Primary Care Provider Familiarity and Compliance With Preferred Practice Patterns for Comprehensive Eye Examinations.

PURPOSE: To assess primary care practitioners' (PCPs) familiarity with American Academy of Ophthalmology Preferred Practice Pattern (PPP) guidelines on the frequency of comprehensive eye examinations (CEEs), and to explore their opinions and practices on counseling and referring patients for CEEs. DESIGN: Cross-sectional study. METHODS: Between February 1, 2019, and June 25, 2019, an anonymous survey was emailed to clinicians holding an MD, DO, PA, or NP degree, and residents at Brigham and Women's Hospital and the University of Oklahoma. Descriptive statistics of participants' responses were reported. RESULTS: Regarding patient counseling on CEEs, 15.4% of PCPs reported "always," 48.1% "usually," and 36.5% "seldom" or "never" doing so. Few PCPs (11.1%) reported being able to describe the guidelines, and 63.9% were unaware of their existence. A strong majority of PCPs (90.7%) correctly referred a type 2 diabetic patient at their time of diagnosis, but a similar majority (77.8%) prematurely referred a newly diagnosed type 1 diabetic patient. One in 7 PCPs (13.4%) would refer a patient with family history of glaucoma only upon developing visual/ocular symptoms. Compared to other providers, PAs/NPs were more likely to recommend unnecessary CEEs for low-risk individuals (P = .009), whereas residents counseled patients less frequently (P = .003), were less likely to be familiar with PPP guidelines (P = .026), and were less likely to recommend appropriate follow-ups for patients with family history of glaucoma (P = .004). CONCLUSIONS: PCPs' awareness of and familiarity with AAO CEE guidelines is variable and improves with provider age and experience. Efforts to improve PCP guideline awareness may be especially well suited to residents and mid-level practitioners.

Structural and computational basis for potent inhibition of glutamate carboxypeptidase II by carbamate-based inhibitors.

A series of carbamate-based inhibitors of glutamate carboxypeptidase II (GCPII) were designed and synthesized using ZJ-43, N-[[[(1S)-1-carboxy-3-methylbutyl]amino]carbonyl]-l-glutamic acid, as a molecular template in order to better understand the impact of replacing one of the two nitrogen atoms in the urea-based GCPII inhibitor with an oxygen atom. Compound 7 containing a C-terminal 2-oxypentanedioic acid was more potent than compound 5 containing a C-terminal glutamic acid (2-aminopentanedioic acid) despite GCPII's preference for peptides containing an N-terminal glutamate as substrates. Subsequent crystallographic analysis revealed that ZJ-43 and its two carbamate analogs 5 and 7 with the same (S,S)-stereochemical configuration adopt a nearly identical binding mode while (R,S)-carbamate analog 8 containing a d-leucine forms a less extensive hydrogen bonding network. QM and QM/MM calculations have identified no specific interactions in the GCPII active site that would distinguish ZJ-43 from compounds 5 and 7 and attributed the higher potency of ZJ-43 and compound 7 to the free energy changes associated with the transfer of the ligand from bulk solvent to the protein active site as a result of the lower ligand strain energy and solvation/desolvation energy. Our findings underscore a broader range of factors that need to be taken into account in predicting ligand-protein binding affinity. These insights should be of particular importance in future efforts to design and develop GCPII inhibitors for optimal inhibitory potency.