PLeDO: Pain Level Detection for Osteoarthritis from EMR Data

Knee osteoarthritis frequently exhibits discordance between structural damage observed in imaging and patient-reported symptoms such as pain. This mismatch complicates clinical interpretation and patient stratification and remains insufficiently modeled in existing decision support systems. We propose a discordance aware multimodal framework that combines machine learning prediction models with a tool grounded multi agent reasoning system. Using baseline data from the FNIH Osteoarthritis Biomarkers Consortium, we trained multimodal models to predict two progression tasks, joint space loss only progression versus non progression, and pain only progression versus non progression. The predictive system integrates three modality specific experts: a CatBoost tabular model using demographic, radiographic, MRI-derived scalar, and biomarker features; MRI image embeddings extracted using a ResNet18 backbone; and Xray embeddings derived from the same architecture. Expert predictions are fused using a stacking ensemble. Residual based models estimate expected pain from structural features, enabling the computation of a pain structure discordance score between observed and expected symptoms. A multi-agent reasoning layer interprets these signals to assign clinically interpretable OA phenotypes and generate phenotype specific management recommendations.

Background and objective. Conventional Deep Learning (DL) approaches for Knee Osteoarthritis (KOA) grading rely on one-hot labels, which fail to capture both the ordinal uncertainty of Kellgren--Lawrence (KL) and Calcium Pyrophosphate Deposition Disease (CPPD) severity scores and the asymmetric relationship between the two scales observed in clinical practice. Methods. We retrospectively collected 2172 knee X-ray images, including 968 radiographs jointly annotated for KL and CPPD severity. An ordinal DL framework based on soft-labelling was developed for both tasks, replacing one-hot targets with unimodal probability distributions centred on the annotated grade. Four formulations were investigated: binomial, beta, triangular, and exponential. Results. All soft-labelling strategies consistently outperformed the nominal baseline. For CPPD grading, the triangular formulation achieved the highest Quadratic Weighted Kappa (QWK) and the lowest Mean Absolute Error (MAE) (QWK = 0.796; MAE = 0.438), while the beta formulation yielded the most balanced class-wise performance considering Average MAE (AMAE) and Maximum MAE (MMAE) across classes (AMAE = 0.458; MMAE = 0.573). For KL grading, the beta-based approach provided the best overall performance, achieving the highest QWK together with the lowest MAE and class-wise errors (QWK = 0.777; MAE = 0.529; AMAE = 0.523; MMAE = 0.775). Statistical analysis demonstrated significant improvements over conventional one-hot supervision (p < 0.001).

Pain is one of the most common and clinically important symptoms, reflecting disease onset, progression, and treatment response. However, pain is difficult to accurately capture and interpret from medical text, as its expression varies across languages, documentation types, and patient demographics, and is often embedded in terminology, negation, temporality, and contextual descriptions. Existing pain-related studies remain largely monolingual or limited to narrow clinical settings. In this study, we introduce PAINT, a multilingual framework for studying pain representation across medical exams and real-world clinical texts. PAINT includes nine pain-focused dataset partitions spanning English, Spanish, Portuguese, and Japanese, with clinician annotations in all four languages. We curated a structured schema covering pain relevance, pain presence, anatomical location, pain descriptors, and demographic information. To capture multilingual pain representations, we leverage large language models (LLMs) and adopt an ensemble strategy to improve performance. Ten clinicians across four languages validate the labels: the ensemble reaches macro-F1 of 0.91-1.00 on pain relevance and pain presence and 92-100% accuracy on demographics, with inter-annotator $κ$ of 0.82-1.00. We release the WorldMedQA-Pain ensemble labels, the extraction pipeline, validation scripts, and clinician annotation sheets for publicly licensed corpora, providing a foundation for pain-centered clinical NLP and for studying pain documentation across languages and healthcare contexts.