Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

BACKGROUND: Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. METHODS: In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. RESULTS: The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. CONCLUSIONS: On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .).

Evidence of effective delivery of the human papillomavirus (HPV) vaccine through a publicly funded, school-based program: the Ontario Grade 8 HPV Vaccine Cohort Study.

BACKGROUND: Proper administration of the human papillomavirus (HPV) vaccine (three doses at 0, 2, and 6 months) will likely influence the vaccine's effectiveness and the impact of vaccination programs on health outcomes. Therefore, we assessed HPV vaccine series completion and on-time dosing in Canada's largest publicly funded, school-based HPV vaccination program. METHODS: Using administrative health and immunization databases, we identified a population-based cohort of girls eligible for Ontario's Grade 8 HPV vaccination program in the 2007/08-2009/10 program years who received at least one dose of the vaccine. We determined the number of doses received and calculated the percentage of girls that completed the three-dose series in Grade 8 and Grades 8-9. To assess on-time dosing, the number of days between doses 1-2, 2-3, and 1-3 was calculated and categorized (e.g., too short, on schedule, too long) based on the manufacturer's recommendations. Analyses were also stratified by program year. RESULTS: We identified a cohort of 55,798 girls who initiated the vaccination series. Series completion was high in the Grade 8 window (81.8%) and increased by approximately 6% in Grade 9. Series completion was similar across the three program years. 70.8%, 98.5%, and 86.1% of girls were classified as 'on schedule' for dosing intervals 1-2, 2-3, and 1-3, respectively; 70.0% of girls received all three doses in perfect accordance with dosing recommendations. Stratification revealed that on-time dosing was highest in the first two years of the program (85.6% and 80.6%), but dropped to 42.1% in the 2009/10 year when H1N1 vaccination programs were prioritized. CONCLUSIONS: Our study demonstrates that delivery of the HPV vaccine through a free, school-based program is an effective method of ensuring high completion and on-time dosing, but may not be sufficient to guarantee high coverage.