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.

Syringe reuse among people who inject drugs in rural Appalachian Kentucky.

BACKGROUND: Personal syringe reuse (i.e., reuse of one's own syringes) can place people who inject drugs at increased risk for infectious disease but has received relatively little attention in published literature. The purpose of this study is to identify factors associated with syringe reuse among people who inject drugs in rural Kentucky. METHODS: Participants (n = 238) completed interviewer-administered questionnaires on syringe reuse and demographic, behavioral, and service access characteristics. Unadjusted negative binomial regression with cluster-robust standard errors was used to model the associations with a logged offset for number of injections in the past 30 days. RESULTS: The average age of the sample was 35 and 59.7 % were male. Most participants (77.7 %) reused syringes at least once in the past 30 days, using each syringe a median of three times. Reuse was higher among those who were older and reported a higher street price for syringes. Syringe reuse was lower among people who were within walking distance to a syringe service program (SSP) and who obtained most of their syringes from SSPs or pharmacies. CONCLUSION: Syringe reuse among people who inject drugs in rural Kentucky is common. However, these data suggest that increased access to syringes from SSPs and pharmacies, as well as policy-level interventions that reduce street syringe price, might reduce syringe reuse and related harms.

The relationship between felt stigma and non-fatal overdose among rural people who use drugs.

BACKGROUND: Drug overdose deaths in the United States exceeded 100,000 in 2021 and 2022. Substance use stigma is a major barrier to treatment and harm reduction utilization and is a priority target in ending the overdose epidemic. However, little is known about the relationship between stigma and overdose, especially in rural areas. We aimed to characterize the association between felt stigma and non-fatal overdose in a multi-state sample of rural-dwelling people who use drugs. METHODS: Between January 2018 and March 2020, 2,608 people reporting past 30-day opioid use were recruited via modified chain-referral sampling in rural areas across 10 states. Participants completed a computer-assisted survey of substance use and substance-related attitudes, behaviors, and experiences. We used multivariable logistic regression with generalized estimating equations to test the association between felt stigma and recent non-fatal overdose. RESULTS: 6.6% of participants (n = 173) reported an overdose in the past 30 days. Recent non-fatal overdose was significantly associated with felt stigma after adjusting for demographic and substance use-related covariates (aOR: 1.47, 95% CI: 1.20-1.81). The association remained significant in sensitivity analyses on component fear of enacted stigma items (aOR: 1.48, 95% CI: 1.20-1.83) and an internalized stigma item (aOR: 1.51, 95% CI: 1.07-2.14). CONCLUSIONS: Felt stigma related to substance use is associated with higher risk of non-fatal overdose in rural-dwelling people who use drugs. Stigma reduction interventions and tailored services for those experiencing high stigma are underutilized approaches that may mitigate overdose risk.

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.

Correlates of overdose among 2711 people who use drugs and live in 7 rural US sites.

BACKGROUND: Overdose rates in rural areas have been increasing globally, with large increases in the United States. Few studies, however, have identified correlates of non-fatal overdose among rural people who use drugs (PWUD). The present analysis describes correlates of nonfatal overdose among a large multistate sample of rural PWUD. METHODS: This is a cross-sectional analysis of data gathered via surveys with PWUD recruited through seven Rural Opioid Initiative (ROI) sites. Descriptive analyses were conducted to assess the prevalence of past 30-day overdose. Generalized estimating equations were used to estimate a series of multivariable models quantifying relationships of select factors to past-month overdose; factors were selected using the Risk Environment Framework. RESULTS: The multisite sample included 2711 PWUD, 6% of whom reported overdosing in the past 30 days. In the fully adjusted model, houselessness (AOR=2.27, 95%CI[1.48, 3.48]), a positive test result for Hepatitis C infection (AOR=1.73 95%CI[1.18, 2.52]) and heroin/fentanyl use (AOR= 8.58 95%CI [3.01, 24.50]) were associated with an increased risk of reporting past 30-day overdose, while having a high-school education or less was associated with reduced odds of overdose (AOR=0.52, 95% CI[0.37, 0.74]). CONCLUSION: As in urban areas, houselessness, Hepatitis C infection, and the use of heroin and fentanyl were significant correlates of overdose. Widespread access to overdose prevention interventions - including fentanyl test strips and naloxone - is critical in this rural context, with particular outreach needed to unhoused populations, people living with Hepatitis C, and people using opioids.

Person-centered hospital discharge data: Essential existing infrastructure to enhance public health surveillance of maternal substance use disorders in the midst of a national maternal overdose crisis.

OBJECTIVES: As crises of drug-related maternal harms escalate, US public health surveillance capacity remains suboptimal for drug-related maternal morbidities. Most state hospital discharge databases (HDDs) are encounter-based, and thus limit ascertainment of morbidities to delivery visits and ignoring those occurring during the 21 months spanning pregnancy and postpartum year. This study analyzes data from a state that curates person-centered HDD to compare patterns of substance use disorder (SUD) diagnoses at delivery vs. the full 21 pregnancy/postpartum months, overall and by maternal social position. METHODS: Among people who experienced an in-hospital birth in New York State between 9/1/2016 and 1/1/2018 (N = 330,872), we estimated SUD diagnosis (e.g., opioids, stimulants, benzodiazepines, cannabis) prevalence at delivery; across the full 9 months of pregnancy and 12 postpartum months; and by trimester and postpartum quarter. Risk ratio and risk difference estimated disparities by race/ethnicity, age, rurality, and payor. RESULTS: The 21-month SUD prevalence rate per 100,000 was 2671 (95% CI 2616-2726), with 31% (29.5%-31.5%) missing SUD indication when ascertained at delivery only (1866; 95% CI 1820-1912). Quarterly rates followed a roughly J-shaped trajectory. Structurally marginalized individuals suffered the highest 21-month SUD prevalence (e.g., Black:White risk ratio=1.80 [CI:1.73-1.88]). CONCLUSION: By spanning the full 21 months of pregnancy/postpartum, person-centered HDD reveal than the maternal SUD crisis is far greater than encounter-based delivery estimates had revealed. Generating person-centered HDD will improve efforts to tailor interventions to help people who use drugs survive while pregnant and postpartum, and eliminate inequities.

Nonrandom foraging and resource distributions affect the relationships between host density, contact rates and parasite transmission.

Nonrandom foraging can cause animals to aggregate in resource dense areas, increasing host density, contact rates and pathogen transmission, but when should nonrandom foraging and resource distributions also have density-independent effects? Here, we used a factorial experiment with constant resource and host densities to quantify host contact rates across seven resource distributions. We also used an agent-based model to compare pathogen transmission when host movement was based on random foraging, optimal foraging or something between those states. Nonrandom foraging strongly depressed contact rates and transmission relative to the classic random movement assumptions used in most epidemiological models. Given nonrandom foraging in the agent-based model and experiment, contact rates and transmission increased with resource aggregation and average distance to resource patches due to increased host movement in search of resources. Overall, we describe three density-independent mechanisms by which host behaviour and resource distributions alter contact rate functions and pathogen transmission.

Kentucky Outreach Service Kiosk (KyOSK) Study protocol: a community-level, controlled quasi-experimental, type 1 hybrid effectiveness study to assess implementation, effectiveness and cost-effectiveness of a community-tailored harm reduction kiosk on HIV, HCV and overdose risk in rural Appalachia.

