Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Possible presence of common tyvelose-containing glycans in Trichinella L1 larvae and embryonated eggs of several nematodes

A monoclonal antibody (mAb US4) recognising an epitope containing tyvelose within the T. spiralis L-1 muscle larvae (TSL-1) antigens was tested in western-blot against various antigenic preparations from different stages of the following nematodes: T. spiralis (L1,adult), T. muris (egg, L1, L3, adult), Ascaris suum (egg, adult), Toxocara canis (egg, adult), Anisakis simplex (L3) and Haemochus contortus (egg). Positive reaction was present in antigen preparations from L1 larvae of T. spiralis and T. muris and from embryonated eggs of T. muris, A. suum, T. canis and H. conlortus

Possible presence of common tyvelose-containing glycans in

A monoclonal antibody (mAb US4) recognising an epitope containing tyvelose within the T. spiralis L-1 muscle larvae (TSL-1) antigens was tested in western-blot against various antigenic preparations from different stages of the following nematodes: T. spiralis (L1,adult), T. muris (egg, L1, L3, adult), Ascaris suum (egg, adult), Toxocara canis (egg, adult), Anisakis simplex (L3) and Haemochus contortus (egg). Positive reaction was present in antigen preparations from L1 larvae of T. spiralis and T. muris and from embryonated eggs of T. muris, A. suum, T. canis and H. conlortus

Real-Time Reverse Transcription-PCR Quantification of Cytokine mRNA Expression in Golden Syrian Hamster Infected with Leishmania infantum and Treated with a New Amphotericin B Formulation

A real-time quantitative reverse transcription-PCR assay was developed for the quantification of cytokine mRNA expression in the golden Syrian hamster Mesocricetus auratus infected with Leishmania infantum and treated with amphotericin B (AMB) formulated in microspheres made of human serum albumin (HSA). Treatment was administered intravenously on days 69, 71, and 73 postinfection (p.i.) with 10(7) metacyclic promastigotes, at doses of 2 and 40 mg/kg of AMB. High infection levels were recorded for untreated animals by day 76 p.i., with parasite loads always about 2 log(10) per gram higher in the liver than in the spleen. Treatment was highly effective with both doses, but at 40 mg/kg, almost complete parasite elimination was achieved. mRNA expression of gamma interferon (IFN-γ) and, to a lesser extent, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) in spleen cells was up-regulated in most animals of the untreated group. The mRNA expression of interleukin-4 was strongly down-regulated in untreated as well as treated infected animals. Treatment with the lower dose of AMB-HSA down-regulated the mRNA expression of IFN-γ and TNF-α, with no effect on the deactivating cytokine TGF-β. In contrast, treatment with the higher dose (40 mg/kg) of the formulation caused moderate up-regulation of IFN-γ and TNF-α and strong suppression of TGF-β. Treatment of noninfected animals did not alter the cytokine expression pattern with regard to untreated controls. Our results suggest that treatment of L. infantum-infected Syrian hamsters with highly effective nontoxic doses of AMB-HSA causes deactivation of the anti-inflammatory cytokine TGF-β, which in turn results in up-regulation of the Th1 cytokines IFN-γ and TNF-α

Stopping power of large homonuclear clusters: influence of cluster structure

A theoretical investigation based on the linear dielectric formalism is presented of the stopping of large clusters in metals at velocities above the Fermi velocity. Calculations are carried out for hydrogen clusters of 4, 13, and 100 H2 molecules stopping in aluminum. Emphasis is placed on the influence of the internal cluster structure, which enters in the present description via the pair-correlation function for the relative positions of nuclei. The target properties are modeled by Lindhard’s dielectric function for a free-electron gas. Interference effects with respect to both collective and individual excitations are quantified separately for intra- and intermolecular terms, and are evaluated as a function of cluster velocity. Effects of short-range order, in particular the importance of an exclusion volume around each molecule, are clearly visible. The results indicate, however, that beyond the nearest neighbor the detailed molecular arrangement has only little influence on the stopping power for the clusters studied. The partitioning of contributions due to close and distant collisions, as it is known for the stopping of point charges, is found to be substantially different in the case of cluster projectiles. The effect of Coulomb repulsion is commented upon.This collaboration was made possible through financial support to M. Vicanek, sponsored by the Spanish Ministerio de Educación y Ciencia. N.R. Arista received support under the program PROPI (Conselleria d Educació i Ciència de la Generalitat Valenciana). Partial support from the Dirección General de Investigación Científica y Técnica (DGICYT) (Projects Nos. PS88-0066 and PS89-0065), and a NATO Grant (No. CRG 901013) is recognized

Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD\u2013Atrial Fibrillation (GARFIELD-AF). Among 17\ua0168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (\ub1antiplatelet therapy) at enrolment, and of these patients, 5066 with 653 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70\ua0905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56\ub70% vs 49\ub78%; median, 59\ub77% vs 50\ub70%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0\ub7860 [0\ub7852\u20130\ub7867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0\ub7829 [0\ub7821\u20130\ub7837]). The difference between FIR and TTR explained 17\ub74% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)