Targeted tissue delivery of RNA therapeutics using antibody-oligonucleotide conjugates (AOCs).

Although targeting TfR1 to deliver oligonucleotides to skeletal muscle has been demonstrated in rodents, effectiveness and pharmacokinetic/pharmacodynamic (PKPD) properties remained unknown in higher species. We developed antibody-oligonucleotide conjugates (AOCs) towards mice or monkeys utilizing anti-TfR1 monoclonal antibodies (αTfR1) conjugated to various classes of oligonucleotides (siRNA, ASOs and PMOs). αTfR1 AOCs delivered oligonucleotides to muscle tissue in both species. In mice, αTfR1 AOCs achieved a > 15-fold higher concentration to muscle tissue than unconjugated siRNA. A single dose of an αTfR1 conjugated to an siRNA against Ssb mRNA produced > 75% Ssb mRNA reduction in mice and monkeys, and mRNA silencing was greatest in skeletal and cardiac (striated) muscle with minimal to no activity in other major organs. In mice the EC50 for Ssb mRNA reduction in skeletal muscle was >75-fold less than in systemic tissues. Oligonucleotides conjugated to control antibodies or cholesterol produced no mRNA reduction or were 10-fold less potent, respectively. Tissue PKPD of AOCs demonstrated mRNA silencing activity primarily driven by receptor-mediated delivery in striated muscle for siRNA oligonucleotides. In mice, we show that AOC-mediated delivery is operable across various oligonucleotide modalities. AOC PKPD properties translated to higher species, providing promise for a new class of oligonucleotide therapeutics.

Single-Dose Antibiotic Prophylaxis with Ertapenem Increases Compliance with Recommendations for Surgical Antibiotic Prophylaxis in Elective Colorectal Surgery: A Retrospective, Single-Center Analysis.

Background: Compliance with guideline recommendations for surgical antibiotic prophylaxis (SAP) in colorectal surgery, particularly redosing, has been suboptimal at many institutions including ours. This study aimed to evaluate if single-dose antibiotic prophylaxis with ertapenem improves compliance with guideline recommendations for SAP versus multiple-dose antibiotic prophylaxis in elective colorectal surgery. Methods: A retrospective, cohort study of the use of ertapenem compared with standard of care antibiotic agents was performed in adult patients undergoing elective colorectal surgery at an academic medical center between January 2020 and February 2022. The primary outcome was compliance with guideline-recommended SAP for colorectal surgery. The secondary outcome was surgical site infections (SSIs) within 30 days after surgery. Results: A total of 135 patients were included in this study. Fifty-eight patients received single-dose antibiotic prophylaxis with ertapenem and 77 patients received multiple-dose antibiotic prophylaxis. Cefazolin plus metronidazole was the most common multiple-dose regimen (65 of 77). Single-dose antibiotic prophylaxis with ertapenem increased overall SAP compliance (96.6% vs. 64.9%; p < 0.001) as well as compliance with antibiotic administration within the recommended time period before incision (96.6% vs. 84.4%; p = 0.022), compliance with intra-operative antibiotic redosing when warranted (100% vs. 83.1%; p < 0.001), and compliance with guideline-recommended dosing (100% vs. 92.2%; p = 0.037). Surgical site infection rates were not statistically different between the groups (12.1% vs. 19.4%; p = 0.248). Conclusions: Single-dose antibiotic prophylaxis with ertapenem increased compliance with guideline-recommended SAP for elective colorectal surgeries. No statistically significant difference was observed in SSI rates regardless of the antibiotic regimen used.

Does a Positive Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screen Predict the Risk for MRSA Skin and Soft Tissue Infection?

BACKGROUND: Skin and soft tissue infections (SSTIs) are often caused by gram-positive bacteria that colonize the skin. Given the overuse of antibiotics, SSTIs are increasingly caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Guidance on the utility of MRSA nasal screening for MRSA SSTI is limited. OBJECTIVE: To determine whether MRSA nasal screening predicts the risk of MRSA SSTIs. METHODS: This was a single-center, retrospective cohort study of adult patients with an SSTI diagnosis that had MRSA nasal screening and wound cultures obtained within 48 hours of starting antibiotics. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated using VassarStats. Pretest and posttest probabilities were estimated with Microsoft Excel. RESULTS: A total of 884 patient encounters were reviewed between December 1, 2018, and October 31, 2021, and 300 patient encounters were included. The prevalence of MRSA SSTI was 18.3%. The MRSA nasal colonization had a sensitivity of 63.6%, specificity of 93.9%, positive predictive value of 70.0% (95% CI = 55.2%-81.7%), negative predictive value of 92.0% (95% CI = 87.7%-94.9%), positive likelihood ratio of 10.39 (95% CI = 6.12-17.65), negative likelihood ratio of 0.39 (95% CI = 0.27-0.55), positive posttest probability of 70.0%, and negative posttest probability of 8.0%. CONCLUSIONS: Given the high positive likelihood ratio, a positive MRSA nasal screen was associated with a large increase in the probability of MRSA SSTI at our institution, and a negative MRSA nasal screen was associated with a small but potentially significant decrease in the probability of MRSA SSTI.

Accuracy of 4 Free Online Dosing Calculators in Predicting the Vancomycin Area Under the Concentration-Time Curve Calculated Using a 2-Point Pharmacokinetic Approach.

BACKGROUND: Free online adaptive vancomycin dosing calculators are available to estimate area under the concentration-time curve (AUC), but the accuracy of predicting vancomycin AUC using these calculators compared with using a 2-point pharmacokinetic approach has not been described. OBJECTIVE: To evaluate the accuracy of calculator-predicted AUC (cpAUC) using 4 free online calculators compared with reference AUC (rAUC), and to assess pharmacists' impressions of the ease of use. METHODS: Vancomycin AUC was estimated using (1) the reference method via the Sawchuk-Zaske method and linear-logarithmic trapezoidal rule using 2 steady-state postdistributional vancomycin serum concentrations and (2) 4 free online vancomycin dosing calculators including ClinCalc, VancoPK, TDMx, and DMC. Accuracy was calculated by dividing cpAUC by rAUC. Ease of cpAUC estimation was determined by using a 10-point Likert scale. RESULTS: All 4 calculators had a median cpAUC accuracy ranging from 89% to 110%. Concordance between cpAUC and rAUC determinations of AUC <400 and > 600 mg·h/L occurred 63.3% to 71.4% and 74.5% to 78.6% of the time, respectively. Pharmacist investigators agreed that ClinCalc and VancoPK calculators were easiest to use. CONCLUSION AND RELEVANCE: cpAUC accuracy varied among the 4 calculators, but all consistently identified patients with an rAUC <400 mg·h/L and an rAUC > 600 mg·h/L at comparable frequencies. All 4 calculators demonstrated some imprecision based on their wide 95% CIs and potential inaccuracies in predicting an rAUC <400 mg·h/L or an rAUC > 600 mg·h/L. Clin Calc and VancoPK were most user friendly based on our pharmacists' impressions.

Comparison of vancomycin area under the concentration-time curve (AUC) using two-point pharmacokinetics versus two open-access online single-concentration vancomycin calculators.

