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Purpose: To provide key pharmacological concepts underlying drug-drug interactions (DDIs), a decision-making framework, and a list of DDIs that should be considered in the context of contemporary acutely ill patients with COVID-19., Summary: DDIs are frequently encountered in the acutely ill. The implications of DDIs include either increased risk of drug toxicity or decreased effectiveness, which may have severe consequences in the acutely ill due to lower physiological and neurocognitive reserves in these patients. In addition, an array of additional therapies and drug classes have been used for COVID-19 that were not typically used in the acute care setting. In this update on DDIs in the acutely ill, we provide key pharmacological concepts underlying DDIs, including a discussion of the gastric environment, the cytochrome P-450 (CYP) isozyme system, transporters, and pharmacodynamics in relation to DDIs. We also provide a decision-making framework that elucidates the identification of DDIs, risk assessment, selection of alternative therapies, and monitoring. Finally, important DDIs pertaining to contemporary acute care clinical practice related to COVID-19 are discussed., Conclusion: Interpreting and managing DDIs should follow a pharmacologically based approach and a systematic decision-making process to optimize patient outcomes., (© American Society of Health-System Pharmacists 2023.)

Purpose: To identify the proportion of patients with continued opioid use after total hip or knee arthroplasty., Methods: This systematic review and meta-analysis searched Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts for articles published from January 1, 2009, to May 26, 2021. The search terms (opioid, postoperative, hospital discharge, total hip or knee arthroplasty, and treatment duration) were based on 5 key concepts. We included studies of adults who underwent total hip or knee arthroplasty, with at least 3 months postoperative follow-up., Results: There were 30 studies included. Of these, 17 reported on outcomes of total hip arthroplasty and 19 reported on outcomes of total knee arthroplasty, with some reporting on outcomes of both procedures. In patients having total hip arthroplasty, rates of postoperative opioid use at various time points were as follows: at 3 months, 20% (95% CI, 13%-26%); at 6 months, 17% (95% CI, 12%-21%); at 9 months, 19% (95% CI, 13%-24%); and at 12 months, 16% (95% CI, 15%-16%). In patients who underwent total knee arthroplasty, rates of postoperative opioid use were as follows: at 3 months, 26% (95% CI, 19%-33%); at 6 months, 20% (95% CI, 17%-24%); at 9 months, 23% (95% CI, 17%-28%); and at 12 months, 21% (95% CI, 12%-29%). Opioid naïve patients were less likely to have continued postoperative opioid use than those who were opioid tolerant preoperatively., Conclusion: Over 1 in 5 patients continued opioid use for longer than 3 months after total hip or knee arthroplasty. Clinicians should be aware of this trajectory of opioid consumption after surgery., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Cost-avoidance studies are common in pharmacy practice literature. This scoping review summarizes, critiques, and identifies current limitations of the methods that have been used to determine cost avoidance associated with pharmacists' interventions in acute care settings., Methods: An Embase and MEDLINE search was conducted to identify studies that estimated cost avoidance from pharmacist interventions in acute care settings. We included studies with human participants and articles published in English from July 2010 to January 2021, with the intent of summarizing the evidence most relevant to contemporary practice., Results: The database search retrieved 129 articles, of which 39 were included. Among these publications, less than half (18 of 39) mentioned whether the researchers assigned a probability for the occurrence of a harmful consequence in the absence of an intervention; thus, a 100% probability of a harmful consequence was assumed. Eleven of the 39 articles identified the specific harm that would occur in the absence of intervention. No clear methods of estimating cost avoidance could be identified for 7 studies. Among all 39 included articles, only 1 attributed both a probability to the potential harm and identified the cost specific to that harm., Conclusion: Cost-avoidance studies of pharmacists' interventions in acute care settings over the last decade have common flaws and provide estimates that are likely to be inflated. There is a need for guidance on consistent methodology for such investigations for reporting of results and to confirm the validity of their economic implications., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Cost-avoidance studies of pharmacist interventions are common and often the first type of study conducted by investigators to quantify the economic impact of clinical pharmacy services. The purpose of this primer is to provide guidance for conducting cost-avoidance studies pertaining to clinical pharmacy practice., Summary: Cost-avoidance studies represent a paradigm conceptually different from traditional pharmacoeconomic analysis. A cost-avoidance study reports on cost savings from a given intervention, where the savings is estimated based on a counterfactual scenario. Investigators need to determine what specifically would have happened to the patient if the intervention did not occur. This assessment can be fundamentally flawed, depending on underlying assumptions regarding the pharmacists' action and the patient