RESUMO
Background: Hospitalized pediatric patients and their caregivers often experience anxiety and fear, resulting in withdrawal and aggression. Despite virtual reality (VR) being a safe and effective anxiolytic, it is unknown what software design aspects contribute to its effectiveness. This prospective observational study evaluated which VR application elements increased awe, which is correlated with improved behavior and satisfaction. Methods: Patients aged 6 to 25 years and their caregivers at an academic pediatric hospital interacted with a custom VR application that compared design aspects, including environment, graphics fidelity, and presence of a motivational character. Outcomes investigated self-reported awe, vastness, accommodation, and engagement. Data were analyzed using repeated measure ANOVA tests and correlation analyses. Results: A total of 202 participants were enrolled, and 179 (88 pediatric patients, 91 adult caregivers) were included in the final analysis. A fictional environment was more effective at increasing awe in pediatric patients (P = 0.030) compared with a realistic environment. However, increased graphics fidelity was more effective at increasing awe in caregiver adults (P = 0.023) compared with low resolution graphics. Presence of a motivational character did not influence awe in either patients or caregivers (P = 0.432, P = 0.904, respectively). All measures of awe were positively correlated with application engagement (P < 0.005). Conclusion: In conclusion, when software developers design VR software for pediatric patients and their caregivers, fictional settings and increased graphic fidelity should be considered for pediatric patients and adults, respectively. Future studies will explore other VR elements in gameplay settings.
RESUMO
Background: SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials. Methods: Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis. Findings: Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]). Interpretation: In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD. Funding: National Institutes of Health, United States Department of Veterans Affairs.