DNA damage causes ATM-dependent heterochromatin loss leading to nuclear softening, blebbing, and rupture.

The nucleus must maintain stiffness to protect the shape and integrity of the nucleus to ensure proper function. Defects in nuclear stiffness caused from chromatin and lamin perturbations produce abnormal nuclear shapes common in aging, heart disease, and cancer. Loss of nuclear shape via protrusions called blebs leads to nuclear rupture that is well-established to cause nuclear dysfunction, including DNA damage. However, it remains unknown how increased DNA damage affects nuclear stiffness, shape, and ruptures, which could create a negative feedback loop. To determine if increased DNA damage alters nuclear physical properties, we treated MEF cells with DNA damage drugs cisplatin and bleomycin. DNA damage drugs caused increased nuclear blebbing and rupture in interphase nuclei within a few hours and independent of mitosis. Micromanipulation force measurements reveal that DNA damage decreased chromatin-based nuclear mechanics but did not change lamin-based strain stiffening at long extensions relative to wild type. Immunofluorescence measurements of DNA damage treatments reveal the mechanism is an ATM-dependent decrease in heterochromatin leading to nuclear weaken, blebbing, and rupture which can be rescued upon ATM inhibition treatment. Thus, DNA damage drugs cause ATM-dependent heterochromatin loss resulting in nuclear softening, blebbing, and rupture.

Barriers to Healthcare and Social Service Utilization Among Rural Older Adults Who Use Drugs.

The objective of this study was to understand barriers to healthcare and social service utilization among older adults residing in rural areas who use drugs. A cross-sectional survey of persons who use opioids or inject drugs in rural counties with high overdose rates across ten states was conducted. For this analysis, participants were restricted to only the 375 individuals aged 50 and older. They were asked about barriers to utilizing healthcare and social services. Multivariate analyses were conducted. The most common barriers were a lack of transportation and a fear of stigma. The average number of barriers was 2.53. Those who were either uninsured or homeless endorsed 37% more barriers. For every five-year increase in age, the number of barriers reduced by 15%. Efforts to reduce these barriers may include expanding eligibility for transportation and housing services and leveraging trusted community members to broker linkages to providers to overcome stigma.

Corrigendum to "Stigma towards persons who use methamphetamine: Results from a nationally representative survey of U.S. Adults" [Pre. Med. Rep. 36 (2023) 102496].

[This corrects the article DOI: 10.1016/j.pmedr.2023.102496.].

Opioid use, prescribing and fatal overdose patterns among racial/ethnic minorities in the United States: A scoping review and conceptual risk environment model.

ISSUES: To date, there has been no synthesis of research addressing the scale and nuances of the opioid epidemic in racial/ethnic minority populations in the United States that considers the independent and joint impacts of dynamics such as structural disadvantage, provider bias, health literacy, cultural norms and various other risk factors. APPROACH: Using the "risk environment" framework, we conducted a scoping review on PubMed, Embase and Google Scholar of peer-reviewed literature and governmental reports published between January 2000 and February 2024 on the nature and scale of opioid use, opioid prescribing patterns, and fatal overdoses among racial/ethnic minorities in the United States, while also examining macro, meso and individual-level risk factors. KEY FINDINGS: Results from this review illuminate a growing, but fragmented, literature lacking standardisation in racial/ethnic classification and case reporting, specifically in regards to Indigenous and Asian subpopulations. This literature broadly illustrates racial/ethnic minorities' increasing nonmedical use of opioids, heightened burdens of fatal overdoses, specifically in relation to polydrug use and synthetic opioids, with notable elevations among Black/Latino subgroups, in addition uneven opioid prescribing patterns. Moreover, the literature implicates a variety of unique risk environments corresponding to dynamics such as residential segregation, provider bias, overpolicing, acculturative stress, patient distrust, and limited access to mental health care services and drug treatment resources, including medications for opioid use disorder. IMPLICATIONS: There has been a lack of rigorous, targeted study on racial/ethnic minorities who use opioids, but evidence highlights burgeoning increases in usage, especially polydrug/synthetic opioid use, and disparities in prescriptions and fatal overdose risk-phenomena tied to multi-level forms of entrenched disenfranchisement. CONCLUSION: There is a need for further research on the complex, overlapping risk environments of racial/ethnic minorities who use opioids, including deeper inclusion of Indigenous and Asian individuals, and efforts to generate greater methodological synergies in population classification and reporting guidelines.

