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 differential diagnosis


DDXPlus: A New Dataset For Automatic Medical Diagnosis

Neural Information Processing Systems

There has been a rapidly growing interest in Automatic Symptom Detection (ASD) and Automatic Diagnosis (AD) systems in the machine learning research literature, aiming to assist doctors in telemedicine services. These systems are designed to interact with patients, collect evidence about their symptoms and relevant antecedents, and possibly make predictions about the underlying diseases. Doctors would review the interactions, including the evidence and the predictions, collect if necessary additional information from patients, before deciding on next steps. Despite recent progress in this area, an important piece of doctors' interactions with patients is missing in the design of these systems, namely the differential diagnosis. Its absence is largely due to the lack of datasets that include such information for models to train on. In this work, we present a large-scale synthetic dataset of roughly 1.3 million patients that includes a differential diagnosis, along with the ground truth pathology, symptoms and antecedents for each patient. Unlike existing datasets which only contain binary symptoms and antecedents, this dataset also contains categorical and multi-choice symptoms and antecedents useful for efficient data collection. Moreover, some symptoms are organized in a hierarchy, making it possible to design systems able to interact with patients in a logical way. As a proof-of-concept, we extend two existing AD and ASD systems to incorporate the differential diagnosis, and provide empirical evidence that using differentials as training signals is essential for the efficiency of such systems or for helping doctors better understand the reasoning of those systems.


Towards Trustworthy Automatic Diagnosis Systems by Emulating Doctors' Reasoning with Deep Reinforcement Learning

Neural Information Processing Systems

The automation of the medical evidence acquisition and diagnosis process has recently attracted increasing attention in order to reduce the workload of doctors and democratize access to medical care. However, most works proposed in the machine learning literature focus solely on improving the prediction accuracy of a patient's pathology. We argue that this objective is insufficient to ensure doctors' acceptability of such systems. In their initial interaction with patients, doctors do not only focus on identifying the pathology a patient is suffering from; they instead generate a differential diagnosis (in the form of a short list of plausible diseases) because the medical evidence collected from patients is often insufficient to establish a final diagnosis. Moreover, doctors explicitly explore severe pathologies before potentially ruling them out from the differential, especially in acute care settings. Finally, for doctors to trust a system's recommendations, they need to understand how the gathered evidences led to the predicted diseases.


PsychiatryBench: A Multi-Task Benchmark for LLMs in Psychiatry

Fouda, Aya E., Hassan, Abdelrahamn A., Hanafy, Radwa J., Fouda, Mohammed E.

arXiv.org Artificial Intelligence

Large language models (LLMs) offer significant potential in enhancing psychiatric practice, from improving diagnostic accuracy to streamlining clinical documentation and therapeutic support. However, existing evaluation resources heavily rely on small clinical interview corpora, social media posts, or synthetic dialogues, which limits their clinical validity and fails to capture the full complexity of diagnostic reasoning. In this work, we introduce PsychiatryBench, a rigorously curated benchmark grounded exclusively in authoritative, expert-validated psychiatric textbooks and casebooks. PsychiatryBench comprises eleven distinct question-answering tasks ranging from diagnostic reasoning and treatment planning to longitudinal follow-up, management planning, clinical approach, sequential case analysis, and multiple-choice/extended matching formats totaling 5,188 expert-annotated items. {\color{red}We evaluate a diverse set of frontier LLMs (including Google Gemini, DeepSeek, Sonnet 4.5, and GPT 5) alongside leading open-source medical models such as MedGemma using both conventional metrics and an "LLM-as-judge" similarity scoring framework. Our results reveal substantial gaps in clinical consistency and safety, particularly in multi-turn follow-up and management tasks, underscoring the need for specialized model tuning and more robust evaluation paradigms. PsychiatryBench offers a modular, extensible platform for benchmarking and improving LLM performance in mental health applications.



