Anesthesia providers as stakeholders to adoption of pharmacogenomic information in perioperative care.

OBJECTIVES: Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care and pain medicine providers would uncover unique considerations for future implementation within perioperative care. METHODS: A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources and barriers. RESULTS: Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1-10 years of experience, and nearly two-thirds with 11+ years (P < 0.05). Regarding barriers, providers reported uncertainty about availability of testing, turnaround time and whether testing is worth financial costs. CONCLUSIONS: Anesthesiology, critical care and pain medicine providers are optimistic about the potential clinical utility of pharmacogenomics, but are uncertain about practical aspects of testing and desire clear guidelines on the use of results. These findings may inform future institutional efforts toward greater integration of genomic results to improve medication-related outcomes.

Pilot Findings of Pharmacogenomics in Perioperative Care: Initial Results From the First Phase of the ImPreSS Trial.

BACKGROUND: Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care. METHODS: The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers. RESULTS: Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P < .0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow. CONCLUSIONS: Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes.

Impact of electronic interventions on guideline concordant ordering of rituximab infusion rate.

INTRODUCTION: Rituximab carries a boxed warning for severe or fatal infusion reactions; most occurring with the initial infusion. Prior studies established that if the initial rituximab infusion is tolerated, subsequent infusions can be given safely over 90 min. The University of Chicago Medicine (UCM) did not have a standardized method to document infusion reactions for outpatient chemotherapy patients, making it challenging for providers to know a patients' eligibility for rapid infusion. This quality improvement project focused on a series of interventions to improve documentation and electronic ordering of rituximab. METHODS: A flowsheet for nurses to record patients' tolerance of chemotherapy infusions was created within the electronic health record (EHR). Following results of flowsheet impact, a second intervention was implemented to modify ordering of rituximab. The primary endpoint was the incidence of guideline concordant rate ordering of rituximab. Secondary endpoints included the incidence of accurate chair time scheduling pre- and post-interventions and nursing compliance with flowsheet documentation. RESULTS: Prior to flowsheet implementation, 85% of patients were infused at the guideline concordant rate, compared to 79% post-implementation. Prior to modification of rituximab ordering in the EHR, 85% of patients were infused at the guideline concordant rate, compared to 87% after implementation. Complete nursing documentation was done 89% of the time when the flowsheet was utilized, compared to 11% pre-interventions. CONCLUSION: No difference in primary or secondary endpoints was found following our interventions. However, the infusion documentation flowsheet, when used, provided more complete reaction data compared to when it was not used.

Impact of Ketamine in the Management of Painful Sickle Cell Disease Vaso-Occlusive Crisis.

The aim of the study is to determine if ketamine infusions in combination with opioid therapy for the management of sickle cell disease (SCD) presenting with vaso-occlusive crisis (VOC) resulted in a length-of-stay difference compared to when ketamine was not utilized. This single center, retrospective, observational study performed at an academic medical center evaluated 12 adult patients with SCD-VOC who received a ketamine infusion with standard opioid therapy between 2014 and 2017. Patients were excluded if the primary diagnosis was not VOC or they did not survive to discharge. Additionally, safety and oral morphine equivalents at various time points were compared. Patients were used as their own control using the previous SCD-VOC hospitalization to evaluate the relative impact of ketamine. Wilcoxon signed-rank and rank sum were used in statistical analysis. When comparing opioid doses during the ketamine infusion, a P-value <.005 was considered statistically significant to account for multiple comparisons. The median length-of stay when ketamine was employed was similar to the previous admission with only opioid therapy (12 vs 12 days, P = .317). The median opioid dose 24 hours prior to starting ketamine was greater than during the first 24 hours of ketamine use (1278 vs 1020 mg, P = .022) and 24 hours after stopping ketamine (1278 vs 1035 mg, P = .014); however, this was not statistically significant. During 5 ketamine infusions, patients experienced side effects; however, only 1 necessitated transfer to the intensive care unit. Compared to standard opioid therapy, ketamine infusions were generally well tolerated and may be effective at reducing opioid use during SCD-VOC but did not decrease hospital length-of-stay.

Analysis of comprehensive pharmacogenomic profiling to impact in-hospital prescribing.

