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Introduction Studies have reported that antidiabetic medications (ADMs) were associated with lower risk of dementia, but current findings are inconsistent. This study compared the risk of dementia onset in patients with type 2 diabetes (T2D) treated with sulfonylurea (SU) or thiazolidinedione (TZD) to patients with T2D treated with metformin (MET). Research design and methods This is a prospective observational study within a T2D population using electronic medical records from all sites of the Veterans Affairs Healthcare System. Patients with T2D who initiated ADM from January 1, 2001, to December 31, 2017, were aged ≥60 years at the initiation, and were dementia-free were identified. A SU monotherapy group, a TZD monotherapy group, and a control group (MET monotherapy) were assembled based on prescription records. Participants were required to take the assigned treatment for at least 1 year. The primary outcome was all-cause dementia, and the two secondary outcomes were Alzheimer’s disease and vascular dementia, defined by International Classification of Diseases (ICD), 9th Revision, or ICD, 10th Revision, codes. The risks of developing outcomes were compared using propensity score weighted Cox proportional hazard models. Results Among 559 106 eligible veterans (mean age 65.7 (SD 8.7) years), the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15). Conclusions Among patients with T2D, TZD use was associated with a lower risk of dementia, and SU use was associated with a higher risk compared with MET use. Supplementing SU with either MET or TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia.
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Evaluation of Sepsis Prediction Models before Onset of Treatment
BACKGROUND Timely interventions, such as antibiotics and intravenous fluids, have been associated with reduced mortality in patients with sepsis. Artificial intelligence (AI) models that accurately predict risk of sepsis onset could speed the delivery of these interventions. Although sepsis models generally aim to predict its onset, clinicians might recognize and treat sepsis before the sepsis definition is met. Predictions occurring after sepsis is clinically recognized (i.e., after treatment begins) may be of limited utility. Researchers have not previously investigated the accuracy of sepsis risk predictions that are made before treatment begins. Thus, we evaluate the discriminative performance of AI sepsis predictions made throughout a hospitalization relative to the time of treatment. METHODS We used a large retrospective inpatient cohort from the University of Michigan’s academic medical center (2018–2020) to evaluate the Epic sepsis model (ESM). The ability of the model to predict sepsis, both before sepsis criteria are met and before indications of treatment plans for sepsis, was evaluated in terms of the area under the receiver operating characteristic curve (AUROC). Indicators of a treatment plan were identified through electronic data capture and included the receipt of antibiotics, fluids, blood culture, and/or lactate measurement. The definition of sepsis was a composite of the Centers for Disease Control and Prevention’s surveillance criteria and the severe sepsis and septic shock management bundle definition. RESULTS The study included 77,582 hospitalizations. Sepsis occurred in 3766 hospitalizations (4.9%). ESM achieved an AUROC of 0.62 (95% confidence interval [CI], 0.61 to 0.63) when including predictions before sepsis criteria were met and in some cases, after clinical recognition. When excluding predictions after clinical recognition, the AUROC dropped to 0.47 (95% CI, 0.46 to 0.48). CONCLUSIONS We evaluate a sepsis risk prediction model to measure its ability to predict sepsis before clinical recognition. Our work has important implications for future work in model development and evaluation, with the goal of maximizing the clinical utility of these models. (Funded by Cisco Research and others.)
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- Award ID(s):
- 2124127
- PAR ID:
- 10522981
- Publisher / Repository:
- Massachusetts Medical Society
- Date Published:
- Journal Name:
- NEJM AI
- Volume:
- 1
- Issue:
- 3
- ISSN:
- 2836-9386
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1056/AIoa2300032
