scholarly journals Discovering Non-Invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 173-173
Author(s):  
Amir Levine ◽  
Kelly Clemenza ◽  
Shira Weiss ◽  
Adam Bisaga ◽  
Erez Eitan ◽  
...  
Keyword(s):  
Treatment Response ◽  
Mononuclear Cells ◽  
Specific Treatment ◽  
The United States ◽  
Opioid Use Disorder ◽  
Response To Treatment ◽  
Post Translational Modification ◽  
Opioid Use ◽  
Peripheral Blood Mononuclear ◽  
Long Term Treatment

AbstractBackgroundOpioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.MethodsWe obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.ResultsWe found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.DiscussionNaltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.

scholarly journals Development of an Emergency Department-Based Intervention to Expand Access to Medications for Addiction Treatment for Opioid Use Disorder in Appalachia: Protocol for Engagement and Community Collaboration (Preprint)

2020 ◽  
Author(s):  
Lauren A. Walter ◽  
LI Y. Li ◽  
Joel Rodgers ◽  
Jennifer Hess ◽  
Rachel Skains ◽  
...  
Keyword(s):  
Addiction Treatment ◽  
The United States ◽  
Opioid Use Disorder ◽  
Term Treatment ◽  
Opioid Overdose ◽  
Jefferson County ◽  
Opioid Use ◽  
Resource Limited ◽  
Long Term Treatment

BACKGROUND The opioid epidemic has disproportionately impacted the Appalachian region of the United States (US), a region characterized by higher poverty rates, healthcare access challenges, and higher opioid overdose death rates than other parts of the country. Jefferson County, Alabama, located in Southern Appalachia, has been especially affected, with overdose rates over two times greater than the statewide average (48.8 versus 19.9 overdoses per 10,000 persons). Emergency Departments (EDs) have been recognized as a major source of healthcare for persons with Opioid Use Disorder (OUD). A program to initiate medications for addiction treatment (MAT) for OUD in the ED has been shown to be effective. Likewise, continued patient engagement in a recovery or treatment program after ED discharge has been shown to be efficacious and impactful for long-term treatment success. OBJECTIVE This protocol outlines a framework for ED-initiated MAT for OUD in a resource-limited region of the US, made possible through community partnerships with referral resources for definitive OUD care. METHODS When a patient presents to the ED with symptoms of opioid withdrawal, non-fatal opioid overdose, or requesting opioid detoxification, clinicians will screen for OUD using the Diagnostic and Statistical Manual of Mental Disorders-5 diagnosis. All patients who screen positive for OUD will be further engaged and assessed for study eligibility. Recruited subjects will be evaluated for signs and symptoms of withdrawal, treated with buprenorphine/naloxone as appropriate, and given a prescription for take-home induction along with an intranasal naloxone kit. At the time of ED discharge, a peer navigator from a local substance use coordinating center will be engaged to facilitate patient referral to a regional substance abuse coordinating center for longitudinal addiction treatment. RESULTS This project is currently ongoing. It was funded in February, 2019, and approved by the University of Alabama at Birmingham IRB in June, 2019. Data collection began on July 7th, 2019 with projected end date February, 2022. Seventy-nine subjects have been enrolled to date. Results to be published in summer 2022. CONCLUSIONS ED recognition of OUD accompanied by buprenorphine/naloxone induction and referral for subsequent long-term treatment engagement have been shown to be one component of an effective strategy for addressing the ongoing opioid crisis. Establishing community and local partnerships, particularly in resource limited areas such as Appalachia, are crucial for the continuity of addiction care and rehabilitation outcomes.

scholarly journals Assessing the Relationships Between COVID-19 Stay-at-Home Orders and Opioid Overdoses in the State of Pennsylvania

2021 ◽  
pp. 002204262110063
Author(s):  
Brian King ◽  
Ruchi Patel ◽  
Andrea Rishworth
Keyword(s):  
Age Groups ◽  
The United States ◽  
Opioid Use Disorder ◽  
Opioid Overdose ◽  
Policy Recommendations ◽  
Opioid Use ◽  
Fentanyl Analogs ◽  
Measure Change ◽  
Using Data ◽  
At Home

COVID-19 is compounding opioid use disorder throughout the United States. While recent commentaries provide useful policy recommendations, few studies examine the intersection of COVID-19 policy responses and patterns of opioid overdose. We examine opioid overdoses prior to and following the Pennsylvania stay-at-home order implemented on April 1, 2020. Using data from the Pennsylvania Overdose Information Network, we measure change in monthly incidents of opioid-related overdose pre- versus post-April 1, and the significance of change by gender, age, race, drug class, and naloxone doses administered. Findings demonstrate statistically significant increases in overdose incidents among both men and women, White and Black groups, and several age groups, most notably the 30–39 and 40–49 ranges, following April 1. Significant increases were observed for overdoses involving heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids, and carfentanil. The study emphasizes the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

scholarly journals “It’s way more than just writing a prescription”: A qualitative study of preferences for integrated versus non-integrated treatment models among individuals with opioid use disorder

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Elizabeth C. Saunders ◽  
Sarah K. Moore ◽  
Olivia Walsh ◽  
Stephen A. Metcalf ◽  
Alan J. Budney ◽  
...  
Keyword(s):  
Qualitative Study ◽  
The United States ◽  
Opioid Use Disorder ◽  
Integrated Treatment ◽  
Medical Setting ◽  
Integrated Models ◽  
Opioid Use ◽  
Medical Settings ◽  
Psychosocial Services ◽  
Treatment Models

Abstract Background Increasingly, treatment for opioid use disorder (OUD) is offered in integrated treatment models addressing both substance use and other health conditions within the same system. This often includes offering medications for OUD in general medical settings. It remains uncertain whether integrated OUD treatment models are preferred to non-integrated models, where treatment is provided within a distinct treatment system. This study aimed to explore preferences for integrated versus non-integrated treatment models among people with OUD and examine what factors may influence preferences. Methods This qualitative study recruited participants (n = 40) through Craigslist advertisements and flyers posted in treatment programs across the United States. Participants were 18 years of age or older and scored a two or higher on the heroin or opioid pain reliever sections of the Tobacco, Alcohol, Prescription Medications, and Other Substances (TAPS) Tool. Each participant completed a demographic survey and a telephone interview. The interviews were coded and content analyzed. Results While some participants preferred receiving OUD treatment from an integrated model in a general medical setting, the majority preferred non-integrated models. Some participants preferred integrated models in theory but expressed concerns about stigma and a lack of psychosocial services. Tradeoffs between integrated and non-integrated models were centered around patient values (desire for anonymity and personalization, fear of consequences), the characteristics of the provider and setting (convenience, perceived treatment effectiveness, access to services), and the patient-provider relationship (disclosure, trust, comfort, stigma). Conclusions Among this sample of primarily White adults, preferences for non-integrated versus integrated OUD treatment were mixed. Perceived benefits of integrated models included convenience, potential for treatment personalization, and opportunity to extend established relationships with medical providers. Recommendations to make integrated treatment more patient-centered include facilitating access to psychosocial services, educating patients on privacy, individualizing treatment, and prioritizing the patient-provider relationship. This sample included very few minorities and thus findings may not be fully generalizable to the larger population of persons with OUD. Nonetheless, results suggest a need for expansion of both OUD treatment in specialty and general medical settings to ensure access to preferred treatment for all.

scholarly journals What Differs between Patients under Methadone and under Buprenorphine for Opioid Use Disorder (OUD) in Daily Clinical Practice in France? A Short Report

2021 ◽  
Vol 18 (4) ◽  
pp. 1425
Author(s):  
Morgane Guillou-Landreat ◽  
Antoine Dany ◽  
Gaëlle Challet-Bouju ◽  
Edouard Laforgue ◽  
Juliette Leboucher ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Opioid Use Disorder ◽  
Term Treatment ◽  
Pharmacological Therapy ◽  
Daily Clinical Practice ◽  
Short Report ◽  
Opioid Use ◽  
Cross Sectional ◽  
Long Term Treatment ◽  
Social Profiles

(1) Background: Opioid use disorder (OUD) is a complex condition that can require long-term treatment. Pharmacological therapy for OUD involves treatment with opioid agonists (OMT) tailored to individual profiles. The aim of our study in daily clinical practice was to compare the profiles of patients treated with methadone (MTD) and those using buprenorphine (BHD or BHD-naloxone-NX). (2) Methods: A cross-sectional multicentre study explored the psychological, somatic and social profiles of patients with Opioid Use Disorder (OUD) following Opioid Maintenance Treatment (BHD, BHD/NX, or MTD). Descriptive and comparative analyses were performed (3) Results: 257 patients were included, a majority were men using heroin. 68% (178) were on MTD, 32% (79) were on BHD. Patients with MTD were significantly more likely to report socio-affective damage, and more likely to be younger and not to report oral or sublingual use as the main route for heroin or non-medical opioids (4) Conclusions: In daily clinical practice, regarding OUD damage, only socio-affective damage was significantly more prevalent among patients on MTD than among those on BHD in the multivariate model. Age and route of administration also differed, and our results could raise the issue of the type of OMT prescribed in case of non-medical use of prescribed opioids. These hypothesis should be confirmed in larger studies.

