395 research outputs found

    Cosmological evolution, future singularities, Little Rip and Pseudo-Rip in viable f(R) theories and their scalar-tensor counterpart

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    Modified f(R) gravity is one of the most promising candidates for dark energy, and even for the unification of the whole cosmological evolution, including the inflationary phase. Within this class of theories, the so-called viable modified gravities represent realistic theories that are capable of reproducing late-time acceleration, and satisfy strong constraints at local scales, where General Relativity is recovered. The present manuscript deals with the analysis of the cosmological evolution for some of these models, which indicates that the evolution may enter into a phantom phase, but the behavior may be asymptotically stable. Furthermore, the scalar-tensor equivalence of f(R) gravity is considered, which provides useful information about the possibility of the occurrence of a future singularity. The so-called Little Rip and Pseudo-Rip are also studied in the framework of this class of modified gravities.Comment: 20 pages. Extended version, new figures and additional analysis. Version to be published in Class. Quant. Gra

    Novel Echocardiographic Biomarkers in the Management of Atrial Fibrillation

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    Purpose of Review: Atrial fibrillation (AF) is the most common arrhythmia in adults. The number of patients with AF is anticipated to increase annually, mainly due to the aging population alongside improved arrhythmia detection. AF is associated with a significantly elevated risk of hospitalization, stroke, thromboembolism, heart failure, and all-cause mortality. Echocardiography is one of the key components of routine assessment and management of AF. Therefore, the aim of this review is to briefly summarize current knowledge on “novel” echocardiographic parameters that may be of value in the management of AF patients. Recent Findings: Novel echocardiographic biomarkers and their clinical application related to the management of AF have been taken into consideration. Both standard parameters such as atrial size and volume but also novels like atrial strain and tissue Doppler techniques have been analyzed. Summary: A number of novel echocardiographic parameters have been proven to enable early detection of left atrial dysfunction along with increased diagnosis accuracy. This concerns particularly experienced echocardiographers. Hence, these techniques might improve the prediction of stroke and thromboembolic events among AF patients and need to be further developed and disseminated. Nonetheless, even the standard imaging parameters could be of significant value and should not be discontinued in everyday clinical practice. © 2019, The Author(s)

    A genome-wide DNA methylation signature for SETD1B-related syndrome

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    SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients

    Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

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    OBJECTIVE: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin-K-antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. METHODS: Individual patient data analysis from 7 prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. RESULTS: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y =0.65, 95%-CI [0.52, 0.81]) and <85 years (HR<85y =0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction =0.129), adjusted (pinteraction =0.094) or weighted (pinteraction =0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and <85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). INTERPRETATION: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old

    A randomised controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalised with COVID-19: the C19-ACS trial

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    BACKGROUND: Patients hospitalised with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with COVID-19 and coronary disease risk factors. PATIENTS/METHODS: A randomised controlled open-label trial across acute hospitals (UK and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. The trial terminated early due to low recruitment. At 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted OR 0.73, 95%CI 0.38 to 1.41, p=0.355). Significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR 1.46, 95% CrI 0.88 to 2.37, Pr(Beta>0)=93%; adjusted OR 1.50, 95% CrI 0.91 to 2.45, Pr(Beta>0)=95%) and median time to discharge home was two days shorter (95% CrI -4 to 0, 2% probability that it was worse). CONCLUSIONS: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality

    Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease

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    Background: Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. Methods: One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM+CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. Results: Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r=0.57, p<0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD+DM (p=0.030). Patients suffering from CVD+DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p=0.006) and time needed to reach arterial maximum dilation (p=0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD+DM compared to the other two groups (p≤0.02), whilst sEsel was raised in CVD+DM compared to DM alone (p=0.044). Conclusions: Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression

    Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

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    New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

    Effect of Chronic Kidney Diseases on Mortality among Digoxin Users Treated for Non-Valvular Atrial Fibrillation: A Nationwide Register-Based Retrospective Cohort Study.

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    PURPOSE: This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin. METHODS: All patients with non-valvular atrial fibrillation and/or atrial flutter as hospitalization diagnosis from January 1, 1997 to December 31, 2012 were identified in Danish nationwide administrative registries. Cox proportional hazard model was used to compare the adjusted risk of all-causes and cardiovascular mortality among patients with and without chronic kidney disease and among patients with different chronic kidney disease stages within 180 days and 2 years from the first digoxin prescription. RESULTS: We identified 37,981 patients receiving digoxin; 1884 patients had the diagnosis of chronic kidney disease. Cox regression analysis showed no statistically significant differences in all-causes (Hazard Ratio, HR 0.89; 95% confident interval, CI 0.78-1.03) and cardiovascular mortality (HR 0.88; 95%CI 0.74-1.05) among patients with and without chronic kidney disease within 180 days of follow-up period. No statistically significant differences was found using a 2 years follow-up period neither for all causes mortality (HR 0.90; 95%CI 0.79-1.03), nor for cardiovascular mortality (HR 0.87; 95%CI 0.74-1.02). No statistically significant differences was found comparing patients with and without estimated Glomerular Filtration Rate <30ml/min/1.73m2 and patients with different stages of chronic kidney disease, for all-causes and cardiovascular mortality within 180 days and 2 years from the first digoxin prescription. CONCLUSIONS: This study suggest no direct effect of chronic kidney disease and chronic kidney disease stages on all-causes and cardiovascular mortality within both 180 days and 2 years from the first digoxin prescription in patients treatment-naïve with digoxin for non-valvular atrial fibrillation
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