Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Single nucleotide polymorphism (SNP) array-based signature of low hypodiploidy in acute lymphoblastic leukemia.

Low hypodiploidy (30-39 chromosomes) is one of the most prevalent genetic subtypes among adults with ALL and is associated with a very poor outcome. Low hypodiploid clones can often undergo a chromosomal doubling generating a near-triploid clone (60-78 chromosomes). When cytogenetic techniques detect a near triploid clone, a diagnostic challenge may ensue in differentiating presumed duplicated low hypodiploidy from good risk high hyperdiploid ALL (51-67 chromosomes). We used single-nucleotide polymorphism (SNP) arrays to analyze low hypodiploid/near triploid (HoTr) (n=48) and high hyperdiploid (HeH) (n=40) cases. In addition to standard analysis, we derived log2 ratios for entire chromosomes enabling us to analyze the cohort using machine-learning techniques. Low hypodiploid and near triploid cases clustered together and separately from high hyperdiploid samples. Using these approaches, we also identified three cases with 50-60 chromosomes, originally called as HeH, which were, in fact, HoTr and two cases incorrectly called as HoTr. TP53 mutation analysis supported the new classification of all cases tested. Next, we constructed a classification and regression tree model for predicting ploidy status with chromosomes 1, 7 and 14 being the key discriminators. The classifier correctly identified 47/50 (94%) HoTr cases. We validated the classifier using an independent cohort of 44 cases where it correctly called 7/7 (100%) low hypodiploid cases. The results of this study suggest that HoTr is more frequent among older adults with ALL than previously estimated and that SNP array analysis should accompany cytogenetics where possible. The classifier can assist where SNP array patterns are challenging to interpret. This article is protected by copyright. All rights reserved

Isolated Distal Deep Vein Thrombosis: Perspectives from the GARFIELD-VTE Registry

Isolated distal deep vein thrombosis (IDDVT) represents up to half of all lower limb DVT. This study investigated treatment patterns and outcomes in 2,145 patients with IDDVT in comparison with those with proximal DVT (PDVT; n = 3,846) and pulmonary embolism (PE; n = 4,097) enrolled in the GARFIELD-VTE registry. IDDVT patients were more likely to have recently undergone surgery (14.6%) or experienced leg trauma (13.2%) than PDVT patients (11.0 and 8.7%, respectively) and PE patients (12.7 and 4.5%, respectively). Compared with IDDVT, patients with PDVT or PE were more likely to have active cancer (7.2% vs. 9.9% and 10.3%). However, influence of provoking factors on risk of recurrence in IDDVT remains controversial. Nearly all patients (IDDVT, PDVT, and PE) were given anticoagulant therapy. In IDDVT, PDVT, and PE groups the proportion of patients receiving anticoagulant therapy was 61.4, 73.9, and 81.1% at 6 months and 45.8, 54.7, and 61.9% at 12 months. Over 12 months, the incidence of all-cause mortality, cancer, and recurrence was significantly lower in IDDVT patients than PDVT patients (hazard ratio [HR], 0.61 [95% confidence interval [CI], 0.48-0.77]; sub-HR [sHR], 0.60 [95% CI, 0.39-0.93]; and sHR, 0.76 [95% CI, 0.60-0.97]). Likewise, risk of death and incident cancer was significantly (both p < 0.05) lower in patients with IDDVT compared with PE. This study reveals a global trend that most IDDVT patients as well as those with PDVT and PE are given anticoagulant therapy, in many cases for at least 12 months

The influence of anemia on clinical outcomes in venous thromboembolism: Results from GARFIELD-VTE.

