"Nicotiana tabacum" L. cv Xanthi como sistema heterólogo para la producción de lactógeno placentario humano (hPL)

152 p. : il., col.El lactógeno placentario humano (hPL) es una hormona polipeptídica que forma parte de la pequeña lista de factores del crecimiento capaces de tratar la diabetes tipo 1 mediante el transplante de islotes humanos. Esta hormona tiene la capacidad de mejorar la supervivencia de los islotes humanos antes y/o después de su transplante. En este trabajo se aborda la producción de hPL en sistemas heterólogos vegetales basados en Nicotiana tabacum cv Xanthi. El cDNA del hPL ha sido introducido en el genoma vegetal del tabaco mediante Agrobacterium tumefaciens, portando los vectores de expresión pNEKhPL1 y pNEKhPL2. La actividad transcripcional se ha confirmado mediante PCR en tiempo real, y los niveles de producción de hPL en plantas transgénicas han alcanzado el 1% de la cantidad de proteína total soluble (PTS). Tras purificar la proteína mediante cromatografía de afinidad a iones metálicos, se ha testado su actividad biológica. Los ensayos in vitro de proliferación y señalización intracelular han demostrado que la proteína producida en plantas mantiene su actividad intacta, y por lo tanto, que las plantas son capaces de producir la hormona funcional. En este trabajo también se han caracterizado la estabilidad de la proteína hPL a lo largo del ciclo de vida del tabaco, y su transmisión a la siguiente generación. La cantidad de proteína recombinante en las hojas jóvenes de las plantas cultivadas en el invernadero ha sufrido un 26% de disminución tras 90 días de cultivo, obteniendo el máximo de proteína a los 30 días. La progenie de plantas pNEKhPL2 han alcanzado el 1.1% de la PTS. También se ha analizado la producción de hPL en callos obtenidos a partir de tejido foliar de plantas transgénicas, que se han utilizado para establecer suspensiones celulares. En este sistema se han obtenido 280.5 µg l-1 de hPL total demostrando que tanto las plantas como las suspensiones son sistemas idóneos para producir hPL recombinant

Estrategia diagnóstica eficiente en la sospecha de sobrecarga férrica

146 p.La elevación de los marcadores séricos del metabolismo férrico es un problema muy frecuente. Existen algoritmos para su manejo pero ninguno se ha realizado en base a hechos clínicos sino que sea basado en consenso de expertos. El objetivo principal fue crear y validar un algoritmo diagnóstico efectivo y eficiente de alta sobrecarga férrica en los pacientes con sobrecarga bioquímica de hierro. Métodos: Se realizaron dos fases, una fase de derivación o creación del algoritmo y una fase de validación del algoritmo. El diseño empleado fue el de un corte transversal de una cohorte retrospectiva para la derivación del algoritmo y un corte transversal de una cohorte prospectiva para la validación del algoritmo. Los sujetos del estudio fueron pacientes consecutivos remitidos por los servicios de hematología, digestivo y medicina interna con sobrecarga bioquímica de hierro (ferritina y/o IST) confirmada en una segunda extracción a los que se les realizan pruebas genéticas y una RM 1,5 teslas para la medición de la concentración hepática de hierro. Resultados: El algoritmo con los puntos de corte de la OMS, permite descartar alta sobrecarga de hierro hepático en el 70% de la población con la ferritina y el IST con un valor predictivo negativo muy alto (99%). La ferritina, el IST y la mutación C282Y Hmz confirman alta sobrecarga de Hierro hepático en un 3% con un valor predictivo positivo del 78%. En 1 de cada 4 pacientes habría que hacer RM

Estrategia diagnóstica eficiente en la sospecha de sobrecarga férrica

146 p.La elevación de los marcadores séricos del metabolismo férrico es un problema muy frecuente. Existen algoritmos para su manejo pero ninguno se ha realizado en base a hechos clínicos sino que sea basado en consenso de expertos. El objetivo principal fue crear y validar un algoritmo diagnóstico efectivo y eficiente de alta sobrecarga férrica en los pacientes con sobrecarga bioquímica de hierro. Métodos: Se realizaron dos fases, una fase de derivación o creación del algoritmo y una fase de validación del algoritmo. El diseño empleado fue el de un corte transversal de una cohorte retrospectiva para la derivación del algoritmo y un corte transversal de una cohorte prospectiva para la validación del algoritmo. Los sujetos del estudio fueron pacientes consecutivos remitidos por los servicios de hematología, digestivo y medicina interna con sobrecarga bioquímica de hierro (ferritina y/o IST) confirmada en una segunda extracción a los que se les realizan pruebas genéticas y una RM 1,5 teslas para la medición de la concentración hepática de hierro. Resultados: El algoritmo con los puntos de corte de la OMS, permite descartar alta sobrecarga de hierro hepático en el 70% de la población con la ferritina y el IST con un valor predictivo negativo muy alto (99%). La ferritina, el IST y la mutación C282Y Hmz confirman alta sobrecarga de Hierro hepático en un 3% con un valor predictivo positivo del 78%. En 1 de cada 4 pacientes habría que hacer RM

Prevalence study of intermittent hormonal therapy of Prostate Cancer patients in Spain

