Varicella-zoster virus clades circulating in Spain over two decades

BACKGROUND: Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain. OBJECTIVES: To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016. STUDY DESIGN: In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs. RESULTS: Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001). CONCLUSIONS: Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population.This work was supported by a grant from Instituto de Salud Carlos III. Project code MPY1372/12. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Enteroviruses in Spain: virological and epidemiological studies over 10 years (1988-97)

A total of 15,662 clinical samples were analysed for enterovirus (EV) isolation in cell cultures during a 10-year period (1988-97). Furthermore, 210 isolates of EV obtained in primary laboratories within Spain from patients with meningitis were characterized. The total number of EV typed was 758, including 727 non-polio EV and 31 Sabin-like (SL) polioviruses. Twenty-eight EV serotypes were represented. Echoviruses comprised 90% (653/727) of fully typed non-polio EV. The four most prevalent serotypes were echovirus 30, echovirus 9, echovirus 6 and echovirus 4. Echovirus 30 was the main serotype associated with meningitis. Echovirus 9 was the aetiological agent in 20 outbreaks of meningitis while the occurrence of echovirus 6 was localized in 1 year (1997). Coxsackieviruses A and B occurred in 3 and 7% of the non-polio EV respectively. Coxsackievirus B5 presented the relative greater abundance. This paper examines the epidemiology of EV in Spain to serotype level over a 10-year period with special attention to non-polio EV associated with meningitis.Dr I. Casas is a postdoctoral fellow supported by the Institute de Salud Carlos III, Becas de Perfeccionamiento (97/4165). We acknowledge the assistance provided by clinical colleagues in other virology laboratories: Gurutze Rubio (Cruces, Bilbao, Hospital), Nuria Rabella (Santa Cruz y San Pablo, Barcelona Hospital), Joaquin Otero (Doce de Octubre, Madrid Hospital). We also thank Raquel Noguerol, Hortensia del Pozo and Isidoro Bustillo for their technical assistance and an anonymous referee for many useful suggestions. This work was partially supported by Fondo de Investigación Sanitaria grant FIS 96/0304.S

European mitochondrial haplogroups predict liver-related outcomes in patients coinfected with HIV and HCV: a retrospective study

BACKGROUND: Mitochondrial DNA (mtDNA) haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Our aim was to determine whether mtDNA haplogroups are associated with liver-related events (LREs) in HIV/HCV-coinfected patients. METHODS: We carried out a retrospective cohort study in HIV/HCV-coinfected patients who were potential candidates for therapy with interferon and ribavirin (IFN/Rib) between 2000 and 2009. The primary endpoint was the occurrence of LREs (decompensation or hepatocellular carcinoma). mtDNA genotyping was performed using the Sequenom MassARRAY platform. We used Fine and Gray proportional hazards model to test the association between mtDNA haplogroups and LREs, considering death as a competitive risk. RESULTS: The study population comprised 243 patients, of whom 40 had advanced fibrosis or cirrhosis. After a median follow-up of 7.7 years, 90 patients treated with IFN/Rib achieved sustained viral response (SVR), 18 patients had LREs, and 11 patients died. Patients with haplogroup H had lower cumulative incidence than patients with other haplogroups (p = 0.012). However, patients with haplogroup T had higher cumulative incidence than patients with other haplogroups (p = 0.074). In the multivariate analysis, haplogroup T was associated with an increased hazard of developing LREs [adjusted subhazard ratio (aSHR) = 3.56 (95% CI 1.13;11.30); p = 0.030]; whereas haplogroup H was not associated with lower hazard of LREs [aSHR = 0.36 (95% CI 0.10;1.25); p = 0.105]. When we excluded patients who achieved SVR during follow-up, we obtained similar SHR values. CONCLUSIONS: European mitochondrial haplogroups may influence the natural history of chronic hepatitis C.This study was supported by grants from Fondo de Investigación de Sanidad en España (Spanish Funds for Health Research [FIS]), grant numbers PI14/01094 and PI17/00657 to JB, PI14CIII/00011 and PI17CIII/00003 to SR. The study was also funded by the RD16CIII/0002/0002 and RD16/0025/0017 projects as part of the Plan Nacional R + D + I and cofunded by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT15/00079 and INT16/00100. LMM, MAJS, and PGB are supported by “Instituto de Salud Carlos III” (grant numbers CD14/00002, CD13/00013, CP14/0010, and FI12/00036; respectively).S

Prediction of hepatic fibrosis in patients coinfected with HIV and hepatitis C virus based on genetic markers

