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The Pharmacogenomics Journal Jun 2024The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide...
The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) μM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.
Topics: Humans; Morphine; Male; Female; Cancer Pain; Middle Aged; Analgesics, Opioid; Delayed-Action Preparations; Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; Morphine Derivatives; Adult; Pharmacogenomic Variants; Toll-Like Receptor 2
PubMed: 38824169
DOI: 10.1038/s41397-024-00339-w -
Annals of Medicine Dec 2024Racial and ethnic disparities are evident in the accessibility of treatment for opioid use disorder (OUD). Even when medications for OUD (MOUD) are accessible, racially...
BACKGROUND
Racial and ethnic disparities are evident in the accessibility of treatment for opioid use disorder (OUD). Even when medications for OUD (MOUD) are accessible, racially and ethnically minoritized groups have higher attrition rates from treatment. Existing literature has primarily identified the specific racial and ethnic groups affected by these disparities, but has not thoroughly examined interventions to address this gap. Recovery peer navigators (RPNs) have been shown to improve access and overall retention on MOUD.
PATIENTS AND METHODS
In this retrospective cohort study, we evaluate the role of RPNs on patient retention in clinical care at an outpatient program in a racially and ethnically diverse urban community. Charts were reviewed of new patients seen from January 1, 2019 through December 31, 2019. Sociodemographic and clinical visit data, including which providers and services were utilized, were collected, and the primary outcome of interest was continuous retention in care. Bivariate analysis was done to test for statistically significant associations between variables by racial/ethnic group and continuous retention in care using Student's t-test or Pearson's chi-square test. Variables with p value ≤0.10 were included in a multivariable regression model.
RESULTS
A total of 131 new patients were included in the study. RPNs improved continuous retention in all-group analysis (27.6% pre-RPN compared to 80.2% post-RPN). Improvements in continuous retention were observed in all racial/ethnic subgroups but were statistically significant in the non-Hispanic Black (NHB) group ( < 0.001). Among NHB, increases in continuous retention were observed post-RPN in patients with male sex ( < 0.001), public health insurance ( < 0.001), additional substance use ( < 0.001), medical comorbidities ( < 0.001), psychiatric comorbidities ( = 0.001), and unstable housing ( = 0.005). Multivariate logistic regression demonstrated that patients who lacked insurance had lower odds of continuous retention compared to patients with public insurance (aOR = 0.17, 95% CI 0.039-0.70, = 0.015).
CONCLUSIONS
RPNs can improve clinical retention for patients with OUD, particularly for individuals experiencing several sociodemographic and clinical factors that are typically correlated with discontinuation of care.
Topics: Humans; Retrospective Studies; Male; Female; Opioid-Related Disorders; Buprenorphine; Adult; Opiate Substitution Treatment; Patient Navigation; Middle Aged; Retention in Care; Peer Group; Ambulatory Care; Healthcare Disparities; Ethnicity; Outpatients
PubMed: 38823420
DOI: 10.1080/07853890.2024.2355566 -
Harm Reduction Journal May 2024Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to...
BACKGROUND
Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to concerns for legal repercussions. Rural communities face unique challenges in reducing overdose deaths compared to urban communities, including limited access to harm reduction services as well as greater concerns about stigma and privacy.
METHODS
The Rural Opioid Initiative was funded in 2017 to better understand the health-related harms associated with the opioid crisis in rural US communities and consists of eight studies spanning ten states and 65 counties. Each study conducted semi-structured qualitative interviews with people who use drugs to understand contextual factors influencing drug use and health behaviors. We analyzed qualitative data from seven studies with data available at the time of analysis to understand peer response to overdose.
RESULTS
Of the 304 participants interviewed, 55% were men, 70% were white, 80% reported current injection drug use, and 60% reported methamphetamine use. Similar to what has been found in studies focused on urban settings, people who use drugs in rural communities use a range of strategies to reverse overdoses, including non-evidence-based approaches. Several reported that multiple doses of naloxone are needed to reverse overdose. Three themes emerged around the willingness to call 911, including (1) hesitancy to call 911 for fear of legal consequences, (2) negative perceptions or experiences with law enforcement officers, and (3) efforts to obtain medical intervention while avoiding identification/law enforcement involvement.
CONCLUSION
People who use drugs employ multiple strategies to attempt overdose reversal, including non-evidence-based approaches. Greater education about the most effective and least harmful strategies is needed. Reluctance to call 911 is rooted in concerns about potential legal consequences as well as perceptions about law enforcement officers, which may be heightened in rural communities where people who use drugs are more easily identified by law enforcement. People who use drugs will go to great strides to connect their peers to needed medical services, suggesting that comprehensive interventions to reduce interactions with law enforcement officers and eliminate legal consequences for reporting overdoses are critical.
