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EMPIRE ESSAY: Dr Strangelove or How I Learned to Stop Worrying

Strangelove essay

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Satire And Black Humor In Dr Strangelove - Essay - 1394 Words

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Film essay for "Dr Strangelove" - Library of Congress

Rivaroxaban or Aspirin for Extended Treatment of strangelove, Venous Thromboembolism. Jeffrey I. Essay Introduction! Weitz, M.D., Anthonie W.A. Lensing, M.D., Ph.D., Martin H. Prins, M.D., Ph.D., Rupert Bauersachs, M.D., Jan Beyer-Westendorf, M.D., Henri Bounameaux, M.D., Timothy A. Brighton, M.D., Alexander T. Cohen, M.D., Bruce L. Davidson, M.D., M.P.H., Herve Decousus, M.D., Maria C.S. Freitas, M.D., Ph.D., Gerlind Holberg, V.D., Ph.D., Ajay K. Kakkar, M.B., B.S., Ph.D., Lloyd Haskell, M.D., Bonno van Bellen, M.D., Akos F. Pap, M.Sc., Scott D. Berkowitz, M.D., Peter Verhamme, M.D., Philip S. Wells, M.D., and Paolo Prandoni, M.D., Ph.D., for the EINSTEIN CHOICE Investigators * N Engl J Med 2017; 376:1211-1222 March 30, 2017 DOI: 10.1056/NEJMoa1700518. Comments open through April 5, 2017. Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of essay, anticoagulation therapy and were in equipoise regarding the need for business plan sample free download continued anticoagulation.

Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. A total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in essay 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of independent review, rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to essay, 0.47; P0.001 for both comparisons). On The! Rates of major bleeding were 0.5% in the group receiving 20 mg of strangelove essay, rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in block contrast the aspirin group; the rates of strangelove, clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups. Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by business sample free, Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439.) Venous thromboembolism, which includes deep-vein thrombosis and pulmonary embolism, is the third most common cause of essay, vascular death after myocardial infarction and stroke. 1-3 The mainstay of treatment is anticoagulation, 4 and in patients without active cancer, guidelines suggest the use of direct oral anticoagulant agents such as rivaroxaban over vitamin K antagonists such as warfarin.

4 Anticoagulation therapy is administered for book 3 months or longer, depending on the balance between the risk of recurrent venous thromboembolism and strangelove essay, the risk of bleeding. Contrast Essay! 4 In patients without reversible risk factors, the risk of recurrent venous thromboembolism is as much as 10% in the first year if anticoagulation therapy is stopped. 5-9 Patients in whom thrombosis was triggered by nonsurgical risk factors or who have persistent risk factors are at higher risk for recurrence than are those with postoperative thrombosis. 10 In addition, because of overlapping risk factors, patients with venous thromboembolism are at increased risk for arterial thrombotic events, including myocardial infarction, stroke, and vascular death. 11-13 Although extended anticoagulation therapy is effective for the prevention of recurrent venous thromboembolism, 5-9 concern about strangelove essay, bleeding often leads to a reluctance to continue anticoagulant treatment beyond 6 to 12 months. Attempts to reduce the risk of bleeding when treatment is extended include the use of lower-dose anticoagulant therapy and the use of aspirin in place of an anticoagulant agent. 6,12-14. At a dose of 20 mg once daily, rivaroxaban is effective for stroke prevention in patients with atrial fibrillation 15 and for the treatment of venous thromboembolism after an essay, initial 21-day course of higher-dose therapy. 7,16,17 At a dose of 10 mg once daily, rivaroxaban provides effective thromboprophylaxis after elective hip or knee arthroplasty. 18-21 In the Reduced-dosed Rivaroxaban in strangelove the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial, 22 we compared the efficacy and safety of these two doses of independent book, rivaroxaban with those of aspirin in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was equipoise regarding the need for strangelove continued anticoagulation. Secondary aims of the essay editing study were to determine whether the lower dose of rivaroxaban was as effective as the higher dose and whether it was associated with less bleeding.

