The current standard method for the analysis of potential drug–drug interactions (pDDIs) is time‐consuming and includes the use of multiple clinical decision support systems (CDSSs) and the interpretation by healthcare professionals. With the emergence of large language models developed with artificial intelligence, an interesting alternative arose. This retrospective study included 30 patients with polypharmacy, who underwent a pDDI analysis between October 2022 and August 2023, and compared the performance of Chat GPT and established CDSSs (MediQ®, Lexicomp®, Micromedex®) in the analysis of pDDIs. A multidisciplinary team interpreted the obtained results and decided upon clinical relevance and assigned severity grades using three categories: (i) contraindicated, (ii) severe, (iii) moderate. The expert review identified a total of 280 clinically relevant pDDIs (3 contraindications, 13 severe, 264 moderate) using established CDSSs, compared with 80 pDDIs (2 contraindications, 5 severe, 73 moderate) using Chat GPT. Chat GPT almost entirely neglected pDDIs with the risk to QTc prolongation (85 vs. 8), which could also not be sufficiently improved by using a specific prompt. To assess the consistency of the results provided by Chat GPT, we repeated each query and found inconsistent results in 90% of the cases. In contrast, Chat GPT provided acceptable and comprehensible recommendations for specific questions on side effects. The use of Chat GPT for the identification of pDDIs cannot be recommended currently, because clinically relevant pDDIs were not detected, there were obvious errors and results were inconsistent. However, if these limitations are addressed accordingly, it is a promising platform for the future.

Background: Intramuscular adrenaline (epinephrine) is the first‐line treatment for anaphylaxis. This recommendation is based purely on consensus, not randomised controlled trials. In humans, hypotension and shock strongly correlate with plasma histamine concentrations. The efficacy of intramuscular adrenaline in reversing histamine‐induced hypotension remains unproven. This trial evaluated whether intramuscular adrenaline reverses histamine‐induced shock. Methods: We conducted an exploratory open‐label trial and a confirmatory randomised, double‐blind, placebo‐controlled, crossover trial. Healthy volunteers received a 15‐min continuous intravenous histamine infusion to induce hypotension. At 5 min, participants received either intramuscular adrenaline (300–500 μg) or placebo. A second adrenaline dose was administered if the mean arterial pressure (MAP) remained below 60 mmHg at 10 min. The primary endpoint was area under the effect curve for change in MAP. Results: During histamine‐induced hypotension, intramuscular adrenaline failed to produce a pressor response and was indistinguishable from placebo in the majority of participants. Excluding two subjects who needed a simultaneous dose reduction of histamine, only 5 of 20 participants (25%; 95% CI 8.7%–49.1%) demonstrated a transient MAP recovery after a single dose. A second adrenaline dose administered to participants who did not reach a MAP > 60 mmHg also failed to reverse hypotension. The primary outcome in the confirmatory cohort, excluding two subjects with histamine dose adjustments, was not different between treatments (adrenaline‐placebo: 7 mmHg·min, 95% CI −2 to 25; p = 0.06). Conclusion: In this study of a limited number of healthy human subjects, intramuscular adrenaline injections did not provide a sustained response in severe histamine‐mediated hypotension in a majority of recipients. Trial Registration: CTIS (2022–003591‐16) and ISRCTN (Nr. 11335622; https://doi.org/10.1186/ISRCTN11335622 )

2-deoxy-D-glucose is a synthetic glucose analog and a potent inhibitor of glycolysis. Preclinical models demonstrated antiviral effects of 2-deoxy-D-glucose by inducing a glucose-deprived state in cells, which interferes with viral replication. This was a phase I, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single (cohort 1: 100µl in one nostril, cohort 2: 200µl in one nostril, cohort 3: 200µl in both nostrils) and multiple (cohort 4: four-times 200µl/day in one nostril, cohort 5: four-times 200µl/day in both nostrils, cohort 6: six-times 200µl/day in both nostrils; all for seven days) ascending doses of intranasal 3.5% 2-deoxy-D-glucose in normal healthy volunteers with the primary objective of investigating safety and tolerability. Drug concentrations were measured in plasma and in nasal wash fluid. Forty-five healthy volunteers participated in this study. Single and multiple doses of 2-deoxy-D-glucose were well-tolerated, with no safety signals or treatment-related serious or severe adverse events observed throughout the trial. Pharmacokinetics showed virtually absent systemic absorption of intranasal 2-deoxy-D-glucose, while intranasal maximum drug concentrations were comparable to those shown to have antiviral effects in vitro. Intranasal 2-deoxy-D-glucose, a novel intranasal therapeutic treatment for acute viral infections was safe and well-tolerated in healthy volunteers. These data support the further clinical development of 2-deoxy-D-glucose for treating viral infections in the target population (NCT05314933).

Acute respiratory distress syndrome (ARDS) is a potential life-threatening, heterogenous, inflammatory lung disease. There are no data available on potential drug–drug interactions (pDDIs) in critically ill patients with ARDS. This study analyzed pDDIs in this specific cohort and aimed to investigate possible associations of coronavirus disease 2019 (COVID-19) as an underlying cause of ARDS and treatment with extracorporeal membrane oxygenation (ECMO) with the occurrence of pDDIs. This retrospective study included patients ≥18 years of age diagnosed with ARDS between January 2010 and September 2021. The Janusmed database was used for the identification of pDDIs. A total of 2694 pDDIs were identified in 189 patients with a median treatment duration of 22 days. These included 323 (12%) clinically relevant drug combinations that are best avoided, corresponding to a median rate of 0.05 per day. There was no difference in the number of pDDIs between COVID-19- and non-COVID-19-associated ARDS. In patients treated with ECMO, the rate of the most severely graded pDDIs per day was significantly higher compared with those who did not require ECMO. PDDIs occur frequently in patients with ARDS. On average, each patient may encounter at least one clinically relevant drug combination that should be avoided during their intensive care unit stay.