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Objective: Describe continuous infusion (CI) ketamine practices in pediatric intensive care units (PICUs) and evaluate its effect on pain/sedation scores, exposure to analgesics/sedatives, and adverse effects (AEs). Methods: Multicenter, retrospective, observational study in children <18 years who received CI ketamine between 2014 and 2017. Time spent in goal pain/sedation score range and daily cumulative doses of analgesics/sedatives were compared from the 24 hours (H) prior to CI ketamine to the first 24H and 25-48H of the CI. Adverse effects were collected over the first 7 days of CI ketamine. Results: Twenty-four patients from 4 PICUs were included; median (IQR) age 7 (1-13.25) years, 54% female (n = 13), 92% intubated (n = 22), 25% on CI vasopressors (n = 6), and 33% on CI paralytics (n = 8). Ketamine indications were analgesia/sedation (n = 21, 87.5%) and status epilepticus (n = 3, 12.5%). Median starting dose was 0.5 (0.48-0.70) mg/kg/hr and continued for a median of 2.4 (1.3-4.4) days. There was a significant difference in mean proportion of time spent within goal pain score range (24H prior: 74% ± 14%, 0-24H: 85% ± 10%, and 25-48H: 72% ± 20%; p=0.014). A significant reduction in median morphine milligram equivalents (MME) was seen (24H prior: 58 (8-195) mg vs. 0-24H: 4 (0-69) mg and p=0.01), but this was not sustained (25-48H: 24 (2-246) mg and p=0.29). Common AEs were tachycardia (63%), hypotension (54%), secretions/suctioning (29%), and emergence reactions (13%). Conclusions: Ketamine CI improved time in goal pain score range and significantly reduced MME, but this was not sustained. Larger prospective studies are needed in the pediatric population.

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There are unique challenges associated with the evaluation of faculty in pharmacy departments or divisions that have a mix of nontenure-track and tenure-track faculty members. Such evaluations are intended to provide feedback on performance and personal growth but have the potential to demotivate faculty and add to existing stress if improperly performed. The purpose of this commentary is to suggest best practices for department chairs involved in performing evaluations of faculty in pharmacy departments or divisions that have a mix of nontenure-track and tenure-track faculty members. The paper is intended to help ensure these evaluations not only capture the quality and quantity of each faculty member's full range of activities and responsibilities but also are conducted in a supportive and constructive fashion. This commentary is targeted at new department chairs, new faculty members unfamiliar with academic evaluation processes, and departments contemplating changes in their existing evaluation procedures.

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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: The purpose of this article is to discuss how the structural and presumably functional integrity of albumin, as described by the concept of effective albumin concentration (eAlb), has potentially important clinical implications beyond the total albumin concentration (tAlb) routinely reported by clinical laboratories. SUMMARY: Albumin has several functions beyond its oncotic effects, including molecule binding, substance transport, detoxification actions, and serving as an antioxidant. However, there are conformational changes that occur during or following the manufacture of albumin and during its administration to patients with various disease states, such as decompensated liver disease, that often impair these functions. Such impairments are not reflected in tAlb values reported by clinical laboratories and might explain the disconnect often seen between albumin's proposed beneficial mechanistic functions and its less-than-predicted clinical effectiveness as noted in published studies. The concept of eAlb has been introduced to describe albumin with structural and functional integrity. Limited studies have found associations between eAlb values and patient prognostic indicators, but the techniques used to decide these effective concentrations to date are complicated and require specialized equipment and experienced researchers for proper interpretation. CONCLUSION: Estimation of eAlb may provide valuable information on the functional ability of albumin beyond the tAlb reported by clinical laboratories, but more research is needed to decide how this information is best used in the clinical setting.

