Processes and perceptions of chemotherapy supply chain in Ethiopia: A mixed-method study.

BACKGROUND: The impact and downstream effects of the chemotherapy supply chain in Ethiopia are not well understood. The purpose of this study was to identify perceived gaps in supply chain and characterize their impact on patient care. METHODS: A concurrent mixed-method study was conducted at a large academic cancer center in Ethiopia. In-depth interviews (IDIs) and surveys were completed in collaboration with external stakeholders with knowledge about chemotherapy supply chain in Ethiopia. Thematic coding was used for qualitative analysis of IDI and descriptive statistics were used to summarize quantitative survey data. RESULTS: Six stakeholders participated in the IDIs and seven completed surveys. IDIs revealed that most chemotherapeutic agents are purchased by the Ethiopian Pharmaceutical Supply Agency (EPSA) and are distributed to cancer treatment centers. A free-market purchasing option also exists, but for chemotherapy obtained outside of government-subsidized channels, the potential for substandard or falsified chemotherapy was a concern. Participants expressed confidence that the correct treatment was administered to patients, but viewpoints on reliability and consistency of medication supply were variable. Quantitative data from the survey showed that participants were not confident that medications are prepared safely and correctly. Improper storage and manipulation of high-risk medications remain a significant risk to staff. CONCLUSIONS: This study provides insight from a healthcare staff perspective on how gaps in the chemotherapy supply chain process impact patient care in a low-income country. Inventory management, disruptions in supply chain, and product integrity were perceived as the largest gaps in the current chemotherapy supply chain structure.

Chemotherapy supply chain management, safe-handling and disposal in Ethiopia: the case of Tikur Anbessa specialized hospital.

Optimal chemotherapy management is substandard in low and middle-income countries. We aimed to identify major gaps to design interventional strategies for improved chemotherapy management at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. This study was conducted using an observational checklist, open-ended questions, record review, and key informant interviews of department heads and focal persons at TASH. Findings were categorized into specific themes that developed. Chemotherapy represented 60.2% of the hospital medication budget. Drug utilization was quantified via monthly consumption documentation and forecasting. However, unreliable data resulted in frequent stockouts (unavailability of the item when it is needed) of chemotherapy with only 67.8% availability. Thirteen healthcare personnel (9 nurses, 2 pharmacists and 2 hospital cleaners) were interviewed: all clinical staff but neither of hospital cleaners believed that they were at risk of hazardous agents. Challenges identified included inadequate and frequent stockouts (unavailability of the item when it is needed) of personal protective equipment, lack of standardized guidelines for chemotherapy handling, admixture, and disposal, lack of designated preparation rooms, and lack of training. All nine nurses handled chemotherapy admixtures despite only two nurses previously receiving in-service training. Most of the participants had never witnessed the disposal of anticancer drugs. Prompted by the results of this study, a dialogue was initiated among members of TASH, the American Cancer Society and the University of North Carolina to implement action-oriented projects to address the gaps identified at TASH. These gaps directly and indirectly affect care and treatment outcomes of patients at a large cancer center. Collaborations with well-resourced centers are potential models for improving chemotherapy management.

Safety of Intravenous Bisphosphonates for the Treatment of Hypercalcemia in Patients With Preexisting Renal Dysfunction.

BACKGROUND: Although intravenous (IV) bisphosphonates are first-line medications for the management of hypercalcemia, studies examining their use in patients with preexisting renal dysfunction are limited. OBJECTIVE: The objective of this study is to describe the safety and efficacy of pamidronate and zoledronic acid in the treatment of hypercalcemia in patients with baseline renal dysfunction. METHODS: A retrospective analysis was conducted of IV pamidronate and zoledronic acid in adult patients with hypercalcemia and creatinine clearance (CrCl) <60 mL/min. The primary endpoint was incidence of all-grade serum creatinine (SCr) elevations. Secondary endpoints included refractory hypercalcemia, hypocalcemia, osteonecrosis of the jaw (ONJ), corrected serum calcium (CSC) decrease ≥1.0 mg/dL by day 7 of bisphosphonate administration, and normalization of CSC ≤10.5 mg/dL by days 10 and 30. RESULTS: A total of 113 patients were included (n = 55 pamidronate, n = 58 zoledronic acid). The primary endpoint of all-grade SCr elevation occurred in 28 (24.8%) patients. Grades 3/4 SCr elevations occurred in 10.9% of patients treated with pamidronate and 1.7% of patients receiving zoledronic acid. Approximately 16% and 14% of patients developed grades 1 and 2 hypocalcemia, respectively, and there were no cases of ONJ. Overall, 64.6% of patients achieved normalization of CSC by day 10, and there were no statistical differences between bisphosphonate type and renal function. CONCLUSIONS AND RELEVANCE: The analysis suggests an association between IV bisphosphonates and increased rates of SCr elevations among patients with preexisting renal dysfunction. Future prospective studies are necessary to elucidate these findings.

