Profiling of the genetic features of patients with breast, ovarian, colorectal and extracolonic cancers: Association to CHEK2 and PALB2 germline mutations.

BACKGROUND AND AIMS: Cancer predisposition goes beyond BRCA and DNA Mismatch Repair (MMR) genes since multi-gene panel testing has become the routine diagnostic tool for hereditary cancer suspicion (HCS) cases. CHEK2 and PALB2 are some of the foremost-mutated non-BRCA/MMR actionable genes in families with a significant familial aggregation. Therefore, the purpose of this work is to unravel which tumours other than breast, ovary or colorectal display the patients. MATERIALS AND METHODS: We have analysed 528 probands that meet the inclusion criteria for Hereditary Breast and Ovarian Cancer and Lynch Syndrome established by our Hereditary Cancer Regional Program with a customized 35 genes-panel by using Ion Torrent™ Technology. RESULTS: We have identified pathogenic variants (PVs) in 61 families (1.55%), of which more than half (31 probands) harboured PVs in CHEK2 and PALB2 genes. Ours results reveal that not only were PVs CHEK2 and PALB2 carriers more likely to have family history of cancer not limited to breast, ovarian or colorectal cancers, but also they are prone to other extracolonic cancers, noteworthy endometrial and gastric cancers. CONCLUSIONS: Multigene panel testing improves the chance of finding PVs in actionable genes in families with HCS. In addition, the coexistence of variants should be recorded to implement a polygenic risk algorithm that might explain the missing heritability in the aforementioned families.

Enrichment of effector memory T cells in the CD4 and CD8 T cell compartment during chronic graft versus host disease in children.

BACKGROUND: During allogeneic Hematopoietic stem cell transplantation (HSCT), frequent pathological scenarios include graft versus host disease (GVHD) and viral infections. We hypothesized if exogenous stimulus as alloantigen and viral antigens might impact on central and effector memory T cells in pediatric recipients. PATIENTS AND METHODS: Subjects included 21 pediatric recipients and 20 healthy children (control group). Peripheral blood samples of patients were collected along the first 712 days post-HSCT. T cell phenotyping of naïve, central, and effector memory T cells (TCMs and TEMs, respectively) was conducted using flow cytometry. Viral nucleic acids were detected using real-time PCR. RESULTS: T cell reconstitution was not reached after 1 year post-HSCT. Chronic GVHD was associated with increased numbers of naïve CD4 T cells (p < 0.05) as well as an increase in TEM and TCM cells of the CD4 (p < 0.0001 and p < 0.05, respectively) and CD8 T cell TEM (p < 0.0001). and TCM (p < 0.001) populations too. Moreover, BK and Epstein-Barr viruses were the main viral pathogens detected (<104 copies), which were associated with a decrease in all T cell compartments. CONCLUSION: During chronic GVHD, alloantigen persistence generates TEM cell enrichment among CD4 and CD8 T cells, and viral infections are associated with deficient recovery of T cells after HSCT.

Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?

The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH) for both BRCA1/BRCA2, one ovarian cancer case DH for BRCA1/RAD51C, and another breast and colorectal cancer who is DH for BRCA2/PMS2 were identified in our cohort. Ages at diagnosis and severity of disease in BRCA1/BRCA2 DH resembled BRCA1 single-carrier features. Similarly, the co-existence of the BRCA2 and PMS2 mutations prompted the development of breast and colorectal cancer in the same patient. The first BRCA1/BRCA2 DH was identified by HA-based and Sanger sequencing (1 of 623 families with BRCA PVs). However, this ratio has increased up to 2.9% (1 DH carrier vs. 103 single PV carriers) since using a custom 35-cancer gene on-demand panel. The type of cancer developed in each DH patient was consistent with the independently inherited condition, and the clinical outcome was no worse than in patients with single BRCA1 mutations. Therefore, the clinical impact, especially in patients with two hereditary syndromes, lies in genetic counseling tailor-made for each family based on the clinical guidelines for each syndrome. The number of DH is expected to be increased in the future as a result of next generation sequencing routines.

From virtual screening hits targeting a cryptic pocket in BACE-1 to a nontoxic brain permeable multitarget anti-Alzheimer lead with disease-modifying and cognition-enhancing effects.

