Radical hospitality: Innovative programming to build community and meet the needs of people who use drugs at a government-sanctioned overdose prevention site in San Francisco, California.

BACKGROUND: The Tenderloin Center (TLC), a multi-service center where people could receive or be connected to basic needs, behavioral health care, housing, and medical services, was open in San Francisco for 46 weeks in 2022. Within a week of operation, services expanded to include an overdose prevention site (OPS), also known as safe consumption site. OPSs have operated internationally for over three decades, but government-sanctioned OPSs have only recently been implemented in the United States. We used ethnographic methods to understand the ways in which a sanctioned OPS, situated in a multi-service center, impacts the lives of people who use drugs (PWUD). METHODS: We conducted participant observation and in-depth interviews June-December 2022. Extensive field notes and 39 in-depth interviews with 24 TLC guests and 15 TLC staff were analyzed using an inductive analysis approach. Interviewees were asked detailed questions about their experiences using and working at the TLC. RESULTS: TLC guests and staff described an atmosphere where radical hospitality-welcoming guests with extraordinary warmth, generosity, and unconditional acceptance-was central to the culture. We found that the co-location of an OPS within a multi-service agency (1) allowed for the culture of radical hospitality to flourish, (2) yielded a convenient one-stop shop model, (3) created a space for community building, and (4) offered safety and respite to guests. CONCLUSIONS: The co-location of an OPS within a multi-service drop-in center is an important example of how such an organization can build positive sociality among PWUD while protecting autonomy and reducing overdose mortality. Overdose response and reversal is an act of relational accountability in which friends, peers, and even strangers intervene to protect and revive one another. This powerful intervention was operationalized as an anti-oppressive, horizontal activity through radical hospitality with a built environment that allowed PWUD to be both social and safe.

Funding and Delivery of Syringe Services Programs in the United States, 2022.

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).

Organize and mobilize for implementation effectiveness to improve overdose education and naloxone distribution from syringe services programs: a randomized controlled trial.

BACKGROUND: The United States (US) continues to face decades-long increases in opioid overdose fatalities. As an opioid overdose reversal medication, naloxone can dramatically reduce opioid overdose mortality rates when distributed to people likely to experience or witness an opioid overdose and packaged with education on its use, known as overdose education and naloxone distribution (OEND). Syringe services programs (SSPs) are ideal venues for OEND with staff who are culturally competent in providing services for people who are at risk of experiencing or observing an opioid overdose. We carried out a randomized controlled trial of SSPs to understand the effectiveness of the organize and mobilize for implementation effectiveness (OMIE) approach at improving OEND implementation effectiveness within SSPs. METHODS: Using simple randomization, 105 SSPs were enrolled into the trial and assigned to one of two study arms - (1) dissemination of OEND best practice recommendations (Control SSPs) or the OMIE approach along with dissemination of the OEND best practice recommendations (i.e., OMIE SSPs). OMIE SSPs could participate in 60-min OMIE sessions once a month for up to 12 months. At 12-month post-baseline, 102 of 105 SSPs (97%) responded to the follow-up survey. RESULTS: The median number of sessions completed by OMIE SSPs was 10. Comparing OMIE SSPs to control SSPs, we observed significant increases in the number of participants receiving naloxone (incidence rate ratio: 2.15; 95% CI: 1.42, 3.25; p < 0.01) and the rate of naloxone doses distributed per SSP participant (adjusted incidence rate ratio: 1.97; 95% CI: 1.18, 3.30; p = 0.01). We observed no statistically significant difference in the number of adopted best practices between conditions (difference in means 0.2, 95% CI: - 0.7, 1.0; p = 0.68). We also observed a threshold effect where SSPs receiving a higher OMIE dose had greater effect sizes with regard to the number of people given naloxone and the number of naloxone doses distributed. CONCLUSIONS: In conclusion, the multifaceted OMIE approach was effective at increasing naloxone distribution from SSPs, despite substantial external shocks during the trial. These findings have major implications for addressing the overdose crisis, which has continued unabated for decades. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03924505 . Registered 19 April 2019.

Impact of a high-volume overdose prevention site on social and drug disorder in surrounding areas in San Francisco.

