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A. G. Rigutini

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Open access Aug 2026

Phenotypic clustering and ABC pathway adherence in patients with atrial fibrillation at high risk of bleeding and stroke: Insights from three global registries.

BACKGROUND Patients with atrial fibrillation (AF) who are at increased risk of both thrombotic and haemorrhagic events represent a heterogeneous and broad clinical entity, characterized by the presence of several Janus-faced risk factors. We aimed to identify clinical phenotypes and assess the association of ABC pathway adherence with one-year outcomes in patients with AF at high risk of both stroke and bleeding. METHODS AF patients who had HAS-BLED score ≥3 and CHA2DS2-VASc score ≥2 were included. Hierarchical clustering was applied to identify phenotypic subgroups. We assessed the impact on net adverse clinical event (NACE) of adherence to the integrated care based on the Atrial fibrillation Better Care (ABC) pathway. RESULTS A total of 2,535 patients (mean age 75.4 ± 7.8 years; 58.3% male) were enrolled. Cluster I had the highest rates of prior thromboembolic and haemorrhagic events with the lowest comorbidity burden; Cluster II comprised the oldest patients with the highest prevalence of dyslipidaemia, heart failure, and peripheral artery disease; Cluster III was the youngest with the highest BMI and alcohol use. Cluster II (aOR 1.93, 95% CI 1.37-2.78), and Cluster III (aOR 1.65, 95% CI 1.10-2.50) were associated with a higher risk of all-cause death compared to Cluster I. Among patients with available ABC pathway data, adherence was associated with lower odds of 1-year MACE (OR 0.39, 95% CI 0.15-0.82). CONCLUSION Three distinct phenotypic clusters were identified, each with heterogeneous clinical characteristics and outcomes, underscoring the need for more individualised, phenotype-informed management strategies in this complex patient population.

A. Askarinejad, T. Bucci, Enrico Tartaglia et al. · 0 citations
Review Open access Aug 2026

Risk-of-bias assessment in prognostic cohort studies: a methodological comparison study of structured appraisal tools in acute pulmonary embolism research

Abstract Objectives To compare the reliability of four commonly used structured tools for risk-of-bias assessment in prognostic cohort studies and evaluate their agreement with expert appraisal. Design Methodological comparison study. Setting Secondary analysis of published prognostic cohort studies in patients with acute pulmonary embolism from a previously conducted systematic review. Participants Sixty-three cohort studies assessing the prognostic role of echocardiography in patients with acute pulmonary embolism. Primary and secondary outcome measures Four independent reviewers assessed study quality/risk of bias using the Newcastle-Ottawa Scale (NOS), Risk Of Bias in Non-Randomised Studies of Interventions (ROBINS-I), Quality In Prognostic Studies (QUIPS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Concomitantly and independently, expert reviewers’ implicit global judgements were used as an external comparator. Inter-rater reliability, agreement with expert appraisal, internal consistency and floor/ceiling effects were assessed. Results Inter-rater agreement was fair for NOS (Gwet’s agreement coefficient 1, 0.25, 95% CI 0.15 to 0.34), ROBINS-I (0.38, 95% CI 0.28 to 0.47) and QUADAS-2 (0.35, 95% CI 0.27 to 0.43) and almost perfect for QUIPS (0.85, 95% CI 0.73 to 0.93). Agreement with expert appraisal was limited for all tools except ROBINS-I, which showed fair concordance. QUIPS frequently classified studies as low risk of bias, suggesting potential overestimation of study quality. Internal consistency was generally low across tools, while ceiling effects were observed for NOS and QUIPS. ROBINS-I showed the most balanced distribution of ratings. Conclusions Structured tools for risk-of-bias assessment in prognostic cohort studies have variable reliability and limited agreement with expert appraisal. ROBINS-I showed the strongest concordance with expert judgement, whereas QUIPS may provide optimistic ratings. These findings support further refinement and standardisation of risk-of-bias assessment methods for observational prognostic research.

L. Cimini, F. Klok, M. Carrier et al. · 0 citations

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