Purpose: This study describes the implementation of an electronic medical record (EMR)-based initiative aimed at reducing the number of patients with glaucoma-related diagnoses lost to follow-up (LTF) and reviews its short-term outcomes.Design: Retrospective, comparative case series.Participants: Patients with glaucoma-related diagnoses seen 1 year prior at the Lahey Medical Center and who had not returned within the 6-month period between January 1, 2020, and June 30, 2020, which spanned the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic in the United States.Methods: An EMR-based tool was designed to identify patients suspected of being LTF with glaucomarelated diagnoses. Providers were enlisted to review the EMR for each of these patients and re-engage them, as appropriate. One month later, the initiative was evaluated by means of a retrospective chart review. Binary logistic regression analysis was used to identify demographic, clinical, and sociomedical factors associated with being LTF.Main Outcome Measures: Patients who completed a telemedicine or in-person appointment, or had a future scheduled or ordered return appointment, were considered re-engaged.Results: Of the 3551 patients seen during the study period, 384 patients were identified as LTF (11%), with 60 identifying COVID-19 as the reason for canceling their visit (16%). Patients who lived farther from the eye clinic (P < 0.001) or who had a history of canceling or missing an appointment (P < 0.001) were more likely to be LTF. Patients with open-angle glaucoma (P ¼ 0.042) or who had completed a visual field (P < 0.001) or ophthalmic imaging (P < 0.001) within the past year were less likely to be LTF. One month after the re-engagement initiative, 124 LTF patients (32%) had been re-engaged (40% through telemedicine), 238 patients (62%) had future scheduling orders in place, and 22 patients (6%) had no active plan for future follow-up.Conclusions: An EMR-based tool is an effective method for identifying patients at risk of being LTF and provides an opportunity for providers to recall and re-engage patients. Use of telemedicine to recontact LTF patients shows promise of improving the management of glaucoma, enhancing clinical productivity, and documenting treatment plans, thereby potentially reducing medicolegal liability. Ophthalmology

In this study, it has been demonstrated that administration of CV has a therapeutic potential on CIA. The data suggest that CV could have a potential role in the treatment of RA patients.

Purpose We conducted a cross-sectional study to assess the utilization of a tele-ophthalmology screening program in a low-risk, suburban population of patients with diabetes. Methods A total of 214 diabetic patients without previously documented diabetic retinopathy (DR) underwent point-of-care non-mydriatic fundus photography through their primary care providers at five Beth Israel Lahey Health locations. The characteristics of the patients who received remote screening were compared with those patients who were eligible for screening but did not take part in the program. Time-driven activity-based costing (TDABC) was implemented to examine the cost of screening by tele-ophthalmology compared with in-person examinations. Results Tele-ophthalmology screening was more likely to be provided for patients who were younger (OR 0.985; 95% CI 0.973–0.997, p =0.016), who were obese (OR 2.04; 95% CI: 1.47–2.84, p =0.008), who had an HbA1c above 8.0% (OR 1.60; 95% CI: 1.13–2.26, p =0.031), or who had an eye examination in the past year (OR 5.55; 95% CI: 3.89–7.92, p <0.001). Those patients newly diagnosed with DR because of the program were more likely to have diabetic nephropathy (OR 7.79; 95% CI: 1.73–35.05, p =0.007). TDABC identified a health system cost-savings of between $8 and $29 per patient screened by tele-ophthalmology compared with the cost of in-person eye examinations. Conclusion Tele-ophthalmology presents an opportunity to reduce the costs of screening patients without prior evidence of DR, especially those who have completed a comprehensive eye examination within the prior year.