scholarly journals Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions

2021 ◽  
Author(s):  
Samantha P. L. Law ◽  
Prudence N. Gatt ◽  
Stephen D. Schibeci ◽  
Fiona C. McKay ◽  
Steve Vucic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immunological Response ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Risk Genes ◽  
Inflammatory Models

AbstractAlthough genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk. We evaluated if the expression of vitamin D responsive MS risk genes could be used to assess vitamin D response in immune cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and people with MS treated with dimethyl fumarate. We assayed changes in expression of vitamin D responsive MS risk (VDRMS) genes in response to treatment with 25 hydroxy vitamin D in the presence or absence of inflammatory stimuli. Expression of CYP24A1 and other VDRMS genes was significantly altered in PBMCs treated with vitamin D in the homeostatic and inflammatory models. Gene expression in MS samples had similar responses to controls, but lower initial expression of the risk genes. Vitamin D treatment abrogated these differences. Expression of CYP24A1 and other MS risk genes in blood immune cells indicate vitamin D response and could enable assessment of immunological response to vitamin D in clinical trials and on therapy.

scholarly journals Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 916-928 ◽  
Author(s):  
BERTALAN MESKO ◽  
SZILARD POLISKA ◽  
SZILVIA SZAMOSI ◽  
ZOLTAN SZEKANECZ ◽  
JANOS PODANI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Peripheral Blood ◽  
Multiple Testing ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Gene Sets

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

Neurofeedback for Opioid Dependent Patients in an Outpatient Setting: A Pilot Feasibility Study

2021 ◽  
Author(s):  
Helena A. Rempala ◽  
Justin A. Barterian
Keyword(s):  
Large Scale ◽  
The United States ◽  
Outpatient Setting ◽  
Opioid Use Disorder ◽  
High Rate ◽  
Treatment Center ◽  
Opioid Use ◽  
Treatment As Usual ◽  
Factors Affecting ◽  
Study Approach

Abstract Background: Neurofeedback (NF) has been described as “probably efficacious” when used in conjunction with other interventions for substance use disorders, including the most recent studies in population of individuals with opioid use disorder. Despite these promising outcomes, the seriousness of the opioid epidemic, and the high rate of relapse even with the most effective medication-assisted maintenance treatments NF continues to be an under-researched treatment modality. This article explores factors that affected the feasibility of adding Alpha/Theta Neurofeedback to treatment as usual for opioid dependence in an outpatient urban treatment center. The study strived to replicate previous research completed in Iran that found benefits of NF for opioid dependence.Methods: Out of approximately two dozen patients eligible for Alpha/Theta NF, about 60% (n=15) agreed to participate; however, only 2 participants completed treatment. The rates of enrollment in response to active treatment were monitored. Results: The 4 factors affecting feasibility were: 1) the time commitment required of participants, 2) ineffectiveness of standard incentives to promote participation, 3) delayed effects of training, and 4) the length and number of treatments required.Conclusion: The findings indicate a large scale study examining the use of NF for the treatment of opioid use disorder in the United States will likely be difficult to accomplish without modification to the traditional randomized control study approach and suggests challenges to the implementation of this treatment in an outpatient setting.

scholarly journals Patient and Clinician Perspectives on Adolescent Opioid Use Disorder Treatment During a Pandemic: One Step Back, but Two Forward? (Preprint)

2020 ◽  
Author(s):  
Samuel W Stull ◽  
Erin R McKnight ◽  
Andrea E Bonny
Keyword(s):  
The United States ◽  
Opioid Use Disorder ◽  
Drop Out ◽  
Mobile Technologies ◽  
Opioid Use ◽  
The Face ◽  
One Step ◽  
Clinician Perspectives ◽  
Receive Treatment

UNSTRUCTURED Opioid use disorder (OUD) is one of the most pressing public health problems in the United States and is highly prevalent among adolescents and young adults (AYAs). However, only a small percentage of AYAs with OUD ever receive treatment. Further, among those that do receive treatment, a substantial proportion of patients continue to struggle with OUD, and many prematurely drop out of treatment. These challenges have only been heightened in the face of the COVID-19 pandemic, but greater utilization of telehealth and mobile technologies by OUD patients may help counter these barriers, which ultimately may improve AYA OUD treatment in the postpandemic period. This viewpoint presents the perspective of a person in OUD recovery using online and mobile technology to support his own OUD recovery combined with thoughts from two clinicians supporting AYAs with OUD. Their perspectives may provide insights to help counter COVID-19–related consequences and offer clues to improving AYA OUD treatment in the long term.

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