Medication-Related Problems in Older Adults: A Focus on Underuse of Warfarin and Warfarin-Antibiotic Interactions

The work presented in this dissertation focuses on two important medication-related problems in older adults, that is, untreated indication and drug-drug interactions, specifically with respect to a high-risk medication such as warfarin. Warfarin is a challenge to use in clinical practice due to its narrow therapeutic index, variability in dose-response and its interactions with numerous foods and drugs. This dissertation presents the research from two projects. In the first project the prevalence and predictors of warfarin use in nursing home (NH) residents with atrial fibrillation (AF), and use of secondary stroke prevention strategies was determined, in order to understand the patterns of anticoagulant use in frail NH residents and to identify patient characteristics associated with warfarin use. In the second project the effect of oral antibiotics on anticoagulation outcomes, when prescribed concomitantly with warfarin, was determined, in order to provide evidence on the clinical significance of warfarin-antibiotic interactions in older adults. In the first project a cross-sectional analysis of the prescription and resident files from the 2004 National Nursing Home Survey was done to determine the prevalence of AF and rates of use of warfarin and other anti-platelet agents, such as aspirin and clopidogrel. A multiple logistic regression model was used to determine factors associated with warfarin use. In this sample of older NH residents, 13% of residents had a diagnosis of AF, with indications for warfarin use and no contraindications to warfarin. From these patients, 30% received anticoagulant therapy with warfarin and 23% of the remaining patients received either aspirin or clopidogrel, suggesting that more than 50% of residents with AF did not receive any form of anticoagulant therapy. Non-white race, history of bleeding, and use of anti-platelet medications were associated with reduced odds of receiving warfarin. The second project was a retrospective medical record review of older patients from an outpatient anticoagulation clinic at a Veterans Affairs medical center. Results of the repeated measures ANOVA suggested a significant increase in post-antibiotic INR values with fluoroquinolones, azithromycin and amoxicillin. In addition, the percentage of patients with warfarin dose adjustments was significantly greater with fluoroquinolones and azithromycin as compared to cephalexin. No bleeding events were reported for any of these patients. In conclusion, the results of the projects suggest that there is underuse of warfarin in NH settings. Furthermore, antibiotics may be safely prescribed with warfarin in older adults as long as the INR is monitored closely

Rotavirus vaccination in the US: a systematic review of vaccination coverage and completion

A systematic literature review of Medline and Embase databases was conducted to describe rotavirus (RV) vaccine coverage for a complete series, timing of receipt of all doses in the series, and predictors of RV vaccination coverage in the US for two licensed RV vaccines (RV1, RV5). Nine publications were included in the review. RV vaccination coverage rates of under 80% suggest RV vaccines are underutilized relative to the Healthy People 2020 target and other childhood vaccines. About 50–90% of children initiating RV vaccination complete the series and coverage for a complete series is lower for black and Hispanic children (vs. whites), uninsured or Medicaid insured (vs. privately insured), and for foreign-born (vs. US-born) children. Series completion is significantly greater in children receiving DTaP, RV1 (vs. RV5), and for those receiving routine care from a pediatrician. There is a need to design and implement better RV immunization strategies for US children

Hepatitis A, B, and A/B vaccination series completion among US adults: A claims-based analysis

Hepatitis A and B disease burden persists in the US. We assessed hepatitis A and hepatitis B vaccination series completion rates among 350,240 commercial/Medicare and 12,599 Medicaid enrollees aged ≥19 years. A vaccination series was considered as completed provided that the minimum interval between doses, as defined by the CDC, and the minimum number of doses were reached. We stratified completion rates by vaccine type (i.e. monovalent or bivalent) at initial vaccination for each cohort. In the commercial/Medicare cohort, the series completion rate was 32.0% for hepatitis A and 39.6% for hepatitis B among those who initiated with a monovalent vaccine, and it was 36.2% for hepatitis A and 48.9% for hepatitis B among those who initiated with a bivalent vaccine. In the Medicaid cohort, the series completion rate was 21.0% for hepatitis A and 24.0% for hepatitis B among those who initiated with a monovalent vaccine, and it was 19.0% for hepatitis A and 24.6% for hepatitis B among those who initiated with a bivalent vaccine. In conclusion, hepatitis A and B vaccination series completion rates were low, and appeared to be lower among Medicaid than among commercial/Medicare enrollees. Commercial/Medicare enrollees who initiated with a bivalent vaccine had higher series completion rates than those who initiated with monovalent vaccines – an observation that was not made among Medicaid enrollees

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults.

Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation. In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed. Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group. A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.)