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Anesthesiology Apr 2024More than 500,000 elective tonsillectomies are performed in US children annually. Pain after pediatric tonsillectomy is common, often severe, and undertreated. There is...
BACKGROUND
More than 500,000 elective tonsillectomies are performed in US children annually. Pain after pediatric tonsillectomy is common, often severe, and undertreated. There is no consensus on the optimal management of perioperative tonsillectomy pain. Methadone, with an elimination half-life of 1-2 days, has a longer duration of effect than short-duration opioids such as fentanyl. The primary objective of this study was to investigate the intraoperative use of methadone for pediatric tonsillectomy. It tested the hypothesis that methadone would result in less postoperative opioid use compared with short-duration opioids in children post-tonsillectomy.
METHODS
This double-bind, randomized, parallel group trial in children (3-17 years) undergoing tonsillectomy compared single-dose intravenous methadone (0.1 mg/kg then 0.15 mg/kg age-ideal body weight, in a dose escalation paradigm) versus as-needed short-duration opioid (fentanyl) controls. Opioid use, pain, and side effects were assessed in-hospital and 7 days postoperatively via electronic surveys. The primary outcome was total 7-day opioid use in oral morphine equivalents per kilogram (OME/kg). Secondary outcomes were opioid use in the Post-Anesthesia Care Unit (PACU), daily pain scores, and total number of 7-day opioid doses used.
RESULTS
Data analysis included 60 children (20/group), age 5.9±3.7 years (mean±SD; median 4, range 3-17). Total 7-day opioid use (OME/kg median [interquartile range]) was 1.5 [1.2,2.1] in controls, 0.9 [0.1,1.4] after methadone 0.1 mg/kg (P=0.045), and 0.5 [0,1.4] after methadone 0.15 mg/kg (P=0.023). PACU opioid use (OME/kg) in controls was 0.15 [0.1,0.3], 0.04 [0,0.1] after methadone 0.1 mg/kg (P=0.061) and 0.0 [0,0.1] after methadone 0.15mg/kg (P=0.021). Postoperative pain scores were not different between groups. No serious opioid-related adverse events occurred.
CONCLUSIONS
This small initial study in children undergoing tonsillectomy found that single-dose intraoperative methadone at 0.15 mg/kg age ideal body weight was opioid-sparing compared with intermittent fentanyl.
PubMed: 38669011
DOI: 10.1097/ALN.0000000000005031 -
Addiction & Health Feb 2024The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal... (Review)
Review
The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal addiction because of the separation. Maternal separation (MS) leads to the development of behavioural and neuropsychiatric issues in the future. Despite the importance of this issue, empirical investigations of the influences of maternal substance use and separation on substance use problems in offspring are limited, and studies that consider both effects are rare. This study aims to review a few studies on the mechanisms, treatments, genetics, epigenetics, molecular and psychological alterations, and neuroanatomical regions involved in the dependence of offspring who underwent maternal addiction and separation. The PubMed database was used. A total of 95 articles were found, including the most related ones in the review. The brain's lateral paragigantocellularis (LPGi), nucleus accumbens (NAc), caudate-putamen (CPu), prefrontal cortex (PFC), and hippocampus, can be affected by MS. Dopamine receptor subtype genes, alcohol biomarker minor allele, and preproenkephalin mRNA may be affected by alcohol or substance use disorders. After early-life adversity, histone acetylation in the hippocampus may be linked to brain-derived neurotrophic factor (BDNF) gene epigenetics and glucocorticoid receptors (GRs). The adverse early-life experiences differ in offspring›s genders and rewire the brain›s dopamine and endocannabinoid circuits, making offspring more susceptible to dependence. Related psychological factors rooted in early-life stress (ELS) and parental substance use disorder (SUD). Treatments include antidepressants, histone deacetylase inhibitors, lamotrigine, ketamine, choline, modafinil, methadone, dopamine, cannabinoid 1 receptor agonists/antagonists, vitamins, oxytocin, tetrahydrocannabinol, SR141716A, and dronabinol. Finally, the study emphasizes the need for multifaceted strategies to prevent these outcomes.
