A multicriteria decision analysis (MCDA) applied to three long-term prophylactic treatments for hereditary angioedema in Spain

Introduction: Hereditary angioedema (HAE) is a rare genetic disease that impairs quality of life and could be life-threatening. The aim of this study was to apply a multicriteria decision analysis to assess the value of three long-term prophylactic (LIP) therapies for HAE in Spain. Methods: A multidisciplinary committee of 10 experts assessed the value of lanadelumab (subcutaneous use), C1-inhibitor (C1-INH; intravenous), and danazol (orally), using placebo as comparator. We followed the EVIDEM methodology that considers a set of 13 quantitative criteria. The overall estimated value of each intervention was obtained combining the weighting of each criterion with the scoring of each intervention in each criterion. We used two alternative weighting methods: hierarchical point allocation (HPA) and direct rating scale (DRS). A reevaluation of weightings and scores was performed. Results: Lanadelumab obtained higher mean scores than C1-INH and danazol in all criteria, except for the cost of the intervention and clinical practice guidelines. Under the HPA method, the estimated values were 0.51 (95% confidence interval [CI]: 0.44-0.58) for lanadelumab, 0.47 (95%CI: 0.41-0.53) for C1-INH, and 0.31 (95%CI: 0.240.39) for danazol. Similar results were obtained with the DRS method: 0.51 (95%CI: 0.42-0.60), 0.47 (95%CI: 0.40-0.54), and 0.27 (95%CI: 0.18-0.37), respectively. The comparative cost of the intervention was the only criterion that contributed negatively to the values of lanadelumab and C1-INH. For danazol, four criteria contributed negatively, mainly comparative safety. Conclusion: Lanadelumab was assessed as a high-value intervention, better than C1-INH and substantially better than danazol for LTP treatment of HAE

Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project

BACKGROUND: There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. METHODS/DESIGN: Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains. DISCUSSION: To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version

Deciphering the genetics of primary angioedema with normal levels of C1 inhibitor

The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with F12 alterations as well as those with histaminergic acquired angioedema were excluded. A variant pathogenicity curation strategy was followed, including a comparison of the results with those of genotyping 169 patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), and only filtered-in variants were studied further. Among the examined nl-C1-INH-HAE patients, carriers of neither the ANGPT1 p.Ala119Ser nor the KNG1 p.Met379Lys variant were found, whereas the PLG p.Lys330Glu was detected in four (3%) unrelated probands (one homozygote). In total, 182 different variants were curated, 21 of which represented novel mutations. Although the frequency of variants per gene was comparable between nl-C1-INH-HAE and C1-INH-HAE, variants of the KNG1 and XPNPEP1 genes were detected only in nl-C1-INH-HAE patients (six and three, respectively). Twenty-seven filtered variants in 23 different genes were detected in nl-C1-INH-HAE more than once, whereas 69/133 nl-C1-INH-HAE patients had compound heterozygotes of filtered variants located in the same or different genes. Pedigree analysis was performed where feasible. Our results indicate the role that alterations in some genes, like KNG1, may play in disease pathogenesis, the complex trait that is possibly underlying in some cases, and the existence of hitherto unrecognized disease endotypes