WHAT IS KNOWN AND OBJECTIVE: Current vancomycin monitoring guidelines recommend the use of area under the concentration-time curve (AUC24 ) monitoring in patients with serious Methicillin-Resistant Staphylococcus aureus (MRSA) infections by utilizing either a Bayesian approach or first-order analytic equations. Several open-access websites exist that allow estimation of vancomycin AUC24 with the use of a single steady-state concentration. It is uncertain how these open-access calculators perform against guideline-recommended methods. The objective was to compare AUC24 estimates from two online, open-access, single-concentration vancomycin calculators compared with the two-point pharmacokinetic (2PK) method. METHODS: AUC24 estimates were made using the 2PK reference method and the single-concentration vancomycin calculators, ClinCalc and VancoPK. The AUC24 estimates from the 2PK reference method were compared to the online calculators by assessing bias (median AUC24 difference) and precision (AUC24 difference ± 100 mg*h/L). Clinical precision was also assessed by characterizing the frequency that the 2PK reference method and the online calculators showed clinical disagreement based on the following AUC24 categories: (1) AUC24 < 400 mg*h/L; (2) AUC24 400-600 mg*h/L and (3) AUC24 > 600 mg*h/L. RESULTS AND DISCUSSION: A total of 253 patients were included in the study. The AUC24 estimates from the ClinCalc and VancoPK single-concentration vancomycin calculators showed some bias and imprecision, though VancoPK appeared to have less. Clinical disagreement versus the 2PK reference method occurred in 31.2% and 19.4% of AUC24 estimates from the ClinCalc and VancoPK single-concentration vancomycin calculators, suggesting clinical imprecision. WHAT IS NEW AND CONCLUSION: The AUC24 estimates from single-concentration, online vancomycin calculators showed some bias and imprecision in comparison to the 2PK method. Institutions should validate these online, trough-only calculators relative to a 2PK method in their patient populations prior to adoption as standard-of-care.

Prophylactic Enoxaparin in Critically Ill Trauma Patients: Evaluation of the Initial Dose.

Background: Trauma patients are at increased risk of developing venous thromboembolism given alterations in the coagulation cascade. Chemoprophylaxis with standard dosing of enoxaparin 30 mg subcutaneously twice daily has evolved to incorporate the use of anti-factor Xa (AFXa) trough level monitoring given concerns for decreased enoxaparin bioavailability in this patient population. Current available evidence suggests low rates of goal AFXa trough level achievement with standard enoxaparin dosing. Our study aims to identify the incidence of critically ill trauma patients that did not achieve goal AFXa trough levels and attempts to identify predictors that may influence the lack of achievement of goal levels. Methods: This was a retrospective, cohort analysis performed at a single academic medical center. Adult patients 18 years or older admitted to the surgical intensive care unit secondary to trauma who were initiated on standard prophylactic enoxaparin and had at least 1 AFXa trough level representative of steady state were included. Patient demographics and clinical data were collected, and descriptive statistics were utilized. All statistical tests were 2-tailed and a P < .05 was considered significant. Variables with a P < .10 on univariable analysis were included in a multivariable logistic regression analysis. Results: A majority of our patient population did not achieve goal AFXa trough levels while receiving standard doses of prophylactic enoxaparin (82.4% [108/131]). Sub-target AFXa levels were associated with higher creatinine clearance values. Positive predictors of obtaining target AFXa levels included automobile versus pedestrian mechanism of injury and requiring an enoxaparin dose escalation to at least 40 mg twice daily. Conclusions: Our study found low rates of achievement of goal AFXa trough levels in critically ill trauma patients receiving standard prophylactic enoxaparin dosing. Certain variables were identified as negative and positive predictors for achievement of goal AFXa trough levels, although the biologic plausibility of these predictors is questionable and requires further investigation.

Validation of Methicillin-Resistant Staphylococcus aureus (MRSA) Risk Factors in Predicting MRSA Community-Acquired Pneumonia at an Academic Medical Center.

Background: The 2019 Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend antimethicillin- resistant Staphylococcus aureus (MRSA) therapy in patients with CAP based on previously identified risk factors for MRSA with an emphasis on local epidemiology and institutional validation of risk. Thus, we sought to assess the ability of guideline-recognized risk factors to predict MRSA CAP at our institution. Methods: This was a single-center, retrospective cohort study from January 2016 to March 2020. Patients were included if they were >18 years old, diagnosed with CAP, and had a MRSA nasal screen and respiratory culture obtained on admission. Patients were excluded if CAP diagnosis was not met, respiratory cultures were not obtained within 48 hours of antibiotic initiation, or they had cystic fibrosis. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios (LR) were calculated using Vasser Stats 2019. Pre/post-test odds and pre/post-test probabilities were calculated using Excel 2019. Results: Of 705 screened patients, 221 were included. MRSA prevalence in CAP patients at our institution was 3.6%. History of MRSA isolated from a respiratory specimen had high specificity (98%), high positive LR of 20 (95% CI 5.3-74.8), and high post-test probability of 42.8%. Receipt of IV antibiotics during hospitalization within the past 90 days had a positive LR of 1.9 (95% CI 0.74-4.84). A positive MRSA nasal screen on admission had a positive LR of 6.9 (95% CI 4.0-12.1), negative LR 0.28 (95% CI 0.08-0.93), positive post-test probability of 20.7%, and negative post-test probability of 1.04%. Conclusion: Our study utilized institutional data to validate guideline recognized risk factors for MRSA CAP specifically at our institution. Risk factors including history of MRSA isolated from a respiratory specimen, and positive post-admission MRSA nasal screen were validated as significant risk factors; receipt of IV antibiotics during hospitalization within the past 90 days was not shown to be a risk factor for MRSA CAP based on our institutional data. Validated risk factors may help providers discern which patients with CAP at our institution would benefit most from empiric MRSA treatment.

