EPCAT III leads July 14 papers

This issue covers the weekly PubMed tracking window from July 7 9:00 a.m. to July 14 9:00 a.m. (UTC-5). Same-week citation counts are still thin, so the ranking uses the channel's usual mix of journal tier, trial design, sample size, early indexed-paper visibility when available, and clinical decision value.

EPCAT III leads because it asks a common postoperative question in a large double-blind randomized trial: after total hip or knee arthroplasty, can patients start with aspirin rather than 5 days of rivaroxaban before switching to aspirin? The answer was yes within the trial's noninferiority margin. 1

Paper link: PubMed record

What the paper did. EPCAT III randomized 5,429 patients after total hip or knee arthroplasty to either 81 mg aspirin once daily or 10 mg rivaroxaban once daily for the first 5 postoperative days. Both groups then received aspirin for 9 additional days after knee arthroplasty or 30 additional days after hip arthroplasty. 1 The primary effectiveness outcome was symptomatic venous thromboembolism at 90 days, defined as proximal deep-vein thrombosis or pulmonary embolism. 1

Primary result. Symptomatic VTE occurred in 13 of 2,718 patients (0.48%) in the aspirin-alone group and 12 of 2,647 patients (0.45%) in the rivaroxaban-aspirin group. The risk difference was 0.02 percentage points, with 95% CI -0.34 to 0.39 and P<0.001 for noninferiority against a 0.7 percentage-point margin. 1 Major bleeding or clinically relevant nonmajor bleeding occurred in 1.66% with aspirin alone and 2.04% with rivaroxaban-aspirin, for a risk difference of -0.38 percentage points and 95% CI -1.11 to 0.34. 1

Evidence strength and limitation. The sample size, double-blind design, and clinically direct endpoint make this the strongest practice-facing paper in the window. The result applies to the trial's postoperative prophylaxis strategy and 90-day follow-up; it does not settle thromboprophylaxis decisions for higher-risk surgical or hematologic subgroups not represented well in the enrolled population.

Clinical implication. Orthopedic and perioperative groups now have a large NEJM trial supporting aspirin from day 1 after routine total hip or knee arthroplasty, rather than a mandatory initial rivaroxaban lead-in. The trial was funded by the Canadian Institutes of Health Research; lead author affiliations include Dalhousie University, Nova Scotia Health Authority, McMaster University, McGill University, and other Canadian centers. 1

Paper link: PubMed record

What the paper did. LatAm-FINGERS randomized at-risk adults aged 60 to 77 years across 11 Latin American countries to a 2-year structured multidomain lifestyle intervention or flexible health advice. 2 The structured arm combined supervised support and monitoring across lifestyle domains; outcome assessors were masked, but participants and intervention staff were not. 2

Primary result. In the analytic sample of 1,065 participants, 877 completed 2-year follow-up. The global cognitive composite increased by 0.31 SD per year in the structured-intervention group and 0.20 SD per year in the flexible-advice group, for a between-group difference of 0.11 SD per year, 95% CI 0.06 to 0.15, and P<0.0001. 2 Mean adherence in the structured arm was 71.6%; dropouts were lower in the structured arm than in the flexible-advice arm, 15.2% vs 20.2%, P=0.042. 2

Evidence strength and limitation. This is a large, multicountry randomized implementation study in a population that dementia-prevention trials often under-sample. The limitation is built into the intervention: participants and intervention staff could not be masked, adverse events were reported more often in the structured arm, and the effect is on cognitive trajectory over 2 years rather than dementia incidence.

Clinical implication. For dementia-prevention programs, the paper is less about a single ingredient and more about whether a structured package can travel across health systems. The funding source listed in the PubMed abstract is the Alzheimer's Association; first author Lucía Crivelli is affiliated with Fleni in Buenos Aires, and the author list spans neurology, geriatrics, and dementia centers across Latin America, Europe, and the United States. 2

Paper link: PubMed record

What the paper did. The Hydra study randomized 698 patients with active cancer and suspected acute pulmonary embolism to diagnostic management with the YEARS algorithm or CTPA only. 3 The trial was open-label, investigator-initiated, and used blinded central outcome adjudication. It recruited patients from 21 hospitals in the Netherlands, Italy, Switzerland, Belgium, France, and Spain. 3

Primary result. Among patients in whom PE was considered excluded, symptomatic VTE or possible PE-related death within 90 days occurred in 5 of 282 patients (1.8%) in the per-protocol YEARS group and 15 of 273 patients (5.5%) in the CTPA-only group. The absolute risk difference was -3.7 percentage points, with 99.9% CI -8.8 to 1.4 and P=3.4 x 10^-5 for noninferiority. 3 Diagnostic management was completed without CTPA in 77 of 352 patients (22%) assigned to YEARS. 3

Evidence strength and limitation. The trial addresses a real guideline tension: cancer patients often go straight to CTPA because PE prevalence and D-dimer complexity are higher. The main constraint is that the design was open-label and the no-CTPA gain was meaningful but not huge; it avoided scans in about one in five patients, not in most patients.

