BACKGROUND: It is estimated that over 111,000 people in the U.S. died from a drug overdose in the twelve-month period ending in July 2023. More than three-quarters of those deaths were attributed to opioids. Naloxone has long been available in healthcare facilities to reverse opioid overdose rapidly and safely but is not universally accessible for use in community settings where overdoses occur. We conducted a systematic literature review and meta-analysis to assess the effectiveness of overdose education and naloxone distribution (OEND) programs in three types of community settings to reduce overdose deaths among people who use opioids nonmedically. METHODS: We systematically searched electronic databases, including Medline (OVID), Embase (OVID), Psycinfo (OVID), and Global Health (OVID), for peer-reviewed studies of OEND programs published during 2003-2018 (Group 1) that reported overdose outcomes individual level survivals or deaths immediately following naloxone administration. The PRISMA checklist guided screening, quality assessment, and data abstraction. We later identified studies published during 2018-2022 (Group 2), when drug usage and fentanyl-related overdose deaths notably increased, differed from earlier ones. We conducted meta-analyses on both Groups using random effects models to estimate summary survival proportions. RESULTS: Among the 44 Group 1 studies published during 2003-2018, survival did not differ by time (year), location, naloxone dose, or route of administration, but studies of OEND programs serving people who use drugs reported 98.3% (95% CI: 97.5-98.8) survival; those serving family of people who use drugs or other community members reported 95.0% (95% CI: 91.4-97.1) survival; and those for police reported 92.4% (95% CI: 88.9-94.8) survival (p < 0.01). Five Group 2 studies (2018-2022) yielded similar results. CONCLUSIONS: Community-based naloxone distribution programs can be effective in preventing opioid overdose deaths. The paper demonstrates that in the face of increasing overdose deaths over time, survival after naloxone administration has been sustained. The very high survival rates provide clear evidence for public health to continue efforts to expand channels for naloxone distribution in community settings.

BACKGROUND: Medications for opioid use disorder (MOUD) are key to preventing opioid overdose. Despite the high risk of opioid overdose among recently incarcerated people who use drugs, missed opportunities for engagement in MOUD treatment persist in this population. We examined the association between unmet need for MOUD and non-fatal opioid overdose among recently incarcerated people who inject drugs (PWID) and assessed prevalence of non-fatal opioid overdose by selected characteristics. METHODS: We analyzed 2022 data from the National HIV Behavioral Surveillance (NHBS) system among PWID from 20 large U.S. cities. Adjusted prevalence ratios (aPR) and 95 % confidence intervals (95 % CI) were calculated to examine the association between unmet need for MOUD and non-fatal opioid overdose. RESULTS: Among 1648 recently incarcerated PWID, 28 % reported an unmet need for MOUD and 39 % reported a non-fatal opioid-involved overdose in the past 12 months. Experiencing homelessness in the last 12 months (aPR=1.43, 95 % CI=1.27-1.61) and living in the Midwest region of the U.S. (aPR=1.18, 95 % CI=1.01-1.38) were significantly associated with reporting a non-fatal opioid overdose. Recently incarcerated PWID with an unmet need for MOUD were 1.4 times as likely to report a non-fatal opioid overdose in the past 12 months (50 %; aPR=1.42, 95 % CI=1.29-1.56) compared with recently incarcerated PWID without an unmet need for MOUD (35 %). CONCLUSIONS: Unmet need for MOUD was significantly associated with non-fatal opioid overdose among PWID who were incarcerated in the past 12 months, suggesting the need to investigate specific strategies to improve to MOUD treatment among recently incarcerated PWID.

OBJECTIVE: Using an innovative data sharing model, we assessed the impacts of the COVID-19 pandemic on the health of people who inject drugs (PWID). DESIGN: The PWID Data Collaborative was established in 2021 to promote data sharing across PWID studies in North America. Contributing studies submitted aggregate data on 23 standardized indicators during four time periods: prepandemic (March 2019 to February 2020), early-pandemic (March 2020 to February 2021), mid-pandemic (March 2021 to February 2022), and late pandemic (March 2022 to February 2023). METHODS: We present study-specific and meta-analyzed estimates for the percentage of PWID who took medications for opioid use disorder, received substance use treatment, shared syringes or injection equipment, had a mental health condition, had been incarcerated, or had experienced houselessness. To examine change over time across indicators, we fit a random effects meta-regression model to prevalence estimates using time as a moderator. RESULTS: Thirteen studies contributed estimates to the Data Collaborative on these indicators, representing 6213 PWID interviews. We observed minimal change across prevalence of the six indicators between the prepandemic (March 2019 to February 2020) and three subsequent time periods, overall or within individual studies. Considerable heterogeneity was observed across study-specific and time-specific estimates. CONCLUSION: Limited pandemic-related change observed in indicators of PWID health is likely a result of policy and supportive service-related changes and may also reflect resilience among service providers and PWID themselves. The Data Collaborative is an unprecedented data sharing model with potential to greatly improve the quality and timeliness of data on the health of PWID.

BACKGROUND: Syringe services programs (SSPs) provide harm reduction supplies and services to people who use drugs and are often required by funders or partners to collect data from program participants. SSPs can use these data during monitoring and evaluation (M&E) to inform programmatic decision making, however little is known about facilitators and barriers to collecting and using data at SSPs. METHODS: Using the Consolidated Framework for Implementation Research (CFIR), we conducted 12 key informant interviews with SSP staff to describe the overall landscape of data systems at SSPs, understand facilitators and barriers to data collection and use at SSPs, and generate recommendations for best practices for data collection at SSPs. We used 30 CFIR constructs to develop individual interview guides, guide data analysis, and interpret study findings. RESULTS: Four main themes emerged from our analysis: SSP M&E systems are primarily designed to be responsive to perceived SSP client needs and preferences; SSP staffing capacity influences the likelihood of modifying M&E systems; external funding frequently forces changes to M&E systems; and strong M&E systems are often a necessary precursor for accessing funding. CONCLUSIONS: Our findings highlight that SSPs are not resistant to data collection and M&E, but face substantial barriers to implementation, including lack of funding and disjointed data reporting requirements. There is a need to expand M&E-focused funding opportunities, harmonize quantitative indicators collected across funders, and minimize data collection to essential data points for SSPs.

To determine if decreasing lifetime use of methamphetamines, cocaine, ecstasy, and inhalants among high school students occurring from 2009 to 2019 in the U.S. also occurred in five southeastern states, Youth Risk Behavior Survey data representative of high school students in grades 9-12 in 2009 and 2019 were analyzed. In a classroom setting, lifetime use of methamphetamines, cocaine, ecstasy, and inhalants were self-reported. Students nationwide (n = 30,087) were compared to students in Alabama, Georgia, Louisiana, Mississippi, and South Carolina (n = 18,237). Lifetime methamphetamine use significantly increased from 4.8% in 2009 to 6.2% in 2019 in the southeast but decreased from 4.1 to 2.2% nationwide. Use of cocaine, ecstasy, and inhalants remained stable in the southeast while decreasing significantly nationwide from 2009 to 2019. During a period when use of methamphetamines, cocaine, ecstasy, and inhalants among high school students in the U.S. decreased, use in southeastern states did not change. Culturally specific programs and interventions may be needed to prevent illicit drug use in communities of southeastern states where youth remain at risk.

OBJECTIVES: We aimed to determine the prevalence of self-reported naloxone use during pregnancy among people in the United States with a recent live birth. A secondary objective was to characterize people at increased risk of overdose who did and did not use naloxone. METHODS: We analyzed data from the Pregnancy Risk Assessment Monitoring System from 26 US jurisdictions that conducted an opioid supplement survey from 2019 to 2020. Respondents with increased risk of experiencing an opioid overdose were identified based on self-reported use of illicit amphetamines, heroin, cocaine, or receiving medication for opioid use disorder (MOUD) during pregnancy. Weighted prevalence estimates and 95% confidence intervals were calculated for reported naloxone use at any point during pregnancy among people with an increased risk of overdose. RESULTS: Naloxone use during pregnancy was reported by <1% of the overall study population (unweighted N = 88/34,528). Prevalence of naloxone use was 5.0% (95% CI: 0.0-10.6) among respondents who reported illicit amphetamine use, 15.2% (1.8-28.6) among those who reported heroin use, and 17.6% (0.0-38.1) among those who reported cocaine use. Naloxone use was 14.5% (8.4-20.6) among those who reported taking MOUD. Among people with increased risk of overdose, no significant differences in naloxone use were observed by age, race/ethnicity, education level, residential metropolitan status, or insurance status. CONCLUSIONS: Prevalence of naloxone use among people with an increased risk of overdose during pregnancy ranged from 5.0% to 17.6%. Access to naloxone, overdose prevention education, and treatment for substance use disorders may help reduce morbidity and mortality.

BACKGROUND: Characterizing acute and chronic hepatitis C virus (HCV) infection and HIV/HCV co-infection among persons who inject drugs (PWID) can inform elimination efforts. METHODS: During 2018 National HIV Behavioral Surveillance in 10 U.S. metropolitan statistical areas (MSAs), PWID were recruited using respondent-driven sampling and offered a survey, HIV testing, and HCV antibody and RNA testing. We examined prevalence and associated characteristics of HCV infection and HIV/HCV co-infection. Associations were assessed using log-linked Poisson regression models with robust standard errors accounting for clustering by recruitment chain and adjusting for MSA and network size. RESULTS: Overall, 44.2% had current HCV infection (RNA detected), with 3.9% classified as acute infection (HCV antibody non-reactive/RNA detected) and 40.3% as chronic (HCV antibody reactive/RNA detected). Four percent had HIV/HCV co-infection. Current HCV infection was significantly higher among PWID who were male, White, injected >1 time/day, shared syringes in past year, and shared injection equipment in past year. PWID who were transgender, injecting >5 years, and most often injected speedball (heroin and cocaine together) or stimulants alone were more likely to have HIV/HCV co-infection. Among PWID who never previously had HCV infection, 9.9% had acute HCV infection. Among PWID who started injecting ≤5 years ago, 41.5% had already acquired HCV infection. CONCLUSIONS: Acute and chronic HCV infections were substantial among a sample of PWID in 10 U.S. MSAs. Accessibility to HCV RNA testing, promoting safer practices, and intervening early with harm reduction programs for recent injection initiates will be critical to disease elimination efforts for PWID.

In June of 2022, the U.S. Centers for Disease Control and Prevention (CDC) Mpox Response wanted timely answers to important epidemiological questions which can now be answered more effectively through infectious disease modeling. Infectious disease models have shown to be valuable tools for decision making during outbreaks; however, model complexity often makes communicating the results and limitations of models to decision makers difficult. We performed nowcasting and forecasting for the 2022 mpox outbreak in the United States using the R package EpiNow2. We generated nowcasts/forecasts at the national level, by Census region, and for jurisdictions reporting the greatest number of mpox cases. Modeling results were shared for situational awareness within the CDC Mpox Response and publicly on the CDC website. We retrospectively evaluated forecast predictions at four key phases (early, exponential growth, peak, and decline) during the outbreak using three metrics, the weighted interval score, mean absolute error, and prediction interval coverage. We compared the performance of EpiNow2 with a naïve Bayesian generalized linear model (GLM). The EpiNow2 model had less probabilistic error than the GLM during every outbreak phase except for the early phase. We share our experiences with an existing tool for nowcasting/forecasting and highlight areas of improvement for the development of future tools. We also reflect on lessons learned regarding data quality issues and adapting modeling results for different audiences.

BACKGROUND: The 2022 mpox outbreak has infected over 30 000 people in the USA, with cases declining since mid-August. Infections were commonly associated with sexual contact between men. Interventions to mitigate the outbreak included vaccination and a reduction in sexual partnerships. Understanding the contributions of these interventions to decreasing cases can inform future public health efforts. METHODS: We fit a dynamic network transmission model to mpox cases reported by Washington DC through 10 January 2023. This model incorporated both vaccine administration data and reported reductions in sexual partner acquisition by gay, bisexual or other men who have sex with men (MSM). The model output consisted of daily cases over time with or without vaccination and/or behavioural adaptation. RESULTS: We found that initial declines in cases were likely caused by behavioural adaptations. One year into the outbreak, vaccination and behavioural adaptation together prevented an estimated 84% (IQR 67% to 91%) of cases. Vaccination alone averted 79% (IQR 64% to 88%) of cases and behavioural adaptation alone averted 25% (IQR 10% to 42%) of cases. We further found that in the absence of vaccination, behavioural adaptation would have reduced the number of cases, but would have prolonged the outbreak. CONCLUSIONS: We found that initial declines in cases were likely caused by behavioural adaptation, but vaccination averted more cases overall and was key to hastening outbreak conclusion. Overall, this indicates that outreach to encourage individuals to protect themselves from infection was vital in the early stages of the mpox outbreak, but that combination with a robust vaccination programme hastened outbreak conclusion.

Background: The 2022 mpox outbreak infected over 30,000 people in the United States. Infections were commonly associated with sexual contact between men. Interventions included vaccination and reductions in sexual partnerships. We estimated the averted infections attributable to each intervention using mathematical modeling. Method(s): We fit a dynamic network transmission model to mpox cases reported by the District of Columbia through January 2023. We incorporated vaccine administration data and reported reductions in sexual partnerships among gay, bisexual, or other men who have sex with men (MSM). Model output consisted of predicted cases over time with or without vaccination and/or behavior change. Result(s): We estimated initial case reductions were due to behavior change. Vaccination alone averted 64% [IQR:57%-72%] and behavior change alone averted 21% [IQR:11%-29%] of cases. Vaccination and behavior change together averted 80% [IQR:74%-85%] of cases. In the absence of vaccination, behavior change reduced cumulative cases but also prolonged the outbreak. Conclusion(s): Initial case declines were likely caused by behavior change, but vaccination averted more cases overall. Overall, this indicates that encouraging individuals to protect themselves was vital in the early outbreak, but that combination with a robust vaccination program was ultimately required for control. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Mpox is a zoonotic disease endemic in Central and West Africa. In May 2022, an outbreak of mpox characterized by human-to-human transmission was detected in multiple non-endemic countries. We performed nowcasting and forecasting for the 2022 mpox outbreak in the United States using the R package EpiNow2. We generated nowcasts/forecasts at the national level, by Census region, and for jurisdictions reporting the greatest number of mpox cases. Modeling results were shared for situational awareness within the Centers for Disease Control and Prevention (CDC) Mpox Response and publicly on the CDC website. We retrospectively evaluated forecast predictions at four key phases during the outbreak using three metrics, the weighted interval score, mean absolute error, and prediction interval coverage. We compared the performance of EpiNow2 with a naive Bayesian generalized linear model (GLM). The EpiNow2 model had less probabilistic error than the GLM during every outbreak phase except for the early phase. We share our experiences with an existing tool for nowcasting/forecasting and highlight areas of improvement for the development of future tools. We also reflect on lessons learned regarding data quality issues and adapting modeling results for different audiences. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Using data collected by 12 U.S. health departments, we report mean estimated serial interval for monkeypox virus infection of 8.5 (95% CrI: 7.3 - 9.9) days for symptom onset from 57 case pairs and mean estimated incubation period of 5.6 (4.3 - 7.8) days from 35 case pairs for symptom onset. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

BACKGROUND: People who inject drugs (PWID) have likely borne disproportionate health consequences of the COVID-19 pandemic. PWID experienced both interruptions and changes to drug supply and delivery modes of harm reduction, treatment, and other medical services, leading to potentially increased risks for HIV, hepatitis C virus (HCV), and overdose. Given surveillance and research disruptions, proximal, indirect indicators of infectious diseases and overdose should be developed for timely measurement of health effects of the pandemic on PWID. METHODS: We used group concept mapping and a systems thinking approach to produce an expert stakeholder-generated, multi-level framework for monitoring changes in PWID health outcomes potentially attributable to COVID-19 in the U.S. This socio-ecological measurement framework elucidates proximal and distal contributors to infectious disease and overdose outcomes, many of which can be measured using existing data sources. RESULTS: The framework includes multi-level components including policy considerations, drug supply/distribution systems, the service delivery landscape, network factors, and individual characteristics such as mental and general health status and service utilization. These components are generally mediated by substance use and sexual behavioral factors to cause changes in incidence of HIV, HCV, sexually transmitted infections, wound/skin infections, and overdose. CONCLUSION: This measurement framework is intended to increase the quality and timeliness of research on the impacts of COVID-19 in the context of the current pandemic and future crises. Next steps include a ranking process to narrow the drivers of change in health risks to a concise set of indicators that adequately represent framework components, can be written as measurable indicators, and are quantifiable using existing data sources, as well as a publicly available web-based platform for summary data contributions.

The United States is experiencing a syndemic of homelessness, substance use disorder, and mental health conditions, which has been further exacerbated by the COVID-19 pandemic. Although it is expected that mitigation strategies will curb community transmission of COVID-19, the unintended consequences of social isolation on mental health and substance use are a growing public health concern. Awareness of changing mental health and substance use treatment needs due to the pandemic is critical to understanding what additional services and support are needed during and post-pandemic, particularly among people experiencing homelessness who have pre-existing serious mental illness or substance use disorder. To evaluate these effects and support our understanding of mental health and substance use outcomes of the COVID-19 pandemic, we conducted a qualitative study where behavioral health providers serving people experiencing homelessness described the impact of COVID-19 among their clients throughout the United States. Behavioral health providers shared that experiencing social isolation worsened mental health conditions and caused some people to return to substance use and fatally overdose. However, some changes initiated during the pandemic resulted in positive outcomes, such as increased client willingness to discuss mental health topics. Our findings provide additional evidence that the social isolation experienced during the pandemic has been detrimental to mental health and substance use outcomes, especially for people experiencing homelessness.

BACKGROUND: Public health data signal increases in the number of people who inject drugs (PWID) in the United States during the past decade. An updated PWID population size estimate is critical for informing interventions and policies aiming to reduce injection-associated infections and overdose, as well as to provide a baseline for assessments of pandemic-related changes in injection drug use. METHODS: We used a modified multiplier approach to estimate the number of adults who injected drugs in the United States in 2018. We deduced the estimated number of non-fatal overdose events among PWID from two of our previously published estimates: the number of injection-involved overdose deaths and the meta-analyzed ratio of non-fatal to fatal overdose. The number of non-fatal overdose events was divided by prevalence of non-fatal overdose among current PWID for a population size estimate. RESULTS: There were an estimated 3,694,500 (95% CI: 1,872,700-7,273,300) PWID in the U.S. in 2018, representing 1.46% (95% CI: 0.74% - 2.87%) of the adult population. The estimated prevalence of injection drug use was highest among male persons (2.1%; 95% CI: 1.1-4.2%), non-Hispanic White persons (1.8%; 95% CI: 0.9-3.6%), and adults aged 18-39 years (1.8%; 0.9-3.6%). CONCLUSIONS: Using transparent, replicable methods and largely publicly available data, we provide the first update to the number of people who inject drugs in the U.S. in nearly ten years. Findings suggest the population size of PWID has substantially grown in the past decade and that prevention services for PWID should be proportionally increased.

BACKGROUND: Syringe services programs (SSPs) are an important venue for reaching people who inject drugs (PWID) to offer preventive services; however, not all SSPs offer vaccinations. We aimed to describe barriers and opportunities for SSPs to offer vaccinations. METHODS: During June-August 2021, we conducted a descriptive, cross-sectional survey of SSP providers in the United States. SSPs were recruited from national listservs using purposive sampling to ensure geographic diversity. The survey included questions about SSP characteristics, client demographics, existing vaccination resources, resource needs, and staff perspectives on client vaccination barriers. Statistical comparisons were made using Pearson's chi-square test. RESULTS: In total, 105 SSPs from 34 states responded to the survey; 46 SSPs (43.8%) offered on-site vaccinations. SSPs without on-site vaccinations were more likely operated by community-based organizations (81.4% vs 30.4%, p < 0.001) in urban areas (71.4% vs 40.0%, p = 0.002) than SSPs offering on-site vaccinations. The most common staffing need was for personnel licensed to administer vaccines (74/98, 75.5%). Over half of SSPs reported vaccine supply, administration supplies, storage equipment, and systems to follow-up clients for multidose series as important resource needs. The most common resource need was for reminder/recall systems for vaccines with multidose series (75/92, 81.5%). Vaccine safety concerns (92/95, 96.8%) and competing priorities (92/96, 95.8%) were the most common staff-reported client barriers to vaccinations. CONCLUSIONS: Addressing missed opportunities for offering vaccinations to PWID who use SSPs will require increased numbers of on-site personnel licensed to administer vaccines and additional training, vaccination supplies, and storage and handling equipment.

BACKGROUND: People who use drugs are at increased risk for hepatitis A virus infection. Since 1996, the Advisory Committee on Immunization Practices has recommended hepatitis A vaccination for people who use drugs. Since 2016, the U.S. has experienced widespread hepatitis A outbreaks associated with person-to-person transmission. PURPOSE: To describe the prevalence of drug use, route of use, and drugs used among hepatitis A outbreak-associated patients. METHODS: State outbreak and medical records were reviewed to describe the prevalence, type, and route of drug use among a random sample of 812 adult outbreak-associated hepatitis A patients from Kentucky, Michigan, and West Virginia during 2016-2019. Differences in drug-use status were analyzed by demographic and risk-factor characteristics using the X (2) test. RESULTS: Among all patients, residents of Kentucky (55.6%), Michigan (51.1%), and West Virginia (60.1%) reported any drug use, respectively. Among patients that reported any drug use, methamphetamine was the most frequently reported drug used in Kentucky (42.3%) and West Virginia (42.1%); however, opioids were the most frequently reported drug used in Michigan (46.8%). Hepatitis A patients with documented drug use were more likely (p<0.05) to be experiencing homelessness/unstable housing, have been currently or recently incarcerated, and be aged 18-39 years compared to those patients without documented drug use. IMPLICATIONS: Drug use was prevalent among person-to-person hepatitis A outbreak-associated patients, and more likely among younger patients and patients experiencing homelessness or incarceration. Increased hepatitis A vaccination coverage is critical to prevent similar outbreaks in the future.

BACKGROUND: In the United States, drug overdose mortality has increased. Death records categorize overdose deaths by type of drug involved, but do not include information about the route of drug administration. METHODS: We utilized data from drug treatment admissions (Treatment Episodes Dataset, TEDS-A) and National Vital Statistics Systems to estimate the percentage of reported drug overdose deaths that were injection-involved from 2000 to 2018 in the U.S. Data on reported route of administration at admission were used to calculate the percent injecting each drug type, by demographic group (race/ethnicity, sex, age group) and year. Using the resulting probabilities, we estimated the number of overdose deaths that were injection-involved. Estimates were compared across drug types, demographic characteristics, and year. FINDINGS: The number of overdose deaths among adults increased more than 3-fold from 2000 (n = 17,196) to 2018 (n = 67,021). During that timeframe, the number of estimated injection-involved overdose deaths increased more than 8-fold from 2000 (n = 3467, 95% CI: 3449-3485) to 2018 (n = 28,257, 95% CI: 28,192-28,322). From 2000-2007, the percent of overdose deaths that were injection-involved remained stable around 20%. From 2007-2018, the percent of overdose deaths that were injection-involved increased from 18.4% (95% CI: 18.3-18.6%) to 42.2% (95% CI: 42.1-42.3%). In 2018, most estimated injection-involved overdose deaths were due to injecting heroin/synthetic opioids (n = 24,860, 95% CI: 24,800-24,919), which accounted for 88.0% of all injection-involved deaths. CONCLUSIONS: Much of the recent increase in overdose mortality is likely attributable to rising injection-involved overdose deaths.

BACKGROUND: COVID-19 stay-at-home orders may reduce access to substance use treatment and naloxone, an opioid overdose reversal drug. The objective of this analysis was to compare monthly trends in pharmacy-based dispensing rates of medications for opioid use disorder (MOUD) (buprenorphine and extended-release [ER] naltrexone) and naloxone in the United States during March 2019-December 2020 by age and sex. METHODS: We calculated monthly prescription dispensing rates per 100,000 persons using IQVIA New to Brand. We used Joinpoint regression to calculate monthly percent change in dispensing rates and Wilcoxon Rank Sum tests to examine differences in median monthly rates overall, and by age and sex between March 2019-December 2019 and March 2020-December 2020. RESULTS: Buprenorphine dispensing increased among those aged 40-64 years and ≥ 65 years from March 2019 to December 2020. Median rates of total ER naltrexone dispensing were lower in March 2020-December 2020 compared to March 2019-December 2019 for the total population, and for females and males. From March 2019 to December 2020, ER naltrexone dispensing decreased and naloxone dispensing increased for those aged 20-39 years. CONCLUSIONS: Dispensing ER naltrexone declined during the study period. Given the increase in substance use during the COVID-19 pandemic, maintaining equivalent access to MOUD may not be adequate to accommodate rising numbers of new patients with opioid use disorder. Access to all MOUD and naloxone could be further expanded to meet potential needs during and after the public health emergency, given their importance in preventing opioid overdose-related harms.

BACKGROUND: Hepatitis C virus (HCV) infection has been increasing among people who inject drugs (PWID), younger than 30 years, and living in rural or suburban areas. We examined injection-related behaviors of young PWID to determine factors associated with HCV infection. METHODS: From September 2013-May 2015, respondent-driven and snowball sampling were used in 3 suburban areas of Wisconsin to recruit PWID 18-29 years who reported injection drug use in the previous 12 months. Participants were tested for HCV antibody (anti-HCV) and reported injection-related behaviors/practices via self-administered computer-based survey. We calculated anti-HCV prevalence and assessed associated factors using multivariable logistic regression. RESULTS: Forty-two percent (117/280) of participants were male, 83% (231/280) were white, and median age was 23 years. Overall HCV prevalence was 33%, but HCV prevalence among males was 39%. Adjusting for age, sex, race/ethnicity, education, relationship status, insurance status and income, anti-HCV positivity was associated with higher injection frequency (> 100 times in the past six months) (aOR = 3.07; 95% Confidence Interval (95% CI): 1.72-5.45), ever shared syringes (aOR = 5.15; 95% CI: 2.52-10.51), past week/last use receptive rinse water sharing (aOR = 1.88; 95% CI: 1.06-3.33), past week/last use receptive filter sharing (aOR = 3.25; 95% CI: 1.61-6.54), reusing syringes (aOR = 1.91, 95% CI: 1.08-3.37), history of overdose (aOR = 8.82; 95% CI: 2.26-3.95), and having ever injected another PWID (aOR = 8.82; 95%CI 3.94-19.76). DISCUSSION: Anti-HCV positivity is associated with high-risk injection practices. Young PWID would benefit from access to evidence-based interventions that reduce their risk of infection, link those infected to HCV treatment, and provide education to reduce further transmission.

INTRODUCTION: Sociodemographic factors and chronic conditions associated with coronavirus disease 2019 (COVID-19) among persons with substance use disorder (PWSUD) are not well understood. We identified risk factors associated with COVID-19 among PWSUD with hospital visits. METHODS: Using the Premier Healthcare Database Special COVID-19 Release, we conducted a case-control study using ICD-10-CM codes to identify PWSUD aged 12 years and older with hospital visits for any reason during April-December 2020. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) to identify factors associated with COVID-19 diagnosis among PWSUD (age, sex, race/ethnicity, U.S. Census Region, urban/rural classification, insurance payor type, comorbidities, and substance use disorder [SUD] type), and then stratified by SUD type. RESULTS: From April-December 2020, 18,298 (1.3%) of 1,429,154 persons with SUD in the database had a COVID-19 diagnosis. Among PWSUD, opioid use disorder (OUD; aOR = 1.24, 95% CI = 1.18-1.32), alcohol use disorder (AUD; aOR = 1.16, 95% CI = 1.11-1.22), cocaine or other stimulant use disorder (COUD; aOR = 1.28, 95% CI = 1.22-1.34), and multiple SUDs (aOR = 1.20, 95% CI = 1.15-1.26) were associated with higher odds of COVID-19, as were comorbidities such as chronic lower respiratory disease (aOR = 1.32, 95% CI = 1.26-1.37), chronic hepatitis (aOR = 1.45, 95% CI = 1.34-1.57), and diabetes (aOR = 1.78, 95% CI = 1.71-1.86). CONCLUSIONS: Among a sample of PWSUD, OUD, AUD, COUD, multiple SUDs, and associated comorbidities were associated with COVID-19 diagnosis. Integration of COVID-related care, care of other comorbidities, and SUD treatment may benefit PWSUD. Future studies are needed to better understand COVID-19 prevention in this population and to reduce disparities among subpopulations at increased risk.

Diagnoses of HIV among people who inject drugs have increased in the U.S. during 2014-2018 for the first time in 2 decades, and multiple HIV outbreaks have been detected among people who inject drugs since 2015. These epidemiologic trends pose a significant concern for achieving goals of the federal initiative for Ending the HIV Epidemic in the U.S. Syringe services programs are cost effective, safe, and highly effective in reducing HIV transmission and are an essential component of a comprehensive, integrated approach to addressing these concerns. Yet, geographic coverage of these programs remains limited in the U.S., and many jurisdictions continue to have laws and policies that limit or disallow syringe services programs. An in-depth literature review was conducted on the role of syringe services programs in the Ending the HIV Epidemic initiative. Empirical and model-based evidence consistently shows that syringe services programs have the highest impact in HIV prevention when combined with access to medications for substance use disorder and antiretroviral therapy. Their effectiveness is further maximized when they provide services without restrictions and include proven and innovative strategies to expand access to harm-reduction and clinical services (e.g., peer outreach, telehealth). Increasing geographic and service coverage of syringe services programs requires strong and sustainable policy, funding, and community support and will need to address new challenges related to the COVID-19 pandemic. Syringe services programs have a key role in all 4 Ending the HIV Epidemic initiative strategies-Prevent, Diagnose, Treat, and Respond-and thus are instrumental to its success in preventing disease and saving lives.

Syringe service programs (SSP) increasingly serve rural areas of the United States, yet little is known about access and perceived need for their services. Objectives: This paper presents the HIV and viral hepatitis prevention, testing, and treatment, and, substance use disorder treatment and overdose prevention services offered at three SSPs and which services their clients accessed. Across the three SSPs, 45 clients (people who inject drugs [PWID]), 11 staff, and five stakeholders were interviewed. Results: Most clients (n = 34) reported accessing SSP services weekly and primarily for sterile syringes and injection-related supplies. All clients reported testing for HIV at least once, though concern for acquiring or transmitting HIV was divided between some or no concern. Most clients (n = 43) reported testing for hepatitis C virus (HCV). Concern for acquiring or transmitting HCV was also mixed. Vaccination for hepatitis A and/or B teetered around half (HAV: n = 23) to a third (HBV: n = 15). Most clients (n = 43) knew where to access the overdose countering medication, Narcan. Feelings about substance use treatment options varied, yet most felt not enough were available. Of note, not all assessed services were offered by the sampled SSPs. Conclusions/Importance: The findings help us understand PWIDs' rationale regarding services accessed and preference for particular services. The need for some services was not perceived by those at risk for the illness the services addressed. Discussing risk and providing tailored education is important when providing SSP services to rural residing PWIDs.

Syringe services programs (SSPs) are essential to preventing injection drug use-related infections and overdose death among people who use drugs (PWUD). The novel coronavirus (COVID-19) pandemic initially impeded SSPs' operations. To effectively support these programs, information is needed regarding SSPs' experiences adapting their services and the challenges posed by COVID-19. We conducted qualitative interviews with leadership and staff from a sample of 31 U.S. SSPs. Respondents discussed urgent concerns including reduced reach of services, suspended HIV/hepatitis C testing, high COVID-19 risk among PWUD, and negative impacts of isolation on overdose and mental health. They also noted opportunities to improve future services for PWUD, including shifting to evidence-based distribution practices and maintaining regulatory changes that increased access to opioid use disorder medications post-pandemic. Findings can inform efforts to support SSPs in restoring and expanding services, and provide insight into SSPs' role in engaging PWUD during the COVID-19 response and future emergencies.

After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.

CONTEXT: Local agencies across the United States have identified public health isolation sites for individuals with coronavirus disease 2019 (COVID-19) who are not able to isolate in residence. PROGRAM: We describe logistics of establishing and operating isolation and noncongregate hotels for COVID-19 mitigation and use the isolation hotel as an opportunity to understand COVID-19 symptom evolution among people experiencing homelessness (PEH). IMPLEMENTATION: Multiple agencies in Atlanta, Georgia, established an isolation hotel for PEH with COVID-19 and noncongregate hotel for PEH without COVID-19 but at risk of severe illness. PEH were referred to the isolation hotel through proactive, community-based testing and hospital-based testing. Daily symptoms were recorded prospectively. Disposition location was recorded for all clients. EVALUATION: During April 10 to September 1, 2020, 181 isolation hotel clients (77 community referrals; 104 hospital referrals) were admitted a median 3 days after testing. Overall, 32% of community referrals and 7% of hospital referrals became symptomatic after testing positive; 83% of isolation hotel clients reported symptoms at some point; 93% completed isolation. Among 302 noncongregate hotel clients, median stay was 18 weeks; 61% were discharged to permanent housing or had a permanent housing discharge plan. DISCUSSION: Overall, a high proportion of PEH completed isolation at the hotel, suggesting a high level of acceptability. Many PEH with COVID-19 diagnosed in the community developed symptoms after testing, indicating that proactive, community-based testing can facilitate early isolation. Noncongregate hotels can be a useful COVID-19 community mitigation strategy by bridging PEH at risk of severe illness to permanent housing.

Hepatitis C virus (HCV) infection remains an important cause of morbidity and mortality throughout the world, leading to serious health problems among those who are chronically infected. Since 1992, the Centers for Disease Control and Prevention has been collecting data on the incidence of HCV infection in the United States. In 2018, more than 50 000 individuals were estimated to have acute HCV infection.The most recently reported data on the prevalence of infection indicate that approximately 2.4 million people are living with hepatitis C in the United States. Transmission of HCV occurs predominantly through sharing contaminated equipment for injecting drugs.Two major events have had a significant impact on the incidence and prevalence of hepatitis C in the past few decades: the US opioid crisis and the discovery of curative treatments for HCV infection. To better understand the impact of these events, we examine reported trends in the incidence and prevalence of infection. (Am J Public Health. Published online ahead of print March 18, 2021: e1-e7. https://doi.org/10.2105/AJPH.2020.306149).

BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10(3) IU per milliliter and 1804.93×10(3) IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.).

Recent studies in animal models demonstrate that certain misfolded proteins associated with neurodegenerative diseases can support templated misfolding of cognate native proteins, to propagate across neural systems, and to therefore have some of the properties of classical prion diseases like Creutzfeldt-Jakob disease. The National Institute of Aging convened a meeting to discuss the implications of these observations for research priorities. A summary of the discussion is presented here, with a focus on limitations of current knowledge, highlighting areas that appear to require further investigation in order to guide scientific practice while minimizing potential exposure or risk in the laboratory setting. The committee concluded that, based on all currently available data, although neurodegenerative disease-associated aggregates of several different non-prion proteins can be propagated from humans to experimental animals, there is currently insufficient evidence to suggest more than a negligible risk, if any, of a direct infectious etiology for the human neurodegenerative disorders defined in part by these proteins. Given the importance of this question, the potential for noninvasive human transmission of proteopathic disorders is deserving of further investigation.