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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: To demonstrate the challenges with current diagnosis and treatment strategies for precipitated opioid withdrawal secondary to naloxone the emergency department (ED) setting and describe the role of the emergency medicine (EM) pharmacist in its management. SUMMARY: There are no standardized criteria to define precipitated opioid withdrawal syndrome, so the diagnosis is typically based on sentinel signs and symptoms and time course. Complicating factors include a positive urine toxicology screen for nonopioid substances, comorbidities and associated medications prior to admission, medications given in the ED, and a fluctuating patient course during the ED stay that likely involves all these issues. Although buprenorphine is frequently recommended as the primary treatment for precipitated withdrawal, its use can be complicated if patients are on methadone maintenance or other long-acting opioids. The EM pharmacist plays a key role in managing patients with precipitated withdrawal. CONCLUSION: Practice changes related to the diagnosis and treatment of opioid use disorder (OUD) with precipitated withdrawal in the ED are needed. EM pharmacists as part of the interprofessional care team have an important role in the management of patients with OUD, including those patients undergoing possible precipitated withdrawal.

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OBJECTIVE: The purpose of this scoping review was to evaluate literature involving opioid-sparing medications in critically ill patients with a focus on clinically meaningful outcomes. DESIGN: Scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. SETTING: Intensive care unit. PATIENTS OR PARTICIPANTS: Adult patients in an intensive care unit setting. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: PubMed and Cochrane Library were searched from October 1, 2019 to June 1, 2023. Inclusion criteria consisted of randomized controlled trials evaluating adjunctive analgesic use in adult patients in an intensive care unit setting. RESULTS: There were 343 citations and titles identified in the initial search, with 328 remaining after removal of duplicates, 294 excluded at title and abstract screening, 34 available for full text review, and six included in the scoping review. Most studies reported modest reductions in opioid use as a secondary endpoint. Improvement in clinical outcomes such as reduction in duration of mechanical ventilation or delirium were reported in two trials with dexmedetomidine. CONCLUSIONS: In recently published trials of adjunctive agents in critically ill patients, opioid-sparing effects were small. Data to support improvements in clinical outcomes remains limited.

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INTRODUCTION: We evaluated the comparative efficacy of 6 later-line (≥3) therapies for metastatic colorectal cancer (mCRC) over placebo. We applied a novel statistical method of reconstructing pseudo patient-level data (pseudo-IPD) to inform a network meta-analysis of survival curves that considers shape in addition to scale parameters. METHODS: A literature search yielded 10 phase II/III trials. We digitized all survival curves and applied a novel method incorporating curve coordinates, patients-at-risk, and events reported to generate pseudo-IPD. Using fitted random effects lognormal distributions, we estimated the survival proportions and HRs(95CrI) of progression-free (PFS) and overall survival(OS) over 12 months of follow-up. RESULTS: Compared to placebo, in ascending order, 12-month OS HRs were 0.50(95%CrI = 0.35, 0.69; PFS = 0.11(95%CrI = 0.06, 0.14)) for TAS+bevacizumab; 0.71(95%CrI = 0.51, 0.97; PFS = 0.26(95%CrI = 0.16, 0.41)) for regorafenib; 0.75(95%CrI = 0.61, 0.91; (PFS = 0.24(95%CrI = 0.17, 0.31)) for TAS-102; 0.80(95%CrI = 0.79, 0.90; PFS = 0.18(95%CrI = 0.13, 0.24)) for fruquintinib; 0.83(95%CrI = 0.50, 0.99; PFS = 0.42(95%CrI = 0.20, 0.75)) for atezolizumab+cobimetinib; and 1.03(95%CrI = 0.55, 1.65; PFS = 0.67(95%CrI = 0.29, 1.01)) for atezolizumab. CONCLUSION: In this independent NMA of survival data all later-line mCRC therapies but atezolizumab monotherapy exhibited superiority in 12-month PFS and OS over placebo. TAS+bevacizumab emerged as the most dominant option and may be the preferred choice; with fruquintinib, regorafenib and TAS-102 monotherapy showing statistically significant but lower PFS and OS benefits. REGISTRATION: PROSPERO: CRD42022371953.

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The removal of the X-waiver in the Mainstreaming Addiction Treatment (MAT) Act of 2023 has substantial implications for buprenorphine prescribing as one of the options to treat opioid use disorder. The purpose of this commentary is to discuss the unanswered questions regarding buprenorphine in the intensive care unit (ICU) including how the passage of the MAT Act will affect ICU providers, which patients should receive buprenorphine, what is the most appropriate route of administration and dose of buprenorphine, what medications interact with buprenorphine, and how can transitions of care be optimized for these patients.