The COVID-19 pandemic had a disproportionate impact on patients from racial and/or ethnic minority groups, causing many to delay healthcare. This study evaluates the role telehealth visits played in helping patients with diabetes mellitus (DM) return for subsequent, in-person eye examinations after the outbreak of COVID-19. Methods: This retrospective, cross-sectional study analyzed 8147 patients with DM who had completed an outpatient ophthalmology and/or optometry visit in 2019 and who were due for return evaluation after the outbreak of COVID-19 in 2020. Factors associated with return for subsequent, in-person eye examination were assessed. Results: The mean age of patients was 68.8 (±13.0) years, and 42% were women. 7.4% of patients identified as Asian; 2.9% as Black; 3.4% as Hispanic or Latin American; 0.92%, as more than one race; 1.78%, as other races; and 80.7% as White. Patients from racial and/or ethnic minority groups completed fewer in-person eye examinations after the outbreak of COVID-19 compared with White patients (35.6% versus 44.5%, χ 2 =36.172, P<0.001). However, both groups accessed telehealth services at a similar rate during this period (21.1% versus 21.9%, χ 2 =0.417, P=0.518). Importantly, patients who received telehealth services returned for subsequent, inperson eye examinations at substantially higher rates, regardless of race (51.0% and 46.6%, respectively, χ 2 =1.840, P=0.175). This offset the otherwise lower rate of return experienced by patients from racial and/or ethnic minority groups compared with White patients among the group of patients who did not receive any telehealth services (32.7% versus 42.7%, χ 2 =36.582, P<0.001). The impact of telehealth on the likelihood of in-person return remained significant after taking into account age, gender, race, language, residence, severity of diabetic retinopathy (DR), and vision in a multivariate model. Conclusion:Telehealth initiatives benefited patients from racial and/or ethnic minority groups by reducing disparities in access to eye care experienced during the COVID-19 pandemic.

Loss of Function (LOF) mutations in the NOTCH receptors are found in several different cancers most notably in small cell lung cancer (SCLC) and squamous cell carcinomas (SCC). We previously developed genetically engineered mouse models (GEMM) of SCLC using CRISPR/Cas9 engineered to be NOTCH1-Mutant, NOTCH2-Mutant, and NOTCH-WT. Synthetic lethality provides a paradigm for targeting cancers with LOF mutations in tumor suppressor genes. In applying this paradigm, one looks for specific vulnerabilities that are created upon loss of the gene of interest. Using 6 cell lines developed from these CRISPR-based SCLC GEMMs which are isogenic to NOTCH, we performed CRISPR/Cas9 LOF negative selection screens (using an sgRNA library enriched in druggable enzymes) to identify synthetic lethal interactors with LOF NOTCH mutations. Our CRISPR/Cas9 screen identified TRIM28 (Tripartite Motif Containing 28, or KAP1) as a highly significant synthetic lethal interactor with NOTCH1 or NOTCH2. We validated the synthetic lethal interaction between NOTCH1/2 and TRIM28 using both human and mouse NOTCH-isogenic cell lines. Interestingly, RNA-sequencing of NOTCH2-Mutant or NOTCH-WT SCLC cell lines after TRIM28 CRISPR inactivation showed robust increases in endogenous retroviral (ERV) expression and the MDA5/RIG-I/MAVS RNA-sensing machinery leading to hyperactivation of the TBK1/IRF3/7 innate immune signaling pathway and the pro-inflammatory cytokine CXCL10 selectively in cells with NOTCH inactivated. Notably, inactivation of TBK1 activity or JAK-STAT activity using specific small molecule inhibitors of TBK1 or JAK completely reversed the synthetic lethality between NOTCH and TRIM28 suggesting that the synthetic lethality phenotype is a consequence of hyperactivation of innate immune signaling, which is known to be cytotoxic. Together our findings uncover a novel vulnerability in SCLCs with LOF NOTCH mutations and perhaps other cancers with LOF NOTCH mutations and suggest a strategy that could also potentiate anti-tumor immunity by increasing innate immune signaling in tumor cells. Citation Format: Deli Hong, Matthew A. Booker, Sidrah Anjum, Yixiang Li, Tran C. Thai, Michelle Y. Wang, David A. Barbie, Michael Y. Tolstorukov, Jun Qi, Matthew G. Oser. Identification of synthetic lethal vulnerabilities in cancers with loss of function mutations in NOTCH. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5727.