Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

DISCLAIMER: 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. PURPOSE: Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. RESULTS: Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. CONCLUSION: Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Pharmacy-driven performance improvement initiative to increase compliance with intravenous smart pump drug error reduction systems at a large urban academic medical center.

DISCLAIMER: 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. PURPOSE: Smart pump dose error reduction systems (DERS) reduce errors for intravenous (IV) administration medications by warning users of order, calculation, and programming errors. The purpose of this performance improvement initiative was to increase IV smart pump DERS usage from 77% to 95% at a large, urban academic medical center. METHODS: A pharmacy-led team with nurses, physicians, and quality improvement specialists executed interventions from July 2020 through April 2022 to increase DERS compliance. A discovery phase (phase I) was followed by 6 Plan-Do-Study-Act (PDSA) cycles created to address barriers to DERS utilization. Phase I revealed that problems involving the DERS library and bedside nurse training were the major drivers of noncompliance. Phase II consisted of 3 system-level PDSA cycles, and phase III included 3 focused group PDSA cycles. Data were collected monthly from the smart pump reporting software by the informatics pharmacist and analyzed by the team to assess compliance rates in response to the corresponding interventions. RESULTS: The median DERS compliance increased from 77% to 83% over the 2-year period, which correlates with approximately 109,000 additional infusions run on DERS each year within our institution. The implementation of a DERS problem reporting tool accessed through the medication administration record resulted in the most pronounced improvement. CONCLUSION: DERS compliance improved following system-level sustainable interventions, although further PDSA cycles are needed to meet the goal DERS utilization rate of 95%. The results of this study may help other institutions attempting to improve DERS utilization create targeted interventions.

Evaluating Pharmacist-Led Heart Failure Transitions of Care Clinic: Impact of Analytic Approach on Readmission Rate Endpoints.

Studies evaluating pharmacist-led transitions of care (TOC) services for heart failure patients reported profound decreases in hospital readmissions. Most studies restricted their analysis to clinic attendees (as-treated analysis), which can introduce selection and immortal time bias. In this study, we evaluated the impact of including only clinic attendees vs all clinic referrals in assessing the effectiveness of a pharmacist-led heart failure transitions of care (PharmD HF TOC) clinic program on 30-day readmissions. This is a retrospective, observational study of patients discharged from a heart failure hospitalization at a large urban academic medical center from August 2016 to December 2018. Primary exposure was the provision of a PharmD HF TOC clinic appointment in the intent-to-treat analysis and the attendance of the clinic in the as-treated analysis. Primary outcome was all-cause readmissions within 30 days of discharge. There were 766 and 1015 patients included in the as-treated and intent-to-treat analyses, respectively. In the as-treated analysis, 30-day all-cause readmissions were significantly lower in the intervention group compared to the control group (12.4% vs 19.6%, P = 0.018). In contrast, the intent-to-treat analysis did not reveal a significant difference in 30-day all-cause readmissions between the intervention group and the control group (18.2% vs 19.6%, P = 0.643). Pharmacist-led heart failure TOC program is associated with a reduction in 30-day all-cause readmissions only when restricting the analysis to clinic attendees. Future studies evaluating the effectiveness of post-discharge TOC services need to carefully consider the biases inherent in the evaluation methods employed.

Assessment of Patiromer Monotherapy for Hyperkalemia in an Acute Care Setting.

Importance: Hyperkalemia is a common electrolyte disorder in hospitalized patients; however, the clinical usefulness of administering patiromer for reduction of serum potassium levels in this setting is unknown. Objective: To evaluate the outcomes associated with patiromer as monotherapy in patients with acute hyperkalemia in an acute care setting. Design, Setting, and Participants: This cohort study used electronic health record data from adult patients treated with patiromer for acute hyperkalemia in emergency departments, inpatient units, and intensive care units at an urban, academic medical center in the Bronx, New York, between January 30, 2018, and December 30, 2019. Data analysis was conducted between June 2020 and February 2021. Exposures: A single dose of oral patiromer (8.4 g, 16.8 g, or 25.2 g). Main Outcomes and Measure: The primary outcome was the mean absolute reduction in serum potassium level from baseline at 3 distinct time intervals after patiromer administration: 0 to 6 hours, greater than 6 to 12 hours, and greater than 12 to 24 hours. Key secondary outcomes were the incidence of hypokalemia and potassium reduction stratified by baseline potassium level and care setting. Results: Among 881 encounters of patiromer treatment, the mean (SD) age of patients was 67.4 (14.4) years; 463 encounters (52.6%) were for male patients, and most (338 [38.4%]) were for patients who identified as non-Hispanic Black. The mean (SD) baseline serum potassium level was 5.60 (0.35) mEq/L (to convert to mmol/L, multiply by 1.0), and within the first 6 hours after patiromer administration, the mean (SD) potassium reduction was 0.50 (0.56) mEq/L (P < .001). Both absolute and relative potassium reduction from baseline varied across baseline hyperkalemia severity but not by care setting. The lowest dose of patiromer (8.4 g) was used in 721 encounters (81.8%), and in 725 encounters (82.3%), no further doses of a potassium binder were required. Hypokalemia was noted in 2 encounters (0.2%) at 24 hours after patiromer administration. Conclusions and Relevance: In this cohort study of patients with acute, non-life-threatening hyperkalemia, a single dose of patiromer was associated with a significant decrease in serum potassium levels and a low incidence of hypokalemia. These findings suggest that patiromer monotherapy may be useful in an institutional setting for managing elevated potassium levels and minimizing the risk of hypokalemia associated with other potassium control measures.

