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BACKGROUND: Consolidation immunotherapy with the programmed death ligand 1 (PD-L1) inhibitor durvalumab improves survival in patients with stage III non-small-cell lung cancer responding to radiochemotherapy. The aim of this study was to assess the cost-effectiveness of durvalumab in Switzerland based on the most recent PACIFIC survival follow-up. MATERIALS AND METHODS: We constructed a Markov model based on the 3-year follow-up data of the PACIFIC trial and compared consolidation durvalumab with observation. We used published utility values and assessed costs for treatment strategies from the perspective of the Swiss health care payers. Cost-effectiveness was tested both in the intention-to-treat population of the PACIFIC trial unselected for PD-L1 tumor expression and in patients with PD-L1-expressing tumors (≥1%). RESULTS: In the unselected/PD-L1-positive patients, durvalumab showed an incremental effectiveness of 0.76/1.18 quality-adjusted life year (QALY) and incremental costs of Swiss Francs (CHF) 67 239/78 177, resulting in incremental cost-effectiveness ratios of CHF 88 703/66 131 per QALY gained, respectively. The most influential factors for the incremental cost-effectiveness ratio were the utility before first progression, costs for durvalumab, and the hazard ratio for overall survival under durvalumab versus observation. The cost-effectiveness of durvalumab was better than CHF 100 000 per QALY gained in 75% of the simulations in probabilistic sensitivity analysis. CONCLUSION: Assuming a willingness-to-pay threshold of CHF 100 000 per QALY gained, consolidation durvalumab is likely to be cost-effective both in patients with inoperable stage III non-small-cell lung cancer (NSCLC) unselected for PD-L1 status and in patients with PD-L1-expressing tumors in Switzerland.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioradioterapia , Análisis Costo-Beneficio , Humanos , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Años de Vida Ajustados por Calidad de Vida , SuizaRESUMEN
The treatment of a patient with a vertebral fracture requires an accurate diagnosis and categorization of the problem. Treatment decisions must be based on clinical data and information about the lesion itself, which is provided by imaging studies and their interpretation.
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Fracturas de la Columna Vertebral/diagnóstico por imagen , Humanos , Fracturas de la Columna Vertebral/clasificaciónRESUMEN
Cultural heritage has become a keystone for comprehending our society, as it represents and reflects our origins, passions, beliefs and traditions. Furthermore, it provides fundamental information about specific temporary spaces, materials' availability, technology, artist's intention, and site weather conditions. Our aim was to develop a multidisciplinary approach with a main focus on investigating two Italian large-format paintings located in highly diverse environments such as the National Theater of Costa Rica. We monitored environmental conditions and quantified fungal aerial spores. Then, we determined regions of possible biodeterioration with the software MicroorganismPattern and used the software PigmentArrangement to elucidate the apparent colour of the paintings based on distribution and arrangement of the pigment crystals. Finally, we characterized eight genera of calcareous nannofossils found in the ground layers of the artwork. The former Men's Canteen at the National Theater of Costa Rica presented a mean air temperature of 23.5 [Formula: see text]C, a relative humidity of 72.7% and a concentration of CO[Formula: see text] of 570 ppm. The fungal aerial concentration was 1776 spores/m[Formula: see text]. The software MicroorganismPattern identified 32 sampling regions, out of which 11 were positive for microbial contamination. The software PigmentArrangement determined that the blue crystals (ultramarine pigment) had the shortest distances between themselves (29 [Formula: see text]m). Finally, the nanofossils identified enabled us to restrict the age of the material to a biostratigraphic interval ranging from Coniacian to Maastricthian ages. By using a multidisciplinary approach we were able to explore the diptych, suggest a set of minimally invasive perspectives in tropical environments to be used worldwide and obtain key information about the artist's artistic process, materials used along with better understand its state of conservation.