Evaluation of ß-lactam therapeutic drug monitoring among US health systems with postgraduate year 2 infectious diseases pharmacy residency programs.

PURPOSE: While some guidelines recognize the need for ß-lactam therapeutic drug monitoring (TDM), there is still a paucity of data regarding the prevalence of and barriers to performing ß-lactam TDM in the United States. We sought to estimate the prevalence of ß-lactam TDM, describe monitoring practices, and identify actual and perceived barriers to implementation among health systems in the US. METHODS: A multicenter, cross-sectional, 40-item electronic survey was distributed to all postgraduate year 2 (PGY2) infectious diseases (ID) pharmacy residency program directors (RPDs) listed in the American Society of Health-System Pharmacists pharmacy residency directory. The primary outcome was the percentage of institutions with established ß-lactam TDM. Secondary outcomes included assessing ß-lactam TDM methods and identifying potential barriers to implementation. RESULTS: The survey was distributed to 126 PGY2 ID RPDs, with a response rate of 31.7% (40 of 126). Only 8% of respondents (3 of 39) performed ß-lactam TDM. Patient populations, therapeutic targets, and frequency and timing of obtaining repeat ß-lactam concentration measurements varied among institutions. The greatest barrier to implementation was lack of access to testing with a rapid turnaround time. Institutions were unlikely to implement ß-lactam TDM within the next year but were significantly more inclined to do so within 5 years (P < 0.001). CONCLUSION: ß-lactam TDM was infrequently performed at the surveyed US health systems. Lack of access to serum concentration testing with rapid turnaround and lack of US-specific guidelines appear to be considerable barriers to implementing ß-lactam TDM. Among institutions that have implemented ß-lactam TDM, there is considerable variation in monitoring approaches.

Andexanet alfa effectiveness and safety versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage while on apixaban or rivaroxaban: A single-center, retrospective, matched cohort analysis.

BACKGROUND: There is limited information directly comparing andexanet alfa (AA) versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage (ICH) on apixaban or rivaroxaban. OBJECTIVE: The objective of this study was to compare the effectiveness and safety of AA versus 4F-PCC in ICH on apixaban or rivaroxaban. METHODS: This retrospective, matched, cohort analysis was conducted at a single healthcare system. Patients were matched based on baseline ICH volume. The primary outcome was good or excellent ICH hemostasis, which was defined as a 35% or less increase in ICH volume within 24 h following AA or 4F-PCC administration. The secondary outcome was thrombotic events within 14 days following AA or 4F-PCC administration. RESULTS: In total, 26 AA and 26 4F-PCC patients were included in this matched cohort analysis. Both groups had comparable rates of good or excellent ICH hemostasis (AA: 92.3% vs. 4F-PCC: 88.5%, p = 1.000). Thrombotic events within 14-days were not significantly different (AA: 26.9% vs. 4F-PCC: 11.5%, p = 0.159). CONCLUSION AND RELEVANCE: This study found no significant differences in good or excellent ICH hemostasis within 24-h or new thrombotic events within 14-days in a cohort given AA or 4F-PCC for ICH while on apixaban or rivaroxaban. However, this single-center analysis is underpowered due to sample size constraints, therefore further high-quality research comparing AA safety and effectiveness versus 4F-PCC is needed.

