Lfng and Dll3 cooperate to modulate protein interactions in cis and coordinate oscillatory Notch pathway activation in the segmentation clock.

In mammalian development, oscillatory activation of Notch signaling is required for segmentation clock function during somitogenesis. Notch activity oscillations are synchronized between neighboring cells in the presomitic mesoderm (PSM) and have a period that matches the rate of somite formation. Normal clock function requires cyclic expression of the Lunatic fringe (LFNG) glycosyltransferase, as well as expression of the inhibitory Notch ligand Delta-like 3 (DLL3). How these factors coordinate Notch activation in the clock is not well understood. Recent evidence suggests that LFNG can act in a signal-sending cell to influence Notch activity in the clock, raising the possibility that in this context, glycosylation of Notch pathway proteins by LFNG may affect ligand activity. Here we dissect the genetic interactions of Lfng and Dll3 specifically in the segmentation clock and observe distinctions in the skeletal and clock phenotypes of mutant embryos showing that paradoxically, loss of Dll3 is associated with strong reductions in Notch activity in the caudal PSM. The patterns of Notch activity in the PSM suggest that the loss of Dll3 is epistatic to the loss of Lfng in the segmentation clock, and we present direct evidence for the modification of several DLL1 and DLL3 EGF-repeats by LFNG. We further demonstrate that DLL3 expression in cells co-expressing DLL1 and NOTCH1 can potentiate a cell's signal-sending activity and that this effect is modulated by LFNG, suggesting a mechanism for coordinated regulation of oscillatory Notch activation in the clock by glycosylation and cis-inhibition.

Transition From Pediatric to Adult Care for Individuals With Type 1 Diabetes: Opportunities and Challenges.

OBJECTIVES: Type 1 diabetes (T1D) is a chronic disease with patients across the age spectrum that has high potential for morbidity and mortality. Unfortunately, patients transitioning from pediatric to adult care continue to demonstrate worsened glycemic control in part due to lack of understanding of transition of care best practices. METHODS: This review highlights the impact of existing transition of care interventions, assessment tools, and other recently published strategies for providers to consider to improve care of adolescent and young adult (AYA) patients with T1D in both hospital- and clinic-based settings. RESULTS: Many barriers impact patients with T1D during the transition period and disparities by race, sex, insurance status, and comorbid illness persist. As diabetic care continues to evolve and the prevalence of adolescents and young adults living with T1D increases, an intentional approach to transition of care is more pressing than ever. While current literature on transition of care models is limited, many show promise in improving clinic attendance and decreasing hospitalization. There are critical discussions that providers should lead with AYA patients to improve their outcomes and increase diabetes self-management, such as re-addressing carbohydrate counseling, sleep hygiene, and reproductive planning. CONCLUSION: While further research on transition of care is needed, many care models offer the promise of improved T1D outcomes, enhancements in our approach to care, and increased value for our health care system at large.

The Evolution of Primary Care Telehealth Disparities During COVID-19: Retrospective Cohort Study.

BACKGROUND: Telehealth has become widely used as a novel way to provide outpatient care during the COVID-19 pandemic, but data about telehealth use in primary care remain limited. Studies in other specialties raise concerns that telehealth may be widening existing health care disparities, requiring further scrutiny of trends in telehealth use. OBJECTIVE: Our study aims to further characterize sociodemographic differences in primary care via telehealth compared to in-person office visits before and during the COVID-19 pandemic and determine if these disparities changed throughout 2020. METHODS: We conducted a retrospective cohort study in a large US academic center with 46 primary care practices from April-December 2019 to April-December 2020. Data were subdivided into calendar quarters and compared to determine evolving disparities throughout the year. We queried and compared billed outpatient encounters in General Internal Medicine and Family Medicine via binary logic mixed effects regression model and estimated odds ratios (ORs) with 95% CIs. We used sex, race, and ethnicity of the patient attending each encounter as fixed effects. We analyzed socioeconomic status of patients in the institution's primary county based on the patient's residence zip code. RESULTS: A total of 81,822 encounters in the pre-COVID-19 time frame and 47,994 encounters in the intra-COVID-19 time frame were analyzed; in the intra-COVID-19 time frame, a total of 5322 (11.1%) of encounters were telehealth encounters. Patients living in zip code areas with high utilization rate of supplemental nutrition assistance were less likely to use primary care in the intra-COVID-19 time frame (OR 0.94, 95% CI 0.90-0.98; P=.006). Encounters with the following patients were less likely to be via telehealth compared to in-person office visits: patients who self-identified as Asian (OR 0.74, 95% CI 0.63-0.86) and Nepali (OR 0.37, 95% CI 0.19-0.72), patients insured by Medicare (OR 0.77, 95% CI 0.68-0.88), and patients living in zip code areas with high utilization rate of supplemental nutrition assistance (OR 0.84, 95% CI 0.71-0.99). Many of these disparities persisted throughout the year. Although there was no statistically significant difference in telehealth use for patients insured by Medicaid throughout the whole year, subanalysis of quarter 4 found encounters with patients insured by Medicaid were less likely to be via telehealth (OR 0.73, 95% CI 0.55-0.97; P=.03). CONCLUSIONS: Telehealth was not used equally by all patients within primary care throughout the first year of the COVID-19 pandemic, specifically by patients who self-identified as Asian and Nepali, insured by Medicare, and living in zip code areas with low socioeconomic status. As the COVID-19 pandemic and telehealth infrastructure change, it is critical we continue to reassess the use of telehealth. Institutions should continue to monitor disparities in telehealth access and advocate for policy changes that may improve equity.