BACKGROUND: Between January and December 2022 a multi-service center incorporating an overdose prevention site (OPS) operated with city government sanction in San Francisco. One concern often expressed about OPS is that they may increase social nuisance associated with drug use in the surrounding area, despite international evidence that this is not the case. METHODS: We conducted systematic street observation of 10 indicators of drug- and homelessness-related social nuisance in a 500 m radius around the OPS and around a comparison point in the same city before and after the introduction of the OPS. We estimated the risk that any given street within sampling areas would have nuisance post-intervention relative to the control area using Poisson regression. RESULTS: Ratio of relative risks of any reported nuisance in the 500 m area surrounding the OPS from pre- to post-intervention to that of the comparison area was 0.69 (95% CI: 0.54, 0.87; p=0.002). The relative risk of drug-specific nuisance was similar to the comparison area pre/post intervention (0.90; 95% CI 0.66, 1.24; p=0.53). The risk of homelessness-specific nuisance decreased around the OPS (RR 0.7., 95% CI 0.52, 0.93; p=0.02) whereas they increased around the comparison area (RR 1.33, 95% CI 1.06, 1.68; p=0.02). CONCLUSION: We found that implementing authorized OPS services in a U.S. city did not increase the prevalence of visible signs of drug use and homelessness in the surrounding area. These findings are similar to those found at OPS outside the U.S.

Evaluating oxygen monitoring and administration during overdose responses at a sanctioned overdose prevention site in San Francisco, California: A mixed-methods study.

BACKGROUND: Overdose prevention sites (OPSs) are spaces where individuals can use pre-obtained drugs and trained staff can immediately intervene in the event of an overdose. While some OPSs use a combination of naloxone and oxygen to reverse overdoses, little is known about oxygen as a complementary tool to naloxone in OPS settings. We conducted a mixed methods study to assess the role of oxygen provision at a locally sanctioned OPS in San Francisco, California. METHODS: We used descriptive statistics to quantify number and type of overdose interventions delivered in 46 weeks of OPS operation in 2022. We used qualitative data from OPS staff interviews to evaluate experiences using oxygen during overdose responses. Interviews were coded and thematically analyzed to identify themes related to oxygen impact on overdose response. RESULTS: OPS staff were successful in reversing 100% of overdoses (n = 333) during 46 weeks of operation. Oxygen became available 18 weeks after opening. After oxygen became available (n = 248 overdose incidents), nearly all involved oxygen (91.5%), with more than half involving both oxygen and naloxone (59.3%). Overdoses involving naloxone decreased from 98% to 66%, though average number of overdoses concomitantly increased from 5 to 9 per week. Interviews revealed that oxygen improved overdose response experiences for OPS participants and staff. OPS EMTs were leaders of delivering and refining the overdose response protocol and trained other staff. Challenges included strained relationships with city emergency response systems due to protocol requiring 911 calls after all naloxone administrations, inconsistent supplies, and lack of sufficient staffing causing people to work long shifts. CONCLUSIONS: Although the OPS operated temporarily, it offered important insights. Ensuring consistent oxygen supplies, staffing, and removing 911 call requirements after every naloxone administration could improve resource management. These recommendations may enable success for future OPS in San Francisco and elsewhere.

Buprenorphine implementation at syringe service programs following waiver of the Ryan Haight Act in the United States.

INTRODUCTION: Among people with an opioid use disorder in the United States, only 10% receive buprenorphine treatment. The Ryan Haight Act is a federal law that has regulated buprenorphine delivery, requiring an in-person examination between a patient and provider before initiating treatment. At the beginning of the COVID-19 pandemic, federal agencies waived in-person examination requirements for buprenorphine treatment initiation. We examined whether Ryan Haight Act waiver improved implementation of telehealth buprenorphine within syringe service programs (SSPs) - organizations that serve people with historically low access to treatment. METHODS: We surveyed all known SSPs operating in the US in 2021 (N = 421) of which 77% responded (n = 325). We calculated the prevalence and accompanying 95% confidence intervals (CI) for implementation of telehealth buprenorphine inductions at SSPs in 2020. Multivariable logistic regression was used to assess differences in implementing telehealth buprenorphine inductions by organizational characteristics. RESULTS: In 2020, the prevalence of implementing buprenorphine inductions via telehealth was 24% (95% CI:19-30%). Non-governmental SSPs had a higher odds of telehealth buprenorphine inductions (adjusted odds ratio (aOR)= 2.92; 95% CI:1.22-7.00; p = 0.016), compared to governmental SSPs. Furthermore, the larger the organization's annual budget, the higher the odds of telehealth buprenorphine implementation (aOR=2.00 per quartile (95% CI:1.33-2.99; p = 0.001). SSPs located in states with higher opioid overdose mortality rates did not have significantly higher likelihood of telehealth buprenorphine implementation. CONCLUSION: A substantial number of SSPs implemented telehealth buprenorphine after waiver of the Ryan Haight Act. Permanent adoption of this waiver will be critical and providing financial resources to SSPs is vital to support implementation of new innovations.

Best practices for community-based overdose education and naloxone distribution programs: results from using the Delphi approach.

BACKGROUND: Opioid-related overdose deaths have surged in the USA over the last two decades. Overdose fatalities are preventable with the timely administration of naloxone. Syringe service programs (SSP) have pioneered community-based naloxone distribution through overdose prevention and naloxone distribution (OEND) programs. There is a dearth of information with regards to best practices for community-based OEND. METHODS: We utilized a modified Delphi approach to develop a set of best practices for OEND delivery. Starting with an initial list of best practices, we engaged 27 experts, in the field of OEND programming who reviewed, made recommendations for changes, and assigned a priority to each best practice. RESULTS: Two rounds of input resulted in a final list of 20 best practices organized into four categories. The mean priority scores ranged from 1.17 to 2.17 (range 1 to 3). The top 5 ranked best practices were ensuring that SSP participants have low barrier, consistent, needs-based access to naloxone and that there is ample naloxone available within communities. While the remaining fifteen best practices were deemed important, they had more to do with organizational culture and implementation climate. CONCLUSIONS: Increasing community-based OEND delivery is essential to reduce opioid overdose deaths; however, it will be insufficient to add programs without an eye toward quality of implementation and fidelity to the model upon which the evidence is based. This list of best practices summarizes the consensus among OEND experts and can serve as a tool for SSPs providing OEND programming to improve services.

Ingenuity and resiliency of syringe service programs on the front lines of the opioid overdose and COVID-19 crises.

As COVID-19 accelerated throughout 2020, syringe service programs (SSPs) faced challenges necessitating programmatic adaptations to prevent overdose deaths while simultaneously keeping workers and participants safe from COVID-19. We used qualitative methods to gain an understanding of the social context within which SSPs are operating during the COVID-19 pandemic. We conducted 36 in-depth interviews with program representatives from 18 programs and used the Exploration, Preparation, Implementation, Sustainment (EPIS) implementation framework to guide data analysis. We focused on 3 of the 4 EPIS constructs: Outer context, inner context, and innovation factors. Our data indicate that responding to the pandemic led to innovations in service delivery such as secondary and mail-based distribution, adoption of telemedicine for enrolling participants in medications for opioid use disorder (MOUD) and use of virtual training platforms for overdose prevention. We found high levels of staff and volunteer commitment, which was a cornerstone to the success of these innovations. We observed that many SSPs were short-staffed because of their commitment to safety, and some lost current funding as well as opportunities for future funding. Despite minimal staffing and diminished funding, SSPs innovated at an accelerated pace. To ensure the sustainability of these new approaches, a supportive external context (federal, state, and local policies and funding) is needed to support the development of SSPs' inner contexts (organizational characteristics, characteristics of individuals) and sustainment of the innovations achieved regarding delivery of naloxone and MOUD.

Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats.

Recent evidence indicates that the renin-angiotensin system (RAS) plays a major role in liver fibrosis. Here, we investigate whether the circulatory RAS, which is frequently activated in patients with chronic liver disease, contributes to fibrosis progression. To test this hypothesis, we increased circulatory angiotensin II (Ang II) levels in rats undergoing biliary fibrosis. Saline or Ang II (25 ng/kg/h) were infused into bile duct-ligated rats for 2 weeks through a subcutaneous pump. Ang II infusion increased serum levels of Ang II and augmented bile duct ligation-induced liver injury, as assessed by elevated liver serum enzymes. Moreover, it increased the hepatic concentration of inflammatory proteins (tumor necrosis factor alpha and interleukin 1beta) and the infiltration of CD43-positive inflammatory cells. Ang II infusion also favored the development of vascular thrombosis and increased the procoagulant activity of tissue factor in the liver. Livers from bile duct-ligated rats infused with Ang II showed increased transforming growth factor beta1 content, collagen deposition, accumulation of smooth muscle alpha-actin-positive cells, and lipid peroxidation products. Moreover, Ang II infusion stimulated phosphorylation of c-Jun and p42/44 mitogen-activated protein kinase and increased proliferation of bile duct cells. In cultured rat hepatic stellate cells (HSCs), Ang II (10(-8) mol/L) increased intracellular calcium and stimulated reactive oxygen species formation, cellular proliferation and secretion of proinflammatory cytokines. Moreover, Ang II stimulated the procoagulant activity of HSCs, a newly described biological function for these cells. In conclusion, increased systemic Ang II augments hepatic fibrosis and promotes inflammation, oxidative stress, and thrombogenic events.

The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation.

During fibrosis the hepatic stellate cell (HSC) undergoes a complex activation process characterized by increased proliferation and extracellular matrix deposition. The 70-kDa ribosomal S6 kinase (p70S6K) is activated by mitogens, growth factors, and hormones in a phosphatidylinositol 3-kinase-dependent manner. p70S6K regulates protein synthesis, proliferation, and cell cycle control. Because these processes are involved in HSC activation, we investigated the role of p70S6K in HSC proliferation, cell cycle control, and type I collagen expression. Platelet-derived growth factor (PDGF) stimulated p70S6K phosphorylation, which was blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase. Rapamycin blocked phosphorylation of p70S6K but had no affect on PDGF-induced Akt phosphorylation, positioning p70S6K downstream of Akt. Transforming growth factor-beta, which inhibits HSC proliferation, did not affect PDGF-induced p70S6K phosphorylation. Rapamycin treatment did not affect alpha1(I) collagen mRNA but reduced type I collagen protein secretion. Expression of smooth muscle alpha-actin was not affected by rapamycin treatment, indicating that HSC activation was not altered. Rapamycin inhibited serum-induced DNA synthesis approximately 2-fold. Moreover, rapamycin decreased expression of cyclins D1, D3, and E but not cyclin D2, Rb-Ser780, and Rb-Ser795. Together, p70S6K plays a crucial role in HSC proliferation, collagen expression, and cell cycle control, thus representing a potential therapeutic target for liver fibrosis.

Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and proinflammatory events in liver.

Recent evidence indicates that angiotensin II (ANG II) plays an important role in liver fibrogenesis. However, the underlying mechanisms are largely unknown. In advanced chronic liver diseases, circulating levels of ANG II are frequently elevated. We investigated the hepatic effects of prolonged systemic infusion of ANG II in normal rats. Saline or ANG II at subpressor and pressor doses (15 and 50 ng.kg-1.min-1, respectively) were infused to normal rats for 4 wk through a subcutaneous osmotic pump. Infusion of ANG II resulted in liver injury, as assessed by elevated serum liver enzymes. Livers from ANG II-perfused rats showed activation of JNK and ERK as well as increased NF-kappaB and activating protein-1 DNA-binding activity. Moreover, ANG II perfusion induced oxidative stress, increased concentration of proinflammatory cytokines, and upregulated the inflammatory proteins inducible nitric oxide synthase and cyclooxygenase-2. Histological examination of the livers from ANG II-infused rats showed mild portal inflammation as well as thickening and thrombosis of small hepatic vessels. ANG II-treated livers showed accumulation of CD43-positive inflammatory cells and activated hepatic stellate cells (HSCs) at the pericentral areas. A slight increase in collagen synthesis was observed, as assessed by Sirius red staining and hepatic hydroxyproline. All of these effects were observed when ANG II was perfused at subpressor and pressor doses. ANG II also accelerated the activation of primary cultured rat HSCs. In conclusion, increased systemic ANG II can induce liver injury by promoting proinflammatory events and vascular damage. ANG II-induced hepatic effects are not dependent on increase in arterial pressure.

Enhancement of presynaptic calcium current by cysteine string protein.

The isolated chick ciliary neuron calyx synapse preparation was used to test cysteine string protein (CSP) action on presynaptic N-type Ca(2+) channels. Endogenous CSP was localized primarily to secretory vesicle clusters in the presynaptic nerve terminal. Introduction of recombinant CSP into the voltage clamped terminal resulted in a prominent increase in Ca(2+) current amplitude. However, this increase could not be attributed to a change in Ca(2+) channel kinetics, voltage dependence, prepulse inactivation, or G protein inhibition but was attributed to the recruitment of dormant channels. Secretory vesicle associated endogenous CSP may play an important role in enhancing Ca(2+) channel activity at the transmitter release site.