PubMed: 38651025
DOI: 10.34172/ahj.2024.1478 -
Anaesthesia and Intensive Care May 2024Optimal pain relief in day-case surgery is imperative to patient comfort and timely discharge from hospital. Short-acting opioids are commonly used for analgesia in... (Randomized Controlled Trial)
Randomized Controlled Trial
Optimal pain relief in day-case surgery is imperative to patient comfort and timely discharge from hospital. Short-acting opioids are commonly used for analgesia in modern anaesthesia, allowing rapid recovery after surgery. Plasma concentration fluctuations from repeated dosing of short-acting opioids can cause patients to oscillate between analgesia with potential adverse effects, and inadequate analgesia requiring rescue dosing. Methadone's unique pharmacology may offer effective and sustained analgesia with less opioid consumption, potentially reducing adverse effects. Using a double-blind, randomised controlled trial, we compared post-anaesthesia care unit opioid consumption between day-case gynaecological laparoscopy patients who received either intravenous methadone (10 mg), or short-acting opioids intraoperatively. The primary outcome was post-anaesthesia care unit opioid consumption in oral morphine equivalents. Secondary outcomes included total opioid consumption, discharge opioid consumption, pain scores (0-10) until discharge, adverse effects (respiratory depression, postoperative nausea and vomiting, excess sedation), and rate of admission. Seventy patients were randomly assigned. Patients who received methadone consumed on average 9.44 mg fewer oral morphine equivalents in the post-anaesthesia care unit than the short-acting group (18.02 mg 27.46 mg, respectively, 95% confidence interval 0.003 to 18.88, = 0.050) and experienced lower postoperative pain scores at every time point, although absolute differences were small. There was no evidence of lower hospital or discharge opioid consumption. No significant differences between the methadone and short-acting groups in other outcomes were identified: respiratory depression 41.2% versus 31.4%, >0.99; postoperative nausea and vomiting 29.4% versus 42.9%, >0.99; overnight admission 17.7% versus 11.4%, >0.99; excess sedation 8.82% versus 8.57%, >0.99. This study provides evidence that, although modestly, methadone can reduce post-anaesthesia care unit opioid consumption and postoperative pain scores after day-case gynaecological laparoscopy. There were no significant differences in any secondary outcomes.
Topics: Humans; Double-Blind Method; Female; Laparoscopy; Methadone; Analgesics, Opioid; Adult; Middle Aged; Pain, Postoperative; Gynecologic Surgical Procedures; Ambulatory Surgical Procedures; Intraoperative Care
PubMed: 38649297
DOI: 10.1177/0310057X231214551 -
Frontiers in Pediatrics 2024
PubMed: 38646511
DOI: 10.3389/fped.2024.1396595 -
Frontiers in Biophysics 2024P-glycoprotein (Pgp) is known for its dichotomous roles as both a safeguarding efflux transporter against xenobiotics and as a catalyst for multidrug resistance. Given...
P-glycoprotein (Pgp) is known for its dichotomous roles as both a safeguarding efflux transporter against xenobiotics and as a catalyst for multidrug resistance. Given the susceptibility of numerous therapeutic compounds to Pgp-mediated resistance, compliance with Food and Drug Administration (FDA) guidelines mandates an in-depth transport assay during drug development. This study introduces an innovative transport assay that aligns with these regulatory imperatives but also addresses limitations in the currently established techniques. Using Pgp-reconstituted liposomes and employing surface plasmon resonance (SPR), this study developed a distinct method of measuring the relative transport rates of Pgp substrates in a controlled microenvironment. The Pgp substrates selected for this study-quinidine, methadone, and desipramine-resulted in transport ratios that corroborate with trends previously observed. To assess the kinetics of Pgp-mediated transport, the results were analyzed by fitting the data to both currently proposed Pgp substrate translocation models-the vacuum cleaner and flippase models. While the resulting kinetic analysis in this study lends support predominantly to the vacuum cleaner model, this study most notably developed a novel method of assessing Pgp-mediated transport rates and real-time kinetics using surface plasmon resonance.
PubMed: 38645731
DOI: 10.3389/frbis.2024.1367511 -
Drug and Alcohol Dependence Jun 2024We introduce the concept of harm reduction capital (HRCap) as the combination of knowledge, resources, and skills related to substance use risk reduction, which we...
LatinX harm reduction capital, medication for opioid use disorder, and nonfatal overdose: A structural equation model analysis among people who use drugs in Massachusetts.
BACKGROUND
We introduce the concept of harm reduction capital (HRCap) as the combination of knowledge, resources, and skills related to substance use risk reduction, which we hypothesize to predict MOUD use and opioid overdose. In this study, we explored the interrelationships between ethnicity, HRCap, nonfatal overdose, and MOUD use among PWUD.
