Background/objectives

Despite lower major bleeding rates associated with direct oral anticoagulants (DOACs) as compared to conventional warfarin therapy, bleeding rates remain higher in older patients compared to younger patients suggesting a potential role for DOAC measurements. The objective of this study is to examine the effect of age on the relationship between apixaban concentrations and anti-Factor Xa activity in patients with non-valvular atrial fibrillation (NVAF).

Methods

This is a retrospective analysis based on a database created using data from the ARISTOTLE study. Outpatient, stable adult patients with NVAF receiving apixaban were included in this study. Data collection consisted of apixaban concentration, anti-Factor Xa activity, age, weight, creatinine, and co-medications.

Results

The database composed of 2058 patients receiving apixaban. Distribution of race, NVAF subtype, and aspirin use was fairly similar across each age quantile. Older patients received a higher number of co-medications and received the 2.5 mg apixaban dose more often as compared to younger patients (22% vs. < 1%). Linear regression demonstrated that the unadjusted slope for apixaban concentration effect on anti-Factor Xa activity was similar across each age quantile. Although, the overall adjusted linear regression analysis demonstrated that the age by concentration interaction was statistically significant, relative differences in anti-Factor Xa activity (< 8%) were not clinically meaningful.

Conclusion

Data on apixaban concentrations and anti-Factor Xa activity from a pivotal randomized double-blind study of apixaban for the prevention of stroke in NVAF patients have confirmed that the chromogenic anti-Factor Xa activity assay can accurately assess apixaban concentrations in patients regardless of age. Age was not associated with a clinically relevant change in the apixaban vs. anti-Factor Xa activity response relationship and target ranges are unchanged.

The realization of graphene gapped states with large on/off ratios over wide doping ranges remains challenging. Here, we investigate heterostructures based on Bernal-stacked bilayer graphene (BLG) atop few-layered CrOCl, exhibiting an over-1-GΩ-resistance insulating state in a widely accessible gate voltage range. The insulating state could be switched into a metallic state with an on/off ratio up to 10⁷ by applying an in-plane electric field, heating, or gating. We tentatively associate the observed behavior to the formation of a surface state in CrOCl under vertical electric fields, promoting electron-electron (e-e) interactions in BLG via long-range Coulomb coupling. Consequently, at the charge neutrality point, a crossover from single particle insulating behavior to an unconventional correlated insulator is enabled, below an onset temperature. We demonstrate the application of the insulating state for the realization of a logic inverter operating at low temperatures. Our findings pave the way for future engineering of quantum electronic states based on interfacial charge coupling.

Combination therapy has proven to be an effective strategy for treating many of the worlds most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimers disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimers Disease Coalition, the Critical Path Institute and the Alzheimers Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.