Impact of Allocation on Survival During Intermittent Chemotherapy Shortages: A Modeling Analysis.

BACKGROUND: Intermittent shortages of chemotherapeutics used to treat curable malignancies are a worldwide problem that increases patient mortality. Although multiple strategies have been proposed for managing these shortages (eg, prioritizing patients by age, scarce treatment efficacy per volume, alternative treatment efficacy difference), critical clinical dilemmas arise when selecting a management strategy and understanding its impact. PATIENTS AND METHODS: We developed a model to compare the impact of different allocation strategies on overall survival during intermittent chemotherapy shortages and tested it using vincristine, which was recently scarce for 9 months in the United States. Demographic and treatment data were abstracted from 1,689 previously treated patients in our tertiary-care system; alternatives were abstracted from NCCN Clinical Practice Guidelines in Oncology for each disease and survival probabilities from the studies cited therein. Modeled survival was validated using SEER data. Nine-month shortages were modeled for all possible supply levels. Pairwise differences in 3-year survival and risk reductions were calculated for each strategy compared with standard practice (first-come, first-served) for each 50-mg supply increment, as were supply thresholds above which each strategy maintained survival similar to scenarios without shortages. RESULTS: A strategy prioritizing by higher vincristine efficacy per volume and greater alternative treatment efficacy difference performed best, improving survival significantly (P<.01) across 86.5% of possible shortages (relative risk reduction, 8.3%; 99% CI, 8.0-8.5) compared with standard practice. This strategy also maintained survival rates similar to a model without shortages until supply fell below 72.2% of the amount required to treat all patients, compared with 94.3% for standard practice. CONCLUSIONS: During modeled vincristine shortages, prioritizing patients by higher efficacy per volume and alternative treatment efficacy difference significantly improved survival over standard practice. This approach can help optimize allocation as intermittent chemotherapy shortages continue to arise.

Implementation of Pharmacy Executive Quality and Safety Walkrounds at a Tertiary Academic Medical Center.

Background: Executive Quality and Safety WalkRounds (EWRs) is a tool that engages department leadership in discussion with the front-line employees to solicit feedback to improve quality and safety. The purpose of this study was to evaluate the impact of the implementation of pharmacy department specific EWRs on quality and safety at a tertiary academic medical center. Method: This was a single-center, retrospective analysis conducted at Brigham and Women's Hospital between November 2016 and November 2019. This study aimed to analyze the implementation of EWRs conducted every other month throughout various service areas and satellites of the pharmacy department. Data evaluated included the number of EWRs conducted, the specific areas visited, the total number of action items recommended by the staff, along with the total number of action items that were completed or remained in process. Results: During the study period, 17 visits were completed in 12 different BWH pharmacy sub-departments. A total of 98 operational, technological, and environmental action items were recommended by staff to improve quality and safety. Of the 98 action items documented, 95 (96.9%) were completed by time of our analysis. Conclusion: Pharmacy department EWRs are an important and systematic process of communication between the pharmacy leadership and frontline staff. Pharmacy department EWRs have resulted in safety and quality improvements at different levels in the pharmacy department. The EWRs program at the pharmacy department was effective in identifying and completing safety initiatives to improve the safety culture of the department.

Denosumab in hypercalcemia of malignancy: a case series.

BACKGROUND: Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with bone metastases from solid tumors. In clinical trials, the incidence of severe hypocalcemia has been reported as 3.1-10.8%. To date, case reports and two clinical trials have reported the use of denosumab in the management of hypercalcemia of malignancy. No reports of denosumab-induced hypocalcemia have been reported for the hypercalcemia of malignancy population. METHODS: We performed a retrospective chart review of all patients who received denosumab for hypercalcemia of malignancy to describe the effects of denosumab on calcium levels at our institution. RESULTS: Seven patients received doses of denosumab for hypercalcemia of malignancy. The most common tumor types were breast cancer (n = 3) and hematologic malignancies (n = 2). All patients had bone involvement. Two patients received single doses of 60 mg. The other five patients received 120 mg. The mean corrected calcium levels were 13.7 mg/dL and 12.24 mg/dL for the days of admission and denosumab administration, respectively (p = 0.1889). The mean corrected calcium level for the last known value was 9.92 mg/dL, while in house (p = 0.0016). Supportive care prior to denosumab included hydration (n = 7), bisphosphonates (n = 6), and calcitonin (n = 5). One patient had a calcium level of 6.6 mg/dL on day 4 after denosumab, requiring calcium supplementation and telemetry. Of the seven patients treated with denosumab for hypercalcemia of malignancy at our institution, six patients were discharged alive. Of these, one patient died two days after discharge. Last-known follow-up was a median of 26 days, range, 3-195, for all patients. CONCLUSIONS: Denosumab helped decrease calcium in patients with hypercalcemia of malignancy. However, symptomatic hypocalcemia may result from denosumab in hypercalcemia of malignancy.

Enhanced responsibilities for pharmacy interns at a teaching hospital.

OBJECTIVE: To describe the implementation of a pharmacy intern distribution coordinator position and its impact on the intern's professional development. SETTING: Tertiary academic medical center. PRACTICE DESCRIPTION: In 2009, our institution implemented a pharmacy intern distribution coordinator position, which was previously staffed by a pharmacist. Interns, who are in their first through fourth professional year, take the lead in the medication distribution process while under the direct supervision of a pharmacist. The intern adjudicates the medication distribution process by ensuring proper processing, filling and timely delivery of the medications, as well as triaging inventory issues and maintaining open communication with the pharmacists about any medication issues. Additionally, the intern can make clinical interventions during the various checkpoints in the final verification process and answer drug information questions for fellow medical professionals. PRACTICE INNOVATION: Pharmacy intern resources and development are maximized via staffing in a medication distribution coordinator position previously staffed by a pharmacist. By adapting to the role of pharmacist early on in one's career, pharmacy interns are provided with a valuable opportunity to grow professionally. The position can foster the development of pharmacotherapy knowledge, communication skills, leadership experience, time management, and critical thinking by allowing pharmacy interns to practice at the top of their licensure. CONCLUSION: Our pharmacy intern distribution coordinator position provides interns with a professional development opportunity by assuming enhanced roles and responsibilities in a hospital pharmacy department. The expansion of the pharmacy intern's role can increase pharmacy department resources and provide a valuable platform for their development. Institutions should seek to maximize the opportunities for pharmacy interns to work at the peak of their licensure.

Parenteral medication use in hospital at home: Challenges and opportunities.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Non-Sterile to Sterile Compounding: An Unconventional Response During the COVID-19 Pandemic.

The drug supply chain has suffered many interruptions over the past decade. The COVID-19 pandemic exacerbated an already fragile infrastructure for supplying critical medications to hospitals and health-systems. The purpose of this paper is to provide insight to the history, thought-processes, and response to critical medication shortages during the COVID-19 pandemic, with a focus on hydromorphone infusions and the action steps taken to engage in non-sterile to sterile (NSTS) compounding. Over a period of 6 weeks, we compounded 1,613 NSTS hydromorphone infusion bags. All lots were cleared for sterility, particulate, potency, and endotoxin testing by an outside FDA registered laboratory. We did not have any safety reports filed specific to the NSTS compounded hydromorphone infusion bags. Over a period of 15 weeks, 715 infusions were consumed. The drug supply chain suffers frequent interruptions and critical shortages, particularly in times of a natural disaster or a global pandemic. Non-sterile to sterile compounding is often associated with risks of inaccuracies, impurities, and contamination. There are instances in which non-sterile to sterile compounding is appropriate and should be considered in times of drug shortages to support the care of hospitalized patients.

Management of a parenteral opioid shortage using ASHP guidelines.

PURPOSE: Management of an acute shortage of parenteral opioid products at a large hospital through prescribing interventions and other guideline-recommended actions is described. SUMMARY: In early 2018, many hospitals were faced with a shortage of parenteral opioids that was predicted to last an entire year. The American Society of Health-System Pharmacists (ASHP) has published guidelines on managing drug product shortages. This article describes the application of these guidelines to manage the parenteral opioid shortage and the impact on opioid dispensing that occurred in 2018. Our approach paralleled that recommended in the ASHP guidelines. Daily dispensing reports generated from automated dispensing cabinets and from the electronic health record were used to capture dispenses of opioid medications. Opioid prescribing and utilization data were converted to morphine milligram equivalents (MME) to allow clinical leaders and hospital administrators to quickly evaluate opioid inventories and consumption. Action steps included utilization of substitute opioid therapies and conversion of opioid patient-controlled analgesia (PCA) and opioid infusions to intravenous bolus dose administration. Parenteral opioid supplies were successfully rationed so that surgical and elective procedures were not canceled or delayed. During the shortage, opioid dispensing decreased in the inpatient care areas from approximately 2.0 million MME to 1.4 million MME and in the operating rooms from 0.56 MME to 0.29 million MME. The combination of electronic health record alerts, increased utilization of intravenous acetaminophen and liposomal bupivacaine, and pharmacist interventions resulted in a 67% decline in PCA use and a 65% decline in opioid infusions. CONCLUSION: A multidisciplinary response is necessary for effective management of drug shortages through implementation of strategies and practices for notifying clinicians of shortages and identifying optimal alternative therapies.

