Background To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov ( NCT04860739 ), and is ongoing. Findings Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. Interpretation BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. Funding Instituto de Salud Carlos III. Translations For the French and Spanish translations of the abstract see Supplementary Materials section.

Pulmonary hypertension is a serious complication of chronic obstructive pulmonary disease (COPD) that currently has no established pharmacological treatment. This study aimed to assess whether concomitant treatment with sildenafil would enhance the results of pulmonary rehabilitation in patients with COPD and increased pulmonary arterial pressure (PAP).In this double-blind, randomised controlled trial patients received 20 mg sildenafil or placebo three times daily and underwent pulmonary rehabilitation for 3 months. The primary end-point was the gain in the cycle endurance time at a constant work-rate. Secondary end-points included performance in the incremental exercise test, 6-min walk distance and quality of life.63 patients with severe COPD and moderately increased PAP were randomised. Cycle endurance time increased by 149 s (95% CI 26-518 s) in the sildenafil group and by 169 s (95% CI 0-768 s) in the placebo group (median change difference -7 s, 95% CI -540-244 s; p50.77). Gains in the incremental exercise test, 6-min walk distance and quality of life at the end of the study did not differ between groups. Measurements of arterial oxygenation and adverse events were similar in both groups.In patients with severe COPD and moderately increased PAP, concomitant treatment with sildenafil does not improve the results of pulmonary rehabilitation in exercise tolerance. @ERSpublications Sildenafil did not improve respiratory rehabilitation outcomes in patients with severe COPD and moderately increased PAP

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Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre-and post-capillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre-and post-capillary PH (CpcPH).

Adolescence is the stage of development where the reward and emotional regulation systems are yet to be adjusted and where most excessive behaviors start, like smartphone abuse. In addition, in this evolutionary period adolescents are more susceptible to behavioral changes through specific interventions or educational programs. Thus, it is fundamental to analyze the personality profile of those adolescents showing excessive mobile phone usage to properly approach later prevention strategies. Impulsivity is one of the most repeated variables associated with teenage addictions, although it has been observed that not all impulsive behaviors need to be detrimental. The aim of this study is to analyze how impulsivity affects smartphone addiction directly, but also indirectly, by assessing its association with sensation seeking variables (thrill and adventure seeking, experience seeking, disinhibition, and boredom susceptibility) which are in turn decisive when using these technologies improperly. The sample was made up of 614 adolescents aged 13–18 attending secondary education from Burgos, Spain. Dickman Impulsivity Inventory, Sensation Seeking Scale, and Ad-hoc questionnaire on adolescent self-perception as to smartphone use were applied. Results show that 41.4% of participants admit to abusing smartphones sometimes, while 18.3% admit to abusing them more frequently and 24% to, at least ever, having defined themselves as smartphone addicts. Stepwise regression analysis revealed that gender (female), dysfunctional impulsivity and sensation seeking (disinhibition and thrill and adventure seeking) evidence 15.7% of variance in smartphone abuse. In addition, sensation seeking (thrill and adventure seeking, disinhibition, and boredom susceptibility) were found to mediate the relationship between dysfunctional impulsivity and smartphone abuse. Therefore, dysfunctional impulsivity was directly connected with teenage smartphone abuse, but also had an indirect stronger association through thrill and adventure seeking, disinhibition and boredom susceptibility.