INTRODUCTION: Clinical characteristics and outcomes of venous thromboembolism (VTE) patients with concomitant anemia are unclear. This study compares baseline characteristics, treatment patterns, and 24-month outcomes in patients with and without anemia within GARFIELD-VTE. MATERIALS AND METHODS: GARFIELD-VTE (ClinicalTrials.gov: NCT02155491) is a global, prospective, non-interventional registry of real-world treatment practices. Of the 10,679 patients enrolled in GARFIELD-VTE, 7698 were eligible for analysis. Primary outcomes were all-cause mortality, recurrent VTE, and major bleeding in VTE patients with or without concomitant anemia over 24-months after diagnosis. Event rates and 95% confidence intervals were estimated using Poisson regression. Adjusted hazard ratios were calculated using Cox proportional hazard models. RESULTS: Distribution of VTE events in 2771 patients with anemia and 4927 without anemia was similar (deep-vein thrombosis alone: 61·1% vs. 55·9%, pulmonary embolism ± deep vein thrombosis: 38·9% vs. 44·0%, respectively). Patients with anemia were older (62.6 year vs. 58.9 years) than those without. At baseline, VTE risk factors that were more common in patients with anemia included hospitalization (22·0% vs. 6·8%), surgery (19·2% vs. 8·2%), cancer (20·1% vs. 5·6%) and acute medical illness (8·3% vs. 4·2%). Patients with anemia were more likely to receive parenteral anticoagulation therapy alone than those without anemia (26·6% vs. 11·7%) and less likely to receive a direct oral anticoagulant (38·5% vs. 53·5%). During 24-months of follow-up, patients with anemia had a higher risk (adjusted hazard ratio [95% confidence interval]) of all-cause mortality (1·84 [1·56-2·18]), major bleeding (2·83 [2·14-3·75]). Among anemia patients, the risk of all-cause mortality and major bleeding remained higher in patients with severe anemia than in those with mild/moderate anemia, all-cause mortality: HR 1·43 [95% CI: 1·21-1·77]; major bleeding: HR 2·08 [95% CI: 1·52-2·86]). CONCLUSIONS: VTE patients with concomitant anemia have a higher risk of adverse clinical outcomes compared with those without anemia. Further optimization of anticoagulation therapy for VTE patients with anemia is warranted

Assessment of Outcomes Among Patients With Venous Thromboembolism With and Without Chronic Kidney Disease