Starting from six potential hits identified in a virtual screening campaign directed to a cryptic pocket of BACE-1, at the edge of the catalytic cleft, we have synthesized and evaluated six hybrid compounds, designed to simultaneously reach BACE-1 secondary and catalytic sites and to exert additional activities of interest for Alzheimer's disease (AD). We have identified a lead compound with potent in vitro activity towards human BACE-1 and cholinesterases, moderate Aß42 and tau antiaggregating activity, and brain permeability, which is nontoxic in neuronal cells and zebrafish embryos at concentrations above those required for the in vitro activities. This compound completely restored short- and long-term memory in a mouse model of AD (SAMP8) relative to healthy control strain SAMR1, shifted APP processing towards the non-amyloidogenic pathway, reduced tau phosphorylation, and increased the levels of synaptic proteins PSD95 and synaptophysin, thereby emerging as a promising disease-modifying, cognition-enhancing anti-AD lead.

Is acute lymphoblastic leukemia with mature B-cell phenotype and KMT2A rearrangements a new entity? A systematic review and meta-analysis.

The association between mature B-cell phenotype and KMT2A rearrangements in acute lymphoblastic leukemia is a very rare finding. It identifies a group of patients with similar clinical and biological characteristics that clearly differs from the entity B-cell lymphoblastic leukemia/lymphoma with t(v;11q23)/KMT2A-rearranged, which typically presents an immature pro B-cell phenotype. We describe the clinical-biological characteristics and disease outcome of three pediatric ALL patients with these features treated at our institution, and review 28 cases described in the literature. Most cases occur in children under 2 years-old, presenting a mature B-cell phenotype that uniformly expresses cytoplasmic and surface IgM with lambda light chain restriction, with heterogeneous co-expression of immaturity antigens. Patients do not have MYC rearrangements and all show KMT2A abnormalities, with 76% presenting t(9;11)(p21;q23)/MLLT3-KMT2A. These patients have an unfavorable clinical outcome and a 48% relapse rate. In-depth knowledge of this disease entity is needed to improve outcome.

Incidence and costs of cardiovascular events in Spanish patients with type 2 diabetes mellitus: a comparison with general population, 2015.

INTRODUCTION: Cardiovascular (CV) disease affects a high percentage of patients with type 2 diabetes mellitus (T2DM), especially in the hospital setting, impacting on mortality, complications, quality of life and use of health resources. The aim of this study was to estimate the incidence, mean length of hospital stay (LOHS) and costs attributable to hospital admissions due to CV events in patients with T2DM versus patients without diabetes mellitus (non-DM) in Spain. RESEARCH DESIGN AND METHODS: Retrospective observational study based on the Spanish National Hospital Discharge Database for 2015. Hospital admissions for patients aged ≥35 years with a diagnosis of CV death, non-fatal acute myocardial infarction (AMI), non-fatal stroke, unstable angina, heart failure and revascularization were evaluated. The International Classification of Diseases, Ninth Revision (250.x0 or 250.x2) coding was used to classify records of patients with T2DM. For each CV complication, the hospital discharges of the two groups, T2DM and non-DM, were precisely matched and the number of hospital discharges, patients, LOHS and mean cost were quantified. Additional analyses assessed the robustness of the results. RESULTS: Of the 276 925 hospital discharges analyzed, 34.71% corresponded to patients with T2DM. A higher incidence was observed in all the CV complications studied in the T2DM population, with a relative risk exceeding 2 in all cases. The mean LOHS (days) was longer in the T2DM versus the non-DM group for: non-fatal AMI (7.63 vs 7.02, p<0.001), unstable angina (5.11 vs 4.78, p=0.009) and revascularization (7.96 vs 7.57, p<0.001). The mean cost per hospital discharge was higher in the T2DM versus the non-DM group for non-fatal AMI (€6891 vs €6876, p=0.029) and unstable angina (€3386 vs €3304, p<0.001). CONCLUSIONS: Patients with T2DM had a higher incidence and number of hospital admissions per patient due to CV events versus the non-DM population. This generates a significant clinical and economic burden given the longer admission stay and higher costs associated with some of these complications.

A comprehensive custom panel evaluation for routine hereditary cancer testing: improving the yield of germline mutation detection.

