Unlike most primary headaches, secondary headaches need specialized care and can have devastating consequences if not treated promptly. Clinical guidelines highlight several 'red flag' features, such as thunderclap onset, meningismus, papilledema, focal neurologic deficits, signs of temporal arteritis, systemic illness, and the 'worst headache of their life' presentation. Despite these guidelines, determining which patients require urgent evaluation remains challenging in primary care settings. Clinicians often work with limited time, incomplete information, and diverse symptom presentations, which can lead to under-recognition and inappropriate care. We present a large language model (LLM)-based multi-agent clinical decision support system built on an orchestrator-specialist architecture, designed to perform explicit and interpretable secondary headache diagnosis from free-text clinical vignettes. The multi-agent system decomposes diagnosis into seven domain-specialized agents, each producing a structured and evidence-grounded rationale, while a central orchestrator performs task decomposition and coordinates agent routing. We evaluated the multi-agent system using 90 expert-validated secondary headache cases and compared its performance with a single-LLM baseline across two prompting strategies: question-based prompting (QPrompt) and clinical practice guideline-based prompting (GPrompt). We tested five open-source LLMs (Qwen-30B, GPT-OSS-20B, Qwen-14B, Qwen-8B, and Llama-3.1-8B), and found that the orchestrated multi-agent system with GPrompt consistently achieved the highest F1 scores, with larger gains in smaller models. These findings demonstrate that structured multi-agent reasoning improves accuracy beyond prompt engineering alone and offers a transparent, clinically aligned approach for explainable decision support in secondary headache diagnosis.

Clinical decision support systems (CDSS) are used to improve clinical and service outcomes, yet evidence from low- and middle-income countries (LMICs) is dispersed. This protocol outlines methods to quantify the impact of CDSS on patient and healthcare delivery outcomes in LMICs. We will include comparative quantitative designs (randomized trials, controlled before-after, interrupted time series, comparative cohorts) evaluating CDSS in World Bank-defined LMICs. Standalone qualitative studies are excluded; mixed-methods studies are eligible only if they report comparative quantitative outcomes, for which we will extract the quantitative component. Searches (from inception to 30 September 2024) will cover MEDLINE, Embase, CINAHL, CENTRAL, Web of Science, Global Health, Scopus, IEEE Xplore, LILACS, African Index Medicus, and IndMED, plus grey sources. Screening and extraction will be performed in duplicate. Risk of bias will be assessed with RoB 2 (randomized trials) and ROBINS-I (non-randomized). Random-effects meta-analysis will be performed where outcomes are conceptually or statistically comparable; otherwise, a structured narrative synthesis will be presented. Heterogeneity will be explored using relative and absolute metrics and a priori subgroups or meta-regression (condition area, care level, CDSS type, readiness proxies, study design).

The increasing complexity of clinical decision-making, alongside the rapid expansion of electronic health records (EHR), presents both opportunities and challenges for delivering data-informed care. This paper proposes a clinical decision support system powered by Large Language Models (LLMs) to assist prescribing clinicians. The system generates therapeutic suggestions by analyzing historical EHR data, including patient demographics, presenting complaints, clinical symptoms, diagnostic information, and treatment histories. The framework integrates natural language processing with structured clinical inputs to produce contextually relevant recommendations. Rather than replacing clinician judgment, it is designed to augment decision-making by retrieving and synthesizing precedent cases with comparable characteristics, drawing on local datasets or federated sources where applicable. At its core, the system employs a retrieval-augmented generation (RAG) pipeline that harmonizes unstructured narratives and codified data to support LLM-based inference. We outline the system's technical components, including representation representation alignment and generation strategies. Preliminary evaluations, conducted with de-identified and synthetic clinical datasets, examine the clinical plausibility and consistency of the model's outputs. Early findings suggest that LLM-based tools may provide valuable decision support in prescribing workflows when appropriately constrained and rigorously validated. This work represents an initial step toward integration of generative AI into real-world clinical decision-making with an emphasis on transparency, safety, and alignment with established practices.

Over the past few years, the field of artificial intelligence (AI) has shown great promise in various domains, including medicine. A potential use case for AI in medicine is its application in managing advanced-stage cancer treatment, where limited evidence often makes treatment choices reliant on the personal expertise of the physicians. The complex nature of oncological disease processes and the multitude of factors that need to be considered when making treatment decisions make it difficult to rely solely on evidence-based trial data, which is often limited and may exclude certain patient populations. This results in physicians making decisions on a case-by-case basis, drawing on their experience of previous cases, which is not always objective and may be limited by the small number of cases they have observed. In this context, the use of clinical decision support systems (CDSS) using similaritybased AI approaches can potentially contribute to better oncology treatment by supporting physicians in the selection of treatment methods [1, 2]. One approach is Case-Based Reasoning (CBR), a subfield of AI that deals with experience-based problem solving.

Explainable AI (XAI) has become a crucial component of Clinical Decision Support Systems (CDSS) to enhance transparency, trust, and clinical adoption. However, while many XAI methods have been proposed, their effectiveness in real-world medical settings remains underexplored. This paper provides a survey of human-centered evaluations of Explainable AI methods in Clinical Decision Support Systems. By categorizing existing works based on XAI methodologies, evaluation frameworks, and clinical adoption challenges, we offer a structured understanding of the landscape. Our findings reveal key challenges in the integration of XAI into healthcare workflows and propose a structured framework to align the evaluation methods of XAI with the clinical needs of stakeholders.