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The Neolithic transition has been widely debated particularly regarding the extent to which this revolution implied a demographic expansion from the Near East. We attempted to shed some light on this process in northeastern Iberia by combining ancient DNA (aDNA) data from Early Neolithic settlers and published DNA data from Middle Neolithic and modern samples from the same region. We successfully extracted and amplified mitochondrial DNA from 13 human specimens, found at three archaeological sites dated back to the Cardial culture in the Early Neolithic (Can Sadurní and Chaves) and to the Late Early Neolithic (Sant Pau del Camp). We found that haplogroups with a low frequency in modern populations-N* and X1-are found at higher frequencies in our Early Neolithic population (â¼31%). Genetic differentiation between Early and Middle Neolithic populations was significant (F(ST) â¼0.13, P<10(-5)), suggesting that genetic drift played an important role at this time. To improve our understanding of the Neolithic demographic processes, we used a Bayesian coalescence-based simulation approach to identify the most likely of three demographic scenarios that might explain the genetic data. The three scenarios were chosen to reflect archaeological knowledge and previous genetic studies using similar inferential approaches. We found that models that ignore population structure, as previously used in aDNA studies, are unlikely to explain the data. Our results are compatible with a pioneer colonization of northeastern Iberia at the Early Neolithic characterized by the arrival of small genetically distinctive groups, showing cultural and genetic connections with the Near East.
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ADN Mitocondrial/historia , Haplotipos/genética , Agricultura/historia , Arqueología , ADN Mitocondrial/genética , Flujo Genético , Historia Antigua , Humanos , Medio Oriente , Filogeografía/historia , EspañaRESUMEN
BACKGROUND: External quality assessment is essential in modern andrology laboratories. To assess the proficiency of laboratories participating in an external quality assessment programme (EQAP), limits for acceptable variability must be determined. Limits currently specified largely depend on criteria set by the organizers of individual EQAP schemes. The objective of this study was to evaluate the different criteria described in ISO 13528: 2005 for calculating acceptable variability in EQAP when applied to basic semen analysis parameters. METHODS AND RESULTS: The data used in this study were the means and standard deviations obtained for independent samples from two EQAPs, one national (Spanish) and one international (European). The acceptable variability according to ISO 13528: 2005 was calculated using four types of criteria: (i) ± 3 standard deviations of the results of all participating laboratories; (ii) ± 3 standard deviations of the results of expert laboratories; (iii) quality specifications based on biological variability, state-of-the-art and clinicians' opinions and (iv) the same quality specifications adjusted for the uncertainty of the assigned value. The first two strategies resulted in very wide ranges of acceptable variability. Conversely, the strategy based only on quality specifications resulted in very narrow ranges. For the fourth strategy, acceptable ranges were intermediate between the results produced with the other strategies. The third and fourth strategies did not produce observable differences in acceptable ranges when the model used for calculating the specifications of analytical quality was changed. CONCLUSIONS: It is essential that EQAPs for semen parameters should determine the ranges for acceptable variability in results. Moreover, these ranges must be clinically useful, i.e. the variability should have a minimal negative impact on clinical decisions. The exact definition of 'expert laboratory' is more important than the model chosen for estimating analytical quality specifications in an EQAP for semen parameters in basic semen analysis.
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Garantía de la Calidad de Atención de Salud , Análisis de Semen/normas , Europa (Continente) , Humanos , Ensayos de Aptitud de Laboratorios , Masculino , Guías de Práctica Clínica como Asunto , Reproducibilidad de los Resultados , España , Estadística como AsuntoRESUMEN
The endangered twoline skiffia Neotoca bilineata, a viviparous fish of the subfamily Goodeinae, endemic to central Mexico (inhabiting two basins, Cuitzeo and Lerma-Santiago) was evaluated using genetic and habitat information. The genetic variation of all remaining populations of the species was analysed using both mitochondrial and microsatellite markers and their habitat conditions were assessed using a water quality index (I(WQ)). An 80% local extinction was found across the distribution of N. bilineata. The species was found in three of the 16 historical localities plus one previously unreported site. Most areas inhabited by the remaining populations had I(WQ) scores unsuitable for the conservation of freshwater biodiversity. Populations showed low but significant genetic differentiation with both markers (mtDNA φ(ST) = 0.076, P < 0.001; microsatellite F(ST) = 0.314, P < 0.001). Borbollon, in the Cuitzeo Basin, showed the highest level of differentiation and was identified as a single genetic unit by Bayesian assignment methods. Rio Grande de Morelia and Salamanca populations showed the highest genetic diversity and also a high migration rate facilitated by an artificial channel that connected the two basins. Overall, high genetic diversity values were observed compared with other freshwater fishes (average N(a) = 16 alleles and loci and mean ±S.D. H(o) = 0.63 ± 0.10 and nucleotide diversity π = 0.006). This suggests that the observed genetic diversity has not diminished as rapidly as the species' habitat destruction. No evidence of correlation between habitat conditions and genetic diversity was found. The current pattern of genetic diversity may be the result of both historical factors and recent modifications of the hydrological system. The main threat to the species may be the rapid habitat deterioration and associated demographic stochasticity rather than genetic factors.
