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Sleep Sep 2023Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found...
Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.
Topics: Humans; Mice; Animals; Dogs; Orexins; Sodium Oxybate; Cataplexy; Locus Coeruleus; Narcolepsy; Neurons; Opiate Alkaloids
PubMed: 37155728
DOI: 10.1093/sleep/zsad135 -
The Western Journal of Emergency... Jun 2022Medications for opioid use disorder (MOUD), including buprenorphine, represent an evidence-based treatment that supports long-term recovery and reduces risk of overdose... (Review)
Review
INTRODUCTION
Medications for opioid use disorder (MOUD), including buprenorphine, represent an evidence-based treatment that supports long-term recovery and reduces risk of overdose death. Patients in crisis from opioid use disorder (OUD) often seek care from emergency departments (ED). The New York Medication for Addiction Treatment and Electronic Referrals (MATTERS) network is designed to support ED-initiated buprenorphine and urgent referrals to long-term care for patients suffering from OUD.
METHODS
Using the PRECEDE-PROCEED implementation science framework, we provide an overview of the creation of the MATTERS network in Western New York. We also include an explanation of how the network was designed and launched as a response to the opioid epidemic. Finally, we analyzed the program's outputs and outcomes, thus far, as it continues to grow across the state.
RESULTS
The New York MATTERS network was created and implemented in 2019 with a single hospital referring patients with OUD to three local clinics. In the social assessment and situational analysis phase, we describe the opioid epidemic and available resources in the region at the outset of the program. In the epidemiological assessment phase, we quantify the epidemic on the state and regional levels. In the educational and ecological assessment, we review local ED practices and resources. In the administrative and policy assessment and intervention alignment phase, the program's unique framework is reviewed. In the piloting phase, we describe the initial deployment of New York MATTERS. Finally, in the process evaluation phase, we depict the early lessons we learned. By the beginning of 2021, the New York MATTERS network included 35 hospitals that refer to 47 clinics throughout New York State.
CONCLUSION
The New York MATTERS network provides a structured approach to reduce barriers to ED-initiated buprenorphine and urgent referral to long-term care. An implementation framework provides a structured means of evaluating this best practice model.
Topics: Analgesics, Opioid; Buprenorphine; Emergency Service, Hospital; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 35980408
DOI: 10.5811/westjem.2022.3.54680 -
JAMA Network Open Oct 2023Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies...
IMPORTANCE
Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies examining associations between OM and clinical outcomes were performed in the era of 3-dimensional conformal RT planning with low rates of concurrent chemotherapy, and thus may not reflect current practice.
OBJECTIVE
To prospectively assess patient-reported OM and identify its associations with clinical outcomes and quality of life.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study performed at a single institution included 702 consecutive patients who underwent definitive or adjuvant intensity-modulated RT (IMRT) for primary HNC from February 9, 2015, to May 27, 2022. Data were analyzed from November 28, 2022, to August 18, 2023.
MAIN OUTCOMES AND MEASURES
Severity of OM was assessed based on highest reported mouth and throat soreness (MTS) score during radiotherapy according to the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer survey, which was administered weekly during IMRT. Linear mixed models were used to compare mean MTS scores grouped by disease site and chemotherapy regimen. Fisher exact tests and 1-way analysis of variance tests were performed to identify associations between severity of OM and clinical outcomes.
RESULTS
Among 576 eligible patients, the median age was 62.5 (IQR, 56.3-69.1) years, and 451 patients (78.3%) were men. In terms of race and ethnicity, 6 patients (1.0%) were American Indian or Alaska Native; 2 (0.3%), Asian; 31 (5.4%), Black; 8 (1.4%), Hispanic or Latino; 509 (88.4%), White; and 28 (4.9%), unknown. The most common treatment site was oropharynx (268 [46.5%]), and most patients received concurrent chemotherapy (464 [80.6%]). By the end of treatment, 360 patients (62.5%) developed severe OM and 568 (98.6%) developed some degree of OM. Linear mixed models found no significant differences in OM between HNC disease sites. Groups with greater highest severity of OM reported had higher rates of measured outcomes (listed respectively by MTS score 0, 1, 2, 3, and 4): feeding tube placement (0%, 3.6% [2 of 56], 6.6% [10 of 152], 14.7% [40 of 272], and 21.6% [19 of 88]; P = .001), hospitalization (12.5% [1 of 8], 10.7% [6 of 56], 15.1% [23 of 152], 23.9% [65 of 272], and 28.4% [25 of 88]; P = .02), opiate use (0%, 19.6% [11 of 56], 42.8%[65 of 152], 61.4% [167 of 272], and 64.8% [57 of 88]; P < .001) and experienced greater weight loss (median, -0.7 [IQR, -1.7 to -0.4] kg; median, 3.9 [IQR, 1.1 to 6.1] kg; median, 5.0 [IQR, 2.2 to 7.7] kg; median, 4.7 [IQR, 2.1 to 7.7] kg; and median, 7.7 [IQR, 2.8 to 10.6] kg; P < .001).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with HNC, 62.5% developed severe OM. Higher severity of OM was associated with feeding tube placement, hospitalization, opiate use, and weight loss. Improvements in OM prevention and management are needed.