Topics: Humans; Female; Male; Rural Population; Adult; Drug Overdose; Harm Reduction; Narcotic Antagonists; Naloxone; Middle Aged; Qualitative Research; United States; Young Adult; Drug Users
PubMed: 38822387
DOI: 10.1186/s12954-024-01007-9 -
JAMA Network Open May 2024Many US states are substantially increasing community-based naloxone distribution, supported in part through settlements from opioid manufacturers and distributors.
IMPORTANCE
Many US states are substantially increasing community-based naloxone distribution, supported in part through settlements from opioid manufacturers and distributors.
OBJECTIVES
To evaluate the potential impact of increased naloxone availability on opioid overdose deaths (OODs) and explore strategies to enhance this impact by integrating interventions to address solitary drug use.
DESIGN, SETTING, AND PARTICIPANTS
This decision analytical modeling study used PROFOUND (Prevention and Rescue of Fentanyl and Other Opioid Overdoses Using Optimized Naloxone Distribution Strategies), a previously published simulation model, to forecast annual OODs between January 2023 and December 2025. The simulated study population included individuals from Rhode Island who misused opioids and stimulants and were at risk for opioid overdose.
EXPOSURES
The study modeled expanded naloxone distribution supported by the state's opioid settlement (50 000 naloxone nasal spray kits each year). Two approaches to expanding naloxone distribution were evaluated: one based on historical spatial patterns of naloxone distribution (supply-based approach) and one based on the spatial distribution of individuals at risk (demand-based approach). In addition, hypothetical interventions to enhance the likelihood of witnessed overdoses in private or semiprivate settings were considered.
MAIN OUTCOMES AND MEASURES
Annual number of OODs and ratio of fatal to nonfatal opioid overdoses.
RESULTS
Modeling results indicated that distributing more naloxone supported by the state's opioid settlement could reduce OODs by 6.3% (95% simulation interval [SI], 0.3%-13.7%) and 8.8% (95% SI, 1.8%-17.5%) in 2025 with the supply-based and demand-based approaches, respectively. However, increasing witnessed overdoses by 20% to 60% demonstrated greater potential for reducing OODs, ranging from 8.5% (95% SI, 0.0%-20.3%) to 24.1% (95% SI, 8.6%-39.3%). Notably, synergistic associations were observed when combining both interventions: increased naloxone distribution with the 2 approaches and a 60% increase in witnessed overdoses could reduce OODs in 2025 by 33.5% (95% SI, 17.1%-50.4%) and 37.4% (95% SI, 19.6%-56.3%), respectively.
CONCLUSIONS AND RELEVANCE
These findings suggest that interventions to address solitary drug use are needed to maximize the impact of continued efforts to increase community-based naloxone distribution, which may be particularly important for jurisdictions that have strong community-based naloxone distribution programs.
Topics: Naloxone; Humans; Narcotic Antagonists; Rhode Island; Opiate Overdose; Analgesics, Opioid; Opioid-Related Disorders; Drug Overdose
PubMed: 38814644
DOI: 10.1001/jamanetworkopen.2024.13861 -
Drugs & Aging Jun 2024Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate... (Review)
Review
Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate effect, especially in central nervous system-acting drugs, is fundamental. While considering pharmacokinetics, it should be noted that the absorption of most drugs from the gastrointestinal tract does not change in advanced age. There are only few data about the effect of age on the transdermal absorption of medications such as fentanyl. Absorption from an intramuscular injection may be similar in older adults as in younger patients. The distribution of lipophilic drugs (such as diazepam) is increased owing to a relative increase in the percentage of body fat, causing drug accumulation and prolonged drug elimination following cessation. Phase I drug biotransformation is variably decreased in aging, impacting elimination, and hepatic drug clearance has been shown to decrease in older individuals by 10-40% for most drugs studied. Lower doses of phenothiazines, butyrophenones, atypical antipsychotics, antidepressants (citalopram, mirtazapine, and tricyclic antidepressants), and benzodiazepines (such as diazepam) achieve the same extent of exposure. For renally cleared drugs with no prior metabolism (such as gabapentin), the glomerular filtration rate appropriately estimates drug clearance. Important pharmacodynamic changes in older adults include an increased sedative effect of benzodiazepines at a given drug exposure, and a higher sensitivity to mu opiate receptor agonists and to opioid adverse effects. Artificial intelligence, physiologically based pharmacokinetic modeling and simulation, and concentration-effect modeling enabling a differentiation between the pharmacokinetic and the pharmacodynamic effects of aging might help to close some of the gaps in knowledge.
Topics: Humans; Aged; Central Nervous System Agents; Aging
PubMed: 38814377
DOI: 10.1007/s40266-024-01117-w -
Journal of Medicinal Chemistry Jun 2024Despite the availability of numerous pain medications, the current array of Food and Drug Administration-approved options falls short in adequately addressing pain...