Medication errors significantly threaten patient safety, leading to adverse drug events and substantial economic burdens on healthcare systems. Clinical Decision Support Systems (CDSSs) aimed at mitigating these errors often face limitations, including reliance on static databases and rule-based algorithms, which can result in high false alert rates and alert fatigue among clinicians. This paper introduces HELIOT, an innovative CDSS for drug allergy management, integrating Large Language Models (LLMs) with a comprehensive pharmaceutical data repository. HELIOT leverages advanced natural language processing capabilities to interpret complex medical texts and synthesize unstructured data, overcoming the limitations of traditional CDSSs. An empirical evaluation using a synthetic patient dataset and expert-verified ground truth demonstrates HELIOT's high accuracy, precision, recall, and F1 score, uniformly reaching 100\% across multiple experimental runs. The results underscore HELIOT's potential to enhance decision support in clinical settings, offering a scalable, efficient, and reliable solution for managing drug allergies.

Background: The adherence of clinicians to clinical practice guidelines is known to be low, including for the management of COVID-19, due to their difficult use at the point of care and their complexity. Clinical decision support systems have been proposed to implement guidelines and improve adherence. One approach is to permit the navigation inside the recommendations, presented as a decision tree, but the size of the tree often limits this approach and may cause erroneous navigation, especially when it does not fit in a single screen. Methods: We proposed an innovative visual interface to allow clinicians easily navigating inside decision trees for the management of COVID-19 patients. It associates a multi-path tree model with the use of the fisheye visual technique, allowing the visualization of large decision trees in a single screen. To evaluate the impact of this tool on guideline adherence, we conducted a randomized controlled trial in a near-real simulation setting, comparing the decisions taken by medical students using Orient-COVID with those taken with paper guidelines or without guidance, when performing on six realistic clinical cases. Results: The results show that paper guidelines had no impact (p=0.97), while Orient-COVID significantly improved the guideline adherence compared to both other groups (p<0.0003). A significant impact of Orient-COVID was identified on several key points during the management of COVID-19: ordering troponin lab tests, prescribing anticoagulant and oxygen therapy. A multifactor analysis showed no difference between male and female participants. Conclusions: The use of an interactive decision tree for the management of COVID-19 significantly improved the clinician adherence to guidelines. Future works will focus on the integration of the system to electronic health records and on the adaptation of the system to other clinical conditions.

Current clinical decision support systems (DSS) are trained and validated on observational data from the target clinic. This is problematic for treatments validated in a randomized clinical trial (RCT), but not yet introduced in any clinic. In this work, we report on a method for training and validating the DSS using the RCT data. The key challenges we address are of missingness -- missing rationale for treatment assignment (the assignment is at random), and missing verification evidence, since the effectiveness of a treatment for a patient can only be verified (ground truth) for treatments what were actually assigned to a patient. We use data from a multi-armed RCT that investigated the effectiveness of single- and combination- treatments for 240+ tinnitus patients recruited and treated in 5 clinical centers. To deal with the 'missing rationale' challenge, we re-model the target variable (outcome) in order to suppress the effect of the randomly-assigned treatment, and control on the effect of treatment in general. Our methods are also robust to missing values in features and with a small number of patients per RCT arm. We deal with 'missing verification evidence' by using counterfactual treatment verification, which compares the effectiveness of the DSS recommendations to the effectiveness of the RCT assignments when they are aligned v/s not aligned. We demonstrate that our approach leverages the RCT data for learning and verification, by showing that the DSS suggests treatments that improve the outcome. The results are limited through the small number of patients per treatment; while our ensemble is designed to mitigate this effect, the predictive performance of the methods is affected by the smallness of the data. We provide a basis for the establishment of decision supporting routines on treatments that have been tested in RCTs but have not yet been deployed clinically.

The accurate recognition of symptoms in clinical reports is significantly important in the fields of healthcare and biomedical natural language processing. These entities serve as essential building blocks for clinical information extraction, enabling retrieval of critical medical insights from vast amounts of textual data. Furthermore, the ability to identify and categorize these entities is fundamental for developing advanced clinical decision support systems, aiding healthcare professionals in diagnosis and treatment planning. In this study, we participated in SympTEMIST - a shared task on the detection of symptoms, signs and findings in Spanish medical documents. We combine a set of large language models fine-tuned with the data released by the task's organizers.

Health management has become a primary problem as new kinds of diseases and complex symptoms are introduced to a rapidly growing modern society. Building a better and smarter healthcare infrastructure is one of the ultimate goals of a smart city. To the best of our knowledge, neural network models are already employed to assist healthcare professionals in achieving this goal. Typically, training a neural network requires a rich amount of data but heterogeneous and vulnerable properties of clinical data introduce a challenge for the traditional centralized network. Moreover, adding new inputs to a medical database requires re-training an existing model from scratch. To tackle these challenges, we proposed a deep learning-based clinical decision support system trained and managed under a federated learning paradigm. We focused on a novel strategy to guarantee the safety of patient privacy and overcome the risk of cyberattacks while enabling large-scale clinical data mining. As a result, we can leverage rich clinical data for training each local neural network without the need for exchanging the confidential data of patients. Moreover, we implemented the proposed scheme as a sequence-to-sequence model architecture integrating the attention mechanism. Thus, our objective is to provide a personalized clinical decision support system with evolvable characteristics that can deliver accurate solutions and assist healthcare professionals in medical diagnosing.