Cardiovascular events, such as heart attacks and strokes, remain a leading cause of mortality globally, necessitating meticulous monitoring and adjudication in clinical trials. This process, traditionally performed manually by clinical experts, is time-consuming, resource-intensive, and prone to inter-reviewer variability, potentially introducing bias and hindering trial progress. This study addresses these critical limitations by presenting a novel framework for automating the adjudication of cardiovascular events in clinical trials using Large Language Models (LLMs). We developed a two-stage approach: first, employing an LLM-based pipeline for event information extraction from unstructured clinical data and second, using an LLM-based adjudication process guided by a Tree of Thoughts approach and clinical endpoint committee (CEC) guidelines. Using cardiovascular event-specific clinical trial data, the framework achieved an F1-score of 0.82 for event extraction and an accuracy of 0.68 for adjudication. Furthermore, we introduce the CLEART score, a novel, automated metric specifically designed for evaluating the quality of AI-generated clinical reasoning in adjudicating cardiovascular events. This approach demonstrates significant potential for substantially reducing adjudication time and costs while maintaining high-quality, consistent, and auditable outcomes in clinical trials. The reduced variability and enhanced standardization also allow for faster identification and mitigation of risks associated with cardiovascular therapies.

Medical QA systems powered by Retrieval-Augmented Generation (RAG) models support clinical decision-making but may introduce biases related to race, gender, and social determinants of health. We systematically evaluate biases in RAG-based LLM by examining demographic-sensitive queries and measuring retrieval discrepancies. Using datasets like MMLU and MedMCQA, we analyze retrieval overlap and correctness disparities. Our findings reveal substantial demographic disparities within RAG pipelines, emphasizing the critical need for retrieval methods that explicitly account for fairness to ensure equitable clinical decision-making.

Large language models (LLMs) are increasingly utilized in healthcare applications. However, their deployment in clinical practice raises significant safety concerns, including the potential spread of harmful information. This study systematically assesses the vulnerabilities of six LLMs to three advanced black-box jailbreaking techniques within medical contexts. To quantify the effectiveness of these techniques, we propose an automated and domain-adapted agentic evaluation pipeline. Experiment results indicate that leading commercial and open-source LLMs are highly vulnerable to medical jailbreaking attacks. To bolster model safety and reliability, we further investigate the effectiveness of Continual Fine-Tuning (CFT) in defending against medical adversarial attacks. Our findings underscore the necessity for evolving attack methods evaluation, domain-specific safety alignment, and LLM safety-utility balancing. This research offers actionable insights for advancing the safety and reliability of AI clinicians, contributing to ethical and effective AI deployment in healthcare.

Recent advancements in large language models have demonstrated their potential in numerous medical applications, particularly in automating clinical trial matching for translational research and enhancing medical question answering for clinical decision support. However, our study shows that incorporating non decisive sociodemographic factors such as race, sex, income level, LGBT+ status, homelessness, illiteracy, disability, and unemployment into the input of LLMs can lead to incorrect and harmful outputs for these populations. These discrepancies risk exacerbating existing health disparities if LLMs are widely adopted in healthcare. To address this issue, we introduce EquityGuard, a novel framework designed to detect and mitigate the risk of health inequities in LLM based medical applications. Our evaluation demonstrates its efficacy in promoting equitable outcomes across diverse populations.

Secure training, while protecting the confidentiality of both data and model weights, typically incurs significant training overhead. Traditional Fully Homomorphic Encryption (FHE)-based non-inter-active training models are heavily burdened by computationally demanding bootstrapping. To develop an efficient secure training system, we established a foundational framework, CryptoTrain-B, utilizing a hybrid cryptographic protocol that merges FHE with Oblivious Transfer (OT) for handling linear and non-linear operations, respectively. This integration eliminates the need for costly bootstrapping. Although CryptoTrain-B sets a new baseline in performance, reducing its training overhead remains essential. We found that ciphertext-ciphertext multiplication (CCMul) is a critical bottleneck in operations involving encrypted inputs and models. Our solution, the CCMul-Precompute technique, involves precomputing CCMul offline and resorting to the less resource-intensive ciphertext-plaintext multiplication (CPMul) during private training. Furthermore, conventional polynomial convolution in FHE systems tends to encode irrelevant and redundant values into polynomial slots, necessitating additional polynomials and ciphertexts for input representation and leading to extra multiplications. Addressing this, we introduce correlated polynomial convolution, which encodes only related input values into polynomials, thus drastically reducing the number of computations and overheads. By integrating CCMul-Precompute and correlated polynomial convolution into CryptoTrain-B, we facilitate a rapid and efficient secure training framework, CryptoTrain. Extensive experiments demonstrate that CryptoTrain achieves a ~5.3X training time reduction compared to prior methods.