BACKGROUND: In the context of our Regional Program of Hereditary Cancer, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our standard diagnostic approach focuses on sequencing a few classic high-risk genes, a method that frequently renders uninformative genetic results. This study aims to examine the improved yield offered by an On-Demand panel. METHODS: We designed an On-Demand panel for the analysis of 35-genes associated with inherited cancer susceptibility in a total of 128 cases of Hereditary Breast and Ovarian Cancer (HBOC) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC). RESULTS: Eighteen deleterious mutations were detected, in both routinely (BRCA2, MLH1, MSH2, PMS2) and non-routinely (ATM, BLM, BRIP1, CHEK2, MUTYH) tested genes. The screening extended to 35 genes rendered by patients carrying several- up to 6-Variants of Unknown Significance (VUS). Moreover, we confirmed the splicing disruption at RNA level for a not previously reported BRIP1 splicing mutation. Using an On-Demand panel, we identified 18 pathogenic mutation carriers, seven of which would have gone unnoticed with traditional analysis. CONCLUSIONS: Our results reinforce the utility of NGS gene panels in the diagnostic routine to increase the performance of genetic testing, especially in individuals from families with overlapping cancer phenotypes.

Natural killer cell reconstitution after hematopoietic stem-cell transplantation in children.

INTRODUCTION: After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cells reconstitution is the main barrier against viral infections. OBJECTIVE: To determine that the knowledge on the kinetics of NK cell reconstitution after HSCT contributes to transplant efficient monitoring, which increases the possibility of its success. METHOD: Twenty-one patients undergoing HSCT were included, as well as a control group of clinically healthy individuals. At different time points after transplantation (range of 21 to 670 days), CD3- CD16+ CD56+ NK cells were quantified by flow cytometry in peripheral blood samples. RESULTS: NK cell recovery occurs at three to six months and 10 to 12 months post-transplantation; their number was significantly lower (in comparison with the control group) in the rest of the monitoring time. CONCLUSIONS: The first period of NK cell recovery occurs between three and six months after transplantation. Reconstitution is transient and the number of NK cells varies in the first years.

INTRODUCCIÓN: Después de un trasplante de células progenitoras hematopoyéticas (TCPH), la reconstitución de las células natural killer (NK) es la principal barrera contra las infecciones virales. OBJETIVO: Determinar que el conocimiento sobre la cinética de la reconstitución de las células NK posterior al TCPH contribuye a un eficiente monitoreo del trasplante, lo que incrementa la posibilidad de éxito de este. MÉTODO: Se incluyeron 21 pacientes sometidos a TCPH, así como un grupo control de individuos clínicamente sanos. En diferentes momentos después del trasplante (intervalo de 21 a 670 días), mediante citometría de flujo se cuantificaron las células NK CD3− CD16+ CD56+ en muestras de sangre periférica. RESULTADOS: La recuperación de las células NK ocurre a los tres a seis meses y a los 10 a 12 meses postrasplante; su número fue significativamente menor (en comparación con el grupo control) en el tiempo restante del monitoreo. CONCLUSIONES: El primer periodo de recuperación de las células NK ocurre entre los tres y seis meses posteriores al trasplante. La reconstitución es transitoria y el número de células NK varía en los primeros años.

Reconstitución de células natural killer después del trasplante de células progenitoras hematopoyéticas en niños / Natural killer cell reconstitution after hematopoietic stem-cell transplantation in children

Resumen Introducción: Después de un trasplante de células progenitoras hematopoyéticas (TCPH), la reconstitución de las células natural killer (NK) es la principal barrera contra las infecciones virales. Objetivo: Determinar que el conocimiento sobre la cinética de la reconstitución de las células NK posterior al TCPH contribuye a un eficiente monitoreo del trasplante, lo que incrementa la posibilidad de éxito de este. Método: Se incluyeron 21 pacientes sometidos a TCPH, así como un grupo control de individuos clínicamente sanos. En diferentes momentos después del trasplante (intervalo de 21 a 670 días), mediante citometría de flujo se cuantificaron las células NK CD3− CD16+ CD56+ en muestras de sangre periférica. Resultados: La recuperación de las células NK ocurre entre los tres y seis meses y entre los 10 y 12 meses postrasplante; su número fue significativamente menor (en comparación con el grupo control) en el tiempo restante del monitoreo. Conclusiones: El primer periodo de recuperación de las células NK ocurre entre los tres y seis meses posteriores al trasplante. La reconstitución es transitoria y el número de células NK varía en los primeros años.

Abstract Introduction: After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cells reconstitution is the main barrier against viral infections. Objective: To determine that the knowledge on the kinetics of NK cell reconstitution after HSCT contributes to transplant efficient monitoring, which increases the possibility of its success. Method: Twenty-one patients undergoing HSCT were included, as well as a control group of clinically healthy individuals. At different time points after transplantation (range of 21 to 670 days), CD3- CD16+ CD56+ NK cells were quantified by flow cytometry in peripheral blood samples. Results: NK cell recovery occurs at three to six months and 10 to 12 months post-transplantation; their number was significantly lower (in comparison with the control group) in the rest of the monitoring time. Conclusions: The first period of NK cell recovery occurs between three and six months after transplantation. Reconstitution is transient and the number of NK cells varies in the first years.