Cleveland Clinic International IV Robotics Summit.

PURPOSE: The proceedings of an international summit on the current and desired future state of use of robotic systems to compound intravenous (IV) solutions are summarized. SUMMARY: The International IV Robotics Summit was held at the Cleveland Clinic main campus in Cleveland, OH, on April 29 and 30, 2019. The purpose of the summit was 2-fold: (1) to define the current state of robotic IV compounding and (2) to develop a guide for automation companies, pharmacy departments, and drug manufacturers to improve the technology and expand the use of IV robotics in health systems in the future. The first day of the summit included 45-minute presentations by each of the speakers. Each lecturer recounted a different hospital's experience implementing and using IV robotics. On day 2 of the summit, an expert panel dedicated to mapping the future of IV robotics was convened to determine barriers to widespread adoption of IV robotics in health systems and offer potential solutions to remove these barriers. The expert panel targeted 3 specific audiences: robot manufacturers, drug manufacturers, and fellow pharmacy leaders. CONCLUSION: It is the hope of the international faculty that the information that emerged from the summit can be used by others to successfully implement IV compounding robotics in their sterile products areas to maximize patient safety. The summit also served as a call to action for pharmacy leaders, drug manufacturers, and robotic companies to develop a safer, more efficient future for patients by working together to optimize the development and operation of IV robotics.

Single Center Experience with Robot Technologies for Sterile Compounding: A Retrospective Review.

The compounding of sterile medication admixtures is a labor-intensive process and subject to potential human error. The addition of robotic devices and workflow technology may mitigate some of the challenges of compounding sterile product admixtures, especially for those associated with antineoplastic and hazardous medications. This article discusses the single-center experiences from October 2009 through August 2017 with various sterile compounding robotic technologies. The robotic devices included Intellifill  i.v., Cytocare, i.v.Station, i.v.Station ONCO, and i.v.Soft Assist. The objective of this analysis was to describe the experience with robotic technology and workflow devices in compounding sterile medication admixtures. The number of prepared doses for each device was tracked, and each device had a tool to validate the dose accuracy via specific gravity measurement. Nonhazardous preparations with a dose variation of > (+/- 10%) were considered failures. For hazardous medications, variation of > (+/- 5%) was considered a failure. Doses that were prepared manually were also analyzed. The Intellifill i.v. robot was used to compound more than 1,000,000 admixtures (75% of all compounded  products). The i.v.Station, Cytocare, i.v.Station  ONCO, and i.v.Soft Assist robots compounded 14%, 7%,  3%, and 0.7% of the total chemotherapy doses required. Identified barriers to optimal performance included device (hardware) and software failures as well as shortages with specific fluid and drug containers. The qualitative analysis was done for 36 drugs that were prepared using i.v.Station and i.v.Station ONCO. The passing rate was estimated to be 95%. Barriers to use the device included lack of the appropriate medication container, diluent supplies issues, and software failure. Robotic devices and workflow technology for compounding sterile medication admixtures were unable to produce all routine parenteral doses required daily.

Reducing Medication Waste While Improving Access to Sugammadex: A Quality Improvement Project in Medication Stewardship.

The relatively high cost of sugammadex compared to neostigmine limits its widespread use to reverse neuromuscular blockade, despite its faster onset and more complete clinical effect. While ensuring timely access to sugammadex is important in improving perioperative safety, it is also vital to control unnecessary spending. We describe a quality improvement initiative to reduce excess spending on sugammadex while improving access for anesthesia providers. Monthly spending on sugammadex decreased by 52% ($70,777 vs $33,821), while medication access increased via automated medication dispensers in each operating room. Clinical usage decreased by one-third, with presumed increased adherence to dosing guidelines.

Role of pharmacist counseling in preventing adverse drug events after hospitalization.

BACKGROUND: Hospitalization and subsequent discharge home often involve discontinuity of care, multiple changes in medication regimens, and inadequate patient education, which can lead to adverse drug events (ADEs) and avoidable health care utilization. Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs. METHODS: We conducted a randomized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital. Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later. Interventions focused on clarifying medication regimens; reviewing indications, directions, and potential side effects of medications; screening for barriers to adherence and early side effects; and providing patient counseling and/or physician feedback when appropriate. The primary outcome was rate of preventable ADEs. RESULTS: Pharmacists observed the following drug-related problems in the intervention group: unexplained discrepancies between patients' preadmission medication regimens and discharge medication orders in 49% of patients, unexplained discrepancies between discharge medication lists and postdischarge regimens in 29% of patients, and medication nonadherence in 23%. Comparing trial outcomes 30 days after discharge, preventable ADEs were detected in 11% of patients in the control group and 1% of patients in the intervention group (P = .01). No differences were found between groups in total ADEs or total health care utilization. CONCLUSIONS: Pharmacist medication review, patient counseling, and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge. Medication discrepancies before and after discharge were common targets of intervention.

Evaluation of the maximum beyond-use-date stability of regular human insulin extemporaneously prepared in 0.9% sodium chloride in a polyvinyl chloride bag.

BACKGROUND: Regular human insulin 100 units added to a sufficient quantity of 0.9% sodium chloride, to yield a total volume of 100 mL within a polyvinylchloride bag, is accepted to be stable for 24 hours due to physical denaturation and chemical modification. The objective of this study was to evaluate the extended stability of such extemporaneously prepared regular human insulin, stored under refrigeration, to the maximum beyond-use-date allowed by United States Pharmacopeia chapter 797. METHODS: At time "0" three admixtures of regular human insulin were prepared by withdrawing 1 mL of regular human insulin with a concentration of 100 units/mL and adding it to a sufficient quantity of 0.9% sodium chloride for injection in a polyvinylchloride bag to yield a total volume of 100 mL. The three admixtures were stored under refrigeration (2°C-8°C [36°F-46°F]), and one sample of each admixture was withdrawn and tested in duplicate at 0, 6, 24, 48, 72, 144, 168, 192, 216, 240, 312, and 336 hours. Utilizing high performance liquid chromatography, each sample underwent immediate testing. The time points were stable if the mean concentration of the samples exceeded 90% of the equilibrium concentration at 6 hours. RESULTS: The equilibrium concentration was 0.89 units/mL. Time points were stable if the mean concentration was at least 0.80 units/mL. All time points retained at least 90% of the equilibrium concentration, with the exception of hour 168 (0.79 ± 0.03 units/mL). At 192 hours the mean concentration was 0.88 ± 0.03 units/mL. At 336 hours the mean concentration was 0.91 ± 0.02 units/mL. CONCLUSION: Based on these results, regular human insulin 100 units added to 0.9% sodium chloride for injection in a polyvinylchloride bag to yield a total volume of 100 mL is stable for up to 336 hours when stored at 2°C-8°C (36°F-46°F).

Impact of robotic antineoplastic preparation on safety, workflow, and costs.

PURPOSE: Antineoplastic preparation presents unique safety concerns and consumes significant pharmacy staff time and costs. Robotic antineoplastic and adjuvant medication compounding may provide incremental safety and efficiency advantages compared with standard pharmacy practices. METHODS: We conducted a direct observation trial in an academic medical center pharmacy to compare the effects of usual/manual antineoplastic and adjuvant drug preparation (baseline period) with robotic preparation (intervention period). The primary outcomes were serious medication errors and staff safety events with the potential for harm of patients and staff, respectively. Secondary outcomes included medication accuracy determined by gravimetric techniques, medication preparation time, and the costs of both ancillary materials used during drug preparation and personnel time. RESULTS: Among 1,421 and 972 observed medication preparations, we found nine (0.7%) and seven (0.7%) serious medication errors (P = .8) and 73 (5.1%) and 28 (2.9%) staff safety events (P = .007) in the baseline and intervention periods, respectively. Drugs failed accuracy measurements in 12.5% (23 of 184) and 0.9% (one of 110) of preparations in the baseline and intervention periods, respectively (P < .001). Mean drug preparation time increased by 47% when using the robot (P = .009). Labor costs were similar in both study periods, although the ancillary material costs decreased by 56% in the intervention period (P < .001). CONCLUSION: Although robotically prepared antineoplastic and adjuvant medications did not reduce serious medication errors, both staff safety and accuracy of medication preparation were improved significantly. Future studies are necessary to address the overall cost effectiveness of these robotic implementations.