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1.
Ophthalmol Sci ; 3(3): 100295, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37063252

ABSTRACT

Objective: To develop a novel methodology to identify lapses in diabetic retinopathy care in electronic health records (EHRs) and evaluate health disparities by race and ethnicity. Design: Retrospective cohort study. Subjects: Adult patients with diabetes mellitus who were evaluated at the Wilmer Eye Institute from January 1, 2013 to April 2, 2022. Methods: The methodology to identify lapses in care first identified diabetic retinopathy screening or treatment visits and then compared the providers' recommended follow-up timeframe with the patient's actual time to next encounter. The association of race and ethnicity with odds of lapses in care was evaluated using a mixed-effects logistic regression model controlling for age, sex, insurance, severity of diabetic retinopathy, presence of other retinal disorders, and glaucoma. Main Outcome Measures: Lapses in diabetic retinopathy care. Results: The methodology to identify diabetic retinopathy-related visits had a 95.0% (95% confidence interval, 93.0-96.6) sensitivity and 98.8% (98.1-99.3) specificity as compared with a gold standard grader. The methodology resulted in a 97.3% (96.2-98.4) sensitivity and 98.1% (97.3-98.9) specificity for detecting a follow-up recommendation, with an average error of -0.05 (-0.31 to 0.21) weeks in extracting the precise timeframe. A total of 39 561 patients with 91 104 office visits were included in the analysis. The average age was 61.4 years. More than 3 (77.6%) in 4 patients had a lapse in care. In multivariable analysis, non-Hispanic Black patients had 1.24 (1.19-1.30) odds and Hispanic patients had 1.26 (1.13-1.40) odds of ever having a lapse in care compared with non-Hispanic White patients (P < 0.001, respectively). Conclusions: We have developed a reliable methodology for identifying lapses in diabetic retinopathy care that is tailored to a provider's recommended follow-up. Using this approach, we find that 3 in 4 patients experience a lapse in diabetic retinopathy care and that these rates are higher among non-Hispanic Black and Hispanic patients. Deploying this methodology in the EHR is one potential means by which to identify and mitigate lapses in critical ophthalmic care in patients with diabetes. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

2.
Nucleic Acids Res ; 49(21): 12377-12393, 2021 12 02.
Article in English | MEDLINE | ID: mdl-34850123

ABSTRACT

Human telomeres are protected by shelterin proteins, but how telomeres maintain a dynamic structure remains elusive. Here, we report an unexpected activity of POT1 in imparting conformational dynamics of the telomere overhang, even at a monomer level. Strikingly, such POT1-induced overhang dynamics is greatly enhanced when TRF2 engages with the telomere duplex. Interestingly, TRF2, but not TRF2ΔB, recruits POT1-bound overhangs to the telomere ds/ss junction and induces a discrete stepwise movement up and down the axis of telomere duplex. The same steps are observed regardless of the length of the POT1-bound overhang, suggesting a tightly regulated conformational dynamic coordinated by TRF2 and POT1. TPP1 and TIN2 which physically connect POT1 and TRF2 act to generate a smooth movement along the axis of the telomere duplex. Our results suggest a plausible mechanism wherein telomeres maintain a dynamic structure orchestrated by shelterin.


Subject(s)
Recombinant Proteins/metabolism , Shelterin Complex/metabolism , Telomere-Binding Proteins/metabolism , Telomere/metabolism , Telomeric Repeat Binding Protein 2/metabolism , Fluorescence Resonance Energy Transfer/methods , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Humans , Microscopy, Fluorescence/methods , Protein Binding , Shelterin Complex/genetics , Telomere/genetics , Telomere-Binding Proteins/genetics , Telomeric Repeat Binding Protein 2/genetics , Tripeptidyl-Peptidase 1/genetics , Tripeptidyl-Peptidase 1/metabolism
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