Topics: Male; Humans; Middle Aged; Female; Radiotherapy, Intensity-Modulated; Cohort Studies; Quality of Life; Head and Neck Neoplasms; Stomatitis; Opiate Alkaloids; Weight Loss
PubMed: 37819659
DOI: 10.1001/jamanetworkopen.2023.37265 -
Journal of Substance Abuse Treatment Feb 2022In 2018, the Baltimore City Health Department launched a mobile clinic called Healthcare on The Spot, which offers low-threshold buprenorphine services integrated with...
INTRODUCTION
In 2018, the Baltimore City Health Department launched a mobile clinic called Healthcare on The Spot, which offers low-threshold buprenorphine services integrated with health care services to meet the needs of people who use drugs. In addition to buprenorphine management, The Spot offers testing and treatment for hepatitis C, sexually transmitted infections, and HIV, as well as pre-exposure prophylaxis for HIV, wound care, vaccinations, naloxone distribution, and case management.
METHODS AND MATERIALS
This cohort analysis includes clinical service data from the first 15 months of The Spot mobile clinic, from September 4, 2018, to November 23, 2019. The Spot co-located with the Baltimore syringe services program in five locations across the city. Descriptive data are provided for patient demographics and services provided, as well as percent of patients retained in buprenorphine treatment at one and three months. Logistic regression identified factors associated with retention at three months.
RESULTS
The Spot mobile clinic provided services to 569 individuals from September 4, 2018, to November 23, 2019, including prescribing buprenorphine to 73.8% and testing to more than 70% for at least one infectious disease. Patients receiving a prescription for buprenorphine were more likely to be tested for HIV, hepatitis C, and sexually transmitted infections, as well as receive treatment for hepatitis C and preventive services including vaccination and naloxone distribution. The Spot initiated HIV treatment for four patients and HIV pre-exposure prophylaxis for twelve patients. More than 32% of patients had hepatitis C; nineteen of these patients initiated treatment for hepatitis C with eight having a documented cure. Buprenorphine treatment retention was 56.0% at one month and 26.2% at three months. Patients who were Black or receiving treatment for hepatitis C were more likely to be retained in buprenorphine treatment at three months.
CONCLUSIONS
Increasing access to integrated medical services and drug treatment through low-threshold, community-based models of care can be an effective tool for addressing the effects of drug use.
Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Hepatitis C; Humans; Mobile Health Units; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34238629
DOI: 10.1016/j.jsat.2021.108553 -
The International Journal on Drug Policy Apr 2022A mounting body of evidence suggests that polysubstance use (PSU) is common among people who use opioids (PWUO). Measuring PSU, however, is statistically and... (Review)
Review
BACKGROUND
A mounting body of evidence suggests that polysubstance use (PSU) is common among people who use opioids (PWUO). Measuring PSU, however, is statistically and methodologically challenging. Person-centered analytical approaches (e.g., latent class analysis) provide a holistic understanding of individuals' substance use patterns and help understand PSU heterogeneities among PWUO and their specific needs in an inductive manner. We reviewed person-centered studies that characterized latent patterns of PSU among PWUO.
METHODS
We searched MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Google Scholar from inception, through to June 15, 2020, for empirical peer-reviewed studies or gray literature that reported on latent classes of PSU among PWUO. Two independent reviewers completed the title, abstract, full-text screening, and data extraction. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale, and quality of reporting was evaluated using the Guidelines for Reporting on Latent Trajectory Studies checklist. Studies' findings were summarized and presented in a narrative fashion.
RESULTS
Out of the 3372 initial unique studies identified, 30 were included. PSU operationalization varied substantially among the studies. We identified five distinct PSU latent classes frequently observed across the studies: Infrequent/low PSU, PSU primarily involving heroin use, PSU primarily involving heroin and stimulant use, PSU primarily involving stimulant use, and frequent PSU. Belonging to higher frequency or severity PSU classes were associated with frequent injection drug use, sharing needles and paraphernalia, high-risk sexual behaviours, as well as experiences of adversities, such as homelessness, incarceration, and poor mental health.
CONCLUSION
PSU patterns vary significantly across different subgroups of PWUO. The substantial heterogeneities among PWUO need to be acknowledged in substance use clinical practices and policy developments. Findings call for comprehensive interventions that recognize these within-group diversities and address the varying needs of PWUO.