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BACKGROUND: The potential uses of artificial intelligence have extended into the fields of health care delivery and education. However, challenges are associated with introducing innovative technologies into health care, particularly with respect to information quality. OBJECTIVE: This study aimed to evaluate the accuracy of answers provided by a chatbot in response to questions that patients should ask before taking a new medication. METHODS: Twelve questions obtained from the Agency for Healthcare Research and Quality were asked to a chatbot for the top 20 drugs. Two reviewers independently evaluated and rated each response on a 6-point scale for accuracy and a 3-point scale for completeness with a score of 2 considered adequate. Accuracy was determined using clinical expertise and a drug information database. After the independent reviews, answers were compared, and discrepancies were assigned a consensus score. RESULTS: Of 240 responses, 222 (92.5%) were assessed as completely accurate. Of the inaccurate responses, 10 (4.2%) were mostly accurate, 5 (2.1%) were more accurate than inaccurate, 2 (0.8%) were equal parts accurate and inaccurate, and 1 (0.4%) was more inaccurate than accurate. Of the 240 responses, 194 (80.8%) were comprehensively complete. There were 235 (97.9%) responses that scored 2 or higher. Five responses (2.1%) were considered incomplete. CONCLUSION: Using a chatbot to answer questions commonly asked by patients is mostly accurate but may include inaccurate information or lack valuable information for patients.

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OBJECTIVE: To describe an evaluation of a generative language model tool to write examination questions for a new elective course focused on the interpretation of common clinical laboratory results being developed as an elective for students in a Bachelor of Science in Pharmaceutical Sciences program. METHODS: A total of 100 multiple-choice questions were generated using a publicly available large language model for a course dealing with common laboratory values. Two independent evaluators with extensive training and experience in writing multiple-choice questions evaluated each question for appropriate formatting, clarity, correctness, relevancy, and difficulty. For each question, a final dichotomous judgment was assigned by each reviewer, usable as written or not usable written. RESULTS: The major finding of this study was that a generative language model (ChatGPT 3.5) could generate multiple-choice questions for assessing common laboratory value information but only about half the questions (50% and 57% for the 2 evaluators) were deemed usable without modification. General agreement between evaluator comments was common (62% of comments) with more than 1 correct answer being the most common reason for commenting on the lack of usability (N = 27). CONCLUSION: The generally positive findings of this study suggest that the use of a generative language model tool for developing examination questions is deserving of further investigation.

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TOPIC IMPORTANCE: Critical care clinicians are likely to see an increasing number of patients admitted to the ICU who are receiving US Food and Drug Administration-approved medications for opioid use disorder (MOUDs) given the well-documented benefits of these agents. Oral methadone, multiple formulations of buprenorphine, and extended-release naltrexone are the three types of MOUD most likely to be encountered by ICU clinicians; however, these drugs vary with respect to formulations, pharmacokinetics, and adverse effects. REVIEW FINDINGS: No published clinical practice guidelines or consensus statements are available to guide decision-making in patients admitted to the ICU setting who are receiving MOUDs before admission. Additionally, no randomized trials and limited observational studies have evaluated issues related to MOUD use in the ICU. Therefore, ICU clinicians caring for patients admitted who are taking MOUDs must base their decision-making on data extrapolation from pharmacokinetic, pharmacologic, and clinical studies performed in non-ICU settings. SUMMARY: Despite the challenges in administering MOUDs in critically ill patients, extrapolation of data from other hospital settings suggests that the benefits of continuing MOUD therapy outweigh the risks in patients able to continue therapy. This article provides guidance for critical care clinicians caring for patients admitted to the ICU already receiving methadone, buprenorphine, or extended-release naltrexone. The guidance includes algorithms to aid clinicians in the clinical decision-making process, recognizing the inherent limitations of the existing evidence on which the algorithms are based and the need to account for patient-specific considerations.