INTRODUCTION: In-hospital adverse medication events result in increased morbidity and mortality. Many implicated drugs carry pharmacogenomic information. We hypothesized that comprehensive pre-emptive pharmacogenomic profiling could have high relevance for in-hospital prescribing. PATIENTS AND METHODS: We retrospectively analyzed the in-hospital medications of a genotyped outpatient cohort admitted at our institution from 2012 to 2015. The endpoints were medication changes (new medications initiated, dose adjustments, or medications discontinued) involving drugs with pharmacogenomic annotations from three sources: Clinical Pharmacogenetics Implementation Consortium guidance, Food and Drug Administration label information, and drugs with clinical decision supports in our institutional pharmacogenomic Genomic Prescribing System. RESULTS: Of 867 genotyped outpatients, 20 were hospitalized (mean: 78.2 years, 65% male). This hospitalized cohort was significantly older (78.2 vs. 61.3 years, P<0.0001) and took more medications (8.9 vs. 5.0 medications, P<0.0001). Out of 159 medication changes made, most (67.9%) were new medications (average: 2.5/hospitalization) with one-third of these having clinically annotated pharmacogenomic information. Half of all hospitalizations involved at least one pharmacogenomic medication. Over half (55%) of the hospitalized cohort was newly prescribed at least one of eight key pharmacogenomic medications, including high-risk drugs such as clopidogrel, codeine, and warfarin. CONCLUSION: Our study suggested that older patients and those with polypharmacy were at increased risk for hospitalizations, where many new prescriptions included frequently used pharmacogenomic drugs. Targeting this group for pre-emptive genotyping would facilitate the delivery of highly relevant information to inform inpatient prescribing.

TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

BACKGROUND: The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear. METHODS: We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols. RESULTS: Of the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles. CONCLUSIONS: Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400 .).

Moxifloxacin versus levofloxacin for antibacterial prophylaxis in acute leukemia patients.

OBJECTIVE: The primary endpoint of this study was to determine the incidence of febrile neutropenia among patients receiving either moxifloxacin or levofloxacin for antibacterial prophylaxis. Secondary endpoints were number of documented infections and in-hospital mortality in patients who develop febrile neutropenia. METHODS: A single-center retrospective cohort analysis at a large tertiary care academic medical center was conducted. This study included adult acute leukemia patients (age ≥18 years old) who received inpatient antibacterial prophylaxis (moxifloxacin or levofloxacin) from 1 July 2012 to 1 October 2014. Patients were excluded from the study if they were treated with antimicrobial therapy in the preceding five days or admitted to the hospital with neutropenic fever. Fisher's exact test was used for categorical data and Mann-Whitney test for continuous data. Logistic regression analysis was used to determine risk factors for febrile neutropenia. RESULTS: Eighty-five patients were included in the final analysis with 40 patients who received moxifloxacin and 45 patients who received levofloxacin. Baseline characteristics were similar between the two groups. Twenty-two patients experienced febrile neutropenia requiring intravenous antibiotics in the moxifloxacin group and 30 patients in the levofloxacin group (P = 0.190). Age and duration of neutropenia appeared to predict for febrile neutropenia; however, after multivariate analysis, longer duration of neutropenia was shown to be the best predictor for febrile neutropenia with an odds ratio of 4.69 (95% CI, 1.697-12.968). Both groups had similar rates of documented infections and in-hospital morality. CONCLUSION: Moxifloxacin and levofloxacin showed similar rates of febrile neutropenia when used for neutropenic antibacterial prophylaxis in acute leukemia patients.

Posaconazole-digoxin drug-drug interaction mediated by inhibition of P-glycoprotein.

Drug-drug interactions between digoxin and the triazole antifungal agents, mediated via various cytochrome P450 isozymes, have been described in the literature. Posaconazole is not extensively metabolized by these isozymes but is both a p-glycoprotein (P-gp) substrate and inhibitor. To our knowledge, there have been no published cases of clinically significant posaconazole-digoxin drug-drug interactions. We report an interaction between posaconazole (300 mg by mouth daily) and digoxin (0.25 mg by mouth daily, Monday through Friday) resulting in atrial fibrillation with slow ventricular response and degenerating into polymorphic ventricular tachycardia.

Pepsi® or Coke®? Influence of acid on dasatinib absorption.

