BACKGROUND: There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. OBJECTIVES: The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. METHODS: Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. RESULTS: Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients' age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p < 0.001) with both increased CHA2DS2-VASc and HAS-BLED scores, but decreased in the presence of diabetes. On multivariable analysis adjusting for established risk factors and treatment, tertile groups of ADMA concentrations were significantly associated with stroke/systemic embolism (p = 0.034), and death (p < 0.0001), whereas tertile groups of SDMA were associated with major bleeding and death (p < 0.001 for both). Incorporating ADMA and SDMA into CHA2DS2-VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither ADMA nor SDMA predicted differential responses to warfarin or apixaban. CONCLUSIONS: In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984).

• MeSH
• antikoagulancia terapeutické užití   MeSH
• arginin analogy a deriváty   krev   MeSH
• biologické markery krev   MeSH
• dvojitá slepá metoda MeSH
• fibrilace síní krev   diagnóza   farmakoterapie   MeSH
• inhibitory faktoru Xa terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• pyrazoly terapeutické užití   MeSH
• pyridony terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• warfarin terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry. METHODS: Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA. RESULTS: Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs. CONCLUSION: Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• aplikace orální MeSH
• cévní mozková příhoda * prevence a kontrola   etiologie   MeSH
• fibrilace síní * farmakoterapie   komplikace   MeSH
• hodnocení rizik metody   MeSH
• inhibitory faktoru Xa * terapeutické užití   aplikace a dávkování   MeSH
• lidé MeSH
• pyrazoly * terapeutické užití   MeSH
• pyridony * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• registrace MeSH
• rivaroxaban * aplikace a dávkování   terapeutické užití   MeSH
• rizikové faktory MeSH
• senioři MeSH
• vitamin K antagonisté a inhibitory   MeSH
• výběr pacientů * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

• MeSH
• etika MeSH
• náboženské filosofie MeSH

• Konspekt
• Věda. Všeobecnosti. Základy vědy a kultury. Vědecká práce
• NLK Obory
• etika, bioetika, lékařská etika
• humanitní vědy a umění

• MeSH
• filozofie MeSH

• Konspekt
• Věda. Všeobecnosti. Základy vědy a kultury. Vědecká práce
• NLK Obory
• humanitní vědy a umění

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the "bottom up" approach) and (4) how to infer the nature of the last universal common ancestor (the "top down" approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin. We also describe another family of paths motivated by a" circularity" approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question.

• MeSH
• biologie dějiny   MeSH
• chemie dějiny   MeSH
• dějiny 16. století MeSH
• dějiny 17. století MeSH
• dějiny 18. století MeSH
• dějiny 19. století MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• filozofie dějiny   MeSH
• historiografie * MeSH
• informatika dějiny   MeSH
• molekulární biologie dějiny   MeSH
• paleontologie dějiny   MeSH
• původ života * MeSH
• Check Tag
• dějiny 16. století MeSH
• dějiny 17. století MeSH
• dějiny 18. století MeSH
• dějiny 19. století MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• přehledy MeSH

• MeSH
• filozofie MeSH

• Konspekt
• Věda. Všeobecnosti. Základy vědy a kultury. Vědecká práce
• NLK Obory
• humanitní vědy a umění

První komplexní monografie o lékařské etice u nás! První část popisuje lékařskou etiku v současné filozofii, druhá uvádí její obecné pojetí a třetí aplikuje obecné teze na konkrétních tématech.

• Klíčová slova
• Ostatní lékařské obory, Jazyky, komunikace, etika,
• MeSH
• asistovaná reprodukce etika   MeSH
• bioetická témata MeSH
• biomedicínský výzkum MeSH
• etika dějiny   MeSH
• eutanazie MeSH
• filosofie lékařská MeSH
• informovaný souhlas pacienta MeSH
• lékařská etika MeSH
• lidská práva MeSH
• práva pacientů MeSH
• rozhodování etika   MeSH
• transplantace etika   MeSH

• NLK Obory
• etika, bioetika, lékařská etika

První komplexní monografie o lékařské etice u nás! První část popisuje lékařskou etiku v současné filozofii, druhá uvádí její obecné pojetí a třetí aplikuje obecné teze na konkrétních tématech.

• MeSH
• asistovaná reprodukce etika   MeSH
• bioetická témata MeSH
• biomedicínský výzkum MeSH
• etika dějiny   MeSH
• eutanazie MeSH
• filosofie lékařská MeSH
• informovaný souhlas pacienta MeSH
• lékařská etika MeSH
• lidská práva MeSH
• práva pacientů MeSH
• rozhodování etika   MeSH
• transplantace etika   MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• etika, bioetika, lékařská etika