Objective: To assess the ability of the cirrhosis risk score (CRS) to predict liver fibrosis progression in HIV/hepatitis C virus (HCV)-coinfected patients. Design: Retrospective follow-up study. Methods: Based on a minimum follow-up time of 10 years with HCV infection, 190 HIV/HCV-coinfected patients were classified according to their METAVIR score: (1) 25 nonprogressor patients who did not develop fibrosis (F0) and (2) 165 progressor patients who developed fibrosis (F ≥ 1). Seven polymorphisms of CRS signature and IL28B genotype were performed using the GoldenGate assay. The CRS signature was calculated by naive Bayes formula as previously described. Results: Nonprogressors had CRS values significantly lower than progressors (0.61 versus 0.67; P = 0.043). Among the progressors, we observed similar CRS values through all the fibrosis stages (F1/F2/F3/F4). The percentage of patients with CRS > 0.70 (high risk of developing fibrosis) was higher in progressors than in nonprogressors; but the percentages with values between 0.50 and 0.70 (intermediate risk) and <0.50 (low risk) were quite similar for each of the fibrosis stages (P = 0.047). The area under the receiver-operating characteristic curve of CRS for discriminating nonprogressor versus progressor was 0.625 (P = 0.043). When clinical variables were considered (age at HCV infection, intravenous drug use, gender, IL28B, and HCV genotype), the area under the receiver-operating characteristic curve of CRS improved up to 0.739 (P < 0.001). Conclusions: CRS itself seems not to be a good marker for identifying HIV/HCV-coinfected patients who are at high risk of developing liver fibrosis. However, CRS score coupled with clinical factors might help to distinguish between nonprogressors and progressors patients.Supported by Fondo de Investigacion de Sanidad en España (FIS) (Spanish Health Founds for Research) Grants PI08/0738, PI11/00245; PI08/0928, and PI11/01556; Red Española de Investigación en SIDA (RIS) (AIDS Research Network) Grants RD12/0017/0024 and RD12/0017/0004; and “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE) Grant 361020/10. A. F. R., M. G. F., P. G. B., and M. A. J. S. are supported by “Instituto de Salud Carlos III” Grants UIPY-1377/08, CM09/00031, FI12/00036, and CM10/00105, respectively.S

rs7903146 polymorphism at transcription factor 7 like 2 gene is associated with total cholesterol and lipoprotein profile in HIV/hepatitis C virus-coinfected patients

Transcription factor 7 like 2 (TCF7L2) rs7903146 polymorphism has been associated with metabolic disturbance and cardiovascular disease. The aim of this study was to analyze the association between TCF7L2 rs7903146 polymorphism and potential disturbances on the lipid profile in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We performed a cross-sectional study on 263 HIV/HVC-coinfected patients. TCF7L2 polymorphism was genotyped by GoldenGate assay. The analysis was performed by linear and logistic regression under a dominant model of inheritance. The variables analyzed were total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), non-HDL-C, and triglycerides. Patients harboring the rs7903146 TT/TC genotype showed a diminished concentration of TC (p=0.003), LDL-C (p=0.004), HDL-C (p=0.012), and non-HDL-C (p=0.013), a lower percentage of TC≥200 mg/dl (p=0.038), and a higher percentage of HDL≤40 mg/dl (p=0.023). In addition, we observed that rs7903146 was differently related to fasting serum lipid levels according to the HCV-genotype (HCV-GT). With regard to HCV-GT1 patients, the rs7903146 TT/TC genotype was associated with lower levels of HDL-C [adjusted arithmetic mean ratio (aAMR)=0.91; p=0.049] and an elevated percentage of patients with HDL-C≤40 mg/dl [adjusted odds ratio (aOR)=3.26; p=0.003]. For HCV-GT3 patients, the rs7903146 TT/TC genotype was associated with lower serum values of TC (aAMR=0.81; p=0.037), LDL-C (aAMR=0.67; p=0.001), and non-HDL-C (aAMR=0.75; p=0.002) and a reduced percentage of TC≥200 mg/dl (aOR=0.089; p=0.037). In conclusion, the TCF7L2 rs7903146 TT/TC genotype was associated with lower levels of TC, LDL, and HDL in HCV-GT3 patients, and lower levels of HDL-C in HCV-GT1 patients, suggesting a role in cardiovascular disease and a potential use as a biomarker in HIV/HCV-coinfected patients.D.P.T., M.A.JS., and M.G.A. have received research funding from “Instituto de Salud Carlos III” [grants CM12/00043, CM10/00105, and CD12/00442, respectively]. J.B. is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS). This work has been supported by grants from Fondo de Investigación de Sanidad en España (FIS) [Spanish Health Funds for Research] [grants PI08/0738, PI11/00245; PI08/0928, and PI11/01556], and “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE) [grant 361020/10]. This work has been (partially) funded by the RD12/0017/0024 and RD12/0017/0004 projects as part of the Plan Nacional R+D+I and cofinanced by ISCIII––Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).S