Dasatinib is a second generation ABL kinase inhibitor used in the management of chronic myeloid leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib's bioavailability is highly dependent on gastric pH. When proton-pump inhibitors (PPIs) are co-administered with dasatinib, absorption is significantly reduced. Cola intake at the time of drug administration has been demonstrated to lead to relevant increases in the bioavailability for other acid labile drugs during PPI treatment. This manuscript reviews the relevant literature supporting a strategy of temporarily lowering the gastric pH with a carbonated beverage at the time of drug administration. The use of cola provides an easy to implement way to significantly improve dasatinib bioavailability, especially during concomitant use of a PPI.

Incidence of asparaginase-related hepatotoxicity, pancreatitis, and thrombotic events in adults with acute lymphoblastic leukemia treated with a pediatric-inspired regimen.

Asparaginase is a critical component of acute lymphoblastic leukemia (ALL) treatment in children; however, its use in adults is often avoided as a result of toxicities including hepatotoxicity, thrombosis, and pancreatitis which have been reported more commonly in adults than in children. In this retrospective analysis, short-acting L-asparaginase (L-ASP) and long-acting polyethylene glycol (PEG)-asparaginase (PEG-ASP) were compared for grade 3-4 toxicities and characterized by patient and drug-related factors to identify strategies for toxicity avoidance in adults with ALL. Asparaginase was administered during sequential courses of chemotherapy using a pediatric-inspired treatment regimen. Forty-eight patients who received PEG-ASP and nine patients who received L-ASP were identified. The rates of toxicity were as follows for the PEG-ASP and L-ASP groups, respectively: hepatotoxicity (60% vs. 33%, P = 0.275), pancreatitis (17% vs. 22%, P = 0.650), thrombosis (19.0% vs. 0%, P = 0.328), or any grade 3-4 toxicity (71% vs. 44%, P = 0.143). Toxicity did not correlate with dose, either by individual dose based on flat or BSA-based measures. Logistic regression identified obesity as a risk factor for heptatotoxicity (OR = 8.44, 95% CI: 1.395-51.117). Hypofibrinogenemia was identified as a pharmacodynamic marker for predicting hepatotoxicity. In conclusion, grade 3-4 toxicity was not statistically different between adult ALL patients receiving PEG-ASP and L-ASP, but toxicity was strongly associated with obesity and hypofibrinogenemia, not dose.

Impact of a Clinical Decision Support Tool on Cancer Pain Management in Opioid-Tolerant Inpatients.

Background: Pain is both common and undertreated in the hematology/oncology population despite national guidelines and a focus from The Joint Commission. Objective: Herein, we describe the features of a pain clinical decision support tool (PCDST) embedded into the electronic medical record (EMR) and report its impact on oncology inpatients at risk for uncontrolled pain. Methods: The PCDST was developed to identify patients with potentially uncontrolled pain, defined as a pain score ≥4. Clinical pharmacists were encouraged to use the tool to determine whether interventions were needed to better control pain. Pain and safety outcomes between 2 cohorts of opioid-tolerant adult inpatients presenting with severe pain were compared prior to and following the implementation of the PCDST. Results: The primary endpoint, attainment of analgesia at 24 hours from admission, was met in 10 of 30 (33.3%) patients in the preimplementation group and in 14 of 32 (43.8%) of patients in the postimplementation group (P = .78). Secondary endpoints including time to analgesia, mean pain score, frequency of pharmacy intervention, and National Comprehensive Cancer Network (NCCN) guideline-adherent pain regimens were not found to be statistically significantly different between the 2 groups. The number of mean nursing pain assessments in the first 24 hours from admission was found to be significantly higher in the postimplementation group compared with the preimplementation group (12 vs 7.4, P < .001). Safety events were rare and not statistically different between groups. Conclusion: Overall, a modest, but statistically nonsignificant, improvement in pain outcomes was associated with patients admitted after the implementation of a pharmacist-managed electronic pain scoring tool.

Retrospective chart evaluation of hypercalcemia management in oncology patients at the University of Chicago Medical Center.

