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Background: Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients., Methods: A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed., Results: Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I 2  = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I 2  = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I 2  = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I 2  = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates., Conclusions: Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness., Methods: Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of < 30 on the Bowel Function Index (BFI), measured on day 14. The Rome IV criteria for constipation, side effects of and satisfaction with laxatives, pain scores, quality of life (using the EQ-5D-5L), daily use of laxatives and escape medication, and cost-effectiveness will also be assessed., Discussion: In this study we aim to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. The outcome of our study will contribute to prevention of OIC and scientific evidence of guidelines on (opioid-induced) constipation., Trial Registration: This trial is registered at clinicaltrials.gov: NCT05216328 and in the Dutch trial register: NTR80508. EudraCT number 2022-000408-36., (© 2023. The Author(s).)

Background: Debriefing is a critical component to promote effective learning during simulation-based training. Traditionally, debriefing is provided only after the end of a scenario. A possible alternative is to debrief specific portions during an ongoing simulation session (stop-and-go debriefing). While this alternative has theoretical advantages, it is not commonly used due to concerns that interruptions disturb the fidelity and adversely affect learning. However, both approaches have not been rigorously compared, and effects on skill acquisition and learning experience are unknown., Methods: We randomly assigned 50 medical students participating in a simulation-based cardiopulmonary resuscitation training to either a post-scenario debriefing or stop-and-go debriefing. After four weeks, participants performed a repeat scenario, and their performance was assessed using a generic performance score (primary outcome). A difference of 3 or more points was considered meaningful. A 5-item questionnaire was used to assess the subjective learning experience and the perceived stress level (secondary outcomes)., Results: There was no significant difference between the groups for the performance score (mean difference: -0.35, 95%CI: -2.46 to 1.77, P = 0.748, n = 48). The confidence limits excluding the specified relevant 3-point difference suggest equivalence of both techniques with respect to the primary outcome. No significant differences were observed for secondary outcomes., Conclusions: Stop-and-go debriefing does not adversely affect skill acquisition compared to the classic post-scenario debriefing strategy. This finding is reassuring when interruptions are deemed necessary and gives simulation instructors the latitude to tailor the timing of the debriefing individually, rather than adhering to the unsupported dogma that scenarios should not be interrupted., Trial Registration: As this study is not a clinical trial, it was not registered in a clinical trials register.

Due to the high rates of epidural failure (3-32%), novel techniques are required to objectively assess the successfulness of an epidural block. In this study we therefore investigated whether thermographic temperature measurements have a higher predictive value for a successful epidural block when compared to the cold sensation test as gold standard. Epidural anesthesia was induced in 61 patients undergoing elective abdominal, thoracic or orthopedic surgery. A thermographic picture was recorded at 5, 10 and 15 min following epidural anesthesia induction. After 15 min a cold sensation test was performed. Epidural anesthesia is associated with a decrease in skin temperature. Thermography predicts a successful epidural block with a sensitivity of 54% and a PPV of 92% and a specificity of 67% and a NPV of 17%. The cold sensation test shows a higher sensitivity and PPV than thermography (97 and 93%), but a lower specificity and NPV than thermography (25 and 50%). Thermographic temperature measurements can be used as an additional and objective method for the assessment of the effectiveness of an epidural block next to the cold sensation test, but have a low sensitivity and negative predictive value. The local decrease in temperature as observed in our study during epidural anesthesia is mainly attributed to a core-to-peripheral redistribution of body heat and vasodilation.