Citations

Abstract Background Sepsis is a life-threatening condition in which delayed recognition and treatment are associated with increased mortality. While predictive models such as Epic’s Early Detection of Sepsis Model (ESM) were developed to support early intervention, their real-world impact after integration into clinical workflows remains difficult to evaluate. Objectives To evaluate the real-world impact of ESM integrated into clinical workflow on clinical outcomes, antibiotic use, and harm-benefit tradeoffs. Methods We conducted a quasi-experimental study in a single healthcare system using encounter-level data from inpatient settings. Inpatient mortality, prolonged hospitalization, antibiotic use, and sepsis prevalence were compared between the pre-implementation period (3 June 2023 to 20 August 2024) and the online period (21 August 2024 to 26 December 2024) when the model became visible to clinicians. We also applied a counterfactual framework using models trained on pre-implementation data to estimate expected outcomes without ESM and to quantify harms related to overtreatment and delayed treatment. Results Among 101,138 encounters, 86,884 occurred during the pre-implementation period and 14,254 during the online period. In unadjusted analyses, the online period had lower inpatient mortality, prolonged hospitalization, antibiotic use, and sepsis prevalence (all p≤0.002). In the counterfactual analyses, observed outcomes were lower than expected without ESM for mortality (1.21% vs 1.82%; p<0.001), prolonged hospitalization (5.56% vs 7.95%; p<0.001), and antibiotic use (43.52% vs 47.04%; p<0.001). False positive harm (37.72% vs 41.68%; p<0.001) was also lower than expected. Conclusions Integration of ESM into clinical workflow was associated with improved patient outcomes, reduced antibiotic use, and decreased harm from overtreatment, without evidence of increased harm from delayed treatment, supporting a positive net clinical benefit and the safety and effectiveness of ESM under Software as a Medical Device principles.

Abstract Introduction: Gastrin release from G cells stimulates cholecystokinin (CCK2) receptors throughout the body, most of which promote gastric acid secretion. However, gastrin also stimulates CCK2 receptors located elsewhere, including the islet of the pancreas. In turn, gastrin increases insulin secretion1. Gastrin also promotes pancreatic β cell neogenesis and replication. Proton pump inhibitors (PPIs) decrease the pH of the stomach and stimulate gastrin secretion, which may indirectly promote insulin secretion and improve hemoglobin A1c (HbA1c). Objective: To understand the effect of PPIs on insulin-glucose homeostasis (c-peptide, HbA1c, and glucose) in patients with type 2 diabetes mellitus (T2DM). Methodology: We retrospectively reviewed the charts of patients with T2DM at least 18 years of age who received care at AnMed Health facilities from Jan. 1, 2018 through Dec. 31, 2018 to compare HbA1c, C-peptide, and glucose levels in patients with and without active PPI therapy. Slicer-dicer software was used to identify study population with diagnosis of T2DM and labs including both HbA1c and C-peptide. Out of total 215 patients satisfying inclusion criteria, 71 patients were on PPI. Statistical analyses were performed using SPSS version 20.0 (SPSS, Armonk, NY: IBM Corp). All values are presented as means ± SD. A p value of &lt; 0.05 was considered to be significant. Independent T-test and chi-square test were performed to compare parameters in between groups. Results: The PPI and non-PPI groups had no statistical difference regarding age, sex, race and BMI. There was no significant difference in HbA1c levels between PPI and non-PPI groups (8.6% ± 2.1 vs 8.3% ± 2.0, respectively; p value = 0.37). However, we found a significant increase in C-peptide levels (3.1 ng/mL ± 2.4 vs 2.4 ng/mL ± 2.3; p value = 0.037) and decrease in LDL levels (79.6 mg/dL ± 34.0 vs 89.73 mg/dL ± 32.9; p value = 0.046) in the PPI group compared to non-PPI group. In addition, there was a significantly greater prevalence of coronary artery disease in the PPI group (p = 0.01). Conclusion: PPI therapy in patients with T2DM was not associated with improved glycemic control. However, C-peptide levels were significantly higher in patients with T2DM who were on PPI therapy suggesting higher insulin secretion. The lack of difference in HbA1c levels may be a result of aggressive diabetic management by treating clinicians to achieve similar goal HbA1c in both groups. Further research is needed to understand the gastrin pathway as a potential option for improving glycemic control. References: 1. Rehfeld JF. Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides. Acta Physiol (Oxf). 2011 Apr;201(4):405–11.

AbstractMotivation: A central problem in biomarker discovery from large-scale gene expression or single nucleotide polymorphism (SNP) data is the computational challenge of taking into account the dependence among all the features. Methods that ignore the dependence usually identify non-reproducible biomarkers across independent datasets. We introduce a new graph-based semi-supervised feature classification algorithm to identify discriminative disease markers by learning on bipartite graphs. Our algorithm directly classifies the feature nodes in a bipartite graph as positive, negative or neutral with network propagation to capture the dependence among both samples and features (clinical and genetic variables) by exploring bi-cluster structures in a graph. Two features of our algorithm are: (1) our algorithm can find a global optimal labeling to capture the dependence among all the features and thus, generates highly reproducible results across independent microarray or other high-thoughput datasets, (2) our algorithm is capable of handling hundreds of thousands of features and thus, is particularly useful for biomarker identification from high-throughput gene expression and SNP data. In addition, although designed for classifying features, our algorithm can also simultaneously classify test samples for disease prognosis/diagnosis.Results: We applied the network propagation algorithm to study three large-scale breast cancer datasets. Our algorithm achieved competitive classification performance compared with SVMs and other baseline methods, and identified several markers with clinical or biological relevance with the disease. More importantly, our algorithm also identified highly reproducible marker genes and enriched functions from the independent datasets.Availability: Supplementary results and source code are available at http://compbio.cs.umn.edu/Feature_Class.Contact: kuang@cs.umn.eduSupplementary information: Supplementary data are available at Bioinformatics online.