Introduction Due to the lack of formal guideline recommendations, available primary literature was used to develop a proposed protocol for management of hypercalcemia of malignancy at the University of Chicago Medical Center. Methods A retrospective, single center, observational study was performed including adult patients hospitalized with a diagnosis of hypercalcemia and active malignancy. Patients were retrospectively identified as treated in a manner aligned with the proposed protocol ("per protocol") or not treated according to the proposed protocol ("off protocol"), and the outcomes were compared. The primary outcome for efficacy was normalization of corrected calcium within four and seven days of treatment. Results Normalization of corrected calcium was observed in 66% of patients managed per protocol compared to 65% of patients managed off protocol ( p = 1.00) at day four, and in 73% of per protocol patients compared to 65% of off protocol patients ( p = 0.44) at day seven. Areas identified where prospective implementation of the proposed protocol can improve management include: decreasing utilization of bisphosphonates in mild hypercalcemia, optimizing bisphosphonate dosing in renal impairment, decreasing intravenous phosphate repletion, and ensuring proper fluid management and calcitonin dosing. Conclusion Although a statistical difference was not detected in terms of normalization of corrected calcium levels, areas for optimization in management were identified. Therefore, implementation of the proposed protocol is expected to promote evidence-based management of hypercalcemia of malignancy management at University of Chicago Medical Center.

Impact of a clinical pathway on appropriate empiric vancomycin use in cancer patients with febrile neutropenia.

Objectives Febrile neutropenia management guidelines recommend the use of vancomycin as part of an empiric antimicrobial regimen when specific criteria are met. Often, vancomycin use among patients with febrile neutropenia is not indicated and may be over utilized for this indication. We sought to evaluate the impact of implementing a febrile neutropenia clinical pathway on empiric vancomycin use for febrile neutropenia and to identify predictors of vancomycin use when not indicated. Methods Adult febrile neutropenia patients who received initial therapy with an anti-pseudomonal beta-lactam with or without vancomycin were identified before (June 2008 to November 2010) and after (June 2012 to June 2013) pathway implementation. Patients were assessed for appropriateness of therapy based on whether the patient received vancomycin consistent with guideline recommendations. Using a comorbidity index used for risk assessment in high risk hematology/oncology patients, we evaluated whether specific comorbidities are associated with inappropriate vancomycin use in the setting of febrile neutropenia. Results A total of 206 patients were included in the pre-pathway time period with 35.9% of patients receiving vancomycin therapy that was inconsistent with the pathway. A total of 131 patients were included in the post-pathway time period with 11.4% of patients receiving vancomycin inconsistent with the pathway ( p = 0.001). None of the comorbidities assessed, nor the comorbidity index score were found to be predictors of vancomycin use inconsistent with guideline recommendations. Conclusion Our study has demonstrated that implementation of a febrile neutropenia pathway can significantly improve adherence to national guideline recommendations with respect to empiric vancomycin utilization for febrile neutropenia.

Impact of COVID-19 Pandemic, Social Vulnerability, and Opioid Overdoses in Chicago.

Introduction: This research was undertaken to examine the individual and neighborhood drivers that contributed to increases in opioid overdose deaths during the COVID-19 pandemic. Methods: The incident location and Centers for Disease Control and Prevention Social Vulnerability Index (along with the individual indicators) were then geocoded to 1 of the 77 Chicago Community Areas. Changes in opioid overdose death rates were calculated and compared for each Chicago Community Area using linear regression between 2019 and 2020. Results: Opioid overdose deaths increased by 45% from 2019 to 2020. Chicago Community Areas in the highest 25th percentile of social vulnerability before the pandemic had a 2.8 times higher rate of opioid overdose deaths than Chicago Community Areas in the lowest 25th percentile. The increase in opioid overdose death rate observed from 2019 to 2020 was 10.2 times higher in the most socially vulnerable Chicago Community Areas than in the least vulnerable communities. Chicago Community Areas with the highest degree of social vulnerability had a higher baseline and disproportionate relative increase in opioid overdose death rate compared with the least vulnerable Chicago Community Areas. Conclusions: COVID-19 has revealed the urgent need for policies that better support the social and economic security of disadvantaged communities, particularly for residents who use opioids.

Alternative Trastuzumab Dosing Schedules Are Associated With Reductions in Health Care Greenhouse Gas Emissions.

