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1.
Ann Intern Med ; 176(4): 515-523, 2023 04.
Article in English | MEDLINE | ID: mdl-36940444

ABSTRACT

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.


Subject(s)
COVID-19 Vaccines , COVID-19 , Hemorrhage , Venous Thromboembolism , Adult , Female , Humans , Male , Middle Aged , Anticoagulants/adverse effects , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Hemorrhage/chemically induced , Hospitalization , Prospective Studies , SARS-CoV-2 , Treatment Outcome , Venous Thromboembolism/drug therapy
2.
Appl Opt ; 60(8): 2288-2303, 2021 Mar 10.
Article in English | MEDLINE | ID: mdl-33690328

ABSTRACT

The advanced radiographic capability (ARC) laser system, part of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, is a short-pulse laser capability integrated into the NIF. The ARC is designed to provide adjustable pulse lengths of ∼1-38ps in four independent beamlets, each with energies up to 1 kJ (depending on pulse duration). A detailed model of the ARC lasers has been developed that predicts the time- and space-resolved focal spots on target for each shot. Measurements made to characterize static and dynamic wavefront characteristics of the ARC are important inputs to the code. Modeling has been validated with measurements of the time-integrated focal spot at the target chamber center (TCC) at low power, and the space-integrated pulse duration at high power, using currently available diagnostics. These simulations indicate that each of the four ARC beamlets achieves a peak intensity on target of up to a few 1018W/cm2.

3.
Curr Opin Hematol ; 22(5): 420-7, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26248002

ABSTRACT

PURPOSE OF REVIEW: Blood coagulation exists to halt excessive blood loss. It is paradoxical that surgery and trauma simultaneously represent major risk factors for both hemorrhagic and thrombotic complications. A summary of the available evidence used to guide contemporary approaches to perioperative care will be reviewed. RECENT FINDINGS: Although the advent of factor-specific products has safely allowed for intervention on patients with congenital hemostatic defects, the presence of an increasingly complex surgical population (chronic liver disease, traumatic injuries, and requirements for chronic anticoagulation) has renewed concerns about hemorrhagic risks. However, the past three decades of clinical sciences have supported a re-emphasis on the prevention of venous thromboembolism (VTE), a major cause of morbidity and mortality in hospitalized surgical patients. There is now an abundance of data confirming the robust risk:benefit ratio of antithrombotic prophylaxis in the vast majority of surgical patients, regardless of their medical comorbidities. SUMMARY: Perioperative hemorrhage is a natural risk of any surgical intervention and deserves careful evaluation and prompt intervention. However, in order to support ongoing efforts in the prevention of medical errors, the application of evidence-based guidelines for the prophylaxis of VTE in surgical patients must become a standard part of daily practice.


Subject(s)
Anticoagulants/therapeutic use , Fibrinolytic Agents/therapeutic use , Hemorrhage/prevention & control , Hemostasis, Surgical/methods , Venous Thromboembolism/prevention & control , Anticoagulants/adverse effects , Blood Coagulation Disorders/complications , Blood Transfusion/methods , Fibrinolytic Agents/adverse effects , Humans , Perioperative Care , Plasma , Risk Assessment/methods , Risk Factors , Surgical Procedures, Operative
4.
Exp Clin Transplant ; 19(3): 269-272, 2021 03.
Article in English | MEDLINE | ID: mdl-29766777

ABSTRACT

Liver transplant has occasionally been performed in the presence of congenital afibrinogenemia and has been rarely used to treat it. Historically, to safely manage coagulopathy during transplant, these patients have been administered a combination of fresh frozen plasma and cryoprecipitate. In this case report, we discuss the first reported use of recombinant fibrinogen to treat such a patient and the decision-making process considered to balance the thrombotic and hemorrhagic risks.


Subject(s)
Afibrinogenemia , Fibrinogen/therapeutic use , Liver Transplantation , Afibrinogenemia/drug therapy , Humans , Recombinant Proteins/therapeutic use
5.
Blood Adv ; 4(18): 4574-4583, 2020 09 22.
Article in English | MEDLINE | ID: mdl-32960959

ABSTRACT

Systems-based hematology is dedicated to improving care delivery for patients with blood disorders. First defined by the American Society of Hematology in 2015, the idea of a systems-based hematologist arose from evolving pressures in the health care system and increasing recognition of opportunities to optimize the quality and cost effectiveness of hematologic care. In this review, we begin with a proposed framework to formalize the discussion of the range of initiatives within systems-based hematology. Classification by 2 criteria, project scope and method of intervention, facilitates comparison between initiatives and supports dialogue for future efforts. Next, we present published examples of successful systems-based initiatives in the field of hematology, including efforts to improve stewardship in the diagnosis and management of complex hematologic disorders (eg, heparin-induced thrombocytopenia and thrombophilias), the development of programs to promote appropriate use of hematologic therapies (eg, blood products, inferior vena cava filters, and anticoagulation), changes in care delivery infrastructure to improve access to hematologic expertise (eg, electronic consultation and disorder-specific care pathways), and others. The range of projects illustrates the broad potential for interventions and highlights different metrics used to quantify improvements in care delivery. We conclude with a discussion about future directions for the field of systems-based hematology, including extension to malignant disorders and the need to define, expand, and support career pathways.


Subject(s)
Hematologic Diseases , Hematology , Delivery of Health Care , Hematologic Diseases/diagnosis , Hematologic Diseases/therapy , Humans
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