Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

BACKGROUND: Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. METHODS: A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. RESULTS: Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). CONCLUSION: No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Immune outcomes of lung transplant recipients with different cytochrome P450 3A5 phenotypes after discontinuation of voriconazole antifungal prophylaxis.

INTRODUCTION: Tacrolimus forms the backbone of immunosuppression regimens in lung transplant recipients (LTRs). It is extensively metabolized by cytochrome P450 (CYP) 3A5 enzymes, of which polymorphisms can significantly affect tacrolimus dose requirements. It is unknown how coadministration of tacrolimus with voriconazole, a potent CYP3A5 inhibitor, affects rejection rates or empiric dose adjustments needed after voriconazole discontinuation. METHODS: This retrospective cohort study compares LTRs with poor (PR) versus intermediate/extensive (IE) CYP3A5 metabolizer phenotypes. The primary endpoint is cumulative immune outcomes within three months of voriconazole discontinuation; secondary endpoints include change in tacrolimus dose-to-concentration ratios after voriconazole discontinuation. RESULTS: Thirty-four patients underwent full analysis: 13 IE and 21 PR metabolizers. A higher proportion of IE metabolizers were African American (46.2% vs. 9.5%, p = .03). There was no significant difference in composite immune outcomes, though there was a proportionally higher frequency of new donor-specific antibody development in PR metabolizers (14.3% vs 7.7%, p = .56). Both groups required approximately 2.5 to 3-fold tacrolimus dose increases post-voriconazole discontinuation to re-attain therapeutic levels. CONCLUSION: This novel investigation sheds light on how CYP3A5 phenotype could be used to guide tacrolimus dosing, with the goal of preventing both toxicity and organ rejection.

Crystal structures of 2,6-di-bromo-4-methyl-benzo-nitrile and 2,6-di-bromo-4-methyl-phenyl isocyanide.

In the title crystals, C8H5Br2N, which are isomorphous, the steric bulk of the methyl group causes neighboring mol-ecules to become mutually inclined. This prevents the formation of planar or nearly planar sheets, which were observed in the tri-chloro and tri-bromo analogs. Instead of CN/NC⋯Br contacts, tetra-meric Br⋯Br contacts are observed. These contacts form tetra-gonally puckered sheets parallel to (001). The CN/NC and methyl groups are grouped at the peaks and troughs. Both mol-ecules lie across crystallographic mirror planes; thus, the methyl H atoms are disordered over two sets of sites with equal occupancy. The title nitrile is a redetermination. The refinement converged at R[F2 > 2σ(F2)] = 0.020, whereas the original determination [Gleason & Britton, (1976 ▸). Cryst. Struct. Commun.5, 229-232] had R = 0.112.

A 2:1 co-crystal of 3,5-di-bromo-4-cyano-benzoic acid and anthracene.

The title co-crystal, C8H3Br2NO2·0.5C14H10, was self-assembled from a 2:1 mixture of the components in slowly evaporating di-chloro-methane. The mol-ecules adopt a sheet structure parallel to (1-12) in which carb-oxy hydrogen-bonded dimers and anthracene mol-ecules stagger in both dimensions. Within the sheets, six individual cyano acid mol-ecules surround each anthracene mol-ecule. Cyano acid mol-ecules form one of the two possible R22(10) rings between neighboring cyano and bromo groups. Compared to the di-chloro analog [Britton (2012 ▸). J. Chem. Crystallogr.42, 851-855], the dihedral angle between the best-fit planes of acid and anthracene mol-ecules has decreased from 7.1 to 0.9 (2)°.