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PURPOSE: The purpose of this review is to discuss important considerations when prescribing buprenorphine for opioid use disorder (OUD) in the intensive care unit (ICU) setting, recognizing the challenges of providing detailed recommendations in the setting of limited available evidence. SUMMARY: Buprenorphine is a partial mu-opioid receptor agonist that is likely to be increasingly prescribed for OUD in the ICU setting due to the relaxation of prescribing regulations. The pharmacology and pharmacokinetics of buprenorphine are complicated by the availability of several formulations that can be given by different administration routes. There is no single optimal dosing strategy for buprenorphine induction, with regimens ranging from very low-dose to high dose regimens. Faster induction with higher doses of buprenorphine has been studied and is frequently utilized in the emergency department. In patients admitted to the ICU who were receiving opioids either medically or illicitly, analgesia will not occur until their baseline opioid requirements are covered when their preadmission opioid is either reversed or interrupted. For patients in the ICU who are not on buprenorphine at the time of admission but have possible OUD, there are no validated tools to diagnose OUD or the severity of opioid withdrawal in critically ill patients unable to provide the subjective components of instruments validated in outpatient settings. When prescribing buprenorphine in the ICU, important issues to consider include dosing, monitoring, pain management, use of adjunctive medications, and considerations to transition to outpatient therapy. Ideally, addiction and pain management specialists would be available when buprenorphine is prescribed for critically ill patients. CONCLUSION: There are unique challenges when prescribing buprenorphine for OUD in critically ill patients, regardless of whether they were receiving buprenorphine when admitted to the ICU setting for OUD or are under consideration for buprenorphine initiation. There is a critical need for more research in this area.

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Monoclonal antibody products are an increasing portion of novel drug approvals. The labeling of initial drug approvals frequently involves body-size-based rather than fixed-dose administration regimens for adults without clear rationale for doing so. This presents challenges when prescribing these products for patients with extremes of body habitus who constitute a small portion of enrollment in pre-approval investigations. Fixed-dose regimens allow for standardized preparation with the potential to reduce the risk of calculation errors, drug waste, and make home administration more practical. Fixed-dose rather than body-size-based monoclonal antibody regimens should serve as the initial approach in early phase 1 clinical trials.

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OBJECTIVES: To review the current definitions and diagnostic criteria for acute kidney injury (AKI) and type 1 hepatorenal syndrome (HRS) now termed HRS-AKI and discuss the challenges in deciding the most appropriate medication regimens to treat patients with HRS-AKI. DATA SOURCES: PubMed (inception to April 2023) with bibliographies of retrieved articles searched for additional articles; organizational websites for clinical practice guidelines (CPGs). STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials (RCTs) evaluating albumin and vasoconstrictors for HRS-AKI. DATA SYNTHESIS: A major change in the most recent revision of definitions and diagnostic criteria for HRS-AKI is the elimination of the set cutoff serum creatinine values for AKI. This change should be considered when comparing studies of HRS-AKI over time. Albumin has been administered to both vasoconstrictor treatment and placebo groups in all recent RCTs; however, there has never been a large RCT evaluating a no-albumin group. Most prospective trials comparing a midodrine/octreotide combination or norepinephrine to placebo or terlipressin have enrolled less than 100 patients limiting any conclusions regarding clinically important outcomes. Terlipressin with albumin has shown mixed results for complete HRS-AKI reversal with no reductions in crude mortality but adverse effect concerns involving ischemic and pulmonary events. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Type 1 hepatorenal syndrome with acute kidney injury is a potentially life-threatening syndrome with diagnostic and treatment challenges. Albumin plus a vasoconstrictor has become the routine HRS-AKI treatment even though there has not been a large RCT evaluating a no-albumin group. Terlipressin is the vasoconstrictor of choice for HRS-AKI in current CPGs, but it has adverse effect concerns and, until recently, was not available in the United States. CONCLUSIONS: In conjunction with changes in the definitions and diagnostic criteria for HRS-AKI, debate continues regarding the optimal therapy for HRS-AKI, particularly considering recent trials demonstrating ischemic and pulmonary adverse events with terlipressin used in combination with albumin.