Topics: Analgesics, Opioid; Central Nervous System Stimulants; Heroin; Humans; Substance-Related Disorders
PubMed: 35074608
DOI: 10.1016/j.drugpo.2022.103584 -
The International Journal on Drug Policy Apr 2022Opioid use disorder (OUD) is a global public health concern. The standard of care for OUD involves treatment using medications such as buprenorphine, methadone, or... (Review)
Review
BACKGROUND
Opioid use disorder (OUD) is a global public health concern. The standard of care for OUD involves treatment using medications such as buprenorphine, methadone, or naltrexone. No known review exists to assess the contextual factors associated with medication for opioid use disorder (MOUD) in the Arab World. This systematic review serves as an implementation science study to address this research gap and improve the uptake of MOUD in the Arab World.
METHODS
Systematic searches of Medline, PsycINFO, and EMBASE, and a citation analysis, were used to identify peer-reviewed articles with original data on MOUD in the Arab World. Quality assessment was conducted using the CASP appraisal tools, and main findings were extracted and coded according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.
RESULTS
652 research articles were identified, and 10 met inclusion criteria for final review. Four studies considered health-systems aspects of MOUD administration, such as cost-effectiveness, the motivations for and impact of national MOUD policies, the types of social, political, and scientific advocacy that led to the adoption of MOUD in Arab countries, and the challenges limiting its wide-scale adoption in the Arab World. Six papers considered MOUD at individual and group patient levels by evaluating patient quality of life, addiction severity, patient satisfaction, and patient perspectives on opioid agonist therapy.
CONCLUSION
Despite financial and geographic barriers that limit access to MOUD in the Arab World, this review found MOUD to be cost-effective and associated with positive health outcomes for OUD patients in the Arab World. MOUD can be successfully established and scaled to the national level in the Arab context, and strong coalitions of health practitioners can lobby to establish MOUD programs in Arab countries. Still, the relative novelty of MOUD in this context precludes an abundance of research to address its long-term delivery in the Arab World.
Topics: Analgesics, Opioid; Arab World; Buprenorphine; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pharmaceutical Preparations; Quality of Life
PubMed: 35182841
DOI: 10.1016/j.drugpo.2022.103617 -
Molecules (Basel, Switzerland) Feb 2020Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law...
Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law enforcement. A rapid liquid chromatography-tandem mass spectrometry method using "dilute-and-shoot" analysis without the need for extraction, hydrolysis and/or derivatization has been developed and validated. The approach provides linear ranges of 2.5-1000 ng mL for 6-acetylmorphine, codeine, chlorpheniramine, and carbinoxamine, 2.5-800 ng mL for morphine and morphine-3-β-d-glucuronide, and 2.5-600 ng mL for morphine-6-β-d-glucuronide and codeine-6-β-d-glucuronide, with excellent correlation coefficients (R > 0.995) and matrix effects (< 5%). Urine samples collected from the ten participants orally administered cold syrups were analyzed. The results concluded that participants consuming codeine-containing cold syrups did not routinely pass urine tests for opiates, and their morphine-codeine concentration ratios (M/C) were not always < 1. In addition, the distribution map of the clinical total concentration of the sum of morphine and codeine against the antihistamines (chlorpheniramine or carbinoxamine) were plotted for discrimination of people who used cold syrups. The 15 real cases have been studied by using M/C rule, cutoff value, and distribution map, further revealing a potential approach to determine opiate metabolite in urine originating from cold syrups.
Topics: Adult; Analgesics, Opioid; Chlorpheniramine; Codeine; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Histamine Antagonists; Humans; Male; Middle Aged; Morphine; Morphine Derivatives; Opiate Alkaloids; Pyridines; Young Adult
PubMed: 32098143
DOI: 10.3390/molecules25040972 -
Anesthesiology Dec 2023Oliceridine (Olinvyk) is a μ-opioid receptor agonist that in contrast to conventional opioids preferentially engages the G-protein-coupled signaling pathway. This study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Oliceridine (Olinvyk) is a μ-opioid receptor agonist that in contrast to conventional opioids preferentially engages the G-protein-coupled signaling pathway. This study was designed to determine the utility function of oliceridine versus morphine based on neurocognitive tests and cold pressor test.
METHODS
The study had a randomized, double-blind, placebo-controlled, partial block three-way crossover design. Experiments were performed in 20 male and female volunteers. The subjects received intravenous oliceridine (1 or 3 mg; cohorts of 10 subjects/dose), morphine (5 or 10 mg; cohorts of 10 subjects/dose), or placebo on three separate occasions. Before and after dosing, neurocognitive tests, cold pressor test, and plasma drug concentrations were obtained at regular intervals. Population pharmacokinetic-pharmacodynamic analyses served as the basis for construction of a utility function, which is an objective function of probability of benefit minus probability of harm. Antinociception served as the measure of benefit, and slowing of saccadic peak velocity and increased body sway as the measures of neurocognitive harm.
