Estimating the cost-effectiveness of fluticasone propionate for treating chronic obstructive pulmonary disease in the presence of missing data

Objectives: To explore the cost-effectiveness of fluticasone propionate (FP) for the treatment of chronic obstructive pulmonary disease (COPD), we estimated costs and qualityadjusted life-years (QALYs) over 3 years, based on an economic appraisal of a previously reported clinical trial (Inhaled Steroids in Obstructive Lung Disease in Europe [ISOLDE]). Methods: Seven hundred forty-two patients enrolled in the ISOLDE trial who received either FP or placebo had data available on health-care costs and quality of life over the period of the study. The SF-36-based utility scores for quality of life were used to calculate QALYs. A combined imputation and bootstrapping procedure was employed to handle missing data and to estimate statistical uncertainty in the estimated cumulative costs and QALYs over the study period. The imputation approach was based on propensity scoring and nesting this approach within the bootstrap ensured that multiple imputations were performed such that statistical estimates included imputation uncertainty. Results: Complete data were available on mortality within the follow-up period of the study and a nonsignificant trend toward improved survival of 0.06 (95% confidence interval [CI] –0.01 to 0.15) life-years was observed. In an analysis based on a propensity scoring approach to missing data we estimated the incremental costs of FP versus placebo to be £1021 (95% CI £619–1338) with an additional effect of 0.11 QALYs (CI 0.04–0.20). Cost-effectiveness estimates for the within-trial period of £17,700 per life-year gained (£6900 to ∞) and £9500 per QALY gained (CI £4300–26,500) were generated that include uncertainty due to the imputation process. An alternative imputation approach did not materially affect these estimates. Conclusions: Previous analyses of the ISOLDE study showed significant improvement on disease-specific health status measures and a trend toward a survival advantage for treatment with FP. This analysis shows that joint considerations of quality of life and survival result in a substantial increase in QALYs favoring treatment with FP. Based on these data, the inhaled corticosteroid FP appears costeffective for the treatment of COPD. Confirmation or refutation of this result may be achieved once the Towards a Revolution in COPD Health (TORCH) study reports, a large randomized controlled trial powered to detect mortality changes associated with the use of FP alone, or in combination with salmeterol, which is also collecting resource use and utility data suitable for estimating cost-effectiveness

Electrical stimulation enhances the acetylcholine receptors available for neuromuscular junction formation

Neuromuscular junctions (NMJ) are specialized synapses that link motor neurons with muscle fibers. These sites are fundamental to human muscle activity, controlling swallowing and breathing amongst many other vital functions. Study of this synapse formation is an essential area in neuroscience; the understanding of how neurons interact and control their targets during development and regeneration are fundamental questions. Existing data reveals that during initial stages of development neurons target and form synapses driven by biophysical and biochemical cues, and during later stages they require electrical activity to develop their functional interactions. The aim of this study was to investigate the effect of exogenous electrical stimulation (ES) electrodes directly in contact with cells, on the number and size of acetylcholine receptor (AChR) clusters available for NMJ formation. We used a novel in vitro model that utilizes a flexible electrical stimulation system and allows the systematic testing of several stimulation parameters simultaneously as well as the use of alternative electrode materials such as conductive polymers to deliver the stimulation. Functionality of NMJs under our co-culture conditions was demonstrated by monitoring changes in the responses of primary myoblasts to chemical stimulants that specifically target neuronal signaling. Our results suggest that biphasic electrical stimulation at 250 Hz, 100 ¿s pulse width and current density of 1 mA/cm2 for 8 h, applied via either gold-coated mylar or the conductive polymer PPy, significantly increased the number and size of AChRs clusters available for NMJ formation. This study supports the beneficial use of direct electrical stimulation as a strategic therapy for neuromuscular disorders

Educación y cooperación para el desarrollo mediante estándares universales de accesibilidad

II FORO «IBEROAMÉRICA EN LA ESCENA ECONÓMICA INTERNACIONAL: INVERSIONES Y EDUCACIÓN PARA EL DESARROLLO». UNIVERSIDAD REY JUAN CARLOS, MADRID (ESPAÑA), 14 DE DICIEMBRE DE 200

Accesibilidad a Internet: requisitos para la calidad en la docencia e investigación