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Ciprinodontiformes/genética , Ecosistema , Variación Genética , Animales , Teorema de Bayes , Conservación de los Recursos Naturales , ADN Mitocondrial/genética , Genética de Población , México , Repeticiones de Microsatélite , Filogenia , Análisis de Secuencia de ADNRESUMEN
Research is a systematic process designed to answer a question. This is the starting point of the whole project and specifically formulates a problem observed in the analysis of the reality. The answer to this attempts to clarify an uncertainty in our knowledge. The conceptual hypothesis is the theoretical answer to the question set out. The operational hypothesis is the particular form that which sets out to demonstrate the conceptual hypothesis. The objectives are the justification for conducting the research. They help to define what it attempts to obtain, and what answers it will give to the formulated questions. It must show a clear and consistent relationship with the description of the problem and, specifically, with the questions and/or hypothesis that are to be resolved.
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Radiología , Proyectos de Investigación/normasRESUMEN
The development of full superconducting motors for electric distributed aircraft propulsion requires to test the stator coils at the operation temperature, usually between 20 and 40 K. Here, we study the AC loss of a test racetrack coil made of REBCO tape. We developed a measurement system within a non-metallic cryostat where a cryocooler cools the test coil in combination with liquid or solid nitrogen. We present transport AC loss measurements by electrical means down to 25 K for current amplitudes up to 140 A and frequency 18-576 Hz. The AC loss increased with second power with current, and did not depend on frequency or temperature. Later, we measured the AC parallel magnetization loss in a stack of tapes made of the same material as the coil, and in a stack of tapes without superconducting layer. The results in both samples is almost identical and presents the same behavior as the coil. We conclude that the main contribution to the AC loss in the tape stack and in the coil was from the magnetism of the Hastelloy substrate or buffer layers. Therefore, researchers need to take this into account in tape production and in superconducting motor design.
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INTRODUCTION: The treatment of metastatic castration-resistant prostate cancer (mCRPC) has changed significantly in recent years. Inhibitors of androgen receptors have shown especially significant benefits in overall (OS) and progression-free survival (PFS), with a good toxicity profile. Treatment selection depends on the patient's individual clinical, radiological, and biological characteristics. OBJECTIVE: To describe treatment outcomes (efficacy, toxicity) in a cohort of patients with mCRPC in Spain. MATERIALS AND METHODS: Multicenter, retrospective study of patients with mCRPC included in a database of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR). Metastatic CRPC was defined according to the prostate cancer working group 3 (PCWG3) criteria. The Kaplan-Meier technique was used to evaluate OS and the Common Terminology Criteria for Adverse Events (CTCAE, v.4.0) were used to assess toxicity. Univariate and multivariate Cox regression analyses were performed to identify the factors significantly associated with OS. RESULTS: A total of 314 patients from 17 hospitals in Spain diagnosed with mCRPC between June 2010 and September 2017 were included in this study. Mean age at diagnosis was 68 years (range 45-89). At a median follow-up of 35 months, OS at 1, 3, and 5 years were 92%, 38%, and 28%, respectively. Grades 1-2 and grade 3 toxicity rates were, respectively, 68% and 19%. No grade 4 toxicities were observed. On the multivariate analysis, the following factors were significantly associated with OS: age (hazard ratio [HR] 0.42, p = 0.010), PSA value at diagnosis of mCRPC (HR 0.55, p = 0.008), and Gleason score (HR 0.61, p = 0.009). CONCLUSIONS: Age, Gleason score, and PSA at diagnosis of mCRPC are independently associated with overall survival in patients with mCRPC. The efficacy and toxicity outcomes in this patient cohort treated in radiation oncology departments in Spain are consistent with previous reports.
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Factores de Edad , Antineoplásicos/uso terapéutico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Neoplasias Óseas/secundario , Progresión de la Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Oncología por Radiación , Análisis de Regresión , Estudios Retrospectivos , Sociedades Médicas , España , Terminología como AsuntoRESUMEN
The male-mediated genetic legacy of the Pyrenean population was assessed through the analysis of 12 Y-STR and 27 Y-SNP loci in a sample of 169 males from 5 main geographical areas in the Spanish Pyrenees: Cinco Villas (Western Pyrenees), Jacetania and Valle de Arán (Central Pyrenees) and Alto Urgel and Cerdaña (Eastern Pyrenees). In the Iberian context, the Pyrenean samples present some specificities, being characterizeded by a high proportion of chromosomes R1b1b2-M269 (including the usually uncommon R1b1b2d-SRY(2627) and R1b1b2c-M153 types) or I2a2-M26 and low proportions of other haplogroups. Our results indicate that an old pre-Neolithic substrate is preponderant in populations of the whole Pyrenean fringe. However, AMOVA revealed a high level of substructure within Pyrenean populations, partially explained by drift effects as well as by the signature of an ancient genetic differentiation between Western and Eastern Pyrenees.