Prevalence of Symptomatic Osteoarthritis in Spain: EPISER2016 Study

[Resumen] Introducción. La Sociedad Española de Reumatología elaboró en el año 2000 el estudio EPISER2000 para conocer la prevalencia de la artrosis y otras enfermedades reumáticas en España. Los cambios sociodemográficos y en los hábitos de vida ocurridos en los últimos años en España justifican actualizar los datos de las enfermedades reumáticas (EPISER2016). Objetivo. Estimar la prevalencia de artrosis sintomática de columna cervical, columna lumbar, cadera, rodilla y mano, en población adulta en España. Material y métodos. Estudio transversal de base poblacional. Se realizó un muestreo aleatorizado polietápico estratificado y por conglomerados. Los participantes fueron contactados por teléfono para cumplimentar un cuestionario de cribado de artrosis. El reumatólogo confirmaba o descartaba el diagnóstico. Se utilizaron los criterios-clínicos-ACR para diagnosticar artrosis de manos y los criterios clínico-radiológicos-ACR para diagnosticar la artrosis de rodilla y cadera. Resultados. La prevalencia de artrosis en España en una o más de las localizaciones estudiadas fue de 29,35%. La prevalencia de artrosis-cervical fue del 10,10% y de artrosis-lumbar del 15,52%. Ambas son más frecuentes en mujeres y a mayor edad, así como en personas con niveles de estudios bajos y obesidad. La prevalencia de artrosis de cadera fue del 5,13% y la de artrosis de rodilla del 13,83%; estas se asocian con el sexo femenino, sobrepeso y obesidad, menor frecuencia en nivel de estudios alto y con la edad. La prevalencia de la artrosis de mano fue del 7,73%. Es más frecuente en mujeres, obesas, con bajo nivel de estudios y mayor edad. Conclusiones. El estudio EPISER2016 es el primero que analiza la prevalencia de artrosis sintomática en 5 localizaciones (columna cervical, lumbar, rodilla, cadera y manos) en España. La artrosis de la columna lumbar es la más prevalente.[Abstract] Introduction. The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). Objective. To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. Material and methods. Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. Results. The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. Conclusion. The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent.EPISER2016 ha sido financiado por Celgene, Laboratorios, Gebro Pharma, Merck Sharp and Dohme de España, Pfizer y Sanofi-Aventis. Los financiadores no han intervenido en el diseño del estudio, recogida ni análisis de datos, ni en la redacción de este artículo. IRP yMS fueron financiados con programas Miguel Servet II y Contrato Río Hortega-Fondo de Investigación Sanitaria (CPII17/00026 y CM17/00101), respectivamente. El Fondo de Investigación Sanitaria, integrado en el Plan Nacional de Programa Científico, Desarrollo e Innovación Tecnológica 2013-2016, es financiado por el ISCIII-Subdirección General de Evaluación y Promoción de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) «Una forma de hacer Europa

Prevalence of Symptomatic Axial Osteoarthritis Phenotypes in Spain and Associated Socio-Demographic, Anthropometric, and Lifestyle Variables

Epidemiology of RMDFinanciado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Objective. Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. Methods. EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. Results. Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82–20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. Conclusions. This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. EPISER2016 was supported by Celgene, Gebro Pharma, Merck Sharp & Dohme in Spain, Pfizer, and Sanofi-Aventis, none of whom had any role in the study design, data collection, data analysis, interpretation, or writing of this manuscript. MS was financed via the Rio Hortega Contract—Health Research Fund (CM17/00101), the Sanitary Research Fund integrated in the National Plan of Scientific Program, Technological Development and Innovation 2013–2016 and funded by the ISCIII-Subdirectorate General Evaluation and Promotion of Research-European Regional Development Fund (ERDF) "A way of making Europe

Evaluation of antimicrobial and antifungal activity of hydroethanolic extracts of in vitro and ex vitro seedlings of Dionaea muscipula J. Ellis

Objective: To assess the antibacterial and antifungal activity of hydroethanolic extracts of Dionaea muscipula J. Ellis against model bacteria and fungi of agricultural importance. Design/Methodology/Approach: In vitro plants of D. muscipula were propagated and acclimatized for three months. The antibacterial activity of the hydroethanolic extracts against Escherichia coli and Bacillus cereus and the antifungal activity against Aspergillus niger, Fusarium oxysporum and Pseudocercospora fijiensis were evaluated. An analysis of variance (ANOVA) was performed to compare the means obtained with a Tukey test (p?0.05). Results: The hydroethanolic extracts of D. muscipula in vitro and acclimatized showed a bacteriostatic activity against the bacteria E. coli (65.20 and 69.78% inhibition) and B. cereus (91.75 and 92.61% inhibition) and an antifungal activity against the fungus P. fijiensis of 7.56 and 14.21% of inhibition, respectively. Study Limitations/Implications: The hydroethanolic extracts of D. muscipula in vitro and acclimatized did not show antifungal activity against A. niger and F. oxysporum. Findings/Conclusions: The hydroethanolic extracts of D. muscipula in vitro and acclimatized showed a bacteriostatic activity against the bacteria E. coli and B. cereus and antifungal activity against the fungus P. fijiensis.Objective: To evaluate the antibacterial and antifungal activity of hydroethanolic extracts of Dionaea muscipula J. Ellis against bacteria models and fungi of agricultural importance. Design/Methodology/Approach: In vitro plants of D. muscipula were propagated and acclimatized for three months. The antibacterial activity of the hydroethanolic extracts against Escherichia coli and Bacillus cereus was evaluated, and the antifungal activity against Aspergillus niger, Fusarium oxysporum and Pseudocercospora fijiensis. Analysis of variance (ANOVA) was carried out to compare the means obtained with Tukey’s test (p≤0.05). Results: The hydroethanolic extracts of in vitro and acclimatized D. muscipula presented bacteriostatic activity against the bacteria E. coli (65.20 and 69.78 % of inhibition) and B. cereus (91.75 and 92.61 % of inhibition), and antifungal activity against the fungus P. fijiensis of 7.56 and 14.21 % of inhibition, respectively. Study Limitations/Implications: The hydroethanolic extracts of in vitro and acclimatized D. muscipula did not show antifungal activity against A. niger and F. oxysporum. Findings/Conclusions: The hydroethanolic extracts of in vitro and acclimatized D. muscipula presented bacteriostatic activity against bacteria E. coli and B. cereus and antifungal activity against the fungus P. fijiensis