PURPOSE: Cancer care-related greenhouse gas (GHG) emissions harm human health. Many cancer drugs are administered at greater-than-necessary doses, frequencies, and durations. Alternative dosing strategies may enable reductions in cancer care GHG emissions without compromising patient outcomes. MATERIALS AND METHODS: We used streamlined life-cycle analysis in a case-control simulation to estimate the relative reductions in GHG emissions that would be expected to result from using each of three alternative dosing strategies of trastuzumab (6-month adjuvant treatment duration, once every 4-week dosing, and both) in human epidermal growth factor receptor 2 (HER2)+ breast cancer. Using primary data and conversion factors from the environmental science literature, we estimated per-patient relative reduction in GHG emissions and, using SEER data, health impacts (in terms of disability-adjusted life-years [DALYs] and excess mortality per kg CO2) on bystanders for each alternative dosing strategy. RESULTS: Compared with the trastuzumab dosing strategy commonly used at baseline (12-month duration of adjuvant therapy and once every 3-week dosing in all settings), adoption of both 6-month adjuvant trastuzumab and once every 4-week trastuzumab dosing would reduce GHG emissions by 4.5%, 18.7%, and 14.6% in the neoadjuvant, adjuvant, and metastatic settings, respectively. We estimate that US-based adoption of alternative trastuzumab dosing would reduce annual DALYs and excess lives lost due to environmental impact of US-based trastuzumab therapy for HER2+ breast cancer by 1.5 and 0.9, respectively. CONCLUSION: Alternative dosing strategies may materially reduce the population health impacts of cancer care by reducing environmental impact. Regulatory decision making and health technology assessments should consider a treatment's environmental and population health impacts. Clinical trials of alternative dosing strategies are justified on the basis of environmental and population health impacts.

Implementation of Debriefing Services for Pharmacy Residents in a 24-Hour, In-House Clinical Pharmacy On-Call Program: A Pilot Study.

Background: This clinical pharmacy on-call program (CPOP) is a 24-hour, in-house service provided by pharmacy residents. During shifts, challenging situations may arise, which may correlate with depression, anxiety, and stress. Objective: This pilot study aims to describe the implementation of a debriefing program and characterize mental health patterns of residents in the CPOP. Methods: A structured debriefing process was developed to provide support to residents in the CPOP. Over a 1-year period, twelve outgoing pharmacy residents and ten incoming pharmacy residents completed a modified Depression Anxiety Stress Scale (mDASS-21) questionnaire and received a stress perception score (SPS) during debriefing. Data from first and final on-call shifts were compared via a paired Wilcoxon signed-rank test. Residents were referred to an Employee Assistance Program (EAP) based on mDASS-21 and SPS results. Scores from final on-call shifts were compared between residency classes via a Wilcoxon rank sum test. Results: Following successful implementation, 106 debriefing sessions were completed. Pharmacy residents responded to a median number of 38 events per shift. Significant reductions in anxiety and stress scores were observed from the first and final on-call shifts. Six residents were referred to EAP. A lower incidence of depression, anxiety, and stress was observed in pharmacy residents who received debriefing compared to previous residents. Conclusion: The debriefing program provided emotional support to pharmacy residents participating in the CPOP. Implementation of debriefing demonstrated a reduction of anxiety and stress from the beginning to the end of the academic year and in comparison to the previous year.

Lidocaine and Ketamine Infusions as Adjunctive Pain Management Therapy: A Retrospective Analysis of Clinical Outcomes in Hospitalized Patients Admitted for Pain Related to Sickle Cell Disease.

Objective: In this study, we aim to evaluate the efficacy of adjunctive lidocaine and ketamine infusions for opioid reduction in the treatment of sickle cell disease in patients with vaso-occlusive crisis (VOC). Design: We retrospectively reviewed a cohort of 330 adult sickle-cell crisis hospital encounters with 68 patients admitted to our institution from July 2017 to August 2018. Methods: Upon institutional IRB approval, we obtained initial data from billing records and performed chart reviews to obtain pain scores and confirm total opioid consumption. If provided by the acute pain consultation service, the patients received either a lidocaine or a ketamine infusion of 0.5-2 mg/min or 2-3 mcg/kg, respectively, for a maximum of 24-48 h. We compared the change in opioid consumption before and after infusion therapy to patients that did not receive ketamine or lidocaine. Results: Compared to patients that did not receive infusion therapy, ketamine and lidocaine accounted for respective relative decreases of 28 and 23% in average daily morphine consumption (p = 0.02). Patients that received either infusion were 3 to 4 times more likely to decrease their opioid consumption independent of treatment length or baseline opioid doses (p < 0.01). Ketamine and lidocaine therapies were not associated with change in pain scores. When a patient had multiple admissions, opioid reduction was strongly correlated with initiation of infusions in the later visits. Conclusion: Both ketamine and lidocaine infusion therapies are effective in reducing opioid consumption for patients with vaso-occlusive crisis. Lidocaine infusion is emerging as an agent for stabilizing opioid doses in VOC for patients with high daily MME.

