TY  - JOUR
AU  - Hama, Tuankasfee
AU  - Alsaleh, Mohanad M
AU  - Allery, Freya
AU  - Choi, Jung Won
AU  - Tomlinson, Christopher
AU  - Wu, Honghan
AU  - Lai, Alvina
AU  - Pontikos, Nikolas
AU  - Thygesen, Johan H
PY  - 2025
DA  - 2025/3/18
TI  - Enhancing Patient Outcome Prediction Through Deep Learning With Sequential Diagnosis Codes From Structured Electronic Health Record Data: Systematic Review
JO  - J Med Internet Res
SP  - e57358
VL  - 27
KW  - deep learning
KW  - electronic health records
KW  - EHR
KW  - diagnosis codes
KW  - prediction
KW  - patient outcomes
KW  - systematic review
AB  - Background: The use of structured electronic health records in health care systems has grown rapidly. These systems collect huge amounts of patient information, including diagnosis codes representing temporal medical history. Sequential diagnostic information has proven valuable for predicting patient outcomes. However, the extent to which these types of data have been incorporated into deep learning (DL) models has not been examined. Objective: This systematic review aims to describe the use of sequential diagnostic data in DL models, specifically to understand how these data are integrated, whether sample size improves performance, and whether the identified models are generalizable. Methods: Relevant studies published up to May 15, 2023, were identified using 4 databases: PubMed, Embase, IEEE Xplore, and Web of Science. We included all studies using DL algorithms trained on sequential diagnosis codes to predict patient outcomes. We excluded review articles and non–peer-reviewed papers. We evaluated the following aspects in the included papers: DL techniques, characteristics of the dataset, prediction tasks, performance evaluation, generalizability, and explainability. We also assessed the risk of bias and applicability of the studies using the Prediction Model Study Risk of Bias Assessment Tool (PROBAST). We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist to report our findings. Results: Of the 740 identified papers, 84 (11.4%) met the eligibility criteria. Publications in this area increased yearly. Recurrent neural networks (and their derivatives; 47/84, 56%) and transformers (22/84, 26%) were the most commonly used architectures in DL-based models. Most studies (45/84, 54%) presented their input features as sequences of visit embeddings. Medications (38/84, 45%) were the most common additional feature. Of the 128 predictive outcome tasks, the most frequent was next-visit diagnosis (n=30, 23%), followed by heart failure (n=18, 14%) and mortality (n=17, 13%). Only 7 (8%) of the 84 studies evaluated their models in terms of generalizability. A positive correlation was observed between training sample size and model performance (area under the receiver operating characteristic curve; P=.02). However, 59 (70%) of the 84 studies had a high risk of bias. Conclusions: The application of DL for advanced modeling of sequential medical codes has demonstrated remarkable promise in predicting patient outcomes. The main limitation of this study was the heterogeneity of methods and outcomes. However, our analysis found that using multiple types of features, integrating time intervals, and including larger sample sizes were generally related to an improved predictive performance. This review also highlights that very few studies (7/84, 8%) reported on challenges related to generalizability and less than half (38/84, 45%) of the studies reported on challenges related to explainability. Addressing these shortcomings will be instrumental in unlocking the full potential of DL for enhancing health care outcomes and patient care. Trial Registration: PROSPERO CRD42018112161; https://tinyurl.com/yc6h9rwu 
SN  - 1438-8871
UR  - https://www.jmir.org/2025/1/e57358
UR  - https://doi.org/10.2196/57358
DO  - 10.2196/57358
ID  - info:doi/10.2196/57358
ER  -