RESUMENLa adolescencia es una fase crítica del desarrollo por la vulnerabilidad respecto al consumo de sustancias tóxicas. La impulsividad y la búsqueda de sensaciones son rasgos de personalidad que aparecen asociados tradicionalmente con el consumo precoz de cannabis en adolescentes. Se analizan las diferencias en impulsividad (funcional y disfuncional) y en búsqueda de sensaciones (búsqueda de emociones y aventuras, búsqueda de experiencias, desinhibición y susceptibilidad al aburrimiento) por género, edad y consumo de cannabis. La muestra estuvo constituida por 634 adolescentes de colegios públicos y concertados de Burgos (España). Se aplicó el Inventario de Impulsividad, el Cuestionario de Búsqueda de Sensaciones y una pregunta sobre el consumo de cannabis. Las características de la muestra se analizaron con estadística descriptiva y las diferencias en impulsividad y búsqueda de sensaciones por género, edad, consumo de cannabis y su interacción con la prueba MANOVA. Los varones son más impulsivos funcionales y más buscadores de emociones, aventuras y experiencias que las mujeres. Con 14 y 15 años puntúan más alto en búsqueda de emociones y aventuras y menos en búsqueda de experiencias. El 22.5% de los adolescentes consumía cannabis. Estos puntúan más alto en búsqueda de emociones y aventuras, en búsqueda de experiencias, y en desinhibición que los no consumidores. Aparece un incremento de la impulsividad disfuncional y de la susceptibilidad al aburrimiento asociada al consumo en las mujeres. Por lo tanto, los programas preventivos deberían tener en cuenta el género de los adolescentes y algunos rasgos de personalidad para incrementar su efectividad.ABSTRACTAdolescence is a critical phase of development due to the vulnerability to the consumption of toxic substances. Impulsivity and sensation seeking are personality traits that traditionally appear associated with the early consumption of cannabis in adolescents. This study focuses on the analysis of the differences in impulsivity (functional and dysfunctional) and in sensation seeking (thrill and adventure-seeking, disinhibition, experience seeking, and boredom susceptibility) by gender, age and cannabis use. The sample consisted of 634 adolescents from public and private schools of Burgos (Spain). The Dickman’s Impulsivity Inventory, the Sensations Seeking Scale and a question about cannabis consumption were applied. The characteristics of the sample were analyzed with descriptive statistics and the differences in impulsivity and sensation seeking by gender, age, cannabis consumption and its interaction with the MANOVA test. In general, males are more functional impulsive and more thrills and adventures and experiences seekers than female. Participants aged 14 and 15 score higher in thrill and adventure-seeking, and less in experiences seeking. 22.5% of adolescents consumed cannabis. They scored higher in thrill and adventure-seeking, in experience seeking, and in disinhibition than non-consumers. There is an increase in dysfunctional impulsivity and boredom susceptibility associated with consumption in women. Therefore, preventive programs should take into account the gender and certain personality traits of adolescents to increase their effectiveness.

Abstract:FRAGILE X SYNDROME: DETECTION AND INTERVENTION IN THE BEHAVIOURAL PHENOTYPEFragile X syndrome (SXF) constitutes the first cause of hereditary intellectual disability. It is one alteration of the neurodevelopmental produced by a mutation in the FMR1 gene causing inadequate synthesis of the protein FMRP1. The absence of this protein would be responsible for the physical phenotype and behavioral that characterizes these people. This work intends to present the most relevant and significant characteristics that define the behavioral phenotype: hyperactivity and attention deficit, social anxiety, intellectual disabilities and learning problems, linguistic alterations and difficulties of social communication and sensory integration difficulties. The study was conducted on a sample of 26 adults with SXF who attend centers for people with intellectual disabilities. The same socio-educational guidance is provided to respond to the needs and proposed recommendations for the handling of misconduct that people with SXF can present.Keywords: Protein FMRP1, Gene FMR1, Intellectual Disabilities, Alterations of Neurodevelopment, Checklist from HagermanResumen:Síndrome X Frágil (SXF) constituye la primera causa de discapacidad intelectual de tipo hereditario. Es una de las alteraciones del neurodesarrollo producido por una mutación en el gen FMR1 que provoca la sintetización inadecuada de la proteína FMRP1. La ausencia de esta proteína seria la responsable del fenotipo físico y conductual que caracteriza a estas personas. En este trabajo se pretende dar a conocer las características más relevantes y significativa que definen el fenotipo conductual: hiperactividad y dificultades de atención, ansiedad social, discapacidad intelectual y problemas de aprendizaje, alteraciones lingüísticas y de comunicación social y dificultades de integración sensorial. El estudio se llevó a cabo en una muestra de 26 adultos con SXF que acuden a cen tros para personas con discapacidad intelectual. Así mismo se facilitan orientaciones socioeducativas para dar respuesta a las necesidades y se proponen recomendaciones para el manejo de conductas inadecuadas que pueden presentar las personas con SXF.Palabras clave: Proteína FMRP1, Gen FMR1, Discapacidad Intelectual, Alteraciones del Neurodesarrollo, Checklist de Hagerman.

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