trajectory. It requires careful identification of the potential consequence of nonaction, as well as probability and cost assessment. Given the uncertainty of assumptions, sensitivity analyses should be performed. A step-by-step methodology, formula for calculations, and best practice guidance is provided., Conclusions: Cost-avoidance studies focused on pharmacist interventions should be considered low-level evidence. These studies are acceptable to provide pilot data for the planning of future clinical trials. The guidance provided in this article should be followed to improve the quality and validity of such investigations., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To compare an intermittent audit method vs a daily documentation method with regard to the number of interventions documented by clinical pharmacists in the hospital setting., Methods: A 2-phase pre-post cohort study was conducted at an academic hospital to compare numbers and types of pharmacist interventions documented over an 18-month period before implementation of a daily documentation method (the "pre-phase" period) and during the 6 months after implementation (the "post-phase" period). During the pre-phase period (January 2018 to July 2019), pharmacists prospectively documented interventions on specific audit days. The audit days occurred at approximately monthly intervals. During the post-phase period (July 2019 to March 2020) pharmacists used electronic medical record tools to document interventions daily. The primary outcome was the total number of interventions per day. Values for the pre- and post-phase periods were compared using an unpaired Student t test and through interrupted time series analysis., Results: There were a total of 3,628 interventions (on 14 intermittent audit days) during the pre-phase period and 9,300 interventions (on 163 continuous days) in the post-phase period. The mean (SD) number of reported interventions per day decreased from 259 (82) in the pre-phase period to 57 (33) in the post-phase period (P < 0.001). The mean (SD) number of daily reported interventions per pharmacist decreased from 24 (5) in the pre-phase period to 6 (2) in the post-phase period (P < 0.001). This decrease was consistent with results of the interrupted time series analysis. There was a decrease in reported interventions at the time of implementation (change from most recent audit day, -125 interventions; 95% confidence interval [CI], -187 to -62 interventions; P < 0.001). Similarly, there was a decrease in reported interventions per pharmacist at the time of implementation (change from most recent audit day, -22 [95% CI, -26 to -18] interventions; P < 0.001)., Conclusion: A change from intermittent audits to daily documentation of interventions resulted in an approximately 5-fold decrease in the number of interventions recorded by pharmacists., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To summarize recently published research reports and practice guidelines on emergency medicine (EM)-related pharmacotherapy., Summary: Our author group was composed of 14 EM pharmacists, who used a systematic process to determine main sections and topics for the update as well as pertinent literature for inclusion. Main sections and topics were determined using a modified Delphi method, author and peer reviewer groups were formed, and articles were selected based on a comprehensive literature review and several criteria for each author-reviewer pair. These criteria included the document "Oxford Centre for Evidence-based Medicine - Levels of Evidence (March 2009)" but also clinical implications, interest to reader, and belief that a publication was a "key article" for the practicing EM pharmacist. A total of 105 articles published from January 2011 through July 2018 were objectively selected for inclusion in this review. This was not intended as a complete representation of all available pertinent literature. The reviewed publications address the management of a wide variety of disease states and topic areas that are commonly found in the emergency department: analgesia and sedation, anticoagulation, cardiovascular emergencies, emergency preparedness, endocrine emergencies, infectious diseases, neurology, pharmacy services and patient safety, respiratory care, shock, substance abuse, toxicology, and trauma., Conclusion: There are many important recent additions to the EM-related pharmacotherapy literature. As is evident with the surge of new studies, guidelines, and reviews in recent years, it is vital for the EM pharmacist to continue to stay current with advancing practice changes., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: This study aimed to document the ways by which missing data were handled in clinical pharmacy research to provide an insight into the amount of attention paid to the importance of missing data in this field of research., Methods: Our cross-sectional descriptive report evaluated 10 journals affiliated with pharmacy organizations in the United States, Canada, the United Kingdom, and Australia. Randomized controlled trials, cohort studies, case-control studies, and cross-sectional studies published in 2018 were included. The primary outcome measure was the proportion of studies that reported the handling of missing data in their methods or results., Results: A total of 178 studies were included in the analysis. Of these, 19.7% (n = 35) mentioned missing data either in their methods (3.4%, n = 6), results (15.2%, n = 27), or in both sections (1.1%, n = 2). Only 4.5% (n = 8) of the studies mentioned how they handled missing data, the most common method