NAT2 phenotype alters pharmacokinetics of rivaroxaban in healthy volunteers

Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K antagonists (i.e., acenocoumarol, warfarin) the interindividual variability of DOACs is significant, and may be related to adverse drug reaction occurrence or drug inefficacy, namely hemorrhagic or thromboembolic events. Since there is not a consistent analytic practice to monitor the anticoagulant activity of DOACs, previously reported polymorphisms in genes coding for proteins responsible for the activation, transport, or metabolism of DOACs were studied. The study population comprised 60 healthy volunteers, who completed two randomized, crossover bioequivalence clinical trials between two different rivaroxaban formulations. The effect of food, sex, biogeographical origin and 55 variants (8 phenotypes and 47 single nucleotide polymorphisms) in drug metabolizing enzyme genes (such as CYP2D6, CYP2C9, NAT2) and transporters (namely, ABCB1, ABCG2) on rivaroxaban pharmacokinetics was tested. Individuals dosed under fasting conditions presented lower tmax (2.21 h vs 2.88 h, β = 1.19, R2 =0.342, p = 0.012) compared to fed volunteers. NAT2 slow acetylators presented higher AUC∞ corrected by dose/weight (AUC∞/DW; 8243.90 vs 7698.20 and 7161.25 h*ng*mg /ml*kg, β = 0.154, R2 =0.250, p = 0.044), higher Cmax/DW (1070.99 vs 834.81 and 803.36 ng*mg /ml*kg, β = 0.245, R2 =0.320, p = 0.002), and lower tmax (2.63 vs 3.19 and 4.15 h, β = − 0.346, R2 =0.282, p = 0.047) than NAT2 rapid and intermediate acetylators. No other association was statistically significant. Thus, slow NAT2 appear to have altered rivaroxaban pharmacokinetics, increasing AUC∞ and Cmax. Nonetheless, further research should be conducted to verify NAT2 involvement on rivaroxaban pharmacokinetics and to determine its clinical significanceGonzalo Villapalos-García was co-financed by Instituto de Salud Carlos III (ISCIII) and the European Social Fund (PFIS predoctoral grant, number FI20/00090). Marcos Navares-Gomez ´ was financed by the ICI20/00131 grant, Accion ´ Estrat´egica en Salud 2017–2020, ISCIII. Pablo Zubiaur is financed by Universidad Autonoma ´ de Madrid, Margarita Salas contract, grants for the requalification of the Spanish university system. Paula Soria-Chacartegui is financed by Universidad Autonoma ´ de Madrid (FPI-UAM, 2021). This study was co-financed by Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) “A way of making Europe”, number PI19/0093

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Técnicas y tecnologías en hidrología médica e hidroterapia

El objetivo del presente informe es difundir entre los profesionales médicos la información que contribuya a orientarles en la materia, conocer las aplicaciones terapéuticas o rehabilitadoras que pueden ofrecer los distintos centros termales y explorar su interacción con los tratamientos médicos habituales a los que suelen estar sometidos los usuarios de estos programas de termalismo

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

The conceptual map and the CmapTools software as neurodidactic tools to improve learning

