Scaling the EQUIPPED medication safety program: Traditional and hub-and-spoke implementation models.

BACKGROUND: The EQUIPPED (Enhancing Quality of Prescribing Practices for Older Adults Discharged from the Emergency Department) medication safety program is an evidence-informed quality improvement initiative to reduce potentially inappropriate medications (PIMs) prescribed by Emergency Department (ED) providers to adults aged 65 and older at discharge. We aimed to scale-up this successful program using (1) a traditional implementation model at an ED with a novel electronic medical record and (2) a new hub-and-spoke implementation model at three new EDs within a health system that had previously implemented EQUIPPED (hub). We hypothesized that implementation speed would increase under the hub-and-spoke model without cost to PIM reduction or site engagement. METHODS: We evaluated the effect of the EQUIPPED program on PIMs for each ED, comparing their 12-month baseline to 12-month post-implementation period prescribing data, number of months to implement EQUIPPED, and facilitators and barriers to implementation. RESULTS: The proportion of PIMs at all four sites declined significantly from pre- to post-EQUIPPED: at traditional site 1 from 8.9% (8.1-9.6) to 3.6% (3.6-9.6) (p < 0.001); at spread site 1 from 12.2% (11.2-13.2) to 7.1% (6.1-8.1) (p < 0.001); at spread site 2 from 11.3% (10.1-12.6) to 7.9% (6.4-8.8) (p = 0.045); and at spread site 3 from 16.2% (14.9-17.4) to 11.7% (10.3-13.0) (p < 0.001). Time to implement was equivalent at all sites across both models. Interview data, reflecting a wide scope of responsibilities for the champion at the traditional site and a narrow scope at the spoke sites, indicated disproportionate barriers to engagement at the spoke sites. CONCLUSIONS: EQUIPPED was successfully implemented under both implementation models at four new sites during the COVID-19 pandemic, indicating the feasibility of adapting EQUIPPED to complex, real-world conditions. The hub-and-spoke model offers an effective way to scale-up EQUIPPED though a speed or quality advantage could not be shown.

Structural genomics reveals EVE as a new ASCH/PUA-related domain.

We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE. Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links.

Enhancing protein crystallization through precipitant synergy.

Suitable conditions for protein crystallization are commonly identified by screening combinations of independent factors that affect crystal formation. Because precipitating agents are prime determinants of crystallization, we investigated whether a systematic exploration of combinations of mechanistically distinct precipitants would enhance crystallization. A crystallization screen containing 64 precipitant mixtures was devised. Tests with ten HIV envelope-related proteins demonstrated that use of precipitant mixtures significantly enhanced both the probability of crystallization as well as the quality of optimized crystals. Tests with hen egg white lysozyme generated a novel C2 crystal from a salt/organic solvent mixture; structure solution at 2 A resolution revealed a lattice held together by both hydrophobic and electrostatic dyad interactions. The results indicate that mechanistically distinct precipitants can synergize, with precipitant combinations adding unique dimensions to protein crystallization.