Cost of early-stage mycosis fungoides treatments in Spain.

AIM: To identify the most common therapeutic options for the treatment of early-stage mycosis fungoides in Spain, quantify their associated healthcare resource use and costs. METHODS: After reviewing the literature, a panel of 6 Spanish clinical dermatologists validated the treatments and healthcare resource use through a structured questionnaire. Individual responses were collected, analyzed and presented into a face-to-face meeting in order to reach a consensus. Cost categories considered were: drug acquisition and administration, photo/radiotherapy session and maintenance, clinical follow-up visits and laboratory tests. Costs were expressed in euros from 2018. The Spanish National Health System perspective was considered, taking into account direct health costs and time horizons of 1, 3 and 6 months. RESULTS: Costs for the skin-directed treatments (SDT) assessed at 1, 3 and 6 months, were: Topical carmustine [€6,593.36, €19,780.09 and €27,592.78]; Phototherapy with psoralens and ultraviolet A light (PUVA) [€1,098.68, €2,999.99 and €3,187.60]; Narrow-band ultraviolet B phototherapy [€1,657.47, €4,842.10 and €4,842.10]; Total skin electron beam therapy (TSEBT) [€6,796.45, €7,913.34 and €7,913.34]. Cost for topical corticosteroids, being considered an adjuvant option, were €17.16, €51.49 and €102.97. Costs for the assessed systemic treatments alone or in combination with SDT at 1, 3 and 6 months, were: Systemic retinoids [€2,026.03, €5,206.63 and €7,426.42]; Systemic retinoids + PUVA phototherapy [€3,066.50, €8,271.26 and €10,046.58]; Interferon alfa + PUVA phototherapy [€1,541.09, €5,167.57 and €6,404.55]. CONCLUSION: According to the Spanish clinical practice, phototherapies in monotherapy were the treatments with the lowest associated costs regardless of the time horizon considered. TSEBT turned out as the treatment with the highest associated costs when considering 1 month. However, while considering 3 and 6 months the treatment with the highest associated costs was topical carmustine. The results of this analysis may provide critical information to measure the disease burden, to detect unmet medical needs and to advocate towards better treatments for this rare disease.

Impacto sobre entorno laboral de un proyecto de gestión de enfermería en el turno de noche / A Nursing Management Project's Impact on the Work Environment during the Night Shift

Introducción: Para garantizar los cuidados 24h en instituciones hospitalarias es esencial la existencia de Equipos de Enfermería cuya actividad se desarrolle en horario nocturno. Existen factores organizativos que provocan, entre los equipos nocturnos, la percepción de menos oportunidades de desarrollo profesional y menos atención institucional. Esto puede repercutir en la calidad de los cuidados e incluso en la salud de los profesionales. Las enfermeras líderes tienen la responsabilidad de crear y mantener un entorno laboral con influencia positiva. Objetivo: Evaluar un proyecto de gestión de enfermería mediante el impacto sobre la percepción del entorno laboral en el turno de noche. Métodos: Estudio casi-experimental pre-post, con intervención sobre la población. De una población de enfermeras del turno de noche n = 268 se obtuvo muestra n = 159. Se utilizó el instrumento "Practice Environment Scale of the Nursing Work Index", que permite evaluar y comparar factores del entorno de la práctica de enfermería. Se realizaron estadísticos univariables de tendencia central y dispersión, y estadísticos de contraste con significancia p < 0,05. Resultados: En el 41,94 por ciento de las cuestiones obtuvieron diferencias significativas, destacando el Factor 3 "Habilidad, liderazgo y apoyo a las enfermeras por parte de sus responsables". El valor medio global obtenido en la prueba PRE fue de 2,37 (IC95 por ciento 2,22 2,52) y la media global para el valor POST fue 2,49 (IC95 por ciento 2,34 2,95), con p = 0,0254. Conclusiones: La evaluación de un proyecto de gestión de enfermería mediante el impacto sobre la percepción del entorno laboral en turno de noche muestra mejoras con diferencias significativas(AU)