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Cromosomas Humanos Y/genética , Población Blanca/genética , Variación Genética , Haplotipos , Humanos , Masculino , Filogenia , Polimorfismo de Nucleótido Simple , Población Blanca/clasificación , Población Blanca/etnologíaRESUMEN
Bird fancier's or breeder's lung is an unusual hypersensitivity pneumonitis found in pediatric patients, due to avian antigen inhalation. A case of pigeon breeder's lung in a 12 years old child is presented. Clinical symptoms were dry cough for 15 days, dyspnea and weight loss. Physical examination of the patient showed cyanosis, chest tightness, tachypnea, inspiratory crackles and oxygen saturation of 91% in room air. Laboratory data revealed hypergammaglobulinemia and elevated LDH. Pulmonary function testing showed a mixed ventilatory pattern and a decreased carbon monoxide diffusion (DLCO) capacity. Radiological findings were compatible with hypersensitivity pneumonitis, and pigeon IgG antibodies (ELISA) and skin tests with pigeon serum were positive. The child improved with corticoid therapy and antigen avoidance.
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Pulmón de Criadores de Aves , Pulmón de Criadores de Aves/diagnóstico , Niño , Humanos , MasculinoRESUMEN
PURPOSE: Radiotherapy-induced dysfunction of the gastrointestinal tract is common in cancer patients and has a significant impact on their quality of life. In this study, we investigated the prevalence of breakthrough cancer pain (BTcP) in patients undergoing 3D pelvic radiotherapy and who had proctalgia. METHODS: This observational, multicenter, cross-sectional epidemiological study was performed in 13 Spanish hospitals. Data were obtained on the presence and characteristics of BTcP, demographics, common comorbidities, and treatments prescribed to the patients. RESULTS: The prevalence of BTcP in patients undergoing pelvic 3D external radiotherapy with proctalgia (N = 105) was 48.6% (95% CI 39.0-58.1%). BTcP was further characterized in 59 patients. The mean (± SD) intensity of the BTcP episodes was 7.45 ± 1.47 in a visual analog scale. We found several statistically significant associations between the descriptive variables of BTcP with demographic and clinical variables associated with the tumor or the patient, such as an increased number of BTcP episodes per day depending on the presence or absence of diabetes (p = 0.001, Chi-square) or time to the onset of pain relief depending on the location of the tumor (p = 0.019, Chi-square). Fentanyl was the drug of choice in BTcP episodes for 95% of the patients. CONCLUSIONS: This study demonstrated a high prevalence of BTcP prevalence in cancer patients undergoing pelvic 3D radiotherapy and with proctalgia. Although the variables determining the onset of BTcP are still unclear, our results could help in the design of future clinical studies addressing the treatment of BTcP in these patients.
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Dolor Irruptivo/epidemiología , Dolor en Cáncer/epidemiología , Neoplasias/radioterapia , Dolor/epidemiología , Radioterapia Conformacional/efectos adversos , Enfermedades del Recto/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/tratamiento farmacológico , Neoplasias del Ano/radioterapia , Dolor Irruptivo/tratamiento farmacológico , Dolor Irruptivo/etiología , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/etiología , Distribución de Chi-Cuadrado , Estudios Transversales , Neoplasias Endometriales/radioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Dolor/tratamiento farmacológico , Prevalencia , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Enfermedades del Recto/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , España/epidemiología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
INTRODUCTION: Cerebral palsy describes a group of developmental and posture disorders, which cause a limitation of activity due to non-progressive damage occurring in the developing brain. A population register facilitates the identification of cerebral palsy cases within a specific geographic population. Its usefulness is recognized in the world literature but in Spain, published databases focus on the treatment or complications of cerebral palsy. AIMS: To propose a population register that can be useful in different areas of our environment and to evaluate its validity through its application in two differentiated and geographically delimited health areas. SUBJECTS AND METHODS: The registry consists of 124 items divided into seven sections: data on the child filiations, maternal history and parents' information, pregnancy and neonatal period data, diagnoses and classification, neuroimaging tests, therapeutic interventions and others. Patients attended in external consultations in Navarre and Andorra were included. RESULTS: In the register, 53 patients (52.8% females) were evaluated. 56.5% were premature. Spastic cerebral palsy is the most frequent presentation. 42% have associated epilepsy. CONCLUSIONS: The use of population registers allows a better knowledge of cerebral palsy as well as the evaluation and development of prevention strategies and optimization of care resources with objective data. It is necessary to generalize the use of this type of records in our environment.
