Physicians' Preferences for Communication of Pharmacist-Provided Medication Therapy Management in Community Pharmacy.

OBJECTIVES: (1) To identify physicians' preferences in regard to pharmacist-provided medication therapy management (MTM) communication in the community pharmacy setting; (2) to identify physicians' perceived barriers to communicating with a pharmacist regarding MTM; and (3) to determine whether Missouri physicians feel MTM is beneficial for their patients. METHODS: A cross-sectional prospective survey study of 2021 family and general practice physicians registered with MO HealthNet, Missouri's Medicaid program. RESULTS: The majority (52.8%) of physicians preferred MTM data to be communicated via fax. Most physicians who provided care to patients in long-term care (LTC) facilities (81.0%) preferred to be contacted at their practice location as opposed to the LTC facility. The greatest barriers to communication were lack of time and inefficient communication practices. Improved/enhanced communication was the most common suggestion for improvement in the MTM process. Approximately 67% of respondents reported MTM as beneficial or somewhat beneficial for their patients. CONCLUSIONS: Survey respondents saw value in the MTM services offered by pharmacists. However, pharmacists should use the identified preferences and barriers to improve their currently utilized communication practices in hopes of increasing acceptance of recommendations. Ultimately, this may assist MTM providers in working collaboratively with patients' physicians.

Rural health systems' perceptions of referral to community pharmacists during transitions of care.

OBJECTIVES: To identify rural health systems' perceptions of value, benefits, barriers, and opportunities associated with community pharmacist involvement in patient transitions of care. SETTING: Rural health systems in northwest and central Missouri. PRACTICE DESCRIPTION AND INNOVATION: Qualitative descriptive study of key informant interviews with self-identified decision makers of rural health systems within a 50-mile radius of 15 independent community pharmacy chain locations. EVALUATION: Interviews were recorded, transcribed, and coded to evaluate themes in participant responses. RESULTS: Fifteen interviews were conducted at 8 rural health systems. Participants expressed significant value in community pharmacist involvement in transitions of care and highlighted several benefits, barriers, and opportunities related to potential collaboration. Benefits that were identified included medication monitoring, resource for patient information, and desire among health care providers to work with community pharmacists. Barriers included legal and regulatory issues with referral, communication, and prescriber utilization. Opportunities described included: patient education, monitoring, and follow-up; targeted interventions; medication access assistance; bedside medication delivery; and collaboration between community pharmacies and health care entities. CONCLUSION: Rural health system informants perceived community pharmacy involvement to be valuable and were receptive to collaboration during transitional care to improve patient outcomes. They highlighted barriers to overcome to truly incorporate community pharmacists into the transitional care arena. Understanding these rural health systems' perceptions can guide community pharmacies in developing collaborative relationships and patient care services to assist with care transitions.

Breaking the covalent connection: Chain connectivity and the catalytic reaction of PMM/PGM.

Fragment complementation has been used to investigate the role of chain connectivity in the catalytic reaction of phosphomannomutase/phosphoglucomutase (PMM/PGM) from Pseudomonas aeruginosa, a human pathogen. A heterodimer of PMM/PGM, created from fragments corresponding to its first three and fourth domains, was constructed and enzyme activity reconstituted. NMR spectra demonstrate that the fragment corresponding to the fourth (C-terminal) domain exists as a highly structured, independent folding domain, consistent with its varied conformation observed in enzyme-substrate complexes. Steady-state kinetics and thermodynamics studies reported here show that complete conformational freedom of Domain 4, because of the break in the polypeptide chain, is deleterious to catalytic efficiency primarily as a consequence of increased entropy. This extends observations from studies of the intact enzyme, which showed that the degree of flexibility of a hinge region is controlled by the precise sequence of amino acids optimized through evolutionary constraints. This work also sheds light on the functional advantage gained by combining separate folding domains into a single polypeptide chain.

Backbone flexibility, conformational change, and catalysis in a phosphohexomutase from Pseudomonas aeruginosa.

The enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) from the bacterium Pseudomonas aeruginosa is involved in the biosynthesis of several complex carbohydrates, including alginate, lipopolysaccharide, and rhamnolipid. Previous structural studies of this protein have shown that binding of substrates produces a rotation of the C-terminal domain, changing the active site from an open cleft in the apoenzyme into a deep, solvent inaccessible pocket where phosphoryl transfer takes place. We report herein site-directed mutagenesis, kinetic, and structural studies in examining the role of residues in the hinge between domains 3 and 4, as well as residues that participate in enzyme-substrate contacts and help form the multidomain "lid" of the active site. We find that the backbone flexibility of residues in the hinge region (e.g., mutation of proline to glycine/alanine) affects the efficiency of the reaction, decreasing k cat by approximately 10-fold and increasing K m by approximately 2-fold. Moreover, thermodynamic analyses show that these changes are due primarily to entropic effects, consistent with an increase in the flexibility of the polypeptide backbone leading to a decreased probability of forming a catalytically productive active site. These results for the hinge residues contrast with those for mutants in the active site of the enzyme, which have profound effects on enzyme kinetics (10 (2)-10 (3)-fold decrease in k cat/ K m) and also show substantial differences in their thermodynamic parameters relative to those of the wild-type (WT) enzyme. These studies support the concept that polypeptide flexibility in protein hinges may evolve to optimize and tune reaction rates.

The reaction of phosphohexomutase from Pseudomonas aeruginosa: structural insights into a simple processive enzyme.

The enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) from Pseudomonas aeruginosa catalyzes the reversible conversion of 1-phospho to 6-phospho-sugars. The reaction entails two phosphoryl transfers, with an intervening 180 degrees reorientation of the reaction intermediate (e.g. glucose 1,6-bisphosphate) during catalysis. Reorientation of the intermediate occurs without dissociation from the active site of the enzyme and is, thus, a simple example of processivity, as defined by multiple rounds of catalysis without release of substrate. Structural characterization of two PMM/PGM-intermediate complexes with glucose 1,6-bisphosphate provides new insights into the reaction catalyzed by the enzyme, including the reorientation of the intermediate. Kinetic analyses of site-directed mutants prompted by the structural studies reveal active site residues critical for maintaining association with glucose 1,6-bisphosphate during its unique dynamic reorientation in the active site of PMM/PGM.