Introduction: To guarantee 24 hours of care in hospital institutions, the existence of nursing teams is essential whose activity is carried out at night. There are organizational factors that provoke, among night teams, the perception of fewer opportunities for professional development and less institutional attention. This can have an impact on the quality of care and even on the health of professionals. Leader nurses are responsible for creating and maintaining a positively influencing work environment. Objective: To evaluate a nursing management project through the impact on the perception about the work environment on the night shift. Methods: Pre-post quasi-experimental study carried out with intervention on the population. From a population of night-shift nurses (n=268), we obtained a sample of 268. The instrument "Practice Environment Scale of the Nursing Work Index" was used, which allows evaluating and comparing factors from the nursing practice setting. Univariate statistics of central tendency and dispersion were determined, as well as contrast statistics with significance p < 0.05. Results: In 41.94 percent of the questions, significant differences were obtained, highlighting factor 3 (nurses' skill, leadership and support by their heads). The global mean value obtained in the PRE test was 2.37 (95 percent CI, 2.22-2.52) and the global mean for the POST value was 2.49 (95 percent CI, 2.34-2.95), with p=0.0254. Conclusions: A nursing management project's evaluation through the impact on the perception about the work environment in the night shift shows improvements with significant differences(AU)

Determinación y cuantificación de subpoblaciones de linfocitos T y células natural killer en sangre periférica de individuos sanos por citometría de flujo / Detection and quantification of T-cell subpopulations and NK cells in peripheral blood from healthy individuals

Resumen Introducción: La determinación de las diferentes subpoblaciones de los linfocitos T en las diversas patologías y el monitoreo postratamiento ayuda a que el médico tome decisiones terapéuticas teniendo como referencia la cinética de los linfocitos T localizados en sangre periférica. Métodos: Se realizó la estandarización de un perfil de moléculas de superficie para la caracterización de subpoblaciones de linfocitos T: naïve, activados y de memoria, así como las células natural killer o asesinas naturales (CD3− CD56+) en sangre periférica de individuos clínicamente sanos. Resultados: Se identificaron las subpoblaciones de linfocitos: naïve (CD3+, CD4+ o CD8+, CD45RA+, CD62L+, CCR7+), activados (CD3+, CD4+ o CD8+, CD45RA+ o CD45RO+, CD69+ y/o CRTAM+), efectores (CD3+, CD4+ o CD8+, CD45RA+, CD62L−, CCR7−), de memoria central (CD3+, CD4+ o CD8+, CD45RO+, CD62L+, CCR7+) y de memoria efectora (CD3+, CD4+ o CD8+, CD45RO+, CD62L−, CCR7−) en las poblaciones de linfocitos T CD4+ y CD8+. Se integraron los datos obtenidos con estadística descriptiva (valores mínimos, valores máximos, media, mediana). Conclusiones: Este panel será de gran utilidad para monitorear pacientes en quienes se requiera valorar el estado inmunológico desde el punto de vista celular. Particularmente, puede apoyar en el seguimiento de los pacientes en los que se requiera evaluar la reconstitución inmunológica (componente celular de estirpe T).

Abstract Background: The knowledge of the participation of different subpopulations of T lymphocytes in various pathologies helps to make therapeutic decisions, having as reference the presence of the different subpopulations of the T lymphocytes associated with the disease. Methods: A profile standardization of surface molecules for the characterization of subpopulations of T cells was conducted: naïve, activated and memory, as well as natural killer (CD3− CD56+) cells in peripheral blood of clinically healthy individuals. Results: Naïve (CD3+, CD4+ or CD8+, CD45RA+, CD62L+, CCR7+), activated (CD3+, CD4+ or CD8+, CD45RA+ or CD45RO+, CD69+ and/or CRTAM+), effectors (CD3+, CD4+ o CD8+, CD45RA+, CD62L−, CCR7−), central memory (CD3+, CD4+ o CD8+, CD45RO+, CD62L+, CCR7+), memory effectors (CD3+, CD4+ or CD8+, CD62RO+, CD62L−, CCR7−) subpopulations were analyzed by flow cytometry. Descriptive statistics parameters were calculated (minimum values, maximum values, mean values, median). Conclusions: This panel can be very useful for monitoring patients in whom the immunological status from a cellular perspective is needed. Particularly, it can support the follow-up of patients who require an immunological reconstitution (T-cell component) evaluation.

Determinación y cuantificación de subpoblaciones de linfocitos T y células natural killer en sangre periférica de individuos sanos por citometría de flujo.

