COVID-19-Related Changes to Drug-Selling Networks and Their Effects on People Who Use Illicit Opioids.

OBJECTIVE: The COVID-19 pandemic has significantly affected people's ability to buy, sell, and obtain items that they use in their daily lives. It may have had a particularly negative effect on the ability of people who use illicit opioids to obtain them because the networks they relied on are illicit and not part of the formal economy. Our objective in this research was to examine if, and how, disruptions related to COVID-19 of illicit opioid markets have affected people who use illicit opioids. METHOD: We collected 300 posts--including replies to posts--related to the intersection of COVID-19 and opioid use from Reddit.com, a forum that has several discussion threads (i.e., subreddits) dedicated to opioids. We then coded posts from the two most popular opioid subreddits during the early pandemic period (March 5, 2020-May 13, 2020) using an inductive/deductive approach. RESULTS: We found two themes related to active opioid use during the early pandemic: (a) changes in drug supply and difficulty obtaining opioids, and (b) buying less-trustworthy drugs from lesser-known sources. CONCLUSIONS: Our findings suggest that COVID-19 has created market conditions that place people who use opioids at risk of adverse outcomes, such as fatal overdose.

I Don't Believe a Person Has to Die When Trying to Get High: Overdose Prevention and Response Strategies in Rural Illinois.

BACKGROUND: Overdose is a leading cause of morbidity and mortality among people who inject drugs. Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths. METHODS: Semi-structured interviews were conducted with 23 participants (19 persons who inject drugs and 4 service providers) from rural southern Illinois. Data were analyzed using constant comparison and theoretical sampling methods. RESULTS: Participants were concerned about the growing presence of fentanyl in both opioids and stimulants, and many disclosed overdose experiences. Strategies participants reported using to lower overdose risk included purchasing drugs from trusted sellers and modifying drug use practices by partially injecting and/or changing the route of transmission. Approximately half of persons who inject drugs sampled had heard of fentanyl test strips, however fentanyl test strip use was low. To reverse overdoses, participants reported using cold water baths. Use of naloxone to reverse overdose was low. Barriers to naloxone access and use included fear of arrest and opioid withdrawal. CONCLUSIONS: People who inject drugs understood fentanyl to be a potential contaminant in their drug supply and actively engaged in harm reduction techniques to try to prevent overdose. Interventions to increase harm reduction education and information about and access to fentanyl test strips and naloxone would be beneficial.

How the rural risk environment underpins hepatitis C risk: Qualitative findings from rural southern Illinois, United States.

BACKGROUND: Hepatitis C virus (HCV) infection has increased among persons who inject drugs (PWID) in the United States with disproportionate burden in rural areas. We use the Risk Environment framework to explore potential economic, physical, social, and political determinants of hepatitis C in rural southern Illinois. METHODS: Nineteen in-depth semi-structured interviews were conducted with PWID from August 2019 through February 2020 (i.e., pre-COVID-19 pandemic) and four with key informants who professionally worked with PWID. Interviews were recorded, professionally transcribed, and coded using qualitative software. We followed a grounded theory approach for coding and analyses. RESULTS: We identify economic, physical, policy, and social factors that may influence HCV transmission risk and serve as barriers to HCV care. Economic instability and lack of economic opportunities, a lack of physically available HCV prevention and treatment services, structural stigma such as policies that criminalize drug use, and social stigma emerged in interviews as potential risks for transmission and barriers to care. CONCLUSION: The rural risk environment framework acknowledges the importance of community and structural factors that influence HCV infection and other disease transmission and care. We find that larger structural factors produce vulnerabilities and reduce access to resources, which negatively impact hepatitis C disease outcomes.

Lessons from the First Wave of COVID-19 for Improved Medications for Opioid Use Disorder (MOUD) Treatment: Benefits of Easier Access, Extended Take Homes, and New Delivery Modalities.

