High-risk subgroups were not identified to benefit from thromboprophylaxis after hospitalization for COVID-19.

Background: The Accelerating COVID-19 Therapeutic Interventions and Vaccines-4c (ACTIV-4c) trial investigated prophylactic apixaban for 30 days following hospitalization for COVID-19. The overall incidence of early postdischarge death or thromboembolism was low, and the trial was closed early. Objectives: To identify a high-risk patient population who might benefit from postdischarge thromboprophylaxis through subgroup analyses stratified by age, race/ethnicity, obesity, D-dimer elevation, World Health Organization score, and modified International Medical Prevention Registry on Venous Thromboembolism score on 30-day composite outcome of all-cause death, arterial thromboembolism (ATE), and venous thromboembolism (VTE). Methods: Cumulative incidences of all-cause death, ATE, and VTE within 30 days were described for each subgroup. Time to death, ATE, or VTE by 30 days was analyzed using Cox proportional hazard models with interaction testing for each subgroup. Results: Among 1217 patients randomized to apixaban or placebo group, 32% were >60 years old. Modified International Medical Prevention Registry on Venous Thromboembolism score was ≥4 in 2% and 2 or 3 with an elevated D-dimer in an additional 9% of participants. The overall incidence of the primary endpoint was 2.13% in the apixaban group and 2.31% in the placebo group. At day 30, similar rates of the primary endpoint occurred within subgroups, except for participants aged >60 years. No benefit of thromboprophylaxis was seen in any subgroup. Conclusion: The combined incidence of 30-day death, ATE, and VTE was low in patients who survived COVID-19 hospitalization, except in patients over age 60 years. Due to the limited number of events, the findings remain inconclusive; nonetheless, the study did not identify a high-risk subgroup that would derive benefits from extended thromboprophylaxis.

Combined effect of copper, cadmium, and lead upon Cucumis sativus growth and bioaccumulation.

Cucumis sativus (cucumber) was tested to assess an ecotoxicity in soils contaminated by the heavy metals copper (Cu), cadmium (Cd), and lead (Pb) separately and in combinations. The toxicity endpoint was plant growth, which was measured as shoot and root lengths after 5 day exposure. Sum of toxic unit (TU) at 50% inhibition for the mixture (EC50mix) was calculated from the dose (TU-based)-response relationships by the Trimmed Spearman-Karber method. Binary metal combinations of Cu+Cd, Cu+Pb, and Cd+Pb produced all three types of interactions; concentration additive (EC50mix=1TU), synergistic (EC50mix<1TU), and antagonistic (EC50mix>1TU) responses. Ternary combination of Cu+Cd+Pb produced an antagonistic response for the growth of Cucumis sativus. Bioaccumulations of Cu, Cd, and Pb were observed in Cucumis sativus and the bioaccumulation of one metal was influenced by the presence of other metals in metal mixtures. In general, antagonistic and/or synergistic responses reflected bioaccumulation patterns in some binary combinations, but the patterns in mixtures were not always consistent with toxicity data. This study indicated that TU approach appears to be a good model to estimate the combined effect of metals in plant systems, and mixture toxicity may be closely-related to the bioaccumulation pattern within plants. Combined effects of mixtures have to be taken into account to ecological risk assessment.