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Objectives: We determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia. Methods: In this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.3% Δ9-tetrahydrocannabinol and 8% cannabidiol (max. times inhalation sessions/day), or a combination of both for 6 weeks. The primary endpoint was treatment-related adverse events, assessed using a 10-point composite adverse event (cAE) score; additionally, we recorded daily reported pain relief and daily tablet and cannabis consumption. Results: In total, 23 patients were treated with oxycodone, 29 with cannabis, and 29 with the oxycodone/cannabis combination. Three patients from the oxycodone group (13%) and 18 patients from the cannabis groups (31%, 9 in each group) withdrew from the trial within 2–3 weeks because of the severity of AEs. There were no differences in treatment-related cAE scores among the three groups that completed the study (p = 0.70). The analgesic responder rate showed a ≥1- point reduction in pain in 50% and a ≥2-point reduction in 20% of patients, while 50% of patients experienced no treatment benefit. The combination treatment reduced oxycodone tablet consumption by 35% (p = 0.02), but it did not affect the number of cannabis inhalation sessions. Conclusions: Cannabis combined with oxycodone offered no advantage over either treatment alone, except for a reduction in opioid tablet intake; however, the overall drug load was the highest in the combination group. Moreover, cannabis was poorly tolerated and led to treatment discontinuation in one-third of participants treated with cannabis. Clinical Trial Registration: The trial was registered at the WHO International Clinical Trials Registry Platform (trialsearch.who.int) on July 26, 2019, identifier NL7902. [ABSTRACT FROM AUTHOR]

Medical education must equip future professionals with the necessary skills to navigate the complex healthcare landscape. Clinical knowledge is essential, and critical and creative thinking skills are vital to meet the challenges of the system. Design thinking offers a structured approach that integrates creativity and innovation, yet its application in medical education is absent. The compulsory MasterMinds Challenge course at Leiden University Medical Center utilizes design thinking principles to address real world healthcare challenges. Final-year medical students participated in a two-day program. The course encompassed empathizing with stakeholders, problem definition, ideation, prototyping, and refining solutions. Presentation skills were emphasized, culminating in a symposium where teams showcase their outcomes. Implementation of the MasterMinds Challenge course was successful with 33 sessions delivered to 1217 medical students. Challenges covered various healthcare topics, yielding creative yet practical outcomes. Students appreciate the real world healthcare challenge, team-based approach, and the applicability of design thinking principles. Challenge owners expressed satisfaction with students' commitment, creativity, and empathizing abilities. To further enhance the MasterMinds Challenge course, a more longitudinal format is being designed, enabling greater autonomy and emphasizing the refining and implementation phases. The course can be extended to medical postgraduate professionals and interdisciplinary collaborations, fostering innovative ideas beyond current practices. By developing problem-solving skills, the MasterMinds Challenge course contributes to a future-proof medical education program and prepares students to meet the evolving needs of healthcare. [ABSTRACT FROM AUTHOR]

Background: Recent advances in artificial intelligence (AI) have enabled development of natural language algorithms capable of generating coherent texts. We evaluated the quality, validity, and safety of this generative AI in preoperative anaesthetic planning., Methods: In this exploratory, single-centre, convergent mixed-method study, 10 clinical vignettes were randomly selected, and ChatGPT (OpenAI, 4.0) was prompted to create anaesthetic plans, including cardiopulmonary risk assessment, intraoperative anaesthesia technique, and postoperative management. A quantitative assessment compared these plans with those made by eight senior anaesthesia consultants. A qualitative assessment was performed by an adjudication committee through focus group discussion and thematic analysis. Agreement on cardiopulmonary risk assessment was calculated using weighted Kappa, with descriptive data representation for other outcomes., Results: ChatGPT anaesthetic plans showed variable agreement with consultants' plans. ChatGPT, the survey panel, and adjudication committee frequently disagreed on cardiopulmonary risk estimation. The ChatGPT answers were repetitive and lacked variety, evidenced by the strong preference for general anaesthesia and absence of locoregional techniques. It also showed inconsistent choices regarding airway management, postoperative analgesia, and medication use. While some differences were not deemed clinically significant, subpar postoperative pain management advice and failure to recommend tracheal intubation for patients at high risk for pulmonary aspiration were considered inappropriate recommendations., Conclusions: Preoperative anaesthetic plans generated by ChatGPT did not consistently meet minimum clinical standards and were unlikely the result of clinical reasoning. Therefore, ChatGPT is currently not recommended for preoperative planning. Future large language models trained on anaesthesia-specific datasets might improve performance but should undergo vigorous evaluation before use in clinical practice., Competing Interests: Declaration of interest MAM is founder of medical data platform Delphyr, which is unrelated to this work. All other authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The acute hypoxic ventilatory response is a critical chemoreflex originating at the carotid bodies. This study investigates the impact of low-dose i.v. esketamine on the ventilatory response to 20 min of isocapnic hypoxia to test the hypothesis that esketamine does not affect hypoxic ventilation., Methods: In this open-label study, 18 healthy subjects received a 3-h escalating i.v. infusion of esketamine, totalling 1.0 mg kg -1 . Before the esketamine infusion (control condition) and during the last 30 min of infusion, the ventilatory response to 20 min of isocapnic hypoxia (oxygen saturation ∼80%) was measured. We assessed the increase in ventilation from baseline to its peak during the first 5 min of isocapnic hypoxia (hypoxic ventilatory response) and the increase in ventilation from baseline to 20 min of isocapnic hypoxia (sustained hypoxia). Haemodynamics and acute brain function were also measured., Results: Independent of hypoxia, a small excitatory effect of ketamine on isocapnic ventilation was observed: the mean increase in ventilation (95% confidence interval) was 3.1 (2.4-3.7) L min -1 (P<0.0001). Esketamine had no effect on the isocapnic ventilatory response to acute and sustained hypoxia but increased MAP (+10 mm Hg) and heart rate (+10 beats min -1 ), similarly during normoxia and hypoxia. Esketamine increased anxiety and alertness and affected external perception., Conclusions: I.V. esketamine up to 1 mg kg -1 does not affect the ventilatory response to hypoxia, but affects haemodynamics and acute brain function. Increases in anxiety and alertness could be a cause of the sustained ventilatory response to hypoxia during esketamine infusion., Clinical Trial Registration: The trial was registered at the ISRCTN registry on June 27, 2023 under identifier ISRCTN 42617929 (https://www.isrctn.com/ISRCTN42617929)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The anesthetic, analgesic and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following N -methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial. Seventeen healthy volunteers were treated with 0.5 μg.kg -1 .min -1 SNP or placebo during a 3-h infusion of escalating doses of racemic ketamine (total dose 140 mg) or esketamine (70 mg). Pain pressure threshold (PPT) and arterial blood samples for measurement of S- and R-ketamine and their metabolites, S- and R-norketamine, were obtained. The data were analyzed with a population pharmacokinetic-pharmacodynamic model that incorporated the measured S- and R- ketamine and S- and R-norketamine isomers as input and PPT as output to the model. The potency of the 2 formulations in increasing PPT from baseline by 100% was 0.47 ± 0.12 (median ± standard error of the estimate) nmol/mL for esketamine and 0.62 ± 0.19 nmol/mL for racemic ketamine, reflecting the 52 ± 27% lower analgesic potency of R-ketamine versus S-ketamine. Modeling showed that SNP had no effect on S-ketamine potency but abolished the R-ketamine analgesic effect. Similar observations were made for S- and R-norketamine. Since SNP had no effect on S-ketamine analgesia, we conclude that SNP interacts on R-ketamine nociceptive pathways, possibly similar to its effects on R-ketamine activated dissociation pathways., Competing Interests: The authors declare the following competing financial interest(s): Prof. Dahan received consultancy fees from Enalare and from Trevena for work done outside of the scope of the current paper., (© 2024 The Authors. Published by American Chemical Society.)