Pharmacists Act on Care Transitions in Stroke (PACT-Stroke): A Systems Approach.

PURPOSE: Stroke is one of the leading causes of disability in the United States. Prompt secondary prevention decreases the risk for recurrence. Pharmacists have taken a more active role in poststroke care and are initiating prompt follow-up after hospital discharge. There are, however, limited descriptions providing insight on how to implement programs that address this need. The purpose of this article is to provide insights into the development of a pharmacist-driven transitions of care program for patients with stroke. METHODS: This study was a single-center, retrospective assessment of patients contacted by a pharmacist. All data were analyzed descriptively. Our initial evaluation of the Pharmacists Act on Care Transitions in Stroke (PACT-Stroke) service was to quantify and categorize drug-related problems (DRPs), which included drug selection, drug form, dose selection, treatment duration, dispensing, drug use process, patient-related problems, and other. Patients were included if they were adults who experienced an ischemic stroke. Exclusion criteria for this service included pediatric patients, patients with hemorrhagic strokes, patients with transient ischemic attacks, patients >89 years of age, pregnant patients, and patients discharged to a rehabilitation facility immediately after stroke. FINDINGS: A total of 27 patients were included in this analysis, with a total of 30 DRPs identified. After pharmacist intervention, roughly 83% of these DRPs were resolved. IMPLICATIONS: Implementing secondary prevention measures for patients with stroke is crucial. A pharmacist-led transitions of care pilot program was implemented to address this high-risk patient population. This article serves as a framework for implementation at other institutions that aim to provide similar services and can potentially be applied to other high-risk groups.

Hospital Discharge: An Opportune Time for Antimicrobial Stewardship.

BACKGROUND: Approximately 30% of antimicrobials prescribed in the outpatient setting are unnecessary and up to 50% are inappropriate. Despite this, antimicrobial stewardship (AS) efforts mostly focus on the inpatient setting, and limited data describe AS interventions at hospital discharge. Acknowledging the potential value of discharge AS, we used our existing resources to review discharge oral antimicrobial prescriptions. OBJECTIVE: The primary objective of this retrospective, single-center study was to evaluate the impact of an AS program on discharge oral antimicrobial prescriptions. METHODS: Discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy, reviewed by an infectious diseases (ID) pharmacist, and recorded into our data collection tool from September 1, 2020, to February 28, 2021, were evaluated retrospectively. The primary outcome was to identify the frequency a drug-related problem (DRP) was identified by an ID pharmacist. Secondary outcomes included DRP characterization, percentage of prescriptions with interventions, intervention acceptance rate, and reduction in antimicrobial days dispensed at discharge when interventions to limit treatment duration were accepted. RESULTS: Of the 803 discharge oral antimicrobial prescriptions reviewed, at least 1 DRP was identified in 43.1% (346/803). The most frequently identified DRPs pertained to treatment duration, drug selection, and dose selection. At least 1 intervention was recommended in 42.8% (344/803) of prescriptions. In total, 438 interventions were made and the acceptance rate was 75.6% (331/438). The most common types of interventions included recommendations for a different duration, a different dose or frequency, and antimicrobial discontinuation. When interventions to reduce treatment duration were accepted, the median (interquartile range) number of antimicrobial days decreased from 8 (5-10) days to 4 (0-5.5) days (P < 0.001). CONCLUSION AND RELEVANCE: An ID pharmacist's review of discharge oral antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy resulted in identification of DRPs and subsequent interventions in a substantial number of prescriptions.

Chemical and Physical Stability of an Admixture Containing Cefepime and Vancomycin in Lactated Ringer Solution.