Background: The knowledge of the participation of different subpopulations of T lymphocytes in various pathologies helps to make therapeutic decisions, having as reference the presence of the different subpopulations of the T lymphocytes associated with the disease. Methods: A profile standardization of surface molecules for the characterization of subpopulations of T cells was conducted: naïve, activated and memory, as well as natural killer (CD3- CD56+) cells in peripheral blood of clinically healthy individuals. Results: Naïve (CD3+, CD4+ or CD8+, CD45RA+, CD62L+, CCR7+), activated (CD3+, CD4+ or CD8+, CD45RA+ or CD45RO+, CD69+ and/or CRTAM+), effectors (CD3+, CD4+ o CD8+, CD45RA+, CD62L-, CCR7-), central memory (CD3+, CD4+ o CD8+, CD45RO+, CD62L+, CCR7+), memory effectors (CD3+, CD4+ or CD8+, CD62RO+, CD62L-, CCR7-) subpopulations were analyzed by flow cytometry. Descriptive statistics parameters were calculated (minimum values, maximum values, mean values, median). Conclusions: This panel can be very useful for monitoring patients in whom the immunological status from a cellular perspective is needed. Particularly, it can support the follow-up of patients who require an immunological reconstitution (T-cell component) evaluation.

Introducción: La determinación de las diferentes subpoblaciones de los linfocitos T en las diversas patologías y el monitoreo postratamiento ayuda a que el médico tome decisiones terapéuticas teniendo como referencia la cinética de los linfocitos T localizados en sangre periférica. Métodos: Se realizó la estandarización de un perfil de moléculas de superficie para la caracterización de subpoblaciones de linfocitos T: naïve, activados y de memoria, así como las células natural killer o asesinas naturales (CD3− CD56+) en sangre periférica de individuos clínicamente sanos. Resultados: Se identificaron las subpoblaciones de linfocitos: naïve (CD3+, CD4+ o CD8+, CD45RA+, CD62L+, CCR7+), activados (CD3+, CD4+ o CD8+, CD45RA+ o CD45RO+, CD69+ y/o CRTAM+), efectores (CD3+, CD4+ o CD8+, CD45RA+, CD62L−, CCR7−), de memoria central (CD3+, CD4+ o CD8+, CD45RO+, CD62L+, CCR7+) y de memoria efectora (CD3+, CD4+ o CD8+, CD45RO+, CD62L−, CCR7−) en las poblaciones de linfocitos T CD4+ y CD8+. Se integraron los datos obtenidos con estadística descriptiva (valores mínimos, valores máximos, media, mediana). Conclusiones: Este panel será de gran utilidad para monitorear pacientes en quienes se requiera valorar el estado inmunológico desde el punto de vista celular. Particularmente, puede apoyar en el seguimiento de los pacientes en los que se requiera evaluar la reconstitución inmunológica (componente celular de estirpe T).

Comparative economic study of the use of corifollitropin alfa and daily rFSH for controlled ovarian stimulation in older patients: Cost-minimization analysis based on the PURSUE study.

This study presents an economic assessment of controlled ovarian stimulation in assisted reproductive technology procedures in Spain, comparing the use of corifollitropin alfa and various forms of recombinant follicle-stimulating hormone (rFSH) in women of advanced maternal age. A cost-minimization analysis (CMA) was performed to assess the cost per cycle of controlled controlled ovarian stimulation, including only direct costs associated with the stimulation phase. The CMA was based on the population characteristics, the protocol, and the results obtained from the PURSUE study, taking into account 9 days of controlled controlled ovarian stimulation and 300 IU rFSH/day. The primary analysis included pharmacological costs alone. Different scenarios were evaluated including various doses and possible additional days (0-5) for rFSH. For the alternative analyses, the total costs (direct pharmacological costs, costs of visits and follow-up tests, and any additional pharmacological costs) were considered in both the private and public sectors. Treatment with corifollitropin alfa resulted in a lower pharmacological cost compared with rFSH (€757.25 and €950.30, respectively), creating a saving of approximately -20%. The results of the scenario analyses showed that corifollitropin alfa reduced the pharmacological cost of controlled ovarian stimulation in comparison with daily administration of doses ≥ 250 IU rFSH (considering same daily dose for all days), regardless of the additional days required (7-12 days) (average -€223; range -€488 to -€44). In conclusion, in addition to the efficacy shown in the PURSUE study, the use of corifollitropin alfa results in a decrease in the direct costs associated with controlled ovarian stimulation in older women in Spain.