We conducted a randomized, double-blind, phase 3 study comparing the efficacy and strangelove, safety of two doses of rivaroxaban with those of aspirin for the extended treatment of venous thromboembolism for up to 1 year after the hotel sample initial 6 to 12 months of therapy. Essay! 22 The trial was sponsored by Bayer Pharmaceuticals. The steering committee, which included both academic authors and those employed by the sponsor, had final responsibility for the design of the block study, the development of the protocol, the essay oversight of the study, the verification of the data, and the analyses. The sponsor collected, maintained, and analyzed the data; the academic authors had access to the data at all times through the sponsor. The protocol (available with the full text of this article at NEJM.org) was approved by the institutional review board at each participating center. Written informed consent was obtained from all the patients. An independent committee whose members were unaware of the study-group assignments adjudicated the qualifying initial diagnosis (deep-vein thrombosis or pulmonary embolism) and all suspected outcomes that occurred during the study. An independent data and editing site, safety monitoring committee periodically reviewed the study outcomes.

All the members of the steering committee contributed to the interpretation of the results. The first three authors wrote the first draft of the manuscript, and all the steering committee members contributed to subsequent versions, made the decision to submit the essay manuscript for publication, and vouch for the accuracy and introduction structure, completeness of the data and for the fidelity of the study to the protocol. Patients were eligible for inclusion in the study if they were 18 years of age or older; had objectively confirmed, symptomatic proximal deep-vein thrombosis or pulmonary embolism; had been treated for strangelove 6 to hotel business download, 12 months with an essay, anticoagulant agent, including a vitamin K antagonist or a direct oral anticoagulant agent such as dabigatran, rivaroxaban, apixaban, or edoxaban; and essay, had not interrupted therapy for more than 7 days before randomization. Patients were ineligible if they had a contraindication to continued anticoagulant therapy or if they required extended anticoagulant therapy at therapeutic doses or antiplatelet therapy. Additional ineligibility criteria included a calculated creatinine clearance of less than 30 ml per essay minute 23,24 or hepatic disease associated with a coagulopathy. A full list of inclusion and exclusion criteria is block essay, provided in the Supplementary Appendix, available at essay NEJM.org. Randomization with a block size of six was performed with the use of an interactive voice-response system and site, was stratified according to the index diagnosis (deep-vein thrombosis or pulmonary embolism) and country. Essay! Patients were enrolled at business least 24 hours after they had received the last dose of a direct oral anticoagulant agent or, if they were receiving a vitamin K antagonist, when the international normalized ratio was 2.5 or lower.

Patients were assigned, in a 1:1:1 ratio, to receive 20 mg of rivaroxaban, 10 mg of essay, rivaroxaban, or 100 mg of aspirin, all given once daily with food. Rivaroxaban (20 mg and 10 mg) and structure, matching placebo were provided as identical-appearing, immediate-release film-coated tablets, whereas aspirin and matching placebo were provided as enteric-coated tablets. The intended duration of strangelove essay, administration of the study drug was 12 months, but patients who underwent randomization after the requisite number of essay, primary efficacy outcomes had been reached were treated for at least 6 months. The primary efficacy outcome was a composite of symptomatic, recurrent fatal or nonfatal venous thromboembolism and strangelove essay, unexplained death for which pulmonary embolism could not be ruled out. Recurrent venous thromboembolism included fatal and editing, nonfatal pulmonary embolism and deep-vein thrombosis. Other efficacy outcomes were myocardial infarction, ischemic stroke, systemic embolism, venous thrombosis in strangelove essay locations other than the deep veins of the lower limbs, and death from any cause. The definitions of the efficacy outcomes are provided in the Supplementary Appendix. The principal safety outcome was major bleeding.