Implementation of a Standardized Approach to Improve the Pediatric Discharge Medication Process.

BACKGROUND AND OBJECTIVES: The pediatric inpatient discharge medication process is complicated, and caregivers have difficulty managing instructions. Authors of few studies evaluate systematic processes for ensuring quality in these care transitions. We aimed to improve caregiver medication management and understanding of discharge medications by standardizing the discharge medication process. METHODS: An interprofessional team at an urban, tertiary care children's hospital trialed interventions to improve caregiver medication management and understanding. These included mnemonics to aid in complete medication counseling, electronic medical record enhancements to standardize medication documentation and simplify dose rounding, and housestaff education. The primary outcome measure was the proportion of discharge medication-related failures in each 4-week period. Failure was defined as an incorrect response on ≥1 survey questions. Statistical process control was used to analyze improvement over time. Process measures related to medication documentation and dose rounding were compared by using the χ2 test and process control. RESULTS: Special cause variation occurred in the mean discharge medication-related failure rate, which decreased from 70.1% to 36.1% and was sustained. There were significantly more complete after-visit summaries (21.0% vs 85.1%; P < .001) and more patients with simplified dosing (75.2% vs 95.6%; P < .001) in the intervention period. Special cause variation also occurred for these measures. CONCLUSIONS: A systematic approach to standardizing the discharge medication process led to improved caregiver medication management and understanding after pediatric inpatient discharge. These changes could be adapted by other hospitals to enhance the quality of this care transition.

Clinical Pharmacists: An Invaluable Part of the Coronavirus Disease 2019 Frontline Response.

Although coronavirus disease 2019 was first identified in December 2019, it rapidly spread and became a global pandemic. The number of patients infected with the novel coronavirus (severe acute respiratory syndrome coronavirus 2) rose rapidly in New York State, placing great stress on healthcare systems. The traditional roles and practices of healthcare providers were dramatically redefined to meet the demand to care for the large number of ill patients. While literature reports on the experiences of many frontline staff, there is a scarcity of reports on the role of clinical pharmacists during this crisis. We report the role of critical care clinical pharmacists at a large academic medical center in New York City during this pandemic. Effective crisis management required clinical pharmacists to employ a wide array of skills and knowledge. Areas included clinical expertise, education, data analysis, health informatics infrastructure, and inventory management in times of surging medication use and manufacturer shortages. Clinical pharmacists fulfilled an essential service during the coronavirus pandemic by working to ensure the best possible outcomes for the patients they served on the frontline.

Caregiver Medication Management and Understanding After Pediatric Hospital Discharge.

OBJECTIVES: Caregivers frequently make mistakes when following instructions on discharge medications, and these instructions often contain discrepancies. Minimal literature reflects inpatient discharges. Our objective was to describe failures in caregiver management and understanding of inpatient discharge medications and to test the association of documentation discrepancies and sociodemographic factors with medication-related failures after an inpatient hospitalization. METHODS: This study took place in an urban tertiary care children's hospital that serves a low-income, minority population. English-speaking caregivers of children discharged on an oral prescription medication were surveyed about discharge medication knowledge 48 to 96 hours after discharge. The primary outcome was the proportion of caregivers who failed questions on a 10-item questionnaire (analyzed as individual question responses and as a composite outcome of any discharge medication-related failure). Bivariate tests were used to compare documentation errors, complex dosing, and sociodemographic factors to having any discharge medication-related failure. RESULTS: Of 157 caregivers surveyed, 70% had a discharge medication-related failure, most commonly because of lack of knowledge about side effects (52%), wrong duration (17%), and wrong start time (16%). Additionally, 80% of discharge instructions provided to caregivers lacked integral medication information, such as duration or when the next dose after discharge was due. Twenty five percent of prescriptions contained numerically complex doses. In bivariate testing, only race and/or ethnicity was significantly associated with having any failure (P = .03). CONCLUSIONS: The majority of caregivers had a medication-related failure after discharge, and most discharge instructions lacked key medication information. Future work to optimize the discharge process to support caregiver management and understanding of medications is needed.

