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

Caractérisation hydrochimique et qualité des eaux de l'aquifère karstique du Lez

International audienc

Global vector field reconstruction from a chaotic experimental signal in copper electrodissolution

cited By 24International audienceno abstrac

Zn isotopic fractionation caused by sorption on goethite and 2-Lines ferrihydrite

International audienc

Towards a History of Mass Violence in the Etat Indépendant du Congo, 1885-1908

The present article provides an up-to-date scholarly introduction to mass violence in the Etat Indépendant du Congo (Congo Free State, EIC). Its aims are twofold: to offer a point of access to the extensive literature and historical debates on the subject, and to make the case for exchanging the currently prevalent top-down narrative, with its excessive focus on King Leopold's character and motives, for one which considers the EIC's culture of violence as a multicausal, broadly based and deeply engrained social phenomenon. The argument is divided into five sections. Following a general outline of the EIC's violent system of administration, I discuss its social and demographic impact (and the controversy which surrounds it) to bring out the need for more regionally focused and context sensitive studies. The dispute surrounding demographics demonstrates that what is fundamentally at stake is the place the EIC's extreme violence should occupy in the history of European ‘modernity’. Since approaches which hinge on Leopoldian exceptionalism are particularly unhelpful in clarifying this issue, I pause to reflect on how such approaches came to dominate the distinct historiographical traditions which emerged in Belgium and abroad before moving on to a more detailed exploration of a selection of causes underlying the EIC's violent nature. While state actors remain in the limelight, I shift the focus from the state as a singular, normative agent, towards the existence of an extremely violent society in which various individuals and social groups within and outside of the state apparatus committed violent acts for multiple reasons. As this argument is pitched at a high level of abstraction, I conclude with a discussion of available source material with which it can be further refined and updated

Why is quinidine an inhibitor of cytochrome P450 2D6? The role of key active site residues in quinidine binding

We have previously shown that residues Asp301, Glu216 and Phe120 in the active site of cytochrome P450 2D6 (CYP2D6) play a key role in substrate recognition by this important drug-metabolising enzyme. We have now examined the effect of mutations of these residues on interactions of the enzyme with the prototypical CYP2D6 inhibitor, quinidine. Abolition of the negative charge on either or both residues 216 and 301 decreased quinidine inhibition of bufuralol 1'-hydroxylation and dextromethorphan O-demethylation by at least 100-fold. The apparent dissociation constants (Kd) for quinidine binding to wild type enzyme or to the Glu216Asp and Asp301Glu mutants were 0.25-0.50 μM. The amide substitutions of Glu216 or Asp301 resulted in 30 to 64-fold increases in Kd for quinidine. The double mutant Glu216Gln/Asp301Gln showed the largest decrease in quinidine affinity with a Kd of 65 μM. Changes in the mode of quinidine binding were indicated by changes in the optical difference spectra on binding. Alanine substitution of Phe120, Phe481 or Phe483 had only a minor effect on the inhibition of bufuralol 1'-hydroxylation and dextromethorphan O-demethylation, and on binding. In contrast to the wild-type enzyme, a number of the mutants studied were found to be able to metabolise quinidine. CYP2D6 Asp301Gln and Asp301Asn produced small amounts of 3-hydroxyquinidine, Asp301Ala and Asp301Phe produced O-demethylated quinidine, and Phe120Ala and Glu216Gln/Asp301Gln produced both these metabolites. Homology modelling and molecular docking were used to predict the modes of quinidine binding to wild type and mutant enzymes; these were able to rationalise the experimental observations