Evaluation of a Treatment-Dose Enoxaparin Protocol for Patients With Obesity.

BACKGROUND: Treatment-dose enoxaparin is not well studied in obese patients. Guidelines suggest that obese patients receiving enoxaparin therapy for acute venous thromboembolism (VTE) should receive a standard initial dose, 1 mg/kg, based on actual body weight. It is possible that this dosing strategy in obese patients may be overestimated, leading to a higher bleeding risk compared to non-obese patients. OBJECTIVE: To gather data regarding enoxaparin treatment dosing and anti-Xa level monitoring in patients who are obese to guide dose adjustments. METHODS: A single-center, retrospective chart review that included patients who were ordered treatment-dose enoxaparin and had a BMI ≥ 40 kg/m2, which resulted in an automatic pharmacy consult.The primary endpoint of this study was incidence of bleeding. RESULTS: The analysis included 102 patients. Most patients (92.1%) had a BMI of ≥ 40-60 kg/m2 while 7.8% of patients had a BMI of > 60 kg/m2. The average initial and final doses were 1.0 ± 0.1 mg/kg and 0.9 ± 0.2 mg/kg, respectively. The incidence of bleeding was 4.9%. The average dose for those that bled was 0.7 ± 0.1 mg/kg. On average, patients who bled had higher BMIs than patients who did not bleed (51.6 kg/m2 vs. 48.0 kg/m2). Of the 71 patients with an initial anti-Xa level, 42 of the levels were considered supratherapeutic (59.2%). CONCLUSION: A 1 mg/kg starting dose of enoxaparin may be too high for patients who are obese as many patients required an adjustment to their dose after initial anti-Xa levels.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis.

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

Evaluation of drug-drug interactions in hospitalized patients on medications for OUD.

INTRODUCTION: Medications used to treat OUD have common metabolic pathways and pharmacodynamic properties that can lead to drug-drug interactions (DDIs) that may go unnoticed in the inpatient setting. The purpose of this study was to identify the frequency of DDIs between medications prescribed for OUD and commonly used inpatient medications. METHODS: This was a retrospective review of orders for buprenorphine, buprenorphine-naloxone, and methadone to identify potential DDIs. Adult inpatients with an order for one of these medications for OUD were included. Medication regimens were evaluated throughout the inpatient stay and on day of discharge for DDIs. DDIs were classified by severity and type of interaction (increased risk of QT prolongation, additive CNS effects/respiratory depression, and opioid withdrawal). The primary endpoint was the number of potential DDIs. Other endpoints included number of each classification/severity of DDI, duration of therapy of interacting medications, and modifications made to OUD medications because of DDIs. RESULTS: A total of 102 patients were included, with 215 inpatient interactions and 83 interactions at discharge identified. While inpatient, 85% of patients were on an interacting medication, and 46% of patients were on an interacting medication at discharge. The most common classification of DDI was additive CNS effects/respiratory depression (68.8% inpatient, 50.6% discharge), followed by QT prolongation (24.2% inpatient, 45.8% discharge). The majority of DDIs were classified as requiring close monitoring rather than contraindicated. DISCUSSION: There are opportunities to optimize the prescribing practices surrounding OUD medications in both the inpatient setting and at discharge to ensure patient safety.

Improving pharmacist documentation of clinical interventions through focused education.

PURPOSE: The impact of a focused education initiative to increase pharmacists' documentation of clinical interventions is described. SUMMARY: A focused education initiative was developed to increase the consistency of pharmacists' documentation of clinical interventions in order to achieve pharmacy goals and to demonstrate the value of pharmacy services at Carolinas Medical Center in Charlotte, North Carolina. Education was provided through weekly pharmacy newsletter publications, weekly huddles, and monthly staff meetings. Pharmacy clinical specialists were tasked with providing examples of activities that should be documented as interventions, reviewing the selection of intervention categories to best capture the specific activity, and emphasizing the need for appropriate documentation. Monthly progress was monitored, and results were posted publicly to incentivize staff and assist with accountability. Increases in the number of clinical interventions was reported at monthly pharmacy staff meetings to reinforce the value of this process. The total number of pharmacy clinical interventions increased from an average of 12,493 per month in the first quarter of 2012 to an average of 27,978 per month in the second quarter of 2013, representing a 120% improvement. Associated cost-avoidance dollars also increased proportionally, such that the average cost-avoidance dollars in the second quarter of 2013 was $1.5 million per month. In addition, the pharmacy department far exceeded the health system's division of pharmacy targets for established quality indicators. Effects were sustained during the 12 months after completion of the education initiative. CONCLUSION: Implementation of a focused pharmacist education initiative led to increased numbers of clinical interventions reported and increased documentation of costs avoided.

Inducible hyaluronan production reveals differential effects on prostate tumor cell growth and tumor angiogenesis.

Prostate cancer progression can be predicted in human tumor biopsies by abundant hyaluronan (HA) and its processing enzyme, the hyaluronidase HYAL1. Accumulation of HA is dictated by the balance between expression levels of HA synthases, the enzymes that produce HA polymers, and hyaluronidases, which process polymers to oligosaccharides. Aggressive prostate tumor cells express 20-fold higher levels of the hyaluronan synthase HAS3, but the mechanistic relevance of this correlation has not been determined. We stably overexpressed HAS3 in prostate tumor cells. Adhesion to extracellular matrix and cellular growth kinetics in vitro were significantly reduced. Slow growth in culture was restored either by exogenous addition of hyaluronidase or by stable HYAL1 coexpression. Coexpression did not improve comparably slow growth in mice, however, suggesting that excess hyaluronan production by HAS3 may alter the balance required for induced tumor growth. To address this, we used a tetracycline-inducible HAS3 expression system in which hyaluronan production could be experimentally controlled. Adjusting temporal parameters of hyaluronan production directly affected growth rate of the cells. Relief from growth suppression in vitro but not in vivo by enzymatic removal of HA effectively uncoupled the respective roles of hyaluronan in growth and angiogenesis, suggesting that growth mediation is less critical to establishment of the tumor than early vascular development. Collectively results also imply that HA processing by elevated HYAL1 expression in invasive prostate cancer is a requirement for progression.