Can a novel constructivist theory-informed feedback intervention reduce prescribing errors ? A pre-post study.

CONTEXT: Medical interns (interns) find prescribing challenging and many report lacking readiness when commencing work. Errors in prescribing puts patients' safety at risk. Yet error rates remain high, despite education, supervision and pharmacists' contributions. Feedback on prescribing may improve performance. Yet, work-based prescribing feedback practices focus on rectifying errors. We aimed to explore if prescribing can be improved using a theory-informed feedback intervention. METHODS: In this pre-post study, we designed and implemented a constructivist-theory informed prescribing feedback intervention, informed by Feedback-Mark 2 Theory. Interns commencing internal medicine terms in two Australian teaching hospitals were invited to engage in the feedback intervention. Their prescribing was evaluated by comparing errors per medication order of at least 30 orders per intern. Pre/baseline (weeks 1-3) were compared with post intervention (weeks 8-9). Interns' baseline prescribing audit findings were analysed and discussed at individualised feedback sessions. These sessions were with a clinical pharmacologist (Site 1) and a pharmacist educator (Site 2). RESULTS: Eighty eight intern's prescribing over five 10-week terms was analysed from two hospitals. The frequency of prescribing errors significantly reduced at both sites after the intervention, across all five terms (p < 0.001).There were initially 1598 errors in 2750 orders (median [IQR] 0.48 [0.35-0.67] errors per order) and after the intervention 1113 errors in 2694 orders (median [IQR] 0.30 [0.17-0.50] errors per order). CONCLUSION: Our findings suggest interns' prescribing practices may improve as a result of constructivist -theory learner centred, informed feedback with an agreed plan. This novel intervention, contributed, to a reduction in interns' prescribing errors. This study suggests new strategies for improving prescribing safety should include the design and implementation of theory-informed feedback interventions.

The impact of a Post-Take Ward Round Pharmacist on the Risk Score and Enactment of Medication-Related Recommendations.

There is a scarcity of published research describing the impact of a pharmacist on the post-take ward round (PTWR) in addition to ward-based pharmacy services. The aim of this paper was to evaluate the impact of clinical pharmacists' participation on the PTWR on the risk assessment scores of medication-related recommendations with and without a pharmacist. This includes medication-related recommendations occurring on the PTWR and those recommendations made by the ward-based pharmacist on the inpatient ward. A pre-post intervention study was undertaken that compared the impact of adding a pharmacist to the PTWR compared with ward-based pharmacist services alone. A panel reviewed the risk of not acting on medication recommendations that was made on the PTWR and those recorded by the ward-based pharmacist. The relationship between the risk scores and the number and proportion of recommendations that led to action were compared between study groups. There were more medication-related recommendations on the PTWR in the intervention group when a pharmacist was present. Proportionately fewer were in the 'very high and extreme' risk category. Although there was no difference in the number of ward pharmacist recommendations between groups, there was a significantly higher proportion of ward pharmacist recommendations in the "very high and extreme" category in those patients who had been seen on a PTWR attended by a pharmacist than when a pharmacist was not present. There were a greater proportion of "low and medium" risk actionable medication recommendations actioned on the PTWR in the intervention group; and no difference in the risk scores in ward pharmacist recommendations actioned between groups. Overall, the proportion of recommendations that were actioned was higher for those made on the PTWR compared with the ward. The addition of a pharmacist to the PTWR resulted in an increase in low, medium, and high risk recommendations on the PTWR, more very high and extreme risk recommendations made by the ward-based pharmacist, plus an increased number of recommendations being actioned during the patients' admission.

A systematic review of the costs and cost-effectiveness of clinical pharmacists on hospital ward rounds.

Introduction: There is a lack of good quality economic evidence for the inclusion of pharmacists on hospital ward rounds in addition to, or as an alternative to, traditional ward-based clinical pharmacy services. There has been no systematic review of the cost or cost-effectiveness of pharmacists attending and contributing on ward rounds. Areas covered: A literature search was conducted in Medline, Embase, Cochrane, and CINAHL and reported in accordance with the PRISMA guidelines in May 2019. As well, a search using Google Scholar and a targeted hand search were undertaken. Studies that reported any estimate of the cost or cost-effectiveness were included if pharmacist participation on inpatient hospital ward rounds was the predominant focus of the intervention. The identified studies were subsequently screened by three reviewers who extracted data on their clinical and economic design. A bias assessment was completed using the ROBINS-I tool. Expert opinion: Seven studies were identified investigating a clinical pharmacist's inclusion on hospital ward rounds where there was a cost estimated. However, none were deemed to be a full economic evaluation and all were found to be open to a serious risk of bias. Future evaluations should include a comparator group and investigate the cost and cost savings of the service, alongside their clinical outcomes.

Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design.

Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. One critical limitation is the limited set of design tools for identifying oligomer sequences that can adopt desired conformations. Here, we present expansions to the ROSETTA platform that enable structure prediction and design of five non-peptidic oligomer scaffolds (noncanonical backbones), oligooxopiperazines, oligo-peptoids, [Formula: see text]-peptides, hydrogen bond surrogate helices and oligosaccharides. This work is complementary to prior additions to model noncanonical protein side chains in ROSETTA. The main purpose of our manuscript is to give a detailed description to current and future developers of how each of these noncanonical backbones was implemented. Furthermore, we provide a general outline for implementation of new backbone types not discussed here. To illustrate the utility of this approach, we describe the first tests of the ROSETTA molecular mechanics energy function in the context of oligooxopiperazines, using quantum mechanical calculations as comparison points, scanning through backbone and side chain torsion angles for a model peptidomimetic. Finally, as an example of a novel design application, we describe the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein-protein interaction. For the general biological and bioengineering community, several noncanonical backbones have been incorporated into web applications that allow users to freely and rapidly test the presented protocols (http://rosie.rosettacommons.org). This work helps address the peptidomimetic community's need for an automated and expandable modeling tool for noncanonical backbones.

Plucking the high hanging fruit: a systematic approach for targeting protein-protein interactions.

Development of specific ligands for protein targets that help decode the complexities of protein-protein interaction networks is a key goal for the field of chemical biology. Despite the emergence of powerful in silico and experimental high-throughput screening strategies, the discovery of synthetic ligands that selectively modulate protein-protein interactions remains a challenge for bioorganic and medicinal chemists. This Perspective discusses emerging principles for the rational design of PPI inhibitors. Fundamentally, the approach seeks to adapt nature's protein recognition principles for the design of suitable secondary structure mimetics.

Assessing helical protein interfaces for inhibitor design.

Structure-based design of synthetic inhibitors of protein-protein interactions (PPIs) requires adept molecular design and synthesis strategies as well as knowledge of targetable complexes. To address the significant gap between the elegant design of helix mimetics and their sporadic use in biology, we analyzed the full set of helical protein interfaces in the Protein Data Bank to obtain a snapshot of how helices that are critical for complex formation interact with the partner proteins. The results of this study are expected to guide the systematic design of synthetic inhibitors of PPIs. We have experimentally evaluated new classes of protein complexes that emerged from this data set, highlighting the significance of the results described herein.

Guest-accelerated molecular rotor.

A molecular rotor was designed in which the rate of rotation is accelerated by guest complexation. The binding of an acetate guest to the urea groups lowers the barrier of the adjacent C(aryl)-N(imide) bond by 2 to 4 kcal/mol. This behavior is in contrast to most molecular rotors in which guest complexation slows rotation.

Mini review: protein-protein interactions in transcription: a fertile ground for helix mimetics.

Designed ligands that inhibit protein-protein interactions involved in gene expression are valuable as reagents for genomics research and as leads for drug discovery efforts. Selective modulation of protein-protein interactions has proven to be a daunting task for synthetic ligands; however, the last decade has seen significant advances in inhibitor design, especially for helical protein interfaces. This review discusses examples of transcriptional complexes targeted by designer helices.

A small molecule diacid with long-term chiral memory.

A small, axially chiral diacid was designed with chiral memory based on restricted rotation. Heating a racemic sample with a chiral alkaloid led to an enantiomeric excess of up to 40% ee. The guest-induced chirality was preserved on cooling to rt, which was maintained even in the absence of guest (t(1/2) = 14y). The chiral enrichment process was also reversible, allowing the diacid to be used as a chiral switch.