Hypermedia : taller de configuración arquitectónica

El Grupo "Hypermedia. Taller de configuración arquitectónica" lo formamos un colectivo de profesores (doctores y asociados), doctorandos y becarios agrupados en la enseñanza del dibujo y el dibujar como herramienta para la elaboración profesional de proyectos de arquitectura en los primeros (1º y 2º año) semestres de la carrera de Arquitecto Superior. Algunos de nosotros empezamos hace más de 35 años alrededor de los ordenadores, estudiando y simulando procesos de generación de propuestas arquitectónicas. Trabajábamos en el Centro de Cálculo de la Universidad Complutense de Madrid (desde el año 1968, en un seminario denominado: "Análisis y generación de formas arquitectónicas"). Después, desde el 1974, en la Cátedra de Análisis de Formas Arquitectónicas, hemos participado y contribuido a la definición del Área de conocimiento denominada "Expresión Gráfica Arquitectónica" y hemos constituido la asociación de Departamentos del Área de todas las Escuelas de Arquitectura del Estado Español, que, en paralelo, ha creado una Revista especializada (EGA lleva editados 10 números anuales) y sostiene la convocatoria bianual de un Congreso Internacional sobre los temas propios de nuestra especialización. Hoy el Grupo, amplio por razón de la situación estratégica del dibujar (inespecífico, geométrico y arquitectónico) como medio indispensable en el trabajo de proyectar arquitectura, se organiza en varios subgrupos que se reparten puntualmente las preocupaciones y temáticas globales (colectivas) que sistemáticamente aparecen, produciendo gran cantidad de trabajos que, en forma de encargos subvencionados, tesis doctorales, monografías, ponencias y artículos aparecen año tras año en diversos medios de difusión (u edición). Nuestros trabajos no son todos estratégicos, pero son todos (sean o no aplicaciones) centrales en la formación arquitectónica, concernidos con la fundamentación teórica, social, científica y técnica de lo medio ambiental (lo arquitectónico entendido como lo envolvente adecuado al albergue de actividades humanas socializadas)

Plan estratégico para la eliminación del sarampión y la rubeola en España 2021-2025

Consejo Interterritorial del Sistema Nacional de Salud. Plan estratégico para la eliminación del sarampión y la rubeola en España. Ministerio de Sanidad. Enero 2021[ES] El sarampión y la rubeola constituyen importantes problemas de salud pública y ambas enfermedades son potencialmente candidatas a erradicarse mediante vacunación. La Organización Mundial de la Salud (OMS) coordina a nivel mundial la eliminación del sarampión y la rubeola y realiza un seguimiento anual de los progresos que se van alcanzando en las diferentes Regiones. La Comisión Regional de Verificación de la eliminación del sarampión y la rubeola declaró que España está en situación de eliminación de la rubeola desde 2015 y del sarampión desde 2016, manteniéndose esta situación en las evaluaciones anuales sucesivas. El 2º Estudio de Seroprevalencia en España, realizado en 2017-2018, muestra un descenso de la población con títulos de anticuerpos frente a sarampión protectores en la población que los ha obtenido mediante vacunación, en un contexto sin circulación del virus salvaje. En relación a la rubeola, se observa una muy elevada inmunidad de la población frente al virus de la rubeola en todos los grupos de edad, demostrando el mantenimiento de la inmunidad conferida por la vacunación. Este Plan Estratégico para la Eliminación del Sarampión y la Rubeola en España 2021-2025, en adelante el Plan, actualiza el Plan Nacional de Eliminación del Sarampión, del año 2000 y el Protocolo de Vigilancia de la Rubeola y el Síndrome de Rubeola Congénita, de 2007, que juntos formaban el Plan de Eliminación del Sarampión y la Rubeola para España. El Plan para 2021-2025 está estructurado en tres estrategias y seis objetivos: Estrategia 1 – Fortalecer la inmunidad de la población: Objetivo 1 – Alcanzar y mantener coberturas de vacunación de al menos el 95% con dos dosis de vacuna triple vírica en España y en cada una de las CCAA y ciudades de Ceuta y Melilla mediante el programa sistemático de vacunación. Objetivo 2 – Identificar, captar y asegurar la vacunación de la población susceptible. Estrategia 2 – Fortalecer el sistema de vigilancia y la actuación en brotes: Objetivo 3 – Detectar, investigar y controlar los casos aislados y los brotes de sarampión y rubeola. Objetivo 4 – Garantizar una investigación de laboratorio de calidad. Objetivo 5 – Implementar de forma rápida las medidas de control de brotes que supongan un evento de salud pública e importancia nacional o internacional. Estrategia 3 – Crear y reforzar estrategias de comunicación, información y asesoría: Objetivo 6 – Informar, capacitar, relacionar e involucrar a todos los agentes de los que depende directa o indirectamente la eliminación del sarampión y la rubeola. Para cada uno de los objetivos se han establecido actividades para su consecución. Se realizará un seguimiento anual del Plan, en el que se recogerá una evaluación de las actividades realizadas mediante la recogida de los indicadores que se han definido para cada una de las estrategias y objetivos. El informe técnico anual se revisa y evalúa por el Comité Nacional de Verificación y se envía online para la evaluación que a su vez realiza la Comisión Regional Europea de Verificación de la Eliminación del Sarampión y la Rubeola. [EN] Measles and rubella are major public health problems, and both diseases are potentially candidates for eradication by vaccination. The World Health Organization (WHO) coordinates the elimination of measles and rubella at a global level and annually monitors the progress made in the different Regions. The Regional Commission for the Verification of the elimination of measles and rubella at European level declared that Spain has been in a situation of elimination of rubella since 2015 and measles since 2016, maintaining this situation in successive annual evaluations. The 2nd Seroprevalence Study in Spain carried out in 2017-2018, shows a decrease in the population with protective measles antibody titers is observed in those that obtained immunity by vaccination, and in a context without circulation of the wild virus. Regarding rubella, a very high immunity of the population against the virus is observed in all age groups, demonstrating the maintenance of the immunity conferred by vaccination. The Strategic Plan for the Elimination of Measles and Rubella in Spain 2021-2025, hereinafter the Plan, updates the National Plan for the Elimination of Measles, of the year 2000 and the Protocol for the Surveillance of Rubella and Congenital Rubella Syndrome, of 2007, which together formed the Measles and Rubella Elimination Plan for Spain. The Plan for 2021-2025 is structured in three strategies and six objectives: Strategy 1 - Strengthen the immunity of the population: Objective 1 - Achieve and maintain vaccination coverage of at least 95% with two doses of MMR vaccine in Spain and in each of the Autonomous Communities and cities of Ceuta and Melilla through the systematic vaccination program. Objective 2 - Identify, capture and ensure vaccination of the susceptible population. Strategy 2 - Strengthen the surveillance system and action in outbreaks: Objective 3 - Detect, investigate and control isolated cases and outbreaks of measles and rubella. Objective 4 - Guarantee quality laboratory research. Objective 5 - Quickly implement outbreak control measures that involve a public health event of national or international importance. Strategy 3 - Create and reinforce communication, information and advice strategies: Objective 6 - Inform, train, relate and involve all the agents on whom the elimination of measles and rubella depends directly or indirectly. Activities have been established for each of the objectives. Annual monitoring of the Plan, including an evaluation of the activities, will be carried out by collecting the defined indicators for each of the strategies and objectives. The National Verification Committee will review and evaluate the annual technical report that will be sent for the assessment conducted by the European Regional Commission for the Verification of the Elimination of Measles and Rubella.N