METHODS
Between 2017 and 2019, people who currently or in the past used opioids and who lived in Massachusetts completed a one-time survey on substance use history, treatment experiences, and use of harm reduction services. We fit first-order measurement constructs for positive and negative HRCap (facilitators and barriers). We used generalized structural equation models to examine the inter-relationships of the latent constructs with LatinX self-identification, past year overdose, and current use of MOUD.
RESULTS
HRCap barriers were positively associated with past-year overdose (b=2.6, p<0.05), and LatinX self-identification was inversely associated with HRCap facilitators (b=-0.49, p<0.05). There was no association between overdose in the past year and the current use of MOUD. LatinX self-identification was positively associated with last year methadone treatment (b=0.89, p<0.05) but negatively associated with last year buprenorphine treatment (b=-0.68, p<0.07). Latinx PWUD reported lower positive HRCap than white non-LatinX PWUD and had differential utilization of MOUD.
CONCLUSION
Our findings indicate that a recent overdose was not associated with the current use of MOUD, highlighting a severe gap in treatment utilization among individuals at the highest risk. The concept of HRCap and its use in the model highlight substance use treatment differences, opportunities for intervention, and empowerment.
Topics: Humans; Massachusetts; Male; Female; Hispanic or Latino; Harm Reduction; Adult; Opioid-Related Disorders; Drug Overdose; Middle Aged; Latent Class Analysis; Buprenorphine; Young Adult; Opiate Overdose; Drug Users; Opiate Substitution Treatment
PubMed: 38643530
DOI: 10.1016/j.drugalcdep.2024.111293 -
The International Journal on Drug Policy May 2024Long-acting injectable depot buprenorphine has become an important treatment option for the management of opioid dependence. However, little is known about patients'...
BACKGROUND
Long-acting injectable depot buprenorphine has become an important treatment option for the management of opioid dependence. However, little is known about patients' experiences of depot buprenorphine and its embodied effects. This qualitative study aims to explore patients' experiences of depot buprenorphine treatment, including how it feels within the body, experiences of dosing cycles across time, and how this form of treatment relies on wider ecologies of care beyond the clinical encounter.
METHODS
Participants were recruited from sites in Sydney, regional New South Wales, and Melbourne, Victoria, Australia. Thirty participants (16 men, 14 women) participated in semi-structured interviews. Participants had histories of both heroin and prescription opioid consumption, and opioid agonist therapy including daily dosing of buprenorphine and methadone.
RESULTS
Our analysis illuminates: (1) how patients' expectations and concerns about treatment are linked to past embodied experiences of withdrawal and uncertainty about the effectiveness of depot buprenorphine; (2) the diverse meanings patients attribute to the depot buprenorphine substrate 'under the skin'; and, (3) how depot buprenorphine is embedded within wider ecologies of care, such as counselling and social supports.
CONCLUSION
Our analysis destabilises commonplace assumptions about a linear, causal relationship between the pharmacological action of depot buprenorphine and experiences of treatment. Instead, it highlights patients' variable experiences of depot buprenorphine, tracing the everyday practices, embodied feelings, expectations and wider networks of care that shape patient experiences. We conclude with some reflections on the implications of our analysis for alcohol and other drug treatment, specifically how they might inform the design of client education materials and care.
Topics: Humans; Buprenorphine; Male; Female; Opioid-Related Disorders; Adult; Opiate Substitution Treatment; Delayed-Action Preparations; Middle Aged; Australia; Qualitative Research; Narcotic Antagonists; Interviews as Topic; Methadone
PubMed: 38636315
DOI: 10.1016/j.drugpo.2024.104399 -
International Journal of Molecular... Mar 2024Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children....
Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis. Bile specimens were obtained from 25 forensic cases of suspected death from overdose and intoxication. Sample preparation for bile screening consists simply in centrifugation and dilution. Confirmation analysis allows simultaneous identification of 108 drugs and was validated on bile. Kappa analysis assessed a perfect agreement (0.81-1) between the assays for benzodiazepines, methadone, opiates, cocaine, oxycodone, cannabinoids, buprenorphine and pregabalin; a substantial agreement (0.41-0.6) was reported for barbiturates. No agreement was assessed for amphetamines, due to an abundance of putrefactive amines in postmortem specimens. In conclusion, this fast and easy immunoassay could be used for initial screening of bile specimens, identifying presence of drugs, except amphetamines, with reliability.
