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1.
Eur Heart J Cardiovasc Pharmacother ; 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1702320

ABSTRACT

Coronavirus disease 2019 (COVID-19) is characterized by striking dysregulation of the immune system, with evidence of hyperinflammation, an impaired induction of interferons, and delayed adaptive immune responses. In addition to dysfunctional immune responses, thrombosis is a hallmark of severe COVID-19. Because traditional anticoagulation strategies are associated with increased bleeding, novel strategies that address both the immune and thrombotic dysfunction associated with COVID-19 would be of tremendous benefit. In this commentary, we discuss the unique properties of low dose naltrexone (LDN) which could be leveraged to reduce the immune-mediated thrombotic complications in COVID-19. Mechanistically, LDN can blunt innate immune responses and Toll-like receptor (TLR) signaling, reducing interleukin1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferon (IFN) levels. Because of the immune-mediated thrombotic mechanisms that underlie COVID-19, we hypothesize that the immune-modulating and known pharmacologic properties of LDN could be leveraged as a novel therapeutic strategy in COVID-19.

2.
Drug Alcohol Depend ; 232: 109192, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1536512

ABSTRACT

BACKGROUND: COVID-19 stay-at-home orders may reduce access to substance use treatment and naloxone, an opioid overdose reversal drug. The objective of this analysis was to compare monthly trends in pharmacy-based dispensing rates of medications for opioid use disorder (MOUD) (buprenorphine and extended-release [ER] naltrexone) and naloxone in the United States during March 2019-December 2020 by age and sex. METHODS: We calculated monthly prescription dispensing rates per 100,000 persons using IQVIA New to Brand. We used Joinpoint regression to calculate monthly percent change in dispensing rates and Wilcoxon Rank Sum tests to examine differences in median monthly rates overall, and by age and sex between March 2019-December 2019 and March 2020-December 2020. RESULTS: Buprenorphine dispensing increased among those aged 40-64 years and ≥ 65 years from March 2019 to December 2020. Median rates of total ER naltrexone dispensing were lower in March 2020-December 2020 compared to March 2019-December 2019 for the total population, and for females and males. From March 2019 to December 2020, ER naltrexone dispensing decreased and naloxone dispensing increased for those aged 20-39 years. CONCLUSIONS: Dispensing ER naltrexone declined during the study period. Given the increase in substance use during the COVID-19 pandemic, maintaining equivalent access to MOUD may not be adequate to accommodate rising numbers of new patients with opioid use disorder. Access to all MOUD and naloxone could be further expanded to meet potential needs during and after the public health emergency, given their importance in preventing opioid overdose-related harms.


Subject(s)
Buprenorphine , COVID-19 , Opioid-Related Disorders , Pharmacy , Adult , Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Female , Humans , Male , Middle Aged , Naloxone/therapeutic use , Naltrexone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Pandemics , SARS-CoV-2 , United States/epidemiology , Young Adult
3.
Subst Abuse Treat Prev Policy ; 16(1): 78, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1477437

ABSTRACT

BACKGROUND: Expanding access to medications for opioid use disorder (MOUD), such as buprenorphine and extended release (XR) naltrexone, is critical to addressing the US opioid epidemic, but little is known about prescriber satisfaction with delivering these two types of MOUD. The current study describes the satisfaction of prescribers delivering buprenorphine and XR-naltrexone while examining whether satisfaction is associated with current patient census and organizational environment. METHODS: As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 41 MOUD prescribers in Florida, Ohio, and Wisconsin completed a web-based survey. The survey included measures of prescriber satisfaction with delivering buprenorphine treatment and XR-naltrexone. In addition, the survey measured several prescriber characteristics and their perceptions of the organizational environment. RESULTS: Prescribers were generally satisfied with their work in delivering these two types of MOUD. Prescribers reporting a greater number of patients (r = .46, p = .006), those who would recommend the center to others (r = .56, p < .001), and those reporting positive relationships with staff (r = .56, p < .001) reported significantly greater overall satisfaction with delivering buprenorphine treatment. Prescribers who more strongly endorsed feeling overburdened reported lower overall buprenorphine satisfaction (r = -.37, p = .02). None of the prescriber characteristics or perceptions of the organizational environment were significantly associated with overall satisfaction with delivering XR-naltrexone treatment. CONCLUSIONS: The generally high levels of satisfaction with both types of MOUD is notable given that prescriber dissatisfaction can lead to turnover and impact intentions to leave the profession. Future research should continue to explore the prescriber characteristics and organizational factors associated with satisfaction in providing different types of MOUD. REGISTRATION: ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482 .


Subject(s)
Buprenorphine , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Humans , Naltrexone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy , Personal Satisfaction
4.
Pharmacol Ther ; 233: 108019, 2022 May.
Article in English | MEDLINE | ID: covidwho-1458814

ABSTRACT

Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This emphasis is perhaps unsurprising because opioid overdose is both the number-one cause of death for individuals between 25 and 64 years old (Dezfulian et al., 2021) and a significant contributor to the decline in average lifespan (Dowell et al., 2017). Exacerbated by the COVID 19 pandemic, it was estimated there were 93,400 drug overdose deaths in the United States during the 12 months ending December 2020, with more than 69,000 (that is, >74%) of these fatalities attributed to opioid overdose (Ahmad et al., 2021). However, the focus on mortality statistics (Ahmad et al., 2021; Shover et al., 2020) tends to obscure the broader medical impact of nonfatal opioid overdose. Analyses of multiple databases indicate that for each opioid-induced fatality, there are between 6.4 and 8.4 non-fatal overdoses, exacting a significant burden on both the individual and society. Over the past 7-8 years, there has been an alarming increase in the misuse of synthetic opioids ("synthetics"), primarily fentanyl and related piperidine-based analogs. Within the past 2-3 years, a structurally unrelated class of high potency synthetics, benzimidazoles exemplified by etonitazene and isotonitazene ("iso"), have also appeared in illicit drug markets (Thompson, 2020; Ujvary et al. 2021). In 2020, it was estimated that over 80% of fatal opioid overdoses in the United States now involve synthetics (Ahmad et al., 2021). The unique physicochemical and pharmacological properties of synthetics described in this review are responsible for both the morbidity and mortality associated with their misuse as well as their widespread availability. This dramatic increase in the misuse of synthetics is often referred to as the "3rd wave" (Pardo et al., 2019; Volkow and Blanco, 2020) of the opioid epidemic. Among the consequences resulting from misuse of these potent opioids is the need for higher doses of the competitive antagonist, naloxone, to reverse an overdose. The development of more effective reversal agents such as those described in this review is an essential component of a tripartite strategy (Volkow and Collins, 2017) to reduce the biopsychosocial impact of opioid misuse in the "synthetic era".


Subject(s)
COVID-19 , Drug Overdose , Opiate Overdose , Adult , Analgesics, Opioid/adverse effects , COVID-19/drug therapy , Drug Overdose/drug therapy , Drug Overdose/epidemiology , Humans , Middle Aged , Naloxone/therapeutic use , Opiate Overdose/drug therapy , Opiate Overdose/epidemiology , United States/epidemiology
6.
J Subst Abuse Treat ; 128: 108275, 2021 09.
Article in English | MEDLINE | ID: covidwho-1012463

ABSTRACT

A major driver of the U.S. opioid crisis is limited access to effective medications for opioid use disorder (MOUD) that reduce overdose risks. Traditionally, jails and prisons in the U.S. have not initiated or maintained MOUD for incarcerated individuals with OUD prior to their return to the community, which places them at high risk for fatal overdose. A 2018 law (Chapter 208) made Massachusetts (MA) the first state to mandate that five county jails deliver all FDA-approved MOUDs (naltrexone [NTX], buprenorphine [BUP], and methadone). Chapter 208 established a 4-year pilot program to expand access to all FDA-approved forms of MOUD at five jails, with two more MA jails voluntarily joining this initiative. The law stipulates that MOUD be continued for individuals receiving it prior to detention and be initiated prior to release among sentenced individuals where appropriate. The jails must also facilitate continuation of MOUD in the community on release. The Massachusetts Justice Community Opioid Innovation Network (MassJCOIN) partnered with these seven diverse jails, the MA Department of Public Health, and community treatment providers to conduct a Type 1 hybrid effectiveness-implementation study of Chapter 208. We will: (1) Perform a longitudinal treatment outcome study among incarcerated individuals with OUD who receive NTX, BUP, methadone, or no MOUD in jail to examine postrelease MOUD initiation, engagement, and retention, as well as fatal and nonfatal opioid overdose and recidivism; (2) Conduct an implementation study to understand systemic and contextual factors that facilitate and impede delivery of MOUDs in jail and community care coordination, and strategies that optimize MOUD delivery in jail and for coordinating care with community partners; (3) Calculate the cost to the correctional system of implementing MOUD in jail, and conduct an economic evaluation from state policy-maker and societal perspectives to compare the value of MOUD prior to release from jail to no MOUD among matched controls. MassJCOIN made significant progress during its first six months until the COVID-19 pandemic began in March 2020. Participating jail sites restricted access for nonessential personnel, established other COVID-19 mitigation policies, and modified MOUD programming. MassJCOIN adapted research activities to this new reality in an effort to document and account for the impacts of COVID-19 in relation to each aim. The goal remains to produce findings with direct implications for policy and practice for OUD in criminal justice settings.


Subject(s)
Buprenorphine , COVID-19 , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Humans , Massachusetts , Opiate Substitution Treatment , Opioid-Related Disorders/drug therapy , Pandemics , SARS-CoV-2
7.
J Subst Abuse Treat ; 124: 108216, 2021 05.
Article in English | MEDLINE | ID: covidwho-957252

ABSTRACT

The Franklin County Sheriff's Office (FCSO), in Greenfield, Massachusetts, is among the first jails nationwide to provide correctional populations with access to all three medications to treat opioid use disorder (MOUD, i.e., buprenorphine, methadone, naltrexone). In response to the COVID-19 pandemic, FCSO quickly implemented comprehensive mitigation policies and adapted MOUD programming. Two major challenges for implementation of the MOUD program were the mandated rapid release of nonviolent pretrial individuals, many of whom were being treated with MOUD and released too quickly to conduct continuity of care planning; and establishing how to deliver physically distanced MOUD services in jail. FCSO implemented and adapted a hub-and-spoke MOUD model, developed telehealth capacity, and experimented with take-home MOUD at release to facilitate continuity-of-care as individuals re-entered the community. Experiences underscore how COVID-19 accelerated the uptake and diffusion of technology-infused OUD treatment and other innovations in criminal justice settings. Looking forward, to address both opioid use disorder and COVID-19, jails and prisons need to develop capacity to implement mitigation strategies, including universal and rapid COVID-19 testing of staff and incarcerated individuals, and be resourced to provide evidence-based addiction treatment. FCSO quickly pivoted and adapted MOUD programming because of its history of applying public health approaches to address the opioid epidemic. Utilizing public health strategies can enable prisons and jails to mitigate the harms of the co-occurring epidemics of OUD and COVID-19, both of which disproportionately affect criminal justice populations, for persons who are incarcerated and the communities to which they return.


Subject(s)
Buprenorphine/therapeutic use , COVID-19 , Methadone/therapeutic use , Naltrexone/therapeutic use , Opioid-Related Disorders , Prisoners , Humans , Massachusetts , Opiate Substitution Treatment , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/rehabilitation , Prisons/organization & administration , Public Health , Telemedicine/organization & administration
8.
J Biomol Struct Dyn ; 40(3): 963-970, 2022 02.
Article in English | MEDLINE | ID: covidwho-759735

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease (COVID-19) that has resulted in a global pandemic. At the time of writing, approximately 16.06 million cases have been reported worldwide. Like other coronaviruses, SARS-CoV-2 relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the host receptor Angiotensin-Converting Enzyme2 (ACE2). SARS-CoV-2 infection induces a profound downstream pro-inflammatory cytokine storm. This release of the pro-inflammatory cytokines is underpinning lung tissue damage, respiratory failure, and eventually multiple organ failure in COVID-19 patients. The phosphorylation status of ERK1/2 is positively correlated with virus load and ERK1/2 inhibition suppressed viral replication and viral infectivity. Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2, or damping hyperinflammatory cytokines storm, blocking ERK1/2 phosphorylation have a great potential to inhibit viral entry along with viral infectivity. Herein, we report that the FDA-approved non-peptide opioid antagonist drug, naltrexone suppresses high fat/LPS induced pro-inflammatory cytokine release both from macrophage cells and Adipose Tissue Macrophage. Moreover, Low Dose Naltrexone (LDN) also showed its activity as an ERK1/2 inhibitor. Notably, virtual docking and simulation data also suggest LDN may disrupt the interaction of ACE2 with RBD. LDN may be considered as a target as the treatment and (or) adjuvant therapy for coronavirus infection. Clinical toxicity measurements may not be required for LDN since naltrexone was previously tested and is an approved drug by the FDA.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Naltrexone , Humans , Molecular Docking Simulation , Naltrexone/pharmacology , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
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