The Use of Idarucizumab for Dabigatran Reversal in Clinical Practice: A Case Series.

PURPOSE: To describe the use of idarucizumab (Praxbind, Boehringer Ingelheim) in routine clinical practice at a large urban academic medical center. SUMMARY: Seven total doses of idarucizumab were administered to six unique patients from October 31, 2015, to October 31, 2016. The reversal agent was used in conjunction with local bleeding control measures, blood product transfusions, and acid-suppressive therapy. In 86% of cases, idarucizumab administration resulted in a successful cessation of bleeding by clinical assessment. Two patients expired due to coexisting conditions. Idarucizumab was administered to patients with normal baseline coagulation tests in 43% of cases. No adverse reactions related to idarucizumab were reported. CONCLUSIONS: Idarucizumab administration resulted in successful resolution of bleeding by clinical assessment. The therapy for acute bleeding with use of dabigatran (Pradaxa, Boehringer Ingelheim) remains supportive care, in addition to idarucizumab in cases of severe or uncontrolled bleeding. Development of institution-specific protocols and better guidance for using baseline coagulation tests are needed.

Ordering Interruptions in a Tertiary Care Center: A Prospective Observational Study.

OBJECTIVES: By self-report, interruptions may contribute to up to 80% of ordering errors. A greater understanding of the frequency and context of interruptions during ordering is needed to identify targets for intervention. We sought to characterize the epidemiology of interruptions during order placement in the pediatric inpatient setting. METHODS: This prospective observational study conducted 1-hour-long structured observations on morning rounds and afternoons and evenings in the resident workroom. The primary outcome was the number of interruptions per 100 orders placed by residents and physician assistants. We assessed the role of ordering provider, number, type and urgency of interruptions and person initiating interruption. Descriptive statistics, χ2, and run charts were used. RESULTS: Sixty-nine structured observations were conducted with a total of 414 orders included. The interruption rate was 65 interruptions per 100 orders during rounds, 55 per 100 orders in the afternoons and 56 per 100 orders in the evenings. The majority of interruptions were in-person (n = 144, 61%). Interruptions from overhead announcements occurred most often in the mornings, and phone interruptions occurred most often in the evenings (P = .002). Nurses initiated interruptions most frequently. Attending physicians and fellows were more likely to interrupt during rounds, and coresidents were more likely to interrupt in the evenings (P = .002). CONCLUSIONS: Residents and physician assistants are interrupted at a rate of 57 interruptions per 100 orders placed. This may contribute to ordering errors and worsen patient safety. Efforts should be made to decrease interruptions during the ordering process and track their effects on medication errors.

Improving hospital venous thromboembolism prophylaxis with electronic decision support.

BACKGROUND: Venous thromboembolism (VTE) disease prophylaxis rates among medical inpatients have been noted to be <50%. OBJECTIVE: Our objective was to evaluate the effectiveness and safety of a computerized decision support application to improve VTE prophylaxis. DESIGN: Observational cohort study. SETTING: Academic medical center. PATIENTS: Adult inpatients on hospital medicine and nonmedicine services. INTERVENTION: A decision support application designed by a quality improvement team was implemented on medicine services in September 2009. MEASUREMENTS: Effectiveness and safety parameters were compared on medicine services and nonmedicine (nonimplementation) services for 6-month periods before and after implementation. Effectiveness was evaluated by retrospective information system queries for rates of any VTE prophylaxis, pharmacologic VTE prophylaxis, and hospital-acquired VTE incidence. Safety was evaluated by queries for bleeding and thrombocytopenia rates. RESULTS: Medicine service overall VTE prophylaxis increased from 61.9% to 82.1% (P < 0.001), and pharmacologic VTE prophylaxis increased from 59.0% to 74.5% (P < 0.001). Smaller but significant increases were observed on nonmedicine services. Hospital-acquired VTE incidence on medicine services decreased significantly from 0.65% to 0.42% (P = 0.008) and nonsignificantly on nonmedicine services. Bleeding rates increased from 2.9% to 4.0% (P < 0.001) on medicine services and from 7.7% to 8.6% (P = 0.043) on nonmedicine services, with nonsignificant changes in thrombocytopenia rates observed on both services. CONCLUSIONS: An electronic decision support application on inpatient medicine services can significantly improve VTE prophylaxis and hospital-acquired VTE rates with a reasonable safety profile.

Periorbital edema associated with separate courses of ibuprofen and naproxen.

