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

Population-level inferences for distributed MEG source localization under multiple constraints: Application to face-evoked fields

We address some key issues entailed by population inference about responses evoked in distributed brain systems using magnetoencephalography (MEG). In particular, we look at model selection issues at the within-subject level and feature selection issues at the between-subject level, using responses evoked by intact and scrambled faces around 170 ms (M170). We compared the face validity of subject-specific forward models and their summary statistics in terms of how estimated responses reproduced over subjects. At the within-subject level, we focused on the use of multiple constraints, or priors, for inverting distributed source models. We used restricted maximum likelihood (ReML) estimates of prior covariance components (in both sensor and source space) and show that their relative importance is conserved over subjects. At the between-subject level, we used standard anatomical normalization methods to create posterior probability maps that furnish inference about regionally specific population responses. We used these to compare different summary statistics, namely; (i) whether to test for differences between condition-specific source estimates, or whether to test the source estimate of differences between conditions, and (ii) whether to accommodate differences in source orientation by using signed or unsigned (absolute) estimates of source activity

In vitro and in vivo effects of treatment by platelet-activating factor on N-formyl-met-leu-phe-mediated responses of polymorphonuclear leucocytes

Two chemoattractants, the peptide N-formyl-met-leu-phe (FMLP), and the ether phospholipid, platelet activating factor (PAF), each stimulate a variety of in vitro responses in polymorphonuclear leucocytes (PMN). Because often more than one inflammatory mediator is active during inflammation, we determined the effect on PMN of sequential stimulation with these two agents. Before FMLP stimulation, human PMN were exposed to PAF, at concentrations which gave little or no response when administered alone. PAF enhanced FMLP-elicited superoxide release in a dose-dependent fashion. Likewise, release of granular lysozyme from the cells was increased in PAF treated cells. Similar treatment with other phospholipids, including the lyso derivation of PAF, failed to produce these effects. Incubation with nordihydro-guaiaretic acid, an inhibitor of arachidonic acid metabolism, had little effect on the enhancement of lysozyme release by PAF. To determine if enhancing effects by PAF might occur also in vivo , we studied rabbits receiving PAF and/or FMLP intravenously. When rabbits received 0·01 Μg PAF (a dose which does not elicit the sustained neutropenia observed with higher doses of PAF) followed by 0·05 Μg FMLP the absolute granulocyte count (AGC) dropped at 1 min (46 ± 11% of original value), and continued to fall (24 ± 12% at 10 min). Controls, treated with the suspending fluid for PAF, and then 0·05 Μg FMLP, had a similar 1 min AGC value, but at 10 min AGC returned to 65±6·1% ( P <0·001 for comparison of 10 min values). Thus PAF pretreatment enhanced FMLP-elicited granulocytopenia in vivo . Study of in vitro human PMN aggregation revealed that, at certain relative concentrations of PAF and FMLP. aggregation was enhanced. These studies show that both in vitro and in vivo responses of FMLP-stimulated PMN may be exaggerated by pre-exposure to PAF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72047/1/j.1365-2141.1987.tb01302.x.pd