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.

Medicaid expansion and opioid overdose mortality among socioeconomically disadvantaged populations in the US: A difference in differences analysis.

BACKGROUND: Opioid-related overdoses are a major cause of mortality in the US. Medicaid Expansion is posited to reduce opioid overdose-related mortality (OORM), and may have a particularly strong effect among people of lower socioeconomic status. This study assessed the association between state Medicaid Expansion and county-level OORM rates among individuals with low educational attainment. METHODS: This quasi-experimental study used lagged multilevel difference-in-difference models to test the relationship of state Medicaid Expansion to county-level OORM rates among people with a high-school diploma or less. Longitudinal (2008-2018) OORM data on 2978 counties nested in 48 states and the District of Columbia (DC) were drawn from the National Center for Health Statistics. The state-level exposure was a time-varying binary-coded variable capturing pre- and post-Medicaid Expansion under the Affordable Care Act (an "on switch"-type variable). The main outcome was annual county-level OORM rates among low-education adults adjusted for potential underreporting of OORM. FINDINGS: The adjusted county-level OORM rates per 100,000 among the study population rose on average from 10.26 (SD = 13.56) in 2008-14.51 (SD = 18.20) in 2018. In the 1-year lagged multivariable model that controlled for policy and sociodemographic covariates, the association between state Medicaid Expansion and county-level OORM rates was statistically insignificant. CONCLUSIONS: We found no evidence that expanding Medicaid eligibility reduced OORM rates among adults with lower educational attainment. Future work should seek to corroborate our findings and also identify - and repair - breakdowns in mechanisms that should link Medicaid Expansion to reduced overdoses.

Capacity for sustainment of recently established syringe service programs in Appalachian Kentucky: The central role of staff champions.

INTRODUCTION: Ensuring adequate harm reduction infrastructure in rural areas is imperative, as drug-related epidemics expand into them. Here, we explore the capacity for sustainment of syringe service programs (SSP) in Appalachian Kentucky. METHODS: We interviewed all staff (n = 16) of all SSPs (n = 7) in two Kentucky health districts in 2018-2019 using semi-structured one-on-one qualitative interviews; local departments of health (DOH) operated the SSPs. Interview domains encompassed: (i) SSP establishment; (ii) day-to-day operations, participation and health impacts; (iii) perceived prospects for sustainment; and (iv) perceived influences on #i-#iii. We analysed verbatim transcripts using thematic analytic methods; Schell's 'capacity for sustainment' constructs were treated as sensitising concepts during the analysis. RESULTS: Most community members, law enforcement and DOH staff opposed SSPs before they opened, because of stigma and concerns about enabling and needlestick injuries; DOH staff also opposed SSPs because they believed they lacked the capacity to operate them. Training, technical assistance, visible evidence of the programs' public health impact and contact with SSP participants transformed DOH staff into program champions. As champions, SSP staff developed programs that had strong capacity for sustainment, as defined by Schell (e.g. visible public health impact, stable funding, political support). Staff reported that the SSPs had high prospects for sustainment. DISCUSSION AND CONCLUSION: As in SSPs that opened in cities decades ago, staff in emerging SSPs in these rural areas appear to have become crucial champions for these controversial programs, and may serve as vital resources for expanding harm reduction programming more broadly in these underserved areas.

A qualitative study on pharmacy policies toward over-the-counter syringe sales in a rural epicenter of US drug-related epidemics.

BACKGROUND: Expanding access to sterile syringes in rural areas is vital, as injection-related epidemics expand beyond metropolitan areas globally. While pharmacies have potential to be an easily accessible source of sterile syringes, research in cities has identified moral, legal and ethical barriers that preclude over-the-counter (OTC) sales to people who inject drugs (PWID). The current study builds on prior urban-based research by elucidating (1) pharmacy OTC policies and (2) pharmacists' rationale for, and barriers and facilitators to, OTC syringe sales in a US rural area hard hit by drug-related epidemics. METHODS: We conducted 14 semi-structured interviews with pharmacists recruited from two Eastern Kentucky health districts. Interview domains included experiences with, and attitudes toward, selling OTC syringes to PWID. Constructivist grounded theory methods were used to analyze verbatim transcripts. RESULTS: Most pharmacists operated "restrictive OTC" pharmacies (n = 8), where patients were required to have a prescription or proof of medical need to purchase a syringe. The remainder (n = 6) operated "open OTC" pharmacies, which allowed OTC syringe sales to most patients. Both groups believed their pharmacy policies protected their community and pharmacy from further drug-related harm, but diverging policies emerged because of stigma toward PWID, perceptions of Kentucky law, and belief OTC syringe sales were harmful rather than protective to the community. CONCLUSION: Our results suggest that restrictive OTC pharmacy policies are rooted in stigmatizing views of PWID. Anti-stigma education about substance use disorder (SUD), human immunodeficiency virus (HIV), and Hepatitis C (HCV) is likely needed to truly shift restrictive pharmacy policy.

Factors that influence enrollment in syringe services programs in rural areas: a qualitative study among program clients in Appalachian Kentucky.

BACKGROUND: Enrolling sufficient number of people who inject drugs (PWID) into syringe services programs (SSP) is important to curtail outbreaks of drug-related harms. Still, little is known about barriers and facilitators to SSP enrollment in rural areas with no history of such programs. This study's purpose was to develop a grounded theory of the role of the risk environment and individual characteristics of PWID in shaping SSP enrollment in rural Kentucky. METHODS: We conducted one-on-one semi-structured interviews with 41 clients of 5 SSPs that were established in rural counties in Appalachian Kentucky in 2017-2018. Interviews covered PWID needs, the process of becoming aware of SSPs, and barriers and facilitators to SSP enrollment. Applying constructivist grounded theory methods and guided by the Intersectional Risk Environment Framework (IREF), we applied open, axial and selective coding to develop the grounded theory. RESULTS: Stigma, a feature of IREF's meso-level social domain, is the main factor hampering SSP enrollment. PWID hesitated to visit SSPs because of internalized stigma and because of anticipated stigma from police, friends, family and healthcare providers. Fear of stigma was often mitigated or amplified by a constellation of meso-level environmental factors related to healthcare (e.g., SSPs) and social (PWID networks) domains and by PWID's individual characteristics. SSPs mitigated stigma as a barrier to enrollment by providing low threshold services in a friendly atmosphere, and by offering their clients program IDs to protect them from paraphernalia charges. SSP clients spread positive information about the program within PWID networks and helped their hesitant peers to enroll by accompanying them to SSPs. Individual characteristics, including child custody, employment or high social status, made certain PWID more susceptible to drug-related stigma and hence more likely to delay SSP enrollment. CONCLUSIONS: Features of the social and healthcare environments operating at the meso-level, as well as PWID's individual characteristics, appear to enhance or mitigate the effect of stigma as a barrier to SSP enrollment. SSPs opening in locations with high stigma against PWID need to ensure low threshold and friendly services, protect their clients from police and mobilize PWID networks to promote enrollment.

Buprenorphine dispensing in an epicenter of the U.S. opioid epidemic: A case study of the rural risk environment in Appalachian Kentucky.

BACKGROUND: Buprenorphine is a cornerstone to curbing opioid epidemics, but emerging data suggest that rural pharmacists in the US sometimes refuse to dispense this medication. We conducted a case study to explore buprenorphine dispensing practices in 12 rural Appalachian Kentucky counties, and analyze whether and how they were shaped by features of the rural risk environment. METHODS: In this case study, we conducted one-on-one semi-structured interviews with 14 pharmacists operating 15 pharmacies in these counties to explore buprenorphine dispensing practices and perceived influences on these practices. Thematic analyses of the resulting transcripts revealed three features of the rural risk environment that shaped dispensing. To explore these three risk environment features, we analyzed policy documents (e.g., Attorney General lawsuits) and administrative databases (e.g., incarceration data). Textual documents were analyzed using thematic analyses and administrative data were analyzed using descriptive statistics; memoes explored relationships among risk environment features and dispensing practices. RESULTS: Twelve of the 15 pharmacies limited dispensing, by refusing to serve new patients; limiting dispensing to known patients or prescribers; or refusing to dispense buprenorphine altogether. Concerns about exceeding a "Drug Enforcement Administration (DEA) cap" on opioid dispensing stifled dispensing. A legacy of aggressive and fraudulent marketing of opioid analgesics (OAs) by pharmaceutical companies and physician OA overprescribing undermined pharmacist trust in buprenorphine and in its prescribers. The escalating local war on drugs may have undermined dispensing by reinforcing stigma against people who use drugs. CONCLUSIONS: Initiatives to increase buprenorphine prescribing must be accompanied by policy changes to increase dispensing. Specifically, buprenorphine should be removed from opioid monitoring systems; efforts to de-escalate the war on drugs should be extended to encompass rural areas; initiatives to dismantle aggressive OA marketing should be strengthened; and efforts to re-build pharmacist trust in physicians are needed.

People, places, and stigma: A qualitative study exploring the overdose risk environment in rural Kentucky.

BACKGROUND: Though overdose rates have been increasing in US rural areas for two decades, little is known about the rural risk environment for overdoses. This qualitative study explored the risk environment for overdoses among young adults in Eastern Kentucky, a rural epicenter of the US opioid epidemic. METHODS: Participants were recruited via community-based outreach. Eligibility criteria included living in one of five rural Eastern Kentucky counties; being aged 18-35; and using opioids to get high in the past 30 days. Semi-structured interviews explored the rural risk environment, and strategies to prevent overdose and dying from an overdose. Interviews were transcribed verbatim and analyzed using constructivist grounded-theory methods. RESULTS: In this sample (N = 19), participants reported using in a range of locations, including homes and outdoor settings; concerns about community stigma and law enforcement shaped the settings where participants used opioids and the strategies they deployed in these settings to prevent an overdose, and to survive an overdose. Almost half of participants reported using opioids in a "trap house" or other dealing locations, often to evade police after buying drugs, and reported that others present pressed them to use more than usual. If an overdose occurred in this setting, however, these same people might refuse to call EMS to protect themselves from arrest. Outdoor settings presented particular vulnerabilities to overdose and dying from an overdose. Most participants reported using opioids outdoors, where they skipped overdose prevention steps to reduce their risk of arrest; they worried that no one would find them if they overdosed, and that cell phone coverage would be too weak to summon EMS. CONCLUSION: Findings suggest that initiatives to reduce overdoses in Eastern Kentucky would be strengthened by de-escalating the War on Drugs and engaging law enforcement in initiatives to protect the health of people who use opioids.

Are Cocaine-Seeking "Habits" Necessary for the Development of Addiction-Like Behavior in Rats?

Drug self-administration models of addiction typically require animals to make the same response (e.g., a lever-press or nose-poke) over and over to procure and take drugs. By their design, such procedures often produce behavior controlled by stimulus-response (S-R) habits. This has supported the notion of addiction as a "drug habit," and has led to considerable advances in our understanding of the neurobiological basis of such behavior. However, to procure such drugs as cocaine, addicts often require considerable ingenuity and flexibility in seeking behavior, which, by definition, precludes the development of habits. To better model drug-seeking behavior in addicts, we first developed a novel cocaine self-administration procedure [puzzle self-administration procedure (PSAP)] that required rats to solve a new puzzle every day to gain access to cocaine, which they then self-administered on an intermittent access (IntA) schedule. Such daily problem-solving precluded the development of S-R seeking habits. We then asked whether prolonged PSAP/IntA experience would nevertheless produce "symptoms of addiction." It did, including escalation of intake, sensitized motivation for drug, continued drug use in the face of adverse consequences, and very robust cue-induced reinstatement of drug seeking, especially in a subset of "addiction-prone" rats. Furthermore, drug-seeking behavior continued to require dopamine neurotransmission in the core of the nucleus accumbens (but not the dorsolateral striatum). We conclude that the development of S-R seeking habits is not necessary for the development of cocaine addiction-like behavior in rats.SIGNIFICANCE STATEMENT Substance-use disorders are often characterized as "habitual" behaviors aimed at obtaining and administering drugs. Although the actions involved in consuming drugs may involve a rigid repertoire of habitual behaviors, evidence suggests that addicts must be very creative and flexible when trying to procure drugs, and thus drug seeking cannot be governed by habit alone. We modeled flexible drug-seeking behavior in rats by requiring animals to solve daily puzzles to gain access to cocaine. We find that habitual drug-seeking isn't necessary for the development of addiction-like behavior, and that our procedure doesn't result in transfer of dopaminergic control from the ventral to dorsal striatum. This approach may prove useful in studying changes in neuropsychological function that promote the transition to addiction.