Machine Learning-Driven Analysis of Individualized Treatment Effects Comparing Buprenorphine and Naltrexone in Opioid Use Disorder Relapse Prevention.

OBJECTIVE: A trial comparing extended-release naltrexone and sublingual buprenorphine-naloxone demonstrated higher relapse rates in individuals randomized to extended-release naltrexone. The effectiveness of treatment might vary based on patient characteristics. We hypothesized that causal machine learning would identify individualized treatment effects for each medication. METHODS: This is a secondary analysis of a multicenter randomized trial that compared the effectiveness of extended-release naltrexone versus buprenorphine-naloxone for preventing relapse of opioid misuse. Three machine learning models were derived using all trial participants with 50% randomly selected for training (n = 285) and the remaining 50% for validation. Individualized treatment effect was measured by the Qini value and c-for-benefit, with the absence of relapse denoting treatment success. Patients were grouped into quartiles by predicted individualized treatment effect to examine differences in characteristics and the observed treatment effects. RESULTS: The best-performing model had a Qini value of 4.45 (95% confidence interval, 1.02-7.83) and a c-for-benefit of 0.63 (95% confidence interval, 0.53-0.68). The quartile most likely to benefit from buprenorphine-naloxone had a 35% absolute benefit from this treatment, and at study entry, they had a high median opioid withdrawal score (P < 0.001), used cocaine on more days over the prior 30 days than other quartiles (P < 0.001), and had highest proportions with alcohol and cocaine use disorder (P ≤ 0.02). Quartile 4 individuals were predicted to be most likely to benefit from extended-release naltrexone, with the greatest proportion having heroin drug preference (P = 0.02) and all experiencing homelessness (P < 0.001). CONCLUSIONS: Causal machine learning identified differing individualized treatment effects between medications based on characteristics associated with preventing relapse.

Alcohol Withdrawal Severity Measures for Identifying Patients Requiring High-Intensity Care.

OBJECTIVES: Alcohol withdrawal syndrome (AWS) may progress to require high-intensity care. Approaches to identify hospitalized patients with AWS who received higher level of care have not been previously examined. This study aimed to examine the utility of Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) for alcohol scale scores and medication doses for alcohol withdrawal management in identifying patients who received high-intensity care. DESIGN: A multicenter observational cohort study of hospitalized adults with alcohol withdrawal. SETTING: University of Chicago Medical Center and University of Wisconsin Hospital. PATIENTS: Inpatient encounters between November 2008 and February 2022 with a CIWA-Ar score greater than 0 and benzodiazepine or barbiturate administered within the first 24 hours. The primary composite outcome was patients who progressed to high-intensity care (intermediate care or ICU). INTERVENTIONS: None. MAIN RESULTS: Among the 8742 patients included in the study, 37.5% (n = 3280) progressed to high-intensity care. The odds ratio for the composite outcome increased above 1.0 when the CIWA-Ar score was 24. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at this threshold were 0.12 (95% CI, 0.11-0.13), 0.95 (95% CI, 0.94-0.95), 0.58 (95% CI, 0.54-0.61), and 0.64 (95% CI, 0.63-0.65), respectively. The OR increased above 1.0 at a 24-hour lorazepam milligram equivalent dose cutoff of 15 mg. The sensitivity, specificity, PPV, and NPV at this threshold were 0.16 (95% CI, 0.14-0.17), 0.96 (95% CI, 0.95-0.96), 0.68 (95% CI, 0.65-0.72), and 0.65 (95% CI, 0.64-0.66), respectively. CONCLUSIONS: Neither CIWA-Ar scores nor medication dose cutoff points were effective measures for identifying patients with alcohol withdrawal who received high-intensity care. Research studies for examining outcomes in patients who deteriorate with AWS will require better methods for cohort identification.

Association of Fentanyl Test Strip Use, Perceived Overdose Risk, and Naloxone Possession among People Who Use Drugs.

Background: As opioid overdoses continue rising, interventions are needed to expand naloxone carriage, an opioid overdose reversal agent. Use of fentanyl test strips (FTS) might promote naloxone carriage. This study examines the relationship between FTS use, perceived overdose risk, and naloxone carriage in Wisconsin, United States. Methods: In a survey of people who use drugs (n = 341) in southern Wisconsin, respondents were asked about FTS use, perceived overdose risk, and how often they (1) have naloxone, (2) have more than one dose of naloxone, and (3) the number of naloxone doses possessed currently. Likert responses were mapped to an integer scale. Ordinal and linear multivariable regression examined the relationship between FTS use and study outcomes while adjusting for respondent characteristics. Results: Most respondents were male (59.6%), identified heroin as their drug of choice (70.7%) and reported intravenous use (87.9%). In unadjusted models, FTS use was associated with more often having naloxone (OR: 2.10; p = 0.005), more often having multiple naloxone doses (OR: 2.98; p < 0.001), and possessing a greater number of naloxone doses (dose count difference: 2.85; p = 0.001). In adjusted models, FTS use was associated with more often having multiple naloxone doses (OR: 2.29; p = 0.005) and possessing a greater number of naloxone doses (dose count difference: 2.25, p = 0.020). Conclusions: Individuals who use FTS more often carry multiple doses relative to individuals who do not use FTS. Given that naloxone carriage is critical for reducing opioid overdose risk, expanding FTS use may offer a strategy to reduce opioid overdose rates via improved naloxone carriage.

Creation of a data commons for substance misuse related health research through privacy-preserving patient record linkage between hospitals and state agencies.

Objectives: Substance misuse is a complex and heterogeneous set of conditions associated with high mortality and regional/demographic variations. Existing data systems are siloed and have been ineffective in curtailing the substance misuse epidemic. Therefore, we aimed to build a novel informatics platform, the Substance Misuse Data Commons (SMDC), by integrating multiple data modalities to provide a unified record of information crucial to improving outcomes in substance misuse patients. Materials and Methods: The SMDC was created by linking electronic health record (EHR) data from adult cases of substance (alcohol, opioid, nonopioid drug) misuse at the University of Wisconsin hospitals to socioeconomic and state agency data. To ensure private and secure data exchange, Privacy-Preserving Record Linkage (PPRL) and Honest Broker services were utilized. The overlap in mortality reporting among the EHR, state Vital Statistics, and a commercial national data source was assessed. Results: The SMDC included data from 36 522 patients experiencing 62 594 healthcare encounters. Over half of patients were linked to the statewide ambulance database and prescription drug monitoring program. Chronic diseases accounted for most underlying causes of death, while drug-related overdoses constituted 8%. Our analysis of mortality revealed a 49.1% overlap across the 3 data sources. Nonoverlapping deaths were associated with poor socioeconomic indicators. Discussion: Through PPRL, the SMDC enabled the longitudinal integration of multimodal data. Combining death data from local, state, and national sources enhanced mortality tracking and exposed disparities. Conclusion: The SMDC provides a comprehensive resource for clinical providers and policymakers to inform interventions targeting substance misuse-related hospitalizations, overdoses, and death.

Treatment Updates for Pain Management and Opioid Use Disorder.

The medical community has proposed several clinical recommendations to promote patient safety and health amid the opioid overdose public health crisis. For a frontline practicing physician, distilling the evidence and implementing the latest guidelines may prove challenging. This article aims to highlight pertinent updates and clinical care pearls as they relate to primary care management of chronic pain and opioid use disorder.

Differences in drug use behaviors that impact overdose risk among individuals who do and do not use fentanyl test strips for drug checking.

BACKGROUND: Opioid-involved overdose continues to rise, largely explained by fentanyl adulteration of the illicit opioid supply. Fentanyl test strips are a novel drug checking tool that can be used by people who use drugs to detect the presence of fentanyl in drug products. However, it is unclear whether fentanyl test strip use can prompt behavior changes that impact risk of overdose. METHODS: In this mixed-methods study involving a structured survey (n = 341) of syringe service program clients in southern Wisconsin, we examined the association between fentanyl test strip use and overdose risk behaviors in scenarios where the presence of fentanyl is confirmed and unknown. Individual items were transformed into summary scales representing the performance of riskier and safer behaviors. Linear regression examined the association of behaviors with FTS use. Models are adjusted for study site, race/ethnicity, age, gender, drug of choice, indicator of polysubstance use, times used per day, and lifetime overdose count. RESULTS: In response to survey questions before prompting about fentanyl risk, people who used fentanyl test strips reported an increased number of safer (p = 0.001) as well as riskier behaviors (p = 0.018) relative to people who did not use fentanyl test strips. The same held true in situations when fentanyl adulteration was suspected, though fentanyl test strip use lost significance in the fully adjusted model examining safer behaviors (safer: p = 0.143; riskier: p = 0.004). Among people who use fentanyl test strips, in unadjusted models, a positive test result was associated with more safer behaviors and fewer riskier behaviors, but these associations became nonsignificant in fully adjusted models (safer: p = 0.998; riskier: p = 0.171). Loss of significance was largely due to the addition of either polysubstance use or age to the model. CONCLUSIONS: Fentanyl test strip use is associated with behaviors that may impact overdose risk, including safer and riskier behaviors. Specifically, a positive test result may promote more risk reducing behaviors and fewer risk enhancing behaviors than a negative test result. Results suggest that while FTS may promote safer drug use behaviors, outreach and education should emphasize the need for multiple harm reduction techniques in all scenarios.

Patterns of opioid use behaviors among patients seen in the emergency department: Latent class analysis of baseline data from the POINT pragmatic trial.

INTRODUCTION: The nation's overdose epidemic has been characterized by increasingly potent opioids resulting in more emergency department (ED) encounters over time. ED-based opioid use interventions are growing in popularity; however, they tend to treat people who use opioids as a homogenous population. The current study sought to understand heterogeneity among people who use opioids who encounter the ED by identifying qualitatively different subgroups among participants in an opioid use intervention clinical trial at baseline and examining associations between subgroup membership and multiple correlates. METHODS: Participants were from a larger pragmatic clinical trial of the Planned Outreach, Intervention, Naloxone, and Treatment (POINT) intervention (n = 212; 59.2 % male, 85.3 % Non-Hispanic White, mean age = 36.6 years). The study employed latent class analysis (LCA) using five indicators of opioid use behavior: preference for opioids, preference for stimulants, usually use drugs alone, injection drug use, and opioid-related problem at ED encounter. Correlates of interest included participants' demographics, prescription histories, health care contact histories, and recovery capital (e.g., social support, naloxone knowledge). RESULTS: The study identified three classes: (1) noninjecting opioid preferers, (2) injecting opioid and stimulant preferers, and (3) social nonopioid preferers. We identified limited significant differences in correlates across the classes: differences existed for select demographics, prescription histories, and recovery capital but not for health care contact histories. For example, members of Class 1 were the most likely to be a race/ethnicity other than non-Hispanic White, oldest on average, and most likely to have received a benzodiazepine prescription, whereas members of Class 2 had the highest average barriers to treatment and members of Class 3 were the least likely to have been diagnosed with a major mental health illness and had the lowest average barriers to treatment. CONCLUSIONS: LCA identified distinct subgroups among POINT trial participants. Knowledge of such subgroups assists with the development of better-targeted interventions and can help staff to identify the most appropriate treatment and recovery pathways for patients.

Contraception and Healthcare Utilization by Reproductive-Age Women Who Use Drugs in Rural Communities: a Cross-Sectional Survey.

BACKGROUND: Women who use drugs (WWUD) have low rates of contraceptive use and high rates of unintended pregnancy. Drug use is common among women in rural U.S. communities, with limited data on how they utilize reproductive, substance use disorder (SUD), and healthcare services. OBJECTIVE: We determined contraceptive use prevalence among WWUD in rural communities then compared estimates to women from similar rural areas. We investigated characteristics of those using contraceptives, and associations between contraceptive use and SUD treatment, healthcare utilization, and substance use. DESIGN: Rural Opioids Initiative (ROI) - cross-sectional survey using respondent-driven sampling (RDS) involving eight rural U.S. regions (January 2018-March 2020); National Survey on Family Growth (NSFG) - nationally-representative U.S. household reproductive health survey (2017-2019). PARTICIPANTS: Women aged 18-49 with prior 30-day non-prescribed opioid and/or non-opioid injection drug use; fecundity determined by self-reported survey responses. MAIN MEASURES: Unweighted and RDS-weighted prevalence estimates of medical/procedural contraceptive use; chi-squared tests and multi-level linear regressions to test associations. KEY RESULTS: Of 855 women in the ROI, 36.8% (95% CI 33.7-40.1, unweighted) and 38.6% (95% CI 30.7-47.2, weighted) reported contraceptive use, compared to 66% of rural women in the NSFG sample. Among the ROI women, 27% had received prior 30-day SUD treatment via outpatient counseling or inpatient program and these women had increased odds of contraceptive use (aOR 1.50 [95% CI 1.08-2.06]). There was a positive association between contraception use and recent medications for opioid use disorder (aOR 1.34 [95% CI 0.95-1.88]) and prior 6-month primary care utilization (aOR 1.32 [95% CI 0.96-1.82]) that did not meet the threshold for statistical significance. CONCLUSION: WWUD in rural areas reported low contraceptive use; those who recently received SUD treatment had greater odds of contraceptive use. Improvements are needed in expanding reproductive and preventive health within SUD treatment and primary care services in rural communities.

Substance use disorder treatment and technology access among people who use drugs in rural areas of the United States: A cross-sectional survey.

PURPOSE: To evaluate how technology access affected substance use disorder (SUD) treatment prior to COVID-19 for people who use drugs in rural areas. METHODS: The Rural Opioid Initiative (January 2018-March 2020) was a cross-sectional study of people with prior 30-day injection drug or nonprescribed opioid use from rural areas of 10 states. Using multivariable mixed-effect regression models, we examined associations between participant technology access and SUD treatment. FINDINGS: Of 3,026 participants, 71% used heroin and 76% used methamphetamine. Thirty-five percent had no cell phone and 10% had no prior 30-day internet use. Having both a cell phone and the internet was associated with increased days of medication for opioid use disorder (MOUD) use (aIRR 1.29 [95% CI 1.11-1.52]) and a higher likelihood of SUD counseling in the prior 30 days (aOR 1.28 [95% CI 1.05-1.57]). Lack of cell phone was associated with decreased days of MOUD (aIRR 0.77 [95% CI 0.66-0.91]) and a lower likelihood of prior 30-day SUD counseling (aOR 0.77 [95% CI 0.62-0.94]). CONCLUSIONS: Expanding US rural SUD treatment engagement via telemedicine may require increased cell phone and mobile network access.

Perceptions and Experiences With Evidence-based Treatments Among People Who Use Opioids.

OBJECTIVES: Even where treatment is available, people who use drugs (PWUD) may not seek help. Few published studies examine beliefs, experiences, and perceptions of evidence-based treatment among PWUD who are not actively engaged in care. This study aimed to explore the experiences of PWUD in considering or accessing treatment and gauge receptiveness to low-threshold treatment models. METHODS: A purposeful sample of participants actively using opioids and with previous interest in or experience with treatment was recruited from a harm reduction program in Chicago. Semistructured interviews were conducted to explore key phenomena while allowing for unanticipated themes. The instrument included questions about historical drug use, treatment experience, and perceptions of how to improve treatment access and services. Private interviews were audio recorded, transcribed, and double coded by 2 analysts. Queries of coded data were analyzed using issue-focused analysis to identify themes. RESULTS: The sample (N = 40) approximated groups at highest risk of fatal overdose in Chicago, with more than 80% between the ages of 45 to 64 years, 65% African American, and 62% male identified. The majority had prior treatment experience, although all resumed use after completing or leaving treatment. The most prevalent barriers to treatment included structural barriers related to social determinants, lack of readiness for abstinence, burdensome intake procedures, and regulatory/programmatic requirements. Most participants expressed interest in low-threshold treatment. CONCLUSIONS: Existing treatment barriers may be addressed by shifting to lower-threshold intake processes and/or outreach-based delivery of opioid agonist treatment. Engaging PWUD in efforts to create lower-threshold treatment programs is necessary to ensure that needs are met.

Characteristics and context of fentanyl test strip use among syringe service clients in southern Wisconsin.

BACKGROUND: Fentanyl adulteration of illicit drugs is a major driver of opioid-involved overdose in the USA. Fentanyl test strips are increasingly used by people who use drugs to check for fentanyl. However, little is known about factors that influence test strip use in this population. METHODS: In this mixed-methods study employing semi-structured open-ended interviews (n = 29) and a structured survey (n = 341), we examined characteristics associated with test strip use, characteristics of test strip use, and situational, logistical and psychosocial factors influencing test strip use. Respondents were recruited from a syringe service program in southern Wisconsin. Bivariate tests of association and multivariable logistic regression examined the relationship between respondent characteristics and test strip use. Summary statistics were used to describe how situational, logistical and psychosocial factors impact test strip use. RESULTS: Most respondents were male (59.6%), non-Hispanic white (77.4%), young (mean 35.7 years), reported heroin as their primary drug (70.7%), injection as their primary route (87.9%), and use ≥ 3 times daily (78.6%). In multivariable models, site, race and ethnicity, drug of choice, and seeking fentanyl were associated with test strip use. Among test strip users, 36.5% use them most of the time or more and 80.6% get positive results half the time or more. Among individuals reporting heroin, fentanyl, methamphetamine, or cocaine or crack cocaine at least once per month, 99.1%, 56.8%, 42.2%, and 55.7% reported testing these drugs, respectively. Test strip use is supported by information from suppliers, regular transportation, diverse distribution locations, recommendations from harm reduction staff, and having a safe or private place to use. CONCLUSIONS: We found that individuals who use fentanyl test strips are more often non-Hispanic white, use heroin, and seek drugs with fentanyl relative to individuals without test strip use. Findings confirm high fentanyl penetration in the Wisconsin drug supply. Low rates of stimulant testing suggest inadequate awareness of fentanyl penetration. Findings support outreach to key populations, increased diversity of distributing locations, efforts to correct misperceptions about drug wasting, emphasis on pre-consumption testing, and the importance of adjunct behaviors to prevent overdose given high rates of intentional fentanyl use.

American College of Preventive Medicine: Addressing the Opioid Epidemic Through a Prevention Framework.

The opioid epidemic has resulted in significant morbidity and mortality in the U.S. Health systems, policymakers, payers, and public health have enacted numerous strategies to reduce the harms of opioids, including opioid use disorder (OUD). Much of this implementation has occurred before the development of OUD‒related comparative effectiveness evidence, which would enable an understanding of the benefits and harms of different approaches. This article from the American College of Preventive Medicine (ACPM) uses a prevention framework to identify the current approaches and make recommendations for addressing the opioid epidemic, encompassing strategies across a primordial, primary, secondary, and tertiary prevention approach. Key primordial prevention strategies include addressing social determinants of health and reducing adverse childhood events. Key primary prevention strategies include supporting the implementation of evidence-based prescribing guidelines, expanding school-based prevention programs, and improving access to behavioral health supports. Key secondary prevention strategies include expanding access to evidence-based medications for opioid use disorder, especially for high-risk populations, including pregnant women, hospitalized patients, and people transitioning out of carceral settings. Key tertiary prevention strategies include the expansion of harm reduction services, including expanding naloxone availability and syringe exchange programs. The ACPM Opioid Workgroup also identifies opportunities for de-implementation, in which historical and current practices may be ineffective or causing harm. De-implementation strategies include reducing inappropriate opioid prescribing; avoiding mandatory one-size-fits-all policies; eliminating barriers to medications for OUD, debunking the myth of detoxification as a primary solo treatment for opioid use disorder; and destigmatizing care practices and policies to better treat people with OUD.

The Impact of the COVID-19 Pandemic on Drug Use Behaviors, Fentanyl Exposure, and Harm Reduction Service Support among People Who Use Drugs in Rural Settings.

BACKGROUND: The COVID-19 pandemic has worsened the opioid overdose crisis in the US. Rural communities have been disproportionately affected by opioid use and people who use drugs in these settings may be acutely vulnerable to pandemic-related disruptions due to high rates of poverty, social isolation, and pervasive resource limitations. METHODS: We performed a mixed-methods study to assess the impact of the pandemic in a convenience sample of people who use drugs in rural Illinois. We conducted 50 surveys capturing demographics, drug availability, drug use, sharing practices, and mental health symptoms. In total, 19 qualitative interviews were performed to further explore COVID-19 knowledge, impact on personal and community life, drug acquisition and use, overdose, and protective substance use adaptations. RESULTS: Drug use increased during the pandemic, including the use of fentanyl products such as gel encapsulated "beans" and "buttons". Disruptions in supply, including the decreased availability of heroin, increased methamphetamine costs and a concomitant rise in local methamphetamine production, and possible fentanyl contamination of methamphetamine was reported. Participants reported increased drug use alone, experience and/or witness of overdose, depression, anxiety, and loneliness. Consistent access to harm reduction services, including naloxone and fentanyl test strips, was highlighted as a source of hope and community resiliency. CONCLUSIONS: The COVID-19 pandemic period was characterized by changing drug availability, increased overdose risk, and other drug-related harms faced by people who use drugs in rural areas. Our findings emphasize the importance of ensuring access to harm reduction services, including overdose prevention and drug checking for this vulnerable population.

Expanding Access to Medications for Opioid Use Disorder Treatment Through Incentivized Continuing Education.

INTRODUCTION: Buprenorphine treatment for opioid use disorder (OUD) has positive outcomes including reducing opioid-related morbidity and mortality. In March 2018, 58 of 102 counties in Illinois lacked access to medication for OUD. METHODS: Rush University created a fellowship training program with financial incentives to help expand buprenorphine treatment in Illinois. Fellows first completed an online waiver course, then attended an in-person intensive training weekend, and finally participated in a 9-month webinar series. Demographic and prescribing data were collected from fellows, as well as a comparison group of providers outside the fellowship who only completed a waiver training. RESULTS: At the fellowship's end, 31 of 37 fellows (84%) reported they were actively prescribing buprenorphine. Of the 23 fellows who were not prescribing at the fellowship's beginning, 17 (74%) initiated prescribing by the end. Among the 16 nonfellowship subjects who only completed a waiver training, just two (13%) reported they were prescribing buprenorphine at the study period's end. DISCUSSION: Our study indicates that providers need more training beyond the waiver to initiate buprenorphine prescribing. When resources are available to address a health crisis such as OUD, this model offers an innovative mechanism for delivering continuing medical education that produces outcomes quickly.

Opioid-related overdose deaths by race and neighborhood economic hardship in Chicago.

Compared to national findings, Chicago has both a higher rate of opioid-related overdose death and a markedly different distribution by demographics. The Chicago Department of Public Health analyzed fatal overdoses by level of neighborhood economic hardship. The highest rate of opioid-related deaths occurred in neighborhoods with high economic hardship (36.9 per 100,000 population) compared to medium- (20.5) and low- (12.3) hardship neighborhoods. However, these patterns were not consistent across racial/Hispanic ethnicity subgroups. These data support the need to consider the role of racism and other structural, social, and economic factors when designing interventions to reduce opioid-related overdose deaths.

Results from a mobile drug checking pilot program using three technologies in Chicago, IL, USA.

BACKGROUND: Opioid overdose deaths in the United States continue to rise, with the majority of deaths involving fentanyl. Drug checking has been used in Europe and Canada to assess adulteration of the illegal drug supply, but faces legal barriers in the United States. We are presenting information from a pilot mobile program offering drug checking services to participants of a harm reduction program in Chicago, Illinois, USA. METHODS: Drug checking services were provided at five mobile outreach and one fixed-point drop-in location in Chicago, IL, between March 2019 and August 2020. Three technologies were used: a Fourier transform infrared spectroscopy (FTIR) spectrometer, a handheld high-pressure mass spectrometer (HPMS), and immunoassay fentanyl test strips (FTS). We report on results generated by this combination of technology during the study period. RESULTS: During the study period, 422 total samples were tested, the majority of which were sold as dope/heroin (66.7 %). Of the 282 samples sold as dope/heroin, 12.8 % matched to fentanyl on the FTIR, 47.5 % had fentanyl identified on the HPMS, and 57.8 % produced a positive FTS. CONCLUSIONS: This pilot program demonstrated the feasibility of using three technologies to assess for the presence of fentanyl in user-submitted samples, revealed discordant results from the technologies, and provided information on the local drug market.