Immunological and inflammatory changes after simplifying to dual therapy in virologically suppressed HIV-infected patients through week 96 in a randomized trial

Objectives: To evaluate whether simplification of antiretroviral treatment to dual therapy (DT) negatively impacts immune recovery (IR), immune activation and inflammation (IA/I), and HIV reservoir. Methods: An open-label, single-centre, randomized controlled trial conducted in adult virologically suppressed HIV-infected patients on triple therapy (TT) with elvitegravir-cobicistat, emtricitabine and tenofovir alafenamide or dolutegravir (DTG), abacavir, and lamivudine (3TC). Participants were randomized to continue TT or switch to DTG, or darunavir/cobicistat (DRVc) plus 3TC. IR was assessed by CD4þ/CD8þ ratio at 48 and 96 weeks. Changes in immune activation, proliferation, exhaustion, senescence, and apoptosis in CD4þ and CD8þ T cells, plasma sCD14, hsCRP, D-dimers, b2-microglobulin, IL-6, TNF-a and IP-10 levels, cell-associated HIV-DNA (CA-DNA), and unspliced HIV-RNA (usRNA) were also analysed. Results: One hundred and fifty-one participants were enrolled. Fourteen patients did not complete the follow up. In the ITT and PP analysis, the IR was similar between the treatment arms. In the ITT analysis, the median increase in CD4þ/CD8þ ratio was 0.10, 0.04, and 0.07 at week 48, and 0.09, 0.05, and 0.08 at week 96 for TT, DTG/3TC, and DRVc/3TC, respectively. After adjusting for confounding factors, the slopes of changes in CD4þ/CD8þ ratio over time were independent of treatment (F ¼ 1.699; p ¼ 0.436) and related only to baseline values (F ¼ 756.871; p ¼ 0.000). There were no differences in IA/I, CA-DNA, or usRNA between treatment arms. Discussion: Both IR and IA/I, CA-DNA, and usRNA were similar in the three treatment groups, regardless of maintaining TT or simplifying to DTG/3TC or DRVc/3TC in virologically suppressed HIV-infected patients

Evolución temporal del uso de las técnicas estadísticas en las publicaciones médicas españolas (2002-2012)

Falta palabras clavesObjetivo: Describir la metodología estadística empleada por los autores y accesibilidad de los artículos originales publicados en las revistas españolas, indexadas en el JCR (Journal Citation Reports), más representativas de las áreas familiar y comunitaria (Atención Primaria), médico-quirúrgica (Cirugía Española), salud pública (Gaceta Sanitaria), clínica (Medicina Clínica) y mixta (Revista Española de cardiología), en los años 2002 y 2012. Material y Métodos: Estudio observacional descriptivo analizando los artículos originales, por un único revisor, publicados durante el año 2002 y el 2012 en cinco revistas españolas seleccionadas como representativas de cada una de las áreas por un panel de expertos. Los análisis estadísticos han sido clasificados según el método de Emerson y Colditz, de 18 categorías jerárquicas, adaptado por Mora et al. Resultados: De 752 artículos originales recopilados, se utilizó alguna prueba estadística en 730 artículos. En estos 730 artículos contabilizamos 1.780 pruebas estadísticas. El uso de pruebas estadísticas más allá de la descriptiva fue del 90,10% (IC95%:87,97%-91,96%).en el año 2002 y del 95,87% (IC95%:94,32%-97,10%).en el año 2012. Las pruebas estadísticas más frecuentes usadas en 2002 y 2012 fueron: “Pruebas ji-cuadrado” (22,55% y 19,75%, en 2002 y 2012 respectivamente), “Pruebas t de Student y pruebas z” (16,72% y 17,11%%, en 2002 y 2012 respectivamente) y “Análisis de supervivencia” (11,44% y 13,20%%, en 2002 y 2012 respectivamente). En 2012 hubo un descenso notable del 58,00% en el uso de sólo “estadísticas descriptiva” y aumentaron el uso de “Ajuste y estandarización de tasas” (3,3 veces más que en el año 2002), “Regresión múltiple” (72,00%) y “Regresión simple” (48,00%). Un lector con conocimientos de análisis bivariantes tenía acceso a dichos análisis en el 67,55% (IC95%: 64,39%-70,58%) en el año 2002 y un 63,26% (IC95%: 59,96%-66,47%) en 2012. Igualmente, tuvieron acceso a los artículos en el 50,36% (IC95%: 45,45%-55,26%) en el año 2002 y un 35,14% (IC95%: 29,86%-40,71%) en 2012. El 47,96% en el año 2002 y el 66,13% en el año 2012 de los artículos originales revisados indicaron el tipo de diseño metodológico. El uso de intervalos de confianza (IC) en los originales publicados en 2012 aumentó un 48,40% con respecto al año 2002. Han recibido financiación directa para la realización de la investigación el 20,38% en 2002 y en 42,49% en 2012. La aplicación informática más citada fue SPSS con un 66,18% y sólo el 12,66% fueron de adquisición gratuita o libre. Conclusiones: Los resultados obtenidos no están en discordancia con lo publicados por otros autores. La estadística es una herramienta primordial para la investigación biomédica española, ya que un bajo porcentaje de los artículos examinados no necesitaban de su uso. Se produce un aumento de análisis bivariantes y complejos en el año 2012 con respecto al 2002. En ambos años se mantienen las mismas pruebas estadísticas como las más representativas del estudio. Aumenta la accesibilidad tanto del entendimiento de los análisis como a los artículos de los lectores con conocimientos avanzados (Nivel III) en el año 2012