Angioedema Due to Acquired Deficiency of C1-Inhibitor: A Cohort Study in Spain and a Comparison With Other Series

[Background] Data on acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) from 4 European countries (France, Italy, Germany, and Hungary) were recently published.[Objective] To report data from a group of 50 patients with acquired C1-INH deficiency from Spain, of whom 46 had angioedema, and compare them with other European series.[Methods] We performed a retrospective observational study of 46 patients with C1-INH-AAE and 4 asymptomatic patients. Clinical and biological characteristics and associated diseases were assessed and compared with other European series.[Results] Women accounted for 73.9% of cases. The prevalence of C1-INH-AAE related to hereditary forms was 1/10.1. Overall, 8.7% patients were aged <40 years. Diagnostic delay was 1.1 years. Angioedema mainly affected the face (91.3%), followed by the oropharynx (63%), extremities (50%), and abdomen (37%). Only 1 patient underwent orotracheal intubation. Erythema marginatum was present in 1 patient. A hematologic disorder was recorded in 50% of patients. Angioedema preceded all benign conditions, mostly monoclonal gammopathy of undetermined significance, but appeared very close to or after malignant hematologic diseases (median, 2.2 and 0.29 years). Autoimmune diseases were associated in 50% (autoimmune thyroiditis, 21.5%; systemic lupus erythematosus, 10.9%). Half of them coexisted with hematologic disorders. Anti-C1-INH antibodies were found in 67% of tested patients and were not related to the associated disease. Long-term prophylaxis was necessary in 52.2%, most of whom responded to tranexamic acid.[Conclusions] This study emphasizes the possibility of C1-INH-AAE in patients younger than 40 and in autoimmune diseases other than systemic lupus erythematosus such as autoimmune thyroiditis.Peer reviewe

Anuario de administración y tecnología para el diseño 2017

En este año, el Área de Administración y Tecnología de la Universidad Autónoma Metropolitana presenta el Anuario de Administración y Tecnología para el Diseño con ISSN 2007-7572. De manera sistemática, se busca mejorar la calidad tanto de las investigaciones como de la presentación de la versión impresa como de la digital. Y en este volumen se ha cambiado el diseño editorial con objeto de mejorar la identidad visual para dar a conocer los productos del trabajo de investigación que allí se maneja y para generar un mejor posicionamiento de la publicación. Se pretende incrementar el reconocimiento interno y externo para que se amplíe el número de lectores especialmente en la página de Internet del Área y que sea atractivo a los lectores interesados en este campo del conocimiento y, por medio de una mezcla de colores, diseños, formas e imagen, se desea incorporar los adelantos del diseño gráfico de la publicación como medio para la difusión de las investigaciones. Desde el punto de vista del contenido, los investigadores del Área están conscientes del constante avance de la tecnología y de la constante innovación en todos los campos, algunas pequeñas, pero otras de gran magnitud. Esto hace que el mundo progrese y con ello, que la gente pueda mejorar sus condiciones de vida o encontrar nuevas formas de hacer todo más satisfactorio y accesible

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain

In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries