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Background: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined., Aims: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD., Method: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy., Results: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to -32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %)., Conclusion: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased VTE diagnosis failure rate that exceeds the safety threshold. Further studies are needed to improve diagnostic management in this population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Couturaud reports having received research grant support from Bristol-Myers Squibb/Pfizer and Bayer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme, Merck Sharp and Dohme, Sanofi, Leo Pharma, Janssen and Astra Zeneca and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Leo Pharma, Pfizer. Dr. Bertoletti reports having received research grant support from Bayer and fees for board memberships or symposia from Actelion, Aspen, Bayer, Bristol-Myers Squibb/Pfizer and MSD, and having received travel support from Aspen, Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Leo Pharma, MSD and Actelion. Dr. Pastre declares he has no conflict of interest related to this research. Dr. Roy declares he has no conflict of interest related to this research. Dr. Rambaud declares he has no conflict of interest related to this research. Dr. Mai declares she has no conflict of interest related to this research. Dr. Motreff declares she has no conflict of interest related to this research. Dr. Auffret declares he has no conflict of interest related to this research. Dr. Le Mao declares he has no conflict of interest related to this research. Dr. Gagnadoux declares he has no conflict of interest related to this research. Dr. Paleiron declares he has no conflict of interest related to this research. Dr. Schmidt declares he has no conflict of interest related to this research. Dr. Schmidt declares he has no conflict of interest related to this research. Dr. Sanchez reports having received research grant support from Bayer, Daiichi-Sankyo and Portola Pharmaceuticals, and fees or non-financial support for consultancy activities from Actelion, GlaxoSmithKline, Boehringer Ingelheim and Chiesi. Dr. Bressollette declares he has no conflict of interest related to this research. Dr. Nonent declares he has no conflict of interest related to this research. Dr. Tromeur declares she has no conflict of interest related to this research. Dr. Salaun declares he has no conflict of interest related to this research. Dr. Mismetti reports having received research grants from Bayer, fees for board memberships from Bayer, Bristol-Myers Squibb/Pfizer and Daiichi Sankyo, for lectures from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo and Sanofi, and for development of educational presentations from Bayer and Bristol-Myers Squibb/Pfizer. Dr. Girard reports having received personal fees and non-financial support from Bayer and Leo Pharma. Dr. Lacut reports having received personal fees from Bayer-Health Care, Bristol-Myers Squibb and Boehringer Ingelheim. Dr. Lemarie declares she has no conflict of interest related to this research. Dr. Meyer reports having received research grant support from Bayer, Boehringer Ingelheim, LEO Pharma Research Foundation and Sanofi, having been an uncompensated board member and a consultant for Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Leo Pharma and Pfizer, and having received travel support from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Leo Pharma and Sanofi. Dr. Leroyer reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Leo Pharma. No other potential conflict of interest relevant to this article was reported., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Particular interest is now given to the potential of dietary supplements as alternative non-pharmacological approaches in intestinal inflammation handling. In this aim, this study evaluates the efficiency of fish collagen peptides, Naticol ® Gut, on colonic inflammation., Methods: Wild type and Mannose receptor-deficient in the myeloid lineage C57BL/6 mice were administered with Dextran Sodium Sulfate (DSS), Naticol ® Gut, DSS, and Naticol ® Gut or only water for 4 or 8 days. Inflammatory status was evaluated by establishing macroscopic and microscopic scores, by measuring cytokine and calprotectin production by ELISA and the myeloperoxidase activity by chemiluminescence. Colonic macrophages were phenotyped by measuring mRNA levels of specific markers of inflammation and oxidative status. Colonic immune populations and T-cell activation profiles were determined by flow cytometry. Mucosa-associated gut microbiota assessment was undertaken by qPCR. The phenotype of human blood monocytes from inflammatory bowel disease (IBD) subjects was characterized by RT-qPCR and flow cytometry and their oxidative activity by chemiluminescence., Results: Naticol ® Gut-treated DSS mice showed attenuated colonic inflammation compared to mice that were only exposed to DSS. Naticol ® Gut activity was displayed through its ability to orient the polarization of colonic macrophage towards an anti-inflammatory and anti-oxidant phenotype after its recognition by the mannose receptor. Subsequently, Naticol ® Gut delivery modulated CD4 T cells in favor of a Th2 response and dampened CD8 T-cell activation. This immunomodulation resulted in an intestinal eubiosis. In human monocytes from IBD subjects, the treatment with Naticol ® Gut also restored an anti-inflammatory and anti-oxidant phenotype., Conclusion: Naticol ® Gut acts as a protective agent against colitis appearing as a new functional food and an innovative and complementary approach in gut health., (© 2022. The Author(s).)

Competing Interests: L. Mabon déclare n’avoir aucun lien d’intérêts. - Y. Auffret déclare avoir été pris en charge à l’occasion de déplacements pour congrès par Astra Zeneca.

Nitrous oxide is increasingly consumed during parties for its euphoric properties. But unfortunately, in several cases it leads to real addictions. Unfortunately because its use leads to neurological, psychiatric, pulmonary and even death -by hypoxia-. It is important that the medical community be informed. It is important that the medical community be informed that in the face of atypical and poorly explained disorders doctors may think about the use of laughing gas, especially among young students., Competing Interests: Y. Auffret déclare avoir été pris en charge lors de congrès par Aspen, Mundipharma, Daiichi Sankyo et AstraZeneca.

Background: Acute pain is a common condition among prehospital patients and prompt management is pivotal. Opioids are the most frequently analgesics used in the prehospital setting. However, opioids are highly addictive, and some patients may develop opioid dependence, even when they are exposed to brief opioid treatments. Therefore, alternative non-opioid analgesia should be developed to manage pain in the prehospital setting. Used at subdissociative doses, ketamine, a noncompetitive N-methyl-D-aspartate and glutamate receptor antagonist, provides analgesic effects accompanied by preservation of protective airway reflexes. In this context, we will carry out a randomized controlled, open-label, multicenter trial to compare a subdissociative dose of ketamine to morphine to provide pain relief in the prehospital setting, in patients with traumatic and non-traumatic pain., Methods/design: This will be a multicenter, single-blind, randomized controlled trial. Consecutive adults will be enrolled in the prehospital setting if they experience moderate to severe, acute, non-traumatic and traumatic pain, defined as a numeric rating scale score greater or equal to 5. Patients will be randomized to receive ketamine or morphine by intravenous push. The primary outcome will be the between-group difference in mean change in numeric rating scale pain scores measured from the time before administration of the study medication to 30 min later., Discussion: This upcoming randomized clinical trial was design to assess the efficacy and safety of ketamine, an alternative non-opiate analgesia, to manage non-traumatic and traumatic pain in the prehospital setting. We aim to provide evidence to change prescribing practices to reduce exposition to opioids and the subsequent risk of addiction., Trial Registration: ClinicalTrials.gov, ID: NCT03236805 . Registered on 2 August 2017.

Importance: Bag-mask ventilation (BMV) is a less complex technique than endotracheal intubation (ETI) for airway management during the advanced cardiac life support phase of cardiopulmonary resuscitation of patients with out-of-hospital cardiorespiratory arrest. It has been reported as superior in terms of survival., Objectives: To assess noninferiority of BMV vs ETI for advanced airway management with regard to survival with favorable neurological function at day 28., Design, Settings, and Participants: Multicenter randomized clinical trial comparing BMV with ETI in 2043 patients with out-of-hospital cardiorespiratory arrest in France and Belgium. Enrollment occurred from March 9, 2015, to January 2, 2017, and follow-up ended January 26, 2017., Intervention: Participants were randomized to initial airway management with BMV (n = 1020) or ETI (n = 1023)., Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 28 days defined as cerebral performance category 1 or 2. A noninferiority margin of 1% was chosen. Secondary end points included rate of survival to hospital admission, rate of survival at day 28, rate of return of spontaneous circulation, and ETI and BMV difficulty or failure., Results: Among 2043 patients who were randomized (mean age, 64.7 years; 665 women [32%]), 2040 (99.8%) completed the trial. In the intention-to-treat population, favorable functional survival at day 28 was 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, -1.64% to infinity]; P for noninferiority = .11). Survival to hospital admission (294/1018 [28.9%] in the BMV group vs 333/1022 [32.6%] in the ETI group; difference, -3.7% [95% CI, -7.7% to 0.3%]) and global survival at day 28 (55/1018 [5.4%] in the BMV group vs 54/1022 [5.3%] in the ETI group; difference, 0.1% [95% CI, -1.8% to 2.1%]) were not significantly different. Complications included difficult airway management (186/1027 [18.1%] in the BMV group vs 134/996 [13.4%] in the ETI group; difference, 4.7% [95% CI, 1.5% to 7.9%]; P = .004), failure (69/1028 [6.7%] in the BMV group vs 21/996 [2.1%] in the ETI group; difference, 4.6% [95% CI, 2.8% to 6.4%]; P < .001), and regurgitation of gastric content (156/1027 [15.2%] in the BMV group vs 75/999 [7.5%] in the ETI group; difference, 7.7% [95% CI, 4.9% to 10.4%]; P < .001)., Conclusions and Relevance: Among patients with out-of-hospital cardiorespiratory arrest, the use of BMV compared with ETI failed to demonstrate noninferiority or inferiority for survival with favorable 28-day neurological function, an inconclusive result. A determination of equivalence or superiority between these techniques requires further research., Trial Registration: clinicaltrials.gov Identifier: NCT02327026.

Purpose: Midazolam comedication with morphine is a routine practice in pre and postoperative patients but has not been evaluated in prehospital setting. We aimed to evaluate the comedication effect of midazolam in the prehospital traumatic adults., Methods: A prehospital prospective randomized double-blind placebo-controlled trial of intravenous morphine 0.10 mg/kg and midazolam 0.04 mg/kg vs morphine 0.10 mg/kg and placebo. Pain assessment was done using a validated numeric rating scale (NRS). The primary end point was to achieve an efficient analgesic effect (NRS≤3) 20 minutes after the baseline. The secondary end points were treatment safety, total morphine dose required until obtaining NRS≤3, and efficient analgesic effect 30 minutes after the baseline., Findings: Ninety-one patients were randomized into midazolam (n=41) and placebo (n=50) groups. No significant difference in proportion of patients with a pain score≤3 was observed between midazolam (43.6%) and placebo (45.7%) after 20 minutes (P=.849). Secondary end points were similar in regard with proportion of patients with a pain score≤3 at T30, the side effects and adverse events except for drowsiness in midazolam vs placebo, 43.6% vs 6.5% (P<.001). No significant difference in total morphine dose was observed, that is, midazolam (14.09 mg±6.64) vs placebo (15.53 mg±6.27) (P=.315)., Conclusions: According to our study, midazolam does not enhance pain control as an adjunctive to morphine regimen in the management of trauma-induced pain in prehospital setting. However, such midazolam use seems to be associated with an increase in drowsiness., (Copyright © 2014 Elsevier Inc. All rights reserved.)