Spanish adaptation and validation of the supportive & palliative care indicators tool - SPICT-ESTM.

OBJECTIVE To culturally adapt and validate the SPICTTM to Spanish, which is a brief and simple tool to support a better identification of chronic patients who have palliative care needs. METHODS For this study, we designed a multicenter and national project between the centers of Galicia, Balearic Islands, and Andalusia. For the process of translation and cross-cultural adaptation of the SPICTTM to Spanish, we followed the steps proposed by Beaton et al. with successive translations and subsequent consensus of experts using the debriefing methodology. After the content validation was completed, the psychometric properties were validated. A prospective longitudinal study was designed with 188 patients from Galicia, the Balearic Islands, and Andalusia. The internal consistency and reliability of the test and retest was analyzed for 10 days by the same researcher. RESULTS For more than 90% of the participants of the SPICT-ESTM, it seems simple to be filled out, and they consider it written in an understandable language. The average time to apply the questionnaire without prior knowledge was 4 minutes and 45 seconds. To evaluate the internal consistency of the instrument, we used the Kuder-Richardson formula 20. Internal consistency is 0.71. The agreement index of the Kappa test is between 0.983 and 0.797 for the different items. CONCLUSIONS In this study, we demonstrate the equivalence of content with the original. In addition, the validation of the psychometric properties establishes that the SPICT-ESTM maintains adequate reliability and stability. If we add the satisfaction shown by the professionals and the ease of use, the SPICT-ESTM is an adequate tool for the identification of palliative patients with chronic diseases and palliative care needs.

Spanish adaptation and validation of the supportive & palliative care indicators tool - SPICT-ESTM / Adaptación y validación al español del cuestionario de identificación paliativa SPICT-ESTM

ABSTRACT OBJECTIVE To culturally adapt and validate the SPICTTM to Spanish, which is a brief and simple tool to support a better identification of chronic patients who have palliative care needs. METHODS For this study, we designed a multicenter and national project between the centers of Galicia, Balearic Islands, and Andalusia. For the process of translation and cross-cultural adaptation of the SPICTTM to Spanish, we followed the steps proposed by Beaton et al. with successive translations and subsequent consensus of experts using the debriefing methodology. After the content validation was completed, the psychometric properties were validated. A prospective longitudinal study was designed with 188 patients from Galicia, the Balearic Islands, and Andalusia. The internal consistency and reliability of the test and retest was analyzed for 10 days by the same researcher. RESULTS For more than 90% of the participants of the SPICT-ESTM, it seems simple to be filled out, and they consider it written in an understandable language. The average time to apply the questionnaire without prior knowledge was 4 minutes and 45 seconds. To evaluate the internal consistency of the instrument, we used the Kuder-Richardson formula 20. Internal consistency is 0.71. The agreement index of the Kappa test is between 0.983 and 0.797 for the different items. CONCLUSIONS In this study, we demonstrate the equivalence of content with the original. In addition, the validation of the psychometric properties establishes that the SPICT-ESTM maintains adequate reliability and stability. If we add the satisfaction shown by the professionals and the ease of use, the SPICT-ESTM is an adequate tool for the identification of palliative patients with chronic diseases and palliative care needs.

RESUMEN OBJETIVO Adaptar culturalmente al español y validar el SPICTTM, una herramienta breve y sencilla para apoyar una mejor identificación de pacientes crónicos que presentan necesidades de atención paliativa. MÉTODOS Para este estudio se diseñó un proyecto multicéntrico y nacional entre centros de Galicia, Islas Baleares y Andalucía. Para el proceso de traducción y adaptación transcultural del SPICTTM al castellano, se siguieron los pasos propuestos por Beaton et al. con sucesivas traducciones y posterior consenso de expertos mediante la metodología debriefing. Tras finalizar la validación de contenido se procedió a la validación de las propiedades psicométricas. Se diseñó un estudio longitudinal prospectivo en 188 pacientes de Galicia, Baleares y Andalucía. Fue analizada la consistencia interna y la fiabilidad test-retest a los 10 días por el mismo investigador. RESULTADOS A más del 90% de los participantes SPICT-ESTM les parece sencillo cumplimentarlo, y consideran que está escrito en un lenguaje comprensible. El tiempo medio para aplicar el cuestionario sin conocimiento previo fue de 4 minutos y 45 segundos. Para la evaluación de la consistencia interna del instrumento, se ha utilizado la fórmula Kuder Richardson 20. La consistencia interna es de 0,71. El índice de concordancia del test Kappa se encuentra entre 0,983 y 0,797 para los distintos ítems. CONCLUSIONES En este estudio se ha demostrado la equivalencia de contenido con el original. Además, la validación de las propiedades psicométricas establece que SPICT-ESTM mantiene una adecuada fiabilidad y estabilidad. Si añadimos la satisfacción mostrada por los profesionales y la facilidad de uso, SPICT-ESTM es una herramienta adecuada para la identificación de pacientes paliativos con enfermedades crónicas y necesidad de cuidados paliativos.

