Revefenacin Area Under the Curve Spirometry in Patients with Moderate to Very Severe COPD.

Purpose: Several lung function endpoints are utilized in clinical trials of inhaled bronchodilators for chronic obstructive pulmonary disease (COPD). Trough forced expiratory volume in 1 second (FEV1) is a commonly reported endpoint in COPD trials and can be complemented by area under the FEV1 vs time curve (FEV1 AUC), which provides information on duration and consistency of bronchodilation over a dosing interval. Revefenacin, a once-daily bronchodilator, significantly improved lung function in patients with COPD when measured by trough FEV1 in two replicate Phase 3 trials. Here, we report an FEV1 AUC substudy using data from these trials. Patients and Methods: This post hoc analysis examined substudy data from 12-week replicate Phase 3 trials (NCT02459080/NCT02512510); patients with moderate to very severe COPD were randomized 1:1 to revefenacin 175 µg or placebo once daily. The substudy patients had FEV1 AUC0-2h assessed on Day 1, and those who continued to Day 84 also underwent 24-hour serial spirometry postdose where FEV1 AUC0-2h, AUC0-12h, AUC12-24h, and AUC0-24h were evaluated. Results: Fifty and 47 patients who received revefenacin and placebo underwent 24-hour serial spirometry; most baseline characteristics were aligned between groups. At Day 84 postdose, revefenacin demonstrated sustained improvements in bronchodilation over 24 hours; differences in least squares mean vs placebo were 282, 220, 205, and 212 mL for FEV1 AUC0-2h, AUC0-12h, AUC12-24h, and AUC0-24h (all P <0.001), respectively. Conclusion: This substudy analysis supplements previous findings that revefenacin provides sustained bronchodilation over 24 hours. Assessing additional complementary COPD clinical trial endpoints can help clinicians make treatment decisions.

Experience of a peer prereview service including a junior reviewer program in a professional association.

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: Scientific journals have reportedly low acceptance rates. Peer review support services offering manuscript review before journal submission are uncommon but may increase success with the publication process. The purpose of this report is to describe the development and experience with a peer prereview (PPR) service offered by the Clinical Pharmacy and Pharmacology (CPP) section of the Society of Critical Care Medicine. SUMMARY: The CPP PPR service provides comprehensive review on research manuscripts before submission to a scientific journal. A junior reviewer program provides an opportunity for mentorship and professional development of reviewers. After the review is complete, authors and reviewers complete a survey regarding their experience with the service. Authors are also contacted biannually to determine their manuscript's status. From the program's start in 2011 through June 2022, 64% of the 58 manuscripts reviewed were accepted or published in journals with impact factors ranging from 0.915 to 9.296. Of the 31 (82%) authors responding to the survey, 94% said that the service met or exceeded their expectations and 84% would recommend the service to a colleague. Of the 29 (76%) reviewers responding to the survey, 100% said that the service met or exceeded their expectations and 92% would be willing to review again. CONCLUSION: The majority of manuscripts that went through the CPP PPR service were accepted for publication, and both authors and reviewers were highly satisfied with their experience. The CPP PPR service can be used as a framework for other institutions to implement.

Major Publications in the Critical Care Pharmacotherapy Literature: 2022.

OBJECTIVES: A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. DATA SOURCES: PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. CONCLUSIONS: This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

The Safety of Continuous Infusion Propofol in Mechanically Ventilated Adults With Coronavirus Disease 2019.