TITLE: Diseño de un registro de paralisis cerebral de ambito poblacional: aplicacion y analisis en Andorra y Navarra.Introduccion. La paralisis cerebral describe un grupo de trastornos del desarrollo y la postura que causan una limitacion de la actividad debido a alteraciones no progresivas ocurridas en el cerebro en desarrollo. El registro poblacional facilita la identificacion de los casos de paralisis cerebral dentro de una poblacion geografica especifica. Esta reconocida su utilidad en la bibliografia, pero en España, las bases de datos publicadas se centran en el tratamiento o las complicaciones de la paralisis cerebral. Objetivos. Proponer un registro poblacional que pueda ser util en diferentes areas de nuestro entorno y evaluar su validez mediante su aplicacion en dos areas de salud diferenciadas y geograficamente delimitadas. Sujetos y metodos. El registro elaborado constaba de 124 items divididos en siete apartados: datos de filiacion del niño, historia materna e informacion de los padres, datos del embarazo y periodo neonatal, diagnosticos y clasificacion, pruebas de neuroimagen, intervenciones terapeuticas y otros. Se incluyo a los pacientes atendidos en consultas externas en Navarra y Andorra. Resultados. En el registro se evaluo a 53 pacientes (52,8% mujeres). El 56,5% fueron prematuros. La paralisis cerebral espastica es la presentacion mas frecuente. Un 42% asociaba epilepsia. Conclusiones. El uso de registros poblacionales permite un mejor conocimiento de la paralisis cerebral, asi como la evaluacion y el desarrollo de estrategias de prevencion y optimizacion de los recursos asistenciales con datos objetivos. Es necesaria la generalizacion del uso de este tipo de registros en nuestro entorno.
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Parálisis Cerebral/epidemiología , Sistema de Registros , Andorra/epidemiología , Parálisis Cerebral/clasificación , Preescolar , Comorbilidad , Educación Especial , Epilepsia/epidemiología , Femenino , Edad Gestacional , Humanos , Lactante , Recien Nacido Prematuro , Enfermedades del Prematuro/epidemiología , Masculino , España/epidemiologíaRESUMEN
INTRODUCTION AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to ascertain the prevalence of COPD and whether such prevalence was positively or negatively associated with COPD admissions, using all the data of a regional health care system. MATERIALS AND METHODS: We designed a descriptive cross-sectional study which included all subjects aged over 45 years, diagnosed with COPD in primary care in 2013. We also calculated the number of such patients who had a record of hospital admissions due to this disease. COPD prevalence and incidence of admissions were calculated. Poisson regression models were then used to analyse the association between cases with diagnosis of COPD and admissions due to COPD, by sex, adjusting for socio-demographic variables and distance to hospital. Sensitivity subanalyses were performed by reference to the respective municipal rurality indices. RESULTS: Median municipal prevalence of COPD was 5.29% in men and 2.19% in women. Among patients with COPD, 28.22% of men and 16.00% of women had at least one hospital admission. The relative risk of admission per unit of the standardised prevalence ratio was 0.37 (95% CI 0.34-0.41) for men and 0.39 (95% CI 0.34-0.45) for women. CONCLUSIONS: There is a significant negative association between COPD prevalence and hospital admissions due to this disease. The proportion of admissions is lower in municipalities lying furthest from hospitals. There is considerable municipal variability in terms of COPD prevalence and proportion of admissions. In-depth attention should be given to disease-management training programmes.