Results of a pre-implementation analysis of Ethiopia's National Pediatric Cancer Registry.

In Ethiopia, cancer accounts for about 5.8% of total national mortality, with an estimated annual incidence of cancer of approximately 60,960 cases and an annual mortality of over 44,000 persons. This is likely an underestimation. Survival rates for pediatric malignancies are likewise suboptimal although exact figures are unknown since a national cancer registry is unavailable. The World Health Organization (WHO) provides recommendations for the creation of cancer registries to track such data. Here we describe our pharmacist-led, pre-implementation assessment of introducing an enhanced national pediatric cancer registry in Ethiopia. Our assessment project had three specific aims around which the methods were designed: 1) characterization of the current spreadsheet-based tool across participating sites, including which variables were being collected, how these variables compared to standards set by the WHO, and a description of how the data were entered and its completeness; 2) assessment of the perceptions of an enhanced registry from hospital staff; and 3) evaluation of workflow gaps regarding documentation. The hospital staff and leadership have generally positive perceptions of an enhanced pediatric cancer registry, which were further improved by our interactions. The workflow assessment revealed several gaps, which were addressed systematically using a three-phase implementation science approach. The assessment also demonstrated that the existing spreadsheet-based tool was missing WHO-recommended variables and had inconsistent completion due to the workflow gaps. A pediatric oncology summary sheet will be implemented in upcoming trips in patient charts to better summarize the patients' journey starting from diagnosis. This document will be used by the data clerks in an enhanced-spreadsheet to have a more complete data set.

Evaluation of thiamine for the prevention of ifosfamide-induced encephalopathy.

STUDY OBJECTIVE: To determine whether thiamine prophylaxis decreases the incidence of ifosfamide-induced encephalopathy in patients receiving ifosfamide for the treatment of lymphoma. DESIGN: Retrospective, multi-center, cohort study. PATIENTS: A total of 73 patients who received 187 total cycles of ifosfamide, carboplatin, and etoposide chemotherapy for the treatment of lymphoma were included in this study. Forty-four of these patients (114 cycles) were included in the no-thiamine group and 29 (65 cycles) in the thiamine group. MEASUREMENTS AND MAIN RESULTS: The incidence of ifosfamide-induced encephalopathy was measured using the Common Terminology Criteria for Adverse Events and documentation in the patient chart. Regarding the primary endpoint of ifosfamide-induced encephalopathy, eight patients (18.2%) in the no-thiamine group and three patients (10.3%) in the thiamine group experienced an event (p = 0.5087). No patient experienced more than one neurotoxic event. CONCLUSION: There was no significant difference found in the incidence of ifosfamide-induced encephalopathy with the addition of thiamine prophylaxis in patients receiving ifosfamide, carboplatin, and etoposide-based chemotherapy regimens for lymphoma. Larger, prospective studies assessing the use of thiamine prophylaxis in this patient population are warranted to better assess its impact on the incidence of ifosfamide-induced encephalopathy.

Dose-related mucositis with hydroxyurea for cytoreduction in acute myeloid leukemia.

Hyperleukocytosis occurs in 15-20% of all newly diagnosed acute myeloid leukemia patients and requires emergent treatment with leukapheresis or hydroxyurea when accompanied by signs or symptoms of leukostasis. Currently, there is no standardized hydroxyurea dosing strategy, although usual dosing ranges from 50 to 150 mg/kg/day, and prescribing patterns vary significantly among oncologists and institutions. In addition to other hematologic and dermatologic toxicities, the use of hydroxyurea may be associated with significant mucositis and mucositis-related pain. The purpose of this study was to compare mucositis-related pain between two different hydroxyurea dosing strategies in patients who received hydroxyurea for cytoreduction during induction. A retrospective chart review of adult patients with acute myeloid leukemia treated with chemotherapy at UNC Medical Center from April 2014 to April 2016 who received at least one dose of hydroxyurea for cytoreduction was conducted. This study compared the safety and toxicity profiles of hydroxyurea in patients who received high-dose hydroxyurea (≥75 mg/kg/day) versus low-dose hydroxyurea (<75 mg/kg/day). Safety and toxicity were evaluated based on indicators of mucositis and cumulative intravenous narcotic requirements following induction chemotherapy. Data collection included baseline demographics, mucositis risk factors, baseline laboratory values, hydroxyurea dosing, mucositis indicators, and pain indicators. A total of 55 patients were included in the study, 21 patients (38.2%) received the high-dose hydroxyurea dosing strategy. The high-dose hydroxyurea dosing strategy had a significantly higher white blood cell count at diagnosis, increased duration of hydroxyurea, and received a higher cumulative dose of hydroxyurea. Additionally, the high-dose hydroxyurea dosing strategy patients were associated with significantly more grade 3 or 4 mucositis requiring a formulation change (0% versus 28.6%, p = 0.002) and significantly higher cumulative intravenous narcotic requirements during induction (p = 0.019). No significant differences in baseline demographics or mucositis risk factors between dosing strategies were identified. The high-dose hydroxyurea dosing strategy patients had a significant increase in cumulative intravenous narcotic requirements and formulation changes, both common interventions made for the treatment of mucositis. Additional studies are needed to further elucidate the safety and toxicity profiles of hydroxyurea dosing strategies and to explore the correlation between total cumulative hydroxyurea dose and total cumulative narcotic requirements.