25 Other safety outcomes were clinically relevant nonmajor bleeding, a composite of major or clinically relevant nonmajor bleeding, and nonmajor bleeding that led to study-drug interruption for essay editing more than 14 days. 12,13 Major bleeding was defined as overt bleeding that was associated with a decrease in the hemoglobin level of 2 g per deciliter or more, led to transfusion of 2 or more units of red cells, occurred in a critical site, or contributed to death. Clinically relevant nonmajor bleeding was defined as overt bleeding that did not meet the criteria for major bleeding but was associated with the strangelove essay need for medical intervention, unscheduled contact with a physician, interruption or discontinuation of the study drug, or discomfort or impairment of activities of daily living. Contrast Essay! 26 (Further details regarding the criteria are provided in the Supplementary Appendix.) Patients underwent assessment, either in the clinic or by telephone, at days 30, 90, 180, 270, and 360 and at 30 days after stopping the strangelove study medication. All the patients who stopped a study treatment earlier than scheduled were followed until the end of the intended treatment period. Patients were instructed to block contrast essay, report to the study center if they had symptoms suggestive of recurrent venous thromboembolism or bleeding. Prespecified objective testing was required for patients in whom an strangelove essay, outcome event was suspected.

22 Continuation of anticoagulant or antiplatelet therapy after study completion was at thematic essay the discretion of the treating physician. The study was designed to test the hypothesis that each dose of rivaroxaban would be superior to aspirin with respect to the primary efficacy outcome. We determined that the essay occurrence of 80 primary efficacy outcome events would provide a power of thematic essay on the new deal, 90% to show the superiority of each dose of strangelove essay, rivaroxaban over aspirin (each at a two-sided alpha level of 0.05), assuming a relative risk reduction of 70% with 20 mg of rivaroxaban and of 60% with 10 mg of rivaroxaban. 7 On the basis of an on hospitality, expected frequency of the primary efficacy outcome of 5.0% at 12 months with aspirin, 12,13 we calculated that we would need to strangelove, enroll 2850 patients. However, this number was increased to 3300 when review of blinded data revealed a lower-than-expected overall incidence of the primary efficacy outcome. The efficacy and safety analyses included all the on the new deal patients who had undergone randomization with valid informed consent and who had received at least one dose of a study medication (intention-to-treat population). Essay! The per-protocol population excluded patients who had a rate of adherence to the study-drug regimen of less than 80% or who had other major protocol violations. Efficacy outcomes were considered during the individual intended treatment period, whereas safety outcomes were considered during the time from administration of the first dose of a study drug to 48 hours after the administration of the essay on hospitality last dose. Efficacy and safety outcomes were analyzed with the use of a Cox proportional-hazards model, stratified according to the index diagnosis (deep-vein thrombosis or pulmonary embolism). Kaplan–Meier curves were constructed to display the distribution of events over time.

From March 2014 through March 2016, a total of 3396 patients from 244 sites in strangelove 31 countries were enrolled. After the exclusion of on the, 31 patients (0.9%) because they did not receive any study drug, 3365 patients were included in the primary analyses. Essay! The characteristics of patients in the three study groups were similar at baseline, as was the median duration of study treatment ( Table 1 Table 1 Demographic and thematic on the, Clinical Characteristics of the Patients at essay Baseline. ). Figure 1 Figure 1 Enrollment and Outcomes. The intention-to-treat population included all the patients who had undergone randomization with valid informed consent and contrast essay, who had received at least one dose of a study medication. The per-protocol population included all those in essay the intention-to-treat population with the exception of those who had a rate of adherence to the study-drug regimen of less than 80% or who had other major protocol violations. The main reasons for premature discontinuation of a study medication were adverse events, nonadherence to the study-drug regimen, protocol violations, and efficacy or safety outcomes. Block Essay! shows the random assignment and follow-up of the patients. A primary efficacy outcome event occurred in 17 of 1107 patients (1.5%) who were receiving 20 mg of rivaroxaban and in strangelove 13 of 1127 patients (1.2%) who were receiving 10 mg of rivaroxaban, as compared with 50 of odyssey essay, 1131 patients (4.4%) who were receiving aspirin. Strangelove Essay! Fatal venous thromboembolism occurred in 2 patients (0.2%) who were receiving 20 mg of essay, rivaroxaban, in no patients who were receiving 10 mg of rivaroxaban, and in 2 patients (0.2%) who were receiving aspirin ( Table 2 Table 2 Prespecified Efficacy Outcomes. ). Both rivaroxaban doses were superior to aspirin with respect to the primary efficacy outcome (hazard ratio for 20 mg of strangelove, rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of essay on the, rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P0.001 for both comparisons).

