Christopher Giuliano

Purpose: Non-acetaminophen-induced acute liver failure (NAI-ALF) is associated with high mortality, with limited treatment options beyond supportive care and liver transplantation. While intravenous (IV) N-acetylcysteine (NAC) is the standard of care in acetaminophen-induced ALF, its benefit in NAI-ALF remains uncertain. Therefore, the purpose of this study is to evaluate the effect of IV NAC on in-hospital mortality. Methods: We conducted a retrospective cohort study that included adult patients with NAI-ALF. Inverse probability of treatment weighting (IPTW) based on baseline demographics, severity of ALF, comorbidity burden, and etiology of ALF was conducted to balance the two groups. The primary outcome was all-cause in-hospital mortality at 21 days. Secondary outcomes included time to INR normalization, time to liver function test (LFT) normalization, and hospital length of stay. Results: A total of 200 patients were included in the study, with 85 patients in the NAC group and 115 in the non-NAC group. After IPTW, groups were balanced with standardized mean differences of P < .01), with an odds ratio of 0.59 (95% CI 0.39 - 0.88). No difference was observed in time to INR normalization [HR 1.49 (95% CI 0.87 - 2.56, P = .15)], time to LFT normalization [HR 1.12 (95% CI 0.72 - 1.74, P = .61)], and length of hospital stay (11.9 vs 15.1 days, P = .84). Conclusion: For patients with NAI-ALF, IV NAC administration was associated with a reduction in in-hospital mortality at 21 days. These findings suggest NAC could play a role in the management of patients with NAI-ALF. Larger prospective studies are needed to further clarify the role of NAC in this population.

Objective: To analyze practicing pharmacists' use of drug information (DI) resources in the United States. Methods: An electronic survey was distributed to practicing US pharmacists through professional organization email lists and social media. The survey questionnaire asked respondents which subscription-based DI resources are provided through their employer, whether they personally pay for additional resources, how often they use subscription-based resources, and other related questions. Results: The survey received 430 responses, 387 of which were able to be fully analyzed. The resources that respondents most frequently had access to through their employer were UpToDate (77.0%), Lexicomp (74.9%), and Micromedex (62.3%). Many respondents (40.8%) paid for subscriptions with personal funds, and 28.9% reported never experiencing access issues due to payment barriers. Respondents in community settings were more likely to have paid for resources with personal funds (57.1%, p<0.05) and have less access to resources (51.4%, p<0.05). In the open-text responses, the most desired resources were point-of-care tools (UpToDate) and DI databases (Lexicomp). Conclusions: US pharmacists experience a varied level of access to DI resources through their employer. Pharmacy educators should focus their instruction on resources that are the most accessible to practicing pharmacists. Many, especially community pharmacists, pay out of pocket for desired resources, presenting an opportunity to advocate for increased resources.

Background: Unfractionated heparin (UFH) is widely used for treatment of acute venous thromboembolism (VTE); however, its anticoagulant response is highly variable. Delays in achieving therapeutic anticoagulation have been associated with increased mortality, suggesting a potential role for predictive modeling to guide dosing. Objective: To develop predictive models to estimate probability of therapeutic or supratherapeutic level attainment at the time of first activated partial thromboplastin time (aPTT) and the UFH infusion rate at the time of first therapeutic aPTT. Methods: This retrospective, cohort study included hospitalized patients with a new diagnosis of VTE receiving protocolized UFH (80 units/kg bolus followed by 18 units/kg/h infusion). Patients were excluded for protocol deviations, anticoagulation reversal, hypothermia, or pregnancy. The primary outcome was development of a predictive model for attainment of therapeutic or supratherapeutic aPTT at first follow-up. A secondary model was developed that predicted heparin infusion rate at the time of first therapeutic aPTT. Multivariable logistic and linear regression models were developed with variable selection using least absolute shrinkage and selection operator. Model performance was assessed using discrimination and calibration. Results: Among 398 included patients, 83.2% achieved a therapeutic or supratherapeutic aPTT at initial follow-up. Eleven predictors were included in the primary model (age, sex, race, white blood cell count, creatinine clearance, body mass index, total bilirubin, albumin, platelets, propofol exposure, and coagulopathy) and demonstrated moderate discrimination (area under the curve [AUC] = 0.744) with acceptable calibration for predicting UFH response. Prediction of heparin dose at initial therapeutic aPTT incorporated a subset of these variables along with additional predictors (weight, Glasgow Coma Scale, baseline aPTT, active viral infection, and aspartate aminotransferase) and demonstrated substantial performance ( R ² = .714). Conclusion and Relevance: Clinical and laboratory factors influence UFH response and dosing requirements. These models may support individualized dosing strategies to improve time to therapeutic anticoagulation, although external validation is needed before clinical application.

Scoping reviews are similar to systematic reviews in that they are designed to be transparent and reproducible processes to answer a question while reducing bias. The key difference between scoping reviews and the better‐known systematic review method is the scope of the question being answered. Scoping reviews are best suited to answering broad questions about a topic including mapping the current literature, identifying strengths and gaps in the literature, and tracking the use of terminology or methods used within a field. Scoping reviews can be standalone reviews or used to guide where a systematic review may be needed. Users should understand the purpose of a scoping review and be able to assess the quality of a scoping review before applying it to practice. This article provides an overview of the principles involved in conducting a scoping review, along with a clinical example illustrating each step.

Background: No standardized nomogram has been established to reduce hypoglycemia events while optimizing clinical outcomes for patients with diabetic ketoacidosis (DKA). Objective: To evaluate the safety and effectiveness of two DKA nomograms. Methods: We conducted a multicenter, retrospective cohort study in adult patients (≥18 years) treated with IV insulin for DKA. Cohorts were categorized based on the insulin nomogram utilized: Standard Incremental Nomogram with Glucose-Level Evaluation (SINGLE) and Multiple Algorithm Nomogram using Insulin Change and Rate Estimate (MULTIPLE). Patients were excluded if they were experiencing pregnancy, euglycemic DKA, or hyperosmolar hyperglycemic state. The primary outcome was hypoglycemic events (BG < 70 mg/dL). Secondary outcomes included time to DKA resolution and DKA recurrence. Results: A total of 234 patients were included (SINGLE n = 117, MULTIPLE n = 117). Hypoglycemia occurred in eight patients in the MULTIPLE group (6.8%) versus 25 patients in the SINGLE group (21.4%) ( P < 0.01) after controlling for confounders, hypoglycemia remained highest in the SINGLE cohort versus the MULTIPLE cohort (OR 3.0 [95% CI 1.2-7.2], P < 0.01). After controlling for confounders, hypoglycemia remained highest in the SINGLE cohort versus the MULTIPLE cohort (OR 3.0 [95% CI 1.2-7.2], P < 0.01). Significant differences were not observed between the two nomograms in time to DKA resolution (16.4 hours [IQR 10.2-28.3] vs 16.1 [IQR 10.0-22.8], P = 0.19), recurrence rates (11.1% vs 15.4%, P = 0.34) or ICU LOS ( P = 0.06). Conclusion: The MULTIPLE nomogram had fewer hypoglycemia events with no difference in time to DKA resolution. Additional studies are needed to evaluate varying nomograms to determine the optimal approach.

Background: In 2019, the Food and Drug Administration issued a warning regarding the risk of respiratory depression with gabapentin use, especially when combined with opioids or other central nervous system depressants. While prior inpatient studies have observed increased respiratory risks in postoperative patients, data are limited in hospitalized patients with renal dysfunction. Objective: The objective of the study is to evaluate the association between gabapentinoid use and respiratory depression in hospitalized patients with chronic kidney disease (CKD). Methods: This single-center retrospective cohort study included adult inpatients receiving a multimodal pain regimen with or without gabapentinoid and CKD stage III, IV, or V. Patients were excluded if they had a history of epilepsy, generalized anxiety disorder, restless leg syndrome, acute respiratory conditions, hepatic disease, or were initially admitted to the intensive care unit. The primary outcome was a composite measure of respiratory depression, including use of high-flow nasal cannula, bilevel positive airway pressure, mechanical ventilation, oxygen escalation, naloxone or flumazenil administration, or rapid response/code activation. Secondary outcomes included altered mental status, falls, and individual components of the primary outcome. Results: A total of 320 patients were included. In the unadjusted analysis, respiratory depression occurred in 35.6% of gabapentinoid users versus 24.1% of nonusers ( P = 0.10). After controlling for confounders, gabapentinoid use was associated with a significantly higher risk of respiratory depression (odds ratio: 1.71; 95% confidence interval: 1.02-2.89). A dose-dependent relationship was observed with respiratory depression: gabapentin >1400 mg/d (83.3%), 800 to 1400 mg/d (42.3 %), and 100 to 700 mg/d (29.7%); pregabalin >150 mg/d (66.7%) and ≤150 mg (26.3%). Secondary outcomes were not significantly different between groups. Conclusion and Relevance: Gabapentinoid use in hospitalized CKD patients was associated with respiratory depression. These findings support the need for careful dosing and monitoring of gabapentinoids in this high-risk population.

Oral factor Xa inhibitors are preferred treatments for venous thromboembolism (VTE). While apixaban and rivaroxaban require an initial lead-in period, clinicians may reduce the period if patients have received prior therapeutic parenteral anticoagulation, although supporting evidence is limited. The purpose of this study is to evaluate bleeding and thrombotic events associated with reducing factor Xa inhibitor lead-in duration in patients who have received prior parenteral anticoagulation. This multicenter retrospective cohort study was conducted across 29 hospitals and included adult patients hospitalized with a new diagnosis of VTE who received at least 24 h of therapeutic parenteral anticoagulation before starting apixaban or rivaroxaban. Patients with active bleeding on admission, anticoagulation prior to admission, antiphospholipid syndrome, severe liver disease, or contraindicated medications were excluded. The primary outcome was time to VTE recurrence within six months. Cox proportional hazard model was used to control for potential confounding factors and a sensitivity analysis was performed using propensity matching. Among 1,424 patients included, 1,068 received a full lead-in and 356 a reduced lead-in regimen. No significant difference in time to recurrent VTE (HR 0.53; 95% CI, 0.20–1.37;p = 0.19) or major bleeding (HR 0.69; 95% CI, 0.31–1.56;p = 0.45) was observed after controlling for confounding factors. No difference in recurrent VTE and major bleeding persisted after propensity matching. Among patients transitioning from parenteral anticoagulation to oral factor Xa inhibitors, a reduced lead-in duration was not associated with increased VTE recurrence or major bleeding. Graphical Abstract

Background: The use of artificial intelligence (AI)–based large language model chatbots such as ChatGPT has become increasingly popular in many disciplines. However, concerns exist regarding ethics, legal considerations, accuracy, and reproducibility with its use in health care practice, education, and research. Objective: This study aimed to assess current perceptions and use of AI chatbots in pharmacy practice from the perspective of pharmacist preceptors and determine factors that may influence the use of AI chatbots in practice. Methods: A cross-sectional survey of pharmacy practice preceptors from Indiana, Illinois, and Michigan was conducted using the validated Technology Acceptance Model Edited to Assess ChatGPT Adoption (TAME-ChatGPT) survey tool to collect information regarding current use of AI chatbots and factors associated with use, including ease of use, perceived risk, technology or social influences, anxiety, and perceived usefulness. Results: A total of 194 responses (194/1877, 10.34% response rate) were received. Approximately one-third (n=59, 30.4%) of respondents reported having used an AI chatbot, with 51.5% (n=100) indicating that they planned to start or would continue using chatbots in the future. In practice, common uses for AI chatbots included summarizing information (n=90, 46.4%), letter of recommendation writing (n=64, 32.9%), and obtaining disease state information (n=63, 32.5%). The 2 main constructs associated with the use of chatbots identified from the TAME-ChatGPT tool included perceived risk of using AI and attitude toward AI. Factors that predicted pharmacists’ current use of AI chatbots included positive attitude toward technology (odds ratio [OR] 3.64, 95% CI 2.08-6.36), coworker use of AI (OR 7.41, 95% CI 2.64-20.8), and working in academia (OR 5.62, 95% CI 1.30-24.23). Conclusions: Most pharmacist respondents had not used an AI chatbot and were unlikely to make patient care decisions based on information from a chatbot. The TAME-ChatGPT survey is validated for assessing chatbot use and attitudes among pharmacists, and future studies using this survey tool can guide the implementation of chatbots into pharmacy practice.