An Evaluation of the Effect of Pharmacist-Led Comprehensive Chemotherapy Consultation Services on Outpatient Appointment Adherence.

BACKGROUND: The North Carolina Cancer Hospital at the University of North Carolina Medical Center serves patients with a variety of malignant conditions and discharges more than 130 patients each month. Processes to improve transitions of care prompted implementation of a first-cycle, pharmacist-led chemotherapy consultation service on the inpatient oncology units. This process provides education to improve patient engagement and activation. High patient activation has been associated with better patient outcomes; poor patient activation has been associated with increased health care costs. OBJECTIVE: To determine the effect of pharmacist-led comprehensive chemotherapy consultation services on adherence to outpatient follow-up appointments within 30 days of discharge. METHODS: This was a single-center, retrospective chart review. This study consisted of 2 groups: adult patients who received comprehensive consultation services between April 2017 and September 2017 and a 2:1 historical group of adult control patients randomly selected from a list of patients who received their first cycle of chemotherapy during a hospital admission between April 2014 and April 2017. The primary endpoint was the effect of comprehensive consultation services on adherence to outpatient follow-up appointments within 1 month after discharge. RESULTS: Ninety-six patients were included in this study. The percentage of appointments attended was 98.0% for the intervention group and 92.3% for the control group (P = 0.0018). CONCLUSIONS: This study demonstrates that pharmacy consultation in the inpatient oncology setting is associated with improved adherence to outpatient appointments within 30 days of discharge. This represents the first published data on pharmacist interventions resulting in improved outpatient appointment adherence. DISCLOSURES: Funding for this study was contributed by the Hematology/Oncology Pharmacy Association (HOPA). This publication was also supported by Grant Number UL1TR002489 from the National Center for Advancing Translational Sciences at the National Institutes of Health. Auten reports fees from PTCE and ASHP/ACCP, unrelated to this study. Clark reports consulting fees from Ellion Benson Research, unrelated to this study. The other authors do not have any conflicts of interest to report. This study was presented as a trainee poster on April 5, 2019, at the HOPA Ahead 15th Annual Conference in Fort Worth, TX.

Complete remission with ibrutinib after allogeneic stem cell transplant for central nervous system relapse of mantle cell lymphoma: A case report and literature review.

Central nervous system (CNS)-relapsed mantle cell lymphoma (MCL) is a rare, aggressive non-Hodgkin lymphoma without a standard treatment. Ibrutinib has shown promising results for inducing remission in other non-Hodgkin lymphomas and may be considered as successful treatment for CNS-relapsed MCL in the future as well.

Prognostic value of complete remission with superior platelet counts in acute myeloid leukemia.

BACKGROUND: Complete remission (CR) in acute myeloid leukemia (AML) is defined as having ≤5% leukemic blast cells in the bone marrow and return of normal hematopoiesis after the first induction cycle. There is a subset of patients, however, who achieve reduction of leukemic blast cells with a subnormal platelet count, designated as CR with incomplete platelet recovery (platelet count, ≤100,000/mcL; normal, 150,000-450,000/mcL), which is associated with inferior outcomes when compared with CR. Furthermore, there is another subset of patients with CR but superior platelet counts (≥400,000/mcL) whose prognostic significance is unclear. OBJECTIVE: To establish whether CR with superior platelet counts is associated with better outcomes and can be used as a separate entity for prognostication. METHODS: A retrospective chart review of 104 cases of AML was conducted. The highest platelet count during days 25-35 from initiation of induction chemotherapy (designated as day 30 platelet count) was documented. A multivariate analysis for other factors such as age, sex, risk categories, day 14+ plasma cell count (average plasma cell percentage at days 14-21), infections, allogeneic bone marrow transplant, and remission status was done. RESULTS: Day 30 platelet count was found to be an independent predictor of survival in AML. On the multivariate analysis, the subgroup with superior platelet counts (≥400,000/mcL) was found to be associated with better outcomes. LIMITATIONS: Results need to be validated in a larger cohort. CONCLUSIONS: CR with superior platelet recovery (≥400,000/mcL) is a unique subcategory in itself and has prognostic significance. This may help better assess response to chemotherapeutic agents and aid in further decision-making regarding treatment.