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Sistemas de Información en Salud , Admisión del Paciente/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , España/epidemiologíaRESUMEN
INTRODUCTION: Glioblastoma is the most common primary brain tumour. Despite advances in treatment, its prognosis remains dismal, with a mean survival time of about 14 months. Many articles have addressed direct costs, those associated with the diagnosis and treatment of the disease. Indirect costs, those associated with loss of productivity due to the disease, have seldom been described. MATERIAL AND METHOD: We conducted a retrospective study in patients diagnosed with glioblastoma at Hospital Universitario Donostia between January 1, 2010 and December 31, 2013. We collected demographics, data regarding the treatment received, and survival times. We calculated the indirect costs with the human capital approach, adjusting the mean salaries of comparable individuals by sex and age and obtaining mortality data for the general population from the Spanish National Statistics Institute. Past salaries were updated to 2015 euros according to the annual inflation rate and we applied a discount of 3.5% compounded yearly to future salaries. RESULTS: We reviewed the records of 99 patients: 46 women (mean age 63.53) and 53 men (mean age 59.94); 29 patients underwent a biopsy and the remaining 70 underwent excisional surgery. Mean survival was 18.092 months for the whole series. The total indirect cost for the series was 11 080 762 (2015). Mean indirect cost per patient was 111 926 (2015). DISCUSSION: Although glioblastoma is a relatively uncommon type of tumour, accounting for only 4% of all cancers, its poor prognosis and potential sequelae generate disproportionately large morbidity and mortality rates which translate to high indirect costs. Clinicians should be aware of the societal impact of glioblastoma and indirect costs should be taken into account when cost effectiveness studies are performed to better illustrate the overall consequences of this disease.
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Neoplasias Encefálicas , Costo de Enfermedad , Glioblastoma/cirugía , Hospitales , Neoplasias Encefálicas/economía , Análisis Costo-Beneficio , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
A vast impact on molecular nanoscience can be achieved using simple transition metal complexes as dynamic chemical systems to perform specific and selective tasks under the control of an external stimulus that switches "ON" and "OFF" their electronic properties. While the interest in single-ion magnets (SIMs) lies in their potential applications in information storage and quantum computing, the switching of their slow magnetic relaxation associated with host-guest processes is insufficiently explored. Herein, we report a unique example of a mononuclear cobalt(ii) complex in which geometrical constraints are the cause of easy and reversible water coordination and its release. As a result, a reversible and selective colour and SIM behaviour switch occurs between a "slow-relaxing" deep red anhydrous material (compound 1) and its "fast-relaxing" orange hydrated form (compound 2). The combination of this optical and magnetic switching in this new class of vapochromic and thermochromic SIMs offers fascinating possibilities for designing multifunctional molecular materials.
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The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated. In this study, we present a novel periosteum tissue engineering concept utilizing a multiphasic scaffold design in combination with different human cell types for periosteal regeneration in an orthotopic in vivo platform. Human endothelial and bone marrow mesenchymal stem cells (BM-MSCs) were used to mirror both the vascular and osteogenic niche respectively. Immunohistochemistry showed that the BM-MSCs maintained their undifferentiated phenotype. The human endothelial cells developed into mature vessels and connected to host vasculature. The addition of an in vitro engineered endothelial network increased vascularization in comparison to cell-free constructs. Altogether, the results showed that the human TEPC (hTEPC) successfully recapitulated the osteogenic and vascular niche of native periosteum, and that the presented orthotopic xenograft model provides a suitable in vivo environment for evaluating scaffold-based tissue engineering concepts exploiting human cells.
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Órganos Bioartificiales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Periostio/citología , Periostio/crecimiento & desarrollo , Ingeniería de Tejidos/instrumentación , Andamios del Tejido , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Humanos , Técnicas de Cultivo de Órganos/instrumentación , Técnicas de Cultivo de Órganos/métodos , Ingeniería de Tejidos/métodosRESUMEN
The aim of this work was to study the combined effects of water activity (aw, 0.75-0.99), temperature (10-30 degrees C) and isolate on spore germination and mycelial growth of ochratoxigenic Penicillium verrucosum isolates on barley meal extract agar (BMEA). Lag phases prior to germination (h), germination rates (h(-1)) and growth rates (mm day(-1)) were obtained at each set of conditions and for all the isolates. Analysis of variance showed a significant influence of the abiotic factors assayed on fungal development. Minimum aw levels found for germination and mycelial growth were 0.80 and 0.85, respectively, while maximum germination and growth rates were obtained at 0.95-0.99 aw level. Although maximum germination was obtained at 20 degrees C, significant differences were not found between growth rates at 20 and 30 degrees C. Data were modelled by MLR regressions and response surface models were obtained. Spore germination and mycelial growth of ochratoxigenic P. verrucosum isolates are significantly affected by water activity and temperature. Moreover, different isolates may have slightly different response to environmental factors. Predictive models obtained may allow a rough prediction of germination/growth as a function of the storage temperature and moisture content of barley grains.