RESULTS
The oliceridine and morphine C50 values, i.e., the effect-site concentrations causing 50% effect, were as follows: antinociception, 13 ± 2 and 23 ± 7 ng/ml; saccadic peak velocity, 90 ± 14 and 54 ± 15 ng/ml; and body sway, 10 ± 2 and 5.6 ± 0.8 ng/ml, respectively. The ratio oliceridine/morphine of the therapeutic indices, C50(benefit)/C50(harm), were 0.34 (95% CI, 0.17 to 0.7; P < 0.01) for saccadic peak velocity and 0.33 (0.16 to 0.50; P < 0.01) for body sway. The oliceridine utility was positive across the effect-site concentration 5 to 77 ng/ml, indicative of a greater probability of benefit than harm. The morphine utility was not significantly different from 0 from 0 to 100 ng/ml. Over the concentration range 15 to 50 ng/ml, the oliceridine utility was superior to that of morphine (P < 0.01). Similar observations were made for body sway.
CONCLUSIONS
These data indicate that over the clinical concentration range, oliceridine is an analgesic with a favorable safety profile over morphine when considering analgesia and neurocognitive function.
Topics: Male; Humans; Female; Morphine; Analgesics, Opioid; Spiro Compounds; Receptors, Opioid
PubMed: 37656771
DOI: 10.1097/ALN.0000000000004758 -
Bioengineered Dec 2021Morphine tolerance poses a great challenge for clinicians, whose pathogenesis has a close connection with microglial activation and neuroinflammation. Dihydroartemisinin...
Morphine tolerance poses a great challenge for clinicians, whose pathogenesis has a close connection with microglial activation and neuroinflammation. Dihydroartemisinin (DHA) that derives from artemisinin, may serve as a potential anti-inflammatory drug. In this study, the effects as well as the underlying mechanism of DHA on suppressing microglial activation and neuroinflammation were explored. The microglial cell line BV-2 cells were induced by morphine and treated with DHA or minocycline. With the application of CCK-8, the cell viability was detected. Western blot was employed to assess the expressions of Ki67, IBa-1, and TLR4 and quantitative real-time PCR (qRT-PCR) was adopted to evaluate miRNA-16 (miR-16) expression. With the adoption of ELISA kits and qRT-PCR, the release of inflammatory cytokines was evaluated. Besides, luciferase reporter assay was applied to testify the binding relationship between miR-16 and TLR4. NF-κB expression was measured by immunofluorescence. DHA reduced cell viability and decreased protein expression of Ki67 and IBa-1 in morphine-induced BV-2 cells. Additionally, DHA contributed to the declined release of pro-inflammatory cytokines. miR-16 was down-regulated by morphine but was up-regulated by DHA concentration-dependently in BV-2 cells. The inhibition of miR-16 partly abolished the inhibitory effects of DHA on morphine-induced microglial activation and neuroinflammation. Moreover, TLR4 was found to be bound to miR-16, and the inhibitory effect of DHA on TLR4/NF-κB was partly reversed by miR-16 inhibition. In conclusion, DHA remarkably suppressed microglial activation and neuroinflammation through regulating miR-16-mediated TLR4/NF-κB signaling. This study may provide a new solution to improve clinical analgesic efficacy of morphine.
Topics: Animals; Artemisinins; Cell Line; Gene Expression Regulation; Inflammation; Mice; Microglia; Morphine; Nerve Tissue Proteins
PubMed: 34854364
DOI: 10.1080/21655979.2021.1982311 -
Analytical Chemistry Dec 2022Organoids, i.e., laboratory-grown organ models developed from stem cells, are emerging tools for studying organ physiology, disease modeling, and drug development....
Organoids, i.e., laboratory-grown organ models developed from stem cells, are emerging tools for studying organ physiology, disease modeling, and drug development. On-line analysis of organoids with mass spectrometry would provide analytical versatility and automation. To achieve these features with robust hardware, we have loaded liquid chromatography column housings with induced pluripotent stem cell (iPSC) derived liver organoids and coupled the "organ-in-a-column" units on-line with liquid chromatography-mass spectrometry (LC-MS). Liver organoids were coloaded with glass beads to achieve an even distribution of organoids throughout the column while preventing clogging. The liver organoids were interrogated "on column" with heroin, followed by on-line monitoring of the drug's phase 1 metabolism. Enzymatic metabolism of heroin produced in the "organ-in-a-column" units was detected and monitored using a triple quadrupole MS instrument, serving as a proof-of-concept for on-line coupling of liver organoids and mass spectrometry. Taken together, the technology allows direct integration of liver organoids with LC-MS, allowing selective and automated tracking of drug metabolism over time.
Topics: Heroin; Chromatography, Liquid; Mass Spectrometry; Automation; Liver
PubMed: 36484723
DOI: 10.1021/acs.analchem.2c04530