Assessing medication adherence in inflammatory bowel diseases. A comparison between a self-administered scale and a pharmacy refill index.

BACKGROUND: Medication non-adherence in inflammatory bowel disease (IBD) has a negative impact on disease outcome. Different tools have been proposed to assess non-adherence. We aimed to compare a self-administered scale and a pharmacy refill index as a reliable measure of medication adherence and to determine what factors are related to adherence. METHODS: Consecutive non-active IBD outpatients were asked to fill in the self-reported Morisky Medication Adherence Scale (MMAS-8) and the Beliefs about Medication Questionnaire (BMQ). Pharmacy refill data were reviewed from the previous three or six months and the medication possession ratio (MPR) was calculated. Non-adherence was defined as MMAS-8 scores < 6 or MPR < 0.8. RESULTS: Two-hundred and three patients were enrolled (60% ulcerative colitis, 40% Crohn's disease); 51% were men, and the mean age was 46.3 (14) years. Seventy-four per cent of patients were on monotherapy and 26% on combination therapy; altogether, 65% received mesalazine, 46% thiopurines and 16% anti-tumor necrosis factor alfa. Non-adherence rate assessed by MPR was 37% and 22.4% by MMAS-8. Receiver operator curve analysis using a MMAS-8 cut-off of six gave an area under the curve of 0.6 (95% CI 0.5-0.7), p = 0.001. This score had an 85% sensitivity and 34% specificity to predict medication non-adherence, with negative and positive predictive values of 57% and 70% respectively. High scores in the BMQ potential for harm of medication were significantly associated with MPR non-adherence (p = 0.01). CONCLUSION: The accuracy of MMAS-8 to identify medication non-adherence in inactive IBD outpatients in our setting is poor due to a low specificity and a negative predictive value. Psychosocial factors such as beliefs about medication seem to be related to IBD non-adherence.

Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

OBJECTIVE: To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain. METHODS: A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model. RESULTS: Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions. LIMITATIONS: The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously. CONCLUSIONS: Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab + mFOLFOX6 could be considered a cost-effective option compared with bevacizumab + mFOLFOX6 for the Spanish NHS.

Enfisema lobar congénito. Presentación de caso clínico / Congenital lobar emphysema. Clinical case

El enfisema lobar congénito (ELC), es una malformación pulmonar rara. Se trata de una sobre distención de uno o más lóbulos pulmonares. Las causas principales son la deficiencia del desarrollo del cartílago bronquial y la obstrucción bronquial de tipo valvular generalmente causada por estenosis bronquial idiopática. El tratamiento, en general es quirúrgico. Laboratorios de ingreso normales. Ecocardiografía: Dextro posición cardiaca en situs solitus por desplazamiento de una masa, CIV, FOP. Ecografía Diafragmática y abdominal normal. Colon por enema: Marco colonico buen pasaje localizado en topografía habitual. TAC Tórax múltiples quistes en campo pulmonar izquierdo. Se realiza lobectomía inferior izquierda. Histopatología confirma enfisema lobar congénito. Es dado de alta a los 10 días posquirúrgico.

Congenital lobar emphysema (ELC) is a rare lung malformation. This is an over distension of one or more lung lobes. The main causes are deficieney of development of bronchial cartilage and bronchial obstruction of valve type usually caused by idiopathic bronchial stenosis. Treatment generally is fitness for repair. Case Report: baby delivered by caesarean section. At 16 days of life starts with mild respiratory distress, coughing and vomiting, chest radiography impressive left diaphragmatic hernia so is hospitalized. Laboratories normal income. Echocardiography Cardiac situs solitus dextroposition in a mass displacement, CIV, FOP. Normal diaphragmatic and abdominal ultrasound. Barium enema: Colonic Marco usual good passage located in topografía. TAC Torax multiple cysts in the left lung field. It is performed left lower lobectomy. Congenital lobar emphysema histopathology confirmed. It is discharged 10 days after surgery.