Topics: Adult; Child; Humans; Bile; Chromatography, Liquid; Luminescence; Reproducibility of Results; Tandem Mass Spectrometry; Drug Overdose; Amphetamines
PubMed: 38612632
DOI: 10.3390/ijms25073825 -
Scientific Reports Apr 2024The simultaneous identification of drugs has considerable difficulties due to the intricate interplay of analytes and the interference present in biological matrices. In...
The simultaneous identification of drugs has considerable difficulties due to the intricate interplay of analytes and the interference present in biological matrices. In this study, we introduce an innovative electrochemical sensor that overcomes these hurdles, enabling the precise and simultaneous determination of morphine (MOR), methadone (MET), and uric acid (UA) in urine samples. The sensor harnesses the strategically adapted carbon nanotubes (CNT) modified with graphitic carbon nitride (g-CN) nanosheets to ensure exceptional precision and sensitivity for the targeted analytes. Through systematic optimization of pivotal parameters, we attained accurate and quantitative measurements of the analytes within intricate matrices employing the fast Fourier transform (FFT) voltammetry technique. The sensor's performance was validated using 17 training and 12 test solutions, employing the widely acclaimed machine learning method, partial least squares (PLS), for predictive modeling. The root mean square error of cross-validation (RMSECV) values for morphine, methadone, and uric acid were significantly low, measuring 0.1827 µM, 0.1951 µM, and 0.1584 µM, respectively, with corresponding root mean square error of prediction (RMSEP) values of 0.1925 µM, 0.2035 µM, and 0.1659 µM. These results showcased the robust resiliency and reliability of our predictive model. Our sensor's efficacy in real urine samples was demonstrated by the narrow range of relative standard deviation (RSD) values, ranging from 3.71 to 5.26%, and recovery percentages from 96 to 106%. This performance underscores the potential of the sensor for practical and clinical applications, offering precise measurements even in complex and variable biological matrices. The successful integration of g-CN-CNT nanocomposites and the robust PLS method has driven the evolution of sophisticated electrochemical sensors, initiating a transformative era in drug analysis.
Topics: Morphine; Uric Acid; Nanotubes, Carbon; Reproducibility of Results; Nanocomposites; Electrochemical Techniques
PubMed: 38582770
DOI: 10.1038/s41598-024-58843-9 -
Addiction Science & Clinical Practice Apr 2024Long-acting injectable buprenorphine (LAIB) formulations are a novel treatment approach in opioid agonist treatment (OAT), which provide patients with a steady dose...
BACKGROUND
Long-acting injectable buprenorphine (LAIB) formulations are a novel treatment approach in opioid agonist treatment (OAT), which provide patients with a steady dose administered weekly or monthly and thus reduce the need for frequent clinic visits. Several studies have analyzed patient experiences of LAIB but the perspective of OAT staff is unknown. This study aimed to explore how healthcare staff working in OAT clinics in Sweden perceive and manage treatment with LAIB.
METHODS
Individual qualitative interviews were conducted with OAT physicians (n = 10) in tandem with nine focus group sessions with OAT nurses and other staff categories (n = 41). The data was analyzed with thematic text analysis.
RESULTS
Five central themes were identified in the data: (1) advantages and disadvantages of LAIB, (2) patient categories that may or may not need LAIB, (3) patients' degrees of medication choice, (4) keeping tabs, control and treatment alliance, and (5) LAIB's impact on risk and enabling environments in OAT. Overall staff found more advantages than disadvantages with LAIB and considered that patients with ongoing substance use and low adherence were most likely to benefit from LAIB. However, less frequent visits were viewed as problematic in terms of developing a treatment alliance and being able to keep tabs on patients' clinical status. Clinics differed regarding patients' degrees of choice in medication, which varied from limited to extensive. LAIB affected both risk and enabling environments in OAT.
CONCLUSIONS
LAIB may strengthen the enabling environment in OAT for some patients by reducing clinic visits, exposure to risk environments, and the pressure to divert medication. A continued discussion about the prerequisites and rationale for LAIB implementation is needed in policy and practice.
Topics: Humans; Buprenorphine; Opiate Substitution Treatment; Opioid-Related Disorders; Delivery of Health Care; Qualitative Research; Analgesics, Opioid; Methadone
PubMed: 38581022
DOI: 10.1186/s13722-024-00458-6