Towards Efficient Medical Reasoning with Minimal Fine-Tuning Data

Zhuang, Xinlin, Tang, Feilong, Yang, Haolin, Liu, Xiwei, Hu, Ming, Li, Huifa, Xue, Haochen, He, Junjun, Ge, Zongyuan, Li, Yichen, Qian, Ying, Razzak, Imran

arXiv.org Artificial Intelligence

Supervised Fine-Tuning (SFT) plays a pivotal role in adapting Large Language Models (LLMs) to specialized domains such as medical reasoning. However, existing SFT practices often rely on unfiltered datasets that contain redundant and low-quality samples, leading to substantial computational costs and suboptimal performance. Although existing methods attempt to alleviate this problem by selecting data based on sample difficulty, defined by knowledge and reasoning complexity, they overlook each sample's optimization utility reflected in its gradient. Interestingly, we find that gradient-based influence alone favors easy-to-optimize samples that cause large parameter shifts but lack deep reasoning chains, while difficulty alone selects noisy or overly complex cases that fail to guide stable optimization. Based on this observation, we propose a data selection strategy, Difficulty-Influence Quadrant (DIQ), which prioritizes samples in the high-difficulty-high-influence quadrant to balance complex clinical reasoning with substantial gradient influence, enabling efficient medical reasoning with minimal fine-tuning data. Furthermore, Human and LLM-as-a-judge evaluations show that DIQ-selected subsets demonstrate higher data quality and generate clinical reasoning that is more aligned with expert practices in differential diagnosis, safety check, and evidence citation, as DIQ emphasizes samples that foster expert-like reasoning patterns. Extensive experiments on medical reasoning benchmarks demonstrate that DIQ enables models fine-tuned on only 1% of selected data to match full-dataset performance, while using 10% consistently outperforms baseline methods, highlighting the superiority of principled data selection over brute-force scaling. The code and data are available at https://github.com/mihara-bot/DIQ.



Generative Medical Event Models Improve with Scale

Waxler, Shane, Blazek, Paul, White, Davis, Sneider, Daniel, Chung, Kevin, Nagarathnam, Mani, Williams, Patrick, Voeller, Hank, Wong, Karen, Swanhorst, Matthew, Zhang, Sheng, Usuyama, Naoto, Wong, Cliff, Naumann, Tristan, Poon, Hoifung, Loza, Andrew, Meeker, Daniella, Hain, Seth, Shah, Rahul

arXiv.org Artificial Intelligence

Realizing personalized medicine at scale calls for methods that distill insights from longitudinal patient journeys, which can be viewed as a sequence of medical events. Foundation models pretrained on large-scale medical event data represent a promising direction for scaling real-world evidence generation and generalizing to diverse downstream tasks. Using Epic Cosmos, a dataset with medical events from de-identified longitudinal health records for 16.3 billion encounters over 300 million unique patient records from 310 health systems, we introduce the Curiosity models, a family of decoder-only transformer models pretrained on 118 million patients representing 115 billion discrete medical events (151 billion tokens). We present the largest scaling-law study of medical event data, establishing a methodology for pretraining and revealing power-law scaling relationships for compute, tokens, and model size. Consequently, we pretrained a series of compute-optimal models with up to 1 billion parameters. Conditioned on a patient's real-world history, Curiosity autoregressively predicts the next medical event to simulate patient health timelines. We studied 78 real-world tasks, including diagnosis prediction, disease prognosis, and healthcare operations. Remarkably for a foundation model with generic pretraining and simulation-based inference, Curiosity generally outperformed or matched task-specific supervised models on these tasks, without requiring task-specific fine-tuning or few-shot examples. Curiosity's predictive power consistently improves as the model and pretraining scale. Our results show that Curiosity, a generative medical event foundation model, can effectively capture complex clinical dynamics, providing an extensible and generalizable framework to support clinical decision-making, streamline healthcare operations, and improve patient outcomes.