How do people who use opioids express their qualities and capacities? An assessment of attitudes, behaviors, and opportunities.

People who nonmedically use drugs (PWUD) face intricate social issues that suppress self-actualization, communal integration, and overall health and wellness. "Strengths-based" approaches, an under-used pedagogy and practice in addiction medicine, underscore the significance of identifying and recognizing the inherent and acquired skills, attributes, and capacities of PWUD. A strengths-based approach engenders client affirmation and improves their capacity to reduce drug use-related harms by leveraging existing capabilities. Exploring this paradigm, we conducted and analyzed interviews with 46 PWUD who were clients at syringe services programs in New York City and rural southern Illinois, two areas with elevated rates of opioid-related morbidity and mortality, to assess respondents' perceived strengths. We located two primary thematic modalities in which strengths-based ethos is expressed: individuals (1) being and advocate and resource for harm reduction knowledge and practices and (2) engaging in acts of continuous self-actualization. These dynamics demonstrate PWUD strengths populating and manifesting in complex ways that both affirm and challenge humanist and biomedical notions of individual agency, as PWUD refract enacted, anticipated, and perceived stigmas. In conclusion, programs that blend evidence-based, systems-level interventions on drug use stigma and disenfranchisement with meso and micro-level strengths-based interventions that affirm and leverage personal identity, decision-making capacity, and endemic knowledge may help disrupt health promotion cleavages among PWUD.

Evaluation of respondent-driven sampling in seven studies of people who use drugs from rural populations: findings from the Rural Opioid Initiative.

BACKGROUND: Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. METHODS: RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. RESULTS: Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. CONCLUSIONS: RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations.

Nuclear shape is affected differentially by loss of lamin A, lamin C, or both lamin A and C.

Lamin intermediate filaments form a peripheral meshwork to support nuclear shape and function. Knockout of the LMNA gene that encodes for both lamin A and C results in an abnormally shaped nucleus. To determine the relative contribution of lamin A and C to nuclear shape, we measured nuclear blebbing and circular deviation in separate lamin A and lamin C knockdown and LMNA-/- stable cells. Lamin A knockdown increased nuclear blebbing while loss of lamin A, C, or both increased circular deviation. Overall, loss of lamin A, lamin C or both lamin A/C affect nuclear shape differentially.

Actin contraction controls nuclear blebbing and rupture independent of actin confinement.

The nucleus is a mechanically stable compartment of the cell that contains the genome and performs many essential functions. Nuclear mechanical components chromatin and lamins maintain nuclear shape, compartmentalization, and function by resisting antagonistic actin contraction and confinement. Studies have yet to compare chromatin and lamins perturbations side-by-side as well as modulated actin contraction while holding confinement constant. To accomplish this, we used nuclear localization signal green fluorescent protein to measure nuclear shape and rupture in live cells with chromatin and lamin perturbations. We then modulated actin contraction while maintaining actin confinement measured by nuclear height. Wild type, chromatin decompaction, and lamin B1 null present bleb-based nuclear deformations and ruptures dependent on actin contraction and independent of actin confinement. Actin contraction inhibition by Y27632 decreased nuclear blebbing and ruptures while activation by CN03 increased rupture frequency. Lamin A/C null results in overall abnormal shape also reliant on actin contraction, but similar blebs and ruptures as wild type. Increased DNA damage is caused by nuclear blebbing or abnormal shape which can be relieved by inhibition of actin contraction which rescues nuclear shape and decreases DNA damage levels in all perturbations. Thus, actin contraction drives nuclear blebbing, bleb-based ruptures, and abnormal shape independent of changes in actin confinement.

Recent Incarceration, Substance Use, Overdose, and Service Use Among People Who Use Drugs in Rural Communities.

Importance: Drug use and incarceration have a substantial impact on rural communities, but factors associated with the incarceration of rural people who use drugs (PWUD) have not been thoroughly investigated. Objective: To characterize associations between recent incarceration, overdose, and substance use disorder (SUD) treatment access among rural PWUD. Design, Setting, and Participants: For this cross-sectional study, the Rural Opioid Initiative research consortium conducted a survey in geographically diverse rural counties with high rates of overdose across 10 US states (Illinois, Wisconsin, North Carolina, Oregon, Kentucky, West Virginia, Ohio, Massachusetts, New Hampshire, and Vermont) between January 25, 2018, and March 17, 2020, asking PWUD about their substance use, substance use treatment, and interactions with the criminal legal system. Participants were recruited through respondent-driven sampling in 8 rural US regions. Respondents who were willing to recruit additional respondents from their personal networks were enrolled at syringe service programs, community support organizations, and through direct community outreach; these so-called seed respondents then recruited others. Of 3044 respondents, 2935 included participants who resided in rural communities and reported past-30-day injection of any drug or use of opioids nonmedically via any route. Data were analyzed from February 8, 2022, to September 15, 2023. Exposure: Recent incarceration was the exposure of interest, defined as a report of incarceration in jail or prison for at least 1 day in the past 6 months. Main Outcomes and Measures: The associations between PWUD who were recently incarcerated and main outcomes of treatment use and overdose were examined using logistic regression. Results: Of 2935 participants, 1662 (56.6%) were male, 2496 (85.0%) were White; the mean (SD) age was 36 (10) years; and in the past 30 days, 2507 (85.4%) reported opioid use and 1663 (56.7%) reported injecting drugs daily. A total of 1224 participants (41.7%) reported recent incarceration, with a median (IQR) incarceration of 15 (3-60) days in the past 6 months. Recent incarceration was associated with past-6-month overdose (adjusted odds ratio [AOR], 1.38; 95% CI, 1.12-1.70) and recent SUD treatment (AOR, 1.62; 95% CI, 1.36-1.93) but not recent medication for opioid use disorder (MOUD; AOR, 1.03; 95% CI, 0.82-1.28) or currently carrying naloxone (AOR, 1.02; 95% CI, 0.86-1.21). Conclusions and Relevance: In this cross-sectional study of PWUD in rural areas, participants commonly experienced recent incarceration, which was not associated with MOUD, an effective and lifesaving treatment. The criminal legal system should implement effective SUD treatment in rural areas, including MOUD and provision of naloxone, to fully align with evidence-based SUD health care policies.

Stigma towards persons who use methamphetamine: Results from a nationally representative survey of U.S. Adults.

This study seeks to understand the general adult population's knowledge, attitudes, and stigma towards methamphetamine use and people with a history of methamphetamine use utilizing a cross-sectional national survey. We analyzed data from a cross-sectional survey drawn from AmeriSpeak®, a probability-based ongoing panel of over 35,000 households representative of the U.S. household population. We developed a 10-item social stigma scale, and estimated a multivariable generalized linear regression model for public stigma towards methamphetamine use as our dependent variable and a series of covariates. Six adjusted independent variables were noted to be significantly associated with higher stigma towards methamphetamine use: older age, higher household income, married status, Republican party affiliation, no history of methamphetamine use, and higher racism score. Sex assigned at birth, race (with Black as reference category), education level, and history of arrest or incarceration showed no statistical significance in stigma scores. In a separate regression model limited to people with a history of methamphetamine use (n = 727), notably White respondents had lower stigma compared to Black respondents. Our large population-based survey identified several factors associated with higher stigma towards those who use methamphetamines, including higher racist attitudes which was associated with a higher stigma score and higher internalized stigma amongst Black respondents with a history of methamphetamine use. Given the scope of methamphetamine use in the U.S., addressing stigma, in particular in regard to race, may impact the nation's public health efforts to reduce methamphetamine-associated adverse outcomes.

Houselessness and syringe service program utilization among people who inject drugs in eight rural areas across the USA: a cross-sectional analysis.

BACKGROUND: Research conducted in urban areas has highlighted the impact of housing instability on people who inject drugs (PWID), revealing that it exacerbates vulnerability to drug-related harms and impedes syringe service program (SSP) use. However, few studies have explored the effects of houselessness on SSP use among rural PWID. This study examines the relationship between houselessness and SSP utilization among PWID in eight rural areas across 10 states. METHODS: PWID were recruited using respondent-driven sampling for a cross-sectional survey that queried self-reported drug use and SSP utilization in the prior 30 days, houselessness in the prior 6 months and sociodemographic characteristics. Using binomial logistic regression, we examined the relationship between experiencing houselessness and any SSP use. To assess the relationship between houselessness and the frequency of SSP use, we conducted multinomial logistic regression analyses among participants reporting any past 30-day SSP use. RESULTS: Among 2394 rural PWID, 56.5% had experienced houselessness in the prior 6 months, and 43.5% reported past 30-day SSP use. PWID who had experienced houselessness were more likely to report using an SSP compared to their housed counterparts (adjusted odds ratio [aOR] = 1.24 [95% confidence intervals [CI] 1.01, 1.52]). Among those who had used an SSP at least once (n = 972), those who experienced houselessness were just as likely to report SSP use two (aOR = 0.90 [95% CI 0.60, 1.36]) and three times (aOR = 1.18 [95% CI 0.77, 1.98]) compared to once. However, they were less likely to visit an SSP four or more times compared to once in the prior 30 days (aOR = 0.59 [95% CI 0.40, 0.85]). CONCLUSION: This study provides evidence that rural PWID who experience houselessness utilize SSPs at similar or higher rates as their housed counterparts. However, housing instability may pose barriers to more frequent SSP use. These findings are significant as people who experience houselessness are at increased risk for drug-related harms and encounter additional challenges when attempting to access SSPs.

