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Objective: Menopause symptoms affect quality of life and financial well-being but are often unaddressed in primary care clinics. Therefore, we evaluated the extent of menopause symptom documentation in electronic health records (EHRs) by primary health care professionals., Methods: We retrospectively reviewed adult women who reported moderate or higher vasomotor symptoms on a Mayo Clinic survey conducted from March 1, 2021, through June 30, 2021. We then assessed adequacy of menopause symptom documentation in the EHRs of these women who had primary care visits during the survey period. We reviewed the percentage of documented vasomotor symptoms from May 1, 2019, through May 1, 2021., Results: In the Mayo Clinic Health System-Northwest Wisconsin Region, 229 women self-reported moderate or higher vasomotor symptoms in the Mayo Clinic survey. Although only 23% of these women had vasomotor symptoms listed in the EHR clinical problem lists, 60% of these women had vasomotor symptoms documented in their clinic notes from the primary care visit. Approximately 6% of women reported hormone therapy use for management of menopause symptoms, and nearly 15% reported use of nonhormone prescription therapies for vasomotor symptoms., Conclusions: A greater proportion of women in our study had EHR documentation of bothersome menopause symptoms than those reported in other studies, but vasomotor symptoms remain generally untreated. We need better methods for identifying midlife women with bothersome menopause symptoms in primary care clinics so that appropriate treatment options, including hormone therapy, can be discussed and offered., Competing Interests: Financial disclosure/conflicts of interest: E.K.: consultant for Mithra Pharmaceuticals, Astellas Pharmaceuticals, and Womaness, grant support from Mithra Pharmaceuticals, advisory board for Scynexis. S.S.F.: past funding from Optum Health and Primed, current funding from Atria Health. The other authors have none reported., (Copyright © 2024 by The Menopause Society.)

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods : In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Activated partial thromboplastin time (aPTT) is the standard for monitoring bivalirudin but demonstrates a nonlinear response at higher drug concentrations. The objective of this study was to assess the relationship between bivalirudin dose and aPTT in patients receiving extracorporeal membrane oxygenation (ECMO) to determine a threshold where aPTT unresponsiveness occurs. Two hundred fourteen adults receiving bivalirudin during ECMO between 2018 and 2022 were included. Piecewise regression in a linear mixed effects model was used to determine a bivalirudin dose threshold of 0.21 mg/kg/hr for aPTT unresponsiveness. For doses of less than 0.21 mg/kg/hr (n = 135), every 0.1 mg/kg/hr dose increase led to an aPTT increase of 11.53 (95% confidence interval [CI] = 9.85-13.20) seconds compared to only a 3.81 (95% CI = 1.55-6.06) seconds increase when dose was greater than or equal to 0.21 mg/kg/hr (n = 79) ( pinteraction < 0.001). In multivariable logistic regression, venovenous configuration (odds ratio [OR] = 2.83, 95% CI = 1.38-5.77) and higher fibrinogen concentration (OR = 1.22, 95% CI = 1.05-1.42) were associated with greater odds of unresponsiveness, whereas older age (OR = 0.79, 95% CI = 0.63-0.98), kidney dysfunction (OR = 0.48, 95% CI = 0.25-0.92), and a higher baseline aPTT (OR = 0.89, 95% CI = 0.82-0.97) were associated with lower odds. Alternative methods are necessary to ascertain bivalirudin's hemostatic impact when doses exceed 0.21 mg/kg/hr during ECMO., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background and Aim: Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function., Methods: We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups., Results: The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30-59; OR 1.46 for eGFR 15-29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2., Conclusions: Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gonzalez Suarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Limited evidence exists regarding methotrexate (MTX) resumption after patients with lymphoma receive glucarpidase for toxic MTX levels and acute kidney injury (AKI)., Methods: This retrospective review included adults with lymphoma treated with glucarpidase after MTX at Mayo Clinic between January 31, 2020, and October 10, 2022. Descriptive statistics summarize patient characteristics and clinical outcomes., Results: Of 11 patients treated with glucarpidase after MTX, seven (64%) were rechallenged with MTX. Indications for MTX rechallenge included confirmed CNS disease (n = 6, 86%) and intravascular lymphoma (n = 1, 14%). Compared with the nonrechallenged subgroup, before receiving MTX that required glucarpidase rescue, the rechallenged patients had lower median pretreatment serum creatinine (Scr; 0.7 v 1.2 mg/dL), and none had AKI with previous MTX doses, n = 0 (0%) versus n = 2 (50%). During the MTX dose requiring glucarpidase rescue, the rechallenged group had lower median peak Scr (1.26 v 3.32 mg/dL) and lower incidence of AKI stage III (n = 1 [14%] v n = 3 [75%]), and none of the rechallenged patients required renal replacement therapy (RRT; n = 0 [0%] v n = 1 [25%]). At the first rechallenge after glucarpidase administration, the median MTX dose reduction was 56% (range, 46%-75%), and the lowest used dose when prescribed according to each treatment protocol schedule was 1.5 g/m 2 . Two (29%) patients experienced AKI (n = 1 stage I, n = 1 stage II) after MTX rechallenge. Zero patients required RRT, and zero required another glucarpidase administration. Six (86%) patients completed all recommended MTX doses., Conclusion: In selected adults with lymphoma who required glucarpidase for toxic MTX levels after administration of high-dose MTX, resumption of MTX therapy at lower doses is safe. Patients selected for MTX resumption had experienced less severe AKI during the previous cycle compared with those not selected for MTX resumption.

Objectives: Female sexual dysfunction (FSD), a common concern affecting women of all ages, is often mediated by important psychological factors. Resilience has been shown to correlate with psychological well-being across different groups of people. The aim of this study was to assess if there is an association between resilience and FSD., Study Design: This cross-sectional study included 4,366 women (mean [SD] age, 51.7 [11]) seen in women's health clinics at 1 of 3 geographic Mayo Clinic locations. Participants completed the Brief Resilience Scale, the Female Sexual Function Index (FSFI), and the Female Sexual Distress Scale-Revised (FSDS-R)., Main Outcome Measures: We used univariate and multivariable logistic regression analyses to assess associations between resilience, sexual function, and sexual distress, adjusting for potential confounding variables., Results: FSD criteria (FSFI ≤26.55 and FSDS-R ≥ 11) were met by 55.8 % of women. Low, normal, and high levels of resilience were reported by 17.3 %, 57.1 %, and 25.6 % of participants, respectively. The univariate analysis showed that higher resilience was associated with lower sexual distress, lower odds of FSD, and better sexual function. Multivariable analysis adjusted for potential confounders showed that the association persisted and that higher resilience correlated with better sexual function and lower odds of FSD., Conclusions: In this large cross-sectional study, women with higher resilience scores had better sexual function and lower odds of FSD. Additional studies with diverse women are needed to confirm this association and to determine whether women with FSD could benefit from enhancing resilience as a therapeutic strategy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens., Design: Multicenter retrospective observational study., Setting: Tertiary care hospital and 15 community and academic centers of a large healthcare system., Patients: Hospitalized patients with PE treated with systemic alteplase., Interventions: None., Measurements and Main Results: Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively ( p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting., Conclusions: In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications., Competing Interests: Dr. Tierney received funding from the American College of Physicians and the Society of Hospital Medicine. Dr. Brown received funding from Alexion, Astra Zeneca, and Trevena Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: We characterize the most recent natural history of necrotizing enterocolitis (NEC), as this is an essential first step in guiding the prevention and treatment of this disease in the present day., Study Design: We performed a retrospective cohort study of neonates who were born at 23 to 29 weeks' gestation and birth weight <1,500 g who received care from the Pediatrix Medical Group between 2004 and 2019. We assessed the incidence of medical and surgical NEC and the patterns of initial antibiotic treatment to develop a contemporary cohort for further analysis. Among patients discharged between 2015 and 2019, we characterized the stage-specific risk factors for patients diagnosed with medical or surgical NEC, as well as patterns of disease onset, progression, biomarkers, and outcomes. We used the same approach to characterize patients diagnosed with suspected NEC., Results: Among 34,032 patients in the contemporary cohort, 1,150 (3.4%) were diagnosed with medical NEC and 543 (1.6%) were diagnosed with surgical NEC. The temporal pattern of disease onset was different for medical and surgical NEC, with gestational age- and birth weight-specific risk disparities emerging earlier in surgical NEC. Thirty-day mortality was much greater among surgical NEC patients (medical NEC 16.4% vs. surgical NEC 43.0%), as were rates of various in-hospital and long-term outcomes. Suspected NEC was diagnosed in 1,256 (3.7%) patients, among whom risk factors and disease onset, progression, and outcomes closely resembled those of medical NEC., Conclusion: Analyzing data from a contemporary cohort enabled us to characterize the current, stage-specific natural history of NEC, including novel insights into suspected NEC. Future studies could leverage this cohort to characterize how specific patient characteristics, care processes, or biomarkers may influence or predict disease outcomes., Key Points: · The incidence of NEC has reached a stable baseline in recent years.. · Risk factors for NEC vary in a stage-specific manner.. · The stage-specific onset and progression of NEC differ by gestational age and birth weight.., Competing Interests: W.A.C. reports serving on a scientific advisory board of Plakous Therapeutics (Winston-Salem, NC). The other authors have no conflicts of interest relevant to this article to declare., (Thieme. All rights reserved.)

Study Objective: Several simulation models have been evaluated for gynecologic procedures such as hysterectomy, but there are limited published data for myomectomy. This study aimed to assess the validity of a low-cost robotic myomectomy model for surgical simulation training., Design: Prospective cohort simulation study., Setting: Surgical simulation laboratory., Participants: Twelve obstetrics and gynecology residents and 4 fellowship-trained minimally invasive gynecologic surgeons were recruited for a 3:1 novice-to-expert ratio., Interventions: A robotic myomectomy simulation model was constructed using <$5 worth of materials: a foam cylinder, felt, a stress ball, bandage wrap, and multipurpose sealing wrap. Participants performed a simulation task involving 2 steps: fibroid enucleation and hysterotomy repair. Video-recorded performances were timed and scored by 2 blinded reviewers using the validated Global Evaluative Assessment of Robotic Skills (GEARS) scale (5-25 points) and a modified GEARS scale (5-40 points), which adds 3 novel domains specific to robotic myomectomy. Performance was also scored using predefined task errors. Participants completed a post-task questionnaire assessing the model's realism and utility., Measurements and Main Results: Median task completion time was shorter for experts than novices (9.7 vs 24.6 min, p = .001). Experts scored higher than novices on both the GEARS scale (median 23 vs 12, p = .004) and modified GEARS scale (36 vs 20, p = .004). Experts made fewer task errors than novices (median 15.5 vs 37.5, p = .034). For interrater reliability of scoring, the intraclass correlation coefficient was calculated to be 0.91 for the GEARS assessment, 0.93 for the modified GEARS assessment, and 0.60 for task errors. Using the contrasting groups method, the passing mark for the simulation task was set to a minimum modified GEARS score of 28 and a maximum of 28 errors. Most participants agreed that the model was realistic (62.5%) and useful for training (93.8%)., Conclusion: We have demonstrated evidence supporting the validity of a low-cost robotic myomectomy model. This simulation model and the performance assessments developed in this study provide further educational tools for robotic myomectomy training., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion., Design: Retrospective cohort study., Setting: A large multi-site health system with hospitals across the United States., Patients: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC., Interventions: None., Measurements and Main Results: Between May 5 th , 2018, to January 31 st , 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71-2.20) or multivariable analysis (OR 1.34, 95% CI 0.68-2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37-16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74-12.18, p < 0.001)., Conclusion: There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC., Competing Interests: Declaration of Competing Interest All authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate whether the process of conferring academic rank or components of the promotion packet contribute to the lack of parity in academic advancement for women and individuals underrepresented in medicine (URMs)., Patients and Methods: We retrospectively reviewed prospective promotion applications to the position of associate professor or professor at Mayo Clinic from January 2, 2015, through July 1, 2019. Individuals with doctorate degrees who applied for either rank were included in the study. Data collected included demographic characteristics, curriculum vitae at time of application, committee score sheets, and deferral and approval decisions. Deferral rates for women compared with men and for URMs compared with non-URMs was the primary outcome., Results: Of 462 people who applied for associate professor, 10% (n=46) were deferred. Those promoted had worked longer at Mayo Clinic (median, 6 years vs 2 years; P=.01), had more mentees (median, 6 vs 4; P=.02), authored more publications (median [interquartile range (IQR)], 39 [32-52] vs 30 [24-35]; P<.001), and were more likely to be on a National Institutes of Health or institutional grant (P<.05). Of the 320 people who applied for professor, 8.8% (n=28) were deferred. Those promoted had authored more publications (median [IQR], 77 [60-99] vs 56 [44-66]; P<.001) and were less likely to hold an elected office to a professional society (22.6% vs 39.3%; P=.05). There was no significant association between deferral status and sex (P>.4) or race/ethnicity (P>.9) for either rank., Conclusion: The process for academic advancement for professorships does not contribute to the gap in promotion rates for women and URMs., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: The new ultra-short-acting benzodiazepine, remimazolam, offers a pharmacokinetic and pharmacodynamic advantage over commonly used procedural sedation medication. This retrospective study explored the real-world utilization of remimazolam during procedural sedation to support the development of a nurse sedation protocol. The primary outcome was to identify associations between recovery time, adverse reactions, and dose-response in expanded patient populations., Methods: This study reviewed charts of 292 adult patients from 3 hospitals within one institution who received remimazolam during procedural sedation between June 1, 2021 and December 31, 2021. Data were analyzed using logistic and linear regression., Findings: The median time to alert in patients receiving remimazolam alone was 12 minutes (interquartile range 10, 17) and increased when additional sedation medications were utilized. Receiving additional sedative medication significantly increased the odds of hypoxia (OR 2.77, 95% CI 1.30-5.91, P = 0.008) after adjusting for body mass index (BMI), American Society of Anesthesiologists physical status (ASA-PS), and total remimazolam dose. There was a 25% increase in odds of experiencing hypoxia for every 5 kg/m2 increase in BMI (95% CI 1.01-1.54, P = 0.037)., Implications: Remimazolam presents as a promising option for nurse procedural sedation, offering minimal impact on hemodynamics and respirations, quick recovery, and no residual sedative effects., Competing Interests: Declaration of Competing Interest This work was supported through funding by the Mayo Clinic Department of Pharmacy for the statistical analysis and interpretation of data., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Since the 1970s, a plethora of tools have been introduced to support the medication use process. However, automation initiatives to assist pharmacists in prospectively reviewing medication orders are lacking. The review of many medications may be protocolized and implemented in an algorithmic fashion utilizing discrete data from the electronic health record (EHR). This research serves as a proof of concept to evaluate the capability and effectiveness of an electronic prospective medication order review (EPMOR) system compared to pharmacists' review., Materials and Methods: A subset of the most frequently verified medication orders were identified for inclusion. A team of clinical pharmacist experts developed best-practice EPMOR criteria. The established criteria were incorporated into conditional logic built within the EHR. Verification outcomes from the pharmacist (human) and EPMOR (automation) were compared., Results: Overall, 13 404 medication orders were included. Of those orders, 13 133 passed pharmacist review, 7388 of which passed EPMOR. A total of 271 medication orders failed pharmacist review due to order modification or discontinuation, 105 of which passed EPMOR. Of the 105 orders, 19 were duplicate orders correctly caught by both EPMOR and pharmacists, but the opposite duplicate order was rejected, 51 orders failed due to scheduling changes., Discussion: This simulation was capable of effectively discriminating and triaging orders. Protocolization and automation of the prospective medication order review process in the EHR appear possible using clinically driven algorithms., Conclusion: Further research is necessary to refine such algorithms to maximize value, improve efficiency, and minimize safety risks in preparation for the implementation of fully automated systems., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Objectives: Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting., Design: Retrospective cohort study., Setting: Academic medical center in Minnesota., Patients: Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours., Interventions: None., Measurements: Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected., Main Results: Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1-4.5) and ICU length of stay of 4.9 days (3-8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1-0.3) and 30 hours (15.1-51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33-96%), while 64% (37-91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients., Conclusions: Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy., Competing Interests: The authors have no disclosures or conflicts of interest relevant to this work., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Study Objective: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure., Design: Retrospective analysis., Setting: Multisite integrated health system throughout Minnesota and Wisconsin., Patients: Adult patients with lymphoma who received HDMTX as a 4-h infusion., Measurements and Main Results: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort., Conclusion: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma., (© 2023 Pharmacotherapy Publications, Inc.)

Importance: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill., Objectives: This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance., Design Setting and Participants: This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort ( n = 19) and an opportunistically sampled qualification cohort ( n = 32)., Main Outcomes and Measures: A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations., Results: The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias., Conclusions and Relevance: Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients., Competing Interests: Dr. Scheetz declares a consultancy with DoseMe. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objective: To determine whether the gender of clinicians making antimicrobial stewardship recommendations has an impact on intervention acceptance rate., Design: A retrospective, multivariable analysis of antimicrobial stewardship prospective audit and feedback outcomes., Setting: A multisite healthcare system including Mayo Clinic Rochester (MN), Mayo Clinic Arizona, Mayo Clinic Florida and 17 health-system hospital sites, where prospective audit and feedback is performed and documented within an electronic tool embedded in the medical record., Participants: The study included 143 Mayo Clinic clinicians (84 cisfemales and 59 cismales)., Methods: Outcomes were analyzed from July 1, 2017, to June 30, 2022, for intervention rates, communication methods, and intervention acceptance by clinician gender, profession, patient age, and intensive care unit (ICU) status of patient., Results: Of 81,927 rules, 71,729 rules met study inclusion. There were 18,175 (25%) rules associated with an intervention. Most of the rules were reviewed by pharmacists (86.2%) and stewardship staff (85.5%). Of 10,363 interventions with an outcome documented, 8,829 (85.2%) were accepted and 1,534 (14.8%) were rejected. Female clinicians had 6,782 (86.5%) of 7,843 interventions accepted, and male clinicians had 2,047 (81.2%) of 2,520 interventions accepted ( P = .19). Female patients had more interventions than male patients (female vs male: 25.9% vs 24.9%; OR, 1.04; 95% CI, 1.02-1.08; P = .001). Patients in the ICU had a significantly lower intervention acceptance rate (ICU vs non-ICU: 78.2% vs 86.7%; OR, 0.56; 95% CI, 0.45-0.7; P < .001)., Conclusions: Female and male clinicians were equally effective at prospective audit and feedback in a multisite antimicrobial stewardship program. Patients in the ICU were less likely to have stewardship interventions accepted.

Objectives: Hydroxocobalamin inhibits nitric oxide pathways contributing to vasoplegic shock in patients undergoing cardiopulmonary bypass (CPB). The objective of this study was to evaluate the effect of intraoperative versus postoperative application of hydroxocobalamin for vasoplegic shock in patients undergoing CPB., Design: This was a historic cohort study., Setting: The study was conducted at a quaternary academic cardiovascular surgery program., Participants: Adults undergoing cardiac surgery using CPB were participants in the study., Interventions: Hydroxocobalamin (5 g) intravenously over 15 minutes., Measurements and Main Results: The treatment groups were assigned based on the receipt location of hydroxocobalamin (ie, intensive care unit [ICU] versus operating room [OR]). The primary outcome was vasopressor-free days in the first 14 days after CPB. Of the 112 patients included, 37 patients received hydroxocobalamin in the OR and 75 in the ICU. Patients in the OR group were younger than those in the ICU group (57.5 v 63.9 years, p = 0.007), with statistically similar American Society of Anesthesiologists scores. The mean CPB duration was 3.4 hours in the OR group and 2.9 hours in the ICU group (p = 0.09). In both groups, the norepinephrine-equivalent dose of vasopressors at hydroxocobalamin was 0.27 µg/kg/min. Days alive and free of vasopressors were not different between the OR and ICU groups (estimated difference 0.48 [95% CI -1.76-2.72], p = 0.67). The odds of postoperative renal failure, mesenteric ischemia, ICU, hospital length of stay, and in-hospital mortality were also similar between groups., Conclusions: A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock., Competing Interests: Declaration of Competing Interest E.D.W. serves as a consultant for Pacira Biosciences, Inc. P.M.W. has previously served as a consultant for La Jolla Pharmaceutical Company. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the association between ACEs and the development of psychiatric disorders by age 25 among individuals who sustained TBI prior to age 10., Design: Population-based case-control study., Setting: Olmsted County, Minnesota., Participants: 566 individuals (N=566) who sustained a TBI prior to age 10 were identified and classified using a validated TBI classification system. Among these individuals, cases with a subsequent mood or anxiety disorder prior to age 25 were identified through clinical diagnostic codes and manual record review. For each case, a 1:1 matched control was randomly selected from individuals with a pediatric TBI who did not have a mood/anxiety disorder prior to the matched case's mood/anxiety disorder., Interventions: Not applicable MAIN OUTCOME MEASURES: Development of a mood/anxiety disorder., Results: Among the 114 matched pairs of individuals with a TBI prior to age 10, a subsequent mood/anxiety diagnosis was significantly associated with a history of 10 of 14 ACE categories and with having an ACE score ≥1 (odds ratio 5.17; 95% confidence interval 2.78-9.59)., Conclusions: This is the first population-based study to the authors' knowledge showing that among children who sustained a TBI prior to age 10, those who experienced ACEs are at increased risk of developing a mood or anxiety disorder., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: With the implementation of a new electronic health record (EHR) system across Mayo Clinic, a project was approved to standardize and converge 9 region-specific large-volume infusion pump (LVP) drug libraries for Baxter SIGMA Spectrum pumps., Summary: The objectives of the project were to (1) develop recommendations for identified variances in practice, (2) consolidate regional drug libraries into a converged enterprise library, (3) improve the drug library management process, and (4) maintain or exceed previous Dose Error Reduction System (DERS) compliance for infusions administered. Harmonization efforts with infusion pumps decreased the number of drug libraries maintained, reduced content maintenance time, and increased readiness for smart infusion pump-EHR interoperability. Seven of the 8 regions for which change in DERS compliance was assessed showed improved compliance relative to baseline in the 30-day postwashout period. Furthermore, when comparing pre- and postimplementation DERS compliance, the number of regions meeting the minimum compliance rate of 95% increased from 5 to 6 regions., Conclusion: The project improved the drug library management process, allowed for DERS compliance to be accurately compared across regions, and ensured that patients across the enterprise receive the same standard of care with the administration of intravenous medications., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cefepime exhibits highly variable pharmacokinetics in critically ill patients. The purpose of this study was to develop and qualify a population pharmacokinetic model for use in the critically ill and investigate the impact of various estimated glomerular filtration rate (eGFR) equations using creatinine, cystatin C, or both on model parameters. This was a prospective study of critically ill adults hospitalized at an academic medical center treated with intravenous cefepime. Individuals with acute kidney injury or on kidney replacement therapy or extracorporeal membrane oxygenation were excluded. A nonlinear mixed-effects population pharmacokinetic model was developed using data collected from 2018 to 2022. The 120 included individuals contributed 379 serum samples for analysis. A two-compartment pharmacokinetic model with first-order elimination best described the data. The population mean parameters (standard error) in the final model were 7.84 (0.24) L/h for CL1 and 15.6 (1.45) L for V1. Q was fixed at 7.09 L/h and V2 was fixed at 10.6 L, due to low observed interindividual variation in these parameters. The final model included weight as a covariate for volume of distribution and the eGFR cr-cysC (mL/min) as a predictor of drug clearance. In summary, a population pharmacokinetic model for cefepime was created for critically ill adults. The study demonstrated the importance of cystatin C to prediction of cefepime clearance. Cefepime dosing models which use an eGFR equation inclusive of cystatin C are likely to exhibit improved accuracy and precision compared to dosing models which incorporate an eGFR equation with only creatinine., Competing Interests: M.H.S. reports a previous research contract with Allecra; DoseMe consultancy. No other authors indicate potential conflicts of interest.

Objective: To investigate patterns and trends of co-prescriptions of stimulants and sedatives within the last 6 years at a tertiary care center., Method: Patients 18 years of age and older who were dispensed at least one stimulant prescription from an institutional pharmacy between 1/1/2015 and 7/1/2021 were included. Prescription data for any co-prescribed sedative/hypnotic were collected., Results: Both the number of stimulant dispenses and the number of patients with stimulant dispenses increased significantly with yearly incidence rate ratios of 1.115 (95% CI [1.110, 1.119]) and 1.090 (95% CI [1.084, 1.096]), respectively. The number of patients with a stimulant dispensed who also had a benzodiazepine or "Z-drug" sedative-hypnotic dispensed at any point in the search timeframe increased significantly with incidence rate ratios of 1.077 and 1.092, respectively. The number of stimulant dispenses, number of patients with stimulant dispenses, and number of patients with a stimulant dispensed who also had both a benzodiazepine and Z-drug dispensed at any point in the search timeframe increased significantly more in Non-White than in White patients., Conclusions: The results confirm previous findings of increases in dispensing of stimulants over the past 6 years and report increased polypharmacy of stimulants and sedative-hypnotics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Objective: In critically ill patients, adequacy of early antibiotic exposure has been incompletely evaluated. This study characterized factors associated with inadequate cefepime exposure in the first 24 h of critical illness., Design: Prospective cohort study., Setting: Academic Medical Center., Patients: Critically ill adults treated with cefepime. Patients with acute kidney injury or treated with kidney replacement therapy or extracorporeal membrane oxygenation were excluded., Intervention: None., Measurements: A nonlinear mixed-effects pharmacokinetic (PK) model was developed to estimate cefepime concentrations for each patient over time. The percentage of time the free drug concentration exceeded 8 mg/L during the first 24 h of therapy was calculated (%ƒT>8; appropriate for the susceptible breakpoint for Pseudomonas aeruginosa). Factors predictive of low %ƒT>8 were explored with multivariable regression., Main Results: In the 100 included patients, a one-compartment PK model was developed with first-order elimination with covariates for weight and estimated glomerular filtration rate based on creatinine and cystatin C (eGFRSCr-CysC). The median (interquartile range) %ƒT>8 for cefepime in the first 24 h of therapy based on this model was 85% (66%, 100%). Less than 100% ƒT>8 during first 24 h of therapy occurred in 70 (70%) individuals. Lower Sequential Organ Failure Assessment score (p = 0.032) and higher eGFRSCr-CysC (p < 0.001) predicted a lower %ƒT>8. Central nervous system infection source was protective (i.e., associated with a higher %ƒT>8; p = 0.008)., Conclusions: During early critical illness, cefepime concentrations were inadequate in a significant proportion of patients. Antimicrobial optimization is needed to improve the precision of pharmacotherapy in the critically ill patients., (© 2023 Pharmacotherapy Publications, Inc.)

Objective: Adverse childhood experiences (ACEs) are reported in more than half of the women in the United States and have been shown to negatively impact the menopause experience. The objective of this study was to evaluate the association between ACEs and age at natural menopause., Methods: This is a cross-sectional study conducted among participants of the Data Registry on the Experiences of Aging, Menopause, and Sexuality (DREAMS). The registry included women who were seen for consultations in the women's health clinic at Mayo Clinic, Rochester, between May 2015 and December 2016. Only postmenopausal women were included in this analysis. Childhood adversity was assessed with the validated ACE questionnaire. Age at natural menopause was self-reported. The association between ACEs and age at menopause was evaluated using a multivariable linear regression model adjusting for multiple confounders., Results: A total of 350 women were evaluated. The mean age was 59.2 years, and a majority were White (92.9%), married/partnered (82%), and educated (91.2% with at least some college education). Women with a history of at least four ACEs were estimated to reach natural menopause 1.3 years sooner than women with no ACE in multivariable analysis, but the results were not statistically significant (95% confidence interval, -3.2 to 0.6; P = 0.18)., Conclusions: Although stressful life experiences such as ACEs may negatively influence health for midlife women, this study did not find an association with the age at natural menopause., Competing Interests: Financial disclosures/conflicts of interest: J.M.K. was a past consultant for Kindra with Proctor and Gamble and Triangle Insights group, and is a medical editor for Everyday health. M.S., C.S., and K.M. have nothing to disclose. S.F. is primed for CME lecture and Clinical Overviews (online educational content), and has received fellowship fees from Atria Academy of Science and Medicine. F.E. has received grant support from the National Institutes of Health and the Agency for Healthcare Quality Research. P.D. is a speaker for Med IQ. E.K. has no conflicts of interest directly related to the subject of this article. Over the past 36 months, she, however, has had the following conflicts of interest: She has been a consultant for Astellas and Mithra Pharmaceuticals, Scynexis, and Womaness. She receives grant support from Mithra Pharmaceuticals. She has received payment for development of educational content from Med Learning Group and Academy of Continued Healthcare Learning. She has received honoraria for CME activity from CogniMed, PriMed, and OBG Management., (Copyright © 2023 by The Menopause Society.)

Importance: The outcomes of critically ill adults with obesity on continuous renal replacement therapy (CRRT) are poorly characterized. The impact of CRRT dose on these outcomes is uncertain., Objectives: This study aimed to determine if obesity conferred a survival advantage for critically ill adults with acute kidney injury (AKI) on CRRT. Secondarily, we evaluated whether the dose of CRRT predicted mortality in this population., Design Setting and Participants: A retrospective, observational cohort study performed at an academic medical center in Minnesota. The study population included critically ill adults with AKI managed with CRRT., Main Outcomes and Measures: The primary outcome of 30-day mortality was compared between obese (body mass index [BMI] ≥ 30 kg/m 2 ) and nonobese (BMI < 30 kg/m 2 ) patients. Multivariable regression assessed was used to assess CRRT dose as a predictor of outcomes. An analysis included dose indexed according to actual body weight (ABW), adjusted body weight (AdjBW), or ideal body weight (IBW)., Results: Among 1033 included patients, the median (interquartile range) BMI was 26 kg/m 2 (23-28 kg/m 2 ) in the nonobese group and 36 kg/m 2 (32-41 kg/m 2 ) in the obese group. Mortality was similar between groups at 30 days (54% vs. 48%; p = 0.06) but lower in the obese group at 90 days (62% vs. 55%; p = 0.02). CRRT dose predicted an increase in mortality when indexed according to ABW or AdjBW (hazard ratio [HR], 1.2-1.16) but not IBW (HR, 1.04)., Conclusions and Relevance: In critically ill adults with AKI requiring CRRT, short-term mortality appeared lower in obese patients compared with nonobese patients. Among weight calculations, IBW appears to be preferred to promote safe CRRT dosing in obese patients., Competing Interests: Dr. Barreto is a consultant for Wolters Kluwer for topics unrelated to the studied subject matter. Dr. Kashani receives funds from National Institute of Diabetes and Digestive and Kidney Diseases, research funds from Baxter, as well as speaker funds for Nikkiso and Baxter for subject matter unrelated to the research performed. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Importance: Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients., Objectives: We designed this study to derive and validate a novel equation to predict free VPAC using data from ICU patients and to compare its performance to published equations., Design: Retrospective cohort study., Setting: Two academic medical centers., Participants: Patients older than 18 years old with concomitant free and total VPACs measured in the ICU were included in the derivation cohort if admitted from 2014 to 2018, and the validation cohort if admitted from 2019 to 2022., Main Outcomes and Measures: Multivariable linear regression was used to derive an equation to predict free VPAC. Modified Bland-Altman plots and the rate of therapeutic concordance between the measured and predicted free VPAC were compared., Results: Demographics, median free and total VPACs, and valproate free fractions were similar among 115 patients in the derivation cohort and 147 patients in the validation cohort. The Bland-Altman plots showed the new equation performed better (bias, 0.3 [95% limits of agreement, -13.6 to 14.2]) than the Nasreddine (-9.2 [-26.5 to 8.2]), Kodama (-9.7 [-30.0 to 10.7]), Conde Giner (-7.9 [-24.9 to 9.1]), and Parent (-9.9 [-30.7 to 11.0]) equations, and similar to Doré (-2.0 [-16.0 to 11.9]). The Doré and new equations had the highest therapeutic concordance rate (73%)., Conclusions and Relevance: For patients at risk of altered protein binding such as ICU patients, existing equations to predict free VPAC are discordant with measured free VPAC. A new equation had low bias but was imprecise. External validation should be performed to improve its precision and generalizability. Until then, monitoring free valproate is recommended during critical illness., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objective: The severity of menopause-related symptoms varies considerably among women. The determinants of this variation are incompletely understood. The aim of this study was to assess the association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms., Methods: This was a cross-sectional study of 60 peri- and postmenopausal women in the Mayo Clinic RIGHT study (which involved sequencing of genes involved in drug metabolism and transport), who had also been evaluated in the Women's Health Clinic at Mayo Clinic in Rochester, MN. All participants completed the Menopause Rating Scale (MRS) for assessment of menopause symptoms, including hot flashes. The association between severity of menopause symptoms and the variation in genes encoding 8 enzymes and transporters involved in estrogen metabolism was evaluated., Results: Lower CYP3A4 activity and higher COMT activity were associated with lower severity of somatic menopause symptoms (p = 0.04 and 0.06, respectively). These associations did not persist after adjustment for hormone therapy use. No differences in MRS scores or hot flash severity were noted among other genetic variant groups. Age at natural menopause was not affected by variations in the genes studied., Conclusion: The current study did not show an association between genetic variation in estrogen metabolism and transport pathways and the severity of menopause symptoms. Further studies with larger sample sizes may be required to understand this potentially complex association., Competing Interests: Declaration of competing interest Dr. Kapoor is funded in part by the National Institute on Aging (NIA grant U54 AG044170). Dr. Kapoor has no conflicts of interest directly related to the subject of this manuscript. However, over the past 36 months she has had the following conflicts of interest: She has been a consultant for Astellas and Mithra Pharmaceuticals, Scynexis and Womaness. She receives grant support form Mithra Pharmaceuticals. She has received payment for development of educational content from Med Learning Group and Academy of Continued Healthcare Learning. She has received honoraria for CME activity from PriMed and OBG Management. JMK: Prior consulting for Proctor and Gamble, Triangle Insights Group. Medical editor for Everyday Health. All other authors have no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work. The content of this article is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health (NIH), or of the Mayo Clinic., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue., Competing Interests: Conflict of Interest EDW serves as a consultant for Pacira Biosciences, Inc. PMW has previously served as a consultant for La Jolla Pharmaceutical Company. All other authors declare no conflict of interest or sources of funding related to the content of this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Daptomycin doses 8-12 mg/kg are recommended for susceptible dose-dependent Enterococcus species. However, data remain limited on safety outcomes of such dosing, compared to standard 4-6 mg/kg dosing., Methods: In this retrospective cohort study, patients were stratified into daptomycin standard-dose (≤ 6.5 mg/kg) versus high-dose (≥ 7.5 mg/kg) groups. The primary outcome was daptomycin safety based on a composite of creatine kinase elevation, daptomycin-related peripheral blood eosinophilia, eosinophilic pneumonitis, alanine aminotransferase elevation, and alkaline phosphatase elevation. A secondary aim was to identify risk factors for daptomycin adverse effects. Inclusion criteria were age ≥ 18 years old, daptomycin receipt for ≥ 48 h, and Enterococcus cultures with a daptomycin minimal inhibitory concentration 2-4 mg/L., Results: A total of 119 patients were included for analysis. Median daptomycin doses were 6.0 mg/kg (IQR 5.4, 6.1) and 8.1 mg/kg (IQR 7.9, 9.6) in the standard- and high-dose cohorts, respectively. Median durations were 13.5 days (standard-dose) and 16 days (high-dose) (p = 0.02). The composite safety endpoint occurred in 32.0% of the standard-dose group and 32.5% of the high-dose group (p = 0.96). Daptomycin was dose-reduced or held in 8.1% of patients experiencing an adverse effect. Concurrent antihistamine usage was associated with the composite outcome; however, there was no association with daptomycin dose or concurrent statin use., Conclusion: High-dose daptomycin was not associated with increased laboratory abnormalities or adverse drug reactions compared to standard-dose daptomycin., (© 2023. The Author(s).)

Background: Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin-tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT)., Methods: This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed., Results: AKI occurred in 14.4% of patients in the VPT group ( n  = 15/104) compared to 5.5% in the other BL group ( n  = 40/722) ( p  < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7-12.0) days in the VPT group and 10.9 (5-22.7) days in the other BL group ( p  = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33-4.65), p  = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group ( n  = 15/104) and 5.3% in the other BL group ( n  = 11/208) ( p  = 0.006). Receipt of VPT [HR: 2.55 (1.36-4.78), p  = 0.004] and acyclovir [HR: 2.38 (1.19-4.74), p  = 0.014) remained significantly associated with AKI in the multivariable model., Conclusion: Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy., Competing Interests: C.G.R. has served on the advisory board for Gilead Sciences, Inc. She has also received speaker compensation/honoraria from Insmed, CE Impact, Jobson Health Information, and the Continuing Education Network. A.V. reports being an inventor for Mayo Clinic Travel App interaction with Smart Medical Kit and Medical Kit for Pilgrims and received funding from Moderna Inc for being on the Moderna Advisory Board in 2021. K.L.J. reports receiving speaker fees from OncInfo. K.N.A.H. reports receiving speaker fees from Dar Al Shifa Hospital. Other authors reported no conflicts of interest., (© The Author(s), 2023.)

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs. 58.8%; P = 0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000 ng/mL should be considered., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Acute pain accounts for over 70% of Emergency Department (ED) visits. Sub-dissociative dose ketamine (0.1-0.6 mg/kg) is safe and effective for the management of acute pain in the ED. However, the optimal dose of intravenous ketamine that provides effective analgesia and minimizes the risk of adverse effects has yet to be identified. The objective of this study was to describe an effective analgesia dose range of IV ketamine for acute pain in the ED., Methods: This multi-center, retrospective cohort study evaluated adult patients who received analgesic and sub-dissociative dose ketamine for the management of acute pain between May 5, 2018, and August 30, 2021, in 21 emergency departments at academic, community, and critical access hospitals across four states. Patients were excluded if they received ketamine for an indication other than pain, such as procedural sedation or intubation, or for whom there was incomplete documentation for the primary outcome. Patients who received a ketamine dose <0.3 mg/kg were stratified into the low-dose group, and those who received a dose of 0.3 mg/kg or higher to the high-dose group. The primary outcome was change in pain scores within 60 min using a standard 11-point numeric rating scale (NRS). Secondary outcomes included incidence of adverse effects and use of rescue analgesics. Continuous variables were compared between dose groups using student t-test or Wilcoxon Rank-Sum test. Linear regression was used to assess the association between the change in NRS pain scores within 60 min and dose after adjusting for baseline pain, requiring an additional dose of ketamine, and receiving an opioid., Results: From 3796 patient encounters screened for receipt of ketamine, 384 patients met inclusion criteria including 258 in the low-dose group, and 126 in the high-dose group. The primary reason for exclusion was incomplete documentation of pain scores, or ketamine used for sedation. Median baseline pain scores were 8.2 in the low-dose group and 7.8 in the high-dose group (difference 0.5; 95% CI 0 to 1, p = 0.04). Both groups demonstrated significant reductions in their mean NRS pain scores within 60 min following the first administration of IV ketamine. There were no differences in the change in pain scores between both groups (-2.2 vs -2.6, mean difference 0.4, 95% CI -0.4 to 1.1, p = 0.34). Use of rescue analgesics (40.7% vs 36.5%, p = 0.43) and adverse effects were similar between groups, including early discontinuation of the ketamine infusion (37.2% vs. 37.3%, p = 0.99). Overall, the most common adverse effects were agitation (7.3%) and nausea (7.0%)., Conclusion: The analgesic efficacy and safety of high-dose sub-dissociative ketamine (≥0.3 mg/kg) was not superior to low-dose (< 0.3 mg/kg) for the management of acute pain in the ED. Low-dose ketamine <0.3 mg/kg is an effective and safe pain management strategy in this population., Competing Interests: Declaration of Competing Interest The authors of this study have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. However, only 10%-20% of hospitals have implemented BL TDM. This study aimed to characterize provider perceptions and key considerations for successfully implementing BL TDM., Methods: This was a sequential mixed-methods study from 2020 to 2021 of diverse stakeholders at 3 academic medical centers with varying degrees of BL TDM implementation (not implemented, partially implemented, and fully implemented). Stakeholders were surveyed, and a proportion of participants completed semistructured interviews. Themes were identified, and findings were contextualized with implementation science frameworks., Results: Most of the 138 survey respondents perceived that BL TDM was relevant to their practice and improved medication effectiveness and safety. Integrated with interview data from 30 individuals, 2 implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation, which was positively influenced by repeated exposure to evidence and expertise. The process of internalization appeared more complex with BL TDM than with other antibiotics (ie, vancomycin). Organizational considerations relevant to BL TDM implementation (eg, infrastructure, personnel) were similar to those identified in other TDM settings., Conclusions: Broad enthusiasm for BL TDM among participants was found. Prior literature suggested that assay availability was the primary barrier to implementation; however, the data revealed many more individual and organizational attributes, which impacted the BL TDM implementation. Internalization should particularly be focused on to improve the adoption of this evidence-based practice., Competing Interests: M. H. Scheetz reports a previous research contract with Allecra. E. F. Barreto reports an ongoing consultancy agreement with Wolters-Kluwer. For the remaining authors, no conflicts of interest were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To examine glucagon prescribing trends among patients at high risk of severe hypoglycemia and assess if a glucagon prescription is associated with lower rates of severe hypoglycemia requiring hospital care., Methods: Retrospective analysis of electronic health records from a large integrated healthcare system between May 2019 and August 2021. We included adults (≥18 years) with type 1 diabetes or with type 2 diabetes treated with short-acting insulin and/or recent history of hypoglycemia-related emergency department visit or hospitalization. We calculated rates of glucagon prescribing overall and by patient characteristics. We then matched 1:1 those who were and were not prescribed glucagon and assessed subsequent hypoglycemia-related hospitalization., Results: Of 9,200 high risk adults, 2063 (22.4%) were prescribed glucagon. Among patients more likely to be prescribed glucagon were those younger, female, White, living in urban areas, with prior severe hypoglycemia, and with a recent endocrinology specialist visit. In the matched cohort (N = 1707 per arm), 62 prescribed glucagon and 33 not prescribed glucagon were hospitalized for hypoglycemia (adjusted incidence rate ratio 1.71, 95% CI 1.10-2.66; P = 0.018)., Conclusion: Glucagon prescribing was infrequent with significant racial and rural disparities. Patients with glucagon prescriptions did not have lower rates of hospitalization for hypoglycemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The hip-spine relationship is increasingly recognized as critical for optimizing stability following total hip arthroplasty (THA). However, these measurements are not routinely obtained during THA workup. It has been suggested that insight can be gained from supine antero-posterior pelvis radiograph, measuring the distance from the superior border of the pubic symphysis to the sacro-coccygeal joint (PSCD). This study assessed the correlation between PSCD and lateral lumbar radiographic metrics in a cohort of preoperative THA patients., Methods: We retrospectively evaluated 250 consecutive patients who underwent THA with preoperative supine antero-posterior pelvis and lateral lumbar radiographs. The mean age was 68 years (range, 42 to 89), 61% were women, and the mean body mass index was 30 kg/m 2 (range, 19 to 52). Two reviewers measured PSCD, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), and lumbar lordosis (LL). Inter-observer reliability was calculated for all measurements, and correlation coefficients were calculated for PSCD with respect to PT, SS, PI, and LL., Results: Correlations between PSCD and lumbar radiographic metrics were all statistically significant, except for PI in men but graded as "weak" or "very weak" for men and women, respectively, as follows: PT = -0.30 (P < .01) and -0.46 (P < .01); SS = 0.27 (P < .01) and 0.22 (P < .01); PI = -0.04 (P = .70) and -0.19 (P = .02); and LL = 0.45 (P < .01) and 0.30 (P < .01). Inter-observer reliability was graded as "strong" for every metric., Conclusion: The PSCD was weakly correlated with all evaluated lateral lumbar radiographic metrics in both sexes, despite strong inter-observer reliability. Therefore, PSCD cannot reliably serve as a proxy for evaluating the hip-spine relationship., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The aim of this study was to understand the risk of developing attention-deficit/hyperactivity disorder (ADHD) or learning disability (LD) after childhood traumatic brain injury (TBI) in a population-based birth cohort. Cases of TBI for children from birth to 10 years were confirmed and stratified by severity of injury. For each TBI case, two age-matched and sex-matched referents without TBI were identified from the same birth cohort. Presence of ADHD and LD before age 19 were confirmed using medical and/or school records. Associations between TBI exposure and subsequent ADHD or LD were assessed in multivariable Cox regression models, adjusting for maternal age, education, and race. The incidence rate of TBI before age 10 was 1,156 per 100,000 person-years. Children who had a TBI before age 10 were more likely to have met the research criteria for ADHD (hazard ratio [HR], 1.68; 95% CI, 1.15-2.45) or LD (HR, 1.29; 95% CI, 1.00-1.68) by age 19. No statistically significant associations were shown between TBI and ADHD or LD when restricted to definite and probable TBI cases (consistent with moderate to severe and mild TBI, respectively) and their referents. Significant associations were shown when the analysis was confined to possible TBI cases (consistent with concussive TBI) and their referents (ADHD: HR, 2.05; 95% CI, 1.31-3.20; and LD: HR, 1.42; 95% CI, 1.05-1.91). Increased risk for developing ADHD and LD by adulthood was shown particularly for children with the least-severe injuries, indicating that factors other than trauma-related altered brain function likely contribute to this risk.

Background: The optimal alignment technique for total knee arthroplasty (TKA) remains controversial. We previously reported 6-month and 2-year results of a randomized controlled trial comparing kinematically versus mechanically aligned TKA. In the present study, we report the mean 13-year (range, 12.6-14.4) follow-up results from this trial., Methods: The original cohort included 88 TKAs (44 kinematically aligned using patient-specific guides and 44 mechanically aligned using conventional instrumentation), performed from 2008 to 2009. After institutional review board approval, the health records of the original 88 patients were queried. Revisions, reoperations, and complications were recorded. There were 26 patients who died, leaving 62 patients for follow-up. Of these, 48 patients (77%) were successfully contacted via phone. Reoperations and complications were documented. Furthermore, a battery of patient-reported outcome measures (PROMs) (including Western Ontario and McMaster University Index, Oxford Knee Score, Knee Injury and Osteoarthritis Outcome Score Junior, Forgotten Joint Score, Modified-Single Assessment Numerical Evaluation, and patient satisfaction) were obtained., Results: Of the original 88 patients in the study, 15 patients had at least one reoperation (17%) and 5 patients had undergone complete revision surgery (6%). There was no difference between the 2 alignment methods for major and minor reoperations (P = .66). The kinematically aligned total knees self-reported a nonstatistically significant (P = .16) improved satisfaction (96% versus 82%), but no difference in other PROMs compared to mechanically aligned TKAs., Conclusion: Kinematically aligned TKA demonstrates excellent mean 13-year results, comparable to mechanically aligned TKA with similar reoperations, complications, and PROMs., (Published by Elsevier Inc.)

Glucagon is critically underutilized, and we explored whether this is due to inadequate glucagon prescribing or the patient's inability to fill prescriptions. Of 216 commercially insured, high-risk individuals with diabetes who were prescribed glucagon in our healthcare system, 142 (65.4%) had a claim indicating its fill within 30 days., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In the last 36 months, Dr. McCoy has received support from NIDDK, National Institute on Aging (NIA) of the NIH, Patient Centered Outcomes Research Institute (PCORI), National Center for Advancing Translational Sciences (NCATS), and AARP® for unrelated work. She also served as a consultant to Emmi® (Wolters Kluwer) on developing patient education materials related to diabetes., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: The intravenous (IV) medication compounding workflow has long been associated with preventable medication errors. This has led to the development of technologies designed to enhance the safety of IV compounding workflows. Digital image capture is a component of this technology about which there is relatively limited published literature. This study evaluates image capture implemented within an electronic health record's existing first-party IV workflow solution., Methods: A retrospective case-control study was conducted to measure IV preparation times before and after digital imaging implementation. Preparations during 3 periods (preimplementation, ≤1 month post implementation, and >1 month post implementation) were matched for 5 variables. A less stringent analysis with matching for 2 variables, as well as an unmatched analysis, were performed post hoc. An employee survey assessed satisfaction with the digital imaging workflow, and revised orders were reviewed to identify new problems introduced by image capture., Results: A total of 134,969 IV dispenses were available for analysis. Median preparation time in the preimplementation and >1 month post implementation cohorts was unchanged in the 5-variable matched analysis (6.87 minutes vs 6.58 minutes, P = 0.14) and increased in the 2-variable matched analysis (6.98 minutes vs 7.35 minutes, P < 0.001) and unmatched analysis (6.55 minutes vs 8.02 minutes, P < 0.001). A large majority of survey respondents (92%) felt that image capture improved patient safety. Of the 105 postimplementation preparations identified as requiring revisions by the checking pharmacist, 24 (22.9%) required revisions directly related to camera functionality., Conclusion: Implementation of digital image capture likely increased preparation times. Most IV room staff felt that image capture increased preparation times and were satisfied with how the technology improved patient safety. Image capture introduced camera-specific issues that led to preparations requiring revisions., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Innovative care models are needed to address gaps in kidney care follow-up among acute kidney injury (AKI) survivors. We developed the multidisciplinary AKI in Care Transitions (ACT) program, which embeds post-AKI care in patients' primary care clinic., Objective: The objective of this randomized pilot trial is to test the feasibility and acceptability of the ACT program and study protocol, including recruitment and retention, procedures, and outcome measures., Methods: The study will be conducted at Mayo Clinic in Rochester, Minnesota, a tertiary care center with a local primary care practice. Individuals who are included have stage 3 AKI during their hospitalization, do not require dialysis at discharge, have a local primary care provider, and are discharged to their home. Patients unable or unwilling to provide informed consent and recipients of any transplant within 100 days of enrollment are excluded. Consented patients are randomized to receive the intervention (ie, ACT program) or usual care. The ACT program intervention includes predischarge kidney health education from nurses and coordinated postdischarge laboratory monitoring (serum creatinine and urine protein assessment) and follow-up with a primary care provider and pharmacist within 14 days. The usual care group receives no specific study-related intervention, and any aspects of AKI care are at the direction of the treating team. This study will examine the feasibility of the ACT program, including recruitment, randomization and retention in a trial setting, and intervention fidelity. The feasibility and acceptability of participating in the ACT program will also be examined in qualitative interviews with patients and staff and through surveys. Qualitative interviews will be deductively and inductively coded and themes compared across data types. Observations of clinical encounters will be examined for discussion and care plans related to kidney health. Descriptive analyses will summarize quantitative measures of the feasibility and acceptability of ACT. Participants' knowledge about kidney health, quality of life, and process outcomes (eg, type and timing of laboratory assessments) will be described for both groups. Clinical outcomes (eg, unplanned rehospitalization) up to 12 months will be compared with Cox proportional hazards models., Results: This study received funding from the Agency for Health Care Research and Quality on April 21, 2021, and was approved by the Institutional Review Board on December 14, 2021. As of March 14, 2023, seventeen participants each have been enrolled in the intervention and usual care groups., Conclusions: Feasible and generalizable AKI survivor care delivery models are needed to improve care processes and health outcomes. This pilot trial will test the ACT program, which uses a multidisciplinary model focused on primary care to address this gap., Trial Registration: ClinicalTrials.gov NCT05184894; https://www.clinicaltrials.gov/ct2/show/NCT05184894., International Registered Report Identifier (irrid): DERR1-10.2196/48109., (©Heather P May, Joan M Griffin, Joseph R Herges, Kianoush B Kashani, Andrea G Kattah, Kristin C Mara, Rozalina G McCoy, Andrew D Rule, Angeliki G Tinaglia, Erin F Barreto. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.05.2023.)

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined., Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals., Results: Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p  < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p  = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p  < 0.001)., Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir., Competing Interests: RRR received research funds from Regeneron and Roche on projects not related to this study, as a member of the DSMB for Novartis and is on the Board of Directors of the American Society of Transplantation. CGR is a member of an advisory board for Gilead. All other authors declare no potential conflicts of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P  < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P  < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min ( P  = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P  = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P  = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Background: Postdischarge follow-up in primary care is an opportunity for pharmacists to re-evaluate medication use in acute kidney injury (AKI) survivors. Of the emerging AKI survivor care models described in literature, only one involved a pharmacist with limited detail about the direct impact., Objective: This study aimed to describe pharmacist contributions to a comprehensive postdischarge AKI survivorship program in primary care (the AKI in Care Transitions [ACT] program)., Methods: The ACT program was piloted from May to December of 2021 at Mayo Clinic as a bundled care strategy for patients who survived an episode of AKI and were discharged home without the need for hemodialysis. Patients received education and care coordination from nurses before discharge and later completed postdischarge laboratory assessment and clinician follow-up in primary care. During the follow-up encounter, patients completed a 30-minute comprehensive medication management visit with a pharmacist focusing on AKI survivorship considerations. Medication therapy recommendations were communicated to a collaborating primary care provider (PCP) before a separate 30-minute visit with the patient. PCPs had access to clinical decision support with evidence-based post-AKI care recommendations. Medication-related issues were summarized descriptively., Results: Pharmacists made 28 medication therapy recommendations (median 3 per patient, interquartile range 2-3) and identified 14 medication discrepancies for the 11 patients who completed the pilot program, and 86% of the medication therapy recommendations were acted on by the PCP within 7 days. Six recommendations were made to initiate renoprotective medications, and 5 were acted on (83%)., Conclusion: During the pilot phase of a multifaceted transitional care program for AKI survivors, pharmacists' successfully identified and addressed multiple medication therapy problems, including for renally active drugs. These results demonstrate the potential for pharmacist-provider collaborative visits in primary care to improve safe and effective medication use in AKI survivors., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: It is unknown whether serum procalcitonin (PCT) concentration monitoring can differentiate between bacterial infection or cytokine release syndrome (CRS) when chimeric antigen receptor T-cell (CAR-T) recipients present with a constellation of signs and symptoms that may represent both complications., Objective: The objective of the study was to assess the utility of serum PCT concentrations as a biomarker of bacterial infection in CAR-T recipients., Study Design: This single-center, retrospective, medical record review evaluated patients prescribed CAR-T therapy until death or 30 days after infusion. Logistic regression modeling determined the association between elevated serum PCT concentrations within 48 h of fever onset and microbiologically confirmed infection. Secondary outcomes included clinically suspected infection, CAR-T toxicity rates, and broad-spectrum antibiotic usage. Predictive performance of PCT was assessed by area under the receiver operating characteristic curve (AUC)., Results: The 98 included patients were a median age of 63 (IQR: 55-69) years old, 47 (48%) were male, and 87 (89%) were Caucasian. Baseline demographics and clinical characteristics were similar between patients with and without a bacterial infection. Serum PCT >0.4 ng/mL within 48 h of fever was significantly associated with a microbiologically confirmed bacterial infection (OR: 2.75 [95% CI: 1.02-7.39], p = 0.045). Median PCT values in patients with and without confirmed infections were 0.40 ng/mL (IQR: 0.26, 0.74) and 0.26 ng/mL (IQR: 0.13, 0.47), respectively. The AUC for PCT to predict bacterial infection was 0.62 (95% CI 0.48-0.76). All patients experienced CRS of some grade, with no difference in CRS severity based on elevated PCT. Broad-spectrum antibiotics were used for a median of 45% and 23% of days in those with and without confirmed infection, respectively (p = 0.075)., Conclusion: Elevated serum PCT concentrations above 0.4 ng/mL at time of first fever after CAR-T infusion was significantly associated with confirmed bacterial infection. Furthermore, rigorous, prospective studies should validate our findings and evaluate serial PCT measurements to optimize antimicrobial use after CAR-T therapy., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)