Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.

BACKGROUND: Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS: In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS: During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS: In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Effect of the Communities That HEAL Intervention on Overdose Education and Naloxone Distribution: A Cluster-Randomized, Wait-List Controlled Trial.

Objectives. To determine whether the Communities That HEAL (CTH) intervention is effective in increasing naloxone distribution compared with usual care. Methods. The HEALing (Helping to End Addiction Long-Term) Communities Study (HCS) is a cluster-randomized, parallel-arm, wait-list controlled implementation science trial testing the impact of the CTH intervention on increasing the use of evidence-based practices to lower opioid-related overdose deaths. Communities (n = 67) highly impacted by opioid overdose in Kentucky, Massachusetts, New York, and Ohio were allocated to CTH intervention (n = 34) or wait-list comparison (usual care; n = 33) arms. The primary outcome for this study was the number of naloxone units distributed in HCS communities during the comparison period (July 1, 2021‒June 30, 2022), examined using an intent-to-treat negative binomial regression model. Results. Naloxone distribution was 79% higher in the CTH intervention versus usual care arm (adjusted relative rate = 1.79; 95% confidence interval = 1.28, 2.51; P = .001; adjusted rates of naloxone distribution 3378 vs 1884 naloxone units per 100 000 residents), when controlling for urban‒rural status, state, baseline opioid-related overdose death rate, and baseline naloxone distribution rate. Conclusions. The CTH intervention increased naloxone distribution compared with usual care in communities highly impacted by the opioid crisis. Trial Registration. ClinicalTrials.gov identifier: NCT04111939. (Am J Public Health. Published online ahead of print October 10, 2024:e1-e12. https://doi.org/10.2105/AJPH.2024.307845).

Reducing perceived barriers to scaling up overdose education and naloxone distribution and medications for opioid use disorder in the United States in the HEALing (Helping End Addiction Long-Term®) communities study.

BACKGROUND: Scaling up overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD) is needed to reduce opioid overdose deaths, but barriers are pervasive. This study examines whether the Communities That HEAL (CTH) intervention reduced perceived barriers to expanding OEND and MOUD in healthcare/behavioral health, criminal-legal, and other/non-traditional venues. METHODS: The HEALing (Helping End Addiction Long-Term®) Communities Study is a parallel, wait-list, cluster randomized trial testing the CTH intervention in 67 communities in the United States. Surveys administered to coalition members and key stakeholders measured the magnitude of perceived barriers to scaling up OEND and MOUD in November 2019-January 2020, May-June 2021, and May-June 2022. Multilevel linear mixed models compared Wave 1 (intervention) and Wave 2 (wait-list control) respondents. Interactions by rural/urban status and research site were tested. RESULTS: Wave 1 respondents reported significantly greater reductions in mean scores for three outcomes: perceived barriers to scaling up OEND in Healthcare/Behavioral Health Venues (-0.26, 95% confidence interval, CI: -0.48, -0.05, p = 0.015), OEND in Other/Non-traditional Venues (-0.53, 95% CI: - 0.84, -0.22, p = 0.001) and MOUD in Other/Non-traditional Venues (-0.34, 95% CI: -0.62, -0.05, p = 0.020). There were significant interactions by research site for perceived barriers to scaling up OEND and MOUD in Criminal-Legal Venues. There were no significant interactions by rural/urban status. DISCUSSION: The CTH Intervention reduced perceived barriers to scaling up OEND and MOUD in certain venues, with no difference in effectiveness between rural and urban communities. More research is needed to understand facilitators and barriers in different venues.

Examining buprenorphine diversion through a harm reduction lens: an agent-based modeling study.

BACKGROUND: Recent policies have lessened restrictions around prescribing buprenorphine-naloxone (buprenorphine) for the treatment of opioid use disorder (OUD). The primary concern expressed by critics of these policies is the potential for buprenorphine diversion. However, the population-level effects of increased buprenorphine diversion are unclear. If replacing the use of heroin or fentanyl, use of diverted buprenorphine could be protective. METHODS: Our study aim was to estimate the impact of buprenorphine diversion on opioid overdose using an agent-based model calibrated to North Carolina. We simulated the progression of opioid misuse and opioid-related outcomes over a 5-year period. Our status quo scenario assumed that 50% of those prescribed buprenorphine diverted at least one dose per week to other individuals with OUD and 10% of individuals with OUD used diverted buprenorphine at least once per week. A controlled prescription only scenario assumed that no buprenorphine would be diverted, while an increased diversion scenario assumed that 95% of those prescribed buprenorphine diverted and 50% of individuals with OUD used diverted buprenorphine. We assumed that use of diverted buprenorphine replaced the use of other opioids for that day. Sensitivity analyses increased the risk of overdose when using diverted buprenorphine, increased the frequency of diverted buprenorphine use, and simulated use of diverted buprenorphine by opioid-naïve individuals. Scenarios were compared on opioid overdose-related outcomes over the 5-year period. RESULTS: Our status quo scenario predicted 10,658 (credible interval [CI]: 9699-11,679) fatal opioid overdoses. A scenario simulating controlled prescription only of buprenorphine (i.e., no diversion) resulted in 10,741 (9895-11,650) fatal opioid overdoses versus 10,301 (9439-11,244) within a scenario simulating increased diversion. Compared to the status quo, the controlled prescription only scenario resulted in a similar number of fatal overdoses, while the scenario with increased diversion of buprenorphine resulted in 357 (3.35%) fewer fatal overdoses. Even when increasing overdose risk while using diverted buprenorphine and incorporating use by opioid naïve individuals, increased diversion did not increase overdoses compared to a scenario with no buprenorphine diversion. CONCLUSIONS: A similar number of opioid overdoses occurred under modeling conditions with increased rates of buprenorphine diversion among persons with OUD, with non-statistical trends toward lower opioid overdoses. These results support existing calls for low- to no-barrier access to buprenorphine for persons with OUD.

Long-term Patterns of Self-reported Opioid Use, VACS Index, and Mortality Among People with HIV Engaged in Care.

Longitudinal analyses of opioid use and overall disease severity among people with HIV (PWH) are lacking. We used joint-trajectory and Cox proportional hazard modeling to examine the relationship between self-reported opioid use and the Veterans Aging Cohort Study (VACS) Index 2.0, a validated measure of disease severity and mortality, among PWH engaged in care. Using data from 2002 and 2018, trajectory modeling classified 20% of 3658 PWH in low (i.e., lower risk of mortality), 40% in moderate, 28% in high, and 12% in extremely high VACS Index trajectories. Compared to those with moderate VACS Index trajectory, PWH with an extremely high trajectory were more likely to have high, then de-escalating opioid use (adjusted odds ratio [AOR], 95% confidence interval [CI] 5·17 [3·19-8·37]) versus stable, infrequent use. PWH who report high frequency opioid use have increased disease severity and mortality risk over time, even when frequency of opioid use de-escalates.

Risk Factor Reversal in Studies of Infectious Disease: Making Counterintuitive Results Intuitive Again.

A previously published study reported the seemingly paradoxical finding that men who have sex with men status was strongly protective and recent sexual abstinence strongly deleterious in relation to mortality prognosis. We explain why these results are entirely logical and that the counterintuitive direction of the effects derives from the comparison group implied by the study design.

Association of Cannabis, Stimulant, and Alcohol use with Mortality Prognosis Among HIV-Infected Men.

Questionnaires over a 9-year study period (2002-2010) were used to characterize cannabis, stimulant, and alcohol use among 3099 HIV-infected men participating in the Veterans Aging Cohort Study (VACS) to determine whether use of these substances is associated with changes in the VACS Index, a validated prognostic indicator for all-cause mortality. At baseline, 18% of participants reported no substance use in the past year, 24% lower risk alcohol use only, 18% unhealthy alcohol use only, 15% cannabis use (with or without alcohol), and 24% stimulant use (with or without alcohol or cannabis). In adjusted longitudinal analyses, cannabis use [ß = -0.97 (95% CI -1.93, 0.00), p = 0.048] was not associated with mortality risk, while stimulant use [1.08 (0.16, 2.00), p = 0.021] was associated with an increased mortality risk, compared to lower risk alcohol use. Our findings show no evidence of a negative effect of cannabis use on mortality risk, while stimulant use was associated with increased mortality risk among HIV-infected men. Interventions to reduce stimulant use in this patient population may reduce mortality.

Correction to: Association of Cannabis, Stimulant, and Alcohol use with Mortality Prognosis Among HIV-Infected Men.

In the original publication of the article, the given and family name of the third author was not correct. The name has been corrected with this erratum.

Potential drivers of HIV acquisition in African-American women related to mass incarceration: an agent-based modelling study.

BACKGROUND: The United States has the highest incarceration rate in the world. Incarceration can increase HIV risk behaviors for individuals involved with the criminal justice system and may be a driver of HIV acquisition within the community. METHODS: We used an agent-based model to simulate HIV transmission in a sexual-contact network representing heterosexual African American men and women in Philadelphia to identify factors influencing the impact of male mass incarceration on HIV acquisition in women. The model was calibrated using surveillance data and assumed incarceration increased the number of sexual contacts and decreased HIV care engagement for men post-release. Incarceration of a partner increased the number of sexual contacts for women. We compared a counterfactual scenario with no incarceration to scenarios varying key parameters to determine what factors drove HIV acquisition in women. RESULTS: Setting the duration of male high-risk sexual behavior to two years post-release increased the number of HIV transmissions to women by more than 20%. Decreasing post-release HIV care engagement and increasing HIV acquisition risk attributable to sexually transmitted infections (STIs) also increased the number of HIV transmissions to women. Changing the duration of risk behavior for women, the proportion of women engaging in higher risk behavior, and the relative risk of incarceration for HIV-infected men had minimal impact. CONCLUSION: The mass incarceration of African American men can increase HIV acquisition in African American women on a population-level through factors including post-release high-risk behaviors, disruption of HIV care engagement among formerly incarcerated men, and increased STI prevalence. These findings suggest that the most influential points of intervention may be programs seeking to reduce male risk behaviors and promote HIV care engagement post-release, as well as STI testing and treatment programs for recently incarcerated men, as well as women with incarcerated partners.

Postpartum Engagement in HIV Care: An Important Predictor of Long-term Retention in Care and Viral Suppression.

BACKGROUND: Human immunodeficiency virus (HIV)-infected women are at risk of virologic failure postpartum. We evaluated factors influencing retention in care and viral suppression in postpartum HIV-infected women. METHODS: We conducted a retrospective cohort analysis (2005-2011) of 695 deliveries involving 561 HIV-infected women in Philadelphia. Multivariable logistic regression evaluated factors, including maternal age, race/ethnicity, substance use, antiretroviral therapy during pregnancy, timing of HIV diagnosis, previous pregnancy with HIV, adequacy of prenatal care, and postpartum HIV care engagement (≥ 1 CD4 count or viral load [VL] test within 90 days of delivery), associated with retention in care (≥ 1 CD4 count or VL test in each 6-month interval of the period with ≥ 60 days between tests) and viral suppression (VL ≤ 200 copies/mL at the last measure in the period) at 1 and 2 years postpartum. RESULTS: Overall, 38% of women engaged in HIV care within 90 days postpartum; with 39% and 31% retained in care and virally suppressed, respectively, at 1 year postpartum, and 25% and 34% retained in care and virally suppressed, respectively, at 2 years postpartum. In multivariable analyses, women who engaged in HIV care within 90 days of delivery were more likely to be retained (adjusted odds ratio [AOR], 11.38; 95% confidence interval [CI], 7.74-16.68) and suppressed (AOR, 2.60 [95% CI, 1.82-3.73]) at 1 year postpartum. This association persisted in the second year postpartum for both retention (AOR, 6.19 [95% CI, 4.04-9.50]) and suppression (AOR, 1.40 [95% CI, 1.01-1.95]). CONCLUSIONS: The prevalence of postpartum HIV-infected women retained in care and maintaining viral suppression is low. Interventions seeking to engage women in care shortly after delivery have the potential to improve clinical outcomes.

Simulating the effects of medicaid expansion on the opioid epidemic in North Carolina.

Expanding Medicaid plays a large role in ensuring that people across the United States have access to health care services. Although North Carolina recently moved toward Medicaid expansion, the impact of expansion on overdoses and overdose mortality may vary based on the type of treatment (offering medications for opioid use disorder [MOUD] vs. offering inpatient medically managed withdrawal without linkage to further MOUD treatment or non-MOUD-based treatment) accessed by individuals newly eligible for treatment through expansion. Based on official North Carolina statistics and published peer-reviewed literature, we developed a simulation model that forecasts opioid overdose and mortality under different scenarios for type of treatment accessed (MOUD-based vs. non-MOUD-based) and Medicaid coverage levels. An optimistic scenario assuming 70 % of individuals newly eligible for treatment would enter treatment during the first year of expansion estimated that 332 (Simulation Interval: 246-412) overdose deaths would be averted. A scenario more in line with recent historical trends assuming 38 % of individuals newly eligible for treatment would enter treatment resulted in 213 (Simulation Interval: 157-263) averted overdose deaths. In all scenarios, MOUD-based treatment approaches increased the number of lives saved compared with approaches expanding opioid treatment through non-MOUD-based treatment. Our study emphasized the need to ensure access to MOUD-based treatment for individuals newly covered by the Medicaid expansion.

Trends in Opioid Misuse Among Individuals Aged 12 to 21 Years in the US.

Importance: Although opioid misuse has been decreasing among US youths and adolescents in recent years, it is unclear what has contributed to this trend and how this trend differs by age group and sex over time. Objective: To identify trends in opioid misuse among youths and young adults across and between ages, birth cohorts, and sexes. Design, Setting, and Participants: Cross-sectional National Survey on Drug Use and Health (NSDUH) public-use files were used to produce nationally representative pseudocohorts. The survey population includes the civilian US population in the 50 states and Washington, DC. Individuals without a fixed address and institutionalized individuals were excluded. Respondents to the NSDUH are a population-based sample selected using a stratified cluster design. For the years (January 1, 2002, to December 31, 2019) and ages (12-21 years) analyzed, the sample sizes ranged from 1607 to 3239 respondents. Data were analyzed from January 1, 2022, to April 12, 2023, for the main outcome by age, sex, and pseudocohort. Main Outcomes and Measures: Respondents were asked whether they misused prescription opioids or used heroin in the past year. The analysis hypotheses were formulated and tested after data collection. Results: In a total of 5 pseudocohorts, data from 114 412 respondents aged 12 to 21 years were analyzed; the unweighted distribution of male sex (complement was female) ranged from 47.7% to 52.6% (mean [SD], 50.6% [1.1%]). Response rates ranged from 45.8% to 71.3%. High school-aged youths and young adults had distinctly lower rates of opioid misuse in later pseudocohorts compared with earlier ones. Rates of misuse among individuals aged 16 years were 2.80% (95% CI, 1.06%-4.54%) higher in 2002 vs 2008; among those aged 18 years, rates were 4.36% (95% CI, 1.85%-6.87%) higher in 2002. Similarly, rates of misuse among individuals aged 16 years were 3.93% (95% CI, 2.15%-5.71%) higher in 2008 vs 2014; among those aged 17 years, rates were 3.41% (95% CI, 1.94%-4.88%) higher in 2008. Similar patterns were observed by sex. In earlier cohorts, younger female participants had higher rates of opioid misuse than their male counterparts and older male participants had higher rates than their female counterparts. Sex differences decreased in later cohorts. Conclusions and Results: The findings of this cross-sectional study of US youths and young adults suggest that high school-aged individuals consistently misused fewer opioids in later pseudocohorts overall and by sex. Sex differences in opioid rates also diminished in later pseudocohorts. A decrease in drug availability and general exposure to the harms of opioid use could be contributing to these findings. Future planned research using this pseudocohort approach will examine polysubstance use and evaluate how substance use differs by other sociodemographic characteristics.

Evaluating Policies to Decrease the Risk of Introducing SARS-CoV-2 Infections to Nursing Home Facilities.

We used an individual-based microsimulation model of North Carolina to determine what facility-level policies would result in the greatest reduction in the number of individuals with SARS-CoV-2 entering the nursing home environment from 12/15/2021 to 1/3/2022 (e.g., Omicron variant surge). On average, there were 14,287 (Credible Interval [CI]: 13,477-15,147) daily visitors and 17,168 (CI: 16,571-17,768) HCW coming from the community into 426 nursing home facilities. Policies requiring a negative rapid test or vaccinated status for visitors resulted in the greatest reduction in the number of individuals with SARS-CoV-2 infection entering the nursing home environment with a 29.6% (26.9%-32.0%) and 24.0% (CI: 22.2%-25.5%) reduction, respectively. Policies halving visits (21.2% [20.0%-28.2%]), requiring all vaccinated HCW to receive a booster (7.8% [CI: 7.4%-8.7%]), and limiting visitation to a primary visitor (6.5% [CI: 3.5%-9.7%]) reduced infectious contacts to a lesser degree.

Estimate of undetected severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in acute-care hospital settings using an individual-based microsimulation model.

OBJECTIVE: Current guidance states that asymptomatic screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) prior to admission to an acute-care setting is at the facility's discretion. This study's objective was to estimate the number of undetected cases of SARS-CoV-2 admitted as inpatients under 4 testing approaches and varying assumptions. DESIGN AND SETTING: Individual-based microsimulation of 104 North Carolina acute-care hospitals. PATIENTS: All simulated inpatient admissions to acute-care hospitals from December 15, 2021, to January 13, 2022 [ie, during the SARS-COV-2 ο (omicron) variant surge]. INTERVENTIONS: We simulated (1) only testing symptomatic patients, (2) 1-stage antigen testing with no confirmatory polymerase chain reaction (PCR) test, (3) 1-stage antigen testing with a confirmatory PCR for negative results, and (4) serial antigen screening (ie, repeat antigen test 2 days after a negative result). RESULTS: Over 1 month, there were 77,980 admissions: 13.7% for COVID-19, 4.3% with but not for COVID-19, and 82.0% for non-COVID-19 indications without current infection. Without asymptomatic screening, 1,089 (credible interval [CI], 946-1,253) total SARS-CoV-2 infections (7.72%) went undetected. With 1-stage antigen screening, 734 (CI, 638-845) asymptomatic infections (67.4%) were detected, with 1,277 false positives. With combined antigen and PCR screening, 1,007 (CI, 875-1,159) asymptomatic infections (92.5%) were detected, with 5,578 false positives. A serial antigen testing policy detected 973 (CI, 845-1,120) asymptomatic infections (89.4%), with 2,529 false positives. CONCLUSIONS: Serial antigen testing identified >85% of asymptomatic infections and resulted in fewer false positives with less cost per identified infection compared to combined antigen plus PCR testing.

Clinical impact, costs, and cost-effectiveness of hospital-based strategies for addressing the US opioid epidemic: a modelling study.

BACKGROUND: The syndemic of injection drug use and serious injection-related infections is leading to increasing mortality in the USA. Although outpatient treatment with medications for opioid use disorder reduces overdose risk and recurrent infections, hospitalisation remains common. We evaluated the clinical impact, costs, and cost-effectiveness of hospital-based strategies to address the US opioid epidemic. METHODS: We developed a microsimulation model to compare the cost-effectiveness of: standard hospital care-detoxification for opioids, no addiction consult service (status quo); expanded inpatient prescribing of medications for opioid use disorder, including bridge prescriptions (ie, medication until they can see an outpatient provider) when possible (medications for opioid use disorder with bridge); implementation of addiction consult services within the hospital (addiction consult services alone); and a combined medication for opioid use disorder with addiction consult services strategy (combined). We used clinical trials and observational cohorts to inform model inputs. Outcomes were life-years, discounted costs, incremental cost-effectiveness ratios, hospitalisations, and deaths. We did deterministic sensitivity analyses on key model inputs related to costs and sequelae of drug use and probabilistic sensitivity analysis to further address uncertainty. FINDINGS: Among people who inject opioids in the USA, we estimated that expanding medications for opioid use disorder with bridge prescriptions would reduce hospitalisations and overdose deaths by 3·2% and 3·6%, respectively, and the combination of expanded medications with opioid use disorder along with addiction consult sevices would reduce hospitalisations and overdoses by 5·2% and 6·6%, respectively, compared with the status quo. Mean lifetime costs ranged from US$731 400 (95% credible interval 447 911-859 189 for the medications for opioid use disorder strategy) to $741 200 (470 930-868 551 for the combined strategy) per person. Assuming a willingness-to-pay threshold of $100 000 per life-year gained, medications for opioid use disorder with bridge and combined strategies were cost-effective ($7600 and $14 300, respectively). A scenario that assumed ideal access to harm reduction services came to the same conclusions as the base case and our results were robust in deterministic and probabilistic sensitivity analyses. INTERPRETATION: The combined interventions of expanding hospital-based prescribing of medications for opioid use disorder and implementing addiction consult services could improve life expectancy, be cost-effective, and could be the basis for a comprehensive hospital-based strategy for addressing the opioid epidemic in the USA and countries with similar opioid epidemics. FUNDING: National Institute on Drug Abuse and National Institute of Allergy and Infectious Diseases.

Modeling the cost-effectiveness and impact on fatal overdose and initiation of buprenorphine-naloxone treatment at syringe service programs.

AIM: To estimate the number of treatment initiations, averted fatal opioid overdoses and the cost-effectiveness associated with offering buprenorphine-naloxone (buprenorphine) treatment on-site within existing syringe service programs (SSPs) in Massachusetts, USA. DESIGN, SETTING AND PARTICIPANTS: This was a cohort-based mathematical model and cost-effectiveness analysis. We derived model inputs from state and national surveillance data, clinical trials and observational cohort studies. We compared an intervention scenario where 30% of SSP clients initiated buprenorphine treatment on-site at least once annually to a status quo scenario where no buprenorphine was available on-site among community treatment providers in Massachusetts, 2020-30. In individuals with opioid use disorder (OUD) we assumed that 80% of SSP clients had recently injected drugs and that treatment within SSPs would have similar or improved retention compared with standard-of-care buprenorphine programs, but higher rates of active opioid use while in treatment. MEASUREMENTS: Number of treatment initiations (i.e. individuals began treatment on a medication for opioid use disorder or entered medically managed withdrawal), averted fatal opioid overdoses, quality-adjusted life-years (QALYs) and life-time discounted costs from a health sector and a limited societal perspective. FINDINGS: The status quo scenario resulted in 23 051 fatal overdoses and 1 511 613 treatment initiations over a 10-year simulation period. An intervention scenario with on-site SSP buprenorphine treatment averted 4797 (-20.8%) fatal opioid overdoses and resulted in 129 359 (+8.6%) additional treatment initiations compared with the status quo. The intervention scenario was the dominating scenario: providing OUD treatment through Massachusetts SSPs cost less (-$3612 per person) with patients accumulating more QALYs (0.2 per person) compared with the status quo scenario. CONCLUSIONS: Offering buprenorphine treatment on-site within syringe service programs has the potential to decrease fatal overdoses substantially, improve treatment engagement and save on costs.

Simulated Cost-effectiveness and Long-term Clinical Outcomes of Addiction Care and Antibiotic Therapy Strategies for Patients With Injection Drug Use-Associated Infective Endocarditis.

IMPORTANCE: Emerging evidence supports the use of outpatient parenteral antimicrobial therapy (OPAT) and, in many cases, partial oral antibiotic therapy for the treatment of injection drug use-associated infective endocarditis (IDU-IE); however, long-term outcomes and cost-effectiveness remain unknown. OBJECTIVE: To compare the added value of inpatient addiction care services and the cost-effectiveness and clinical outcomes of alternative antibiotic treatment strategies for patients with IDU-IE. DESIGN, SETTING, AND PARTICIPANTS: This decision analytical modeling study used a validated microsimulation model to compare antibiotic treatment strategies for patients with IDU-IE. Model inputs were derived from clinical trials and observational cohort studies. The model included all patients with injection opioid drug use (N = 5 million) in the US who were eligible to receive OPAT either in the home or at a postacute care facility. Costs were annually discounted at 3%. Cost-effectiveness was evaluated from a health care sector perspective over a lifetime starting in 2020. Probabilistic sensitivity, scenario, and threshold analyses were performed to address uncertainty. INTERVENTIONS: The model simulated 4 treatment strategies: (1) 4 to 6 weeks of inpatient intravenous (IV) antibiotic therapy along with opioid detoxification (usual care strategy), (2) 4 to 6 weeks of inpatient IV antibiotic therapy along with inpatient addiction care services that offered medication for opioid use disorder (usual care/addiction care strategy), (3) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by OPAT (OPAT strategy), and (4) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by partial oral antibiotic therapy (partial oral antibiotic strategy). MAIN OUTCOMES AND MEASURES: Mean percentage of patients completing treatment for IDU-IE, deaths associated with IDU-IE, life expectancy (measured in life-years [LYs]), mean cost per person, and incremental cost-effectiveness ratios (ICERs). RESULTS: All modeled scenarios were initialized with 5 million individuals (mean age, 42 years; range, 18-64 years; 70% male) who had a history of injection opioid drug use. The usual care strategy resulted in 18.63 LYs at a cost of $416 570 per person, with 77.6% of hospitalized patients completing treatment. Life expectancy was extended by each alternative strategy. The partial oral antibiotic strategy yielded the highest treatment completion rate (80.3%) compared with the OPAT strategy (78.8%) and the usual care/addiction care strategy (77.6%). The OPAT strategy was the least expensive at $412 150 per person. Compared with the OPAT strategy, the partial oral antibiotic strategy had an ICER of $163 370 per LY. Increasing IDU-IE treatment uptake and decreasing treatment discontinuation made the partial oral antibiotic strategy more cost-effective compared with the OPAT strategy. When assuming that all patients with IDU-IE were eligible to receive partial oral antibiotic therapy, the strategy was cost-saving and resulted in 0.0247 additional discounted LYs. When treatment discontinuation was decreased from 3.30% to 2.65% per week, the partial oral antibiotic strategy was cost-effective compared with OPAT at the $100 000 per LY threshold. CONCLUSIONS AND RELEVANCE: In this decision analytical modeling study, incorporation of OPAT or partial oral antibiotic approaches along with addiction care services for the treatment of patients with IDU-IE was associated with increases in the number of people completing treatment, decreases in mortality, and savings in cost compared with the usual care strategy of providing inpatient IV antibiotic therapy alone.

Optimizing the impact of medications for opioid use disorder at release from prison and jail settings: A microsimulation modeling study.

BACKGROUND: We examined the impact of expanded access to medications for opioid use disorder (MOUD) in a unified prison and jail system on post-release, opioid-related overdose mortality. METHODS: We developed a microsimulation model to simulate a population of 55,000 persons at risk of opioid-related overdose mortality in Rhode Island. The effect of an extended-release (XR) naltrexone only intervention and the effect of providing access to all three MOUD (i.e., methadone, buprenorphine, and XR-naltrexone) at release from incarceration on cumulative overdose death over eight years (2017-2024) were compared to the standard of care (i.e., limited access to MOUD). RESULTS: In the standard of care scenario, the model predicted 2385 opioid-related overdose deaths between 2017 and 2024. An XR-naltrexone intervention averted 103 deaths (4.3% reduction), and access to all three MOUD averted 139 deaths (5.8% reduction). Among those with prior year incarceration, an XR-naltrexone only intervention and access to all three MOUD reduced overdose deaths by 22.8% and 31.6%, respectively. CONCLUSIONS: Expanded access to MOUD in prison and jail settings can reduce overdose mortality in a general, at-risk population. However, the real-world impact of this approach will vary by levels of incarceration, treatment enrollment, and post-release retention.

Preexposure prophylaxis strategies for African-American women affected by mass incarceration.

OBJECTIVE: We aimed to determine the effectiveness of various preexposure prophylaxis (PrEP) prescription strategies for African-American women impacted by mass incarceration within an urban setting. DESIGN: An agent-based model was utilized to evaluate prevention strategies in an efficient, ethical manner. By defining agents, their characteristics and relationships, we assessed population-level effects of PrEP on HIV incidence. METHODS: We tested hypothetical PrEP prescription strategies within a simulation representing the African-American population of Philadelphia, Pennsylvania. Four strategies were evaluated: PrEP for women meeting CDC indicators regarding partner characteristics, PrEP for women with a recently incarcerated male partner, PrEP for women with a recently released male partner and couples-based PrEP at time of release. Interventions occurred alongside scale-up of HAART. We evaluated reductions in HIV transmissions, the number of persons on PrEP needed to avert one HIV transmission (NNT) and the resulting proportions of people on PrEP. RESULTS: Scenarios prescribing PrEP based on criminal justice system involvement reduced HIV transmissions. The NNT ranged from 147 (couples-based scenario) to 300 (recently released scenario). The percentage of the female population covered by PrEP at any one time ranged from 0.14% (couples-based) to 10.8% (CDC-based). CDC-guideline scenarios were consistently less efficient compared to the justice-involved interventions. CONCLUSION: Expanding PrEP for African-American women and their male partners affected by incarceration should be considered in national HIV prevention goals and correctional facilities leveraged as intervention sites. Partner characteristics in the current CDC indications may be more effective and efficient if guidelines considered criminal justice involvement.

Receipt of opioid agonist treatment halves the risk of HIV-1 RNA viral load rebound through improved ART adherence for HIV-infected women who use illicit drugs.

BACKGROUND: Women living with HIV who use illicit drugs may be particularly vulnerable to HIV-1 RNA viral load (VL) rebound. METHODS: We used longitudinal data from 2006 to 2017 to evaluate the impact of sociodemographic, behavioral, social-structural, and clinical factors on the hazard of viral rebound for women enrolled in the ACCESS study, a prospective cohort with systematic VL monitoring. Women were included if they achieved VL suppression (<50 copies/mL) following antiretroviral therapy (ART) initiation and had more than one study interview. Sociodemographic as well as substance use, social-structural, addiction treatment, and HIV clinical factors were evaluated as predictors of viral rebound (VL > 1000 copies/mL). Cox regressions using a recurrent events framework, time-varying covariates, robust standard errors, and a frailty component were used. RESULTS: Of the 185 women included, 62 (34%) experienced at least one viral rebound event over an 11-year period, accumulating a total of 87 viral rebound events. In adjusted analysis, stimulant use more than doubled the hazard of viral rebound (adjusted hazard ratio [AHR]: 2.35, 95% confidence interval [CI]: 1.07-5.14) while the only factor protective against viral rebound was receipt of opioid agonist treatment (OAT) in the past six months (AHR: 0.46, 95% CI: 0.26-0.81). After adjusting for ART adherence in the past six months, the effect of OAT was attenuated (AHR: 0.57, 95% CI: 0.32-1.02). CONCLUSIONS: Efforts to improve access to and retention within OAT programs and decrease stimulant use may improve rates of viral suppression for HIV-positive women who use illicit drugs.