Clinical implication. Oncology, emergency medicine, and thrombosis services should read the protocol details before applying YEARS wholesale. The practical question is where local PE prevalence, D-dimer handling, and follow-up reliability make the algorithm safe enough to reduce imaging. Lead author affiliations include Leiden University Medical Center, with participating centers across six European countries. 3

Paper link: PubMed record

What the paper did. This JAMA individual participant data meta-analysis pooled cross-sectional amyloid PET scans from 49,227 participants across 53 studies in 15 countries. 4 The aim was to define robust Centiloid cutoffs for amyloid positivity using data-driven Gaussian mixture models and correspondence with binary visual reads. 4

Primary result. The data-driven approach produced a single amyloid-positivity cutoff of 18 Centiloids, with 95% CI 16 to 19. The double-cutoff approach classified scans as negative below 11 Centiloids and positive above 26 Centiloids; scans from 11 to 26 Centiloids were the caution zone. 4 In the visual-read analysis of 35,045 scans across 36 studies, Centiloids predicted visual positivity with Cohen kappa 0.86, 95% CI 0.83 to 0.89, and the visual-read cutoff was 27 Centiloids. 4

Evidence strength and limitation. The sample size and individual-participant pooling make this a useful diagnostic-standardization paper. The high heterogeneity values, including I2 values near or above 80% in the cutoff analyses, mean readers should treat the cutoffs as decision aids rather than a universal clinical boundary. 4

Clinical implication. Anti-amyloid therapy has made amyloid PET interpretation more consequential. This paper gives imaging groups a more explicit framework: below 11 Centiloids is relatively secure negative territory, above 26 to 27 is relatively secure positive territory, and the middle band should be interpreted in clinical context. The lead group is based at the University of California, San Francisco; the study includes the Meta-Centiloid Study Group and large international cohorts. 4

Paper link: PubMed record

What the paper did. This double-blind randomized phase 2 trial tested the oral O-linked N-acetylglucosaminidase inhibitor ceperognastat in early symptomatic Alzheimer disease. 5 Participants were randomized 1:1:1 to ceperognastat 0.75 mg, ceperognastat 3 mg, or placebo; the primary outcome was change in Integrated AD Rating Scale score. 5

Primary result. Among the 259 participants in the primary outcome population, posterior mean iADRS change at 100 weeks was -8.39 with ceperognastat 0.75 mg, -13.27 with ceperognastat 3 mg, and -10.07 with placebo. 5 The disease progression ratio relative to placebo was 0.84, 95% credible interval 0.66 to 1.04, for the 0.75 mg dose, and 1.32, 95% credible interval 1.10 to 1.58, for the 3 mg dose. 5 Serious treatment-emergent adverse events occurred in 12.0% with 0.75 mg, 26.4% with 3 mg, and 15.7% with placebo. 5

Evidence strength and limitation. The paper earns a slot because negative AD trials are operationally important when they test a mechanistically plausible target with biomarker readouts. The imaging signals complicate the read: the 3 mg group had a smaller lateral-temporal tau PET increase and less whole-brain volume loss, yet no clinical benefit and more serious or severe adverse events. 5

Clinical implication. This is a trial to read for target-risk assessment, not for practice change. It warns that biomarker movement in an AD mechanism program may not translate into iADRS benefit over 100 weeks. All listed author affiliations in the PubMed abstract are Eli Lilly and Company, Indianapolis. 5

If you open one paper outside your specialty, start with EPCAT III because it is large, double-blind, and directly changes a common perioperative prophylaxis question. LatAm-FINGERS is the broader public-health read: the effect size is modest, but the multicountry implementation signal matters because the trial population is closer to where dementia burden is rising fastest.

The YEARS trial is the most actionable diagnostic paper in the set. The amyloid PET meta-analysis is the standards paper to save for imaging and memory-clinic protocols. Ceperognastat is the negative trial worth reading because it separates biomarker movement from clinical benefit in a crowded Alzheimer drug-development field.