Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.

Importance: Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION). Objective: To investigate whether there is an association between semaglutide and risk of NAION. Design, Setting, and Participants: In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023. Exposures: Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight. Main Outcomes and Measures: Cumulative incidence and hazard ratio of NAION. Results: Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non-GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non-GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non-GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non-GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non-GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001). Conclusions and Relevance: This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.

Cumulated time to chart closure: a novel electronic health record-derived metric associated with clinician burnout.

Objective: We sought to determine whether average cumulated time to chart closure (CTCC), a novel construct to measure clinician workload burden, and electronic health record (EHR) measures were associated with a validated measure of burnout. Materials and methods: Physicians at a large academic institution participated in a well-being survey that was linked to their EHR use data. CTCC was defined as the average time from the start of patient encounters to chart closure over a set of encounters. Established EHR use measures including daily total time in the EHR (EHR-Time8), time in the EHR outside scheduled hours, work outside of work (WOW8), and time spent on inbox (IB-Time8) were calculated. We examined the relationship between CTCC, EHR use metrics, and burnout using descriptive statistics and adjusted logistic regression models. Results: We included data from 305 attendings, encompassing 242 432 ambulatory encounters (2021). Among them, 42% (128 physicians) experienced burnout. The median CTCC for all clinicians was 32.5 h. Unadjusted analyses revealed significant associations between CTCC, WOW8, IB-Time8, and burnout. In a final adjusted model, only CTCC remained statistically significant with an odds ratio estimate of 1.42 (95% CI, 1.00-2.01). Discussion: These results suggest that CTCC is predictive of burnout and that purely measuring duration of interaction with the EHR itself is not sufficient to capture burnout. Conclusion: Workload burden as manifested by average CTCC has the potential to be a practical, quantifiable measure that will allow for identification of clinicians at risk of burnout and to assess the success of interventions designed to address burnout.

Improving Assessment and Learning Environments for Graduate Medical Trainees to Advance Healthcare Language Equity.

Language-appropriate care is critical for equitable, high-quality health care, but educational standards to assure graduate medical trainees are prepared to give such care are lacking. Detailed guidance for graduate medical education is provided by the Accreditation Council for Graduate Medical Education through the following: (1) an assessment framework for competencies, subcompetencies, and milestones for trainees and (2) the Clinical Learning Environment Review (CLER) Pathways for assessment of trainees' learning environments. These tools do not include a robust framework to evaluate trainees' abilities to offer language-appropriate care. They also do not address the learning environment's potential to support such care. A multidisciplinary group of linguistic, medical, and educational experts drafted a new subcompetency with milestones and an expanded CLER Pathway to highlight the importance of equitable care for patients who prefer languages other than English. These resources offer residency and fellowship programs tools to guide assessment, curriculum development, and learning-environment improvements related to language-appropriate care. Recognizing that programs have unique needs and resources, we propose a range of initial actions to address language equity. A focus on language diversity in the learning environment can have a broad and lasting impact on care quality, patient safety, and health equity.

The Role of Epigenetics in Accelerated Aging: A Reconsideration of Later-Life Visual Loss After Early Optic Neuropathy.

BACKGROUND: In 2005, we reported 3 patients with bilateral optic nerve damage early in life. These patients had stable vision for decades but then experienced significant bilateral vision loss with no obvious cause. Our hypothesis, novel at that time, was that the late decline of vision was due to age-related attrition of retinal ganglion cells superimposed on a reduced neuronal population due to the earlier injury. EVIDENCE ACQUISITION: The field of epigenetics provides a new paradigm with which to consider the normal aging process and the impact of neuronal injury, which has been shown to accelerate aging. Late-in-life decline in function after early neuronal injury occurs in multiple sclerosis due to dysregulated inflammation and postpolio syndrome. Recent studies by our group in mice have also demonstrated the possibility of partial reversal of cellular aging and the potential to mitigate anatomical damage after injury and even improve visual function. RESULTS: The results in mice and nonhuman primates published elsewhere have shown enhanced neuronal survival and visual function after partial epigenetic reprogramming. CONCLUSIONS: Injury promotes epigenetic aging , and this finding can be observed in several clinically relevant scenarios. An understanding of the epigenetic mechanisms at play opens the opportunity to restore function in the nervous system and elsewhere with cellular rejuvenation therapies. Our earlier cases exemplify how reconsideration of previously established concepts can motivate inquiry of new paradigms.

Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma.

Glaucoma, a chronic neurodegenerative disease, is a leading cause of age-related blindness worldwide and characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Previously, we developed a novel epigenetic rejuvenation therapy, based on the expression of the three transcription factors Oct4, Sox2, and Klf4 (OSK), which safely rejuvenates RGCs without altering cell identity in glaucomatous and old mice after 1 month of treatment. In the current year-long study, mice with continuous or cyclic OSK expression induced after glaucoma-induced vision damage had occurred were tracked for efficacy, duration, and safety. Surprisingly, only 2 months of OSK fully restored impaired vision, with a restoration of vision for 11 months with prolonged expression. In RGCs, transcription from the doxycycline (DOX)-inducible Tet-On AAV system, returned to baseline 4 weeks after DOX withdrawal. Significant vision improvements remained for 1 month post switching off OSK, after which the vision benefit gradually diminished but remained better than baseline. Notably, no adverse effects on retinal structure or body weight were observed in glaucomatous mice with OSK continuously expressed for 21 months providing compelling evidence of efficacy and safety. This work highlights the tremendous therapeutic potential of rejuvenating gene therapies using OSK, not only for glaucoma but also for other ocular and systemic injuries and age-related diseases.

Patient and Clinician Satisfaction With Shared Medical Appointments for Glaucoma.

Shared Medical Appointments (SMAs) are patient-centered care tools designed to administer patient counseling and education, typically delivered individually, in a group setting. SMAs are effective in facilitating peer-learning, resulting in improvement in knowledge and health behavior. This study aimed to implement what we know of as the first ophthalmology SMA done in the United States. We evaluated the implementation feasibility, patient and provider experience, changes in patient knowledge, and provider stress. Five glaucoma patients who expressed issues with adherence during their clinic visit at Boston Medical Center (BMC) who were interested in the SMA were recruited. Patients and staff had a positive experience with the SMA. There was a marked increase in patient glaucoma knowledge and a decrease in average staff member stress level score during the SMA. From all standpoints, including billing and management, we conclude that SMA implementation is feasible in ophthalmology departments in academic settings.

Deletion of translin (Tsn) induces robust adiposity and hepatic steatosis without impairing glucose tolerance.

OBJECTIVE: Translin knockout (KO) mice display robust adiposity. Recent studies indicate that translin and its partner protein, trax, regulate the microRNA and ATM kinase signaling pathways, both of which have been implicated in regulating metabolism. In the course of characterizing the metabolic profile of these mice, we found that they display normal glucose tolerance despite their elevated adiposity. Accordingly, we investigated why translin KO mice display this paradoxical phenotype. METHODS: To help distinguish between the metabolic effects of increased adiposity and those of translin deletion per se, we compared three groups: (1) wild-type (WT), (2) translin KO mice on a standard chow diet, and (3) adiposity-matched WT mice that were placed on a high-fat diet until they matched translin KO adiposity levels. All groups were scanned to determine their body composition and tested to evaluate their glucose and insulin tolerance. Plasma, hepatic, and adipose tissue samples were collected and used for histological and molecular analyses. RESULTS: Translin KO mice show normal glucose tolerance whereas adiposity-matched WT mice, placed on a high-fat diet, do not. In addition, translin KO mice display prominent hepatic steatosis that is more severe than that of adiposity-matched WT mice. Unlike adiposity-matched WT mice, translin KO mice display three key features that have been shown to reduce susceptibility to insulin resistance: increased accumulation of subcutaneous fat, increased levels of circulating adiponectin, and decreased Tnfα expression in hepatic and adipose tissue. CONCLUSIONS: The ability of translin KO mice to retain normal glucose tolerance in the face of marked adipose tissue expansion may be due to the three protective factors noted above. Further studies aimed at defining the molecular bases for this combination of protective phenotypes may yield new approaches to limit the adverse metabolic consequences of obesity.