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Huan Jing Ke Xue= Huanjing Kexue May 2024It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are...
It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.
Topics: Morphine; Wastewater; Papaverine; Thebaine; Noscapine; Reproducibility of Results; Codeine; Morphine Derivatives; Alkaloids; Papaver
PubMed: 38629538
DOI: 10.13227/j.hjkx.202306005 -
British Journal of Anaesthesia Dec 2023Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of non-neuraxial analgesic techniques for midline laparotomy: a systematic review and frequentist network meta-analysis of randomised controlled trials.
BACKGROUND
Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic review and network meta-analysis of randomised controlled trials to synthesise the evidence with respect to pain, opioid consumption, and adverse events.
METHODS
We searched Ovid MEDLINE, Embase, Cochrane Central, and Scopus databases for studies comparing commonly used non-neuraxial analgesic techniques for midline laparotomy in adult patients. The co-primary outcomes of the study were 24-h cumulative opioid consumption and 24-h resting pain score, reported as i.v. morphine equivalents and 11-point numerical rating scale, respectively. We performed a frequentist meta-analysis using a random-effects model and a cluster-rank analysis of the co-primary outcomes.
RESULTS
Of 6115 studies screened, 67 eligible studies were included (n=4410). Interventions with the greatest reduction in 24-h cumulative opioid consumption compared with placebo/no intervention were single-injection quadratus lumborum block (sQLB; mean difference [MD] -16.1 mg, 95% confidence interval [CI] -29.9 to -2.3, very low certainty), continuous transversus abdominis plane block (cTAP; MD -14.0 mg, 95% CI -21.6 to -6.4, low certainty), single-injection transversus abdominis plane block (sTAP; MD -13.7 mg, 95% CI -17.4 to -10.0, low certainty), and continuous rectus sheath block (cRSB; MD -13.2 mg, 95% CI -20.3 to -6.1, low certainty). Interventions with the greatest reduction in 24-h resting pain score were cRSB (MD -1.2, 95% CI -1.8 to -0.6, low certainty), cTAP (MD -1.0, 95% CI -1.7 to -0.2, low certainty), and continuous wound infusion (cWI; MD -0.7, 95% CI -1.1 to -0.4, low certainty). Clustered-rank analysis including the co-primary outcomes showed cRSB and cTAP blocks to be the most efficacious interventions.
CONCLUSIONS
Based on current evidence, continuous rectus sheath block and continuous transversus abdominis plane block were the most efficacious non-neuraxial techniques at reducing 24-h cumulative opioid consumption and 24-h resting pain scores after midline laparotomy (low certainty). Future studies should compare techniques for upper vs lower midline laparotomy and other non-midline abdominal incisions.
CLINICAL TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021269044.
Topics: Adult; Humans; Analgesics, Opioid; Laparotomy; Network Meta-Analysis; Morphine; Pain; Pain, Postoperative
PubMed: 37770254
DOI: 10.1016/j.bja.2023.08.024 -
JAMA Network Open Jan 2024Questions have emerged as to whether standard intranasal naloxone dosing recommendations (ie, 1 dose with readministration every 2-3 minutes if needed) are adequate in... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Questions have emerged as to whether standard intranasal naloxone dosing recommendations (ie, 1 dose with readministration every 2-3 minutes if needed) are adequate in the era of illicitly manufactured fentanyl and its derivatives (hereinafter, fentanyl).
OBJECTIVE
To compare naloxone plasma concentrations between different intranasal naloxone repeat dosing strategies and to estimate their effect on fentanyl overdose.
DESIGN, SETTING, AND PARTICIPANTS
This unblinded crossover randomized clinical trial was conducted with healthy participants in a clinical pharmacology unit (Spaulding Clinical Research, West Bend, Wisconsin) in March 2021. Inclusion criteria included age 18 to 55 years, nonsmoking status, and negative test results for the presence of alcohol or drugs of abuse. Data analysis was performed from October 2021 to May 2023.
INTERVENTION
Naloxone administered as 1 dose (4 mg/0.1 mL) at 0, 2.5, 5, and 7.5 minutes (test), 2 doses at 0 and 2.5 minutes (test), and 1 dose at 0 and 2.5 minutes (reference).
MAIN OUTCOMES AND MEASURES
The primary outcome was the first prespecified time with higher naloxone plasma concentration. The secondary outcome was estimated brain hypoxia time following simulated fentanyl overdoses using a physiologic pharmacokinetic-pharmacodynamic model. Naloxone concentrations were compared using paired tests at 3 prespecified times across the 3 groups, and simulation results were summarized using descriptive statistics.
RESULTS
This study included 21 participants, and 18 (86%) completed the trial. The median participant age was 34 years (IQR, 27-50 years), and slightly more than half of participants were men (11 [52%]). Compared with 1 naloxone dose at 0 and 2.5 minutes, 1 dose at 0, 2.5, 5, and 7.5 minutes significantly increased naloxone plasma concentration at 10 minutes (7.95 vs 4.42 ng/mL; geometric mean ratio, 1.95 [1-sided 97.8% CI, 1.28-∞]), whereas 2 doses at 0 and 2.5 minutes significantly increased the plasma concentration at 4.5 minutes (2.24 vs 1.23 ng/mL; geometric mean ratio, 1.98 [1-sided 97.8% CI, 1.03-∞]). No drug-related serious adverse events were reported. The median brain hypoxia time after a simulated fentanyl 2.97-mg intravenous bolus was 4.5 minutes (IQR, 2.1-∞ minutes) with 1 naloxone dose at 0 and 2.5 minutes, 4.5 minutes (IQR, 2.1-∞ minutes) with 1 naloxone dose at 0, 2.5, 5, and 7.5 minutes, and 3.7 minutes (IQR, 1.5-∞ minutes) with 2 naloxone doses at 0 and 2.5 minutes.
CONCLUSIONS AND RELEVANCE
In this clinical trial with healthy participants, compared with 1 intranasal naloxone dose administered at 0 and 2.5 minutes, 1 dose at 0, 2.5, 5, and 7.5 minutes significantly increased naloxone plasma concentration at 10 minutes, whereas 2 doses at 0 and 2.5 minutes significantly increased naloxone plasma concentration at 4.5 minutes. Additional research is needed to determine optimal naloxone dosing in the community setting.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04764630.
Topics: Male; Humans; Adolescent; Young Adult; Adult; Middle Aged; Female; Ethanol; Commerce; Fentanyl; Naloxone; Opiate Overdose; Hypoxia, Brain
PubMed: 38261323
DOI: 10.1001/jamanetworkopen.2023.51839 -
Gut Microbes 2024Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain...
Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were divided into control, CP, CP with morphine/oxycodone, and either morphine or oxycodone alone groups. CP was induced by administration of caerulein (50ug/kg/h, i.p. hourly x7, twice a week for 10 weeks). The mouse-to-pancreas weight ratio, histology, and Sirius red staining were performed to measure CP severity. Tail flick and paw pressure assays were used to measure thermal and mechanical pain. DNA was extracted from the fecal samples and subjected to whole-genome shotgun sequencing. Germ-free mice were used to validate the role of gut microbiome in sensitizing acute pancreatic inflammation. Opioid treatment exacerbates CP by increasing pancreatic necrosis, fibrosis, and immune-cell infiltration. Opioid-treated CP mice exhibited enhanced pain hypersensitivity and showed distinct clustering of the gut microbiome compared to untreated CP mice, with severely compromised gut barrier integrity. Fecal microbiota transplantation (FMT) from opioid-treated CP mice into germ-free mice resulted in pancreatic inflammation in response to a suboptimal caerulein dose. Together, these analyses revealed that opioids worsen the severity of CP and induce significant alterations in pain sensitivity and the gut microbiome in a caerulein CP mouse model. Microbial dysbiosis plays an important role in sensitizing the host to pancreatic inflammation.
Topics: Animals; Mice; Analgesics, Opioid; Oxycodone; Dysbiosis; Ceruletide; Gastrointestinal Microbiome; Mice, Inbred C57BL; Pancreatitis, Chronic; Morphine; Pain; Inflammation
PubMed: 38329115
DOI: 10.1080/19490976.2024.2310291 -
JAMA Network Open Aug 2023Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training...
IMPORTANCE
Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors.
OBJECTIVE
To assess whether THN training is associated with changes in overdose risk behaviors, indexed through injecting frequency, in a cohort of people who inject drugs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used prospectively collected self-reported behavioral data before and after THN training of participants in The Melbourne Injecting Drug User Cohort Study (SuperMIX). Annual interviews were conducted in and around Melbourne, Victoria, Australia, from 2008 to 2021. SuperMIX participants were adults who regularly injected heroin or methamphetamine in the 6 months preceding their baseline interview. The current study included only people who inject drugs who reported THN training and had participated in at least 1 interview before THN training.