The hazard ratio for the comparison between the 20-mg and 10-mg rivaroxaban regimens was 1.34 (95% CI, 0.65 to 2.75; P=0.42). Similar results were found for strangelove the other efficacy outcomes ( Table 2 , and Table S4 in the Supplementary Appendix). With aspirin, the review rate of recurrent venous thromboembolism was 3.6% among the patients in whom the index event was provoked (i.e., associated with a known event, such as surgery or hospital admission) and 5.6% among those in whom the index event was unprovoked (i.e., idiopathic) ( Table 3 Table 3 Rates of Recurrent Venous Thromboembolism and Major Bleeding, According to Risk Profile and Duration of essay, Anticoagulation before Randomization. ). Rates of odyssey, recurrence in patients whose index events were provoked or unprovoked were lower in both the essay 20-mg rivaroxaban group (1.4% and 1.8%, respectively) and the 10-mg rivaroxaban group (0.9% and 1.5%, respectively) than in the aspirin group. Figure 2A Figure 2 Kaplan–Meier Rates of Recurrent Fatal or Nonfatal Venous Thromboembolism and Major Bleeding. Kaplan–Meier curves are shown for independent review the first event of recurrent fatal or nonfatal venous thromboembolism during the individual intended treatment periods (Panel A) and for essay the first episode of major bleeding during the period between the administration of the first dose of structure, a study drug and 48 hours after the administration of the last dose (Panel B). Essay! In each panel, the inset shows the same data on an enlarged y axis. shows the time course of symptomatic fatal or nonfatal recurrent venous thromboembolism. Review! Of the 31 patients who were excluded from the analyses because they did not take any study drug, 1 patient who was assigned to receive 20 mg of rivaroxaban had a nonfatal primary efficacy outcome event. Major bleeding occurred in 6 patients (0.5%) in the 20-mg rivaroxaban group and in 5 patients (0.4%) in essay the 10-mg rivaroxaban group, as compared with 3 patients (0.3%) in essay new deal the aspirin group ( Table 4 Table 4 Prespecified Safety Outcomes. ). Figure 2B shows the time course of strangelove essay, major bleeding episodes. Clinically relevant nonmajor bleeding occurred in block contrast essay 30 patients (2.7%) in the 20-mg rivaroxaban group and in 22 patients (2.0%) in the 10-mg rivaroxaban group, as compared with 20 patients (1.8%) in the aspirin group ( Table 4 ). Strangelove! Similar results were found for independent the composite outcome of strangelove essay, major or clinically relevant nonmajor bleeding. Nonmajor bleeding that was associated with a study-drug interruption for more than 14 days occurred in 17 patients (1.5%) in the 20-mg rivaroxaban group and in 12 patients (1.1%) in the 10-mg rivaroxaban group, as compared with 12 patients (1.1%) in the aspirin group. Myocardial infarction, stroke, or systemic embolism occurred in 3 patients (0.3%) in the 20-mg rivaroxaban group, in 5 patients (0.4%) in the 10-mg rivaroxaban group, and in 7 patients (0.6%) in odyssey on hospitality the aspirin group ( Table 2 ). The rates of death from any cause were 0.7% and 0.2% in the 20-mg and 10-mg rivaroxaban groups, respectively, as compared with 0.6% in strangelove essay the aspirin group.

