Acute poly-substance intoxication requires rapid, life-saving decisions under substantial uncertainty, as clinicians must rely on incomplete ingestion details and nonspecific symptoms. Effective diagnostic reasoning in this chaotic environment requires fusing unstructured, non-medical narratives (e.g. paramedic scene descriptions and unreliable patient self-reports or known histories), with structured medical data like vital signs. While Large Language Models (LLMs) show potential for processing such heterogeneous inputs, they struggle in this setting, often underperforming simple baselines that rely solely on patient histories. To address this, we present DeToxR (Decision-support for Toxicology with Reasoning), the first adaptation of Reinforcement Learning (RL) to emergency toxicology. We design a robust data-fusion engine for multi-label prediction across 14 substance classes based on an LLM finetuned with Group Relative Policy Optimization (GRPO). We optimize the model's reasoning directly using a clinical performance reward. By formulating a multi-label agreement metric as the reward signal, the model is explicitly penalized for missing co-ingested substances and hallucinating absent poisons. Our model significantly outperforms its unadapted base LLM counterpart and supervised baselines. Furthermore, in a preliminary clinical validation study, the model indicates a clinical advantage by achieving higher micro-F1 (0.644 vs 0.473) and recall in identifying the correct poisons. These results demonstrate the potential of RL-aligned LLMs to synthesize unstructured pre-clinical narratives and structured medical data for decision support in high-stakes environments.
Deploying Large Language Models (LLMs) in healthcare requires robust performance across two complementary dimensions - diagnostic reasoning: the convergent, evidence-driven task of inferring a patient's condition from clinical data to produce a diagnosis, and clinical healthcare reasoning: the broader, navigational judgment required to communicate, plan, and adapt across multi-turn clinical interactions where a single correct answer may not exist. Recent benchmarks such as HealthBench and MedXpertQA reveal persistent weaknesses in both areas, exposing failures in complex diagnostic scenarios and limitations in contextual, patient-centered dialogue. We introduce a sequential training framework that targets these facets using synthetic data and rubric-based reinforcement learning. First, we improve diagnostic reasoning using MedBullets-derived questions with rule- and rubric-guided Reinforcement Learning (RL). We then shift to clinical reasoning by generating 5.3k synthetic multi-turn scenarios, each paired with multi-dimensional rubrics to comprehensively assess the response. This approach yields over 10% improvement on MedXpertQA, and our 30B model achieves 50.1% accuracy on HealthBench-Hard, surpassing proprietary baselines including GPT-5 (thinking). Our results show that targeted synthetic datasets and rubric-based training can systematically improve both diagnostic and interactive clinical reasoning in medical LLMs.
Recent reasoning-centric Large Language Models (LLMs) have made significant strides, yet they predominantly operate on a passive-inference pattern that assumes complete information. In contrast, real-world clinical intelligence is inherently an iterative investigative process requiring strategic evidence acquisition. To bridge this gap, we formalize medical diagnosis as an Iterative Evidence-Seeking Task. We leverage Reinforcement Learning with Verifiable Rewards (RLVR) to elicit intrinsic reasoning within a closed-loop environment, guided by a novel suite of rewards that enforce diagnostic precision and examination consistency. To facilitate this, we introduce the Retrieval-Augmented Generation-based Examination Simulator (RAGES), a high-fidelity clinical oracle that provides realistic, knowledge-grounded follow-up evidence. Empirical results across diverse datasets demonstrate that our framework enables LLMs to transition from passive responders to autonomous assistants. Notably, our model demonstrates comparable performance to larger and reasoning-enhanced baselines, while RAGES proves superior to vanilla LLMs in generating biologically plausible clinical feedback.
Diagnostic prediction and clinical reasoning are critical tasks in healthcare applications. While Large Language Models (LLMs) have shown strong capabilities in commonsense reasoning, they still struggle with diagnostic reasoning due to limited domain knowledge. Existing approaches often rely on internal model knowledge or static knowledge bases, resulting in knowledge insufficiency and limited adaptability, which hinder their capacity to perform diagnostic reasoning. Moreover, these methods focus solely on the accuracy of final predictions, overlooking alignment with standard clinical reasoning trajectories. To this end, we propose MultiDx, a two-stage diagnostic reasoning framework that performs differential diagnosis by analyzing evidence collected from multiple knowledge sources. Specifically, it first generates suspected diagnoses and reasoning paths by leveraging knowledge from web search, SOAP-formatted case, and clinical case database. Then it integrates multi-perspective evidence through matching, voting, and differential diagnosis to generate the final prediction.~Extensive experiments on two public benchmarks demonstrate the effectiveness of our approach.