EXPOSURE
In 2017, the SuperMIX baseline or follow-up survey began asking participants if and when they had received THN training. The first THN training date that was recorded was included as the exposure variable. Subsequent participant interviews were excluded from analysis.
MAIN OUTCOMES AND MEASURES
Injecting frequency was the primary outcome and was used as an indicator of overdose risk. Secondary outcomes were opioid injecting frequency, benzodiazepine use frequency, and the proportion of the time drugs were used alone. Fixed-effects generalized linear (Poisson) multilevel modeling was used to estimate the association between THN training and the primary and secondary outcomes. Time-varying covariates included housing status, income, time in study, recent opioid overdose, recent drug treatment, and needle and syringe coverage. Findings were expressed as incidence rate ratios (IRRs) with 95% CIs.
RESULTS
There were 1328 participants (mean [SD] age, 32.4 [9.0] years; 893 men [67.2%]) who completed a baseline interview in the SuperMIX cohort, and 965 participants completed either a baseline or follow-up interview in or after 2017. Of these 965 participants, 390 (40.4%) reported THN training. A total of 189 people who inject drugs had pretraining participant interviews with data on injecting frequency and were included in the final analysis (mean [SD] number of interviews over the study period, 6.2 [2.2]). In fixed-effects regression analyses adjusted for covariates, there was no change in the frequency of injecting (IRR, 0.91; 95% CI, 0.69-1.20; P = .51), opioid injecting (IRR, 0.95; 95% CI, 0.74-1.23; P = .71), benzodiazepine use (IRR, 0.96; 95% CI, 0.69-1.33; P = .80), or the proportion of reported time of using drugs alone (IRR, 1.04; 95% CI, 0.86-1.26; P = .67) before and after THN training.
CONCLUSIONS AND RELEVANCE
This cohort study of people who inject drugs found no evidence of an increase in injecting frequency, along with other markers of overdose risk, after THN training and supply. The findings suggest that THN training should not be withheld because of concerns about risk compensation and that advocacy for availability and uptake of THN is required to address unprecedented opioid-associated mortality.
Topics: Male; Adult; Humans; Naloxone; Narcotic Antagonists; Analgesics, Opioid; Cohort Studies; Drug Overdose; Victoria
PubMed: 37540514
DOI: 10.1001/jamanetworkopen.2023.27319 -
Journal of Pain and Symptom Management Apr 2024Constipation is a common problem among patients with cancer. By some accounts, about 60% of cancer patients experience constipation. There is limited empirical evidence... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Constipation is a common problem among patients with cancer. By some accounts, about 60% of cancer patients experience constipation. There is limited empirical evidence of the clinical effectiveness of pharmacologic agents in opioid-induced constipation in advanced diseases.
OBJECTIVES
We sought to quantitatively summarize the therapeutic effectiveness of the pharmacologic means of managing opioid-induced constipation.
METHODS
Randomized control trials (RCTs) identified from medical literature databases that reported quantitative measures of the effect of pharmacotherapeutic agents to treat opioid induced constipation in patients with cancers and other advanced illnesses were included in this study. A conventional random effects meta-analysis was conducted including >3 trials with the same exposure and outcome assessed, and a network-meta-analysis was conducted for all placebo-controlled trials.
RESULTS
Eighteen studies that examined the effect of various pharmacotherapeutic agents were included. The medications were Methylnatrexone (N = 5), Naldemedine (N = 5), other conventional agents (N = 4) and herbal medicines (N = 4). In conventional meta-analysis, methylnaltrexone increased the proportion achieving rescue-free laxation by 2.68 fold (95% CI: 1.34, 5.37; P = 0.0054) within 4 hours of the administration compared to placebo. In network meta-analysis, the pooled RR of the pharmacotherapeutic agents on rescue-free bowel movements as 2.26 (95% CI: 1.52, 3.36) for methylnaltrexone, 1.58 (95% CI: 0.94, 2.66) for naldemedine, and 0.74 (95% CI: 0.45, 1.23) for polyethylene glycol, compared to placebo.
CONCLUSION
Methylnatrexone and Naldemedine have currently shown promise in randomized trials concerning opioid-induced constipation in cancer and advanced illness. It is imperative that future research ascertain not just the relative therapeutic efficacy but also the cost-benefit analyses of these newer regimens with more commonly used and accessible laxatives.
Topics: Humans; Opioid-Induced Constipation; Narcotic Antagonists; Analgesics, Opioid; Naltrexone; Constipation; Laxatives; Neoplasms; Randomized Controlled Trials as Topic; Quaternary Ammonium Compounds
PubMed: 38092261
DOI: 10.1016/j.jpainsymman.2023.12.010 -
Expert Opinion on Drug Safety 2023The association between dental problems and sublingual/buccal buprenorphine is unclear. We conducted an analysis of dental adverse drug reactions reported with...
BACKGROUND
The association between dental problems and sublingual/buccal buprenorphine is unclear. We conducted an analysis of dental adverse drug reactions reported with sublingual/buccal buprenorphine in VigiBase®, the pharmacovigilance database of the World Health Organization.
RESEARCH DESIGN AND METHODS
We performed disproportionality analyses to compare the reporting rates of dental problems with sublingual/buccal buprenorphine, compared to other buprenorphine formulations and methadone. Significant signals were considered if the lower boundary of the 95% confidence interval of the Reporting Odds Ratio (ROR) was > 1; cases were ≥ 3 and p-value <0.05. We conducted sensitivity analyses by calculating the ROR according to the reporter's qualification and the reporting continent (United States of America and Europe).
RESULTS
We included 30,769 reports with all buprenorphine forms. We found 20 cases of dental problems with sublingual/buccal buprenorphine. Sublingual/buccal buprenorphine was associated with an overreporting of dental problems compared to other buprenorphine formulations (ROR = 15.10; 95% CI [7.50-30.39]; < 0.005) and compared to methadone (ROR = 6.02; 95% CI [3.21-11.30]; < 0.005). Overreporting of dental problems was consistent in sensitivity analyses, except in Europe compared with other buprenorphine formulations and with methadone.
CONCLUSIONS
Sublingual/buccal buprenorphine might increase the risk of reporting dental problems. However, these results do not modify the benefits of sublingual/buccal buprenorphine in the treatment of opioid use disorders.
Topics: Humans; United States; Buprenorphine; Pharmacovigilance; Methadone; Opioid-Related Disorders; Administration, Sublingual
PubMed: 37584264
DOI: 10.1080/14740338.2023.2247962 -
Surgery Nov 2023Excessive opioid prescribing has resulted in opioid diversion and misuse. In July 2018, Michigan's Public Act 251 established a state-wide policy limiting opioid...
BACKGROUND
Excessive opioid prescribing has resulted in opioid diversion and misuse. In July 2018, Michigan's Public Act 251 established a state-wide policy limiting opioid prescriptions for acute pain to a 7-day supply. Traumatic injury increases the risk for new persistent opioid use, yet the impact of prescribing policy in trauma patients remains unknown. To determine the relationship between policy enactment and prescribing in trauma patients, we compared oral morphine equivalents prescribed at discharge before and after implementation of Public Act 251.
METHODS
In this cross-sectional study, adult patients who received any oral opioids at discharge from a Level 1 trauma center between January 1, 2016, and June 30, 2021, were identified. The exposure was patients admitted starting July 1, 2018. Inpatient oral morphine equivalents per day 48 hours before discharge and discharge prescription oral morphine equivalents per day were calculated. Student's t test and an interrupted time series analysis were performed to compare mean oral morphine equivalents per day pre- and post-policy. Multivariable risk adjustment accounted for patient/injury factors and inpatient oral morphine equivalent use.
RESULTS
A total of 3,748 patients were included in the study (pre-policy n = 1,685; post-policy n = 2,063). Implementation of the prescribing policy was associated with a significant decrease in mean discharge oral morphine equivalents per day (34.8 ± 49.5 vs 16.7 ± 32.3, P < .001). After risk adjustment, post-policy discharge prescriptions differed by -19.2 oral morphine equivalents per day (95% CI -21.7 to -16.8, P < .001). The proportion of patients obtaining a refill prescription 30 days post-discharge did not increase after implementation (0.38 ± 0.48 vs 0.37 ± 0.48, P = .7).
CONCLUSION
Discharge prescription amounts for opioids in trauma patients decreased by approximately one-half after the implementation of opioid prescribing policies, and there was no compensatory increase in subsequent refill prescriptions. Future work is needed to evaluate the effect of these policies on the adequacy of pain management and functional recovery after injury.
Topics: Adult; Humans; Analgesics, Opioid; Cross-Sectional Studies; Aftercare; Pain, Postoperative; Patient Discharge; Practice Patterns, Physicians'; Morphine
PubMed: 37709648
DOI: 10.1016/j.surg.2023.08.006 -
The Journal of Physiology Oct 2023This study provides an in-depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid-induced respiratory depression (OIRD). We...
This study provides an in-depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid-induced respiratory depression (OIRD). We explored the physiological implications of both drugs on ventilation and airway patency in anaesthetized mice. Our results revealed a similar reduction in respiratory frequency with equivalent scaled dosages of fentanyl and morphine, though the onset of suppression was more rapid with fentanyl. Additionally, fentanyl resulted in transient airflow obstructions during the inspiratory cycle, which were absent following morphine administration. Notably, these fentanyl-specific obstructions were eliminated with tracheostomy, implicating the upper airways as a major factor contributing to fentanyl-induced respiratory depression. We further demonstrate that bronchodilators salbutamol and adrenaline effectively reversed these obstructions, highlighting the bronchi's contribution to fentanyl-induced airflow obstruction. Our study also uncovered a significant reduction in sighs during OIRD, which were eliminated by fentanyl and markedly reduced by morphine. Finally, we found that fentanyl-exposed mice had reduced survival under hypoxic conditions compared to mice given morphine, demonstrating that fentanyl becomes more lethal in the context of hypoxaemia. Our findings shed light on the distinct and profound impacts of these opioids on respiration and airway stability and lay the foundation for improved opioid use guidelines and more effective OIRD prevention strategies. KEY POINTS: Both morphine and fentanyl significantly suppressed respiratory frequency, but the onset of suppression was faster with fentanyl. Also, while both drugs increased tidal volume, this effect was more pronounced with fentanyl. Fentanyl administration resulted in transient obstructions during the inspiratory phase, suggesting its unique impact on airway stability. This obstruction was not observed with morphine. The fentanyl-induced obstructions were reversed by administering bronchodilators such as salbutamol and adrenaline. This suggests a possible therapeutic strategy for mitigating the adverse airway effects of fentanyl. Both drugs reduced the frequency of physiological sighs, a key mechanism to prevent alveolar collapse. However, fentanyl administration led to a complete cessation of sighs, while morphine only reduced their occurrence. Fentanyl-treated mice showed a significantly reduced ability to survive under hypoxic conditions compared to those administered morphine. This indicates that the impacts of hypoxaemia during opioid-induced respiratory depression can vary based on the opioid used.
Topics: Mice; Animals; Morphine; Fentanyl; Analgesics, Opioid; Bronchodilator Agents; Respiration; Respiratory Insufficiency; Hypoxia; Albuterol; Epinephrine
PubMed: 37778015
DOI: 10.1113/JP285163 -
Journal of Addictions NursingSubstance use disorders are economically and socially devastating to families and societies. Expectations of the patients and their families during the posttreatment...
BACKGROUND
Substance use disorders are economically and socially devastating to families and societies. Expectations of the patients and their families during the posttreatment phase of substance use disorder need to be emphasized to maintain a patient's sobriety and prevent relapse.
AIM
The aim of this study was to examine the prediction power of personal and sociodemographic factors of patients and their families to treatment outcomes.
METHODS
A descriptive, correlational, cross-sectional design was used. Data were collected from 80 patients treated for substance use disorders from a major psychiatric hospital and their family members regarding social, health, and psychological expectations. A three-step multiple hierarchical regression analysis was used to predict the power of personal and sociodemographic characteristics of patients' and their families' expectations to treatment outcomes.
RESULTS
Heroin use, codeine use, family education, and family support were significant predictors of rehabilitation expectation ( p < .05). Level of education and heroin use were predictors for lower levels of rehabilitation expectation, whereas family support and codeine use were indicators for higher scores of rehabilitation expectation.
CONCLUSION
Emphasis should be given to expectations of the patient and their family through appropriate psychoeducation and enhanced understanding and partnership.
Topics: Humans; Motivation; Cross-Sectional Studies; Heroin; Substance-Related Disorders; Codeine
PubMed: 37669350
DOI: 10.1097/JAN.0000000000000472