previously been exposed for 48 hours to fungi. Of these mortality rates, 23 and 38% respectively, were infections acquired by copulations where insemination occurred. The LT₅₀for sexually-infected females were 7.92 (± 0.46) and 8.82 (± 0.45) days for both strains, while the one in control was 13.92 (± 0.58). Likewise, fecundity decreased by 95% and 60% for both Bb-CBG2 and Bb-CBG4 isolates in comparison with control. The role of mating attempts in this delivery procedure of <it>B. bassiana </it>is discussed.</p> <p>Conclusions</p> <p>This is the first report about transmission of <it>B. bassiana </it>by mating behavior from virgin, fungus-contaminated males to females in <it>A. aegypti</it>. Fungal infections acquired by this route (autodissemination) infringed high mortality rates (90%) in mated or approached females. However, prior to releasing virgin, fungus-contaminated males to spread <it>B. basasiana </it>among females of <it>A. aegypti</it>, this novel alternative needs further investigations.</p

Determination of the economically justifiable price of cenobamate in the treatment of focal-onset seizures in adult patients with drug-resistant epilepsy in Spain

Anti-seizure medications; Cenobamate; Economically justifiable priceMedicamentos anticonvulsivos; Cenobamato; Precio económicamente justificableMedicaments anticonvulsius; Cenobamat; Preu econòmicament justificableObjective To determine the economically justifiable price (EJP) of cenobamate to become a cost-effective alternative compared with third-generation anti-seizure medications in the treatment of focal-onset seizures (FOS) in adult patients with drug-resistant epilepsy (DRE) in Spain. Methods Cost-effectiveness analysis compared cenobamate with brivaracetam, perampanel, eslicarbazepine acetate, and lacosamide. Markov model simulation of treatment pathway over a 60-year time horizon is presented. We determined the effectiveness and quality-adjusted life-years (QALYs) of health status and disutilities associated with treatment-related adverse events. Acquisition costs and use of medical resources were obtained from published literature and expert opinion. Base-case of cenobamate’s EJP calculated applying a willingness-to-pay (WTP) threshold of €21,000/QALY. Analyses were performed at different thresholds, including dominant price scenario. Result robustness was assessed through sensitivity analyses. Results Base-case shows that cenobamate’s daily EJP of €7.30 is cost-effective for a threshold of €21,000/QALY. At a daily price of €5.45, cenobamate becomes dominant over all treatment alternatives producing cost-savings for the national health system (NHS). Sensitivity analyses supported the robustness of base-case findings. Conclusions Treatment with cenobamate produces incremental clinical benefit over third-generation ASMs, and at the base-case, EJP could represent a cost-effective option for the adjunctive treatment of FOS in adult patients with DRE in Spain

The interaction of slaughtering, drying, and defatting methods differently affects oxidative quality of the fat from black soldier fly (Hermetia illucens) larvae

The interrelation effect of slaughtering, drying, and defatting methods of BSFL on the oxidative quality of the derived fat was studied. Blanching and freezing were compared as slaughtering methods, followed by oven or freeze-drying for drying and mechanical pressing or SFE for defatting. The oxidative state and stability of the extracted fat and defatted meals were monitored immediately after their production, using peroxide value (PV) and Rancimat test, and over 24 weeks of storage. Slaughtering and drying methods had an independent effect on PV, with freezing and freeze-drying being the best methods. Mechanical pressing and SFE were comparable and superior to conventional hexane defatting. Interactions were observed between slaughtering and defatting, drying and defatting, and between all three factors. Generally, freeze-drying combined with any of the slaughtering and defatting methods resulted in the lowest PVs, with mechanical pressing being preferred. Freeze-drying plus mechanical pressing also produced the most stable fats during storage according to the evolution of PV, while the combination of blanching and SFE produced the least stable. A significant correlation was found between the PV at 24 weeks and the antioxidant activity of the fats. Contrary to storage assays, in accelerated Rancimat assays, freeze-dried samples were the least stable, which was partially attributed to the significant correlation with the acid values of the samples. Defatted meals followed a similar pattern to the extracted fat, except for worse oxidation for SFE defatting. Therefore, the different processing methods of slaughtering, drying, and defatting of BSFL differently affect lipid oxidation, with interactions between such successive stepsThis research was funded by the Spanish National Plans of Aquaculture of the Ministry of Agriculture, Fisheries and Food, project ACUINSECT (Optimization of insect flours as sustainable ingredient for aquaculture fee

