A Multi-Phase Analysis of Blood Culture Stewardship: Machine Learning Prediction, Expert Recommendation Assessment, and LLM Automation

Blood cultures are often over ordered without clear justification, straining healthcare resources and contributing to inappropriate antibiotic use pressures worsened by the global shortage. In study of 135483 emergency department (ED) blood culture orders, we developed machine learning (ML) models to predict the risk of bacteremia using structured electronic health record (EHR) data and provider notes via a large language model (LLM). The structured models AUC improved from 0.76 to 0.79 with note embeddings and reached 0.81 with added diagnosis codes. Compared to an expert recommendation framework applied by human reviewers and an LLM-based pipeline, our ML approach offered higher specificity without compromising sensitivity. The recommendation framework achieved sensitivity 86%, specificity 57%, while the LLM maintained high sensitivity (96%) but over classified negatives, reducing specificity (16%). These findings demonstrate that ML models integrating structured and unstructured data can outperform consensus recommendations, enhancing diagnostic stewardship beyond existing standards of care.

Embedding-Driven Diversity Sampling to Improve Few-Shot Synthetic Data Generation

Accurate classification of clinical text often requires fine-tuning pre-trained language models, a process that is costly and time-consuming due to the need for high-quality data and expert annotators. Synthetic data generation offers an alternative, though pre-trained models may not capture the syntactic diversity of clinical notes. We propose an embedding-driven approach that uses diversity sampling from a small set of real clinical notes to guide large language models in few-shot prompting, generating synthetic text that better reflects clinical syntax. We evaluated this method using the CheXpert dataset on a classification task, comparing it to random few-shot and zero-shot approaches. Using cosine similarity and a Turing test, our approach produced synthetic notes that more closely align with real clinical text. Our pipeline reduced the data needed to reach the 0.85 AUC cutoff by 40% for AUROC and 30% for AUPRC, while augmenting models with synthetic data improved AUROC by 57% and AUPRC by 68%. Additionally, our synthetic data was 0.9 times as effective as real data, a 60% improvement in value.

Diagnostic Reasoning Prompts Reveal the Potential for Large Language Model Interpretability in Medicine

One of the major barriers to using large language models (LLMs) in medicine is the perception they use uninterpretable methods to make clinical decisions that are inherently different from the cognitive processes of clinicians. In this manuscript we develop novel diagnostic reasoning prompts to study whether LLMs can perform clinical reasoning to accurately form a diagnosis. We find that GPT4 can be prompted to mimic the common clinical reasoning processes of clinicians without sacrificing diagnostic accuracy. This is significant because an LLM that can use clinical reasoning to provide an interpretable rationale offers physicians a means to evaluate whether LLMs can be trusted for patient care. Novel prompting methods have the potential to expose the black box of LLMs, bringing them one step closer to safe and effective use in medicine.