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Since 2020, there have been changes in Food and Drug Administration guidance and in recommendations by national organizations with a focus on kidney diseases pertaining to the choice of equations used to estimate creatinine clearance and glomerular filtration rate in patients with renal impairment. This includes a recommendation by the National Kidney Foundation to avoid the use of the Cockcroft-Gault equation for drug dosing in patients with renal impairment. This commentary provides an overview of recent recommendations concerning kidney function assessment that have important implications for drug dosing in patients with renal impairment and provides suggestions for implementing these recommendations.

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The purpose of this commentary is to discuss the qualifications, responsibilities, and keys to success for pharmacy faculty considering a department (or division) chair (head) or dean (including assistant or associate dean) position. The perspectives are those of a department chair, vice dean, and past dean of colleges of pharmacy with extensive experience in pharmacy administration. The qualifications for these administrative positions vary by institution, particularly with respect to the institution's focus on research. Because the dean is the chief executive officer of a college of pharmacy, previous administrative experience is almost always a basic requirement for the position. For associate/assistant deans and department chairs, previous experience as a faculty member is a typical minimum requirement and may include experience as a department vice chair or director of a unit within the department or division. The dean has a fiduciary duty to university administration, as well as to other external and internal stakeholders, to educate and graduate competent pharmacists and to operate within budget. Associate/assistant deans often have responsibility for specific functions of the college, such as student or professional affairs, and it is common for deans to delegate authority, responsibility, and accountability to associate/assistant deans. Department chairs have a unique perspective with respect to college activities because they must not only think about the "big picture" when considering issues with other college administrators but must oversee the implementation and monitoring of strategic initiatives through the faculty and staff who report to them.

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Evaluation of clinical faculty involves an assessment of the quality of their publications in addition to quantity (number) of publications. In contrast to assessing quantity, assessing quality is difficult. The purpose of this paper is to discuss practical considerations and provide recommendations related to quality of publications that clinical faculty members should bear in mind as part of their overall scholarship activity. College and schools of pharmacy may not provide written criteria for assessing quality of publications, so it is important that clinical faculty members seek guidance from their department chair or direct supervisor, experienced colleagues, and formal or informal mentors or advisers. One criterion for assessing quality is whether a publication was evaluated through a peer-review process although there are other considerations including dissemination of the paper via search engines such as PubMed. Clinical faculty also need to consider authorship order on their papers and potential journals for submission.

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Faculty retention is an issue of concern to schools and colleges of pharmacy. The reasons why faculty leave are multifactorial but often involve a breach of unwritten contract obligations between the faculty member and the organization. This article provides strategies for retaining faculty based on published literature that include perceived breaches of unwritten contracts and our own perspectives as departmental and university administrators and senior faculty members who have been involved in devising and implementing institutional change. Retention begins with recruitment but then needs to be nurtured during onboarding and as part of the overall enculturation process for new faculty members. Particular attention to the factors that influence the retention of underrepresented minorities must be incorporated to help ensure that pharmacy educators reflect the diversity of the US population.

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OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

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PURPOSE: The purpose of this review is to discuss infectious disease-related adverse effects associated with long-term proton pump inhibitor (PPI) therapy in patients with cirrhosis and to provide recommendations for appropriate use and choice of PPI when such therapy is indicated. SUMMARY: Long-term PPI therapy in patients with cirrhosis increases the risk of infections, with infections in turn increasing the risk of mortality in this patient population. Expert recommendations include restricting long-term PPI use in cirrhosis to patients with appropriate gastrointestinal indications, using a PPI for the shortest possible duration and at the lowest possible dose, and avoiding PPIs with unfavorable pharmacogenetic properties. CONCLUSION: Long-term PPI use in patients with cirrhosis has been associated with increased infections. The risk of adverse effects in observational studies, including decompensation, severe infection (especially spontaneous bacterial peritonitis), and increased mortality, appears to increase as the dose and duration of PPI increase.

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