Patterns of Postpartum Primary Care Follow-up and Diabetes-Related Care After Diagnosis of Gestational Diabetes.

Importance: Gestational diabetes (GD) affects up to 10% of pregnancies and increases lifetime risk of type 2 diabetes 10-fold; postpartum diabetes evaluation and primary care follow-up are critical in preventing and detecting type 2 diabetes. Despite clinical guidelines recommending universal follow-up, little remains known about how often individuals with GD access primary care and type 2 diabetes screening. Objective: To describe patterns of primary care follow-up and diabetes-related care among individuals with and without GD in the first year post partum. Design, Setting, and Participants: This cohort study used a private insurance claims database to compare follow-up in the first year post partum between individuals with GD, type 2 diabetes, and no diabetes diagnosis. Participants included postpartum individuals aged 15 to 51 years who delivered between 2015 and 2018 and had continuous enrollment from 180 days before to 366 days after the delivery date. Data were analyzed September through October 2021 and reanalyzed November 2022. Main Outcomes and Measures: Primary care follow-up visits and diabetes-related care (blood glucose testing and diabetes-associated visit diagnoses) were determined by evaluation and management, Current Procedural Terminology, and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, respectively. Results: A total of 280 131 individuals were identified between 2015 and 2018 (mean age: 31 years; 95% CI, 27-34 years); 12 242 (4.4%) had preexisting type 2 diabetes and 18 432 (6.6%) had GD. A total of 50.9% (95% CI, 49.9%-52.0%) of individuals with GD had primary care follow-up, compared with 67.2% (95% CI, 66.2%-68.2%) of individuals with preexisting type 2 diabetes. A total of 36.2% (95% CI, 35.1%-37.4%) of individuals with GD had diabetes-related care compared with 56.9% (95% CI, 55.7%-58.0%) of individuals with preexisting diabetes. Only 36.0% (95% CI, 34.4%-37.6%) of individuals with GD connected with primary care received clinical guideline concordant care with blood glucose testing 12 weeks post partum. Conclusions and Relevance: In this cohort study of postpartum individuals, individuals with GD had lower rates of primary care and diabetes-related care compared with those with preexisting type 2 diabetes, and only 36% of those with GD received guideline-recommended blood glucose testing in the first 12 weeks post partum. This illustrates a missed opportunity for early intervention in diabetes surveillance and prevention and demonstrates the need to develop a multidisciplinary approach for postpartum follow-up.

Establishing a clinical informatics umbilical cord: lessons learned in launching infrastructure to support dyadic mother/infant primary care.

The Multimodal Maternal Infant Perinatal Outpatient Delivery System (MOMI PODS) was developed to facilitate the pregnancy to postpartum primary care transition, particularly for individuals at risk for severe maternal morbidity, via a unique multidisciplinary model of mother/infant dyadic primary care. Specialized clinical informatics platforms are critical to ensuring the feasibility and scalability of MOMI PODS and a smooth perinatal transition into longitudinal postpartum primary care. In this manuscript, we describe the MOMI PODS transition and management clinical informatics platforms developed to facilitate MOMI PODS referrals, scheduling, evidence-based multidisciplinary care, and program evaluation. We discuss opportunities and lessons learned associated with our applied methods, as advances in clinical informatics have considerable potential to enhance the quality and evaluation of innovative maternal health programs like MOMI PODS.

Patient Perceptions on Facilitating Follow-Up After Heart Failure Hospitalization.

BACKGROUND: Timely follow-up after hospitalization for heart failure (HF) is recommended. However, follow-up is suboptimal, especially in lower socioeconomic groups. Patient-centered solutions for facilitating follow-up post-HF hospitalization have not been extensively evaluated. METHODS AND RESULTS: Face-to-face surveys were conducted between 2015 and 2016 among 83 racially diverse adult patients (61% African American, 34% Caucasian, and 5% Other) hospitalized for HF at a university hospital centered in a low-income area of Columbus, Ohio. Patient perceptions of methods to facilitate follow-up post-HF hospitalization and likelihood of using interventions were investigated using a Likert scale: 1=very much to 5=not at all. Results were analyzed by Wilcoxon signed-rank test with Bonferroni correction. The response rate was 82%. The annual household income was <$35 000 for 49% of patients. An appointment near the patient's home was the most desired intervention (77%), followed by reminder message (73%), transportation to appointment (63%), and elimination of copayment (59%). Interventions most likely to be used if provided were similarly ranked: reminder message (48%), appointment near home (46%), elimination of copay (46%), and transportation to appointment (39%). There were significant differences (P=0.001) in high-ranking interventions related to location (appointment near home, transportation, home appointment) and reminder for visit compared with low-ranking interventions related to time (weekend appointment, appointment after 5 pm) and telemedicine. CONCLUSIONS: Among this cohort of racially diverse low-income patients hospitalized with HF, an appointment near the patient's home and a reminder message were the most desired interventions to facilitate follow-up. Further study of similar populations nationwide is warranted.