Quality improvement and reconciliation process for automated dispensing cabinet medication overrides.

PURPOSE: To describe a pharmacist-led reconciliation process for automated dispensing cabinet (ADC) medication override setting maintenance at an academic medical center. SUMMARY: ADC override management requires alignment of people, processes, and technology. This evaluation describes system-wide improvements to enhance institutional medication override policy compliance by establishing a formalized evaluation and defined roles to streamline ADC dispense setting management. A pharmacist-led quality improvement initiative revised the institutional medication override list to improve medication dispensing practices across an academic medical center campus with a pediatric hospital and 2 adult hospitals. This initiative included removal of patient care unit designations from the medication override list, revision of institutional override policy, creation of an online submission form, and selection of ADC override metrics for surveillance. A conceptual framework guided decisions for unique dosage forms and interdisciplinary engagement. Employing this framework revised workflows for stakeholders in the medication-use process through clinical pharmacist evaluation, existing shared governance structure communication, and pharmacy automation support.The revised policy increased the number of medications available for override from 80 to 106 (33% increase) and unique dosage forms from 166 to 191 (15% increase). The total number of medication dispense settings was reduced from 5,600 to 541 (90% decrease). The proportion of override dispenses compliant with policy increased from 59% to 98% (P < 0.001). Median monthly ADC overrides remained unchanged following policy revision (P = 0.995). ADC override rate reduction was observed across the institution, with the rate decreasing from 1.4% to 1.2% (P < 0.001). Similar ADC override rate reductions were observed for adult, pediatric, and emergency department ADCs. CONCLUSION: This initiative highlights pharmacists' role in leading institutional policy changes that influence the medication-use process through ADC dispensing practices. A pharmacist-led reconciliation process that removed practice area designations from our medication override policy streamlined ADC setting maintenance, increased the compliance rate of ADC override transactions, and provided a formalized process for future evaluation of medication overrides.

Alternative trastuzumab dosing strategies in HER2-positive early breast cancer are associated with patient out-of-pocket savings.

Patients with breast cancer frequently experience financial hardship, often due to the high costs of anti-cancer drugs. We sought to develop alternative trastuzumab dosing strategies, compare their pharmacokinetic effectiveness to standard dosing, and assess the expected financial implications of transitioning to them. We extracted clinical data from the records of 135 retrospectively identified patients with HER2-positive early breast cancer at a single, urban comprehensive cancer center who were treated with trastuzumab between 2017 and 2019. We performed pharmacokinetic simulations on a range of trastuzumab dose levels and frequencies, assessing efficacy by trough trastuzumab concentration (Ctrough) and population and individual likelihoods of Ctrough exceeding trastuzumab minimum effective concentration (MEC). We performed deterministic financial modeling to estimate the treatment-associated financial savings from alternative dosing strategies. Trastuzumab maintenance doses of 4 mg/kg every 3 weeks (Q3W) and 6 mg/kg every 4 weeks (Q4W) had nearly identical probabilities of Ctrough being above MEC as standard of care 6 mg/kg every 3 weeks. In the primary financial analysis, both trastuzumab 4 mg/kg Q3W and 6 mg/kg Q4W were associated with significant drug- and administration-related out-of-pocket cost savings over the duration of therapy, ranging from $765 (neoadjuvant, Q4W) to $2791 (adjuvant, Q4W). In particular, Q4W trastuzumab increased savings related to lost wages and travel cost avoidance. Low-dose and reduced frequency trastuzumab in appropriately selected patients may significantly reduce total drug utilization and meaningfully reduce patient financial toxicity. Prospective clinical trials evaluating low-dose or reduced-frequency administration of therapeutic monoclonal antibodies are warranted and needed.