Background: Although intermittent androgen deprivation therapy was introduced many years ago to improve patients' quality of life with the same carcinologic efficiency as continuous hormonal therapy, recent data suggest that intermittency could be underutilised. This study aims to estimate the prevalence of prostate cancer patients receiving intermittent androgen deprivation therapy in Spain. Methods: A retrospective, longitudinal study was conducted using electronic drug dispensation data from four Spanish autonomous communities, which encompass 17.23 million inhabitants (36.22% of the total population in Spain). We estimated intermittent androgen therapy use (%IAD) and the prevalence of patients under intermittent androgen therapy in reference to the total number of PC patients using hormonal therapy (P IAD) and stratified by region. Other outcome variables included the pharmaceutical forms dispensed and the total direct annual expenditure on androgen deprivation therapy-associated medications. Results: A total of 863,005 dispensations corresponding to a total of 65,752 men were identified, treated with either luteinizing hormone-releasing hormone (LHRH) analogues (353,162) administered alone or in combination with anti-androgens (509,843). Overall, the mean (±SD) age of the patients was 76.9 (±10.4) years. Results revealed that the mean annual P IAD along the study was 6.6% in the total population studied, and the overall %IAD during the five-year study period was 5.6%. The mean cost of hormonal therapy per year was 25 million euros for LHRH analogues and 6.3 million euros for anti-androgens. Conclusions: Few prostate cancer patients in Spain use the intermittent androgen deprivation therapy suggesting underutilization of a perfectly valid option for a significant proportion of patients, missing the opportunity to improve their quality of life and to reduce costs for the National Health Service with comparable overall survival rates than continuous therapy.</p

Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights

Composite endpoints; Correlation; Sample sizePuntos finales compuestos; Correlación; Tamaño de la muestraPunts finals compostos; Correlació, Grandària de la mostraBackground The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE). Methods A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015–2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs. Results Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between − 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%. Conclusions The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE.Intramural CIBER-ESP PR22 from the Center for Biomedical Research in Epidemiology and Public Health Network (CIBERESP)

Piloting the informed health choices resources in Barcelona primary schools: A mixed methods study

IntroductionThe main objective of the Informed Health Choices (IHC) project is to teach people to assess treatment claims and make informed health choices. For this purpose, the IHC learning resources were developed for primary school children. The aim of this study is to explore students' and teachers' experience when using the IHC resources in primary schools in Barcelona (Spain). MethodsWe conducted a mixed methods study for piloting the IHC resources in a convenience sample of primary schools in Barcelona. The intervention included a workshop with teachers, and nine lessons with students. We collected data using multiple approaches. We performed quantitative and qualitative analyses, and integrated the findings in a joint display. Finally, we formulated recommendations for using the IHC resources in this setting. ResultsTwo schools, with a total of 143 students in 4th and 5th grade and six teachers, participated in the study. One school followed the suggested IHC teaching plan and competed all the lessons; the other school modified the plan substantially and did not complete all the lessons. Overall, students and teachers from both schools understood, were interested in, and were able to apply the content of the lessons. During the lessons, the textbook was useful for students; nevertheless, for the teachers, the usefulness of the IHC resources was variable. Teachers adapted the IHC resources to increase student participation and used Information and Communications Technologies tools. We observed more facilitators than barriers to teach the lessons. The teachers suggested some ideas to improve the lessons based on activities they developed and implemented. The integration analysis showed great convergence of the quantitative and qualitative findings. We propose seven recommendations for using the IHC resources in this setting. ConclusionsStudents and teachers from primary schools in Barcelona showed a positive experience when using IHC resources; however, these resources should be adapted to promote classroom participation

Learning to make informed health choices: Protocol for a pilot study in schools in Barcelona.

--- - b: - "Introduction:" - "Methods:" - "Ethical considerations:" sup: - th - th i: - ad hoc content: - " The Informed Health Choices (IHC) project has developed learning resources to teach primary school children (10 to 12-year-olds) to assess treatment claims and make informed health choices. The aim of our study is to explore both the students' and teachers' experience when using these resources in the context of Barcelona (Spain). " - " During the 2019-2020 school year, we will conduct a pilot study with 4 " - " and 5 " - "-year primary school students (9 to 11-year-olds) from three schools in Barcelona. The intervention in the schools will include: 1) assessment of the IHC resources by the teachers before the lessons, 2) non-participatory observations during the lessons, 3) semi-structured interviews with the students after a lesson, 4) assessment of the lessons by the teachers after a lesson, 5) treatment claim assessment by the students at the end of the lessons, and 6) assessment of the IHC resources by the teachers at the end of the lessons. We will use " - " questionnaires and guides to register the data. We will perform a quantitative and qualitative analysis of the data to explore understandability, desirability, suitability, usefulness, facilitators and barriers of the resources. The most relevant results will be discussed and some recommendations on how to use, how to adapt (if needed), and how to implement the IHC resources to this context will be agreed. The findings of the contextualization activities could inform the design of a cluster-randomised trial, to determine the effectiveness of the IHC resources in this context prior to scaling-up its use. " - " The study protocol has obtained an approval exemption from the Ethics Committee of the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain).