Managing opioid waste, cost, and opportunity for drug diversion in the emergency department.

INTRODUCTION: Management of pain is a component of 80% of all emergency department (ED) visits, and intravenous (IV) opioids are most commonly used to treat moderate to severe pain. Since the dose of stock vials is rarely purchased based on provider ordering patterns, there is often a discrepancy between ordered doses and the dose of the stock vial, leading to waste. Here, waste is defined as the difference between the dose of the stock vials used to fill an order and the ordered dose. Drug waste is problematic as it increases the chance of administering the incorrect dose, it is a source of lost revenue, and in the context of opioids, it increases the opportunity for drug diversion. In this study, we sought to utilize real-world data to describe the magnitude of morphine and hydromorphone waste in the studied EDs. We also applied scenario analyses based on provider ordering patterns to simulate the effects of cost versus opioid waste minimization when making purchasing decisions for the dose of stock vial of each opioid. METHODS: This was an observational analysis of IV morphine and hydromorphone orders across three EDs within a health care system between December 1, 2014 and November 30, 2015. In the primary analysis we measured total waste and cost of all ordered hydromorphone and morphine, and we created logistic regression models for each opioid to estimate the odds that a given ordered dose would create waste. In the secondary scenario analysis we determined the total waste created and total cost to satisfy all written orders for both opioids with respect to prioritizing minimizing waste versus cost. RESULTS: Among a total of 34,465 IV opioid orders, 7866 (35%) of morphine orders created 21,767 mg of waste, and 10,015 (85%) of hydromorphone orders created 11,689 mg of waste. Larger dose orders were associated with a smaller likelihood of waste in both morphine and hydromorphone due to the doses of stock vials available. In the waste optimization scenario, relative to the base scenario, total waste, which included waste from both morphine and hydromorphone, was reduced by 97% and cost was reduced by 11%. In the cost optimization scenario, cost was reduced by 28% but waste increased by 22%. CONCLUSION: As hospitals continue to seek strategies to reduce costs and mitigate the harms of opioid diversion amidst the opioid epidemic, this study shows that optimizing the dose of the stock vial to minimize waste using provider ordering patterns, could mitigate risk while also reducing cost. Limitations included the use of data from EDs within a single health system, drug shortages that affected stock vial availability, and finally, the actual cost of stock vials, used for cost calculations, can differ based on a variety of factors.

Evolution of Patient Decision-Making Regarding Medical Treatment of Rheumatoid Arthritis.

OBJECTIVE: The migration of health care toward a consumer-driven system favors increased patient participation during the treatment decision-making process. Patient involvement in treatment decision discussions has been linked to increased treatment adherence and patient satisfaction. Previous studies have quantified decision-making styles of patients with rheumatoid arthritis (RA); however, none of them have considered the evolution of patient involvement after living with RA for many years. We conducted a qualitative study to determine the decision-making model used by long-term RA patients, and to describe the changes in their involvement over time. METHODS: Twenty participants were recruited from the ongoing Silicone Arthroplasty in Rheumatoid Arthritis study. Semistructured interviews were conducted and data were analyzed using grounded theory methodology. RESULTS: Nineteen out of 20 participants recalled using the paternalistic decision-making (PDM) model immediately following their diagnosis. Fourteen of the 19 participants who initially used PDM evolved to shared decision-making (SDM). Participants attributed the change in involvement to the development of a trusting relationship with their physician, as well as to becoming educated about the disease. CONCLUSION: When initially diagnosed with RA, patients may let their physician decide on the best treatment course. However, over time patients may evolve to exercise a more collaborative role. Physicians should understand that even within SDM, each patient can demonstrate a varied amount of autonomy. It is up to the physician to have a discussion with each patient to determine his or her desired level of involvement.

Design of triazole-stapled BCL9 α-helical peptides to target the ß-catenin/B-cell CLL/lymphoma 9 (BCL9) protein-protein interaction.

The interaction between ß-catenin and B-cell CLL/lymphoma 9 (BCL9), critical for the transcriptional activity of ß-catenin, is mediated by a helical segment from BCL9 and a large binding groove in ß-catenin. Design of potent, metabolically stable BCL9 peptides represents an attractive approach to inhibit the activity of ß-catenin. In this study, we report the use of the Huisgen 1,3-dipolar cycloaddition reaction to generate triazole-stapled BCL9 α-helical peptides. The high efficiency and mild conditions of this "click" reaction combined with the ease of synthesis of the necessary unnatural amino acids allows for facile synthesis of triazole-stapled peptides. We have performed extensive optimization of this approach and identified the optimal combinations of azido and alkynyl linkers necessary for stapling BCL9 helices. The unsymmetrical nature of the triazole staple also allowed the synthesis of double-stapled BCL9 peptides, which show a marked increase in helical character and an improvement in binding affinity and metabolic stability relative to wild-type and linear BCL9 peptides. This study lays the foundation for further optimization of these triazole-stapled BCL9 peptides as potent, metabolically stable, and cell-permeable inhibitors to target the ß-catenin and BCL9 interaction.

Analysis of the interaction of BCL9 with beta-catenin and development of fluorescence polarization and surface plasmon resonance binding assays for this interaction.

The transcriptional activator beta-catenin is the primary mediator of the canonical Wnt signaling pathway and is frequently upregulated in many types of human cancer. Recent studies have suggested that the interaction of beta-catenin and its cofactor, B-cell lymphoma 9 (BCL9), is crucial for its transcriptional activity. Targeting this interaction using small molecules will improve our understanding of the beta-catenin/Wnt signaling pathway and may lead to the development of a new class of anticancer drugs. In this study, we developed a fluorescence polarization (FP)-based BCL9 binding assay. Using our initial FP assay, we performed extensive mutational analysis on four critical hydrophobic residues in the BCL9 peptide and determined the precise region in BCL9 responsible for binding to beta-catenin. These results led to further optimization of our FP assay, making it amenable for high-throughput screening (HTS). We also developed and validated a complementary surface plasmon resonance (SPR)-based binding assay and showed that our synthetic BCL9-based peptides are capable of fully inhibiting the binding of beta-catenin to wild-type BCL9 protein. Our studies provide not only further insight into the interaction between BCL9 and beta-catenin but also quantitative and reliable biochemical binding assays for the discovery of potent and specific small-molecule inhibitors of this interaction.