Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes.

BACKGROUND: Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. OBJECTIVE: The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. METHODS: A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. RESULTS: Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). CONCLUSION AND RELEVANCE: Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.

Implementation of Pharmacist-Led Medication Review Service for Parkinson's Disease Patients Admitted for Deep Brain Stimulation.

Objective The purpose of this study was to determine the clinical impact of a specialized pharmacist-led medication assessment on the incidence of dopamine antagonists administered for patients with Parkinson's disease after deep brain stimulation (DBS). Methods This was a single-center, Institutional Review Board-approved, two-phase study with pre- and post-implementation cohorts of patients who were 18 years of age or older who underwent DBS for treatment of Parkinson's disease. The primary endpoint was the incidence of dopamine antagonists administered after DBS procedure. Secondary endpoints included the incidence of dopamine antagonists ordered; restarting home Parkinson's disease regimen; rate of tardive dyskinesia; length of hospital stay; and incidence of sitters, restraints, and medications administered for acute agitation. Statistical analysis included Fisher's exact test for categorical data, unpaired t-test for continuous data, and descriptive statistics for all other data. Results The incidence of dopamine antagonists administered was 1 (1.2%) versus 1 (25%) for the pre- and post-implementation groups, respectively (P = 0.09). Restarting of home Parkinson's disease regimen was 30 (36.1%) versus 4 (100%); P = 0.021. The average length of stay was 1.9 days versus 1.3 days. Incidence of sitters was 1 (1.2%) versus 0 (0%), and incidence of restraints was 0 (0%) versus 0 (0%). Incidence of acute agitation medications administered was 9 (10.8%) versus 0 (0%). The secondary endpoints were not significant except for the restarting of home medication regimen. Conclusion The specialized pharmacist-led medication review service identified a single incident of inappropriate medications administered for Parkinson's disease patients status post DBS. However, it did significantly increase the incidence of the restart of Parkinson's disease home regimen.

The prevalence of major drug-drug interactions in older adults with cancer and the role of clinical decision support software.

OBJECTIVES: Drug-drug interactions (DDIs) represent an escalating concern for older adults attributed to polypharmacy, multi-morbidity and organ dysfunction. Few studies have evaluated the prevalence of major DDIs and the variability between DDI detection software which confuses management. MATERIALS AND METHODS: Prevalence of major DDIs was examined as a secondary analysis of outpatients aged ≥65 years. Demographic and clinical information was collected from electronic health records including age, sex, race, cancer type, comorbidities, and medications. All DDIs were screened by a clinical pharmacist using Lexi-Interact® and Micromedex®. Major DDIs were defined as Lexi-Interact® category D or X and/or Micromedex® category major or contraindication. Summary statistics of patient characteristics and DDIs were computed. RESULTS: Our cohort included 142 patients (mean age, 77.7 years; 56% women, 73% Caucasian). The mean medications was 9.8 including 6.7 prescriptions, 2.6 non-prescriptions, and 0.5 herbals. Lexi-Interact® identified 310 major DDIs in 69% of patients (n = 98) with an average of 2.2 DDIs per patient. Micromedex® identified 315 major DDIs in 61% of patients (n = 87) with an average of 2.2 DDIs per patient. DDIs mostly involved opioids, antiplatelets, electrolyte supplements, antiemetics, and antidepressants. Variability existed with the severity rating reporting of the clinical decision support software. CONCLUSIONS: There was a high prevalence of major DDIs in older adults with cancer. Utilizing clinical decision support software was beneficial for detecting DDIs however, variability existed with severity reporting. Future studies need to identify the relevant DDIs with clinical implications in order to optimize medication safety in this population.

FT-IR spectroscopy and density functional theory calculations of 13C isotopologues of the helical peptide Z-Aib6-OtBu.

Isotope-edited FT-IR spectroscopy is a combined synthetic and spectroscopic method used to characterize local (e.g., residue-level) vibrational environments of biomolecules. We have prepared the 3(10) helical peptide Z-Aib6-OtBu and seven (13)C-enriched analogues that vary only in the number and position(s) of (13)C═O isotopic enrichment. FT-IR spectra of these eight peptides solvated in the nonpolar aprotic solvent dichloromethane have been collected and compared to frequency, intensity, and normal mode results of DFT calculations. Single (13)C enrichment of amide functional groups tends to localize amide I vibrational eigenmodes, providing residue-specific information regarding the local environment (e.g., hydrogen bonding or solvent exposure) of the peptide bond. Double (13)C enrichment of Z-Aib6-OtBu allows for examination of interamide coupling between two labeled amide functional groups, providing experimental evidence of interamide coupling in the context of 3(10) helical structure. Although the calculated and observed interamide couplings of Z-Aib6-OtBu are a few cm(-1) and less, the eight peptides exhibit distinct infrared spectra, revealing details of interamide coupling and residue level vibrational environments.