A Dual-Use Framework for Clinical Gait Analysis: Attention-Based Sensor Optimization and Automated Dataset Auditing

Sadeghsalehi, Hamidreza

arXiv.org Artificial Intelligence

Objective gait analysis using wearable sensors and AI is critical for managing neurological and orthopedic conditions. However, models are vulnerable to hidden dataset biases, and task-specific sensor optimization remains a challenge. We propose a multi-stream attention-based deep learning framework that functions as both a sensor optimizer and an automated data auditor. Applied to the Voisard et al. (2025) multi-cohort gait dataset on four clinical tasks (PD, OA, CVA screening; PD vs CVA differential), the model's attention mechanism quantitatively discovered a severe dataset confound. For OA and CVA screening, tasks where bilateral assessment is clinically essential, the model assigned more than 70 percent attention to the Right Foot while statistically ignoring the Left Foot (less than 0.1 percent attention, 95 percent CI [0.0-0.1]). This was not a clinical finding but a direct reflection of a severe laterality bias (for example, 15 of 15 right-sided OA) in the public dataset. The primary contribution of this work is methodological, demonstrating that an interpretable framework can automatically audit dataset integrity. As a secondary finding, the model proposes novel, data-driven sensor synergies (for example, Head plus Foot for PD screening) as hypotheses for future optimized protocols.


Inflated Excellence or True Performance? Rethinking Medical Diagnostic Benchmarks with Dynamic Evaluation

Zhang, Xiangxu, Li, Lei, Zhou, Yanyun, Zhou, Xiao, Zhang, Yingying, Wu, Xian

arXiv.org Artificial Intelligence

Medical diagnostics is a high-stakes and complex domain that is critical to patient care. However, current evaluations of large language models (LLMs) are fundamentally misaligned with real-world clinical practice. Most of them rely on static benchmarks derived from public medical exam items, which tend to overestimate model performance and ignore the difference between textbook cases and the ambiguous, varying conditions in the real world. Recent efforts toward dynamic evaluation offer a promising alternative, but their improvements are limited to superficial perturbations and a narrow focus on accuracy. To address these gaps, we propose DyReMe, a dynamic benchmark for medical diagnostics that better reflects real clinical practice. Unlike static exam-style questions, DyReMe generates fresh, consultation-like cases that introduce distractors such as differential diagnoses and common misdiagnosis factors. It also varies expression styles to mimic diverse real-world query habits. Beyond accuracy, DyReMe evaluates LLMs on three additional clinically relevant dimensions: veracity, helpfulness, and consistency. Our experiments demonstrate that this dynamic approach yields more challenging and realistic assessments, revealing significant misalignments between the performance of state-of-the-art LLMs and real clinical practice. These findings highlight the urgent need for evaluation frameworks that better reflect the demands of trustworthy medical diagnostics.


H-DDx: A Hierarchical Evaluation Framework for Differential Diagnosis

Lim, Seungseop, Kim, Gibaeg, Lee, Hyunkyung, Han, Wooseok, Seo, Jean, Yoo, Jaehyo, Yang, Eunho

arXiv.org Artificial Intelligence

An accurate differential diagnosis (DDx) is essential for patient care, shaping therapeutic decisions and influencing outcomes. Recently, Large Language Models (LLMs) have emerged as promising tools to support this process by generating a DDx list from patient narratives. However, existing evaluations of LLMs in this domain primarily rely on flat metrics, such as Top-k accuracy, which fail to distinguish between clinically relevant near-misses and diagnostically distant errors. To mitigate this limitation, we introduce H-DDx, a hierarchical evaluation framework that better reflects clinical relevance. H-DDx leverages a retrieval and reranking pipeline to map free-text diagnoses to ICD-10 codes and applies a hierarchical metric that credits predictions closely related to the ground-truth diagnosis. In benchmarking 22 leading models, we show that conventional flat metrics underestimate performance by overlooking clinically meaningful outputs, with our results highlighting the strengths of domain-specialized open-source models. Furthermore, our framework enhances interpretability by revealing hierarchical error patterns, demonstrating that LLMs often correctly identify the broader clinical context even when the precise diagnosis is missed.