Background Medications for Opioid Use Disorder (MOUD) are associated with important public health benefits. Program changes implemented in response to COVID-19 hold promise as ongoing strategies to improve MOUD treatment. Methods: MOUD patients on buprenorphine or methadone, providers, government regulators, and persons who use drugs not in MOUD were recruited in the Northeast region of the United States between June and October of 2020 via advertisements, fliers, and word of mouth. Semi-structured qualitative interviews were conducted. Interviews were professionally transcribed and thematically coded by two independent coders. Results: We conducted interviews with 13 people currently on buprenorphine, 11 currently on methadone, 3 previously on buprenorphine, 4 previously on methadone, and 6 who used drugs but had never been on MOUD. In addition, we interviewed MOUD providers, clinic staff, and government officials at agencies that regulate MOUD. Most participants found increased take-home doses, home medication delivery, and telehealth implemented during COVID-19 to be favorable, reporting that these program changes reduced travel time to clinics, facilitated retention in care, and reduced stigma associated with clinic attendance. However, some participants reported negative consequences of COVID-19, most notably, decreased access to basic resources, such as food, clothing, and harm reduction materials that had previously been distributed at some MOUD clinics. Conclusion: Access to and retention in MOUD can be lifesaving for persons using drugs. COVID-19-impelled program changes, including increased take-home doses, home medication delivery, and telehealth generally improved participants' experiences with MOUD. Making these permanent could improve retention in care.

The Methadone Manifesto: Treatment Experiences and Policy Recommendations From Methadone Patient Activists

[...]we take on projects in two-person teams, share skills, and provide mentorship. [...]for many reasons, MMT is vital, especially now that fentanyl dominates the illicit opioid supply.12 In the absence of safer, legal, short-acting opioids, as one member said, "methadone is our safe supply." According to one USU member: MMT programs drastically reduce doses after two to three missed days and, after additional missed doses, may terminate treatment. [...]many patients are at increased risk for overdose because they supplement reduced or missed doses with illicit street opioids or rely on them after treatment has been terminated.

Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability.

Vascular permeability triggered by inflammation or ischemia promotes edema, exacerbates disease progression and impairs tissue recovery. Vascular endothelial growth factor (VEGF) is a potent inducer of vascular permeability. VEGF plays an integral role in regulating vascular barrier function physiologically and in pathologies, including cancer, stroke, cardiovascular disease, retinal conditions and COVID-19-associated pulmonary edema, sepsis and acute lung injury. Understanding temporal molecular regulation of VEGF-induced vascular permeability will facilitate developing therapeutics to inhibit vascular permeability, while preserving tissue-restorative angiogenesis. Here, we demonstrate that VEGF signals through signal transducer and activator of transcription 3 (STAT3) to promote vascular permeability. We show that genetic STAT3 ablation reduces vascular permeability in STAT3-deficient endothelium of mice and VEGF-inducible zebrafish crossed with CRISPR/Cas9-generated Stat3 knockout zebrafish. Intercellular adhesion molecule 1 (ICAM-1) expression is transcriptionally regulated by STAT3, and VEGF-dependent STAT3 activation is regulated by JAK2. Pyrimethamine, an FDA-approved antimicrobial agent that inhibits STAT3-dependent transcription, substantially reduces VEGF-induced vascular permeability in zebrafish, mouse and human endothelium. Collectively, our findings suggest that VEGF/VEGFR-2/JAK2/STAT3 signaling regulates vascular barrier integrity, and inhibition of STAT3-dependent activity reduces VEGF-induced vascular permeability. This article has an associated First Person interview with the first author of the paper.

"I'm pretty sure it's either food poisoning or Covid-19": Lived experience versus medical knowledge in diagnosing substance use problems.

People who use drugs, or who have in the past, often report that doctors and/or treatment providers devalue, or are unwilling to believe their claims in regards to substance use issues, in particular the presence and severity of withdrawal. In the case of benzodiazepine withdrawal this can not only lead to significant discomfort, frustration, and trauma for patients, but can lead to serious medical problems. This commentary uses the authors' recent first-person experience with a disbelieving doctor in order to illustrate the lack of value often given to the claims and narratives of people with lived substance use experience. I outline some of the potential problems with this approach, including the effects on patients themselves and the loss of an important source of evidence-based knowledge. It also discusses potential risks associated with the recent increase in benzodiazepine prescription due to Covid-19 and offers suggestions for improving treatment outcomes.