Despite the availability of numerous pain medications, the current array of Food and Drug Administration-approved options falls short in adequately addressing pain states for numerous patients and consequently worsens the opioid crisis. Thus, it is imperative for basic research to develop novel and nonaddictive pain medications. Toward addressing this clinical goal, nalfurafine (NLF) was chosen as a lead and its structure-activity relationship (SAR) systematically studied through design, syntheses, and characterization of 24 analogues. Two analogues, and , showed longer durations of action than NLF in a warm-water tail immersion assay, produced effects primarily mediated by KOR and DOR, penetrated the blood-brain barrier, and did not function as reinforcers. Additionally, produced fewer sedative effects than NLF. Taken together, these results aid the understanding of NLF SAR and provide insights for future endeavors in developing novel nonaddictive therapeutics to treat pain.
Topics: Structure-Activity Relationship; Spiro Compounds; Animals; Morphinans; Mice; Male; Humans; Receptors, Opioid, kappa; Pain Management; Pain; Analgesics
PubMed: 38814086
DOI: 10.1021/acs.jmedchem.4c00646 -
Korean Journal of Radiology Jun 2024
Topics: Humans; Diagnosis, Differential; Tomography, X-Ray Computed; Female; Adult; Middle Aged
PubMed: 38807341
DOI: 10.3348/kjr.2024.0244 -
Harm Reduction Journal May 2024People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in...
BACKGROUND
People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary.
METHODS
We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons.
RESULTS
Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime.
CONCLUSIONS
Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.
Topics: Humans; Connecticut; Naloxone; Opioid-Related Disorders; Narcotic Antagonists; Cost-Benefit Analysis; Drug Overdose; Opiate Overdose; Harm Reduction; Adult; Male; Quality-Adjusted Life Years; Female; Prisoners
PubMed: 38807226
DOI: 10.1186/s12954-024-01026-6 -
Substance Use & Addiction Journal Jul 2024The United States is grappling with an unprecedented overdose crisis, exacerbated by the proliferation of potent synthetic opioids like illicitly manufactured fentanyl....
Methadone's Resurgence in Bridging the Treatment Gap in the Overdose Crisis: Position Statement of AMERSA, Inc (Association for Multidisciplinary Education, Research, Substance Use, and Addiction).
BACKGROUND
The United States is grappling with an unprecedented overdose crisis, exacerbated by the proliferation of potent synthetic opioids like illicitly manufactured fentanyl. Despite the efficacy of methadone treatment in managing opioid use disorder, regulatory barriers hinder its widespread utilization. This article examines the complex landscape of methadone regulation across federal, state, and local levels, highlighting disparities and opportunities for reform.
ISSUE
The COVID-19 public health emergency prompted temporary flexibility in methadone regulations, including expanded take-home doses and telehealth counseling, leading to improved treatment experiences and retention. Permanent revisions to federal guidelines have since been introduced by the Substance Abuse and Mental Health Services Administration, reflecting a progressive shift toward patient-centered care and streamlined access. State regulations, managed by Single State Agencies and State Opioid Treatment Authorities, vary widely, often imposing additional restrictions that impede access to methadone treatment. Local OTP clinics further exacerbate barriers through stringent policies, despite federal and state guidelines advocating for flexibility.
RECOMMENDATIONS
Coordinated efforts among policymakers, healthcare providers, and communities are needed to promote the development of accountability measures, incentives, and community involvement to ensure equitable access and quality of care. To truly meet the demand needed to end the existing overdose crisis and enhance accessibility and comprehensive healthcare services, methadone treatment expansion beyond traditional OTP settings into primary care offices and community pharmacies should take place.
Topics: Humans; Methadone; Opiate Substitution Treatment; United States; Opioid-Related Disorders; COVID-19; Drug Overdose; Analgesics, Opioid; Health Services Accessibility
PubMed: 38804606
DOI: 10.1177/29767342241255480 -
Frontiers in Public Health 2024Medications for opioid use disorder (MOUD) are especially important for formerly incarcerated individuals with opioid use disorder (OUD) and can reduce the risk of... (Review)
Review
Medications for opioid use disorder (MOUD) are especially important for formerly incarcerated individuals with opioid use disorder (OUD) and can reduce the risk of re-arrest and overdose during community reentry. Unfortunately, few formerly incarcerated individuals are able to access MOUD within the community, missing a critical tool for rehabilitation. A mini narrative review was conducted to highlight the published work that has been done to improve access to MOUD for formerly incarcerated individuals during reentry. The results yielded 15 records describing intervention evaluations, program descriptions, and research in progress. Most work is ongoing, showing promise that researchers have identified the importance of this problem. However additional research should be done to include other stakeholders and address the limitations of existing interventions and programs. Continued efforts can help ensure that formerly incarcerated individuals can safely and successfully reintegrate into society.
Topics: Humans; Opioid-Related Disorders; Prisoners; Health Services Accessibility; Opiate Substitution Treatment; Analgesics, Opioid
PubMed: 38803812
DOI: 10.3389/fpubh.2024.1377193