Impact of Visit Volume on the Effectiveness of Electronic Tools to Improve Heart Failure Care.

BACKGROUND: Electronic health record (EHR) tools can improve prescribing of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), but their effectiveness may vary by physician workload. OBJECTIVES: This paper aims to assess whether physician workload modifies the effectiveness of EHR tools for HFrEF. METHODS: This was a prespecified subgroup analysis of the BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) cluster-randomized trial, which compared effectiveness of an alert vs message vs usual care on prescribing of mineralocorticoid antagonists (MRAs). The trial included adults with HFrEF seen in cardiology offices who were eligible for and not prescribed MRAs. Visit volume was defined at the cardiologist-level as number of visits per 6-month study period (high = upper tertile vs non-high = remaining). Analysis at the patient-level used likelihood ratio test for interaction with log-binomial models. RESULTS: Among 2,211 patients seen by 174 cardiologists, 932 (42.2%) were seen by high-volume cardiologists (median: 1,853; Q1-Q3: 1,637-2,225 visits/6 mo; and median: 10; Q1-Q3: 9-12 visits/half-day). MRA was prescribed to 5.5% in the high-volume vs 14.8% in the non-high-volume groups in the usual care arm, 10.3% vs 19.6% in the message arm, and 31.2% vs 28.2% in the alert arm, respectively. Visit volume modified treatment effect (P for interaction = 0.02) such that the alert was more effective in the high-volume group (relative risk: 5.16; 95% CI: 2.57-10.4) than the non-high-volume group (relative risk: 1.93; 95% CI: 1.29-2.90). CONCLUSIONS: An EHR-embedded alert increased prescribing by >5-fold among patients seen by high-volume cardiologists. Our findings support use of EHR alerts, especially in busy practice settings. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure [BETTER CARE-HF]; NCT05275920).

Cluster-Randomized Trial Comparing Ambulatory Decision Support Tools to Improve Heart Failure Care.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are underprescribed for patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study sought to compare effectiveness of 2 automated, electronic health record-embedded tools vs usual care on MRA prescribing in eligible patients with HFrEF. METHODS: BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) was a 3-arm, pragmatic, cluster-randomized trial comparing the effectiveness of an alert during individual patient encounters vs a message about multiple patients between encounters vs usual care on MRA prescribing. This study included adult patients with HFrEF, no active MRA prescription, no contraindication to MRAs, and an outpatient cardiologist in a large health system. Patients were cluster-randomized by cardiologist (60 per arm). RESULTS: The study included 2,211 patients (alert: 755, message: 812, usual care [control]: 644), with average age 72.2 years, average ejection fraction 33%, who were predominantly male (71.4%) and White (68.9%). New MRA prescribing occurred in 29.6% of patients in the alert arm, 15.6% in the message arm, and 11.7% in the control arm. The alert more than doubled MRA prescribing compared to usual care (relative risk: 2.53; 95% CI: 1.77-3.62; P < 0.0001) and improved MRA prescribing compared to the message (relative risk: 1.67; 95% CI: 1.21-2.29; P = 0.002). The number of patients with alert needed to result in an additional MRA prescription was 5.6. CONCLUSIONS: An automated, patient-specific, electronic health record-embedded alert increased MRA prescribing compared to both a message and usual care. These findings highlight the potential for electronic health record-embedded tools to substantially increase prescription of life-saving therapies for HFrEF. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations-Heart Failure [BETTER CARE-HF]; NCT05275920).

DeepVelo: Single-cell transcriptomic deep velocity field learning with neural ordinary differential equations.

Recent advances in single-cell sequencing technologies have provided unprecedented opportunities to measure the gene expression profile and RNA velocity of individual cells. However, modeling transcriptional dynamics is computationally challenging because of the high-dimensional, sparse nature of the single-cell gene expression measurements and the nonlinear regulatory relationships. Here, we present DeepVelo, a neural network-based ordinary differential equation that can model complex transcriptome dynamics by describing continuous-time gene expression changes within individual cells. We apply DeepVelo to public datasets from different sequencing platforms to (i) formulate transcriptome dynamics on different time scales, (ii) measure the instability of cell states, and (iii) identify developmental driver genes via perturbation analysis. Benchmarking against the state-of-the-art methods shows that DeepVelo can learn a more accurate representation of the velocity field. Furthermore, our perturbation studies reveal that single-cell dynamical systems could exhibit chaotic properties. In summary, DeepVelo allows data-driven discoveries of differential equations that delineate single-cell transcriptome dynamics.

The Effect of Body Mass Index on Pelvic Floor Support 1 Year Postpartum.

Elevated body mass index (BMI) is associated with the incidence, prevalence, and progression of pelvic organ prolapse (POP). This study investigated the effect of peripartum BMI on pelvic floor support 1 year postpartum (PP1y). One hundred eight nulliparous women had their BMI recorded and underwent POP assessments using the Pelvic Organ Prolapse Quantification System at baseline, third trimester (36th to 38th week of pregnancy [G36-38w]), and PP1y. Pelvic organ prolapse was defined as ≥stage II. Women gained on average 1.9 kg between baseline and PP1y. After adjustment, increasing BMI PP1y was associated with increasing anterior wall descent (P < .0001) and higher odds of having POP PP1y (odds ratio: 1.41, 95% confidence interval: 1.01-1.97, P = .045). Trial of labor compared to unlabored cesarean delivery, POP G36-38w, and decreased fetal weight were independently associated with anterior vaginal wall laxity PP1y. Our finding suggests that postpartum BMI influences pelvic floor laxity 1 year after delivery. Postpartum weight reduction may serve as a strategy for POP prevention in some women.

Interferon-gamma inhibits cell cycle exit in differentiating oligodendrocyte progenitor cells.

The developmental processes of the oligodendrocyte progenitor cell (OPC) lineage that are targeted by interferon-gamma (IFN-gamma) were studied in primary rat OPC cultures. Under conditions of thyroid hormone-mediated oligodendrocyte differentiation, IFN-gamma produced a dose-dependent apoptotic response in OPCs. The lowest dose tested (15 ng/ml or 75 U/ml) was nonapoptotic, but activated detectable STAT1 DNA-binding. At this dose, IFN-gamma reduced the percentage of mature O1+ cells and increased the percentage of immature A2B5+ OPCs. This was observed without significant change in total cell number and cytotoxicity, and was accompanied by an increase in BrdU-labeled A2B5+ and O4+ cells. FACS analysis confirmed a lack of apoptotic sub-G1 cells and revealed a greater percentage of S- and G2/M-phase OPCs with IFN-gamma treatment. Dual immunostaining with Ki-67 and Olig2 showed a smaller percentage of Olig2+ cells in G0 phase in IFN-gamma-treated OPCs, indicating loss of G1 control. Instead, increased levels and phosphorylation of the checkpoint protein p34cdc2 by IFN- suggested increased partial arrest in G2. IFN-gamma not only sustained expression of PCNA and the G1-S regulators retinoblastoma protein, cyclin D1, cyclin E, and cdk2, but also decreased p27 levels. In addition to changes in cell proliferation and differentiation, IFN-gamma attenuated myelin basic protein (MBP) expression significantly, which was associated with decreased expression of both MBP and Sox10 RNAs. These findings indicate that IFN-gamma not only maintains cell cycle activity that could predispose OPCs to apoptosis, but also overrides G1-G0 signals leading to thyroid hormone-mediated terminal differentiation and myelin gene expression.