A good Internet platform for teaching and research must be accessible, independently of the computer platform used, language and other peculiarities (personal or external). This work analyzes the current limitations of Internet access, as well as the potentialities that would represent an access being truly independent of the computer platform, discapacities, availability and speed of access, language and legislation. Thus, the benefits for a more accesible network for lecturing and investigation, overcoming the geographic location or possible discapacity, would be immediate and would have a broad impact spectrum. A more accesible Internet would enhace not only the dissemination of the information, approaching us to the 'global village', but also others aspects like university principles and values that sould be considered: an improvement of the equality of opportunities and the access to the culture and the education, that are the basis of the progress and the individual and collective liberties.Una buena plataforma de docencia e investigación en la red debe ser accesible, independientemente del entorno informático, idioma y condicionantes( personales o externos). Es este trabajo se analizan, por una parte, las limitaciones actuales que se presentan en el acceso a Internet, y por otra las potencialidades que tendría un acceso un acceso independiente de las plataforma informáticas, discapacidades, disponibilidad y velocidad de acceso, idioma y legislación. Así, los beneficios para la docencia y la investigación de una red más accesible, por encima de la localización geográfica o posible discapacidad, serán inmediatos y redundaría en otros campos. Una Internet más accesible abriría una nueva vía no sólo para la difusión de la información, acercándonos a la 'aldea global', sino también para otros aspectos de lo que entenderemos como principios y valores universitarios y que deben ser considerados: una mejora en la igualdad de oportunidades y en el acceso a la cultura y la formación, que son las bases del progreso y de las libertades tanto individuales como colectivas

Microporous Polymer Networks for Carbon Capture Applications

Producción CientíficaA new generation of porous polymer networks has been obtained in quantitative yield by reacting two rigid trifunctional aromatic monomers (1,3,5-triphenylbenzene and triptycene) with two ketones having electron-withdrawing groups (trifluoroacetophenone and isatin) in superacidic media. The resulting amorphous networks are microporous materials, with moderate Brunauer–Emmett–Teller surface areas (from 580 to 790 m2 g–1), and have high thermal stability. In particular, isatin yields networks with a very high narrow microporosity contribution, 82% for triptycene and 64% for 1,3,5-triphenylbenzene. The existence of favorable interactions between lactams and CO2 molecules has been stated. The materials show excellent CO2 uptakes (up to 207 mg g–1 at 0 °C/1 bar) and can be regenerated by vacuum, without heating. Under postcombustion conditions, their CO2/N2 selectivities are comparable to those of other organic porous networks. Because of the easily scalable synthetic method and their favorable characteristics, these materials are very promising as industrial adsorbents.Ministerio de Economía, Industria y Competitividad (grants MAT2013-45071-R / MAT2016-76413-C2-R1 / MAT2016-76413-C2-R2 / MAT2015-69844-R / CTQ2016-80913-P / CTQ2014-52796-P)Junta de Castilla y León (projects VA248U13 / VA051P17

Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab

There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein–Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach

Efecto del clorhidrato de clembuterol en la ganancia de peso y lesiones histológicas en ratones

El clorhidrato de clembuterol (CCL) es un b-agonista promotor del crecimiento en animales para abasto, pero su uso ilícito ha generado repercusiones en salud pública. Se realizó un modelo biológico con ratones, con el objeto de evaluar el efecto del CCL sobre la ganancia de peso y las lesiones histológicas que ocasiona. Los ratones fueron alimentados con carne de conejo, que previamente fue suplementada con CCL. Treinta y cinco días posexposición se registró el peso corporal se obtuvo la concentración muscular y sérica de CCL a través de la prueba de ELISA, y se colectaron tejidos (hígado y corazón) para análisis histopatológico. Los valores obtenidos de los animales experimentales (G1 y G2) se analizaron mediante un diseño experimental completamente al azar con dos tratamientos (n = 10), sometidos a un análisis de varianza y comparación de medias con la prueba de Tukey (p \u3c 05). Se registró un incremento de peso corporal de 7 g en el G1, contra 4,0 g del G2. El peso del hígado fue de 2,58 g y 1,79, respectivamente (p \u3c 05). En el G1 la concentración muscular de CCL fue 5324 pg g–1 y en suero sanguíneo de 4378 pg g–1. Solo se observaron cambios histológicos en tejidos de los ratones del G1. El hígado mostró tumefacción celular, mitosis moderada, picnosis y degeneración hidrópica en corazón, engrosamiento de fibras, pleomorfismo e hileración nuclear. El CCL favoreció el incremento de peso en los ratones expuestos, y provocó alteraciones estructurales en hígado y corazón

Childhood asthma exacerbations and the Arg16 b2-receptor polymorphism: a meta-analysis stratified by treatment

Background: The Gly-to-Arg substitution at the 16 position (rs1042713) in the b2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of b2-receptors. Objectives: We sought to undertake a meta-analysis to test the hypothesis that there is an interaction between the A allele of rs1042713 (Arg16 amino acid) and long-acting b-agonist (LABA) exposure for asthma exacerbations in children. Methods: Children with diagnosed asthma were recruited in 5 populations (BREATHE, Genes-Environments and Admixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharmacogenetics of Adrenal Suppression with Inhaled Steroid Study). A history of recent exacerbation and asthma treatment was determined from questionnaire data. DNA was extracted, and the Gly16Arg genotype was determined. Results: Data from 4226 children of white Northern European and Latino origin were analyzed, and the odds ratio for exacerbation increased by 1.52 (95% CI, 1.17-1.99; P 5 .0021) for each copy of the A allele among the 637 children treated with inhaled corticosteroids (ICSs) plus LABAs but not for treatment with ICSs alone (n 5 1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n 5 354) or ICSs plus LABAs plus LTRAs (n 5 569). Conclusions: The use of a LABA but not an LTRA as an ‘‘addon controller’’ is associated with increased risk of asthma exacerbation in children carrying 1 or 2 A alleles at rs1042713. Prospective genotype-stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalized asthma therapy in children. (J Allergy Clin Immunol 201