Rates of adverse events were similar in the three study groups (Table S1 in the Supplementary Appendix). In prespecified subgroup analyses of the primary efficacy outcome and business plan sample free download, the composite outcome of strangelove essay, major and clinically relevant nonmajor bleeding, results were consistent with the overall treatment effects (Figs. S1 through S4 in the Supplementary Appendix). During the 30-day follow-up after the end of the active study period, symptomatic recurrent venous thromboembolism occurred in 2 patients (0.2%) in the 20-mg rivaroxaban group, in 4 patients (0.4%) in the 10-mg rivaroxaban group, and in 6 patients (0.6%) in the aspirin group. Clinical strategies for extended anticoagulation in odyssey on hospitality patients with venous thromboembolism are uncertain. Previous studies have shown that as compared with placebo, aspirin reduced the relative risk of recurrent venous thromboembolism by 32% (2.4 percentage points), 12,13 whereas a 20-mg dose of rivaroxaban reduced the relative risk by strangelove, 82% (6.8 percentage points). 7 Consistent with those findings, our study shows that as compared with aspirin, both the 20-mg and on the new deal, 10-mg doses of rivaroxaban reduced the relative risk of recurrent venous thromboembolism by about 70% (approximately 3 percentage points). Strangelove Essay! These benefits were observed with rates of major and clinically relevant nonmajor bleeding that were low and similar to those with aspirin.

Therefore, we found that rivaroxaban was more effective than aspirin for the prevention of recurrent venous thromboembolism and was associated with a similar risk of essay, bleeding. What are the clinical implications of these findings? This study included patients with both provoked and unprovoked venous thromboembolism for whom there was equipoise regarding the essay need for continued anticoagulation. Patients with unprovoked venous thromboembolism are known to be at high risk for introduction recurrence, but the risk of recurrence among those in whom venous thromboembolism was provoked by essay, minor transient or persistent risk factors is on hospitality, less certain. Essay! We found that patients with venous thromboembolism with ongoing risk factors have an appreciable risk of recurrence because even with aspirin, the rate of recurrent venous thromboembolism in such patients was 3.6%, as compared with a rate of recurrence of 5.6% in those with unprovoked venous thromboembolism. Rivaroxaban reduced the relative risk of recurrence by about 70% in patients with both unprovoked and provoked venous thromboembolism. Consequently, the number of odyssey essay, patients who would need to be treated for essay up to 12 months with rivaroxaban instead of aspirin to prevent one episode of independent review, fatal or nonfatal recurrent venous thromboembolism without increasing the risk of essay, bleeding was 33 with the hotel business plan sample free download 20-mg dose and 30 with the 10-mg dose. Prevention of recurrent pulmonary embolism is particularly important, because the strangelove case-fatality rate at review 30 days is at essay least twice as high with pulmonary embolism as with deep-vein thrombosis.

27. Our study has several potential limitations. First, patients who required extended treatment with therapeutic doses of anticoagulant agents were excluded. Therefore, it remains unknown whether the 10-mg dose of rivaroxaban would be sufficient to prevent recurrence in such patients. Second, in this study and in the previous trial comparing rivaroxaban with placebo for extended treatment of venous thromboembolism, therapy was given for up to 12 months. Consequently, additional studies are needed to determine the utility of continuing treatment for essay longer periods. Strangelove Essay! Third, our study was not powered to plan free download, show the noninferiority of the strangelove 10-mg dose of rivaroxaban to the established treatment regimen of 20 mg, so any conclusions with respect to this issue are speculative. In conclusion, we found that rivaroxaban, at both a treatment dose (20 mg) and a thromboprophylactic dose (10 mg), was more effective than aspirin for essay on the the prevention of recurrent venous thromboembolism among patients who were in equipoise for essay continued anticoagulation.

The lower risk of a recurrent event among the patients who received rivaroxaban was associated with a rate of bleeding similar to that with aspirin. Supported by essay introduction structure, Bayer Pharmaceuticals. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Dr. Weitz reports receiving consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Portola, and Pfizer; Drs. Lensing, Freitas, Holberg, Pap, and Berkowitz, being employees of Bayer; Dr.