being multiple imputation (n = 3), followed by indicator (n = 2), complete case analysis (n = 2), and simple imputation (n = 1). One study using multiple imputation and both studies using an indicator method also combined other strategies to account for missing data. One study only used complete case analysis for subgroup analysis, and the other study only used this method if a specific baseline variable was missing., Conclusions: Very few studies in clinical pharmacy literature report any handling of missing data. This has the potential to lead to biased results. We advocate that researchers should report how missing data were handled to increase the transparency of findings and minimize bias., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Results of a comparison of blood product use and cost outcomes with use of 3-factor versus 4-factor prothrombin complex concentrate (PCC) for indications other than warfarin reversal are presented., Methods: Consecutive patients who received 3-factor PPC (PCC3) or 4-factor PCC (PCC4) for non-warfarin-related indications at 2 U.S. hospitals during a 19-month period were identified. The primary outcome was in-hospital blood product use, with a focus on plasma use. Total hemostasis costs, intensive care unit (ICU) and hospital lengths of stay, and other outcomes were evaluated., Results: Indications for PCC3 use ( n = 118) or PCC4 use ( n = 64) included intraoperative bleeding, nonintraoperative bleeding, coagulopathy of liver disease, and reversal of direct-acting oral anticoagulant effects. The proportion of patients who received plasma was 56.8% with PCC3 use versus 53.1% with PCC4 use ( p = 0.643); the corresponding median volumes of plasma received were 638 mL (interquartile range [IQR], 550-1,355 mL) and 656 mL (IQR, 532-1,136 mL), respectively. The median total hemostasis costs were $5,559 (IQR, $3,922-$8,159) with PCC3 use and $7,771 (IQR, $6,366-$9,205) with PCC4 use ( p < 0.001)., Conclusion: PCC3 use and PCC4 use were associated with similar blood product use, ICU length of stay, hospital length of stay, and in-hospital mortality when given for non-warfarin-related indications. However, relative to PCC3 use, PCC4 use was associated with an increase in costs that was primarily due to drug costs., Competing Interests: DisclosuresDr. Patanwala has previously received grant funding from CSL Behring; he has declared no other potential conflicts of interest. The other authors have declared no potential conflicts of interest., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: A practical guide to conducting and reporting medical record review studies, including instruction and insights on topics ranging from idea conception to manuscript submission, is provided., Summary: Research based on the retrospective collection and analysis of data from medical records is often the first type of research conducted by new investigators; such research can be particularly useful in high-acuity populations and is often more feasible and cost-effective than prospective studies. The research process begins with formulating a valid hypothesis-driven or exploratory research question and refining it into one that is testable; this can be facilitated by incorporating information from various sources (e.g., relevant literature, consultation with experts, observations of practice). Accurate sample size calculations are important in ensuring study feasibility (i.e., the estimated sample sizes required can be obtained). Appropriate data collection methods are particularly crucial in medical record review studies; key considerations include pertinent variables, systematic subject identification, standardized data collection instruments, training of data collectors to minimize interrater variability, processes to ensure the accuracy and reliability of data, and blinded collection of the outcome variable. Checklists are provided to guide investigators in retrospective data collection, manuscript preparation, and decisions regarding authorship eligibility and sequencing., Conclusion: The quality of medical record review studies and the likelihood of their acceptance for publication can be improved through adherence to recommended standards of research design, data collection and analysis, ethical authorship, and manuscript preparation., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: The results of a survey to characterize pharmacy practice in emergency department (ED) settings are reported., Methods: An electronic survey was sent to all members of the American Society of Health-System Pharmacists' Emergency Medicine Connect group and the American College of Clinical Pharmacy's Emergency Medicine Practice and Research Network. Approximately 400 nontrainee pharmacy practitioners were invited to participate in the survey, which was open for 30 days. Descriptive statistics were used for all analyses., Results: Two hundred thirty-three responses to the survey that were at least partially completed were received. After the removal of duplicate responses and null records, 187 survey responses were retained. The majority of respondents were from community hospitals (59.6%) or academic medical centers (36.1%). A pharmacist's presence in the ED of more than eight hours per day on weekdays and weekends was commonly reported (68.7% of respondents); 49.4% of institutions provided more than eight hours of coverage daily. Nearly one in three institutions (34.8%) provided no weekend ED staffing. The most frequently reported hours of coverage were during the 1 p.m.