The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation: an analysis of the ARISTOTLE trial

AIMS: Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial.METHODS AND RESULTS: Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P=0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P=0.001.CONCLUSION: In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin

State of the climate in 2015

In 2015, the dominant greenhouse gases released into Earth\u2019s atmosphere\u2014carbon dioxide, methane, and nitrous oxide\u2014all continued to reach new high levels. At Mauna Loa, Hawaii, the annual CO2 concentration increased by a record 3.1 ppm, exceeding 400 ppm for the first time on record. The 2015 global CO2 average neared this threshold, at 399.4 ppm. Additionally, one of the strongest El Ni\uf1o events since at least 1950 developed in spring 2015 and continued to evolve through the year. The phenomenon was far reaching, impacting many regions across the globe and affecting most aspects of the climate system. Owing to the combination of El Ni\uf1o and a long-term upward trend, Earth observed record warmth for the second consecutive year, with the 2015 annual global surface temperature surpassing the previous record by more than 0.1\ub0C and exceeding the average for the mid- to late 19th century\u2014commonly considered representative of preindustrial conditions\u2014by more than 1\ub0C for the first time. Above Earth\u2019s surface, lower troposphere temperatures were near-record high. Across land surfaces, record to near-record warmth was reported across every inhabited continent. Twelve countries, including Russia and China, reported record high annual temperatures. In June, one of the most severe heat waves since 1980 affected Karachi, Pakistan, claiming over 1000 lives. On 27 October, Vredendal, South Africa, reached 48.4\ub0C, a new global high temperature record for this month. In the Arctic, the 2015 land surface temperature was 1.2\ub0C above the 1981\u20132010 average, tying 2007 and 2011 for the highest annual temperature and representing a 2.8\ub0C increase since the record began in 1900. Increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 25 February 2015, the lowest maximum sea ice extent in the 37-year satellite record was observed, 7% below the 1981\u20132010 average. Mean sea surface temperatures across the Arctic Ocean during August in ice-free regions, representative of Arctic Ocean summer anomalies, ranged from ~0\ub0C to 8\ub0C above average. As a consequence of sea ice retreat and warming oceans, vast walrus herds in the Pacific Arctic are hauling out on land rather than on sea ice, raising concern about the energetics of females and young animals. Increasing temperatures in the Barents Sea are linked to a community-wide shift in fish populations: boreal communities are now farther north, and long-standing Arctic species have been almost pushed out of the area. Above average sea surface temperatures are not confined to the Arctic. Sea surface temperature for 2015 was record high at the global scale; however, the North Atlantic southeast of Greenland remained colder than average and colder than 2014. Global annual ocean heat content and mean sea level also reached new record highs. The Greenland Ice Sheet, with the capacity to contribute ~7 m to sea level rise, experienced melting over more than 50% of its surface for the first time since the record melt of 2012. Other aspects of the cryosphere were remarkable. Alpine glacier retreat continued, and preliminary data indicate that 2015 is the 36th consecutive year of negative annual mass balance. Across the Northern Hemisphere, late-spring snow cover extent continued its trend of decline, with June the second lowest in the 49-year satellite record. Below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska, increasing by up to 0.66\ub0C decade\u20131 since 2000. In the Antarctic, surface pressure and temperatures were lower than the 1981\u20132010 average for most of the year, consistent with the primarily positive southern annular mode, which saw a record high index value of +4.92 in February. Antarctic sea ice extent and area had large intra-annual variability, with a shift from record high levels in May to record low levels in August. Springtime ozone depletion resulted in one of the largest and most persistent Antarctic ozone holes observed since the 1990s. Closer to the equator, 101 named tropical storms were observed in 2015, well above the 1981\u20132010 average of 82. The eastern/central Pacific had 26 named storms, the most since 1992. The western north Pacific and north and south Indian Ocean basins also saw high activity. Globally, eight tropical cyclones reached the Saffir\u2013Simpson Category 5 intensity level. Overlaying a general increase in the hydrologic cycle, the strong El Ni\uf1o enhanced precipitation variability around the world. An above-normal rainy season led to major floods in Paraguay, Bolivia, and southern Brazil. In May, the United States recorded its all-time wettest month in its 121-year national record. Denmark and Norway reported their second and third wettest year on record, respectively, but globally soil moisture was below average, terrestrial groundwater storage was the lowest in the 14-year record, and areas in \u201csevere\u201d drought rose from 8% in 2014 to 14% in 2015. Drought conditions prevailed across many Caribbean island nations, Colombia, Venezuela, and northeast Brazil for most of the year. Several South Pacific countries also experienced drought. Lack of rainfall across Ethiopia led to its worst drought in decades and affected millions of people, while prolonged drought in South Africa severely affected agricultural production. Indian summer monsoon rainfall was just 86% of average. Extremely dry conditions in Indonesia resulted in intense and widespread fires during August\u2013November that produced abundant carbonaceous aerosols, carbon monoxide, and ozone. Overall, emissions from tropical Asian biomass burning in 2015 were almost three times the 2001\u201314 average

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis