Girish Nadkarni

Seyed Amir Ahmad Safavi-Naini, Shuhaib Ali, Omer Shahab et al.

Background and Aims: This study evaluates the medical reasoning performance of large language models (LLMs) and vision language models (VLMs) in gastroenterology. Methods: We used 300 gastroenterology board exam-style multiple-choice questions, 138 of which contain images to systematically assess the impact of model configurations and parameters and prompt engineering strategies utilizing GPT-3.5. Next, we assessed the performance of proprietary and open-source LLMs (versions), including GPT (3.5, 4, 4o, 4omini), Claude (3, 3.5), Gemini (1.0), Mistral, Llama (2, 3, 3.1), Mixtral, and Phi (3), across different interfaces (web and API), computing environments (cloud and local), and model precisions (with and without quantization). Finally, we assessed accuracy using a semiautomated pipeline. Results: Among the proprietary models, GPT-4o (73.7%) and Claude3.5-Sonnet (74.0%) achieved the highest accuracy, outperforming the top open-source models: Llama3.1-405b (64%), Llama3.1-70b (58.3%), and Mixtral-8x7b (54.3%). Among the quantized open-source models, the 6-bit quantized Phi3-14b (48.7%) performed best. The scores of the quantized models were comparable to those of the full-precision models Llama2-7b, Llama2--13b, and Gemma2-9b. Notably, VLM performance on image-containing questions did not improve when the images were provided and worsened when LLM-generated captions were provided. In contrast, a 10% increase in accuracy was observed when images were accompanied by human-crafted image descriptions. Conclusion: In conclusion, while LLMs exhibit robust zero-shot performance in medical reasoning, the integration of visual data remains a challenge for VLMs. Effective deployment involves carefully determining optimal model configurations, encouraging users to consider either the high performance of proprietary models or the flexible adaptability of open-source models.

Akhil Vaid, Joy Jiang, Ashwin Sawant et al.

The electrocardiogram (ECG) is a ubiquitous diagnostic modality. Convolutional neural networks (CNNs) applied towards ECG analysis require large sample sizes, and transfer learning approaches result in suboptimal performance when pre-training is done on natural images. We leveraged masked image modeling to create the first vision-based transformer model, HeartBEiT, for electrocardiogram waveform analysis. We pre-trained this model on 8.5 million ECGs and then compared performance vs. standard CNN architectures for diagnosis of hypertrophic cardiomyopathy, low left ventricular ejection fraction and ST elevation myocardial infarction using differing training sample sizes and independent validation datasets. We show that HeartBEiT has significantly higher performance at lower sample sizes compared to other models. Finally, we also show that HeartBEiT improves explainability of diagnosis by highlighting biologically relevant regions of the EKG vs. standard CNNs. Thus, we present the first vision-based waveform transformer that can be used to develop specialized models for ECG analysis especially at low sample sizes.

Mohammadreza Ghaffarzadeh-Esfahani, Mahdi Ghaffarzadeh-Esfahani, Arian Salahi-Niri et al.

This study compared the performance of classical feature-based machine learning models (CMLs) and large language models (LLMs) in predicting COVID-19 mortality using high-dimensional tabular data from 9,134 patients across four hospitals. Seven CML models, including XGBoost and random forest (RF), were evaluated alongside eight LLMs, such as GPT-4 and Mistral-7b, which performed zero-shot classification on text-converted structured data. Additionally, Mistral- 7b was fine-tuned using the QLoRA approach. XGBoost and RF demonstrated superior performance among CMLs, achieving F1 scores of 0.87 and 0.83 for internal and external validation, respectively. GPT-4 led the LLM category with an F1 score of 0.43, while fine-tuning Mistral-7b significantly improved its recall from 1% to 79%, yielding a stable F1 score of 0.74 during external validation. Although LLMs showed moderate performance in zero-shot classification, fine-tuning substantially enhanced their effectiveness, potentially bridging the gap with CML models. However, CMLs still outperformed LLMs in handling high-dimensional tabular data tasks. This study highlights the potential of both CMLs and fine-tuned LLMs in medical predictive modeling, while emphasizing the current superiority of CMLs for structured data analysis.

Akhil Vaid, Joshua Lampert, Juhee Lee et al.

Generative Large Language Models (LLMs) hold significant promise in healthcare, demonstrating capabilities such as passing medical licensing exams and providing clinical knowledge. However, their current use as information retrieval tools is limited by challenges like data staleness, resource demands, and occasional generation of incorrect information. This study assessed the potential of LLMs to function as autonomous agents in a simulated tertiary care medical center, using real-world clinical cases across multiple specialties. Both proprietary and open-source LLMs were evaluated, with Retrieval Augmented Generation (RAG) enhancing contextual relevance. Proprietary models, particularly GPT-4, generally outperformed open-source models, showing improved guideline adherence and more accurate responses with RAG. The manual evaluation by expert clinicians was crucial in validating models' outputs, underscoring the importance of human oversight in LLM operation. Further, the study emphasizes Natural Language Programming (NLP) as the appropriate paradigm for modifying model behavior, allowing for precise adjustments through tailored prompts and real-world interactions. This approach highlights the potential of LLMs to significantly enhance and supplement clinical decision-making, while also emphasizing the value of continuous expert involvement and the flexibility of NLP to ensure their reliability and effectiveness in healthcare settings.

Stefan Konigorski, Sarah Wernicke, Tamara Slosarek et al.

N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully-functional platforms are not yet available. Here, we present the open source StudyU platform which includes the StudyU designer and StudyU app. With the StudyU designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. The StudyU app is a smartphone application with innovative user-centric elements for participants to partake in the published trials and assess the effects of different interventions on their health. Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.

Nariman Naderi, Seyed Amir Ahmad Safavi-Naini, Thomas Savage et al.

This study evaluated self-reported response certainty across several large language models (GPT, Claude, Llama, Phi, Mistral, Gemini, Gemma, and Qwen) using 300 gastroenterology board-style questions. The highest-performing models (GPT-o1 preview, GPT-4o, and Claude-3.5-Sonnet) achieved Brier scores of 0.15-0.2 and AUROC of 0.6. Although newer models demonstrated improved performance, all exhibited a consistent tendency towards overconfidence. Uncertainty estimation presents a significant challenge to the safe use of LLMs in healthcare. Keywords: Large Language Models; Confidence Elicitation; Artificial Intelligence; Gastroenterology; Uncertainty Quantification

Seyed Amir Ahmad Safavi-Naini, Elahe Meftah, Josh Mohess et al.

The competency of any intelligent agent is bounded by its formal account of the world in which it operates. Clinical AI lacks such an account. Existing frameworks address evaluation, regulation, or system design in isolation, without a shared model of the clinical world to connect them. We introduce the Clinical World Model, a framework that formalizes care as a tripartite interaction among Patient, Provider, and Ecosystem. To formalize how any agent, whether human or artificial, transforms information into clinical action, we develop parallel decision-making architectures for providers, patients, and AI agents, grounded in validated principles of clinical cognition. The Clinical AI Skill-Mix operationalizes competency through eight dimensions. Five define the clinical competency space (condition, phase, care setting, provider role, and task) and three specify how AI engages human reasoning (assigned authority, agent facing, and anchoring layer). The combinatorial product of these dimensions yields a space of billions of distinct competency coordinates. A central structural implication is that validation within one coordinate provides minimal evidence for performance in another, rendering the competency space irreducible. The framework supplies a common grammar through which clinical AI can be specified, evaluated, and bounded across stakeholders. By making this structure explicit, the Clinical World Model reframes the field's central question from whether AI works to in which competency coordinates reliability has been demonstrated, and for whom.

Mohammad Amin Khalafi, Seyed Amir Ahmad Safavi-Naini, Ameneh Salehi et al.

Introduction: This study provides a comprehensive performance assessment of vision-language models (VLMs) against established convolutional neural networks (CNNs) and classic machine learning models (CMLs) for computer-aided detection (CADe) and computer-aided diagnosis (CADx) of colonoscopy polyp images. Method: We analyzed 2,258 colonoscopy images with corresponding pathology reports from 428 patients. We preprocessed all images using standardized techniques (resizing, normalization, and augmentation) and implemented a rigorous comparative framework evaluating 11 distinct models: ResNet50, 4 CMLs (random forest, support vector machine, logistic regression, decision tree), two specialized contrastive vision language encoders (CLIP, BiomedCLIP), and three general-purpose VLMs ( GPT-4 Gemini-1.5-Pro, Claude-3-Opus). Our performance assessment focused on two clinical tasks: polyp detection (CADe) and classification (CADx). Result: In polyp detection, ResNet50 achieved the best performance (F1: 91.35%, AUROC: 0.98), followed by BiomedCLIP (F1: 88.68%, AUROC: [AS1] ). GPT-4 demonstrated comparable effectiveness to traditional machine learning approaches (F1: 81.02%, AUROC: [AS2] ), outperforming other general-purpose VLMs. For polyp classification, performance rankings remained consistent but with lower overall metrics. ResNet50 maintained the highest efficacy (weighted F1: 74.94%), while GPT-4 demonstrated moderate capability (weighted F1: 41.18%), significantly exceeding other VLMs (Claude-3-Opus weighted F1: 25.54%, Gemini 1.5 Pro weighted F1: 6.17%). Conclusion: CNNs remain superior for both CADx and CADe tasks. However, VLMs like BioMedCLIP and GPT-4 may be useful for polyp detection tasks where training CNNs is not feasible.