Importance: Patients with venous thromboembolism (VTE) and concomitant chronic kidney disease (CKD) have been reported to have a higher risk of thrombosis and major bleeding complications compared with patients without concomitant CKD. The use of anticoagulation therapy is challenging, as many anticoagulant medications are excreted by the kidney. Large-scale data are needed to clarify the impact of CKD for anticoagulant treatment strategies and clinical outcomes of patients with VTE. Objective: To compare clinical characteristics, treatment patterns, and 12-month outcomes among patients with VTE and concomitant moderate to severe CKD (stages 3-5) vs patients with VTE and mild to no CKD (stages 1-2) in a contemporary international registry. Design, Setting, and Participants: The Global Anticoagulant Registry in the Field–Venous Thromboembolism (GARFIELD-VTE) study is a prospective noninterventional investigation of real-world treatment practices. A total of 10 684 patients from 415 sites in 28 countries were enrolled in the GARFIELD-VTE between May 2014 and January 2017. This cohort study included 8979 patients (6924 patients with mild to no CKD and 2055 patients with moderate to severe CKD) who had objectively confirmed VTE within 30 days before entry in the registry. Chronic kidney disease stages were defined by estimated glomerular filtration rates. Data were extracted from the study database on December 8, 2018, and analyzed between May 1, 2019, and July 30, 2020. Exposure: Moderate to severe CKD vs mild to no CKD. Main Outcomes and Measures: The primary outcomes were all-cause mortality, recurrent VTE, and major bleeding. Event rates and 95% CIs were calculated and expressed per 100 person-years. Hazard ratios (HRs) were estimated with Cox proportional hazards regression models and adjusted for relevant confounding variables. All-cause mortality was considered a competing risk for other clinical outcomes in the estimation of cumulative incidences. Results: Of the 10 684 patients with objectively confirmed VTE, serum creatinine data were available for 8979 patients (84.0%). Of those, 4432 patients (49.4%) were female and 5912 patients (65.8%) were White; 6924 patients (77.1%; median age, 57 years; interquartile range [IQR], 44-69 years) were classified as having mild to no CKD, and 2055 patients (22.9%; median age, 70 years; IQR, 59-78 years) were classified as having moderate to severe CKD. Calculations using the equation from the Modification of Diet in Renal Disease study indicated that, among the 6924 patients with mild to no CKD, 2991 patients had stage 1 CKD, and 3933 patients had stage 2 CKD; among the 2055 patients with moderate to severe CKD, 1650 patients had stage 3 CKD, 190 patients had stage 4 CKD, and 215 patients had stage 5 CKD. The distribution of VTE presentation was comparable between groups. In total, 1171 patients (57.0%) with moderate to severe CKD and 4079 patients (58.9%) with mild to no CKD presented with deep vein thrombosis alone, 547 patients (26.6%) with moderate to severe CKD and 1723 patients (24.9%) with mild to no CKD presented with pulmonary embolism alone, and 337 patients (16.4%) with moderate to severe CKD and 1122 patients (16.2%) with mild to no CKD presented with both pulmonary embolism and deep vein thrombosis. Compared with patients with mild to no CKD, patients with moderate to severe CKD were more likely to be female (3259 women [47.1%] vs 1173 women [57.1%]) and older than 65 years (2313 patients [33.4%] vs 1278 patients [62.2%]). At baseline, the receipt of parenteral therapy alone was comparable between the 2 groups (355 patients [17.3%] with moderate to severe CKD vs 1253 patients [18.1%] with mild to no CKD). Patients with moderate to severe CKD compared with those with mild to no CKD were less likely to be receiving direct oral anticoagulant therapy, either alone (557 patients [27.1%] vs 2139 patients [30.9%]) or in combination with parenteral therapy (319 patients [15.5%] vs 1239 patients [17.9%]). Patients with moderate to severe CKD had a higher risk of all-cause mortality (adjusted hazard ratio [aHR], 1.44; 95% CI, 1.21-1.73), major bleeding (aHR, 1.40; 95% CI, 1.03-1.90), and recurrent VTE (aHR, 1.40; 95% CI, 1.10-1.77) than patients with mild to no CKD. Conclusions and Relevance: In this study of patients with VTE, the presence of moderate to severe CKD was associated with increases in the risk of death, VTE recurrence, and major bleeding compared with the presence of mild to no CKD

New AI Prediction Model Using Serial PT-INR Measurements in AF Patients on VKAs: GARFIELD-AF

Aims: Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment. Methods and results: Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0–30 after starting treatment and clinical outcomes over days 31–365 in a derivation cohort (cohorts 1–3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4–5; n = 1523). The model’s c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively. Conclusions: Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes

Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation

Objective We studied evolving antithrombotic therapy patterns in patients with newly diagnosed non-valvular atrial fibrillation (AF) and ≥1 additional stroke risk factor between 2010 and 2015.Methods 39 670 patients were prospectively enrolled in four sequential cohorts in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF): cohort C1 (2010–2011), n=5500; C2 (2011–2013), n=11 662; C3 (2013–2014), n=11 462; C4 (2014–2015), n=11 046. Baseline characteristics and antithrombotic therapy initiated at diagnosis were analysed by cohort.Results Baseline characteristics were similar across cohorts. Median CHA2DS2-VASc (cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65–74 and sex category (female)) score was 3 in all four cohorts. From C1 to C4, the proportion of patients on anticoagulant (AC) therapy increased by almost 15% (C1 57.4%; C4 71.1%). Use of vitamin K antagonist (VKA)±antiplatelet (AP) (C1 53.2%; C4 34.0%) and AP monotherapy (C1 30.2%; C4 16.6%) declined, while use of non-VKA oral ACs (NOACs)±AP increased (C1 4.2%; C4 37.0%). Most CHA2DS2-VASc ≥2 patients received AC, and this proportion increased over time, largely driven by NOAC prescribing. NOACs were more frequently prescribed than VKAs in men, the elderly, patients of Asian ethnicity, those with dementia, or those using non-steroidal anti-inflammatory drugs, and current smokers. VKA use was more common in patients with cardiac, vascular, or renal comorbidities.Conclusions Since NOACs were introduced, there has been an increase in newly diagnosed patients with AF at risk of stroke receiving guideline-recommended therapy, predominantly driven by increased use of NOACs and reduced use of VKA±AP or AP alone.</div

