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

Storage Experimentation: Midyear Progress Report

This report summarizes technical work conducted by LANL staff and international collaborators insupport of the UFD Storage Experimentation effort. The current focus of this technical work is two-fold:1) on the stainless steel (304L) failure mechanism known as stress corrosion cracking (SCC), and 2) onthe concrete integrity under degradation conditions (e.g., thermal, radiation, alkali-aggregate reactions).As these issues are common among our international partners, a significant effort has been put forth toengage foreign programs in a mutually beneficial collaborative program on these topics. Results fromthese collaborations, notably with Japan, France and Switzerland, are highlighted

Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy

BACKGROUND AND PURPOSE: Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors) with intracranial hemorrhage (ICrH). METHODS: ANNEXA-4 was a single-arm study evaluating andexanet in patients presenting with major bleeding ≤18 hours after taking an FXa inhibitor. Patients received a bolus plus 2-hour infusion of andexanet. Brain imaging in patients with ICrH was performed at baseline and at 1 and 12 hours postandexanet infusion. Coprimary efficacy outcomes were change in anti-FXa activity and hemostatic efficacy at 12 hours (excellent/good efficacy defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included occurrence of thrombotic events and death at 30 days. RESULTS: A total of 227 patients with ICrH were included in the safety population (51.5% male; mean age 79.3 years) and 171 in the efficacy population (99 spontaneous and 72 traumatic bleeds). In efficacy evaluable patients, excellent/good hemostasis 12 hours postandexanet occurred in 77 out of 98 (78.6%) and in 58 out of 70 (82.9%) patients with spontaneous and traumatic bleeding, respectively. In the subanalysis by FXa inhibitor treatment group in the efficacy population, median of percent change in anti-FXa from baseline to nadir showed a decrease of 93.8% for apixaban-treated patients (n=99) and by 92.6% for rivaroxaban-treated patients (n=59). Within 30 days, death occurred in 34 out of 227 (15.0%) patients and thrombotic events occurred in 21 out of 227 (9.3%) patients (safety population). CONCLUSIONS: Andexanet reduced anti-FXa activity in FXa inhibitor-treated patients with ICrH, with a high rate of hemostatic efficacy. Andexanet may substantially benefit patients with ICrH, the most serious complication of anticoagulation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02329327

Pollination of two species of Vellozia (Velloziaceae) from high-altitude quartzitic grasslands, Brazil Polinização de duas espécies de Vellozia (Velloziaceae) de campos quartzíticos de altitude, Brasil

The pollinators and breeding system of two species of Vellozia (Velloziaceae) from high-altitude quartzitic grasslands in SE Brazil were studied. Vellozia leptopetala is shrubby and grows solely on rocky outcrops, V. epidendroides is herbaceous and grows on stony soils. Both bear solitary, hermaphrodite flowers, and have massive, short-lasting annual blooms. We evaluated the level of self-compatibility and need for pollinators of 50 plants of each species and 20-60 flowers per treatment: hand self- and cross-pollination, spontaneous pollination, agamospermy and control. The behavior of floral visitors on flowers and within plants was recorded. Both species are mostly self-incompatible, but produce a small number of seeds by self-fertilization. The pollen-ovule ratio suggests facultative xenogamy. They were visited primarily by bees, of which the most important pollinators were two leaf-cutting bees (Megachile spp.). Vellozia leptopetala was also pollinated by a territorial hummingbird. Low natural seed production compared to cross-pollination seed numbers suggests that pollen limitation is the main cause of low seed set. This was attributed to the combined effect of five mechanisms: selfing prior to anthesis, enhanced geitonogamy as a result of large floral displays, low number of visits per flower for the same reason, pollen theft by many insect species, and, in V. leptopetala, delivery of mixed pollen loads on the stigma as a consequence of hummingbird promiscuity.<br>Foram pesquisados os polinizadores e o sistema reprodutivo de duas espécies de Vellozia (Velloziaceae) de campos rupestres quartzíticos do sudeste do Brasil. Vellozia leptopetala é arborescente e cresce exclusivamente sobre afloramentos rochosos, V. epidendroides é de porte herbáceo e espalha-se sobre solo pedregoso. Ambas têm flores hermafroditas e solitárias, e floradas curtas em massa. Avaliou-se o nível de auto-compatibilidade e a necessidade de polinizadores, em 50 plantas de cada espécie e 20-60 flores por tratamento: polinização manual cruzada e autopolinização, polinização espontânea, agamospermia e controle. O comportamento dos visitantes florais nas flores e nas plantas foi registrado. As espécies são auto-incompatíveis, mas produzem poucas sementes autogâmicas. A razão pólen-óvulo sugere xenogamia facultativa em ambas. Foram visitadas principalmente por abelhas, das quais as mais importantes polinizadoras foram duas cortadeiras (Megachile spp.). Vellozia leptopetala também foi polinizada por uma espécie de beija-flor territorial. A produção de sementes em frutos de polinização cruzada sugere que limitação por pólen é a causa principal da baixa produção natural de sementes. Isto foi atribuído ao efeito combinado de cinco mecanismos: autopolinização prévia à antese, elevada geitonogamia resultante de arranjo floral, número reduzido de visitas por flor pelo mesmo motivo, pilhagem de pólen por diversas espécies de insetos e, em V. leptopetala, deposição de pólen heteroespecífico em conseqüência da promiscuidade dos beija-flores