Publications by authors named "G M Clore"

523 Publications

Acceptability and effectiveness of antimicrobial stewardship implementation strategies on fluoroquinolone prescribing.

Infect Control Hosp Epidemiol 2021 Apr 12:1-8. Epub 2021 Apr 12.

Department of Infectious Diseases, VA Greater Los Angeles Healthcare System, Los Angeles, California.

Objective: To assess the effectiveness and acceptability of antimicrobial stewardship-focused implementation strategies on inpatient fluoroquinolones.

Methods: Stewardship champions at 15 hospitals were surveyed regarding the use and acceptability of strategies to improve fluoroquinolone prescribing. Antibiotic days of therapy (DOT) per 1,000 days present (DP) for sites with and without prospective audit and feedback (PAF) and/or prior approval were compared.

Results: Among all of the sites, 60% had PAF or prior approval implemented for fluoroquinolones. Compared to sites using neither strategy (64.2 ± 34.4 DOT/DP), fluoroquinolone prescribing rates were lower for sites that employed PAF and/or prior approval (35.5 ± 9.8; P = .03) and decreased from 2017 to 2018 (P < .001). This decrease occurred without an increase in advanced-generation cephalosporins. Total antibiotic rates were 13% lower for sites with PAF and/or prior approval, but this difference did not reach statistical significance (P = .20). Sites reporting that PAF and/or prior approval were "completely" accepted had lower fluoroquinolone rates than sites where it was "moderately" accepted (34.2 ± 5.7 vs 48.7 ± 4.5; P < .01). Sites reported that clinical pathways and/or local guidelines (93%), prior approval (93%), and order forms (80%) "would" or "may" be effective in improving fluoroquinolone use. Although most sites (73%) indicated that requiring infectious disease consults would or may be effective in improving fluoroquinolones, 87% perceived implementation to be difficult.

Conclusions: PAF and prior approval implementation strategies focused on fluoroquinolones were associated with significantly lower fluoroquinolone prescribing rates and nonsignificant decreases in total antibiotic use, suggesting limited evidence for class substitution. The association of acceptability of strategies with lower rates highlights the importance of culture. These results may indicate increased acceptability of implementation strategies and/or sensitivity to FDA warnings.
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http://dx.doi.org/10.1017/ice.2021.10DOI Listing
April 2021

Probing Side-Chain Dynamics in Proteins by NMR Relaxation of Isolated C Magnetization Modes in CH Methyl Groups.

J Phys Chem B 2021 04 26;125(13):3343-3352. Epub 2021 Mar 26.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, United States.

The dynamics of methyl-bearing side chains in proteins were probed by C relaxation measurements of a number of C magnetization modes in selectively CH-labeled methyl groups of proteins. We first show how C magnetization modes in a CH spin-system can be isolated using acute-angle H radio-frequency pulses. The parameters of methyl-axis dynamics, a measure of methyl-axis ordering () and the correlation time of fast local methyl-axis motions (τ), derived from C relaxation in CH groups are compared with their counterparts obtained from C relaxation in CHD methyl isotopomers. We show that in high-molecular-weight proteins, excellent correlations are obtained between the [CHD]-derived values and those extracted from relaxation of the C magnetization of the = 1/2 manifold in CH methyls. In smaller proteins, a certain degree of anticorrelation is observed between the and τ values obtained from C relaxation of the = 1/2 manifold magnetization in CH methyls. These parameters can be partially decorrelated by inclusion in the analysis of relaxation data of the = 3/2 manifold C magnetization.
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http://dx.doi.org/10.1021/acs.jpcb.1c00989DOI Listing
April 2021

Probing the Interaction of Huntingtin Exon-1 Polypeptides with the Chaperonin Nanomachine GroEL.

Chembiochem 2021 Feb 28. Epub 2021 Feb 28.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, 5 Memorial Drive, Bethesda, MD 20892-0520, USA.

Huntington's disease arises from polyQ expansion within the exon-1 region of huntingtin (htt ), resulting in an aggregation-prone protein that accumulates in neuronal inclusion bodies. We investigate the interaction of various htt constructs with the bacterial analog (GroEL) of the human chaperonin Hsp60. Using fluorescence spectroscopy and electron and atomic force microscopy, we show that GroEL inhibits fibril formation. The binding kinetics of htt constructs with intact GroEL and a mini-chaperone comprising the apical domain is characterized by relaxation-based NMR measurements. The lifetimes of the complexes range from 100 to 400 μs with equilibrium dissociation constants (K ) of ∼1-2 mM. The binding interface is formed by the N-terminal amphiphilic region of htt (which adopts a partially helical conformation) and the H and I helices of the GroEL apical domain. Sequestration of monomeric htt by GroEL likely increases the critical concentration required for fibrillization.
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http://dx.doi.org/10.1002/cbic.202100055DOI Listing
February 2021

Development of a fully automated surgical site infection detection algorithm for use in cardiac and orthopedic surgery research.

Infect Control Hosp Epidemiol 2021 Feb 23:1-6. Epub 2021 Feb 23.

Center for Access & Delivery Research & Evaluation (CADRE), Iowa City Veterans' Affairs Health Care System, Iowa City, Iowa.

Objective: To develop a fully automated algorithm using data from the Veterans' Affairs (VA) electrical medical record (EMR) to identify deep-incisional surgical site infections (SSIs) after cardiac surgeries and total joint arthroplasties (TJAs) to be used for research studies.

Design: Retrospective cohort study.

Setting: This study was conducted in 11 VA hospitals.

Participants: Patients who underwent coronary artery bypass grafting or valve replacement between January 1, 2010, and March 31, 2018 (cardiac cohort) and patients who underwent total hip arthroplasty or total knee arthroplasty between January 1, 2007, and March 31, 2018 (TJA cohort).

Methods: Relevant clinical information and administrative code data were extracted from the EMR. The outcomes of interest were mediastinitis, endocarditis, or deep-incisional or organ-space SSI within 30 days after surgery. Multiple logistic regression analysis with a repeated regular bootstrap procedure was used to select variables and to assign points in the models. Sensitivities, specificities, positive predictive values (PPVs) and negative predictive values were calculated with comparison to outcomes collected by the Veterans' Affairs Surgical Quality Improvement Program (VASQIP).

Results: Overall, 49 (0.5%) of the 13,341 cardiac surgeries were classified as mediastinitis or endocarditis, and 83 (0.6%) of the 12,992 TJAs were classified as deep-incisional or organ-space SSIs. With at least 60% sensitivity, the PPVs of the SSI detection algorithms after cardiac surgeries and TJAs were 52.5% and 62.0%, respectively.

Conclusions: Considering the low prevalence rate of SSIs, our algorithms were successful in identifying a majority of patients with a true SSI while simultaneously reducing false-positive cases. As a next step, validation of these algorithms in different hospital systems with EMR will be needed.
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http://dx.doi.org/10.1017/ice.2020.1387DOI Listing
February 2021

A simple and cost-effective protocol for high-yield expression of deuterated and selectively isoleucine/leucine/valine methyl protonated proteins in Escherichia coli grown in shaker flasks.

J Biomol NMR 2021 Mar 4;75(2-3):83-87. Epub 2021 Feb 4.

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892-0520, USA.

A simple and cost-effective protocol is presented for expression of perdeuterated, Ile/Leu/Val H/C methyl protonated proteins from 100 ml cultures in M9 ++ /DO medium induced at high (OD ~ 10) cell density in shaker flasks. This protocol, which is an extension of our previous protocols for expression of H/N/C and H/C labeled proteins, yields comparable quantities of protein from 100 ml cell culture to those obtained using a conventional 1 L culture with M9/DO medium, while using three-fold less α-ketoisovaleric (1,2,3,4-C; 3,4',4',4'-d) and α-ketobutyric (C; 3,3-d) acid precursors.
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http://dx.doi.org/10.1007/s10858-021-00357-xDOI Listing
March 2021