Determining the value contribution of emicizumab (Hemlibra®) for the prophylaxis of haemophilia A with inhibitors in Spain by multi-criteria decision analysis

Haemophilia A; Inhibitors; Drug valueHemofilia A; Inhibidores; Valores del medicamentoHemofília A; Inhibidors; Valors del medicamentPatients with moderate to severe haemophilia A are at a higher risk of developing FVIII inhibitors that require the use of more costly and less effective treatments. The objective of this study was to determine the value of emicizumab for the prophylaxis of haemophilia A with inhibitors compared to the current therapeutic alternatives, activated prothrombin complex concentrate and recombinant factor VIIa through reflective Multi-Criteria Decision Analysis. The EVIDEM framework adapted to orphan drugs and weighted by a sample of 98 national and regional Spanish evaluators was used. Two structured evidence matrices were developed: emicizumab against activated prothrombin complex concentrate and emicizumab against recombinant factor VIIa. A multidisciplinary team of haemophilia experts rated each of the criteria. Mean and standard deviation were calculated by each criterion and discussed among all participants. Haemophilia A with inhibitors was perceived as a severe disease with high unmet needs. Emicizumab was rated with higher efficacy, therapeutic benefit and quality of life than comparators. When administered alone for the prevention of bleeding events, emicizumab had slightly better safety and tolerability profile than activated prothrombin complex concentrate and similar with recombinant factor VIIa. The inclusion of emicizumab in clinical practice guidelines was valued positively by the members of the panel. Overall, value of emicizumab was higher than activated prothrombin complex concentrate and recombinant factor VIIa, mostly because of efficacy and therapeutic benefit in reducing treated haemorrhages. Reflective Multi-Criteria Decision Analysis has proven to be a feasible method to determine the value contribution of comparative therapies in haemophilia.This work was supported by Hoffmann-La Roche

La Personería Jurídica y el rol de la mujer en la Empresa Familiar.

La estructura legal de las empresas familiares es la forma de organización jurídica que permite la gestión administrativa y fuente primordial de resolución de conflictos que pueden existir en una empresa familiar. El estudio de la empresa familiar y su estructura se centra en el estudio de la personería jurídica que genera riesgos para la propiedad de la familia y es motivo de conflictos dentro de la organización. Al mismo tiempo se encuentra que los conflictos son solucionados dentro de la familia con la participación principal de la madre dentro de ellos, de los conflictos que llegan a instancias judiciales el riesgo de rompimiento de lazos familiares es más grande que la desaparición de la empresa familiar.The legal structure of family businesses is the form of legal organization that allows administrative management and main source of conflict resolution that can exist in a family business. The study of family business and its structure focuses on the study of legal personality that creates risks for the property of the family and is a source of conflict within the organization. At the same time, it is discovered that conflicts are solved within the family having the mother as the main part of it, besides the risk of breaking of family ties is higher than the disappearance of the family business when conflicts come to courts

La Personería Jurídica y el rol de la mujer en la Empresa Familiar.

La estructura legal de las empresas familiares es la forma de organización jurídica que permite la gestión administrativa y fuente primordial de resolución de conflictos que pueden existir en una empresa familiar. El estudio de la empresa familiar y su estructura se centra en el estudio de la personería jurídica que genera riesgos para la propiedad de la familia y es motivo de conflictos dentro de la organización. Al mismo tiempo se encuentra que los conflictos son solucionados dentro de la familia con la participación principal de la madre dentro de ellos, de los conflictos que llegan a instancias judiciales el riesgo de rompimiento de lazos familiares es más grande que la desaparición de la empresa familiar.The legal structure of family businesses is the form of legal organization that allows administrative management and main source of conflict resolution that can exist in a family business. The study of family business and its structure focuses on the study of legal personality that creates risks for the property of the family and is a source of conflict within the organization. At the same time, it is discovered that conflicts are solved within the family having the mother as the main part of it, besides the risk of breaking of family ties is higher than the disappearance of the family business when conflicts come to courts

Rapid evolutionary change of common bean (Phaseolus vulgaris L) plastome, and the genomic diversification of legume chloroplasts

<p>Abstract</p> <p>Background</p> <p>Fabaceae (legumes) is one of the largest families of flowering plants, and some members are important crops. In contrast to what we know about their great diversity or economic importance, our knowledge at the genomic level of chloroplast genomes (cpDNAs or plastomes) for these crops is limited.</p> <p>Results</p> <p>We sequenced the complete genome of the common bean (<it>Phaseolus vulgari</it>s cv. Negro Jamapa) chloroplast. The plastome of <it>P. vulgaris </it>is a 150,285 bp circular molecule. It has gene content similar to that of other legume plastomes, but contains two pseudogenes, <it>rpl</it>33 and <it>rps</it>16. A distinct inversion occurred at the junction points of <it>trn</it>H-GUG/<it>rpl</it>14 and <it>rps</it>19/<it>rps</it>8, as in adzuki bean <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. These two pseudogenes and the inversion were confirmed in 10 varieties representing the two domestication centers of the bean. Genomic comparative analysis indicated that inversions generally occur in legume plastomes and the magnitude and localization of insertions/deletions (indels) also vary. The analysis of repeat sequences demonstrated that patterns and sequences of tandem repeats had an important impact on sequence diversification between legume plastomes and tandem repeats did not belong to dispersed repeats. Interestingly, <it>P. vulgaris </it>plastome had higher evolutionary rates of change on both genomic and gene levels than <it>G. max</it>, which could be the consequence of pressure from both mutation and natural selection.</p> <p>Conclusion</p> <p>Legume chloroplast genomes are widely diversified in gene content, gene order, indel structure, abundance and localization of repetitive sequences, intracellular sequence exchange and evolutionary rates. The <it>P. vulgaris </it>plastome is a rapidly evolving genome.</p