INTRODUCTION: Many rural communities bear a disproportionate share of drug-related harms. Innovative harm reduction service models, such as vending machines or kiosks, can expand access to services that reduce drug-related harms. However, few kiosks operate in the USA, and their implementation, impact and cost-effectiveness have not been adequately evaluated in rural settings. This paper describes the Kentucky Outreach Service Kiosk (KyOSK) Study protocol to test the effectiveness, implementation outcomes and cost-effectiveness of a community-tailored, harm reduction kiosk in reducing HIV, hepatitis C and overdose risk in rural Appalachia. METHODS AND ANALYSIS: KyOSK is a community-level, controlled quasi-experimental, non-randomised trial. KyOSK involves two cohorts of people who use drugs, one in an intervention county (n=425) and one in a control county (n=325). People who are 18 years or older, are community-dwelling residents in the target counties and have used drugs to get high in the past 6 months are eligible. The trial compares the effectiveness of a fixed-site, staffed syringe service programme (standard of care) with the standard of care supplemented with a kiosk. The kiosk will contain various harm reduction supplies accessible to participants upon valid code entry, allowing dispensing data to be linked to participant survey data. The kiosk will include a call-back feature that allows participants to select needed services and receive linkage-to-care services from a peer recovery coach. The cohorts complete follow-up surveys every 6 months for 36 months (three preceding kiosk implementation and four post-implementation). The study will test the effectiveness of the kiosk on reducing risk behaviours associated with overdose, HIV and hepatitis C, as well as implementation outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: The University of Kentucky Institutional Review Board approved the protocol. Results will be disseminated in academic conferences and peer-reviewed journals, online and print media, and community meetings. TRIAL REGISTRATION NUMBER: NCT05657106.

Validation of dried blood spots for capturing hepatitis C virus diversity for genomic surveillance.

Dried blood spots (DBS) have emerged as a promising alternative to traditional venous blood for hepatitis C virus (HCV) testing. However, their capacity to accurately reflect the genetic diversity of HCV remains poorly understood. We employed deep sequencing and advanced phylogenetic analyses on paired plasma and DBS samples from two common subtypes to evaluate the suitability of DBS for genomic surveillance. Results demonstrated that DBS captured equivalent viral diversity compared to plasma with no phylogenetic discordance observed. The ability of DBS to accurately reflect the profile of viral genetic diversity suggests it may be a promising avenue for future surveillance efforts to curb HCV outbreaks.

Correlates of Recent HIV Testing Among People Who Inject Drugs in Rural Areas: A Multi-site Cross-Sectional Study, 2018-2020.

The Rural Opioid Initiative surveyed 2693 people who inject drugs (PWID) in eight rural U.S. areas in 2018-2020 about self-reported HIV testing in the past 6 months. Correlates of interest included receipt of any drug-related services, incarceration history, and structural barriers to care (e.g., lack of insurance, proximity to syringe service programs [SSP]). Overall, 20% of participants reported receiving an HIV test within the past 6 months. Multivariable generalized estimating equations showed that attending substance use disorder (SUD) treatment (OR 2.11, 95%CI [1.58, 2.82]), having health insurance (OR 1.42, 95%CI [1.01, 2.00]) and recent incarceration (OR 1.49, 95%CI [1.08, 2.04]) were positively associated with HIV testing, while experiencing a resource barrier to healthcare (inability to pay, lack of transportation, inconvenient hours, or lack of child care) had inverse (OR 0.73, 95%CI [0.56, 0.94]) association with HIV testing. We found that the prevalence of HIV testing among rural PWID is low, indicating an unmet need for testing. While SUD treatment or incarceration may increase chances for HIV testing for rural PWID, other avenues for expanding HIV testing, such as SSP, need to be explored.

Association of Medicaid expansion with health insurance, unmet need for medical care and substance use disorder treatment among people who inject drugs in 13 US states.

BACKGROUND AND AIMS: Impoverished people who inject drugs (PWID) are at the epicenter of US drug-related epidemics. Medicaid expansion is designed to reduce cost-related barriers to care by expanding Medicaid coverage to all US adults living at or below 138% of the federal poverty line. This study aimed to measure whether Medicaid expansion is (1) positively associated with the probability that participants are currently insured; (2) inversely related to the probability of reporting unmet need for medical care due to cost in the past year; and (3) positively associated with the probability that they report receiving substance use disorder (SUD) treatment in the past year, among PWID subsisting at ≤ 138% of the federal poverty line. DESIGN: A two-way fixed-effects model was used to analyze serial cross-sectional observational data. SETTING: Seventeen metro areas in 13 US states took part in the study. PARTICIPANTS: Participants were PWID who took part in any of the three waves (2012, 2015, 2018) of data gathered in the Center for Disease Control and Prevention's National HIV Behavioral Surveillance (NHBS), were aged ≤ 64 years and had incomes ≤ 138% of the federal poverty line. For SUD treatment analyses, the sample was further limited to PWID who used drugs daily, a proxy for SUD. MEASUREMENTS: State-level Medicaid expansion was measured using Kaiser Family Foundation data. Individual-level self-report measures were drawn from the NHBS surveys (e.g. health insurance coverage, unmet need for medical care because of its cost, SUD treatment program participation). FINDINGS: The sample for the insurance and unmet need analyses consisted of 19 946 impoverished PWID across 13 US states and 3 years. Approximately two-thirds were unhoused in the past year; 41.6% reported annual household incomes < $5000. In multivariable models, expansion was associated with a 19.0 [95% confidence interval (CI) = 9.0, 30.0] percentage-point increase in the probability of insurance coverage, and a 9.0 (95% CI = -15.0, -0.2) percentage-point reduction in the probability of unmet need. Expansion was unrelated to SUD treatment among PWID who used daily (n = 17 584). CONCLUSIONS: US Medicaid expansion may curb drug-related epidemics among impoverished people who inject drugs by increasing health insurance coverage and reducing unmet need for care. Persisting non-financial barriers may undermine expansion's impact upon substance use disorder treatment in this sample.

Willingness to utilize a mobile treatment unit in five counties at the epicenter of the US rural opioid epidemic.

INTRODUCTION: US federal policies are evolving to expand the provision of mobile treatment units (MTUs) offering medications for opioid use disorder (MOUD). Mobile MOUD services are critical for rural areas with poor geographic access to fixed-site treatment providers. This study explored willingness to utilize an MTU among a sample of people who use opioids in rural Eastern Kentucky counties at the epicenter of the US opioid epidemic. METHODS: The study analyzed Cross-sectional survey data from the Kentucky Communities and Researchers Engaging to Halt the Opioid Epidemic (CARE2HOPE) study covering five rural counties in the state. Logistic regression models investigated the association between willingness to utilize an MTU providing buprenorphine and naltrexone and potential correlates of willingness, identified using the Behavioral Model for Vulnerable Populations. RESULTS: The analytic sample comprised 174 people who used opioids within the past six months. Willingness to utilize an MTU was high; 76.5 % of participants endorsed being willing. Those who had recently received MOUD treatment, compared to those who had not received any form of treatment or recovery support services, had six-fold higher odds of willingness to use an MTU. However, odds of being willing to utilize an MTU were 73 % lower among those who were under community supervision (e.g., parole, probation) and 81 % lower among participants who experienced an overdose within the past six months. CONCLUSIONS: There was high acceptability of MTUs offering buprenorphine and naltrexone within this sample, highlighting the potential for MTUs to alleviate opioid-related harms in underserved rural areas. However, the finding that people who were recently under community supervision or had overdosed were significantly less willing to seek mobile MOUD treatment suggest barriers (e.g., stigma) to mobile MOUD at individual and systemic levels, which may prevent improving opioid-related outcomes in these rural communities given their high rates of criminal-legal involvement and overdose.

Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease.

Objective: To determine the ages at acquisition of developmental milestones, loss of motor function, and clinical symptoms in Alexander disease. Methods: Patients with confirmed cerebral Alexander disease were included. Data abstraction of developmental and disease-specific milestones was performed from medical records, physical exams, and questionnaires. Mixed effects logistic regression was used to determine if key clinical features were associated with milestone achievement, controlling for patient age. Results: 51 patients with cerebral/infantile Alexander disease were evaluated at a mean age of 10.96 years (range 2.29-31.08 years). Developmental milestones in Alexander disease were often achieved but delayed. Ambulation was achieved in 44 subjects (86%); 34 (67%) subjects walked independently (mean age 1.9 years, range 0.91-3.25 years) and an additional 10 (20%) subjects walked with assistance (mean age 3.9 years, range 1.8-8 years) but did not progress to independent ambulation. Developmental delay was the earliest and most prevalent symptom (N = 48 [94%], mean age 0.58 years), compared to an initial seizure (N = 41 [80%], mean age 2.80 years), and macrocephaly (N = 28 [55%], mean age 4.04 years), P < .0001 between these ages of onset. Loss of independent ambulation occurred in 11 of the 34 (32%) children who had acquired ambulation (range 3.41-15.10 years). Presence of seizures or macrocephaly did not predict the achievement or loss of ambulation. Conclusions: The clinical triad of developmental delay, seizures, and macrocephaly are not universally present in cerebral Alexander disease. Clinicians should have a high index of suspicion for Alexander disease in patients with mild delays and a first seizure.

"I'm not going to lay back and watch somebody die": a qualitative study of how people who use drugs' naloxone experiences are shaped by rural risk environment and overdose education/naloxone distribution intervention.

BACKGROUND: Overdoses have surged in rural areas in the U.S. and globally for years, but harm reduction interventions have lagged. Overdose education and naloxone distribution (OEND) programs reduce overdose mortality, but little is known about people who use drugs' (PWUD) experience with these interventions in rural areas. Here, we analyze qualitative data with rural PWUD to learn about participants' experiences with an OEND intervention, and about how participants' perceptions of their rural risk environments influenced the interventions' effects. METHODS: Twenty-nine one-on-one, semi-structured qualitative interviews were conducted with rural PWUD engaged in the CARE2HOPE OEND intervention in Appalachian Kentucky. Interviews were conducted via Zoom, audio-recorded, and transcribed verbatim. Thematic analysis was conducted, guided by the Rural Risk Environment Framework. RESULTS: Participants' naloxone experiences were shaped by all domains of their rural risk environments. The OEND intervention transformed participants' roles locally, so they became an essential component of the local rural healthcare environment. The intervention provided access to naloxone and information, thereby increasing PWUDs' confidence in naloxone administration. Through the intervention, over half of participants gained knowledge on naloxone (access points, administration technique) and on the criminal-legal environment as it pertained to naloxone. Most participants opted to accept and carry naloxone, citing factors related to the social environment (responsibility to their community) and physical/healthcare environments (overdose prevalence, suboptimal emergency response systems). Over half of participants described recent experiences administering intervention-provided naloxone. These experiences were shaped by features of the local rural social environment (anticipated negative reaction from recipients, prior naloxone conversations). CONCLUSIONS: By providing naloxone paired with non-stigmatizing health and policy information, the OEND intervention offered support that allowed participants to become a part of the healthcare environment. Findings highlight need for more OEND interventions; outreach to rural PWUD on local policy that impacts them; tailored strategies to help rural PWUD engage in productive dialogue with peers about naloxone and navigate interpersonal conflict associated with overdose reversal; and opportunities for rural PWUD to formally participate in emergency response systems as peer overdose responders. Trial registration The ClinicalTrials.gov ID for the CARE2HOPE intervention is NCT04134767. The registration date was October 19th, 2019.

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.

Macrophage phenotype impacts in vitro equine intrasynovial deep digital flexor tenocyte matrix metalloproteinase gene expression and secretion.

OBJECTIVE: To investigate matrix metalloproteinase (MMP) and their inhibitors tissue inhibitor matrix metalloproteinase (TIMP) gene expression and secretion during equine deep digital flexor tendon (DDFT) tenocyte and macrophage (undifferentiated, proinflammatory, and regulatory) co-culture. SAMPLE: Third passage DDF tenocytes and donor-matched macrophages differentiated from peripheral blood CD14+ monocytes from 5 healthy horses ages 9-11 years, euthanized for reasons unrelated to musculoskeletal conditions. METHODS: Passage 3 DDT tenocyte aggregate cultures were co-cultured with undifferentiated (control), proinflammatory (granulocyte-macrophage colony-stimulating factor; GM-CSF pretreated and lipopolysaccharide + interferon gamma-primed; LPS+IFN-γ) or regulatory (interleukin-4 and interleukin-10-primed; IL-4 + IL-10) macrophages in direct and transwell co-cultures for 72 hours. MMP-1, -2, -3, -9, -13, and TIMP -1, -2 mRNA were measured via real-time Polymerase Chain Reaction (rtPCR). Co-culture media MMP -3, -9, and TIMP -1, -2 concentrations were quantified via ELISA. RESULTS: Direct co-culture of DDF tenocytes with proinflammatory macrophages for 72 hours increased MMP-1, -3, and -13 mRNA levels whereas, MMP-9 mRNA levels decreased. Direct and transwell co-culture with proinflammatory and regulatory macrophages resulted in increased MMP-3 and decreased MMP-9 media concentrations. While direct co-culture with regulatory macrophages significantly increased TIMP-1 mRNA, overall, TIMP mRNA and culture media concentrations were largely unchanged. CLINICAL RELEVANCE: Cell-to-cell contact between DDF tenocytes and macrophages is not essential to induce MMP gene expression and secretion. Co-culture systems offer a viable in vitro platform to screen and evaluate immunomodulatory properties of therapies aimed at improving equine intrasynovial tendon healing.

"I'm not going to lay back and watch somebody die": A qualitative study of how people who use drugs' naloxone experiences are shaped by rural risk environment and naloxone distribution/overdose education intervention.

Background: Overdoses have surged in rural areas in the U.S. and globally for years, but harm reduction interventions have lagged. Overdose education and naloxone distribution (OEND) programs are highly effective to prevent overdose mortality, but little is known about people who use drugs' (PWUD) experience with these interventions in rural areas. Here, we analyze qualitative data with rural PWUD to learn about their experiences with an OEND intervention, and about how their perceptions of their rural risk environments influenced the interventions' effects. Methods: Twenty-nine one-on-one, semi-structured qualitative interviews were conducted with rural PWUD engaged in the CARE2HOPE OEND intervention in Appalachian Kentucky. Interviews were conducted via Zoom, audio-recorded, and transcribed verbatim. Thematic analysis was conducted, guided by the Rural Risk Environment Framework. Results: The OEND intervention transformed participants' roles locally, so they became an essential component of the local rural healthcare environment. The intervention provided access to naloxone and information, thereby increasing PWUD's confidence in naloxone administration. Through the intervention, over half of participants gained knowledge on naloxone (access points, administration technique) and on the criminal-legal environment as it pertained to naloxone. Most participants opted to accept and carry naloxone, citing factors related to the social environment (sense of responsibility to their community) and physical/healthcare environments (high overdose prevalence, suboptimal emergency response systems). Over half of participants described recent experiences administering intervention-provided naloxone. These experiences were shaped by features of the local rural social environment (anticipated negative reaction from recipients, prior naloxone conversations). Conclusions: By providing naloxone paired with non-stigmatizing health and policy information, the OEND intervention offered the material and informational support that allowed participants to become a part of the healthcare environment. Findings highlight need for more outreach to rural PWUD on local policy that impacts them; tailored strategies to help rural PWUD engage in productive dialogue with peers about naloxone and navigate interpersonal conflict associated with overdose reversal; and opportunities for rural PWUD to formally participate in emergency response systems as peer overdose responders. Trial registration: The ClinicalTrials.gov ID for the CARE2HOPE intervention is NCT04134767. The registration date was October 19th, 2019.

Socioeconomic and racial/ethnic spatial polarization and incarceration among people who inject drugs in 19 US metropolitan areas, 2015.

The purpose of this study is to test, for the first time, the association between spatial social polarization and incarceration among people who inject drugs (PWID) in 19 large U.S. metropolitan statistical areas (MSAs) in 2015. PWID were recruited from MSAs for the Centers for Disease Control and Prevention's 2015 National HIV Behavioral Surveillance. Administrative data were used to describe the ZIP-code areas, counties, and MSAs where PWID lived. We operationalized spatial polarization using the Index of Concentration at the Extremes (ICE), a measure that reflects polarization in race and household income at the ZIP-code level. We tested the association between spatial polarization and odds of past-year arrest and detainment using multilevel multivariable models. We found 37% of the sample reported being incarcerated in the past year. Report of past-year incarceration varied by race/ethnicity: 45% of non-Hispanic white PWID reported past-year incarceration, as did 25% of non-Hispanic Black PWID, and 43% of Hispanic/Latino PWID (N = 9047). Adjusted odds ratios suggest that Black PWID living in ZIP-code areas with a higher ICE score, meaning more white and affluent, had higher odds of past-year incarceration, compared to white PWID. In previous research, incarceration has been found to be associated with HIV acquisition and can deter PWID from engaging in harm reduction activities.

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.