Importance:Plasma phosphorylated p-tau 217 levels vary with biological factors such as kidney dysfunction, body mass index (BMI), and anemia. It remains unclear whether a biological subgroup-specific optimal cutoff or a double-cutoff strategy could enhance diagnostic accuracy and cost efficiency beyond the standard single cutoff. Objective:To compare the diagnostic and economic performance of 3 plasma p-tau217 classification strategies for detecting amyloid-β (Aβ) positivity: standard single cutoff, subgroup-specific optimal cutoff, and double cutoff. Design, Setting, and Participants:This cohort study was a multicenter cross-sectional study conducted from 2016 to 2023; analyses were completed in 2025. Participants were recruited from multiple memory clinics and community-based cohorts. All participants had amyloid positron emission tomography (PET) imaging, clinical evaluation, and p-tau217 testing with measures of estimated glomerular filtration rate (eGFR), BMI, and hemoglobin. Measurements of p-tau217 were made using UGOT Simoa and Roche Elecsys, and the %p-tau217 ratio was assessed using a tau multianalyte assay (C2N Diagnostics LLC). Exposures:Kidney function (chronic kidney disease [CKD], eGFR <60 mL/min/1.73 m2; advanced CKD, eGFR <45 mL/min/1.73 m2), underweight (BMI <18.5), obesity (BMI ≥27.5), and anemia (hemoglobin <12 g/dL in women, <13 g/dL in men). Main Outcomes and Measures:Plasma p-tau217 concentration; standard single cutoff, optimal cutoffs, and double cutoff for Aβ positivity (Centiloid ≥25.5); accuracy; and cost-effectiveness estimated from false-positive, false-negative, and confirmatory imaging costs. Results:A total of 2571 participants were analyzed with UGOT, 1578 with Roche, and 304 with the C2N %p-tau217 ratio. The mean (SD) age was similar across cohorts (71.3 [8.6] years in the UGOT cohort, 71.3 [8.5] years in the Roche cohort, and 71.8 [7.8] years in the C2N cohort); there were 1633 (63.5%), 1006 (63.8%), and 191 (62.8%) women and 938 (36.5%), 572 (36.2%), and 113 (37.2%) men, respectively. In the UGOT cohort, the optimal cutoff improved diagnostic accuracy compared with the standard single cutoff, particularly in CKD and anemia (CKD: from 0.65; 95% CI, 0.57-0.72; to 0.83; 95% CI, 0.76-0.89; anemia: from 0.80; 95% CI, 0.76-0.84; to 0.86; 95% CI, 0.82-0.90), with consistent findings in the Roche cohort. In all biological subgroups, the double-cutoff strategy also increased accuracy relative to the single cutoff and reduced false classifications but yielded 12% to 39% intermediate results. When compared directly, the optimal cutoff provided higher accuracy than the double cutoff for CKD while lowering total diagnostic costs. For anemia, the double cutoff showed slightly higher accuracy but required confirmatory PET in up to 25% of cases, offsetting its economic advantage. In obesity, the double cutoff remained superior for both diagnostic accuracy and cost efficiency. Conclusions and Relevance:This study found that both the optimal cutoff and the double-cutoff strategy outperformed the standard single cutoff, each showing distinct strengths across subgroups. These findings support biologically informed thresholds to improve diagnostic accuracy and cost efficiency when implementing plasma p-tau217.
BACKGROUND:The role of long-term beta-blocker therapy after a myocardial infarction in patients without left ventricular systolic dysfunction or heart failure is unclear in the era of contemporary coronary-artery reperfusion and secondary prevention interventions. METHODS:We conducted an open-label, randomized, noninferiority trial at 25 centers in South Korea. Patients whose condition remained stable after a myocardial infarction, who had a left ventricular ejection fraction of at least 40% and no heart failure, and who had received beta-blocker therapy for at least 1 year after the myocardial infarction were randomly assigned in a 1:1 ratio to discontinue or to continue beta-blocker therapy. The primary end point was a composite of death from any cause, recurrent myocardial infarction, or hospitalization for heart failure. The prespecified noninferiority margin was an upper limit of the 95% confidence interval for the hazard ratio of 1.4. RESULTS:A total of 2540 patients underwent randomization; 1246 were assigned to beta-blocker discontinuation and 1294 to beta-blocker continuation. The mean age of the patients was 63.2 years, and 12.8% were women. At a median follow-up of 3.1 years (interquartile range, 2.5 to 3.5), a primary end-point event had occurred in 58 patients (4-year Kaplan-Meier estimate, 7.2%) in the discontinuation group and in 74 patients (4-year Kaplan-Meier estimate, 9.0%) in the continuation group (hazard ratio, 0.80; 95% confidence interval, 0.57 to 1.13; P = 0.001 for noninferiority). The incidence of serious adverse events was similar in the two groups. CONCLUSIONS:Among patients who received beta-blocker therapy beyond the first year after a myocardial infarction, discontinuation of beta-blocker therapy was noninferior to continuation with respect to a composite of death from any cause, recurrent myocardial infarction, or hospitalization for heart failure. (Funded by Patient-Centered Clinical Research Coordinating Center in the Ministry of Health and Welfare, South Korea; SMART-DECISION ClinicalTrials.gov number, NCT04769362.).
OBJECTIVES:To provide the clinically validated, nationwide estimates of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in Korea, and to describe their relative proportions. METHODS:From January to March 2025, 47 referral hospitals participating in a nationwide hospital-based registry identified actively followed patients with MS, NMOSD, or MOGAD. Diagnoses followed international criteria, and antibody status was confirmed using validated CBAs. Actively followed patients had ≥1 outpatient visit in the prior 6 months. Centers provided demographics, treatments, and Expanded Disability Status Scale. Prevalence used national population data. RESULTS:A total of 4,196 patients were identified, 1,799 MS, 1,616 NMOSD, and 781 MOGAD (ratio 2.3:2.1:1). Mean age at onset was 33.4 ± 12.0 years for MS, 42.7 ± 14.7 for NMOSD, and 41.7 ± 17.8 for MOGAD, and the female-to-male ratios were 2.2:1 for MS, 5.1:1 for NMOSD (6.5:1 in aquaporin-4-IgG positive cases), and 1.5:1 for MOGAD. Crude prevalence estimates were 3.48, 3.13, and 1.51 per 100,000, respectively. DISCUSSION:This nationwide registry demonstrates a distinctive Korean CNS inflammatory demyelinating disease profile, with a relatively higher proportion of NMOSD and MOGAD reflecting the low prevalence of MS in East Asia.