Rationale and design of a randomised controlled trial evaluating the effectiveness of an exercise program to improve the quality of life of patients with heart failure in primary care : the EFICAR study protocol

Background: Quality of life (QoL) decreases as heart failure worsens, which is one of the greatest worries of these patients. Physical exercise has been shown to be safe for people with heart failure. Previous studies have tested heterogeneous exercise programs using different QoL instruments and reported inconsistent effects on QoL. The aim of this study is to evaluate the effectiveness of a new exercise program for people with heart failure (EFICAR), additional to the recommended optimal treatment in primary care, to improve QoL, functional capacity and control of cardiovascular risk factors. Methods/Design: Multicenter clinical trial in which 600 patients with heart failure in NYHA class II-IV will be randomized to two parallel groups: EFICAR and control. After being recruited, through the reference cardiology services, in six health centres from the Spanish Primary Care Prevention and Health Promotion Research Network (redIAPP), patients are followed for 1 year after the beginning of the intervention. Both groups receive the optimized treatment according to the European Society of Cardiology guidelines. In addition, the EFICAR group performs a 3 month supervised progressive exercise program with an aerobic (high-intensity intervals) and a strength component; and the programme continues linked with community resources for 9 months. The main outcome measure is the change in health-related QoL measured by the SF-36 and the Minnesota Living with Heart Failure Questionnaires at baseline, 3, 6 and 12 months. Secondary outcomes considered are changes in functional capacity measured by the 6-Minute Walking Test, cardiac structure (B-type natriuretic peptides), muscle strength and body composition. Both groups will be compared on an intention to treat basis, using multi-level longitudinal mixed models. Sex, age, social class, co-morbidity and cardiovascular risk factors will be considered as potential confounding and predictor variables. Discussion: A key challenges of this study is to guarantee the safety of the patients; however, the current scientific evidence supports the notion of there being no increase in the risk of decompensation, cardiac events, hospitalizations and deaths associated with exercise, but rather the opposite. Safety assurance will be based on an optimized standardised pharmacological therapy and health education for all the participants

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension