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.