Prins, receiving consulting fees from Pfizer and Daiichi Sankyo; Dr. Essay! Bauersachs, receiving consulting and lecture fees from Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo; Dr. Beyer-Westendorf, receiving grant support, lecture fees, and independent, fees for serving on advisory boards from Boehringer Ingelheim, Daiichi Sankyo, and Pfizer; Dr. Essay! Bounameaux, receiving grant support and fees for serving on the Thrombosis Research Institute Garfield Registry steering committee, fees for serving on the Bayer EINSTEIN CHOICE Study steering committee, consulting fees from Amgen, and fees for serving on advisory boards from Bayer, Pfizer, and Sanofi Aventis; Dr. Brighton, receiving lecture fees from Bayer, Novo Nordisk, and GlaxoSmithKline; Dr. Essay On The New Deal! Cohen, receiving fees for serving on a committee for Boehringer Ingelheim, grant support and fees for serving on committees from Bristol-Myers Squibb and Daiichi Sankyo, consulting fees and fees for serving on steering committees from Johnson Johnson and Portola, grant support, consulting fees, and fees for strangelove essay serving on committees from Pfizer, and consulting fees from Sanofi, Janssen, and Ono Pharmaceuticals; Dr. Davidson, receiving consulting fees from Janssen and Portola; Dr. Decousus, receiving fees for attending symposia from Aspen, fees for serving on advisory boards from Pfizer and Bristol-Myers Squibb, and grant support and fees for board membership from Daiichi Sankyo and on hospitality, Bayer; Dr. Strangelove Essay! Kakkar, receiving grant support, consulting fees, and lecture fees from Bayer and consulting and lecture fees from Sanofi, Janssen, Boehringer Ingelheim, and Daiichi Sankyo; Dr. Haskell, being an employee of essay, Johnson Johnson; Dr. van Bellen, receiving lecture fees and fees for serving on an advisory board from Bayer and strangelove, Daiichi Sankyo and for site serving on an advisory board from Bristol-Myers Squibb; Dr.

Verhamme, receiving grant support, lecture fees, and fees for serving on an advisory board from strangelove, Boehringer Ingelheim and LEO Pharma, lecture fees from Pfizer and Bristol-Myers Squibb, grant support from Sanofi, lecture fees and fees for serving on an advisory board from Daiichi Sankyo, and editing site, fees for serving on an advisory board from Portola Pharmaceuticals; Dr. Wells, receiving grant support, lecture fees, and fees for serving on an advisory board from strangelove, Bayer, fees for serving on contrast essay a writing committee from Itreas, consulting fees from Janssen Scientific Affairs, grant support from strangelove, Bristol-Myers Squibb and Pfizer, and download, lecture fees from Daiichi Sankyo; and Dr. Essay! Prandoni, receiving consulting and new deal, lecture fees from Bayer, Sanofi, Daiichi Sankyo, and Pfizer. No other potential conflict of strangelove essay, interest relevant to this article was reported. This article was published on March 18, 2017, at NEJM.org. From the Thrombosis and contrast essay, Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) — both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and strangelove essay, Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) — all in hotel business sample free Germany; the essay Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of essay, Geneva, Geneva (H.B.); the Department of Haematology, Prince of strangelove essay, Wales Hospital, Sydney (T.A.B.); the Department of Haematology and independent, Oncology, King’s College London (J.B.-W.), the Department of Haematological Medicine, Guy’s and St.

Thomas’ Hospitals, King’s College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) — all in London; the strangelove essay University of essay on the new deal, Washington School of Medicine, Seattle (B.L.D.); Centre d’Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Medecine Vasculaire et Therapeutique, Centre Hospitalo-Universitaire, Hopital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficencia Portuguesa, Sao Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of strangelove, Padua, Padua, Italy (P.P.). Address reprint requests to block contrast essay, Dr. Weitz at the Thrombosis and essay, Atherosclerosis Research Institute, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, or at weitzj@taari.ca. A list of the editing Reduced-dosed Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) investigators and collaborators is provided in essay the Supplementary Appendix, available at NEJM.org. ISTH Steering Committee for plan sample free World Thrombosis Day . Thrombosis: a major contributor to global disease burden. Thromb Res 2014;134:931-938.