Clinical, laboratory data and inflammatory biomarkers at baseline as early discharge predictors in hospitalized SARS-CoV-2 infected patients

Background The SARS-CoV-2 pandemic has overwhelmed hospital services due to the rapid transmission of the virus and its severity in a high percentage of cases. Having tools to predict which patients can be safely early discharged would help to improve this situation. Methods Patients confirmed as SARS-CoV-2 infection from four Spanish hospitals. Clinical, demographic, laboratory data and plasma samples were collected at admission. The patients were classified into mild and severe/critical groups according to 4-point ordinal categories based on oxygen therapy requirements. Logistic regression models were performed in mild patients with only clinical and routine laboratory parameters and adding plasma pro-inflammatory cytokine levels to predict both early discharge and worsening. Results 333 patients were included. At admission, 307 patients were classified as mild patients. Age, oxygen saturation, Lactate Dehydrogenase, D-dimers, neutrophil-lymphocyte ratio (NLR), and oral corticosteroids treatment were predictors of early discharge (area under curve (AUC), 0.786; sensitivity (SE) 68.5%; specificity (S), 74.5%; positive predictive value (PPV), 74.4%; and negative predictive value (NPV), 68.9%). When cytokines were included, lower interferon-γ-inducible protein 10 and higher Interleukin 1 beta levels were associated with early discharge (AUC, 0.819; SE, 91.7%; S, 56.6%; PPV, 69.3%; and NPV, 86.5%). The model to predict worsening included male sex, oxygen saturation, no corticosteroids treatment, C-reactive protein and Nod-like receptor as independent factors (AUC, 0.903; SE, 97.1%; S, 68.8%; PPV, 30.4%; and NPV, 99.4%). The model was slightly improved by including the determinations of interleukine-8, Macrophage inflammatory protein-1 beta and soluble IL-2Rα (CD25) (AUC, 0.952; SE, 97.1%; S, 98.1%; PPV, 82.7%; and NPV, 99.6%). Conclusions Clinical and routine laboratory data at admission strongly predict non-worsening during the first two weeks; therefore, these variables could help identify those patients who do not need a long hospitalization and improve hospital overcrowding. Determination of pro-inflammatory cytokines moderately improves these predictive capacities.Consejeria de Salud y Familia COVID-00052020 RH-0037-2020Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades PY20/01276Instituto de Salud Carlos III CP19/00159 CP19/00146 FI19/00304 FI19/00083 COV20/00698Red Tematica de Investigacion Cooperativa en SIDA RD16/0025/0020 RD16/0025/0006 RD16/0025/0026European CommissionCentro de Investigacion Biomedica en Red de Enfermedades Infecciosas-ISCIII Madrid, Spain CB21/13/00020Spanish Research Council (CSIC)IISPV 2019/IISPV/05GeSID

The Impact of the Second Wave of the COVID-19 Pandemic on Non-COVID Hospital Care in a Tertiary Hospital in Spain