BACKGROUND: Propofol is commonly used to achieve ventilator synchrony in critically ill patients with coronavirus disease 2019 (COVID-19), yet its safety in this patient population is unknown. OBJECTIVE: To evaluate the safety, in particular the incidence of hypertriglyceridemia, of continuous infusion propofol in patients with COVID-19. METHODS: This was a retrospective study at 1 academic medical center and 1 affiliated teaching hospital in New York City. Adult, critically ill patients with COVID-19 who received continuous infusion propofol were included. Patients who received propofol for <12 hours, were transferred from an outside hospital while on mechanical ventilation, or did not have a triglyceride concentration obtained during the infusion were excluded. RESULTS: A total of 252 patients were included. Hypertriglyceridemia (serum triglyceride concentration ≥ 400 mg/dL) occurred in 38.9% of patients after a median cumulative dose of 4307 mg (interquartile range [IQR], 2448-9431 mg). The median time to triglyceride elevation was 3.8 days (IQR, 1.9-9.1 days). In the multivariable regression analysis, obese patients had a significantly greater odds of hypertriglyceridemia (odds ratio = 1.87; 95% CI = 1.10, 3.21). There was no occurrence of acute pancreatitis. The incidence of possible propofol-related infusion syndrome was 3.2%. CONCLUSION AND RELEVANCE: Hypertriglyceridemia occurred frequently in patients with COVID-19 who received propofol but did not lead to acute pancreatitis. Elevated triglyceride concentrations occurred more often and at lower cumulative doses than previously reported in patients without COVID-19. Application of these data may aid in optimal monitoring for serious adverse effects of propofol in patients with COVID-19.

The Safety and Efficacy of Desmopressin in Patients With Intracranial Hemorrhage and a History of Alcohol Use.

BACKGROUND: Patients with a history of alcohol use disorder are at an increased risk of hematoma expansion following intracranial hemorrhage (ICH) due to the effects of alcohol on platelet aggregation. Desmopressin (DDAVP) improves platelet aggregation and may decrease hematoma expansion in patients with ICH. However, DDAVP may also increase the risk of hyponatremia and thrombotic events. Evidence is limited regarding the safety and efficacy of DDAVP in alcohol use (AU)-associated ICH. METHODS: This was a retrospective chart review of adult patients with radiographic evidence of ICH and a confirmed or suspected history of alcohol use upon admission. Patients were categorized into groups based on DDAVP administration. Safety outcomes included hyponatremia (serum sodium <135 mEq/L or decrease in serum sodium of ≥ 5 mEq/L for patients with baseline sodium <135 mEq/L) within 24 hours of ICH and thrombotic events within 7 days of ICH. The primary efficacy outcome was the incidence of hematoma expansion, defined as any expansion of the hemorrhage noted on repeat imaging within 32 hours. RESULTS: In total, 52 patients were included in the safety analysis (27 DDAVP and 25 non-DDAVP). Although hyponatremia was numerically higher in the DDAVP group, there was no significant difference between groups (19.2% vs 4.2%, P = 0.192). Thrombotic complications were similar between the DDAVP and non-DDAVP groups (11.1% vs. 8%, P = 1.0). Thirty-nine patients met criteria for hemostatic efficacy analysis. There was no difference in hematoma expansion between the DDAVP and non-DDAVP groups (23.1% vs 34.6%, P = 0.71) and these findings were consistent after adjusting for differences in baseline characteristics (OR 0.63, 95% CI 0.1-3.3). CONCLUSION: The administration of DDAVP was not associated with adverse safety events, but did not significantly reduce the incidence of hematoma expansion in patients with AU-associated ICH.

Rethinking the Drug Distribution and Medication Management Model: How a New York City Hospital Pharmacy Department Responded to COVID-19.

Beginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork-Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus.

Serotonin syndrome caused by fentanyl and methadone in a burn injury.

Serotonin syndrome is a syndrome identified by a triad of altered mental status, neuromuscular overactivity, and autonomic instability caused by the overstimulation of serotonin in the central nervous system and periphery. Serotonin syndrome may be provoked with the addition or increase in serotonergic agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors as well as other agents with serotonergic properties. Some narcotics, including fentanyl and methadone, have these properties and may be associated with the development of serotonin syndrome when used in conjunction with other agents. Currently, there are no identified case reports of narcotics as the sole agent causing serotonin syndrome. This report provides a brief overview of serotonin syndrome, particularly with cases involving administration of narcotics such as fentanyl and methadone. The case described is the first report associated with fentanyl and methadone without the coadministration of other serotonergic agents, and a possible drug interaction with voriconazole is discussed. This raises awareness of using multiple serotonergic narcotics and the potential precipitation of serotonin syndrome.