Cohen AT , Agnelli G , Anderson FA , et al. Strangelove! Venous thromboembolism (VTE) in Europe: the essay on hospitality number of VTE events and associated morbidity and mortality. Thromb Haemost 2007;98:756-764. Venous thromboembolism in adult hospitalizations — United States, 2007–2009. MMWR Morb Mortal Wkly Rep 2012;61:401-404.

Kearon C , Akl EA , Ornelas J , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Essay! Chest 2016;149:315-352. Prandoni P , Lensing AW , Cogo A , et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1-7.

Ridker PM , Goldhaber SZ , Danielson E , et al. History Essay Structure! Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003;348:1425-1434. The EINSTEIN Investigators . Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-2510.

Schulman S , Kearon C , Kakkar AK , et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013;368:709-718. Agnelli G , Buller HR , Cohen A , et al. Apixaban for strangelove extended treatment of venous thromboembolism. N Engl J Med 2013;368:699-708.

Baglin T , Luddington R , Brown K , Baglin C . Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003;362:523-526. Prandoni P , Bilora F , Marchiori A , et al. An association between atherosclerosis and venous thrombosis. Thematic Essay New Deal! N Engl J Med 2003;348:1435-1441. Brighton TA , Eikelboom JW , Mann K , et al. Low-dose aspirin for preventing recurrent venous thromboembolism.

N Engl J Med 2012;367:1979-1987. Becattini C , Agnelli G , Schenone A , et al. Essay! Aspirin for preventing the essay recurrence of venous thromboembolism. N Engl J Med 2012;366:1959-1967. Kearon C , Ginsberg JS , Kovacs MJ , et al.

Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. Strangelove! N Engl J Med 2003;349:631-639. Patel MR , Mahaffey KW , Garg J , et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. Essay Editing! N Engl J Med 2011;365:883-891. The EINSTEIN–PE Investigators . Essay! Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-1297.

Prins MH , Lensing AW , Bauersachs R , et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 2013;11:21-21. Eriksson BI , Borris LC , Friedman RJ , et al. Rivaroxaban versus enoxaparin for essay thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358:2765-2775. Kakkar AK , Brenner B , Dahl OE , et al.

Extended duration rivaroxaban versus short-term enoxaparin for strangelove essay the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008;372:31-39. Lassen MR , Ageno W , Borris LC , et al. Rivaroxaban versus enoxaparin for essay new deal thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;358:2776-2786. Turpie AG , Lassen MR , Davidson BL , et al.

Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373:1673-1680. Weitz JI , Bauersachs R , Beyer-Westendorf J , et al. Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism: rationale for strangelove and design of the EINSTEIN CHOICE study. Thromb Haemost 2015;114:645-650. Cockcroft DW , Gault MH . Prediction of independent book, creatinine clearance from serum creatinine. Nephron 1976;16:31-41. Levey AS , Stevens LA , Schmid CH , et al. A new equation to estimate glomerular filtration rate.

Ann Intern Med 2009;150:604-612. Schulman S , Kearon C . Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. Strangelove! J Thromb Haemost 2005;3:692-694. Kaatz S , Ahmad D , Spyropoulos AC , Schulman S . Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the on hospitality SSC of the ISTH. Essay! J Thromb Haemost 2015;13:2119-2126. Spencer FA , Gore JM , Lessard D , Douketis JD , Emery C , Goldberg RJ . Patient outcomes after deep vein thrombosis and pulmonary embolism: the essay on hospitality Worcester Venous Thromboembolism Study. Arch Intern Med 2008;168:425-430. Gualtiero Palareti. . Strangelove! (2017) Optimal long-term pharmacological treatment of patients with venous thromboembolism that was unprovoked or associated with weak risk factors. Expert Review of Hematology 10 :10, 921-931. L. Man, A. Morris, J. Brown, S. Odyssey Essay! Palkimas, K. Davidson. . Essay! (2017) Use of direct oral anticoagulants in patients on immunomodulatory agents.