Purpose: To evaluate the chemical and physical stability of an admixture containing cefepime and vancomycin in a single volume of lactated Ringer solution at refrigerated temperatures. Methods: Cefepime 2000 mg and vancomycin 1000 mg were, respectively, reconstituted with 10 and 20 mL of sterile water for injection (SWFI) per manufacturer instructions. This resulted in cefepime and vancomycin concentrations of 200 and 50 mg/mL, respectively. The resulting cefepime and vancomycin solutions at 10 and 20 mL, respectively, were drawn up and injected into 1000 mL lactated Ringer solution. Aliquot samples were obtained on days 0 to 9, visually inspected for gross incompatibility, and then stored at -80°C. Samples were thawed on the day of the analysis and run through ultraperformance liquid chromatography. Area under the concentration-time curve (AUC) on each day was compared with baseline AUC values. Chemical stability was defined as an AUC more than 93% of the baseline value. Results: No evidence of gross physical incompatibility was observed by visual inspection. Cefepime and vancomycin replicants were more than 94.5% and 98% of baseline AUC values. Therefore, all sample replicants were found to be more than 93% of their baseline AUC value. Conclusion: An admixture containing cefepime 2000 mg and vancomycin 1000 mg in 1000 mL lactated Ringer solution appears to be chemically and physically stable at refrigerated temperatures for up to 9 days.

Trust your gut: Effect of a pharmacist-driven pilot project to decrease alvimopan use past gastrointestinal recovery in postsurgical patients.

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these 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: Alvimopan is a peripherally acting opioid receptor antagonist indicated to accelerate gastrointestinal (GI) recovery following surgery, but its benefits past GI recovery are unknown and evidence suggests that it may increase risk for myocardial infarction. The purpose of this study was to evaluate the efficacy of a pilot alvimopan stewardship program aimed at intervening to discontinue alvimopan use following GI recovery. METHODS: This was a retrospective, observational study examining the first 5 months of the alvimopan stewardship pilot program. During this initial period, a pharmacy resident assessed whether each patient met criteria for GI recovery, defined as solid food toleration and first bowel movement or flatus. If a patient met the criteria for GI recovery, the resident intervened and recommended that the primary team discontinue alvimopan. Primary outcomes were the percentage of patients with alvimopan continued past GI recovery and the percentage of patients for whom alvimopan ordered past GI recovery was discontinued following intervention by stewardship. Secondary outcomes included the percentage of accepted recommendations to discontinue alvimopan following GI recovery and the number of alvimopan doses ordered following GI recovery. RESULTS: In total, 73 patients were included in the study analysis, all of whom underwent abdominal and/or urologic surgery. Alvimopan was ordered to be administered in 35.6% (26/73) of patients after GI recovery. The stewardship program intervened and recommended discontinuation on 50% (13/26) of the alvimopan doses ordered past GI recovery. Recommendations were accepted by the primary team for 92.3% (12/13) of the patients. A total of 51 doses of alvimopan were ordered for administration past GI recovery, with an average of 2 doses per patient. CONCLUSION: A pilot pharmacy-driven alvimopan stewardship program was able to identify and intervene on alvimopan orders continued past GI recovery. Interventions decreasing alvimopan use past GI recovery could be of benefit by minimizing potential risk and decreasing potential costs without a negative impact on patient outcomes.

Implementation of a formal pharmacy residency research certificate program.

PURPOSE: We describe the structure, implementation, and initial evaluation of a formal residency research certificate program (RRCP) designed to further advance residents' knowledge and skills in research in an effort to better prepare residents for research involvement during their careers. SUMMARY: Pharmacy residency programs vary in the degree of emphasis on research education and training and the structure of resident research activities. Limited data describing formal research education and training for pharmacy residents are available. To better educate and prepare residents in the research process, State University of New York Upstate University Hospital developed and implemented a formal RRCP designed to educate and train residents in essential areas of the research process. Research seminars are delivered by preceptors with experience and training in research throughout the academic year to align with residency project tasks. Residents are also required to complete at least 1 residency project and submit a manuscript suitable for publication in a peer-reviewed journal. Upon successful completion of the program and project requirements, residents earn a certificate of completion. Initial data collected through formal resident assessments before and after RRCP completion demonstrated significant improvement in research knowledge (from an average score of 61.3% out of 100% to an average score of 84.7%, P = 0.002). CONCLUSION: Post-RRCP assessment showed improvements in residents' confidence in several areas of research, including but not limited to research project design, ethical and regulatory principles of research, data collection, selection of appropriate statistical tests, manuscript writing, and the publication process. Residents strongly agreed that the RRCP improved their overall knowledge and perceptions of research.