Cuando se desarrollan nuevos conceptos en cualquier cambio científico y, por supuesto, en el ámbito de la educación, se genera en muchos casos la idea de que se trata de algo nuevo va a afectar radicalmente, en nuestro caso, la forma de educar y aprender. ¿Podría ser este el caso de la Neurodidáctica? Es necesario contrastar desde la investigación estas nuevas conceptualizaciones, como en el caso de la neurociencia y la neurodidáctica, que dotan del marchamo «neuro» a muchas estrategias didácticas utilizadas tradicionalmente. Han aparecido alrededor de la neurociencia multitud de modelos «neuropedagógicos» que pretenden dar al profesional de la educación potentes herramientas para la mejora del aprendizaje apoyándose en los avances de las neurociencias. En el caso de los concept mapping de Novak, se ha demostrado a lo largo de las últimas décadas su eficacia como herramientas de presentación del conocimiento experto y como promotores del aprendizaje significativo, permitiendo detectar con facilidad los errores conceptuales. Actualmente ha sido confirmada esta eficacia didáctica desde las investigaciones realizadas con técnicas neurocientíficas (TAC, TOC, MRI, fNIRs, entre otras) que presentamos en este artículo. Estas investigaciones confirman su valor metodológico, que sí podemos denominar neurodidáctico, a través de las evidencias de actividad cerebral diferencial o nivel de esfuerzo neurocognitivo que se produce cuando se comparan mapas conceptuales con otras herramientas didácticas.Quando novos conceitos são desenvolvidos em qualquer mudança científica e, claro, no campo da educa- ção, em muitos casos gera-se a ideia de que é algo novo que vai mudar radicalmente, no nosso caso, na forma de educar e de aprender. Seria este o caso da Neurodidática? É necessário contrastar essas novas conceituações da pesquisa, como no caso da neurociência e da neurodidática, que dão o rótulo de ”neuro” a muitas estratégias didáticas tradicionalmente utilizadas. Uma infinidade de modelos ”neuropedagógicos” surgiram em torno da neurociência que visam fornecer ao profissional da educação ferramentas poderosas para melhorar o aprendizado com base nos avanços da neurociência. No caso do mapa conceitual de Novak, sua eficácia como ferramenta de apresentação de conhecimento especializado e como promotora de aprendizagem significativa tem sido demonstrada nas últimas décadas, permitindo que erros conceituais sejam facilmente detectados. Atualmente, essa eficácia didática foi comprovada a partir das pesquisas realizadas com técnicas neurocientíficas (CAT, TOC, MRI, fNIRs, entre outras) que apresentamos neste artigo. Essas investigações confirmam seu valor metodológico, que podemos chamar de neurodidático, através da evidência de atividade cerebral diferencial ou nível de esforço neurocognitivo que ocorre quando mapas conceituais são comparados com outras ferramentas didáticas.When new concepts are developed in any scientific change and, of course, in the field of education, in many cases the idea is generated that it is something new that is going to change radically, in our case, in the way of educating and to learn. Could this be the case of Neurodidactics? It is necessary to contrast these new conceptualizations from research, as in the case of neuroscience and neurodidactics, which give the ”neuro” label to many traditionally used didactic strategies. A multitude of “neuropedagogical” models have appeared around neuroscience that aim to give the education professional powerful tools for improving learning based on advances in neuroscience. In the case of Novak’s concept mapping, its effectiveness as tools for presenting expert knowledge and as promoters of meaningful learning has been demonstrated over the last few decades, allowing conceptual errors to be easily detected. Currently, this didactic efficacy has been confirmed from the research carried out with neuroscientific techniques (CAT, TOC, MRI, fNIRs, among other) that we present in this article. These investigations confirm its methodological value, which we can call neurodidactic, through the evidence of differential brain activity or level of neurocognitive effort that occurs when conceptual maps are compared with other didactic tools

Primary stability and PES/WES evaluation for immediate implants in the aesthetic zone: a pilot clinical double-blind randomized study

© 2021. This manuscript version is made available under the CC-BY-4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Scientific Reports. To access the final edited and published work see doi.org/10.1038/s41598-021-99218-8The use of immediate implants in the aesthetic area is a technique widely used in modern implantology. The characteristics of the patient, the implant, and the surgical procedure used may influence the final results. The aim was to assess whether the implant design affects primary (P.S.) and secondary stability (S.S.), bone level (B.L.), and PES/WES evaluation. Twenty implants with two different designs (n = 10) were immediately placed and randomly located in the upper anterior maxilla with no grafting material. Implant-Stability-Quotient (ISQ), B.L., and Pink-Esthetic-Score/White-Esthetic-Score (PES/WES) were evaluated. Shapiro–Wilk normality test was performed to determine the sample normality, as the data did not follow a normal distribution, the Wilcoxon-Mann–Whitney test was applied (p < 0.05). ISQ was determined at placement (PS): control 59.1 (C.I.54.8–63.3); experimental 62.2(C.I.60.1–64.2) and three months after placement (SS): control 62.2.1 (C.I.53.3–71.0); experimental 67.2(C.I.65.8–68.5). The BL was measured at three months after placement: control 0.38 mm (C.I.− 0.06 to + 0.83); experimental 0.76 mm (C.I.0.33–1.19) and at 12 months post-loading: control 0.07 mm (C.I.− 0.50–0.65); experimental 0.90 mm (C.I.0.38–1.42). PES/WES values were evaluated for the control group: 15 (C.I.12.68–17.32), and for the experimental group 15.20 (C.I.11.99–18.41). No significant differences were shown between both implant designs. A good grade of osseointegration and primary/secondary stability was achieved, as well as proper maintenance of crestal bone and adequate PES/WES scores. The criteria for selection for the ideal patient for immediate implant placement is essential