Journal of free, Thrombosis and Thrombolysis 44 :3, 298-302. Julia Czuprynska, Jignesh P. Patel, Roopen Arya. . (2017) Current challenges and future prospects in oral anticoagulant therapy. British Journal of Haematology 178 :6, 838-851. A. Tosetto, S. Testa, I. Martinelli, D. Poli, B. Cosmi, C. Lodigiani, W. Ageno, V. De Stefano, A. Falanga, I. Nichele, O. Paoletti, P. Bucciarelli, E. Antonucci, C. Legnani, E. Banfi, F. Dentali, F. Bartolomei, L. Strangelove! Barcella, G. Palareti. . (2017) External validation of the DASH prediction rule: a retrospective cohort study. Editing Site! Journal of Thrombosis and Haemostasis 149 . Davide Imberti, Daniela Mastroiacovo. . (2017) Is it reasonable to use a lower DOACs dose in some patients with VTE? Yes. Internal and Emergency Medicine 12 :5, 561-563. Beate Schumacher. . (2017) Tiefe Venenthrombose: Wie lang antikoagulieren?. Strangelove! CME 14 :7-8, 54-54. Raphael Le Mao, Cecile Tromeur, Francis Couturaud. . (2017) Quel traitement anticoagulant au decours d’une embolie pulmonaire.

La Presse Medicale . Rachel Rosovsky, Geno Merli. . (2017) Anticoagulation in Pulmonary Embolism: Update in the Age of essay, Direct Oral Anticoagulants. Techniques in Vascular and essay, Interventional Radiology . (2017) Extended Treatment of Venous Thromboembolism. New England Journal of thematic essay new deal, Medicine 376 :25, 2491-2492. (2017) Scientific Surgery June 2017 BJS. British Journal of Surgery 104 :7, 946-946. (2017) ACC highlights promising studies. Pharmacy Today 23 :6, 2. Paolo Prandoni, Valentina Vedovetto, Maurizio Ciammaichella, Eugenio Bucherini, Sara Corradini, Iolanda Enea, Benilde Cosmi, Nicola Mumoli, Adriana Visona, Giovanni Barillari, Carlo Bova, Roberto Quintavalla, Nello Zanatta, Simona Pedrini, Sabina Villalta, Giuseppe Camporese, Sofie Testa, Roberto Parisi, Cecilia Becattini, Stefano Cuppini, Vittorio Pengo, Gualtiero Palareti. . (2017) Residual vein thrombosis and serial D-dimer for the long-term management of strangelove essay, patients with deep venous thrombosis.

Thrombosis Research 154 , 35-41. Paolo Prandoni, Walter Ageno, Nicola Mumoli, Nello Zanatta, Davide Imberti, Adriana Visona, Maurizio Ciammaichella, Livio Simioni, Roberto Cappelli, Eugenio Bucherini, Marcello Di Nisio, Giampiero Avruscio, Giuseppe Camporese, Roberto Parisi, Stefano Cuppini, Giacomo Turatti, Franco Noventa, Lucia Sarolo. . Thematic Essay On The! (2017) Recanalization rate in patients with proximal vein thrombosis treated with the direct oral anticoagulants. Thrombosis Research 153 , 97-100. Peter Overbeck. . (2017) Verlangerte VTE-Prophylaxe: Rivaroxaban deutlich besser als ASS. CardioVasc 17 :2, 18-19. Crowther, Mark A., Cuker, Adam, . Strangelove! . (2017) Reduced-Intensity Rivaroxaban for the Prevention of essay editing, Recurrent Venous Thromboembolism.

New England Journal of strangelove, Medicine 376 :13, 1279-1280. Takafumi Hiro. . (2017) Report of the Annual Scientific Sessions of the American College of on the, Cardiology (ACC), Washington DC. Circulation Journal 81 :6, 777-782. Jeffrey I. Weitz, Iqbal H. Jaffer, James C. Strangelove Essay! Fredenburgh. . (2017) Recent advances in the treatment of venous thromboembolism in the era of the direct oral anticoagulants. F1000Research 6 , 985.

E. A. Ilyukhin, I. A. Zolotukhin. Odyssey On Hospitality! . (2017) Current Tendencies in the Prevention of Recurrent Venous Thromboembolism. Flebologiia 11 :2, 83.

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