Low back pain (LBP) is a leading cause of disability globally. Following the onset of LBP and subsequent treatment, adequate patient education is crucial for improving functionality and long-term outcomes. Despite advancements in patient education strategies, significant gaps persist in delivering personalized, evidence-based information to patients with LBP. Recent advancements in large language models (LLMs) and generative artificial intelligence (GenAI) have demonstrated the potential to enhance patient education. However, their application and efficacy in delivering educational content to patients with LBP remain underexplored and warrant further investigation. In this study, we introduce a novel approach utilizing LLMs with Retrieval-Augmented Generation (RAG) and few-shot learning to generate tailored educational materials for patients with LBP. Physical therapists manually evaluated our model responses for redundancy, accuracy, and completeness using a Likert scale. In addition, the readability of the generated education materials is assessed using the Flesch Reading Ease score. The findings demonstrate that RAG-based LLMs outperform traditional LLMs, providing more accurate, complete, and readable patient education materials with less redundancy. Having said that, our analysis reveals that the generated materials are not yet ready for use in clinical practice. This study underscores the potential of AI-driven models utilizing RAG to improve patient education for LBP; however, significant challenges remain in ensuring the clinical relevance and granularity of content generated by these models.

This paper introduces the RAG-RLRC-LaySum framework, designed to make complex biomedical research understandable to laymen through advanced Natural Language Processing (NLP) techniques. Our Retrieval Augmented Generation (RAG) solution, enhanced by a reranking method, utilizes multiple knowledge sources to ensure the precision and pertinence of lay summaries. Additionally, our Reinforcement Learning for Readability Control (RLRC) strategy improves readability, making scientific content comprehensible to non-specialists. Evaluations using the publicly accessible PLOS and eLife datasets show that our methods surpass Plain Gemini model, demonstrating a 20% increase in readability scores, a 15% improvement in ROUGE-2 relevance scores, and a 10% enhancement in factual accuracy. The RAG-RLRC-LaySum framework effectively democratizes scientific knowledge, enhancing public engagement with biomedical discoveries.

In this study, we utilized statistical analysis and machine learning methods to examine whether rehabilitation exercises can improve patients post-stroke functional abilities, as well as forecast the improvement in functional abilities. Our dataset is patients' rehabilitation exercises and demographic information recorded in the unstructured electronic health records (EHRs) data and free-text rehabilitation procedure notes. We collected data for 265 stroke patients from the University of Pittsburgh Medical Center. We employed a pre-existing natural language processing (NLP) algorithm to extract data on rehabilitation exercises and developed a rule-based NLP algorithm to extract Activity Measure for Post-Acute Care (AM-PAC) scores, covering basic mobility (BM) and applied cognitive (AC) domains, from procedure notes. Changes in AM-PAC scores were classified based on the minimal clinically important difference (MCID), and significance was assessed using Friedman and Wilcoxon tests. To identify impactful exercises, we used Chi-square tests, Fisher's exact tests, and logistic regression for odds ratios. Additionally, we developed five machine learning models-logistic regression (LR), Adaboost (ADB), support vector machine (SVM), gradient boosting (GB), and random forest (RF)-to predict outcomes in functional ability. Statistical analyses revealed significant associations between functional improvements and specific exercises. The RF model achieved the best performance in predicting functional outcomes. In this study, we identified three rehabilitation exercises that significantly contributed to patient post-stroke functional ability improvement in the first two months. Additionally, the successful application of a machine learning model to predict patient-specific functional outcomes underscores the potential for precision rehabilitation.

As generative artificial intelligence (AI), particularly Large Language Models (LLMs), continues to permeate healthcare, it remains crucial to supplement traditional automated evaluations with human expert evaluation. Understanding and evaluating the generated texts is vital for ensuring safety, reliability, and effectiveness. However, the cumbersome, time-consuming, and non-standardized nature of human evaluation presents significant obstacles to the widespread adoption of LLMs in practice. This study reviews existing literature on human evaluation methodologies for LLMs within healthcare. We highlight a notable need for a standardized and consistent human evaluation approach. Our extensive literature search, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, spans publications from January 2018 to February 2024. This review provides a comprehensive overview of the human evaluation approaches used in diverse healthcare applications.This analysis examines the human evaluation of LLMs across various medical specialties, addressing factors such as evaluation dimensions, sample types, and sizes, the selection and recruitment of evaluators, frameworks and metrics, the evaluation process, and statistical analysis of the results. Drawing from diverse evaluation strategies highlighted in these studies, we propose a comprehensive and practical framework for human evaluation of generative LLMs, named QUEST: Quality of Information, Understanding and Reasoning, Expression Style and Persona, Safety and Harm, and Trust and Confidence. This framework aims to improve the reliability, generalizability, and applicability of human evaluation of generative LLMs in different healthcare applications by defining clear evaluation dimensions and offering detailed guidelines.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.