Supplementary Materials: The supplementary information can be accessed and downloaded at: https://www.mdpi.com/article/10.3390/jcm12175507/s1In 2020, Spain ranked fourth among European countries with the highest excess mortality due to COVID-19 disease. This study evaluates the impact of the COVID-19 pandemic on non-COVID patients in a tertiary hospital during the second pandemic wave in Spain (22 June 2020-6 December 2020). Data from Virgen del Rocio University Hospital in Seville during that timeframe were compared with the data from the same period in the preceding two years (2018-2019). Between-group comparisons were performed using the Chi-squared test, Student's t-test, or Mann-Whitney U tests, as appropriate. A total of 63,137 non-COVID patients were included in this study. During the second pandemic wave, a 19% decrease was observed in the annual number of non-COVID admissions overall (18,260 vs. 22,439, p < 0.001), but a 10% increase in the proportion of emergency admissions (60.6% vs. 54.93%, p < 0.001), a higher severity level of patients (1.79 vs. 1.72, p < 0.001), a longer in-hospital stay (7.02 vs. 6.74 days, p < 0.001), a 26% increase in non-COVID mortality (4.9% vs. 3.9%, p < 0.001), and a 50% increase in global mortality (5.9 vs. 3.9, p < 0.001) were also observed. In terms of both medical and surgical diagnoses, a significant reduction in the number of admissions and an increase in in-hospital mortality were observed. These results demonstrate the significant impact of the pandemic on hospital care, similar to what was previously observed during the initial wave in the same hospital. Our findings emphasize the need to include non-COVID patients when assessing the broad impact of the pandemic on healthcare, beyond its direct effects on COVID-19 patients.“Programa Beatriz Galindo” Ministry of Universities, the Government of SpainUniversity of Seville, Spai

Decay kinetics of HIV-1-RNA in seminal plasma with dolutegravir/ lamivudine versus dolutegravir plus emtricitabine/tenofovir alafenamide in treatment-naive people living with HIV

Background: This was a substudy of a Phase IV, randomized clinical trial (ClinicalTrials.gov identifier: NCT04295460) aiming to compare the activity of dolutegravir/lamivudine versus dolutegravir plus tenofovir alafenamide/emtricitabine (DTG + TAF/FTC) in the male genital tract. Methods: Participants were asymptomatic adults without sexually transmitted diseases, treatment-naive people living with HIV (PLWH), with CD4+ T cell counts >200 cells/mm3 and plasma HIV-1-RNA levels >5000 and <500 000 copies/mL, randomized (1:1) to DTG + TAF/FTC or dolutegravir/lamivudine. Blood plasma (BP) and seminal plasma (SP) were collected at baseline and Weeks 4, 8, 12 and 24. HIV-1-RNA was measured in BP and SP using the Cobas 6800 system (Roche Diagnostics) with a lower detection limit of 20 copies/mL. The primary efficacy endpoint was the proportion of subjects with undetectable SP HIV-1-RNA at Week 12 by intention-to-treat analysis. Results: Fifteen participants in the DTG + TAF/FTC and 16 in the dolutegravir/lamivudine arms were analysed, with basal SP viral load of 4.81 (4.30–5.43) and 4.76 (4.09–5.23), P = 0.469, respectively. At Week 12, only one participant in each treatment arm had a detectable SP HIV-1-RNA (DTG + TAF/FTC, 141 copies/mL; dolutegravir/ lamivudine, 61 copies/mL). Based on the estimated means, there was no significant difference in the decay of HIV-1-RNA in both BP and SP over time between the two arms of treatment (F = 0.452, P = 0.662, and F = 1.147, P = 0.185, respectively). Conclusions: After 12 weeks of treatment, there were no differences in the percentage of undetectable SP HIV-1-RNA in naive PLWH who started dolutegravir/lamivudine compared with DTG + TAF/FTC.Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI)ViiV Healthcare UK Ltd. The funders had no role in study design, data collectionInstituto de Salud Carlos III(CP19/00159)PFIS contracts (FI19/00304)Ministerio de Ciencia e Innovación, SpainEuropean Regional Development Fund ‘a way to make Europ

Nursing Students’ Knowledge, Awareness, and Experiences of Emergency Contraception Pills’ Use

The emergency contraception pill (ECP) is a non-prescribed medication in Spain. However, there is not enough evidence of its use among young people to define sex education contents. The aims of this research were to describe the experiences of the use of the ECP in university students and analyze their knowledge, attitude, and awareness regarding the ECP. The cross-sectional, analytic study was conducted with nursing degree students at the University of Seville. A total of 478 students answered the questionnaire. All of the students (100%) had heard about the ECP and had a positive attitude towards this contraceptive. A total of 25.7% had used the ECP, mainly because a condom had failed or because they did not use any contraceptive at all. Deficiencies in knowledge are related with the ECPs’ mechanism of action, efficacy after repeated use, and the type of ECP available. Female students who used no method at all or withdrawal, and who were over 20 years old, used ECP to a greater extent (p < 0.005). Further education initiatives focused on the use of the ECP, its efficacy, and typology are needed, particularly among future health professionals who will later educate other young people

miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

Background: Sorafenib constitutes a suitable treatment alternative for patients with advanced hepatocellular carcinoma (HCC) in whom atezolizumab + bevacizumab therapy is contraindicated. The aim of the study was the identification of a miRNA signature in liquid biopsy related to sorafenib response. Methods: miRNAs were profiled in hepatoblastoma HepG2 cells and tested in animal models, extracellular vesicles (EVs), and plasma from HCC patients. Results: Sorafenib altered the expression of 11 miRNAs in HepG2 cells. miR-200c-3p and miR-27a-3p exerted an anti-tumoral activity by decreasing cell migration and invasion, whereas miR-122-5p, miR-148b-3p, miR-194-5p, miR-222-5p, and miR-512-3p exerted pro-tumoral properties by increasing cell proliferation, migration, or invasion, or decreasing apoptosis. Sorafenib induced a change in EVs population with an increased number of larger EVs, and promoted an accumulation of miR-27a-3p, miR-122-5p, miR-148b-3p, miR-193b-3p, miR-194-5p, miR-200c-3p, and miR-375 into exosomes. In HCC patients, circulating miR-200c-3p baseline levels were associated with increased survival, whereas high levels of miR-222-5p and miR-512-3p after 1 month of sorafenib treatment were related to poor prognosis. The RNA sequencing revealed that miR-200c-3p was related to the regulation of cell growth and death, whereas miR-222-5p and miR-512-3p were related to metabolic control. Conclusions: The study showed that Sorafenib regulates a specific miRNA signature in which miR-200c-3p, miR-222-5p, and miR-512-3p bear prognostic value and contribute to treatment response.Instituto de Salud Carlos IIIEuropean Commission PI16/00090 PI19/01266Consejeria de Igualdad, Salud y Politicas Sociales PI-0198-2016Spanish Government FPU17/00026GEIVEX Mobility Fellowships 2020German Research Foundation (DFG)National Health and Medical Research Council (NHMRC) of Australia EST19/01091European CommissionInstituto de Salud Carlos IIIEuropean Commission PI15/00145 PI18/0358 PI18/00768AECC PI044031Instituto de Salud Carlos II

Validity and Reliability of the Portuguese Version of the Connor–Davidson Resilience Scale of 10 Elements for Young University Students

Background: Resilience is an important aspect of mental health in young people, which has become more relevant after the COVID-19 pandemic. It is therefore of paramount importance to have valid and reliable instruments that measure the globality of this aspect. One of the instruments that has been shown to have good psychometric properties and which has been widely adapted in several languages is the Connor–Davidson resilience scale, composed of 10 elements (10-item CD-RISC). Aim: The aim of this study was to evaluate the validity and reliability of the Portuguese version of the 10-item CD-RISC among young university students. Methods: a cross-sectional observational study of psychometric validation was conducted with a sample of 206 university students. Results: Good and adequate fit indices were obtained for the confirmatory factor analysis (CFA): Standardized Root-Mean-Square Residual [SRMR] = 0. 056; comparative fit index [CFI] = 0.958; and the Tucker–Lewis index [TLI] = 0.946. It also showed an average degree of convergent validity with the Depression, Anxiety and Stress Scale (DASS-21) and the General Health Scale (SF-36), and its internal consistency was good (Cronbach’s alpha = 0.842) with a range of factor loadings between 0.42 and 0.77. Conclusions: the results show that the 10-item CD-RISC is a valid, reliable scale to measure resilience among young Portuguese university students.Grant for the internal mobility of personnel dedicated to research (Modality A-13A of the own research plan) from the University of Sevill

Nursing Students’ Knowledge, Awareness, and Experiences of Emergency Contraception Pills’ Use

The emergency contraception pill (ECP) is a non-prescribed medication in Spain. However, there is not enough evidence of its use among young people to define sex education contents. The aims of this research were to describe the experiences of the use of the ECP in university students and analyze their knowledge, attitude, and awareness regarding the ECP. The cross-sectional, analytic study was conducted with nursing degree students at the University of Seville. A total of 478 students answered the questionnaire. All of the students (100%) had heard about the ECP and had a positive attitude towards this contraceptive. A total of 25.7% had used the ECP, mainly because a condom had failed or because they did not use any contraceptive at all. Deficiencies in knowledge are related with the ECPs’ mechanism of action, efficacy after repeated use, and the type of ECP available. Female students who used no method at all or withdrawal, and who were over 20 years old, used ECP to a greater extent (p < 0.005). Further education initiatives focused on the use of the ECP, its efficacy, and typology are needed, particularly among future health professionals who will later educate other young people