A survey of performance enhancement of transmission control protocol (TCP) in wireless ad hoc networks

This Article is provided by the Brunel Open Access Publishing Fund - Copyright @ 2011 Springer OpenTransmission control protocol (TCP), which provides reliable end-to-end data delivery, performs well in traditional wired network environments, while in wireless ad hoc networks, it does not perform well. Compared to wired networks, wireless ad hoc networks have some specific characteristics such as node mobility and a shared medium. Owing to these specific characteristics of wireless ad hoc networks, TCP faces particular problems with, for example, route failure, channel contention and high bit error rates. These factors are responsible for the performance degradation of TCP in wireless ad hoc networks. The research community has produced a wide range of proposals to improve the performance of TCP in wireless ad hoc networks. This article presents a survey of these proposals (approaches). A classification of TCP improvement proposals for wireless ad hoc networks is presented, which makes it easy to compare the proposals falling under the same category. Tables which summarize the approaches for quick overview are provided. Possible directions for further improvements in this area are suggested in the conclusions. The aim of the article is to enable the reader to quickly acquire an overview of the state of TCP in wireless ad hoc networks.This study is partly funded by Kohat University of Science & Technology (KUST), Pakistan, and the Higher Education Commission, Pakistan

Pregnancy-Associated Venous Thromboembolism: Insights from GARFIELD-VTE.

Introduction  The risk of venous thromboembolism (VTE) increases during pregnancy and the puerperium such that VTE is a leading cause of maternal mortality. Methods  We describe the clinical characteristics, diagnostic strategies, treatment patterns, and outcomes of women with pregnancy-associated VTE (PA-VTE) enrolled in the Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE. Women of childbearing age (<45 years) were stratified into those with PA-VTE ( n  = 183), which included pregnant patients and those within the puerperium, and those with nonpregnancy associated VTE (NPA-VTE; n  = 1,187). Patients with PA-VTE were not stratified based upon the stage of pregnancy or puerperium. Results  Women with PA-VTE were younger (30.5 vs. 34.8 years), less likely to have pulmonary embolism (PE) (19.7 vs. 32.3%) and more likely to have left-sided deep vein thrombosis (DVT) (73.9 vs. 54.8%) compared with those with NPA-VTE. The most common risk factors in PA-VTE patients were hospitalization (10.4%), previous surgery (10.4%), and family history of VTE (9.3%). DVT was typically diagnosed by compression ultrasonography (98.7%) and PE by chest computed tomography (75.0%). PA-VTE patients more often received parenteral (43.2 vs. 15.1%) or vitamin K antagonists (VKA) (9.3 vs. 7.6%) therapy alone. NPA-VTE patients more often received a DOAC alone (30.2 vs. 13.7%). The risk (hazard ratio [95% confidence interval]) of all-cause mortality (0.59 [0.18-1.98]), recurrent VTE (0.82 [0.34-1.94]), and major bleeding (1.13 [0.33-3.90]) were comparable between PA-VTE and NPA-VTE patients. Uterine bleeding was the most common complication in both groups. Conclusion  VKAs or DOACs are widely used for treatment of PA-VTE despite limited evidence for their use in this population. Rates of clinical outcomes were comparable between groups

Towards a science of climate and energy choices

The linked problems of energy sustainability and climate change are among the most complex and daunting facing humanity at the start of the twenty-first century. This joint Nature Energy and Nature Climate Change Collection illustrates how understanding and addressing these problems will require an integrated science of coupled human and natural systems; including technological systems, but also extending well beyond the domain of engineering or even economics. It demonstrates the value of replacing the stylized assumptions about human behaviour that are common in policy analysis, with ones based on data-driven science. We draw from and engage articles in the Collection to identify key contributions to understanding non-technological factors connecting economic activity and greenhouse gas emissions, describe a multi-dimensional space of human action on climate and energy issues, and illustrate key themes, dimensions and contributions towards fundamental understanding and informed decision making