Search Results (71)

Background: Patients with Crohn’s disease (CD) suffer from a relevant burden of abdominal pain and psychological distress that can aggravate postoperatively. While systematic strategies for postoperative pain management are lacking, the potential benefit of perioperative epidural analgesia (EDA) in CD patients is unclear. Methods: All patients receiving an ileocecal resection due to CD at a tertiary hospital were included. The impact of epidural versus non-epidural analgesia on postoperative pain perception was evaluated by analyzing the numeric rating scale (NRS), analgesic consumption, and clinical outcomes. Results: In this monocentric study, 172 patients receiving ileocecal resection due to CD were included, with 122 receiving EDA. The epidural pain catheters were kept for an average of 4.4 days (±1.3) before being removed. EDA resulted in significantly decreased pain as well as a decreased amount of analgesic consumption (adjuvant analgesics: 16.4% vs. 32%, p = 0.021; strong opioids: 30.3% vs. 72.0%, p < 0.001) at the early postoperative course (1 vs. 3 at rest and 2 vs. 4 movement-evoked, p < 0.001). No difference in pain perception was detected on day 5 between EDA and non-EDA patients. Patients with EDA had a significantly longer length of hospital stay (7.5 versus 6 days, p = 0.002) and an increased intake of weak opioids at discharge (p = 0.024). Conclusions: While EDA in CD patients resulted in significantly decreased pain and decreased amounts of analgesic adjuvants and strong opioids at the early postoperative course, intravenous and oral analgesia provide sufficient postoperative pain control after surgery and earlier patient autonomy. Full article

The gastrointestinal (GI) tract is under neural, endocrine and paracrine control. The release (basal and in the presence of either cholinergic and opioid antagonists) of Met-enkephalin, insulin-like growth factor 1 (IGF-1) and somatostatin (SRIF) was determined quantitatively in vitro using explants of the crop, proventriculus and duodenum from either day 0 or day 1 chicks. In addition, the effects of cholinergic and opioid antagonists on PENK gene expression were examined. Thus, the aim of this study was to determine the roles of cholinergic and opioid receptors in the GI tract in newly hatched chickens. Moreover, the effect of IGF-1 and Met-enkephalin on cell division in duodenal explants in vitro was determined. There was both the release of Met-enkephalin from, and PENK expression in, the explants of the crop, proventriculus and duodenum tissue. This is the first report of any neuropeptide(s) being synthesized in and/or released from the crop. In vitro release of Met-enkephalin, IGF-1 and SRIF from duodenal and proventriculus explants was influenced (p < 0.01) by either cholinergic or opioid antagonists; for instance, in the presence of atropine, decreases (p < 0.001) of 17.8% and 57.7% are seen, respectively, in Met-enkephalin release and PENK expression in crop explants from day 1 chicks. Moreover, in the presence of atropine, there were increases (p < 0.001) of 47.7% and 70.9% in IGF-1 release in proventriculus explants from, respectively, day 0 and day 1 chicks. Met-enkephalin and/or IGF-1 stimulated the cell division of duodenal explants in vitro. This is the first report of Met-enkephalin release and PENK expression in the avian crop and of the effects of cholinergic or opioid antagonists on these factors. It is also the first report of either cholinergic or opioid control of IGF-1 release in the periphery of any species. There were strong relationships (p < 0.05) between the release of Met-enkephalin and that of IGF-1 in the duodenum and between the release of SRIF and that of IGF-1 in the proventriculus. This is the first report of IGF-1 and Met-enkephalin stimulating (p < 0.001) the proliferation of duodenal cells and, together, exerting a synergist effect. It is concluded that the release of Met-enkephalin, IGF-1 and SRIF from foregut regions is under tonic cholinergic and opioid control. Full article

Background/Objectives: The homeless population (HP) is a heterogeneous group characterized by the absence of stable and conventional housing, often relying on public spaces and deteriorated environments for shelter and survival, either temporarily or permanently. This group is exposed to multiple health vulnerabilities, with substance use disorder (SUD) identified as a significant risk factor for suicidal behavior. The aim of this study was to conduct a scoping review of the relationship between PAS use and suicide among homeless individuals. Methods: A comprehensive literature search was performed using five databases: PubMed, Scopus, SciELO, LILACS, and Google Scholar. Studies were selected based on their relevance to the topic, and data were extracted regarding substance use, suicide-related outcomes, and associated sociodemographic and clinical factors. Results: The findings indicated a strong association between PAS use and increased suicidal ideation and behavior among homeless individuals, particularly among youth, men, and women. Opioids and alcohol were the most frequently reported substances in this context. Additional factors such as unemployment, exposure to violence, social inequalities, and mental health disorders further exacerbated the risk of suicide in this population Conclusions: The reviewed literature underscores the urgent need for integrated, context-sensitive interventions addressing both substance use and mental health among the homeless. Tailored public health strategies focused on prevention, harm reduction, and psychosocial support are essential to reducing suicide risk and promoting overall well-being in this highly vulnerable group. Full article

Naldemedine, a peripherally acting μ-opioid receptor antagonist, is used to treat opioid-induced constipation (OIC). However, it causes diarrhea as an adverse effect. This retrospective study aimed to investigate whether the occurrence of diarrhea was dependent on the timing of naldemedine treatment initiation. Inpatients who were initially treated with naldemedine at the Department of Respiratory Medicine, NHO Iwakuni Medical Center, Japan, between 1 December 2017 and 31 March 2021 were included in this study and divided into the simultaneous combination group, in which naldemedine was introduced at the same time as strong opioid analgesics, and the non-simultaneous combination group, in which naldemedine was introduced after the initiation of treatment with strong opioid analgesics. This study included 45 patients, 15 (33.3%) of whom developed diarrhea. Among the patients in the simultaneous combination group and non-simultaneous combination group, diarrhea occurred in 2 (11.1%) and 13 (48.1%) patients, respectively. Multivariate logistic regression analysis revealed that the delayed introduction of naldemedine was significantly associated with the development of diarrhea (odds ratio: 6.68, 95% confidence interval: 1.220–36.700, p = 0.028). Our analysis reveals that the simultaneous administration of naldemedine and oxycodone may prevent the development of diarrhea associated with naldemedine use for OIC. Full article

Xylazine, commonly called “tranq” or “sleep cut”, is a strong α2-adrenergic agonist used in veterinary practice as a sedative, analgesic, and muscle-relaxing agent. It has never been approved by the Food and Drug Administration for human use, but its use by people is on the rise. In the last decades, due to its low cost and ease of availability, it has often been illicitly used due to its abuse potential as a drug for attempted sexual assault and intended poisoning. In addition, xylazine’s presence in the human body has also been related to domestic accidental events. Generally, it is combined with multiple other drugs, typically by intravenous injection, potentiating the doping effects. Xylazine’s mechanism of action is different from that of other illicit opioids, such as heroin and fentanyl, and it has no known antidote approved for use in humans. The combination with fentanyl prolongs the euphoric sensation and may heighten the risk of fatal overdose. Furthermore, it may cause adverse effects, including central nervous system (CNS) and respiratory depression, bradycardia, hypotension, and even death. Recent reports of xylazine misuse have risen alarmingly and describe people who become “zombies” because of the drug’s harmful effects on the human body, including serious wound formation that could even lead to limb amputation. This paper is an extensive review of the existing literature about xylazine and specifically deals with the chemistry, pharmacokinetics, pharmacodynamic, and toxicological aspects of this compound, highlighting the most recent studies. Full article

Background: Iatrogenic withdrawal syndrome (IWS) poses a significant clinical challenge in pediatric intensive care units (PICUs) within Japan. Despite the existing availability of tools to assess pain and delirium, a validated instrument specifically designed for IWS has been notably absent in Japanese clinical practice. The Sophia Observation withdrawal Symptoms-Paediatric Delirium (SOS-PD) scale is globally recognized as an effective tool for IWS evaluation. To bridge this gap, this study aimed to validate the Japanese version of the SOS-PD scale. Methods: A prospective, cohort, observational study was undertaken in a single-center PICU in Japan. Participants ranged from neonates to children aged 20 years, excluding those with pre-existing neurological conditions or coma. Criterion validity was evaluated by comparing Japanese SOS-PD scale scores between a Weaning Group (WEAN) undergoing sedative/opioid tapering and a Maintenance Group (MAIN) receiving stable medication. Correlation analysis was also conducted against pediatric intensivists’ observational NRS (NRSobs). Inter-rater reliability of the Japanese SOS-PD scale was assessed utilizing kappa statistics and intraclass correlation coefficient (ICC). Results: In support of criterion validity, the WEAN group demonstrated significantly higher scores in both NRSobs and the IWS component of the Japanese SOS-PD scale compared to the MAIN group (p < 0.001). A strong correlation was observed between the Japanese SOS-PD IWS component and NRSobs (r = 0.91, p < 0.001). Inter-rater reliability was also robust, with a kappa coefficient of 0.95 and an ICC of 0.98. Conclusions: The Japanese version of the SOS-PD scale exhibits strong validity and inter-rater reliability for IWS assessment within Japanese PICUs. This validated instrument can support the early detection and appropriate management of pediatric IWS in Japan, with the potential to enhance the quality of patient care. Full article

Background: Enhanced Recovery After Surgery (ERAS) protocols have been implemented in various surgical specialties to improve patient outcomes and reduce opioid consumption. In cardiac surgery, the traditionally high-dose opioid use is associated with prolonged ventilation, intensive care unit (ICU) stays, and opioid-related adverse drug events (ORADEs). This study evaluates the impact of an ERAS^® Society-certified program on opioid consumption in patients undergoing elective cardiac surgery at Lausanne University Hospital. Methods: A retrospective, monocentric observational study was conducted comparing two patient cohorts: one treated with ERAS protocols (2023–2024) and a retrospective control group from 2019. Data were collected from the hospital’s electronic medical records and the ERAS program database. The primary outcome was total opioid consumption, measured intraoperatively and postoperatively (postoperative day (POD) 0–3). Secondary outcomes included pain control, length of stay, complications, and recovery parameters. Statistical analyses included multivariate logistic regression to identify factors associated with reduced opioid consumption. Results: Patients in the ERAS group demonstrated significantly lower total opioid consumption, whether intraoperatively (median sufentanil: 40 mcg vs. 51 mcg, p < 0.0001) or postoperatively (POD 0–3: p < 0.001). The ERAS group had faster extubation times, earlier mobilization and pain control with non-opioid analgesics, fewer complications, and shorter hospital stays (9 vs. 12 days, p < 0.001). Logistic regression identified fast-track extubation and absence of complications as strong predictors of reduced opioid use. Conclusions: The implementation of an ERAS protocol in cardiac surgery significantly reduces opioid consumption while enhancing recovery. Full article

Background: Patient-controlled intravenous analgesia (PCIA) after hip surgery should be focused on sufficient analgesia, recovery, and the risk of adverse effects. Sufentanil PCIA offers effective analgesia but with obvious side effects. Oxycodone, a semi-synthetic opioid, is reported to have good analgesic effects with fewer adverse effects compared to strong opioids. We hypothesize that in hip surgery, compared with sufentanil PCIA, oxycodone PCIA in an equipotent dose to sufentanil could achieve similar postoperative analgesia while reducing the incidence of adverse effects associated with strong opioids. Methods: This multi-centered, randomized, controlled open-label clinical trial compares the efficacy of oxycodone and sufentanil for PCIA in hip surgery patients. Results: A total of 570 subjects will be randomly allocated in a 1:1 ratio into either the oxycodone group or sufentanil group. The primary outcome is the resting numerical rating scale (NRS) pain scores at 2 h after surgery. The secondary outcomes include the incidence of postoperative nausea and vomiting (PONV), NRS pain scores on movement, complications, mobilization time, length of hospital stay, total in-hospital cost, etc. Conclusions: This trial will provide evidence for the choice of PCIA in hip surgery by comparing the analgesic efficacy and side effects of oxycodone and sufentanil, serving as a foundation for postoperative pain management guidelines and recommendations. Trial Registration: Clinical Trials NCT03685188. Full article

Background/Objectives: There exist multiple opioid-based treatments in palliative care, each with distinct side effect profiles. When adverse events occur, switching opioids can help maintain effective pain management. However, owing to limited clinical evidence, no comprehensive guidelines exist for opioid switching. This study employed the Side Effect Resource (SIDER) database, which aggregates adverse event data from clinical trials and package inserts, to analyze the side effects of five commonly used “strong opioids” in palliative care in Japan, namely morphine, fentanyl, oxycodone, hydromorphone, and tapentadol. Methods: Data on the names and incidence of adverse events for each opioid were extracted from SIDER 4.1, developed by the Max Delbrück Center for Molecular Medicine. Cluster analysis and principal component analysis were performed to interpret the data. Results: The key side effects of opioids were nausea, vomiting, constipation, and drowsiness. Fentanyl was more frequently associated with nausea and vomiting but less frequently with constipation and drowsiness. Tapentadol caused nausea relatively more frequently and constipation less frequently. Oxycodone was prominently linked to drowsiness, whereas morphine was frequently associated with constipation and drowsiness. Hydromorphone was associated with higher rates of constipation and vomiting but lower incidences of nausea and drowsiness. Conclusions: All side effects characterizing the opioids were related to μ-opioid receptor stimulation, although the present study findings highlight differences in the frequency of specific side effects among the opioids. These results provide objective insights that can guide opioid switching in response to adverse effects. Full article

Background: Chronic non-cancer pain (CNCP) is one of the leading causes of disability. The use of strong opioids (SOs) in the management of CNCP is increasing, although evidence supporting their use remains limited. Primary care (PC) plays a key role in this context. Objectives: Our objectives were to determine the prevalence and profile of patients using SOs for CNCP in PC consultations in Valladolid in 2022, and to describe the consumption of SO prescribed for CNCP from 2020 to 2023. Methods: We conducted a descriptive and retrospective study using data extracted from the Pharmaceutical Consumption Information System of Castilla y León. Patients in Valladolid with SO use for more than three months due to CNCP were analyzed. Sociodemographic and clinical characteristics of these patients in 2022 were described. The number of defined daily doses (nº DDDs) and costs from 2020 to 2023 were analyzed. Results: A total of 3642 patients were included (0.7% of the population of Valladolid), 71.8% of whom were women. Of the patients, 62.4% were aged 70 or older, 39.8% lived in rural areas, and 9.9% resided in nursing homes. The most frequently prescribed SOs in nº DDDs were fentanyl and tapentadol. The highest consumption in nº DDDs was in patients who lived in nursing homes, were over 70 years old and were resident in rural areas. The number of DDDs from 2020 to 2023 for SOs in DCNO increased by 41%. Conclusions: In total, 0.7% of the population of Valladolid consumes SOs for CNCP, mostly women and people over 70 years old. The consumption of strong opioids in DDDs grew by 41% from 2020 to 2023. Full article

Objectives: Chronic pain is a common symptom in Post-Acute COVID-19 Syndrome (PACS), affecting 11–60% of patients, but the link between COVID-19 and chronic pain remains unclear. This study assesses healthcare resource utilization (HRU) for pain management among French COVID-19 survivors, using the National French Claims Database (SNDS). We analyzed medical consultations, rehabilitation services, diagnostic procedures, and medication dispensing to identify PACS-related pain patterns and their impact on the healthcare system. Methods: The cohort included 68,822 patients hospitalized during the first COVID-19 wave (March–June 2020), with 13,939 ICU survivors. HRU was assessed for six months pre- and post-hospitalization in four areas: (1) medical consultations and rehabilitation; (2) pain-related medication dispensing; (3) neuropathic diagnostic procedures; (4) hospital admissions for chronic pain. A post–pre ratio (PP-Ratio) compared post-COVID to pre-COVID HRU. Results: Significant changes in HRU were observed, particularly for ICU survivors. Neurology consultations (PP-Ratio 1.41) and outpatient physical therapy (PP-Ratio 1.69) increased. Dispensing of strong opioids, antiepileptics, anxiolytics, and hypnotics rose, while NSAID use decreased. Hospitalizations for chronic pain also increased (PP-Ratio 1.52). Similar trends were seen among ICU survivors, with notable increases in opioid and antiepileptic use. No distinct PACS-related pain patterns emerged. Conclusions: Non-specific increases in HRU for pain management were found following COVID-19 hospitalization, likely due to disease severity and ICU care rather than PACS-related chronic pain. Further research is needed to explore long-term pain outcomes in this population. Full article

Background/Objectives: Opium consumption was recently classified by the International Agency for Research on Cancer (IARC) monograph as carcinogenic to humans based on strong evidence for cancers of the larynx, lung, and urinary bladder, and limited evidence for cancers of the oesophagus, stomach, pancreas, and pharynx. This poses the question of a potential pro-cancer effect of pharmaceutical opioid analgesics. In vitro studies employing a variety of experimental conditions suggest that opioid alkaloids have proliferative or antiproliferative effects. We set out to reconcile this discrepancy and explore the hypothesis that opioids promote cancer cell proliferation in an organ-dependent fashion. Methods: Using strictly controlled conditions, we tested the effect of morphine on the proliferation of a series of human cancer cell lines isolated from organs where cancer risk was linked causally to opium consumption in human studies (i.e., lung, bladder, and larynx), or control organs where no link between cancer risk and opium consumption has been reported in human studies (i.e., breast, colon, prostate). Results: Our results showed a minimal effect on proliferation on any cell line and no trend supporting an organ-specific effect of morphine. Conclusions: This argues against a direct effect of opioids on tumour cell proliferation to support their organ-specific effect. Full article

Purpose: To assess (I) whether, in autopsy-proven lethal intoxications with opiates/opioids, a dilatation of the common bile duct (CBD) is still visible in postmortem computed tomography (PMCT) and (II) if a dilatation of the CBD might also be measurable for other substance groups (e.g., stimulants, hypnotics, antipsychotics, etc.). Methods: We retrospectively measured the CBD using PMCT in cases with lethal intoxication (n = 125) and as a control group in cases with a negative toxicological analysis (n = 88). Intoxicating substances were classified into the subgroups (opiates, opioids, stimulants, hypnotics, antipsychotics, gasses, and others). Significance between the study and control groups was tested with the Mann–Whitney U test, and correlations were examined by using crosstables. Results: There was a statistically significant difference between the CBD diameters in the intoxication group overall, when compared to the CBD diameter in the control group (p < 0.001). For both subgroups of “opiates” and “opioids”, there was a strong statistically significant difference between the CBD diameter (being wider) in those groups compared to the control group (both p = 0.001). For the three subgroups “hypnotics”, “stimulants”, and “psychotropic drugs”, there was no statistically significant difference between the CBD diameters in the intoxication subgroups when compared with the control group. The other subgroups were too small for statistical analysis. Conclusion: A dilated common bile duct in postmortem computed tomography might be used as an indication for a lethal opioid or opiate intoxication only in regard to the specific case circumstances or together with other indicative findings in a postmortem investigation. Full article

The availability of metamizole varies greatly around the world. There are countries such as the USA, UK, or Australia where the use of metamizole is completely forbidden, and there are also countries where this drug is available only on prescription (e.g., Greece, Italy, Spain, etc.) and those in which it is sold OTC—over the counter (e.g., most Asian and South American countries). Metamizole, as a drug with a strong analgesic effect, is used as an alternative to other non-steroidal anti-inflammatory drugs, alone or in combination with opioid drugs. Risedronate sodium is a third-generation bisphosphonate commonly used in orthopaedic and metabolic diseases of the musculoskeletal system, including hypercalcemia, postmenopausal osteoporosis, Paget’s disease, etc. The aim of this study was to check whether there were any pharmacological interactions between metamizole and risedronate sodium in in vitro studies. Cell viability was assessed using the MTT method, the number of apoptotic cells was assessed using the labelling TUNEL method, and the cell cycle assessment was performed with a flow cytometer and propidium iodide. This was a pilot study, which is why only two cancer cell lines were tested: D-17 of canine osteosarcoma and U-2 OS of human osteosarcoma. Exposure of the canine osteosarcoma cell line to a combination of risedronate sodium (100 µg/mL) and metamizole (50, 5, and 0.5 µg/mL) resulted in the complete abolition of the cytoprotective activity of metamizole. In the human osteosarcoma cell line, the cytotoxic effect of risedronate sodium was entirely eliminated in the presence of 50 µg/mL of metamizole. The cytoprotective and anti-apoptotic effect of metamizole in combination with risedronate sodium in the tested human and canine osteosarcoma cell lines indicates an urgent need for further in vivo studies to confirm or disprove the potential dose-dependent undesirable effect of such a therapy. Full article

Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms “fentanyl” AND “overdose” AND “children”. The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures. Full article