Screening for Atrial Fibrillation in the Older Population: A Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention. Objective: To evaluate 2 home-based AF screening interventions. Design, Setting, and Participants: This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices. Interventions: The control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods. Main Outcomes and Measures: With intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors. Results: Of the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%). Conclusions and Relevance: In this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard clinical outcomes are now needed to evaluate the potential benefits and harms of AF screening. Trial Registration: ClinicalTrials.gov Identifier: NCT02392754.

Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine.

BACKGROUND: Data on duration of protection against invasive meningococcal disease post-vaccination with the recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) are limited. We evaluated bactericidal activity persistence in adolescents/young adults up to 7.5 years post-primary vaccination with 4CMenB, and response to a booster dose compared with vaccine-naïve controls. METHODS: This open-label, multicenter study (NCT02446743) enrolled 15-24 year-old-previously vaccinated participants from Canada, Australia (group Primed_4y) 4 years post-priming with 4CMenB (2 doses; 0,1-month schedule), and Chile (Primed_7.5y) 7.5 years after priming with 4CMenB (2 doses; 0,1/0,2/0,6-month schedule) and vaccine-naïve participants of similar age (Naïve_4y and Naïve_7.5y groups). Primed participants received a booster dose; vaccine-naïve participants received 2 catch-up doses of 4CMenB, 1 month apart. We evaluated antibody persistence and immune responses using hSBA in terms of geometric mean titers and percentages of participants with hSBA titers ≥4, the kinetics of bactericidal activity post-booster (previously vaccinated) or post-2 doses (vaccine-naïve), and safety. RESULTS: Antibody levels declined at 4 (Primed_4y) and 7.5 (Primed_7.5y) years post-primary vaccination, but remained higher than in vaccine-naïve participants at baseline (≤44% vs ≤ 13% [fHbp]; ≤84% vs ≤ 24% [NadA]; ≤29% vs ≤ 14% [PorA]) for all vaccine antigens except NHBA (≤81% vs ≤ 79%). One month post-booster and post-second dose, 93-100% of primed and 79-100% of vaccine-naïve participants had hSBA titers ≥4 for all antigens. Kinetics of the antibody response were similar across groups with an early robust response observed 7 days post-booster/second dose. No vaccine-related serious adverse event was reported. CONCLUSION: For all antigens except NHBA, a higher proportion of primed participants had hSBA titers ≥4, at 4 and 7.5 years post-vaccination, compared with vaccine-naïve participants. A more robust immune response after booster compared to a first dose in vaccine-naïve individuals, showed effective priming in an adolescent/young adult population. No safety or new reactogenicity issues were identified.

Diagnostic accuracy and yield of screening tests for atrial fibrillation in the family practice setting: a multicentre cohort study.

BACKGROUND: Detection of undiagnosed or undertreated ("actionable") atrial fibrillation could increase the use of appropriate oral anticoagulant therapy and reduce the risk of stroke. We sought to compare newer screening technologies with a pulse-check for the detection of atrial fibrillation and to determine whether the detection of actionable atrial fibrillation increases the use of oral anticoagulant agents. METHODS: This prospective multicentre cohort study involved 22 primary care clinics. We recruited participants aged 65 years and older who were attending routine appointments. Each participant underwent 3 methods of screening: a 30-second radial pulse-check; single-lead electrocardiogram; and screening by blood pressure machine with atrial fibrillation detection algorithms. Participants who received a positive result on 1 or more test underwent 12-lead electrocardiogram with or withour 24-hour Holter. Screening tests were compared using the McNemar test. Participants with confirmed atrial fibrillation received follow-up at 90 days. RESULTS: The mean age of participants was 73.7 (± 6.9) years, and 53.4% of participants were female. Of 2171 patients, we had data from all 3 screening tests for 2054 patients. Both single-lead electrocardiogram and the blood pressure device showed superior specificity compared with pulse-check (p < 0.001 for each). Fifty-six patients (2.7%) had confirmed atrial fibrillation: 12 patients had newly detected atrial fibrillation (none of the patients were using anticoagulation agents), and 44 patients had previously diagnosed atrial fibrillation (42 patients were receiving anticoagulant therapy, 2 were not). Thus, 14 patients had actionable atrial fibrillation (0.7%). By 90 days, 77% of patients with actionable atrial fibrillation had started anticoagulant therapy. INTERPRETATION: Newer screening technologies showed superior specificity compared with a pulse-check. Screening detected undiagnosed or undertreated atrial fibrillation in 0.7% of participants, and 77% started appropriate anticoagulant therapy. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02262351.

Is Screening for Atrial Fibrillation in Canadian Family Practices Cost-Effective in Patients 65 Years and Older?

We present an economic evaluation of a recently completed cohort study in which 2054 seniors were screened for atrial fibrillation (AF) in 22 Canadian family practices. Using a Markov model, trial and literature data were used to project long-term outcomes and costs associated with 4 AF screening strategies for individuals aged 65 years or older: no screening, screen with 30-second radial manual pulse check (pulse check), screen with a blood pressure machine with AF detection (BP-AF), and screen with a single-lead electrocardiogram (SL-ECG). Costs and outcomes were discounted at 1.5% and the model used a lifetime horizon from a public payer perspective. Compared with no screening, screening for AF in Canadian family practice offices using pulse check or screen with a blood pressure machine with AF detection is the dominant strategy whereas screening with SL-ECG is a highly cost-effective strategy with an incremental cost per quality-adjusted life-year (QALY) gained of CAD$4788. When different screening strategies were compared, screening with pulse check had the lowest expected costs ($202) and screening with SL-ECG had the highest expected costs ($222). The no-screening arm resulted in the lowest number of QALYs (8.74195) whereas pulse check and SL-ECG resulted in the highest expected QALYs (8.74362). Probabilistic analysis confirmed that pulse check had the highest probability of being cost-effective (63%) assuming a willingness to pay of $50,000 per QALY gained. Screening for AF in seniors during routine appointments with Canadian family physicians is a cost-effective strategy compared with no screening. Screening with a pulse check is likely to be the most cost-effective strategy.