Socially-supportive norms and mutual aid of people who use opioids: An analysis of Reddit during the initial COVID-19 pandemic.

BACKGROUND: Big events (i.e., unique historical disruptions) like the COVID-19 epidemic and its associated period of social distancing can transform social structures, social interactions, and social norms. Social distancing rules and the fear of infection have greatly reduced face-to-face interactions, increased loneliness, reduced ties to helping institutions, and may also have disrupted the opioid use behaviors of people who use drugs. This research used Reddit to examine the impact of COVID-19 on the social networks and social processes of people who use opioids. METHODS: Data were collected from the social media forum, Reddit.com. At the beginning of the COVID-19 pandemic in the U.S. (March 5, 2020, to May 13, 2020), 2,000 Reddit posts were collected from the two most popular opioid subreddits (r/OpiatesRecovery, r/Opiates). Posts were reviewed for relevance to COVID-19 and opioid use resulting in a final sample of 300. Thematic analysis was guided by the Big Events framework. RESULTS: The COVID-19 pandemic was found to create changes in the social networks and daily lives among persons who use opioids. Adaptions to these changes shifted social networks leading to robust social support and mutual aid on Reddit, including sharing and seeking advice on facing withdrawal, dealing with isolation, managing cravings, and accessing recovery resources. CONCLUSIONS: Reddit provided an important source of social support and mutual aid for persons who use opioids. Findings indicate online social support networks are beneficial to persons who use opioids, particularly during big events where isolation from other social support resources may occur.

"How will I get my next week's script?" Reactions of Reddit opioid forum users to changes in treatment access in the early months of the coronavirus pandemic.

BACKGROUND: The COVID-19 pandemic poses significant challenges to people with opioid use disorder (OUD). As localities enforce lockdowns and pass emergency OUD treatment regulations, questions arise about how these changes will affect access and retention in care. In this study, we explore the influence of COVID-19 on access to, experiences with, and motivations for OUD treatment through a qualitative analysis of public discussion forums on Reddit. METHODS: We collected data from Reddit, a free and international online platform dedicated to public discussions and user-generated content. We extracted 1000 of the most recent posts uploaded between March 5th and May 13th, 2020 from each of the two most popular opioid subreddits "r/Opiates" and "r/OpiatesRecovery" (total 2000). We reviewed posts for relevance to COVID-19 and opioid use and coded content using a hybrid inductive-deductive approach. Thematic analysis identified common themes related to study questions of interest. RESULTS: Of 2000 posts reviewed, 300 (15%) discussed topics related to the intersection of opioid use and COVID-19. Five major themes related to OUD treatment were identified: Concern about closure of OUD treatment services; transition to telehealth and virtual care; methadone treatment requirements and increased exposure to COVID-19; reactions to changing regulations on medications for OUD; and influences of the pandemic on treatment motivation and progress. CONCLUSION: In the face of unprecedented challenges due to COVID-19, reactions of Reddit opioid forum users ranged from increased distress in accessing and sustaining treatment, to encouragement surrounding new modes of treatment and opportunities to engage in care. New and less restrictive avenues for treatment were welcomed by many, but questions remain about how new norms and policy changes will be sustained beyond this pandemic and impact OUD treatment access and outcomes long-term.

A chance to do it better: Methadone maintenance treatment in the age of Covid-19.

Methadone maintenance treatment (MMT) in the United States, and particularly the clinic system of distribution, is often criticized as punitive, over-regulated, and misaligned to the needs of many patients. However, changes to the regulations that COVID-19 caused may have provided an opportunity for improving service. This commentary uses literature and my own experience to provide a brief description of how MMT programs responded to the threat of Covid-19 and how such responses fit into the larger context of attempts to reform treatment. It discusses, in particular, opportunities for liberalizing "take-home" doses and implementing office-based MMT.