Large language models (LLMs) hold significant promise in clinical practice, yet their real-world adoption is constrained by their propensity to produce erroneous and occasionally harmful outputs, particularly in the intricate domain of rare diseases (RDs). This study introduces RDguru, a conversational intelligent agent leveraging the LangChain framework and powered by GPT-3.5-turbo. RDguru offers a comprehensive suite of functionalities, encompassing evidence-traceable knowledge Q&A and professional medical consultations for differential diagnosis (DDX), integrating authoritative knowledge sources and reliable tools. A novel multi-source fusion diagnostic model, rooted in deep Q-network, amalgamates three diagnostic recommendation strategies (GPT-4, PheLR, and phenotype matching) to enhance diagnostic recall during medical consultations. Through tailored tools and advanced algorithms for retrieval-augmented generation, RDguru excels in knowledge Q&A, automated phenotype annotation, and RD DDX. A multi-aspect Q&A analysis demonstrates RDguru outperforms ChatGPT in generating descriptions aligned with authoritative knowledge, quantified by ROUGE scores, GPT-4-based automatic rating, and RAGAs evaluation metrics. Testing on 238 published RD cases reveals that RDguru's top 5 multi-source fusion diagnoses recapture 63.87% of actual diagnoses, marking a 5.47% improvement over the state-of-the-art diagnostic method PheLR. Furthermore, RDguru's consultation strategy proves effective in eliciting diagnostically beneficial phenotypes and refining the prioritization of genuine diagnoses through multi-round phenotype-orient questioning. Evaluations against established benchmarks and real-world patient data demonstrate RDguru's efficacy and reliability, highlighting its potential to enhance clinical decision-making in the realm of RDs.

Phenotype-based prioritization of candidate genes and diseases has become a well-established approach for multi-omics diagnostics of rare diseases. Most current algorithms exploit semantic analysis and probabilistic statistics based on Human Phenotype Ontology and are commonly superior to naive search methods. However, these algorithms are mostly less interpretable and do not perform well in real clinical scenarios due to noise and imprecision of query terms, and the fact that individuals may not display all phenotypes of the disease they belong to. We present a Phenotype-driven Likelihood Ratio analysis approach (PheLR) assisting interpretable clinical diagnosis of rare diseases. With a likelihood ratio paradigm, PheLR estimates the posterior probability of candidate diseases and how much a phenotypic feature contributes to the prioritization result. Benchmarked using simulated and realistic patients, PheLR shows significant advantages over current approaches and is robust to noise and inaccuracy. To facilitate clinical practice and visualized differential diagnosis, PheLR is implemented as an online web tool (https://phelr.nbscn.org).

OBJECTIVE: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery, and the early detection of AKI may allow for timely preventive or therapeutic measures. However, current AKI prediction researches pay less attention to time information among time-series clinical data and model building strategies that meet complex clinical application scenario. This study aims to develop and validate a model for predicting postoperative AKI that operates sequentially over individual time-series clinical data. MATERIALS AND METHODS: A retrospective cohort of 3386 pediatric patients extracted from PIC database was used for training, calibrating, and testing purposes. A time-aware deep learning model was developed and evaluated from 3 clinical perspectives that use different data collection windows and prediction windows to answer different AKI prediction questions encountered in clinical practice. We compared our model with existing state-of-the-art models from 3 clinical perspectives using the area under the receiver operating characteristic curve (ROC AUC) and the area under the precision-recall curve (PR AUC). RESULTS: Our proposed model significantly outperformed the existing state-of-the-art models with an improved average performance for any AKI prediction from the 3 evaluation perspectives. This model predicted 91% of all AKI episodes using data collected at 24 h after surgery, resulting in a ROC AUC of 0.908 and a PR AUC of 0.898. On average, our model predicted 83% of all AKI episodes that occurred within the different time windows in the 3 evaluation perspectives. The calibration performance of the proposed model was substantially higher than the existing state-of-the-art models. CONCLUSIONS: This study showed that a deep learning model can accurately predict postoperative AKI using perioperative time-series data. It has the potential to be integrated into real-time clinical decision support systems to support postoperative care planning.

Machine learning (ML) is increasingly applied to Electronic Health Records (EHRs) to solve clinical prediction tasks. Although many ML models perform promisingly, issues with model transparency and interpretability limit their adoption in clinical practice. Directly using existing explainable ML techniques in clinical settings can be challenging. Through literature surveys and collaborations with six clinicians with an average of 17 years of clinical experience, we identified three key challenges, including clinicians' unfamiliarity with ML features, lack of contextual information, and the need for cohort-level evidence. Following an iterative design process, we further designed and developed VBridge, a visual analytics tool that seamlessly incorporates ML explanations into clinicians' decision-making workflow. The system includes a novel hierarchical display of contribution-based feature explanations and enriched interactions that connect the dots between ML features, explanations, and data. We demonstrated the effectiveness of VBridge through two case studies and expert interviews with four clinicians, showing that visually associating model explanations with patients' situational records can help clinicians better interpret and use model predictions when making clinician decisions. We further derived a list of design implications for developing future explainable ML tools to support clinical decision-making.

Clinical pathways leave traces, described as event sequences with regard to a mixture of various latent treatment behaviors. Measuring similarities between patient traces can profitably be exploited further as a basis for providing insights into the pathways, and complementing existing techniques of clinical pathway analysis (CPA), which mainly focus on looking at aggregated data seen from an external perspective. Most existing methods measure similarities between patient traces via computing the relative distance between their event sequences. However, clinical pathways, as typical human-centered processes, always take place in an unstructured fashion, i.e., clinical events occur arbitrarily without a particular order. Bringing order in the chaos of clinical pathways may decline the accuracy of similarity measure between patient traces, and may distort the efficiency of further analysis tasks. In this paper, we present a behavioral topic analysis approach to measure similarities between patient traces. More specifically, a probabilistic graphical model, i.e., latent Dirichlet allocation (LDA), is employed to discover latent treatment behaviors of patient traces for clinical pathways such that similarities of pairwise patient traces can be measured based on their underlying behavioral topical features. The presented method provides a basis for further applications in CPA. In particular, three possible applications are introduced in this paper, i.e., patient trace retrieval, clustering, and anomaly detection. The proposed approach and the presented applications are evaluated via a real-world dataset of several specific clinical pathways collected from a Chinese hospital.