Explore the vast range of titles available.

There is some evidence that the subjective effects of ketamine and other psychedelics like psilocybin are crucial for their therapeutic outcomes, such as treatment of depression or substance use disorder (SUD). We performed a meta-analysis and systematic review on the correlation of subjective symptoms and dissociation versus ketamine-induced therapeutic outcomes in patients with depression or SUD. A similar analysis was conducted for psilocybin-induced therapeutic improvement. We retrieved 23 papers studying ketamine (21 on depression, 2 on SUD) in 471 patients and 8 papers studying psilocybin (6 on depression, 2 on SUD) in 183 patients. Our study demonstrated a modest role for subjective effects mediating therapeutic outcomes, with R 2 -values ranging from 5–10% for ketamine and for psilocybine the R 2 was 24%. A greater mediating effect for psilocybin compared to ketamine was detected, particularly when restricting the analysis to depression. Additionally there is a greater mediating effect in SUD than depression, irrespective of treatment.

Severe opioid-induced respiratory depression (OIRD) can be treated with intranasal (IN) or intramuscular (IM) naloxone. It is relevant to compare their efficacy and determine the optimal strategy to restore breathing following OIRD. In this open label, crossover, one-on-one randomized trial, conducted in a research unit of an academic medical center, we compared the required number of IM (5 mg/0.5 mL) versus IN (4 mg/0.1 mL) naloxone doses following 10 µg/kg intravenous fentanyl-induced apnea in opioid-naïve participants and participants who chronically use an opioid. After 2 min of apnea, IM or IN naloxone was given at 2 min intervals until return of adequate ventilation. The primary outcome was the number of naloxone doses needed to achieve full reversal of breathing. If necessary, rescue intravenous naloxone was administered. Eighteen opioid-naïve participants were randomized, 16 analyzed. The required median IM naloxone doses were 1.5 (IQR 1-2) versus 2 (1-3) for IN naloxone ( p  = 0.0002); one participant required rescue naloxone. No serious adverse events occurred. Similarly, in participants who chronically used an opioid, IM was more effective than IN naloxone. In these participants, adverse effects included muscle rigidity in the IN treated participants and mild to moderate withdrawal irrespective of treatment. Here we show the superiority of IM over IN naloxone in the number of doses required for full reversal of breathing following opioid-induced apnea. While the trial shows superiority for IM naloxone with products used in the community, we relate our findings to the higher naloxone plasma concentrations after IM naloxone compared to IN naloxone. The study was registered at https://doi.org/10.1186/ISRCTN21068708 . Opioid-induced respiratory depression can be treated with intranasal (IN) or intramuscular (IM) naloxone. Here the authors report a randomized, crossover, open-label trial showing that lower number of IM doses are required for full reversal of breathing following fentanyl-induced apnea by comparison to IN doses.

Opioids are commonly prescribed in the Emergency Department (ED) for acute pain management. However, their use carries significant risks, including dependence and misuse. This study aims to gain insight into the perspectives of ED physicians and physician assistants (PAs) concerning the multifaceted role of the ED in problematic opioid use. This is crucial for reducing opioid-related harms. A qualitative study, using semi-structured interviews. Interviews were conducted with twenty-five ED physicians and PAs from four hospitals in the Netherlands. A diverse group participated in the study, representing different hospital settings and levels of working experience. Reflexive thematic analysis was performed to develop key themes reflecting participants' perspectives and attitudes towards the role of the ED in opioid related harms. Two key themes were developed from the analysis. The first theme 'Preventing opioid-related harms from an ED perspective' underscores the careful approach emergency physicians take when prescribing opioids. This involves restricting opioid prescriptions to specific indications, considering alternative pain management options, limiting prescription durations, and involving patients in shared decision-making. Beyond their own prescribing practices, emergency care providers also collaborate with general practitioners, navigate patient expectations, and operate within a broader societal landscape where pain is increasingly viewed as intolerable. The second theme 'Managing problematic opioid use at the ED' highlights the difficulties faced by emergency care providers in treating individuals who are already using or dependent on opioids. This includes recognizing, intervening, referring, and managing cases of problematic opioid use. This theme also considers the involvement of other healthcare professionals, such as pain specialists and psychiatrists, as well as the roles and responsibilities of patients. Additionally, it considers the broader societal context, particularly the extent of opioid-related harms in the Netherlands. This study sheds light on the complexities surrounding opioid use and emergency care providers' approach to mitigating opioid related harms while navigating patient needs and systemic challenges. EDs play a critical role in addressing opioid-related harms but face significant challenges. Strengthening provider education, integrating patient records, and enhancing partnerships with addiction services are key steps toward refining healthcare responses and policies for this ongoing public health crisis.

It remains unknown whether the administration of a deep neuromuscular block (NMB) during bariatric surgery improves surgical conditions and patient outcome. The authors studied the effect of deep versus moderate NMB in laparoscopic bariatric surgery on surgical conditions and postoperative pain. One hundred patients scheduled to undergo elective bariatric surgery were randomized to a deep NMB (post-tetanic-count 2-3) or a moderate NMB (train-of-four 1-2). The quality of the surgical field was scored using the Leiden-Surgical Rating Scale (L-SRS), a 5-point scale ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Three surgeons scored the L-SRS at 10-min intervals during surgery; postoperative pain scores were obtained in the postanesthesia-care-unit (PACU) and on the ward. Mean (95% confidence interval) L-SRS scores in moderate NMB 4.2 (4.0-4.4) versus 4.8 (4.7-4.9) in deep NMB (p < 0.001). Moderate NMB resulted in 17% of scores at L-SRS scores of 1-3, while deep NMB resulted in 100% scores at the high end of the L-SRS (4-5). Deep NMB led to improved pain scores in the PACU (4.6 (4.2-4.9) versus 3.9 (3.6-4.4), p = 0.03) and reduced shoulder pain on the ward (1.8 (1.5-2.1) versus 1.3 (1.1-1.5), p = 0.03). A composite score of pain and opioid use in the PACU favoured deep NMB (p = 0.001). In bariatric surgery, deep relaxation has advantages for surgeon and patient. Compared to moderate NMB, deep NMB produced stable and improved surgical conditions with less postoperative pain.

Opioid-induced respiratory depression driven by ligand binding to mu-opioid receptors is a leading cause of opioid-related fatalities. Buprenorphine, a partial agonist, binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects. The authors examined whether sustained buprenorphine plasma concentrations similar to those achieved with some extended-release injections used to treat opioid use disorder could reduce the frequency and magnitude of fentanyl-induced respiratory depression. In this two-period crossover, single-centre study, 14 healthy volunteers (single-blind, randomized) and eight opioid-tolerant patients taking daily opioid doses ≥90 mg oral morphine equivalents (open-label) received continuous intravenous buprenorphine or placebo for 360 minutes, targeting buprenorphine plasma concentrations of 0.2 or 0.5 ng/mL in healthy volunteers and 1.0, 2.0 or 5.0 ng/mL in opioid-tolerant patients. Upon reaching target concentrations, participants received up to four escalating intravenous doses of fentanyl. The primary endpoint was change in isohypercapnic minute ventilation (VE). Additionally, occurrence of apnea was recorded. Fentanyl-induced changes in VE were smaller at higher buprenorphine plasma concentrations. In healthy volunteers, at target buprenorphine concentration of 0.5 ng/mL, the first and second fentanyl boluses reduced VE by [LSmean (95% CI)] 26% (13-40%) and 47% (37-59%) compared to 51% (38-64%) and 79% (69-89%) during placebo infusion (p = 0.001 and < .001, respectively). Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection. In opioid-tolerant patients, fentanyl reduced VE up to 49% (21-76%) during buprenorphine infusion (all concentration groups combined) versus up to 100% (68-132%) during placebo infusion (p = 0.006). In opioid-tolerant patients, the risk of experiencing apnea requiring verbal stimulation following fentanyl boluses was lower with buprenorphine than with placebo (odds ratio: 0.07; 95% CI: 0.0 to 0.3; p = 0.001). Results from this proof-of-principle study provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids like fentanyl.

Objective The aim of this systematic review is to identify pain profiling parameters that are reliably different between patients with migraine and healthy controls, using Quantitative Sensory Testing (QST) including Temporal Summation (TS), Conditioned Pain Modulation (CPM), and Corneal Confocal Microscopy (CCM). Methods A comprehensive literature search was conducted (up to 23 May 2024). The quality of the research was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies. Results Twenty-eight studies were included after screening. The QST studies indicate that migraine patients exhibit lower pressure pain thresholds (PPT), particularly in the trigeminal region. A previous meta-analysis reported lower heat pain thresholds (HPT). CPM studies suggest a (mild) inhibitory or absent response in migraine patients, not different from controls. High-frequency and chronic migraine patients may exhibit a facilitatory CPM response. With repeated executions of CPM, migraine patients display a diminishing CPM response, a phenomenon not observed in control subjects. CCM investigations in migraine patients revealed conflicting outcomes, likely as a result of small sample sizes and limited characterization of migraine features. Conclusion Pain profiling migraine patients varies due to sensory modality, applied methods, anatomical sites, and migraine features. Understanding pain profiling offers insights into migraine pathophysiology, requiring careful selection of parameters and differentiation among migraine subtypes.

Both unexpected pain and unexpected pain absence can drive avoidance learning, but whether they do so via shared or separate neural and neurochemical systems is largely unknown. To address this issue, we combined an instrumental pain-avoidance learning task with computational modeling, functional magnetic resonance imaging (fMRI), and pharmacological manipulations of the dopaminergic (100 mg levodopa) and opioidergic (50 mg naltrexone) systems ( N = 83). Computational modeling provided evidence that untreated participants learned more from received than avoided pain. Our dopamine and opioid manipulations negated this learning asymmetry by selectively increasing learning rates for avoided pain. Furthermore, our fMRI analyses revealed that pain prediction errors were encoded in subcortical and limbic brain regions, whereas no-pain prediction errors were encoded in frontal and parietal cortical regions. However, we found no effects of our pharmacological manipulations on the neural encoding of prediction errors. Together, our results suggest that human pain-avoidance learning is supported by separate threat- and safety-learning systems, and that dopamine and endogenous opioids specifically regulate learning from successfully avoided pain.

Opioids are known to constrict pupils, and mobile phone-based self-administered eye scanning (MPSES) offers a potential method for monitoring opioid use in real-world settings. A clinical trial with 12 volunteers measured pupil size using MPSES under different light conditions (approx. 50 or approx. 500 lux) in the lab and over a week at home. Each participant made approximately 21 home tests, 12 in the lab without oxycodone and 16 in the lab after oxycodone intake. At the second visit the participants received a single dose of 20 mg oxycodone, and their pupil size was monitored hourly for 5 h. The pupil size after oxycodone intake was compared to drug-naïve tests performed at the lab and at home. Logistic regression models were built using measured pupil size and light conditions measured by the phone during each test, and a dichotomous variable indicating tests before or after oxycodone dosing as the outcome. The model demonstrated high classification accuracy (AUC = 0.94), with 82% true positives, 9% false positives, 91% true negatives and 18% false negatives. Misclassifications were largely due to difficulties measuring pupil size in individuals with corneal arcus, causing most of the false positive findings, and other interindividual differences. This shows that MPSES, including monitoring of ambient light conditions, can effectively detect opioid use within the 50–500 lux range. Our study paves the way for using MPSES to detect opioid use.

While opioid use confers a known risk for respiratory depression, the incremental risk of in-hospital cardiopulmonary arrest, respiratory arrest, or cardiopulmonary resuscitation (CPRA) has not been studied. Our aim was to investigate the prevalence, outcomes, and risk profile of in-hospital CPRA for patients receiving opioids and medications with central nervous system sedating side effects (sedatives). A retrospective analysis of adult inpatient discharges from 2008-2012 reported in the Premier Database. Patients were grouped into four mutually exclusive categories: (1) opioids and sedatives, (2) opioids only, (3) sedatives only, and (4) neither opioids nor sedatives. Among 21,276,691 inpatient discharges, 53% received opioids with or without sedatives. A total of 96,554 patients suffered CPRA (0.92 per 1000 hospital bed-days). Patients who received opioids and sedatives had an adjusted odds ratio for CPRA of 3.47 (95% CI: 3.40-3.54; p<0.0001) compared with patients not receiving opioids or sedatives. Opioids alone and sedatives alone were associated with a 1.81-fold and a 1.82-fold (p<0.0001 for both) increase in the odds of CPRA, respectively. In opioid patients, locations of CPRA were intensive care (54%), general care floor (25%), and stepdown units (15%). Only 42% of patients survived CPRA and only 22% were discharged home. Opioid patients with CPRA had mean increased hospital lengths of stay of 7.57 days and mean increased total hospital costs of $27,569. Opioids and sedatives are independent and additive risk factors for in-hospital CPRA. The impact of opioid sparing analgesia, reduced sedative use, and better monitoring on CPRA incidence deserves further study.

The increasing use of recreational nitrous oxide ( O) in the Netherlands and its link to traffic accidents highlights the need for reliable detection methods for law enforcement. This study focused on ex vivo detection of O in exhaled breath and examining its persistence in the human body. Firstly, a low-cost portable infrared based detector was selected and validated to detect O in air. Then, the influence of interferents and conditions potentially influencing the analysis were evaluated including relative humidity, ethanol, acetaldehyde and . Subsequently, O breathing dynamics were evaluated in vitro and ex vivo . Initially, a lung simulator was used to model respiratory mechanics and O decay, revealing detectable O levels up to 90 min after exposure. In the final part of this study, a controlled single and double dose of O gas was administered to 24 volunteers in an operating theatre. The presence of O in exhaled breath of the volunteers was analysed using infra red spectroscopy every 12-15 min. Our results show that O was detectable in exhaled breath for a minimum of 60 min post-administration and revealed a window of detection to potentially measure O for law enforcement and forensic purposes.