Autosuficiencia energética en la vivienda

Resumen Los edificios, junto al transporte suponen más de la mitad del consumo energético actual de combustible y de la contaminación a este asociada, de difícil solución por la dispersión de los procesos de combustión en poblaciones o carreteras. Esta distribución en la edificación de la demanda favorece el uso de energía solar, el recurso renovable más abundante y de fácil acceso sobre la superficie terrestre, especialmente adecuado en nuestro clima. El uso de tecnología solar requiere procesos de acumulación que garanticen la disponibilidad del calor excesivo del verano durante las frías noches de invierno así como la iluminación o las comunicaciones durante la noche en base a la radiación recibida en las horas de radiación solar. El trabajo describe la posibilidad de captura térmica en la cubierta con almacenamiento selectivo en el subsuelo capaz de satisfacer la demanda de energía para climatización de la vivienda a lo largo del año a un coste ,muy bajo. La energía eléctrica de "alta calidad" se genera y acumulé1localmente en forma de hidrógeno para alimentar según demanda mediante una pila de combustible. Con la tecnología actual, aún en pleno desarrollo, el balance es claramente positivo lo que significa la posibilidad de autosuficiencia energética para una parte considerable de las viviendas.El MEC ha financiado el desarrollo de nuevos dispositivos de hidrógeno en el proyecto "Diseño y realización de una nueva Pila de Combustible polimérica de bajo coste y alta eficacia" MCYT- ENE2005-09124-C04-02/ALT. y el CSIC ha financiado la generación de hidrógeno a partir de residuos orgánicos. El P.S.E. INVISO para industrialización de la vivienda sostenible financia el desarrollo integral de estos sistemas.Peer reviewe

Modelo matemático del comportamiento mecánico en flexión del cartón-yeso

The article proposes a mathematical model which predicts the bearing load capacity of gypsum plasterboard sheets in bending tests, based on the geometric dimensions and the mechanical properties of the constituent materials. Thus obtained values are compared with those proposed by various European and American Standards for the minimum bearing load capacity as well as with experimental laboratory measurements. In both cases the results obtained reached an excellent level of agreement.Se presenta un modelo matemático que predice la carga de rotura de las placas de cartón-yeso en ensayos a flexotracción, a partir del conocimiento de sus dimensiones geométricas y de las propiedades mecánicas de los materiales componentes. Los valores así obtenidos se comparan con los que proponen diversas normas europeas y americanas para la carga de rotura mínima, así como con medidas experimentales en laboratorio, obteniéndose en ambos casos un acuerdo excelente

Modelación hidrológica de una microcuenca para prevenir inundaciones en el AMG

La Zona Metropolitana de Guadalajara (ZMG) no cuenta con agua potable suficiente para abastecer a sus habitantes y ello lo ha llevado a sobreexplotar sus aguas subterráneas. Simultáneamente, sufre inundaciones periódicas porque las intensas lluvias son derivadas al colector pluvial que se conecta con el drenaje, lo que genera un flujo que excede la capacidad de retención y conducción para la que fue diseñada la red. Una forma de solucionar los problemas antes descritos son los pozos de inyección profunda, que se utilizan en muchas ciudades del mundo para recargar los mantos acuíferos con las aguas superficiales. Para ponerlos en práctica se requieren condiciones geohidrológicas favorables; como escurrimientos superficiales disponibles, un acuífero amplio con una capa freática profunda, una alta permeabilidad en el subsuelo y una calidad de agua que permita ser infiltrada sin contaminar los mantos freáticos. Todas estas condiciones las tiene la ZMG, y teóricamente el problema de las inundaciones podría solucionarse, los acuíferos recuperarse y la ciudad autoabastecerse de agua. Sin embargo, hay escepticismo en el gremio respecto a la posibilidad de que el acuífero pueda recargarse mediante esta técnica. Las objeciones se basan en el desconocimiento del comportamiento hidráulico del subsuelo, en la falta de comprensión acerca de los alcances de esta tecnología, y en la posibilidad de que los escurrimientos superficiales no posean la calidad ambiental suficiente para ser infiltrados. Aquí se propone modelar y validar el comportamiento hídrico de una microcuenca problemática de la ZMG y con esa base simular el arrastre de contaminantes. Esto permitirá demostrar los alcances de esta técnica y sería la base para establecer un plan de intervención. En primer lugar, se construirá un modelo hidrogeológico capaz de simular escurrimientos superficiales, arrastre de contaminantes y la infiltración en el subsuelo. Después, el modelo será calibrado a partir de datos de lluvia y escurrimiento tomados en el campo a lo largo del temporal, y a partir del monitoreo de la infiltración de un pozo de recarga. Durante estas campañas, también se evaluará la concentración de contaminantes de los escurrimientos y las mediciones se aplicarán al modelo para inferir los puntos de generación de contaminantes. Así se llegará a un modelo hidrogeológico robusto que nos permita plantear un plan de manejo para la conducción e infiltración de las aguas pluviales de la zona de estudio, elaborar una propuesta de saneamiento y contar con una metodología que permitiría intervenir otras microcuencas que presenten condiciones similares