Safety and Efficacy of Direct Oral Anticoagulant Therapy in Patients With Cancer.

BACKGROUND: Venous thromboembolism (VTE) is the second leading cause of death in patients with malignancy. The currently available guidelines have shown greater support for utilization of low-molecular-weight heparin (LMWH) over direct oral anticoagulants (DOACs) in cancer-associated VTE. Current data on the safety and efficacy of DOAC therapy in patients with cancer are lacking. OBJECTIVE: To evaluate the safety and efficacy of the use of DOACs compared to LMWH in patients with cancer. METHODS: A retrospective review of outpatient records was completed to identify patients with documented cancer diagnosis and either a DOAC or LMWH as a listed medication. Patients were excluded if they had atrial fibrillation, valvular disease, antiphospholipid antibody syndrome, current pregnancy, body mass index (BMI) >40 kg/m2 or weight >120 kg, severe renal or hepatic impairment, or were on concomitant therapy with a significant interacting medication. The primary outcome was frequency of VTE recurrence, and secondary outcomes included the frequency of major and minor bleeding and other thrombotic events. RESULTS: One hundred fifty-six patients were included in the study population, 78 in both the DOAC and LMWH groups. Venous thromboembolism recurrence occurred in 5 (6.4%) patients in the DOAC group and 8 (10.3%) patients in the LMWH group (P = .39). There was no significant difference in major or minor bleeding or other thrombotic events between the 2 groups. CONCLUSION: The frequency of VTE recurrence was similar between DOACs and LMWH in patients with cancer. DOACs may be an alternative agent to LMWH for the prevention of recurrent VTE in patients with cancer.

Effect of a Standardized Treatment Panel on Hypoglycemic Events in Hospitalized Acute Hyperkalemic Patients Treated With Intravenous Regular Insulin.

Purpose: Regular insulin is a commonly utilized treatment option for acute hyperkalemia. Despite its benefit, hypoglycemia and associated morbidity/mortality remain important concerns. This institution recently created a treatment panel to standardize regular insulin dosing (0.1 unit/kg) and blood glucose (BG) monitoring in patients with acute hyperkalemia. The purpose of this study is to investigate whether the order panel reduces hypoglycemic events in adults treated with intravenous (IV) regular insulin for hyperkalemia and to determine the effect the treatment panel has on regular insulin dosing, serum potassium, BG monitoring, and dextrose supplementation. Methods: This retrospective study was performed at a single academic medical center. Adults receiving IV regular insulin for acute hyperkalemia were included if BG was assessed prior to and following regular insulin administration. Primary outcome was hypoglycemia within 4 hours of regular insulin administration. Secondary outcomes were the change from baseline serum potassium, frequency of severe hypoglycemia, BG checks within 30 minutes prior to and within 4 hours following insulin administration, regular insulin dosing, and administration of dextrose 50% in water (D50W) following regular insulin administration. Hypoglycemia and severe hypoglycemia were defined as a BG concentration of <70 mg/dL and <50 mg/dL, respectively. Results: One hundred sixty-five patients were included; 75 using the treatment panel and 90 not. Patients using the treatment panel received a lower median (interquartile range [IQR]) regular insulin dose (.10 [0.09-0.10 unit/kg] vs 0.11 [0.09-0.14 unit/kg], P = .004) and had more frequent BG checks during the 4 hours following regular insulin administration (median [IQR]: 4 [3-5] vs 2 [1-3], P < .001). Hypoglycemia (13.3% vs 27.8%, P = .024) and severe hypoglycemia (2.7% vs 11.1%, P = .038) occurred less frequently with the treatment panel. Similar decreases in serum potassium were noted following IV regular insulin administration. Conclusions: Acute hyperkalemic patients utilizing a standardized treatment panel for the dosing and monitoring of IV regular insulin experienced fewer hypoglycemic and severe hypoglycemic episodes and had similar potassium lower effects. The treatment panel decreased regular insulin dosing and increased BG monitoring prior to and following regular insulin administration.

