Impact of Neuromyelitis Optica Spectrum Disorder on Quality of Life from the Patients' Perspective : An Observational Cross-Sectional Study

Altres ajuts: Medical Department of Roche Farma, Spain (ML41397).Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors. Methods: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis. Results: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29. Conclusion: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions

Quantifying the patient´s perspective in neuromyelitis optica spectrum disorder: Psychometric properties of the SymptoMScreen questionnaire

Background: The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. Methods: A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. Results: A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach's alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken's criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). Conclusions: The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD

Perception of Stigma in Patients with Neuromyelitis Optica Spectrum Disorder

Background: Perception of stigma was associated with low self-esteem, psychological problems, and decreased health-seeking behavior among patients with different neurological disorders. The purpose of this study was to assess stigmatization and its impact in patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: A non-interventional study was conducted at thirteen neuroimmunology clinics in Spain. Patients with a diagnosis of NMOSD (2015 Wingerchuk criteria) were included. The 8-item Stigma Scale for Chronic Illness (SSCI-8), the Expanded Disability Status Scale (EDSS), the 29-item Multiple Sclerosis Impact Scale (MSIS-29), the Beck Depression Inventory-Fast Screen (BDI-FS), the MOS Pain Effects Scale (MOS-PES) and the Fatigue Impact Scale for Daily Use (D-FIS) were used to assess the perception of stigma, disability, quality of life, mood, pain, and fatigue, respectively. Associations between outcome measures were analyzed using Spearman's rank correlation. Results: Seventy-one patients were studied (mean age: 47.4 years ± 14.9, 81.7% female, mean time since disease onset: 9.9 years ± 8.1). The median EDSS score was 3.0 (interquartile range 1.5, 4.5). Stigma prevalence was 61.4% (n=43). Thirty-one patients (43.6%) had depression. The SSCI-8 score showed a significant correlation with both physical (rho=0.576, p<0.0001) and psychological (rho=0.608, p<0.0001) MSIS-29 scales scores, EDSS score (rho=0.349, p=0.0033), BDI-FS score (rho= 0.613, p<0.0001), MOS-PES score (rho= 0.457, p<0.0001), and D-FIS score (rho=0.556, p<0.0001). Conclusion: Stigma is a common phenomenon affecting over 6 out of 10 patients with NMOSD. Understanding stigma may be useful to develop educational strategies improving NMOSD knowledge

Anti-TNF-a therapy in patients with refractory uveitis due to Behçet's disease: a 1-year follow-up study of 124 patients

Objective: The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçet's disease (BD). Methods: We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. Results: Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 μm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 μm) that improved from 420 μm (s.d. 119.5) at baseline to 271 μm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. Conclusion: Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.This work was partially supported by the RETICS Program [RD12/0009/0013 (RIER)] from the Instituto de Salud Carlos III (ISCIII), Madrid, Spain.Medicin

SARS-CoV-2 Infection in Multiple Sclerosis

To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal diseas

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U

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

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología