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Objectives. To describe the current financial health of syringe services programs (SSPs) in the United States and to assess the predictors of SSP budget levels and associations with delivery of public health interventions. Methods. We surveyed all known SSPs operating in the United States from February to June 2022 (n = 456), of which 68% responded (n = 311). We used general estimating equations to assess factors influencing SSP budget size and estimated the effects of budget size on multiple measures of SSP services. Results. The median SSP annual budget was $100 000 (interquartile range = $20 159‒$290 000). SSPs operating in urban counties and counties with higher levels of opioid overdose mortality had significantly higher budget levels, while SSPs located in counties with higher levels of Republican voting in 2020 had significantly lower budget levels. SSP budget levels were significantly and positively associated with syringe and naloxone distribution coverage. Conclusions. Current SSP funding levels do not meet minimum benchmarks. Increased funding would help SSPs meet community health needs. Public Health Implications. Federal, state, and local initiatives should prioritize sustained SSP funding to optimize their potential in addressing multiple public health crises. (Am J Public Health. 2024;114(4):435-443. https://doi.org/10.2105/AJPH.2024.307583).

BACKGROUND: More than half a million Americans died of an opioid-related overdose between 1999 and 2020, the majority occurring between 2015 and 2020. The opioid overdose mortality epidemic disproportionately impacts Black, Indigenous, and people of color (BIPOC): since 2015, overdose mortality rates have increased substantially more among Black (114%) and Latinx (97%) populations compared with White populations (32%). This is in part due to disparities in access to naloxone, an opioid antagonist that can effectively reverse opioid overdose to prevent death. Our recent pilot work determined that many barriers to naloxone access can be identified and addressed by syringe service programs (SSPs) using the Systems Analysis and Improvement Approach to Naloxone distribution (SAIA-Naloxone). This randomized controlled trial will test SAIA-Naloxones ability to improve naloxone distribution in general and among BIPOC specifically. METHODS: We will conduct a trial with 32 SSPs across California, randomly assigning 16 to the SAIA-Naloxone arm and 16 to receive implementation as usual. SAIA-Naloxone is a multifaceted, multilevel implementation strategy through which trained facilitators work closely with SSPs to (1) assess organization-level barriers, (2) prioritize barriers for improvement, and (3) test solutions through iterative change cycles until achieving and sustaining improvements. SSPs receiving SAIA-Naloxone will work with a trained facilitator for a period of 12 months. We will test SAIA-Naloxones ability to improve SSPs naloxone distribution using an interrupted time series approach. Data collection will take place during a 3-month lead-in period, the 12-month active period, and for an additional 6 months afterward to determine whether impacts are sustained. We will use a structured approach to specify SAIA-Naloxone to ensure strategy activities are clearly defined and to assess SAIA-Naloxone fidelity to aid in interpreting study results. We will also assess the costs associated with SAIA-Naloxone and its cost-effectiveness. DISCUSSION: This trial takes a novel approach to improving equitable distribution of naloxone amid the ongoing epidemic and associated racial disparities. If successful, SAIA-Naloxone represents an important organizational-level solution to the multifaceted and multilevel barriers to equitable naloxone distribution.

BACKGROUND: Opioid overdose fatalities are preventable with timely administration of naloxone, an opioid antagonist, during an opioid overdose event. Syringe service programs have pioneered naloxone distribution for potential bystanders of opioid overdose. The objective of this study was to pilot test a multi-component implementation strategy-the systems analysis and improvement approach for naloxone (SAIA-Naloxone)-with the goal of improving naloxone distribution by syringe service programs. METHODS: Two syringe service programs participated in a 6-month pilot of SAIA-Naloxone, which included (1) analyzing program data to identify gaps in the naloxone delivery cascade, (2) flow mapping to identify causes of attrition and brainstorm programmatic changes for improvement, and (3) conducting continuous quality improvement to test and assess whether modifications improve the cascade. We conducted an interrupted time series analysis using 52 weeks of data before and 26 weeks of data after initiating SAIA-Naloxone. Poisson regression was used to evaluate the association between SAIA-Naloxone and the weekly number of participants receiving naloxone and number of naloxone doses distributed. RESULTS: Over the course of the study, 11,107 doses of naloxone were distributed to 6,071 participants. Through SAIA-Naloxone, syringe service programs prioritized testing programmatic modifications to improve data collection procedures, proactively screen and identify naloxone-naïve participants, streamline naloxone refill systems, and allow for secondary naloxone distribution. SAIA-Naloxone was associated with statistically significant increases in the average number of people receiving naloxone per week (37% more SPP participants; 95% CI, 12% to 67%) and average number of naloxone doses distributed per week (105% more naloxone doses; 95% CI, 79% to 136%) beyond the underlying pre-SAIA-Naloxone levels. These initial increases were extended by ongoing positive changes over time (1.6% more SSP participants received naloxone and 0.3% more naloxone doses were distributed in each subsequent week compared to the weekly trend in the pre-SAIA Naloxone period). CONCLUSIONS: SAIA-Naloxone has strong potential for improving naloxone distribution from syringe service programs. These findings are encouraging in the face of the worsening opioid overdose crisis in the United States and support testing SAIA-Naloxone in a large-scale randomized trial within syringe service programs.

BackgroundSafe consumption sites (SCSs) serve diverse populations of people who use drugs (PWUD) and public health objectives. SCS implementation began in the 1980s, and today, there are at least 200 known SCSs operating in over twelve countries. While a growing literature supports their effectiveness as a harm reduction strategy, there is limited information on contextual factors that may support or hinder SCS implementation and sustainability. We aimed to fill this gap in knowledge by reviewing existing qualitative studies on SCSs.MethodsWe conducted a systematic review and thematic synthesis of qualitative studies. We identified all peer-reviewed, English-language qualitative studies on SCSs containing original data in PubMed, Web of Science, Google Scholar, and Science Direct as of September 23, 2019. Two authors independently screened, abstracted, and coded content relating to SCS implementation and sustainment aligned with the Exploration, Preparation, Implementation, Sustainment (EPIS) implementation science framework.ResultsAfter removing duplicates, we identified 765 unique records, of which ten qualitative studies met inclusion criteria for our synthesis. Across these ten studies, 236 total interviews were conducted. Overall, studies described how SCSs can (1) keep drug use out of public view while fostering a sense of inclusion for participants, (2) support sustainment by enhancing external communities' acceptability of SCSs, and (3) encourage PWUD utilization. Most studies also described how involving PWUD and peer workers (i.e., those with lived experience) in SCS operation supported implementation and sustainability.DiscussionOur thematic synthesis of qualitative literature identified engagement of PWUD and additional factors that appear to support SCS planning and operations and are critical to implementation success. However, the existing qualitative literature largely lacked perspectives of SCS staff and other community members who might be able to provide additional insight into factors influencing the implementation and sustainability of this promising public health intervention.

BackgroundGiven the housing instability and frequent residential relocation (both volitional and hegemonic) of people who inject drugs, we sought to determine whether residential relocation (defined as sleeping in a different place in the past 30 days) is associated with health outcomes in a sample of people who inject drugs (PWID).MethodsWe recruited 601 PWID using targeted sampling and interviewed them between 2016 and 2018 in San Francisco and Los Angeles, CA about housing, drug use practices, and service utilization. We then developed multivariable regression models to investigate how residential relocation is associated with violence, health outcomes, and social service access. We analyzed our data between June 2018 and October 2019.ResultsParticipants who relocated in the past 30 days had lower odds of being in substance use treatment (Adjusted Odds Ratio [AOR] = 0.62, 95% Confidence Interval [CI] = 0.42, 0.89) and higher odds of nonfatal overdose (AOR = 2.50, CI = 1.28, 4.90), receptive syringe sharing (AOR = 2.26, CI = 1.18, 4.32), severe food insecurity (AOR = 1.69, CI = 1.14, 2.50), having belongings stolen (AOR = 2.14, CI = 1.42, 3.21), experiencing physical assault (AOR = 1.58, CI = 1.03, 2.43), arrest (AOR = 1.64, CI = 1.02, 2.65), and jail (AOR = 1.90, CI = 1.16, 3.13) in the past 6 months when compared to those who did not relocate.ConclusionsPWID who have relocated in the past 30 days have higher odds of experiencing violence and life- threatening adverse outcomes, and policies that disrupt living circumstances of PWID should be ended in favor of those that support housing stability.

BackgroundSafe consumption sites (SCS) are an evidence-based intervention to prevent drug use-related harm. In late 2014, an organisation in an undisclosed location in the USA opened an unsanctioned SCS.ObjectiveTo evaluate whether use of the unsanctioned SCS affected medical outcomes.DesignA prospective cohort study.SettingNeighbourhoods surrounding the SCS.ParticipantsPeople who injected drugs were recruited and interviewed at baseline and 6 and 12 months from 2018 to 2020.InterventionPeople using the SCS could bring pre-obtained drugs to consume via injection, which were monitored by trained staff with naloxone.Main measuresAny overdose, number of non-fatal overdoses, skin and soft tissue infections, emergency department utilisation, number of emergency department visits, hospitalisation and number of nights spent in hospital.Key resultsA total of 494 participants enrolled in the study; 59 (12%) used the SCS at least once. We used propensity score weighting to analyse the association between SCS utilisation and measures. People using the SCS were 27% (95% CI: 12-46%) less likely to visit the emergency department, had 54% (95% CI: 33-71%) fewer emergency department visits, were 32% (95% CI: 4-57%) less likely to be hospitalised, and spent 50% (95% CI: 1-85%) fewer nights in hospital. Though not significant, people using the SCS had a lower likelihood of overdosing and slightly higher likelihood of skin and soft tissue infections.ConclusionsOur findings support the use of SCS in the USA to reduce the growing burden of acute care service utilisation related to injection drug use.

BACKGROUND: Many law enforcement agencies across the United States equip their officers with the life-saving drug naloxone to reverse the effects of an opioid overdose. Although officers can be effectively trained to administer naloxone, and hundreds of law enforcement agencies carry naloxone to reverse overdoses, little is known about what happens on scene during an overdose call for service from an officers perspective, including what officers perceive their duties and responsibilities to be as the incident evolves. METHODS: The qualitative study examined officers experiences with overdose response, their perceived roles, and what happens on scene before, during, and after an overdose incident. In-person interviews were conducted with 17 officers in four diverse law enforcement agencies in the United States between January and May 2020. RESULTS: Following an overdose, the officers described that overdose victims are required to go to a hospital or they are taken to jail. Officers also described their duties on scene during and after naloxone administration, including searching the belongings of the person who overdosed and seizing any drug paraphernalia. CONCLUSION: These findings point to a pressing need for rethinking standard operating procedures for law enforcement in these situations so that the intentions of Good Samaritan Laws are upheld and people get the assistance they need without being deterred from asking for future help.

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQβ1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQβ1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQβ1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQβ1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQβ1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

BACKGROUND: The introduction of illicitly made fentanyl in the United States has slowly replaced heroin. New illicit drugs are often associated with changes in frequency and modes of administration. We assessed changes in injection frequency and smoking fentanyl in the new era of fentanyl availability in San Francisco. METHODS: We used targeted sampling to recruit 395 people who inject drugs (PWID) into an observational cohort study in San Francisco 2018-2020. We assessed changes in injection frequency, opioid injection frequency and fentanyl smoking frequency in four six-month periods. We also conducted qualitative interviews with PWID asking about motivations for injecting and smoking opioids. RESULTS: The median number of past-month injections steadily decreased by semi-annual calendar year from 92 injections in July to December 2018 to 17 injections in January to June 2020. The rate of opioid injections reduced by half (Adjusted Incidence Rate Ratio = 0.41; 95 % Confidence Interval = 0.25, 0.70; p < 0.01). The number of days smoking fentanyl was associated with fewer number of injections (X2(2) = 11.0; p < 0.01). Qualitative interviews revealed that PWIDs motivation for switching from injecting tar heroin to smoking fentanyl was related to difficulties accessing veins. After switching to smoking fentanyl, they noticed many benefits including how the drug felt, improved health, fewer financial constraints, and reduced stigma. CONCLUSION: Between 2018 and 2020, there was a shift from injecting tar heroin to smoking fentanyl in San Francisco. Reductions in injection of illicit drugs may offer public health benefit if it reduces risk of blood-borne viruses, abscesses and soft-tissue infections, and infective endocarditis.

California's Welfare and Institutions code 5150 allows for a temporary psychiatric hold (TPH) of individuals who present a danger to themselves or others and/or may be gravely disabled due to mental illness. Little is known about the frequency and predictors of involuntary holds among people who inject drugs (PWID).MethodsWe sought to identify the prevalence and predictors of recent TPHs (within the past 12 months) among a community-recruited sample of PWID in Los Angeles and San Francisco, California during 2017-2018 (N = 531). Multivariable logistic regression modeling was used to evaluate demographic (e.g., age), economic (e.g., homelessness), drug use (e.g., types of drugs used), incarceration (e.g., recent arrest history) and mental health (e.g., lifetime mental health diagnosis) variables associated with recent TPH.ResultsAge (40-49 years old vs age 50 or older: AOR = 5.85; 95 % CI = 2.18, 15.67), current homelessness (AOR = 3.75; 95 % CI = 1.28, 11.0), lifetime mental health history (AOR = 6.23; 95 % CI = 2.08, 18.66), and frequency of methamphetamine use (AOR = 1.01; 95 % CI = 1.00, 1.01) were statistically associated with increased odds of having experienced a TPH, while frequency of past month heroin/opioid use was associated with decreased odds of reporting a TPH (AOR = 0.99; 95 % CI = 0.99, 1.00) in multivariable analysis.ConclusionsDiverse factors were associated with TPH among PWID. Our analysis underscores the need for research on PWID with co-occurring substance-use and mental illness disorders and homelessness. There is urgent need for expanding access to lower barrier publicly funded mental health treatment from a harm-reduction approach.

BackgroundSpontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors.MethodsTo identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group.ResultsA male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor.ConclusionsThese novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P

Overdose prevention sites (OPS) are places where people use previously obtained drugs under the supervision of a health professional. They have been proposed in six United States (US) cities, including Philadelphia, to help reduce opioid-related overdose deaths and public injection. Philadelphia has the highest overdose rate among large cities in the US, which has led a local community-based organization to plan the implementation of OPS. Kensington, a neighborhood with the highest drug mortality overdose rates in the city, is a likely site for the proposed OPS. Given the dearth of research systematically assessing public opinion towards OPS prior to implementation, we enrolled 360 residents and 79 business owners/staff in the Kensington neighborhood in a cross-sectional acceptability study. Face-to-face surveys assessed participant characteristics, experiences with drug-related social problems, and OPS acceptability. Using descriptive statistics, we estimated factors associated with favorability towards opening an OPS in the Kensington neighborhood. Ninety percent of residents were in favor of an OPS opening in Kensington. Support was significantly higher among unstably housed individuals and persons who currently use opioids. In the business sample, 63% of owners/staff were in favor of opening an OPS in Kensington. A greater proportion of Asian/Pacific Islanders, Hispanic/Latinx respondents, and non-Hispanic/Latinx Black respondents were in favor of an OPS opening in Kensington compared with white respondents (p

Background & aimsSpontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry.MethodsWe performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed.ResultsIn the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P = 5.99 × 10-50) and the MHC locus 6p21.32 (P = 1.15 × 10-21). We also associated HCV clearance with polymorphisms in the G-protein-coupled receptor 158 gene (GPR158) at 10p12.1 (P = 1.80 × 10-07). These 3 loci had independent, additive effects of HCV clearance, and account for 6.8% and 5.9% of the variance of HCV clearance in persons of European and African ancestry, respectively. Persons of African or European ancestry carrying all 6 variants were 24-fold and 11-fold, respectively, more likely to clear HCV infection compared with individuals carrying none or 1 of the clearance-associated variants.ConclusionsIn a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.

BackgroundHeroin use is increasing in the US. Heroin use may predispose users towards injection routes of drug administration as compared to other illicit substances.ObjectiveTo explore the relationship between heroin use and drug injection, we compared time from first use to first injection (referred to as time to injection onset by drug [TTIOD]) of heroin, methamphetamine/speed, cocaine, and crack cocaine among people who inject drugs (PWID).MethodsAge of first use and first injection by drug was collected from 776 PWID. Survival analyses were used to determine TTIOD and to examine demographic factors associated with TTIOD. Cox regression analysis was used to determine demographic factors associated with drug-specific injection onset.ResultsThe eventual injection onset rate by the drug was 99% for participants who used heroin, 85% for participants who used methamphetamine/speed, 80% for participants who used powder cocaine, and 38% for participants who used crack cocaine. Hazard ratios for injection use within one year of first use by drug were: 1.37 (median survival time [MST] = 0.61 years) for heroin, 0.66 (MST = 1.10 years) for methamphetamine/speed, 0.50 (MST = 2.93 years) for powder cocaine, and 0.12 (MST = 39.59 years) for crack cocaine. Demographic differences in TTIOD were found for each drug. Demographic differences were found for eventual injection by drug for all substances except heroin.ConclusionAmong PWID, heroin use was associated with a more rapid transition to injection and a higher rate of eventual heroin injection regardless of demographics. More robust, innovative efforts to reduce heroin use and prevent injection initiation are urgently needed.

BackgroundSeveral studies suggest that U.S. state-level legalization of cannabis for medical purposes may be associated with reductions in opioid use; yet its relationship with stimulant use, particularly in high-risk populations like unstably housed women, has received less attention. The purpose of this study was to estimate independent associations between medical and non-medical use of cannabis and use of stimulants and opioids among unstably housed women.MethodsCross-sectional data were analyzed from 245 women in the SHADOW study, a community based cohort in San Francisco, CA, in which HIV+ women were oversampled (126 HIV+ and 119 HIV-).ResultsCompared to no cannabis use in the past 6 months (51%), non-medical cannabis use (28%) was associated with a higher adjusted odds of using stimulants (Adjusted Odds Ratio [AOR]=4.34, 95% confidence interval [CI]: 2.17-8.70) and opioids (AOR=3.81, 95% CI: 1.78-8.15). Compared to no cannabis use, medical cannabis use (21%) was not significantly associated with stimulant or opioid use. Compared to non-medical cannabis use, however, medical cannabis use was associated with lower adjusted odds of using stimulants (AOR=0.42, 95% CI: 0.18-0.96). These associations were not modified by HIV status.ConclusionsAssociations between use of cannabis and "street drugs" depend on whether the cannabis is obtained through a medical context. Interventions, research, and policy considering the influence of cannabis on the use of other drugs may benefit by distinguishing between medical and non-medical cannabis use.