-midnight time frame. The distribution of ED pharmacist activities, by category, was as follows (data are median reported time commitments): clinical, 25% (interquartile range [IQR], 15-40%); emergency response, 15% (IQR, 10-20%); order processing, 15% (IQR, 5-25%); medication reconciliation/history-taking, 10% (IQR, 5-25%); teaching, 10% (IQR, 5-15%); administrative, 5% (IQR, 3-10%); and scholarly endeavors, 0% (IQR, 0-5%)., Conclusion: Pharmacists from academic and community EDs perform a variety of clinical, educational, and administrative activities., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: Pharmacists' impact in reducing the time interval from intubation to sedative and analgesic use during trauma patient resuscitations is investigated., Methods: A retrospective cohort study was conducted at a level 1 trauma center to compare medication-use outcomes in consecutive cases in which trauma patients underwent rocuronium-assisted rapid-sequence intubation (RSI) and subsequent sedation and analgesia with or without a pharmacist's participation on the resuscitation team. The primary and secondary outcomes were, respectively, the time to sedative provision and the time to analgesic provision after intubation., Results: Relative to resuscitation cases not involving a pharmacist, the presence of the pharmacist during RSI was associated with decreased mean times to provision of postintubation sedation (9 minutes versus 28 minutes, p = 0.007) and analgesia (21 minutes versus 44 minutes, p = 0.057). The cumulative proportions of patients receiving appropriate sedation 5, 10, and 15 minutes after intubation were 11%, 26%, and 41% in the pharmacist-absent group and 33%, 53%, and 63% in the pharmacist-present group (p = 0.009, 0.008, and 0.045, respectively); for postintubation analgesic use, the corresponding figures were 9%, 14%, and 23% in the pharmacist-absent group and 17%, 30%, and 43% in the pharmacist-present group (p = 0.236, 0.066, and 0.039, respectively)., Conclusion: The presence of a pharmacist during RSI procedures was associated with decreased times to postintubation sedative and analgesic use, indicating that pharmacist participation in trauma-resuscitation responses can facilitate appropriate drug therapy.

Purpose: The safety of using ketamine-propofol combinations as an alternative to using either agent alone for procedural sedation is discussed., Summary: A total of 10 trials comparing the combination of ketamine and propofol with either agent alone for procedural sedation in the emergency department were examined. The evidence reviewed suggests that combining these agents may help to minimize adverse effects such as hypotension and respiratory depression. Ketamine is not commonly used as a single agent in adults because of the risk for emergence reactions; however, when combined with propofol, no significant increase in this adverse effect was found compared with propofol monotherapy. Administering ketamine and propofol can be accomplished by using a two-syringe technique or combining both medications into a single syringe. When two syringes are used, a ketamine 0.3-0.5-mg/kg i.v. bolus dose is administered, followed by a propofol 0.4-1-mg/kg i.v. bolus dose. Sedation is maintained with intermittent i.v. boluses of propofol 0.1-0.5 mg/kg. A 1:1 ratio of ketamine and propofol can also be combined into a single syringe by using the same concentration (10 mg/mL) and equal volumes of each drug, yielding a final concentration of 5 mg/mL for each component., Conclusion: The combined use of ketamine and propofol is a reasonable alternative to propofol alone for procedural sedation in patients at higher risk for respiratory depression or hypotension. Use of the combination requires the development of standardized protocols for drug preparation and dosage to minimize the potential for errors.

Purpose: The use of hypertonic saline injection in trauma patients is discussed., Summary: Patients with hemorrhage, burns, and traumatic brain injury (TBI) may develop hypovolemic shock and require resuscitation. Compared with conventional isotonic crystalloids, hypertonic saline has several advantages, including hemodynamic, immune-modulating, and antiinflammatory effects, for use in trauma patients for resuscitation. In addition, hypertonic saline is also used in patients with TBI to reduce intracranial pressure (ICP). Overall, studies have not shown a difference in mortality or other clinically important outcomes with the use of hypertonic saline for resuscitation in trauma patients; however, most of these studies were not adequately powered to show significant differences. A recent Cochrane review concluded that there is no evidence that hypertonic crystalloids are better than isotonic or near-isotonic crystalloids for fluid resuscitation in trauma patients. Two recent trials that were adequately powered to investigate a mortality endpoint were halted for futility. A few small randomized controlled studies found that hypertonic saline was more effective than mannitol as a hyperosmolar agent for ICP reduction. Recent guidelines from the American Burn Association have suggested that hypertonic saline may be used for burn shock resuscitation by experienced providers with close monitoring to avoid excessive hypernatremia. One of the main concerns with the use of hypertonic saline is its potential to cause central pontine myelinolysis due to a rapid increase in serum sodium levels., Conclusion: There is no evidence that hypertonic saline provides any additional benefit over isotonic crystalloid solutions for trauma resuscitation. Hypertonic saline may be more effective than mannitol at reducing ICP in patients with TBI.

Purpose: The interventions of a clinical pharmacist on an emergency department (ED) trauma response team were studied., Methods: The study site was an academic, tertiary care hospital designated as a level 1 trauma center, with a clinical pharmacist present in the ED 40 hours per week. For a two-month period, interventions by the pharmacist in trauma cases were documented in an electronic quality-improvement database., Results: A total of 304 interventions were recorded; the most common were dosage recommendations (60%) and provision of drug information (27%). The top five drug classes involved were analgesics, sedatives, antimicrobials, vaccines, and fluids. In 83% of the interventions, the pharmacist documented involvement in facilitating drug administration., Conclusion: A pharmacist participating on the ED trauma response team commonly provided dosage recommendations and drug information, facilitated drug administration, and optimized sedation, analgesia, and antimicrobial therapy.

Purpose: The case of a patient who developed aseptic meningitis, hemolytic anemia, hepatitis, and orthostatic hypotension simultaneously during treatment with trimethoprim-sulfamethoxazole is described., Background: A healthy 37-year-old African- American man was receiving treatment with trimethoprim-sulfamethoxazole double strength. This was the patient's first experience with trimethoprim- sulfamethoxazole, and he was not taking any other medications during the treatment period. He had been taking trimethoprim-sulfamethoxazole for approximately eight days when he revisited his family physician, complaining of headaches, dizziness, difficulty with speech, weakness, and itching on the trunk of his body and legs, where a maculopapular rash was noted. Orthostatic hypotension was also noted at that visit, with a standing blood pressure measurement of 95/80 mm Hg. Based on these findings and since the patient had no signs of infection, his physician instructed him to discontinue the drug. The patient was admitted to the emergency department of a local hospital within two days due to ongoing headache, elevated temperature, and nuchal rigidity, symptoms suggestive of meningitis. Because of the presence of hemolysis, the patient underwent testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency, for which he tested positive. The patient was discharged five days after admission and referred to a hematology clinic for follow-up. The patient has since returned to his routines of daily living and has reported no fatigue or other lingering adverse symptoms., Conclusion: A 37-year-old African- American man with G6PD deficiency developed hemolytic anemia, hepatitis, orthostatic hypotension, and aseptic meningitis simultaneously after using trimethoprim-sulfamethoxazole.

Purpose: The use of factor VIIa (recombinant) for the treatment of acute traumatic hemorrhage is reviewed., Summary: Factor VIIa (recombinant) has received considerable attention as a hemostatic agent and is increasingly being used for the management of bleeding associated with a variety of conditions. Severely injured trauma patients with uncontrolled bleeding are at high risk for coagulopathy and may benefit from the administration of factor VIIa (recombinant). A literature review was conducted to identify original research in the form of randomized controlled trials investigating the use of factor VIIa (recombinant) for the treatment of traumatic hemorrhage. Due to the paucity of such trials, three retrospective evaluations and three large case series pertaining to this topic were also reviewed. Of the two randomized controlled trials, one found a reduction in red blood cell (RBC) transfusion requirements in patients with blunt traumatic hemorrhage after the administration of factor VIIa (recombinant). This reduction in RBC requirements was not found in the study conducted with patients with penetrating trauma. These trials were not powered to show a mortality difference, and the effect of factor VIIa (recombinant) on survival in blunt and penetrating traumatic hemorrhage is unknown. Ongoing clinical trials may answer questions regarding its effect on mortality and other clinically important outcomes., Conclusion: Factor VIIa (recombinant) reduces RBC transfusion requirements in patients with blunt traumatic hemorrhage, and its effect on mortality is currently being investigated. Adjunctive use of factor VIIa (recombinant) should be considered only after other treatment modalities have been optimized.