Background/Objectives: COPD instability is heterogeneous; GOLD 2026 lowers the prior-year threshold to ≥1 moderate or severe exacerbation. We assessed whether this low-threshold criterion behaves as a high-sensitivity operational signal in primary-care EHRs. Methods: A retrospective multicenter same-window EHR pilot study in two Spanish primary-care centers (n = 106). Predictors and six binary endpoints were aggregated over the same 12-month window: any exacerbation, high-risk history, severe hospitalization, SABA dispensing, SAMA dispensing, and any rescue dispensing. We fitted Bayesian multi-outcome hierarchical logistic models with patient-level random intercepts, cross-endpoint partial pooling, regularizing priors, and missingness indicators. Robustness used prespecified scenarios, 10-fold ELPD cross-validation, and high-missingness exclusion. Results: Any exacerbation occurred in 53/106 patients; high-risk history in 25/106; hospitalization in 16/106; and any rescue dispensing in 65/106. Diagnostics were stable, and posterior predictive checks supported marginal adequacy. Heart failure showed the clearest positive pattern across exacerbation-defined endpoints; reliever-dispensing endpoints showed a distinct care-pathway-sensitive pattern. No scenario improved out-of-sample adequacy. High-missingness exclusion preserved directionality in 120/120 overlapping pairs; the median |ΔlogOR| was 0.061; and 119/120 remained within ±log(1.25). Conclusions: GOLD 2026 “any exacerbation” behaved as a high-sensitivity operational signal in an endpoint-operating-point sense, not as a homogeneous phenotype. Findings are within-window associations, not causal, medication-effect, or prospective prediction estimates; external validation is required.

Background/Objectives: Comparative effects of oral second-generation H1-antihistamines vary by rhinitis category, outcome, and treatment period. We assessed evidence structure, estimability, and differentiation among regimens. Methods: PubMed, Embase, Web of Science Core Collection, CENTRAL, WHO ICTRP, ClinicalTrials.gov, and the EU Clinical Trials Register were searched on 1–3 July 2026 for records through 30 June 2026. Eligible studies were natural-exposure randomized trials. Continuous outcomes were analyzed using covariance-aware generalized least squares, and binary harms were analyzed using Bayesian arm-level models. RoB 2, CINeMA, and ROB-MEN were applied in duplicate. Registration was retrospective. Results: Sixty-one reports generated 66 report–randomization entries from 64 cohorts (34,831 participants); 35 model-ready randomizations informed nine structures. In seasonal allergic rhinitis, six of seven TNSS estimates, two of three ocular estimates, and four RQLQ estimates favored active treatment. Any-adverse-event estimates were imprecise. Under the primary prior, cetirizine yielded a WDAE OR of 0.25 (95% CrI 0.08–0.66), but predictive classification was prior-sensitive. Of 34 continuous active–active comparisons, seven were directly informed and 27 indirect-only. All 147 estimable binary active–active contrasts were reported as secondary derivations: 141 CrIs included one and six excluded one, all indirect-only and not formally appraised with CINeMA. Six of 14 regimen-level nodes contributed only to tolerability structures, precluding balanced regimen-specific benefit–harm assessment. All 89 estimable comparisons within the defined CINeMA appraisal scope were rated very low; two non-estimable effects were not evaluable. Conclusions: Predominantly placebo-anchored and sparse evidence established neither a reliable regimen hierarchy nor therapeutic equivalence. Findings were hypothesis-generating, and somnolence remained an evidence gap. No external funding supported conduct; NEXUS PEOPLE, S.L. funded the APC. OSF registration was retrospective: doi:10.17605/OSF.IO/DPT5N.