PURPOSE: A case of periorbital edema associated with separate courses of ibuprofen and naproxen is reported. SUMMARY: An 80-year-old African- American woman with a history of osteoarthritis and hypertension came to the clinic. Her medication regimen included fosinopril sodium 40 mg daily, which she began two years prior. She had no known drug allergies and denied consuming any over-the-counter medications or herbal substances and reported a negative atopic status. She had seen her primary care provider several days prior and reported pain in the hands, fingers, and ankles, which would escalate in the morning and progressively lessen during the course of the day. Her physician prescribed naproxen 375 mg every eight hours as needed. After ingesting two doses of naproxen, she developed itching, swelling, and erythema around the left eye that became progressively worse and spread to the right eye. She contacted her primary care physician, who instructed her to discontinue the naproxen, and the reaction resolved within three days. The patient was maintained on acetaminophen for the arthritic pain with no issues. Approximately three months prior, ibuprofen 600 mg every eight hours as needed was prescribed for the same pain. She stated that after ingesting two doses of ibuprofen, she experienced a reaction similar to that recently experienced with naproxen. At that time, she was instructed to discontinue the ibuprofen, and her symptoms resolved. CONCLUSION: An elderly woman developed periorbital edema after taking ibuprofen on one occasion and naproxen on another.

Peak antifactor xa activity produced by dalteparin treatment in patients with renal impairment compared with controls.

STUDY OBJECTIVE: To evaluate the relationship between impaired renal function and antifactor Xa activity in patients receiving dalteparin. DESIGN: Open-label prospective study. SETTING: Inpatient and outpatient units of a large teaching hospital. SUBJECTS: Eleven patients with renal impairment and 11 control subjects with normal renal function. INTERVENTION: Subjects were administered dalteparin at a dosage of approximately 100 U/kg subcutaneously every 12 hours. MEASUREMENTS AND MAIN RESULTS: Peak steady-state antifactor Xa levels were compared between the groups. Mean +/- SD levels were similar for patients with and without renal impairment: 0.47 +/- 0.25 and 0.55 +/- 0.20 U/ml, respectively. A test of equivalency showed statistical significance (p=0.0001). CONCLUSION: No meaningful difference in peak antifactor Xa activity was found between patients with renal impairment and control subjects. To the extent that peak antifactor Xa levels can be used as markers for adjusting doses of dalteparin, these data suggest that such adjustments are not necessary for patients with renal impairment who are not receiving dialysis.

A randomized trial of calcium supplementation for childhood lead poisoning.

OBJECTIVE: Lead (Pb) poisoning remains a common disease among children despite successful public health efforts that have reduced its prevalence. Treatment options for children with blood Pb levels (BPbs) <45 micro g/dL are limited because chelation therapy is generally not indicated. Calcium (Ca) and Pb interactions are well documented. Competition for binding to Ca-binding proteins may underlie a mechanism for Pb absorption. The purpose of this study was to determine the role, if any, of supplemental Ca at reducing BPbs in moderately poisoned children. METHODS: Children aged 1 to 6 years with BPbs 10 to 45 micro g/dL were enrolled in a double-blinded, placebo-controlled trial of the effects of Ca supplementation on BPbs. Children received either a Ca-containing liquid or an indistinguishable placebo. Dosage was adjusted biweekly on the basis of responses to a dietary Ca intake questionnaire to reach 1800 mg in the Ca-supplemented group. Samples for BPbs and measures to assess safety were collected before and after 3 months of supplementation and after an additional 3 months of follow-up. Bivariate and multiple regression analyses were performed. RESULTS: A total of 67 of 88 enrolled children with a mean age of 3.6 years completed 3 months of supplementation. There were no statistically significant differences between groups on hematologic and biochemical measures, including serum and urinary Ca, at any time points. The average compliance rate was estimated to be 80% for each group during the 3-month supplementation period. CONCLUSIONS: At enrollment, the average daily Ca intake in this group of inner-city children was greater than the recommended daily intake for age. Although BPbs declined during a 3-month period in both groups, Ca supplementation aimed at providing 1800 mg of Ca/day had no effect on the change in BPbs. Ca supplementation should not be routinely prescribed for mild to moderately Pb-poisoned children who are dietarily Ca sufficient.

Quantifying value for physician order-entry systems: a balance of cost and quality.

Healthcare CFOs commonly demand hard data to prove that an investment in computerized physician order entry (CPOE) will be worthwhile. However, a balanced analysis of cost and quality of the CPOE system has advantages over traditional return-on-investment appraisals. Montefiore Medical Center (MMC), Bronx, New York, assessed the value of its CPOE system by quantifying cost and quality measures rather than relying solely on dollar returns. MMC collected process times for medication ordering before and after the CPOE system was introduced and demonstrated that the use of CPOE increased medication ordering efficiency by 92 percent. MMC calculated additional process times for ward clerks, nurses, and pharmacists before and after CPOE implementation and determined the time saved per employee. From that number, the dollars potentially saved per employee and total potential dollar value of time savings per year were calculated.