Cost comparison of AUC:MIC- versus trough-based vancomycin monitoring for MRSA bacteremia.

OBJECTIVES: It is anticipated that the updated vancomycin monitoring guidelines will reconsider area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC)-based monitoring instead of trough-based monitoring for methicillin-resistant Staphylococcus aureus (MRSA) infections. The AUC:MIC can be estimated using 2 steady-state serum concentrations and first-order pharmacokinetic equations or Bayesian modeling. The cost of AUC:MIC-based monitoring compared with trough-based monitoring is unknown and has been cited as a potential barrier to implementing this monitoring method. The objective of this study was to compare the total vancomycin drug and monitoring cost for patients with MRSA bacteremia who received AUC:MIC- or trough-based monitoring. DESIGN: This was a single-center, retrospective cohort study. SETTING AND PARTICIPANTS: This study included patients who were treated for MRSA bacteremia between May 1, 2013 and December 31, 2018, with an 8-month washout period between trough and AUC:MIC-based monitoring at our institution. OUTCOME MEASURES: The primary outcome was the aggregate cost of vancomycin therapy, which included the cost associated with sample collection (i.e., supply cost and nursing time), sample analysis (i.e., assay cost and laboratory technician time), result interpretation (i.e., pharmacist time), and drug cost (i.e., cost of total administered vancomycin dose) during the hospital stay. RESULTS: A total of 52 patients met inclusion criteria with 26 patients in each group. The median (interquartile range) total vancomycin drug and monitoring cost was $338.14 ($235.07-$601.05) for the AUC:MIC-based group compared with $316.79 ($253.36-$520.96) for the trough-based group (P = 0.687). CONCLUSION: Vancomycin monitoring using 2 steady-state serum concentrations and first-order pharmacokinetic equations to calculate AUC:MIC was no more costly than a trough-based approach in patients with MRSA bacteremia at our institution.

Verifying Medication Orders in the Older Population: Are We Using Enough Caution?

OBJECTIVE: To test the common hypothesis that pharmacists may use more caution and resources when processing pediatric versus geriatric medication orders in the hospital setting.
DESIGN: A 26-item electronic survey was distributed to a sample of participating academic medical-center pharmacy directors with the request to disseminate it to staff pharmacists. The survey was resent at two-week intervals on two occasions.
MAIN OUTCOME MEASURE(S): To identify if pharmacists take more caution when processing geriatric or pediatric medication orders, to characterize the frequency pharmacists use drug information resources when processing these orders, and to assess the level of importance pharmacists place on guidelines for medication error prevention when processing medication orders.
RESULTS: A total of 173 out of 271 pharmacists completed the survey, resulting in a high final completion rate of 63.8%. Most were clinical, residencytrained pharmacists. A majority of respondents stated that they take more caution when verifying pediatric medication orders than they do for orders for older people (125 out of 172, or 72.7%). Pharmacists report they were 4.2 times more likely to refer to a drug information resource for ≥ 50% of pediatric orders versus geriatric orders (pediatric: 118 out of 171, or 69.0% vs. geriatric: 59 out of 172, or 34.3%; P < 0.001, or 95% confidence interval [CI] 4.156 [2.647-6.524]). Finally, pharmacists familiar with the guidelines for medication error prevention were 2.3 times more likely to state the pediatric guidelines were very important (pediatric: 51/171, or 29.8% vs. geriatric: 27/172, or 15.7%; P = 0.002, or 95% CI 2.28 [1.35-3.86]).
CONCLUSION: This survey reveals evidence for attitudinal differences in work practices for pharmacists working with medication orders relating to different age groups. Given the challenges involved in drug treatment for the older patient population, a similar level of caution, preparedness to refer to drug information, and to use guidelines should apply for both pediatric medication orders and those for older people, in order to provide safe and comprehensive care.