Design of a charge regulator for application in an isolated micro grid with photovoltaic generation

This paper presents the design of a charge regulator operating in an isolated micro grid with photovoltaic generation. The converter selected for this application is a SEPIC with a MPPT algorithm for the cases in which the energy demand is greater than the energy available. The algorithm is able to modify its point of maximum power, in order to perform the recharging and supply of power to the battery bank of the system (isolated microgrid) and a group of charges set at a level of determined of voltage. Finally, the results of the tests carried out are presented and the conclusions are given.This paper presents the design of a charge regulator operating in an isolated micro grid with photovoltaic generation. The converter selected for this application is a SEPIC with a MPPT algorithm for the cases in which the energy demand is greater than the energy available. The algorithm is able to modify its point of maximum power, in order to perform the recharging and supply of power to the battery bank of the system (isolated microgrid) and a group of charges set at a level of determined of voltage. Finally, the results of the tests carried out are presented and the conclusions are given

Design of a charge regulator for application in an isolated micro grid with photovoltaic generation

This paper presents the design of a charge regulator operating in an isolated micro grid with photovoltaic generation. The converter selected for this application is a SEPIC with a MPPT algorithm for the cases in which the energy demand is greater than the energy available. The algorithm is able to modify its point of maximum power, in order to perform the recharging and supply of power to the battery bank of the system (isolated microgrid) and a group of charges set at a level of determined of voltage. Finally, the results of the tests carried out are presented and the conclusions are given.This paper presents the design of a charge regulator operating in an isolated micro grid with photovoltaic generation. The converter selected for this application is a SEPIC with a MPPT algorithm for the cases in which the energy demand is greater than the energy available. The algorithm is able to modify its point of maximum power, in order to perform the recharging and supply of power to the battery bank of the system (isolated microgrid) and a group of charges set at a level of determined of voltage. Finally, the results of the tests carried out are presented and the conclusions are given

Actividad física, ejercicio y deporte en la lucha contra la obesidad infantil y juvenil

El propósito del presente documento es proponer desde el grupo de expertos en ejercicio físico y salud de EXERNET (Red Española de Investigación en Ejercicio Físico y Salud) una serie de recomendaciones sobre la práctica de la actividad física y deportiva que a nivel individual, familiar e institucional ayuden a prevenir y tratar la obesidad infantil y juvenil, basadas en la evidencia científi ca actual

Impact of hospitalization on nutritional status in persons aged 65 years and over (NUTRIFRAG Study): Protocol for a prospective observational study

Background: Malnutrition is a recurring problem that has become more relevant in recent years. The aim of this study is to assess the risk of malnutrition and nutritional status on admission and its evolution until discharge in patients aged 65 and over admitted to medical and surgical hospitalization units in hospitals of the Spanish National Health System. Methods: Prospective observational study to be carried out in the medical-surgical hospitalization units of 9 public hospitals between 01/09/2022 and 31/12/2024. Using consecutive sampling, a total of 4077 patients will be included (453 in each hospital). Variables included are related to the care process, functionality, cognition and comorbidity, risk profile, nutritional status and dysphagia; as well as frailty, dietary quality and contextual variables. The incidence of risk of malnutrition, undernutrition and dysphagia during the care process and at discharge will be calculated. The association with risk factors will be studied with logistic regression models and multivariate Cox regression models. In addition, an analysis of participants' satisfaction with food services will be carried out. The study was approved by the Ethics and Research Committee on 30/09/2020, approved for funding on 02/12/2021 and with registration number RBR-5jnbyhk in the Brazilian clinical trials database (ReBEC) for observational studies. Discussion: Some studies address nutritional status or dysphagia in older people in various care settings. However, there is a lack of large sample studies including both processes of the impact of hospitalization. The results of the project will provide information on the incidence and prevalence of both pathologies in the study subjects, their associated factors and their relationship with the average length of stay, mortality and early readmission. In addition, early detection of a problem such as malnutrition related to the disease and/or dysphagia during a hospital stay will favor the action of professionals to resolve both pathologies and improve the health status of patients.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "PI21/00738" and co-funded by the European Union. The funders did not and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation

BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins) exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta) in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII), and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs