Search

Background: Community pharmacists commonly see individuals with chronic kidney disease (CKD) and are in an ideal position to mitigate harm from inappropriate prescribing. We sought to develop a relevant medication list for community pharmacists to dose adjust or avoid in individuals with an estimated glomerular filtration rate (eGFR) below 30 mL/min informed through a scoping review and modified Delphi panel of nephrology, geriatric and primary care pharmacists., Methods: A scoping review was undertaken to identify higher risk medications common to community pharmacy practice, which require a dose adaptation in individuals with advanced CKD. A 3-round modified Delphi was conducted, informed by the medications identified in our scoping review, to establish consensus on which medications community pharmacists should adjust or avoid in individuals with stage 4 and 5 CKD (non-dialysis)., Results: Ninety-two articles and 88 medications were identified from our scoping review. Of which, 64 were deemed relevant to community pharmacy practice and presented for consideration to 27 panel experts. The panel consisted of Canadian pharmacists practicing in nephrology (66.7%), geriatrics (18.5%) and primary care (14.8%). All participants completed rounds 1 and 2 and 96% completed round 3. At the end of round 3, the top 40 medications to adjust or avoid were identified. All round 3 participants selected metformin, gabapentin, pregabalin, non-steroidal anti-inflammatory drugs, nitrofurantoin, ciprofloxacin and rivaroxaban as the top ranked medications., Conclusion: Medications eliminated by the kidneys may accumulate and cause harm in individuals with advanced chronic kidney disease. This study provides an expert consensus of the top 40 medications that community pharmacists should collaboratively adjust or avoid to enhance medication safety and prescribing for individuals with an eGFR below 30 mL/min., (© 2024. The Author(s).)

Background: ChatGPT is an AI platform whose relevance in the peer review of scientific articles is steadily growing. Nonetheless, it has sparked debates over its potential biases and inaccuracies. This study aims to assess ChatGPT's ability to qualitatively emulate human reviewers in scientific research., Methods: We included the first submitted version of the latest twenty original research articles published by the 3rd of July 2023, in a high-profile medical journal. Each article underwent evaluation by a minimum of three human reviewers during the initial review stage. Subsequently, three researchers with medical backgrounds and expertise in manuscript revision, independently and qualitatively assessed the agreement between the peer reviews generated by ChatGPT version GPT-4 and the comments provided by human reviewers for these articles. The level of agreement was categorized into complete, partial, none, or contradictory., Results: 720 human reviewers' comments were assessed. There was a good agreement between the three assessors (Overall kappa >0.6). ChatGPT's comments demonstrated complete agreement in terms of quality and substance with 48 (6.7 %) human reviewers' comments, partially agreed with 92 (12.8 %), identifying issues necessitating further elaboration or recommending supplementary steps to address concerns, had no agreement with a significant 565 (78.5 %), and contradicted 15 (2.1 %). ChatGPT comments on methods had the lowest proportion of complete agreement (13 comments, 3.6 %), while general comments on the manuscript displayed the highest proportion of complete agreement (17 comments, 22.1 %)., Conclusion: ChatGPT version GPT-4 has a limited ability to emulate human reviewers within the peer review process of scientific research., Competing Interests: Declaration of competing interest Maximilian S. Schaefer received funding for investigator-initiated studies from Merck & Co., which do not pertain to this manuscript. He is an associate editor for BMC Anesthesiology. He received honoraria for presentations from Fisher & Paykel Healthcare and Mindray Medical International Limited and an unrestricted philantropic grant from Jeffrey and Judith Buzen. All other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting., Methods: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied., Results: A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a -5.5% (95% CI, -9.6 to -1.4%; P = 0.009; adjusted absolute difference, -0.19 mg OME; 95% CI, -0.33 to -0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, -0.06 to 0.05; P = 0.93; P for interaction = 0.013)., Conclusions: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Introduction: Perioperative opioid use has been associated with adverse clinical outcomes. Additionally, opioid disposal carries significant costs, due to the waste of pharmaceutical products and the time needed by skilled labor to report the waste. In this study, we aimed to estimate costs and predict factors of opioid-associated intraoperative product waste, as well as to evaluate whether higher intraoperative opioid doses are associated with increased risk of adverse postoperative outcomes., Methods: We included 170,607 patients undergoing general anesthesia and receiving intraoperative fentanyl, hydromorphone, or morphine at Beth Israel Deaconess Medical Center, Boston, MA, USA, between January 2010 and June 2020. We estimated product waste-associated costs based on various opioid syringe sizes and determined predictors of opioid waste. Further, we evaluated whether higher opioid doses were associated with postoperative adverse events according to the severity-indexed, incident report-based medication error-reporting program classification. The primary outcome included post-extubation desaturation, postoperative nausea or vomiting, or postoperative somnolence or sedation., Results: The use of the smallest syringe sizes (50 mcg for fentanyl, 0.2 mg for hydromorphone, and 2 mg for morphine) resulted in the lowest product waste-associated costs. The main predictor of opioid waste was the administration of more than one intraoperative opioid (adjusted odds ratio [aOR] = 7.64, 95% CI 7.40-7.89, P < 0.001). Intraoperative doses of fentanyl > 50-100 mcg (aOR = 1.17 [1.10-1.25], P < 0.001, adjusted risk difference [ARD] 2%) and > 100 mcg (aOR = 1.24 [1.16-1.33], P < 0.001, ARD 3%), hydromorphone > 1 mg (aOR = 1.13 [1.06-1.20], P < 0.001, ARD 2%), and morphine > 2-4 mg (aOR = 1.26 [1.02-1.56], P = 0.04, ARD 3%) and > 4 mg (aOR = 1.45 [1.18-1.77], P < 0.001, ARD 5%) were associated with higher risk of the primary outcome., Conclusion: Smaller syringe sizes of intraoperative opioids may help to reduce product waste and associated costs, as well postoperative adverse events through utilization of lower intraoperative opioid doses., (© 2024. The Author(s).)

This study evaluates the administration time-of-day effects on propofol pharmacokinetics and sedative response in rabbits. Nine rabbits were sedated with 5 mg/kg propofol at three local clock times: 10:00, 16:00, and 22:00 h. Each rabbit served as its own control by being given a single infusion at the three different times of day on three separate occasions. Ten arterial blood samples were collected during each clock-time experiment for propofol assay. A two-compartment model was used to describe propofol pharmacokinetics, and the pedal withdrawal reflex was used as the sedation pharmacodynamic response. The categorical data comprising the presence or absence of pedal withdrawal reflex was described by a logistic model. The typical volume of the central compartment equaled 7.67 L and depended on rabbit body weight. The elimination rate constant depended on drug administration time; it was lowest at 10:00 h, highest at 16:00 h, and intermediate at 22:00 h. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment, with the rate constant for the distribution to the effector compartment equal to 0.335 min(-1). Drug concentration had a large effect on the probability of anesthesia. The degree of anesthesia was largest at 10:00 h, lowest at 16:00 h, and intermediate at 22:00 h. In summary, both the pharmacokinetics and pharmacodynamics of propofol in rabbits depended on administration time. The developed population approach may be used to assess chronopharmacokinetics and chronopharmacodynamics of medications in animals and humans.