Associations of hepatitis C virus (HCV) antibody positivity with opioid, stimulant, and polysubstance injection among people who inject drugs (PWID) in rural U.S. communities.

BACKGROUND: People who inject drugs (PWID) in the rural U.S. often inject stimulants, alone or with opioids. The impact of these substance use patterns may influence HCV risk behaviors. This analysis examines the associations of HCV antibody positivity with injecting only opioids, only stimulants (methamphetamine/cocaine), and opioids and stimulants together among rural PWID. METHODS: The Rural Opioid Initiative (ROI) consists of eight research sites that enrolled people who use drugs in rural communities in ten U.S. states from 2018 to 2020. This cross-sectional analysis included adult participants who resided in a study area and injected any drug in the past 30 days. The primary outcome was HCV antibody positivity. The exposure of interest was injection drug use classified as only opioids, only stimulants, separate injections of opioids and stimulants, and same-syringe injection of both in the past 30 days. We used multivariable log-binomial regression with generalized linear mixed models to generate prevalence ratios (P.R.) adjusted for demographics, injection history, health insurance, and substance use treatment. RESULTS: Among 3,084 participants enrolled in the ROI, 1,982 met inclusion criteria. Most participants injected opioids and stimulants in the same syringe (34%) or separately (21%), followed by injecting only stimulants (26%), and injecting only opioids (19%). Half (51%) were HCV antibody positive. Compared to people who injected only stimulants, HCV antibody positivity was more prevalent among people who injected opioids alone (aPR=1.62, 95% CI:(1.29-2.03)), injected both opioids and stimulants separately (aPR=1.61, 95% CI:(1.32-1.95)), and in the same syringe (aPR=1.54, 95% CI:(1.28-1.85)). CONCLUSION: HCV antibody positivity, indicating prior exposure, was highest among those who had recently injected opioids, alone or with stimulants. Additional nucleic acid testing is necessary to confirm active infection. More research is needed to determine the underlying causes of HCV antibody positivity by injection use.

Transcription inhibition suppresses nuclear blebbing and rupture independently of nuclear rigidity.

Chromatin plays an essential role in the nuclear mechanical response and determining nuclear shape, which maintain nuclear compartmentalization and function. However, major genomic functions, such as transcription activity, might also impact cell nuclear shape via blebbing and rupture through their effects on chromatin structure and dynamics. To test this idea, we inhibited transcription with several RNA polymerase II inhibitors in wild-type cells and perturbed cells that presented increased nuclear blebbing. Transcription inhibition suppressed nuclear blebbing for several cell types, nuclear perturbations and transcription inhibitors. Furthermore, transcription inhibition suppressed nuclear bleb formation, bleb stabilization and bleb-based nuclear ruptures. Interestingly, transcription inhibition did not alter the histone H3 lysine 9 (H3K9) modification state, nuclear rigidity, and actin compression and contraction, which typically control nuclear blebbing. Polymer simulations suggested that RNA polymerase II motor activity within chromatin could drive chromatin motions that deform the nuclear periphery. Our data provide evidence that transcription inhibition suppresses nuclear blebbing and rupture, in a manner separate and distinct from chromatin rigidity.

Methamphetamine use and utilization of medications for opioid use disorder among rural people who use drugs.

BACKGROUND: Methamphetamine use is common among persons with opioid use disorder. This study evaluated associations between methamphetamine use and treatment with agonist medications for opioid use disorder (MOUD, specifically buprenorphine, and/or methadone) in U.S. rural communities. METHODS: The Rural Opioid Initiative (ROI) is a consortium spanning 10 states and 65 rural counties that included persons who reported past 30-day use of opioids and/or injection drug use between 1/2018 and 3/2020. Analyses were restricted to participants who had ever used opioids and had data on past 30-day methamphetamine use. Multivariable models examined the relationship between methamphetamine use and utilization of agonist MOUD. RESULTS: Among 2899 participants, 2179 (75.2%) also reported recent methamphetamine use. Persons with methamphetamine use compared to those without were younger, more likely to have injected drugs, be unhoused, criminal justice involved, and less likely to have health insurance. Adjusted for age, sex, race, and study site, recent methamphetamine use was associated with lower relative odds of past 30-day methadone treatment (aOR=0.66; 95% CI: 0.45-0.99) and fewer methadone treatment days (aIRR=0.76; 0.57-0.99), but not past 30-day buprenorphine receipt (aOR=0.90; 0.67-1.20), buprenorphine treatment days in past 6 months: aIRR=0.88; 0.69-1.12) or perceived inability to access buprenorphine (aOR=1.12; 0.87-1.44) or methadone (aOR=1.06; 0.76-1.48). CONCLUSION: Methamphetamine use is common among persons who use opioids in rural U.S. areas and negatively associated with current treatment and retention on methadone but not buprenorphine. Future studies should examine reasons for this disparity and reduce barriers to methadone for persons who use opioids and methamphetamine.

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.

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.

Attitudes toward harm reduction and low-threshold healthcare during the COVID-19 pandemic: qualitative interviews with people who use drugs in rural southern Illinois.

BACKGROUND: Chronic health conditions associated with long-term drug use may pose additional risks to people who use drugs (PWUD) when coupled with COVID-19 infection. Despite this, PWUD, especially those living in rural areas, may be less likely to seek out health services. Previous research has highlighted the increased disease burden of COVID-19 among PWUD. Our manuscript supplements this literature by exploring unique attitudes of PWUD living in rural areas toward the pandemic, COVID-19 vaccination, and the role of harm reduction (HR) organizations in raising health awareness among PWUD. METHODS: Semi-structured interviews were conducted with 20 PWUD living in rural southern Illinois. Audio recordings were professionally transcribed. A preliminary codebook was created based on interview domains. Two trained coders conducted iterative coding of the transcripts, and new codes were added through line-by-line coding and thematic grouping. RESULTS: Twenty participants (45% female, mean age of 38) completed interviews between June and November 2021. Participants reported negative impacts of the pandemic on mental health, financial wellbeing, and drug quality. However, the health impacts of COVID-19 were often described as less concerning than its impacts on these other aspects of life. Many expressed doubt in the severity of COVID-19 infection. Among the 16 unvaccinated participants who reported receiving most of their information from the internet or word of mouth, uncertainty about vaccine contents and distrust of healthcare and government institutions engendered wariness of the vaccination. Distrust of healthcare providers was related to past stigmatization and judgement, but did not extend to the local HR organization, which was unanimously endorsed as a positive institution. Among participants who did not access services directly from the HR organization, secondary distribution of HR supplies by other PWUD was a universally cited form of health maintenance. Participants expressed interest in low-threshold healthcare, including COVID-19 vaccination, should it be offered in the local HR organization's office and mobile units. CONCLUSION: COVID-19 and related public health measures have affected this community in numerous ways. Integrating healthcare services into harm reduction infrastructures and mobilizing secondary distributors of supplies may promote greater engagement with vaccination programs and other healthcare services. TRIAL NUMBER: NCT04427202.

Applying Project ECHO (Extension for Community Health Care Outcomes) to improve addiction care in rural emergency departments.

Background: Advancements in research and legislation have improved emergency provider ability to treat opioid use disorder (OUD), but dissemination into rural emergency departments (EDs) is limited. Project Extension for Community Healthcare Outcomes (ECHO) allows community generalists to learn from specialists through telementoring. We aimed to use ECHO to facilitate knowledge translation, increase confidence, and change behavior of rural ED providers treating patients with OUD. Methods: Stakeholder interviews were conducted with rural ED providers. A group of ED addiction experts created an ECHO curriculum with eight OUD topics. ED health professionals were recruited and completed pre/post surveys centered around knowledge and comfort with treating OUD in the ED, with focus on clinical practice and stigma. Following the ECHO model, sessions included a 20-min didactic followed by two cases presented by participants, with discussion facilitated by faculty. Results: Twenty-seven participants registered; seven attended ≥75% of sessions and completed both surveys. Of the seven, three were physicians, two advanced practice providers, one nurse, and one clinical pharmacist. Eight 1-hour sessions were conducted in two cohorts between January and December 2021. On a 5-point Likert scale, respondents on average agreed with questions evaluating acceptability (mean ± SD 3.96 ± 0.64), appropriateness (mean ± SD 4.18 ± 1.18), and feasibility (mean ± SD 4.00 ± 1.17). Participants had a 1.09-point increase (paired t-test = 2.43, p = 0.05) on 7-point Likert-scale questions measuring self-efficacy and a 0.13-point change (paired t-test = 2.64, p = 0.04) on 4-point Likert scale questions measuring stigmatizing attitudes (reduction of attitudes). A total of 71% (5/7) reported changes in clinical practice and 57% (4/7) in departmental protocols after participation. Conclusions: Our ED OUD ECHO course successfully created a model for rural ED providers to learn from ED addiction experts. It was well received and impacted self-reported provider stigmatizing attitudes, patient-facing behavior, and departmental initiatives. Recruitment was challenging and participation was limited. Future efforts will target maximizing recruitment.

The Rural Opioid Initiative Consortium description: providing evidence to Understand the Fourth Wave of the Opioid Crisis.

OBJECTIVE: To characterize and address the opioid crisis disproportionately impacting rural U.S. regions. METHODS: The Rural Opioid Initiative (ROI) is a two-phase project to collect and harmonize quantitative and qualitative data and develop tailored interventions to address rural opioid use. The baseline quantitative survey data from people who use drugs (PWUD) characterizes the current opioid epidemic (2018-2020) in eight geographically diverse regions. RESULTS: Among 3,084 PWUD, 92% reported ever injecting drugs, 86% reported using opioids (most often heroin) and 74% reported using methamphetamine to get high in the past 30 days; 53% experienced homelessness in the prior 6 months; and 49% had ever overdosed. Syringe service program use varied by region and 53% had ever received an overdose kit or naloxone prescription. Less than half (48%) ever received medication for opioid use disorder (MOUD). CONCLUSIONS: The ROI combines data across eight rural regions to better understand drug use including drivers and potential interventions in rural areas with limited resources. Baseline ROI data demonstrate extensive overlap between opioid and methamphetamine use, high homelessness rates, inadequate access to MOUD, and other unmet needs among PWUD in the rural U.S. By combining data across studies, the ROI provides much greater statistical power to address research questions and better understand the syndemic of infectious diseases and drug use in rural settings including unmet treatment needs.

Structural and community changes during COVID-19 and their effects on overdose precursors among rural people who use drugs: a mixed-methods analysis.

BACKGROUND: Drug overdose rates in the United States have been steadily increasing, particularly in rural areas. The COVID-19 pandemic and associated mitigation strategies may have increased overdose risk for people who use drugs by impacting social, community, and structural factors. METHODS: The study included a quantitative survey focused on COVID-19 administered to 50 people who use drugs and semi-structured qualitative interviews with 17 people who use drugs, 12 of whom also participated in the quantitative survey. Descriptive statistics were run for the quantitative data. Qualitative coding was line-by-line then grouped thematically. Quantitative and qualitative data were integrated during analysis. RESULTS: Findings demonstrate how COVID-19 disruptions at the structural and community level affected outcomes related to mental health and drug use at the individual level. Themes that emerged from the qualitative interviews were (1) lack of employment opportunities, (2) food and housing insecurity, (3) community stigma impacting health service use, (4) mental health strains, and (5) drug market disruptions. Structural and community changes increased anxiety, depression, and loneliness on the individual level, as well as changes in drug use patterns, all of which are likely to increase overdose risk. CONCLUSION: The COVID-19 pandemic, and mitigation strategies aimed at curbing infection, disrupted communities and lives of people who use drugs. These disruptions altered individual drug use and mental health outcomes, which could increase risk for overdose. We recommend addressing structural and community factors, including developing multi-level interventions, to combat overdose. Trial registration Clinicaltrails.gov: NCT04427202. Registered June 11, 2020: https://clinicaltrials.gov/ct2/show/NCT04427202?term=pho+mai&draw=2&rank=3.