Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID-19 severity. OBJECTIVE: To compare outcomes in hospitalized adults with severe COVID-19 treated with standard prophylactic versus intermediate dose enoxaparin. METHODS: We conducted a multi-center, open-label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID-19 and admitted to an intensive care unit (ICU) and/or had laboratory evidence of coagulopathy. Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weight-adjusted dose enoxaparin. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included arterial or venous thromboembolism and major bleeding. RESULTS: A total of 176 patients (99 males and 77 females) underwent randomization. In the intention-to-treat population, all-cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30-1.45; P = .31 by Chi-square test). Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33-1.37; P = .28). Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm. CONCLUSION: In hospitalized adults with severe COVID-19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.

Chart validation of inpatient International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) administrative diagnosis codes for venous thromboembolism (VTE) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database.

The Sentinel Distributed Database (SDD) is a database of patient administrative healthcare records, derived from insurance claims and electronic health records, sponsored by the US Food and Drug Administration for evaluation of medical product outcomes. There is limited information on the validity of diagnosis codes for acute venous thromboembolism (VTE) in the SDD and administrative healthcare data more generally.In this chart validation study, we report on the positive predictive value (PPV) of inpatient administrative diagnosis codes for acute VTE-pulmonary embolism (PE) or lower-extremity or site-unspecified deep vein thrombosis (DVT)-within the SDD. As part of an assessment of thromboembolic adverse event risk following treatment with intravenous immune globulin (IGIV), charts were obtained for 75 potential VTE cases, abstracted, and physician-adjudicated.VTE status was determined for 62 potential cases. PPVs for lower-extremity DVT and/or PE were 90% (95% CI: 73-98%) for principal-position diagnoses, 80% (95% CI: 28-99%) for secondary diagnoses, and 26% (95% CI: 11-46%) for position-unspecified diagnoses (originating from physician claims associated with an inpatient stay). Average symptom onset was 1.5 days prior to hospital admission (range: 19 days prior to 4 days after admission).PPVs for principal and secondary VTE discharge diagnoses were similar to prior study estimates. Position-unspecified diagnoses were less likely to represent true acute VTE cases.

Outcomes among North American patients with diffuse large B-cell lymphoma are independent of tumor Epstein-Barr virus positivity or immunosuppression.

The prevalence, presenting clinical and pathological characteristics, and outcomes for patients with diffuse large B-cell lymphoma that is Epstein-Barr virus positive remain uncertain as does the impact of congenital or iatrogenic immunosuppression. Patients with newly diagnosed diffuse large B-cell lymphoma with available tissue arrays were identified from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource. Patients infected with human immunodeficiency virus or who had undergone a prior organ transplant were excluded. Epstein-Barr virus-associated ribonucleic acid testing was performed on all tissue arrays. A history of significant congenital or iatrogenic immunosuppression was determined for all patients. At enrollment, 16 of the 362 (4.4%) biopsies were positive for Epstein-Barr virus. Thirty-nine (10.8%) patients had a significant history of immunosuppression. Patients with Epstein-Barr-positive diffuse large B-cell lymphoma had no unique clinical characteristics but on pathology exhibited a higher frequency of CD30 positivity (25.0% versus 8.1%, respectively; P<0.01), and non-germinal-center subtype (62.5% versus 34.1%, respectively; P<0.01). No baseline clinical characteristics were associated with a history of immunosuppression. With a median follow up of 59 months, and after adjustment for International Prognostic Index, there was no association of Epstein-Barr virus positivity or immunosuppression with event-free survival at 24 months (odds ratio=0.49; 95% confidence interval: 0.13-1.84 and odds ratio=0.81; 95% confidence interval: 0.37-1.77) or overall survival (hazard ratio=0.86; 95% confidence interval: 0.38-1.97 and hazard ratio=1.00; 95% confidence interval: 0.57-1.74). In contrast to non-Western populations, our North American population had a low prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma that did not convey an adverse prognosis. A history of immunosuppression, while known to be a risk factor for the development of diffuse large B-cell lymphoma, did not affect subsequent prognosis.