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

Structure of the C123S mutant of dienelactone hydrolase (DLH) bound with the PMS moiety of the protease inhibitor phenylmethylsulfonyl fluoride (PMSF)

The structure of DLH (C123S) with PMS bound was solved to 2.5 Å resolution (R factor = 15.1%). PMSF in 2-propanol was delivered directly to crystals in drops and unexpectedly caused the crystals to dissolve. New crystals displaying a different morpholog

Survey of International Members of the American Thoracic Society on Climate Change and Health

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed international members of the society to assess perceptions, clinical experiences, and preferred policy responses related to global climate change. A recruitment email was sent by the ATS President in October 2015 to 5,013 international members. Subsequently, four reminder emails were sent to nonrespondents. Responses were received from 489 members in 68 countries; the response rate was 9.8%. Half of respondents reported working in countries in Asia (25%) or Europe (25%), with the remainder in South America (18%), North America (Canada and Mexico) (18%), Australia or New Zealand (9%), and Africa (6%). Survey estimate confidence intervals were ± 5% or smaller. A high percentage of international ATS survey respondents judged that climate change is happening (96%), that it is driven by human activity (70%), and that it is relevant to patient care ("a great deal"/"a moderate amount") (80%). A majority of respondents also indicated they are already observing health impacts of climate change among their patients; most commonly as increases in chronic disease severity from air pollution (88%), allergic symptoms from exposure to plants or mold (72%), and severe weather injuries (69%). An even larger majority anticipated seeing these climate-related health impacts in the next two decades. Respondents further indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. International ATS respondents, like their counterparts in the U.S., observed that human health is already adversely affected by climate change, and support responses to address this situation

American Thoracic Society Member Survey on Climate Change and Health

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed a random sample of ATS members to assess their perceptions of, clinical experiences with, and preferred policy responses to climate change. An e-mail containing an invitation from the ATS President and a link to an online survey was sent to 5,500 randomly selected U.S. members; up to four reminder e-mails were sent to nonrespondents. Responses were received from members in 49 states and the District of Columbia (n = 915); the response rate was 17%. Geographic distribution of respondents mirrored that of the sample. Survey estimates' confidence intervals were ±3.5% or smaller. Results indicate that a large majority of ATS members have concluded that climate change is happening (89%), that it is driven by human activity (68%), and that it is relevant to patient care ("a great deal"/"a moderate amount") (65%). A majority of respondents indicated they were already observing health impacts of climate change among their patients, most commonly as increases in chronic disease severity from air pollution (77%), allergic symptoms from exposure to plants or mold (58%), and severe weather injuries (57%). A larger majority anticipated seeing these climate-related health impacts in the next 2 decades. Respondents indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. Overall, ATS members are observing that human health is already adversely affected by climate change and support responses to address this situation

Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types.

STK15 (Aurora-A) is a serine/threonine kinase involved in mitotic chromosomal segregation. A genetic variant in STK15 T+91A (resulting in the amino acid substitution F31I) is associated with increased aneuploidy in colon tumors and cell transformation in vitro. Since this polymorphism plays a role in mitotic control-a process critical for all cancer types-we conducted association analyses for risk of cancer development of the colon, breast, prostate, skin, lung and esophagus in 10 independent case-control populations. We carried out a meta-analysis of these 10 case-control studies together with 5 additional published studies for a total of 9549 cases of breast, colon, ovarian, prostate, lung, esophageal and non-melanoma skin cancer and 8326 population or hospital-based controls. Meta-analysis of three colorectal cancer studies showed an increased risk in T+91A homozygotes (OR=1.50; 95% CI of 1.14-1.99). Meta-analysis of four breast cancer studies showed increased risk for T+91A homozygotes (OR=1.35, 95% CI of 1.12-1.64). The results of the multiple cancer type meta-analysis for all 15 studies combined were significant for cancer risk in both homozygotes and heterozygotes. The T+91A heterozygotes show an OR of 1.10 (95% CI of 1.03-1.18, P-value=0.006) and the T+91A homozygotes show an OR of 1.40 (95% CI of 1.22-1.59, P-value<0.001) for cancer risk. These results confirm that the STK15 T+91A variant is a low penetrance cancer susceptibility allele affecting multiple cancer types, and provide genetic evidence from large-scale human population studies that genetic stability at the chromosome level is an important determinant of cancer susceptibility. The data also underline the advantages of comparative association studies involving study populations from different ethnic groups for determination of disease risk

The E-cigarette or Vaping Product Use–Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes