Increasing Guideline-Concordant Durations of Antibiotic Therapy for Acute Otitis Media.

OBJECTIVE: To compare the effectiveness of 2 interventions in improving prescribing of guideline-concordant durations of therapy for acute otitis media (AOM). STUDY DESIGN: This was a quasi-experimental mixed methods analysis that compared a bundled quality improvement intervention consisting of individualized audit and feedback, education, and electronic health record (EHR) changes to an EHR-only intervention. The bundle was implemented in 3 pediatric clinics from January to August 2020 and an EHR-only intervention was implemented in 6 family medicine clinics. The primary outcome measure was prescription of an institutional guideline-concordant 5-day duration of therapy for children ≥2 years of age with uncomplicated AOM. Propensity score matching and differences-in-differences analysis weighted with inverse probability of treatment were completed. Implementation outcomes were assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance Framework. Balance measures included treatment failure and recurrence. RESULTS: In total, 1017 encounters for AOM were included from February 2019 to August 2020. Guideline-concordant prescribing increased from 14.4% to 63.8% (difference = 49.4%) in clinics that received the EHR-only intervention and from 10.6% to 85.2% (difference = 74.6%) in clinics that received the bundled intervention. In the adjusted analysis, the bundled intervention improved guideline-concordant durations by an additional 26.4% (P < .01) compared with the EHR-only intervention. Providers identified EHR-prescription field changes as the most helpful components. There were no differences in treatment failure or recurrence rates between baseline and either intervention. CONCLUSIONS: Both interventions resulted in improved prescribing of guideline-concordant durations of antibiotics. The bundled intervention improved prescribing more than an EHR-only intervention and was acceptable to providers.

Separation of highly charged (+5 to +10) amphipathic α-helical peptide standards by cation-exchange and reversed-phase high-performance liquid chromatography.

We are currently examining the potential of amphipathic cationic α-helical peptides as a new generation of peptide standards for both cation-exchange high-performance liquid chromatography and reversed-phase chromatography. Thus, amphipathic peptides are particularly suitable for high-performance liquid chromatography standards due to the preferred binding of the non-polar face to the hydrophobic stationary phase of reversed-phase packings or the preferred binding of the polar face to the charged/hydrophilic stationary phase of cation-exchange packings. The ability of different reversed-phase or cation-exchange matrices to separate mixtures of peptide standards with only subtle hydrophilicity/hydrophobicity variations in both the non-polar and polar face of the peptides can then be assessed. Currently, we have designed de novo a mixture of six 26-residue all D-conformation amphipathic cationic α-helical peptides with a single, positively charged lysine residue in the center of the non-polar face and an increasing number of lysine residues (4-9 residues) replacing neutral residues in the polar face, resulting in an overall net positive charge of +5 to +10. Thus, the non-polar, preferred reversed-phase chromatography binding face remains constant, with only the polar face varying in hydrophilicity/hydrophobicity. Interestingly, even with the non-polar face remaining constant, reversed-phase columns of varying functional group properties (e.g., C8, C18, phenyl, polar endcapped, polar embedded) and porosity (porous versus superficially porous) were able to separate the six peptides in aq. TFA/acetonitrile gradients, albeit with different selectivities. The value of the standards in cation-exchange chromatography was expressed by monitoring the requirement of acetonitrile (0-40% in the mobile phase) to overcome hydrophobic interactions of the peptides with the cation-exchange matrix matrix when eluting with sodium perchlorate gradients at pH 6.5. Interestingly, the resolution of the higher charged peptides (+8,+9,+10) was particularly sensitive to acetonitrile levels. Our results clearly demonstrate the excellent potential of these novel peptide standards to enable optimal column choice and mobile phase conditions for reversed-phase chromatography and cation-exchange chromatography for peptide separations.