Gas separation membranes obtained by partial pyrolysis of polyimides exhibiting polyethylene oxide moieties

Aromatic copolyimides (PIx) and aromatic-aliphatic copolyimides (PIxEOy) were synthesized by reacting 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) with mixtures obtained from 2,2′-bis(4-aminophenyl)hexafluoropropane (6FpDA), 5-diaminobenzoic acid (DABA) and Jeffamine ED-2003 (PEO). The selective thermal removal of PEO from PIxEOy yielded membranes with high thermal stability and good mechanical properties. The presence of carboxylic groups minimized the shrinkage during the cross-linking process. The membranes containing 10 mol% DABA exhibited good O2/N2 and CO2/CH4 separation performance, and resistance to CO2 plasticization. PIx/PIxEOy blends containing less than 10 wt% PEO were prepared. The CO2/CH4 selectivity/permeability balance of cross-linked membranes largely exceeded that of PIx. The results highlight a possible strategy for using analogous cross-linkable polymers exhibiting ethylene oxide moieties as mere additive to prepare high free volume polyimide's membranes, exhibiting enhanced separation properties and high resistance to plasticization.This work was supported by the Spanish Government (AEI) through projects PID2019-109403RB-C21, PID2019-109403RB-C22 and PID2020-118547 GB-I00, and by the Regional Government of Castilla y León and the EU-FEDER program (CLU2017-09, UIC082, VA088G19 and VA224P20). M.G. acknowledges support of this work from the University of Oklahoma (VPR OfficePeer reviewe

Prevalence and features of ICF-disability in Spain as captured by the 2008 National Disability Survey

<p>Abstract</p> <p>Background</p> <p>Since 1986, the study of disability in Spain has been mainly addressed by National Disability Surveys (NDSs). While international attempts to frame NDS designs within the International Classification of Functioning, Disability and Health (ICF) have progressed, in general, the ICF has hardly been used in either the NDS or epidemiological studies. This study sought to identify ICF Activity- and Participation-related content in the most recent Spanish NDS, the 2008 Survey on Disabilities, Independence and Dependency Situations (<it>Encuesta sobre discapacidades, autonomía personal y situaciones de Dependencia </it>- <it>EDAD 2008</it>), and estimate the prevalence of such ICF-framed disability.</p> <p>Methods</p> <p><it>EDAD 2008 </it>methods and questions were perused. Of the 51 EDAD items analysed, 29 were backcoded to specific d2-d7 domains of the ICF Checklist and, by rating the recorded difficulty to perform specific tasks with or without help, these were then taken as performance and capacity respectively. A global ICF score was also derived, albeit lacking data for d1, "Learning and applying knowledge", d8, "Major Life Areas" and d9, "Community, Social and Civic Life". Data were grouped by sex, age, residence and initial positive screening, and prevalence figures were calculated by disability level both for the general population, using the originally designed weights, and for the population that had screened positive to disability. Data for institutionalised persons were processed separately.</p> <p>Results</p> <p>Crude prevalence of ICF severe/complete and moderate disability among the community-dwelling population aged ≥6 years was 0.9%-2.2% respectively, and that of severe/complete disability among persons living in sheltered accommodation was 0.3%.</p> <p>Prevalence of severe/complete disability was: higher in women than in men, 0.8% vs. 0.4%; increased with age; and was particularly high in domains such as "Domestic Life", 3.4%, "Mobility", 1.8%, and "Self-care", 1.9%, in which prevalence decreased when measured by reference to performance. Moreover, global scores indicated that severe/complete disability in these same domains was frequent among the moderately disabled group.</p> <p>Conclusions</p> <p>The <it>EDAD 2008 </it>affords an insufficient data set to be ICF-framed when it comes to the Activity and Participation domains. Notwithstanding their unknown validity, ratings for available ICF domains may, however, be suitable for consideration under the ADL model of functional dependency, suggesting that there are approximately 500,000 persons suffering from severe/complete disability and 1,000,000 suffering from moderate disability, with half the latter being severely disabled in domains capable of benefiting from technical or personal aid. Application of EDAD data to the planning of services for regions and other subpopulations means that need for personal help must be assessed, unmet needs ascertained, and knowledge of social participation and support, particularly for the mentally ill, improved. International, WHO-supported co-operation in ICF planning and use of NDSs in Spain and other countries is needed.</p